1600 John F.

Kennedy Boulevard
Suite 1800
Philadelphia, Pennsylvania 19103-2899

ESSENTIAL FAMILY MEDICINE ISBN-13: 978-1-4160-2377-7

Fundamentals and Case Studies, Third Edition ISBN-10: 1-4160-2377-1
Copyright © 2006, 1998, 1993 by Elsevier Inc.

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage and retrieval system,
without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Health
Sciences Rights Department in Philadelphia, PA, USA: phone: (+1) 215-239-3804, fax: (+1) 215-239-3805, e-mail:
[email protected]. You may also complete your request on-line via the Elsevier homepage (http://
www.elsevier.com), by selecting “Customer Support” and then “Obtaining Permissions.”

NOTICE

Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate.
Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the
manufacturer of each product to be administered, to verify the recommended dose or formula, the method
and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on
his or her own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of
the law, neither the Publisher nor the Editor assumes any liability for any injury and/or damage to persons or
property arising out of or related to any use of the material contained in this book.

Library of Congress Cataloging-in-Publication Data

Essential family medicine : fundamentals and case studies / [edited by] Robert E. Rakel. — 3rd ed.
p. ; cm.
Rev. ed. of: Essentials of family practice. 2nd ed. c1998.
Includes bibliographical references and index.
ISBN-13: 978-1-4160-2377-7
ISBN-10: 1-4160-2377-1
1. Family medicine. 2. Family medicine—Case studies. I. Rakel, Robert E II. Essentials of family practice.
[DNLM: 1. Family Practice—Case Reports. WB 110 E782 2006]
RC49.E87 2006
610—dc22
2006048302

Acquisitions Editor: Rolla Couchman

Developmental Editor: Joanie Milnes
Senior Project Manager: Cecelia Bayruns
Design Direction: Karen O’Keefe Owens
Cover Designer: Louis Forgione
Marketing Manager: Laura Meiskey

Printed in the United States of America.

Last digit is the print number: 9 8 7 6 5 4 3 2 1

 Contributors

Allan V. Abbott, MD Robert A. Baldor, MD

Associate Dean for Curriculum and CME, Family Professor and Vice-Chairman, Family Medicine and
Medicine, Keck School of Medicine, University of Community Health, University of Massachusetts Medical
Southern California, Los Angeles, California School; Vice-Chairman, Family Medicine, University of
Elbow Pain (Epicondylitis) Massachusetts Memorial Health Center, Worcester,
Thomas Agresta, MD Massachusetts
University of Connecticut, St. Francis Hospital, Hartford, Cough (Possible Asthma); Breast Mass
Connecticut David M. Barclay III, MS, MPH
Tender Swelling of Hands and Feet (Sickle Cell Disease) Associate Professor, Department of Family and
Virginia D. Aguila, MD Community Medicine, Temple University School of
Assistant Professor, Department of Family Medicine, Medicine, Philadelphia, Pennsylvania
Creighton University Medical Center, Omaha, Nebraska Ringing in Ears (Tinnitus); Irregular Menstruation and
Breast Cancer Fatigue (Cushing’s Syndrome)

Janet R. Albers, MD Amber Barnhart, MD

Program Director and Associate Chair, Department of Director of Predoctoral Education; Associate Professor,
Family and Community Medicine, Southern Illinois Department of Family and Community Medicine,
University, Springfield, Illinois Southern Illinois University School of Medicine;
Irregular Menses (Dysfunctional Uterine Bleeding) Residency Faculty, Department of Family Medicine,
Memorial Medical Center; Residency Faculty,
Michael Altman, MD Department of Family Medicine, St. John’s Hospital,
Assistant Professor, Family and Community Medicine, Springfield, Illinois
University of Texas, Houston Medical School; Family Clumsiness and Difficulty Walking (Brain Tumor)
Medicine, Memorial-Hermann Hospital, Houston, Texas
Acne Wendy Brooks Barr, MD, MPH
Instructor, Department of Family Practice and
Mark Andrews, MD Community Medicine, University of Pennsylvania,
Assistant Professor, Family and Community Medicine, Philadelphia, Pennsylvania
Wake Forest University School of Medicine, Winston- Cervical Cancer Screening
Salem, North Carolina
Red Area on Left Temple (Basal Cell Carcinoma); Rash Bruce Barrett, MD, PhD
on Right Shoulder (Actinic Keratosis) Assistant Professor, Department of Family Medicine,
University of Wisconsin-Madison, Madison, Wisconsin
Ann M. Aring, MD Productive Cough (Acute Bronchitis)
Assistant Clinical Professor, Department of Family
Medicine, Ohio State University; Assistant Program Max Bayard, MD
Director, Riverside Family Practice Residency Program, Associate Professor and Program Director, Department of
Riverside Methodist Hospital, Columbus, Ohio Family Medicine, East Tennessee State University James
Lower Abdominal Pain (Pelvic Inflammatory Disease) H. Quillen College of Medicine, Johnson City, Tennessee
Restless Legs Syndrome; Bleeding Peptic Ulcer (Alcohol
Brian S. Bacak, MD Withdrawal Syndrome)
Assistant Professor of Family Medicine, University of
Colorado Health Science Center; Rose Family Medicine J. Mark Beard, MD
Residency, Denver, Colorado Assistant Professor, Family Medicine, University of
Heartburn (Gastroesophageal Reflux Disease) Washington; Active Staff, Family Medicine, University of
Washington Medical Center; Associate Staff, Family
Bruce Bagley, MD Medicine, Seattle Cancer Care Alliance, Seattle, Washington
Medical Director, Quality Improvement, American Selecting Radiographic Tests: Radiographs, Computed
Academy of Family Physicians, Leawood, Kansas Tomography, Magnetic Resonance Imaging, Ultrasound,
The Electronic Medical Record and Nuclear Imaging

v
 Contributors

Ian M. Bennett, MD, PhD Richard D. Clover, MD

Assistant Professor, Family Practice and Community Dean, School of Public Health and Information Sciences,
Medicine, University of Pennsylvania, Philadelphia, University of Louisville; Associate Vice President for Health
Pennsylvania Informatics, University of Louisville, Louisville, Kentucky
Contraception Nasal Congestion in a 15-Month-Old Girl
Baruch A. Brody, PhD (Immunization)
Leon Jaworski Professor of Biomedical Ethics; Director, Stephen G. Cook, MD
Center for Medical Ethics and Health Policy, Baylor Community Health Clinic, Lakewood, Washington
College of Medicine, Houston, Texas Hiccups; Cold and Numb Hands and Feet (Frostbite);
Ethics in Family Medicine Gallstones
Leslie Brott, MD Jane E. Corboy, MD
Staff Physician, Medicine/Pediatrics, Williamette Valley Associate Professor and Director of Graduate Medical
Medical Center, McMinnville, Oregon Education, Family and Community Medicine, Baylor
Pancreatitis (Acute Pancreatitis); Bizarre Behavior College of Medicine, Houston, Texas
(Schizophrenia); Influenza Chest Pain (Angina Pectoris)
Chester R. Burns, MD, PhD Peter F. Cronholm, MD, MSCE
James Wade Rockwell Professor of Medicine, University Assistant Professor, Department of Family Medicine and
of Texas Medical Branch at Galveston, Institute for the Community Health; Adjunct Scholar, Center for Clinical
Medical Humanities, Galveston, Texas Epidemiology and Biostatistics; Senior Fellow, Leonard
The Relevance of Medical History to Family Medicine Davis Center for Healthcare Economics; Associate,
Kara L. Cadwallader, MD Firearm and Injury Center at Penn, University of
Assistant Clinical Professor, Family Practice Residency of Pennsylvania, Philadelphia, Pennsylvania
Idaho, Boise, Idaho Sexually Transmitted Diseases (Gonorrhea); Domestic
Dyspnea on Exertion (Congestive Heart Failure) Violence
Jon C. Calvert, MD Michael Crouch, MD, MSPH
Clinical Professor, Department of Family Practice, Associate Professor, Family and Community Center
University of Oklahoma College of Medicine; Active Staff, Medicine, Baylor College of Medicine; Active Staff, Family
Department of Obstetrics and Gynecology, Hillcrest Medicine, St. Lukes Episcopal; Active Staff, Family
Medical Center; Active Staff, Department of Obstetrics Medicine Division of Medicine Department, The
and Gynecology, Saint John Medical Center, Tulsa, Methodist Hospital, Houston, Texas
Oklahoma Abdominal Pain and Loose Bowel Movements
Cervical Dysplasia: Diagnosis and Management (Hypercholesterolemia)
Roberto Cardarelli, DO, MPH Loren A. Crown, MD
Assistant Professor; Director, Center for Evidence-Based Clinical Professor, Department of Family Medicine,
Medicine, Department of Family Medicine, University of University of Tennessee, Covington, Tennessee
North Texas Health Science Center at Fort Worth; Snakebite
Network Research Director, North Texas Primary Care Timothy P. Daaleman, DO, MPH
Practice-Based Research Network (NorTex), University of Associate Professor, Department of Family Medicine,
North Texas Health Science Center at Fort Worth, Fort University of North Carolina; Attending Physician,
Worth, Texas Department of Family Medicine, University of North
Sore Throat (Acute Pharyngitis); High Blood Pressure Carolina Hospitals; Research Associate, Program on
(Hypertension) Aging, Disability and Long-Term Care, Cecil G. Sheps
Cheng-Chieh Chuang, MD Center for Health Services Research, Chapel Hill, North
Clinical Instructor, Family Medicine, Brown University Carolina
School of Medicine, Providence, Rhode Island; President, Terminal Illness
Lakeside Family Medicine, Raynham, Massachusetts James M. Daniels, MD, MPH
Swollen Foreskin (Diabetes Mellitus Type 2); Changing Professor, Department of Family and Community
Nevus (Melanoma) Medicine, Southern Illinois University School of
Heidi Chumley, MD Medicine; Director, Southern Illinois University School
Director of Predoctoral Education, Unviersity of Kansas of Medicine, Quincy, Illinois
School of Medicine, Kansas City, Kansas Upper Extremity Numbness and Pain (Double Crush
Genital Warts (Condyloma Acuminata) Syndrome); Low Back Pain

vi
 Contributors

Lloyd A. Darlow, MD Robert S. Fawcett, MD, MS

Clinical Assistant Professor of Family Practice, Weill Assistant Clinical Professor, Family Medicine, Penn State
Medical College of Cornell University, New York, Hershey Medical Center, Hershey, Pennsylvania; Medical
New York; Chairman, Department of Family Practice, Director, Thomas Hart Family Medicine; Active Staff
Cayuga Medical Center at Ithaca, Ithaca, New York Member, Family Medicine, York Hospital, York,
Difficulty Paying Attention (Attention- Pennsylvania
Deficit/Hyperactivity Disorder) Pigmented Thumbnail (Nail Lentigo)
Darwin Deen, MD, MS Jeanne M. Ferrante, MD
Director, Undergraduate Medical Education, Department Associate Professor, Department of Family Medicine,
of Family and Social Medicine, Albert Einstein College of University of Medicine and Dentistry of New Jersey,
Medicine, Bronx, New York Newark, New Jersey
Abdominal Obesity (Metabolic Syndrome) Dizziness (Vestibular Neuritis)
Jennifer DeVoe, MD, DPhil Matthew J. Fleig, MD
Instructor, Department of Family Medicine, Oregon Assistant Professor, Family Medicine, University of
Health and Science University (OHSU), Portland, Oregon Rochester; Attending Family Medicine, Highland
Leg Pain and Swelling (Venous Thrombosis); Bedwetting Hospital, Rochester, New York
(Childhood Nocturnal Enuresis) Newborn Distress (Neonatal Resuscitation)
Lisa Dolovich, MD, BScPham, PharmD, MSc Robert S. Freelove, MD
Associate Professor, Departments of Family Medicine, Associate Director, Smoky Hill Family Medicine
Medicine, and Clinical Epidemiology and Biostatistics, Residency Program; Clinical Instructor, University of
McMaster University, Hamilton, Ontario, Canada Kansas School of Medicine–Wichita, Salina, Kansas
Patient Compliance Delirium (Hypomagnesemia); Hand Swollen and Red
(Spider Bite)
Frank J. Domino, MD
Associate Professor and Clerkship Professor, Department David L. Gaspar, MD
of Family Medicine and Community Health, University of Associate Professor, Director of Predoctoral Education,
Massachusetts Medical School, Worchester, Massachusetts Department of Family Medicine, University of Colorado
Cough (Possible Asthma) at Denver Health Sciences Center, Denver, Colorado
Vesicular Rash (Varicella); Pruritic Rash (Urticaria)
Marguerite R. Duane, MD
Clerkship Director and Associate Professor, Department James M. Gill, MD, MPH
of Medicine, Georgetown University Medical Center, Associate Professor, Family and Community Medicine,
Washington, D.C. Thomas Jefferson University; Senior Scholar, Health
Fever and Cough (Influenza); Shortness of Breath in a Policy, Philadelphia, Pennsylvania; Director, Health
12-Year-Old Girl (Asthma) Services Research, Family and Community Medicine,
Wilmington, Delaware
Charles B. Eaton, MD, MS Shoulder and Back Pain (Fibromyalgia)
Professor, Family Medicine, Brown Medical School,
Providence, Rhode Island; Director, Center for Primary Gary R. Gray, DO
Care and Prevention, Memorial Hospital of Rhode Island, Assistant Clinical Professor, Family and Community
Pawtucket, Rhode Island Medicine, University of California, San Francisco,
Hyperlipidemia (Mixed Lipid Disorder) California; Program Director, Family Practice Residency,
Natividad Medical Center, Salinas, California
John W. Ely, MD, MSPH Toe Pain and Swelling (Gout); Ear Pain (Bell’s Palsy)
Associate Professor, Family Medicine, University of Iowa,
Roy J. and Lucille A. Carver College of Medicine, Iowa Larry A. Green, MD
City, Iowa Professor of Family Medicine and Director of the
Sinus Congestion (Sinusitis) National Program Office for Prescription for Health,
University of Colorado Health Sciences Center, Denver,
Bernard Ewigman, MD, MSPH Colorado; Senior Scholar in Residence, Robert Graham
University of Chicago Pritzker School of Medicine, Center: Policy Studies in Family Medicine and Primary
Chicago, Illinois Care, Washington, D.C.
Evidence-Based Medicine The Future of Family Medicine
Ruth Falik, MD Kenneth J. Grimm, MD, MS
Assistant Professor of Medicine, Baylor College of Associate Program Director, Family Medicine, Oakwood
Medicine; Attending Physician, General Internal Hospital and Medical Center, Dearborn, Michigan;
Medicine, Ben Taub General Hospital, Houston, Texas Clinical Instructor, Family Medicine, University of
Episodic Chest Pain (Angina Pectoris); Palpitations Michigan, Ann Arbor, Michigan
(Atrial Fibrillation) Abdominal Pain (Endometriosis); Back Pain
(Osteoporosis)

vii
 Contributors

Rahul Gupta, MD Keith B. Holten, MD

Assistant Professor of Medicine, Internal Medicine, Clinical Professor, Family Medicine, University of
University of Alabama at Birmingham, Huntsville Cincinnati College of Medicine, Cincinnati, Ohio;
Regional Medical Campus; Attending Physician, Residency Director, Family Medicine, Clinton Memorial
Medicine, Huntsville Hospital, Huntsville, Alabama Hospital, University of Cincinnati, Wilmington, Ohio
Widespread Pruritic Rash (Adverse Drug Reaction); Evaluating the Medical Literature; Diagnosis and
Headache Management of an Acute Exacerbation (Chronic
R. Brian Haynes, MD, PhD Obstructive Pulmonary Disease)
Michael Gent Professor and Chair, Department of William Y. Huang, MD
Clinical Epidemiology and Biostatistics, DeGroote School Associate Professor, Department of Family and
of Medicine at McMaster University; Active Staff, Section Community Medicine, Baylor College of Medicine,
of General Internal Medicine, Hamilton Health Sciences; Houston, Texas
Professor, Department of Medicine, DeGroote School of Problem Solving in Family Medicine
Medicine at McMaster University, Hamilton, Ontario, Matthew L. Hunsaker, MD
Canada Director, Rural Medical Education Program (RMED),
Patient Compliance National Center for Rural Health Professions, University
Valerie L. Hearns, MD of Illinois College of Medicine at Rockford, Rockford,
Associate Professor and Vice Chair, Department of Family Illinois; Physician, Family Medicine, KSB Hospital, Dixon,
Medicine, University of South Dakota School of Illinois; Medical Director, Family Medicine, Tri-County
Medicine; Medical Staff, Family Medicine, Sioux Valley Clinic, Northern Illinois University, Malta, Illinois
Hospital, University of South Dakota Medical Center; Type 2 Diabetes Mellitus
Medical Staff, Family Medicine, Avera McKennan David Q. Hutcheson-Tipton, MD
Hospital, Sioux Falls, South Dakota Lieutenant Commander, Medical Corps, United States Navy;
Nausea and Vomiting (Pyelonephritis); Vaginal Itching Department Head, Family Practice Department, Makalapa
and Discharge (Vaginitis); Left Lower Abdominal Pain Clinic, Naval Health Clinic Hawaii, Pearl Harbor, Hawaii
(Ectopic Pregnancy) Nasal Congestion (Allergic Rhinitis); Difficulty
Joel J. Heidelbaugh, MD Maintaining an Erection (Erectile Dysfunction)
Clinical Assistant Professor, Department of Family Medicine, David M. Jester, MD
University of Michigan, Ann Arbor, Michigan; Medical Associate Professor and Predoctoral Director, Department
Director, Ypsilanti Health Center, Ypsilanti, Michigan of Family Medicine, Medical College of Georgia, Augusta,
Right Upper Quadrant Abdominal Pain (Cholelithiasis); Georgia
Peptic Ulcer Disease; Gastroesophageal Reflux Disease Confusion in a Man 70 Years Old (Sepsis); Ankle Edema
David Henderson, MD and Superficial Ulcer Stasis (Venus Stasis Ulcer)
Assistant Professor, Department of Family Medicine, Norman B. Kahn, Jr., MD
Family Medicine Residency Program, University of Vice President, Science and Education, American
Connecticut School of Medicine, Hartford, Connecticut; Academy of Family Physicians, Leawood, Kansas
Saint Francis Hospital and Medical Center, Farmington, The Future of Family Medicine
Connecticut
Tender Swelling of Hands and Feet (Sickle Cell Disease) Victoria S. Kaprielian, MD
Clinical Professor, Community and Family Medicine,
Charles E. Henley, DO, MPH Duke University Medical Center; Attending Staff,
Professor and Founders and Associates Research Chair in Community and Family Medicine, Duke University
Family Medicine, Department of Family Medicine, Hospital; Attending Staff, Family Medicine, Durham
University of Oklahoma College of Medicine, Tulsa; Regional Hospital, Durham, North Carolina
Active Staff, Family Medicine, Hillcrest Medical Center; Urinary Frequency and Dysuria (Urinary Tract
Active Staff and Chair, Family Medicine, Tulsa Regional Infection)
Medical Center, Tulsa, Oklahoma
Disease Prevention Michael G. Kavan, MD
Associate Dean for Student Affairs, Associate Professor of
Warren L. Holleman, PhD Family Medicine, Associate Professor of Psychiatry,
Assistant Professor, Department of Family and Community Creighton University School of Medicine, Omaha, Nebraska
Medicine, Baylor College of Medicine, Houston, Texas Multiple Somatic Complaints (Generalized Anxiety
Ethics in Family Medicine Disorder)

viii
 Contributors

Louis A. Kazal, Jr., MD Sarah Ellen Lesko, MD

Chief Clinical Officer, Department of Community and Family Physician, Carolyn Downs Family Medical Center,
Family Medicine, Dartmouth Medical School, Hanover, Seattle, Washington
New Hampshire Fatigue (Hypothyroidism); Irregular Bowel Movements
Arm Laceration (Laceration Repair) (Colon Cancer)
David Kibbe, MD, MBA Walter D. Leventhal, MD
Director, Center for Health Information Technology, Clinical Associate Professor of Family Medicine, Medical
American Academy of Family Physicians, Leawood, Kansas University of South Carolina, Charleston, South Carolina;
The Electronic Medical Record Senior Partner, Dorchester Medical Associates,
Summerville, South Carolina
Sanford R. Kimmel, MD
Rash and Fever (Rocky Mountain Spotted Fever)
Professor of Family Medicine, Department of Family
Medicine; Associate Residency Director; Family Practice Kenneth Lin, MD
Residency, Medical University of Ohio, Toledo, Ohio Assistant Professor, Department of Family Medicine,
Short Child (Constitutional Growth Delay) Georgetown University, Washington, D.C.
Behavior Problem in a 2-Year-Old Boy (Autism)
T. Alex King, MD
Assistant Professor, Department of Family Practice and Kurt A. Lindberg, MD
Community Medicine, University of Texas Southwestern Pisacano Leadership Foundation Alumnus, Lakewood
Medical Center at Dallas, Dallas, Texas Family Medicine, Holland, Michigan
Skin Papule (Basal Cell Carcinoma) Nausea, Vomiting, and Lethargy (Acute Renal Failure);
Pain “Everywhere” (Fibromyalgia); Diarrhea
Scott Kinkade, MD, MSPH
Assistant Professor of Family Medicine, Director of Jennifer E. Lochner, MD
Predoctoral Education, Department of Family and Assistant Professor, Department of Family Medicine,
Community Medicine, University of Texas Southwestern Oregon Health and Science University, Portland, Oregon
Medical School, Dallas, Texas Fever without Source in Children (Fever); Pruritus
Acne (Acne Vulgaris); Disorientation (Heat Stroke) (Atopic Dermatitis)
Kurt Kurowski, MD David P. Losh, MD
Associate Professor, Department of Family and Preventive Professor, Department of Family Medicine, University of
Medicine, The Chicago Medical School at RFUMS, North Washington, Seattle, Washington
Chicago, Illinois; Staff Physician, Family Medicine, Selecting Radiographic Tests: Radiographs, Computed
Swedish Covenant Hospital, Chicago, Illinois; Staff Tomography, Magnetic Resonance Imaging, Ultrasound,
Physician, Family Practice, ENH-Highland Park Hospital, and Nuclear Imaging
Highland Park, Illinois Linda Lou, MD, MPH
Dysuria and Urinary Frequency (Urinary Tract Practicing Physician, Community Health Center,
Infection); Alzheimer’s Disease Tucson, Arizona
Elizabeth Laffey, MD Right Flank Pain (Nephrolithiasis)
Assistant Professor, Department of Community and Barbara A. Majeroni, MD
Family Medicine, Saint Louis University School of Associate Clinical Professor of Family Medicine,
Medicine, Belleville, Illinois University at Buffalo School of Medicine and Biomedical
Lymphadenopathy (HIV Infection); Abnormal Liver Sciences, State University of New York, Buffalo, New York
Function Tests (Chronic Viral Hepatitis) Unexplained Weight Loss (Hyperthyroidism)
Frederick Lambert, MD Geoffrey Margo, MD, PhD
Assistant Professor, Department of Family Medicine, Clinical Associate Professor, Psychiatry, University of
Albert Einstein College of Medicine, MMG-Castle Hill Pennsylvania Health System; Director,
Family Practice, Bronx, New York Consultation/Liaison Psychiatry Service, Psychiatry,
Worsening Low Back Pain (Metastatic Cancer Pain Pennsylvania Hospital, Philadelphia, Pennsylvania
Management) Anxiety (Social Phobia)
Greg L. Ledgerwood, MD Katherine Margo, MD, PhD
Clinical Assistant Professor, Department of Family Director of Student Activities; Assistant Professor,
Medicine, University of Washington School of Medicine, Department of Family Practice and Community
Seattle, Washington; Private Practice, Omak, Medicine, University of Pennsylvania School of Medicine,
Washington Philadelphia, Pennsylvania
Multiple Allergies (Allergic Rhinitis Asthma) Chest Pain and Fatigue (Anxiety Disorder)

ix
Contributors

James C. Martin, MD Donald E. Nease, Jr., MD

Program Director, Family Practice Residency Program, Associate Professor, Department of Family Medicine,
CHRISTUS Santa Rosa Health Care; Clinical Professor, University of Michigan; Attending Physician, Family
University of Texas Health Science Center, San Medicine, University of Michigan Hospitals and Health
Antonio, Texas Centers, Ann Arbor, Michigan
The Future of Family Medicine Fatigue and Difficulty Concentrating (Depression)
Jeffrey Alan May, MD Giang T. Nguyen, MD, MPH
Clinical Instructor, Family Medicine, University of Clinical Instructor, Family Practice and Community
Tennessee-Memphis College of Health Sciences, Medicine, University of Pennsylvania School of Medicine;
Covington, Tennessee Attending Physician, Family Practice and Community
Spider Bites Medicine, Hospital of the University of Pennsylvania, and
Eugene A. Merzon, MD Pennsylvania Presbyterian Medical Center, Philadelphia,
Department of Family Medicine, Sackler School of Pennsylvania
Medicine, Tel Aviv University, Tel Aviv, Israel; Tutor, Vaginal Bleeding (Endometrial Cancer)
Department of Family Medicine and Family Practice Melissa Nothnagle, MD
Residency, Leumit Health Fund, Israel; Family Physician, Assistant Professor, Department of Family Medicine,
Jonathan Clinic, Leumit Health Fund, Ariel, Israel Brown Medical School, Providence, Rhode Island
Vitamin B12 Deficiency Third-Trimester Vaginal Bleeding (Placenta Previa);
James S. Millar, MD, MPH Severe Menstrual Cramps (Primary Dysmenorrhea)
Associate Professor and Medical Director, Department of Alice Anne O’Donell, MD
Family Medicine, University of Oklahoma–Tulsa, Tulsa, Professor, Department of Family Medicine, John Sealy
Oklahoma Hospital, The University of Texas Medical Branch,
Penile Discharge (Gonorrhea) Galveston, Texas
Karl E. Miller, MD The Relevance of Medical History to Family Medicine
Professor and Vice Chair, Family Medicine, Chattanooga John G. O’Handley, MD
Unit, University of Tennessee College of Medicine, Mount Carmel Family Practice, Columbus, Ohio
Chattanooga, Tennessee Fever and Fussiness in a 22-Month-Old Child (Acute
Vaginal Discharge (Vulvovaginal Candidiasis) Otitis Media)
Eugene Mochan, PhD, DO Trish Palmer, MD
Associate Dean, Primary Care and Continuing Education; Assistant Professor, Family Medicine, Midwest
Professor, Philadelphia College of Osteopathic Medicine, Orthopaedics at Rush, Chicago, Illinois
Philadelphia, Pennsylvania Ankle Injury (Ankle Sprain); Persistent Productive Cough
Bilateral Knee Pain (Osteoarthritis) (Mountain Sickness)
Venita W. Morell, MD Jon S. Parham, DO, MPH
Affiliate Associate Professor, Family and Community Associate Professor, Predoctoral Director, Family
Medicine, Wake Forest University School of Medicine, Medicine, University of Tennessee Graduate School of
Winston-Salem, North Carolina; Medical Director, Medicine; Active Staff Member, Family Medicine,
Okaloosa County Health Department, Fort Walton Beach, University of Tennessee Medical Center, Knoxville,
Florida Tennessee; Active Staff Member, Consulting, Family
Insomnia Medicine, Peninsula Hospital, Louisville, Tennessee
R. Michael Morse, MD Skin “Spots” and Bruising (Thrombocytopenia)
Founders and Associates Professor, Chair of Family Paul Paulman, MD
Medicine, Department of Family Medicine, University Professor and Predoctoral Director, Family Medicine,
of Oklahoma, College of Medicine, Tulsa, Oklahoma University of Nebraska Medical Center, Omaha, Nebraska
Disease Prevention Tiredness (Anemia)
Scott E. Moser, MD Layne A. Prest, PhD
Associate Professor, Family and Community Medicine, Director of Behavioral Medicine and Associate
The University of Kansas School of Medicine–Wichita, Professor of Family Medicine, University of Nebraska
Wichita, Kansas Medical Center; Medical Family Therapist,
Cramping Abdominal Pain (Irritable Bowel Syndrome); Department of Family Medicine, Nebraska Medical
Hyperactive Child (Attention-Deficit/Hyperactivity Center, Omaha, Nebraska
Disorder) Chest Pain and Shortness of Breath (Panic Disorder)

x
 Contributors

David P. Rakel, MD Timothy Scanlan, MD, MBA

Director, University of Wisconsin Integrative Medicine; Associate Clinical Professor, Family and Community
Assistant Professor, Department of Family Medicine, University of Kansas School of Medicine;
Medicine, University of Wisconsin Medical School; Medical Director, Addiction Specialists of Kansas,
University of Wisconsin Hospitals and Clinics, Wichita, Kansas
Department of Family Medicine, Feeling Depressed (Drug Dependency); Heartburn
University of Wisconsin; Saint Mary’s Hospital and (Alcohol Problem)
Medical Center, Madison, Wisconsin Stephen Scott, MD
Integrative Medicine Assistant Professor, Family and Community Medicine,
Robert E. Rakel, MD Baylor College of Medicine, Houston, Texas
Professor, Department of Family and Community Interpreting Laboratory Tests
Medicine, Baylor College of Medicine, Houston, Texas John W. Sellors, MSc, MD
The Family Physician; The Problem-Oriented Medical Visiting Professor, Department of Family Medicine,
Record University of Washington; Senior Medical Advisor,
Kalyanakrishnan Ramakrishnan, MD Reproductive Health, Program for Appropriate
Associate Professor of Family and Preventive Medicine, Technology in Health, Seattle, Washington; Clinical
University of Oklahoma Health Sciences Center, Professor, Department of Family Medicine, McMaster
Oklahoma City, Oklahoma University, Hamilton, Ontario, Canada
Bilateral Leg Pain (Peripheral Arterial Disease); Patient Compliance
Hyperthyroidism Douglas R. Smucker, MD, MPH
Dino William Ramzi, MD Associate Professor, Family Medicine, University of
Medical Director, Community Clinic, Inc., Rockville, Cincinnati, Cincinnati, Ohio
Maryland Evaluating the Medical Literature
Dyspnea and Confusion (Pulmonary Embolism) Daniel L. Stulberg, MD
Anna Mies Richie, MD Associate Professor, Family Medicine, University of
Assistant Professor, Department of Family and Colorado; Chair, Department of Family Medicine, Rose
Community Medicine, Springfield Family Medicine Medical Center; Residency Director, Rose Family Medical
Residency Program, Southern Illinois University School Residency, University of Colorado, Denver, Colorado
of Medicine; Southern Illinois University Family and Thorn in Bottom of Foot (Plantar Wart)
Community Medicine, Springfield, Illinois Jeffrey Susman, MD
Obesity and Elevated Blood Pressure (Metabolic Professor and Chair, Family Medicine, University of
Syndrome); Shoulder and Wrist Pain (Rheumatoid Cincinnati; Chair, Family Medicine, University Hospital;
Arthritis) Family Medicine, The Christ Hospital, Cincinnati, Ohio;
Rodney Riedel, MD Family Medicine, Clinton Memorial Hospital,
Primary Care Sports Medicine Fellow, University of Wilmington, Ohio
Connecticut, St. Francis Hospital, Hartford, Connecticut Evaluating the Medical Literature
Right Elbow Pain (Tendinosis) Richard R. Terry, DO
Patrick Riley, MD Director, Wilson Family Practice Residency; Director,
Resident, Saint Louis University School of Medicine, Osteopathic Medical Education, United Health Services
Belleville, Illinois Hospitals; Associate Clinical Professor, SUNY Upstate
Abnormal Liver Function Tests (Chronic Viral Hepatitis) Medical University, Clinical Campus at Binghamton,
Adam Rindfleisch, MD Johnson City, New York
Family Medicine Physician, University of Wisconsin Overweight (Obesity)
Northeast Family Medical Center; St. Mary’s Hospital, Barbara Thompson, MD
Madison, Wisconsin Sealy Hutchings and Lucille Wright Hutchings Chair and
Integrative Medicine Professor, Family Medicine; Assistant Dean for Faculty
John C. Rogers, MD, MPH Practice, University of Texas Medical Branch; Medical
Professor and Vice Chair for Education, Family and Director, University of Texas Medical Branch Hospitals
Community Medicine, Baylor College of Medicine, and Clinics, Galveston, Texas
Houston, Texas The Relevance of Medical History to Family Medicine
Problem Solving in Family Medicine

xi
 Contributors

Pamela H. Tietze, MD Veronica Wilbur, RN, MSN

Associate Professor, Family Medicine, University of Assistant Professor, Nursing, Wilmington College, New
Oklahoma College of Medicine, Tulsa, Oklahoma Castle, Delaware
Perianal Itching (Pinworms) Type 1 Diabetes Mellitus
John W. Tipton, MD W. Michael Woods, MD
Associate Professor and Vice Chair, Department of Family Associate Professor, Program Director, University of
Medicine, University of Oklahoma College of Medicine, Oklahoma College of Medicine, Tulsa, Oklahoma;
Tulsa, Oklahoma Department of Family Medicine, Rural Program,
Giardiasis Ramona, Oklahoma
Chest Pain and Shortness of Breath (Iron Deficiency Anemia)
Richard P. Usatine, MD
Professor and Vice Chair for Medical Student Education, Therese Zink, MD, MPH
Department of Family and Community Medicine, Assistant Professor, Department of Family and
University of Texas Health Science Center at San Antonio, Community Medicine, University of Minnesota,
San Antonio, Texas Minneapolis, Minnesota
Genital Warts (Condyloma Acuminata) Family Dynamics and Health
Miriam Vincent, MD, PhD Kira Zwygart, MD
Professor and Chair, Department of Family Medicine, Assistant Professor, Family Medicine, University of South
SUNY–Downstate Medical Center; University Hospital of Florida College of Medicine; Family Medicine, Tampa
Brooklyn, Brooklyn, New York General Hospital, Tampa, Florida
Sore Throat (Pharyngitis) Tremor (Parkinson’s Disease)
Randy Wertheimer, MD
Associate Professor, Department of Family Medicine and
Community Health, University of Massachusetts School
of Medicine, Worcester, Massachusetts; Chair of Family
Medicine, Cambridge Health Alliance, Cambridge,
Massachusetts
Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

xii
 Preface

This third edition is designed as were the first two: to and alternative medicine techniques that make
serve as a resource for medical students and others family physicians truly comprehensive primary
learning the essentials of our discipline. Although the care physicians.
title has been modified to reflect the name change of ● The Electronic Medical Record. This information
the American Board of Family Practice to the is essential to the future practice of modern family
American Board of Family Medicine, the focus medicine.
remains the same as in previous editions.
A number of significant changes have been Following the Fundamentals section are 138
made in this edition: case studies covering the entire spectrum of family
medicine. These cases illustrate the variety of chal-
● Advancing technology has made it possible to lenges in family medicine and the rewards of manag-
make the entire text plus valuable additional mate- ing patients over time. Of the problems presented, 82
rial available electronically. are in the printed version and 56 more in the elec-
● Online access provides not only the text but also
tronic version. Patients present just as they would to
additional cases and links to other Elsevier publi-
a family physician and a differential diagnosis is
cations.
developed using problem solving techniques typical
● The printed version and the additional material
of those used in family medicine.
can be downloaded to a personal computer or a
Additional material that is available in the elec-
PDA (personal digital assistant).
tronic version includes:
● Evidence-based ratings are used throughout the
text to indicate the strength of the evidence pre- ● Integrative Medicine–21 tables, including Popular
sented.
Herbal Remedies: Key Facts for Primary Providers,
● Color is used to highlight important features.
Points to Consider When Advising Patients about
●
Key Points are boxed for easy retrieval of essential Herbal Remedies, Important Considerations
information. Regarding Supplementation of Specific Nutrients,
● Evidence-based medicine content is enhanced
Points to Consider When Referring Patients
through a relationship with FPIN (Family
for Manipulative Therapies, and Mind Body
Physicians Inquiries Network), a national consor-
Techniques and Therapies.
tium dedicated to using information technology to ●
Evidence-Based Medicine–Three appendixes that
improve healthcare.
include five Critical Appraisal Worksheets, a glossary
of EBM terms, and a list of EBM electronic resources.
In this edition there are six new chapters in the ● Disease Prevention—39 tables, including Actual
Fundamentals section: causes of Death in the United States in 1990 and
● The Future of Family Medicine. The authors are 2000, Eating Plan for Healthy Americans, and
among leaders from the seven U.S. family medicine Probability of Developing Invasive Cancers by Age
organizations that participated in the Future of and Sex, 1998–2000.
Family Medicine Project.
●
56 additional case studies.
●
The Relevance of Medical History to Family
● ABFM Board (American Board of Family Medicine)
Medicine. Those who ignore history are destined style questions.
to repeat it.
●
Evidence-Based Medicine. This chapter is written Primary care is unique in that diseases present in
by the president and executive editor of FPIN, who their early undifferentiated stage when it is most dif-
is also Chairman of Family Medicine at the ficult to make a specific diagnosis. The fact that fam-
University of Chicago. ily physicians feel comfortable with a variety of often
● Evaluating the Medical Literature. This chapter vague presenting complaints distinguishes them
outlines how to understand and evaluate studies from physicians in a narrow specialty. It is this vari-
published in the medical literature. ety that keeps the family physician professionally
● Integrative Medicine. This chapter presents a stimulated and perpetually challenged, and that sus-
thorough approach to the use of complementary tains the excitement of practicing medicine.

xiii
 Preface

My special thanks to colleagues who have taken on quality, and to my wife Peggy, who for more than
the time to share their knowledge and experience 50 years has supported my passion for the written
with us by providing cases drawn from their prac- word.
tices. My thanks also to the excellent staff at W.B.
Saunders for their attention to detail and insistence Robert E. Rakel, MD

xiv
 C h a p t e r

1 The Family Physician

Robert E. Rakel

porating this shared knowledge and using it uniquely

KEY POINTS to deliver primary medical care. In addition to shar-
ing content with other medical specialties, family
1. The American Board of Family Practice was medicine emphasizes knowledge from areas such as
established in 1969 and changed its name to family dynamics, interpersonal relations, counseling,
the American Board of Family Medicine in and psychotherapy. The specialty’s foundation, how-
2004. ever, remains clinical, with the primary focus on the
2. The AAFP is the American Academy of Family medical care of people who are ill.
Physicians, not the American Academy of Devotion to continuing, comprehensive, per-
Family Practice. sonalized care, early detection and management of
3. Primary care is the provision of continuing, illness, prevention of disease and maintenance of
comprehensive care to a population undifferen- health, and the ongoing management of patients in a
tiated by gender, disease, or organ system. community setting uniquely qualify the family
4. The most cost-effective health care systems physician to deliver primary care.
depend on a strong primary care base. The The curriculum for training family physicians is
United States has the most expensive health designed to represent realistically the skills and body
care system in the world but ranks among the of knowledge that the physicians will require in prac-
worst in overall quality of care because of its tice. This curriculum relies heavily on an accurate
weak primary care base. analysis of the problems seen and the skills used by
5. The most challenging diagnoses are those that family physicians in their practices. Unfortunately,
present in their early, undifferentiated stage the content of residency training programs for the
when there are often only subtle differences primary care specialties has not always been appro-
between serious disease and minor ailments. priately directed toward solving the problems most
6. The family physician is the quarterback, orches- commonly encountered by physicians practicing in
trating the skills of a variety of health profes- these specialties. The almost randomly educated pri-
sionals who may be involved in the care of a mary physician of previous years is being replaced by
seriously ill patient. one specifically prepared to address the kinds of
problems likely to be encountered in practice. For
this reason, the “model office” is an essential compo-
The family physician provides continuing, compre- nent of all family practice residency programs.
hensive care in a personalized manner to patients of
all ages and to their families, regardless of the pres-
ence of disease or the nature of the presenting com-
plaint. Family physicians accept responsibility for THE JOY OF FAMILY PRACTICE
managing an individual’s total health needs while
maintaining an intimate, confidential relationship If you cannot work with love but only with dis-
with the patient. taste, it is better that you should leave your work
Family medicine emphasizes responsibility for and sit at the gate of the temple and take alms from
total health care—from the first contact and initial those who work with joy.
assessment through the ongoing care of chronic Kahlil Gibran (1883–1931)
problems. Prevention and early recognition of disease
are essential features of the discipline. Coordination The rewards in family medicine come largely from
and integration of all necessary health services with knowing patients intimately over time and sharing
the least amount of fragmentation and the skills to their trust, respect, and friendship. The thrill is the
manage most medical problems allow family physi- close bond (actually friendship) that develops with
cians to provide cost-effective health care. patients. This bond is strengthened with each physi-
Family medicine is a specialty that shares many cal or emotional crisis in a person’s life, when he or
areas of content with other clinical disciplines, incor- she turns to the family physician for help.

3
Chapter 1 The Family Physician

It is especially rewarding when the family physi-

Table 1-1 Physician Attributes
cian cares for a newly married couple, delivers their
Contributing to Patient
first baby, sees them frequently for well-child care,
Satisfaction
and provides ongoing care for the parents, the grow-
ing child, and any subsequent children. No other 1. Does not judge but understands and supports
medical specialty is so privileged. To participate in a 2. Always honest and direct
family’s life in such a close and intimate manner is 3. Acts as partner in maintaining health
uniquely rewarding. 4. Treats both serious, and nonserious conditions
The practice of family medicine involves the joy 5. Attends to emotional/physical health
of greeting old friends in every examining room, and 6. Listens to me
7. Encourages me to lead healthier lifestyle
the variety of problems encountered keeps the physi-
8. Tries to get to know me
cian professionally stimulated and perpetually chal- 9. Can help with any problem
lenged. In contrast, physicians practicing in narrow 10. Someone I can stay with as I grow older
specialties often lose their enthusiasm for medicine
after seeing the same problems every day. The variety From Stock Keister MC, Green LA, Kahn NB, Phillips
RL, McCann J, Fryer GE. What people want from
in family practice sustains the excitement and pre- their family physician. Am Fam Physician
cludes boredom. 2004b;69:2310.

PHYSICIAN AND PATIENT than 70 million, it is important that we have suffi-

SATISFACTION cient primary care physicians to care for them. The
need and the rewards of this type of practice must be
Physician satisfaction is associated with quality of communicated to students before they decide how to
care, particularly as measured by patient satisfaction. spend the rest of their professional lives.
The strongest factor associated with a physician’s Overall, 70% of U.S. physicians are satisfied with
satisfaction is not personal income but the ability their career, with 40% being very satisfied and only
to provide high-quality care to his or her patients. 20% dissatisfied (Leigh et al., 2002).
Physicians are most satisfied with their practice Personal attributes of physicians considered
when they can have an ongoing relationship with most important for patient satisfaction are listed in
their patients, the freedom to make clinical decisions rank order in Table 1-1. In addition, people want their
without financial conflicts of interest, adequate time primary care doctor to meet five basic criteria: “to be
with patients, and sufficient communication with in their insurance plan, to be in a location that is con-
specialists (DeVoe et al., 2002). DeVoe et al. also venient, to be able to schedule an appointment within
found that general internists were more dissatisfied a reasonable period of time, to have good communi-
with their careers than family physicians (20.6% vs. cation skills, and to have a reasonable amount of
17.3%). Not only can such dissatisfaction lead to experience in practice.” They especially want “a physi-
health problems in the physicians themselves, but it cian who listens to them, who takes the time to
is difficult to imagine a patient being satisfied with explain things to them, and who is able to effectively
care provided by a dissatisfied physician. Women integrate their care” (Stock Keister et al., 2004a,b).
have a greater chance of burnout than men.
Landon et al. (2003) found that rather than declin-
ing income, the strongest predictor of decreasing satis- DEVELOPMENT OF THE SPECIALTY
faction in practice is loss of clinical autonomy. This
includes the inability of physicians to obtain services for As long ago as 1923, Francis Peabody commented
their patients, control their time with patients, and that the swing of the pendulum toward specializa-
maintain the freedom to provide high-quality care. tion had reached its apex and that modern medicine
In an analysis of 33 specialties, Leigh et al. had fragmented the health care delivery system to
(2002) found surprisingly that physicians in high- too great a degree. He called for a rapid return of the
income “procedural” specialties such as obstetrics/ generalist physician who would give comprehensive,
gynecology, otolaryngology, ophthalmology, and personalized care.
orthopedics were the most dissatisfied. Physicians in Dr. Peabody’s declaration proved premature;
these specialties and those in internal medicine were society and the medical establishment were not ready
more likely than family physicians to be dissatisfied for such a proclamation. The trend toward special-
with their careers. Among the specialty areas most ization gained momentum through the 1950s, and
satisfying according to the Leigh et al. study was geri- fewer physicians entered general practice. In the early
atrics. Because the population of those older than age 1960s, leaders in the field of general practice began
65 in the United States has doubled since 1960 and advocating a seemingly paradoxical solution to
will double again between 2000 and 2030 to more reverse the trend and correct the scarcity of general

4
 Chapter 1 The Family Physician

practitioners—the creation of still another specialty. the individual and the family. It is the specialty in
These physicians envisioned a specialty that embod- breadth that integrates the biologic, clinical, and
ied the knowledge, skills, and ideals that they knew as behavioral sciences. The scope of family medicine
primary care. In 1966, the concept of a new specialty encompasses all ages, both sexes, each organ system,
in primary care received official recognition in two and every disease entity (AAFP, 1993).
separate reports published 1 month apart. The first In many countries, the term general practice is
of these was the report of the Citizens’ Commission synonymous with family medicine. The Royal New
on Graduate Medical Education of the American Zealand College of General Practitioners emphasizes
Medical Association (1966), also known as the Millis that a general practitioner provides care that is
Commission Report. The second report came from “anticipatory as well as responsive, and is not limited
the Ad Hoc Committee on Education for Family by the age, sex, race, religion or social circumstances
Practice of the Council of Medical Education of the of patients, nor by their physical or mental states.”
American Medical Association (1996), also called The general practitioner must be available and must
the Willard Committee. Three years later, in 1969, provide care that is personal, comprehensive, contin-
the American Board of Family Practice came into uing, and coordinated in the context of family and
being as the 20th medical specialty board, thus giving community. He or she must be the patient’s advocate;
birth to the specialty of family practice. The name of be competent, caring, and compassionate; be able to
the specialty board was changed in 2004 to the live with uncertainty; and be willing to recognize lim-
American Board of Family Medicine (ABFM). itations and refer when necessary (Richards, 1997).
Much of the impetus for the Millis and Both the Council on Graduate Medical Edu-
Willard reports came from the American Academy cation and the Association of American Medical
of General Practice, which was renamed the Colleges define generalist physicians as those who
American Academy of Family Physicians in 1971. have completed 3-year training programs in family
The name change reflected a desire to increase medicine, internal medicine, or pediatrics and do
emphasis on family-oriented health care and to not subspecialize. The Council on Graduate
gain academic acceptance for the new specialty of Medical Education emphasizes that this definition
family practice. should be “based on an objective analysis of train-
The ABFM has distinguished itself by being the ing requirements in disciplines that provide gradu-
first specialty board to require recertification (every 7 ates with broad capabilities for primary care
years), now called maintenance of certification, to practice” (Graduate Medical Education National
ensure the ongoing competence of its members. Advisory Committee, 1980).
Among basic requirements for certification and recer-
tification, the ABFM has included continuing educa-
tion, the foundation on which the American Academy Family Physician
of General Practice had been built when organized in The family physician is a physician who is educated
1947. A diplomate of the ABFM must complete 300 and trained in the discipline of family medicine, a
hours of acceptable continuing education activity broadly encompassing medical specialty. Family
every 6 years and one self-assessment module per year physicians possess unique attitudes, skills, and
over the Internet to be eligible for recertification. Once knowledge that qualify them to provide continuing
eligible, a candidate’s competence is examined by cog- and comprehensive medical care, health mainte-
nitive testing and performance in practice evaluation. nance, and preventive services to each member of a
The ABFM’s emphasis on quality of education, family regardless of sex, age, or type of problem, be it
knowledge, and performance has facilitated the rapid biologic, behavioral, or social. These specialists,
increase in prestige for the family physician in our because of their background and interactions with
health care system. The obvious logic of the ABFM’s the family, are best qualified to serve as each patient’s
emphasis on continuing education to maintain advocate in all health-related matters, including the
required knowledge and skills has been adopted by appropriate use of consultants, health services, and
other specialties and state medical societies. Now, all community resources (American Academy of Family
specialty boards are committed to the concept of Physicians, 1993).
recertification to ensure that their diplomates remain The World Organization of Family Doctors
current with advances in medicine. (World Organization of National Colleges, Academies,
and Academic Associations of General Practitioners/
DEFINITIONS Family Physicians [WONCA]) defines the family
doctor in part as
Family Medicine
the physician who is primarily responsible for
Family medicine is the medical specialty that pro- providing comprehensive health care to every
vides continuing and comprehensive health care for individual seeking medical care, and arranging

5
Chapter 1 The Family Physician

for other health personnel to provide services

1. It is first-contact care, serving as a point of entry
when necessary. The family physician functions
for the patient into the health care system.
as a generalist who accepts everyone seeking
2. It includes continuity by virtue of caring for
care whereas other health providers limit access
patients over a period of time, both in sickness
to their services on the basis of age, sex, and/or
and in health.
diagnosis. (World Organization of National
3. It is comprehensive care, drawing from all the
Colleges, Academies, and Academic Associations
traditional major disciplines for its functional
of General Practitioners/Family Physicians, 1991,
content.
p. 2)
4. It serves a coordinative function for all the health
care needs of the patient.
Of Americans reporting an individual provider
5. It assumes continuing responsibility for individ-
as their usual source of care in 1996, 62% named a
ual patient follow-up and community health
family physician compared with 16% naming an
problems.
internist and 15% naming a pediatrician. Of those
6. It is a highly personalized type of care.
without a primary care physician, twice as many
(12%) went without needed services when compared
with those with a primary care physician (6%)
Primary Care Physician
(Robert Graham Center for Policy Studies in Family
Practice and Primary Care, 2000). A primary care physician is a generalist physician
who provides definitive care to the undifferentiated
Primary Care patient at the point of first contact and takes contin-
uing responsibility for providing the patient’s care.
Primary care is that care provided by physicians Such a physician must be trained specifically to pro-
specifically trained for and skilled in comprehensive vide primary care services.
first-contact and continuing care for ill persons or Primary care physicians devote the majority of
those with an undiagnosed sign, symptom, or health their practice to providing primary care services to a
concern (the “undifferentiated” patient) not limited defined population of patients. The style of primary
by problem origin (biologic, behavioral, or social), care practice is such that the personal primary care
organ system, or gender. physician serves as the entry point for substantially
Primary care includes, in addition to diagnosis all the patient’s medical and health care needs, not
and treatment of acute and chronic illnesses, health limited by problem origin, organ system, gender, or
promotion, disease prevention, health maintenance, diagnosis. Primary care physicians are advocates for
counseling, and patient education, in a variety of the patient in coordinating the use of the entire
health care settings such as office, inpatient, critical health care system to benefit the patient (American
care, long-term care, home care, and day care. Academy of Family Physicians, 1994).
Primary care is performed and managed by a per- The ABFM and the American Board of Internal
sonal physician, using other health professionals for Medicine have agreed on a definition of the general-
consultation or referral as appropriate. ist physician and that “providing optimal generalist
Primary care provides patient advocacy in the care requires broad and comprehensive training that
health care system to accomplish cost-effective care cannot be gained in brief and uncoordinated educa-
by coordination of health care services. Primary care tional experiences” (Kimball and Young, 1994,
promotes effective doctor-patient communication p. 316). They define the generalist physician as one
and encourages the role of the patient as a partner “who provides continuing, comprehensive, and
in health care (American Academy of Family coordinated medical care to a population undiffer-
Physicians, 1994). entiated by gender, disease, or organ system” (p. 315).
The Institute of Medicine defines primary care Physicians who provide primary care should be
as the provision of integrated, accessible health care trained specifically to manage the problems encoun-
services by clinicians who are accountable for tered in a primary care practice. Rivo et al. (1994)
addressing a large majority of personal health care identified the common conditions and diagnoses
needs, developing a sustained partnership with that generalist physicians should be competent to
patients, and practicing in the context of family and manage in a primary care practice and compared
community (Stock Keister et al., 2004a,b). these with the training of the various “generalist”
Because many physicians deliver primary care in specialties. They recommended that the training of
different ways and with varying degrees of prepara- generalist physicians include at least 90% of the key
tion, the staff of the ABFM has further clarified the diagnoses. By comparing the content of residency
definition. According to the ABFM, primary care is a programs, they found that this goal was met by fam-
form of delivery of medical care that encompasses ily practice (95%), internal medicine (91%), and
the following functions: pediatrics (91%) but that obstetrics and gynecology

6
 Chapter 1 The Family Physician

(47%) and emergency medicine (42%) fell far short person when we pass judgment as a superior, only
of this goal. when we see our own frailties as well as his.”
Pellegrino goes on to comment that a compassion-
ate authority figure is effective only when others can
receive the “orders” without being humiliated. The
PERSONALIZED CARE physician must not “put down” the patients but
must be ever ready, in Galileo’s words, “to pro-
It is much more important to know what sort of nounce that wise, ingenuous, and modest state-
patient has a disease than what sort of disease a ment—‘I don’t know.’” Compassion, practiced in
patient has. these terms in each patient encounter, obtunds the
Sir William Osler (1904) inherent dehumanizing tendencies of today’s highly
institutionalized and technologically oriented pat-
Family physicians do not just treat patients; they care terns of patient care.
for people. This caring function of family medicine
emphasizes the personalized approach to understand- The treatment of a disease may be entirely imper-
ing the patient as a person, respecting the person as an sonal; the care of a patient must be completely per-
individual, and showing compassion for his or her dis- sonal. (Peabody, 1930)
comfort. The best illustration of a caring and compas-
sionate physician is “The Doctor” by Sir Luke Fieldes If an intimate relationship with patients remains
(Fig. 1-1), showing a physician at the bedside of an ill our primary concern as physicians, high-quality med-
child in the preantibiotic era. This painting has become ical care will persist, regardless of the way in which it
the symbol for medicine as a caring profession. is organized and financed. For this reason, family
medicine emphasizes consideration of the individual
Caring without science is well-intentioned kind- patient in the full context of his or her life, rather than
ness, but not medicine. On the other hand, science the episodic care of a presenting complaint. The Millis
without caring empties medicine of healing and Commission Report stressed that the family physician
negates the great potential of an ancient profes- “focuses not upon individual organs and systems but
sion. The two complement and are essential to the upon the whole man who lives in a complex social set-
art of doctoring. (Lown, 1996, p. 223) ting, and knows that diagnosis or treatment of a part
often overlooks major causative factors and therapeu-
Compassion means co-suffering and reflects the tic opportunities” (Citizens’ Commission on Graduate
physician’s willingness somehow to share the Medical Education, American Medical Association
patient’s anguish and understand what the sickness [Millis Commission], 1966, p. 35).
means to that person. Compassion is an attempt Family physicians assess the illnesses and com-
to “feel” along with the patient. Pellegrino (1979, plaints presented to them, dealing personally with the
p. 161) stated that “we can never feel with another majority and arranging special assistance for a few.
The family physician serves as the patients’ advocate,
explaining the causes and implications of illness to the
patients and their families, and serves as an advisor
and confidant to the family, both individually and col-
lectively. The family physician receives many intellec-
tual satisfactions from this practice, but the greatest
reward arises from the depth of human understanding
and personal satisfaction inherent in family practice.
Patients have adjusted somewhat to a more
impersonal form of health care delivery and
frequently look to institutions rather than to individ-
uals for their health care; yet, their need for person-
alized concern and compassion remains. Tumulty
(1970) found that patients consider a good physician
to be one who (1) shows genuine interest in them,
(2) thoroughly evaluates their problem, (3) demon-
strates compassion, understanding, and warmth, and
(4) provides clear insight into what is wrong and
what must be done to correct it.
The family physician’s relationship with each
Figure 1-1 The Doctor by Sir Luke Fieldes, 1891. (Tate patient should reflect compassion, understanding, and
Gallery, London, UK) patience combined with a high degree of intellectual

7
Chapter 1 The Family Physician

honesty. The physician must be thorough in 1. A strong sense of responsibility for the total
approaching problems but also possess a keen sense of ongoing care of the individual and the family
humor. He or she must be capable of encouraging in during health, illness, and rehabilitation
each patient optimism, courage, insight, and the self- 2. Compassion and empathy, with a sincere interest
discipline necessary for recovery. in the patient and the family
Bulger (1998) addressed the threats to scientific 3. A curious and constantly inquisitive attitude
compassionate care in today’s managed care environ- 4. Enthusiasm for the undifferentiated medical
ment. “With health care time inordinately rationed problem and its resolution
today in the interest of economy, Americans could 5. An interest in the broad spectrum of clinical
organize themselves right out of compassion. . . . It medicine
would be a tragedy, just when we have so many scien- 6. The ability to deal comfortably with multiple
tific therapies at hand, for scientists to negotiate away problems occurring simultaneously in one
the element of compassion, leaving this crucial patient
dimension of healing to nonscientific healers” 7. A desire for frequent and varied intellectual and
(p. 106). Time for patient care is becoming increas- technical challenges
ingly threatened. Bulger described a study involving a 8. The ability to support children during growth
“Good Samaritan” principle, showing that the deci- and development and during their adjustment
sion of whether to stop and care for a person in dis- to family and society
tress is predominantly a function of having the time 9. The ability to assist patients in coping with
to do so. Even those with the very best intentions everyday problems and in maintaining stability
require time to be of help to a suffering person. in the family and community
Ludmerer (1999) focused on the problems fac- 10. The capacity to act as coordinator of all health
ing medical education in this environment. resources needed in the care of a patient
11. A continuing enthusiasm for learning and for
Some managed care organizations have even urged the satisfaction that comes from maintaining
that physicians be taught to act in part as advo- current medical knowledge through continuing
cates of the insurance payer rather than the medical education
patients for whom they care. . . . Medical educators 12. The ability to maintain composure in times of
would do well to ponder the potential long-term stress and to respond quickly with logic, effec-
consequences of educating the nation’s physicians tiveness, and compassion
in today’s commercial atmosphere in which the 13. A desire to identify problems at the earliest pos-
good visit is a short visit, patients are ‘consumers,’ sible stage (or to prevent disease entirely)
and institutional officials speak more often of the 14. A strong wish to maintain maximal patient sat-
financial balance sheet than of service and the isfaction, recognizing the need for continuing
relief of patients’ suffering. patient rapport
15. The skills necessary to manage chronic illness
Cranshaw et al. (1995) raised similar concerns: and to ensure maximal rehabilitation following
acute illness
Our first obligation must be to serve the good of
those persons who seek our help and trust us to
16. An appreciation for the complex mix of physical,
provide it. Physicians, as physicians, are not, and
emotional, and social elements in holistic and
must never be, commercial entrepreneurs, gate-
personalized patient care
closers, or agents of fiscal policy that runs counter
17. A feeling of personal satisfaction derived from
to our trust. Any defection from primacy of the
intimate relationships with patients that natu-
patient’s well-being places the patient at risk by
rally develop over long periods of continuous
treatment that may compromise quality of or
care, as opposed to the short-term satisfaction
access to medical care. . . . Only by caring and
gained from treating episodic illnesses
advocating for Fthe patient can the integrity of
18. A skill for and commitment to educating
our profession be affirmed. (p. 1553)
patients and families about disease processes and
the principles of good health

CHARACTERISTICS AND FUNCTIONS The ideal family physician is an explorer, driven

OF THE FAMILY PHYSICIAN by a persistent curiosity and the desire to know
more. The family physician is required to be part
Attributes of the Family Physician theologian, as was Paracelsus, part politician, as was
Benjamin Rush, and part humorist, as was Oliver
The following characteristics are certainly desirable Wendell Holmes. At all times, however, the care of
for all physicians, but they are of greatest importance the patient—the whole patient—is the primary
for the physician in family practice: goal.

8
 Chapter 1 The Family Physician

nature and style of operation. This ability to observe

Continuing Responsibility
families over time allows valuable insight that
One of the essential functions of the family physician improves the quality of medical care provided to an
is the willingness to accept ongoing responsibility for individual patient. One of the greatest challenges in
managing a patient’s medical care. Once a patient or family medicine is the need to be alert to the chang-
a family has been accepted into the physician’s prac- ing stresses, transitions, and expectations of family
tice, responsibility for care is both total and continu- members over time and to the effect that these and
ing. The Millis Commission chose the term primary other family interactions have on the health of
physician to emphasize the concept of primary individuals.
responsibility for the patient’s welfare; however, Although the family is the family physician’s pri-
the term primary care physician is more popular mary concern, his or her skills are equally applicable
and refers to any physician who provides first- to the individual living alone or to people in other
contact care. varieties of family living. Individuals with alternative
The family physician’s commitment to patients forms of family living interact with others who have
does not cease at the end of illness but is a continu- a significant effect on their lives. The principles of
ing responsibility, regardless of the patient’s state of group dynamics and interpersonal relationships that
health or the disease process. There is no need to affect health are equally applicable to everyone.
identify the beginning or endpoint of treatment The family physician must assess an individual’s
because care of a problem can be reopened at any personality so that presenting symptoms can be
time, even though a later visit may be primarily for appropriately evaluated and given the proper degree
another problem. This prevents the family physician of attention and emphasis. A complaint of abdominal
from focusing too narrowly on one problem and pain may be treated lightly in one patient who fre-
helps maintain a perspective on the total patient in quently presents with minor problems, but the same
his or her environment. Peabody (1930) believed complaint would be investigated immediately and in
that much patient dissatisfaction results from the depth in another individual who has a more stoic per-
physician’s neglecting to assume personal responsi- sonality. The decision regarding which studies to per-
bility for supervision of the patient’s care: “For some form and when is influenced by knowledge of the
reason or other, no one physician has seen the case patient’s lifestyle, personality, and previous response
through from beginning to end, and the patient may pattern. The greater the degree of knowledge and
be suffering from the very multitude of his coun- insight into the patient’s background, which is gained
selors” (p. 8). through years of ongoing contact, the more capable
The greater the degree of continuing involve- the physician is of making an appropriate early and
ment with a patient, the more capable the physician rapid assessment of the presenting complaint. The
is in detecting early signs and symptoms of organic less background information the physician has to rely
disease and differentiating it from a functional prob- on, the greater is the need to depend on costly labo-
lem. Patients with problems arising from emotional ratory studies and the more likely is overreaction to
and social conflicts can be managed most effectively the presenting symptom. Families receiving continu-
by a physician who has intimate knowledge of the ing, comprehensive care have fewer incidences of
individual and of his or her family and community hospitalization, fewer operations, and fewer physician
background. This knowledge comes only from visits for illnesses compared with those having no
insight gained by observing the patient’s long-term regular physician. This is due, at least in part, to the
patterns of behavior and responses to changing physician’s knowledge of the patients, to the physi-
stressful situations. This longitudinal view is particu- cian’s seeing them earlier for acute problems and thus
larly useful in the care of children and allows the preventing complications that would require hospi-
physician to be more effective in assisting children to talization, to the physician’s being available by tele-
reach their full potential. The closeness that develops phone, and to the physician’s seeing them more
between physicians and young patients increases a frequently in the office for health supervision. Care is
physician’s ability to aid the patients with problems also less expensive because there is less need to rely on
that occur during later periods in life, such as adjust- radiographic and laboratory procedures and visits to
ment to puberty, problems with employment, or emergency departments.
marriage and changing social pressures. As the fam-
ily physician maintains this continuing involvement Collusion of Anonymity
with successive generations within a family, the abil-
ity to manage intercurrent problems increases with The need for a primary physician who accepts con-
knowledge of the total family background. tinuing responsibility for patient care was empha-
By virtue of this ongoing involvement and inti- sized by Michael Balint (1965) in his concept of
mate association with the family, the family physi- “collusion of anonymity.” In this situation, the
cian develops a perceptive awareness of a family’s patient is seen by a variety of physicians, not one of

9
 Chapter 1 The Family Physician

whom is willing to accept total management of the the quality of clinical outcomes of primary care
problem. Important decisions are made—some practitioners is comparable to that of specialists or
good, some bad—but without anyone feeling fully subspecialists in similar, clinically appropriate situ-
responsible for them. ations. . . . Practitioners working within their
Peabody (1930) examined the futility of a domains of practice have higher quality out-
patient’s making the rounds from one specialist to comes than those working outside their regular
another without finding relief, because the patient domains. . . . Physicians and advance practice nurse
generalists trained in and practicing generalist com-
lacked the guidance of a sound general practitioner petencies provide a higher quality of primary care
who understood his physical condition, his nervous to their patients than those whose domains of
temperament and knew the details of his daily life. practice are by definition restricted to specialized
And many a patient who on his own initiative has areas.
sought out specialists, has had minor defects accen-
tuated so that they assume a needless importance, When hospitalized patients with pneumonia are
and has even undergone operations that might cared for by family physicians or full-time specialist
well have been avoided. Those who are particularly hospitalists, the quality of care is comparable, but the
blessed with this world’s goods, who want the best hospitalists incur higher hospital charges, longer
regardless of the cost and imagine that they are lengths of stay, and use more resources (Smith et al.,
getting it because they can afford to consult as 2002).
many renowned specialists as they wish, are often In the United States, a 20% increase in the num-
pathetically tragic figures as they veer from one ber of primary care physicians is associated with a
course of treatment to another. Like ships that lack 5% decrease in mortality (40 fewer deaths per
a guiding hand upon the helm, they swing from 100,000), but the benefit is even greater if the pri-
tack to tack with each new gust of wind but get no mary care physician is a family physician. Adding
nearer to the Port of Health because there is no one more family physician per 10,000 people is asso-
pilot to set the general direction of their course. ciated with 70 fewer deaths per 100,000, which is
(pp. 21–22) a 9% reduction in mortality. Specialists practicing
outside their specialty area have increased mortality
rates for acquired pneumonia, acute myocardial
Chronic Illness
infarction, congestive heart failure, and upper gas-
The family physician must also be committed to trointestinal hemorrhage. Specialists are trained to
managing the common chronic illnesses that have no look for zebras instead of horses, and specialty care
known cure but for which continuing management usually means more tests, which can lead to a cascade
by a personal physician is all the more necessary to effect and consequently greater likelihood of adverse
maintain an optimal state of health for the patient. It effects. A study of the major determinants of health
is a difficult and often trying job to manage these outcomes in all 50 U.S. states found that when the
continuing, unresolvable, and progressively crippling number of specialty physicians increase, outcomes
problems, control of which requires a remodeling of are worse, whereas mortality rates are lower where
the lifestyle of the entire family. there are more primary care physicians (Starfield,
Almost half (45%) of all Americans have a 2005).
chronic condition. The costs both to individuals McGann and Bowman (1990) compared the
and to the health care system are enormous. In 2000, morbidity and mortality of patients hospitalized by
care of chronic illness consumed 75 cents of every family physicians and by internists. They found
health care dollar spent in the United States (The that, even though the family physicians’ patients
Robert Wood Johnson Foundation Annual Report, were older and more severely ill, there was no sig-
2002). nificant difference in morbidity and mortality. In
addition, the total charges for their hospital care
were lower.
Quality of Care
A comparison of family physicians and obstetri-
Primary care provided by physicians specifically cians/gynecologists in the management of low-risk
trained to care for the problems presenting to per- pregnancies showed no difference with respect to
sonal physicians, who know their patients over a neonatal outcomes. However, women cared for by
span of time, is of higher quality than care provided family physicians had fewer cesarean sections and
by other physicians. This has been confirmed by a episiotomies and were less likely to receive epidural
variety of studies comparing the care given by physi- anesthesia (Hueston et al., 1995).
cians in different specialties. Patients of subspecialists practicing outside their
Following a review of the literature on quality specialty have longer lengths of hospital stay and
and cost of care, Boex et al. (1993) noted that higher mortality rates than patients of subspecialists

10
 Chapter 1 The Family Physician

practicing within their specialty or patients of gen- Although the rhetoric suggests that this cost is
eral internists (Weingarten et al., 2002). worth it to have the best health care system in the
The quality of our health care system is being world, the truth is that we are far from that goal. In a
eroded by physicians’ being extensively trained, at comparison of the quality of health care in 13 coun-
great expense, to practice in one area and instead tries using 16 different health indicators, the United
practicing in another, such as anesthesiologists prac- States ranked 12th, second from the bottom. A
ticing in emergency departments and surgeons prac- wealth of evidence indicates that quality of health
ticing as generalists. Primary care, to be done well, care is associated with primary care performance. Of
requires extensive training specifically tailored to the seven countries at the top of the average health
problems frequently seen in primary care. These ranking, five have strong primary care infrastruc-
include the early detection, diagnosis, and treatment tures. “The higher the primary care physician-to-
of depression; the early diagnosis of cancer (espe- population ratio in a state, the better most health
cially of the breast and the colon); the management outcomes are” (Starfield, 2000, p. 485).
of gynecologic problems; and the care of those with Similarly, the greater the number of primary
chronic or terminal illness. care physicians practicing in a country, the lower
As much-needed changes in the American is the cost of health care. Figure 1-2 shows that in
medical system are implemented, it would be wise Great Britain, Canada, and the United States, the
to keep some perspective on the situation regard- cost of health care is inversely proportional to the
ing physician distribution. Beeson (1974) has percentage of generalists practicing in that country.
commented: Countries with strong primary care have lower
overall health care costs, improved health outcomes,
I have no doubt at all that a good family doctor and healthier populations (Starfield, 2001). In a
can deal with the great majority of medical comparison of 11 features of primary care in 11
episodes quickly and competently. A specialist, on Western countries, the United States ranked lowest in
the other hand, feels that he must be thorough, terms of primary care ranking and per capita health
not only because of his training but also because care expenditures and also performed poorly on
he has a reputation to protect. He, therefore, public satisfaction, health indicators, and the use of
spends more time with each patient and orders medication (Starfield, 1994).
more laboratory work. The result is a waste of
doctors’ time and patients’ money. This not only
The Uninsured
inflates the national health bill, but also creates
an illusion of doctor shortage when the only real In 2004, the total number of uninsured in the United
need is to have the existing doctors doing the right States was approximately 44 million, and contrary to
things. (p. 48) widespread belief, the problem is not confined sim-
ply to unemployed or poor persons. More than half
of the uninsured have annual incomes greater than
Cost-effective Care
$75,000 and eight of 10 are in working families.
The physician who is well acquainted with the The number of Americans without health insur-
patient not only provides more personal and ance has been increasing by 1 million per year. In 1995,
humane medical care but does so more economically 14% were without health insurance, and in 2003, the
than does the physician involved in only episodic number rose by 1.4 million to 16% of the population.
care. The physician who knows his or her patients The number of those who are underinsured is growing
well can assess the nature of their problems more
rapidly and accurately. Because of the intimate,
ongoing relationship, the family physician is under
100
less pressure to exclude diagnostic possibilities by use
15% of GDP
Physicians in Primary

of expensive laboratory and radiographic procedures 80

than is the physician who is unfamiliar with the 9%
patient. 60
The United States has the most expensive health 7%
care system in the world. The cost of health care in 40
the United States was just under 6% of the gross 20
domestic product in 1965. It shot up 9.3% in 2002,
the largest increase in 11 years, to a total of $1.55 tril- 0
lion, which is 15% of the gross domestic product, Great Britain Canada U.S.
and continues to increase. Projections put health Figure 1-2 Inverse relationship between percentage of
spending at almost 18% of the gross domestic prod- primary care physicians and cost of health care in Great
uct by 2012. Britain, Canada, and the United States.

11
 Chapter 1 The Family Physician

even more rapidly. “Will we try to save our skins by a physician delivers primary care depends on the
delivering minimally adequate care on the cheap or degree of involvement attained during training and
will we stand up and be counted in the fight for uni- practice. The family physician must be trained com-
versal health insurance?” (Eisenberg, 1999, p. 2256). prehensively to acquire all the medical skills neces-
The United States is the only developed country that sary to care for the majority of patient problems. The
does not have universal health care coverage for all its greater the number of skills omitted from the family
citizens. In 1997, the United States had only 33% of the physician’s training and practice, the more frequent
population covered by government-insured health is the need to refer minor problems to another physi-
insurance, the lowest percentage of any Organization cian. A truly comprehensive primary care physician
for Economic Cooperation and Development country adequately manages acute infections, performs biop-
(Anderson et al., 1999). sies of skin and other lesions, repairs lacerations,
Clearly, the increasing complexity of our health treats musculoskeletal sprains and minor fractures,
care system multiplies expense and wastefulness when removes foreign bodies, treats vaginitis, provides
a patient self-diagnoses his or her problems or selects obstetric care and care for the newborn infant, gives
his or her own specialist rather than developing a firm supportive psychotherapy, and supervises diagnostic
and ongoing relationship with a family physician. The procedures. The needs of a family physician’s patient
most efficient and cost-effective system involves one range from a routine physical examination, when the
personal physician who ensures the most logical and patient feels well and wishes to identify potential risk
economic management of a problem. factors, to a problem that calls for referral to one or
Medical care should be available to patients in more narrowly specialized physicians with highly
the precise degree needed, neither too extensive nor developed technical skills. The family physician must
too limited. This ensures that simple problems will be aware of the variety and complexity of skills and
not be magnified out of proportion. The more com- facilities available to help manage patients and must
plex and involved a diagnostic process is, the more match these to the individual’s specific needs, giving
costly it becomes and the greater is the potential for full consideration to the patient’s personality and
error. Specialists generally treat their patients more expectations.
resource intensively than do generalists, resulting in Management of an illness involves much more
increased cost of care. Cherkin et al. (1987) showed than a diagnosis and an outline for treatment. It also
that internists were 1.7 times more likely to hospital- requires an awareness of all the factors that may aid or
ize patients than were family physicians and 1.3 hinder an individual’s recovery from illness. This
times more likely to refer. requires consideration of religious beliefs; social, eco-
Family physicians order fewer tests than do spe- nomic, or cultural problems; personal expectations;
cialists, perhaps because they know their patients and heredity. The outstanding clinician recognizes
well. MacLean (1993) compared the hospital care the effects that spiritual, intellectual, emotional,
given by family physicians with that of all other spe- social, and economic factors have on a patient’s
cialties for patients with gastrointestinal bleeding, illness.
nonsurgical back pain, and nutritional, metabolic, or The family physician’s ability to confront rela-
dehydration disorders. He found that the effective- tively large numbers of unselected patients with
ness of the care was comparable but that the cost of undifferentiated conditions and carry on a therapeu-
care provided by family physicians was less. tic relationship over time is a unique primary care
The Institute of Medicine report on the unin- skill. The skilled family physician will have a higher
sured, Insuring America’s Health: Principles and level of tolerance for the uncertain than will his or
Recommendations, called for “health care coverage her consultant colleague.
by 2010 that is universal, continuous, affordable, sus- Society will benefit more from a surgeon who
tainable, and enhancing of high-quality care that is has a sufficient volume of surgery to maintain pro-
effective, efficient, safe, timely, patient centered, and ficiency through frequent use of well-honed skills
equitable. . . .While stopping short of advocating a than from one who has a low volume of surgery
specific approach, the IOM’s Committee on the and serves also as a primary care physician. The early
Consequences of Uninsurance acknowledges that the identification of disease while it is in its undifferenti-
single payer model is the most effective in ensuring ated stage requires specific training and is not a skill
continuous universal coverage that would remain that can be automatically assumed by someone
affordable for individuals and for society” (Geyman, whose training has been mostly in hospital intensive
2004, p. 635). care units. It is unfortunate that, when the number of
procedures is inadequate to fully occupy specialists
Comprehensive Care skilled in complex technical procedures, their
remaining time is spent providing care (frequently
The term comprehensive medical care spans the entire primary care) in areas where their training was lim-
spectrum of medicine. The effectiveness with which ited and often deficient.

12
 Chapter 1 The Family Physician

Many physicians eventually enter a type of patient. Charisma can be a useful therapeutic tool,
practice different from what their residency prepared but one must learn how and when to use it effectively
them for; the question remains whether many, espe- because it can also rebound with unfavorable conse-
cially those entering primary care, will undergo the quences. The physician should be aware that the
difficult and costly retraining necessary to do the patient’s needs are paramount. The temptation to
job well. “take an ego trip” is frequent and hazardous.

Interpersonal Skills Accessibility

One of the foremost skills of the family physician is Just as charisma is therapeutic, so too is the mere
the ability to use effectively the knowledge of inter- availability of the physician. The feeling of security
personal relations in the management of patients. that the patient gains just by knowing that he or she
This powerful element of clinical medicine is per- can “touch” the physician, either in person or by
haps the specialty’s most useful tool. Modern society phone, is in itself therapeutic and has a comforting
considers the medical care system inadequate in and calming influence. Accessibility is an essential
those situations in which understanding and com- feature of primary care. Services must be available
passion are important to the patient’s comfort and when needed and should be within geographic prox-
recovery from illness. Physicians too often are seen as imity. When primary care is not available, many
lacking this personal concern and as being unskilled individuals turn to hospital emergency departments.
in understanding personal anxiety and feelings. Emergency department care is, of course, fine for
There is an obvious need to nourish the seed of com- emergencies, but it is no substitute for the personal-
passion and concern for sick people with which stu- ized, long-term, comprehensive care that a family
dents enter medical school. physician can provide.
Family medicine emphasizes the integration of Many practices are going to open-access schedul-
compassion, empathy, and personalized concern to a ing in which patients can be seen the day they call, as
greater degree than does a more technical or task- has been advocated in the Future of Family Medicine
oriented specialty. Some of the earnest solicitude report (see Chapter 2, “Future of Family Medicine”).
of the old country doctor and his or her untiring Open-access scheduling permits patients to be seen
compassion for people must be incorporated as the day they wish to. This tells the patient that he or
effective yet impersonal modern medical procedures she is the highest priority and his or her problem will
are applied. The patient should be viewed compas- be handled immediately. It also is more efficient for
sionately as a person in distress who needs to be the physician who cares for a problem early, before it
treated with concern, dignity, and personal consider- progresses in severity and becomes complicated,
ation. He or she has a right to be given some insight requiring more physician time and patient disability.
into his or her problems, a reasonable appraisal of
the potential outcome, and a realistic picture of the
Diagnostic Skills: Undifferentiated Problems
emotional, financial, and occupational expenses
involved in his or her care. The greatest deterrents to The family physician must be, above all, an out-
filing malpractice claims are patient satisfaction, standing diagnostician. Skills in this area must be
good patient rapport, and active patient participa- honed to perfection because problems are usually
tion in the health care process. seen in their early, undifferentiated state and without
To relate well to patients, a physician must the degree of resolution that is usually present by the
develop compassion and courtesy, the ability to time patients are referred to consulting specialists.
establish rapport and to communicate effectively, the This is a unique feature of family medicine because
ability to gather information rapidly and to organize symptoms seen at this stage are often vague and
it logically, the skills required to identify all signifi- nondescript, with signs being either minimal or
cant patient problems and to manage these problems absent. Unlike the consulting specialist, the family
appropriately, the ability to listen, the skills necessary physician does not evaluate the case after it has been
to motivate people, and the ability to observe and preselected by another physician, and the diagnostic
detect nonverbal clues. procedures used by the family physician must be
Much of the family physician’s effectiveness in selected from the entire spectrum of medicine.
interpersonal relationships depends on his or her At this stage of disease, there are often only sub-
charisma. Charisma is a personal magic of leader- tle differences between the early symptoms of serious
ship, a magnetic charm or appeal that arouses special disease and those of self-limiting, minor ailments. To
loyalty or enthusiasm. The charismatic physician is the inexperienced person, the clinical pictures may
most likely to engender maximal patient compliance appear identical, but to the astute and experienced
and satisfaction. The physician must be aware of his family physician, one symptom will be more suspi-
or her own feelings, however, and their effect on the cious than another because of the greater probability

13
 Chapter 1 The Family Physician

that it signals a potentially serious illness. Diagnoses it is caused by a laryngeal carcinoma similar to that
are frequently made based on probability, and the recently found in a friend. Clinical evaluation must
likelihood that a specific disease is present frequently rule out the possibility of laryngeal carcinoma, but the
depends on the incidence of the disease relative to patient’s fears and apprehension regarding this possi-
the symptom seen in the physician’s community dur- bility must also be allayed. Similarly, a 42-year-old
ing a given time of year. Approximately one fourth of man with influenza and pleuritic chest pain may be
all patients seen will never be assigned a final, defin- anxious and apprehensive because his father died at
itive diagnosis because the resolution of a presenting age 45 years of an acute myocardial infarction. (In fact,
symptom or complaint will come before a specific a frequent reason for a patient’s requesting a complete
diagnosis can be made. Pragmatically, this is an effi- checkup and electrocardiogram is the recent heart
cient method that is less costly and achieves high attack of an acquaintance at work.) Mild thrombo-
patient satisfaction, even though it may be disquiet- phlebitis in a 35-year-old woman could bring her to
ing to the purist physician who believes a thorough the physician in a more anxious state than is war-
workup and specific diagnosis always should be ranted because her mother died of a pulmonary
obtained. Similarly, family physicians are more likely embolus, or a woman’s anxiety about breast cancer
to use a therapeutic trial to confirm the diagnosis. may well stem from a friend’s recent breast surgery.
The family physician is an expert in the rapid Every physical problem has an emotional com-
assessment of a problem presented for the first time. ponent, and although this factor is usually minimal,
He or she evaluates its potential significance, often it can be extremely significant. A patient’s personal-
making a diagnosis by exclusion rather than by ity, fears, and anxieties all play a role in every illness
inclusion, after making certain that the symptoms and are important factors in all primary care.
are not those of a serious problem. Once assured,
some time is allowed to elapse. Time is used as an
The Family Physician as Coordinator
efficient diagnostic aid. Follow-up visits are sched-
uled at appropriate intervals to watch for subtle Francis Peabody, Professor of Medicine at Harvard
changes in the presenting symptoms. The physician Medical School from 1921 to 1927, was a man ahead
usually identifies the symptom that has the greatest of his time; his comments remain appropriate today:
discriminatory value and watches it more closely
than the others. The most significant clue to the true Never was the public in need of wise, broadly
nature of the illness may depend on subtle changes in trained advisors so much as it needs them today to
this key symptom. The family physician’s effective- guide them through the complicated maze of mod-
ness is often determined by his or her knack for per- ern medicine. The extraordinary development of
ceiving the hidden or subtle dimensions of illness medical science, with its consequent diversity of
and following them closely. medical specialism and the increasing limitations
The maxim that an accurate history is the most in the extent of special fields—the very factors,
important factor in arriving at an accurate diagnosis indeed, which are creating specialists, in them-
is especially appropriate to family medicine because selves create a new demand, not for men who are
symptoms may be the only obvious feature of an ill- experts along narrow lines, but for men who are in
ness at the time that it is presented to the family touch with many lines. (Peabody, 1930, p. 20)
physician. Further inquiry into the nature of the
symptoms, time of onset, extenuating factors, and The family physician, by virtue of his or her
other unique subjective features may provide the breadth of training in a wide variety of medical dis-
only diagnostic clues available at such an early stage. ciplines, has unique insights into the skills possessed
Above all, the family physician must be a skilled cli- by physicians in the more limited specialties. The
nician with the ability to evaluate symptoms, verbal family physician is best prepared to select specialists
and nonverbal communication, and early signs of whose skills can be applied most appropriately to a
illness to choose those diagnostic tests that are of given case, as well as to coordinate the activities of
greatest value in diagnosing a problem early. each, so that they are not counterproductive.
The family physician must be a perceptive As medicine becomes more specialized and
humanist, alert to early identification of new prob- complex, the family physician’s role as the integra-
lems. Arriving at an early diagnosis may, in fact, be of tor of health services becomes increasingly impor-
less importance than determining the real reason the tant. The family physician not only facilitates
patient came to the physician. The symptoms may be the patient’s access to the whole health care system
the result of a self-limiting or acute problem, but but also interprets the activities of this system to
anxiety or fear may be the true precipitating factor. the patient, explaining the nature of the illness,
Although the symptom may be hoarseness that has the implication of the treatment, and the effect of
resulted from postnasal drainage accompanying an both on the patient’s way of life. The following
upper respiratory tract infection, the patient may fear statement from the Millis Commission Report

14
 Chapter 1 The Family Physician

concerning expectations of the patient is especially which only a family physician can supply. When
appropriate: their mutual decisions . . . bring hope, comfort and,
ultimately, health to a gravely ill human being, the
The patient wants, and should have, someone of total experience is the essence and the joy of medi-
high competence and good judgment to take cine. (p. 12)
charge of the total situation, someone who can
serve as coordinator of all the medical resources The ability to orchestrate the knowledge and
that can help solve his problem. He wants a com- skills of diverse professionals is a skill to be learned
pany president who will make proper use of his during training and cultivated in practice. It is not an
skills and knowledge of more specialized members automatic attribute of all physicians or merely the
of the firm. He wants a quarterback who will diag- result of exposure to a large number of professionals.
nose the constantly changing situation, coordinate These coordinator skills extend beyond the tradi-
the whole team, and call on each member for the tional medical disciplines into the many community
particular contributions that he is best able to agencies and allied health professions as well.
make to the team effort. (Citizens’ Commission on Because of his or her close involvement with the
Graduate Medical Education, American Medical community, the family physician is ideally suited to
Association [Millis Commission], 1966, p. 39) be the integrator of the patient’s care, coordinating
the skills of consultants when appropriate and
Such breadth of vision is important for a coor- involving community nurses, social agencies, the
dinating physician. He or she must have a realistic clergy, or other family members when needed.
overview of the problem and an awareness of the Knowledge of community health resources and per-
many alternative routes to select the one that is most sonal involvement with the community can be used
appropriate. A physician familiar with one form of to maximal benefit, not only for diagnostic and ther-
treatment tends to rely on it excessively, whereas the apeutic purposes but also to achieve the best possible
family physician can select the best approach from all level of rehabilitation.
possible alternatives. As stated:

It should be clear, too, that no simple addition of THE FAMILY PHYSICIAN IN PRACTICE
specialties can equal the generalist function. To
build a wall one needs more than the aimless pil- The advent of family medicine has led to a renais-
ing up of bricks, one needs an architect. Every sance in medical education involving a reassessment
operation which analyzes some part of the human of the traditional medical education environment in
mechanism requires to be balanced by another a teaching hospital. It is now considered more realis-
which synthesizes and coordinates. (Pellegrino, tic to train a physician in a community atmosphere,
1966, p. 542) providing exposure to the diseases and problems
most closely approximating those that he or she will
The complexity of modern medicine frequently encounter during practice. The ambulatory care
involves a variety of health professionals, each with skills and knowledge that most medical graduates
highly developed skills in a particular area. In plan- will need cannot be taught totally within the tertiary
ning the patient’s care, the family physician, having medical center. The specialty of family practice
established rapport with a patient and family and emphasizes training in ambulatory care skills in an
having knowledge of the patient’s background, per- appropriately realistic environment, using patients
sonality, fears, and expectations, is best able to select representing a cross-section of a community and
and coordinate the activities of appropriate individ- incorporating those problems most frequently
uals from the large variety of medical disciplines. He encountered by physicians practicing primary care.
or she can maintain effective communication among The lack of relevance in the referral medical
those involved as well as function as the patient’s center also applies to the hospitalized patient. Figure
advocate and interpret to the patient and family the 1-3 places the health problems of an average com-
many unfamiliar and complicated procedures being munity in perspective. In any given month, 800 peo-
used. This prevents any one consulting physician, ple will experience at least one symptom. Most of
unfamiliar with the concepts or actions of all others these people will be managed by self-treatment, but
involved, from ordering a test or medication that 217 will consult a physician. Of these, eight will be
would conflict with other treatment. Dunphy (1964) hospitalized, but only one will go to an academic
described the value of the surgeon and the family medical center. It is obvious that patients seen in the
physician working closely as a team: medical center (the majority of cases used for teach-
ing) represent atypical samples of illness occurring
It is impossible to provide high quality surgical within the community. Students exposed to patients
care without that knowledge of the whole patient in only this manner develop an unrealistic concept

15
 Chapter 1 The Family Physician

1000 people

In an average month: 800 have symptoms

327 consider seeking

medical care

217 physician's office

113 visit primary care

65 CAM provider

21 hospital
outpatient clinic

14 home health

13 emergency
department

New Ecology of Medical Care–2000 8 are in a hospital

<1 in an academic
health center

Figure 1-3 Number of persons experiencing an illness during an average month, per 1000 population. (From Green
LA, Fryer GE Jr, Yawn BP, Lanier D, Dovey SM. The ecology of medical care revisited. N Engl J Med 2001;344:2021–2025.)

of the kinds of medical problems prevalent in soci- 1960s of rebuilding the U.S. health care system on
ety and, particularly, those composing primary care. a generalist base, with all Americans having ready
It focuses their training on knowledge and skills of access to comprehensive health care through a
limited usefulness in later practice. Medical schools personal physician, has not been achieved. Over-
should accept the responsibility of providing health specialization was a problem as long as 4000 years
care for a defined population, and the dean’s office ago when Herodotus in 2000 bc noted that “The
should ensure that the curriculum is congruent with art of medicine is thus divided: each physician
the health needs of that population. applies himself to one disease only and not more.”
In a typical family physician’s practice that cares (Geyman, 2004)
for 1500 to 3000 individuals, two-thirds will be seen
at least once each year. Many practicing family physi- The National Ambulatory Medical Care Survey
cians and most family practice residency programs conducted by the National Center for Health Statistics
are recording the type and frequency of problems of the U.S. Department of Health and Human
seen. Undergraduate and graduate curricula now are Services has, since 1975, annually reported the prob-
being revised to address more closely the problems lems seen by office-based physicians (in all specialties)
that will be encountered in practice. in the United States. The 20 most common diagnoses
seen by physicians in their offices are shown in Table
1-2. Characteristics of visits to primary care physicians
Practice Content
are shown in Table 1-3. Note that diabetes mellitus is
Family physicians account for a larger proportion of the third most common problem and reflects the
office visits to U.S. physicians than any other spe- increasing prevalence of this disease.
cialty. However, Primary care physicians manage an average of
1.65 problems per visit. Of visits to primary care physi-
the country’s health care (non) system has under- cians, 61% were for a medical examination compared
gone a major transformation to a market-based with 23% for surgical specialists. Although hyperten-
system largely dominated by corporate interests sion is the most common problem encountered in
and a business ethic. The goal envisioned in the offices (see Table 1-2), primary care physicians checked

16
 Chapter 1 The Family Physician

Table 1-2 Rank Order of Office Visits by Table 1-3 Characteristics of Visits to
Diagnosis Primary Care Specialists
1. Essential hypertension Accounted for 62.7% of all visits in 2002, with
2. Routine infant or child health check 76% to the patient’s designated primary care
3. Acute upper respiratory infections, excluding provider
pharyngitis Major reason for visit to primary care specialists
4. Diabetes mellitus Acute conditions: 41.5%
5. Arthropathies and related disorders Chronic conditions: 29.6%
6. General medical examination Preventive care: 23.3%
7. Spinal disorders Top five illness-related diagnoses are
8. Rheumatism, excluding back Hypertension: 7.8%
9. Normal pregnancy Acute upper respiratory infections (excluding
10. Otitis media and eustachian tube disorders pharyngitis): 5.1%
11. Malignant neoplasms Diabetes mellitus: 3.1%
12. Chronic sinusitis Otitis media: 2.4%
13. Allergic rhinitis Arthropathies: 2.1%
14. Asthma Injury visits accounted for 9.4% of all visits to
15. Gynecologic examination primary care specialists
16. Disorder of lipoid metabolism Common services ordered or provided
17. Heart disease, excluding ischemic General medical examination: 60.8%
18. Ischemic heart disease Blood pressure check: 60.1%
19. Acute pharyngitis Urinalysis: 12.8%
20. Follow-up examination Complete blood count: 10.9%
Diet/nutrition counseling: 19.3%
From National Center for Health Statistics (Woodwell Exercise counseling: 12.2%
DA, Cherry DK): 2002 Summary: National
Ambulatory Medical Care Survey. Advance Data
Top therapeutic drug classes were
Vital Health Stat no. 346, Aug. 26, 2004. Vaccines/antisera: 5.7% of drug mentions
Nonsteroidal anti-inflammatory drugs: 5.5% of
drug mentions
the blood pressure at 60% of the visits compared with Antihistamines: 4.8% of drug mentions
only 20% of surgical specialists and 40% of visits to Antidepressants: 4.0% of drug mentions
Antihypertensives: 3.9% of drug mentions
medical specialists (National Center for Health
Anti-asthmatics: 3.8% of drug mentions
Statistics [Woodwell DA, Cherry DK], 2004). Disposition of visit
Available data concerning primary care indicate Return for an appointment: 53.4%
that more people use this type of medical service Return if needed: 33.4%
than any other kind and that, contrary to popular Referred to another physician: 8.0%
opinion, sophisticated medical technology is not Average face-to-face duration: 17.4 minutes
normally either required or overused in basic pri-
From National Center for Health Statistics (Woodwell
mary care encounters. Indeed, most primary care DA, Cherry DK): 2002 Summary: National
visits arise from patients requesting care for rela- Ambulatory Medical Care Survey. Advance Data
tively uncomplicated problems, many of which are Vital Health Stat no. 346, Aug. 26, 2004.
self-limiting but cause the patients concern or dis-
comfort. Treatment is often symptomatic, consisting
of pain relief or anxiety reduction rather than a cians and found that 63% of family physicians made
“cure.” The greatest cost efficiency results when house calls compared with 47% of general internists
these patients’ needs are satisfied while the self-lim- and 15% of general pediatricians. Those who made
iting course of the disease is recognized without house calls shared the belief that house calls are impor-
incurring unnecessary costs for additional tests. tant for good comprehensive patient care and are satis-
fying for the physician as well as for the patient.
House Calls The house call continues to be a valuable tool
used by family physicians to develop a thorough
Although the number of house calls being made by understanding of patients and their environment,
family physicians has declined significantly, it is now and family practice residencies encourage house calls
on the increase because of increasing need resulting in their training programs. Family physicians who
from shortened hospital stay; increased home care make house calls report an average of 1.6 per week
involving intravenous fluids, chemotherapy, and respi- (American Academy of Family Physicians, 1999).
ratory care previously requiring hospitalization; and Elderly patients, especially the frail elderly, often
the increase in the number of homebound elderly. have considerable difficulty getting to and from the
Adelman et al. (1994) surveyed primary care physi- physician’s office. The patient is more comfortable

17
 Chapter 1 The Family Physician

and under less stress at home, and more problems environmental hazards and to evaluate functional
can be identified, leading to improved care. Ramsdell status accurately.
et al. (1989) have shown that home visit assessments
reveal, on average, two new problems and as many as Material Available on Student Consult
eight new treatment recommendations when home
Review Questions and Answers about The Family
visits follow physician office–based assessments.
Physician
Home visits may be the only way to identify some

REFERENCES
Adelman AM, Fredman L, Knight AL. House call practices: Graduate Medical Education National Advisory Com-
A comparison by specialty. J Fam Pract 1994;38:39–44. mittee. Final Report Vol. 1 (DHHS Publication
Ad Hoc Committee on Education for Family Practice, no. [HRA] 81-651). Hyattsville, MD: Health Resources
Council on Medical Education of the American Administration, 1980.
Medical Association (Willard Committee): Meeting the Hueston WJ, Applegate JA, Mansfield CJ, et al. Practice
Challenge of Family Practice (Report). Chicago: variations between family physicians and obstetricians
American Medical Association, 1966. in the management of low-risk pregnancies. J Fam
American Academy of Family Physicians: Congress Pract 1995;40:345.
Reporter, Congress Adopts Revised Definitions Kimball HR, Young PR. A statement on the generalist
Concerning Family Physician, October 5–7, 1993:4–5. physician from the American boards of family practice
American Academy of Family Physicians. Directors’ and internal medicine. JAMA 1994;271:315–316.
Newsletter, AAFP Revises Primary Care Definition, Landon BE, Reschovsky J, Blumenthal D. Changes in career
and Exhibit 1, February 4, 1994, p 1. satisfaction among primary care and specialist physi-
American Academy of Family Physicians. Facts about: cians, 1997–2001. JAMA 2003;289:442–449.
Family Practice. Kansas City, MO: American Academy Leigh JP, Kravitz RL, Schembri M, et al. Physician career
of Family Physicians, 1999. satisfaction across specialties. Arch Intern Med
Anderson GF, Poullier JP. Health spending, access, and out- 2002;162:1577–1584.
comes: Trends in industrialized countries. Health Lown B. The Lost Art of Healing. Boston: Houghton
Affairs 1999;18:178. Mifflin, 1996.
Balint M. The Doctor, His Patient and the Illness. New Ludmerer KM. Time to heal: American medical education
York: Pitman, 1965. from the turn of the century to the era of managed care.
Beeson PB. Some good features of the British National New York: Oxford University Press, 1999.
Health Service. J Med Educ 1974;49:43–49. MacLean DS. Outcome and cost of family physicians’
Boex JR, Edwards J, Garg M, et al. Generalist and Specialist care: Pilot study of three diagnosis-related groups in
Practitioner: Analyses of Quality and Costs of Care. elderly inpatients. J Am Board Fam Pract
Report to the W. K. Kellogg Foundation, Battle Creek, 1993;6:588–593.
MI, October 7, 1993. McGann KP, Bowman MA. A comparison of morbidity
Bulger RJ. The Quest for Mercy: The Forgotten Ingredient and mortality for family physicians’ and internists’
in Health Care Reform. Charlottesville, VA: Carden admissions. J Fam Pract 1990;31:541–545.
Jennings Publishing, 1998. National Center for Health Statistics (Woodwell DA,
Cherkin DC, Rosenblatt RA, Hart LG, et al. The use of Cherry DK). 2002 Summary: National Ambulatory
medical resources by residency-trained family physi- Medical Care Survey (Advance Data Vital Health Stat
cians and general internists: Is there a difference? Med no. 346, August 26, 2004). Washington, DC:
Care 1987;25:455–469. Government Printing Office, 2004.
Citizens’ Commission on Graduate Medical Education, Osler W. Aequanimitas, and Other Addresses. Philadelphia:
American Medical Association (Millis Commission). Blakiston, 1904.
The Graduate Education of Physicians (Report). Peabody FW. Doctor and Patient. New York: Macmillan,
Chicago: American Medical Association, 1966. 1930.
Cranshaw R, Rogers DE, Pellegrino ED, et al. Patient- Pellegrino ED. The generalist function in medicine. JAMA
physician covenant. JAMA 1995;273:1553. 1966;198:541–545.
DeVoe J, Fryer GE, Hargraves L, et al. Does career dissatis- Pellegrino ED. Humanism and the Physician. Knoxville,
faction affect the ability of family physicians to deliver TN: University of Tennessee Press, 1979.
high-quality patient care? J Fam Pract 2002;51: Ramsdell JW, Swart JA, Jackson JE, et al. The yield of a
223–228. home visit in the assessment of geriatric patients. J Am
Dunphy JE. Responsibility and authority in American sur- Geriatr Soc 1989;37:17–24.
gery. Bull Am Coll Surg 1964;49:9–12. Richards JG. The Nature of General Practice: General
Eisenberg L. Whatever happened to the faculty on the way Practice in New Zealand, 1997. Wellington, New
to the agora? Arch Intern Med 1999;159:2251–2256. Zealand: The Royal New Zealand College of General
Geyman JP. Drawing on the legacy of general practice to Practitioners, 1997.
build the future of family medicine. Fam Med Rivo ML, Saultz JW, Wartman SA, et al. Defining the gen-
2004;36:631–638. eralist physician’s training. JAMA 1994;271:1499–1504.

18
 Chapter 2 The Future of Family Medicine

Robert Graham Center for Policy Studies in Family Practice Stock Keister MC, Green LA, Kahn NB, Phillips RL,
and Primary Care. The importance of having a usual McCann J, Fryer GE. Few people in the United States
source of health care. Am Fam Physician 2000;62:477. can identify primary care physicians. Am Fam
Robert Wood Johnson Foundation Annual Report 2002, Physician 2004a;69:2312.
Princeton, NJ; 2002:1–28. Stock Keister MC, Green LA, Kahn NB, Phillips RL,
Smith PC, Westfall JM, Nicholas RA. Primary care family McCann J, Fryer GE. What people want from
physicians and 2 hospitalist models: Comparison of their family physician. Am Fam Physician 2004b;69:
outcomes, processes, and costs. J Fam Pract 2002;51: 2310.
1021–1027. Tumulty PA. What is a clinician and what does he do?
Starfield B. Is primary care essential? Lancet 1994;344: N Engl J Med 1970;283:20–24.
1129–1133. Weingarten SR, Lloyd L, Chiou CF, Braunstein GD. Do
Starfield B. Is US health really the best in the world? JAMA subspecialists working outside of their specialty pro-
2000;284:483–485. vide less efficient and lower-quality care to hospitalized
Starfield B. New paradigms for quality in primary care. Br patients than do primary care physicians? Arch Intern
J Gen Pract 2001;51:303–309. Med 2002;162:527–532.
Starfield B, Shi L, Grover A, et al. The effects of specialist World Organization of National Colleges, Academies, and
supply on populations’ health: Assessing the evidence. Academic Associations of General Practitioners/Family
Health Affairs 2005;0:W5-97–W5-107 (Web Exclusive). Physicians. The Role of the General Practitioner/Family
Available at http://content.healthaffairs.org/cgi/content/ Physician in Health Care Systems. Victoria, Australia,
abstract/hlthaff.w5.97v1. Accessed 4/4/06. World Organization, 1991.

C h a p t e r

2 The Future of Family Medicine

Larry A. Green, Norman B. Kahn, Jr.,

and James C. Martin

KEY POINTS

1. The American public values the role of a trusted e. Incorporation of clinical technology and
personal physician. information into practice.
2. The American public views the family physician 5. The “New Model” of family medicine is charac-
as a community leader. terized by the following:
3. Characteristics of a family physician include a a. Establishment of a personal medical home.
deep understanding of the dynamics of the b. A defined basket of services.
“whole” person, a generative impact on patients’ c. The use of information technology.
lives, a talent for humanizing the health care d. The achievement of quality as described in the
experience, a natural command of complexity, Institute of Medicine Quality Chasm Report.
and a commitment to being available to patients. e. Continued assessment of quality patient care
4. The key challenges that will affect the success improvement and sound business planning
of a family medicine impact on health care and strategies.
include the following: 6. Future emphasis of family medicine will include
a. Promotion of the discipline and its role in the the following:
health care system. a. Educational innovation at the residency level.
b. A clear public identity and a consistent basket b. The incorporation of adult learning techniques
of services. in lifelong continuing medical education.
c. Respectful enhancement of the role of family c. Consideration of a science research agenda
medicine in academic centers. for the discipline.
d. Development of a more attractive career, d. The reassessment of the discipline’s role in
addressing scope of practice, lifestyle, and academic health centers.
compensation. e. Enhanced political and advocacy roles.

19
 Chapter 2 The Future of Family Medicine

Robert Graham Center for Policy Studies in Family Practice Stock Keister MC, Green LA, Kahn NB, Phillips RL,
and Primary Care. The importance of having a usual McCann J, Fryer GE. Few people in the United States
source of health care. Am Fam Physician 2000;62:477. can identify primary care physicians. Am Fam
Robert Wood Johnson Foundation Annual Report 2002, Physician 2004a;69:2312.
Princeton, NJ; 2002:1–28. Stock Keister MC, Green LA, Kahn NB, Phillips RL,
Smith PC, Westfall JM, Nicholas RA. Primary care family McCann J, Fryer GE. What people want from
physicians and 2 hospitalist models: Comparison of their family physician. Am Fam Physician 2004b;69:
outcomes, processes, and costs. J Fam Pract 2002;51: 2310.
1021–1027. Tumulty PA. What is a clinician and what does he do?
Starfield B. Is primary care essential? Lancet 1994;344: N Engl J Med 1970;283:20–24.
1129–1133. Weingarten SR, Lloyd L, Chiou CF, Braunstein GD. Do
Starfield B. Is US health really the best in the world? JAMA subspecialists working outside of their specialty pro-
2000;284:483–485. vide less efficient and lower-quality care to hospitalized
Starfield B. New paradigms for quality in primary care. Br patients than do primary care physicians? Arch Intern
J Gen Pract 2001;51:303–309. Med 2002;162:527–532.
Starfield B, Shi L, Grover A, et al. The effects of specialist World Organization of National Colleges, Academies, and
supply on populations’ health: Assessing the evidence. Academic Associations of General Practitioners/Family
Health Affairs 2005;0:W5-97–W5-107 (Web Exclusive). Physicians. The Role of the General Practitioner/Family
Available at http://content.healthaffairs.org/cgi/content/ Physician in Health Care Systems. Victoria, Australia,
abstract/hlthaff.w5.97v1. Accessed 4/4/06. World Organization, 1991.

C h a p t e r

2 The Future of Family Medicine

Larry A. Green, Norman B. Kahn, Jr.,

and James C. Martin

KEY POINTS

1. The American public values the role of a trusted e. Incorporation of clinical technology and
personal physician. information into practice.
2. The American public views the family physician 5. The “New Model” of family medicine is charac-
as a community leader. terized by the following:
3. Characteristics of a family physician include a a. Establishment of a personal medical home.
deep understanding of the dynamics of the b. A defined basket of services.
“whole” person, a generative impact on patients’ c. The use of information technology.
lives, a talent for humanizing the health care d. The achievement of quality as described in the
experience, a natural command of complexity, Institute of Medicine Quality Chasm Report.
and a commitment to being available to patients. e. Continued assessment of quality patient care
4. The key challenges that will affect the success improvement and sound business planning
of a family medicine impact on health care and strategies.
include the following: 6. Future emphasis of family medicine will include
a. Promotion of the discipline and its role in the the following:
health care system. a. Educational innovation at the residency level.
b. A clear public identity and a consistent basket b. The incorporation of adult learning techniques
of services. in lifelong continuing medical education.
c. Respectful enhancement of the role of family c. Consideration of a science research agenda
medicine in academic centers. for the discipline.
d. Development of a more attractive career, d. The reassessment of the discipline’s role in
addressing scope of practice, lifestyle, and academic health centers.
compensation. e. Enhanced political and advocacy roles.

19
 Chapter 2 The Future of Family Medicine

Even within the constraints of today’s flawed health error prone, and rarely integrated in a way that satis-
care system, there are major opportunities for fam- fied either patients or clinicians. Public health infra-
ily physicians to realize improvements in both structures were disconnected from primary care.
results for patients and economic performance for Mental health care, while indivisible from primary
physicians. A period of active experimentation and care, remained marginalized. There was renewed
redevelopment of family medicine is called for now. uncertainty about the adequacy and distribution of
The future success of the discipline and its impact the health care workforce, with medical students’
on public well-being depend in large measure on interest in primary care careers declining. The pub-
family medicine’s ability to rearticulate its vision lic’s understanding of both the role of family physi-
and competencies in a fashion that has greater reso- cians and the function of primary care was low, and
nance with the public while substantially revising forecasts of collapse of the health care system were
the organization and processes by which care is frequent fare in the media (Donaldson et al., 1996;
delivered. When these goals are accomplished, fam- Geyman, 2002; Green and Fryer, 2002; Institute of
ily physicians will achieve more fully the aspirations Medicine, 2000, 2001, 2002a,b).
articulated by the specialty’s core values and con- Recognizing the growing frustration among
tribute to the solution of the nation’s serious health family physicians, confusion among the public about
care problems (Martin et al., 2004). the role of family physicians, and continuing under-
performance throughout the U.S. health care system,
the leadership of seven U.S. family medicine organi-
HISTORICAL CONTEXT zations initiated the Future of Family Medicine
(FFM) Project in 2002.
Historically, the prestige and respect of the medical
profession were based on a personal relationship of
trust, a respect for the scientifically inquiring mind, THE FUTURE OF FAMILY MEDICINE
and the commitment to place the needs of others PROJECT
above those of the physician. Before World War II,
American health care was provided primarily by The goal articulated for the FFM Project was to
the general practitioner, a physician who met the “develop a strategy to transform and renew the spe-
characteristics of trust and sacrifice; but, as medical cialty of family medicine to meet the needs of people
knowledge expanded rapidly, the general practi- and society in a changing environment” (Martin
tioner was viewed as less knowledgeable and more et al., 2004). The work was organized into six
limited in the management of complicated disease. national task forces with diverse, interdisciplinary
The rapid growth of medical specialties after representation. The FFM Project was overseen by a
World War II was accompanied by the decline of gen- project leadership committee composed of leaders
eral practice, resulting in fragmented health care. By from the sponsoring organizations, staffed by the
the 1960s, the dominance of medical specialization so American Academy of Family Physicians, and
highlighted the loss of the generalist function in med- financed by the organizations of the discipline and
icine that society called for the return and promi- by both public and private organizations.
nence of the generalist in medicine, ultimately The project commissioned research conducted
resulting in the development of the specialty of fam- by recognized national research organizations not
ily medicine in 1969 (Folsom, 1966; Millis, 1966; familiar with family medicine. A market research
Willard, 1966). The new specialty of family medicine firm performed secondary data analysis of the find-
delivered on its promise to restore what the public ings as well as large representative national data sets
needed and wanted as the new family physicians and literature review and sought opinions of recog-
provided frontline medical care to people of all socio- nized international experts in health care delivery.
economic strata and in all regions of the country Through iterative discussions among the task forces,
(Graham et al., 2002). With the establishment of the project leadership committee, panels of reactors
a sufficient family medicine workforce largely from across the country, and the contracted
addressed after a generation, new challenges emerged. researchers, visions of the future of American health
By the turn of the millennium, a large and grow- care and family medicine were elaborated, with con-
ing proportion of the American population lacked clusions and recommendations published in 2004
health insurance, and almost one fifth of people did (Bucholtz et al., 2004; Dickinson et al., 2004; Green
not have a usual source of care. Compared with other et al., 2004; Jones et al., 2004; Martin et al., 2004;
nations, the United States demonstrated relatively Roberts et al., 2004; Spann et al., 2004).
poor health statistics, with persistent disparities in The key findings, conclusions, attributes, and
health among population subgroups, while health characteristics of family physicians and the major
care expenditures accelerated. Individual health care challenges facing family medicine can be summa-
was recognized once again to be highly fragmented, rized as follows.

20
 Chapter 2 The Future of Family Medicine

KEY FINDINGS AND CONCLUSIONS being available to their patients in the different ways
that different patients require. Family physicians are
Family medicine continues to meet both a funda- committed to fostering health and integrating health
mental public need and the public’s demand for inte- care for the whole person by humanizing medicine
grated, relationship-centered health care. Family and providing science-based, high-quality care
physicians currently play a large and critical role in (Martin et al., 2004).
health care throughout the United States while car- Changes must occur both within the specialty
ing for millions of people with the nation’s priority and perhaps more importantly within the broader
health problems (Martin et al., 2004). health care system to ensure the ability of family
Despite their critical role in American health medicine to fulfill its mission and role. Unless these
care, family physicians are not well recognized by the changes are accomplished, the position of family
public as distinct and differentiated from other medicine in a dysfunctional U.S. health system may
physicians. Nonetheless, approximately two thirds of be untenable in a 10- to 20-year time frame, which
people seeing a family physician correctly identify would have serious detrimental consequences on the
their physician’s specialty (Martin et al., 2004). health of the public.
Family medicine functions within an overall
U.S. health care system that has been characterized
by the Institute of Medicine as unsafe, with gaps in KEY CHALLENGES FACING FAMILY
quality and disparities in care for population groups. MEDICINE IN THE UNITED STATES
The U.S. health care system is challenged to refocus
on the key aims of safety, effectiveness, patient-cen- The FFM Project revealed five challenges for family
teredness, timeliness, efficiency, and equity (Institute medicine to address to increase its impact in the U.S.
of Medicine, 2000, 2001, 2002a,b). health care system.
Family medicine’s core values of continuing,
comprehensive, compassionate, personal care pro- 1. Family medicine should communicate and
vided in the context of family and community are actively promote a broader, more accurate under-
congruent with the requirements of the 21st century standing of the discipline and its role in the U.S.
health care system. Equally important, these values health care system.
are shared by patients (Bucholtz et al., 2004; Green 2. Family medicine should design its practices so
et al., 2004; Jones et al., 2004). that the discipline attains a clear public identity.
Patients want their doctor to be in their insur- As a specialty that admires independence and
ance plan, located conveniently, available by appoint- whose strength is its wide scope and locally
ment quickly, able to communicate with them, and adapted practice, the discipline has not clearly
experienced. Beyond these basics, patients value a communicated to the public who family physi-
relationship with their physician above all else, want- cians are, what family physicians do, and what the
ing a personal physician who will listen to them, take specialty offers to the public.
time to explain things, and integrate their overall 3. Despite well-earned respect in practice, winning
care (Green et al, 2004; Stock Keister et al., 2004). respect for family medicine in academic circles
People judge health care quality on relation- continues to be a challenge. The academic environ-
ships, in which they rate family physicians highly. ment has been recognized as often disparaging of
Patients may forgive inadequate service delivered by primary care and of family medicine in particular.
the system to continue a highly valued relationship 4. Successful implementation of the FFM-recom-
with a physician (Green et al., 2004; Stock Keister mended strategies should make family medicine a
et al., 2004). more attractive career option. Concerns about the
People are skeptical that any one physician can scope of practice, lifestyle, and compensation are
treat people with any condition, believing medicine integral to the challenges facing the role of family
is too complicated for one doctor to “do it all,” yet medicine in U.S. health care.
they define the best physician as someone whom 5. Family medicine should address the public’s per-
they trust or as a specialist. There is an unresolved ception that family medicine is less solidly
tension between the public’s desire for a primary grounded in science and technology than are
physician who treats the patient as a whole person medical subspecialties. Family medicine has the
and the desire for access to highly specialized services opportunity to lead medicine in implementing
(Green et al., 2004; Stock Keister et al., 2004). science-based practice. Family medicine should
Family physicians are recognized to have a deep actively incorporate appropriate information and
understanding of the dynamics of the whole person, clinical technology into practice.
a generative impact on patients’ lives, a talent for
humanizing the health care experience, a natural To address these challenges, changes are needed
command of complexity, and a commitment to nearly simultaneously in clinical practice (how family

21
 Chapter 2 The Future of Family Medicine

Table 2-1 Comparison of Traditional versus New Model Practices

Traditional Model of Practice New Model of Practice

Systems often disrupt the patient-physician Systems support continuous healing relationships
relationship
Care is provided to both genders and all ages and Care is provided to both genders and all ages and
includes all stages of the individual and family includes all stages of the individual and family
life cycles in continuous, healing relationships life cycles in continuous, healing relationships
Physician is center stage Patient is center stage
Unnecessary barriers to access by patients Open access by patients
Care is mostly reactive Care is both responsive and prospective
Care is often fragmented Care is integrated
Paper medical record Electronic health record
Unpredictable package of services is offered Commitment to providing directly and/or
coordinating a defined basket of services
Individual patient oriented Individual and community oriented
Communication with practice is synchronous Communication with the practice is both
(in person or by telephone) synchronous and asynchronous (e-mail, Web
portal, voice mail)
Quality and safety of care are assumed Processes are in place for ongoing measurement
and improvement of quality and safety
Physician is the main source of care Multidisciplinary team is the source of care
Individual physician-patient visits Individual and group visits involving several
patients and members of the health care team
Consumes knowledge Generates new knowledge through practice-based
research
Experience based Evidence based
Haphazard chronic disease management Purposeful, organized chronic disease
management
Struggles financially, undercapitalized Positive financial margin, adequately capitalized

From Martin JC, Avant RF, Bowman MA, et al. The future of family medicine: A collaborative project of the
family medicine community. Ann Fam Med 2004;2(Suppl 1):S3–S32.

physicians organize their practices and how they the future, family physicians must not only have the
function), medical education (how family physicians requisite skills in prevention, counseling, diagnosis,
are trained and how they maintain a high level of per- prognostication, treatment, and performance of
formance throughout a career), and the health care procedures but also competencies in managing rela-
system of the United States to restore its focus on tionships, information, and processes of care. The
caring for and meeting the needs of people. compass headings for the direction of necessary
To transform medical care in an unsatisfying changes in the practice of family medicine were
health care system, family medicine and the rest of articulated as shown in Table 2-1, contrasting
primary care has been swept up in the next period of traditional practice with future practice (Green et al.,
substantial change in medical practice in the United 2004).
States. Given the rich interfaces that family medicine Aspects of this New Model have already been
has with virtually every other aspect of the health implemented on a piecemeal basis by innovative
care system, it is not surprising that those in family family physicians and are thus known to be practical
medicine would feel compelled to respond. It enough to be achievable now. It is the entire spec-
appears to be a time when it is most important to trum of characteristics explicitly centered on the
construct not just a rationale for family medicine but needs of patients, incorporating concepts from
the place of family medicine. A substantial revision industrial engineering and customer service, that
of the practice setting, supported by a viable business represents the change in orientation from a tradi-
plan, is necessary for future family medicine to tional model of family medicine to a New Model
achieve top performance (Roberts et al., 2004). capable of serving as a personal medical home for
The current shortcomings and dissatisfaction any person. The cornerstone of the new model is
with the U.S. health care system provide family patient-centered care based on an ongoing patient-
physicians with a compelling opportunity to physician relationship that is highly satisfying and
improve the health of the nation and shape their own humanizing to the patient as well as to the physician
destinies by redesigning their model of practice. In and practice personnel.

22
 Chapter 2 The Future of Family Medicine

Table 2-2 Basket of Services in the New Model of Family Medicine

Health care is provided to children and adults
Integration of personal health care (coordinate and facilitate care)
Health assessment (evaluate health and risk status)
Disease prevention (early detection of asymptomatic disease)
Health promotion (primary prevention and health behavior/lifestyle modification)
Patient education and support for self-care
Diagnosis and management of acute injuries and illnesses
Diagnosis and management of chronic illness
Supportive care, including end-of-life care
Maternity care, hospital care
Primary mental health care
Consultation and referral services as necessary
Advocacy for the patient within the health care system
Quality improvement and practice-based research
From Martin JC, Avant RF, Bowman MA, et al. The future of family medicine: A collaborative project of the
family medicine community. Ann Fam Med 2004;2(Suppl 1):S3–S32.

The future family physician will need to provide the New Model. This circumstance led to modeling
care to both genders at all stages of the individual the possible financial effects of implementing the
and family life cycle. It is virtually inconceivable to New Model. Based on existing economic policies and
move to the New Model of practice without incor- management procedures displayed in work patterns
porating an electronic health record (EHR), but from 2001 to 2003 in the United States, expected
adopting an EHR alone will not achieve the new workloads, revenues, and expenses associated with
model. Moving toward patient-centeredness and the New Model were projected. The results found the
relationship-based care while working in teams New Model to be more efficient, resulting in the
is likely to be both rewarding and a challenge. options for family physicians of working fewer hours
Incorporating discovery and research into routine with relatively stable income or working the same
practice is necessary to complete medicine’s knowl- number of hours with increased earnings, as much as
edge base and ground future family medicine in 26% for a prototypical five-physician practice. With
science-based care. revisions in how family physicians are paid, such as
Achieving sufficient standardization to allow the payments that blend salary or capitation with fee for
public to know what they can expect from a family service and premium payments for superior results,
physician while adapting family medicine to the the financial models could become even more favor-
specific requirements of each community will be a able (Spann et al., 2004).
critical challenge. In the New Model, every family Additional modeling exercises project that the
physician does not need to provide every service at well-documented salutary effects of primary care
all times, but a New Model practice would guarantee and the New Model of practice would be expected to
the full basket of services, creating a consistent scope result in reduced overall national expenditures for
of services, recognizable by the public. A reliable bas- health care, a highly desirable, if unfamiliar, situa-
ket of services was identified and is summarized in tion. This macrolevel analysis suggested that at least
Table 2-2 (Green et al., 2004). a 5.6% reduction in total health care expenditures
(perhaps $67 billion) would be expected if New
Model practice could be implemented widely and
made available to the entire population (Spann et al.,
FINANCIAL IMPLICATIONS 2004).
OF THE NEW MODEL OF CARE In summary, the New Model of family medicine
as proposed in the FFM Project appears to be feasi-
Scattered across the United States and other coun- ble and attractive to patients, family physicians and
tries are practices that exhibit one or more of the their professional colleagues, purchasers of health
characteristics of New Model practice, confirming care, and governments. From the perspectives of
practical feasibility. However, there is a paucity of patients, family physicians, medical students, and
practices that have implemented the entire package residents inclined to be family physicians, the New
in the U.S. setting, precluding adequate empirical Model has the potential to achieve unprecedented
evaluation of clinical and financial performance of performance.

23
 Chapter 2 The Future of Family Medicine

RECOMMENDATIONS CONCERNING diagnosis and treatment, measurement of processes

THE FUTURE OF FAMILY MEDICINE and results, analysis of the effects of comorbidity,
recording, and coding elements of whole-person care
IN THE UNITED STATES and promote ongoing, healing relationships between
family physicians and their patients.
Family physicians are committed to fostering health
and integrating health care for the whole person by
humanizing medicine and providing science-based, Family Medicine Education
quality care. To remain true to this statement of
identity, while continuing to meet the needs of Family medicine will oversee the training of family
patients and society in a changing health care envi- physicians who are committed to excellence, steeped
ronment, family medicine must promote active in the core values of the discipline, expert in provid-
experimentation and innovation in the delivery of ing family medicine’s basket of services within the
clinical services and in the education of clinicians. New Model of family medicine, skilled at adapting to
Family physicians and their organizations must varying patient and community needs, and prepared
seek out and partner with those who share similar to embrace new evidence-based technologies. Family
values and a commitment to experimentation, medicine education will continue to include training
innovation, and transformation of the U.S. health in maternity care, the care of hospitalized patients,
care system. community and population health, and culturally
The following recommendations, which repre- effective and proficient care. Innovation in family
sent a compilation of major recommendations from medicine residency programs will be supported by
the FFM task forces, are intended to provide a frame- the Residency Review Committee for Family Practice
work to guide such experimentation and innovation through 5 to 10 years of curricular flexibility to per-
within the discipline (Martin et al., 2004). mit active experimentation and ongoing critical eval-
uation of competency-based education, expanded
training programs, and other strategies to prepare
New Model of Family Medicine graduates for the New Model. In preparation for
this process, every family medicine residency will
Family medicine will redesign the work and work-
implement EHRs by 2006.
places of family physicians. This redesign will foster
a New Model of care based on the concept of a rela-
tionship-centered personal medical home, which Lifelong Learning
serves as the focal point through which all individ-
uals, regardless of age, gender, race, ethnicity, or The discipline of family medicine will develop a
socioeconomic status, participate in health care. In comprehensive, lifelong learning program. This pro-
this new medical home, patients receive a basket of gram will provide the tools for each family physician
acute, chronic, and preventive medical care services to create a continuous personal, professional, and
that are accessible, accountable, comprehensive, clinical practice assessment and an improvement
integrated, patient centered, safe, scientifically plan that supports a succession of career stages. This
valid, and satisfying to both patients and their personalized learning and professional development
physicians. This New Model will include technolo- will include self-assessment and learning modules
gies that enhance diagnosis and treatment for a directed at individual physicians and group practices
large portion of problems that patients bring to that incorporate science-based knowledge into edu-
their family physicians. Business plans and reim- cational interventions fostering improved patient
bursement will be developed to enable the re- outcomes. Family medicine residency programs and
engineered practices of family physicians to thrive departments will incorporate continuing profes-
as personal medical homes, and resources will be sional development into their curricula and will ini-
developed to help patients make informed deci- tiate and model the support process for lifelong
sions about choosing a personal medical home. A learning and maintenance of certification.
financially self-sustaining national resource will be
implemented to provide individual practices with
ongoing support in the transition to the New Model Enhancing the Science of Family Medicine
of family medicine. Participation in the generation of new knowledge
will be integral to the activities of all family physi-
cians and will be incorporated into family medicine
Electronic Health Records
training. Practice-based research will be integrated
EHRs that meet standards that support the New into the values, structures, and processes of fam-
Model of family medicine will be implemented. The ily practices. Departments of family medicine
EHR will enhance and integrate communication, will engage in highly collaborative research that

24
 Chapter 2 The Future of Family Medicine

produces new knowledge about the origins of dis- the New Model of family medicine and the concept
ease and illness, how health is gained and lost, and of the personal medical home. As part of this strat-
how the provision of care can be improved. A egy, a new symbol for family physicians will be cre-
national entity should be established to lead and ated and consistent terminology will be established
fund research on the health and health care of whole for the specialty, including use of family medicine
people. Funding for the Agency for Healthcare rather than family practice and family physician
Research and Quality should be increased to at least rather than family practitioner. In addition, a system
$1 billion per year. will be developed to communicate and implement
best practices within family medicine.
Quality of Care
Close working partnerships will be developed Leadership and Advocacy
between academic family medicine, community- A leadership center for family medicine and primary
based family physicians, and other partners to care will be established that will develop strategies to
address the quality goals specified in the Institute promote family physicians and other primary care
of Medicine (IOM) Chasm Report. Family physi- physicians as health policy and research leaders in
cians and their practice partners will have support their communities, in government, and in other
systems to measure and report regularly their per- influential groups. In their capacity as leaders, family
formance on the six IOM aims of quality health physicians will convene leaders to identify and
care (safe, timely, effective, equitable, patient cen- develop implementation strategies for several major
tered, and efficient). Family medicine residency policy initiatives, including ensuring that every
programs will track and report regularly the per- American has access to basic health care services.
formance of their residents during their training Family physicians will partner with others at the
on the six IOM quality measures and will modify local, state, and national levels to engage patients, cli-
their training programs as necessary to improve nicians, and payers in advocating for a redesigned
performance. system of integrated, personalized, equitable, and
sustainable health care.
Role of Family Medicine in Academic Much of the work to create this recommended
Health Centers future must be done by the discipline itself. There
are opportunities to repair broken linkages, particu-
Departments of family medicine will individually larly with public health and mental health, while
and collectively analyze their position within the cultivating partnerships necessary to create a sup-
academic health center setting and will take steps to portive environment for family medicine. These
enhance their contribution to the advancement and actions require collaboration well beyond the disci-
rejuvenation of the academic health center to meet pline and in some instances policy revisions that
the needs of the American people. A summit of pol- depend in part on the action of both the private and
icymakers and family medicine leaders in academia public sectors.
and private practice will be convened to review the
role of and make recommendations on the future of
family medicine in academia.
COMMENTARY
Promoting a Sufficient Family Medicine
As there is much at stake in this proposed transfor-
Workforce mation of family medicine, many people have reason
A comprehensive family medicine career development to be concerned enough to pay attention to it.
program and other strategies will be implemented to Foremost are people in both urban and rural com-
recruit and train a culturally diverse family physician munities who seek health sufficient to live out their
workforce that meets the needs of the evolving U.S. hopes and dreams and yearn for enough of the right
population for integrated health care for the whole health care to enable them to do so. Those who have
person, families, and communities. Departments of critically examined the evidence of the salutary
family medicine will continue to develop, implement, impact of primary care on health and health care sys-
disseminate, and evaluate best practices in expanding tems will want to facilitate the transformation.
student interest in the specialty. Others with much to gain through this transforma-
tion include those concerned with the sustainability
of health care, the avoidance of waste, health care tai-
Communications
lored to each individual, justice in the allocation of
A unified communications strategy will be devel- resources, over- and undertreatment, and disparities
oped to promote an awareness and understanding of in outcomes.

25
 Chapter 2 The Future of Family Medicine

The next generation of physicians, particularly new model practice is economically sustainable in the
those who aspire to be the doctors that people in the market of U.S. medicine. The response of medical
United States identify as their usual source of care, students and residents to the ambitious opportunities
stand to gain a great deal. Physicians in all specialties and daunting challenges facing family medicine and
have much to gain as the New Model integrates care. primary care will also be a major determining factor
Decision makers in and out of health care are likely of the future. How general internists, general pedia-
to have opportunities to support the transformation tricians, nurses, and other health care professionals
through their leadership and financing. respond to family medicine in the future may help
A fundamental result of transforming family reach critical mass, incite productive competition,
medicine and the rest of primary care is integrated or dilute efforts such that no national commitment
care. Integration is the pulling together of what to primary care and personalized, whole-person,
often appear to be disparate parts into a coherent relationship-centered care emerges.
whole that has recognized meaning. This integra- The future of family medicine may depend
tion of health care is the antidote to the frustrat- most on what currently practicing family physi-
ingly fragmented care that most Americans now cians do next. Overwhelmingly, these family physi-
experience. People’s problems do not respect the cians aspire to the opportunity to have a balanced
arbitrary boundaries of single disciplines defined lifestyle while providing personalized care suitable
by who does what and where for a patient. for their patients, patients known by name and
Consequently, if family physicians are to integrate with whom they share experiences that are the
their patients’ care, they must be positioned to work basis of trust. To make the transformation that is
effectively across the health care settings, including necessary in their practices, those in the discipline
hospitals, intermediate care settings, offices, and have committed to the creation of an assistance
homes. Integrating health care is, and will remain, organization to help the typical practice of family
high-order intellectual work worthy of the best physicians through consultation and other sup-
physicians, of great value to patients, and the crux porting structures.
of the doctoring that family physicians aspire to do
and for which patients yearn.
Family medicine may be medicine’s largest CONCLUSION
information management challenge. For the first
time, technology exists sufficient to support asyn- This is the next moment of adaptive change for fam-
chronous communications, establish an interopera- ily medicine in the United States. Acknowledging
ble EHR, and manage the complex information the role that the public expects of family medicine,
requirements of family medicine. Continuity of care the discipline must effectively address the challenges
may be achievable as never before possible because of of transformation. Family medicine must demon-
the Internet. When an EHR is united with innovative strate the competencies of relationship building,
classifications (Lamberts and Wood, 1987) that cap- quality care, cost efficiencies, and health outcomes
ture episodes of care and a robust practice-based while addressing the macro issues of a research
research enterprise (Green and Dovey, 2001), New agenda for its science and influencing future health
Model practice may be able to achieve family medi- care policy.
cine’s and primary care’s long-standing, ambitious If the transformation falters now, it is likely to
aspirations in the near future. be a costly failure affecting millions of people.
It is not possible for anyone to state with cer- Another rebirth of family medicine in some form
tainty the future of family medicine. Its future would be required in the years ahead. It is time to
depends on factors not yet known and how family choose the next adventure and act, from the current
medicine adapts to the challenges and impediments position of strength, to respond to immediate
it now faces. These include what the United States opportunities and honor the historic contract
does in terms of further commercialization and cor- between family physicians and the people, who are
poratization of health care and whether relationship- still waiting for high-performance health care and a
centered care is feasible in the U.S. environment. personal physician who will stick with them and
Whether the United States ever implements universal actually care for them.
health care coverage and whether a foundational pol-
icy of a medical home for every person is imple-
mented will modulate the degree and rapidity with
which family medicine can make the transformation Material Available on Student Consult
now needed.
Review Questions and Answers about The Future
A successful business model will be critical in of Family Medicine
which current inadequacies are corrected such that

26
 Chapter 2 The Future of Family Medicine

REFERENCES
Bucholtz JR, Matheny SC, Pugno PA, et al. Task Force 2 Medicine. Washington, DC: National Academy Press,
Report: Family medicine education and training. Ann 2002a.
Fam Med 2004;2(Suppl 1):S51–S64. Institute of Medicine. Committee on Understanding and
Dickinson JC, Evans KL, Carter J, Burke K. Task Force 4 Eliminating Racial and Ethnic Disparities in Health
Report: Communicating the role of family medicine. Care. Unequal Treatment: What Health Care Providers
Ann Fam Med 2004;2(Suppl 1):S75–S87. Need to Know About Racial and Ethnic Disparities in
Donaldson MS, Yordy KD, Lohr KN, Vanselow NA, eds. Health Care. Institute of Medicine. Washington, DC:
Committee on the Future of Primary Care Services. National Academy Press, 2002b.
Institute of Medicine. Primary Care. America’s Health Jones WA, Avant RF, Davis N, et al. Task Force 3 Report:
in a New Era. Washington, DC, National Academy Continuous Personal, Professional, and Practice
Press, 1996. Development in Family Medicine. Ann Fam Med
Folsom MB. National Commission on Community Health 2004;2(Suppl 1):S65–S74.
Services. Health Is a Community Affair. Cambridge, Lamberts H, Wood M. ICPC: International Classification
MA: Harvard University Press, 1966. of Primary Care. New York: Oxford University Press,
Geyman JP. Health Care in America. Can Our Ailing System 1987.
Be Healed? Boston: Butterworth-Heinemann, 2002. Martin JC, Avant RF, Bowman MA, et al. The future of
Graham R, Roberts RG, Ostergaard DJ, et al. Family prac- family medicine: A collaborative project of the
tice in the United States. A status report. JAMA family medicine community. Ann Fam Med 2004;2
2002;288:1097–1101. (Suppl 1):S3–S32.
Green LA, Dovey SM. Practice based primary care research Millis JS. Citizens Commission on Graduate Medical
networks. They work and are ready for full develop- Education. The Graduate Education of Physicians: The
ment and support. BMJ 2001;322:567–568. Report of the Citizens Commission on Graduate
Green L, Graham R, Bagley B, et al. Task Force 1 Report: Medical Education. Chicago: American Medical
Patient expectations, core values, reintegration and the Association, 1966.
new model of family medicine. Ann Fam Med Roberts RG, Snape PS, Burke K. Task Force 5 Report:
2004;2(Suppl 1):S33–S50. Family medicine’s role in shaping the future health care
Green LA, Fryer GE. Family practice in the United States: delivery system. Ann Fam Med 2004;2(Suppl 1):
Position and prospects. Acad Med 2002;77:781–789. S88–S99.
Institute of Medicine. Committee on Quality of Health Spann S, Task Force and the Executive Editorial Team.
Care in America. To Err Is Human: Building a Safer Report on financing the new model of family medicine.
Health System. Institute of Medicine. Washington, DC: Ann Fam Med 2004;2(Suppl 3):S1–S21.
National Academy Press, 2000. Stock Keister MC, Green LA, Kahn NB, Phillips RL,
Institute of Medicine. Committee on Quality of Health McCann J, Fryer GE. What people want from their fam-
Care in America. Crossing the Quality Chasm: A New ily physician. Am Fam Physician 2004;69:2310.
Health System for the 21st Century. Institute of Willard WR. American Medical Association. Ad Hoc
Medicine. Washington, DC: National Academy Press, Committee on Education for Family Practice. Meeting
2001. the Challenge of Family Practice: The Report of the Ad
Institute of Medicine. Committee on Assuring the Health Hoc Committee on Education for Family Practice of
of the Public in the 21st Century. The Future of the the Council on Medical Education. Chicago: American
Public’s Health in the 21st Century. Institute of Medical Association, 1966.

27
 C h a p t e r

3 The Relevance of Medical History

to Family Medicine
Chester R. Burns, Alice Anne O’Donell,
and Barbara Thompson

Imagine that you are Benjamin Rush and that you— been prepared by outstanding scholar-physicians and
along with other congressional delegates assembled published between 1490 and 1525, Rush (1745–1813)
in Philadelphia on August 2, 1776—have just signed explicitly rejected the theoretical legacies of
the American Declaration of Independence.1 As a Hippocrates and Galen, believing them to be irrele-
very busy general practitioner, you probably need to vant to his practice in Philadelphia.3 As a loyal alum-
see a patient in your office, at your home, or at the nus of the medical school at the University of
patient’s home. Or you may, in keeping with your Edinburgh in Scotland, he accepted the theories of his
unsalaried commitment to impoverished colonials, 18th-century teachers who intentionally rejected the
need to visit a patient in the Pennsylvania Hospital ancient Greco-Roman legacies in favor of the theories
on your way home from the signing ceremony. of “modern” practitioners: Andreas Vesalius, William
What beliefs about health and health care ani- Harvey, Thomas Sydenham, Hermann Boerhaave,
mate your practice? Do you feel responsible for and William Cullen, to name a few.4
attending to the physical, mental, social, and spiritual How could anyone believe the theories of
maladies of your patients, or is that comprehensive Hippocrates and Galen after Vesalius, in 1543, and
viewpoint too broad? What types of rational infor- Harvey, in 1628, showed that the revered ancient
mation about these maladies are reliable and useful? physicians knew next to nothing about the real struc-
What types of medical, surgical, psychosocial, and tures and functions of the human body? Yet Rush (as
spiritual therapies are available for you to use in car- did Vesalius, Harvey, Sydenham, Boerhaave, Cullen,
ing for a patient? What are the prospects for satisfac- and many others) fervently championed the blood-
tory outcomes? letting and purging legacies of Hippocrates and
Do you pay any attention to issues of medical Galen. During the yellow fever epidemic in
ethics and professionalism, and to the realities of the Philadelphia in 1799, for example, Rush probably
economic and political contexts of your medical lost some patients because of too much bloodletting.
practice? In a politically free republic such as the Most formally educated American and European
embryonic United States of America, which citizens doctors in the late 18th and early 19th centuries sub-
should monitor the quality of care offered by a vari- jected their patients to bloodletting and purging. As
ety of medical “professionals” who tout their services practical legacies sacrosanct in their teachings,
as healers? Which citizens are morally and legally Hippocrates and Galen would have rejoiced!5
responsible for securing the “healths” of their fellow Though an apprentice of Rush who “let blood”
Americans: professionals and/or nonprofessionals from some of their patients in 1799, John Redman
(including quacks) who earn income in exchange for Coxe (1773–1864) did not agree with his teacher’s
remedies and services; nonprofessional volunteers rejection of ancient medical theory.6 Instead, he
who tout health-promoting advice and gimmicks; became an extraordinary disciple of the theories of
and/or governmental agencies that attend to the Hippocrates and Galen. Coxe possessed one of the
“public health” needs of all citizens in the specified largest private libraries in Philadelphia (estimated
polity? 15,000 volumes). Proudly positioned in this collec-
Benjamin Rush, probably the most distin- tion was his own synopsis of the medical writings of
guished and influential physician in the colonies and Hippocrates and Galen. He devoted many hours to
early American Republic, answered these and related the preparation of this “Merck Manual” translation
questions in numerous articles and books, and histo- of these ancient writings because he believed that
rians since then have interpreted his answers in they contained many practical aids that would help
numerous articles and books.2 him and fellow American doctors make better clini-
Even though new Latin editions of the writings cal judgments.7
of Hippocrates and Galen (the most important med- In the same year that Coxe’s book was published,
ical authorities in ancient Greece and Rome) had about 100 general practitioners assembled in New

28
 Chapter 3 The Relevance of Medical History to Family Medicine

York City in May to consider the formation of a and ethical, physicians should not choose a remedy
national medical society. These physicians estab- or regimen that would interfere with these “healing
lished two committees for their new national organ- powers.” A professionally conscientious physician
ization: one on medical education that would “did no harm” better than those who made hasty
identify the theoretical and practical subjects that clinical judgments or resorted to any remedy just to
should be taught in any respectable American med- receive a fee.
ical school, and one on medical ethics that would Yet how did these doctors know whether they
prepare a code of medical ethics that should be hon- were really honoring the revered Hippocratic maxim:
ored by all respectable American physicians. Those “Do no harm”? By the middle of the 19th century,
general practitioners who attended the first official only a few “scientifically” controlled investigations of
American Medical Association (AMA) meeting in drugs and surgical techniques had been conducted.
Philadelphia during the following year unanimously Realistically recognizing these conditions, rationally
adopted the reports of these two committees.8 liberal (nonsectarian) physicians and surgeons relin-
Some of these doctors may have known John quished their loyalty to bloodletting and purging,
Redman Coxe, but they did not champion the clinical embraced an attitude of not aggressively interfering
knowledge of Hippocrates and Galen as he did. Like with the healing powers of Nature, and adopted a
other formally educated American doctors in the mid- comprehensive approach to therapy and caregiving. In
19th century, these founders of the AMA had rejected choosing to assess their professional propriety with
Coxe’s viewpoints and the legacies of bloodletting and these standards of care, these mid-century doctors
purging so sacred to their forebears. Instead, they experienced more than one paradox.
placed their diagnostic and therapeutic trust in (1) When to use a drug and when to trust the “heal-
their own interpretations of firsthand clinical observa- ing power of Nature” was an ever-present problem of
tions and experiences, (2) “the healing powers of clinical judgment.12 As John Harley Warner has
Nature,” and (3) a therapeutic approach grounded in demonstrated, these mid-century doctors supple-
a comprehensive view of the physical, mental, social, mented their trust in Nature not by abandoning the
and spiritual dimensions of health.9 use of drugs but by curtailing excessive drug use and
Provoked and sanctioned by the same clinical by systematic efforts to correlate the use of specific
empiricism and experimentalism in France that led drugs with specific clinical outcomes.13
to the discrediting of bloodletting and purging, the Feeling simultaneously rejected and idolized by
leading physicians who practiced and taught in the the public was another paradox that suffused the
United States between 1830 and 1870 encouraged consciences of traditionally educated American doc-
fellow doctors to embrace the clinical philosophies of tors. Rejection by the public was probably the most
their French mentors and marry these philosophies traumatic insult because it affected wallets as well as
to the Emersonian self-reliance that animated liber- self-respect. In the eyes of freedom-loving Americans
ally educated Americans at that time.10 This concep- living in a new country with all of its unexplored
tual marriage resulted in practical maxims that geographic and cultural frontiers, these strikingly
guided every rational physician who made a proper “less-than-heroic” general practitioners who
clinical evaluation of a patient: Be a careful observer, embraced “the healing powers of Nature” and
take a comprehensive history of the course of the dis- rejected the active therapies of bloodletting and
ease, consider the patient’s interpretations of symp- purging were actually behaving as if they did not
toms and signs, consult other practitioners who may care, as if they were “un-American” doctors who
have treated a patient with similar symptoms and apparently did not really want to alter the abnormal
signs, decide on a comprehensive approach to ther- bodily events of their patients in search of more
apy and caregiving, and give “Mother Nature” a favorable outcomes.
chance to show her innate healing powers before and Not only did many Americans reject these “tra-
during the course of therapy.11 ditionally” educated physicians, but they employed
With time and rest and maybe some self-help a host of sectarian practitioners (some formally
remedies, “Mother Nature” often healed herself, so to educated; some not) who rushed into the 19th-cen-
speak. “Bad” colds, vomiting, and diarrhea disap- tury therapeutic vacuum made possible by the
peared regardless of what the patient or healer did. abandonment of bloodletting and purging: home-
Lacerations and broken bones healed themselves, so opaths, hydropaths, botanics, eclectics, osteopaths,
to speak. Because of widespread variations in life and others. Even the home remedies of distant rela-
styles of patients and in therapeutic approaches cho- tives and struggling neighbors seemed better than
sen by a variety of healers, it was very difficult to tell the “do-nothing” behaviors of “regular” physicians.
whether a specific remedy or regimen made any real Pragmatic Americans could not accept passive
difference in outcomes because it seemed that behaviors, especially those of their trusted general
“Mother Nature” took care of many instances of practitioners. Hence, they shifted their trust to
physical disease and injury. To be rational, careful, more aggressive healers who did not reject active

29
 Chapter 3 The Relevance of Medical History to Family Medicine

therapeutics, even though no one could prove that touted more certainty and charged much less for
one therapeutic approach was scientifically better their advertised remedies. If therapeutic outcomes
than another.14 were so uncertain, why spend a lot of money on
Dealing with these clinical paradoxes every time clinically unproven drugs? There was no need to
they treated patients, the general practitioner waste scarce resources on ignorant doctors who,
founders of the AMA really understood the social, despite their goodwill, really did not know how to
economic, and political realities of mid-19th century treat most diseases in ways that would “guarantee”
America. In responding to these realities, these good outcomes.
doctors placed their interpersonal (social) trust in Between 1830 and 1880 especially, Americans
(1) the creation of a national professional association confronted many choices among types of “medical
of formally educated physicians who shared the three practitioners” who offered their wares and services to
diagnostic and therapeutic philosophies previously the sick and injured. These included traditionally
discussed, (2) a code of professional ethics that AMA educated general practitioners; unlicensed, trial-and-
members would use in self-assessment and in moni- error trained midwives; a variety of sectarians
toring the behavior of fellow members, (3) the including homeopaths, hydropaths, and botanics; a
American legal system to administer justice to those few who falsely advertised their services as “special-
physicians who were judged guilty of medical mal- ists”; and a host of nostrum vendors, quacks, and
practices, and (4) the American system of gover- charlatans. Political freedom included the freedom to
nance and its local, state, regional, and national exploit fellow humans who were sick and dying. The
agencies that could adopt public health policies and sectarians and nostrum vendors attracted many
establish appropriate medical institutions to secure patients. Which healers should sick Americans
the welfare of their political constituents. believe and trust, and why?
Even though this interpersonal trust upheld Many sick Americans still viewed general practi-
some of the most important values of medical pro- tioners as the traditionally educated healers who
fessionalism in a democratic society, loyal AMA could be effective, even comprehensively heroic at
members experienced a fourth paradox that involved times. Popular American novelists captured these
their new code of medical ethics. By following the sentiments well in some novels that appeared in the
code and participating as an active member of one’s late 19th century.
local medical society, a physician could be considered In a novel entitled Dr. Sevier (published in1884),
ethically acceptable by fellow doctors despite the George Washington Cable characterized the motives
clinical outcomes for his patients after treatment. If of a general practitioner as follows: “He waged war—
clinical outcomes were so unimportant in assessing against malady. To fight; to stifle; to cut down; to
professional propriety, how could any group of doc- uproot; to overwhelm,—these were the springs of
tors adopt realistic standards for judging their own as action.” In A Country Doctor (1884), Sarah Orne
well as their fellow physicians’ behaviors at the bed- Jewett described Dr. John Leslie as a “self-reliant”
side? To say it another way, the American public commander: “Not only in this farmhouse kitchen,
could (and did) decide that a non-AMA doctor but wherever one might place him, he instinctively
could be an ethically acceptable American physician, took command, while from his great knowledge of
and the same public could (and did) decide that clin- human nature he could understand and help many
ical outcomes were highly important criteria for of his patients whose ailments were not wholly phys-
judging professional competence (goodness). ical.” In Dr. Latimer: A Story of Casco Bay (1893),
In view of these therapeutic perplexities during Clara Burnham celebrated the comprehensive talents
the mid-19th century in America, a sick citizen of this Boston doctor: “You’d be surprised, Miss
trusted a general practitioner because he was a Charlotte, to know the things folks’ll ask o’
church-going, formally educated, law-abiding citizen Dr. Latimer. Sometimes it’s their souls need tinkerin’,
who displayed gentleness toward patients (the and then you’d think he was a minister; sometimes
cultural meaning of “gentleman”), practiced the it’s their bodies, then you’d think he was a doctor;
philosophy of therapeutics previously discussed, sometimes it’s their drains, and then you’d s’pose he
and “swore” allegiance to the AMA code of medical was a plumber; then again they’ve got trouble with
ethics. A traditionally educated doctor was not their servants or their landlords, and want him to
trusted because he could give no real assurances that help ‘em out, and you’d s’pose he was a lawyer.” Sick
his scientific knowledge and clinical remedies would Americans expected their idealized general practi-
bring about some enduring improvement in the tioners to be all things to all people all the time!15
patient’s condition. As heroic as this may have seemed to imagina-
This scientific uncertainty about therapeutic tive novelists and their readers, the social spectrum
results was very troubling to patients and their of actual doctors more realistically included tradi-
anxious families, who decided to give their money tional generalists who were quite habitual in their
and loyalty to sectarian or quack practitioners who choice of remedies, opportunists who tended to

30
 Chapter 3 The Relevance of Medical History to Family Medicine

exploit the sick, caregivers more enthusiastic than Never sued by a patient and having never purchased
knowledgeable, and a steadily growing number of malpractice insurance, Cupp celebrated his 94th
scientifically trained general practitioners who had birthday in 1975 by treating 64 patients and collect-
attended reputable medical schools and gradually ing $430 in fees.18
realized that they could not, as individuals, really Delivered by his grandmother-midwife in
master all of the burgeoning scientific, clinical, and Liberty Hill in 1884, J. Gordon Bryson graduated
technical knowledge that appeared after 1880. from the University of Texas Medical Branch
However, some did try to be comprehensive and (UTMB) in 1910 and returned to his home county to
professionally responsible, struggling incessantly as serve patients in Pearsall and Bastrop until 1947.
they determined acceptable behaviors as persons, Competing with three other doctors when he
professionals, and citizens. Notice the variety of arrived, Bryson firmly established his reputation
responses in the following glimpses of the careers of when he successfully treated a Mexican laborer with
five revered general practitioners in Texas between a gunshot wound to the abdomen in June 1911.
1889 and 1975. During his career, Bryson treated many more
Born on the family ranch in Travis County in injuries, delivered many babies, and attended
1867, Uberto Desaix Ezell received a degree from patients with a host of infectious diseases, including
Tulane Medical School in 1889 and became a general one teenager with maggots “completely blocking the
practitioner in Kimball, a town in Bosque County passage of one nostril.”19
where the Chisholm cattle trail crossed the Brazos Born in Hill County, J.W. Young, Sr., graduated
River. More than once, Ezell almost drowned as he from UTMB in 1907 and moved to the small railroad
spurred his horse across this raging river to attend town of Roscoe (about 1,000 citizens), where he
patients in Hill and Johnson counties during more practiced until 1950. When he began, typhoid fever
than 30 years of practice. In 1918, he moved to and diphtheria were common diseases. His main
Cleburne and became “Uncle Doc” to hundreds of medicines then were castor oil, quinine, bismuth,
patients for more than 30 years, usually carrying his turpentine, and calomel (mercurous chloride). He
“black bag” across his right wrist, because four fin- served patients in the surrounding towns of
gers had been amputated after a severe radiation Blackland, Wastella, Brownlee, Champion, Barnett,
burn from a new x-ray machine.16 Maryneal, Mesquite, and Goode. One night, he rode
Born on a family plantation north of Carthage his horse about 100 miles to attend patients in some
in Rusk County in 1873, Walter D. Biggs worked of these towns. His office was in the back room of a
in a physician-owned drugstore in Sonora as a drugstore that was an “old tin building.”20
teenager, graduated from the Fort Worth School of These and other formally educated general prac-
Medicine in 1898, and practiced in Lometa from titioners did not ignore the new scientific discoveries
1903 to 1945. A Chisholm trail cowtown between about health and disease that emerged from the clin-
1860 and 1880, Lometa was moved to its present ical venues and experimental laboratories of the 19th
site when the Santa Fe Railroad was built in and 20th centuries. Building on Louis Pasteur’s pio-
Lampasas County. “Uncle Walter” was the city’s pri- neering studies about microorganisms and putre-
mary doctor and railway surgeon. He delivered faction, Joseph Lister, a professor of surgery at the
more than 3,000 babies, set hundreds of fractures, University of Glasgow, discovered ways to save many
watched the scars develop on the face of a beautiful lives by controlling infection in surgical wounds.
girl afflicted with smallpox, prescribed castor oil Surgeons in Texas and elsewhere used and improved
more than once, broke his right wrist cranking his these control techniques during the 1870s, 1880s, and
first Model T Ford, and never lost a patient from 1890s.21 Between 1873 and 1889, scientists and clini-
snakebite or pneumonia.17 cians discovered the microorganisms that cause 13
Born in Coleman County in 1881, Charles infectious diseases.22 After it was created in 1891, the
Daniel Cupp was a farm lad in Huron who enjoyed antitoxin for diphtheria became an efficacious cure for
swimming and fishing in the Brazos River. In 1912, most children afflicted with this disease.23 By the
he graduated from Tulane Medical School and turn of the 20th century, humans accurately believed
moved his wife and two boys to Peoria to begin a that they were exerting more rational control over
challenging practice. After a 5-mile horseback ride, infectious diseases than ever before.
for example, Cupp surgically relieved an intestinal As could be gleaned from the previous para-
obstruction in a 10-year-old boy after placing him on graph about Dr. J.W. Young, Sr., however, American
the family’s dining room table that had been moved doctors at the turn of the 20th century could pre-
to a “cooler” back porch. During a long peripatetic scribe only a few reliable drugs that were scientifi-
career as a general practitioner, Cupp followed the cally understood and clinically effective. The quickest
oil-driven boom towns, moving to Whitney (1917), way to confirm this therapeutic predicament at that
Desdemona (1919), Breckenridge (1920), Kilgore time is to read any section about treatment for
(1931), Tyler (1931), and Grand Prairie (1941). almost any disease analyzed in William Osler’s

31
 Chapter 3 The Relevance of Medical History to Family Medicine

Principles and Practice of Medicine, which was pub- For the historical origins of family medicine as a
lished in 1892.24 Two weeks after its publication, the discrete specialty, three of these changes deserve
entire first printing (3,000 copies) had been pur- emphasis: those advances in science and technology
chased.25 By studying this classic text, conscientious that resulted in spectacular improvements in diagnos-
and scientifically trained physicians could learn tic and therapeutic techniques; the expansion of clini-
more about the accurate diagnosis of nonsurgical cal specialization with the creation of 24 specialty
diseases than any cohort of English-speaking physi- boards between 1917 and 1980;29 and the shift of med-
cians had ever understood before. ical care from the homes of patients and the offices of
Yet, during the 1890s and for many years there- solo practitioners to multiple-specialty private clinics
after, these same doctors and their successors would and to multiple-specialty hospitals of varying size and
be as perplexed and uncertain about the rationale for provenance (private, charity, government).
most of their prescriptions as their predecessors had By 1930, the advances in science and technology
been about their prescriptions before 1890. During provided safe blood transfusions, two vitamins
the late 19th century and throughout the 20th cen- (C and D), insulin and other hormones, Pap smears,
tury, a new group of scientifically educated specialist and iron lungs for polio victims. By 1965, there were
physicians (like Osler) emerged as the new medical electron microscopes, maps of DNA structures,
heroes. The public often judged these specialists as ultrasound and radioactive isotopes, amniocentesis,
ethically “better” than general practitioners, because sulfa drugs, penicillin, streptomycin and tetracy-
the clinical outcomes for their patients were typically clines, cortisone, tranquilizers, renal dialysis and
more favorable than the outcomes of those treated by transplants, heart valves and pacemakers, more vita-
general practitioners.26 mins (A, B, E, and K), polio and measles vaccines, the
This did not mean that only specialists were eth- first birth control pills, and laser surgery. By 2000,
ical and that all general practitioners were unethical.27 these advances provided many new drugs including
It did mean that there were significant cultural, scien- Prozac and Viagra, human babies begun as embryos
tific, practical, and social distances between the older by artificial insemination, recombinant gene thera-
generations of general practitioners and the younger pies, chemotherapies that destroyed some cancers,
generations of physicians that included two major AZT for AIDS patients, flexible endoscopes, brain
types: (1) generalists who, as they aged or encoun- scans, artificial hearts, and other organ transplants
tered the scientific and technical changes of medicine (liver, lung, pancreas, cochlea).30
later in their careers, decided to limit their practice to With these advances, clinical specialization
patients with specific diseases, or to patients of cer- and subspecialization became entrenched. In Texas
tain ages, usually infants and children younger than before 1940, for example, most doctors were general
teens; and (2) specialists who were never generalists practitioners. But some became specialists, including
but chose to practice one of the evolving specialties some pioneering women physicians. Sofie Herzog
when they finished medical school. established her surgical practice in Brazoria, and
Between 1890 and 1970, general practitioners and she became the chief surgeon for the St. Louis,
specialists in the United States struggled for accept- Brownsville, and Mexico railroad. Claudia Potter was
ance (some would say prestige, some would say dom- the head of the Anesthesiology Department at Scott
inance) among the formally educated physicians in and White Hospital in Temple between 1906 and
the country’s medical profession. These doctors were 1947.31 Specialization proceeded steadily throughout
vigorously competing for two cultural and social tro- the 20th century, and more women became physi-
phies, so to speak: public acceptance and professional cians, especially after mid-century.
reputation. As Paul Starr documents in The Social The American public was not entirely satisfied
Transformation of American Medicine, the cultural and with the evolution of these physician specialists
social battles involving these doctors and their patrons and subspecialists. Nevertheless, they sought their
(sick and potentially sick Americans) were extensive services when they needed their specialized knowl-
and energetically fought. A sociologist, Starr brilliantly edge and care. By 1949, only 36% of American doc-
analyzes the competing groups and organizations, tors were specialists; by 1969 when the American
and offers numerous provocative interpretations. Board of Family Practice was created, the proportion
Starr’s book is essential reading for anyone who wants had increased to 77%.32 As specialization increased,
to understand the historical changes in American med- general practice flourished at the local level. Pat
icine and health care during the 20th century. As Starr Nixon received his medical degree from Johns
revealed, the vast number of scientific, clinical, thera- Hopkins University School of Medicine in 1909 and
peutic, institutional, and social changes that occurred began a general practice in San Antonio that contin-
between 1882 and 1982 transformed the practice of ued for more than 50 years.33 Henry Wentz received
medicine in so many ways that the contours of practice his medical degree from Jefferson Medical College in
in late-20th-century America were profoundly differ- 1944, and he was a general practitioner and family
ent from those of late-19th-century America.28 physician in the Strasburg, Pennsylvania, area for

32
 Chapter 3 The Relevance of Medical History to Family Medicine

40 years (1948–1988).34 Their reflections and remi- free society. Three path-breaking reports issued in
niscences provide extraordinary insights into the 1966—the Millis Report, the Folsum Report, and the
evolution of medical practice in the United States Willard Report—contained the cultural and social
during the 20th century. “seeds” that generated family medicine and heralded a
The third major change during this century new day for primary care. Using the contents of these
involved the advent of multiple-specialty care in large reports, family medicine pioneers transformed the
clinics and hospitals. When Mavis Kelsey, Sr., began social demands for “rights” and “welfare” and the
practice as a solo practitioner internist in 1949, the exhortations for more primary care into an elaborate
Texas Medical Center was barely beginning. Today it and extensive set of professional obligations for family
is the largest health care complex in the United States, medicine specialists.
with 42 institutions situated on more than 900 acres In 1966, a joint committee of representatives
in Houston. As Kelsey notes many times in his auto- from the American Academy of General Practice
biography, sharing responsibilities with fellow spe- (founded in 1947) and the AMA Section on General
cialists and generalists became a guiding ethic Practice issued a report titled “The Core Content of
sustaining the evolution of medical care during the Family Medicine.” Identifying and emphasizing 26
20th century.35 From approximately 300 hospitals in separate areas of knowledge unique to family med-
the United States in 1882 (about 50 of these mental icine, this report is essential reading for anyone who
hospitals), the number of hospitals exceeded 7,000 in wants to understand the “anatomy and physiology”
1982. The “hospital standardization” movement was of the cultural and social values of those physicians
initiated by the American College of Surgeons in who established family medicine as a new spe-
1918; the Joint Commission on the Accreditation of cialty.37
Hospitals was established in 1951; this commission In February 1969, the AMA officially approved
became the Joint Commission on the Accreditation of family medicine as a specialty and the American
Healthcare Organizations in 1987.36 Home care by Board of Family Practice was created to certify physi-
physicians almost disappeared during these decades. cians who chose to become family practitioners. In
For ethical and practical reasons, solo medical prac- 1971, the American Academy of General Practice
tice was rapidly disappearing into the cultural and became the American Academy of Family Physicians
social “sunset.” (AAFP). By the turn of the 21st century more than
To receive full public acceptance and full respect 500 family practice residencies had been established
by all physician specialists, that is, to be profession- in the United States, and there were more than
ally ethical in all its cultural meanings, the institu- 90,000 AAFP members.38
tionalized care that was replacing solo medical In 1999, Robert Taylor, a member of the faculty
practice required more cooperation and coordina- of the Department of Family Medicine at the Oregon
tion than ever before in the history of humankind. Health Sciences University School of Medicine in
The new breed of family medicine specialists prom- Portland, asserted that the new specialty of family
ised to deliver patient care services grounded in these medicine had advanced the cultural and professional
ultimate values of coordination and cooperation. understanding of medicine in six ways: (1) devel-
Moreover, they promised to harness all of the profes- oped a specialty that emphasized relationship-based
sional and community resources necessary to pro- health care, (2) utilized comprehensive clinical rea-
vide optimum health care to every patient. This was soning, (3) recognized ordinary problems of living as
a tall order of premium ideals addressed by many a health care concern, (4) added nuance and richness
pioneers associated with the advent of family medi- to the meanings of disease, disability, and pain,
cine during the 1960s. (5) advocated a systems approach to primary health
Negotiating and renegotiating the new “social care, and (6) analyzed clinical encounters in terms of
contracts” between family medicine pioneers and a definable unit of family practice.39
public institutions occurred repeatedly during this Benjamin Rush, William Osler, and other reflec-
decade that included the intensely challenging events tive physicians in America’s past would probably cel-
associated with advances in civil rights, women’s ebrate the accomplishments of family physicians and
rights, worker’s rights, and rights for hospitalized other primary care doctors in the United States dur-
patients. The advent of Medicare and Medicaid in ing the last 50 years. A sizeable number of previous
1965 also provoked innovative responses from physi- leaders, such as Rush and Osler, did not ignore the
cians, health care institutions, and community human values contained in the six areas analyzed by
groups participating in these innovative cultural and Taylor. Lawrence Hirsch, the JAMA reviewer of
social negotiations. Robert Rakel’s first edition of this book (published in
Family medicine emerged as a direct response to 1977), acknowledged Rakel’s “pioneering” efforts to
these public and professional processes of negotiating provide a comprehensive look at the “concept of
and renegotiating “social contracts” about the role of family practice” that, even by then, had “matured
physicians and health care institutions in a politically into that of family medicine.”40 With the publication

33
 Chapter 3 The Relevance of Medical History to Family Medicine

of this new edition, the signs of disciplinary maturity tion requires some focused labor by physicians,
for family medicine are even more visible. How these residents, students, and others interested in the evo-
values and behaviors are integrated into future pat- lution of family medicine.43
terns of primary care remain to be negotiated in Medical history is relevant to family doctors
subsequent decades.41 Historical information and because its study can provide them with a unique
interpretation can provide valuable insights for fam- perspective about (1) their social identity as mem-
ily doctors and future negotiations.42 bers of a healing profession, (2) the multiple influ-
Historical inquiry and knowledge can be tools of ences that have caused cultural and social changes in
the human imagination that allow a better under- this identity through time, (3) the moral values
standing of the present and a more deliberate adap- expressed in the choices and deeds of past family
tation to its challenges. To be most effective, each doctors, and (4) the array of choices and values avail-
individual must pay attention to time and its pas- able for family physicians today as they determine
sage, must construct some evidence-based images the destinies and legacies that will be remembered as
about the time-dependent events associated with the tomorrow’s history of family medicine.
individual’s interests, and must find some cultural
coordinates that help explain and interpret the Material Available on Student Consult
choices, changes, and causes of the events leading to
Review Questions and Answers about The
present conditions. As is evident from the contents of
Relevance of Medical History to Family Medicine
this chapter, the exercise of the historical imagina-

NOTES
1. Although formally adopted on July 4, 1776, the Colonial Physician & Other Essays (New York,
Declaration was not signed by every member of Science History Publications, 1975).
the new U.S. Congress until August 2, 1776. See 3. Reliable evidence about the life of Hippocrates is
“The Declaration of Independence,” The Annals sparse. He was born on the island of Cos in
of America, vol 2, 1755–1783 (Chicago, Encyclopae- Greece, probably in 460 BCE and died in 370 BCE.
dia Britannica, 1968, p 447). Family physicians are A member of the Asclepiad guild, he practiced
urged to devote regular attention to the social his- and taught medicine. Because he was revered
tory of the United States and especially to the histo- among the ancient Greeks as the “father of
ries of family life that have appeared in recent years. rational medicine,” those scholars who assembled
For a start, read Steven Mintz and Susan Kellogg, the anonymous medical writings in Greek from
Domestic Revolutions: A Social History of American the centuries before 200 BCE titled their collection,
Family Life (New York, Free Press, 1988). To place The Writings of Hippocrates. We do not know if
these stories in the context of our country’s general Hippocrates actually wrote any of the treatises in
history, spend some time with a recent edition of this collection, including the famous Oath. Galen
George Brown Tindall’s (with D.E. Shi) America: (130 CE –200 CE) was a Greek from Pergamum (in
A Narrative History (New York, WW Norton, 1992). Asia Minor), a city with a popular healing temple
2. For a comprehensive list of these publications, see to Asclepius, the Greek god of health and healing.
Benjamin Rush, M.D. A Bibliographic Guide, com- Galen taught and practiced in Rome for more
piled by Claire G. Fox, Gordon L. Miller, and than 30 years, serving as physician to some
Jacquelyn C. Miller (Westport, CT, Greenwood Roman emperors, including Marcus Aurelius. For
Press, 1996). Also see Chester R. Burns, “Setting an introduction to the historical legacies of
the Stage: Moral Philosophy, Benjamin Rush, and Hippocrates and Galen, see Owsei Temkin and C.
Medical Ethics in the United States before 1846,” Lilian Temkin (eds), Ancient Medicine: Selected
in Robert B. Baker, Arthur L. Caplan, Linda L. Papers of Ludwig Edelstein (Baltimore, Johns
Emmanuel, and Stephen R. Latham (eds), The Hopkins University Press, 1967); Owsei Temkin,
American Medical Ethics Revolution: How the Galenism: Rise and Decline of a Medical Philosophy
AMA’s Code of Ethics Has Transformed Physicians’ (Ithaca, NY, Cornell University Press, 1973); and
Relationships to Patients, Professionals, and Society Owsei Temkin, The Double Face of Janus and
(Baltimore, Johns Hopkins University Press, 1999, Other Essays in the History of Medicine (Baltimore,
pp 3–16). For rich insights about medical practice Johns Hopkins University Press, 1977).
in the colonies and early American republic, see 4. Andreas Vesalius (1514–1564), a Belgian physi-
Richard Harrison Shryock, Medicine and Society cian, was professor of anatomy at the University
in America: 1660–1860 (Ithaca, NY, Great Seal of Padua and wrote the first textbook of human
Books, 1960) and Whitfield J. Bell, Jr., The anatomy based on dissection of a human body.

34
 Chapter 3 The Relevance of Medical History to Family Medicine

Published in 1543, this text revolutionized med- Involved (Madison, University of Wisconsin Press,
ical science. William Harvey (1578–1657) was a 1974 paperback reprint of 1947 edition).
London physician who received his medical 6. “Coxe, John Redman,” in Howard A. Kelly and
degree from the University of Padua. Harvey Walter L. Burrage, Dictionary of American
conducted physiologic experiments on the Medical Biography (New York, D. Appleton,
movement of blood in mammalian bodies and 1928, pp 262–263).
separate experiments on the development of 7. In his synopsis of the writings of Hippocrates
sheep embryos. His theory about the circulation and Galen published in 1846, Coxe gave sum-
of blood in the human body was published in maries of 55 separate “treatises” traditionally
1628, and it had a revolutionary impact on included in The Writings of Hippocrates and
medical science similar to that of the anatomic summaries of more than 150 “treatises” written
discoveries of Vesalius. Thomas Sydenham by Galen—all eventually transmitted from
(1624–1689) was a British doctor who received antiquity to physicians of the “modern” era. The
his medical degree from the University of translations published between 1490 and 1525
Oxford. With his emphasis on detailed observa- were the vehicles for this cultural transfer.
tions of patients and their diseases, Sydenham 8. Morris Fishbein, A History of the American
was heralded as the “English Hippocrates.” Medical Association 1847–1947 (Philadelphia,
Hermann Boerhaave (1668–1738) was Professor WB Saunders, 1947, pp 19–40).
of Botany and Medicine at the University of 9. For an analysis of the major cultural legacies
Leyden. Boerhaave was a superb bedside teacher, about “healths” in Western and American cul-
and his pupils became the leading medical edu- ture, see Chester R. Burns, “Traditions of Healths
cators in Edinburgh, Vienna, and other German- in Western Culture” (Second Opinion
speaking academic institutions during the 18th 1986;2:120–136).
century. William Cullen (1710–1790) was a pop- 10. In the early 19th century in Paris, the clinical stud-
ular and engaging professor of medicine at ies of Pierre-Charles-Alexandre Louis discredited
Glasgow and Edinburgh. His lectures were given the tradition of bloodletting in Western medicine;
in English, not Latin. Benjamin Rush attended for a crisp summary of the impact of these studies,
his lectures when he studied in Edinburgh see Robert P. Hudson, Disease and Its Control
between 1768 and 1769. This is the same (Westport, CT, Greenwood Press, 1983, pp 206–
Edinburgh cited by Robert E. Rakel in the first 207). Ashbel Smith’s experiences with bloodletting
chapter of this textbook. For more details about during a yellow fever epidemic in Galveston in
the lives and careers of these and other physi- 1839 provide vivid examples of the difficult clini-
cians who practiced before 1930, see the very cal decisions about bloodletting experienced by
readable book by Henry Sigerist titled The Great those who knew about the clinical studies of
Doctors (Garden City, NY, Doubleday Anchor Louis. Smith had studied in Paris after graduating
paperback, 1958), and the encyclopedic fourth from Yale Medical School in 1828. See Smith’s
edition of Fielding Garrison’s An Introduction report of cases: An Account of the Yellow Fever
to the History of Medicine (Philadelphia, WB Which Appeared in the City of Galveston, Republic
Saunders, 1929). The various editions of of Texas, in the Autumn of 1839; with Cases and
Garrison’s history of medicine were the most Dissections (Galveston, TX, Cruger & Moore,
accurate and reliable general histories of medi- 1839). When “Self-Reliance” was published in
cine in English during their time because 1841 as the second of 12 essays in his first printed
Garrison had access to the resources of what collection of essays, Ralph Waldo Emerson
is now the National Library of Medicine and (1803–1882) had abandoned the Unitarian min-
because he was a meticulous scholar. The fourth istry 9 years earlier and was vigorously pursuing
edition is still one of the best reference sources his cultural vision of Transcendentalism. For this
for basic facts about much of the world’s med- essay, see Ralph Waldo Emerson Lectures & Essays
ical history before the early 20th century. (New York, Library of America, 1983, pp
5. For an introduction to the context of medical 257–282). For an introduction to Emerson’s
therapeutics during the 19th century, see Charles career, see Peter S. Field, Ralph Waldo Emerson:
E. Rosenberg, “The Therapeutic Revolution: The Making of a Democratic Intellectual (Lanham,
Medicine, Meaning, and Social Change in MD, Rowman & Littlefield, 2002).
Nineteenth-century America” (Persp Biol Med 11. From the day of Hippocrates and Galen until the
1977;20:485–506). For a valuable introduction late 19th century, the “healing power of Nature”
to the evolution of modern medicine from the was a central idea in Western medical therapy.
17th century to the 1940s, see Richard Harrison 12. This foremost therapeutic paradox for all doc-
Shryock, The Development of Modern Medicine: An tors, then and now, is that many self-limited dis-
Interpretation of the Social and Scientific Factors eases do disappear as bodily adaptations occur,

35
 Chapter 3 The Relevance of Medical History to Family Medicine

regardless of the therapies used by either profes- of Texas Medical Branch at Galveston (Austin,
sional doctors or loving grandmothers. Texas State Historical Association, 2003, pp 9–39).
13. John Harley Warner, The Therapeutic Perspective: 24. In the mid-1960s, Mac Harvey and Victor
Medical Practice, Knowledge, and Identity in McKusick, professors of internal medicine at the
America, 1820–1885 (Cambridge, MA, Harvard Johns Hopkins University School of Medicine in
University Press, 1986). Baltimore, selected portions of chapters about
14. The best short introduction to medical self-help 17 diseases from the 7th edition of Osler’s
and sectarian medicine is Medicine Without textbook (1909) and invited fellow internists
Doctors: Home Health Care in American History, teaching in several U.S. schools to provide com-
edited by Guenter Risse, Ronald L. Numbers, mentaries that compared and contrasted the
and Judith Walzer Leavitt (New York, Science diagnosis and treatment of these diseases during
History Publications, 1977). Osler’s time and in the mid-1960s. See Osler’s
15. For these and other examples, and their implica- Textbook Revisited, edited by A. McGeHee
tions for the evolution of general practice in the Harvey and Victor A. McKusick (New York,
United States during the last quarter of the 19th Appleton-Century-Crofts, 1967).
century, see Chester R. Burns, “Fictional Doctors 25. Michael Bliss, William Osler: A Life in Medicine
and the Evolution of Medical Ethics in the (New York, Oxford University Press, 1999,
United States, 1875–1900” (Lit Med 1988; p 191). Born in Bond Head, Ontario, Canada, on
7:39–55). July 12, 1849, to an Anglican evangelist and his
16. Ray McDearmon, Without the Shedding of Blood: wife who had immigrated from England in the
The Story of Dr. U.D. Ezell and of Pioneer Life at spring of 1837, William Osler was the eighth of
Old Kimball (San Antonio, TX, Naylor, 1953). nine children. Educated in medicine at Toronto
17. Roland Windell, The Brush of Angels’ Wings: The Medical College and McGill University’s School
Story of the Country Doctor (San Antonio, of Medicine, Osler received his medical degree
Naylor, 1952). from McGill in 1872. After studying in London,
18. Albert Cupp, Dad (Quanah, TX, Nortex Press, Berlin, Vienna, and Paris for 2 years, he became
1976) and H. Reginald McDaniel, “Dad Cupp” a professor at McGill. After 10 years of teaching
(Tex Med 1981;77:51–53). and writing in Montreal, his career continued in
19. J. Gordon Bryson, One Hundred Dollars & a Philadelphia (5 years), Baltimore (16 years), and
Horse: The Reminiscences of a Country Doctor Oxford (14 years). Osler died in 1919. For a short
(New York, William Morrow, 1965, p 126). introduction to Osler’s life and career, see
20. J.W. Young, Sr., It All Comes Back (Sweetwater, Richard L. Golden, “William Osler at 150: An
TX, Watson-Focht, 1962, pp 21, 24). Overview of a Life,” in The Quotable Osler, edited
21. For a short summary of Lister’s work, see Robert by Mark E. Silverman, T. Jock Murray, and
P. Hudson, Disease and Its Control (Westport, Charles S. Bryan (Philadelphia, American
CT, Greenwood Press, 1983, pp 156–158). For College of Physicians, 2003, xvii–xxxv).
comments about the expansion of surgical treat- 26. The best introduction to the story of clinical spe-
ment in Texas in the 1880s and 1890s, see cialization in the United States and the cultural
Chester R. Burns, “Health and Medicine,” in The and institutional responses of both physicians
New Handbook of Texas, edited by Ron Tyler, and the American public is Rosemary Stevens,
Douglas E. Barnett, Roy R. Barkley, Penelope C. American Medicine and the Public Interest: A
Anderson, and Mark F. Odintz (Austin, Texas History of Specialization (Berkeley, CA, University
State Historical Association, 1996, p 327). of California Press, updated edition, 1998).
22. See Table 4.1 in Kenneth M. Ludmerer, Learning 27. Chester R. Burns, “Colonial North America and
to Heal: The Development of American Medical Nineteenth-Century United States,” in Encyclopedia
Education (New York, Basic Books, 1985, p 77). of Bioethics, revised edition, edited by Warren
23. James Bordley, III, and A. McGehee Harvey, Two Reich (New York, Macmillan, 1995, Vol III, pp
Centuries of American Medicine 1776–1976 1610–1616).
(Philadelphia, WB Saunders, 1976, pp 604–605) 28. Paul Starr, The Social Transformation of
and William Gammon, “The Antitoxine of American Medicine (New York, Basic Books,
Diphtheria in Practice” (Trans Tex State Med 1982). Starr divides his book into what he calls
Assoc 1895, pp 325–334). The John Sealy Hospital Book One and Book Two. After studying his
was the teaching hospital for University of Texas preface and introduction carefully, a first-time
Medical Branch in Galveston. The hospital reader should then read Book One, and then
opened in 1890, and the first class of medical again read the preface and introduction before
students matriculated in 1891. See Chester R. reading Book Two. Even another reading of the
Burns, Saving Lives, Training Caregivers, Making introduction after digesting Book Two will help
Discoveries: A Centennial History of the University a reader better grasp Starr’s sociologic jargon.

36
 Chapter 3 The Relevance of Medical History to Family Medicine

To fully appreciate the changes described and Caregivers, Making Discoveries: A Centennial
analyzed by Starr, read the overview of the History of the University of Texas Medical Branch
development of health care in Texas written by at Galveston (Austin, Texas State Historical
Chester R. Burns and published as “Health and Association, 2003, p 4).
Medicine” in The New Handbook of Texas, 31. For details about these and other pioneering
edited by Ron Tyler, Douglas E. Barnett, Roy R. women doctors in Texas, see Elizabeth
Barkley, Penelope C. Anderson, and Mark F. Silverthorne and Geneva Fulgham, Women
Odintz (Austin, Texas State Historical Asso- Pioneers in Texas Medicine (College Station,
ciation, 1996, vol 3, pp 524–532) and examine Texas A&M University Press, 1997). Also see
two new books about medical practice in Texas. Chester R. Burns, “Health and Medicine,” in The
One describes the incredible changes in a dis- New Handbook of Texas, edited by Ron Tyler,
crete geographic area; see The History of Douglas E. Barnett, Roy R. Barkley, Penelope C.
Medicine in Brazos County (Texas) by Frank G. Anderson, and Mark F. Odintz (Austin, Texas
Anderson, Jr., and Edith Anderson Wakefield State Historical Association, 1996, vol 3, pp
(privately published by Frank G. Anderson, Jr., 527–528).
2001). The other new book describes fantastic 32. Rosemary Stevens, American Medicine and the
changes in a large academic institution in Public Interest: A History of Specialization
Dallas; see H. Lawrence Wilsey, How We Care: (Berkeley, University of California Press,
The Centennial History of Baylor University updated edition, 1998, p 181).
Medical Center Baylor Health Care System 33. See the biographic sketch of Nixon’s life by
1903–2003 (Dallas, TX, Baylor Health Care Chester R. Burns in The New Handbook of Texas,
System, two vols, 2003 and 2004). edited by Ron Tyler, Douglas E. Barnett, Roy R.
29. The following information was compiled from Barkley, Penelope C. Anderson, and Mark F.
American Board of Medical Specialties, The Odintz (Austin, Texas State Historical Asso-
Official ABMS Directory of Board Certified ciation, 1996, vol 4, pp 1021–1022), and Pat
Medical Specialists, 36th edition (St. Louis, Nixon of Texas: Autobiography of a Doctor, by Pat
Elsevier, 2004). Ireland Nixon, edited with an introduction by
Herbert H. Lang (College Station, Texas A&M
1917 American Board of Ophthalmology University Press, 1979).
1924 American Board of Otolaryngology 34. Henry S. Wentz, Patients Are a Virtue: Practicing
1930 American Board of Obstetrics and Gynecology Medicine in the Pennsylvania Amish Country
1932 American Board of Dermatology (Morgantown, PA, Masthof Press, 1997).
1933 American Board of Pediatrics 35. Mavis P. Kelsey, Sr., Twentieth-Century Doctor
1934 American Board of Radiology House Calls to Space Medicine (College Station,
1934 American Board of Psychiatry and Neurology Texas A&M University Press, 1999). Also
1934 American Board of Orthopedic Surgery see Chester R. Burns, “Traditions and Trans-
1934 American Board of Colon and Rectal Surgery formations: How Texas Medicine Changed in the
1935 American Board of Urology 20th Century” (Tex Med 2000;96(1):45–47).
1936 American Board of Pathology 36. The best overviews of these developments are
1936 American Board of Internal Medicine Charles E. Rosenberg, The Care of Strangers: The
1937 American Board of Anesthesiology Rise of America’s Hospital System (New York, Basic
1937 American Board of Plastic Surgery Books, 1987) and Rosemary Stevens, In Sickness
1937 American Board of Surgery and in Wealth: American Hospitals in the Twentieth
1940 American Board of Neurological Surgery Century (New York, Basic Books, 1989).
1947 American Board of Physical Medicine and 37. “The Core Content of Family Medicine” (GP,
Rehabilitation November 1966;34(5):225–246).
1948 American Board of Thoracic Surgery 38. The following publications are valuable resources
1948 American Board of Preventive Medicine for understanding the historical development of
1969 American Board of Family Practice family medicine in the United States: Phillip R.
1971 American Board of Allergy and Immunology Canfield, “Family Medicine: An Historical
1971 American Board of Nuclear Medicine Perspective” (J Med Educ 1976;51:904–911);
1979 American Board of Emergency Medicine Robert M. Lewy, “The Emergence of the Family
1980 American Board of Medical Genetics Practitioner: An Historical Analysis of a New
Specialty” (J Med Educ 1977;52:873–881); P.
30. For an exceedingly valuable historical overview, Curtis, “Three Hundred Years of Family Health
see “Looking Back on the Millenium in Care” (J Fam Pract 1981;12:323–327); William
Medicine” (N Engl J Med 2000;342(1):42–49). J. Doherty, Charles E. Christianson, and Marvin
Also see Chester R. Burns, Saving Lives, Training B. Sussman (eds), Family Medicine: The Maturing

37
 Chapter 3 The Relevance of Medical History to Family Medicine

of a Discipline (New York, Haworth Press, 1987); Branch in Galveston who took an elective course
David P. Adams, “Evolution of the Specialty in medical history with Dr. Burns. Jenny, now a
of Family Practice” (J Florida Med Assoc resident in family medicine in Tyler, Texas, did a
1989;76:325–329); D.P. Adams, American Board superb job of analyzing some of the features
of Family Practice: A History (Lexington, KY, about the history of family medicine that were
American Board of Family Practice, 1999); and described in this chapter. The authors are most
Robert E. Rakel, “Evolution of Family Medicine in grateful for her insights and wish her all the best
the United States: Sisyphus Revisited,” Proceedings in her career as a family physician.
of the 37th International Congress on the History of 43. Online databases make this labor not as difficult
Medicine, edited by Chester R. Burns, Ynez Viole as it was previously. Any reader with access to the
O’Neill, Philippe Albou, and Jose Gabriel Rigau- Internet can go to the UTMB home page at
Perez (Galveston, University of Texas Medical www.utmb.edu and click on Library. Then click
Branch, 2002). on Internet Resources; then Medical Huma-
39. Robert B. Taylor, “Family Practice and the nities; then History of Medicine. Under History
Advancement of Medical Understanding: The of Medicine, click on American Association for
First 50 Years” (J Fam Pract 1999;48:53–57). the History of Medicine (AAHM). More than 30
40. Lawrence L. Hirsch, “Review of Principles of sites about medical history can be accessed by
Family Medicine (1977)” (JAMA 1978;239:2387). clicking on Related Sites on the AAHM home
41. Glimpses of this future may be found in page. The most comprehensive of these sites is
Fitzhugh Mullan, Big Doctoring in America: the one titled History of the Health Sciences
Profiles in Primary Care (Berkeley, University of World Wide Web Links. These links provide
California Press, 2002). access to more than 300 Internet sites providing
42. In the spring of 2004, Jenny Saurette was one of information about many topics in the history of
several seniors at the University of Texas Medical medicine and health care.

SUGGESTED READINGS
Burns CR. Fictional doctors and the evolution of medical Shryock RH. Medicine in America: Historical Essays.
ethics in the United States, 1875–1900. Lit Med 1988; Baltimore, Johns Hopkins University Press, 1966.
7:46–49. Silverthorne E. Ashbel Smith of Texas: Pioneer, Patriot,
Coxe JR. The Writings of Hippocrates and Galen. Statesman, 1805–1886. College Station, Texas A&M
Philadelphia, Lindsay and Blakiston, 1846. University Press, 1982.
Hudson RP. Disease and Its Control. Westport, CT, Tindall GB, with Shi DE. America: A Narrative History.
Greenwood Press, 1983. New York, WW Norton, 1992.
Kaufman M, Galishoff S, Savitt TL, eds. Dictionary of Warner JH. The Therapeutic Perspective: Medical Practice,
American Medical Biography, vols 1 and 2. Westport, Knowledge, and Professional Identity in America,
CT, Greenwood Press, 1984. 1820–1885. Cambridge, MA, Harvard University Press,
Kelly HA, Burrage WL. Dictionary of American Medical 1986.
Biography. New York, D. Appleton, 1928.
Powell JH. Bring Out Your Dead: The Great Plague of
Yellow Fever in Philadelphia in 1793. Philadelphia,
University of Pennsylvania Press, 1949.

38
 C h a p t e r

4 Problem Solving in
Family Medicine
John C. Rogers and William Y. Huang

generic problem-solving skills; they need specific bio-

KEY POINTS medical knowledge as well. Thus, for effective problem
solving in primary care, students need specific knowl-
1. The complete history and physical are not effi- edge about ambulatory problems (see later chapters
cient and often not appropriate for handling about clinical problems) and a foundation of clinical
the brief and varied encounters seen in the reasoning steps, which this chapter provides.
ambulatory setting. Students must learn a new Introduction to clinical medicine courses present
way to approach clinical problems in the ambu- students with one model for approaching clinical
latory setting that enables them to obtain key problems: the complete history and physical exami-
information in a focused manner. nation (H&P), which is the standard assessment per-
2. Different types of ambulatory visits include the formed when a patient enters the hospital. The H&P
new problem visit, chronic illness visit, checkup consists of the chief complaint, statement of the reli-
(prevention) visit, psychosocial visit, and behav- ability of the patient as a historian, history of the
ior change visit. Family physicians often see current illness, medical history, social history, family
“mixed” visits that include two or more of history, review of systems, complete physical exami-
these visit types. nation, and laboratory test data followed by an
3. Five general tasks to perform in ambulatory vis- impression and initial plans. Students follow this map
its include assessing the patient’s expectations for physician-patient encounters on internal medi-
and concerns, acquiring and synthesizing cine rotations when doing complete workups on new
patient information, developing a therapeutic hospital admissions. Students also follow this map
relationship, negotiating a management plan, on pediatrics and in an abbreviated form on surgery
and learning from the encounter. and obstetrics-gynecology rotations, in which a single
4. In performing these general tasks, there is some problem is more typically the focus of the admission.
similarity across different visit types. However, In the ambulatory setting, students quickly realize
for the acquiring and synthesizing patient infor- that a complete H&P is not appropriate for most
mation task, different kinds of information must physician-patient encounters. The main issue is the
be obtained and processed for each visit type. amount of time dedicated to ambulatory visits. The
5. Selecting the correct visit type(s) and using the mean time per encounter for the 25 most frequent
general tasks give students an approach to han- diagnoses ranges between 9 and 17 minutes, with the
dling different ambulatory generalist encounters bulk of the mean times between 10 and 14 minutes
in a focused manner. (Rosenblatt et al., 1982 ●
B). There is simply not enough
time to do an H&P during each ambulatory
encounter. The second issue is the wide variety of
Medical educators are often concerned about the teach- problems seen in ambulatory care. The top 30 diag-
ing and assessment of problem-solving skills. Teachers noses seen by office-based family physicians constitute
presume that students can learn and use a set of rea- only about two thirds of all problems seen in the out-
soning strategies to solve clinical problems successfully, patient setting (Rosenblatt et al., 1982 ● B ). Even the
even novel, complex ones. Research has shown, how- three most common diagnoses (hypertension, general
ever, that problem-solving performance varies across medicine examination, and diabetes mellitus) are seen
different clinical domains, such as nephrology and gas- in only 15% of patient encounters (National Center
troenterology. Students need more than just a set of for Health Statistics, Centers for Disease Control and

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

39
 Chapter 4 Problem Solving in Family Medicine

Prevention, U.S. Department of Health and Human TASK 1: ASSESS THE PATIENT’S
Services, 2002). Parts of an H&P are relevant to the EXPECTATIONS
evaluation of new undiagnosed problems (i.e., history
of current illness), but care of the other problems (i.e., Assessing a patient’s expectations identifies the type
prevention, chronic illnesses, psychosocial issues, and of visit and guides patient education and negotiation
lifestyle or behavior change) requires information that of the management plan. Four key concepts are
is not included in a typical H&P. involved in this task: goals, requests, explanatory
If the complete workup or H&P model from model, and prototypic experiences.
hospital-based practice does not fit well with office- Goals are the ends that patients wish to achieve
based, generalist practice, what model does? with regard to health, functional ability, or symptoms.
Unfortunately, a single approach does not work for Patients often do not make their goals explicit during
all types of encounters that family physicians have the encounter and cannot articulate them easily.
with patients: new patient visit, new problem visit, Sometimes patients state that they need to be well for
follow-up visit, preventive care visit, chronic illness an important event, such as a wedding. Others simply
visit, mental health visit, or procedure visit. The H&P want to be rid of the symptoms or be reassured. Still
map works well for a new patient visit but not for the others wish to be able to function for their job.
others. For example, at a chronic illness visit, the Explicitly identifying a patient’s goals can help form
physician needs to accomplish several tasks: assess an alliance between the physician and the patient.
control of the disease, ask about adherence with the Requests are patients’ notions of the means needed
treatment plan, check for treatment side effects, seek to achieve their goals (Like and Zyzanski, 1986 ● B ).
evidence of end-organ damage, and scan for other Patients often want medical information about a prob-
risk factors for complications. At a well-person lem, such as what it is called, what causes it, how long it
checkup visit, the physician should cover several pre- is going to last, and which tests may be needed. In addi-
ventive medicine topics: cancer detection, coronary tion, patients typically want some biomedical treat-
artery disease risk factors, immunizations and infec- ment such as medications or surgery for their physical
tious disease risks, trauma prevention strategies, and discomfort. At other times, patients want emotional
metabolic disease risk and prevention. assistance or simply want the physician to listen while
At each of the different types of ambulatory vis- they share their own perspective about the problems.
its, primary care physicians attempt to complete spe- Patients also seek advice about general health matters
cific tasks in a time-efficient way. This balance is one such as diet and exercise. Sometimes patients are
of the key skills in ambulatory generalist practice: explicit about what they expect, but often this opinion
how to efficiently accomplish a number of tasks that is only mentioned indirectly during the visit. By deter-
synthesize medical knowledge about what consti- mining a patient’s request for the visit, the clinician can
tutes good patient care. The educational challenge address this issue directly with the patient, especially if
for students is to learn which tasks are important in there seems to be disagreement between the physician’s
what types of visits and then how to do those tasks. recommendation and the patient’s request (Table 4-1).
The task-oriented processes in care model (Rogers One source of patients’ requests is their explana-
et al., 2003 ●B , 2004) summarizes the different tasks
tory model, which is a concept from the anthropo-
for different visit types and provides students with a logic literature that refers to the theory about disease
framework for organizing their approach to these (Kleinman, 1980). The Western biomedical model
different visit types. taught in allopathic and osteopathic schools of med-
In the task-oriented processes in care model, the icine is one of a number of available models about
following major processes apply to all visit types and the causes of diseases, their prognosis, and appropri-
summarize what family physicians do. Together they ate treatments. In the community, there are also
could be seen as the general model for conducting cultural theories that may use terms from the bio-
ambulatory generalist visits. The remainder of this medical model. The beliefs that patients hold often
chapter covers these major processes and describes drive their requests and strongly influence what they
how the student can use them as core problem- expect of physicians.
solving skills. Another determinant of patients’ requests is their
1. Assess the patient’s expectations and concerns. prototypic experiences, which include personal expe-
2. Acquire and synthesize patient information. rience with a problem, experience of a family mem-
3. Develop a therapeutic relationship. ber or friend, or reading or hearing about the issue
4. Negotiate a management plan. through media such as magazines and television
5. Learn from the encounter. (Like and Steiner, 1986 ● B ). Sometimes these sources
of information, particularly significant family mem-
Within these major processes, there are specific bers or friends, have great influence in patients’ lives.
tasks that are unique to each visit type, especially in the Gathering information related to each of these
“acquire and synthesize patient information” process. four concepts helps focus patient education and nego-

40
 Chapter 4 Problem Solving in Family Medicine

learn to listen to the patient’s expectations and con-

Table 4-1 Examples of Patients’
cerns and avoid the temptation to take over the inter-
Expectations and Concerns for
view. In most cases, if the student will allow the patient
Different Types of Ambulatory
to completely express his or her concerns, it will not
Visits
take a significant amount of additional time. This
New problem visit inquiry may reveal that there are no conflicts, no
Diagnose the cause of symptoms critical gaps in the patient’s understanding, and no
Order diagnostic tests to evaluate symptoms need for a long-winded discussion by the physician.
Concern that symptoms may reflect a severe or Alternatively, the physician and patient may discover
life-threatening condition (especially if a family areas in which brief, focused education and dialogue
member or friend with similar symptoms can be very effective and satisfactory for both parties.
turned out to have a severe condition)
This inquiry may even reveal major gaps or conflicts
Checkup (prevention) visit that perhaps can be resolved after serious negotiation
Evaluate overall health status or that may lead to the decision that the physician and
Discuss pros and cons of doing a screening test patient cannot have a successful working relationship.
that the patient wishes to have performed This approach to clinical encounters is sometimes
Desire to be screened for a condition that a described as patient-centered care in contrast to the
family member or friend has focus on diagnostic reasoning or doctor-centered care.
Chronic illness visit
Relieve symptoms or improve control of TASK 2: ACQUIRE AND SYNTHESIZE
condition
Discuss lifestyle or medication issues
PATIENT INFORMATION
Avoid target organ damage or other
complications from the chronic illness After learning the patient’s expectations and con-
cerns, the focus of the visit becomes clearer. Some
Psychosocial visit patients have a new or undiagnosed problem that
Diagnose and treat emotional symptoms that needs evaluation. Others may desire a checkup or
may indicate a mental illness or manifestations health maintenance examination, have known
of a physical illness chronic illnesses that need monitoring, present
Diagnose and treat somatic symptoms that the with psychosocial concerns, or desire help in
physician may conclude are related to an changing a problem behavior. It is also important
emotional condition
to understand that patients in the family physi-
Behavior change visit cian’s office may present with one or more of these
Relieve current physical symptoms that result concerns at the same time. Indeed, one study
from a problem behavior needing change demonstrated that 73% of encounters in the family
Discuss how to deal with a problem behavior physician’s office dealt with more than one prob-
that the patient knows needs changing lem (Flocke et al., 2001 ●B ). Understanding the rea-
Patient may have no expectations or concerns, son for the patient’s visit helps the student gather
but physician may have concerns that a the information necessary for that particular type
behavior change is causing current symptoms of visit.
or aggravating the control of a chronic illness The task-oriented processes in care model
describes the different types of patient visits and the
information to be gathered and synthesized for each
tiation of the management plan. Although collecting type. The task-oriented processes in care model
this information may seem to be relatively easy, it can includes the new problem visit, checkup (preven-
be difficult in the busy ambulatory environment to lis- tion) visit, chronic illness visit, psychosocial visit,
ten to the patient’s entire story due to the limited time and behavior change visit (Table 4-2).
available for each patient encounter. In one study,
physicians interrupted the patient’s opening statement
New Problem Visit
of concerns and redirected the interview toward a
more specific concern after an average of 18 seconds In this visit, the patient presents with an undifferen-
(Beckman and Frankel, 1984 ● B ). A later study con- tiated set of symptoms, and the goal is to diagnose
firmed that physicians redirected patients after letting the condition and begin appropriate treatment. This
them present their opening statement after an average visit is similar to the traditional H&P but more
of 23 seconds. However, in this second study, patients focused. The student elicits the presenting symptom
allowed to completely express their concerns took only and takes a history of current illness, asks about per-
on average six seconds more than those who were tinent history and family and social history, does a
interrupted (Marvel et al., 1999● B ). The student must brief review of systems, and performs a physical

41
 Chapter 4 Problem Solving in Family Medicine

guides recommendations to the patient about what

Table 4-2 Specific Tasks to Perform
preventive measures are indicated in each category.
in Acquiring and Synthesizing
Patient Information
Chronic Illness Visit
New problem visit
Assess presenting complaint In this visit, the patient has a known chronic illness,
Construct a problem list and make a diagnosis and the purpose of the visit is to monitor the current
status and provide care that will prevent further com-
Checkup (prevention) visit plications. The student assesses the severity and con-
Assess risk factors and previous preventive trol of the condition. For patients with diabetes,
services for six major areas: cancer,
cardiovascular disease, infectious diseases,
hemoglobin A1c is one good measure of control. For
injury/trauma, metabolic diseases, and patients with asthma, the frequency of symptoms,
emotional health such as wheezing, and peak flow readings are meas-
Recommend preventive services in each area ures of severity and control. Students ask about
based on risk profile and previous preventive adherence to the management plan of medication
services and lifestyle measures and ask whether there are any
side effects from the medications. Scanning for tar-
Chronic illness visit get organ damage is an important part of the eva-
Assess severity and control of the condition luation of some chronic illnesses. For the patient with
Evaluate adherence to and side effects of diabetes, this includes assessing the patient for
medications
Scan for target organ damage from the
retinopathy, coronary artery disease, nephropathy,
condition neuropathy, and peripheral vascular disease. Review-
Review status of comorbid conditions ing comorbid conditions is also an important aspect
of the evaluation of some chronic illnesses. For the
Psychosocial visit patient with diabetes, this includes blood pressure,
Assess emotional needs of patient and family weight, lipids, smoking status, and family history of
using the BATHE (see text) model cardiovascular disease because all these contribute to
Evaluate for diagnosable mental illness the patient’s risk of developing cardiovascular disease.
Evaluate suicidal risk

Behavior change visit Psychosocial Visit

Get background information on problem
behavior Many patients present to their family physicians with
Assess the patient’s stage of change an emotional disorder or psychosocial symptoms.
In this visit, the student assesses those needs through
use of the BATHE model, which includes understand-
ing the background of the psychosocial situation, the
examination focused on systems relevant to the patient’s affect or emotional response to the situation,
potential diagnoses. While collecting information the most troubling aspect of the situation, and how
during the focused H&P, the student develops the patient is trying to cope or handle the situation.
hypotheses about possible causes and, through an The student completes the assessment by express-
iterative process, tests and revises those hypotheses. ing empathy for the patient’s symptoms and situation
With experience, novices become experts in iterative and pulls the symptoms together to see whether a
hypothesis testing. The products of this process are a diagnosable mental illness exists and whether a risk
differential diagnosis, a working diagnosis, and even- for suicide exists (Stuart and Lieberman, 1986).
tually a final diagnosis and problem list.
Behavior Change Visit
Checkup (Prevention) Visit
In this visit, the patient presents with a need for
In this visit, the patient desires a checkup of current behavior change such as starting a diet and/or exer-
health status and appropriate measures to prevent cise program or stopping a problem behavior such as
illnesses and to screen for detectable conditions. smoking or other substance use. The student seeing a
Prevention and screening services can be organized patient with this issue first gets background informa-
into six categories of major causes of death and dis- tion on the problem to understand why it has been
ability: cardiovascular, cancer, infectious diseases, difficult for the patient to change. In asking ques-
injury/trauma, metabolic, and emotional health. The tions about the patient’s motivation and sense of
student gathers information about the patient’s risk self-efficacy, the student can use the stage of change
factors for particular diseases and about previous model to identify the stage of change or readiness of
preventive and screening services. This information the patient to change (Prochaska and DiClemente,

42
 Chapter 4 Problem Solving in Family Medicine

1992). Patients in the precontemplation or contem- tency, encouraging and answering questions, explain-
plation stage may not be ready for change, and in ing, and referring to a specialist if needed (Thom et al.,
those cases, it is the goal of the student to educate 2001● B). For students to learn to develop a therapeutic
and help patients consider appropriate information relationship, it is important for them to show care, to
that encourages them to advance to the next stage in communicate effectively, and to give the patient confi-
the model. Patients in the determination stage are dence in his or her clinical skills (Table 4-3).
ready to change, and the student can help those
patients devise a plan for changing. Patients in the
action or maintenance stages, who have already TASK 4: NEGOTIATE A MANAGEMENT
made the change, need encouragement and positive PLAN
reinforcement on their new behavior and tips on
how to avoid relapsing (see Table 4-2). Essential elements of the management plan include
medications, diagnostic tests, lifestyle measures,
referrals to other specialists or allied health
TASK 3: DEVELOP A THERAPEUTIC providers, and arranging follow-up.
RELATIONSHIP An important aspect of developing and negoti-
ating the management plan is gaining an under-
To help solve patients’ problems and be healers, standing of the patient’s perspective on the condition.
physicians foster relationships of mutual trust and For example, one study demonstrated that physicians
respect. In situations with continuity of care over focused their attention on managing the laboratory
time, there are many opportunities to establish results of patients with diabetes while failing to take
workable therapeutic relationships. When necessary, into account other psychosocial issues that the
however, skillful physicians can develop therapeutic patients felt were important (Freeman and Loewe,
relationships in one or two visits. 2000● B ). For successful negotiation of the manage-
While physicians’ nonverbal cues are a major ment plan to occur, it is important for physicians and
determinant in establishing an effective relationship, patients to agree on what needs treatment and then
direct questions can foster the desired relationship as what that treatment will entail. For patients with
well. There are four areas the physician can ask about: chronic illnesses, Von Korff et al. (1997) recommend
(1) the patient’s family, work, and sociocultural con- that physicians and patients work together to define
text; (2) the patient’s thoughts about the situation; what the problems are and then set realistic goals and
(3) the patient’s feelings in response to the context; and targets to address the problems. In their suggested
(4) the patient’s efforts to cope with the context, model of care, it is important for physicians to help
thoughts, and feelings (Stuart and Lieberman, 1986). patients know self-management items that can be
Gathering contextual information indicates to performed at home and that active, sustained follow-
the patient that the physician is not interested simply up occur even through telephone contact.
in a diseased organ system or pathophysiologic Although it is not fully understood how experi-
process but is concerned about the person who is enced clinicians make management decisions, there
experiencing the illness. In addition to listening care- are steps that at least help structure and define the
fully and maintaining eye contact, asking a patient’s decisions that must be made (Weinstein et al., 1980).
context demonstrates the physician’s regard for the One approach is to develop a decision tree that
patient as a person. includes the therapeutic options and the outcomes
By gathering information about the patient’s that may result from each option. This structure out-
thoughts, feelings, and coping efforts, the physician lines the treatment alternatives from which the physi-
reinforces the view that the patient’s physical com- cian and patient can choose as well as the potential
plaints cannot be considered in isolation from the outcomes or consequences, both minor and major, of
rest of the patient’s life. This acknowledgment of the each selection. Describing the options and outcomes
interaction of the patient’s emotional life and physi- to patients involves the patients in their own care.
cal well-being also contributes to the development of Obtaining patients’ preferences about treatment
a personal bond between physician and patient, alternatives and outcomes is helpful.
which is necessary for an optimal healing relation- Physicians do not go through these processes
ship. Most patients are grateful when a physician explicitly during every encounter, due to time con-
takes time to ask and listen. Verbally and nonverbally straints and variability in patients’ desire for direct
expressing empathy manifests the unconditional involvement in medical decisions. Instead, physicians
regard necessary in a therapeutic relationship (Stuart often make decisions informally and quickly in their
and Lieberman, 1986). heads. Patients are grateful, however, if physicians at
In one study, the physician behaviors that were least list the management options and major out-
most frequently associated with patient trust included comes. When patients know why tests or treatments
being comforting and caring, demonstrating compe- are recommended, they feel more involved and are

43
 Chapter 4 Problem Solving in Family Medicine

Table 4-3 Examples of Strategies to Help Students Develop a Therapeutic Relationship

with Patients in Different Types of Encounters
All visit types
Ask about family or social situation; seek to make a connection on a nonmedical topic
Demonstrate interest in the patient
Use facilitating, nonverbal behaviors such as appropriate eye contact, body position, and nods
Hold a genuine, positive regard for the patient

New problem visit

Acknowledge that symptoms are of concern to the patient
Be patient centered by focusing on patient’s experiences, thoughts, feelings, and concerns
Include patient preferences in negotiation of the management plan, especially in regard to diagnostic
tests and treatment

Checkup (prevention) visit

Acknowledge the patient’s concern about a particular condition and desire to have a particular screening
test
Patiently work with patients resistant to having a recommended screening

Chronic illness visit

Understand how the chronic illness affects the patient and family
Take a family-focused approach by assessing the needs of patient and family, understanding the relational
context in which disease management occurs, and including the family environment in proposing
interventions
Encourage continuity of care between physician and patient/family
Work collaboratively with patient and family to manage the illness
Encourage compliance
Demonstrate care and compassion, remembering that “care” may be more important than “cure” in
treating many patients who are receiving maximal medical treatment for their chronic illnesses

Psychosocial visit
Recognize that it may be difficult for the patient to share his or her symptoms and situation
Encourage the patient to share his or her symptoms and concerns by being nonjudgmental and
empathetic
Include patient preferences in negotiation of the management plan, especially in regard to medication
and referrals

Behavior change visit

Demonstrate empathy for the difficulty in changing behavior
Offer partnership, support, and optimism in helping the patient through the change process
Avoid negative labels and terms associated with problem behaviors
Anticipate resistance and be patient in working with the patient
Avoid argumentation but seek to guide the patient in the process of self-discovery

more likely to follow the suggestions or directions. This with that patient and the management of that
strategy permits real negotiation between physicians patient’s problems can be improved as the care con-
and patients about medical advice and what to do tinues. This reflection can also lead to a fuller under-
about problems. By providing patients with options standing of the patient’s problems in general terms
and eliciting an idea of patients’ preferences, physicians so that the care of other patients is improved.
can choose a course of action that is based on the best Reviewing the processes by which a diagnosis
medical knowledge and patients’ values (Table 4-4). was made and the management plan implemented
can identify biases or pitfalls that may become habit-
ual and may lead to misdiagnosis or inappropriate
TASK 5: LEARN FROM THE ENCOUNTER management decisions. Errors in problem solving
cannot be completely avoided, but by reflecting on
Learning from patient encounters is a principal encounters and noting when errors occur, clinicians
means by which physicians continue their education. may make these errors less frequently and may avoid
Reflecting on a particular encounter can help the the self-deception that all is well with their decision
physician determine ways in which the relationship making.

44
 Chapter 4 Problem Solving in Family Medicine

Table 4-4 Examples of Strategies to Negotiate a Management Plan in Different Types of

Encounters
All visit types
Management items to discuss
Diagnostic tests
Lifestyle measures
Medications
Referrals to specialists or allied health providers
When to return for follow-up

New problem visit

Discussion of possible diagnoses, tests, and prognosis
Negotiation of diagnostic plan by asking the patient about preferences and encouraging the patient to be
involved
Support self-care by providing information/patient education material and educating the patient on what
he or she can do to care for him- or herself

Checkup (prevention) visit

Recommend preventive or screening services as recommended by accepted guidelines
Negotiation through discussion of options (such as different methods of colorectal cancer screening)
Support the patient’s self-care by encouraging healthy lifestyle choices (diet, exercise) that may prevent
illnesses, and teach patients to screen themselves where possible (e.g., breast self-examination)

Chronic illness visit

Negotiation of achievable goals and measurable targets and discussion of options such as medication
choices, lifestyle measures, and referrals
Support self-care by teaching the patient to mirror what you do in the office: assess severity and control
of the condition, monitor compliance with lifestyle measures and medications, scan for target organ
damage, observe comorbid conditions

Psychosocial visit
Establish diagnosis by evaluating for appropriate medical and psychosocial conditions
Negotiation through discussion of options such as medications, counseling, and who may be best provider
of these services
Support the patient’s self-care by encouraging the use of social support networks and counseling services

Behavior change visit

Negotiation of a feasible plan to change the problem behavior that is acceptable and realistic for the
patient
Increase the patient’s motivation by a discussion of the pros and cons of changing the problem behavior
and helping him or her see that the pros outweigh the cons
Increase the patient’s self-efficacy by a discussion of the aids and barriers to change and helping him or
her see that the aids outweigh the barriers

Individual physician-patient relationships do monitor the effectiveness of therapy and to detect

not remain static but shift over time depending on side effects or complications. A key learning task for
the clinical setting, clinical problem, and stage of the all clinicians is to determine which clinical guidelines
relationship. Reflecting on the relationship after an experts are recommending and how these recom-
encounter may bring insights that will improve mendations are being revised on a continual basis.
future physician-patient encounters (Table 4-5). By reviewing the clinical encounter in these terms,
It also is useful to identify which decision poli- the physician can determine whether his or her prac-
cies, rules, or protocols are pertinent to the clinical tice of medicine is state of the art or behind the
encounter. Each physician develops policies regard- times.
ing the diagnostic process and therapeutic manage-
ment. Some of these policies may be related to the
goals of diagnosis and therapy. Clinicians also adopt SUMMARY: THE AMBULATORY
protocol-related policies developed by others, such ENCOUNTER CHECKLIST
as diagnostic protocols and algorithms, therapeutic
protocols with standard duration and sequencing of These five general tasks—assessing the patient’s
interventions, and standard evaluation procedures to expectations and concerns, acquiring and synthesizing

45
 Chapter 4 Problem Solving in Family Medicine

Table 4-5 Examples of References That Will Help Students Learn from the Encounter

New problem visit

Applicable diagnostic or therapeutic protocols for undifferentiated conditions; many are available at the
National Guideline Clearinghouse Web site (www.guideline.gov)

Checkup (prevention) visit

Applicable preventive and screening guidelines; many are available at the U.S. Preventive Services Task
Force Web site (www.ahcpr.gov/clinic/uspstfix.htm). The U.S. Preventive Services Task Force provides an
excellent summary of the current evidence surrounding each preventive or screening issue and explains
how their recommendations were reached through an evaluation of this evidence.

Chronic illness visit

Applicable clinical practice guidelines for chronic illnesses and conditions; many are available at the
National Guideline Clearinghouse Web site (www.guideline.gov) or the National Institutes of Health
Web site (www.nih.gov)

Psychosocial visit
Diagnostic criteria for mental conditions; many are available from the Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition (DSM-IV), American Psychiatric Association, 1994.

Behavior change visit

Applicable guidelines on changing problem behaviors; some guidelines are available at the National
Guideline Clearinghouse Web site (www.guideline.gov) and the U.S. Preventive Services Task Force Web
site (www.ahcpr.gov/clinic/uspstfix.htm). Students may also learn by reflecting on their own fallibility
and need to change.

patient information, developing a therapeutic rela-

Material Available on Student Consult
tionship, negotiating a management plan, and learn-
ing from the encounter—provide a checklist to guide Review Questions and Answers about Problem
young clinicians through ambulatory generalist Solving in Family Medicine
encounters. Understanding the applicable visit
type(s) will help students use these tasks correctly,
provide a framework for the visit, treat the patient
appropriately, and learn from the encounter.

REFERENCES
Beckman HB, Frankel RM. The effect of behavior on the col- National Center for Health Statistics, Centers for Disease
lection of data. Ann Intern Med 1984;101: 692–696. ● B Control and Prevention, United States Department of
Flocke SA, Frank SH, Wenger DA. Addressing multiple Health and Human Services. National Ambulatory
problems in the family practice office visit. J Fam Pract Medical Survey data, 2002. Taken from the American
2001;50:211–216. ● B Academy of Family Physicians Web site. Available at
Freeman J, Loewe R. Barriers to communication about dia- www.aafp.org/x25061.xml. Accessed October 14,
betes mellitus: Patients’ and physicians’ different views 2004. ● B
of the disease. J Fam Pract 2000;49:507–512. ● B Prochaska JO, DiClemente CC. Stages of change in the
Kleinman A. Patients and Healers in the Context of Culture. modification of problem behaviors. Prog Behav Modif
Berkeley: University of California Press, 1980:106. 1992;28:183–218.
Kleinman A, Eisenberg J, Good B. Culture, illness and care: Rogers J, Corboy J, Dains J, et al. Task-oriented processes in
Clinical lessons from anthropologic and cross-cultural care (TOPIC): A proven model for teaching ambula-
research. Ann Intern Med 1978;88:251–258. tory care. Fam Med 2003;35:337–342. ● B
Like R, Zyzanski S. Patient requests in family practice: Rogers JC, Corboy JE, Huang WY, Monteiro FM. Task-
A focal point for clinical negotiations. Fam Pract Oriented Processes in Care (TOPIC) Model in
1986;3:216–227. ● B Ambulatory Care. New York: Springer, 2004.
Marvel MK, Epstein RM, Flowers K, Beckman HB. Rosenblatt RA, Cherkin OC, Schneeweis R, et al. The struc-
Soliciting the patient’s agenda: Have we improved? ture and content of family practice: Current status and
JAMA 1999;281:283–287. ● B future trends. J Fam Pract 1982;15:681–722. ● B

46
 Chapter 5 Evidence-Based Medicine

Stuart MR, Lieberman JA. The Fifteen Minute Hour: Von Korff M, Gruman J, Schaefer J, et al. Collaborative
Applied Psychotherapy for the Primary Care Physician. management of chronic illness. Ann Intern Med
New York: Praeger, 1986. 1997;127:1097–1102.
Thom DH and the Stanford Trust Study Physicians. Weinstein MC, Fineberg HU, Elstein AS, et al. Clinical
Physician behaviors that predict patient trust. J Fam Decision Analysis. Philadelphia: WB Saunders, 1980.
Pract 2001;50:323–328. ●
B

C h a p t e r

5 Evidence-Based Medicine

Bernard Ewigman

use the Women’s Health Initiative (WHI) random-

KEY POINTS ized trial of hormone replacement therapy (HRT) to
make the case that using the best evidence can save
1. Evidence-based medicine (EBM) evolved from lives, to provide concrete examples of using EBM in
the population-based, quantitative, and empiri- practice, and to explain some of the methods of EBM
cal roots of epidemiology and biostatistics. (Manson et al., 2003).
2. EBM is a recent approach to clinical decision EBM is relatively new, roughly a decade old,
making and complements rather than supplants according to authors writing in a special issue of the
pathophysiologic reasoning, clinical experience, British Medical Journal (BMJ) published in 2004
and clinical judgment. (Coomarasamy and Khan, 2004; Gabbay and Le
3. The key feature that distinguishes EBM from May, 2004; Guyatt et al., 2004; Lockwood, 2004;
other approaches is the use of explicit and Reilly, 2004; Strauss and Jones, 2004; Tovey and
replicable methods to answer clinical questions. Godlee, 2004). A MEDLINE search I conducted
4. InfoRetriever and DynaMed are electronic using the term “evidence-based medicine” resulted
knowledge resources developed by family physi- in no citations prior to 1992, and only two citations
cians that are based on literature surveillance for that year. When the same search term was used
systems. for the year 2003, 3,011 citations were generated. A
5. The Family Physicians Inquiries Network is a perusal of articles in the 2004 special issue of the
binational academic consortium of family medi- BMJ leaves little doubt that EBM has grown expo-
cine departments, residency programs, librari- nentially in medical education, clinical training, and
ans, and other persons and entities dedicated clinical practice in the United States, Canada, and
to using information technology to translate Great Britain (Coomarasamy and Khan, 2004;
research evidence into practice. Gabbay and Le May, 2004; Guyatt et al., 2004;
Lockwood, 2004; Reilly, 2004; Strauss and Jones,
2004; Tovey and Godlee, 2004).
It remains unclear whether patients have actu-
WHAT IS EVIDENCE-BASED MEDICINE? ally benefited from the lofty goals of the EBM phi-
losophy. The EBM model has not yet penetrated
Evidence-based medicine (EBM) is the integration of the processes of patient care sufficiently to sub-
best research evidence with clinical expertise and stantively affect patient care outcomes in easily
patient values (Reilly, 2004; Sackett et al., 2000). The measurable ways, many challenges remain to
ultimate goal of EBM is to improve patient outcomes achieve this objective, and the complex task of
by considering the most current, valid, clinical proving the effectiveness of EBM will be exception-
research evidence in patient care decisions. An excel- ally difficult (Strauss and Jones, 2004). Nonetheless,
lent example of the application of EBM in practice is EBM has definitely had an impact on the know-
described in Chapter 6 of this book, “Evaluating the ledge, attitudes, and behaviors of practitioners
Medical Literature,” by Susman and colleagues. They (Coomarasamy and Khan, 2004; Tovey and Godlee,

47
 Chapter 5 Evidence-Based Medicine

Stuart MR, Lieberman JA. The Fifteen Minute Hour: Von Korff M, Gruman J, Schaefer J, et al. Collaborative
Applied Psychotherapy for the Primary Care Physician. management of chronic illness. Ann Intern Med
New York: Praeger, 1986. 1997;127:1097–1102.
Thom DH and the Stanford Trust Study Physicians. Weinstein MC, Fineberg HU, Elstein AS, et al. Clinical
Physician behaviors that predict patient trust. J Fam Decision Analysis. Philadelphia: WB Saunders, 1980.
Pract 2001;50:323–328. ●
B

C h a p t e r

5 Evidence-Based Medicine

Bernard Ewigman

use the Women’s Health Initiative (WHI) random-

KEY POINTS ized trial of hormone replacement therapy (HRT) to
make the case that using the best evidence can save
1. Evidence-based medicine (EBM) evolved from lives, to provide concrete examples of using EBM in
the population-based, quantitative, and empiri- practice, and to explain some of the methods of EBM
cal roots of epidemiology and biostatistics. (Manson et al., 2003).
2. EBM is a recent approach to clinical decision EBM is relatively new, roughly a decade old,
making and complements rather than supplants according to authors writing in a special issue of the
pathophysiologic reasoning, clinical experience, British Medical Journal (BMJ) published in 2004
and clinical judgment. (Coomarasamy and Khan, 2004; Gabbay and Le
3. The key feature that distinguishes EBM from May, 2004; Guyatt et al., 2004; Lockwood, 2004;
other approaches is the use of explicit and Reilly, 2004; Strauss and Jones, 2004; Tovey and
replicable methods to answer clinical questions. Godlee, 2004). A MEDLINE search I conducted
4. InfoRetriever and DynaMed are electronic using the term “evidence-based medicine” resulted
knowledge resources developed by family physi- in no citations prior to 1992, and only two citations
cians that are based on literature surveillance for that year. When the same search term was used
systems. for the year 2003, 3,011 citations were generated. A
5. The Family Physicians Inquiries Network is a perusal of articles in the 2004 special issue of the
binational academic consortium of family medi- BMJ leaves little doubt that EBM has grown expo-
cine departments, residency programs, librari- nentially in medical education, clinical training, and
ans, and other persons and entities dedicated clinical practice in the United States, Canada, and
to using information technology to translate Great Britain (Coomarasamy and Khan, 2004;
research evidence into practice. Gabbay and Le May, 2004; Guyatt et al., 2004;
Lockwood, 2004; Reilly, 2004; Strauss and Jones,
2004; Tovey and Godlee, 2004).
It remains unclear whether patients have actu-
WHAT IS EVIDENCE-BASED MEDICINE? ally benefited from the lofty goals of the EBM phi-
losophy. The EBM model has not yet penetrated
Evidence-based medicine (EBM) is the integration of the processes of patient care sufficiently to sub-
best research evidence with clinical expertise and stantively affect patient care outcomes in easily
patient values (Reilly, 2004; Sackett et al., 2000). The measurable ways, many challenges remain to
ultimate goal of EBM is to improve patient outcomes achieve this objective, and the complex task of
by considering the most current, valid, clinical proving the effectiveness of EBM will be exception-
research evidence in patient care decisions. An excel- ally difficult (Strauss and Jones, 2004). Nonetheless,
lent example of the application of EBM in practice is EBM has definitely had an impact on the know-
described in Chapter 6 of this book, “Evaluating the ledge, attitudes, and behaviors of practitioners
Medical Literature,” by Susman and colleagues. They (Coomarasamy and Khan, 2004; Tovey and Godlee,

47
 Chapter 5 Evidence-Based Medicine

2004). EBM leaders optimistically predict that the site that estrogen causes strokes and heart attacks
next decade will be as exciting as the last decade, and wanted to know if that was true.
and that the major challenge is to learn how better Dr. E. told her that he would prescribe a low
to use the evidence that is available and how to dose of estrogen for only as long as needed for her
measure the impact on patient care (Guyatt, 1991; hot flushes. He said that her risk of a heart attack
Strauss and Jones, 2004). would not be increased and that if her risk of a stroke
EBM has zealous advocates as well as adamant were increased at all, the risk would be less than one
resistors. Its logical objectivity, rooted in the empiri- in a thousand in the next year. Finally, he told her
cal approach to science, is attractive to physicians as that estrogen would very likely reduce or eliminate
scientists. But it clearly complements rather than the hot flushes altogether.
replaces traditional frameworks for clinical decision After the visit was over, Dr. E. suggested to the
making, including pathophysiologic reasoning, medical student that she answer a clinical question
clinical experience, and clinical judgment. Doing the generated from Mrs. M.’s case as part of fulfilling a
systematic searching and rigorous critical appraisal clerkship requirement to prepare evidenced-based
required for EBM is time-consuming and requires answers to clinical questions about patients seen
specific skills that were not taught in medical school with preceptors. The question he suggested was,
in the past. Even when the evidence is available and What is the risk of stroke and coronary heart disease
has been synthesized into a practice recommenda- in a postmenopausal woman treated with estrogen
tion, there is much more to the practice of medi- only for hot flushes?
cine than scientific evidence. Any physician who
attempted patient care equipped solely with the The Non-EBM Answer
“current best evidence” would be quickly humbled. Our student first looked this up in the most recent
EBM appears to be a major advance in the science edition of a standard textbook on her preceptor’s
of medicine, but it is not a medical panacea for the shelf. The book had been published 3 years earlier.
21st century. She found several statements regarding the benefits
of estrogen therapy in postmenopausal women:
What Are the Distinguishing
Estrogen replacement therapy (ERT) relieves the
Characteristics of EBM?
symptoms of hot flashes. . . . Postmenopausal women
How does EBM differ from more traditional meth- start to experience cardiovascular events at the
ods of clinical decision making? All physicians are same rate as their male counterparts. ERT
expected to be conscientious and judicious, regard- decreases their risk by 50%. . . .
less of their style of practice, so EBM shares those
features with other methods. No well-informed EBM There were no statements about the risk of
adherent would argue with the need to integrate clin- stroke, and no references were given regarding the
ical experience and patient values into patient care decreased risk of cardiovascular events. The student
decisions, nor is that need unique to EBM. The two had learned the basic concepts and methods of
concepts that distinguish EBM as an innovation are clinical epidemiology, biostatistics, and literature
(1) EBM uses systematic methods of identifying and searching in her preclinical years. She recalled the
critiquing research evidence, including prespecified admonition in Evidence-Based Medicine: How to
hierarchical criteria for identifying “current best evi- Practice and Teach EBM (Sackett et al., 2000), which
dence,” and (2) EBM entails explicit descriptions of was, “Burn your (traditional) textbook.” She then
the methods and criteria used, which allows others to proceeded to use her skills in the classic steps of EBM
confirm or refute the findings and recommenda- as shown in Box 5-1, knowing that quoting unrefer-
tions. The teaching case provided here illustrates enced statements from a textbook would earn her a
these concepts and contrasts the findings of an EBM failing grade on the assignment.
approach and a non-EBM approach to answering a
clinical question in a teaching setting. The EBM Answer
The student searched several databases known to
Teaching Case: A third-year medical student on her contain the best evidence, including systematic
first clinical rotation, a family medicine clerkship, reviews and high-quality original research evidence
saw Mrs. M., a 52-year-old menopausal woman who (Cochrane Library, Clinical Evidence, InfoRetriever,
was making a return visit to her family physician. Clinical Inquiries, National Guideline Clearing-
Mrs. M. had seen Dr. E. twice in the past several house, U.S. Preventive Services Task Force,
weeks for bothersome hot flushes that frequently UpToDate, DynaMed), and that are updated with
awakened her at night. Dr. E. had prescribed several current research more or less regularly. In addition,
remedies, but none had helped, and he had suggested she conducted a search of MEDLINE, the compre-
a trial of estrogen. Mrs. M. had read on an Internet hensive research literature database maintained by

48
 Chapter 5 Evidence-Based Medicine

Box 5-1 Classic Steps in Evidence-Based Box 5-2 Methods of Producing Best
Medicine Evidence

1. Formulate a clear, answerable, and specific Clinical Epidemiologic Methods*

patient-related clinical question.
Randomized trials†
2. Conduct a systematic search of the medical
Cohort studies‡
literature to identify the relevant research
Case-control studies
articles.
Case series
3. Select the most valid articles based on a pri-
ori quality criteria and critically appraise the
Integrative Methods
articles for internal and external validity.
4. Integrate the findings into clinical decision Systematic reviews
making about the patient. Meta-analyses
Economic analyses
Decision analyses
the National Library of Medicine, and Current *
For establishing cause-and-effect relationships, RCTs
Contents, a source of more rapidly indexed citations are the strongest design, followed by cohort studies,
that captures just recently published research. case-control studies, and finally case series, the
weakest design for establishing cause and effect.
Although the student’s searches generated a †
Study design of choice for questions about diagnosis
huge number of research articles, reviews, and guide- and prognosis.
lines, using the principles of EBM, she homed in on ‡
Study design of choice for questions about treatment
one recent (published in April 2004) randomized, or preventive interventions.
controlled trial (RCT). This study clearly stood
above numerous older observational studies on type of questions being asked—diagnosis, progno-
estrogen replacement therapy as the strongest study sis, prevention, or treatment (or harm). A complete
design for determining cause-and-effect relation- listing of the criteria for determining the validity of
ships (Table 5-1 and Box 5-2) in studies about ther- a study, which are different for each type of ques-
apy. This trial was also prominently quoted in tion (the RCT is the design of choice only for pre-
UpToDate and DynaMed, and it was the most rele- vention and treatment questions), is provided in
vant title found in InfoRetriever. Using the Critical Appendix 5-1. A full description of these criteria
Appraisal Worksheet for Studies of Therapy (repro- (and much more) is available in Evidence-Based
duced in Appendix 5-1 on the Student Consult), Medicine: How to Practice and Teach EBM (Sackett
adapted from Sackett et al. (2004), she evaluated the et al., 2004), a concise, thorough, and well-written
validity and applicability of the Women’s Health book.
Initiative study of estrogen versus placebo for the pre- Our student’s question was about the harms
vention of osteoporosis to her question and the patient associated with a treatment. The best study design to
case from which the question was generated (Women’s answer this question is an RCT. One of the critical cri-
Health Initiative Steering Committee, 2004). teria for judging validity of an RCT is determining
Table 5-1 lists the study designs of choice and that the random allocation of subjects to treatment
one of the most important primary criteria for and control group was concealed. This helps ensure
determining the validity of a study according to the that the patients in the treatment group are similar to
those in the control group in every way except for the
intervention. This similarity of groups is what makes
Table 5-1 Primary Criteria for Critical RCTs the most powerful design for evaluating treat-
Appraisal of Evidence by Type ment (or harm) and determining cause-and-effect
of Question relationships. Box 5-2 gives the types of study designs
used for generating clinical evidence, and it also gives
Type of Study Design Primary
Question of Choice Criteria
a list of methods of integrating multiple studies.
Integrative methods can be more useful than single
Diagnosis Cohort study Gold studies because they may show consistent findings
standard among studies, or they may have sufficient statistical
Prognosis Cohort study Inception power when data from several studies are pooled
cohort together (meta-analysis).
Prevention RCT Concealed The estrogen-only WHI study was an RCT that
allocation
used concealed allocation. It also addressed unop-
Treatment RCT Concealed
(or harm) allocation
posed estrogen, which is what Dr. E. prescribed for
Mrs. M., since she had undergone a hysterectomy

49
 Chapter 5 Evidence-Based Medicine

and therefore had no need for the addition of prog- 1. Sources that are out of date can be misleading.
estin to the estrogen to prevent endometrial cancer. The reference to a 50% reduction in heart disease
That combination of therapy was evaluated in had likely come from observational case-control
another WHI trial (WHI combined HRT, August 7, studies that, in retrospect, led to erroneous con-
2003). Although this study was an important RCT, it clusions. An accurate critical appraisal of those
did not directly address the question that arose in studies would have led to a far less enthusiastic
Mrs. M.’s case. endorsement than that given by the textbook
The student’s critical appraisal revealed that the author, who did not cite those studies and per-
WHI estrogen-alone study was a double-blind, ran- haps did not even read them.
domized trial with concealed allocation of assign- 2. In addition to assessing the internal validity of a
ment, intention-to-treat analysis, a 98% follow-up of study, it is important to look closely at the actual
study participants, and equal treatment of the two population studied, the intervention studied, and
groups apart from the estrogen therapy in the inter- the duration of treatment, and think about how
vention group. She recognized these factors as the the study findings may or may not apply to an
hallmarks of a well-done RCT. individual patient. The combined estrogen plus
The study showed that there was no increase in progestin WHI trial did show an increase in heart
the rate of coronary heart disease (hazard ratio disease from HRT; however, that trial did not
[HR] = 0.91; 95% confidence interval [CI] = 0.75– apply directly to this particular patient, since she
1.12) (note that the 95% confidence interval was not taking progestins (Manson et al., 2003).
includes 1.0, or no difference) but that there was an On the other hand, since the Salpeter meta-
increase in the incidence of stroke (HR = 1.39; 95% analysis showed decreased mortality in younger
CI = 1.10–1.77) (here the 95% confidence interval patients even though the outcomes in the combi-
does not include 1.0, or the possibility of no differ- nation WHI trial were worse than the outcomes
ence; there is a 95% probability that the true hazard in the estrogen-only WHI trial, she found that
ratio is somewhere between the low of 1.10 or the reassuring. The patient was younger than most
high of 1.77). However, the rate of stroke was quite women in the estrogen-alone WHI study, the dose
low in this population to begin with, so the 39% of estrogen prescribed was half the dose used in
increase (derived from the HR of 1.39) meant that the study, and Mrs. M. was not going to be exposed
the actual increase in the rate of strokes amounted to estrogen for nearly as long. These nuances sig-
to approximately 12 in 10,000 person-years. She also nificantly affected the student’s conclusions and
noted that the mean age of the women in the estro- supported the decision made by her family physi-
gen-alone WHI trial was 63 years. Mrs. M. was only cian preceptor.
52, and Dr. E. had prescribed 0.3 mg of estrogen, 3. Some of the so-called best evidence sources
whereas the estrogen-alone WHI trial used 0.625 mg actually had not yet updated their information
of estrogen in the treatment group. Dr. E. had told to include this RCT by the end of 2004, when the
Mrs. M. that he would prescribe the estrogen only as student conducted her search. Neither the
long as she needed it for relief of her hot flushes, Cochrane Library nor Clinical Evidence, for
which likely would not be nearly as long as the aver- example, had reviews that included the estrogen-
age 6.8 years that women took it in the estrogen- alone WHI trial, even though the student
alone WHI study. Mrs. M.’s younger age, the lower searched these sources 9 months after publica-
dose of estrogen, and the briefer course of therapy tion of the study. These collections of rigorous
all led our student to surmise that Mrs. M.’s risk of a systematic reviews may also be misleading if
stroke was actually less than the 12 in 10,000 person- they are not kept up to date. A quick search
years (or 1.2 in 1,000 person-years) reported in the of certain databases (Current Contents,
study. In addition, she found a meta-analysis of PreMEDLINE) will turn up recently published
26,000 patients in InfoRetriever that showed that studies to supplement rigorous reviews that are
mortality was decreased with hormone therapy becoming outdated.
(combination estrogen and progestin) in women 4. Sources that do not meet strict criteria for being
less than 60 years old (Salpeter et al., 2004). evidence based may nonetheless reflect the best
Although Mrs. M. was taking estrogen only, the stu- evidence. UpToDate (www.uptodate.com), for
dent thought it reasonable to extrapolate these find- example, included this key trial and others and
ings to Mrs. M.’s case. Her basic conclusion was that had incorporated the findings into a clear
Mrs. M. had no increased risk of heart problems and discussion and a set of recommendations.
a maximum increased chance of just over 1 in 1,000 UpToDate continuously scans several hundred
of having a stroke per year while she was being journals and thereby often captures recent evi-
treated, and probably even less. dence. Similarly, DynaMed and InfoRetriever,
The student learned several things through this both of which use the literature surveillance
assignment: method, also had these critical WHI trials in

50
 Chapter 5 Evidence-Based Medicine

their databases. This anecdote suggests that osteoporosis as “Insufficient to Recommend For or
databases employing literature surveillance sys- Against.” The EBM model, which the USPSTF uses,
tems stay abreast of the most important litera- generally requires well-done and consistent RCTs
ture more efficiently than the traditional before it recommends preventive and therapeutic
approach of conducting repeated systematic interventions. Unfortunately, the prevailing non-
searches on specific topics, and a recent RCT EBM approach led hundreds of thousands of women
supports this assertion (Alper et al., 2005). to be exposed to this harmful therapy for years,
perhaps leading to thousands of excess cases of myo-
The findings from the WHI trials drew an enor- cardial infarction, deep vein thrombosis, stroke, or
mous amount of publicity in the media. There was breast cancer.
extensive discussion in the medical literature of the In summary, this example illustrates some of
unexpected findings. Nevertheless, many of the the distinguishing characteristics of EBM listed in
sources searched by the student did not include this Box 5-3.
key evidence. Furthermore, it is uncommon to find a
single study, as happened in this case, that definitely What Are the Non-EBM Approaches
answers a clinical question as clearly as the WHI tri-
to Clinical Decision Making?
als did. Most changes in clinical practice occur slowly
and over time, based on an accumulation of research Our example makes the EBM approach look like the
studies that, when taken together, make the case for only logical choice for physicians, at least compared
a change in practice. Consequently, most EBM with using a standard textbook. One could argue that
searches must seek out multiple studies and stu- traditionalists would have eventually incorporated
diously integrate the findings, none of which indi- the dramatic findings of such well-publicized
vidually draw much attention at the time of their research from the WHI trials. Also, most medical
publication. In other words, practicing EBM using knowledge does not change as abruptly as HRT for
the classic steps is generally more difficult, more osteoporosis prevention did, so most of what is in
time-consuming, and less satisfying than in our recently published reference books, even several years
example. This points to the value of electronic data- after publication, is likely to be still valid. But HRT is
bases with literature surveillance systems (DynaMed, not an isolated example of the potential for harm to
InfoRetriever) and of collections of brief, evidence- patients that is created by adopting or adhering to
based answers to clinical questions (Clinical practices in the absence of rigorous evidence. The
Inquiries).
Another fault line that causes a rift between
what is known in the literature and what is done in Box 5-3 Distinguishing Characteristics
practice is the delay in using evidence that definitely
of EBM
shows a benefit. There is a well-described lag
between the publication of research results in jour-
Explicit methods—Databases searched and
nals and the integration of those results into review
search strategies are described.
articles and books written by experts. In the case of
Systematic searches—The searches are system-
treatments for myocardial infarction, for example,
atic and thorough so that important evi-
many experts were still recommending ineffective or
dence is not missed.
outdated treatments long after definitive evidence
Standardized critical appraisal—Important
showed benefit to new treatments such as throm-
sources of potential systematic and random
bolytic therapy (Antman et al., 1992).
error are assessed in each study.
Non-evidence-based sources may lead clinicians
Hierarchy of study design—More weight is
astray because of the lack of a hierarchical ranking of
given to stronger study designs.
evidence by prespecified criteria, one of the distin-
Designation of levels of evidence—Each study
guishing features of EBM. Prior to the WHI studies,
is designated with respect to the strength of
the existing evidence on estrogen replacement ther-
the study design and the quality of the evi-
apy was not definitive, and the relative benefit versus
dence in that study.
harm was not clear, although an enormous amount
Grading of recommendations—Each recommen-
of research had been published on the topic. A
dation is graded according to the strength of
strictly EBM approach to this problem prior to the
the accumulated evidence from research stud-
WHS trials would not have graded any recommen-
ies that support the recommendation.
dations very highly and therefore would not have
Verifiable findings—The explicitness of the
supported HRT for the prevention of osteoporosis.
methods of searching and critical appraisal
For example, prior to publication of the WHI trials,
allows others to verify (or refute) findings or
the U.S. Preventive Services Task Force (USPSTF)
recommendations.
rated information on HRT for the prevention of

51
 Chapter 5 Evidence-Based Medicine

standard (or non-EBM) practices listed in Table 5-2 Opinion Based on Experience
were adopted with the best of intentions on the basis Experience is a powerful teacher and is essential to the
of one or more traditional models of thinking; defin- development of clinical competence. Incorrect deduc-
itive evidence has now shown each of these examples tions from experience, however, can also mislead the
to be more harmful, or less beneficial, than the prac- physician. Emotional reactions to dramatic experi-
tices based on evidence using an EBM model. ences with a bad outcome or an unhappy patient can
Non-EBM approaches to clinical decision undermine rational thinking. Clinical experience with
making, or learning how to make clinical decisions, single patients or even a large number of patients is
include the apprentice model, deferral to authority, best sifted through the net of science so that the valu-
opinion based on experience, the pathophysiologic able lessons are kept and the rest is discarded.
model, and consensus opinion (Geyman et al., A physician can make the same mistake for 20
2000). Each of these has a place in the practice of years and call it experience.
medicine, despite their deficiencies in comparison
with the EBM model. Pathophysiologic Reasoning
Discoveries about the pathophysiology of disease
Apprentice Mode have revolutionized medical practice over the past
In the apprentice model, an experienced physician 150 years. Basic science and clinical translational
shows or tells a less experienced physician (the research based on an understanding of pathophysiol-
apprentice) how the experienced physician practices, ogy have led to the development of imaging tech-
and the apprentice learns by emulating the teacher. In nology, laboratory methods, laparoscopic surgery,
the apprentice model, knowledge and skills are passed beta-receptor blockers, influenza vaccine, antiretro-
on with no one questioning the veracity of the knowl- virals, and many other powerful diagnostic and ther-
edge or the usefulness of the skills in improving apeutic tools. In addition, understanding the basic
patient well-being. Both harmful and beneficial prac- pathways and mechanisms of disease is essential for
tices are passed on to each subsequent generation; competent management of individual patients, who
evidence from carefully designed studies can help dis- often have more comorbid conditions than patients
tinguish which are harmful and which are beneficial. enrolled in RCTs, whose disease severity may not fit
the spectrum of disease in cohort studies with
Deferral to Authority respect to diagnostic test characteristics, and whose
Most physicians appropriately seek out an expert biology may not fit with the biology of the popula-
specialist for consultation when necessary and defer tion study; most commonly, there simply is no high-
to that specialist’s opinion. Yet the advice of medical quality evidence to guide the clinician. Nevertheless,
experts has been shown in some cases to be the logic of pathophysiologic thinking can lead to
(unknowingly) harmful to patients, as was the case harmful, even fatal conclusions.
with HRT and the other examples in Table 5-2. The We did the logical thing, but we killed the patient.
ideal expert specialist not only has extensive training
and clinical experience but also incorporates a thor- Consensus
ough understanding of the evidence available to Interacting with peers is a powerful and important
guide his or her recommendations. means of establishing standards and making deci-
The definition of an authority is the person who sions about how to diagnose and treat patients. This
speaks with the greatest confidence. may be the primary way that physicians develop local

Table 5-2 Instances in Which Evidence Has Shown That Standard Practices Have Harmed
Patients or Resulted in Withholding Effective Therapies
Standard Practice Evidence-Based Practice
Routine episiotomy performed to prevent Episiotomy avoided to prevent complications of vaginal
complications of vaginal delivery delivery
Corneal patching to improve healing of corneal Corneal patching shown to delay healing of corneal
abrasion abrasion
β-blockers contraindicated in: β-blockers may be used in: Diabetics
Diabetics Depression Depression
Congestive heart failure Congestive heart failure
HRT used to benefit: Harms of HRT overweigh benefit for:
Osteoporosis prevention Osteoporosis prevention
Prevention of heart disease Actually increases rates of heart disease
Narcotics not used in cases of acute abdominal Narcotics used to relieve acute acute abdominal pain;
pain for fear of masking diagnoses do not mask diagnoses

52
 Chapter 5 Evidence-Based Medicine

community standards that reflect the conventional Although it was several hundred years before the
wisdom in “communities of practice” (Gabbay and RCT became the standard by which preventive and
Le May, 2004). The real-world effectiveness of the therapeutic interventions were evaluated, the seeds
recommendations made by consensus of a group of of empirical science gradually grew, reproduced, and
physicians is likely to be no greater than that of the spread to give life to the tremendous advances of
authoritative, apprentice, or pathophysiologic 21st-century scientific medicine. These advances
approach in the absence of current best evidence. include an emphasis on basic science as the founda-
Large groups of intelligent and well-meaning physi- tion of medicine, as well as an emphasis on epidemi-
cians can be wrong and have been wrong on many ology and biostatistics, the foundational sciences of
occasions. Introducing evidence into such commu- EBM. By the mid-20th century the dominant mode
nities of practice is a necessary ingredient for success. of medical teaching and research, historically based
There is more convention in the conventional on theory and experience only, had shifted to empiri-
wisdom than there is wisdom. cism, including direct observation, study of actual
Each of these non-EBM approaches, and others, human functions, and human experimentation.
have merit and cannot be replaced by a strictly EBM EBM is one of many expressions of empiricism in
approach. They also have disadvantages, and the medicine in that it uses actual observations in real
EBM model can help rectify those shortcomings patient populations using careful and replicable
when used as one of several ways of problem solving. methods. Just as Vesalius rebuffed Galen through
The rest of this chapter traces the origins of direct observation, EBM holds that solid empirical
EBM, describes additional instances in which an evidence trumps all else, even when the findings are
EBM approach was clearly superior to a traditional in conflict with prevailing pathophysiologic theory,
approach, identifies how family medicine has conventional wisdom, or clinical experience.
adopted and is shaping EBM, and considers the lim-
itations of EBM.
Epidemiology: Studying Populations to
Care for Individual Patients
THE ORIGINS AND EVOLUTION The value of studying groups of people or popula-
OF EBM tions to understand human disease was first illus-
trated when a British general practitioner, John
Empiricism: Observation over Theory Snow, removed the handle of the pump at the Broad
Street well and interrupted the 1854 cholera epi-
The roots of EBM lie deep in medical history, and demic in London (Snow, 1936). Based on careful
EBM itself has grown into a distinct species of observation of which of his patients did or did not
medical practice style (Feinstein, 1985; Guyatt, 1991; have cholera, he mapped the location of their
Guyatt and Rennie, 1993; Users’ Guides, 2002). As residences and the well from which they drew their
the word evidence suggests, EBM is philosophically drinking water. He showed that those with cholera
an empirical approach to clinical decision making. were far more likely to use the Broad Street well. This
Empiricism in medicine has its roots in the simple intervention, linked to an elegant set of obser-
Renaissance. Vesalius made direct and accurate vations, was seminal in the birth of epidemiology,
observations of human anatomy and functioning the study of diseases in populations and the evalu-
that showed the ignorance of Galen and his anatom- ation of interventions at a population level as a
ical theories. Harvey accurately described the circu- method of solving the problems of diseases in indi-
lation of blood in the 17th century. In the 19th viduals. John Snow’s study was one of many epi-
century Jenner developed an inoculation that gave demiologic studies that have led to basic science and
protection against smallpox (in part by inoculating clinical discoveries, including the discovery of the
himself!). Jenner’s discovery was the first step organism that causes cholera, the human immuno-
toward the development of the vaccines now avail- deficiency virus, and the risk factors for coronary
able for protection against many infectious diseases. artery disease, to name a few of the thousands of
In 1747 a most interesting clinical trial that included examples in which epidemiology has led to major
only ten subjects and led to the eventual discovery of advances in modern medical science.
vitamin C was undertaken. In this 18th-century
experiment, Lind showed that the two British sailors
who were given limes to eat while at sea did not Biostatistics: Measuring Uncertainty
develop scurvy, whereas the other eight sailors did. James Lind had the good fortune of conducting his
He postulated the existence of an antiscorbutic fac- landmark trial of scurvy prevention in British sailors
tor that was later identified as vitamin C. before statistics was invented, or at least well known,
Parenthetically, Lind’s work is the origin of limey, sparing him the embarrassment of having to report that
the sobriquet for British sailors. his findings did not achieve statistical significance

53
 Chapter 5 Evidence-Based Medicine

because of his small sample size and the further 1920s. Austin Bradford Hill, another statistician, rec-
embarrassment of seeing his study shunned as a ognized a similar usefulness of statistics for medicine
POEM (patient-oriented e vidence that matters). We and called for the formal introduction of statistics
now know that all people who lack vitamin C in their into modern medicine in 1937. Ten years later he
diet develop scurvy, and no otherwise healthy person participated in one of the first true RCTs in medi-
with an adequate intake of vitamin C develops scurvy. cine, showing that streptomycin was superior to
Other conditions have a similar all-or-none standard therapy for the treatment of pulmonary
cause-and-effect relationship, such as other vitamin tuberculosis. The RCT is now the gold standard for
deficiencies, antibiotics for bacterial meningitis, and the evaluation of preventive and treatment interven-
appendectomy for acute appendicitis. Most EBM tions, and thousands of RCTs are completed and
advocates will concede that the absence of RCTs eval- published annually (Feinstein, 1985).
uating all-or-none therapies is not a problem. Those
who insist on RCTs for all-or-none therapies can be Systematic Reviews, Clinical Epidemiology,
referred for enrollment in a clinical trial in which
and EBM
EBM zealots who lack clinical judgment are ran-
domly assigned to jump out of an airplane at 5,000 Another general practitioner, Archie Cochrane,
feet with a parachute (intervention group) or with- from Scotland, in 1972 published a book titled
out a parachute (control group) (Smith and Pell, Effectiveness and Efficiency: Random Reflections on
2003). This study, renamed the DUPED study (Does Health Services, which called attention to the impor-
Using Parachutes Eliminate Death) for the purposes tance of systematic reviews, the importance of high-
of this book, has had severe problems enrolling sub- quality evidence, and the fact that many, if not most,
jects. According to rumors (admittedly a non-EBM practices lacked solid evidence demonstrating their
method), the number of hard-headed EBM zealots is efficacy or effectiveness (Cochrane, 1999). He made
steadily decreasing, as they have acknowledged the the argument for the routine application of EBM to
obvious fact that parachutes do prevent death from clinical patient care, emphasizing the need to per-
jumping out of airplanes, despite the absence of form, analyze, and synthesize the findings from RCTs
RCTs or POEMs proving this to be the case. as systematic reviews. The Cochrane Collaboration,
If James Lind were a clinical researcher in the named after him, is an international collaborative of
21st century, he would accept it as axiomatic that the physicians and methodologists who perform system-
all-or-none therapies are unusual and that most med- atic reviews and meta-analyses of RCTs evaluating
ical interventions are effective in some but not all medical interventions. The Cochrane Collaboration
patients. In other words, there is a theoretical proba- maintains an electronic library that contains more
bility that a treatment will be effective in any given than 2,000 Cochrane Reviews, a database of abstracts
patient. He would also know that most diagnostic test of other systematic reviews, and a worldwide registry
results may or may not mean that the patient does or of clinical trials. This collaboration set the standard
does not have the disease of interest; they only for EBM and remains the single most rigorously
increase or decrease the probability. In the early 1920s evaluated collection of evidence on treatment effec-
Sir Ronald Fisher “fathered” statistical theory and tiveness in the world.
testing as a mathematical method for dealing with Alvin Feinstein, an internist at Yale University, is
such probabilities, although statistics as a word dates widely considered the founder of clinical epidemiol-
back several centuries, according to Feinstein, when ogy, or the epidemiology of medical care. Building
rulers began collecting information about their sub- on the work of Feinstein and Cochrane, David
jects (Feinstein, 1985). The people collecting this Sackett, also an internist, and his colleagues at
information were called statists. Those who claim McMaster University in Canada articulated the con-
Fisher as the father of statistics therefore could have a cept of critical appraisal in the 1970s and began the
case of mistaken paternity status. Whoever the father series of 25 Users’ Guides to the Medical Literature,
is, all types of analytic clinical research studies now published in Journal of the American Medical
rely heavily on statistical concepts for their design, Association, thereby organizing and articulating the
analysis, and interpretation: case-control studies, methods that were to form the basis of EBM. Gordon
cohort studies, and RCTs. Guyatt coined the term evidence-based medicine in
1990 after another term, scientific medicine, was
Randomized Controlled Trials roundly rejected by his colleagues, who resisted the
new paradigm for teaching residents at McMaster.
With observers’ recognition that agricultural innova- These individuals and their colleagues in the
tions competed with multiple other uncontrollable Evidence-Based Medicine Working Group (from
variables (such as the weather), producing outcomes multiple specialties, including family medicine) have
more or less likely (again, probabilistic), the first been largely responsible for the dissemination of
modern RCTs were conducted in grain fields in the EBM that has occurred in the past 10 years and

54
 Chapter 5 Evidence-Based Medicine

dotal. Anecdotes are anathema to EBM. By current best

Box 5-4 The Many Descendants of evidence in the EBM usage, we refer primarily to orig-
Evidence-Based Medicine inal research using the methods of clinical epidemiol-
ogy (clinical trials, cohort studies, case-control studies,
Evidence-based practice or case series) or systematic syntheses of such research
Evidence-based clinical practice (systematic reviews, meta-analyses, and evidence-
Evidence-based health care based guidelines) as listed in Box 5-2. Yet I am not
Evidence-based nursing aware of any such evidence that EBM does what it pur-
Evidence-based dermatology ports to do, which is good reason for humbleness and
Evidence-based search engines for maintaining an open mind about the multiple ways
Evidence-based otitis media of thinking about best care for patients.
Evidence-based diabetes The following anecdotes are examples of situa-
Evidence-based obstetrics tions in which the EBM approach was clearly the
Evidence-based pediatrics winner. In each instance, adherence to a traditional
Evidence-based family medicine model of thinking or a particular type of method-
ological error led to incorrect conclusions and, in
two of the examples, unfortunate outcomes for
deserve the lion’s share of credit for laying the foun-
patients. No doubt pathologists could give many
dations and building the primary structures of EBM.
examples of anecdotes in which pathophysiologic
thinking was the clear winner. However, pathology is
Derivations and Mutations of EBM so well accepted in modern medicine that its value is
assumed, and it needs no special chapter to explain
If imitation is the most flattering compliment, then
or justify its place in medicine.
EBM has been flattered extensively. Quite a number
of variations on the EBM style have developed. A list
of examples, not intended to be comprehensive, Patient-Oriented versus Disease-Oriented
is shown in Box 5-4. Most of these simply apply Evidence
traditional EBM or a variation of it to particular
Slawson and Shaughnessy have emphasized the
disciplines or specialties (nursing, dermatology,
importance of paying particular attention to patient-
obstetrics, pediatrics, family medicine) or to diseases
oriented outcomes (e.g., mortality, morbidity, pain,
(otitis media, diabetes) or physical diagnosis.
functional status, quality of life) and of being
Evidence-based literature surveillance employs some
cautious about research evidence that measures
of the principles of EBM to systematically select new
only physiologic or disease-oriented outcomes (e.g.,
research, systematic reviews, and guidelines and
physiologic measures, markers of disease, disease
organize them into electronic databases for easy
states) (Slawson and Shaughnessy, 2000).
retrieval as a way to assist physicians with keeping up
A classic example of the difference between an
with new and important research and reviews.
outcome that matters to patients (a POEM) versus a
DynaMed and InfoRetriever are electronic databases
physiologic outcome is provided by a randomized
built through evidence-based surveillance systems
clinical trial, the CAST study (“Preliminary report,”
and are described later in this chapter.
1989). Published in 1989, the CAST study was
Evidence-based practice, evidence-based clinical
designed to determine if a class of anti-arrhythmic
practice, and evidence-based health care are terms used
drugs that suppressed premature ventricular beats
by authors who want to emphasize the use of EBM in
(a physiologic outcome) prevented sudden death
practice, stress the importance of understanding
(a patient-oriented outcome) as expected. Unfor-
patients’, families’, and practitioners’ beliefs, values, and
tunately, the trial showed that two of these drugs
attitudes as applied to EBM, or more explicitly take evi-
caused an increase in sudden death among asympto-
dence into account when considering public health
matic or mildly symptomatic patients. Prior to the
priority setting, resource utilization, and the organiza-
findings of the CAST study physicians had prescribed
tion and delivery of health care by doctors and other
these drugs for thousands of patients based on the
health care providers. These terms all reflect efforts to
findings of improved physiologic outcomes, which
apply EBM principles in settings other than those in
likely caused many premature deaths. This is not only
which individual physicians provide care for individual
an example of disease-oriented evidence, it is also an
patients, or developing guidelines for doing so.
example of the risks of pathophysiologic thinking
and dependence on expert opinion. It certainly is log-
MORE ANECDOTES FOR EBM ical that the suppression of premature ventricular
beats should reduce sustained ventricular fibrillation
It is interesting, and not without irony, that the current or ventricular tachycardia leading to sudden death.
best evidence supporting the value of EBM is anec- Despite the logic, these drugs had pro-arrhythmic

55
 Chapter 5 Evidence-Based Medicine

effects on the myocardial conduction system that The lymphadenopathy story is not an isolated
were unrecognized, and patients died as a result. example of this impact of selection bias. Prior and sub-
sequent research by primary care physicians has docu-
Selection Bias mented the pervasive distortion that occurs when
clinical experience and research are based on highly
Harrison’s Principles of Internal Medicine was the text- selected populations cared for by specialized physicians
book used when I was a medical student. Harrison’s who limit their practices. Selection bias works in the
was and remains to this day one of most respected opposite direction as well. The clinical experience and
textbooks in internal medicine. But the edition I used clinical research conducted by family physicians may be
in the late 1970s stated that 50% of patients with lym- equally irrelevant to other specialists and subspecialists.
phadenopathy have it because they have cancer. This Williamson’s study showing that lymphadenopathy in a
high risk of such a serious disease should be cause for patient without suspicious signs and symptoms is rarely
great concern and would justify an aggressive diag- due to a serious cause would be equally irrelevant for an
nostic approach, including biopsy. This fact was not oncology practice. Bias in research is not the exclusive
well received by my family medicine preceptors in domain of any particular specialty.
medical school, despite the authoritative stature of
the oncologist who wrote it in Harrison’s. Pathophysiologic Reasoning and
After its inception as the 19th specialty in 1969,
Bad Outcomes
family medicine began to develop its research base,
and the evidence from family medicine showed quite This example illustrates again the hazards of patho-
a different picture from the one painted by the oncol- physiologic reasoning put into practice untested in the
ogist in Harrison’s textbook. Harold Williamson, an real-world laboratory of clinical research. It also illus-
academic family physician in the newly minted spe- trates the fact that large numbers of expert physicians,
cialty, conducted a prospective study to determine the and consensus within communities of physicians, can
percentage of patients presenting to family physicians be dead wrong. Again, the book I studied in medical
with lymphadenopathy who had cancer (or other school, William’s Obstetrics, which was used by every
serious diseases). He identified 249 patients with nearly every obstetrician and family physician attend-
enlarged lymph nodes. Serious or treatable causes of ing births in the 1970s, recommended that an epi-
lymphadenopathy were rare and were always accom- siotomy, a surgical cut of the perineum, be performed
panied by clinical conditions that suggested further prior to delivery of the fetal head in every vaginal birth
evaluation. Lymph nodes were biopsied in only 3% of to prevent urinary and fecal incontinence (routine epi-
patients. No patient was found to have a prolonged, siotomy). The reasoning was that this cut would pro-
disabling illness without a prompt diagnosis. He vide more space for the fetal head to pass through the
concluded that, in patients without associated signs vaginal opening and thereby reduce the excess stretch-
or symptoms, a period of observation is safe and ing of the tissues presumed responsible for maintain-
likely to save unnecessary expense and biopsy. ing urinary retention. It was also believed that the risk
Why the discrepancy of 50% having cancer ver- of extension of a tear into the rectum would be
sus “rare”? Oncologists see a different population of reduced by an episiotomy, and that this in turn would
patients than family physicians do. The patients seen reduce the risk of permanent damage to the anal
by oncologists (and other specialists and subspecial- sphincter and prevent fecal incontinence. Finally, a sur-
ists whose practice is limited to particular diseases, gical cut would result in a much better repair than a
organs, or procedures) are highly selected, whereas jagged tear, or so it was reasoned. Although this prac-
primary care patients are more representative of the tice held sway for many decades, there was no empiri-
general population of patients seeking medical care. cal evidence demonstrating that routine episiotomy
Therefore it should come as no surprise that oncolo- did in fact prevent these complications.
gists would come to believe that half of their patients In the 1990s, another academic family physician
with lymphadenopathy have cancer, an impression and his colleagues published a series of RCTs (Klein
borne out by the study quoted in Harrison’s, which et al., 1994) showing that routine episiotomy in fact
was performed in an oncology clinic. In this case the increased the risks for urinary incontinence,
evidence was valid, but relevant only to patients increased tears through the rectal sphincter, and
referred to oncologists and, because of selection bias, interfered with sexual satisfaction. This and other
was not relevant for primary care. This example also evidence gradually led to a reduction in the routine
illustrates the point that listing references does not use of episiotomies, although there are still some
make a statement evidence based, or even necessarily who ignore (or are ignorant of) the evidence and
accurate. One must also have discovered all of the adhere faithfully to the dusty pronouncements of
studies, critically appraised them for problems such their medical school textbooks and medical school
as selection bias, and based conclusions only on the professors. Some day the pronouncements of this
most valid and relevant evidence. book and this author will be dusty, and hopefully you

56
 Chapter 5 Evidence-Based Medicine

will be more insistent on evidence before acting Having easy access to current best evidence for
(unless it is an all-or-none phenomenon, like limes solving patient problems and answering clinical ques-
for scurvy or parachutes for preventing death from tions during patient care is another unmet informa-
jumping out of airplanes) than your predecessors. tion need. In this case, because the physician has a
patient problem to solve and needs information to do
so, he or she can be said to have a “recognized” infor-
THE FAMILY MEDICINE APPROACH mation need. Research shows that family physicians
TO EBM have an average of about three questions for every five
patients seen, they spend an average of 2 minutes
Family medicine has adopted the EBM model in a seeking answers to these questions, and the majority
variety of ways, as much as or perhaps even more so (about 71%) of their questions never get answered,
than other specialties. EBM is one of several useful much less answered by an EBM process that ensures
ways to manage the volume of knowledge required for current best evidence will be used, mainly because
the broad domain of family medicine. All of the major answers were never pursued (Ely et al., 1999).
clinical journals in family medicine regularly publish Another study showed that physicians do not pursue
evidence-based systematic review articles. Family answers to so many of their questions because of the
physicians routinely participate in national, regional, time required and the difficulty of the steps involved
and local development of evidence-based guidelines. in formulating an adequate answer (Ely et al., 2002).
They may represent the American Academy of Family These observations have led to creative strategies
Physicians or other organizations, or they may serve as for making best evidence easily integrated into the prac-
consultants. All of these activities involve the four tice of family medicine by reducing the time required to
steps of EBM and the distinguishing characteristics find answers and doing much of the work for the clini-
listed in Box 5-3. Many academic family physicians are cian. These strategies include the development of sec-
engaged in teaching clinical epidemiology or EBM at ondary sources, evidence-based surveillance systems,
the medical school, residency, and fellowship levels. and evidence-based answers to clinical questions at the
There are also several initiatives by family physi- point of patient care. All these strategies combine EBM
cians that are designed with the same goals as EBM in methods with the use of electronic knowledge
mind but employ more practical strategies in order to resources such as Web sites, desktop computers, or
make the best available evidence easily accessible to the portable computers for efficient storage and retrieval
practicing physician. Three of these initiatives— of information and the capacity to update frequently.
DynaMed, the Family Physicians’ Inquiries Network, Literature surveillance systems are designed to
and InfoRetriever—are described later in the chapter. assist physicians with meeting unrecognized infor-
The resources developed by these groups do not neces- mation needs and to provide easy retrieval of new
sarily adhere strictly to all the criteria listed in Box 5-1 research to ensure that electronic knowledge
that distinguish EBM in its original formulation, but resources include current best evidence. Two such
each of them has advantages that make them useful. systems, InfoRetriever and DynaMed, have been
These resources share the goal of helping family developed by family physicians and are currently
physicians meet both recognized and unrecognized available by subscription (www.infopoems.com,
information needs. In the next section, the challenge of www.dynamicmedical.com).
meeting these two types of information needs is
addressed, followed by a description of these resources. InfoRetriever
Three family physicians—David Slawson, Mark Ebell,
Recognized and Unrecognized and Henry Berry—and a pharmacologist, Allen
Information Needs Shaughnessy, have performed evidence-based litera-
ture surveillance for InfoRetriever since 1996. They
The EBM mandate to include current best evidence systematically review more than 1,200 studies from
in decision making generates tremendous informa- more than 100 journals monthly to identify an aver-
tion needs for physicians that did not exist 60 years age of 30 POEMs each month (Ebell et al., 1999).
ago. It is estimated that more than 10,000 new POEMs stands for patient-oriented evidence that
research studies per year are published that may matters and is the term used to designate the best
reflect current best evidence relevant to the practice evidence identified by the reviewers. A brief struc-
of family medicine (Ebell et al., 1999). Obviously, no tured summary and critique are written and the cita-
one practicing physician could possibly stay abreast tion of the study is listed. These reviews are then
of all of the relevant original research using the clas- disseminated on a daily and monthly basis (the
sic EBM approach, and generally speaking, the need entire month of POEMs) by e-mail.
to do so is unrecognized in the sense that if a physi- Many family physicians use this system as their
cian does not know about the information, he or she primary strategy for keeping up to date with current
would not recognize the need to access it. best evidence (meeting unrecognized information

57
 Chapter 5 Evidence-Based Medicine

needs). Instead of attempting the impossible, family cian searchers were able to find adequate answers in
physicians can read the Daily POEM in just a few min- DynaMed in just over 2 minutes (Alper et al., 2001).
utes with confidence that they are getting the cream of Young, skilled physicians found their answers in 5
the evidence that has been recently published. minutes. The quality of the answers was equivalent
InfoRetriever is the software program used to to other sources (Alper et al., 2005).
store and retrieve POEMs on a handheld computer
or on the Web. In addition to POEMs, InfoRetriever Family Physicians Inquiries Network
has Cochrane Systematic Review abstracts, 2,200 Members of the Family Physicians Inquiries Network
diagnostic calculators, more than 200 decision sup- (FPIN) are dedicated to producing concise recom-
port tools, and more than 700 summaries of evi- mendations based on multiple sources that integrate
dence-based guidelines. It is updated quarterly and, the best evidence to answer specific clinical questions,
since the available high-quality evidence that popu- provide a pithy summary of the key evidence, and list
lates InfoRetriever answers only a portion of family authoritative recommendations. FPIN is a not-for-
physicians’ questions, it comes bundled with profit international academic consortium of 22 family
5 Minute Medical Consult (5MMC). Although medicine departments, 78 residency programs, 75
5MMC is not an evidence-based resource, it does academic health sciences librarians, and a network of
answer most questions (using expert opinion, con- practice-based research networks (see www.fpin.org).
sensus, and so on). InfoRetriever is therefore useful The FPIN vision is to answer 80% of the practicing
primarily for recognized information needs, and the family physician’s questions at the point of patient
Daily POEMs by e-mail are useful mainly for unrec- care within 60 seconds of their time with the best
ognized information needs (www.infopoems.com). available evidence. The FPIN mission is to translate
research into practice at the point of patient care, to
DynaMed teach the clinical scholarship of research translation,
Brian Alper, a family physician, developed DynaMed and to facilitate the generation of new research from
in 1993 as a medical student and maintains it based practice. FPIN has two electronic publishing initia-
on his surveillance of original research reports, jour- tives, Clinical Inquiries and PEPID PCP.
nal review services, systematic review sources (such
as Cochrane Reviews and Clinical Evidence), drug Clinical Inquiries Clinical Inquiries are evidence-
information sources, and guidelines. DynaMed has based answers to clinical questions developed by
more than 1,800 disease topics, and each disease FPIN members. Questions are generated from actual
is organized using a consistent format. DynaMed patient care problems and selected by Web-based
contains an enormous amount of information, and voting by groups of practicing family physicians. A
much of the best evidence is quoted and briefly sum- thorough and structured search of the world litera-
marized. However, the evidence is not rated, the ture is conducted by one of the trained FPIN librari-
methods are not explicit, and it is not peer reviewed. ans. The clinician author or authors who have
Efforts are under way to peer review the content, and volunteered to prepare the answer then select and
contributors to the database receive a free subscrip- critically appraise the evidence and write the answer
tion. Although DynaMed uses a literature surveil- in a brief structured format designed for use at the
lance system, it is not useful for unrecognized point of care. Each Clinical Inquiry is reviewed by a
information needs because users are not alerted to minimum of four peer reviewers or editors prior to
new evidence. However, it is useful for recognized publication in the Journal of Family Practice or
information needs and is the only electronic data- American Family Physician. FPIN makes all Clinical
base besides electronic collections of textbooks that Inquiries available to contributors without charge in
has been shown through research to answer a major- the FPIN Electronic Library, a Web-based database
ity of family physicians’ questions (www.dynamic- maintained by the FPIN consortium. In addition,
medical.com) (Alper et al., 2001, 2005). Clinical Inquiries are included in the Portable
InfoRetriever and DynaMed both require sort- Electronic Physicians Information Database
ing through a significant volume of material since (PEPID), Primary Care Plus (PCP), that FPIN mem-
they are not designed to directly answer specific bers edit, peer review, provide content for, and
questions with all of the relevant evidence summa- update regularly. The primary limitation of the
rized. InfoRetriever provides a nicely organized list Clinical Inquiries database is that the volume of
of hits, but knowing which source or combination of questions and answers is not yet large enough to
sources provides the answer to the clinical question answer many questions (ca. 300 at the time of this
at hand usually requires looking at multiple hits. writing), although FPIN is completing 15 to 20 new
DynaMed provides an enormous amount of infor- structured reviews (Clinical Inquiries) per month.
mation organized by topic and subtopic, but a fair
amount of reading and comparing may be required PEPID PCP PEPID PCP is a comprehensive elec-
to find an answer. Nonetheless, expert family physi- tronic handheld and Web-based resource with

58
 Chapter 5 Evidence-Based Medicine

2,100+ disease topics, 5,000+ drugs, a dynamic drug icine publications (Ebell et al., 2004). The Strength of
interactions generator, an electronic prescription Recommendation Taxonomy (SORT) is a patient
writing tool, and more than 300 calculators and deci- outcomes-oriented system for classifying the validity
sion aids. PEPID PCP is available by subscription of clinical recommendations based on structured
from the owner, PEPID, Inc. (www.pepid.com), and reviews of the literature. Other taxonomies can be
is free to FPIN contributors. The combination of converted to SORT to provide a standardized and
PEPID PCP content and Clinical Inquiries should user-friendly evidence grading system when drawing
answer most questions, and it has the added advan- on numerous other EBM resources.
tage of a fully integrated drug database. This feature The types of evidence prized in EBM (clinical
is particularly useful because questions about drug trials, prospective cohort studies, systematic reviews,
dosages, side effects, indications, and interactions meta-analyses) are all based on population-level
are among the most common questions the family data. Yet there is almost always both biological and
physicians have at the point of care. statistical variation among individuals in clinical
populations. In clinical practice, the findings are
Other Useful EBM Resources on the Web used for the care of individual patients, not popula-
tions. Any particular patient may respond similarly
There are many other useful sources for finding cur- to most patients in a treatment group or may more
rent best evidence and for learning more about EBM, be like those at the tail end of the distributions and
and new resources are added frequently. Additional not respond at all, or may respond more dramatically
EBM sources are listed in Appendix 5-2 on the Student than the patients in the studies. Individual genetic
Consult. These sources include primary sources for variation between patients or variations in comorbid
searching, search engines designed to prioritize best conditions may result in higher risk, a more aggres-
evidence, secondary sources in which the evidence has sive disease, or a different response to therapy. There
already been synthesized and rated, and sites that pro- are also many social, cultural, and economic factors
vide general information about EBM and specific tools that must be considered, in addition to population-
for EBM. Appendix 5-1 provides Critical Appraisal level evidence. EBM proponents recognize the need
Worksheets for each of the four most common ques- to consider all of these factors in the care of individ-
tion types-diagnosis, prognosis, prevention, and treat- ual patients, but the primary achievement to date in
ment (or harm). It should also be noted that a the EBM movement has been to develop the meth-
systematic review addressing a treatment question is ods and accumulate valid evidence. Less has been
evaluated using a different set of questions. In addition, accomplished in the science of how to apply this evi-
there are also critical appraisal worksheets for dence to individual patient care.
economic analysis, studies of differential diagnosis, As noted earlier, some publications refer to
and many others. Appendix 5-2 lists EBM resources, themselves as evidence based when in fact they are
including general EBM Web sites that provide not only not. Listing references is a time-honored and valu-
worksheets for critical appraisal but also detailed infor- able practice in both journal articles and textbooks,
mation about using the worksheets and a lot of other but it does not make an article or a book chapter
detailed information. A glossary of EBM terms is given evidence based. For example, many of the claims in
in Appendix 5-3 on the Student Consult. this chapter on EBM do not meet the evidentiary
standards of the EBM model, despite the references!
Many publications and electronic databases abuse
LIMITATIONS OF EBM the term evidence based as a marketing tool. Most of
these products have excellent qualities and usually
EBM has limitations, some of which are inherent emphasize original evidence by extensive referenc-
to the model and others of which are due to its ing, but they do not use the explicit, systematic EBM
early stage of development. In addition, EBM has model. How much this matters is debatable. In my
developed a reputation as being synonymous with experience the answers and recommendations in
excellence in medical care. Consequently, in our com- well-referenced and reputable sources (such as
mercially oriented society, the label is often applied UpToDate) are often but not always consistent with
when it is not appropriate, so buyer beware. A simple more explicitly evidence-based sources (and EBM
though not foolproof clue that a resource is evidence sources are extensively quoted or included fre-
based is to look for a grade or strength of recommen- quently in databases such as UpToDate). UpToDate
dation and levels of evidence designations. As of early is particularly useful for reviews, and its authors are
2004, there were 40 such systems in use for articles often leading experts. However, further research is
summarizing two or more studies, creating consider- needed to quantify the relative strengths and weak-
able confusion about how to interpret them. The edi- nesses of strictly EBM sources, those that purport to
tors of FPIN and the major family medicine journals be evidence based or to use variations or shortcuts of
developed a single system for use in most family med- the EBM model, and the clearly non-EBM sources.

59
 Chapter 5 Evidence-Based Medicine

Also, more creative approaches are needed to fully physician in the 21st century, as will be learning when
exploit the combination of EBM principles and elec- evidence is and is not useful in caring for individual
tronic technology to close the gap between what we patients. Finally, in the spirit of the information mastery
know about best care for patients and getting that care model (Slawson et al., 2000), taking advantage of the
to patients so that they benefit from that knowledge. hard work of others makes practicing medicine with
cognizance of the best evidence realistic for all family
physicians, as well as for physicians in other specialties.
CONCLUSION
EBM is a relatively new model for clinical decision mak- Material Available on Student Consult
ing that complements rather than substitutes for tradi-
tional models. It is simply another tool to use as Review Questions and Answers about Evidence-
appropriate for “doing our best” for patients. EBM has Based Medicine
grown enormously in influence in the 10 years since its Appendix 5-1 Critical Appraisal Worksheets
inception and is likely to continue to develop in impor- Appendix 5-2 Glossary of EBM Terms
tance and usefulness. Mastering the basic concepts and Appendix 5-3 EMB Electronic Resources
methods of EBM will be necessary to be a competent

REFERENCES
Alper BS, Stevermer JJ, White DS, Ewigman BG. Answering Guyatt G, Cook D, Haynes B. Evidence-based medicine has
family physicians’ clinical questions using electronic come a long way. BMJ 2004; 329:990–991.
medical databases. J Fam Pract 2001;50:960–965. Klein MC, et al. Relationship of episiotomy to perineal
Alper BS, White DW, Bin G. Physicians answer more clini- trauma and morbidity, sexual dysfunction, and pelvic
cal questions and change clinical decisions more often floor relaxation. Am J Obstet Gynecol 1994;171:591–598.
with synthesized evidence: A randomized trial in pri- Lockwood S. “Evidence of me” in evidence-based medi-
mary care. Ann Fam Med 2005;3:507–513. cine. BMJ 2004;329:1033–1035.
Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC. Manson JE, et al. Estrogen plus progestin and the risk of
A comparison of results of meta-analyses of randomized coronary heart disease. N Engl J Med 2003;349:523–534.
control trials and recommendations of clinical experts: Preliminary report: Effect of encainide and flecainide on
Treatments for myocardial infarction. JAMA 1992;268: mortality in a randomized trial of arrhythmia suppres-
240–248. sion after myocardial infarction: The Cardiac Arrhyth-
Cochrane AL. Effectiveness and Efficiency: Random mia Suppression Trial (CAST) Investigators. N Engl J
Reflections on Health Services (reprint). London, Royal Med 1989;321:406–412.
Society of Medicine, 1999 (London, Nuffield Provincial Reilly BM. The essence of EBM. BMJ 2004;329:991–992.
Hospitals Trust, 1972). Sackett DL, Rosenberg WM, Gray JA, et al. Evidence-based
Coomarasamy A, Khan KS. What is the evidence that post- medicine: What it is and what it isn’t. BMJ 1996;312: 71–72.
graduate teaching of evidence-based medicine changes Sackett DL, Strauss SE, Richardson WS, Rosenberg W, Haynes
anything? A systematic review. BMJ 2004;329: 1017–1019 RB. Evidence-Based Medicine: How to Practice and Teach
Ebell MH, Barry HC, Slawson DC, Shaughnessy AF. EBM, 2nd ed. Edinburgh, Churchill Livingston, 2000.
Finding POEMs in the medical literature. J Fam Pract Salpeter SR, Walsh JME, Greyber E, Ormiston TM, Salpeter
1999;48:350–385. EE. Mortality associated with hormone replacement
Ely JW, Osheroff JA, Ebell MH, Bergus GR, Levy BT, therapy in younger and older women. J Gen Intern Med
Chambliss ML, Evans ER. Analysis of questions asked 2004;19:791–804.
by family doctors regarding patient care. BMJ. 1999; Slawson DC, Shaughnessy AF. Becoming an information
319:358–361. master: Using POEMs to change practice with confi-
Ely JW, Osheroff JA, Ebell MH, Chambliss ML, Vinson DC, dence. Patient-Oriented Evidence that Matters. J Fam
Stevermer JJ, Pifer EA. Obstacles to answering doctors’ Pract 2000;49:63–67.
questions about patient care with evidence: Qualitative Smith G, Pell J. Parachute use to prevent death and major
study. BMJ 2002;324:710. trauma related to gravitational challenge: A systematic
Feinstein A. Clinical Epidemiology. Philadelphia, WB review of randomized trials. BMJ 2003;327:20–27.
Saunders, 1985. Snow J. On the Mode of Communication of Cholera
Gabbay J, Le May A. Evidence based guidelines or collec- (reprint). New York, Commonwealth Fund, 1936
tively constructed “mindlines”? Ethnographic study of (London, John Churchill, 1855).
knowledge management in primary care. BMJ Strauss S, Jones G. What has evidence based medicine done
2004;329:1013–1016. for us? BMJ 2004;329:987–988.
Geyman JP, Deyo RA, Ramsey SD. Evidence-Based Practice: Users’ Guides to the Medical Literature. Chicago, American
Concepts and Approaches. Butterworth Heinemann, 2000. Medical Association, 2002.
Guyatt GH. Evidence-based medicine. ACP Journal Club Women’s Health Initiative Steering Committee. Effects of
1991;114(Suppl 2):A–16. conjugated equine estrogen in postmenopausal women
Guyatt GH, Rennie D. Users’ guides to the medical litera- with hysterectomy: The Women’s Health Initiative ran-
ture. JAMA 1993;270:2096–2097. domized controlled trial. JAMA 2004;291:1701–712.
60
 Chapter 6 Evaluating the Medical Literature

SUGGESTED READINGS
Alper BS. Practical evidence based Internet resources. Fam dence-based answers. J Med Library Assoc 2002;
Practice Manage 2003;10:49–52. 90:298–304.
Dickinson WP, Stange KC, Ebell MH, Ewigman BG, Green Herrington DM, Howard TD. From presumed benefit to
LA. Involving all family physicians and family medicine potential harm: Hormone therapy and heart disease.
faculty members in the use and generation of new N Engl J Med 2003;349:519–521.
knowledge. Fam Med 2000;32:480–490. Kravitz RL, Duan N, Braslow J. Evidence-based medicine,
Ebell MH, Siwek J, Weiss B, Woolf SH, Susman J, Ewigman heterogeneity of treatment effects, and the trouble with
B, Bowman M. Strength of recommendation taxonomy averages. Milbank Q 2004;82:661–687.
(SORT): A patient-centered approach to grading evi- Shaughnessy AF, Slawson DC. What happened to the valid
dence in the medical literature. Am Fam Physician POEMs? A survey of review articles on the treatment of
2004;69:548–556. type 2 diabetes. BMJ 2003;327:266.
Evidence-Based Medicine Working Group. Evidence-based Tovey D, Godlee F. General practitioners say that evidence
medicine: A new approach to the teaching of medicine. based information is changing practice. BMJ 2004;
JAMA 1992;268:2420–2425. 329:1043.
Grandage KK, Slawson DC, Shaughnessy AF. When less White B. Making evidence-based medicine doable in
is more: A practical approach to searching for evi- everyday practice. Fam Pract Manage 2004;51–55.

C h a p t e r

6 Evaluating the Medical Literature

Jeffrey Susman, Keith B. Holten,

and Douglas R. Smucker

changes in practice behavior—has become an essen-

KEY POINTS tial part of medical care. But most busy physicians
have neither the time nor the background to answer
1. Use the highest quality evidence available to critically the questions that arise in practice. Primary
make clinical decisions, prioritizing robust ran- care physicians identify 2.4 clinical questions for
domized controlled trials (RCTs) and systematic every 10 encounters (Barrie and Ward, 1997) yet
reviews, with appropriate patient-oriented out- spend less than 15 minutes on average with each
comes (strength of recommendation [SOR] C). patient. Furthermore, new evidence about common
2. Remember that statistical significance does not primary care problems is accumulating at an over-
always equate to clinical significance (SOR C). whelming pace, and the broad scope of family medi-
3. Useful sources for clinical evidence include the cine presents important challenges. Other barriers to
Cochrane database, the United States the use of EBM include lack of evidence that is per-
Preventive Services Task Force guide to clinical tinent to an individual patient, quick access to infor-
preventive services, and Patient-Oriented mation at the point of care, and potential negative
Evidence that Matters (POEMs) (SOR C). impacts on the art of medicine (McAllister et al.,
1999). How can diligent physicians narrow the gap
between their current behaviors and best practices?
This chapter uses hormone replacement therapy
Evidence-based medicine (EBM)—asking clear, rele- (HRT) for postmenopausal women as a case example
vant clinical questions; finding appropriate studies; for understanding the evolution of medical practice
critically appraising the literature; and implementing vis-à-vis a changing landscape of evidence. Core

61
 Chapter 6 Evaluating the Medical Literature

SUGGESTED READINGS
Alper BS. Practical evidence based Internet resources. Fam dence-based answers. J Med Library Assoc 2002;
Practice Manage 2003;10:49–52. 90:298–304.
Dickinson WP, Stange KC, Ebell MH, Ewigman BG, Green Herrington DM, Howard TD. From presumed benefit to
LA. Involving all family physicians and family medicine potential harm: Hormone therapy and heart disease.
faculty members in the use and generation of new N Engl J Med 2003;349:519–521.
knowledge. Fam Med 2000;32:480–490. Kravitz RL, Duan N, Braslow J. Evidence-based medicine,
Ebell MH, Siwek J, Weiss B, Woolf SH, Susman J, Ewigman heterogeneity of treatment effects, and the trouble with
B, Bowman M. Strength of recommendation taxonomy averages. Milbank Q 2004;82:661–687.
(SORT): A patient-centered approach to grading evi- Shaughnessy AF, Slawson DC. What happened to the valid
dence in the medical literature. Am Fam Physician POEMs? A survey of review articles on the treatment of
2004;69:548–556. type 2 diabetes. BMJ 2003;327:266.
Evidence-Based Medicine Working Group. Evidence-based Tovey D, Godlee F. General practitioners say that evidence
medicine: A new approach to the teaching of medicine. based information is changing practice. BMJ 2004;
JAMA 1992;268:2420–2425. 329:1043.
Grandage KK, Slawson DC, Shaughnessy AF. When less White B. Making evidence-based medicine doable in
is more: A practical approach to searching for evi- everyday practice. Fam Pract Manage 2004;51–55.

C h a p t e r

6 Evaluating the Medical Literature

Jeffrey Susman, Keith B. Holten,

and Douglas R. Smucker

changes in practice behavior—has become an essen-

KEY POINTS tial part of medical care. But most busy physicians
have neither the time nor the background to answer
1. Use the highest quality evidence available to critically the questions that arise in practice. Primary
make clinical decisions, prioritizing robust ran- care physicians identify 2.4 clinical questions for
domized controlled trials (RCTs) and systematic every 10 encounters (Barrie and Ward, 1997) yet
reviews, with appropriate patient-oriented out- spend less than 15 minutes on average with each
comes (strength of recommendation [SOR] C). patient. Furthermore, new evidence about common
2. Remember that statistical significance does not primary care problems is accumulating at an over-
always equate to clinical significance (SOR C). whelming pace, and the broad scope of family medi-
3. Useful sources for clinical evidence include the cine presents important challenges. Other barriers to
Cochrane database, the United States the use of EBM include lack of evidence that is per-
Preventive Services Task Force guide to clinical tinent to an individual patient, quick access to infor-
preventive services, and Patient-Oriented mation at the point of care, and potential negative
Evidence that Matters (POEMs) (SOR C). impacts on the art of medicine (McAllister et al.,
1999). How can diligent physicians narrow the gap
between their current behaviors and best practices?
This chapter uses hormone replacement therapy
Evidence-based medicine (EBM)—asking clear, rele- (HRT) for postmenopausal women as a case example
vant clinical questions; finding appropriate studies; for understanding the evolution of medical practice
critically appraising the literature; and implementing vis-à-vis a changing landscape of evidence. Core

61
 Chapter 6 Evaluating the Medical Literature

concepts of EBM and practical tools for family gov), and evidence-based databases (InfoPOEMs
physicians are highlighted. InfoRetriever) (Table 6-2).

USING EVIDENCE AT THE POINT Case Example

OF CARE A 55-year-old woman sees you because she is expe-
riencing severe vasomotor symptoms (hot flashes).
Physicians have many sources of clinical informa- These symptoms are keeping her awake at night.
tion, from “throw-away” or non–peer-reviewed jour- She had a total abdominal hysterectomy and
nals to evidence-based searchable databases. Each of oophorectomy 1 year ago because of uterine
these has advantages, disadvantages, and different fibroids. She is concerned about the dangers of
methods of access (Table 6-1). HRT. What is the current evidence? How do you
One model to help busy physicians stay clinically counsel this patient?
current, termed information mastery, has been advo- A search was performed on PubMed at
cated by Slawson and Shaugnessy (1999), Ebell www.ncbi.nlm.nih.gov/entrez/query/static/clinical.
(1999), and Geyman (1999). In this model, physicians html. Using Clinical Queries and the research
seek the answer to clinical questions through second- methodology, category “therapy” and emphasis “sen-
ary sources of information that have been created by sitive” were chosen. The search terms were “hormone
experts through a review of the medical literature. replacement therapy” and “vasomotor symptoms.”
Secondary sources include evidence-based sum- An excellent summary, the position statement
maries (Cochrane collaboration reviews, POEMs, from the North American Menopause Society, was
and clinical inquiries as published in the Journal of found (Neff, 2004). The North American Menopause
Family Practice and elsewhere [Geyman, 1999; Ebell Society recommends first considering lifestyle
et al., 1999]), systematic reviews (PubMed Clinical changes, alone or combined with a nonprescription
Inquiries), guidelines (written by professional soci- remedy (such as dietary isoflavones, vitamin E, or
eties and accessed through sites such as the National black cohosh), for the relief of mild vasomotor symp-
Guideline Clearinghouse on the Web at www.ngc. toms. For moderate to severe menopause-related hot

Table 6-1 Examples of Reference Materials for the Busy Physician:

Hormone Replacement Therapy Question
Type of
Literature Advantages Disadvantages Availability Examples

Textbooks Comprehensive Long period from concept Print, hardcover Novak’s

review of topics to printing; bookshelf and paperback; Gynecology
space or CD space some CD-ROMs ($45.00–
requirements; cost; and pocket PC $135.00)
reading time
Unsolicited No cost Some not peer reviewed; Print; some Female Patient
medical unpredictable topics; articles (complimentary)
journals large volume of online
materials
Subscription Peer reviewed; Cost and subscription Print and online Obstetrics and
peer-reviewed pertinent topics management; stacks of Gynecology
journals journals; need to ($257.00
critically appraise annually for
non-ACOG
member)
Evidence-based Peer reviewed; Cost; CD management; CD ROM and Cochrane
summaries pertinent topics searches have learning online Reviews:
curve abstracts
(complimentary)
and full reviews
Searchable Searchable; rapid; Learning curve for Pocket PC and InfoRetriever
evidence focused search searches online ($249.00
databases possible; point annually)
of care access
ACOG, American College of Obstetricians and Gynecologists.

62
 Chapter 6 Evaluating the Medical Literature

Table 6-2 Examples of Evidence Sources

Information
Source Access Description Cost

PubMed www.ncbi.nlm.nih.gov/ Service of National Library of No charge

entrez/query.fcgi Medicine; 15 million
citations back to 1950s,
includes links to many sites
with full text articles
National Guideline www.ngc.gov Collection of guidelines, No charge
Clearinghouse regularly updated; joint
effort of AHRQ, U.S.
Department of Health and
Human Services
U.S. Public Service www.odphp.osophs. Federal prevention guidelines; No charge
Task Force Guide to dhhs.gov/pubs/ public health focus; the
Clinical Preventive guidecps AHRQ is the lead agency
Services for the Guide project
JFP POEMS Database www.jfponline.com/ Contains all POEMs published No charge
display_archives.asp? in the Journal of Family
YEAR=POEMs Practice between August
2000 and the present;
articles are listed in reverse
chronologic order
Bandolier www.jr2.ox.ac.uk/ A UK site; monthly, PubMed No charge
Bandolier and Cochrane Library
searched for systematic
reviews and meta-analyses
published; those “both
interesting and making
sense” appear in Bandolier,
first in the print version,
then 2 months later on the
Web site
Canadian Task www.ctfphc.org Canadian site; Web site; No charge
Force on Preventive practical guide to health
Care care providers, planners,
and consumers for preventive
health interventions
InfoRetriever www.InfoPoems.com Database of filtered, 30 days free, then
synopsized, evidence-based $250/year
information; quarterly
updates; searches a full
spectrum of evidence-based
resources, including POEMs
and Cochrane abstracts,
2200 diagnostic calculators,
and >700 summaries of
evidence-based practice
guidelines
Cochrane Database www.cochrane.org/ An international nonprofit, $250–$460/year;
reviews/index.htm independent organization abstracts free
that produces and
disseminates systematic
reviews of health care
interventions and promotes
the search for evidence in
the form of clinical trials
and other studies of
interventions
Continued

63
 Chapter 6 Evaluating the Medical Literature

Table 6-2 Examples of Evidence Sources (Continued)

Information
Source Access Description Cost

TRIP (Turning Research www.tripdatabase.com UK site; central search engine 5 free searches,
into Practice) for high-quality medical then £35
literature from a wide annually
range of sources: evidence-
based records, clinical
guidelines, clinical questions
and answers, electronic
textbooks, medical images,
>13 million peer-reviewed
journal articles
Clinical Inquiries www.fpin.org Evolving point of care tool Graduated based
that seeks to answer on number of
clinical questions from subscribers
practice using structured, ($100 for single
critical reviews of the membership to
literature; evidence graded FPIN)
and explicit; the FPIN
bundles access to other
products including PEPID,
which covers >1800 disease
topics and >5000 drugs, and
has a drug interactions
calculator and multiple
other tools
AHRQ, Agency for Healthcare Research and Quality; FPIN, Family Practice Inquiries Network; PEPID, Portable
Emergency Physician Database; POEMs, Patient-Oriented Evidence that Matters.

flashes, prescription systemic estrogen-containing “hormone replacement therapy-postmenopausal.”

products are still the therapeutic standard. Possible The category “treatment by drug” (POEMs/
treatment options for women with concerns or Cochrane only prompted “estrogen” as a choice. One
contraindications to estrogen-containing products result (“Are low doses of continuous HRT as effective
include prescription progestogens, venlafaxine, as usual doses for the treatment of vasomotor symp-
paroxetine, fluoxetine, or gabapentin. The search and toms and vaginal atrophy in postmenopausal
review of this article took approximately 3 minutes. women?”) was provided (Utian et al., 2001). This
Another PubMed reference from the New search took approximately 2 minutes. The bottom
England Journal of Medicine summarizes the litera- line was that continuous HRT at less than standard
ture and discusses current recommendations on the doses was effective in reducing both the number and
use of HRT (Timins, 2004). Initially used to treat the severity of hot flashes in postmenopausal women.
vasomotor and vaginal symptoms of menopause, Estrogen alone was a little less effective than estrogen
HRT appeared to have many unexpected beneficial plus progesterone.
effects in early observational trials. It was hailed as a Another InfoRetriever reference under category
deterrent of atherosclerosis, osteoporosis, cognitive “treatment by drug” (POEMs/Cochrane only) was
impairment, and Alzheimer’s disease. Although its titled “hormone replacement overall not beneficial.”
salutary effects on bone mass were substantiated, This reference was a review of the Rossouw et al.
randomized clinical trials noted an increased risk of (2002). This was a large, multiple-site study encom-
breast cancer, coronary artery disease, and throm- passing several different clinical trials of hormone
boembolism and raised doubts about the efficacy of replacement, calcium supplementation, vitamin D
HRT in improving quality of life. This evidence took supplementation, and low-fat diet. The trial of con-
another 2 minutes to review. jugated equine estrogen plus progestin (0.625 mg/
Using the Web-accessed version of the subscrip- 2.5 mg) in more than 16,000 healthy women with a
tion service, InfoRetriever (see Table 6-2), another uterus was stopped early by the study’s safety moni-
search was performed. This search tool is convenient toring board because after an average of 5.2 years of
and rapid and rates the quality of evidence. The follow-up, the HRT group had a higher annual inci-
search was performed using keyword search term dence of coronary heart disease (CHD) (0.37% ver-

64
 Chapter 6 Evaluating the Medical Literature

sus 0.30%), invasive breast cancer (0.38% versus understanding of HRT and its effects on heart
0.30%), stroke (0.29% versus 0.21%,), and venous disease, let us review the progression of research
thromboembolic disease (0.34% versus 0.16%). studies and evidence over the past 30 years.
However, bone fractures were less prevalent in the
HRT group (total annual fracture rate, 1.47% versus The Story of Hormone Replacement
1.91%). It is uncertain whether there is the same risk
Therapy Research
with doses of estrogen and/or progesterone lower
than those used in this trial or whether estrogen A series of observational studies in the 1970s and
treatment alone will cause the same outcomes (level 1980s led to regular prescribing of HRT to prevent a
of evidence 1b). This search took an additional number of significant health conditions in post-
2 minutes. menopausal women.
Looking for patient education material was also
simple and rapid using InfoRetriever. After choosing
Case-Control Studies
search term “hormone replacement therapy-
postmenopausal,” in the category “education: patient Case-control studies are often the first step in a pro-
education” was a reference to AAFP Patient Education gression of building clinical evidence because they are
Handout: Hormone Replacement Therapy: New relatively inexpensive and rapid studies to complete.
Information (American Academy of Family Physi- Case-control studies always look backward in time
cians, 2004). This source summarized the controversy (retrospective) to determine a statistical association
about HRT, reviewed the Women’s Health Initiative between an “exposure” and an “outcome.” To complete
(WHI) trial, discussed options for treating vasomotor a case-control study of the association of HRT and
symptoms of menopause, and referred to two other CHD, a researcher would identify a group of “cases”
excellent sites (National Heart Lung and Blood (women with CHD) and a group of “controls” (women
Institute and Mayo Clinic) for patient information. A without CHD) and look back in time to determine
direct link to the Web page for a printer friendly copy how many women in each group had been on HRT.
was provided at www.familydoctor.org/x2401.xml The association between exposure (HRT) and out-
(another 1 minute of search time). come (CHD) in a case-control study is commonly
This case outlines how a physician with access to summarized by a statistical measure called an odds
searchable databases can quickly review a wide array ratio. An odds ratio is an estimation of the true relative
of clinical evidence and published guidelines. Such risk (RR) for the outcome in question. A common
resources are based on systematic evaluations of evi- form of bias in a case-control study is recall bias: errors
dence and can provide clinicians with practical guid- in accurately determining whether both cases and con-
ance at the point of care. trols had exposure to HRT in the past.

BUILDING CLINICAL EVIDENCE FROM Cohort Studies

PUBLISHED RESEARCH Cohort studies are often the next step in building the
strength of evidence regarding an association
Evidence of interventions such as HRT commonly between an exposure and an outcome. Cohort stud-
begins with observational studies including ies typically are forward looking in their time frame
unblinded case series and case-control and cohort (prospective) and are generally more expensive and
studies and culminates in RCTs (Fig. 6-1). To better take longer to complete than case-control studies.
understand how we have arrived at today’s clinical However, they provide a more accurate estimate of

Observational studies
Case series descriptions→
Case–control studies→
Cohort studies→
Structured reviews of observational studies

Intervention studies
Small randomized trials→
Meta–analysis of small RCTs→
Larger randomized controlled trials→

Progression of studies over time

Figure 6-1 Common progression of research in building strength of evidence. RCTs, randomized controlled trials.

65
 Chapter 6 Evaluating the Medical Literature

the RR between women who are on HRT and those The Power of Randomized Controlled Trials
who are not. A cohort study is also an observational
study, one that observes outcomes in groups but does In RCTs, participants are randomly assigned to two
not assign participants to a particular exposure or or more groups and then assigned to either partici-
treatment. In a cohort study of HRT and CHD, a pate in an intervention such as HRT or continue with
researcher would identify a group of women on HRT their usual care. RCTs greatly add to the confidence
and a similar group of women who have chosen not of measured results because the structure of an RCT
to be on HRT, then follow them over time and count helps eliminate many of the inherent biases of obser-
the number of CHD events. Because outcome events vational studies. For example, in cohort studies of
may be uncommon in each group and may take HRT and CHD, it is hypothesized that women
many months to occur, cohort studies often require who choose to go on HRT are generally healthier and
large numbers of participants and long follow-up to have better healthy lifestyle practices than women
show significant differences between groups. who do not choose to go on HRT. Because partici-
The primary statistical measure from a cohort pants in an RCT are randomly assigned to treatment
study is the RR. This is a ratio of the rate of CHD and control groups, they are less likely to have differ-
events among women who choose to be on HRT ences in other factors that might prevent or promote
divided by the rate among women who choose not to heart disease. The decreased likelihood of a “healthy
be on HRT. A common form of bias in cohort stud- user bias” in an RCT may explain why HRT appeared
ies related to prevention is the healthy user bias, when to be protective in cohort studies but actually proved
participants who choose one preventive measure to be harmful. Because RCTs have this inherent abil-
(such as HRT) also tend to make healthier lifestyle ity to remove many important potential areas of bias,
decisions (diet, exercise) that may also prevent the one can have more confidence that they reflect the
measured outcome (CHD). true association between the HRT and CHD out-
Beginning with case-control studies and then comes. Thus, despite decades of work, dozens of
larger cohort studies, observational research showed observational studies, and structured reviews that
that HRT might reduce the incidence of CHD, frac- strongly suggested a protective effect of HRT for
tures, and colorectal cancer. These observational CHD, a single large RCT trumped them all and
studies also suggested that the same therapy might caused a sudden reversal in physician prescribing
cause harm with a slightly increased risk of breast behavior.
cancer, stroke, and venous thromboembolism. On The release of the major report of a very large
balance, however, even a small positive impact of RCT of HRT in 2002, the WHI study, sent a shock
HRT on preventing CHD was thought to far out- wave through the medical community (Rossouw
weigh the potential adverse effects of HRT et al., 2002). For the first time, a large randomized
trial showed that HRT in otherwise fairly healthy
postmenopausal women caused a statistically signif-
Structured Reviews and Meta-analysis icant increase in CHD events. Within days of the
After a number of studies are completed, whether release of the WHI report, hundreds of thousands of
they are cohort studies or initial small RCTs, they are women called their physicians to inquire whether
often reviewed and summarized in publications they should continue with HRT. Many physicians
called structured reviews. Occasionally, data from drastically changed their prescription of HRT based
a series of studies are combined using statistical on the WHI study: Within 9 months, prescriptions of
techniques called meta-analysis, which allows in- the most popular formulation of HRT decreased by
creased statistical power to determine the weight of as much as 61% (Majumdar et al., 2004). Perhaps
evidence from a series of studies. The use of HRT more than any other single study in modern medical
was greatly increased during the 1990s based not history, the WHI study dramatically changed a wide-
only on a number of case-control and cohort studies spread, common medical practice.
but also on three different meta-analysis studies that
further increased the weight of scientific evidence
that HRT was protective against CHD (Pettite, 1998). UNDERSTANDING THE STATISTICAL
Indeed, one editorial from 1991 in the New SIGNIFICANCE OF STUDY RESULTS
England Journal of Medicine, concluded that “a consen-
sus of epidemiologic reports has demonstrated that Reports from RCTs such as the WHI study fre-
women who are given postmenopausal estrogen ther- quently include the RR as a summary measure of
apy have a reduction of about 40 to 50% in the risk of differences between the treatment and placebo
ischemic heart disease as compared with women who groups (see Table 6-3). To arrive at the RR, the
do not receive such therapy” (Goldman and Tosteson, researcher first measures the incidence rate of an
1991). HRT became a de facto standard for post- outcome in each of the two study groups (treatment
menopausal women through the decade of the 1990s. and placebo). The incidence rate for each group is a

66
 Chapter 6 Evaluating the Medical Literature

ratio of the number of new outcome events, such as INTERPRETING STUDY RESULTS:
CHD events, divided by the number of patients at STATISTICAL AND CLINICAL
risk of the outcome in that group over a specific SIGNIFICANCE
period of time. In multiyear studies, the average
annual incidence rate is often reported as a sum- Although the WHI study showed a statistically sig-
mary measure. In a placebo-controlled RCT, the RR nificant increase in the RR of CHD events among
is then calculated as simply a ratio of the incidence women who were randomly assigned to take HRT, it
rate for the treatment group divided by the inci- is important to consider the absolute difference in
dence rate for the placebo group (Table 6-3). CHD events between the two groups to understand
How can one determine whether the reported the strength of the association and to be able to
RR from a study is “significant” enough to influence thoughtfully discuss the risk of HRT with individual
clinical decisions? The first step is to consider the patients. Calculating the absolute risk (in addition to
statistical significance of the summary measure, in the RR) is a helpful way to understand the level of
this case, the RR. Statistical significance is com- risk that HRT may add for a group of women who
monly summarized in published studies by either a are at risk of CHD events (Table 6-4).
P value or a 95% CI for a given summary measure. In the WHI study, for example, the RR of CHD
The P value describes the statistical probability that for participants who were on HRT was 1.29 and was
the observed difference between the groups could statistically significant with a 95% CI that did not
have happened simply by chance alone. Thus, a P cross 1.0 (95% CI: 1.02 to 1.63). This figure (RR =
value less than 0.05, almost universally recognized 1.29) can generally be interpreted as HRT being
as the cutoff for statistical significance, means that associated with a 29% increase in CHD events. This
there is less than a one in 20 chance (5%) that a dif- summary measure was reported widely in medical
ference as large as that observed would occur by journals and the popular press.
chance. When reported in terms of RR, the weight of the
When the RR is reported as the summary result association between HRT and CHD sounds ominous
of a study, the 95% CI is often used as an alternative (29% increase). However, in terms of the absolute
to the P value to describe the level of statistical sig- risk attributable to HRT, a less ominous picture
nificance of the result. The 95% CI describes the emerges (see Table 6-4). In the WHI study, for exam-
range that will, with 95% certainty, include the stated ple, those on HRT had an average rate of CHD events
RR. For the RR, the 95% CI that does not include 1.0 of 0.37% per year (an average of 37 events per 10,000
(i.e., no difference between the groups) is a statisti- women each year), whereas those in the placebo
cally significant result. For example, if a study group had an annual rate of 0.30% (30 events per
reported a RR of 1.5 with a 95% CI of 1.2 to 1.8, we 10,000 women each year). Although the adjusted RR
could be reasonably certain (95% certain) that the of CHD is 1.29 (0.37 ÷ 0.30), the attributable risk or
reported difference between the groups was not due risk difference between the two groups is 0.07%
to chance. However, if the RR was reported as 1.5 (0.37 − 0.30). In other words, approximately seven
with a 95% CI of 0.90 to 2.1, it would not be consid- additional cases of CHD occurred for 10,000 women
ered statistically significant because the CI includes using HRT during each year over the course of the
the value of “no difference” (RR = 1.0). study. The attributable risk of the treatment group

Table 6-3 Understanding Study Results

Commonly reported summary rates from randomized controlled trials:

Number of new cases of disease over a period of time

Incidence rate =
Number of persons at risk during the time period

Incidence rate among the treated group

Relative risk =
Incidence rate among the placebo group

Summary measures that may be more meaningful for clinicians:

Attributable risk among placebo

= Incidence rate among treated group − Incidence rate among placebo group or risk difference

(Number
number needed to harm )
needed to treat or
= The reciprocal of attributable risk or
1
Attributable risk

67
 Chapter 6 Evaluating the Medical Literature

Table 6-4 An Example of Summary Rates from the Women’s Health Initiative Study
Here is an example of how to take a summary rate commonly reported in published studies (relative risk)
and calculate a summary measure (number needed to treat or number needed to harm) that may be
more useful in describing the results to clinicians and patients. Let us consider the average annual
incidence rates and relative risk of CHD events in the WHI study:
Average annual incidence 37 CHD events per year
=
among HRT treated women 10,000 women

Average annual incidence 30 CHD events per year

=
among placebo treated women 10,000 women
37 CHD events
10,000 women
Relative risk of CHD = = 1.29 (adjusted)
30 CHD events
10,000 women
The relative risk describes a relative 29% increase in CHD events. It may be more useful to consider the
absolute difference in incidence rates between the two groups to understand the magnitude of the
potential risk for a given patient:
37 CHD events 30 CHD events 7 additional CHD events
Attributable risk = − =
10,000 women 10,000 women 10,000 women

The number needed to harm can easily be calculated to describe, on average, how many women must be
treated for 1 year to cause one additional CHD event attributable to HRT

Number needed to harm = 1 = 10,000 = 1430

7 CHD events 7
10,000 women
CHD, coronary heart disease; HRT, hormone replacement therapy; WHI, Women’s Health Initiative.
Based on information from Rossouw JE, Anderson GL, Prentice RL, et al. and the Writing Group for the Women’s
Health Initiative. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal
results. From the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–333.

can be summarized as the number needed to harm osteoporosis, a decrease in fracture incidence would
or, if a study reports a beneficial effect, the number be much more convincing than a change in a physi-
needed to treat. In this case, the number need to ologic parameter. Likewise, all important harms
harm was approximately 1430 patients per year on (risks) and financial endpoints (costs and savings)
average; for every 1430 patients on HRT (the inverse should be reported. In a trial of a new antiresorptive
of absolute difference, 0.07 or 10,000 ÷ 7), one addi- agent, the rate of esophagitis, gastritis, and
tional CHD event occurred (see Table 6-4). The esophageal perforation might be important harms to
number needed to harm or number needed to treat elaborate, along with such measures as patient satis-
tends to be much more understandable for both faction, costs and savings of care, and global well-
physicians and patients when weighing the risks and being.
benefits of a particular therapy. When assessing the benefits and harms of such a
new treatment, appropriate competing alternatives
(including no treatment at all) should be compared.
OTHER KEYS TO INTERPRETING Typically, such a comparison might take the form of
CLINICAL EVIDENCE a balance sheet, a table comparing each intervention
in terms benefits, harms, and, sometimes, economic
One of the major pitfalls in interpreting the results of endpoints. Many studies are randomized, placebo-
a study is to ensure that all relevant patient-oriented controlled trials (in which patients either get an
outcomes are considered. First, it is important to dis- active intervention or a placebo or sham interven-
tinguish among physiologic outcomes (e.g., serum tion). However, the typical question for clinicians is
calcium), intermediate outcomes (e.g., bone den- should I change practice to use this intervention
sity), and patient-oriented outcomes (e.g., fractures). instead of an existing one. Thus, an appropriate
Whenever possible, it is more powerful and relevant consideration of patient-oriented outcomes and
to see results in terms of outcomes that patients competing alternatives is of considerable practical
would deem important. Thus, in a trial of HRT for importance.

68
 Chapter 6 Evaluating the Medical Literature

When a study shows no effect, the question of can be systematic, in which very rigorous attempts
power is raised. Put in simple terms, power is the abil- are made to uncover all studies, published and
ity to detect the effect of an intervention; it depends unpublished, in English and in other relevant lan-
on the number of patients in the study, the magnitude guages, or very haphazard, even biased. Some use
of effect of the intervention, and the variability of the formal mathematical methods to combine the results
effect from one subject to another. For some inter- of studies (meta-analysis), whereas others are quali-
ventions, even a small effect may be important. For tative and synthesize data according to an author’s
example, many nonpharmacologic treatments for overall judgment. Common biases to look for
hypertension (e.g., salt restriction) have relatively include the following: were all sources of evidence
modest but important effects. Practically, be skeptical considered, how were disparate results combined,
of studies of a small number of patients (<100 to 150) were relevant patient-oriented outcomes assessed,
in which statistically insignificant results are found. was there adequate attention to the quality of the
Even when a study is positive or shows statisti- studies and their generalizability, and do the authors
cally significant results, it is important to consider try to analyze why differences in outcomes may have
whether these findings are clinically significant and occurred based on such factors as study design, pop-
applicable to your practice. For example, if a study ulation, and intervention. As noted, review articles
showed that a drug reduces the risk of heart attack by and more elaborate systematic reviews are increas-
one in a million patients, we would probably be ingly important for the busy clinician (see Table 6-1).
skeptical of its utility. Likewise, the findings showing For the neophyte clinician, there are many ways
that daily borscht reduces fractures in a study done to hone your critical appraisal skills including
in Russian dockworkers may or may not be transfer- involvement with local journal clubs, work with the
able to the United States. Moreover, the acceptability Family Practice Inquiries Network, or assisting in the
of an intervention (e.g., electroconvulsive therapy for development of POEMs and reading such references
depression) may vary. This issue of generalizability as EBM (Sackett et al., 1998). EBM, information
or transferability of an intervention is often glossed mastery, and the application of knowledge at the
over. Moreover, the ability to replicate the findings of point of care remain works in progress. By develop-
a study done in a typical research setting is often ing a basic understanding of these resources and
reduced in real-world practice. Thus, an intervention tools, it is hoped that physicians’ care of patients will
for osteoporosis requiring daily injections may be be effective, safe, and efficient.
demonstrated to be efficacious, but in the average
practice setting, its effectiveness might be much
more limited. Material Available on Student Consult
Finally, we are more frequently relying on the
Review Questions and Answers about Evaluating
results from not a single study but the synthesis of the Medical Literature
many studies to change our practices. Such reviews

REFERENCES
American Academy of Family Physicians. Hormone Neff MJ. NAMS releases position statement on the treatment
Replacement Therapy: New Information. Patient educa- of vasomotor symptoms associated with menopause. Am
tion handout. Leawood, KS: American Academy of Fam Physician 2004;70:393–394,396,399.
Family Physicians, 2004. Pettite DB. Hormone replacement therapy and heart dis-
Barrie RA, Ward AM. Questioning behavior in general ease protection. JAMA 1998;280:650–651.
practice: A pragmatic study. BMJ 1997;315:1512–1515. Rossouw JE, Anderson GL, Prentice RL, et al. and the
Ebell M. Evidence-based clinical practice. Information at Writing Group for the Women’s Health Initiative. Risks
the point of care: Answering clinical questions. J Am and benefits of estrogen plus progestin in healthy post-
Board Fam Pract 1999;12:225–235. menopausal women: Principal results. From the
Ebell MH, Messimer SR, Barry HC. Putting computer- Women’s Health Initiative randomized controlled trial.
based evidence in the hands of clinicians. JAMA JAMA 2002;288:321–333.
1999;28:1171–1172. Sackett DL, Richardson WS, Rosenberg W, et al. Evidence-
Geyman JP. POEMs as a paradigm shift in teaching, learn- based Medicine. Edinburgh: Churchill Livingstone, 1998.
ing, and clinical practice. J Fam Pract 1999;48:343–344. Slawson DC, Shaughnessy AF. Teaching information mas-
Goldman L, Tosteson ANA. Uncertainty about post- tery: Creating informed consumers of medical infor-
menopausal estrogen. N Engl J Med 1991;325:800–802. mation. J Am Board Fam Pract 1999;12:444–449.
Majumdar SR, Amasi EA, Stafford RS. Promotion and pre- Timins JK. Current issues in hormone replacement ther-
scribing of hormone therapy after report of harm by the apy. N J Med 2004;101:21–27.
women’s health initiative. JAMA 2004;292:1983–1988. Utian WF, Shoupe D, Bachman G, et al. Relief of vasomo-
McAllister FA, Graham I, Karr GW, et al. Evidence-based tor symptoms and vaginal atrophy with lower doses of
medicine and the practicing clinician. J Gen Intern Med conjugated equine estrogens and medroxyprogesterone
1999;14:236–242. acetate. Fertil Steril 2001;75:1065–1075.

69
 C h a p t e r

7 Ethics in Family Medicine

Warren l. Holleman and Baruch A. Brody

practice of medicine. The ethical issues discussed in

KEY POINTS this chapter have taken on new dimensions as a result
of this transformation.
1. Medicine is a relationship and a profession.
2. When performing evaluations for third-party
payers, always clarify the purpose of the evalua- MEDICINE AS A RELATIONSHIP
tion and what information is to be shared and AND AS A PROFESSION
with whom.
3. Respect for confidentiality is essential to an At its most fundamental level, the practice of medi-
effective doctor-patient relationship. cine should not be regarded as a science, an art, or a
4. When treating adolescent patients, inform the business, even though each of these elements is
parents that you will use your professional judg- essential. The practice of medicine—particularly pri-
ment in determining what information to share mary care medicine—is rooted, instead, in a rela-
with them. tionship between the patient as person and the
5. Informed consent is not a piece of paper but physician as professional (Jonsen et al., 2002; Smith
the verbal agreement between doctor and and Churchill, 1986). Two problems currently
patient. The purpose of the piece of paper is to threaten the quality of that relationship: a misunder-
document that the conversation occurred and standing of patient autonomy and inappropriate
what each party agreed to do. third-party intervention.
6. Noncompliance is usually a misnomer. When physicians respect the autonomy of their
Generally, noncompliance results from poor patients so that patients take control of their health
communication, failures of trust, mental illness, care, the physician is in danger of becoming a hired
or value differences, each of which can be hand of the patient and the physician-patient rela-
addressed by a skilled physician. tionship is in danger of degenerating into a purely
7. A skilled primary care physician will have the commercial relationship. Patients “own” their bod-
courage to address the medical problems that ies, but they should not “own” their physicians.
he or she is qualified to treat and the humility Physicians have an obligation to practice within
to ask for help when faced with problems professional standards of care as well as a right to
beyond his or her expertise. refrain from doing anything that would violate their
8. Physicians can avoid burnout if they learn to own moral and religious convictions (Christie and
distinguish between competence and perfec- Hoffmaster, 1986). Yet they should nurture a coop-
tionism, dedication and “workaholism,” and erative relationship with their patients. This is no
compassion and sentimentalism. easy task, but it is through cooperation that the
9. Physicians have an ethical obligation to help physician and the patient can best work together
patients live and die with as much dignity, con- toward a common goal—to maintain the health of
trol, and comfort as possible. the patient.
The physician-patient relationship also suffers
when outside parties interfere inappropriately. When
third-party payers set the standard of care, the physi-
Economic, social, legal, and political factors have cian is in danger of becoming a hired hand of the
combined in recent years to effect major changes in third party. The physician must balance competing
medical practice and health care policy. Concern for loyalties between patients and third parties as well as
patient rights and patient autonomy, as well as the between professional standards and personal beliefs.
demands of third-party payers, have transformed the In this era of third-party payers, the physician-patient

70
 Chapter 7 Ethics in Family Medicine

relationship can no longer be exclusive, but it must cine as a healing profession. Patients will have diffi-
remain primary. In the remainder of this section, we culty trusting a physician who investigates on one
examine two areas in which these problems are par- occasion but offers therapy on another. We recom-
ticularly prominent: work-related visits and benefits- mend that physicians encourage employers and
related visits. school administrators to develop nonmedical strate-
gies for policing casual absenteeism. Physicians who
Work- and School-related Evaluations do perform these evaluations should minimize the
harm to the physician-patient relationship and to
Preplacement examinations, work release evalua- the integrity of the profession by evaluating only in the
tions, school absence excuses, and athletic physicals context of treatment and by refusing to release confi-
constitute a major component of many primary care dential medical information to employers and school
practices. Inappropriate third-party interventions in administrators.
these areas challenge the primacy of the physician- Many patients present to family physicians seek-
patient relationship and the integrity of the medical ing to be certified as eligible for worker’s compen-
profession. The following guidelines have been sug- sation, long-term disability, group or individual
gested (Holleman and Holleman, 1988; Holleman medical insurance, Medicare, Medicaid, and vet-
and Matson, 1991) and should help alleviate some of eran’s benefits. Many others already have been certi-
the problems most commonly associated with these fied and are seeking proper care under the terms of
evaluations. these programs. Physicians must be familiar with the
The purpose of the preplacement examination is benefits available under these programs as well as the
to determine a person’s fitness for work, to protect potential abuses. For example, if a patient presents
workers from illnesses and injuries, to protect with an on-the-job injury but also requests treat-
employers from the costs of preventable job-related ment for some other problem, the physician should
illnesses and injuries, and to collect baseline data for file separate bills so that the worker’s compensation
the future treatment of such illnesses and injuries. To fund pays for only job-related illnesses and injuries.
enable the physician to make such an evaluation, the Long-term abuse of benefits programs can be pre-
employer must provide the physician with a detailed vented only if primary care physicians insist that
job description, including physical requirements, patients receive continuing comprehensive care from
psychological strains, and exposures to toxins. The one physician or from a small team of physicians
physician then should tell the employer whether the who know the patient well.
prospective employee can perform the job without
posing a risk to him- or herself or others. As dis-
cussed later, the physician should not release medical SPECIAL PROBLEMS IN PRIMARY
records to the employer but should keep them on file CARE SETTINGS
as baseline data. At the beginning of the evaluation,
the physician should advise the patient of the inves- Having introduced the concept of medicine as a rela-
tigative nature of the visit. The physician must warn tionship and as a profession and having seen what
the prospective employee regarding health risks of this concept means in many primary care contexts,
the particular occupation (e.g., toxins affecting preg- we turn in the next sections to problem areas
nancies, stresses affecting hypertensive patients) and that challenge our understanding of the physician-
must tell him or her of any problems detected in the patient relationship and of the professional character
course of the evaluation, regardless of their effect on of medicine.
job performance.
Work release evaluations, school release evalua-
Confidentiality
tions, and athletic physical examinations should be
performed in accordance with the same guidelines as The principle of confidentiality is one of the most
preplacement physical examinations, but they do widely accepted and historically influential princi-
present some additional problems. Most work and ples governing the patient-physician relationship in
school release evaluations involve short-term Western cultures. The Hippocratic Oath mandates
absences for minor problems for which there are that the physician not divulge “whatsoever I shall see
few, if any, objective findings. Often workers and or hear in the course of my profession as well as out-
students present after their illness or injury has side my profession in my intercourse with men, if it
resolved. These absences often reflect personal, be what should not be published abroad.” The 1980
family, or job-related problems that are not strictly Principles of Medical Ethics of the American Medical
medical in nature. Investigating such problems for Association mandate that the physician “shall safe-
employers and school administrators damages the guard patient confidences within the constraints of
physician-patient relationship and discredits medi- the law.”

71
 Chapter 7 Ethics in Family Medicine

Confidentiality is important as a way to encour- The principle of confidentiality extends to not

age patients to be frank in their communications providing information to family members of compe-
with physicians, as a way for physicians to keep an tent adult patients unless the patient wants the infor-
implicit promise to patients that their confidence mation to be shared. An appropriate practice on
will be respected, and as a way to emphasize the admitting a patient to a hospital is to ask the patient
patient’s right to privacy. In all these ways, preserving to identify a particular family member, if any, to
confidentiality strengthens the relationship between whom information should be provided for distribu-
an autonomous patient and a professional physician. tion to the family if the patient is not capable of ful-
As the delivery of health care has changed from filling that role (e.g., in the immediate postsurgical
the model of a single physician caring for individual period).
patients to the model of a team of health care work- Cases involving adolescent patients are particu-
ers in an institutional setting providing care to a wide larly troublesome. Information about pediatric
variety of patients, the mandate of confidentiality patients is, of course, provided directly to the parents
has changed. The emphasis has switched from physi- of the patients and not to the patients themselves;
cians’ keeping secrets to information about patients information about adult patients is, of course, pro-
being divulged only to those members of the health vided directly to the patient and not the patient’s
care team and those institutional employees who parents. What about teenage patients seeking abor-
have a need for the information, either to provide tions, contraceptive advice, or treatment for venereal
appropriate care or to meet appropriate institutional diseases, substance abuse, or psychiatric problems?
needs (e.g., monitoring of quality of care or organiz- Unless confidentiality can be guaranteed, such
ing reimbursement). The underlying theme remains patients may not seek out the care they need. If con-
that information should not be provided to anyone fidentiality is protected, such patients may not get
else without the patient’s consent. the parental counseling and support from which
This last point deserves special emphasis they also could benefit. Considerable confusion
because it structures the decision as to when it is exists about the morally appropriate and legally man-
appropriate to provide information about the dated approach to confidentiality of information
patient to insurance companies and to employers. involving adolescent patients (Ford et al., 2004;
Providing such information is appropriate if the Holder, 1985).
patient consents; otherwise, it is not. The scope of Equally troubling are cases involving elderly
information supplied and the persons to whom it is patients who are less than fully competent but far
supplied are determined by the patient’s instruc- from totally demented. Families of such patients
tions. If, for example, a patient requests a statement often ask physicians to provide them with informa-
certifying that he or she is fit to return to work, it is tion about the patient’s condition, information that
not appropriate to give the employer a full account of they may not want to share with the patient. Such a
the patient’s illness and treatment, only a statement request may be perfectly appropriate for the clearly
about the patient’s fitness to return to work. incompetent demented patient, whereas it is obvi-
There are circumstances in which our society has ously inappropriate for normal geriatric patients.
judged that the need for information outweighs the How to handle cases that fall between these two
principle of confidentiality; these are the circum- extremes is unclear.
stances in which the physician is required by law to
disclose otherwise confidential information regard-
Informed Consent
less of the wishes of the patient. Laws vary from juris-
diction to jurisdiction, but common circumstances The principle of informed consent is a more recently
include child custody disputes, suspected abuse of articulated principle than the principle of confiden-
dependent individuals such as children and the frail tiality; the actual phrase informed consent first
elderly, venereal and communicable diseases, and appeared in 1957 in the court case Salgo v Leland
gunshot wounds (Bruce, 1996). In recent years, fol- Stanford Jr. University Board of Trustees. However, it
lowing the Tarasoff decision in California (Tarasoff v has come to be accepted as a fundamental principle
Regents of The University of California, 1976), the con- governing the relationship between patients and
cept has emerged that physicians are obligated to physicians.
warn and/or to take measures to protect third parties The principle’s basic mandate is that a physician
threatened by the behavior of their patients, even if must obtain the free and informed consent of a
doing so involves a breach of confidentiality. The patient if the patient is competent to give that con-
scope of that principle is far from clear; one obvious sent or of the patient’s surrogate if the patient is not
controversial example is whether physicians should competent before medical treatment is provided.
warn the spouses or regular sexual partners of Two exceptions normally are recognized. The first
patients who test positive for human immunodefi- (the emergency exception) is invoked when emer-
ciency virus about the threat this illness poses. gency treatment is necessary to protect the patient’s

72
 Chapter 7 Ethics in Family Medicine

life or health and consent cannot be obtained in a practice standard (Rozovsky, 1990). Clinicians are,
Table 7-1 Elements of Informed Consent
timely fashion. The second (the therapeutic privilege) we believe, best advised to adopt the reasonable per
Under Reasonable Person
is invoked when there is strong reason to believe that adopted the usually less demanding professional
Standard
the very attempt to obtain consent will be harmful
to the patient because of the psychological impact of Nature of the patient’s condition (e.g.,
the information conveyed (Rozovsky, 1990). hypertension)
Several complementary accounts of the signifi- Description of the treatment proposed
cance of the principle of informed consent are avail- (e.g., particular medication)
able. One stresses the clinical benefits (in terms of Benefits of proposed treatment (e.g., control
building trust and obtaining compliance) from a of hypertension and resulting lowering of risk
of disease)
therapeutic regimen begun as a result of a joint
Risks of proposed treatment (e.g., side effects
patient-physician decision rather than as a result of a for that medication)
unilateral physician decision. The other stresses the Alternatives (e.g., other medications, diet
patient’s right to control what happens to his or her and exercise, no intervention)
body; the resulting obligation of the physician to Costs of proposed treatment
obtain informed consent is the way in which the
From Rakel RE. Textbook of Family Practice, 4th ed.
physician respects that right. Philadelphia: W.B. Saunders, 1990.
The standard practice in many institutions is to
obtain written documentation of informed consent
primarily (if not exclusively) in cases of invasive pro- practice standard (Rozovsky, 1990). Clinicians are,
cedures. This practice should not be understood to we believe, best advised to adopt the reasonable per-
mean that the principle of informed consent does not son standard because it provides all the clinical and
apply to other medical interventions; it applies to all of moral benefits of obtaining informed consent while
them. Signed consent forms are merely written evi- firmly ensuring that the legal requirement of
dence of the informed consent already obtained, and informed consent is satisfied. Clinicians also must be
the practice reflects the prudent desire to obtain writ- careful to provide that information using terminol-
ten documentation in cases in which potential liability ogy that patients are likely to understand.
is highest. Informed consent, as opposed to the writ- A difficult problem arises when one is dealing
ten documentation of that consent, should be with patients whose competency is impaired
obtained in all cases, both as a way of obtaining clini- (Freedman, 1996). Informed consent is obtained
cal benefits and as a way of respecting patient’s rights. from the patient when the patient is clearly compe-
There has been considerable disagreement tent and from the patient’s surrogate (a legally
about the amount and type of information that must appointed guardian, if available, or the closest family
be supplied to the patient. Obviously, only a portion member) if the patient is clearly incompetent. What,
of the relevant information known by the physician however, should one do when the patient’s mental
can be conveyed to the patient. Moreover, any capacities are impaired but present to some degree?
attempt to provide too much information may result This problem is alleviated partially when one remem-
in the physician overwhelming and confusing the bers that the assessment of the patient’s competency
patient. Some selection of information is required, is not an assessment of the patient’s total ability to
and the disagreement centers on which principle of manage all his or her affairs; it is just the assessment
selection to adopt. of whether at this moment the patient can (1) receive
Two different proposals have been adopted by the information relevant to giving or refusing
America’s courts (Rozovsky, 1990). The first is the informed consent for this particular treatment, (2)
professional practice standard, which maintains that a remember that information, (3) appropriately assess
consent is informed if the patient has been provided and use that information to make a decision, and (4)
the information that reasonable medical practition- make a decision (B. A. Brody, 1988). Although no for-
ers would normally provide under similar circum- mal test exists to ensure that the patient has the
stances. The second is the reasonable person standard, capacity to perform items 1 through 4 in the list, a
which maintains that a consent is informed if the careful discussion with the patient usually will enable
patient has been provided the information that a rea- the physician to ascertain whether these criteria are
sonable person would need to have to make a deci- satisfied. If doubt remains, one should obtain consent
sion about whether to undergo the therapy in from both the patient and the surrogate.
question. The information to be provided would pre- A second difficulty involves teenage patients.
sumably fall under the categories shown in Table 7-1. Informed consent is obtained from parents before
Most commentators have argued for the second one treats children, but from patients once they
standard because it best corresponds to the goals of become adults. How should physicians treat teenage
informed consent, but a majority of courts have patients? Most states have passed special laws allow-
adopted the usually less demanding professional ing physicians to treat them after obtaining only

73
 Chapter 7 Ethics in Family Medicine

their consent when (1) the treatment is for venereal Even in those cases in which noncompliance
disease, pregnancy or contraception, or drug-related represents an informed and competent refusal of the
problems; (2) they are living away from their parents physician’s recommendations because the patient’s
and are responsible for their own affairs; or (3) they values differ, mutually acceptable alternative treat-
are married. Other cases, such as abortion, are more ments are often available. Consider a patient who
problematic (Ford et al., 2004; Holder, 1985). refuses to stay in a hospital for a full evaluation
because the patient is concerned about the need to be
The Noncompliant Patient home to handle personal problems. Such a patient
should be scheduled for an outpatient evaluation,
Implicit in the principle of informed consent—the even if it is not as satisfactory as a full evaluation in
principle that medical treatment can be provided the hospital. Respecting patient values in cases of
only after the patient has freely and knowingly con- noncompliance is not a matter of letting the patient
sented to it—is the concept that a patient may win a power struggle; it is, more often, finding a
choose not to comply with the physician’s recom- mutually acceptable, although not necessarily opti-
mendations and that the choice not to comply must mal, course of action. A failure to seek out such alter-
be respected. This concept can be misunderstood, natives often may represent a lack of respect for the
however, leading to a quick, facile, and inappropriate patient.
acceptance of a patient’s noncompliance before its A form of noncompliance that deserves special
meaning is properly understood. attention is the patient who does not fill the pre-
Most cases of noncompliance involve failures of scription that the doctor writes. This is sometimes
communication, lack of trust as a result of previous the result of the patient’s financial condition. The
bad experiences, and psychological and psycho- optimal medication from the physician’s perspective
pathologic factors. Only a minority of cases involve may cost too much from the patient’s perspective.
a true value difference between the physician and Particularly when dealing with patients who have
the patient. This finding has profound implications high medication bills because they need so many
for the clinical management of noncompliance. drugs or with patients who have very limited means,
Physicians confronting noncompliant patients need physicians should raise the question of cost frankly
to assess the noncompliance, evaluate its cause, and and explore less expensive but satisfactory (even if
react appropriately. Table 7-2 indicates how such a not optimal) medications.
noncompliance assessment would proceed. In short, A similar problem often arises when one consid-
morality does not call on the physician to accept at ers the question of side effects of various drugs.
face value every episode of noncompliance on the Different patients with different values and different
part of the patient. Doing so may in fact constitute a tolerances may find certain side effects unacceptable.
form of disrespect for the patient. What morality The physician certainly should not assume that a
does call for is a full evaluation of the cause of the pattern of side effects that is acceptable to the physi-
noncompliance, appropriate responses where possi- cian will be acceptable to the patient. Taking the
ble to eliminate the cause, and respect for patient’s values into account in deciding which anti-
the patient’s noncompliance only when it is an hypertensive medication to order is a far clearer
informed and competent refusal that is based on a example of respecting the patient’s values than sim-
difference between the patient’s and the physician’s ply accepting a patient’s noncompliance with a par-
values. ticular prescription.

Table 7-2 Evaluation of Noncompliance

SPECIAL PROBLEMS IN TERTIARY
Cause Clinical Response CARE SETTINGS
Problem in Patient should be
Quality of care can be improved by careful atten-
communication reinformed about the
need for treatment
tion to the components examined thus far: the
Failure of trust Address question of physician-patient relationship, medicine as a pro-
mistrust; involve other fession, confidentiality, informed consent, and the
health professionals promotion of patient compliance. When the focus
who may be trusted shifts from primary care provided by the family
Psychological factors Treat anxiety, depression, physician to care provided by subspecialists in terti-
and so on ary care settings, new problems arise and old prob-
Value conflict Respect patient wishes lems become even more complicated. The next two
From Rakel RE. Textbook of Family Practice, 4th ed. sections examine ways of resolving some of these
Philadelphia: W.B. Saunders, 1990. problems.

74
 Chapter 7 Ethics in Family Medicine

context of the family, the primary care physician is

Referrals
ideally suited to manage the patient throughout the
Decisions regarding referrals and consultations are referral.
often accompanied by great confusion. Referrals to When initiating a referral, the primary care
subspecialists practicing in tertiary care institutions physician’s responsibilities are to educate the patient
can provoke anxiety on the part of patients. The as to the reasons for referral, to recommend a sub-
referring physician risks losing a patient and a specialist or treatment center best suited to the
substantial amount of money and is subject to em- patient’s medical and personal needs, to prepare the
barrassment if a mistake is discovered. Referrals patient for what lies ahead, and to provide the spe-
sometimes degenerate into power struggles between cialist with data relevant to the patient’s illness. Even
subspecialists and generalists. Because primary care after the referral, the primary care physician remains
is a community-based discipline, there is much responsible for the quality of the patient’s care. This
debate and little consensus as to the primary care may require translating medical jargon to patients or
physician’s role in the tertiary care setting (Christie patient preferences to subspecialists and hospital
and Hoffmaster, 1986). The following guidelines staff, coordinating the activities of the various con-
about appropriate referrals and about continuity sultants, mediating disputes between consultants,
through referrals are intended to help clarify these ensuring that confidentiality is maintained by the
responsibilities and thus ease the tension and health care team, and counseling patients and their
improve the quality of care. families. The referral process is not complete until
Decisions to use consultants should be based on the subspecialist and the primary care physician have
a realistic assessment of the potentialities and limita- discussed all findings, treatments, results, and rec-
tions of primary care as a discipline, of oneself as a ommendations and the primary care physician has
physician, and of the facilities available in one’s geo- discussed these with the patient (Christie and
graphic region. Unfortunately, a number of other Hoffmaster, 1986).
factors (financial and institutional as well as med- Sometimes subspecialists disagree as to how to
ical) often cloud the decision-making process and manage a particular disorder. Consider the different
disrupt relations between primary and tertiary care way that surgeons and cardiologists may treat carotid
physicians. artery disease. Or consider the range of approaches,
Many subspecialists in oversubscribed areas within particular subspecialties, in treating par-
have taken it on themselves to enter primary care as ticular disorders: differences among gynecologists
a means of bolstering their incomes, despite their regarding indications for a hysterectomy and differ-
inadequate training in this area. Conversely, primary ences among neonatologists in managing severely
care physicians sometimes feel pressured to go handicapped infants. This makes the referring physi-
beyond their areas of expertise for financial and cian’s task a difficult and delicate one. The referring
professional reasons: They fear losing the patient and physician must be aware of the differences between
the income and fear that their seeking consultation subspecialties and between particular physicians
might reinforce the misconception that primary care within a subspecialty. The referring physician must
physicians are inferior. know the patient and the patient’s family well
Knowing when to use consultants requires enough to recommend the appropriate subspecialist.
courage and humility. Courage is the ability to act In many cases, the principle of informed consent will
competently and wisely without being swayed by mandate that the referring physician educate the
irrational fears. Some primary care physicians, moti- patient and the family as to the strengths and weak-
vated by unrealistic fears of mistakes and exposure, nesses of the available options. Primary care physi-
refer too early. Humility, on the other hand, is the cians should help their patients find a subspecialist
willingness to recognize one’s actual limitations and who will be appropriate to both their medical needs
to act accordingly. Some primary care physicians, and their personal preferences.
unaware of their limitations, refer too late. A proper
combination of courage and humility, along with Financial Gatekeeping
good working relationships with subspecialists, can
prevent most of the problems involved in referring The soaring costs of health care have led corp-
too early or too late. orations and government agencies to develop
Even if the primary care physician does decide prospective payment systems and capitation plans,
to refer the patient, he or she remains the patient’s with primary care physicians often serving as
primary physician (Christie and Hoffmaster, 1986). gatekeepers of the health care network. It is hoped
Equipped with a strong knowledge of general medi- that this will save money and streamline the
cine, the patient’s medical history, and the patient’s referral process. However, it might drive a bureau-
personal traits and committed to treating the disease cratic wedge into the physician-patient relation-
in the context of the person and the person in the ship, allow money to compete with quality in

75
 Chapter 7 Ethics in Family Medicine

determining the standard of care, and inhibit the In medical school and residency, young doctors
physician’s freedom to practice an individualized often learn to put their careers ahead of self and fam-
style of medicine. ily (Gabbard and Menninger, 1988). This dedication
Prospective reimbursement systems (such as the is, in some ways, good. Young physicians want to do
Medicare Diagnosis-Related Group system) save everything they can to help their patients, but this
money by limiting the reimbursement available to is often coupled with an unrealistic perception of
physicians, thereby encouraging them to do less. their capabilities and those of their profession. They
Designers of such systems have the legitimate right allow their egos to become too closely identified with
to require physicians to avoid wasteful procedures their successes and failures. They become obsessed
and referrals; this prevents unnecessary expenditures with insecurity (they are not good enough) and
and ensures a more just distribution of health care guilt (they do not work hard enough). They worry
expenditures. Such limitations do not, however, pre- that they might have missed a diagnosis and fear that
clude the physician’s responsibility to offer the their patients will die or suffer unnecessarily.
patient the best possible care within the limitations Physicians are not supposed to make mistakes, but
set by those policies. When particular patients they do. Their profession requires staying on top of
require care in excess of the normal level of reim- an ever-expanding field of knowledge; adeptness at a
bursement, the primary care physician confronts a wide range of techniques and skills; making the right
major ethical dilemma. decision when fatigued, hassled, or angry; picking up
Considerable controversy exists as to whether on subtle clues or poorly articulated symptoms; and
physicians should do everything that might benefit juggling a plethora of human needs. Mistakes are
each patient without regard to costs or other societal inevitable, but talking about them is taboo. The only
considerations or whether physicians must not be place mistakes are openly discussed, it seems, is the
allowed to ignore the bottom line (Holleman et al., courtroom (Hilfiker, 1985). To be more effective cli-
1997). Traditionalists tend to ignore the fact that nicians, physicians must learn to acknowledge their
financial considerations always have limited the capacity to err and must learn to discuss errors in a
quality of care available to the poor. The question we constructive manner. Physicians who do not admit
are now confronting is whether these considerations their mistakes are doomed to repeat them. Physicians
may legitimately limit the quality of care available to who discuss their mistakes can learn from them and
everyone. experience healing in the process.
In caring for individual patients, physicians The physician who takes the time to care for per-
should distinguish between providing what the sonal and family needs is a more effective clinician
patient wants and what the patient needs. The con- because he or she is better able to cope with the
troversy concerns whether all procedures and serv- stresses and strains of a demanding profession. Also,
ices likely to benefit the patient, as evidenced by in the case of primary care physicians whose patients
outcome data, should be made available to the know them well, the physician will become a role
patient. When patients request unnecessary or mar- model for personal health and fitness.
ginally beneficial procedures and services, however, Another area in which physicians must learn to
physicians must refuse. accept their humanity, and the humanity of their
patients, is the area of emotions. Clinicians must help
patients recognize, express, and interpret their emo-
THE PHYSICIAN AS HUMAN BEING tions. Clinicians must become aware of their own
emotions, recognize their clinical value, and learn how
The medical profession has, in the past few decades, to express and interpret them. The physician who
achieved truly impressive gains in the battle against ignores the emotions dehumanizes the physician-
sickness, suffering, and death. Diseases that killed patient relationship. The primary care physician who
their victims just a generation ago are now manage- improperly expresses, uses, or interprets emotional
able, curable, or even preventable. Yet physicians factors deprofessionalizes that relationship. Tradi-
seem remarkably inept at maintaining their own tionally, physicians have been trained to maintain
health and well-being; they have high rates of alco- objectivity, affective neutrality, and clinical detach-
holism, substance abuse, divorce, burnout, and sui- ment. To be scientific, however, does not preclude rec-
cide (Doan-Wiggins et al., 1995; Fields et al., 1995; ognizing the legitimacy of emotions or the necessity of
O’Connor and Spickard, 1997). Why can’t the healers empathy as a legitimate clinical and moral response to
heal themselves, and what can they do to get on the suffering. Sometimes a patient’s feelings offer a clue to
road to recovery? To deal with these problems, his or her symptoms. Sometimes a physician’s feelings
we recommend that physicians learn to distin- in response to a patient offer a clue to the patient’s
guish between competence and perfectionism, dedi- problem. Suffering patients need a physician who will
cation and workaholism, and compassion and suffer alongside them and who will help them to
sentimentalism. express and interpret their feelings. When their

76
 Chapter 7 Ethics in Family Medicine

patients suffer, physicians suffer too. The physician 1991). They regard such action as an acknowledgment
who suffers alongside a suffering patient or family of medical hubris and an expression of medical com-
allows the opportunity for healing of self as well as of passion and willingness to support the autonomous
the patient or family. Many of the physician’s feelings, wishes of patients. The American Medical Association
however, cannot be appropriately expressed in the (AMA), however, and a number of prominent physi-
clinical encounter. To maintain personal well-being, cians and ethicists have opposed efforts to legalize
therefore, the physician must find appropriate outlets euthanasia and physician-assisted suicide (Gaylin
for expression and interpretation. et al., 1988). Physician participation in euthanasia and
assisted suicide would, in their view, violate the
Hippocratic Oath, confuse patients, erode trust, and
EUTHANASIA AND ASSISTED SUICIDE tarnish medicine’s image as a healing profession.
The most widely publicized model of physician-
The issues of euthanasia and assisted suicide have endorsed euthanasia is found in The Netherlands,
provoked considerable public debate and challenged where the government does not prosecute physi-
long-standing notions of the physician-patient rela- cians who abide by an agreed-on standard of care (de
tionship and the nature of the medical profession. In Wachter, 1992). The criteria for euthanasia are that
the coming years, patients may turn increasingly to the patient’s suffering must be intolerable despite
their family physicians for assistance in dying, and aggressive relief efforts; there must be a low proba-
thus it is important for family physicians to be pre- bility of improvement; the patient must be rational
pared to respond appropriately. and fully informed; the patient’s requests for
For some time, most Americans have favored euthanasia must be voluntary and repeated consis-
legalization of some methods of ending the life of a tently over a reasonable period of time; and two
seriously ill or impaired person. In November 1993, physicians must accede to the request.
1254 adult Americans were asked whether they Some patient advocacy organizations, most
thought that the law should allow doctors to comply notably the Hemlock Society and Choice in Dying
with the wishes of a dying patient in severe distress (formerly Society for the Right to Die), urge the
who asks to have his or her life ended. Seventy-three adoption of similar standards in the United States,
percent responded “yes.” Public support of assisted with the government protecting physicians from
death has increased steadily over the past decade. In criminal and civil litigation. These parties believe
1982, 53 percent responded affirmatively to the same that aggressive attempts to prolong the lives of ter-
question, and in 1987, 62 percent (Taylor, 1993). minally ill persons are unnatural and torturous and
Many fear that aggressive measures to keep them that euthanasia or assisted suicide is sometimes the
alive, administered against their will, might inflict most humane alternative. Others, including many of
more suffering and indignity than they wish to bear the prolife organizations, hold that the taking of a
(Cowart and Burt, 1998). Others worry that the pain human life is what is unnatural and immoral and
and debilitation of the illness itself might become that patients and physicians should always, in the
unbearable and want the assurance that escape words of the Hebrew scriptures, “choose life.” They
through euthanasia or assisted suicide is available. also express a practical concern that acceptance of
These are legitimate concerns: A recent study sug- this practice will lead to a slippery slope involving
gested that terminally ill patients frequently are involuntary as well as voluntary euthanasia and
overtreated against their will and that physicians euthanasia for patients who are not terminally ill or
continue to undertreat pain despite advances in pain not experiencing unbearable suffering. They point
and symptom management (Solomon et al., 1993). to an apparent erosion of standards in The
Another study has shown that most terminal geri- Netherlands, where, for example, 1000 incompetent
atric patients prefer palliative care but that these patients are euthanized per year (ten Have and Welie,
“patients . . . exert strikingly little influence in the 1992). (Supporters respond that the percentage of
making of the treatment decision” and frequently are life-terminating acts performed without the explicit
misinformed regarding the terminal nature of their request of the patient is relatively small, this percent-
condition (Prigerson, 1992). A major factor, accord- age is stable or shrinking rather than growing,
ing to the study, is physicians’ own discomfort with and most of these cases represent patients who
death. Physicians practicing in teaching hospitals requested euthanasia before becoming incompetent
were found to be particularly uncomfortable with [Pijnenborg et al., 1993; van Delden et al., 1993].)
death, less likely to disclose a terminal diagnosis, and Physician-assisted suicide has been proposed
more likely to provide curative treatment in the last as a way to minimize the role of the physician in
months of life (Prigerson, 1992). the action causing the death of the patient while
Some physicians have urged colleagues to take a enabling the physician to provide expertise necessary
more active role in helping patients who request assis- to make the death as painless as possible. The patient
tance in dying (H. Brody, 1992; Kevorkian, 1991; Quill, feels a greater sense of control, and the image of the

77
 Chapter 7 Ethics in Family Medicine

medical profession is not tainted by a stigma of mur- remains unbearable despite the best care available
der attached to the event. and who requests assistance in dying (H. Brody,
On October 27, 1997, the State of Oregon legal- 1992). Patients with severe physical disabilities, such
ized physician-assisted suicide. The Death with Dignity as those with amyotrophic lateral sclerosis, advanced
Act allows physicians to prescribe a lethal dose of bar- Parkinson’s disease, or quadriplegia, also might
biturates or other controlled substance to patients who request assistance in dying. Hospice care offers much
are terminally ill. To qualify, the patient must be an less for these patients, and they may turn to their
adult resident of Oregon and must make one written family physician for help. Many family physicians
and two oral requests; at least 15 days must separate the would like to assist such patients but fear legal reper-
two oral requests. Primary physician and consultant cussions. What should those physicians do?
must confirm the terminal diagnosis and prognosis as It is disingenuous to deny assistance on the basis
well as the patient’s competence. If either physician of pragmatic considerations, such as slippery slopes,
suspects depression or other psychiatric disorder, they outbreaks of mercy killings, and mistrust of white
must refer for counseling. The primary physician must coats. Withholding and withdrawing treatment also
inform the patient of all reasonable alternatives such as could create slippery slopes and also have been
pain and symptom management and hospice care and opposed on the basis of inflated fears, but these
report all lethal prescriptions to the Oregon Health concerns are now considered insufficient to justify a
Division. The physician may not administer the med- prohibition against these practices. Most Americans
ication (Angell, 1999; Chin et al., 1999). know the difference between the euthanasia as
No significant abuses of the Oregon law have murder and the type of assisted dying currently
been reported to date. During the first year, only being discussed, limited to patients suffering unbear-
15 persons chose to end their lives under the terms of ably despite aggressive efforts to relieve physical and
the law; all but two had metastatic cancer (Angell, psychological pain, who request assistance volun-
1999; Chin et al., 1999). Some ethicists have observed tarily and who receive voluntary, compassionate,
that the preference for assisted suicide over euthanasia competent assistance by their physicians. A review
reflects a cosmetic distinction analogous to the now- process should, of course, be established to ensure
obsolete distinction between withholding and with- that these criteria are met (H. Brody, 1992).
drawing treatment. Regardless of the methods, the From an ethical perspective, the essential issue is
motives and outcome are the same. Preoccupation whether the long-standing prohibition against killing,
with taints and stigmas reflects more concern for which many regard as absolute, should outweigh all
image than integrity and also may indicate a lack of other considerations, such as the patient’s autonomy
courage rather than a commitment to principle. or the degree of pain and suffering. Or does the situ-
Another concern is that, in this era of cost con- ation of unbearable pain and suffering pose a special
tainment, dying patients will feel unduly pressured situation that our society ought to regard as an excep-
to choose suicide rather than spend society’s, and tion to the general prohibition of killing, through
perhaps their family’s, limited resources. Although granting some types of patients the right to waive
such external pressure would be inappropriate, this their right not to be killed? These two horns of the
does raise the question of whether patients have an dilemma embody the crux of the issue, and all other
ethical obligation to limit the costs of their care as concerns should be regarded as peripheral.
they approach the end of life (Hardwig, 1997). At present, assistance in dying is illegal in most
Hospice physicians, who have pioneered in the of the United States and much of the world. Whether
development of pain and symptom management for the legislatures and the courts should stand in the
terminally ill persons (Ogle et al., 1992; Saunders, way of physicians who, with compassion and com-
1967), offer help to get beyond the impasse of those petence, are willing to assist this small category of
physicians who feel torn between wanting to relieve the patients is an issue that our society is in the process
suffering of the dying but not wanting to serve, directly of resolving. The ethical obligation for primary care
or indirectly, as the cause of their patient’s death. physicians remains to help patients live and die with
Hospice medicine has shown that the pain of dying as much dignity, control, and comfort as possible in
persons usually can be palliated by aggressive pharma- light of whatever decision society makes.
cologic treatment as well as by attention to “total pain,”
which includes all the physical, emotional, social, spir-
itual, and financial sources of the patient’s suffering. CONCLUSION
The existence of this expertise, and the relative ease
with which a family physician can master it, implies an The ethical questions faced by physicians have been
obligation to use these methods and, when necessary, transformed, in ways we have indicated, by chang-
to seek consultation from palliative care specialists. ing economic, social, legal, political, and scientific fac-
An ethical dilemma persists, however, in the tors. In the end, however, the ethics of medicine
occasional case of a patient whose pain or suffering remain committed to a view of the patient-physician

78
 Chapter 7 Ethics in Family Medicine

relationship as a relationship between two auto-

Material Available on Student Consult
nomous human beings—a patient who is suffering
and seeks help and a physician who maintains profes- Review Questions and Answers about Ethics in
sionalism, humanity, and a systemic perspective. Family Medicine

REFERENCES
Angell M. Caring for the dying—Congressional mischief. Holleman WL, Holleman MC, Moy JG. Are ethics and
N Engl J Med 1999;341:1923–1925. managed care strange bedfellows or a marriage made in
Brody BA. Life and Death Decision Making. New York: heaven? Lancet 1997;349:350–351.
Oxford University Press, 1988. Holleman WL, Matson CC. Preemployment evaluations:
Brody H. Assisted death—a compassionate response to a Dilemmas for the family physician. J Am Board Fam
medical failure. N Engl J Med 1992;327:1384–1388. Pract 1991;4:95–101.
Bruce JAC. Privacy and Confidentiality of Health Care Jonsen AR, Siegler M, Winslade WJ. Clinical Ethics: A
Information, 3rd ed. Chicago: American Hospital Practical Approach to Ethical Decisions in Clinical
Association, 1996. Medicine, 5th ed. New York: McGraw-Hill, 2002.
Chin AE, Hedberg K, Higginson GK, Fleming DW. Kevorkian J. Prescription-Medicine: The Goodness of
Legalized physician-assisted suicide in Oregon—the Planned Death. Buffalo, NY: Prometheus Books,
first year’s experience. N Engl J Med 1999;340:577–583. 1991.
Christie RJ, Hoffmaster CB. Ethical Issues in Family O’Connor PG, Spickard A Jr. Physician impairment by sub-
Medicine. New York: Oxford University Press, 1986. stance abuse. Med Clin North Am 1997;81:1037–1052.
Cowart D, Burt R. Confronting death: Who chooses, who Ogle KS, Warren D, Plumb JD. Pain management in
controls? Hastings Cent Rep 1998;28:14–24. advanced cancer. Primary Care 1992;19:793–805.
de Wachter MAM: Euthanasia in the Netherlands. Hastings Pijnenborg L, van der Maas PJ, van Delden JJM, Looman
Cent Rep 1992;22:23–30. CWN. Life-terminating acts without explicit request of
Doan-Wiggins L, Zun L, Cooper MA, et al. Practice satis- patient. Lancet 1993;341:1196–1199.
faction, occupational stress, and attrition of emergency Prigerson HG. Socialization to dying: Social determinants
physicians. Acad Emer Med 1995;2:555–563. of death acknowledgment and treatment among termi-
Fields AI, Cuerdon TT, Brasseux CO, et al. Physician nally ill geriatric patients. J Health Soc Behav 1992;
burnout in pediatric critical care medicine. Crit Care 33:378–395.
Med 1995;23:1425–1429. Quill TE. Death and dignity: A case of individualized deci-
Ford C, English A, Sigman G. Confidential health care for sion making. N Engl J Med 1991;324:691–694.
adolescents: Position paper for the society for adoles- Rozovsky FA. Consent to Treatment: A Practical Guide,
cent medicine. J Adolesc Health 2004;35:160. 2nd ed. Boston: Little, Brown, 1990.
Freedman B. Respectful service and reverent obedience: Saunders CM. The Management of Terminal Illness.
A Jewish view on making decisions for incompetent London: Hospital Medicine, 1967.
parents. Hastings Cent Rep 1996;26:31–37. Smith HL, Churchill LR. Professional Ethics and Primary
Gabbard GO, Menninger RW, eds. Medical Marriages. Care Medicine: Beyond Dilemmas and Decorum.
Washington, DC: American Psychiatric Press, 1988. Durham, NC: Duke University Press, 1986.
Gaylin W, Kass LR, Pellegrino ED, Siegler M. “Doctors Tarasoff v Regents of The University of California, 131 Cal
must not kill.” JAMA 1988;259:2139–2140. Rptr 1976.
Hardwig J. Is there a duty to die? Hastings Cent Rep Taylor H. Majority support for euthanasia and Dr.
1997;27:34–42. Kevorkian increases. The Harris Poll 1993;63.
Hilfiker D. A Physician Looks at His Work. New York: ten Have HAMJ, Welie JVM. Euthanasia: Normal medical
Pantheon Books, 1985. practice? Hastings Cent Rep 1992;22:34–38.
Holder A. Legal Issues in Pediatrics and Adolescent van Delden JJM, Pijnenborg L, van der Mass PJ. The
Medicine. New Haven, CT: Yale University Press, 1985. Remmelink study: Two years later. Hastings Cent Rep
Holleman WL, Holleman MC. School and work release 1993;23:24–27.
evaluations. JAMA 1988;260:3629–3634.

79
 C h a p t e r

8 Family Dynamics and Health

Therese Zink

KEY POINTS

1. Domestic violence/intimate partner violence/ out, school problems, withdrawal, aggressiveness

abuse (IPV) includes physical injury and threats, and disrespect toward the mother, increased
sexual coercion or threat, and emotional abuse involvement in risky behaviors (drugs, sex, alco-
(such as humiliating the victim, controlling what hol), psychological problems such as depression,
the victim can and cannot do, and isolating the anxiety, and posttraumatic stress disorder, eating
victim from family and friends). disorders, and chronic physical complaints.
2. The lifetime prevalence of IPV is 7.6% for men 6. Screening should be done in private without
and 25% for women. partner or children present. Family members
3. Domestic violence affects the health of the should not be used to translate conversations
entire family. about abuse.
4. IPV victims have increased risk of poorer health, 7. Be nonjudgmental with the victim. Validate that
depressive symptoms, substance use, developing no one deserves to be hurt, share resources, and
a chronic disease, chronic mental illness, and schedule a follow-up visit at your office.
injury. 8. If you are caring for both the victim and perpe-
5. Exposure to the abuse between adults is associ- trator, maintain strict confidentiality, and always
ated with behavioral problems such as acting be cognizant of the victim’s safety.

INITIAL VISIT vaginal deliveries. Workup for gastric reflux; irritable

bowel syndrome. Postpartum depression after last
Subjective two pregnancies. Many no-show appointments. Once
when she accompanied her child to a visit, Mrs. B.
Patient Identification and Presenting Illness had a black eye. She had an emergency department
Mrs. Mary B. is a 34-year-old woman who is first seen visit for cracked ribs.
with a headache. The headache gets worse as the day
goes on. Sometimes she goes to bed with the headache, Family History
and on other days, she wakes up with the headache. No Father: hypertension. Mother: diabetes, migraines.
photophobia or nausea is present. Pain is described as
throbbing and pounding, involving the entire head,
especially the temples. Health Habits
Her husband and children also are seen at the Occasional glass of wine or bottle of beer, one pack
clinic. Two of the children have been diagnosed with of cigarettes per week, intermittent exercise.
attention-deficit/hyperactivity disorder (ADHD).
Her husband has been treated for depression and Social History
high blood pressure. Mrs. B. lives with her husband and three children.

Medical History Review of Systems

Surgical history: appendectomy, tubal ligation. Ongoing irritable bowel syndrome, current manage-
Obstetrics: Gravida 3, Para 3, normal spontaneous ment plan working.

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

80
 Chapter 8 Family Dynamics and Health

Objective Prevalence
Mrs. B is reserved and gives intermittent eye contact. From 11% to 22% of adult women seeking care in
Blood pressure is 120/70, pulse is 72, weight is 140 lb, primary care practices have experienced physical
height is 5 feet 5 inches. Lung and heart examinations abuse in the past year. IPV affects one of every four
are normal. Her neurologic examination is normal. women in the United States. Men also are victims,
but the prevalence is 1 in every 14 men, and the
Assessment degree of injury is much less. The lifetime prevalence
is 7.6% for men and 25% for women. The 1-year
The diagnosis is tension headache, but her poor eye prevalence of IPV is 0.9% in men and 1.5% in
contact, the history of irritable bowel syndrome, women. IPV occurs in all socioeconomic categories,
postpartum depression, frequent no-shows, and among all ethnic groups, and in both heterosexual
injuries are red flags for intimate partner violence and same-sex relationships. An estimated 3.3 to 10
(IPV)/domestic violence (DV). When Mrs. B is asked million children witness IPV annually in the United
about her relationship with her husband, she replies States (Tjaden and Thoennes, 2000● B).
curtly that all is fine. You respect her answer but
inform her that DV is common and that local
resources are available in case she knows anyone who Health Care Costs
might need them, and you point to the local DV The estimated total cost of IPV (including IPV rape,
agency’s pamphlets in your office. physical assault, and stalking) against adult U.S.
women is $5.9 billion (1995 dollars). Nearly $4.1
Plan billion is for direct medical and mental health care;
$0.9 billion is lost productivity from paid work and
Tension headaches are treated with stretching exer- household chores for victims of nonfatal IPV; and
cises and ibuprofen. Because of the red flags for for IPV homicide, $0.9 billion is lost in lifetime earn-
domestic violence, a follow-up visit is arranged, and ings. Victims of IPV cost the health care system 50%
the need for further DV assessment is noted. more than do nonvictims (National Center for
Injury Prevention and Control, 2003● B).

DISCUSSION
Health Effects
Abusive family dynamics affect the health and well-
being of every family member. To date, identification Domestic violence affects the health of the entire
and care of the adult victim of abuse has received the family. A retrospective cohort survey of adults at
most attention. Intimate partner violence and domes- Kaiser Permanente found that adverse childhood
tic violence are often used interchangeably. experiences (emotional, physical, and sexual abuse;
Although current evidence does not support or a battered mother; parental separation or divorce;
refute the effectiveness of the universal screening for growing up with a substance-abusing, mentally ill, or
DV in the medical setting, professional organizations incarcerated household member) were associated
recommend identifying patients and sharing with more high-risk behaviors and health conditions
resources (American Medical Association, 1992 ● C; than in patients reporting no adverse events in child-
U.S. Preventive Services Task Force, 2004 ● C ). Iden- hood. These conditions include unintended preg-
tifying DV and helping patients understand the nancy, sexually transmitted infections, alcohol abuse,
impact of this stress on their health and the health of smoking, suicide, depression, and risk factors for
their children are important for quality health care. heart disease, chronic lung disease, and liver disease
This chapter reviews the definition of DV/IPV, (Felitti et al., 1998●
B).

prevalence, cost in dollars, health care consequences

for all family members, tools for identification, rec- Victims
ommended management, and mandatory reporting
obligations. Studies show that both male and female IPV victims
have increased risk of poorer health, depressive symp-
Definition toms, substance abuse, developing a chronic disease,
chronic mental illness, and injury (Campbell, 2002 ●B;
The Centers for Disease Control defines IPV as phys- Coker et al., 2002 ●
B ) (Table 8-1).
ical and sexual abuse or threat of physical or sexual
abuse, or emotional/psychological abuse such as Perpetrators
humiliating the victim, controlling what the victim Less is known about the health of IPV perpetrators.
can and cannot do, and isolating the victim from Often substance abuse is a problem. Otherwise
family and friends, or a combination of these. perpetrators are a heterogeneous group with a wide

81
 Chapter 8 Family Dynamics and Health

Table 8-1 Red-flag Symptoms and Table 8-2 Red-flag Symptoms and
Conditions for Victims Conditions for Children
Exposed
■ Injuries (Ask about the mechanism of the
inquiry; if mechanism does not make sense ■ Symptoms of post-traumatic stress
consider probing further in a nonjudgmental ■ Sleep difficulties
manner.) ■ Hypervigilance, poor concentration, and
■
Digestive problems (diarrhea, spastic colon, distractibility (ADHD/hyperactivity)
constipation, nausea, loss of appetite) ■ Behavioral problems, school problems
■ Chronic pain (headache, abdominal pain, pelvic ■ Depression
pain, back pain, etc.) ■ Anxiety
■ Genitourinary problems (infections, sexually ■ Chronic somatic complaints (abdominal pain,
transmitted diseases, pelvic pain, menstrual headaches, etc.)
problems, sexual dysfunction) ■ Aggressiveness toward other children
■ Vague somatic complaints (fatigue, dizziness) ■ Teens are more likely to participate in risk-
■ Mental health issues (depression, anxiety, post- taking behaviors such as smoking, drinking,
traumatic stress disorder, substance abuse, using illegal drugs, eating disorders, and
suicide) pregnancy
■ Eating disorders
■ Pregnancy problems (preterm labor, poor ADHD, attention-deficit/hyperactivity disorder
weight gain)
question. “Have you ever been in a relationship in
variety of needs. Some have depression; others have which your partner has pushed or slapped you?” is a
personality disorders, such as narcissistic or anti- direct screening question. See Table 8-3 for screening
social. Risk factors for perpetrating IPV include tools and questions.
witnessing DV in childhood, disrupted attachment Screening should be done in private without
patterns, high levels of interpersonal dependency partner or children present. Family members should
and jealousy, attitudes condoning DV, and lack of not be used to translate conversations about abuse.
empathy (Coben and Friedman, 2002; Holtzworth- No consensus exists on what method (written vs.
Monroe and Meehan, 2004). verbal) is the best for screening victims about abuse.
The most important factor is that the question is
Intimate Partner Violence–Exposed Child asked in a caring, sincere, and nonjudgmental man-
Exposure to the abuse between adults is associated ner. Often victims choose not to disclose the abuse.
with behavioral problems such as acting out; school This should not discourage the clinician from asking
problems; withdrawal; aggressiveness and disrespect the question, and demonstrating that the office is a
toward the mother; increased involvement in risky safe place to discuss IPV is important. Often patients
behaviors (drug and alcohol use, sex), psychological who initially denied the abuse will return to the
problems such as depression, anxiety, and posttrau- office at a later date and disclose the abuse when they
matic stress disorder; eating disorders; and chronic are ready to ask for assistance. If resources are avail-
physical complaints. A recent study of 5-year-old able to pick up in the office examination rooms and
twins demonstrated that children exposed to high lev- bathrooms, victims have the option of getting assis-
els of DV had IQs that were 8 points lower than those tance without telling anyone (National Advisory
of unexposed children, a dose-response relation. Committee, 2002● C ).
(Studies of lead poisoning document a loss of approx- Professional organizations recommend routine
imately 4 IQ points.) Urban children exposed to DV screening at annual examinations, during prenatal
had higher scores on the Child Behavior Checklist, care, and when associated symptoms/conditions, “red
indicating behavior problems, than did nonexposed flag conditions,” are present (see Table 8-1). The
B) (Table 8-2).
children (Kitzmann et al., 2003● American Academy of Pediatrics (AAP) recommends
routinely asking mothers about IPV at well-child vis-
Identification of the Intimate Partner its, well-teen visits, and when associated conditions
are present (Committee on Child Abuse and Neglect,
Violence Victim
AAP, 1998● C ) (see Table 8-2). Safety and privacy con-
A variety of questions and screening tools have been cerns exist about discussing IPV in front of children.
tested for IPV screening. Some questions are direct, The gravest concern is that the child will report the
and some are indirect. Both patients and clinicians discussion about the abuse to the perpetrator and that
seem to prefer more-indirect questioning for initial the perpetrator will retaliate with further abuse to the
assessment, with more-direct questions for further victim. Minimal documentation should be done in
evaluation. “Do you feel safe in your intimate rela- the child’s chart because the perpetrator, if a guardian,
tionship?” is an example of an indirect screening has access to the chart (Groves et al., 2002● C ).

82
 Chapter 8 Family Dynamics and Health

Table 8-3 Intimate Partner Violence Screening Questions and Tools

HITS (Sherin et al., 1998)
Written instrument
How often does your partner
1. Physically hurt you
2. Insult you or talk down to you
3. Threaten you with harm
4. Scream or curse at you

STaT (Paranjape et al., 2003)

1. Have you ever been in a relationship in which your partner has pushed or slapped you?
2. Have you ever been in a relationship in which your partner has thrown, broken, or punched things?
3. Have you ever been in a relationship in which your partner has threatened you with violence?

Woman Abuse Screening Tool (WAST) and WAST-Short (Brown et al., 2000)
1. In general, how would you describe your relationship? (a lot of tension, some tension, no tension)
2. Do you and your partner work out arguments with (great difficulty, some difficulty, no difficulty)?
3. Do arguments ever result in your feeling down or bad about yourself? (often, sometimes, never)
4. Do arguments ever result in hitting, kicking, or punching? (often, sometimes, never)
5. Do you ever feel frightened by what your partner says or does? (often, sometimes, never)
6. Has your partner ever abused you physically? (often, sometimes, never)
7. Has your partner ever abused you emotionally? (often, sometimes, never)

Partner Violence Screen (PVS) (Feldhaus et al., 1997)

1. Have you been hit, punched, or otherwise hurt by someone in the past year? If so, by whom?
2. Do you feel safe in your current relationship?
3. Is a partner from a previous relationship making you feel unsafe now?

Abuse Assessment Screen (AAS) (McFarlane and Parker, 1994)

1. Have you ever been emotionally or physically abused by your partner or someone important to you?
2. Within the last year, have you been hit, slapped, kicked, or otherwise physically hurt by someone?
If yes, by whom?
Husband, ex-husband, boyfriend, stranger, other
3. Within the past year, has anyone forced you to have sexual activities?
4. Are you afraid of your partner or anyone listed above?

General questions such as “How is your partner ence, their attachment to the abuser, their fear of the
treating you and the kids?” or “Do you feel safe in abuser, the severity of the abuse, their support sys-
your relationship with your partner?” are probably tems, fear of losing the children, and the children’s
okay, but more in-depth questioning or resource attachment to the abuser. A victim’s awareness of the
sharing should be done in private. If IPV is identified, impact of the abuse on the children often compels the
follow the same procedures as outline later. Helping victim to seek help. Seeking a life free of abuse is a
the mother make decisions about her safety is the best process. Some victims must leave the abuser, but
way to assure the safety of the children. Mothers are some will not. Leaving the abuser is the most danger-
often afraid that revealing IPV may put them at risk ous time for the victim. Matching interventions to the
for losing their children (Zink et al., 2003). patient/victim’s stage of coming to terms with his or
Because child abuse occurs in 30% to 60% of her abusive relationship may be helpful (Table 8-4).
homes with DV, the existence of child maltreatment in When a victim discloses abuse, the following
homes with DV should be assessed and, if suspected, steps are critical:
C ).
reported according to state laws (Groves et al., 2002●
■ Create a supportive and nonjudgmental environ-
Management of the Intimate Partner ment
■ Assess the impact of IPV on the victim’s health
Violence Victim
■ Assess the victim’s safety (Table 8-5)
Thinking of IPV management as requiring the same ■ Share local DV agency pamphlets and crisis num-
skills as the management of a chronic illness can help bers or the names of counselors knowledgeable
clinicians to be patient with a victim’s timing and about IPV
choices about seeking assistance. Victims weigh a ■ Respect the victim’s choices
number of issues, such as their financial independ- ■ Schedule a follow-up visit

83
 Chapter 8 Family Dynamics and Health

Table 8-4 Stages of Change and Matched Clinician Management

for Patient/Victims of Intimate Partner Violence
Stage of Change: Definition + Substages Physician Stage-matched Interventions

Precontemplation: patient/victim does not ■ Ask about IPV when there is an injury; ask
see the relationship as abusive how injury occurred.
■
Ask during pregnancy.
■ Ask routinely (annual exam and well-child/teen
exams) and for red-flag symptoms and illnesses.
■ Have and make pamphlets available. Do not
spend time reviewing them in detail.
■ Educate about the impact of IPV on the physical
and mental health of the victim and her children
■ Document suspicions about IPV. Assess safety.*
If any risk factors are present, share your concern
with the patient/victim and/or follow mandated
reporting guidelines.

Contemplation: patient/victim sees the relationship ■ Ask about IPV, as above. Despite nondisclosure,
as abusive and explores the pros and cons of women want to be screened.
different options to increase safety ■ Listen and watch for clues (hints or evidence of
Recognition of nondisclosure abuse). Victims are seeing if you are willing to
discuss the abuse.
■ Discuss observations about the abuser’s controlling
behavior: If you observe this, discuss your concern
in private with the patient/victim.
■ Have and make pamphlets available. Do not spend
time reviewing them in detail.
■
Educate about the impact of IPV on the physical
and mental health of the victim and her children
■ Document suspicions about IPV, Assess safety.*
If any risk factors are present, share your concern
with the patient/victim and/or follow mandated
reporting guidelines.

Recognition of disclosure ■
Affirm that abuse is occurring and that no one
(with disclosure, add the following to deserves to be abused.
other contemplation interventions) ■ Review local IPV crisis numbers with the
patient/victim.
■ Offer to have the patient call the crisis number
from a private room in your office.
■
Make referrals for counseling to a counselor
knowledgable about IPV for the patient and/or
her children.
■ Document subjective and objective findings. Consider
reviewing safety plan* with the patient/victim,
or have staff educated about IPV do this,
or have the patient do this with the IPV agency.

Action: patient/victim takes steps to Continue to ask about abuse, affirm that no one
create safety deserves to be abused, assess safety, review
local resources, and make referrals. Review
safety plan.

Maintenance: patient/victim has created Check on progress, affirm that no one deserves
ongoing safety to be abused.
Support positive changes, be nonjudgmental if
patient returns to abusive/unsafe situation.
Share concerns, and repeat steps from
contemplation.
IPV, intimate partner violence
*
Safety assessment/plan in Table 8-5.

84
 Chapter 8 Family Dynamics and Health

situations of conflict are resolved, before inquiring

Table 8-5 Safety Assessment and Plan
whether hitting or isolating actions are part of this. For
Safety Assessment example, “Do you find you want to hit her to make her
Ask about each of the following: see sense?” Focus on the abusive conduct, not on the
■ Suicide/homicide risk (victim and abuser)
explanations or rationalizations, and make the connec-
■ Abuser’s possession of weapons or threat to
tion between the perpetrator’s behavior and the vic-
use weapons tim’s injuries. For example, “When you hit her on
■
Drug and alcohol use (victim and abuser) Saturday night, you broke her nose. This is a criminal
■ Abuse of children

■ Abuse of pets
offence for which consequences follow. You need to
■ Escalating severity of abuse
make some changes, and we need to consider some
■ Increasing fear of abuser things you could do.” Help the perpetrator to see DV as
a health care issue and to understand that it negatively
Safety Plan affects him as well as his partner and children. Ask
■ Where to go what effect he thinks his violence has on the victim and
■ Important documents (bank account, birth
children and how it might change his relationship with
certificates, insurance records, etc.) them. Ask whether he wants the children to learn about
■ Health care related: medications, children’s
violence in relationships from him.
immunization records Several approaches to working with perpetrators
■ Money, keys, clothes, kids’ toys, etc.
will help increase the safety of the victim.
■
All information from the victim must be kept con-
Proper documentation is critical in case the vic- fidential from the abuser, even though he may be
tim decides to go to court. Include the following in her husband and expect access. Information from
the medical record: third parties also should be kept confidential
unless the victim specifically requests that infor-
■ DV screen completed mation be shared. Even before sharing information
■
Objective, descriptive documentation on all identi- with a perpetrator at the victim’s request, the pos-
fied signs of abuse. Record any noted injuries and sible dangers and consequences should be reviewed
include location, size, color, shape, and tenderness. with her.
■ Documentation of relevant clinical indicators (i.e., ■ Discussion with the perpetrator about DV should
laboratory values, radiographs, diagnoses) never be done in the presence of the victim.
■ Abuser name, date, time, and place that any injuries ■
Ways of discussing DV with perpetrators: Be clear
were sustained that you are discussing DV as a health care issue.
■ Objective descriptions of relevant patient behavior Unless the discussion is specifically covered in a
■ Relevant patient, family, and witness quotes reporting or duty-to-warn situation (fear of dan-
■ Photographs to document injury. Consent for ger to self or others), your discussions can remain
photographs must be obtained from adults. confidential. You are discussing a health care issue
■ Referrals made and resources provided in the same way that it would be discussed with any
Referrals might include the local DV agency or a patient and you are not there to be judgmental or
counselor familiar with IPV. It may take the victim to prosecute a crime.
time to follow up on your referrals. In the meantime, ■ Focus on specific descriptions of the abuser’s
schedule follow-up appointments at your office behaviors: “When you threw her to the couch”
(National Advisory Committee, 2002● C ; Zink et al., rather than “when you abused your wife,” or “your
2004a). use of physical force against your partner” rather
than “your domestic violence.”
■ Use a direct, calm approach, and do not continue if
Identification and Management of the perpetrator becomes angry or objects. He is
Perpetrators not ready to go further. You may simply want to let
Research demonstrates that perpetrators will admit the perpetrator know that you are concerned and
perpetration of IPV when questioned in the medical ready to discuss it further or make a referral when-
setting. However, perpetrators tend to minimize ever he is ready, and move back to the presenting
their violence, and some deny it altogether. Those medical issue. Be prepared that whatever you say
who do appear for help need support in their may be misquoted back to the victim.
decision, encouragement to take responsibility for
their actions, and appropriate referrals (Coben and Treatment Options
Friedman, 2002).
Be direct, starting with broad questions before Referral to accredited behavioral-change programs
becoming more specific. Ask how disagreements or or to therapists who have expertise in domestic

85
 Chapter 8 Family Dynamics and Health

violence counseling may be appropriate for some may be best to refer either the victim or the perpe-
perpetrators. However, the kinds of referrals that we trator to a partner or another clinician (Ferris et al.,
are accustomed to making in marital disputes such as 1997).
couples counseling are not useful and can escalate
the violence. Couples counseling endangers the vic-
Managing the Child Exposed to Intimate
tim if she reveals information about the abuse during
the sessions. It is unsafe for the victim to discuss the Partner Violence
issues that concern her in the abuser’s presence. Helping the mother create safety for herself is the
Anger management and alcoholism or drug- best way to help the children. Some communities
abuse programs deal with one aspect of the perpe- offer programs for children exposed to IPV. These
trator’s problem but do not get to the core. Many may be helpful. What works and what does not is not
communities have batterers’ intervention programs. clearly understood. Some child-protection agencies
What works and what does not is still unclear. No are knowledgeable about DV, and some are not.
program approaches have shown themselves to be Mandatory reporting of cases in which children
superior to other approaches. Your local DV agency witness IPV as child maltreatment is controversial.
can refer you to the local program for perpetrators Most states do not consider witnessing IPV as child
and should have some idea of its quality. abuse or neglect. Knowing the child maltreatment
The number of communities that have estab- and reporting statute of one’s state is the critical step
lished and enforce consequences for abuse is steadily for understanding reporting obligations. However,
growing, as are responses in which law enforcement, county officials and judges may vary in how they
courts, and domestic violence agencies form net- interpret the language (Groves et al., 2002● C ; Zink
works of cooperation for this purpose. et al., 2002●
B ).

Managing the Abusive Couple Mandatory Reporting for Intimate

In family medicine, it is not unusual to see both the Partner Violence
victim and the perpetrator as patients in your office. Most states (except California, Colorado, and
Confidentiality and safety are critical issues (Table Kentucky) do not require the clinician to report DV
8-6). If it becomes too difficult to care for both, it unless a weapon is used. In those states with manda-
tory reporting for DV, the follow-up procedures vary
among counties and are dependent on the amount of
training about DV provided to local law-enforce-
Table 8-6 Key Points for Managing the ment and social-service staff (National Advisory
Abusive Couple Committee, 2002● C).

■ Confidentiality: Maintain confidentiality about

your discussions with the victim and abuser. Do
not share information. Mandatory Reporting for Child
■ Documentation: Document discussions/findings Abuse/Neglect
in the patient’s chart. Do not document
information learned from the abuser in the
Clinicians are mandated to report child maltreatment
victim’s chart or vice versa. in all 50 states and the District of Columbia. Reports
■ Safety assessment of victim: Assess the victim are generally made to a government department of
for safety concerns. See safety assessment in social services, a child welfare agency, or the police.
Table 8-5. If safety becomes a concern, seek Immunity protection (usually civil and criminal)
input from domestic violence service agencies. from prosecution under state and local laws and reg-
■ Manner of leaving information/messages: ulations for individuals making good-faith reports of
Discuss with each patient about how to leave suspected child abuse or neglect was outlined in the
messages about appointments or test results. Child Abuse Prevention and Treatment Act of 1974.
Home okay, not okay? Cell phone? E-mail? You
Currently all jurisdictions provide immunity to
do not want to compromise the victim’s safety
by giving the abuser information that the
reporters. The most commonly encountered limita-
victim does not want the perpetrator to have. tion is the “good faith” reporting requirement.
■ Discuss abuse with the abuser only with the Immunity does not extend to reports made mali-
victim’s permission. Before doing so, develop a ciously or in bad faith. This means that a clinician is
safety plan with the victim. protected from civil or criminal liability for filing a
report made in good faith. Although these provisions
From Ferris L, Norton P, Dunn E, Gort E, Degani N.
Guidelines for managing domestic abuse when
may not prevent the filing of lawsuits, given the
male and female partners are patients of the good-faith limitation in some states, they generally
same physician. JAMA 1997;278:851–857. prevent negative outcomes for the clinician and

86
 Chapter 8 Family Dynamics and Health

other reporters. Clinicians who fail to report sus-

Material Available on Student Consult
pected child abuse may be held criminally or civilly
liable under the state’s reporting laws. In most states, Review Questions and Answers about Family
it is a misdemeanor and involves a fine or a short Dynamics and Health
time in the local jail (Zink et al., 2004b).

RESOURCES
National Domestic Violence Hotline (24-hour). 800-799- American Medical Association Domestic Violence Resources,
SAFE (7233). Translation services available for discus- www.ama-assn.org/ama/pub/article/3216-6827.html
sion about domestic violence. American Medical Women’s Association online CME
Family Violence Prevention Fund. www.endabuse.org course educates physicians about domestic violence.
National Resource Center on Domestic Violence. 800-537- Physicians can earn two CME credits at no charge.
2238 or www.ndvh.org www.dvcme.org

REFERENCES
American Medical Association. American Medical Kitzmann K, Gaylord N, Holt A, Kenny E. Child witness to
Association diagnostic and treatment guidelines for domestic violence: A meta-analytic review. J Consult
domestic violence. Arch Fam Med 1992;1:39–47.● C Clin Psychol 2003;71:339–352.● B
Brown JB, Lent B, Brett PJ, Sas G, Pederson LL. McFarlane J, Parker B. Preventing abuse during pregnancy:
Development of the woman abuse screening tool An assessment and intervention protocol. MCN Am J
for use in the family practice. Fam Med 1996;28: Matern Child Nurs 1994;19:321–324.
422–428. National Advisory Committee. National Consensus
Campbell JC. Health consequences of intimate partner Guidelines: On Identifying and Responding to Domestic
violence. Lancet 2002;359:1331–1336.● B Violence Victimization in the Health Care Setting. San
Coben JH, Friedman DI. Violence: Recognition, manage- Francisco, Family Violence Prevention Fund, 2002.
ment, and prevention: Health care use by perpetrators Available at www.endabuse.org. Accessed 9/27/05. ● C
of domestic violence. J Emerg Med 2002;22:313–317. National Center for Injury Prevention and Control. Costs
Coker AL, Davis KE, Arias I, et al. Physical and mental of Intimate Partner Violence Against Women in the
health effects of intimate partner violence for men and United States. Atlanta, Centers for Disease Control and
women. Am J Prev Med 2002;23:260–268.● B Prevention, 2003.● B
Committee on Child Abuse and Neglect, American Paranjape A, Sullivan L, Liebschutz J. STaT: A three ques-
Academy of Pediatrics. The role of pediatrician in rec- tion screen for intimate partner violence. J Women’s
ognizing and intervening on behalf of abused women. Health 2003;12:233–239.
Pediatrics 1998;101:1091–1092.● C Sherin K, Sinacore J, Li X, Zitter R, Shakil A. HITS: A short
Feldhaus K, Koziol-McLain J, Amsbury H, Norton I, domestic violence screening tool for use in a family
Lowenstein S, Abbott J. Accuracy of 3 brief screen ques- practice setting. Fam Med 1998;30:508–512.
tions for detecting partner violence in the emergency Tjaden P, Thoennes N. Extent, Nature, and Consequences
department. JAMA 1997;277:1357–1361. of Intimate Partner Violence: Findings from the
Felitti V, Anda R, Nordenberg D, et al. Relationship of National Violence Against Women Survey. Washington,
childhood abuse and household dysfunction to many DC, National Institute of Justice and the Centers for
of the leading causes of death in adults: The Adverse Disease Control, 2000.● B
Childhood Experiences (ACE) Study. Am J Prev Med U.S. Preventive Services Task Force. Screening for family
1998;14:245–258.● B and intimate partner violence: Recommendation state-
Ferris L, Norton P, Dunn E, Gort E, Degani N. Guidelines ment. Ann Intern Med 2004;140:382–386.● C
for managing domestic abuse when male and female Zink T, Jacobson J, Elder N. Screening for domestic vio-
partners are patients of the same physician. JAMA lence when the children are present: The victim’s per-
1997;278:851–857. spective. J Interpers Violence 2003;18:872–890.
Groves B, Augustyn M, Lee D, Sawires P. Identifying and Zink T, Elder N. Jacobson J, Klostermann B. Medical man-
Responding to Domestic Violence Consensus Recom- agement of intimate partner violence considering the
mendations for Child and Adolescent Health. San stages of change: Precontemplation and contemplation.
Francisco, Family Violence Prevention Fund, 2002. Ann Fam Med 2004a;2:231–239.
Available at www.endabuse.org. Accessed 9/27/05.● C Zink T, Kamine D, Musk L, Sill M, Field V, Putnam F. What
Holtzworth-Munroe A, Meehan JC. Typologies of men are physicians’ reporting requirements for children who
who are maritally violent: Scientific and clinical impli- witness domestic violence (DV)? Clin Pediatr 2004b;43:
cations. J Interpers Violence 2004;19:1369–1389. 449–460.

87
 C h a p t e r

9 Patient Compliance

Lisa Dolovich, John W. Sellors,

and R. Brian Haynes

KEY POINTS

1. Fifty percent is a representative compliance computerized ticker system can help identify
figure for many long-term therapies. noncompliance.
2. Differentiating whether compliance is intentional 6. Provided that the treatment prescribed is known
(e.g., testing out lower doses or discontinuation) to be efficacious, failure of a patient to respond
or unintentional (e.g., mental deterioration, to treatment can be used as a readily available
change in work schedule) can be helpful when indicator of noncompliance.
developing strategies to improve compliance. 7. Asking the patient directly about compliance
3. Communication with a patient before can be a very valuable and practical way of
prescription to discuss the benefits, adverse determining the pattern of medication con-
effects, and use of a medication as well as com- sumption.
munication after prescription to verify a patient’s 8. Simple clear instructions are sufficient to
medication-taking behavior are important steps improve compliance for short-term
to improve medication compliance. treatments.
4. Family physicians are unable to detect poor 9. Follow-up of nonattenders by telephone or
compliers among their patients, because no mailed reminders and multifaceted strategies
stereotypic poor complier exists. are needed to improve compliance for longer-
5. Dropping out of care is one of the most fre- term treatments.
quent and most severe forms of noncompli- 10. The physician should be aware that patients
ance, and so watching the appointment book often lie when they state that they have taken
and using practice aids such as a manual or certain medicines.

[The physician] should keep aware of the fact that rather than therapeutic potential. Recent incidents
patients often lie when they state that they have of concern with rofecoxib, hormone replacement
taken certain medicines. therapy, nefazodone, and others demonstrate the
Hippocrates complexities of balancing benefits and risks of drug
interventions to ensure that, on balance, therapies
Although physicians have dispensed medicines and will improve health when they are taken according
potions through the centuries in vast quantities, it is to the intended management plan. On the whole,
only in recent years that there has been systematic our armamentarium of useful treatments is sizable
examination occurred of whether patients actually and expanding rapidly; low patient compliance
take the treatment. It was perhaps to the patient’s stands squarely in the way of achieving the full ben-
benefit in the past that little attention was paid to efit of modern therapy.
compliance, as poor compliance probably saved the The extent of poor compliance is distressing.
patient’s life on many occasions. Some treatments, Fifty percent is a representative compliance figure
especially the massive purges and bleeding of the for many long-term therapies. Only 51% to 78% of
eighteenth century and arsenic and hydrochloric patients with newly diagnosed hypertension persisted
acid of the twentieth century, certainly had lethal with antihypertensive therapy 1 year after receiving a

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

88
 Chapter 9 Patient Compliance

new prescription (Caro et al., 1999● B ; Morgan and ered compliant because this amount of medication
Yan, 2004● B ; Wogen et al., 2003●
B ). Fewer than 40% of was found to produce systematic blood pressure
patients continued to receive prescriptions for (S)-3- reduction (Sackett et al., 1975●A). Patients taking less
hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) than 75% of β-blockers prescribed after an acute
reductase inhibitors 2 years after their first prescrip- myocardial infarction were more than 2.5 to 3 times
tion (Jackevicius et al., 2002● B ). Only about two more likely to die within 1 year (for men) or approx-
thirds of those who continue under care take enough imately 2 years (for women) (Gallagher et al., 1993● B;
of their prescribed medication to achieve adequate Horwitz et al., 1990● B).
blood pressure control (Haynes et al., 1978). If we Compliance also can be thought of in terms of
look at compliance with lifestyle changes, such as intentionality. The deliberate not starting, stopping,
diets and smoking cessation, the figures are consider- or altering of a drug regimen by the patient has been
ably more dismal (Best and Block, 1979). called intentional noncompliance. Unintentional
Added to this, physicians—even family physi- noncompliance may be due to forgetfulness or may
cians—are not good at estimating compliance levels be due to other patient characteristics such as
in patients (Gilbert et al., 1980 ●
B ). Physicians have a changes in work shifts, mental deterioration, or
strong tendency to overestimate the compliance of inability to pay for medications (Royal Pharma-
their own patients and are usually unable to predict ceutical Society of Great Britain, 1997 ●C ). The differ-
which patients will comply with treatment. entiation of compliance behavior by intention can be
This chapter reviews the practical methods of helpful when trying to identify noncompliance or to
detecting poor compliance and strategies for develop strategies to improve compliance.
improving it. It makes sense that efforts directed at poor com-
pliers should be concentrated on those not achieving
therapeutic goals. This obviously leads to more effi-
DEFINITIONS cient use of resources. However, some patients who
respond to treatment may be doing so because of
The trend in medicine, and particularly in family overprescribing rather than because of compliance.
medicine, is toward consumerism and a more demo- Should these patients be hospitalized or placed in
cratic approach that involves the patient in medical some other situation in which compliance may be
decisions. The use of the word “compliance” has close to 100%, they may well run into serious effects
raised objections because it implies authoritarianism of overdose.
and anything but an equal relationship between
physician and patient. Alternative terms such as
adherence and concordance have been proposed to FACTORS INFLUENCING COMPLIANCE
recognize that patients have primary control over the
decision to take medications once prescribed and Many approaches, ranging from complex psycho-
that the use of medications will be improved if logical theories to simplistic or intuitive ideas, have
patients are seen as partners in the development of been taken to explain compliance behavior. None is
treatment plans with their physicians (and other entirely satisfactory, and many address only compo-
health care providers) (Marinker and Shaw, 2003; nents of the complex undertaking of compliance;
World Health Organization, 2003 ● C ). Although we many are lamentably wrong (Leventhal and
agree that the debate over terminology is helpful to Cameron, 1987).
gain better insight into how to improve the complex In looking at the many factors involved, a natural
task of taking medications, and we sympathize with tendency exists for the physician to feel that poor
the views of those who oppose the term, we use com- compliance is the patient’s fault; after all, it is the
pliance throughout this chapter because it is still the patient who must swallow the pill or keep the appoint-
most widely used and recognized rubric. ment. But many other factors leading up to the act of
Compliance has been defined as the extent to pill taking or returning for an appointment must be
which a person’s behavior (in terms of keeping considered. For instance, what about the disease or
appointments, taking medications, and executing condition being treated: Is it symptomatic or asymp-
lifestyle changes) coincides with medical advice tomatic, life threatening or purely a nuisance? Is it an
(Sackett, 1976). Poor compliance is more difficult to acute or chronic condition? What about the treatment
define. What percentage of prescribed medication itself: Is it efficacious? Does it have bothersome
can a patient forget or omit before being classed as a adverse effects? Is it unpleasant, inconvenient, or
poor complier? How are patients who take too much expensive? Is the medical environment conducive to
medication classified? One way of looking at the regular follow-up? Does the physician inspire confi-
problem is to use patient outcomes as a guide. For dence in the treatment, or do certain attitudes inter-
instance, in hypertension studies, patients taking fere with compliance? Only some of these factors have
80% or more of prescribed medication were consid- an important effect on compliance behavior.

89
 Chapter 9 Patient Compliance

therapeutic health actions, such as immunizations

The Patient
and medical regimens for acute disease, but the
General attributes such as age, gender, marital sta- extent of its predictive value is modest at best (Janz
tus, education, occupation, intelligence, race, reli- and Becker, 1984).
gion, urban versus rural living, and economic status The information-motivation-behavior skills
bear no consistent relation to compliance. Two model (IBM) is a more recently developed model that
exceptions are the very young and the very old, combines elements from previous literature and
whose compliance characteristics tend to conform models to describe the influences on behavior change
to those of their caregivers. Another exception is the (Fisher and Fisher, 1992; Fisher et al., 1996● B ). This
presence of extreme disturbances in functioning and model proposes that information and motivation
motivation in patients such as those with mental influence behavioral skills (tools and strategies to per-
health disorders (DiMatteo et al., 2000● B ; World form compliance behavior) and that all three of these
Health Organization, 2003● C ). Patients will regularly elements directly influence behavior change. Initial
modify their medication regimens or dosing in an reports evaluating interventions constructed by using
attempt to assert control over their health. As this model have shown some promise in influencing
Conrad states, “People will change their medication behavior change. The model has high face validity;
practice, including stopping medication altogether, however, more studies are needed to better understand
in order to test for the existence or ‘progress’ of the how well the model explains the full extent of behavior
disorder” (Conrad, 1985). Patients will not usually change across a variety of conditions.
share the intentional changes they make to their The transtheoretical stages-of-change model
medications unless they are asked about whether maintains that behavior progresses through five
they have carried out any medication-taking “tests” stages—precontemplation, contemplation, prepara-
within the context of a trusting physician-patient tion, action, and maintenance—and that a decisional
relationship. Numerous theories and models of balance exists between the pros and cons of the behav-
behavior change have been generated or adapted to ior (Prochaska and DiClemente, 1992). It follows that
explain or better understand compliance. Perhaps all patients may not be at the same stage of readiness
the most widely held theory of compliance behavior, for change in compliance (Keefe et al., 2000● B;
probably because of its intuitive appeal, is the Prochaska et al., 1998), so it is more helpful to identify
communications approach (Leventhal and their highest priority and work on this one behavior.
Zimmersman, 1984). In this model, it is proposed Controlled trials have demonstrated that interventions
that patients generally do not know enough about based on the stages-of-change model can improve
their illness or treatment and that this ignorance health behaviors such as increased exercise in older
leads to poor compliance. It follows that adequate women (Conn et al., 2003● ●
A) and smoking cessation
instruction or message generation and reception, (Velicer et al., 1999). Assessment of the stage of change
comprehension, and retention of the message of a noncompliant patient should facilitate counseling
should result in improved compliance. Although it that is appropriately tailored to move him or her
appears that this is true for short-term treatments toward action (Table 9-1) (Willey 1998; Willey et al.,
(<2 weeks in duration), knowledge on its own bears 1999).
little relation to compliance with chronic disease Other models have been studied, including the
regimens (Haynes, 1979). behavioral-learning model, which is based on cogni-
Another popular theory looks at patient motiva- tive and social learning theory, and the self-regulat-
tion and beliefs. By using the health-belief model, ing model. As yet, no model adequately explains a
Becker (1976) argues that the likelihood of “all indi- person’s compliance behavior or gives a clear ration-
viduals undertaking a recommended health action ale for modifying it (Haynes et al., 1982).
depends on the perception of the level of personal The behavior models help clinicians understand
susceptibility to the particular illness or condition; compliance behavior a bit better, but for helping
the degree of severity of the consequences of con- patients to follow prescribed treatments better the
tracting the condition; the potential benefits or effi- strategies from studies showing successful interven-
cacy of the treatment in preventing or reducing tions in the section on prevention and treatment of
susceptibility and/or severity; and the physical, psy- poor compliance may be of more practical use for
chological, financial, and other barriers or costs helping patients follow prescribed treatment.
involved in initiating or continuing the treatment.”
The model also requires a stimulus or cue to action The Disease
to trigger the appropriate behavior (compliance);
this cue can be either internal (e.g., a symptom) or With few exceptions, disease factors are relatively
external (e.g., screening campaign or physician’s unimportant as determinants of compliance.
advice). This model has been shown to have pre- Psychiatric patients with schizophrenia, paranoid
dictive value for some preventive and short-term features, and personality disorders are less compliant

90
 Chapter 9 Patient Compliance

Regimens requiring changes in lifestyle, such as diet-

Table 9-1 Behavior-change Strategies for
ing, exercising, and stopping harmful habits, result in
Improving Compliance
much poorer compliance than does simply taking
Stage Characteristics pills, because of the substantially greater behavioral
changes needed.
Precontemplation Resistant to taking Conventional wisdom and common sense
medication, fearful, in suggest that the greater the number of drugs or
denial, defensive, treatments prescribed for a patient, the greater the
misinformed, or
demoralized
probability of poor compliance. However, recent
Contemplation Ambivalent about taking studies have found that patients prescribed (and dis-
the medication, pensed) more cardiovascular medications had better
concerned about the medication compliance (based on an examination
cons of medication use, of their pharmacy records) (Shalansky and Levy,
lacking commitment to 2002 ● B ; Grant et al., 2004 ● B ). Likely a set of circum-
the regimen stances exists under which compliance does improve
Preparation Understands the pros of with more medications, and more research is
taking the medication as needed to clarify this issue. Despite these recent
directed; planning to reports, simplifying the treatment regimen to reduce
improve adherence soon
Action Recently began taking
the number of medications a patient is taking is
medication as directed, one of the most important strategies to improve
but this new behavior compliance.
may still be an effort Compliance decreases when the frequency of
Maintenance Taking medication as dosing increases. Although no differences in compli-
directed for ≥6 months, ance have been identified between once- and twice-
“Now it’s easy for me” daily dosing, compliance decreases with 3- or
Relapse risk Has been taking the 4-times daily dosing (Claxton et al., 2001● B ; Eisen
medication as directed et al., 1990●B ; Pullar et al., 1988● B ).
for 6 months, but Alternative oral medications for the same
“tests” the degree to
condition do not appear to result in substantial dif-
which adherence is
necessary by taking ferences in compliance, but a difference may be
“drug holidays” found for different problems. For example, Closson
and Kikugawa (1975) found a range from 17% com-
pliance with antacids to 89% with cardiac drugs.
than are other psychiatric patients—a fact that prob- The injection of long-acting preparations, such
ably reduces the compliance of psychiatric patients as benzathine penicillin for acute streptococcal
as a whole below that of patients with nonpsychiatric pharyngitis and rheumatic fever prophylaxis, long-
disorders. acting phenothiazines for schizophrenia, and strep-
No relation has been demonstrated between the tomycin for tuberculosis, has been shown to be
severity of symptoms and compliance. Surprisingly, acceptable to patients and more effective than oral
the more symptoms a patient reports, the lower his or preparations.
her compliance is likely to be. Conversely, increasing The cost of treatment is an important barrier to
disability produced by a disease appears to be associ- compliance for many people (Gregoire et al., 2002● B;
ated with better compliance. Whether this is a result Tamblyn et al., 2001● B ; Tseng et al., 2004● B ). However,
of increased severity of disease or specifically the a complete understanding of the effect of cost is not
result of the increased supervision that often accom- as obvious as it might first appear. For instance, one
panies increased disability has not been sorted out. study showed that hospital admissions increased
Chronic diseases requiring long-term treatment among psychiatric outpatients given drugs at nomi-
have been clearly shown to result in increasingly nal cost compared with admissions for a group pay-
poor compliance. This fact is of great clinical impor- ing regular prices (Cody and Robinson, 1977● B ).
tance in such potentially serious diseases as tubercu- Patients without full drug coverage are more likely to
losis and hypertension and is more likely to be a use less medication, switch medications, use samples,
function of the duration of the treatment regimen and report difficulty paying for medications
than the duration of the disease itself. (Tamblyn et al., 2001● B ; Tseng et al., 2004● B ).

The Regimen The Physician

Generally speaking, the greater the behavioral The physician is obviously in a key position to influ-
demands of a treatment, the poorer the compliance. ence compliance. For example, if the frequency of

91
 Chapter 9 Patient Compliance

dose affects compliance, then by the very act of pre- be compliers with treatment. Many physicians are
scribing a medication to be taken 4 times a day, the unable to detect this type of noncompliance because
physician is potentially reducing compliance below their appointment systems are inadequate or because
the level achievable with a single daily dose. the patients do not make follow-up appointments.
More complex than the mechanics of prescrib- It follows, then, that an important method of
ing, however, is the interaction between physician detecting poor compliance is to watch the appoint-
and patient. Patients are more likely to comply with ment book and to use practice aids such as a manual
treatment if their expectations are met by the visit or computerized tickler system. Although no guaran-
and if they are well satisfied with their care (Francis tee exists that patients who keep appointments will
et al., 1969; Kincey et al., 1975). The concept of a per- comply with treatment, no doubt those who do not
sonal physician or the feeling of knowing a physician appear for follow-up will not be in a position to
well also has been associated with increased compli- comply with treatment. The importance of monitor-
ance (Ettlinger and Freeman, 1981● B ). Dissecting the ing attendance cannot be overstressed: Dropping out
physician-patient relationship and measuring the of care is one of the most frequent and most severe
factors that result in increased satisfaction are not forms of noncompliance (Stephenson et al., 1993).
easy. This is demonstrated in one study in which
some patients felt that they knew their physician well Response to Treatment
after only one visit, whereas others felt that they still
did not know their physicians after as many as 14 vis- Provided that the treatment prescribed is known to
its (Ettlinger and Freeman, 1981● B ). Communication be efficacious, failure of a patient to respond to treat-
with a patient before prescription to discuss the ben- ment can be used as a readily available indicator of
efits, adverse effects, and use of a medication as well compliance levels. For example, high compliance was
as after prescription to verify a patient’s medication- associated with a 10% lower total A1c in patients on
taking behavior are important steps to improve a stable medication regimen for type 2 diabetes rela-
medication compliance (Roberts and Volberding, tive to patients with low compliance (Krapek et al.,
1999● B ). 2004● B ). However, this method of assessing com-
pliance is not infallible. For example, patients who
appear to respond to treatment may do so because
they were misdiagnosed and do not have the condi-
DETECTION OF POOR COMPLIANCE
tion of interest or because their physicians’ overpre-
scribing is compensating for their poor compliance.
Clinical Judgment
Nevertheless, from the compliance perspective at
Most of us would like to believe that a good physician least, concern is less necessary for patients who have
can detect poor compliance in patients; surely, this reached the therapeutic goal. Conversely, patients not
goes along with clinical judgment. Unfortunately, showing a response to treatment will include those
studies have shown that this is not the case: Using who genuinely do not respond to therapy or who
clinical judgment has been shown to be no better than have been prescribed inadequate amounts and will
flipping a coin as a detection method. The first stud- also include a high proportion of poor compliers or
ies demonstrating this were carried out in specialty noncompliers. If therapeutic response is suboptimal,
settings and with physicians who did not have an then noncompliance should be considered and
ongoing relationship with patients. Unfortunately, the explored as a possible reason for lack of response to
hope that family physicians with their ongoing rela- treatment before changing management strategies.
tionships with their patients might be in a better posi-
tion to make predictions also has been dispelled. Not Asking the Patient
only were family physicians unable to detect poor
compliers among their patients, but also the length of Although it is not always reliable, asking the patient
time that they had known their patients had no effect directly about compliance can be a very valuable and
on their ability to predict (Gilbert et al., 1980●
B ). practical way of determining the pattern of medica-
The emphasis on the inaccuracy of clinical judg- tion consumption (see Table 9-2). When asked
ment is important in that it serves to direct us to directly, about half of noncompliant patients will
alternative approaches to detect poor compliance. admit to missing at least some medication (Haynes
et al., 1980●
B ; Stephenson et al., 1993). One can be

Monitoring Attendance assured that it is highly improbable that a compliant

patient will admit to poor compliance, so patients
As mentioned previously, more than 50% of hyper- admitting to missing medication have a very high
tensive patients stop visiting their physicians within a likelihood of being poor compliers. The converse is
year of starting treatment, and those who do not not true, however, as even under optimal interview
appear for follow-up appointments are unlikely to conditions about half of noncompliant patients will

92
 Chapter 9 Patient Compliance

deny the fact. Patients who admit to missing medica- with strict attention to bookkeeping (Haynes et al.,
tion generally overestimate the amount of medication 1980 ●B ). Unless the count can be carried out in such
they do take. In one study, the average overestimate a manner that the patient is unaware of what is
was in the region of 20% (Haynes et al., 1980● B ). going on, it becomes a one-time-only procedure. It
It must be emphasized that the method of ques- follows that whereas pill counts are very important
tioning is of paramount importance. Asking in a research tools, they are not very practical for most
threatening or belligerent manner will result in reflex clinical situations. It can be reasoned that using pill
denial. Approaching the patient with a face-saving, counts in the office or clinic will result in a bias in
nonthreatening, nonjudgmental question will yield a the direction of overestimating compliance, in that
higher proportion of accurate responses. One way of patients will consciously or unconsciously bring
doing this is to use an approach such as the follow- only some of their unused pills with them, giving
ing: “Many people find it difficult to remember to the appearance that they have taken more of the
take medicines: During the past week, have you medication than is actually the case. It is virtually
missed any of your pills?” Taking into account the impossible for the bias to go in the opposite direc-
tendency to overestimate compliance, admission of tion unless the patient is receiving the same pre-
any noncompliance is associated with an average scriptions from two or more physicians at the same
compliance rate of less than 80% (Haynes et al., time. In general, pill counts give higher estimates of
1980 ●B ). A similar approach is to ask the four ques- compliance than do quantitative drug assays and
tions based on the simplified Morisky measure of lower (but more accurate) estimates than do patient
medication adherence (Morisky et al., 1986) (see self-reports or administrative pharmacy claims data
Table 9-2). If the use of either method of questioning (Grymonpre et al., 1998 ● B).
results in the patient answering “yes” to any of
the questions asked, then the clinician has the Pharmacy Refill Records
opportunity to engage in further dialogue with the
patient to better understand factors associated with Pharmacy refill records can be used to identify pat-
noncompliance. terns of dispensed medications as a proxy for med-
The methods of detecting low compliance ication use. These records are especially helpful to
described so far can be easily applied in any treat- detect whether a patient may have stopped taking a
ment setting and, if applied with care, will detect the long-term medication (Jackevicius et al., 2002 ● B;
majority of poor compliers. The methods outlined in Morgan and Yan, 2004 ● B ; Pilon et al., 2001● B;
Table 9-2 may be of help in detecting some of the Rijcken et al., 2004 ●
B) or did not stop an old med-
remainder. ication when a new one was prescribed, especially
in cases in which patients cannot remember this
information. Pharmacies cannot provide complete
Counting Pills
medication refill history profiles without the
As a quantitative estimate of compliance over a cer- patient’s permission; however, pharmacists often
tain period, pill counts can be relatively reliable so provide the date of the previous refill when
long as they are carried out in the patient’s home requesting renewals from the physician’s office, and

Table 9-2 A Simple Method to Detect Noncompliance

Asking the Patient
The easiest way to detect medication noncompliance is to ask the patient
About 40% of noncompliant patients will admit to missing at least some medications
If patients admit to noncompliance, you can believe them
Patients admitting to poor compliance are most responsive to attempts to improve compliance

How to Ask: One Question

Use a matter-of-fact, nonjudgmental, nonthreatening manner
Use an introduction that allows a patient to save face: “Many people find it difficult to
remember to take medicines. During the past week, have you missed any of your pills?” Yes No

How to Ask: Four Questions (Risk Increases with Number of Positive Responses) (Morisky, 1986)
Do you ever forget to take your medicine? Yes No
Are you careless at times about taking your medicine? Yes No
When you feel better, do you sometimes stop taking your medicine? Yes No
Sometimes if you feel worse when you take the medicine, do you stop taking it? Yes No

93
 Chapter 9 Patient Compliance

this information can be useful in determining Another popular and important misconception is
whether the patient appears to be taking his or that all that stops patients from being near-perfect
her medication on schedule. This is an indirect compliers is their ignorance of either the condition
measure, however, and cannot assure whether a being treated or the treatment being used. Although
patient is actually taking a medication. The patient some evidence indicates that written instructions help
could, for example, be sharing or hoarding the improve compliance for short-term regimens, even
medications. mastery learning, in which patients were given detailed
step-by-step instruction on hypertension, had no ben-
Drug Levels eficial effect on long-term compliance (Sackett et al.,
1975 ● A ). The belief that it is possible to scare a patient
A laboratory test to detect the presence or absence of into complying with treatment also has been dispelled
good compliance is an unrealistic dream in the case (Leventhal et al., 1967; Logan, 1978). A survey of pri-
of most drugs. For some drugs, however, especially mary care physicians showed that the methods they
those with long serum half-lives resulting in rela- used to improve compliance were predominantly those
tively steady serum levels, the measurement of serum that have been found lacking. Methods that have been
levels can be an extremely useful indicator of com- shown to be effective were not generally applied. The
pliance. The best examples of this are digoxin and transtheoretical stages-of-change model of readiness to
phenytoin, for which plasma levels have been used change behavior also can be applied to a physician’s
successfully both to monitor compliance and to own counseling behavior and predicts that unless
improve it through feedback to the patient. Other realistic goals are set for improving monitoring and
drugs commonly measured in this way are anticon- follow-up of compliance, the physician may become
vulsants, theophylline, tricyclic antidepressants, frustrated and slip into inaction (precontemplation)
lithium, and a variety of cardiac drugs. The caution (Prochaska and DiClemente, 1992). Changing the
is, however, that a great deal of individual variation is long-term behavior of physicians to manage com-
found in drug absorption, metabolism, and excre- pliance successfully cannot be done by simply inform-
tion. In addition, serum levels of drugs with short ing or instructing them about efficacious interventions
half-lives indicate only how recently a dose was taken (Evans et al., 1986● A ; Haynes et al., 1984● B ).
and give no information on long-term compliance.
Drug levels in urine have also been used as
Prevention
compliance indicators. For instance, the presence or
absence of penicillin can be easily detected by The main thrust in the prevention of poor compli-
observing inhibition of growth of a microorganism, ance is to remove barriers to compliance (see Table
Sarcina lutea. Although these methods and others 9-3). Preventing patients from dropping out of care
involving inactive markers such as riboflavin and is of primary importance. Longer waiting times are
carbon 14 have been used in research, they are not associated with higher no-show rates (Rockart and
practical methods for the clinician. What is more, as Hoffman, 1969), so that one aim is to keep patient
a measure of compliance, single qualitative assess- waiting time to a minimum. Individual appoint-
ments of urine samples have been shown to be ments at mutually convenient times help achieve
inferior to simply asking the patient (Haynes et al., this goal. Ensuring that patients leave the office with
1980 ●B ). a specific time for a future appointment rather than
with instructions to call for an appointment in, for
example, 3 months, makes detection of those who
PREVENTION AND TREATMENT do drop out much easier.
OF POOR COMPLIANCE Simplifying the treatment regimen will remove
another barrier to compliance. An essential element
of this approach is to eliminate unnecessary medica-
Misconceptions
tions. In addition, medications should be prescribed
Before discussing prevention and treatment, it is that should to be taken as few times daily as possible.
worthwhile to reexamine some popular misconcep- The frequency of dosing with many drugs can be
tions about compliance. The first misconception is reduced below usually prescribed levels with no
that a good clinician can identify poor compliers, as reduction in efficacy. For example, tricyclic antide-
no stereotypic poor complier exists (Vik et al., pressants can be given as a single bedtime dose, thus
2004 ●B ). This is very important, because restricting reducing dosing frequency and timing side effects so
prevention and treatment strategies to patients that they occur mainly during sleep. A final strategy
thought to be potentially poor compliers must result is titration to the least amount of medication neces-
in neglect of a large number of patients who need sary to achieve the therapeutic goal. Arranging for a
attention as well as unnecessary attention to some comprehensive medication review carried out by a
patients who do not. clinical pharmacist or clinical pharmacologist may

94
 Chapter 9 Patient Compliance

generate recommendations on how to simplify a the receptionist’s task simpler. Personal contact by
patient’s medication regimen (Dolovich and Levine, the physician and the use of outreach services such
1997● B ; Hanlon et al., 1996●A ; Sellors et al., 2003●
A). as public health nurses are other ways of “treating”
It has been shown that patients who believe that persistent nonattendance. Most successful compli-
they are actively involved in their own care are better ance interventions have two features in common:
compliers than are those who do not (Schulman, increased supervision of, or attention to, the patient;
1979● B ). Studies also have shown that negotiating and intentional reinforcement of, reward for, or
care with the patient rather than simply dictating or encouragement of compliance (Haynes et al., 1987).
prescribing it results in better compliance (Eisenthal Low compliance is a chronic condition without
et al., 1979● B ; Tracy, 1977). Encouraging patients to a “one-shot” cure, so treatment of poor compliance
take greater responsibility for their care by asking must continue as long as the regimen of prescribed
more questions of their physicians results in treatment. To make matters worse, none of the fol-
improved attendance (Roter, 1977● A). It follows that lowing has improved compliance when tested alone:
encouraging patients to participate in and take more special learning packages (Rawlings et al., 2003● A;
responsibility for their own care is another strategy Sackett et al., 1975● A) and pamphlets (Swain and
for preventing poor compliance, and it not only Steckel, 1981); special unit-dose reminder pill pack-
makes scientific sense but also is consistent with aging (Becker et al., 1986● A); counseling about med-
trends in physician-patient relationships. ication and compliance by a health educator (Levine
et al., 1979● A) or by nurses (Morice and Wrench,
2001● A ; Shepard et al., 1979● B ); visits to patients’
Treatment
homes (Johnson et al., 1978● A) or pharmacists
Dropping out of care constitutes a compliance crisis (Nazareth et al., 2001● A ; Stevens et al., 2002● A); provi-
(Table 9-3). Mail and telephone reminders to sion of care at the worksite (Sackett et al., 1975 ● A);
increase attendance, at least in the short term, can self-monitoring of blood pressure (Johnson et al.,
help prevent dropout (Macharia et al., 1992● A). If the 1978● A); tangible rewards (Shepard et al., 1979● B); or
patient does fail to attend, it calls for prompt action group discussions (Shepard et al., 1979● B). Although
by the receptionist or office nurse to reschedule these tactics have not worked alone, many have been
(Takala et al., 1979●A). A simple method of identify- part of more complex interventions that have been
ing those patients for whom compliance is important successful; whether they are essential parts of these
(e.g., the use of chart stickers or special symbols complex interventions or just along for the ride is
on the written or computerized day sheet) may make difficult to say (McDonald et al., 2002● A ; Von Korff
et al., 2003● B ).
A variety of inducements to comply have been
used, including feedback of blood-pressure response
Table 9-3 Keys to Successful Compliance to hypertensive patients either by the provider
Management (McKenney et al., 1973; Takala et al., 1979● A) or by

Detection
patients’ taking their own blood pressure (Haynes
Monitor attendance and achievement of the et al., 1976● A ; Nessman et al., 1980● A); small tangible

therapeutic goal rewards for improved compliance or therapeutic

Ask the patient response or both (Haynes et al., 1976● A ; Shepard
Ask the pharmacist et al., 1979● B ; Swain and Steckel, 1981); medication
tailored to daily schedules to decrease forgetting and
Prevention inconvenience (Haynes et al., 1976● A ; Logan et al.,
Make appointments convenient 1979● A); encouragement of family support (Levine
Simplify the regimen et al., 1979● A); stimulation of self-help through group
Give clear instructions, preferably written support and discussion (Levine et al., 1979● A;
Engage the patient as an active participant
Nessman et al., 1980● A); negotiation of a brief written
Use telephone or mail reminders
contract with the patient to improve health behavior
Treatment (Swain and Steckel, 1981); and calling back patients
Follow up nonattenders who miss appointments (Bass et al., 1986● A ; Peterson
Increase attention and supervision et al., 1984● A ; Sellors et al., 1997● A ; Takala et al.,
Use cuing, feedback, and positive reinforcement 1979● A).
Collaborate with pharmacist on strategies and It is important to note here that many individu-
patient follow-up als other than physicians have taken an effective part
Schedule frequency of visits to compliance need in this process. Nurses, pharmacists, health educa-
Involve spouse or other partner tors, a psychologist, and even an individual with no
Maintain compliance interventions as long as
formal health training played a key role in successful
compliance is desirable
interventions.

95
 Chapter 9 Patient Compliance

In summary, the treatment of poor compliance business purposes, the computerization of appoint-
involves many approaches. For short-term treatments, ment systems and, increasingly, health records
simple clear instructions are sufficient (Al Eidan et al., affords potential for monitoring patient compliance
2002● A ; McDonald et al., 2002● A). For longer-term and assisting in the implementation of reminder sys-
treatments, follow-up of nonattenders by telephone or tems that allow enhanced management of the poor
mailed reminders must occur. In addition, the practi- complier (Hunt et al., 1998● A).
tioner must increase the attention paid to poor com- Computerized appointment systems make it
pliers and provide rewards or positive reinforcement possible to provide patients with appointment times
for good compliance that could include simple praise for long periods ahead and can easily be modified to
and extending the time between appointments for flag nonattenders and produce automatic reminders.
those responding to treatment. Inui and colleagues The ability to record age, gender, and diagnoses
(Inui et al., 1976●
A) showed that such maneuvers can makes it possible to design a system that can improve
be successfully incorporated into regular practice by provider compliance with screening and preventive
simply focusing on compliance for a few moments maneuvers (Bypass et al., 1988● B ). Medication data-
during each encounter, not only to emphasize the bases that store prescribing information can form
importance of following the regimen but also to tailor the basis of a system that monitors whether patients
medication to daily routines. This can be accom- are at least requesting prescription refill on time
plished without necessarily prolonging the visit. It is (Steiner et al., 1988●
B ). Automated telephone messag-
most important that all compliance interventions ing technology, Internet-based computer programs,
applied to noncompliers be maintained for as long as and other new technologies are under development
treatment is prescribed. to help improve compliance. The potential is great,
but it will require both effort and expenditure by
physicians or patients to make it work.
Ethical Issues
What of other advancements? The technology
Am I my brother’s keeper? that brought us the efficacious treatments is also
Genesis 4:9 helping with compliance: drugs with long half-lives,
long-acting parenteral preparations, conjunctival
This question highlights the dilemma in which inserts, and continuous transcutaneous absorption
physicians may find themselves when they are systems. The burgeoning use of high technology
pressed to extend their compliance-improving could result in an artificial pancreas that will not
strategies beyond a simple office visit. only dispense insulin but also adjust the dose accord-
The decision to apply tactics deliberately ing to blood levels. What is to stop the development
designed to change the compliance of patients of implanted arterial pressure sensors with auto-
should meet several ethical standards that apply to all matic dispensing of parenteral antihypertensives?
therapeutic interventions (Levine, 1980). First, the These thoughts make concerns about telephoning
diagnosis must be correct. Second, the therapy to be nonattenders seem trifling.
complied with must be of established efficacy. Third,
neither the illness nor the proposed treatment
should be trivial. Fourth, the patient must be an CONCLUSION
informed and willing partner in any attempt to max-
imize his or her compliance. Finally, the method In dealing with compliance, we have consciously
used to improve compliance must be of demon- concentrated on compliance with medication,
strated effectiveness. emphasizing long-term medications. This is not
After applying these standards and embarking because we think that compliance with short-term
on a course of treatment, it makes no sense, ethi- medications is inconsequential or that no problem of
cally or otherwise, for the physician to abandon a compliance exists with lifestyle or other behavioral
patient at the first sign of poor compliance. Most changes. On the contrary, both these areas are very
physicians consider it unethical to withhold effica- important, and noncompliance with lifestyle changes
cious treatment from a patient with a serious physical is a monster not to be tamed.
disease. Why then should it be ethical to consider It is our hope that we have raised the level of
withholding treatment when the condition is non- compliance consciousness in the reader. Awareness
compliance? of the problem and the difficulties in detecting it is
essential before any of these practical treatments can
be instituted.
Future Trends
The past two decades have brought the therapist
The advent of the personal computer has resulted in together with the patient, the family, and other mem-
increasing use of microcomputers in physicians’ bers of the health care team in jointly working
offices. Although initial applications have been for toward the full effectiveness of potent treatments.

96
 Chapter 9 Patient Compliance

The rewards of this alliance are great: reduction of

Material Available on Student Consult
morbidity, disability, and preventable deaths. The
family physician is in an ideal position to help create Review Questions and Answers about Patient
and share in these rewards. Compliance

REFERENCES
Al Eidan FA, McElnay JC, Scott MG, McConnell JB. Evans CE, Haynes RB, Birkett NJ, et al. Does a mailed
Management of Helicobacter pylori eradication: The continuing education program improve physician per-
influence of structured counselling and follow-up. Br J formance? Results of a randomized trial in antihy-
Clin Pharmacol 2002;53:163–171.● A pertensive care. JAMA 1986;255:501–504.● A
Bass MJ, McWhinney IR, Donner A. Do family physicians Fisher JD, Fisher WA. Changing AIDS-risk behavior.
need medical assistants to detect and manage hyperten- Psychol Bull 1992;111:455–474.
sion? Can Med Assoc J 1986;134:1247–1255.● A Fisher JD, Fisher WA, Misovich SJ, Kimble DL, Malloy TE.
Becker LA, Glanz K, Sobel E, et al. A randomized trial Changing AIDS risk behavior: Effects of an interven-
of special packaging of antihypertensive medications. tion emphasizing AIDS risk reduction information,
J Fam Pract 1986;22:35–36.● A motivation, and behavioral skills in a college student
Becker MH. Sociobehavioral determinants of compliance. population. Psychol Bull 1996;15:114–123.● B
In Sackett DL, Haynes RB, eds. Compliance with Francis V, Korsch BM, Morris MJ. Gaps in doctor-patient
Therapeutic Regimens. Baltimore: Johns Hopkins communication: Patients’ response to medical advice.
University Press, 1976, pp 40–49. N Engl J Med 1969;280:535–540.
Best JA, Block M. Compliance in the control of cigarette Gallagher EJ, Viscoli CM, Horwitz RI. The relationship
smoking. In Haynes RB, Taylor DW, Sackett DL, eds. of treatment adherence to the risk of death after
Compliance in Health Care. Baltimore: Johns Hopkins myocardial infarction in women. JAMA 1993;270:
University Press, 1979, pp 202–222. 742–744.● B
Bypass P, Hanlon PW, Hanlon LC, Marsh VM, Greenwood Gilbert JR, Evans CE, Haynes RB, Tugwell P. Predicting
BM. Microcomputer management of a vaccine trial. compliance with a regimen of digoxin therapy in fam-
Comput Biol Med 1988;18:179–193.● B ily practice. Can Med Assoc J 1980;123:119–122.● B
Caro JJ, Salas M, Speckman JL, Raggio G, Jackson JD. Grant RW, O’Leary KM, Weilburg JB, Singer DE, Meigs JB.
Persistence with treatment for hypertension in actual Impact of concurrent medication use on statin adher-
practice. CMAJ 1999;160:31–37.● B ence and refill persistence. Arch Intern Med
Claxton AJ, Cramer J, Pierce C. A systematic review of the 2004;164:2343–2348.● B
associations between dose regimens and medication Gregoire JP, Moisan J, Guibert R, et al. Determinants of
compliance. Clin Ther 2001;23:1296–1310.● B discontinuation of new courses of antihypertensive
Closson RG, Kikugawa CA. Noncompliance varies with medications. J Clin Epidemiol 2002;55:728–735.● B
drug class. Hospitals 1975;49:89–93. Grymonpre RE, Didur CD, Montgomery PR, Sitar DS. Pill
Cody J, Robinson AM. The effect of low-cost maintenance count, self-report, and pharmacy claims data to
medication on the rehospitalization of schizophrenic measure medication adherence in the elderly. Ann
outpatients. Am J Psychiatry 1977;134:73–76.● B Pharmacother 1998;32:749–754.● B
Conn VS, Burks KJ, Minor MA, Mehr DR. Randomized Hanlon JT, Weinberger M, Samsa GP, et al. A randomized,
trial of 2 interventions to increase older women’s exer- controlled trial of a clinical pharmacist intervention to
cise. Am J Health Behav 2003;27:380–388.● A improve inappropriate prescribing in elderly outpatients
Conrad P. The meaning of medications: Another look at with polypharmacy. Am J Med 1996;100: 428–437.● A
compliance. Soc Sci Med 1985;20:29–37. Haynes RB. Determinants of compliance: The disease and
DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk the mechanics of treatment. In Haynes RB, Taylor DW,
factor for noncompliance with medical treatment: Meta- Sackett DL, eds. Compliance in Health Care. Baltimore:
analysis of the effects of anxiety and depression on patient John Hopkins University Press, 1979, pp 49–62.
adherence. Arch Intern Med 2000;160: 2101–2107.● B Haynes RB, Davis DA, McKibbon A, Tugwell P. A critical
Dolovich L, Levine M. A medication assessment clinic. Can appraisal of the efficacy of continuing medical educa-
J Hosp Pharm 1997;50:182–184.● B tion. JAMA 1984;251:61–64.● B
Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck Haynes RB, Mattson ME, Chobanian AV, et al.
TR. The effect of prescribed daily dose frequency on Management of patient compliance in the treatment of
patient medication compliance. Arch Intern Med hypertension. Hypertension 1982;4:415–423.
1990;150:1881–1884.● B Haynes RB, Sackett DL, Gibson ES, et al. Improvement of
Eisenthal S, Emery R, Lazare A, Udin H. “Adherence” and medication compliance in uncontrolled hypertension.
the negotiated approach to patienthood. Arch Gen Lancet 1976;1:1265–1268.● A
Psychiatry 1979;36:393–398.● B Haynes RB, Sackett DL, Taylor DW. Practical management
Ettlinger PR, Freeman GK. General practice compliance of low compliance with antihypertensive therapy: A
study: Is it worth being a personal doctor? Br Med J guide for the busy practitioner. Clin Invest Med
(Clin Res Ed) 1981;282:1192–1194.● B 1978;1:175–180.

97
 Chapter 9 Patient Compliance

Haynes RB, Taylor DW, Sackett DL, Gibson ES, Bernholz ance with appointment keeping for medical services.
CD, Mukherjee J. Can simple clinical measurements JAMA 1992;267:1813–1817.● A
detect patient noncompliance? Hypertension Marinker M, Shaw J. Not to be taken as directed. BMJ
1980;2:757–764.● B 2003;326:348–349.
Haynes RB, Wang E, Gomes MD. A critical review of inter- McDonald HP, Garg AX, Haynes RB. Interventions to
ventions to improve compliance with prescribed med- enhance patient adherence to medication prescriptions:
ications. Patient Educ Couns 1987;10:155–166. Scientific review. JAMA 2002;288:2868–2879.● A
Horwitz RI, Viscoli CM, Berkman L, et al. Treatment McKenney JM, Slining JM, Henderson HR, Devins D, Barr M.
adherence and risk of death after a myocardial infarc- The effect of clinical pharmacy services on patients with
tion. Lancet 1990;336:542–545.● B essential hypertension. Circulation 1973;48:1104–1111.
Hunt DL, Haynes RB, Hanna SE, Smith K. Effects of com- Morgan SG, Yan L. Persistence with hypertension treat-
puter-based clinical decision support systems on physi- ment among community-dwelling BC seniors. Can J
cian performance and patient outcomes: A systematic Clin Pharmacol 2004;11:e267–e273.● B
review. JAMA 1998;280:1339–1346.● A Morice AH, Wrench C. The role of the asthma nurse in
Inui TS, Yourtee EL, Williamson JW. Improved outcomes treatment compliance and self-management following
in hypertension after physician tutorials: A controlled hospital admission. Respir Med 2001;95:851–856.● A
trial. Ann Intern Med 1976;84:646–651.● A Morisky DE, Green LW, Levine DM. Concurrent and pre-
Jackevicius CA, Mamdani M, Tu JV. Adherence with statin dictive validity of a self-reported measure of medica-
therapy in elderly patients with and without acute tion adherence. Med Care 1986;24:67–74.
coronary syndromes. JAMA 2002;288:462–467.● B Nazareth I, Burton A, Shulman S, Smith P, Haines A,
Janz NK, Becker MH. The Health Belief Model: A decade Timberal H. A pharmacy discharge plan for hospital-
later. Health Educ Q 1984;11:1–47. ized elderly patients: A randomized controlled trial. Age
Johnson AL, Taylor DW, Sackett DL, Dunnett CW, Shimizu Ageing 2001;30:33–40.● A
AG. Self-recording of blood pressure in the manage- Nessman DG, Carnahan JE, Nugent CA. Increasing com-
ment of hypertension. Can Med Assoc J 1978;119: pliance: Patient-operated hypertension groups. Arch
1034–1039.● A Intern Med 1980;140:1427–1430.● A
Keefe FJ, Lefebvre JC, Kerns RD, et al. Understanding the Peterson GM, McLean S, Millingen KS. A randomised trial
adoption of arthritis self-management: Stages of of strategies to improve patient compliance with anti-
change profiles among arthritis patients. Pain 2000; convulsant therapy. Epilepsia 1984;25:412–417.● A
87:303–313.● B Pilon D, Castilloux AM, LeLorier J. Estrogen replacement
Kincey J, Bradshaw P, Ley P. Patients’ satisfaction and therapy: Determinants of persistence with treatment.
reported acceptance of advice in general practice. J R Obstet Gynecol 2001;97:97–100.● B
Coll Gen Pract 1975;25:558–566. Prochaska JO, DiClemente CC. Stages of change in the
Krapek K, King K, Warren SS, et al. Medication adherence modification of problem behaviors. In Hersen M, Eisler
and associated hemoglobin A1c in type 2 diabetes. Ann RM, Mille PM, eds. Progress in Behavior Modifications.
Pharmacother 2004;38:1357–1362.● B Sycamore, Ill: Sycamore Press, 1992, pp 188–214.
Leventhal H, Cameron L. Behavioral theories and the Prochaska JO, Johnson S, Lee P. The transtheoretical model
problem of compliance. Patient Educ Couns 1987; 10: of behaviour change. In Shumaker SA, Shron EB, Ockene
117–138. JK, McBee WL, eds. The Handbook of Health Behaviour
Leventhal H, Watts JC, Pagano F. Effects of fear and Change. New York: Springer, 1998, pp 59–84.
instructions on how to cope with danger. J Pers Soc Pullar T, Birtwell AJ, Wiles PG, Hay A, Feely MP. Use of a
Psychol 1967;6:313–321. pharmacologic indicator to compare compliance with
Leventhal H, Zimmersman R. Compliance: A self-regulation tablets prescribed to be taken once, twice, or three times
perspective. In Gentry D, ed. Handbook of Behavioral daily. Clin Pharmacol Ther 1988;44:540–545.● B
Medicine. New York: Guilford Press, 1984, pp 369–434. Rawlings MK, Thompson MA, Farthing CF, et al.
Levine DM, Green LW, Deeds SG, Chwalow J, Russell RP, NZTA4006 Helping to Enhance Adherence to
Finlay J. Health education for hypertensive patients. Antiretroviral Therapy (HEART) study team. Aliment
JAMA 1979;241:1700–1703.● A Pharmacol Ther 2003;18:1121–1127.● A
Levine RJ. Ethical considerations in the development and Rijcken CA, Tobi H, Vergouwen AC, de Jong-van den Berg
application of compliance strategies for the treatment LT. Refill rate of antipsychotic drugs: An easy and inex-
of hypertension. In Haynes RB, Matteson ME, pensive method to monitor patients’ compliance
Engebretson TOJ, eds. Patient Compliance to by using computerised pharmacy data. Pharma-
Prescribed Antihypertensive Regimens. Washington, coepidemiol.Drug Saf 2004;13:365–370.● B
DC: U.S. Department of Health and Human Services, Roberts KJ, Volberding P. Adherence communication: A
H.I.H. Publication No. 81–2102, 1980:229–246. qualitative analysis of physician-patient dialogue. AIDS
Logan AG, Milne BJ, Achber C, Campbell WP, Haynes RB. 1999;13:1771–1778.● B
Work-site treatment of hypertension by specially trained Rockart JF, Hoffman PB. Physician and patient behavior
nurses: A controlled trial. Lancet 1979;2: 1175–1178.●
A under different scheduling systems in a hospital outpa-
Logan AS. Investigation of Toronto General Practitioners’ tient department. Med Care 1969;7:463.
Treatment of Patients with Hypertension. Toronto: Roter DL. Patient participation in the patient-provider
Canadian Facts, 1978. interaction: The effects of patient question asking on
Macharia WM, Leon G, Rowe BH, Stephenson BJ, Haynes the quality of interaction, satisfaction and compliance.
RB. An overview of interventions to improve compli- Health Educ Monogr 1977;5:281–315.● A

98
 Chapter 9 Patient Compliance

Royal Pharmaceutical Society of Great Britain. From com- Swain MA, Steckel SB. Influencing adherence among
pliance to concordance: Towards shared goals in medi- hypertensives. Res Nurs Health 1981;4:213–222.
cine taking. London: RPS, 1997.● C Takala J, Niemela N, Rosti J, Sievers K. Improving compli-
Sackett DL. Introduction. In Sackett DL, Haynes RB, eds. ance with therapeutic regimens in hypertensive
Compliance with Therapeutic Regimens. Baltimore: patients in a community health center. Circulation
Johns Hopkins University Press, 1976, p 1. 1979;59:540–543.● A
Sackett DL, Haynes RB, Gibson ES, et al. Randomised clin- Tamblyn R, Laprise R, Hanley JA, et al. Adverse events asso-
ical trial of strategies for improving medication com- ciated with prescription drug cost-sharing among poor
pliance in primary hypertension. Lancet 1975;1: and elderly persons. JAMA 2001;285:421–429.● B
1205–1207. ● A Tracy JJ. Impact of intake procedures upon client attrition
Schulman BA. Active patient orientation and outcomes in in a community mental health center. J Consult Clin
hypertensive treatment: Application of a socio-organi- Psychol 1977;45:192–195.
zational perspective. Med Care 1979;17:267–280.● B Tseng CW, Brook RH, Keeler E, Steers WN, Mangione CM.
Sellors J, Kaczorowski J, Sellors C, et al. A randomized con- Cost-lowering strategies used by Medicare beneficiaries
trolled trial of a pharmacist consultation program for who exceed drug benefit caps and have a gap in drug
family physicians and their elderly patients. Can Med coverage. JAMA 2004;292:952–960.● B
Assoc J 2003;169:17–22.● A Velicer WF, Prochaska JO, Fava JL, Laforge RG, Rossi JS.
Sellors J, Pickard L, Mahony JB, et al. Understanding and Interactive versus noninteractive interventions and
enhancing compliance with the second dose of hepati- dose-response relationships for stage-matched smok-
tis B vaccine: A cohort analysis and a randomized con- ing cessation programs in a managed care setting.
trolled trial. Can Med Assoc J 1997;157:143–148.● A Health Psychol 1999;18:21–28.
Shalansky SJ, Levy AR. Effect of number of medications on Vik SA, Maxwell CJ, Hogan DB. Measurement, correlates,
cardiovascular therapy adherence. Ann Pharmacother and health outcomes of medication adherence among
2002;36:1532–1539.● B seniors. Ann Pharmacother 2004;38:303–312.● B
Shepard DS, Foster SB, Stason WB, et al. Cost-effectiveness Von Korff M, Katon W, Rutter C, et al. Effect on disability
of interventions to improve compliance with antihy- outcomes of a depression relapse prevention program.
pertensive therapy. Prev Med 1979;8:229.● B Psychosom Med 2003;65:938–943.● B
Steiner JF, Koepsell TD, Fihn SD, Inui TS. A general Willey C. A comparison of two methods of measuring
method of compliance assessment using centralized stage of change for adherence with medication. Ann
pharmacy records: Description and validation. Med Behav Med 1998;20:S027.
Care 1988;26:814–823.● B Willey C, Stafford J, Geletko S, et al. Stages of change for
Stephenson BJ, Rowe BH, Haynes RB, Macharia WM, Leon adherence with medication. Ann Behav Med 1999;21:
G. The rational clinical examination: Is this patient tak- S156.
ing the treatment as prescribed? JAMA 1993;269: Wogen J, Kreilick CA, Livornese RC, Yokoyama K, Frech F.
2779–2781. Patient adherence with amlodipine, lisinopril, or val-
Stevens VJ, Shneidman RJ, Johnson RE, Boles M, Steele sartan therapy in a usual-care setting. J Manag Care
PE, Lee NL. Helicobacter pylori eradication in dyspep- Pharm 2003;9:424–429.● B
tic primary care patients: A randomized controlled World Health Organization. Adherence to Long-term
trial of a pharmacy intervention. West J Med 2002; Therapies: Evidence for Action: 2003. Geneva: World
176:92–96.● A Health Organization, 2003.● C

99
 C h a p t e r

10 Disease Prevention

R. Michael Morse and Charles E. Henley

ROLE OF THE FAMILY PHYSICIAN care, and patients uninformed concerning the bene-
fits of prevention. However, in a capitated environ-
The family physician has a special opportunity to be ment, family physicians are in a position in which
an effective force in disease prevention and health they have the latitude and expectation to provide a
promotion. As the primary care provider for all ages full range of preventive health services.
in family units, the family physician has an inherent
obligation to screen for a broad range of risk factors EVALUATING PREVENTIVE HEALTH
associated with preventable diseases and to encour- ACTIVITIES
age appropriate preventive measures. Most lifestyle
disease-prevention and health-promotion activities Where appropriate, recommendations from the U.S.
are applicable to the entire family unit and should Preventive Services Task Force (USPSTF) are cited.
serve as the foundation for more age-specific recom- These recommendation categories (Table 10-1)
mendations and interventions for each individual should not be confused with the standard strength-
family member. of-evidence categories used elsewhere in this text.
Although other medical-surgical problem areas Particular attention should be paid to the differ-
may occasionally require subspecialty consultation, ences between C and I recommendations. In both
the family physician is the specialist to whom cases, USPSTF makes no recommendation, but fair
patients and other specialists look for provision of evidence is associated with the C rating (but not
this broad range of health-promotion and disease- enough to weigh benefit vs. harm), and overall
prevention activities. insufficient evidence exists to reach any conclusion
Disease-prevention activities are traditionally for an I rating.
classified according to the phase of the disease Not all diseases lend themselves well to the shift
process in which intervention occurs: tertiary from medical intervention at the tertiary level to pre-
prevention (disease diagnosed and symptoms pres- vention at the secondary or primary levels. Several
ent); secondary prevention (disease present and parameters are used to determine the validity of such
diagnosable, but no symptoms present); and a shift for each disease and to determine the popula-
primary prevention (no diagnosable disease or tion group to whom the intervention should be
symptoms, but risk factors present). applied. The general criteria are as follows:
The bulk of medical education focuses on the
already ill patient (tertiary prevention), whereas pro- 1. Is the disease worth screening for? Does it have a
gressively less time is spent on secondary and pri- significant impact on the quality or length of life,
mary prevention. This may lead medical students and is it of sufficient prevalence in the population
and physicians to provide evaluation and treatment to justify screening?
primarily in reaction to patient symptoms, rather 2. Is sufficient information available to identify
than in a proactive mode of care—that is, attempting accurately, by using risk factors and screening
to anticipate problems and to prevent them. tests, the individual or groups in whom the dis-
Physicians may encounter a variety of obstacles ease is likely to develop? Or by using diagnostic
to providing comprehensive preventive health serv- tests, is it possible to identify those likely already
ices. These include heavy demands on the physician’s to have the disease at a presymptomatic stage?
time by patients already ill, lack of financial resources 3. Are the tests for the screening or early detection
in the patient population, negative third-party atti- satisfactory in terms of accuracy, morbidity, cost,
tudes toward reimbursement for preventive health and acceptability to the patient and physician?

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

100
 Chapter 10 Disease Prevention

Table 10-1 U.S. Preventive Services Task Force Ratings of Recommendations

Recommendation: A
Language: The USPSTF strongly recommends that clinicians routinely provide [the service] to eligible
patients. (The USPSTF found good evidence that [the service] improves important health outcomes and
concludes that benefits substantially outweigh harms.)

Recommendation: B
Language: The USPSTF recommends that clinicians routinely provide [the service] to eligible patients. (The
USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes
that benefits outweigh harms.)

Recommendation: C
Language: The USPSTF makes no recommendation for or against routine provision of [the service]. (The
USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the
balance of the benefits and harms is too close to justify a general recommendation.)

Recommendation: D
Language: The USPSTF recommends against routinely providing [the service] to asymptomatic patients.
(The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.)

Recommendation: I
Language: The USPSTF concludes that the evidence is insufficient to recommend for or against routinely
providing [the service]. (Evidence that [the service] is effective is lacking, of poor quality, or conflicting,
and the balance of benefits and harms cannot be determined.)

4. If it is possible to predict the disease or to diagnose INTERVENTIONS

it before the onset of symptoms, will a known inter- AND RECOMMENDATIONS
vention significantly alter the course of the disease?
5. Is the intervention or treatment satisfactory in The USPSTF findings form the basis for the evi-
terms of proved effectiveness, risk, morbidity, dence-based recommendations in this chapter.
cost, and patient acceptability? Recommendations of other scientific organizations
also are presented when appropriate.
Table 10-2* is a mortality table for the United
States. Table 10-3 shows mortality data by sex, Table
10-4 shows mortality by race, and Table 10-5 shows
mortality trends over time for each major cause of CORONARY HEART DISEASE
death. From these tables, one can begin to under-
stand the relative impact of various diseases on death Epidemiology (American Heart
rates. The mortality trends from 1979 to 1998 in Association, 2003)
Table 10-5 allow assessment of progress in preven- Incidence
tion and treatment. In particular, the decreases in The yearly national incidence of myocardial infarc-
mortality from heart disease, stroke, and accidents tion is estimated to be 1.2 million. The majority of
are highly encouraging and are due primarily to pre- individuals (50% of men and 64% of women) with
ventive health measures. Conversely, the marked coronary heart disease (CHD) have no warning of
increases in chronic pulmonary disease, pneumonia, their disease and are initially seen with either an
influenza, and diabetes are not reassuring when one acute myocardial infarction or sudden death as the
considers how preventable these deaths are. Finally, initial symptoms.
careful examination of the consistent patterns of
increased risk for male and black subjects highlights
a number of lifestyle risks in these groups. Prevalence
As shown in Table 10-6, nearly 50% of the It is estimated that 13.2 million people alive today
deaths in the United States are directly attributable to have a history of either myocardial infarction or
environmental and behavioral issues, most of which symptomatic CHD, and 1 to 2 million middle-aged
are a result of individuals’ lifestyle decisions. men in the United States have asymptomatic but sig-
nificant CHD. The prevalence of CHD is estimated at
*Tables 10-2 through 10-41 appear on the Student Consult. 6.4% of the population older than 20 years.
101
 Chapter 10 Disease Prevention

500
Total cardiovascular disease
Diseases of the heart
Coronary heart disease
400 Stroke

300
Rate

200

100

0
1900 1920 1940 1960 1980 1996
Year
Figure 10-1 Age-adjusted death rates* for total cardiovascular disease, diseases of the heart, coronary heart disease,
and stroke,† by year, United States, 1900–1996. (Data from Mortality and Morbidity, 1998 Chartbook on
Cardiovascular, Lung, and Blood Disease. Rockville, MD, U.S. Department of Health and Human Services, National
Institutes of Health, 1998.)
*Per 100,000 population, standardized to the 1940 U.S. population.
†
Diseases are classified according to International Classification of Diseases (ICD) codes in use when the deaths were
reported. ICD classification revisions occurred in 1910, 1921, 1930, 1939, 1949, 1958, 1968, and 1979. Death rates
before 1933 do not include all states. Comparability ratios were applied to rates for 1970 and 1975.

CHD is a lifelong process. Pathologic studies of Important Facts Relevant to Prevention

men in their 30s dying of noncardiac causes have
shown raised plaque in coronary arteries of up to 1. A major focus for prevention of CHD is encour-
50% (Strong et al., 1999). Men older than 50 years aging healthy lifestyles for all patients.
have a 20% prevalence of asymptomatic CHD 2. Risk-factor identification and reduction will
(Strong et al., 1999). reduce the incidence of CHD, particularly when
Although difficult, predicting the prevalence in concentrated on blood lipid levels, hypertension,
asymptomatic adults is of importance to the physi- cigarette smoking, and a sedentary lifestyle.
cian if early aggressive intervention is to be targeted 3. Changing the American diet to a low–saturated
to the appropriate patients. These high-risk groups fat, low–trans-fatty acid, low-cholesterol diet will
are identified by an analysis of the risk factors pres- reduce the levels of serum cholesterol in the pop-
ent for CHD. ulation.
5. Regression of coronary lesions is possible with
adequate treatment. Even a very low fat diet, com-
Cost of and Impact on Society bined with exercise and meditation, but without
It is estimated that the cost of medical treatment and medication, has been shown to be effective.
lost productivity for CHD in the United States is 6. In patients with significantly elevated low-density
$132.2 billion. lipoprotein (LDL) cholesterol, cholesterol-reduc-
ing medications have proved effective in reducing
Morbidity and Mortality the incidence and mortality of myocardial infarc-
Mortality rates for cardiovascular diseases and for tion in both symptomatic and asymptomatic
CHD in male and female subjects and in black and adults of all ages.
white subjects have been steadily decreasing (Figs.
10-1 and 10-2). Nevertheless, one in every five deaths Screening Test Recommendations for the
in the United States is due to CHD: 669,000 per year. General Population
In addition, 20% of all persons with a myocardial
infarction will die. Of those who survive, about two 1. Screen for lipid disorders in men at 35 years and
thirds do not make a complete recovery, although in women at 45 years (USPSTF, 2001A). Any
88% of those younger than 65 years eventually younger adult with other risk factors also should
return to work. In the 6 years after myocardial infarc- be screened (USPSTF, 2001B). Measure total and
tion, 7% of men and 6% of women experience sud- high-density lipoprotein (HDL) cholesterol for
den death, and 18% of men and 35% of women have screening purposes (USPSTF, 2001A). Patients
another infarction. found to be at high risk based on screening values

102
 Chapter 10 Disease Prevention

450

400 White
350 Black

Rate/100,000 population*
300

250
Male
200

150
Female
100

50

0
1980 1985 1990 1995 2000
Year

Figure 10-2 Age-adjusted death rates from coronary heart disease by sex and race, United States, 1980–1997. (Data
from Cooper R, Cutler J, Desvigne-Nickens P, et al. Trends and disparities in coronary heart disease, stroke, and other
cardiovascular diseases in the United States: Findings of the National Conference on Cardiovascular Disease Prevention.
Circulation 2000;102:3137–3147.)
*Rates are age-adjusted to 2000 standard.

should obtain a complete fasting lipid panel c. Every visit in current smokers.
(total, LDL, and HDL cholesterol plus triglyc- 5. Monitor activity levels at least every 5 years for
erides) to determine risk status most accurately. every patient for the recommended 30 to 40 min-
For patients found not to be at risk, a screening utes of aerobic activity 3 to 4 times weekly.
interval of every 5 years is recommended by 6. Evaluate for obesity (greater than 20% to 30%
the National Cholesterol Education Program more than ideal body weight) yearly.
(NCEP), although insufficient evidence is avail- 7. Monitor stress levels yearly (family, occupation).
able to determine the optimal interval (USPSTF, Although this factor is not used to assess risk, it
2001I). Generally, children do not need to be may have a major impact on the physician’s
screened, but consideration should be made for approach to risk reduction.
those who have a parent with high-risk lipid pro- 8. Physicians may elect to measure fasting blood
file or a history of premature heart disease in a sugar every 5 years because the presence of dia-
first-degree relative (younger than 55 years for betes is a major risk factor, particularly with a
men and younger than 65 years for women). A family history of diabetes.
family history of premature heart disease confers
a relative risk of 1.5 to 2.0. The Adult Treatment
Preventive Activities Recommendations
Panel III (ATP III, 2002) recommends beginning
screening at age 20 years with a full lipid panel Preventive activities are determined based on calcu-
and repetition every 5 years (National Cholesterol lated risk for CHD by using equations derived from
Education Program, 2002). Framingham data. This can be accomplished by
2. Measure blood pressure on all adult patients using the forms shown in Table 10-7 and Table 10-8.
(USPSTF, 2003A). Insufficient evidence exists Computerized calculators are available on the web-
to recommend the optimal interval (USPSTF, site for the National Cholesterol Education Program
2004C). The Seventh Report of the Joint Com- (NCEP, 2004).
mission on Prevention, Detection, and Treat-
ment of High Blood Pressure (JNC 7) does not Cholesterol Control
make a specific recommendation for the inter- Physicians should prescribe a heart-healthy diet for
val. However, the standard family physician all patients regardless of age or risk. It is particularly
practice of measuring blood pressure at each important that children learn healthy eating habits
office visit is reasonable. early in life. The American Heart Association pro-
3. Update family history at least every 5 years. vides online and printed nutritional guidelines for
4. Update smoking status: healthy adults and children as well as for those need-
a. Every 5 years in previous nonsmokers. ing to reduce their cholesterol to desirable levels.
b. Yearly in previous smokers who have quit. Table 10-9 gives very general guidelines that most

103
 Chapter 10 Disease Prevention

patients can easily implement in a progressive man- minutes at each visit and have been associated with a
ner. A diet high in soluble fiber (oat bran products, 30% increase in cessation from 7.9% to 10.2%. In addi-
legumes, and some fruits) has been shown in some tion, adjunctive use of medication is strongly recom-
studies to reduce serum cholesterol, whereas nonsol- mended because of high levels of efficacy in
uble fiber (present primarily in wheat, vegetables, and randomized control trials (Table 10-14).
fruit) has consistently shown no effect on cholesterol.
The presence of risk factors in combination with
LDL levels is used to determine the type of interven- Other Preventive Activities
tion. The first step is to determine if the patient has For patients with CHD or more than 5% 5-year risk of
known CHD or its risk equivalent (Table 10-10). If not, CHD, 75 mg aspirin daily will reduce risk of myocar-
then Table 10-11 is used to determine the number of dial infarction by one third (Sanmuganathan, 2001;
risk factors. Note that HDL may add or subtract from USPSTF, 2002A). It is recommended that physicians
the total, based on its level. Finally, Table 10-12 is used assist all patients to avoid risk-factor development
to determine the goal LDL levels. Note that ATP III has through encouragement of healthy lifestyles (e.g.,
created optional, more-aggressive goals based on proper nutrition, avoidance of smoking, regular phys-
results from randomized clinical trials using medica- ical activity, stress management, maintenance of ideal
tion to reduce LDL levels (Grundy et al., 2004). body weight), as well as provision of periodic preven-
Other methods of altering risk secondary to tive health care. The exact mechanism of risk reduc-
hypercholesterolemia include weight control, exer- tion for many factors has not been clearly defined. For
cise, and drug therapy. The statin family of drugs, in instance, some dietary factors such as high antioxidant
particular, has been shown to significantly reduce the content in the diet (primarily through fruits and veg-
risk of myocardial infarction. etables), a high-fiber diet, moderate alcohol consump-
tion, and intake of three or more servings of fish
Control of Hypertension weekly have been associated with a decreased risk of
Aggressive treatment of all patients with hypertension CHD. Yet, in general, trials attempting to test these
is essential, but hypertension is controlled in only 34% observations with dietary supplements have failed to
of patients (Table 10-13). Risk is doubled for each show benefit. Recently a strong association has been
20 mm Hg increment in systolic blood pressure and shown between serum homocysteine levels and the
10 mm Hg increment in diastolic blood pressure. This incidence of CHD. Homocysteine is elevated by
is true over a blood pressure range of 115/75 to increased intake of animal protein and reduced by
185/115 (Lewiston et al., 2002). In general, a systolic folic acid intake.
pressure greater than 140 or a diastolic pressure
greater than 90 is used as the cutoff point for hyper-
Discussion
tension, but this cutoff point, as well as a treatment
goal, must be individualized. For instance, the goal for The mortality of CHD in the United States has been
patients with diabetes or renal disease is 130/80. decreasing significantly, as shown in Figure 10-2.
Before institution of drug therapy for hyperten- More than 50% of this decline is due to lifestyle
sion, nonpharmacologic methods should be consid- changes, especially diet modification and smoking
ered. These include the “Dietary Approaches to cessation. This encouraging information alone pro-
Stopping Hypertension” diet, which is rich in calcium vides physicians sufficient reason to pursue further
and potassium, salt restriction, weight reduction if aggressive risk-factor prevention and modification
obese, and regular aerobic exercise. on a population-wide basis.
Although total cholesterol measurement may be
Smoking Cessation appropriate for mass public screening, use of total of
Smoking may be the most correctable risk factor for LDL plus HDL levels is more appropriate when deter-
CHD. It presents a serious risk not only for the smok- mining risk for individual patients. Measuring HDL
ers, but also for all those exposed to secondhand smoke, increases the predictive power approximately 6 to 10
particularly in the home. Smokers have a 70% increased times that of measuring total cholesterol alone. A low
risk of CHD and will reduce that in half a year after level of HDL is a strong, independent predictor of
quitting and to the level of nonsmokers after several CHD (see Table 10-11). Up to 20% of high-risk indi-
years. National evidence-based guidelines for clinicians viduals are not identified by using total cholesterol
assisting their patients in quitting smoking (Fiore et al., alone. The USPSTF does not recommend for or
2000) recommend using the “five As” approach: (1) ask against inclusion of triglyceride levels when assessing
patients about smoking, (2) advise all smokers to quit, risk for CHD (USPSTF, 2001I). However, triglycerides
(3) assess willingness to make a quit attempt, (4) assist are a component in making the diagnosis of metabolic
those who want to quit, and (5) arrange follow-up vis- syndrome that conveys a very high risk for CHD.
its with those trying to quit (Glynn, 1993). These brief Whereas national nutritional guidelines continue
clinician interventions can be completed within 2 to 3 to emphasize reduction of fat intake, most evidence

104
 Chapter 10 Disease Prevention

60

SBP 180
50
SBP 120

10-Year risk of CHD (%) 40

30

20

10

Cholesterol 180 240 240 240 240 240

HDL 50 50 35 35 35 35
Smoking No No No Yes Yes Yes
Diabetes No No No No Yes Yes
LVH No No No No No Yes

CHD, coronary heart disease; HDL, high-density lipoprotein; LVH, left ventricular hypertrophy; SBP, systolic
blood pressure

Figure 10-3 Importance of risk factors in determining coronary risk. Estimated 10-year risk of coronary heart disease
at age 55 with progressive addition of major risk factors. (Data from Anderson KM, Wilson PWF, Odell PM, Konnel WB.
An updated coronary risk profile. A statement for health professionals. Circulation 1991;83:356–362.)

suggests that the type of fat is more important than without due consideration of the person’s family and
the amount. In general, many authorities now believe environment. The chances of abstinence from smok-
that use of the monounsaturated fats (olive oil, canola ing are dimmed considerably when other smokers are
oil) and n-3 polyunsaturated fat (found primarily in in the home. Diet changes are especially difficult to
fish) should be emphasized in the total dietary fat implement for only one individual in a family unit.
allowance. Although these fats have modest beneficial Major changes in knowledge, attitudes, and habits in
effects on LDL cholesterol, they are thought also to the entire family are often required so that the desir-
have antioxidant and antithrombotic actions that able foods can be purchased, properly prepared, and
reduce CHD risk. consumed with an agreed-on common family goal of
Data suggest that sedentary lifestyle is a potent, improved health. Anything less can lead to resent-
independent risk factor that has an effect equal to ments, confusion, and outright rebellion.
that of the other major risk factors. Exercise can have
beneficial effects on insulin resistance, HDL, triglyc-
erides, obesity, and blood pressure. The American STROKE
Heart Association considers sedentary lifestyle to be
a major risk for CHD. Epidemiology
Assessing total risk for individual patients may
be complicated by the presence of more than one risk Incidence
factor. Figure 10-3 shows the progressive increase in Incidence of new and recurrent strokes is 700,000
risk as major risk factors are added. However, it must people per year, of which 88% are ischemic. Five
be recognized that most major risk factors vary in hundred thousand of these are new strokes. The
impact as their values change. yearly incidence increases dramatically with age.
The authors also recommend structured long- Overall incidence in men is 25% greater than
term follow-up with maximal support and encour- women, and blacks have twice the incidence of first-
agement from physician and office staff. ever strokes compared with whites. Figure 10-4
shows the increased relative risk of first ischemic
stroke in the most at-risk ethnic and racial popula-
Impact on the Family Unit
tions. Significant decreases have occurred in the last
The lifestyles that are important for prevention of 30 years because of recognition and management of
CHD cannot be easily implemented by an individual risk factors and lifestyle modification.
105
 Chapter 10 Disease Prevention

21.8
85+ 24.7
16.5
16.8
13.5
75– 84 23.3
11.3
11.8
9.8
65–74 10.4
4.2
6.7
4.6
Ages

55–64 4.9
1.6
2.6
2.5
45–54 2.1
0.8
1.4
0.4
35–44 0.1
0.1
Black females
0.1 Black males
0.1 White females
0.0
0–34 0.0 White males
0.0
0 5 10 15 20 25 30
Per 1,000 persons

Figure 10-4 Annual rates of first cerebral infarction by age, sex, and race, Greater Cincinnati/Northern Kentucky
Stroke Study, 1993–1994. (Data from American Heart Association. Heart Disease and Stroke Statistics, 2004 update.
Dallas, TX, American Heart Association, 2003.)

Prevalence Morbidity and Mortality

There are 4.8 million living stroke victims in the Stroke is the cause of 1 in 15 deaths or 282,000 deaths
United States. Prevalence increases markedly after per year and is the third leading cause of death in the
age 74 years (Fig. 10-5). These data do not include United States after CHD and cancer. Acute stroke mor-
the millions of individuals with significant asympto- tality is 20%. Twenty-two percent of male and 25% of
matic atherosclerotic cerebrovascular disease who female stroke victims die within 1 year, and 50% are
are at high risk for stroke. dead within 5 years. In addition to the high mortality,
stroke is the leading cause of long-term disability.
Cost of and Impact on Society The yearly cost of Fifteen percent to 30% of stroke survivors are perma-
stroke to society is estimated at $53.6 billion for med- nently disabled and require special services. Two per-
ical costs and indirect costs, such as lost productivity. cent require institutional care at 3 months after onset.

14

12
Men 12.5
Percent of population

10 Women
10.7

6
5.9 5.8
4
4.0
2 2.7
0.1 0.3 0.5 0.5 0.4 2.2
0.0 1.0
0
20–24 25–34 35–44 45–54 55–64 65–74 75+
Ages

Figure 10-5 Prevalence of stroke by age and sex. (From Third National Health and Nutrition, Examination Survey,
1988–1994.)

106
 Chapter 10 Disease Prevention

Important Facts Relevant to Prevention

the current data are not sufficient to show that these
Physical activity is strongly and inversely related to treatments effectively reduce the risk of stroke in
stroke incidence. A major risk factor for stroke is patients with asymptomatic carotid bruits. Such
hypertension, and risk increases disproportionately studies are in progress and will provide further guid-
at all ages as either systolic or diastolic pressures ance in the future. Other risk factors for stroke
increase (Figs. 10-6 and 10-7). The other major risk include family history of stroke, cigarette smoking,
factors for atherosclerosis, with the exception of dys- oral contraceptive use, hyperlipidemia, and elevated
lipidemia, also are predictive for stroke risk. The hematocrit.
known presence of heart disease (CHD or atrial fib-
rillation) carries a high risk for emboli to the brain. Screening Test Recommendations
Atrial fibrillation increases stroke risk 5 times and is Blood pressure and smoking status are the two major
responsible for 15% of cerebral infarcts. Diabetes modifiable risk factors and should be determined.
mellitus, even if mild, carries a significant increased The optimal interval for this screening is not known,
risk for stroke and this risk increases disproportion- but it is often done each office visit. Other risk fac-
ately if diabetes also is present or if criteria are met tors (similar to those for CHD) for atherosclerosis
for metabolic syndrome (Table 10-15). should be sought, as previously recommended in the
In a large cohort study, a transient ischemic discussion on CHD. The USPSTF has concluded that
attack (TIA) conferred a 10.5% risk of subsequent insufficient evidence exists to recommend for or
stroke in the following 90 days (Johnston et al., against screening asymptomatic persons for carotid
2000). One of five stroke victims has had at least one artery stenosis by using physical examination or
of four major symptoms suggestive of TIA in the carotid ultrasound. (USPSTF, 1996I).
prior year: (1) temporary loss of vision (especially if
in one eye), (2) unilateral numbness, (3) aphasia, and Preventive Activities Recommendations
(4) focal weakness.
Patients with carotid bruits have a 1% to 3% Prevention of stroke is aimed primarily at prevention
incidence of stroke per year. Although aspirin, anti- and treatment of sustained, even mild, hypertension
coagulants, and surgery are commonly prescribed, and other known risk factors for atherosclerosis.

SYSTOLIC BLOOD PRESSURE DIASTOLIC BLOOD PRESSURE

256

Age at risk (years):

floating absolute risk and 95% CI

64 80–89
70–79
Stroke mortality,

60–69
16 50–59

120 140 160 180 70 80 90 100 110

Usual systolic blood Usual diastolic blood
pressure, mm Hg pressure, mm Hg

Stroke mortality rate, pictured on a log scale with 95 percent confidence intervals,
in each decade of age in relation to the estimated usual systolic and diastolic
blood pressure at the start of that decade. Stroke mortality increases with both
higher pressures and older ages. For diastolic pressure, each age-specific regression
line ignores the left-hand point (i.e., at slightly less than 75 mm Hg), for which
the risk lies significantly above the fitted regression line (as indicated by the broken
line below 75 mm Hg).

Figure 10-6 Stroke mortality related to blood pressure and age. Note that mortality is on a log scale. (Data from
Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis
of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903–1913.)

107
 Chapter 10 Disease Prevention

30

Estimated 10-year rate (%)

25 27.0
Men
20 Women 22.4
19.1
15
14.8
10
8.4
5
6.3
1.1 4.0 2.0 5.4 3.5
2.6
0
A B C D E F
A B C D E F
Systolic BP* 95 –105 130 –148 130 –148 130 –148 130 –148 130 –148
Diabetes No No Yes Yes Yes Yes
Cigarettes No No No Yes Yes Yes
Prior atrial
fibrillation No No No No Yes Yes
Prior CVD No No No No No Yes

Figure 10-7 Estimated 10-year stroke risk in 55-year-old adults according to levels of various risk factors, Framingham
Heart Study. (Data from Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: A risk profile from
the Framingham Study. Stroke 1991;22:312–318.)
*Blood pressures are in millimeters of mercury (mm Hg)

Smokers, in particular, should be strongly SUBSTANCE ABUSE, ALCOHOLISM,

advised to stop and should be offered assistance in AND OTHER DRUG DEPENDENCY
that effort. Aspirin has not been shown to be effective
in primary prevention of stroke. Anticoagulation Epidemiology
with warfarin is proven to be effective primary pre-
vention in patients with atrial fibrillation and aver- Incidence
age-to-high risk of stroke (Segal et al., 2000 ● A ). )
Inability to identify a specific time that an individual
Secondary prevention in patients with TIAs includes meets criteria for alcohol, or drug abuse or depend-
prophylaxis with aspirin or other antiplatelet agents ence makes incidence rates very difficult to deter-
(unless otherwise contraindicated), anticoagulation mine reliably. Centers for Disease Control and
in certain circumstances, and carotid endarterec- Prevention (CDC) studies have shown an incidence
tomy, depending on the degree of stenosis. In the of fetal alcohol syndrome (FAS) of 0.2 to 1.5 per
acute phase of an ischemic stroke, thrombolytic ther- 1000 live births. The incidence of less severe variants
apy has been shown to be effective. However, few is approximately 3 times that of FAS.
patients can be treated within the recommended
3-hour time frame. Prevalence
More than 17 million, or 17%, of U. S. individuals 12
years of age or older abused or were dependent on
Discussion alcohol or illicit drugs in 2001 (Substance Abuse and
Despite the lack of evidence that dyslipidemia Mental Health Administration, 2002). Figure 10-8
increases stroke risk, treatment with statin drugs has shows the proportions for users of alcohol and
been shown to lower risk by 24% to 29% (Corvol drugs. The male-to-female ratio is 2:1. The highest
et al., 2003●A ). The most important reason to con- rate of abuse of or dependence on alcohol or illicit
sider screening for carotid bruits is to document the drugs was among 18- to 25-year-olds and American
existence of significant atherosclerosis in high- Indians/Alaska natives. One study of primary care
risk individuals and thus alert the physician to the practices showed that 16.5% of patients were “prob-
need to modify risk factors more aggressively. lem drinkers” (Fleming et al., 1997● A ). )

However, a theoretical risk with this approach is that

it may initiate a process that includes angiography Cost of and Impact on Society
and endarterectomy, procedures that have no clear The estimated yearly cost of alcohol abuse and
consensus as to their proper use in asymptomatic dependence in the United States is $184.6 billion,
individuals. including $134.2 billion from lost employment and

108
 Chapter 10 Disease Prevention

12,000 with small volumes (one drink or less per day) of

10,975 alcohol consumption because of the cardiovascular
benefits, but as volume increases, the many adverse
10,000 effects overcome these benefits (Enlish, 1995).

8,000
Important Facts Relevant to Prevention
A wide variety of serious individual social, psycho-
logical, and physical health problems are strongly
6,000
associated with misuse of alcohol. FAS is a perma-
nent, severe syndrome of mental retardation and
4,000 birth defects that is 100% preventable. Society bears
3,181 a large burden of social, legal, and economic prob-
2,423 lems as a result of alcohol and drug abuse.
2,000 The USPSTF recommends “screening and behav-
ioral counseling interventions to reduce alcohol mis-
use by adults, including pregnant women, in the
0
Both alcohol and Any iIIicit drug Alcohol primary care setting” (USPSTF, 2004B). Insufficient
any illicit drug only only evidence exists to recommend for or against this
approach for adolescents (USPSTF, 2004I).
Figure 10-8 Estimated numbers (in thousands) of per-
sons aged 12 or older reporting past year abuse or
Measures to increase enforcement of drinking
dependence for any illicit drug or alcohol, 2001. and driving laws, to increase prices for alcoholic bev-
erages, and to increase the legal drinking age have
reduced productivity and $26.3 billion in health care been successful in reducing either alcohol consump-
costs (Harwood, 2000). The estimated total cost of tion or the frequency of the legal consequences of
illicit drug use is $160.7 billion of which $14.9 billion drinking. Whether education can reduce the rate of
is for health care (Office of Drug Control Policy, alcoholism is not known. Strong cultural biases (e.g.,
2001). The social consequences of problem drinking, Orthodox Jews) against drunkenness substantially
although not quantifiable, may be as great as the reduce the prevalence of abuse and dependence.
costs of the medical consequences. Abusers have a Children of alcoholics are at 3 to 4 times greater
higher rate of injury, divorce, domestic violence, risk of alcoholism, whether or not their biologic par-
unemployment, and poverty. ents raise them.
Although spontaneous recovery from alco-
Morbidity and Mortality The contribution of alcohol holism is reported in more than 20% of patients
misuse to overall mortality is 3.5% of all deaths, and (American Psychiatric Association, 1994), psychoso-
that of illicit drugs is 0.7% (see Table 10-6). Patients cial treatment has been reported to result in a 30% to
with alcoholism have 2.5 times the normal overall risk 60% 1-year abstinence rate (Finney et al., 1996).
of mortality. Overall mortality is 30% to 38% higher Even brief interventions in the outpatient setting
among men and more than doubled in women who have shown significant reduction in high-risk drink-
drink more than six drinks per day. More than 100,000 ing behavior for up to 48 months (Fleming et al.,
deaths per year are related to alcohol abuse, and half of 2002● A ). Increasing evidence shows that the use of
these are related to accidental deaths. adjunctive pharmacotherapy agents such as naltrex-
The morbidity for chemical dependency (alco- one and acamprosate provides added benefit. One
hol and drug abuse) is substantial, ranging from the must remember that studies use a variety of defini-
extremely high association with crime to cirrhosis, tions of both alcoholism and recovery.
psychosis, depression, cardiomyopathy, peptic ulcer
disease, overdose, cancer of directly exposed organs Screening Test Recommendations
(lips, mouth, larynx, pharynx, esophagus, stomach,
liver), pancreatitis, suicide, various infections (hepa- All patients older than 12 years should be screened
titis, acquired immunodeficiency syndrome [HIV], regularly for alcohol and substance abuse. A yearly
endocarditis, pneumonia), fetal alcohol syndrome, frequency of screening can deliver a strong educa-
violence, and accidents of all types. tional message to the patient, although the optimal
However, it should be kept in mind that regular screening interval has not been determined.
alcohol consumption has a beneficial association with The first step in screening individuals who con-
a 30% to 40% reduction of risk of death from cardio- sume alcohol is evaluating volume and frequency of
vascular diseases (Thun et al., 1997). This benefit is drinking. Risky drinking is defined for female sub-
evident at low to moderate levels of intake and does jects as more than three drinks any day during the
not increase with additional alcohol intake. Overall, prior month or more than seven drinks average per
low point of a J-shaped mortality curve is associated week, and for male subjects, as four drinks any day

109
 Chapter 10 Disease Prevention

or more than 14 drinks average per week. Adverse of their seeking help through the family physician. All
consequences with continued drinking are the pregnant women should be advised against the use of
major common criteria for abuse and dependence alcohol and drugs during pregnancy, and all users
in the Diagnostic and Statistical Manual of Mental should be advised against driving and performing
Diseases (DSM-IV), with additional elements, other dangerous behaviors while intoxicated.
including physiologic effects (tolerance, with- Evidence-based counseling and intervention
drawal) and further loss of control, necessary for guidelines should be followed for those individuals who
dependence (Tables 10-16 and 10-17). screen positive for alcohol abuse or dependence (U.S.
The ultimate goal of screening questions is to Department of Health and Human Services, 2003).
ascertain whether the patient is having or has ever
had a health, legal, or personal problem as a result of
Discussion
drinking alcohol. The CAGE questionnaire is the
most widely used screening tool (Table 10-18). Any A helpful way of understanding the relation between
positive response should be explored. Two or more alcohol consumption and resultant problems is
positive responses to the CAGE questions in the past shown in Figure 10-9.
year are highly suggestive of alcohol abuse or The same questions used for alcohol abuse and
dependence and require further investigation. The dependence may be equally applicable to drug abuse.
T-ACE questions have been validated for use in Certain cues found in alcoholics, and often in other
pregnancy (Table 10-19). The increased sensitivity of drug-dependent patients, help lead to the correct
the T-ACE compared with the CAGE during preg- diagnosis: problems with children, separation,
nancy is shown in Table 10-20. Guidelines published divorce, job changes, depression, anxiety, hyperten-
by the U.S. Department of Health and Human sion, macrocytosis of red blood cells, low resistance
Services are a very useful evidence-based resource for to infections, recurrent accidents, arrests and other
effective strategies for dealing with alcohol problems legal problems, upper gastrointestinal complaints,
in the outpatient medical setting (U.S. Department and abnormal liver enzymes.
of Health and Human Services, 2003).
The Two-Item Conjoint Screen (TICS), a two-
Impact on the Family Unit
question screen for detection of either alcohol or
drug use disorder, has shown a likelihood ratio of The family is at the epicenter of the alcoholic earth-
1.93 for one positive response and 8.77 for two. The quake. As the rumblings of the disease progress, so
two questions are as follows: (1) “In the last year, does pathology within the family. One in four
have you ever drunk or used drugs more than you American children is exposed to alcohol abuse or
meant to?” and (2) “Have you ever felt you wanted or dependence in the family (Grant et al., 2000) and is
needed to cut down on your drinking or drug use the at significant risk of serious physical and psycholog-
last year?” (Brown et al., 2001● B ). ical consequences. Most prominent is the role of the
“co-alcoholic” or “enabler,” who assumes the abne-
Preventive Activities Recommendations gated responsibilities of the alcoholic, covers for the
alcoholic, and makes possible his or her continued
The presence or absence of alcoholism in first-degree drinking. This person is often the major focus of the
relatives should be a part of the family history. A pos- alcoholic’s hostility. Treatment should include heal-
itive answer identifies a high risk for alcohol prob- ing of the entire family.
lems and affords an opportunity to inquire about the
patient’s drinking history and current status. Any
patient with a family history of alcoholism should be CANCER
counseled concerning his or her high-risk status and
General Information
encouraged to become a member of Al-Anon or the
Children of Alcoholics Foundation. About 1,368,030 new cancer cases are expected to be
All patients, including children, should be asked diagnosed in 2004 (Fig. 10-10). Since 1990, more
yearly if any problems within the family involve alcohol. than 18 million new cases of cancer have been diag-
Those caring for female patients during the nosed. However, the National Cancer Institute (NCI)
childbearing years should assure that these patients estimates that approximately 9.6 million Americans
are aware of the risk of FAS and its less severe vari- with a history of cancer were alive in January 2000.
ants. If they might become pregnant, they must not Death rates from all cancers combined have been
consume alcohol. decreasing since the 1990s. Death rates decreased for
Literature concerning the warning signs of alco- 11 of the top 15 cancers in men and 8 of the top 15
holism and sources of help should be freely available in cancers in women (NCI, 2004). The mortality trends
every medical office. If the subject of chemical depend- since 1930 for all major cancers are shown in Figures
ency is dealt with openly, an increased likelihood exists 10-11 and 10-12.

110
 Chapter 10 Disease Prevention

Non
e
Ligh ALC
t OHO
L CO
NSU
MPT
Mod ION
erate
? Subs
? tantia
Alco l
hol-r
elate Abuse Hea
d dis vy
abilit
ies Depe
nden
ce
li s m
ho
ing Alco Seve
re
drink
lem ?
Prob l
tantia
? Subs
MS
erat
e
RO BLE
Mod OL P
OH
Mild ALC

e
Non

Figure 10-9 A terminological map of alcohol use.

LEADING SITES OF NEW CANCER CASES AND DEATHS−−2004 ESTIMATES*

Estimated New Cases* Estimated Deaths

Male Female Male Female
Prostate Breast Lung and bronchus Lung and bronchus
230,110 (33%) 215,990 (32%) 91,930 (32%) 68,510 (25%)

Lung and bronchus Lung and bronchus Prostate Breast

93,110 (13%) 80,660 (13%) 29,500 (10%) 40,110 (15%)

Colon and rectum Colon and rectum Colon and rectum Colon and rectum
73,620 (11%) 73, 320 (11%) 28,320 (10%) 28,410 (10%)

Urinary bladder Urinary corpus Pancreas Ovary

44,640 (6%) 40,320 (6%) 15,440 (5%) 16,090 (6%)

Melanoma of the skin Ovary Leukemia Pancreas

29,900 (4%) 25,580 (4%) 12,990 (5%) 15,830 (6%)

Non-Hodgkin's lymphoma Non-Hodgkin's lymphoma Non-Hodgkin's lymphoma Leukemia

28,850 (4%) 25,520 (4%) 10,390 (4%) 10,310 (4%)

Kidney Melanoma of the skin Esophagus Non-Hodgkin's lymphoma

22,080 (3%) 25,200 (4%) 10,250 (4%) 9,020 (3%)

Leukemia Thyroid Liver Urinary corpus

19,020 (3%) 17,640 (3%) 9,450 (3%) 7,090 (3%)

Oral cavity Pancreas Urinary bladder Multiple myeloma

18,550 (3%) 16,120 (2%) 8,780 (3%) 5,640 (2%)

Pancreas Urinary bladder Kidney Brain

15,740 (2%) 15,600 (2%) 7,870 (3%) 5,490 (2%)

All sites All sites All sites All sites

699,560 (100%) 668,470 (100%) 290,890 (100%) 272,810 (100%)

Figure 10-10 Leading sites of new cancer cases and deaths, 2004 estimates. (Data from The American Cancer Society.
Cancer Facts and Figures 2004. Atlanta, American Cancer Society, 2004.)
*Excludes basal and squamous cell skin cancers and in situ carcinoma except urinary bladder.
Note: Percentages may not total 100% due to rounding.

111
 Chapter 10 Disease Prevention

100

Lung and bronchus

Prostate
80 Colon and rectum
Rate per 100,000 male population

Leukemia
Stomach
Pancreas
60 Liver

40

20

0
1930 1940 1950 1960 1970 1980 1990 1999

Figure 10-11 Age-adjusted death rates, males* by site, United States, 1930–1999. (Data from U.S. Mortality Public Use
Data Tapes, 1960–1999, U.S. Mortality Volumes, 1930–1959. National Center for Health Statistics, Centers for Disease
Control and Prevention, 2002. American Cancer Society, Surveillance Research, 2003)
*Per 100,000, age-adjusted to the 2000 U.S. standard population.
Note: Due to changes in ICD coding, numerator information has changed over time. Rates for cancers of the liver,
lung and bronchus, and colon and rectum are affected by these coding changes.

100

Lung and bronchus

Uterus†
Rate per 100,000 female population

80 Colon and rectum

Breast
Stomach
Pancreas
60 Ovary

40

20

0
1930 1940 1950 1960 1970 1980 1990 1999

Figure 10-12 Age-adjusted death rates, females* by site, United States, 1930–1999. (Data from U.S. Mortality Public
Use Data Tapes, 1960–1999, U.S. Mortality Volumes, 1930–1959. National Center for Health Statistics, Centers for
Disease Control and Prevention, 2002. American Cancer Society, Surveillance Research, 2003.)
*Per 100,000, age-adjusted to the 2000 U.S. standard population.
†
Uterus cancer death rates are for uterine cervix and uterine corpus combined.
Note: Due to changes in ICD coding, numerator information has changed over time. Rates for cancers of the liver, lung
and bronchus, colon and rectum, and ovary are affected by these coding changes.

112
 Chapter 10 Disease Prevention

Definition of Cancer Nation, lung cancer incidence rates among women

have leveled off for the first time, after increasing for
Cancer is a group of diseases characterized by many decades.
uncontrolled growth and spread of abnormal cells.
Cancer is caused by both external factors such as Morbidity and Mortality Lung cancer is the leading
tobacco, ionizing radiation, chemicals, and infectious cause of cancer death in the United States, with
organisms, and internal factors such as inherited 160,440 resulting deaths in 2004, and it remains one
mutations, hormones, immune conditions, and of the leading causes of preventable death world-
mutations that occur from metabolism. All cancers wide. Because of the high case-fatality rate for the
involve some form of gene malfunction that controls disease, the incidence and mortality rates are nearly
cell growth and division. Often a long latent phase identical. The age-adjusted lung cancer death rate in
occurs between exposure and development of the United States is 56.9 per 100,000 population in
detectable cancers. 1988. Small cell carcinoma is the most aggressive
type and carries the worst prognosis, with a median
General Cancer Prevention survival from diagnosis of only 2 to 4 months with-
out treatment. Although the prognosis for the
All cancers related to cigarette smoking and heavy heterogeneous group of cancers classified as
alcohol consumption are completely preventable. non–small cell (epidermoid, large cell, and adenocar-
Evidence suggests that about one third of the 563,700 cinoma) cancers is better, the overall survival rate for
cancer deaths expected to occur in 2004 will be all types is just 5% to 10%.
related to nutrition, physical inactivity, obesity, and
other lifestyle factors, and thus also could be pre- Important Facts Relevant to Prevention
vented. Infectious agents such as hepatitis B virus, A single etiologic agent, cigarette smoking, is the
human papilloma virus, and HIV also are implicated leading cause of lung cancer. This causal relation
in the etiology of certain cancers, and the risk for between cigarette smoking and lung cancer is
acquiring these infections could be reduced signifi- unequivocal and represents one of the most
cantly through behavioral change. Regular screening intensely studied relations in medical research.
can result in the detection of cancers of the breast, Approximately 90% of all new cases of lung cancer
cervix, colon, prostate, oral cavity, and skin at a stage are attributed to cigarette smoking, and smokers
at which treatment is more likely to be beneficial. are at a 20-fold increased risk for developing lung
cancer compared with people who never smoked.
Who Is at Risk? Even with the strong causal association with smok-
ing, a few other etiologies also have been associated
About 76% of all cancers are diagnosed at age 55 or with lung cancer, such as occupational exposures
older. Lifetime risk in the United States is less than one to arsenic, asbestos, chromate, hydrocarbons,
in two for men, and a little more than one in three for chloromethyl ethers, nickel, and radon. Emerging
women. Relative risk is a measure of the strength of evidence also exists for a genetic susceptibility
the relation between risk factors and a particular can- factors such as polymorphism in the cytochrome
cer compared with that in those individuals who do p450 enzymes and mutations in the k-ras oncogene
not have the exposure. For example, in male smokers, and the p53 gene. Environmental tobacco smoke
lung cancer is 20 times more likely to develop than in continues to be an important source of risk and a
nonsmokers, so the relative risk is 20. However, significant public health issue. The only evidence-
women who have a first-degree relative with breast based advice for reducing cancer risk is not to
cancer have a twofold increased risk of breast cancer smoke or to stop smoking; however, 50% of all new
developing compared with women who do not have a lung cancers are diagnosed in former smokers.
family history, so their relative risk is only 2. The
actual probability of cancer developing, by age and sex Screening Test Recommendations
in the general population, is shown in Table 10-21. Even though lung cancer is one of the most preventa-
ble of cancers, no major professional organization
Lung Cancer currently recommends screening for lung cancer,
including the USPSTF. Studies on the use of chest
Epidemiology radiographs and 3-day pooled sputum cytology
Incidence The NCI reports the 2004 incidence for showed an insufficient efficacy in detecting lung can-
both small cell and non–small cell lung cancer in the cer compared with low-dose helical computed tomog-
United States at 173,770 new cases. This makes it the raphy (CT). Although still no evidence exists that
second highest cancer incidence for both males and screening tests reduce the rate of cancer-specific mor-
females in the United States (see Fig. 10-10). tality, a growing interest is found in the potential of
However, in the 2004 NCI Annual Report to the low-dose helical CT for improving screening efficacy.

113
 Chapter 10 Disease Prevention

Preventive Activities Recommendation increased along with the increase in smoking,

Smoking cessation is a key component of any which peaked at around 1965. Even though smok-
prevention strategy. Patients at all ages should receive ing has been in decline, the rates of lung cancer will
a strong health message concerning smoking, includ- continue to increase until the peak incidence rate
ing an offer of assistance for current smokers from for past smokers has been reached. The populations
their physicians (USPSTF, 2003A): “It’s addicting. at greatest risk for lung cancer based on smoking
Don’t start. If you have started, stop.” The risk for lung prevalence are 18- to 24-year-olds, American
cancer decreases among those who quit smoking com- Indians and Alaskan Natives, and those who have
pared with those who continue to smoke. Diet as a not completed high school (Table 10-22, Figs. 10-13
preventive of lung cancer has been studied by various and 10-14). Physicians can continue to have a major
groups (Wright, 2000), and foods such as flax seeds, impact on the risk of this disease through commu-
fruits and vegetables, and foods rich in sulforophane, nity and patient intervention and education.
such as broccoli sprouts, and selenium, folic acid, vita- Targeting certain cohorts at higher risk, such as
min B12, vitamin D, and antioxidants have all been young women and certain ethnic groups, also
implicated in a cancer-prevention diet. β-Carotene makes sense as part of an overall prevention strat-
has been especially touted as being effective in pre- egy. Excellent support materials are available from
venting lung cancer, although randomized placebo- the American Academy of Family Physicians, the
controlled trials have not shown a significant American Cancer Society (ACS), and the American
protective effect. The β-carotene and retinol efficacy Heart Association. Physician recommendation has
trial (CARET) conducted in the United States and the a great potential impact on patients’ decisions to
Alpha Tocopherol Beta-Carotene (ATBC) trial con- stop smoking.
ducted in Finland showed an actual increased risk
associated with β-carotene supplementation. Impact on Family Unit
A single smoker in a family can be a source of
Discussion secondary smoke exposure for the rest of the
The prevention of lung cancer is dependent on the family. Angina, respiratory symptoms, and
identification of exposures to known carcinogens increased risk of lung cancer can result in those
such as cigarette smoking. The epidemiology of exposed. A relatively high number of lung cancer
lung cancer shows irrefutable correlation with the cases from never-smokers have been attributed to
onset of lung cancer and the introduction of the exposure to passive smoking. Children from
first manufactured cigarette by R.J. Reynolds in households with smokers have a higher school
1913. Lung cancer was a rare disease before the turn absence rate as a result of increased incidence of
of the century, but the incidence of lung cancer respiratory illnesses, infections, and middle-ear

45

40
12th grade, non-Hispanic white
35

30
12th grade, Hispanic/Latino
Percent

25

20
12th grade, African American
15

10

0
1977 1982 1987 1992 1997 2002
Year

*Used cigarettes in the last 30 days.

*
Figure 10-13 Current cigarette smoking among 12th graders, by race and ethnicity, 1977–2002. (Data from American
Cancer Society. Cancer Prevention and Early Detection Facts and Figures, 2004. Atlanta, American Cancer Society, 2004.)
* Used cigarettes in the last 30 days.

114
 Chapter 10 Disease Prevention

50

45
No high school degree
40

35
High school degree
Percent 30

25
Some college
20

15

10
College degree
5

0
1974 1983 1987 1990 1992 1994 1997 1999 2001
Year

Figure 10-14 Current* cigarette smoking by education, adults 25 and older, 1974–2001. (Data from National Health
Interview Survey, 1974–2001, National Center for Health Statistics, Centers for Disease Control and Prevention,
American Cancer Society. American Cancer Society, Surveillance Research.)
*Adults 25 and older who have smoked 100 cigarettes in their lifetime and who are current smokers (regular and
irregular).

infections. Infants born to mothers who smoked colaou (Pap) test to screen for preinvasive cancer.
during pregnancy are more likely to die of sudden Cervical cancer that is detected in the preinvasive
infant death syndrome. Couples who smoke create stages, such as carcinoma in situ, has a 100% cure rate
a special problem for the physician who wishes to with proper treatment, whereas localized cancer has a
help. It is difficult to persuade one smoker to quit 91% 5-year survival rate. The Healthy People 2010
while the other continues, and it is equally target for cervical cancer is a reduction in mortality to
problematic to bring two smokers to the point of 2.0 deaths per 100,000 women. Since 1998, the rate
wishing to stop at the same time. The withdrawal has been approximately 3.0 deaths per 100,000.
period is one of great stress and requires family
education and support. Important Facts Relevant to Prevention
Squamous cell carcinoma of the cervix occurs almost
Cervical Cancer exclusively in women who are sexually active, with
the risk for developing a precancerous lesion increas-
Epidemiology ing with increasing numbers of sexual partners. The
Incidence In 2004, the incidence of invasive cervical American Cancer Society guidelines on early detec-
carcinoma (new cases) was 10,520, although declin- tion of cervical neoplasia describe the mean time for
ing. The overall incidence rates in the United States progression from mild dysplasia (CIN I-1) carci-
have decreased from 14.2 per 100,000 women in noma in situ (CIN III) or cancer as 70 to 80 months
1973, to 7.8 cases per 100,000 women in 1994. The in women older than 50 years, 41 to 42 months for
NCI Surveillance, Epidemiology, and End Results women aged 26 to 50 years, and 54 to 60 months in
(SEER) program reports the incidence of invasive women younger than 25 years. The mean time for
cervical cancer from in the United States, from 1995 further progression to invasive carcinoma is an addi-
to 1999, in women age 20 to 24 years, to be tional 10 years. The rate of progression for any one
1.7/100,000 per year. Worldwide, cervical carcinoma individual is unpredictable, with some intraepithelial
is the most common malignancy in women, whereas lesions regressing spontaneously in 30% to 50% of
in the United States it is the 10th most common form cases, depending on age. In adolescent women, aged
of malignancy among woman. 13 to 21 years, 70% of high-grade and 90% of low-
grade lesions have been shown to regress within
Morbidity and Mortality The mortality for invasive 3 years, whereas 30% of older patients with CIN III
carcinoma of the cervix in 2002 was 4100 women, have progression to invasive carcinoma.
although the mortality has declined 70% from the Major risk factors are early age for first inter-
mid-1920s since the introduction of the Papani- course, multiple sexual partners, HIV infection,

115
 Chapter 10 Disease Prevention

herpes simplex virus infection, history of condylo- retical benefits, it also can be strongly recommended
mas (human papilloma virus, or HPV infection), to help prevent sexually transmitted diseases (STDs).
smoking, and low socioeconomic status. Early sex-
ual intercourse has an especially dramatic effect on Discussion
risk. Women who had coitus less than 1 year after Other good reasons exist to request many women to
menarche are 26 times more likely eventually to come in for an examination more often than every
have cervical carcinoma than are women in the gen- 3 years, such as monitoring use of birth control pills,
eral population. From 15% to 20% of American dietary advice, contraceptive counseling, and prepreg-
women do not undergo regular Pap tests, and they nancy counseling. Only a minority of women may
account for the majority of cases of carcinoma of need to visit their physician less often than once yearly.
the cervix. Among previously screened women with Women have been educated for many years that the
a history of normal Pap tests, fewer than 1 in 1000 yearly Pap test is essential but not that other important
will have a high-grade lesion. A single Pap test has a issues should be dealt with during these visits.
sensitivity of around 58% and a specificity of 99%.
Major variability in the effectiveness of the Pap Impact on Family Unit
smear as a screening tool depends on proper sam- Invasive cervical cancer occurring during the child-
pling and specimen handling and on the quality of bearing years is usually treated surgically, ending the
the laboratory. chances of future pregnancy. This has a profound
effect on a single woman’s approach to possible mar-
Screening Test Recommendations riage and on a married couple’s plans and relation-
The USPSTF recommendations for screening for ship. The family physician’s role only begins with
cervical cancer include beginning Pap smears referral for appropriate treatment. Preventive coun-
approximately 3 years after sexual activity begins, seling is necessary in these situations. Women past
but no later than age 21 years, and continued screen- the childbearing years may still have a loss of identity
ing at 3-year intervals (USPSTF, 2005A). Most similar to, but not as intense as, that of the breast
organizations recommend having a Pap test at least cancer victim.
once yearly for 3 years and then, after at least three
negative annual Pap tests, the frequency may be
Skin Cancer
reduced to as little as every 3 years, at the discretion
of the physician. The USPSTF advises against Pap Epidemiology
tests in women older than 65 years who have had Incidence There are 800,000 cases of basal and squa-
consistently negative examination and in women mous skin cell cancer yearly plus an additional
who have had a total hysterectomy for benign dis- 38,300 malignant melanomas. This is more than
ease (USPSTF). Suggestive Pap tests should be eval- twice the cancer incidence of that in any other organ
uated by direct observation with colposcopy. system. Since the 1960s, the incidence of cutaneous
Although the Food and Drug Administration (FDA) squamous cell carcinoma has been increasing dra-
has approved hybrid capture II technology for matically at 4% to 8% per year.
screening for HPV, and a clear association is shown
with HPV as the etiology of cervical cancer, the Morbidity and Mortality Of the 9430 deaths each
USPSTF does not yet recommend testing for HPV year, 7300 are from malignant melanoma. Mortality
with polymerase chain reaction or hybrid capture II is rare with nonmelanoma cancers, but substantial
as an alternative or an adjunct to primary Pap morbidity can be prevented with effective screening.
screening (USPSTF). HPV testing may be worth-
while if it can be shown to distinguish reliably Important Facts Relevant to Prevention
between women who would benefit from more The most important risk factor for all skin cancer is
intensive Pap testing or colposcopy. In women who exposure to ultraviolet (UV) light. Major risk factors
do have HPV DNA testing done, and are positive for include severe sunburns as a child, fair complexion,
one of the high-risk HPV types such as 16, 18, 31, or multiple or atypical moles, a family or personal history
45, colposcopy examination would be warranted, of skin cancer, poor tanning ability, freckles, history of
even if they have normal Pap tests. local treatment with ionizing radiation, and immuno-
suppression (Table 10-23). Occupational exposures to
Preventive Activities Recommendations coal tar, pitch, arsenic, radium, and creosote all increase
Risk status should be re-evaluated at each preventive risk.
health visit, especially in groups who may have an
increased likelihood of multiple sexual partners. Screening Test Recommendations
Women should be advised of their risk status, with The most efficient screening programs target individ-
emphasis on the importance of regular re-evalua- uals at higher risk for the development of skin cancers
tion. Although barrier contraception has only theo- (Wolfe, 1999). For melanoma, that means light-

116
 Chapter 10 Disease Prevention

skinned people a history of excessive skin exposure, a black men. These declines were due to declines in
family history of melanoma, multiple nevi, or dysplas- distant disease mortality, which in turn was due to
tic nevi. During regular preventive health examina- a decrease in distant disease incidence and not to
tions, the skin should be thoroughly examined for improved survival of patients with distant disease.
suggestive lesions. All lesions suggestive of malignancy Because of the potential for morbidity associated
should be sampled by biopsy or prophylactically with progression of prostate cancer to widespread
excised and submitted for pathologic interpretation. metastases, many experts believe that the increased
Randomized trials have not proven the efficacy of detection of prostate cancer with PSA before it
either melanoma or nonmelanoma skin cancer becomes metastatic is responsible for the reduced
screening, yet physicians discover approximately 20% morbidity in both white and black men.
of melanomas when the patient did not notice any-
thing unusual. Unfortunately, many primary care Important Facts Relevant to Prevention
physicians do not take the opportunity to examine the Only a small minority of men with microscopic evi-
skin when patients are seen for other problems. This dence of prostate cancer ever has clinical evidence of
routine screening of the skin for cancerous lesions the disease. Population studies have suggested that
within the usual context of care should become more dietary fat may be related to increased risk of
commonplace, especially for higher-risk patients. prostate cancer.

Preventive Activities Recommendation Screening Recommendations

For primary prevention, all patients at risk should The principal screening tests are digital rectal exam-
be counseled in measures for UV-wave avoidance ination, serum tumor markers such as the PSA, and
(sun or artificial tanning), protection with higher transrectal ultrasound. The sensitivity and specificity
sun protection factor (SPF) number sunscreens of these tests are difficult to calculate. Although these
(15 or greater), and use of protective clothing (see tests have been shown to increase the diagnosis of
Table 10-23) (USPSTF, 2003A). Secondary preven- disease, it remains to be seen whether these screening
tion includes regular self-examination. This is a tests will lead to interventions that will prolong life.
logical activity, especially for patients with already A recommendation for routine screening is contro-
existing melanotic nevi. versial. It is possible that a screening program sensi-
The physician also should be alert to actinic ker- tive to the risk factors and targeting patients with
atoses and treat these as appropriate with 5-fluo- curable disease could decrease the rates of mortality
rouracil or retinoic acid topical application when and morbidity. Conversely, routine screening for
generalized or with local means such as cryocautery. prostate cancer also can result in patients being
offered curative treatments when their disease does
Prostate Cancer not require extensive treatment. Physicians are
advised to counsel all men older than 50 years of the
Epidemiology availability, risks, and benefits of PSA testing.
Incidence Prostate cancer is the second leading cause Insufficient evidence exists to recommend for or
of cancer death in American men age 50 years or against screening (USPSTF, 2002).
older. Approximately 230,000 new cases and 30,000
deaths occur each year in the United States. A dra-
Endometrial Cancer
matic, transient 20% increase in incidence was found
for several years after 1986 when the FDA approved Epidemiology
the prostate-specific antigen (PSA) test for screening Incidence and Mortality See Figures 10-10, 10-11,
for prostate cancer. It continues to increase 6% per and 10-12.
year, probably secondary to increased detection
efforts. African-American men tend to have a higher Important Facts Relevant to Prevention
incidence of prostate cancer, 37% higher than that of Endometrial cancer is the most common cancer of the
white men. genital tract and represents 10% of all cancers diag-
nosed in women. It is primarily a postmenopausal dis-
Prevalence Prevalence increases with age. Some ease, with 97% of endometrial cancers being
studies have found microscopic evidence of prostate adenocarcinoma. Endometrial cancer can arise from
cancer in 30% of autopsies of men age 30 to 49 years. malignant transformation of atrophic endometrium,
Estimates of the prevalence in men older than 80 but the major causative factor appears to be unop-
years range up to 100%. posed estrogen, whether physiologic or iatrogenic,
with estrogen excess giving rise to atypical hyperplasia
Morbidity and Mortality According to the SEER of the endometrium. The most important early-warn-
program, the mortality rates for prostate cancer ing sign is abnormal vaginal bleeding. Risk factors are
declined after 1991 in white men and in 1992 in obesity, prolonged treatment with estrogen alone, age,

117
 Chapter 10 Disease Prevention

chronic anovulation, and increased number of years appears to occur in women with a family history of
of menstruation (early menarche, late menopause, or breast cancer who take estrogen birth control pills,
no pregnancies). Hypertension and diabetes are asso- with an association between the prolonged use (>10
ciated with risk, probably because of the prevalence of years) of HRT and breast cancer risk. The risk seems
obesity in these patients. An association is found to be 6% increase in breast cancer risk for every 5
between the use of tamoxifen as an adjuvant treat- years of estrogen replacement and a 9% increase in
ment for breast cancer and the development of risk for every 5 years of estrogen plus progestin ther-
endometrial cancer (Crabbe, 1996). Tamoxifen works apy. However, the major association seems to be in
as an antiestrogen in breast tissue, but it also has estro- the cancer-susceptibility genes BRCA1 and BRCA2,
genic properties that can affect the endometrium as which account for 45% of the hereditary forms of
well as other tissues, such as bones and the cardiovas- breast cancer (Brewster, 2001). The cumulative risk
cular system. It is estimated that 2 of 1000 women who of breast cancer developing in a woman with a muta-
are taking tamoxifen for breast cancer are at higher tion in BRCA1 and BRCA2 is 84% by age 70 years.
risk for developing endometrial cancer. However, the The use of selective estrogen-receptor modulators
benefits may outweigh the risks. such as tamoxifen has been advocated as a primary
prevention of breast cancer in high-risk women such
Screening Test Recommendations those with a strong family history of first-degree rel-
Insufficient evidence exists to recommend for or atives having breast cancer or carrying the BRCA1 or
against routine screening (NCI, 2005). Most cases of BRCA2 genes. Certainly, evidence exists that hor-
endometrial cancer are diagnosed by symptoms, and monal manipulation will play an important role in
high proportions are diagnosed at an early stage and reducing cancer risks, because prophylactic
have high rates of survival. Endometrial cells are oophorectomy in BRCA1 and BRCA2 carriers has
occasionally found on Pap smear, but this is not an been shown to reduce the risk of breast cancer devel-
adequate screen. Any endometrial cells found on a oping by 50% to 70%. One of the potential side
postmenopausal Pap smear should be considered effects of using tamoxifen is its association with
abnormal. All postmenopausal women with abnor- endometrial cancer. Raloxifene, another selective
mal bleeding of any amount must have endometrial estrogen-receptor modulator, has not been shown to
sampling performed. have the same association with endometrial cancer.
Clinicians should consider both the risks of breast
Preventive Activities Recommendation cancer and the risks of adverse effects when recom-
Risk factors should be established at menopause and mending chemoprophylaxis. USPSTF (2005D) recom-
modified when possible. All women with an intact mends against routine use of tamoxifen or roloxifene
uterus who are treated with estrogen replacement in low or average risk women.
therapy also should be prescribed a progestational
agent, although the use of hormone replacement Screening Test Recommendations
therapy (HRT) is recommended against routine use Although the evidence is inconclusive concerning
(USPSTF, 2005D) for the prevention of osteoporosis the added value of clinical breast examination, most
or other postmenopausal conditions, because of the clinicians believe that the clinical breast examination
potential for serious complications of heart disease is an important part of the detection of breast cancer.
and a higher breast cancer risk. Mammography alone has a sensitivity of 30% in
women with very dense breast tissue and 80% in
Breast Cancer women with fatty breast tissue. The ACS recom-
mends that all women should start having annual
Epidemiology mammograms at age 40 years, or earlier if they have
Incidence, Morbidity, and Mortality Breast cancer is strong risk factors for breast cancer. The USPSTF
the leading cause of death in women worldwide. In now also recommends starting at age 40 years for
the United States, 192,000 new cases of invasive breast routine screening and no longer recommends that
cancer occurred in 2001, with 40,200 deaths, and screening with mammograms cease after age 70 years
1500 cases of breast cancer in men, with 400 deaths. (USPSTF, 2002B). The prevalence of mammography
screening varies by population, with the uninsured
Important Facts Relevant to Prevention having rates of less than 40% (Table 10-25). The clin-
The etiology of breast cancer in men is poorly under- ical breast examination has an I rating from the
stood, but in women, several associations should be USPSTF, whereas the ACS strongly recommends it.
considered. The risk factors for breast cancer are
shown in Table 10-24. Women who delay childbirth Preventive Activities Recommendation
until after age 30 years have a twofold increase in the It is important for family physicians to understand
risk of breast cancer developing. The excessive use of the risk factors and associations with HRT, family
alcohol also may play a role. A small increase in risk history, age of pregnancy, and BRCA carrier state to

118
 Chapter 10 Disease Prevention

advise women on their options for screening and Because of its low specificity, no recommendation
primary prevention. exists to use C-125 in premenopausal women as a
screening device. C-125 can be used in post-
Ovarian Cancer menopausal women with an adnexal mass, or in
detecting relapse of a known ovarian cancer. Other
Epidemiology conditions, such as pancreatitis, chronic hepatitis,
Incidence In the United States, 23,000 women are endometriosis, alcoholic hepatitis, adenomyosis,
diagnosed with ovarian cancer every year, represent- renal failure, pelvic inflammatory disease, and preg-
ing a 1.7% lifetime risk for developing the disease. nancy, also can release small amounts of CA-125,
Two genes, BRCA1 and BRCA2, are linked with both which may confuse the screening process. The diffi-
hereditary breast and ovarian cancer (Modugno, culty is in differentiating between ovarian cancer and
2003). Testing positive for the genetic marker does benign ovarian masses. The risk for ovarian cancer
not mean that cancer will develop, but it does increase increases with increasing size of any ovarian cyst, to
the lifetime risk to between 16% and 60%. The inci- the point at which a cyst on ultrasound that is larger
dence of ovarian cancer also increases with age, with than 10 cm has a 60% chance of being malignant.
the majority of cases occurring between the ages of The FDA and the NCI have jointly published data
55 and 74 years, with the average being 61 years. using artificial intelligence computer programs to
identify correctly patterns of serum proteins from a
Morbidity and Mortality Every year, 14,000 women finger-stick blood sample in patients with ovarian
die of ovarian cancer, accounting for 52% of all cancer. This had a sensitivity of 100% and a speci-
gynecologic cancer deaths. Seventy-five percent of ficity of 95%, with a positive predictive value of 94%,
ovarian cancers are not diagnosed until the cancer compared with 35% for C-125. This may prove to be
has advanced to stage III or IV, giving the patient a a worthwhile screening tool in the future, especially
5-year survival rate of only 20%. for women who are BRCA1 positive or have a strong
family history of ovarian cancer. Currently, a nega-
Important Facts Related to Prevention tive C-125 test cannot rule out the presence of ovar-
A documented decreased risk for ovarian cancer is ian cancer. Fair evidence indicates that screening may
found in women who use birth control pills. This is lead to important harms (USPSTF, 2004D).
probably because of the prolonged suppression of
ovarian function. The risk for ovarian cancer in Preventive Activities Recommendation
women who are positive for the BRCA genes also No proven primary prevention therapies are known
goes down with each live birth, although increased for ovarian cancer, although a case could be made for
risk is associated with the use of HRT for longer than treating high-risk women desiring birth control with
10 years. The use of estrogen replacement for less oral contraceptive pills. Knowing and advising women
than 10 years does not seem to be associated with an about their personal risk factors is presently one of the
increased risk. Other risk factors for ovarian cancer most useful tasks for the primary care physician.
include a documented first-degree relative (mother,
daughter, sister) with ovarian cancer, a high-fat diet,
Colorectal Cancer
nulliparity, infertility, age older than 30 years at time
of first pregnancy, use of talcum powder in feminine Epidemiology
hygiene, and living in North America or Northern Incidence, Morbidity, and Mortality According to
Europe. Having two or more first-degree relatives the ACS, colorectal cancer is the third leading cause
with ovarian cancer increases the lifetime risk of the of cancer-related death in the United States in both
disease developing to almost 50%. men and women, with 148,000 new cases and 56,600
deaths estimated in 2002.
Screening Test Recommendations
The mortality data for ovarian cancer have not Important Facts Related to Prevention
improved in three decades because a reliable screen- An individual’s lifetime risk for developing colorectal
ing mechanism for ovarian cancer still does not cancer is 6%, with 90% of all cases occurring after age
exist. The tumor marker CA-125 is too nonspecific, 50 years. The risk factors for colorectal cancer are
and pelvic examinations are operator dependent. It shown in Table 10-26. Colorectal cancer is considered
is estimated that 10,000 pelvic examinations would a preventable disease. It is the result of accumulated
have to be done to identify one ovarian cancer. genetic mutations over many years, leading to the for-
Today three main approaches to screening exist: mation of adenoma and ultimately to carcinoma. The
transvaginal ultrasound, C-125 tumor marker, and disease can be prevented if this adenoma-to-carci-
pelvic examinations. Only 80% of ovarian cancers noma sequence is not initiated or can be interrupted.
produce C-125, and the C-125 antigen has a low A strong association between high dietary fiber and
specificity, especially in premenopausal women. low incidence of colorectal cancer can play a role in

119
 Chapter 10 Disease Prevention

reducing the incidence of colorectal cancer. The epi- on cost and limited access. A recent Veterans
demiologic strength for such a statement is over- Administration cooperative study showed the majority
whelming, even though it now appears that the major of cancers detected by colonoscopy were identified in
reason for this association is that, in general, popula- an early stage, suggesting that colonoscopy screening
tions with low fiber intake consume higher levels of may be able to identify potentially curable cancers. The
saturated fat. Evidence also indicates that non- current recommendations for screening are to deter-
steroidal anti-inflammatory drugs (NSAIDs), either mine the risk status of the individual in terms of fam-
aspirin or nonaspirin cyclo-oxygenase (COX)-1 and ily history and personal medical history. Individuals
COX-2 inhibitors, can have a beneficial effect in pre- with a history of ulcerative colitis, acromegaly, or a
venting the development of adenomatous polyps. first-degree relative with colorectal cancer or familial
Case reports exist of adenomatous regression in polyposis should undergo colonoscopy examination
patients with familial polyposis using NSAIDs. The every 1 to 3 years. The average-risk person should begin
risk reduction for colorectal cancer with the use of annual fecal occult blood and flexible sigmoidoscopy
NSAIDs may be as much as 40% to 50%. However, no screening or full colonoscopy by age 50 years, with
long-term clinical trials looked at the effect of periodic re-examination every 3 to 5 years (USPSTF,
NSAIDs on the actual reduction of colorectal cancer, 2002A) (Dove, 2001). Compliance with screening
and the evidence for such an association is inferential guidelines is low (Table 10-27). The use of CT colonog-
from other studies. A study sponsored by the NCI was raphy also may show promise in detecting adenoma-
begun in 2000 to study the effectiveness of the COX- tous polyps and cancers without the effects of
2 inhibitor celecoxib (Celebrex) in preventing adeno- conscious sedation. With colonoscopy as the standard,
matous polyps, a precursor of colon cancer. The study this technique has been shown to have a 60% to 90%
(the Adenoma Prevention with Celecoxib, or APC sensitivity in detecting large polyps.
trial) was to run until 2005 but was halted when
analysis by an independent data safety board showed Preventive Activities Recommendation
a 2.5-fold increase in risk of fatal and nonfatal car- Although some evidence exists for the use of aspirin
diovascular events compared with placebo. This fol- or other NSAIDs along with diet in the primary pre-
lows another report in September 2004 that the vention of colorectal cancer, this cannot be consid-
COX-2 inhibitor rofecoxib (Vioxx) also caused a ered a substitute for colorectal cancer screening.
twofold increase in cardiovascular toxicities in a trial Adherence to screening protocols should be the over-
to prevent adenomas. Because of these findings, we riding effort of primary care physicians. Trials of
cannot recommend this class of drugs for prevention population screening with fecal occult blood tests
of adenomatous polyps. have shown a significant decrease in mortality,
whereas trials of once-only flexible sigmoidoscopy
Screening Test Recommendations and colonoscopy are still under way. Patients should
Because primary prevention and lifestyle changes are also be instructed on the long-term health benefits of
difficult to initiate and take many years to accomplish, a high-fiber and low-fat diet. Other possibly effective
it is important that effective screening programs also chemoprevention therapies include the use of oral
be in place. Some controversy exists over the relative folate and calcium. Folate intake should be at the
value of screening with flexible sigmoidoscopy versus level of 400 μg/day. Calcium supplements also have
colonoscopy. Conclusive evidence indicates that fecal been associated with lower colorectal cancer risk,
occult blood testing alone can decrease the mortality of possibly by binding bile and fatty acids in the bowel
colorectal cancer by identifying patients who then lumen or by directly inhibiting the colonic epithelial
undergo colonoscopy to identify their cancers. cell proliferation. The recommended dosage is 1800
However, the false positives encountered with this test mg of calcium daily.
create a large burden of resulting colonoscopies on
patients with no disease, with a huge cost to the health
In Brief: Screening for Other Cancers
care system. The addition of flexible sigmoidoscopy to
fecal occult blood testing means that many more actual Testicular Cancer
polyps will be detected and removed, without the need Testicular cancer is relatively rare. Physician exami-
for conscious sedation. However, several proximal can- nation and self-examination of the testes have not
cers or adenomatous polyps may be missed by not been demonstrated to be effective enough to recom-
visualizing the right and transverse colon. Colono- mend mass screening. However, it is appropriate to
scopy has several advantages in detecting colorectal examine the testes as part of an examination for
cancer. The entire colon is visualized, and suggestive other reasons.
lesions can be sampled or removed. Part of the success
of the fecal occult blood screening is that it results in Pancreatic Cancer
colonoscopies. However, it may be difficult to recom- Cancer of the pancreas is the fourth leading cause of
mend the use of colonoscopy as a screening tool based cancer death in American men and women.

120
 Chapter 10 Disease Prevention

However, because of a lack of evidence of effective- OSTEOPOROSIS

ness, screening in asymptomatic persons by palpa-
tion, ultrasonography, or serologic markers is not Epidemiology
recommended.
Incidence
Oral Cancer Although it is difficult to determine the yearly inci-
Primary care physicians are advised to include an dence of osteoporosis, the major complication of
oral examination in routine preventive health fractures secondary to osteoporosis is estimated to be
screening, particularly in high-risk persons, such as 1.5 million per year. Osteoporosis causes a fracture in
smokers and people using snuff or chewing tobacco. more than half of all women after menopause, most
Patients should be advised against the use of all commonly in the vertebral column, with the remain-
tobacco products, and the heavy use of alcohol. der in the hip, distal forearm, and other sites.

Bladder Cancer Prevalence

Routine screening for bladder cancer is not advised. It is estimated that 5 million women older than 50
However, patients who smoke tobacco double their years have osteoporosis and are therefore at
risk of bladder cancer and should be advised to stop. increased risk for fractures. Another 14 million have
osteopenia. Seventy percent of women older than 70
Thyroid Cancer years have osteoporosis at one or more sites. Black
Thyroid cancer is rare. Screening of asymptomatic women have rates approximately half those of white
patients is not recommended, but examination at women (Fig. 10-15).
intervals may be advised for patients with an
increased risk, such as those with a childhood history Cost of and Impact on Society
of head or neck irradiation. The National Osteoporosis Foundation estimates the
medically related costs of caring for patients with
Childhood Cancer fractures secondary to osteoporosis are $17 billion
Although an estimated 9300 new cases of childhood each year.
cancers are expected in children aged 0 to 14 years
in 2004, childhood cancers showed some of the Morbidity and Mortality
largest improvements in cancer survival, with an Hip fractures are associated with an increased mortal-
absolute survival-rate increase of 20% in boys and ity of 10% to 20% in the following year. Hip and ver-
13% in girls. An estimated 1510 deaths are expected tebral fractures lead to significant morbidity. Chronic
in 2004, about one third from leukemia. In spite of pain, loss of mobility and independence, as well as the
these figures, childhood cancer remains a relatively serious medical consequences of multiple vertebral
rare disease. fractures (restrictive lung disease, gastrointestinal

8,000

7,000
Number needed to screen

6,000

5,000

4,000
Without risk factor
3,000

2,000
With risk factor
1,000

0
50–54 55–59 60–64 65–69 70–74 75–79
Age (y)

Figure 10-15 Number needed to screen to prevent one hip fracture in 5 years with advancing age and for women
younger than 65 with at least one risk factor. (Data from Nelson HD, Helfand M, Woolf SH, Allan JD. Screening for
postmenopausal osteoperosis: A review of the evidence for the U.S. Preventative Services Task Force. Available at
www.preventiveservices.ahrq.gov. Accessed 1/24/2006.)

121
 Chapter 10 Disease Prevention

problems from altered abdominal anatomy) all have screening interval for repeated testing has not been
adverse effects on well-being. determined.

Important Facts Relevant to Prevention Preventive Activities Recommendations

Ultimately, the degree of osteoporosis is dependent All patients, especially women, should be educated
on two major factors: the peak bone density at age 20 regarding the recommended intake of 1000 mg of
to 30 years and the rate of bone loss thereafter. The dietary calcium. Postmenopausal women not receiv-
risk of osteoporosis and resultant fractures increases ing estrogen should increase calcium intake to 1500
with age. Compared with age 50 to 54 years, women mg. Major nutritional sources of calcium are listed in
age 65 to 69 years have 5.9 times the risk of osteo- Table 10-29. Dairy products should be low fat as part
porosis, and those age 75 to 79 years have 14.3 times of the overall prudent diet. Women unable to meet
the risk (Siris et al., 2001). In women, bone loss minimal calcium needs through diet should be
abruptly increases to 2% to 3% per year at advised to use supplemental calcium plus vitamin D,
menopause and then gradually returns to pre- 400 to 800 IU daily.
menopausal rates. Men follow a similar sequence, Risk status should be reviewed for all females,
but without the accelerated phase. Total loss of bone preferably at menarche, and re-evaluated at the time
mass in men is about two thirds that of women. of routine preventive health visits. Additional coun-
Before age 30 years, adequacy of calcium intake seling concerning osteoporosis prevention should be
affects the peak bone mass, and after age 30 years, given to those at higher risk.
slows the rate of loss of bone mass slightly. All All patients should be counseled to maintain reg-
women and men need 1.0 g of elemental calcium ular aerobic weight-bearing activities as part of the
daily to maintain a zero calcium balance. In post- overall program for general preventive health care.
menopausal women not prescribed estrogen replace- Although 50 to 60 minutes of exercise 3 times weekly
ment therapy, increasing this amount to 1.5 g still has been shown to increase bone mass, the minimal
does not maintain zero calcium balance. An 80% levels necessary have not been determined.
prevalence of inadequate calcium intake is found
among female patients of all ages.
Discussion
Bone mineral density measurements using dual
energy x-ray absorptiometry accurately predict risk Falls are one of the major reasons for the increase in
for osteoporotic fractures. morbidity and mortality in individuals with osteo-
Available treatments for osteoporosis in asympto- porosis. Thus evaluating elderly individuals for fall
matic women reduce fracture risk. Effective medica- risk and instituting preventive measures are particu-
tions include bisphosphonates, selective estrogen- larly important for those with osteoporosis.
receptor modulators, and calcitonin. Although no Contributing factors may be easily overlooked
longer recommended because of other associated when an illness that may increase risk of osteoporo-
risks, estrogen replacement therapy is an effective sis consumes the focus of attention. A good example
method of preventing the accelerated phase of bone- might be the elderly white woman in otherwise good
mass loss after menopause and reducing fracture risk. health in whom polymyalgia rheumatica develops.
Other methods of maximizing peak bone mass The attention required to make the diagnosis and the
and slowing bone-mass loss include regular weight- resulting treatment with corticosteroids become the
bearing exercise. Actual gains in lumbar bone mass have major focus. It is easy to forget that such a person, 2
been demonstrated in postmenopausal women placed years later, may be free of polymyalgia symptoms but
on a weight-bearing exercise regimen. This effect was debilitated by vertebral fractures.
sustained as long as the exercise was continued.
Many risk factors exist for osteoporosis plus
Impact on the Family Unit
multiple additional medical conditions that may
place an individual at higher risk (Table 10-28). Family eating patterns primarily determine the peak
Obesity, because of increased endogenous estro- bone mass achieved. Therefore counseling of women
gen levels, and thiazide diuretics, because of decreased in the childbearing years should include recommen-
calcium excretion, have a protective effect. dations for the entire family.
Elderly patients who are already at high risk cre-
Screening Test Recommendations ate a dilemma for the family physician. The resulting
impact of severe fractures is sudden loss of inde-
The USPSTF recommends screening all women pendence. In an elderly family member, this has great
beginning at age 65 years and all high-risk women impact in both emotional and financial terms. The
beginning at age 60 years by using dual energy x-ray resulting major decisions that must be made often
absorptiometry (USPSTF, 2002B). The optimal reverse the parent and child roles. Intimate knowl-

122
 Chapter 10 Disease Prevention

edge of the elderly patient, his or her functional damage, transmission to newborn children and sexual
capacities, and the living situation place the family contacts, cancer of the cervix, death, and others.
physician in a pivotal role in fracture prevention.
Important Facts Relevant to Prevention
SEXUALLY TRANSMITTED DISEASES The fact that many of these infections are incurable
and have a high prevalence of asymptomatic carriers
Epidemiology has led to STDs being categorized as the “hidden
Incidence epidemic.”
More than 25 diseases are transmitted primarily The risk factors for STDs are sexual behaviors in
through sexual activity. Hepatitis A, B, and C, in individuals or groups of individuals that predispose
addition to their primary modes of infection, also to sexual transmission of disease (Table 10-32). Only
can be sexually transmitted. More than 834,000 cases abstinence and properly used condoms are effective
of chlamydia infection, more than 350,000 cases of in reducing the risk of disease transmission through
gonorrhea, and more than 6,800 cases of syphilis are sexual contact.
reported each year in the United States. The rates of The presence of chlamydia or herpes infection
chlamydia and syphilis are slowly increasing, whereas has been shown to enhance significantly the likeli-
gonorrhea incidence is decreasing slightly. The actual hood of sexually transmitted infection when the
incidence of these diseases beyond reported cases is individual is exposed to HIV.
not known, but more than 3 million actual new
infections with chlamydia each year and more than Screening Test Recommendations
650,000 new cases of gonorrhea are estimated. The The USPSTF recommends routine screening for
CDC reports that one fourth of these infections are chlamydia infection in all sexually active women
in teenagers, with the overall incidence of these being younger than 25 years and in all other high-risk non-
highest in women age 15 to 19 years, in men age 20 pregnant women (USPSTF, 2001A) as well as in these
to 24 years, and in blacks. The estimated incidence groups during pregnancy (USPSTF, 2001B). The evi-
and prevalence of the most common STDs (exclud- dence is not strong enough to recommend for or
ing HIV) is shown in Table 10-30. The estimated against screening other women whether pregnant or
annual incidence of new HIV infections is 40,000. not (USPSTF, 2001C). The evidence for and against
Forty-two percent of these are in men who have sex screening men for chlamydia infection is too close to
with men, and 54% are in blacks. justify a general recommendation (USPSTF, 2001C).
The optimal screening interval or timing of screening
Prevalence during pregnancy for chlamydia is not known (USP-
Chlamydia infection is particularly insidious because STF, 2001). In its 1996 Second Report, the USPSTF
70% to 90% of women and a high percentage of men made recommendations for gonorrhea screening sim-
with infections are asymptomatic. At least 45 million ilar to those for chlamydia. The USPSTF has not made
people in the United States are estimated to have recommendations concerning screening for HPV
genital herpes simplex virus infection and 20 million infection, but the Canadian Task Force on Preventive
to have HPV (see Table 10-30). An estimated 850,000 Health Care (2003D) has determined that fair evi-
to 950,000 persons in the United States are living dence exists to recommend against routine screening.
with HIV, including 180,000 to 280,000 who do not The USPSTF recommended that all at-risk indi-
know they are infected. viduals including pregnant women and those who
live in higher-prevalence areas be periodically
Cost of and Impact on Society screened (USPSTF, 1996A).
The total estimated cost of STDs in the United States,
including sexually transmitted HIV, is more than $16.6
Preventive Activities Recommendations
billion. Table 10-31 shows the breakdown by disease.
Areas of the country with the largest declines of
Morbidity and Mortality STDs have been those that have active public health
Of the estimated 15 million individuals in the United education and screening programs. High schools
States who contract one or more STDs each year, half have the highest-risk population and present the best
will have a lifelong infection. This leads to an esti- opportunity for systematic prevention efforts. The
mated prevalence of 65 million persons with an prevalence of sexually active high school students
incurable STD (Cates et al, 1999). HIV is the leading engaging in early intercourse at younger than 13
cause of death in black men, age 25 to 44 years. years and with four or more sexual partners is shown
Each disease has it own short-term and long-term in Table 10-33. Family physicians should support
consequences. These include chronic or recurring and, when possible, actively participate in public
pain, infertility, disseminated disease with multiorgan health efforts to reduce STDs.

123
 Chapter 10 Disease Prevention

The advent of reasonably accurate, noninvasive such as those traveling to areas in which the disease is
screening tests for chlamydia by using urine speci- endemic. The prevalence of coverage for recommended
mens makes the process and acceptability of broader immunizations for children has met or continues to
screening more achievable for both male and female increase toward meeting the Healthy People 2010 goal
subjects. Clinicians should consider routine use of of 90% coverage. The rates for the elderly have been less
these tests for their high-risk patients. successful, with only 66% coverage for influenza and
56% for streptococcal pneumonia disease.
Discussion Cost of and Impact on Society
An example of the epidemiology of the consequences Immunization is highly cost-effective. For instance,
of STDs follows. From 75% to 90% of women with influenza and streptococcal pneumonia immuniza-
chlamydia infection have no symptoms, yet in 40% tion in the elderly produce $30 to $60 of savings for
of women with untreated chlamydia infections, every dollar spent. Measles, mumps, rubella immu-
pelvic inflammatory disease will develop, and one in nization in children saves $16.34 for each dollar
five of these women will become infertile. The usual spent (CDC, 1999).
source of infection is from the 50% of infected men
who have no symptoms. Important Facts Relevant to Prevention
Many of the historically most severe, often epidemic,
Impact on the Family Unit infectious diseases are now well controlled by safe,
The incrimination that can result when a husband effective immunizations that have an excellent cost-
or wife is diagnosed with an STD may lead to to-benefit ratio.
major family disruption. The physician plays the
key role in interpreting the meaning of such an Preventive Activities Recommendations
episode and bringing the couple to a mutual
understanding. It is therefore critical that the Family physicians should regularly update recom-
physician know the natural course of the disease. mended schedules for pediatric (Fig. 10-16) and
Because of the high percentage of asymptomatic adult immunizations (Fig. 10-17). Documentation
infected individuals with many of these infections, and reminder systems are important strategies in
it is often impossible to know accurately when the assuring optimal protection of patients from vac-
patient was initially infected. cine-preventable illness.
The high prevalence of STDs among teens cre- A variety of vaccines also are recommended for
ates some very challenging issues for both the teens individuals with special medical conditions (Fig.
and the parents. Assuring that children are educated 10-18), as well as those undertaking international
concerning their risk is paramount, and creating an travel. Up-to-date information is available at
environment that fosters open and honest commu- www.cdc.gov/nip/default.htm.
nication will help assure appropriate evaluation and
treatment, should infection be suspected.
INJURY PREVENTION
Epidemiology
VACCINE-PREVENTABLE INFECTIONS
Incidence
Epidemiology The medical system cares for 24.6 million injury and
poisoning episodes per year: 104 million by office-
Incidence based physicians, 10.8 million by hospital outpatient
One of the greatest public health achievements of the departments, and 39.2 million by emergency depart-
20th century has been the dramatic effect of immu- ments. The estimated number of total injuries per
nization on the incidence of infectious disease, par- year exceeds 57 million.
ticularly in children. Table 10-34 shows the nearly
100% decrease in the morbidity of diseases for which Morbidity and Mortality
immunizations are universally recommended in More than 160,000 injury deaths occur each year.
children. Poliomyelitis has been virtually eliminated The major causes of those deaths are shown in Table
from the Western Hemisphere, and smallpox has 10-35. Unintentional injury is the leading cause of
been eliminated worldwide. death for all age groups from age 1 to 34 years (Table
10-36). Motor vehicle traffic is the leading cause of
Prevalence unintentional injury death for all age groups except
Vaccines such as childhood immunizations may be rec- those younger than 1 year and older than 65 years,
ommended universally or specifically for at-risk groups for whom it is second (Table 10-37). For intentional

124
 Chapter 10 Disease Prevention

Age Birth 1 mo 2 mo 4 mo 6 mo 12 mo 14 mo 16 mo 24 mo 4–6 y 11–12 y 13–18 y

package in inserts for detailed recommendations. Clinically significant adverse events that follow immunization should be reported to theVaccine Adverse Event Reporting

Figure 10-16 Recommended childhood and adolescent immunization schedule, United States, July through
December 2004. (Data from Advisory Committee in Immunization Practices. Recommended Childhood and Adolescent
Immunization Schedule, United States, July through December 2004. MMWR Morb Mortal Wkly Rep. 2004;53:Q1–Q3.)

Vaccine Age group (yrs) 19–49 50–64 ≥ 65

Tetanus,
1 Dose booster every 10 years
diphtheria (Td)

Influenza 1 Dose annually 1 Dose annually

Pneumococcal 1 Dose 1 Dose

(polysaccharide)

Hepatitis B 3 Doses (0, 1–2, 4–6 mos)

Hepatitis A 2 Doses (0, 6–12 mos)

Measles, mumps,
1 or 2 Doses
rubella (MMR)
Varicella 2 Doses (D, 4–8 wks)

Meningococcal
(polysaccharide) 1 Dose

For all persons in this group For persons lacking documentation For persons at risk (i.e., with
of vaccination or evidence of disease medical/exposure indications)

Figure 10-17 Recommended adult immunization schedule, by vaccine and age group, United States, October 2004
through September 2005. (Data from Centers for Disease Control and Prevention. Recommended Adult Immunization
Schedule, United States, October 2004 through September 2005. MMWR Morb Mortal Wkly Rep 2004;53:Q1–Q4.)

125
 Chapter 10 Disease Prevention

Congenital
immunodeficiency,
cochlear implants,
leukemia,
lymphoma,
Indication

generalized
malignancy,
therapy with Asplenia
Diabetes, heart alkylating agents, Renal fallure/ (including elective
disease, chronic antimetabolites, end-stage renal splenectomy
pulmonary disease, CSF † leaks, disease, recipients and terminal
chronic liver radiation, or of hemodialysis complement
Vaccine disease (including large amounts or clotting factor component Health-care
Pregnancy chronic alcoholism) of corticosteroids concentrates deficiencies) HIV§ infection workers

Telanus,
diphtheria (Td)*

Influenza A, B C

Pneumococcal B D D, E, F D, G
(polysaccharide)

Hepatitis B* H

Hepatitis A*
I

Measles, mumps, J
rubella (MMR)*

Varicella* K

For all persons For persons lacking documentation For persons at risk (i.e., with
Contraindicated
in this group of vaccination or evidence of disease medical/exposure indications)

* Covered by the Vaccine Injury Compensation Program.

† Cerebrospinal fluid.
§ Human immunodeficiency virus.

Special Notes for Medical and Other Indications

A. Although chronic liver disease and alcoholism are not indications for influenza vaccination, administer one dose annually if the patient is aged ≥50 years,
has other indications for influenza vaccine, or requests vaccination.
B. Asthma is an indication for influenza vaccination but not for pneumococcal vaccination.
C. No data exist specifically on the risk for severe or complicated influenza infections among persons with asplenia. However, influenza is a risk factor for
secondary bacterial infections that can cause severe disease among persons with asplenia.
D. For persons aged <65 years, revaccinate once after ≥5 years have elapsed since initial vaccination.
E. Administer meningococcal vaccine and consider Haemophilus influenzae type b vaccine.
F. For persons undergoing elective splenectomy, vaccinate ≥2 weeks before surgery.
G. Vaccinate as soon after diagnosis as possible.
H. For hemodialysis patients, use special formulation of vaccine (40 mg/mL) or two 20 mg/mL doses administered at one body site. Vaccinate early in the
course of renal disease. Assess antibody titers to hepatitis B surface antigen (anti-HB) levels annually. Administer additional doses if anti-HB levels
decline to <10 mlU/mL.
I. For all persons with chronic liver disease.
J. Withhold MMR or other measles-containing vaccines from HIV-infected persons with evidence of severe immunosuppression (see MMWR 1998;47
[No. RR-8]:21-2 and MMWR 2002; 51[No. RR-2]:22–4).
K. Persons with impaired humoral immunity but intact cellular immunity may be vaccinated (see MMWR 1999; 48[No. RR-6]).

Figure 10-18 Recommended adult immunization schedule, by vaccine and medical and other indications, United
States, October 2004 through September 2005. (Data from Centers for Disease Control and Prevention. Recommended
Adult Immunization Schedule, United States, October 2004 through September 2005. MMWR Morb Mortal Wkly Rep
2004;53:Q1–Q4.)

Important Facts Relevant to Prevention

injury deaths, homicide is one of the top five causes
of death for groups age 1 to 34 years, and suicide is Alcohol use is a major factor in multiple types of
one of the top five for groups from ages 10 to 54 intentional and unintentional injuries. The most
years (Table 10-38). effective interventions have been those that are legis-
Based on emergency department treatment lated or require no action on the part of the individ-
records, the large preponderance of more serious ual or family (or both). Examples are safer vehicles
nonfatal injuries is unintentional. Of these nonfatal and child-proof safety caps.
injuries, the leading cause in all age groups except 15 Specific measures that have been shown to
to 24 years is falls (Table 10-39). reduce injury include seat belts, children’s car seats,

126
 Chapter 10 Disease Prevention

vehicle air bags, helmets for cyclists, smoke detectors, include screening for alcohol abuse, because 40% of
and absence of firearms in the home. Office-based fatal motor vehicle accidents are alcohol related.
interventions increase compliance with preventive
recommendations such as seat-belt use.
Impact on the Family Unit

Screening Test Recommendations In addition to the immediate trauma, nonfatal acci-

dents affect the individual and the family directly. An
Physicians should consider screening patients for issue that must be confronted is the injured person’s
injury risk factors such as use of safety restraints and the other family members’ own mortality.
when driving, fire alarms in the home, firearms in Although some families grow closer at these times,
the home, violence in the home or community, and others may distance themselves as a defense mecha-
alcohol abuse. Additional risk-assessment questions nism. Fatal accidents present a special problem. The
are age specific, such as safety measures in the home loss is unexpected and often occurs in those who are
for young children and the elderly. The USPSTF has otherwise young and healthy. The process of grieving
one screening recommendation related to injury pre- may become particularly difficult or pathologic.
vention, which cites insufficient evidence to recom-
mend for or against screening for family and
DIABETES MELLITUS
intimate partner violence (USPSTF, 2004I).
Recommendations
Preventive Activities Recommendations
Despite the high morbidity, mortality, and cost associ-
The guidelines for prevention listed under alcohol ated with diabetes, the long presymptomatic stage, the
abuse and osteoporosis should be followed. The high prevalence, and the ease of diagnosis, the USPSTF
USPSTF recommends counseling all patients and is unable to find sufficient evidence to recommend for
parents of patients concerning use of occupant or against routine screening for type 2 diabetes (USP-
restraints in vehicles, use of helmets when riding STF, 2003I). It is known that aggressive management of
motorcycles, refraining from driving or participating diabetes can reduce microvascular complications, but
in other dangerous activities when under the influ- no evidence indicates that earlier diagnosis and treat-
ence of alcohol or drugs, and reduction of uninten- ment will affect the outcomes. However, the USPSTF
tional injury risk for children, adolescents, and (2003B) has recommended screening for type 2 dia-
adults. Parents should be encouraged to ensure that betes in adults with hypertension or hyperlipidemia.
all children are taught to swim. Homes should be This recommendation is supported by evidence of
safety-proofed. All homes should have working fire improved cardiovascular outcomes in patients with
alarms. Medications, poisons, toxins, and firearms hypertension or hyperlipidemia if the target goals for
should all be inaccessible when small children are in treatment are adjusted when diabetes also is present.
the home. When elderly persons are within the
home, specific measures should be taken to reduce
Discussion
the risk of falls. Families should be counseled to place
sleeping infants on their backs to decrease the inci- As the target levels for blood pressure and LDL now
dence of sudden infant death syndrome. The USP- have been reduced significantly, one could make the
STF evidence ratings for injury prevention are shown case that any patient with higher levels should be
in Table 10-40. screened for diabetes as part of determining what each
individual’s blood pressure and lipid goals should be.
Discussion
Whereas the incidence of many types of injuries is GLAUCOMA
declining, many others are worsening. These include
nonfatal head injuries. Overall, emergency depart- Prevalence
ment visits for injury, nonfatal poisonings, overall The prevalence of glaucoma increases from 0.5% of
unintentional injury deaths, motor vehicle crash persons younger than 65 years to 2% to 4% of those
deaths, nonfatal pedestrian injury, motorcycle hel- older than 75 years. Glaucoma is 4 to 6 times more
met use, child-maltreatment fatalities, and homi- prevalent in blacks than in whites.
cides show a worsening trend.
The facts that the leading cause of death for ages
Important Facts Relevant to Prevention
1 to 34 years is unintentional injury and that the most
frequent source of these fatal injuries is motor vehicle The ultimate result of untreated glaucoma is blindness.
accidents create an important opportunity for screen- Primary open-angle glaucoma is the most common
ing and counseling this age group. This should type of glaucoma and is asymptomatic until severe,

127
 Chapter 10 Disease Prevention

often irreversible damage has occurred. The benefits of The USPSTF (1996B) recommends screening
treatment have not been conclusively demonstrated. high-risk children and pregnant women for iron-
The two major criteria for diagnosis are visual deficiency anemia. Insufficient evidence exists for
field defects and optic disc pallor and cupping. In general screening for iron-deficiency anemia.
glaucoma, the optic cup diameter is 30% greater Obesity is an increasingly prevalent disease in the
than that of the disc. The funduscopic changes on United States (Fig. 10-19). Obesity increases the risk
direct ophthalmoscopy are best seen with the red fil- for cardiovascular disease, diabetes, and other chronic
ter. Patients with upper-normal intraocular pressure illness. The USPSTF (2003) makes a B recommenda-
can have glaucoma and secondary blindness, yet only tion for screening patients for obesity (body mass
in a minority of patients with elevated intraocular index ≥30) and providing access to intensive behav-
pressure does glaucoma develop. ioral counseling.
The risk factors for glaucoma are elevated All children at increased risk should be screened
intraocular pressure, family history, black race, dia- for lead levels at least once at age 1 year (USPSTF,
betes mellitus, and age. 1996B). Very high-risk children and children living
in communities with a high prevalence of lead levels
Screening Test Recommendations should be considered for subsequent testing.

The value of screening for elevated intraocular pres-

sure with the Schiotz tonometer is controversial. If ADDITIONAL PREVENTIVE ACTIVITIES
the family physician elects to use this method,
patients should be screened starting at age 40 years The family physician provides a large amount of gen-
and every 5 years thereafter until age 60 years, at eral medical care and, in the course of this care, may
which time the screening interval should be reduced easily identify patients who can benefit from individu-
to 2 to 3 years. Funduscopic evaluation by a well- alized screening tests not recommended for the general
trained physician at the time of tonometry increases population. These screening activities also include the
the sensitivity of screening. The USPSTF (2005I) discovery of patients who can benefit from lifestyle and
states that insufficient evidence exists to recommend other health-related counseling. These can include
for or against screening. counseling to prevent tobacco use, to optimize physical
activity, to achieve and maintain ideal weight, and to
Preventive Activities Recommendations consume a healthy diet. Other helpful services include
providing information about safe sexual practices and
Although the treatment of elevated intraocular pres- identifying potential occupational hazards. Older
sure is the standard of care, no proven primary or adults should be screened for hearing impairment at
secondary preventive measures are available once least by questioning about a deficit. Examples in the
elevated pressure is found. behavioral science area include screening for dementia,
depression, suicide risk, family and youth violence, as
Discussion well as drug and alcohol abuse in persons at risk.
Prevention of unwanted pregnancies is another
Elevated intraocular pressure has a less than 30% pos- important role for the family physician. Each year an
itive predictive value for glaucoma developing. In addi- estimated 1 million pregnancies occur in teenagers age
tion, up to 50% of patients with glaucoma have normal 15 to 19 years. Of these, 78% are unplanned. Although
intraocular pressure on a single random measurement. rates are declining, the U.S. rate remains the highest
These facts make it important that high-risk patients for developed countries. Family physicians are in a
have more extensive screening by an ophthalmologist, position to identify teenagers at risk for sexual activity
and that patients who are screened only with tonome- and to provide counseling for contraception and pre-
try be advised that they are still at risk. vention of STDs for those who are sexually active.
Yet another area of disease prevention is the pre-
conception obstetric risk assessment. Health promo-
OTHER SCREENING tion, patient education, and therapeutic intervention
RECOMMENDATIONS can reduce risk and improve outcome. Risk is associ-
ated with systemic disease, family history, genetics,
Routine screening for thyroid disease with thyroid- demography, environment, and lifestyle. Regular sup-
stimulating hormone level is effective for detecting plementation of 0.4 mg of folic acid daily is recom-
subclinical thyroid disease in asymptomatic children mended for all women who could become pregnant
and adults. However, the USPSTF (2004I) found insuf- and of 1.0 mg daily once pregnancy has occurred.
ficient evidence to recommend for or against screen- Identifying risks and providing appropriate counsel-
ing. Routine screening of newborns is recommended ing before conception may help formulate important
and is done routinely by all hospitals (USPSTF, 1996A). health-promotional aspects of optimal health care.

128
 Chapter 10 Disease Prevention

70

Overweight, 20–74 years

Obesity, 20–74 years
60
Overweight, 6–11 years
Overweight, 12–19 years
50
Percent

40

30

20

10

0
1960– 1963– 1966– 1971– 1976– 1988– 1999–
62 65 70 74 80 94 2000
Year

Figure 10-19 Percentage of overweight and obese individuals by age, United States, 1960–2000. (Data from National
Center for Health Statistics. Health, United States, 2003. Hyattsville, MD, 2003; Freid VM, Prager K, MacKay AP, Xia H.
Chartbook on Trends in the Health of Americans. Health. United States, 2003. Hyattsville, MD, National Center for
Health Statistics. 2003.)

LIFESTYLES FOR HEALTH have lower incidence in those who exercise, as well as
benefiting individuals already suffering from these
Of the diseases discussed in this chapter, a strikingly disorders. Hypertension, obesity, and type 2 diabetes
common theme is seen in their etiology and preven- are all benefited by regular exercise. It is
tion: An individual’s lifestyle is the major modifiable recommended that all patients be counseled as to the
determinant of health. most appropriate types, amount, and intensity of
Proper diet is of paramount importance to pre- exercise for their current health and risk status.
vent the nation’s number one killer: CHD; it is General guidelines for all healthy adults are to engage
estimated that one third of cancers, the nation’s num- in at least 30 minutes of moderate aerobic physical
ber two killer, are secondary to diet and physical activ- activity most days of each week. These 30 minutes
ity habits (Byers et al., 2002). Fortunately, the specific may be accumulated over the day. Adding additional
dietary recommendations for prevention of one dis- exercise to increase muscle strength and joint flexi-
ease also are beneficial in general. Therefore it is bility also is recommended. Parents should ensure
possible to make broad, prudent nutritional recom- that their children engage in regular activities that
mendations as a basis on which all physicians and involve vigorous exercise.
patients can build: Dietary guidelines are outlined in Another common prevention theme is the critical
Table 10-9, on the Internet (American Heart importance of avoiding toxins, especially the addictive
Association, Dietary Guidelines for Healthy Adults), substances nicotine and alcohol. Smoking accounts for
and in booklets that can be made available in the 18% of all deaths and 30% of all cancer deaths, as well
physician’s office (American Heart Association, 2000). as being a major factor in CHD. Each year, 435,000
Cohort studies have shown a significant deaths can be directly attributed to cigarette smoking.
protective effect for all-cause mortality in both men It is estimated that each pack of cigarettes sold results
and women engaging in even modest levels of in a cost of $7.18 for medical care and lost productiv-
exercise (Blair et al., 1996). Sedentary lifestyle ity (American Cancer Society, 2003). Alcohol is a risk
imparts the same 1.5- to 2-times degree of increased factor for colon and breast cancer, obesity, liver disease,
risk for CHD as do smoking and other major risk suicide, homicide, and accidents of all kinds.
factors. Weight-bearing exercises substantially Table 10-41 shows the major diseases discussed
reduce the risk of osteoporosis and its associated and the lifestyle issues and genetics implicated as risk
fractures. Anxiety and depression both appear to factors for each one.

129
 Chapter 10 Disease Prevention

DEVELOPING A PREVENTIVE HEALTH essential for the continuity and comprehensiveness

CARE FLOWSHEET of preventive health care.

Electronic health records can greatly facilitate health-

maintenance tracking, with automatic reminders Material Available on Student Consult
increasing the family physician’s ability to offer sys-
Review Questions and Answers about Disease
tematically the recommended preventive services in
Prevention
a cost-efficient manner. If an electronic health record Tables 10-2 through 10-41.
is not available, a simple and flexible flowsheet is

REFERENCES
American Cancer Society guideline for early detection of the National Conference on Cardiovascular Disease
cervical neoplasia. Available at http://caonline. Prevention. Circulation 2000;102:3137–3147.
amcancersoc.org/cgi/content/full/52/6/342. Accessed Corvol JC, Bouzamondo A, Sirol M, et al. Differential
American Cancer Society. Facts and Figures, Surveillance effects of lipid-lowering therapies on stroke prevention:
and Research, 2004. A meta-analysis of randomized trials. Arch Intern Med
American Cancer Society. Cancer Facts and Figures 2004. 2003;163:669.● A
Am Cancer Soc 2003;Pub No. 5008.04. Crabbe WW. The tamoxifen controversy. Oncol Nurs
American Heart Association. Dietary guidelines for healthy Forum 1996;23:761–766.
adults. Available at www.americanheart.org/presenter. Dove-Edwin I, Thomas HJW. Review article: The preven-
jhtml?identifier=1330. Accessed 9/11/2004. tion of colorectal cancer. Aliment Pharmacol Ther
American Heart Association. An eating plan for healthy 2001;15:323–336.
Americans: Our American Heart Association Diet. Enlish DR, Holman CDJ, Milne E, et al. The Quantification
Channing Bete Company (Product Code 50–1481), 2000. of Drug Caused Morbidity and Mortality in Australia,
American Heart Association. Heart Disease and Stroke 1992. Canberra, Australia, Canberra Commonwealth
Statistics, 2004 update. Dallas, TX, American Heart Department of Human Services and Health, 1995.
Association, 2003. Finney JW, Hahn AC, Moos RH. The effectiveness of inpa-
American Psychiatric Association. Diagnostic and Statistical tient and outpatient alcohol abuse; the need to focus on
Manual of Mental Disorders, 4th ed. Washington, DC, mediators and moderators of setting effects. Addiction
American Psychiatric Association, 1994:195–204. 1996;91:1773–1796.
Anderson KM, Wilson PWF, Odell PM, Konnel WB. An Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use
updated coronary risk profile. A statement for health and Dependence: Clinical Practice Guideline.
professionals. Circulation 1991;83:356–362. Rockville, MD, U.S. Department of Health and Human
Blair SN, Kampert JB, Kohl HW III, et al. Influences of car- Services, Public Health Service, June 2000.
dio-respiratory fitness and precursors on cardiovascu- Fleming MF, Barry KL, Manwell LB, Johnson K, London
lar disease and all-cause mortality in men and women. R. Brief physician advice for problem alcohol
JAMA 1996;276:205–210. drinkers: A randomized controlled trial in commu-
Brewster A. Breast cancer epidemiology, prevention, and early nity-based primary care practices. JAMA 1997;277:
detection [Review]. Curr Opin Oncol 2001;13:420–425. 1039–1045.● A
Brown RL, Leonard T, Saunders LA, Papasouliotis. A two- Fleming MF, Mundt MP, French MT, Manwell LB,
item conjoint screen for alcohol and other drug prob- Staauffacher EA, Barry KL. Brief physician advice for
lems. J Am Bd Fam Pract 2001;14;95–106.● B problem drinkers: Long-term efficacy and cost-benefit
Byers T, Nestle M, McTiernan A, et al. American Cancer analysis. Alcohol Clin Exp Res 2002;26:36–43.● A
Society guidelines on nutrition and physical activity Glynn TJ, Manley MW, How to Help Your Patients Stop
for cancer prevention: Reducing the risk of cancer Smoking: A National Cancer Institute Manual for
with healthy food choices and physical activity. CA Physicians. Bethesda, MD, U.S. Department of Health
Cancer J Clin 2002;52:92–119. and Human Services, Public Health Service, National
Cates W, et al. Estimates of the incidence and prevalence of Institutes of Health, National Cancer Institute, 1993.
sexually transmitted diseases in the United States. Sex NIH Publication No. 93–3064.
Transm Dis 1999;26(Suppl):S2–S7. Grant BF. Estimates of U.S. children exposed to alcohol
Centers for Disease Control and Prevention. An Ounce of abuse and dependence in the family. Am J Public
Prevention: What Are the Returns? 2nd ed. Atlanta, U.S. Health 2000;90:112–115.
Department of Health and Human Services, 1999. Grundy SM, Cleeman JI, Merz NB, et al. Implications of
Centers for Disease Control and Prevention. Recommen- recent clinical trials for the National Cholesterol
ded Adult Immunization Schedule, United States, Education Program Adult Treatment Panel III
October 2004 through September 2005. MMWR Morb Guidelines. Circulation 2004;110:227–239.
Mortal Wkly Rep, 2004;53:Q1–Q4. Harwood H. Updating estimates of the economic costs of
Cooper R, Cutter J, Desvigne-Nickens P, et al. Trends and alcohol abuse in the United States: Estimates, update
disparities in coronary heart disease, stroke, and other methods, and data. Lewin Group for the National
cardiovascular diseases in the United Staes: Findings of Institute on Alcohol Abuse and Alcoholism, 2000.

130
 Chapter 10 Disease Prevention

Available at http://pubs.niaaa.nih.gov/publications/ Sanmuganathan PS, Ghahramani P, Jackson PR, et al.

economic-2000/alcoholcost.pdf. Accessed 12/27/2005. Aspirin for primary prevention of coronary heart dis-
Johnston SC, Gress DR, Browner WS, Sidney S. Short-term ease: Safety and absolute benefit related to coronary
prognosis after emergency department diagnosis of risk derived from meta-analysis of randomized trials.
TIA. JAMA 2000;284:2901–2906. Heart 2001;85:2. ●
. A
Lewiston S, Clarke R, Qizilbash N, et al. Age-specific Segal JB, McNamara RL, Miller MR, et al. Prevention of
relevance of usual blood pressure to vascular mortality: thromboembolism in atrial fibrillation: A meta-analysis
A meta-analysis of individual data for one million of trials of anticoagulants and antiplatelet drugs. J Gen
adults in 61 prospective studies. Lancet. 2002;360: Intern Med 2000;15:56–67. ● A
1903–1913. Siris ES, Miller PD, Barrett-Connor E, et. al. Identification
Modugno F. Ovarian cancer and high risk women: and fracture outcomes of undiagnosed low bone min-
Implications for prevention, screening and early detec- eral density in postmenopausal women: Results from
tion. Gynecol Oncol 2003;91:15–31. the National Osteoporosis Risk Assessment. JAMA
National Cancer Institute, U.S. National Institutes of 2001;286:2815–2822.
Health. Endometrial cancer (PDQ): Screening health Strong JP, Malcom GT, McMahon CA, et al. Prevalence and
professional version, summary of evidence, 2005. extent of atherosclerosis in adolescents and young
Available at www.cancer.gov. Accessed 5/1/2005. adults. JAMA 1999;281:727–735.
National Cholesterol Education Program Expert Panel of Substance Abuse and Mental Health Administration.
Detection, Evaluation, and Treatment of High Blood Substance abuse or dependence. The NHSDA Report,
Cholesterol in Adults (Adult Treatment Panel III): Third October 11, 2002.
report of the National Cholesterol Education Program Thun MJ, Peto R, Lopez AD, et al. Alcohol and consump-
(NCEP) on detection, evaluation, and treatment of high tion and mortality among middle-aged and elderly U.S.
blood cholesterol in adults (Adult Treatment Panel III) adults. N Engl J Med 1997;337:1705–1714.● B
final report. Circulation 2002;106:3143–51. U.S. Preventive Services Task Force. Screening for cervical
National Cholesterol Education Program. Risk assessment cancer, recommendations and rationale. Available at
tool for estimating 10-year risk of developing hard ARHQ.gov/clinic/3rduspstf/cercanrr.htm. Accessed
CHD (myocardial infarction and coronary death). 12/20/2005.
Available at hin.nhlbi.nih.gov/atpiii/calculator.asp U.S. Preventive Services Task Force. Screening for
Accessed 9/11/2004. chlamydia infections: Recommendations and ration-
NCI, U.S. National Institutes of Health, Annual Report to ale. Am J Prev Med 2001;20:90–94.
the Nation. 2004. Available at www.Cancer.org. U.S. Preventive Services Task Force. Screening for
Accessed 12/20/2005. Osteoporosis in Postmenopausal Women: Recommen-
NCI, U.S. National Institutes of Health Surveillance: dations and Rationale. Rockville, MD, Agency for Health
Epidemiology and End Results, SEER cancer statistics. Care Research and Quality, 2002. Available at
2004. Available at www.Cancer.gov. Accessed 12/20/2005. www.ahrq.gove/clinic/3rduspstf/osteoporosis/osteoorr.
Nelson HD, Helfand M, Woolf SH, Allan JD. Screening htm. Accessed 9/25/2005.
for postmenopausal Osteoperosis: A review of the evi- U.S. Department of Health and Human Services, National
dence for the U.S. Preventative Services Task Force. Institutes of Health, National Institute on Alcohol
Available at www.preventiveservices.ahrq.gov. Accessed Abuse and Alcoholism: Helping Patients with Alcohol
1/24/2006. Problems: A Health Practitioners Guide. Bethesda, MD,
Office of National Drug Control Policy. The economic NIH Publication No. 03–3769, 2003.
costs of drug abuse in the United States, 1992–1998. Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB.
Washington, DC, Executive Office of the President, Probability of stroke: A risk profile from the
2001. Pub no. NCJ 190636. Framingham Study. Stroke 1991;22:312–318.
Prospective Studies Colloboration. Age-specific relevance Wolfe JT. The role of screening in the management of skin
of usual blood pressure to vascular mortality: A meta- cancer. Curr Opin Oncol 1999;11:123.
analysis of individual data for one million adults in 61 Wright GS, Gruidl ME. Early detection and prevention of
prospective studies. Lancet 2002;360:1903–1913. lung cancer. Curr Opin Oncol 2000;12:143–148.

SUGGESTED READINGS
Abenaa B, Helzisouer K. Breast cancer epidemiology, pre- Institute of Medicine. The Hidden Epidemic: Confronting
vention, and early detection. Curr Opin Oncol Sexually Transmitted Diseases. Washington, DC,
2001;13:420–425 National Academy Press, 1997.
Gandelman G, Bodenheimer MM. Screening coronary Ladabaum U, Chopra CL, Huang G, et al. Aspirin as an
arteriography in the primary prevention of coronary adjunct to screening for prevention of sporadic col-
artery disease. Heart Dis 2003;5:335–344. orectal cancer, Ann Intern Med 2001;135:769–781.
Humphrey LL, Tensch S, Johnson M. U.S. Preventive Office of Applied Studies, Substance Abuse and Mental
Services Task Force, lung cancer screening with sputum Health Administration. Results from the National
cytological examination, chest radiography, and com- Osteoporosis Risk Assessment. JAMA 2001;286:
puted tomography: An update for the preventive serv- 2815–2822.
ices task force. Ann Intern Med 2004;140:740–753.

131
 C h a p t e r

11 Integrative Medicine

David P. Rakel and Adam Rindfleisch

INTEGRATIVE MEDICINE IS FAMILY

KEY POINTS
MEDICINE
1. Integrative medicine takes an individualized,
Integrative medicine is healing-oriented medicine that
health-oriented approach to healing, emphasiz-
takes account of the whole person (body, mind, and
ing a strong provider-patient relationship. It
spirit), including all aspects of lifestyle. It emphasizes
incorporates evidence-based medicine as much
the therapeutic relationship and makes use of all appro-
as possible while also taking into account the
priate therapies, both conventional and alternative.
patient’s personal beliefs and cultural back-
The field emerged in response to a need to bring
ground. The patient has an active role in the
a better balance to health care delivery, combining
healing process.
the advances made by disease-oriented care with
2. Integrative medicine makes use of therapies
those that help facilitate health and healing.
commonly referred to as “complementary” or
In the 1990s, a significant increase was found in
”alternative,” provided they are safe, potentially
public interest in complementary and alternative
effective, and likely to benefit the individual
medicine (CAM). This was related in part to the
patient. Evidence of risk and benefit must
deterioration of the physician-patient relationship,
always be carefully weighed for all interventions.
the overutilization of technology, and the inability of
3. Patients commonly use a wide array of comple-
the medical system to treat chronic disease ade-
mentary and alternative therapies. Health care
quately. At that time, more visits to CAM providers
providers must be able to advise them regard-
occurred than those to all primary care medical
ing the safety and efficacy of these approaches.
physicians, and the public paid an estimated $13 bil-
4. In developing a treatment plan for a given
lion out of pocket for such visits (Eisenberg et al.,
patient, care of the patient might be improved
1993). This trend continued throughout the 1990s,
through incorporating any or all of the follow-
with 42% of the public using CAM therapies and
ing into the care plan: nutrition, herbs and
CAM expenditures increasing to $27 billion from
other supplements, physical activity, manipula-
1990 to 1997 (Eisenberg et al., 1998).
tive therapies, energy medicine, mind-body
Integrative medicine reflects an attempt to shift
techniques, spirituality, and other healing sys-
our focus back toward the enhancement of health as
tems, such as traditional Chinese medicine,
part of health care delivery. The foundation of this
Ayurveda, and homeopathy.
approach is based in relationship-centered care, in
5. Primary care providers should understand how
which a caring physician takes time to listen to a
to make reasonable and appropriate referrals to
patient’s story and gain insight into the person who has
practitioners of complementary and alternative
the disease. Developing this relationship allows a physi-
therapies.
cian to more easily create a health plan that outlines
6. No therapy is without associated risks. Be famil-
what actions are needed to improve health. Box 11-1
iar with supplement side effects, potential dan-
highlights key components of an integrative approach.
gers of exercise and manipulative techniques,
Facilitating health and healing is a dynamic
and how various treatments may interact with
process, as illustrated in Figure 11-1. It involves four
standard medical care. Urgently needed bio-
steps:
medical care should not be delayed to try
unvalidated therapeutic techniques. 1. When individuals are in poor health and in need
of medical attention, they will seek care from

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

132
 Chapter 11 Integrative Medicine

treatment. For example, a patient with cancer may

Box 11-1 Defining Integrative Medicine have a team that includes the primary care physi-
cian, an oncologist, a nutritionist, a traditional
Provides relationship-centered care Chinese medicine practitioner, and a spiritual
Integrates conventional and complementary advisor or chaplain. The primary practitioner is
methods for treatment and prevention in the best position to organize the team that will
Involves removing barriers to activate the best suit the patient’s needs. Most important, this
body’s healing response approach requires that the patient be an active
Uses natural, less invasive interventions before participant in the healing process. This includes
costly, invasive ones when possible participating in decisions regarding behaviors
Engages mind, body, spirit, and community to and positive lifestyle changes. Patients are
facilitate healing empowered to make positive changes themselves
Contends that healing is always possible, even instead of simply being passive recipients of care.
when curing is not. 4. The healing process is a dynamic, continuous
process that constantly needs re-evaluation if the
balance that best facilitates health is to be main-
someone they trust. Ideally, the relationship that tained. What works at one time may require mod-
results leads to rapport and empathy, and insight ification and adaptation in the future. These
develops. Insight generates the ideas the physician changes will best occur with the involvement of a
uses to develop an efficient treatment plan that primary care practitioner who knows how the
will facilitate positive changes in individual patient’s unique situation is influenced by biopsy-
health. chosocial and spiritual influences on health.
2. What a physician suggests to optimize individual
health will be influenced by a number of factors. As this process continues to unfold, the physician
The patient’s belief system and culture must be and patient constantly learn from past experiences and
considered. In addition, research findings and sci- develop new insights into how to maintain the balance
ence must guide the choice of which therapeutic of health. In so doing, they often develop a deeper
modalities to use. Individual uniqueness also understanding of the patient’s core health needs. This
must be taken into account. inward journey leads to an understanding of why
3. Once the foundation of relationship-centered symptoms exist and what can be done to resolve them
care is established and insight into the patient’s within a continuously changing environment.
unique situation is developed, the physician and If this inner exploration does not occur, the
the patient must agree on a plan of action that body-mind will continue to rely on external influ-
both believe will lead to improved health. This ences to reduce the severity of symptoms. The learn-
often includes a collaborative approach that may ing that could arise from the illness experience may
involve both conventional and complementary be lost. Symptoms can often be red flags that exist to

Relationship

4 Trust 1
Re-evaluation Empathy
Rapport
Change

Health Insight

Empowerment Belief
Treatment Evidence
Collaboration Culture
3 2

Action

Figure 11-1 Steps in facilitating healing. (Reprinted with permission from Rakel D. The healing power of relationship-
centered care. In Rakel D, Faass N, eds. Complementary Medicine in Clinical Practice. Sudbury, MA: Jones and Bartlett
Publishers, 2005.)

133
 Chapter 11 Integrative Medicine

alert us to lifestyle habits or situations that are not because they make her “loopy,” and her son “would
conducive to health and well-being. If we simply just steal them anyway.” A chiropractic visit several
suppress a symptom without learning what it is try- years ago helped her back pain for several months.
ing to teach us, we may never understand what is Joan has hypertension and was told recently that her
needed to permanently resolve it. An example would lipids are borderline. Past surgeries include an
be the suppression of dyspepsia with a proton-pump appendectomy and a cholecystectomy.
inhibitor. Whereas some medications act on the
underlying cause of a disease, others are strictly for
Medications, Supplements, and Botanicals
symptom control. Both are important, but if the
question of why the problem exists in the first place Medications include aspirin and lisinopril. She lists
is not explored, lasting attempts to improve health multiple drug allergies, many symptoms of which are
are less likely to occur. Why does the patient have not commonly associated with the drugs in question.
symptoms of dyspepsia in the first place? If the main She is not taking any herbals or other supplements,
focus becomes what is needed for healing, fewer but her sister has suggested that she try some. She
symptom-suppressing therapies will be required, wants your opinion first.
resulting in lower health care costs and improved
quality of life for patients. This is health-oriented, as
Patient Profile
opposed to disease-oriented, care.
In this chapter, we use a case study to illustrate Joan is divorced and lives alone. Her 19-year-old son
how integrative medicine can be used to stimulate was arrested a few months ago for possession of mar-
the body’s self-healing mechanisms. We also look ijuana. Her father died at 67 years of a heart attack,
at some key studies illustrating how integrating and her 82-year-old mother lives nearby with Joan’s
complementary therapies into family medicine can sister. Joan’s mother and sister both have type 2 dia-
improve health. We also review common CAM betes. Joan’s father was an alcoholic who was often
therapies. physically abusive. Her son has depression. Joan has
smoked a half pack of cigarettes daily for 35 years
and is a social drinker, but she does not use illicit
AN INTEGRATIVE MEDICINE drugs. She is employed as an administrative assistant
in a busy real estate firm but dreams of becoming a
CASE STUDY
professional artist. She enjoys painting, reading mys-
History and Present Illness tery books, movies, and going to the park. When
asked about stress, she states, “My whole life is a
Joan is a 53-year-old woman who tells you, “Doc, I’m stressor.” Joan was brought up Catholic but attends
a mess. My bowels are giving me trouble again, and mass only on holidays. She states that her sister and
I’m always tired. What else can I do to feel like myself friends at work are her main social contacts.
again?” Joan eats a typical American diet, with significant
Joan has a long history of multiple chronic med- diet soda and coffee consumption. She averages fewer
ical problems. She was diagnosed with irritable than four servings of fruits and vegetables daily and
bowel syndrome (IBS) 4 years ago while she was eats red meat and dairy products frequently. She
going through a divorce, and for the past 3 months, craves cookies and chocolate. She used to enjoy swim-
she has been having two episodes of diarrhea daily. ming and walking but is currently not exercising.
She refuses IBS medications because they led to
dizziness and nausea in the past. In addition, she Review of Systems
notes feeling “tired all the time,” even though she
sleeps at least 8 hours per night. Joan has poor libido, Review of systems is positive for almost every system
anhedonia, and increased appetite. She denies suici- reviewed.
dal thoughts, but states, “No one would really care if
I was gone. My ex and my son would probably throw Physical Examination
a going-away party.” A sleep study and thyroid tests
were normal 2 months ago. Notable examination findings include abdominal
obesity, and a blood pressure of 142/94. She has dif-
Medical History fuse abdominal tenderness with no rebound or
guarding, and pain on palpation of the paralumbar
Joan’s medical history also includes seasonal aller- muscles.
gies, morbid obesity, weekly migraine headaches,
and, according to another provider she saw, Note that an integrative approach incorporates
fibromyalgia. She injured her lower back 20 years ago elements not always covered in a standard history
and still has intermittent pain. She refuses narcotics and physical, including relationships, life stressors,

134
 Chapter 11 Integrative Medicine

nutrition, and spirituality. Such topics provide useful Glycemic load takes the concept of glycemic
additional insights to guide the creation of an indi- index a step further, accounting not only for how
vidualized care plan. Please refer to the boxes labeled rapidly a food’s carbohydrates are converted to glu-
“Suggestions for Joan” after each section of this cose, but also for the relative amounts of carbohy-
chapter for examples of how integrative medicine drate the food contains. Glycemic load is generally
providers might approach Joan’s case. held to be a more accurate measure of a food’s over-
all effect on pancreatic insulin release and serum glu-
cose levels.
INTEGRATIVE MEDICINE: EIGHT
PERSPECTIVES The Anti-inflammatory Diet
Inflammation is a major contributor to many ill-
Integrative medicine makes use of a wide array of ness states, from autoimmune disorders and Alzhei-
healing modalities, each with different philosophical, mer’s disease to cancer and inflammatory bowel
diagnostic, and therapeutic underpinnings. Eight disease. Certain fats (the omega-6 fatty acids in par-
perspectives that can be used to assess a person’s tially hydrogenated oils) lead to the formation of
health needs are outlined. All of them can be relevant arachadonic acid and other inflammatory precur-
to a patient encounter, but areas of focus will differ sors. Conversely, omega-3 fatty acids, found in foods
from one person to the next. such as fish oil and flaxseed, have been found to
reduce inflammation. If omega-3 fatty acid intake is
increased and omega-6 intake decreased, inflamma-
1. Nutrition
tion and its associated symptoms may diminish over
Good nutrition is central to health, but it is given only time.
minimal attention in most medical training pro-
grams. A growing body of research indicates that diet Elimination Diets
can play a key role in preventing and treating a num- Elimination diets are used to determine if a specific
ber of disorders, including hypertension, dyslipi- food or group of foods is contributing to a person’s
demias, and diabetes. Dietary modification also may symptoms. Food allergies tend to arise relatively rap-
improve illnesses associated with chronic inflamma- idly after foods are consumed and can be evaluated
tion, such as rheumatoid arthritis, inflammatory by standard allergy testing. Food intolerances, in
bowel disease, and eczema. Nutritional recommenda- contrast, can be quite challenging to diagnose.
tions are frequently incorporated into integrative Symptoms of food intolerance may arise up to 3 days
treatment plans for various cancers, dementia, multi- after exposure. The causes and manifestations of
ple sclerosis, chronic fatigue, and any number of food intolerance are still hotly debated, but one the-
other diseases (Mahan and Escott-Stump, 2004). ory is that foods cause problems in patients who have
Integrative medicine makes use of several nutri- increased intestinal permeability, or a “leaky gut.”
tional tools. These include the glycemic index and Increased intestinal permeability permits the absorp-
load, the anti-inflammatory diet, elimination diets, tion of larger, potentially harmful molecules into the
and supplementation with vitamins, minerals, and bloodstream; these subsequently trigger an immune
other nutrients. response (Joneja, 1998● B).
In elimination diets, specific foods or groups of
Glycemic Index and Glycemic Load foods are removed entirely from the diet for a set
Glycemic index is an indicator of the immediate period, usually 10 to 14 days. After that time, if
effect a food has on postprandial blood glucose symptoms have improved, eliminated foods are re-
levels. White bread and glucose, which cause the introduced into the diet in 3-day increments. If
fastest and sharpest increase, are assigned a value of symptoms return or worsen after the food is eaten,
100. All other foods are then assigned a value relative that food is considered one to which the subject is
to this reference, based on how they affect test sub- intolerant.
jects’ glucose levels over time. Foods with a higher
glycemic index cause the pancreas to release more Vitamins, Minerals, and Other Nutrients
insulin, leading to a decrease in blood glucose to In a review of vitamin use in chronic disease,
below the fasting level approximately 2 hours after Fairfield and Fletcher (2002●A ) concluded: “We rec-
eating. This rebound hypoglycemia can be character- ommend that all adults take one multivitamin daily.
ized by fatigue, which decreases substantially when This practice is justified mainly by the known and
foods with a higher glycemic index are removed from suspected benefits of supplemental folate and vita-
the diet (Johnson, 2003● B). Interestingly, a low- mins B12, B6, and D in preventing cardiovascular
glycemic-index meal will result in a lower glycemic disease, cancer, and osteoporosis and because multi-
response for the next meal eaten as well (Wolever, vitamins at that dose are safe and inexpensive.” At
1990). Overall, meal size tends to be smaller as well. least 30% of U.S. residents use vitamin supplements

135
 Chapter 11 Integrative Medicine

regularly (Balluz et al., 2000), and many more need many herbs have beneficial therapeutic effects, it is
them. A survey conducted in 2000 found that only important for health care providers to have a work-
20% to 30% of the American population met the ing knowledge of herbal medicine.
goal of at least five servings of fruits and vegetables Information about herb-drug interactions is
daily (Flood and Schatzkin, 2000). derived from a number of sources. Some random-
Dose recommendations for vitamins and min- ized trials exist, but most information is based on
erals are now referred to as reference daily intakes. case reports, animal studies, in vitro studies, or theo-
For a full list of reference daily intakes and food retical assumptions made based on known chemical
sources of various nutrients, see Mahan and Escott- components of the herb. A 2001 review collected
Stump, 2004 (Box 11-2). information from a wide array of sources and scored
them on a 10-point scale based several factors,
2. Herbal Medicine including whether a clear causal relation occurred
between herb consumption and untoward effects
Herbal remedies have been used by cultures world- and whether patients’ comorbidities were taken into
wide for thousands of years, and an estimated 25% of account. In total, 108 herb-drug interaction reports
modern pharmaceuticals are based on compounds were found worldwide. Of these, 74 interactions were
found in plants (Schulz et al., 2001). In the late classed as unevaluable, 20 as possible, and 14 as likely
1990s, the consumption of herbal remedies increased (Fugh-Berman and Ernst, 2001● B) (Box 11-3).
dramatically. Astin (1998) concluded that 12% of
American adults used herbs over the course of a
3. Exercise and Movement Therapies
1-year period. Other studies have placed this number
as high as 49% (Johnston, 2000). Only 25% of American adults meet recommended
For physicians, providing advice regarding the levels of physical activity, and 29% report no regular
use of herbal remedies is fraught with challenges. leisure-time physical activity whatsoever (Centers for
Many people who use herbal remedies do not tell Disease Control and Prevention, 2001). Obesity has
their primary care physicians, largely because the reached epidemic proportions, contributing to an
doctor “never asked” or because they “did not feel it
was important for him/her to know” (Eisenberg
et al., 2001● B). However, given the popularity of Box 11-3 Suggestions for Joan: Herbal
herbal remedies, the potential for herb-drug interac- Remedies
tions, and a growing body of evidence indicating that
Joan is interested in trying herbal remedies.
Some useful suggestions would include:
Box 11-2 Suggestions for Joan: Enteric-coated peppermint oil capsules, which
Nutrition are often effective for diarrhea-predominant
irritable bowel symptoms. Recommending
Evidence-based dietary advice is useful for enteric-coated capsules prevents release in
practically all patients, and Joan is no excep- the stomach, which can relax the lower
tion. Given her obesity (and her abdominal esophageal sphincter resulting in gastro-
body fat distribution), elevated lipids, hyper- esophageal reflux.
tension, and family history of type 2 diabetes, Herbal anti-inflammatories. Boswellia, turmeric,
she is at high risk for vascular disease. An anti- and ginger all have anti-inflammatory prop-
inflammatory diet can decrease this risk and erties and may serve as useful adjuncts or alter-
may help both decrease her chronic pain symp- natives to nonsteroidal anti-inflammatory
toms and improve her mood. Following a diet drugs.
of foods with a low glycemic load can help A treatment for depression is probably indicated
prevent insulin resistance. Since she men- in Joan’s case. St. John’s wort or S-adenosyl
tioned that certain foods seem to worsen her methionine (SAMe) are alternatives that
irritable bowel symptoms, an elimination diet have shown promise in the treatment of mild
trial (especially removing dairy products) to moderate depression.
might prove helpful. Joan’s homocysteine level Probiotics would be suggested. Probiotic supple-
should be checked, and if it is elevated, she can ments contain bacteria that are normally pres-
add folate, Vitamin B6, and B12 for heart dis- ent as part of healthy intestinal flora. They
ease prevention. Calcium and vitamin D intake are often useful in decreasing diarrhea asso-
should be assessed. Magnesium supplementa- ciated with antibiotics; they also may help
tion may be beneficial for her periodic normalize Joan’s intestinal motility and alle-
migraines. viate symptoms related to food intolerance.

136
 Chapter 11 Integrative Medicine

estimated 300,000 deaths in the United States yearly function, and pain are all potentially treatable. Many
(Allison et al., 1999), and pediatric obesity rates are people associate chiropractic with high-velocity, low-
soaring. All-cause mortality rates are doubled for amplitude adjustments, in which a joint is forcibly
those with low activity levels (Blair et al., 1996). moved until a pop or “release sound” is heard. This
Given these sobering statistics, encouraging is but one of many methods used. Techniques are
physical activity is of key importance. Physical activ- modified based on a patient’s individual situation.
ity can lead to improvements in any number of phys- Different techniques may be used on pregnant
ical and emotional symptoms in addition to women, infants, and people with bleeding disorders
improving overall well-being. or bone disease.
A number of therapeutic modalities are based on Now more than 65,000 chiropractors practice
movement. These therapies, including hatha yoga, tai in the United States (Chapman-Smith, 2004). Chiro-
chi, qigong, and Feldenkrais, can be used for both pre- practors train for 4 or 5 academic years, with intense
vention and treatment of various disorders (Box 11-4). basic science experiences, in 16 training institutions
in the United States. Accreditation is regulated
4. Manipulative Therapies through state licensing boards.
A 2005 Cochrane review concluded, based on
Manipulative therapies use direct physical contact to the results of 39 randomized controlled trials, “There
facilitate healing. Practitioners focus on the relation is no evidence that spinal manipulative therapy is
between structure and function; parts of the body superior to other standard treatments for patients
are moved in various ways to alleviate pain and other with acute or chronic low-back pain” (Assendelft
symptoms. Examples include chiropractic, osteo- et al., 2005). However, other reviews and individual
pathic manipulative treatment (OMT), and thera- studies show a consistent overall trend suggesting
peutic bodywork. Although these techniques are chiropractic decreases low back pain (Erickson et al.,
used most commonly to treat musculoskeletal disor- 2004 ● B ). A 2001 systematic review concluded that
ders, they may be used to treat “visceral” problems spinal manipulation was comparable to medical pro-
(e.g., asthma, gastrointestinal problems, or otitis) as phylaxis for treating tension and migraine headaches
well (Erickson et al., 2004● B). (Bronfort et al., 2001● A). Neck-pain data are mixed in
terms of showing a benefit or not (Rindfleisch and
Chiropractic Rakel, 2003● B ) Evidence is thus far limited to ran-
Chiropractic was founded in Iowa in 1895 by D. D. domized or prospective trials that are relatively
Palmer. Palmer believed that manipulation of the small. More methodologically rigorous chiropractic
spine could be used to remove subluxations, or mis- investigations are currently under way. It is worth
alignments of the vertebrae, which he believed were noting that patient-satisfaction ratings tend to be
the underlying causes of many symptoms. The defi- consistently higher for chiropractic than for conven-
nition of subluxation has broadened over the years, tional medical care (Erickson et al., 2004 ● B ).
and chiropractic focuses on restoring proper align-
ment to joints and their related structures. Decreased Osteopathic Medicine
range of motion, inflammation, alterations in motor Osteopathic medicine was developed by Andrew
Taylor Still, MD, who became disillusioned with bio-
medicine when three of his children died of menin-
Box 11-4 Suggestions for Joan: Exercise gitis in 1864. In 1874, he developed OMT, and in
and Movement Therapies 1892, he founded the first medical school to grant
the degree of doctor of osteopathy (DO). Now 20
Exercise counseling should be tailored to Joan’s osteopathic training schools exist in the United
individual needs, recognizing the limitations States. Training overlaps significantly with medical
imposed by her chronic pain. Extremely small doctorate (MD) training, and osteopaths compose
amounts of exercise (even 5 minutes at a time, 6% of practicing physicians in the United States.
increasing only a minute or two every few Currently, only a small percentage of osteopaths
weeks) may be all she can handle with her practice manipulation on a routine basis. Overall,
symptoms of fatigue and her fibromyalgia. research relating to the efficacy of OMT remains lim-
Water-based activities or tai chi are less likely ited in part because of challenges of double-blinding
to exacerbate her back pain. Exercise will likely and in part because of a historical lack of research
reduce her depressive symptoms. A visit with a funding support. However, it has shown promise for
skilled bodyworker may be beneficial, provided many of the indications.
this person has experience working with
fibromyalgia patients’ extremely low pain Therapeutic Bodywork
thresholds. Therapeutic bodywork is a general term used to
describe any of a number of techniques in which the

137
 Chapter 11 Integrative Medicine

practitioner uses a hands-on approach. Many tech- A 2000 review focused on 37 randomized trials
niques bodyworkers use overlap with those used in in which energy therapy was given to human sub-
osteopathy and chiropractic. Massage, one of the jects with a variety of conditions. Only 22 of the
most common forms of bodywork, has a higher rate studies were accessible as published reports, and 10
of physician referral in the United States than does reported a significant effect. Studies measured an
any other complementary modality (Astin et al., array of outcomes, and a variety of energy modali-
1998). A recent Cochrane review concluded, ties were used. Methodologic shortcomings were
“Massage might be beneficial for patients with sub- noted to be significant, and the author ultimately
acute and chronic non-specific low-back pain, espe- concluded that no firm conclusions could be drawn
cially when combined with exercises and education” (Abbot, 2000 ● B).
(Furlan et al., 2004● B). Physical and occupational The challenge facing health care providers is to
therapists often make use of such techniques in their determine how such information could guide clinical
practices (Box 11-5). practice. It is reasonable to inform patients that
energy medicine modalities are, in general, quite safe
5. Energy Medicine but that evidence is inconclusive (Box 11-6).

We are continually surrounded by energy in

6. Mind-Body Influences
various forms. Heat, light, sound, electromagnetic
radiation—all of these can affect our physical state. The mind-body influence goes in both directions,
Modern medicine frequently makes use of various from the mind to the body and vice versa. If we are
energy fields for diagnostic purposes (e.g., electro- more depressed and anxious, pain is exacerbated. If
cardiograms, ultrasounds, and electroencephalo- we have more pain, we are more likely to become
grams), but it remains controversial whether an depressed and anxious. Such topics are the subjects of
energy field exists around the human body, the pat- a field of study called psycho-neuro-endo immunol-
tern of which can be altered to affect a person’s ogy, which explores how our body’s systems are
health (Benor, 2002). uniquely interrelated. What happens in one system
Throughout history, the concept of energy (also affects others. For example, nerve endings have been
referred to as vital force, bioelectric field, chi, and found in the tissues of the immune system such as the
many other names) has played a significant part in spleen, lymph nodes, and bone marrow (Felten and
most cultures’ healing systems. Felten, 1991). Cells in the immune system have been
Research into the scientific basis of energy med- found to produce chemicals previously thought to be
icine is ongoing but far from definitive (Oschman, confined to the neurologic and endocrine systems.
2002). Hundreds of energy medicine studies are now Lymphocytes have been found not only to secrete
listed in various medical databases. In 2000, Astin neuropeptides and hormones, but also to have recep-
and colleagues performed a systematic review of 23 tors for them on their surfaces (Ackerman et al.,
trials that met inclusion criteria (primarily random-
ized controlled trials) involving prayer, therapeutic
touch, or “other distant healing methods.” Thirteen Box 11-6 Suggestions for Joan:
of the 23 trials, which involved a total of 2774
Energy Medicine
patients, showed a positive treatment effect. Only
one trial showed a negative effect, in that wounds
Successful referrals to an energy medicine prac-
treated with energy healing seemed to heal more
titioner rely in part on the openness of the
slowly (Astin et al., 2000● B). A 2003 update to this
patient to the therapy. If Joan were willing,
review, published in Germany, concluded that subse-
information about local energy healers could
quent studies call some of these likely benefits into
be provided. Often these modalities will
question (Ernst, 2003● B).
address deep-seated emotional issues, such as
those related to abuse experienced as a child.
Choosing an appropriately discrete and compe-
Box 11-5 Suggestions for Joan: tent provider is important. The type of energy
Manipulative Therapies medicine recommended would depend in part
on Joan’s past experience and what is available
Joan had a positive interaction with a chiro- in the community. Energy practitioners often
practor previously, and some form of manipu- note that when someone suffers from a myriad
lation could be tried. Her low back pain is likely of complaints or describes his or her problems
to respond well. Given that much of her pain as being related to “low energy levels,” energy
seems to be muscular, a strain-counterstrain or modalities may prove helpful when other
trigger point release could be attempted. approaches fail.

138
 Chapter 11 Integrative Medicine

1991). Just as chemicals of the neuroendocrine sys-

tem have been found in our immune cells, those of Box 11-7 Suggestions for Joan:
the immune system have been found in the neuroen- Mind-Body Therapies
docrine system. Several immunoregulatory cytokines,
including interleukin (IL)-1, IL-2, IL-6, interferon- Joan has a significant amount of stress in her
gamma, and tumor necrosis factor, have been found life. Sources of this include her divorce and
on the brain side of the blood-brain barrier, especially dealing with her teenage son. She reports that
in the region of the hypothalamic-pituitary axis her “whole life is a stressor.” It is no surprise
(Ferencik and Stvrtinova, 1997). Clearly, the body’s that she suffers from stress-related conditions
systems are set up to communicate through multidi- such as irritable bowel syndrome, fatigue,
rectional pathways. and depression. One way to help Joan escape
From a clinical standpoint, how do we positively stressful thoughts is to encourage her to par-
influence this intricate system? Many different ways ticipate in a mindfulness-based stress reduc-
exist. It is important to seek out what lies at the root tion program. As she learns how to control
of a problem so as to cause a fundamental change her stress, you can teach her a relaxation tech-
that can start a cascade of positive effects on health nique to help reduce the severity of her pain
and well-being. Examples of such changes could and emotional distress. Examples of such tech-
include making a career transition, forgiving some- niques include breathing exercises, progressive
one for a past traumatic experience, altering overall muscle relaxation, and self-hypnosis tech-
outlook so that events do not seem as stressful as niques. Joan may also benefit from expressing
they might once have, and disclosing suppressed her emotions through writing (keeping a
emotions. Helping patients make conscious choices journal). She may also benefit from seeing a
that result in a greater sense of peace enhances their therapist for hypnosis for her irritable bowel
bodies’ self-healing so that fewer medications are syndrome.
needed to suppress symptoms.
One important aspect of defining mind-body
influences when taking a medical history is to listen 71% of patients initially responded to therapy. Of
to metaphor. For example, someone with neck pain these, 81% maintained their improvement over time,
may say, “My boss is a pain in the neck.” Someone whereas the majority of the remaining 19% claimed
with irritable bowel may say, “This divorce is eating that worsening of symptoms had only been slight
me up inside.” When people understand how these (Gonsalkorale et al., 2003 ●
B) (Box 11-7).
stressors can influence their physical health, symp-
toms may resolve. 7. Other Medical Systems
A pathologist named William Boyd said at the
turn of the 20th century, “The Sorrow that hath no Other medical systems, based on entirely different
vent in tears, may make other organs weep.” philosophical underpinnings from those of biomed-
Expressing emotions through talking or writing can icine, can play a key role in providing integrative
be very helpful. For example, simply writing about care. Traditional Chinese medicine, Ayurveda, natur-
past stressful life experiences has been found to result opathy, and homeopathy are systems commonly
in symptom reduction in patients with asthma and found in the United States (Box 11-8).
rheumatoid arthritis. One hundred and seven
patients with these diseases were assigned to write 8. Spiritual Connection
about either the most stressful event of their lives
(study group) or daily events (control group) for just Spirituality is difficult to conceptualize. It is similar to
20 minutes over a consecutive 3-day period. Four the wind. It is invisible, but you can feel its effects. It
months after journaling, the asthma patients in the is defined as a journey toward, or experience of, con-
treatment group showed a 20% improvement in lung nection with the source of ultimate meaning. Edgar
function versus no improvement in the control Cayce said,“Spirit is the life, mind is the builder, phys-
group. The patients with rheumatoid arthritis who ical is the result.” When we set our goals according to
wrote about stressful events showed a 28% reduction those things in life that have great meaning and pur-
in disease severity, whereas the control group showed pose for us, our health often improves as a side effect.
no change (Smyth et al., 1999● A ). It is easier to understand how to discuss spiritu-
Other tools also use the mind-body connection to ality with our patients if we realize that religion and
improve symptoms. Examples include hypnosis, spirituality are not synonymous. Think of religion as
guided imagery, biofeedback, and specific relaxation a poem and spirituality as the flower it describes.
exercises. In the treatment of IBS, hypnosis has been Our job is to understand with which poem the indi-
found to have lasting positive effects up to 5 years after vidual resonates the most. We can then know how
therapy. Of more than 200 patients with IBS studied, best to facilitate the connections that give life mean-

139
 Chapter 11 Integrative Medicine

healing. A body can be cured but not healed and vice

Box 11-8 Suggestions for Joan: versa. Although curing can occur without spiritual
Other Medical Systems exploration, it is very difficult to facilitate healing
without it. This is how a disease such as metastatic
Recommendations for Joan will depend on cancer can stimulate spiritual growth. Healing occurs
what is available in her community, but several because the disease encourages an individual to
nonbiomedical systems could be considered. reconnect with what gives life meaning and purpose.
Traditional Chinese medicine would character- These influences cannot be directly defined with
ize Joan’s symptoms in terms of yin and yang medical imaging or serum analysis. Often the only
and the effects of organ systems on one clue we have to see whether this takes place is by
another. Ayurveda would do the same using looking into someone’s eyes or hearing them tell
the three doshas. The Chinese, Ayurvedic, or their story. Seeing and experiencing this is one of the
homeopathic systems can potentially link greatest joys in the practice of medicine.
Joan’s multiple symptoms into an overall There is no “right” answer to how we can
explanatory model that can allow for a simpli- explore spirituality with patients. Each individual
fication of treatment. For example, acupunc- defines spirituality in a unique way. Our task is to
ture along one of the energy channels, or encourage this exploration to help patients draw
meridians, may simultaneously affect her bow- from this powerful and mysterious influence that
els, her back, and her emotional status. results in healing and well-being.

ing and purpose. Spirituality may or may not involve Material Available on Student Consult
formal religion. A person’s poem may be defined Review Questions and Answers about Integrative
through nature or human relationships. Medicine
In exploring how spirituality influences health, Tables 11-1 through 11-21
we can also understand how curing differs from

REFERENCES
Abbot N. Healing as a therapy for human disease: A sys- Blair SN, Kampert JB, Kohl HW, et al. Influences of car-
tematic review. J Altern Complement Med 2000;6: diorespiratory fitness and other precursors on cardio-
159–169.● B vascular disease and all-cause mortality in men and
Ackerman KD, Bellinger DL, Felton SY, et al. Ontogeny and women. JAMA 1996;276:205–210.
senescence of noradrenergic innervation of the rodent Bronfort G, Assendelft WJJ, Evans R, et al. Effects of spinal
thymus and spleen. In Ader R, Cohen N, Felton DL manipulation for chronic headache: A systematic
(eds): Psychoneuroimmunology, 2nd ed. New York, review. J Manipul Physiol Ther 2001;24:457–466.● A
Academic, 1991, pp 71–125. Centers for Disease Control and Prevention. Physical activ-
Allison DB, Fontaine KR, Manson JE, et al. Annual deaths ity trends: United States, 1990–98. MMWR 2001;50:
attributable to obesity in the United States. JAMA 166–169.
1999;282:1530–1538. Chapman-Smith D. Chiropractic report: Origin
Assendelft WJJ, Morton SC, Yu EI, Suttorp MJ, Shekelle and professional organization. Available at www.
PG. Spinal manipulative therapy for low back pain. chiropracticreport.com/chiropractic.htm. Accessed
Cochrane Database Syst Rev 2005;3:CD00047. on 12/5/2004.
Astin J, Marie A, Pelletier K, et al. A review of the incorpo- Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alter-
ration of complementary and alternative medicine by native medicine use in the United States, 1990–1997:
mainstream physicians. Arch Intern Med 1998;79: Results of a follow-up national survey. JAMA 1998;
1440–1447. 280:1569–1575.
Astin JA. Why patients use alternative medicine: Results of Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins
a national study. JAMA 1998;279:1548–1553. DR, Delbanco TL. Unconventional medicine in the
Astin JA, Harkness E, Ernst E. The efficacy of “distant heal- United States: Prevalence, costs and patterns of use.
ing”: A systematic review of randomized trials. AIM N Engl J Med 1993;328:246–252.
2000;132:903–910.● B Eisenberg DM, Kessler RC, Van Rompay MI, et al.
Balluz LS, Kieszak SM, Philen RM, Mulinare J. Vitamin and Perceptions about complementary therapies relative to
mineral supplement use in the United States: Results conventional therapies among adults who use both:
from the third National Health and Nutrition Results from a national survey. Ann Intern Med
Examination Survey. Arch Fam Med 2000;9:258–262. 2001;135:344–351.● B
Benor DJ. Energy medicine for the internist. Med Clin Erickson K, Rosier A, Rainone F. Chiropractic and osteo-
North Am 2002;86:105–125. pathic care. In Kligler B, Lee R (eds): Integrative

140
 Chapter 11 Integrative Medicine

Medicine: Principles for Practice. New York, McGraw Johnson K. The glycemic index. In Rakel D (ed):
Hill, 2004, pp 153–176.●B Integrative Medicine. Philadelphia, WB Saunders, 2003,
Ernst E. Distant healing: An “update” of a systematic pp 661–666.● B
review. Wien Klin Wochenschr 2003;115:241–245.● B Johnston BA. Prevention Magazine assesses use of dietary
Fairfield KM, Fletcher RH. Vitamins for chronic disease supplements. HerbalGram 2000;48:65–72.
prevention in adults: Clinical applications. JAMA 2002; Joneja JV. Dietary Management of Food Allergies and
287:3127–3129.● A Intolerances: A Comprehensive Guide, 2nd ed.
Felten SY, Felten DL. The innervation of lymphoid tissue. Vancouver, BC, Hall Publications, 1998.●B
In Ader R, Cohen N, Felton DL (eds): Psycho- Mahan LK, Escott-Stump S (eds). Krause’s Food,
neuroimmunology, 2nd ed. New York, Academic, 1991, Nutrition and Diet Therapy, 11th ed. Philadelphia,
pp 27–70. Elsevier, 2004.
Ferencik M, Stvrtinova V. Is the immune system our sixth Oschman JL. Energy Medicine: The Scientific Basis. New
sense? Relation between the immune and neuroen- York, Churchill Livingstone, 2002.
docrine systems. Brisl Lek Listy 1997;98:187–198. Rindfleisch JA, Rakel D. Neck pain. In Rakel D (ed):
Flood A, Schatzkin A. Colorectal cancer: Does it matter if Integrative Medicine. Philadelphia, WB Saunders, 2003,
you eat your fruits and vegetables? J Natl Cancer Inst pp 433–445.● B
2000;92:1706–1707. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A
Fugh-Berman A, Ernst E. Herb-drug interactions: Review Physician’s Guide to Herbal Medicine. New York,
and assessment of report reliability. Br J Clin Springer Verlag, 2001.
Pharmacol 2001;52:587–595.● B Smyth JM, Stone AA, Hurewitz A, Kaell A. Effects of writ-
Furlan AD, Brosseau L, Imamura M, Irvin E. Massage ing about stressful experiences on symptom reduction
for low-back pain. Cochrane Database Syst Rev 2004; in patients with asthma and rheumatoid arthritis.
2:CD001929.● B JAMA 1999;281:1304–1309.● A
Gonsalkorale WM, Miller V, Afzel A, Whorwell PJ. Long Wolever TM. The glycemic index: Aspects of some vita-
term benefits of hypnotherapy for irritable bowel syn- mins, minerals, and enzymes in health and disease.
drome. Gut 2003;52: 1623–1629.● B World Rev Nutr Diet 1990;62:120–185.

141
 C h a p t e r

12 The Electronic Medical Record

Bruce Bagley and David Kibbe

KEY POINTS

1. The goal of incorporating information technol- 4. The EMR is especially useful as a tool in practice
ogy into health care practices is to improve management for large physician groups with
patient care and outcomes through efficient multiple practice sites.
management of time, resources, and data. 5. To realize the full advantages of the EMR, stan-
2. The electronic medical record (EMR) provides a dards related to data exchange and interoperabil-
comprehensive mechanism for integrating and ity will need to be in place.
subsequently accessing patient data. 6. Appropriate electronic platforms and solutions to
3. The EMR facilitates exchange of information implementation issues are expected to evolve
with referring physicians, consultants, nurses, over time.
and other care providers.

The contemporary practice of medicine requires a high and data management areas in which the EMR is
level of information management. Electronic applica- proving its worth are discussed in this chapter.
tions can be used to achieve high-quality, consistent
health care outcomes through an integrated, logical
Applications and Functionalities
approach to patient data management. The electronic
medical record (EMR) is the principal tool for effi- Medication Prescription
ciently managing, accessing, and sharing patient data. A provider need only enter the information for a new
This tool represents an advance over existing knowl- prescription in the EMR, and that information is
edge retrieval and sharing capabilities already available put on the patient’s medication list.The computer
through Internet databases and PDA messaging and keeps track of when the prescription was written, the
lookup functions by aggregating patient data in one amount ordered (and later dispensed by the phar-
electronic location with common access. macy), and the number of refills. This capability saves
time and improves communication with the patient,
the pharmacist, and subsequent care providers. Most
THE ELECTRONIC MEDICAL RECORD systems can check to see if medications are on a spe-
cific formulary and can even advise the physician of
The EMR provides clear and concise information the probable cost to the patient for the drug.
about the patient and so improves patient care and
outcomes. Information is organized in a way that is Medication Reconciliation
easy to use and to access. Chart notes, laboratory test Managing multiple medications has increased the
results, and X-ray reports can all be entered into complexity of everyday patient care, especially care of
the EMR, accessed, and reviewed in an efficient the elderly. The computer automatically checks for
and logical manner (Box 12-1). Problem lists, allergies and drug-drug interactions whenever a new
immunization records, and medication lists are all drug is entered. Although not all of the drug interac-
automatically updated during the process of caring tion alerts generated by the computer are clinically
for the patient, and the updated information can be significant, the physician is prompted to consider the
immediately shared with nurses and physicians. severity of the conflict and act accordingly. If the
Because the EMR makes use of relational database physician is not knowledgeable about the type or
concepts and technology, it is no longer necessary to cause of the interaction, a full explanation is available
enter the same information in multiple places in the at the touch of a screen or with a single keystroke.
chart. Some of the most important patient safety Pharmacy computers can keep track of prescription

142
 Chapter 12 The Electronic Medical Record

patient’s history and physical findings, along with

Box 12-1 Electronic Medical Record diagnostic impressions or conclusions.
Functionalities The traditional written narrative in the office
visit note may easily obscure both normal and
Intra-office messaging, phone calls, and prescrip- abnormal findings by embedding them in the middle
tion refills of a paragraph or page, requiring the reader to scan
Prescription writing; allergy and interaction the entire page to find the one piece of information
warnings the reader is looking for. It would be far more effi-
Laboratory tests: order entry, review and track- cient if normal and abnormal items were highlighted
ing of abnormal results in some way for easy recognition. A wad of text may
Referral letters and health plan notification not be the best way to record and communicate
Reimbursement: billing, coding, and documen- important information.
tation for payment Structured data entry allows information to be
Patient education entered into the computer in a way that is easy to
Office visit documentation search and retrieve. Pick-lists allow clinicians to
Comprehensive problem list management choose from standard complaints, history items, and
Efficient filing of clinical information from out- physical findings in the course of constructing the
side the office final note. There is also the option of displaying the
Enhanced e-mail communication with patients note either in tabular form or in narrative form.
Clinical data tracking for quality improvement With structured data entry, the necessary elements
purposes for coding and billing can be determined more read-
ily. However, the pick-lists do limit some of the rich-
ness of the history (which often helps to substantiate
the diagnosis or conclusion), and the time required
refills and alert the physician if the patient appears to construct the note is longer than the time needed
not to be taking a medication regularly. Other physi- to dictate a traditional narrative note. A plan of
cians can access the patient’s medication profile in the action or follow-up recommendations complete the
EMR before prescribing a new drug. office visit note.
Physicians often use a combination of struc-
Laboratory Test Results tured data entry, keyboard entry, dictation, and voice
Ordering laboratory tests and reviewing the results recognition software to enter the visit record.
on a timely basis is an important component of Because of the drawbacks of voice recognition sys-
patient care. When laboratory tests are ordered tems and editing, some combination of structured
electronically, the information is entered into a log, data entry and traditional dictation, with the tran-
so that tracking the return and review of results is scribed note later entered into the record, is likely to
reliable and efficient. For laboratory work that is be most widely used for the near future.
performed in the office, such as blood tests, electro-
cardiograms, or radiographs, the computer automat- Managing the Practice
ically captures the proper information for billing
purposes. When results are returned to the physician, Physicians have used computerized practice manage-
they are reviewed, and the patient can be notified of ment systems for years to help with scheduling,
normal results or of the need for further testing. At billing, and collections. The addition of the EMR
the time blood is drawn or other test is performed, allows clinical and billing information generated
the nurse determines the patient’s preferred method during the process of care to be integrated with busi-
of notification about results. An electronic method ness information in the practice management soft-
of tracking and obtaining results reduces delays in ware. The result is improved accuracy and timely
patient care provision and eliminates periods of con- submission of bills to appropriate payers.
cern for both patient and physican. From this basic union of patient care and
reimbursement data, additional useful information
Record of Office Visit can also be gathered from the EMR. Inventory con-
An accurate record of the office visit is essential to trol is a fairly obvious application of EMR data.
the provision of good patient care. Various members The cost of care can be tracked, as can provider
of the clinical team enter information using tem- efficiency, productivity, and time required for spe-
plates. The nurse or medical assistant may enter cific tasks. This information is crucial to analyzing
a portion of the note, such as the reason for the and managing office systems and process. Tracking
current visit, any concerns expressed by the patient, supply and demand for services enables office
vital signs, and a review of current medications. managers to reduce waiting time for a provider’s
Physicians usually enter information about the services.

143
 Chapter 12 The Electronic Medical Record

Office Workflow fact of the focus on visit-based care) to health care

information that is interactive, real time, and
One of the greatest benefits of the EMR is to facil- prospective. The potential for this technology, how-
itate office workflow. Intra-office messaging, ever, has remained an unfulfilled promise.
responding to patient phone calls or e-mail mes- The CCR is a document standard for basic health
sages, and providing medication refills are all part information that uses XML (extensible markup lan-
of the daily office workload. Even though the aver- guage). A number of groups, among them ASTM
age family physician may see 25 to 30 patients face- International, the Massachusetts Medical Society, the
to-face in the office each day, an additional 75 to Health Information Management and Systems Society,
100 interact with the office through some other the American Academy of Pediatrics, and the
means––phone, fax, or e-mail. They may call for American Academy of Family Physicians, are develop-
advice about minor problems, prescription refills, ing it jointly (Box 12-2). The CCR is intended to foster
or referrals to other providers. In a paper-only sys- continuity of patient care, to reduce medical errors,
tem, each of these 100+ interactions requires a and to increase patients’ role in managing their own
clerk to manually access the chart folder, attach a health care. It will also enable epidemic monitoring,
note, and deliver the chart to the location. The public health research, and ensure at least a minimum
EMR allows any member of the care team to access standard of secure health information transportability.
the medical record at any time, regardless of loca- The CCR is not an electronic health record but rather
tion. Most systems allow multiple users to access a snapshot of the information the medical record
the same patient’s chart at the same time. This contains at a given point in time. The CCR is compat-
capability is essential for efficient time manage- ible with other efforts to standardize health informa-
ment and to reduce waiting times and delays. The tion systems and can work in conjunction with these
ability to access patient records from remote sites is efforts.
especially important for physican groups with The nationwide transmittal of data as impor-
multiple practice sites and for physicians who are tant as health care information should be as easy as
on call while at home or at the hospital. using an ATM card. The number of health informa-
tion system vendors is increasing, however, and
most offer only their own proprietary software. A
STANDARDS survey of nearly 1,300 family physicians who used
electronic health records in their practices found
Most office-based health information technology in
use today, including the EMR, cannot be used to
exchange much information with laboratories,
pharmacies, or patients and family members.
Box 12-2 Continuity of Care Record
Connectivity between the practice EMR and these
important sources of information within and out- ● Provides a snapshot of the individual
side the office practice environment is necessary to patient’s medical history at a given point in
prevent computerized systems from becoming data time.
islands. The acceptance and promulgation of IT ● Contains most of the relevant clinical infor-
standards can increase low-cost connectivity and mation needed for a variety of clinicians, in
data exchange solutions at the level of the medical various settings, to provide safe, efficient and
practice. A growing number of data content, format, informed care to the patient.
vocabulary, and messaging standards play an impor- ● Can be updated anytime changes are made.
tant role in health IT adoption. Perhaps the most ● Data are formatted in XML language, which
significant to family physicians is the new intero- allows any operating system or electronic
perability standard called the Continuity of Care health record to “read” the data and popu-
Record (CCR). late its own data structure.
A quarter of a century ago, a uniform ambula- ● Can be stored and transferred as a digital file
tory medical care minimum basic data set was that can be opened and converted to read-
designed and reported to the U.S. National able text or read by an EMR system.
Committee on Vital and Health Statistics. In the early ● Will serve as the “universal interface” for
2000s, the Institute of Medicine (IOM) articulated clinical information among disparate elec-
yet again the enormous potential for IT to improve tronic health record systems.
health care quality by enabling safe, effective, ● Can serve as a vehicle to collect and report
patient-centered, timely, efficient, and equitable care. clinical data for quality improvement or
The IOM recognized that the health care system will accountability efforts.
move away from the current medical record (an arti-

144
 Chapter 12 The Electronic Medical Record

264 different software vendors were represented, but CHALLENGES

even the largest was used by only 148 physicians.
None of the 264 systems used currently can share Computer Hardware
data with any of the other systems. The software
being developed for the CCR addresses this lack of Computer hardware is constantly evolving, so it is
compatibility by allowing disparate information not possible to make lasting recommendations about
technologies and software programs to read, inter- what configurations are best. Most EMR vendors
pret, and transmit a core summary of personal offer software that can serve the office needs on a
health information. A growing number of clinical completely self-contained system. The enterprise sys-
information systems companies have agreed to tem, as it is called, usually has all the computer
implement the CCR. The prospects are good that equipment installed and maintained in the office.
widespread adoption of this first interoperability Many vendors now offer the application service
standard can be achieved by 2006. provider (ASP) version of software, which can pro-
The CCR is also portable, allowing patients to vide the same functions from remote computers that
carry with them a summary of their most impor- are accessed via high-speed Internet connections.
tant personal medical information. It can be There are pros and cons to both approaches. The cost
printed out, carried on a USB flash drive or smart advantage of ASP systems has diminished as hard-
card, e-mailed directly to a physician, or uploaded ware prices have continued to fall. Maintenance and
to a secure Web site, where it can be accessed with downtime are considerations with both approaches.
consent. Wherever a patient carries or sends the Other useful office technology includes local area
CCR, the data in it, such as recent blood pressure networks (linked intra-office network of comput-
readings, a current list of medications, medication ers), handheld devices on which the EMR can be
allergies, and laboratory test results, can be accessed accessed at the bedside or in the physician’s off-site
for immediate use. location, and portable printers available in each
examination room for printing out results for
patients to take with them (Box 12-3).
QUALITY SYSTEMS EMBEDDED
Calls for better quality of care and more consistent Box 12-3 The ACID Test for EMR
care have come from many different groups.
Systems
Improved patient safety standards and the reduction
of medical errors will be at the top of the health care Electronic medical records systems must pass
policy agenda for the next decade. The EMR allows the ACID test.
quality improvement and patient safety to be built
A Affordability—Office-based IT should be
into systems of care.
affordable to family physicians and other
Quality improvement focuses on reducing waste
office-based clinicians who face challenging
and variability in process and systems. The goal is
economic environments and decreasing
to have office systems that deliver reliable health
reimbursement.
care outcomes and enjoy the support of excellent
customer service. Well-designed EMR systems will C Compatibility—Physicians should not have
include functions that help physicians manage health to replace entire systems when purchasing a
maintenance and chronic illness. A registry is a sys- component or be locked into a single ven-
tem to identify and track patients with a specific con- dor’s products due to proprietary interfaces
dition. It helps to ensure that patients get what they or predatory pricing tactics. Systems should
need, when they need it, to optimally manage their be “plug and play” with regard to inter-
chronic illness such as diabetes or hypertension. facing.
Common office tasks, such as tracking and reporting I Interoperability—Data exchange schemas
laboratory results, can be seamlessly integrated into should facilitate data transfer, import, and
the flow of patient care processes. export among different vendors’ systems
There is great interest in monitoring and collect- and in different settings, such as interoffice
ing data on the quality of care delivered to patients. exchange or office to hospital, to nursing
Performance measures have been developed to mon- home, and to patient/patient home.
itor and improve office systems. The EMR should be D Data stewardship—Physicians reserve the
designed to collect data for these quality improve- right to choose the keepers and guardians
ment measures during the process of care. This step of their data and should have some control
would eliminate costly and time-consuming retro- over how the data are used.
spective chart audits.

145
 Chapter 12 The Electronic Medical Record

The Paperless Office

Box 12-4 Internet Resources
Most physicians still work in a world of paper, and
making the transition to a paperless office envi- Institute for Healthcare Improvement
ronment can be fraught with problems, not least the (www. ihi.org)
need to gain the endorsement of all users. The Institute of Medicine (www.iom.edu)
Electronic Health Record Readiness Assessment tool American Academy of Family Physicians Center
from the AAFP Center for Health Information for Health Information Technology
Technology provides information and guidance on (www. centerforhit.org)
switching over to a paperless environment in stages, Continuity of Care Record (www.centerforhit.
addressing both educational and office-culture needs org)
and technology product evaluation needs. A list National Committee on Vital and Health
of useful Internet sites for obtaining further Statistics (www.cdc.gov/nchs/products/pubs/
information about EMRs, standards, and transition- pubd/other/ncvhs/ncvhs.htm)
ing to a paperless office is provided in Box 12-4. Electronic Health Records Readiness Assess-
The EMR and electronic practice management ment (www.centerforhit.org)
system must support the core business needs of the American Academy of Family Physicians
office. It is tempting to wanst to have all the extra Quality Initiative (www.aafp.org/x3843.xml)
features up and running right away, but it is more Agency for Healthcare Quality and Research.
important to stabilize and refine the basics first. The Healthcare Informatics
computer will serve as a platform for office system (www.ahrq.gov/data/infoix.htm)
redesign, and simply computerizing the same “mess” American Medical Association Physicians
that is currently in place is a missed opportunity. Consortium on Performance Measurement
The benefits of improved efficiency and improved (www.ama-assn.org/ama/pub/category/
patient care will not be realized. Leadership and 4837.html)
change management are important skills for physi-
cians who are going through the transformation to a
paperless office. Forming a project team, providing
good individualized training, and developing and Material Available on Student Consult
implementing strategies that minimize lost produc-
Review Questions and Answers about The
tivity are essential leadership skills. Electronic Medical Record
In summary, the ability to deliver high-quality
health care in the 21st century requires that patient
care teams be supported by IT. Knowledge manage-
ment, clinical information management, and com- SUGGESTED READING
munication with patients and other providers all
benefit from the assistance of computers. IT comes Martin JC, et al. The future of family medicine: A collabo-
in many forms and can be implemented slowly, rative project of the family medicine community. Ann
Fam Med 2004;2(Suppl 1):S3–S32.
with software and knowledge training integrated
into new skills. The EMR is expected to be the
prime patient data management tool in the very
near future, with support from the CCR and similar
standards.

146
 C h a p t e r

13 Interpreting Laboratory Tests

Stephen Scott

means that 5% of normal results will fall outside the

KEY POINTS reference range. This is particularly important to
consider when faced with a large panel of tests. Based
1. Test results are often ambiguous. on probability alone, the chance of having a result
2. Always consider the clinical context when inter- fall outside the reference range will increase simply
preting a laboratory test result. on the basis of an increasing number of tests. At 20
3. The more tests ordered, the more likely that a tests, the probability that all of the results will be
result will fall outside the reference range, within the reference range in a normal individual is
despite being a “normal” result. only 36%. (Stated differently, this means that a 64%
4. Reference ranges may require adjustment based chance exists that at least one result will be outside
on the patient’s age and other factors. the reference range, despite being a normal result.)
Most clinical laboratories report both the result of a
test and the reference range for their laboratory;
these ranges usually do not vary considerably from
INTERPRETING LABORATORY TESTS laboratory to laboratory, but they may take into con-
sideration testing methods or local populations.
Laboratory tests are very useful tools to aid in the Many factors can influence a test result, which
diagnosis and treatment of illness. However, it is often necessitates adjusting a reference range or
important to understand the inherent limitations of interpreting a result with caution. For example, ref-
tests. Whereas it might seem that many tests give erence intervals for adults are often not appropriate
clear “yes” or “no” results, the reality often is not so, for children, and separate reference ranges must be
and test results may be ambiguous or difficult to considered. Other states that affect test results and
interpret. A temptation always exists to order and corresponding reference ranges include gender, preg-
interpret tests without adequately considering the nancy, exercise, ethnicity, lean body mass, some
patient and the clinical context. Falling prey to any of drugs (including hormones, ethanol), physiologic
these pitfalls can lead to unnecessary testing, expen- fluctuations, posture, diet, sampling problems, and
sive workup, and even misdiagnosis. specimen handling.
Some of the reasons for test ambiguity are cov- Reference ranges also may be hard to define. For
ered in Chapter 6, including test characteristics of example, some controversy occurs about the appro-
sensitivity and specificity. Some additional impor- priate upper limit of normal for serum thyroid-
tant areas to consider include reference range, pre- stimulating hormone (TSH). Most laboratories
dictive value, patients with multiple illnesses, and have for some time used values of 4.5 to 5.0 mU/L.
treatment assumptions. However, a recent report indicated that 95% of
rigorously screened euthyroid volunteers have serum
values between 0.4 and 2.5 mU/L, and that the
Reference Ranges
reference range should be adjusted appropriately
Although clinicians and patients often refer to test (Baloch et al., 2003● C ). However, if this change in
results as “normal” or “abnormal,” it is more accurate reference range is implemented, the number of
to define a reference interval for normal individuals patients in the United States diagnosed with subclin-
in an “average” population. For statistical reasons, ical hypothyroidism (asymptomatic persons with
the reference range for a particular test generally TSH > 2.5 mU/L) would increase. Given the accom-
includes 95% of healthy or normal results. This panying uncertainty about whether asymptomatic

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

147
 Chapter 13 Interpreting Laboratory Tests

hypothyroidism should be treated, it is unclear shape interpretation as much as or more than the
whether changing the reference range would provide characteristics of a given test.
any meaningful clinical benefit.
Summary
Predictive Value of a Test
The sources of variation are numerous, and the proper
In conjunction with the sensitivity and specificity of interpretation of test results demands consideration of
a test, it is important to consider the predictive value the entire clinical picture. Even with guidelines and
of the test. The predictive value answers the question, decision-support analyses, the interpretation of a par-
“What is the frequency of disease among all persons ticular result can be a complex process. Rational and
with an abnormal test result?” To calculate the pre- judicious use of testing is always warranted.
dictive value for a particular disease, the prevalence The following sections consider a number of
of the disease in the population under study must be common tests that are used in everyday clinical prac-
known. If the disease prevalence in a population is tice. For each test, the physiologic basis, common
high, then more of the patients who test “positive” indications, causes of abnormal results, potential pit-
will actually have the disease. However, if the disease falls in interpretation, and clinical guidelines are
prevalence is low, then the proportion of patients reviewed, and related tests are grouped. The discus-
who both test positive and have disease will be lower sions and tables are intended to serve as a clinically
(i.e., more false-positive results will be found relative useful, introductory guide. In keeping with this goal,
to true-positive results). specialized testing as well as tests in development are
These important considerations apply in several not covered here, and for these as well as more in-
ways. First, for many diseases, the prevalence is often depth consideration of individual tests, the reader is
1% or less. To be a good screening test in healthy indi- referred to more exhaustive references.
viduals, a test must have a sensitivity that approaches Each section includes “normal” values for the
100%; even in such cases, false positives may out- tests. Although it is more accurate to refer to refer-
number true positives by a factor of 100 or more, ence ranges, in practice, clinicians and patients more
resulting in many “abnormal” results in healthy indi- often refer to tests as normal or abnormal. It should
viduals. Second, predictive value is important to con- be understood that determination of normal or
sider before ordering a test. The more likely a patient abnormal requires consideration of numerous fac-
is to have a disease state, the more predictive an tors, as discussed. Where appropriate, units are given
abnormal result will be; if a patient is unlikely to have both in conventional and système international (SI)
a disease, then an abnormal result is more likely to be units along with conversion factors; in the United
a false-positive result. States, conventional units are commonly used.

Multiple Concurrent Illnesses

BLOOD CELL TESTS
Some test results may be within reference range
despite the presence of underlying disease. For exam-
Hemoglobin and Hematocrit
ple, a patient with iron deficiency and folate defi-
ciency (as can be seen in alcoholism) may have a Most modern hematology instruments directly
normal mean corpuscular volume despite a mixed measure the hemoglobin (Hgb) and calculate the
population of microcytic and macrocytic red cells. hematocrit (Hct) from the measured red blood cell
The same can occur in early treatment of iron defi- (RBC) and mean corpuscular volume (MCV). The
ciency, in which new reticulocytes, which are larger hematocrit also can be measured by centrifugation of
than iron-deficient red cells, may obscure the popu- a microcapillary tube filled with whole blood. The
lation of microcytic cells. hematocrit is defined as the percentage volume of
RBCs after maximal packing has occurred. For most
Treatment Assumptions purposes, the hemoglobin and hematocrit are related
by a factor of three, where Hct = 3 × Hgb.
Even when a reference range is well defined and a It is reasonable to use the hemoglobin and hema-
result is more clearly outside the range, differences tocrit interchangeably except for patients with abnor-
can still occur in interpretation. This can happen mally shaped RBCs (i.e., sickle cell disease). In such
when potentially competing treatment goals exist or patients, the measured hematocrit is artificially high
when the proper follow-up or treatment of an because the RBCs fail to pack maximally. In such
abnormal result is controversial. In these cases, the individuals, the hemoglobin is a better test to follow.
clinicians’ view of which priorities are most impor- Little evidence indicates any benefit from screen-
tant (e.g., minimizing test cost, minimizing adverse ing the general population with routine hemoglobin
outcomes, or minimizing cost of treatment) will or hematocrit measurements. However, screening may

148
 Chapter 13 Interpreting Laboratory Tests

be indicated in groups at high risk for anemia, such as test. It can, however, be a sensitive indicator of dis-
infants, pregnant women, the institutionalized elderly, ease in some clinical situations. Its degree of increase
or menstruating women. It also may be used to screen or decrease often correlates with the severity of the
individuals undergoing a procedure associated with disease process. Monitoring changes in WBC count
blood loss and to screen hospitalized patients on over time can provide useful information about the
admission. In addition to screening, the hemoglobin course of an illness.
or hematocrit is an essential test for any patient sus- Five types of WBCs are commonly counted in
pected to have anemia, blood loss, or polycythemia the WBC differential: neutrophils, lymphocytes,
(Table 13-1). monocytes, eosinophils, and basophils. Changes in
The most common abnormal finding is a mild, the relative percentages of these cells may correlate
unsuspected anemia that is often asymptomatic. with some types of illness (e.g., prominence of neu-
When it is found, it is important to uncover the cause trophils is often seen in acute infections [sometimes
of the anemia, as it is often a clinically important called a left shift ] lymphocytes are often predomi-
diagnosis (e.g., poor nutrition, menorrhagia, perni- nant in viral illnesses, leukemia, and pertussis).
cious anemia, or colon cancer). Leukopenia, which usually indicates neutrope-
A common error when interpreting hemoglobin nia, may occur with severe infections, autoimmune
or hematocrit is to rely on it as an indicator of acute disorders, collagen vascular diseases (including
blood loss. Unfortunately, about 12 to 24 hours is lupus), human immunodeficiency virus (HIV), or
needed before equilibration of hemoglobin and chemotherapy. In patients with congenital neutro-
hematocrit occurs. It is only then that these values penia, levels may be low with or without evidence of
can be used to indicate the extent of blood loss. infection.
Lymphopenia is frequently seen in association
White Blood Cell Count with physiologic stress and is often of no clinical sig-
nificance. Elevation of eosinophils (eosinophilia)
Changes in the white blood cell (WBC) count are may be seen in parasitic infections.
seen with many infectious, hematologic, inflamma- An increased WBC count can be seen in a wide
tory, and neoplastic diseases (Table 13-2). This vari- variety of illnesses, although it is most used as an
ety of influences makes the WBC count a nonspecific indicator of acute infection. Of note, WBC counts

Table 13-1 Hemoglobin

Diagnostic units, g/dL (g/L)
SI conversion factor, 10.0
Normal (adult): males, 13.9–16.3; females, 12.0–15.0
Normal values are higher in the first few months of life and are approximately 18.5–21.5 at birth
Hemoglobin (g/dL) Diagnoses to Consider Actions to Consider
Increased
>16.5 Dehydration Smoking history
Diuretic use Check volume status
Polycythemia vera Check for splenomegaly
Secondary polycythemia Urinalysis
High altitude CBC
Pulmonary disease Platelet count
Cardiac disease Alkaline phosphatase
Renal tumor
>22 Severe polycythemia Consider phlebotomy
Decreased
<11 Blood loss History of chronic disease
Menstrual history Stool for occult blood
Decreased blood cell survival Check for splenomegaly
Decreased marrow production RBC indices
RBC sequestration Reticulocyte count
Iron studies
Folate, B12 studies
<8 Severe anemia Transfusion if patient is symptomatic

CBC, complete blood count; RBC, red blood cell.

149
 Chapter 13 Interpreting Laboratory Tests

Table 13-2 White Blood Cell (WBC) Count

Diagnostic units, cells/mm3 (cells × 109/L)
SI conversion factor, 0.001
Normal (adult), 3200–9800
Varies by age, 9000–30,000 at birth;~5000–18,000 from age 1 wk to 2 yr
WBC Count (cells/mm3) Diagnoses to Consider Actions to Consider
Decreased
500–3200 Infections Complete drug history
Severe bacterial infection Peripheral smear
Influenza Platelet count
Infectious mononucleosis CBC
Typhoid fever Mononucleosis test
Drugs ANA
Cytotoxicity HIV
Idiosyncratic drug reaction Folate, vitamin B12 level
Congestive splenomegaly Bone marrow biopsy
Felty syndrome
SLE If very low (<500), consider frequent exam,
Aplastic anemia antibiotics for fever, given risk of serious
Congenital neutropenia bacterial infections
Increased
9800–30,000 Physiologic reaction to stress Physical exam (looking for sites of infection,
Infection organomegaly)
Tissue destruction Peripheral blood smear
Leukemia
Cancer
Hemorrhage
Splenectomy
>30,000 Leukemia
Leukemoid reaction

ANA, antinuclear antibody; CBC, complete blood count; HIV, human immunodeficiency virus; SLE, systemic lupus
erythematosus.

vary with age and generally are higher in neonates in the spleen. A platelet count also is a useful indica-
and children. They also increase during pregnancy. tor of marrow sensitivity to cytotoxic medications in
Counts greater than 30,000/mm3 often are associated the treatment of cancer.
with leukemia or other blood disorders. It is important to note that platelets may be
adequate in number but defective in function. Medi-
Platelet Count cations, including aspirin, other nonsteroidal anti-
inflammatory drugs, alcohol, and pencillins are the
The platelet count is often routinely performed as a most common reason for abnormal platelet function.
part of a complete blood count, because most auto-
mated cell counters do an automated platelet count as Mean Corpuscular Volume
a part of the test. As a result, the most common platelet
abnormality is a small increase or decrease from nor- The MCV is an indication of the size of the RBCs. It
mal in an otherwise asymptomatic individual (Table is used primarily to differentiate the anemias into
13-3). Usually no benefit is found from further testing macrocytic, normocytic, or microcytic types, which
or repeating the platelet count in such cases. often correlate with specific differential diagnoses
Preoperative screening platelet counts are indi- (Table 13-4). However, it is important to note several
cated for patients when blood loss is expected. They potentially confusing scenarios. First, reticulocytes
also are useful for evaluating patients with abnor- and other young RBCs are larger than mature RBCs,
mal bleeding, bruising, purpura, petechiae, or and a rapid release of RBCs may produce an increase
splenomegaly. in MCV. It is possible to confuse this with other
A low platelet count can be caused by a reduc- causes of macrocytosis. Mixed populations of micro-
tion in the marrow’s production of platelets (due to cytic and macrocytic cells may produce an average
marrow suppression or infiltration), increased MCV in the normal range, despite underlying abnor-
destruction of platelets, or sequestration of platelets malities. This may occur in early treatment of iron

150
 Chapter 13 Interpreting Laboratory Tests

Table 13-3 Platelet Count

Diagnostic units, platelets × 109/L
Normal, first week of life, 84–478; after first week of life, 140–400
Platelets (109/L) Diagnoses to Consider Actions to Consider
Decreased
100–140 Response to viral or bacterial illness Repeat test
50–100 (may have Thrombocytopenic purpura Drug history
bleeding with major After transfusion Alcohol history
surgery) Splenic sequestration Examine for splenomegaly
Marrow infiltration (i.e., leukemia) CBC
Response to cytotoxic drugs Trial off all medications
Marrow infiltration Bone marrow biopsy
DIC
20–50 (may have Platelet transfusion with
bleeding with minor procedure
procedure)
<20 (may have Platelet transfusion
spontaneous GI or
CNS bleeding)
Increased
400–600 Splenectomy
Infection
Blood loss
Inflammatory bowel disease
Collagen vascular disease
600–1000 Malignancy Evaluate for malignancy
Polycythemia vera
>1000 Administer antiplatelet drugs

CBC, complete blood count; CNS, central nervous system; DIC, disseminated intravascular coagulation;
GI, gastrointestinal.

Table 13-4 Mean Corpuscular Volume

Diagnostic units, cubic micrometers (fL)
SI conversion factor, 1
Normal, 76–100 fL
MCV (fL) Diagnoses to Consider Actions to Consider
Increased
100–120 Reticulocytosis Reticulocyte count
Folate deficiency Peripheral smear
Vitamin B12 deficiency Serum vitamin B12, folate
Hypothyroidism TSH
Response to chemotherapy
>120 Folate deficiency
Vitamin B12 deficiency
Decreased
70–76 Iron deficiency Reticulocyte count
Thalassemia Peripheral smear
Anemia of chronic disease Serum iron, TIBC, ferritin
Hereditary sideroblastic anemia Hgb electrophoresis
Lead poisoning
RBC fragmentation (burns, sickle disease)
<70 Severe iron deficiency
Thalassemia

Hgb, hemoglobin; RBC, red blood cell; TIBC, total iron-binding capacity; TSH, thyroid-stimulating hormon.

151
 Chapter 13 Interpreting Laboratory Tests

deficiency (i.e., microcytic cells plus macrocytic mone (ADH), which acts to reduce water excretion
reticulocytes) and in alcoholic patients who may be by the kidneys. When osmolality decreases, thirst dis-
both iron and folate deficient. appears, and ADH secretion is reduced, allowing free
water to be excreted. When the body is adjusting
water levels appropriately, serum sodium concentra-
ELECTROLYTES
tion remains about the same.
However, in situations in which the effective cir-
Sodium
culatory volume is reduced, the body may sacrifice a
Sodium is the major cation in extracellular fluid. It is normal osmolality in an effort to maintain the circu-
most useful to interpret sodium values as a measure latory volume. In this setting, the sodium concentra-
of total body water and effective circulatory volume, tion may decrease as fluid is retained or ingested in
and not simply as a measure of total body sodium. In an effort to maintain circulation. The most common
the normal state, the body maintains a constant causes of hyponatremia result from this effective
serum osmolality, or overall concentration of solutes depletion of circulating volume and include volume
in the blood plasma. When the osmolality increases, losses from sweating, vomiting, diarrhea, or urinary
the body compensates by increasing thirst (increas- losses, heart failure, cirrhosis, and medications
ing free water) and by secreting antidiuretic hor- including thiazide diuretics (Table 13-5). Another

Table 13-5 Sodium

Diagnostic units, mEq/L (mmol/L)
SI conversion factor, 1
Normal, 135–147
Sodium (mEq/L) Diagnoses to Consider Actions to Consider
Increased Fluid loss in excess of salt Assess fluid status
>147 Sweating Serum electrolytes
Diarrhea BUN/Creatinine
Diabetes mellitus (osmotic diuresis) Serum glucose
Diabetes insipidus Urine specific gravity
Hyperaldosteronism Oral fluids
Reduced fluid intake For symptomatic or very elevated
Altered mental status (unable to drink) sodium (>160), slow hydration with
Vomiting isotonic saline to reduce serum
sodium no faster than 10 mEq/L/day;
rapid changes in sodium can induce
CNS changes and serious injury
Excessive salt intake
Infant formula
Hypertonic nasogastric feeding
Salt poisoning
Decreased Excess water Assess fluid status
<135 Psychogenic polydipsia Serum albumin
Excessive IV hydration Serum electrolytes
Decreased circulatory volume BUN/Creatinine
Diuretic therapy Urine and serum osmolality
Congestive heart failure Urine protein
Cirrhosis Urine specific gravity
Nephrotic syndrome Water restriction
Dehydration with free water access
Inability to excrete water
Renal failure (CrCl <15)
SIADH
Sodium depletion
Gastrointestinal loss
Excessive sweating
Adrenal insufficiency
Pseudohyponatremia

BUN, blood urea nitrogen; CNS, central nervous system; CrCl, creatinine clearance; IV, intravenous; SIADH,
syndrome of inappropriate antidiuretic hormone.

152
 Chapter 13 Interpreting Laboratory Tests

important cause is the syndrome of inappropriate osmolality increases, ADH is secreted, and thirst
ADH secretion (SIADH), which often results in a increases. As a result, one of the most common rea-
stable reduction of serum sodium to 125 to 135 sons for hypernatremia is the inability of patients to
mEq/L. In advanced renal failure, ADH may be express thirst normally. This occurs frequently in
secreted appropriately, but the diseased kidney is impaired elderly patients, who may already be prone
simply unable to dilute the urine sufficiently to pre- to volume depletion due to reduced intake, medi-
vent solute and water loss. Dilution of serum sodium cines, or illness.
also may occur in the presence of excess water intake,
as occurs in primary polydipsia. Potassium
Pseudohyponatremia results when marked ele-
vations of other solutes in the plasma occur, effec- Potassium is the major intracellular cation, and
tively reducing the measured serum sodium 98% of total body potassium is contained within
concentration, and may be seen with hyperglycemia, cells. The kidneys regulate the concentration of
severe hyperlipidemia, or hyperproteinemia. extracellular potassium, and hyperkalemia and
Hypernatremia generally occurs in states in hypokalemia occur primarily as a result of renal
which free water losses exceed sodium loss, fluid disorders, medications, or abnormalities in the
intake is reduced, or excessive salt is ingested (includ- intake of potassium.
ing intravenous administration of hypertonic Measuring potassium is useful for patients with
sodium solutions). As noted, the body very effec- renal disease, for patients taking diuretics, and in
tively regulates plasma osmolality. When the serum patients who complain of weakness (Table 13-6). It is

Table 13-6 Potassium

Diagnostic units, mEq/L (mmol/L)
SI conversion factor, 1
Normal, 3.5–5.0
Potassium (mEq/L) Diagnoses to Consider Actions to Consider
Decreased
2.5–3.5 Renal loss Drug and diet history
Thiazide or loop diuretics Serum electrolytes
Renal tubular acidosis Urine electrolytes
Hyperaldosteronism ECG (ST and T depression, presence of U waves)
Gastrointestinal loss
Vomiting Oral potassium replacement
Diarrhea
Inadequate dietary potassium
<2.5 Hypokalemia arrhythmias ECG, close monitoring
Neurologic exam
IV and/or oral potassium
Increased
5.0–7.5 Hemolyzed specimen Repeated K on new specimen
Drugs Drug and diet history
Potassium-sparing diuretics ECG (peaked T waves)
NSAIDs Creatinine
ACE inhibitors Serum electrolytes
Decreased renal excretion Urine electrolytes
Acute renal failure
Chronic renal failure
Addison’s disease
Acidosis
Tissue destruction
>7.5 Hyperkalemic arrhythmias ECG (peaked T waves, wide QRS, absent P waves)
Calcium gluconate
Kayexalate (absorbs potassium from GI tract)
Bicarbonate
Dialysis

ACE, angiotensin-converting enzyme; ECG, electrocardiogram; GI, gastrointestinal; IV, intravenous; NSAID,
nonsteroidal anti-inflammatory drug.

153
 Chapter 13 Interpreting Laboratory Tests

frequently included in a basic metabolic panel, which bolic acidosis or with metabolic compensation for res-
is often performed in acutely ill hospitalized patients piratory alkalosis (where excess CO2 is blown off by the
because of the frequent use of intravenous infusions, lungs). In these situations, chloride levels increase in
nasogastric tubes, or other interventions that poten- response to the decrease in CO2 content. In settings in
tially alter the body’s usual homeostatic mechanisms. which CO2 content is increased (metabolic alkalosis or
The most common potassium disorder is a mild respiratory acidosis), the chloride is reduced to com-
hypokalemia in patients taking thiazide or loop pensate for the increased CO2 content.
diuretics. These patients are often asymptomatic, but Chloride can be depleted by either gastrointesti-
low potassium levels are usually monitored, and oral nal losses (vomiting) or renal losses (salt-losing renal
potassium replacement is given as needed to prevent diseases) (Table 13-7). In these circumstances, chlo-
clinically significant hypokalemia. Mild hypokalemia ride depletion results in a persistent metabolic
can be associated with vague complaints such as alkalosis.
weakness, muscle cramps, and paresthesias. Severe The most frequent use of the chloride test is in
hypokalemia may cause cardiac arrhythmias, para- determining the anion gap, which is calculated by
lytic ileus, or paralysis. subtracting the total measured anions (chloride +
Hyperkalemia is most commonly seen with CO2) from the total cations (sodium + potassium).
hemolysis of red blood cells during blood collection The normal range for anion gap is 16 ± 4 mEq/L.
or processing. If in doubt, serum potassium should Increases in the anion gap indicate the presence of
be retested before having the patient undergo an unmeasured anions such as ketoacids, methanol, or
extensive workup for unknown causes of hyper- salicylates.
kalemia. Other common causes include some med-
ications, such as potassium-sparing diuretics, and
Carbon Dioxide
renal disease. Severe hyperkalemia may be associated
with bradycardia, hypotension, ventricular fibrilla- The CO2 content of blood is made up of bicarbonate,
tion, and cardiac arrest. Clinically significant hyper- carbonic acid, and dissolved CO2. Of the total CO2
kalemia is usually associated with electrocardiogram content, 95% is bicarbonate (HCO3–). Bicarbonate is
(ECG) findings, as noted in Table 13-6. the second most important anion in serum and is the
most available base that is capable of buffering a
Chloride metabolic acid load. As a result, CO2 has a primary
role in the body’s acid-base balance. The two mecha-
Chloride is the major extracellular anion in the body, nisms for control of CO2 are respiratory elimination
but it is clinically useful only in selected circum- of CO2 and renal reabsorption of filtered bicarbon-
stances. ate. Bicarbonate also can be lost pathologically from
Most dietary chloride is absorbed, and the level is the gastrointestinal tract.
controlled by renal excretion. Chloride levels change The most common CO2 content abnormality is
primarily in relation to shifts in the serum carbon a decrease due to metabolic acidosis. In this setting,
dioxide (CO2) content. CO2 content decreases in meta- it is useful to calculate the anion gap (discussed

Table 13-7 Chloride

Diagnostic units, mEq/L (mmol/L)
SI conversion factor, 1
Normal, 95–105
Chloride (mEq/L) Diagnoses to Consider Actions to Consider
Increased Metabolic acidosis HCO3−, Na, K, pH, BUN
>105 Loss of bicarbonate Calculate anion gap
Production of metabolic acids
Respiratory alkalosis with metabolic compensation
Dehydration
Decreased Metabolic alkalosis Urinalysis
<95 Hydrogen ion loss HCO3−, Na, K, pH, BUN
HCO3− retention
Respiratory acidosis with metabolic compensation
Salt-losing renal disease
Thiazide diuretics

BUN, blood urea nitrogen; HCO3−, bicarbonate; K, potassium; Na, sodium.

154
 Chapter 13 Interpreting Laboratory Tests

under Chloride), which may provide a clue to the The serum level of calcium is under the complex
cause of the acidosis (Table 13-8). control of parathyroid hormone (PTH) and calci-
Metabolic alkalosis may be initiated by the loss tonin. These hormones and others control the rate at
of hydrogen ion, as is seen with nasogastric suction. which calcium is absorbed from the gastrointestinal
Maintenance of metabolic alkalosis requires greater tract, excreted in the urine, and gained or lost to
than normal reabsorption of bicarbonate by the kid- bone (Table 13-9).
neys. Therefore in patients with an elevated CO2 The most common abnormality is a low total
content, also consider diseases that affect the han- calcium level in patients with a low serum albumin.
dling of bicarbonate by the kidneys. In this case, the disorder is primarily of albumin, not
serum calcium, and the ionized calcium remains
unchanged. In this setting, it is possible to correct
Calcium
mathematically the total calcium in light of the
Calcium is an essential component of the skeleton decreased albumin (1-g/dL reduction in albumin
and also plays a key role in neuromuscular function. leads to a 1-mg/dL reduction in calcium).
The ionized form is the physiologically active form Hypocalcemia produces symptoms that result
and represents about 43% of the total serum cal- from neuromuscular excitability: carpopedal spasm,
cium; the remainder is bound to plasma proteins, seizures, tetany, stiffness, fatigue, memory loss, and
primarily albumin. Diseases that result in elevated confusion. It can be seen with vitamin D deficiency,
total calcium levels also result in elevated ionized cal- renal insufficiency (mediated by elevated phospho-
cium levels. For simplicity, both tests can be viewed rus, which binds calcium), and gastrointestinal mal-
as a measure of serum calcium levels. absorptive disorders.

Table 13-8 Carbon Dioxide (CO2)

Diagnostic units, mEq/L (mmol/L)
SI conversion factor, 1
Normal, 22–28
CO2 (mEq/L) Diagnoses to Consider Actions to Consider
Decreased Metabolic acidosis Drug history
<22 Bicarbonate loss Serum electrolytes
Diarrhea Blood gas
Renal tubular acidosis Calculate anion gap
Primary hyperparathyroidism
Failure to reabsorb bicarbonate
Triamterene, spironolactone
Renal tubular acidosis
Production of metabolic acids
Renal failure
Diabetic ketoacidosis
Lactic acidosis
Methanol
Ethylene glycol
Salicylates
Alcoholic ketoacidosis
Respiratory alkalosis with compensation
Anxiety
Sepsis
Salicylates
CNS injury
Increased Metabolic alkalosis Serum electrolytes
>28 Volume contraction Blood gas
Nasogastric suction Urine electrolytes
Vomiting
Postassium depletion
Furosemide
Cushing syndrome
Chronic respiratory acidosis with compensation

CNS, central nervous system.

155
 Chapter 13 Interpreting Laboratory Tests

Table 13-9 Total Calcium

Diagnostic units, mg/dL (mmol/L)
SI conversion factor, 0.2495
Normal, 8.8–10.3 (2.20–2.45)
Calcium (mg/dL) Diagnoses to Consider Actions to Consider
Increased
10.3–13.0 Hyperparathyroidism Repeated serum calcium
Cancer Drug history
Thiazide diuretics Diet history
Immobilization Ionized calcium, albumin, phosphorus, PTH, TSH
Vitamin D intoxication Chest radiograph
Milk-alkali syndrome Hand radiographs
Multiple myeloma Evaluation for malignancy
Sarcoidosis
Thyrotoxicosis
>13.0 Hypercalcemic coma Hydration
Furosemide
Close monitoring
Decreased
7.0–8.8 Hypoalbuminemia Serum albumin
Chronic renal failure Drug history
Hypoparathyroidism Alcohol history
(neck surgery) Serum creatinine, phosphate, magnesium, PTH
Malnutrition
Vitamin D deficiency
Nutritional
Anticonvulsants
Malabsorption
Liver disease
Hypomagnasemia
Pancreatitis
<7.0 Hypocalcemic seizures Calcium gluconate IV
Hypocalcemic arrhythmia Ionized calcium
Magnesium level

IV, intravenous; PTH, parathyroid hormone; TSH, thyroid-stimulating hormone.

Hypercalcemia is associated with fatigue, GLUCOSE

depression, constipation, polydipsia, ulcers, and
hypertension. In the outpatient setting, the most Glucose levels are commonly ordered to diagnose
common cause of hypercalcemia is hyperparathy- diabetes, follow up the course of diabetes treatment,
roidism. Many of these patients are asymptomatic. or diagnose hypoglycemia. It is important to distin-
Ionized calcium may be more sensitive in detecting guish between random and fasting glucose levels,
hypercalcemia in these patients. Malignancy is the which are interpreted differently. A random speci-
second most common cause and is often seen in the men taken 2 hours after lunch should not be treated
inpatient setting. The mechanism involves secretion in the same way as a fasting specimen. Fasting glu-
of a PTH-related protein by the tumor. The most cose levels are a key feature of screening and diag-
common cancers that produce hypercalcemia are in nostic tests for diabetes.
the lung (particularly primary squamous cell can- Causes of elevated glucose levels other than dia-
cer), breast, kidney, liver, and ovary. betes include specimens taken after eating, specimens
Calcium has frequently been included in routine that are taken from a vein just above an intravenous
screening chemistry panels, with the rationale that glucose infusion site, stress states, steroid therapy,
many cases of hyperparathyroidism are asympto- Cushing’s syndrome, and other metabolic disorders.
matic. However, it is unclear whether asymptomatic Many causes of hypoglycemia are noted, and
hyperparathyroidism requires treatment. Hence, the before embarking on a detailed workup, it is important
use of calcium as a screening test in healthy individ- to consider whether a patient’s symptoms correlate
uals is of questionable value. with a low blood sugar. If a low blood sugar value does

156
 Chapter 13 Interpreting Laboratory Tests

not produce symptoms, it may not be clinically signif- to the average glucose concentration. The measure-
icant. The lower limit of the reference range for normal ment of glycosylated hemoglobin (HbA1c) has there-
glucose usually is between 40 and 55 mg/dL; hypo- fore become a useful clinical test to assess the
glycemia is then defined as a blood sugar below this “average” glucose control in patients with diabetes.
level at the same time symptoms are present. Increased percentages of glycosylated hemoglobin
Fasting hypoglycemia is seen primarily in those reflect increased hyperglycemia. Glycosylation of the
with diabetes and alcoholism, and it usually occurs only RBC is irreversible, and because the life of the aver-
after a long period of fasting or with excess insulin age RBC is about 3 to 4 months, the HbA1c value can
administration. Symptoms include confusion, jitteri- be viewed as a measure of diabetes control for the
ness, unusual behaviors, or seizures, and may be more previous few months.
gradual in onset in alcoholics. Other causes of hypo- The HbA1c value does not change with rapid
glycemia include insulin-secreting tumors, adrenal hour-to-hour or day-to-day variations in serum glu-
insufficiency, hypopituitarism, and drugs (including cose. As a result, it is inappropriate to use HbA1c val-
insulin, sulfonylureas, and salicylates). ues when making decisions about insulin or drug
Various standards for interpreting glucose levels therapy in acutely ill patients. Although it may influ-
have been established. Glucose values vary slightly by ence treatment decisions in the outpatient who is not
the type of specimen, and venous specimens are used acutely ill, the best source for data, especially for
as the reference standard. When used as a screen- altering insulin regimens, is regular, premeal home
ing test, a fasting glucose greater than or equal to glucose monitoring.
126 mg/dL or any random glucose level greater than Reference values for HbA1c vary by laboratory; a
200 mg/dL is diagnostic of diabetes. The upper limit representative range is given in Table 13-10. The HbA1c
of a normal glucose level may vary by laboratory but may be falsely elevated with uremia, alcoholism, and
usually is about 110. If a fasting glucose is in the aspirin use; it may be falsely reduced in patients with
intermediate range between about 110 mg/dL and anemia, hemoglobinopathies, or pregnancy.
126 mg/dL, repeated testing or glucose tolerance test-
ing may serve as an aid to diagnosis.
Additional testing is most commonly used to HUMAN CHORIONIC GONADOTROPIN
confirm diabetes in pregnancy. If an initial glucose
level is greater than or equal to 140 mEq/dL 1 hour Human chorionic gonadotropin (hCG), a glycopro-
after ingestion of a 50-g glucose load, a 3-hour con- tein secreted by placental trophoblastic tissues, is
firmatory test is performed. In this test, the fasting essential for support of the corpus luteum during
level is obtained, a 100-g glucose load is ingested, and early pregnancy. With sensitive tests, hCG can be
glucose values are measured at 1, 2, and 3 hours. If found in the maternal serum within 24 hours of
more than two of the four values exceed the accepted implantation. The levels then increase rapidly and
reference value (≥95, 180, 155, and 145 for fasting, peak at 10 weeks of gestation. For the remainder of
1-, 2-, and 3-hour values), the woman is considered the pregnancy, levels continue at approximately one
to have gestational diabetes. tenth of the peak level.
Qualitative and quantitative hCG tests are
available. The most common are qualitative tests that
GLYCOSYLATED HEMOGLOBIN are used on urine specimens to diagnose pregnancy.
The sensitivity and specificity of these tests have
The glycosylation of hemoglobin occurs continu- steadily improved since they were first introduced
ously during the life of an RBC and is directly related in the 1970s. Most, including over-the-counter

Table 13-10 Glycosylated Hemoglobin

Diagnostic units, % of total hemoglobin
Normal, 4–6 (varies by laboratory)
HbA1c (%) Diagnoses to Consider Actions to Consider
Increased
<7* Good diabetic control No change in therapy
7–9 Average diabetic control Home glucose monitoring; initiate or change medications
>9 Poor diabetic control Evaluate for causes of poor diabetic control
*
Achieving a more stringent glycemic goal (i.e., to a normal HbA1c of <6.0%) reduces the risk of complications of
diabetes (i.e., cardiovascular disease, retinopathy, and nephropathy) at the cost of an increased risk of
hypoglycemia (particularly in those with type 1 diabetes).
From Diabetes Care 2004;27(Suppl 1):S91–S93.

157
 Chapter 13 Interpreting Laboratory Tests

Table 13-11 Human Chorionic Gonadotropin (hCG)

Diagnostic units, mIU/L
Normal, <5 (women of childbearing age); <0.8 (postmenopausal women); <0.7 (men)

Normal Pregnancy:
Gestational week hCG (mIU/L)
1 <30
2 50–500
3 100–10,000
10 50,000–300,000
2nd trimester 10,000–25,000
3rd trimester 5,000–15,000
hCG (mIU/L) Diagnoses to Consider Actions to Consider
Increased Pregnancy Correlate with ultrasound
>5 Ectopic pregnancy Repeated hCG to document trend
Gestational trophoblastic disease
After abortion (≤2 wk)
Choriocarcinoma
Ovarian cancer
Testicular cancer

commercially available kits, are now sensitive enough most frequently used are iron (Fe), iron-binding
to detect pregnancy several days before the time of capacity (TIBC), and ferritin. In brief, iron is a direct
missed menses. measure of the serum iron. TIBC is a measure of the
If a patient is possibly pregnant but the hCG test is saturation of the serum with iron (and approximates
negative, a repeated test in 1 to 2 days on a concentrated the transferrin saturation, which may be used instead
first-morning specimen can be performed. A quantita- of TIBC); it will be increased in simple iron defi-
tive serum test is not needed in these cases, as serum ciency because of the increased “binding capacity”
tests are not more sensitive than current urine tests. available from reduced iron levels. Ferritin is a pro-
Quantitative serum hCG tests are commonly tein produced by the reticuloendothelial system, and
used to evaluate the viability of an “at risk” preg- it serves as the primary iron-storage protein in the
nancy, such as a pregnant woman with bleeding. body. In general, the ferritin level is proportional to
Quantitative hCG tests may be ordered serially every the total body iron-storage level.
few days. On average, a 66% increase in hCG should Iron deficiency is a frequent cause of anemia,
be found between values, although significant vari- and iron studies are frequently indicated when
ability in doubling times may be seen in normal microcytosis is seen in patients with anemia. In
pregnancies (ranging from 1.4 to 5.0 days). hCG patients with uncomplicated iron deficiency, such as
doubling times are most useful up until the sixth ges- occurs from chronic blood loss or inadequate intake
tational week. By week 9, cardiac activity detected by of iron, the serum iron level will be decreased, the
ultrasonography can be used reliably to determine TIBC (or transferrin) level will be increased, and
fetal viability. Unfortunately, no definitive test deter- the ferritin will be normal or decreased. In iron-
mines viability in women who have bleeding deficiency states, ferritin often decreases before ane-
between 6 and 9 weeks of gestation. mia, microcytosis, a low iron, or an elevated TIBC
If serum hCG values are higher than expected or appears. Therefore it is more sensitive than either
increase more rapidly than expected, diagnoses to iron or TIBC in detecting iron deficiency. Iron,
consider include gestational trophoblastic disease, TIBC, and ferritin levels quickly respond to iron
multiple pregnancy, and cancer. Abnormally low rate therapy, even though total body iron stores may take
of increase of hCG values may be associated with months of therapy to restore.
ectopic pregnancies (Table 13-11). Ferritin is most commonly used to differentiate
iron-deficiency anemia from anemia of chronic dis-
ease in patients with a normal or low MCV (Table 13-
IRON STUDIES 12). It can also be used to determine a patient’s
response to iron therapy, or to evaluate for iron-over-
Multiple studies are used to differentiate among the load states, particularly in patients with hemolytic
various disorders of iron metabolism; of these, the anemia. It is less sensitive as a marker of overload

158
 Chapter 13 Interpreting Laboratory Tests

Table 13-12 Ferritin

Diagnostic units, ng/mL (mg/L)
SI conversion factor, 1
Normal: 20–300 (males); 20–120 (females)
Ferritin (ng/mL) Diagnoses to Consider Actions to Consider
Decreased Iron deficiency Evaluate for GI blood loss
<20 Hypothyroidism CBC
Dietary history
TSH
Increased Iron overload Iron, TIBC
>300 Hemochromatosis CBC
Transfusion ESR
Hemolytic anemia Thyroid studies
Liver disease Liver tests
Chronic inflammation
Malignancies
Hyperthyroidism
CBC, complete blood count; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; TIBC, total iron-binding
capacity; TSH, thyroid-stimulating hormone.

Table 13-13 Interpreting Iron Studies

Disease Ferritin TIBC (or Transferrin) Serum Iron

Iron deficiency ↓ ↑ N or ↓
Anemia of chronic disease N or ↑ N or ↓ ↓
Hemolytic anemia ↑ N or ↓ N or ↑
Hemochromatosis ↑ ↓ ↑↑
Acute liver disease ↑ Varies ↑

N,normal; TIBC, total iron-binding capacity.

than it is of iron deficiency; if iron overload is sus- Albumin

pected, iron and TIBC assays are the preferred tests.
A cause for iron deficiency should always be Albumin is produced by the liver and is the most
sought, as it may lead to diagnosis of an occult gas- abundant plasma protein, accounting for 90% of the
trointestinal tract cancer. plasma oncotic pressure. It is unclear how albumin is
Some common causes of iron overload include processed and degraded, but the half-life is about 20
hemochromatosis, hemolytic anemias, hepatitis, and days. The concentration of plasma albumin depends
inappropriate iron therapy. on the rate of synthesis, degradation, loss, and over-
A brief summary of iron studies is found in all plasma volume.
Table 13-13. Serum albumin testing is not recommended for
general screening of healthy individuals, but it can be
useful for evaluating patients with liver disease, edema,
LIVER TESTS or suspected malnutrition (Table 13-14). An elevated
albumin value is not thought to be of any clinical sig-
These tests are commonly ordered as a group, nificance, although it may occur with dehydration.
although often the investigator is interested in just
one or two of the individual tests. Although com- Protein (Total)
monly called liver-function tests, some tests are a
measure of function (such as manufacture of albu- Total protein measured by laboratory instruments
min and clotting factors), and others more clearly includes albumin plus the various globulins.
indicate whether injury is present (such as the Decreased levels of total protein are seen in a wide
aminotransferase enzymes, levels of which are ele- variety of illnesses. In most cases, these diseases are
vated in settings of hepatic injury). better monitored by measurement of albumin.

159
 Chapter 13 Interpreting Laboratory Tests

Table 13-14 Albumin

Diagnostic units, g/dL (g/L)
SI conversion factor, 10
Normal: 4.0–6.0 (40–60)
Albumin (g/dL) Diagnoses to Consider Actions to Consider
Decreased Decreased synthesis Dietary history
<4.0 Liver insufficiency Urinalysis
Malnutrition 24-hr urine protein
Malignancy Creatinine
Increased loss Other liver-function tests
Nephrotic syndrome Complete blood count
Extensive burns
Protein-losing enteropathy
Pregnancy
Inflammatory illness

Increased levels of total protein are occasionally nostically useful. Further immunologic typing can be
seen and may lead to an evaluation for multiple performed to test for multiple myeloma.
myeloma, which may be associated with increased
(and sometimes decreased or normal) protein levels Alkaline Phosphatase
(Table 13-15). When a question occurs about the
interpretation of any abnormal total protein, a pro- Alkaline phosphatase (ALP) is produced by a large
tein electrophoresis may be considered. This test sep- number of tissues, primarily liver and bone (account-
arates the albumin from the various globulins, and ing for about 80% of total activity) but also including
the electrophoretic pattern that results may be diag- intestine, kidney, and placenta. When elevated, it pro-

Table 13-15 Protein (Total)

Diagnostic units, g/dL (g/L)
SI conversion factor, 10
Normal: 6.0–8.0 (60–80)
Protein (g/dL) Diagnoses to Consider Actions to Consider
Decreased Decreased synthesis Dietary history
<6.0 Liver insufficiency Urinalysis
Malnutrition 24-hr urine protein
Malignancy Creatinine
Increased loss Other liver-function tests
Nephrotic syndrome Complete blood count
Extensive burns
Protein-losing enteropathy
Pregnancy
Inflammatory illness
Myeloma
Increased intravascular volume
Increased Dehydration BUN
>8.0 Chronic inflammation Creatinine
Monoclonal gammopathy Protein electrophoresis
Sarcoidosis Chest radiograph
Multiple myeloma

BUN, blood urea nitrogen.

160
 Chapter 13 Interpreting Laboratory Tests

Table 13-16 Alkaline Phosphatase

Diagnostic units, units/L (g/L)
SI conversion factor, 10
Normal: 50–120*
Alkaline Phosphatase
(units/L) Diagnoses to Consider Actions to Consider
Increased Related to the liver Recheck in 6 mo (if <2× normal and patient
>120 Cirrhosis is asymptomatic)
Hepatitis Other liver tests, including GGT and bilirubin
Infiltrative liver disease Alkaline phosphatase isoenzymes
(sarcoid, TB, amyloidosis, Liver ultrasound
tumor, abscess)
Autoimmune cholangiopathy
Gilbert’s syndrome
Related to bone
Bone growth
Healing fracture
Acromegaly
Osteogenic sarcoma
Liver or bone metastases
Leukemia
Myelofibrosis
Other
Sepsis
Drugs
Nonfasting specimen
*
Normal values are higher in pediatric, pregnant, and menopausal patients.
GGT, γ-glutamyl transferase; TB, tuberculosis.

vides a useful, but not very specific, indication of pos- is AST, which may be elevated with muscle (skeletal or
sible liver or bone disease (Table 13-16). In the liver, cardiac) injury as well as hemolysis. In most circum-
ALP is produced by the biliary epithelium and excreted stances, both will be elevated in the presence of liver
in the bile. When the biliary tract becomes obstructed, injury, and ALT is usually elevated more than AST.
ALP may increase in the serum and usually corre- A useful exception occurs in the case of alcoholic hep-
sponds with elevated bilirubin levels. When in doubt atitis, in which AST is often several-fold greater than
about the source of ALP, serum γ-glutamyl transferase ALT. When the ratio is more than 3:1, 96% of patients
(GGT), an enzyme found in liver and biliary epithe- will have alcoholic liver disease (Table 13-17).
lium, can be measured. GGT is elevated in most dis- Aminotransferase tests are very useful for diag-
eases that cause acute damage to the liver or bile ducts. nosing and monitoring liver disease. They are not
ALP isoenzyme determinations also can be made by useful for screening healthy individuals; however,
electrophoresis and may help to distinguish the source they are frequently ordered as a precursor to or for
of ALP. A low ALP is not commonly encountered but monitoring of potentially hepatotoxic drugs, such as
may be seen with hypothyroidism, drug side effects, isoniazid (for treatment of latent or active tuberculo-
pernicious anemia, or Wilson’s disease. sis), or statin-type medications (for treatment of
hypercholesterolemia).
Aminotransferases Low aminotransferase levels are not usually of
any clinical significance. They may be seen in
Alanine aminotransferase (ALT) and aspartate amino- advanced cirrhosis or fulminant hepatitis, in which a
transferase (AST; ALT was formerly referred to as normal or low level can indicate that the disease has
serum glutamate pyruvate transaminase [SGPT], and progressed so far that few hepatocytes remain.
AST was formerly referred to as serum glutamic-
oxaloacetic transaminase [SGOT]) are enzymes that
Bilirubin
occur primarily in liver cells and appear in the serum
as a result of tissue injury. Of the two enzymes, ALT is Bilirubin is an integral component of the heme ring,
more specific for detection of hepatocyte injury than the oxygen-carrying molecule within RBCs. When

161
 Chapter 13 Interpreting Laboratory Tests

Table 13-17 Aminotransferases

Diagnostic units, units/L (0.17–0.68 μkat/L)
SI conversion factor, 1.0
Normal: males, 10–40; females, 8–35
Aminotransferase
(units/L) Diagnoses to Consider Actions to Consider
Increased AST and ALT increased Repeated testing
>40 Steatohepatitis (fatty liver) Hepatitis exposure history (drugs, travel,
Hepatitis transfusion, blood-borne illness risks)
Alcoholic hepatitis (AST Alcohol history
often > ALT) Other liver function tests, including
Biliary obstruction bilirubin and alkaline phosphatase
Drugs (prescription, over-the- Hepatitis virus testing
counter, and illicit) CBC, peripheral smear (for hemolysis)
Hemochromatosis If initial serologic tests negative, or
Wilson’s disease persistent elevation, consider
α-Antitrypsin deficiency Ultrasound
Only AST elevated ANA
Myocardial infarction Smooth muscle antibody
Hemolysis Ceruloplasmin
Skeletal disorders α-Antitrypsin
Liver biopsy

ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate aminotransferase; CBC, complete blood
count.

RBCs are degraded, the bilirubin attaches to albumin When bilirubin increases above acceptable levels,
and is transported to the liver. There, it is processed treatment with phototherapy or, in severe cases,
into its water-soluble, or conjugated, form and is then exchange transfusions, is warranted. Of primary
excreted in the bile, where it later passes into the concern is the prevention of kernicterus, a devastat-
intestine to be reabsorbed and reprocessed. ing injury caused by deposition of unconjugated
Laboratories measure the total bilirubin and bilirubin in the brain. Transcutaneous bilirubin test-
conjugated (or direct) bilirubin; the unconjugated ing is becoming more widely available, but after 10
(or indirect) bilirubin fraction is then obtained by days of life, endogenous carotenoids interfere with
subtraction. In normal serum, less than 15% of the transcutaneous measurements.
total bilirubin is conjugated.
Common causes of elevated bilirubin are
Prothrombin Time
increased RBC destruction, liver disease, and biliary
tract obstruction (Table 13-18). Interpretation of ele- The prothrombin time (PT) is the only coagulation
vated bilirubin levels is often aided by considering test commonly used in the outpatient setting. It is
other liver test results in conjunction with the clinical defined as the time required to initiate clotting when
picture. For example, most cases of elevated bilirubin tissue thromboplastin is mixed with blood. The PT is
caused by infectious hepatitis will be associated with a measure of both the extrinsic clotting system (i.e.,
marked elevations in aminotransferases; only modest factor VII) and factors common to the intrinsic and
elevation of aminotransferases and marked elevation extrinsic systems (i.e., factor X, factor V, prothrom-
in ALP levels or GGT (or both) with hyperbilirubine- bin, and fibrinogen).
mia suggests an obstructive process, and isolated ele- The thromboplastin reagents used as a part of
vations of bilirubin occur in neonatal jaundice and the test may vary considerably in their clotting activ-
with inborn errors of bilirubin metabolism such as ity; as a result, PT values are converted to a normal-
Gilbert and Dubin-Johnson syndromes. ized value by every laboratory to an international
Hyperbilirubinemia and jaundice are common normalized ratio (INR), which is standardized to the
in newborns, and, in most cases, physiologic. World Health Organization’s reference thromboplas-
Physiologic jaundice and bilirubin levels usually tin. In practice, the INR is what is actually used when
peak by the third or fourth day of life in term interpreting PT results.
neonates, and acceptable upper reference limits vary PT is most commonly used to monitor the anti-
appropriately. A bilirubin level should be obtained in coagulation effects of warfarin (Coumadin) (Table
all infants with suspected jaundice, and in some cen- 13-19). Acceptable therapeutic ranges for PT are
ters, routine testing of all infants may be performed. often defined for specific diagnoses. For example,

162
 Chapter 13 Interpreting Laboratory Tests

Table 13-18 Bilirubin (Total)

Diagnostic units, mg/dL (μmol/L)
SI conversion factor, 17.1
Normal: adults, 0.3–1.0 (5–17); newborns, varies by age and gestation of newborn; for term infants, upper
limit is approximately <6.0 at 24 hr, <10.0 at 24–48 hr, and <12–15 at >48 hr
Bilirubin (mg/dL) Diagnoses to Consider Actions to Consider
Increased: neonates Physiologic Maternal, prenatal, and birth history
(see note above Breast-feeding Maternal and infant blood type
for ranges) ABO or Rh incompatibility Direct Coombs’ test
Hemorrhage, hematomas Hematocrit
Sepsis Phototherapy
Infections (toxoplasmosis, Exchange transfusion
cytomegalovirus, rubella, syphilis)
Maternal diabetes
Inborn errors of metabolism
(galactosemia, G6PD, pyruvate
kinase deficiency)
Adults: >1.0 mg/dL Hepatobiliary disease Alcohol history
Hepatitis Drug history
Cholangitis Travel, dietary, blood exposure history
Cholecystitis ALT, AST, GGT, conjugated bilirubin
Cirrhosis Complete blood count
Hemolytic anemia Reticulocyte count
Transfusion reaction Direct Coombs’ test
Hematoma Viral hepatitis tests
Pulmonary embolus Ultrasound
Congestive heart failure
Drugs
Isolated bilirubin elevation
Dubin-Johnson or Gilbert’s
syndrome
Wilson’s disease (often in
conjunction with decreased
alkaline phosphatase)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; G6PD, glucose 6-phosphate dehydrogenase
deficiency; GGT, γ-glutamyl transferase.

Table 13-19 Prothrombin Time (PT) and International Normalized Ratio (INR)
Units, PT in seconds; INR is a ratio and has no units
Normal, PT varies; INR, 0.8–1.3
INR Diagnoses to Consider Actions to Consider
Increased Liver disease Liver tests
>1.3 Malabsorption PTT
DIC Clotting factor assays
Warfarin therapy Serum carotene
Factor II, V, VII, X deficiency 72-hr stool fat
Vitamin K deficiency Administer vitamin K

DIC, disseminated intravascular coagulation; PTT, partial thromboplastin time.

patients with atrial fibrillation commonly have INR PT also is a useful test for evaluating any
values maintained between 2.0 and 3.0; for patients patient with abnormal bleeding. However, it is
with prosthetic heart valves, the range is usually important to note that PT is normal in people with
slightly higher at 3.0 to 4.5. classic hemophilia (i.e., factor VIII deficiency) and

163
 Chapter 13 Interpreting Laboratory Tests

in those with von Willebrand’s disease. Clotting However, pancreatitis can occur without eleva-
factors are generally produced by the liver; hence tion in amylase levels in up to 10% of patients, espe-
PT also can be used to evaluate the liver’s synthetic cially in those with recurrent disease or long
function. duration of symptoms before testing. In such cases,
serum lipase testing (often ordered at the same time
as amylase testing) may be useful.
PANCREATIC ENZYMES In some individuals, amylase can become bound
to other large serum polysaccharides, which can lead
to macroamylasemia, and these individuals can have
Amylase
persistently elevated, fluctuating amylase levels. This
Amylase is an enzyme that breaks down dietary condition is sometimes associated with chronic ill-
starches into smaller polysaccharides and is pro- nesses such as celiac disease, HIV infection, lym-
duced by the pancreas and the salivary glands. Most phoma, ulcerative colitis, rheumatoid arthritis, and
of the amylase produced goes directly into the gut, monoclonal gammopathy.
but a small amount is absorbed into the circulation. Low serum amylase levels are rarely of clinical
Usually, about one third of the serum amylase is of significance.
pancreatic origin, and two-thirds is from the salivary
glands. Amylase is excreted primarily by the kidneys. Lipase
The most common cause of an elevated serum
amylase is pancreatitis, and a serum amylase is often Pancreatic lipase breaks down triglycerides into glyc-
ordered to evaluate patients with acute unexplained erol and free fatty acids. Similar to amylase, lipase is
abdominal pain (Table 13-20). When the source of produced by several body tissues including the
amylase is in doubt, it is sometimes useful to distin- tongue, pancreas, intestine, and liver. It is excreted by
guish the P (pancreatic) and S (salivary) forms of the the kidney. Bile acids inhibit the activity of lipases,
enzyme, a test that can be performed in most hospi- but the activity of pancreatic lipase is preserved in
tal laboratories. Given its renal excretion, modest ele- the intestine because of the presence of another
vations of 2 to 3 times normal can be seen in patients enzyme, colipase. A commonly used test for lipase
with chronic renal failure. combines bile acids and colipase to the assay to

Table 13-20 Amylase

Diagnostic units, Somogyi units/dL (units/L)
Normal, 50–150 (0–130)
Amylase (Somogyi
units/dL) Diagnoses to Consider Actions to Consider
Increased Gastrointestinal Complete drug history
>150 Pancreatitis Lipase
Alcohol Amylase isoenzymes
Gallstones Ultrasonography
Trauma CT scan abdomen
Hyperlipidemia Amylase-to-creatinine clearance ratio (ratio
Infectious of <1% in a 24-hr collection supports
Drug-induced (thiazide diagnosis of macroamylasemia; ratio is
diuretics, aspirin, increased in acute pancreatitis, severe
some antibiotics) burns, and diabetic ketoacidosis)
Familial
After ERCP
Perforating ulcer
Bowel obstruction
or infarction
Salivary gland disease
Renal
Chronic renal failure
Neoplastic
Cancer that secretes amylase
Macroamylasemia
CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography.

164
 Chapter 13 Interpreting Laboratory Tests

Table 13-21 Lipase

Diagnostic units, units/dL (units/L)
SI conversion factor, 10
Normal, 0–160
Lipase (units/dL) Diagnoses to Consider Actions to Consider
Increased Gastrointestinal Complete drug history
>160 Pancreatitis (see under amylase) Ultrasonography
Cholecystitis CT scan abdomen
Bowel obstruction or infarction MRI or EUS
Salivary gland disease
Renal
Chronic renal failure
Neoplastic
Cancer that secretes amylase
Pancreatic cancer
Iatrogenic
Drugs
Furosemide
Thiazide diuretics
Cholinergics
Narcotics
Oral contraceptives
Decreased Drugs Drug history
Salicylates
Calcium
Hydroxyurea
Protamine
Somatostatin
CT, Computed tomography; EUS, endoscopic ultrasound; MRI, magnetic resonance imaging.

inhibit other forms of lipase, providing a specific Because creatinine is released by skeletal muscle,
assay for pancreatic lipase. it is affected by total muscle mass. Small or elderly
Elevation of lipase levels is most commonly people may have a normal creatinine even with
associated with pancreatitis, and markedly elevated reduced renal function. Hence it is often more useful
levels of lipase are very specific for pancreatitis to estimate creatinine clearance. The following is a
(Table 13-21). Because of its longer half-life (7 to 13 commonly used formula:
hours), lipase remains elevated longer than amylase,
and hence may remain elevated after the amylase has (140 − age)(weight in kg)
Cr clearance =
returned to normal. Low lipase levels may be associ- 72 × Cr in mg/dL
ated with some medications.
As a rough guideline, a creatinine level of
2 mg/dL is equivalent to a creatinine clearance of
RENAL TESTS 50 mL/min; a creatinine level of 4 mg/dL is equal to
a creatinine clearance of 20 mL/min; and a creatinine
level of 6 mg/dL is equivalent to a creatinine clear-
Blood Urea Nitrogen and Creatinine
ance of 10 mL/min. When necessary, creatinine
Urea is the end product of protein metabolism, syn- clearance can be more accurately measured through
thesized by the liver, and freely excreted by the renal collection of a 24-hour urine specimen.
glomeruli. It is commonly used to indicate renal Serum creatinine increases exponentially in
function but may be altered by the nitrogen load, response to a decrease in the GFR, and small
water intake, and urine flow. Creatinine is released increases in creatinine can represent a significant
from skeletal muscle and is excreted unchanged in decline in GFR. This is especially important in early
the urine. Few factors affect its excretion, and it is the decline, because a 50% reduction in GFR leads to
best common test for monitoring renal function. An an increase of creatinine from only 1.0 to 2.0
increase in creatinine represents a decrease in the mg/dL. It also is important to note that creatine
renal glomerular filtration rate (GFR). increases slowly in response to changes in renal

165
 Chapter 13 Interpreting Laboratory Tests

function. In sudden, severe renal failure (e.g., tubu- THYROID TESTS

lar necrosis after shock), the creatinine may
increase as little as 1 mg/dL daily, despite a creati- Thyroid-stimulating Hormone
nine clearance of zero.
The blood urea nitrogen (BUN)/creatinine ratio Thyroid-stimulating hormone (TSH), also known as
can be useful in assessing abnormalities of nitrogen pituitary thyrotropin, is produced by the anterior
load, water intake, or urine flow (Table 13-22). pituitary gland in response to levels of thyroid hor-
A high ratio (>20:1) suggests overproduction or mone in the plasma. Very small changes in the circu-
impaired excretion and is commonly associated with lating thyroid hormone T4 produce large changes in
prerenal failure (decreased renal blood flow or TSH; hence thyroid function is usually best assessed
decreased perfusion); examples include congestive by measurement of TSH. It is often used to screen
heart failure, shock, volume loss, dehydration, and, patients at risk for hypothyroidism (as in patients
when extreme (>36:1), upper gastrointestinal bleed- with diabetes or who have a family history of
ing. Low ratios may be found with low-protein diet, hypothyroidism) (Table 13-23). More often, it is
malnutrition, pregnancy, severe liver disease, or used to monitor therapy in patients taking thyroid
rhabdomyolysis. replacement. If the serum TSH is high (representing
Chronic renal insufficiency is generally defined a hypothyroid state), the dose should to be increased;
as a creatinine level of 1.5 to 3.0 and chronic renal if it is low, the dose should be decreased.
failure, as Cr > 3.0. The dosages of most renally In hyperthyroid patients, TSH is suppressed.
excreted drugs must be adjusted appropriately or First-generation tests for TSH were not sensitive in
avoided altogether in patients with reduced renal the low range, but second- and third-generation
function. tests are sensitive below 0.5 μIU/mL and can be

Table 13-22 Creatinine

Diagnostic units, mg/dL (μmol/L)
SI conversion factor, 88.4
Normal, 0.6–1.2 (50–110)
Creatinine (mg/dL) Diagnoses to Consider Actions to Consider
Increased
1.2–1.6 Mild renal impairment Repeated test
Muscle injury Urinalysis
Creatinine clearance
>1.6 Prerenal cause Urinalysis
Dehydration Creatinine clearance
Blood loss Bladder catheterization
Heart failure Renal imaging
Liver failure
Intrinsic renal failure
Diabetes mellitus
Hypertension
SLE
Nephrotoxins
Glomerulonephritis
Acute tubular necrosis
Postrenal failure
Urethral obstruction
Upper tract obstruction
>6.0 Severe renal failure Electrolyte measurements
Correction of potassium (hyperkalemia), acidosis
Decreased Decreased muscle mass Observation
<0.6 Small stature Treatment of underlying disorder
Muscle diseases
Advanced liver disease
Long-term steroids

SLE, systemic lupus erythematosus.

166
 Chapter 13 Interpreting Laboratory Tests

Table 13-23 Thyroid-stimulating Hormone

Diagnostic units, μIU/mL (mU/L)
SI conversion factor, 1
Normal, 0.5–6.0 (Variations in reference values will depend on laboratory and method used)
TSH (mIU/mL) Diagnoses to Consider Actions to Consider
Increased Primary hypothyroidism (gland failure) Drug history
>6.0 Thyroiditis Physician examination
Inadequate levothyroxine therapy T4, T3 uptake
TRH stimulation test
Decreased Hyperthyroidism Physical examination
<0.5 Excessive levothyroxine intake Drug history
Secondary hypothyroidism (pituitary failure) T4, T3 uptake
Tertiary hypothyroidism (hypothalamic failure) TRH stimulation test

TRH, thyroid-releasing hormone.

useful as an aid to diagnosis of hyperthyroidism. Thyroxine and Triiodothyronine

However, in early stages of treatment, TSH may be
suppressed and remain subnormal for several Thyroxine (T4) is the principal hormone secreted by
months. T3 and T4 levels change more rapidly, and the thyroid gland and is virtually all bound to serum
because T3 concentrations are typically higher than proteins, including thyroxine-binding globulin
T4, serum T3 measurements can be valuable in (TBG), transthyretin, or thyroxine-binding prealbu-
assessing and monitoring patients with hyperthy- min (TBPA). T3, another form of thyroid hormone,
roidism. is less tightly bound to TBG and TBPA, but more

Table 13-24 Thyroxine (T4)

Diagnostic units, μg/dL (nmol/L)
SI conversion factor, 13
Normal, 5.5–12.5 (72–163)
Thyroxine (mg/dL) Diagnoses to Consider Actions to Consider
Increased Hyperthyroidism TSH
>12.5 Elevated TBG Free T4
Birth control pills T3 uptake
Pregnancy Thyroid scan
Estrogen therapy Complete drug history
Liver disease
Drugs
Propranolol
Amphetamines
Cocaine
Amiodarone
Heparin
Decreased Hypothyroidism TSH
<5.5 Decreased TBG Free T4
Malnutrition Albumin
Liver diseases Liver tests
Nephrotic syndrome Urinary protein
Androgens
Glucocorticoids
Sick thyroid syndrome

T3, triiodothyronine; T4, thyroxine; TBG, thyroxine-binding globulin; TSH, thyroid-stimulating

hormone.

167
 Chapter 13 Interpreting Laboratory Tests

Table 13-25 Interpreting Thyroid Function Tests

Total T4 T3-resin uptake or THBI Free T4

Hyperthyroidism ↑ ↑ ↑
TBG excess ↑ ↓ Normal
Hypothyroidism ↓ ↓ ↑
TBG deficiency ↓ ↑ Normal
TBG, thyroid-binding globulin; THBI, thyroid hormone binding index.
From Kamath PS. Clinical approach to the patient with abnormal liver test results. Mayo Clin Proc
1996;71:1089–1095.●C

tightly bound to albumin than is T4; measurements dextran-coated charcoal) is added that traps the
of T3 also are used in the assessment of thyroid func- remaining unbound radiolabeled T3. The percentage
tion (Table 13-24). It is generally held that the active of tracer that is bound to the resin is reported as the
form of the thyroid hormones is the unbound or free T3 uptake, and it varies inversely with the number of
form, which is available for uptake into cells and available free binding sites for T3. For example, if a
interaction with nuclear receptors. The bound hor- large percentage of available T3 is bound to the resin,
mone represents a circulating storage pool. it indicates either excess T3 or a low-ratio TBG-bound
Drugs and illness can alter the concentration of hormone. Using this value in conjunction with other
binding proteins, which may cause elevated total T4 thyroid tests helps distinguish between these two sce-
and T3 measurements even though the free, physio- narios (Table 13-25). Many laboratories convert the
logically active form remains in the normal range. T3-resin uptake to a ratio value called the thyroid hor-
Estrogen may induce production of TBG, which may mone uptake ratio or index (THBR or THBI):
then increase TBG-bound hormone levels, elevating patient’s T3 resin
total T4 measurements. Normal ranges for free T4 THBI =
and T3 measurements depend on the method used; normal pool T3 resin
most methods use a formula to estimate the actual A typical reference range for THBI is 0.83 to 1.16.
free hormone level. Antithyroid antibody tests also are available to
help in the evaluation of other abnormal thyroid
T3-Resin Uptake and Thyroid Hormone states, such as Graves’ disease and other autoimmune
Binding Ratio disorders.
Other tests have been developed to try to measure the
effect of binding protein on hormone levels; among Material Available on Student Consult
these, T3-resin uptake has been traditionally most
Review Questions and Answers about Interpreting
used. The patient’s serum is incubated with a radiola-
Laboratory Tests
beled T3 tracer, and then an insoluble resin (often

REFERENCES
Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory Management of hyperbilirubinemia in the newborn infant
medicine practice guidelines: Laboratory support for at 35 or more weeks of gestation. Pediatrics 2004;114:
the diagnosis and monitoring of thyroid disease. 297–316.●C
Thyroid 2003;13:3–126.● C
Kamath PS. Clinical approach to the patient with abnormal
liver test results. Mayo Clinic Proc 1996;71:1089–1095.●
C

168
 C h a p t e r

14 Selecting Radiographic Tests:

Radiographs, Computed Tomography,
Magnetic Resonance Imaging,
Ultrasound, and Nuclear Imaging
J. Mark Beard and David P. Losh

KEY POINTS

1. Regular x-ray is best for detecting changes in assessment of fractures and hemorrhagic compli-
bone, air, soft tissue, and fat densities but is cations.
limited by its two-dimensional representation of 8. CT scanning is used to acutely evaluate a patient
structures. suffering an evolving or a completed stroke to
2. Compared tomography, with or without con- assess for a hemorrhagic component that would
trast, allows digital reconstruction of cross- preclude systemic anticoagulation.
sectional images of body without the super 9. The occurrence of TIA requires no acute imag-
imposition of other structures that frequently ing, but a carotid Doppler and ultrasound and
occurs on standard x-ray films. echocardiogram are used to determine the cause
3. Standard contrast agents can significantly and source of the ischemic or embolic phenome-
improve the accuracy of imaging modalities but non.
can also increase the cost of the study and, in 10. Most acute low back pain occurring in mini-
some instances, cause mild or serious reactions mally traumatic cases does not require radi-
and renal failure. ographic imaging. When imaging is required, CT
4. Renal failure complications can be prevented is preferred for suspected bone injury. MRI is the
with the use of other imaging modalities that preferred modality for soft tissue injury as it is
do not require nephrotoxic contrast or can be superior in visualizing tissue within surrounding
reduced with the use of nonionic contrast, bone.
good hydration, and prophylactic acetylcysteine. 11. Most causes for headache can be diagnosed
5. MRI uses a strong magnetic field for imaging, with an accurate history and physical. In severe
allowing for better visualization of soft tissues headaches of sudden onset, a non-contrast
surrounded by bone structures without radiation CT is obtained. When imaging is required other-
exposure. MRI should not be used in patients with wise, a CT with contrast is preferred.
ferrous metallic structures or fragments in their 12. Plain x-rays are used in the initial assessment of
body. MRI contrast is nontoxic to the kidney. spinal trauma to assess for fracture or stability
6. Ultrasound utilizes sound waves for imaging of the bone structures and followed by CT when
and is preferred for abdominal and cardiac needed. MRI is preferred to assess the spinal
imaging, gynecologic or pregnant patients, and cord and exiting nerve roots.
children because of its lack of radiation risks. It 13. CT with contrast and MRI are both used to
can be combined with color flow to assess assess cerebral tumors and metastases.
vascular integrity of structures. 14. Echocardiography is the best method for evalua-
7. For most head trauma, head CT scanning tion of heart failure once ischemic causes are
without contrast provides the best method for resolved.

Continued

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

169
 Chapter 14 Selecting Radiographic Tests

KEY POINTS (Continued)

15. A chest x-ray and D-dimer test followed by a 26. A radionuclide thyroid scan is recommended in
ventilation/perfusion scan is the initial choice in the initial evaluation of an enlarged thyroid
evaluating patients with suspected pulmonary without obvious nodule.
embolism. 27. Enlarged or hypersecretory parathyroid glands
16. Chest x-ray followed by CT with contrast is used as well as adrenal masses are assessed with the
for thoracic aneurysms. Ultrasound is used for use of radionuclide scans to assess areas of
the initial evaluation of abdominal aneurysms. increased or decreased function. Plain lateral
17. Cholelithiasis is best diagnosed and evaluated skull x-rays followed by MRI may be used to
with abdominal ultrasound due to ease, avail- assess hyperprolactinemia.
ability, and cost. 28. Standard x-rays are most often used to evaluate
18. Cholecystitis is best evaluated with abdominal possible fractures. CT scan or radionuclide
ultrasound followed by radionuclide scanning, bone scan can be performed if the diagnosis
if needed. remains in question following x-ray films.
19. Ultrasound is the easiest and most cost-effec- 29. DEXA scans are the favored form of evaluation
tive method for evaluating causes of biliary for osteoporosis both for initial diagnosis and
tract obstruction. Other modalities of imag- subsequent exams to follow treatment response.
ing can be used in special circumstances. 30. Standard x-ray can detect 80% of urinary
20. Plain x-rays of the abdomen remain the stan- stones. If not successful, a noncontrast
dard to evaluate small bowel obstruction in spiral CT is done to further evaluate the urinary
its initial phases. Contrast studies can follow for tract and has generally supplanted the intra-
further identification of the cause or location. venous pyelogram as the study of preference.
21. Direct endoscopy of the affected site is pre- 31. Renal failure is best evaluated radiographically
ferred in the evaluation of gastrointestinal with the ultrasound to assess size and structure
bleeding as treatment of the causative site of the kidneys. A Duplex study can be done to
can occur simultaneously. assess renovascular disease.
22. Ultrasound is the imaging modality of choice if 32. Ultrasound is the preferred imaging method for
the biliary tree is compromised by a pancre- renal mass appraisal. CT can be obtained to
atic mass although CT scans have better reso- evaluate a mass further, as indicated.
lution in most other cases. 33. Testicular torsion is best assessed acutely with
23. Radionuclide scanning is the most commonly color flow Doppler ultrasound. Standard ultra-
used approach in evaluating hepatospleno- sound is recommended for the initial evaluation
megaly. of other scrotal masses.
24. Although ultrasound is used for most hepatic 34. Breast mass evaluation begins with a clinical
masses, CT scanning with contrast is best for exam and is frequently followed by a mammo-
hepatic metastases. gram or ultrasound to further define the
25. Fine-needle aspiration biopsy is the best cause of any irregularities. In most cases, a
method for evaluation of a single thyroid biopsy of the palpable mass is clinically
nodule. A radionuclide thyroid scan can assess indicated even if the imaging modalities are
function of a nodule when needed. otherwise normal.

Exponential advances in medical imaging have many new and sometimes expensive choices for
occurred with the advent of progressively more diagnostic testing. It is therefore important for the
sophisticated equipment and more complex com- family physician to judge the cost-benefit ratio of a
puter technology. As computers have become more particular test and to select the most effective imag-
powerful, they have allowed digitalization of images, ing strategy for a particular clinical problem. Medical
integration of numerous pictures in multiple planes, imaging should be used as a diagnostic tool only
and improvement in image clarity. Computerized after a provider performs an appropriate history and
tomography (CT), magnetic resonance imaging physical examination. Individual patient characteris-
(MRI), ultrasound (US), and nuclear medicine tics and circumstances must be considered and a
studies have revolutionized the type and quality of differential diagnosis developed before the most
information obtained from medical imaging. This appropriate imaging study can be selected. The
technology has provided the family physician with imaging results from the consulting radiologist can

170
 Chapter 14 Selecting Radiographic Tests

be fully interpreted only by a physician seeing the

findings in the specific context of an individual
patient (Mettler et al., 2000). Because the field of
diagnostic imaging is quite technical and has so many
new and expensive techniques, the family physician is
encouraged to discuss cases and diagnostic dilemmas
regularly in consultation with radiologists. This chap-
ter provides background information on the most
commonly available imaging studies and provides an
imaging strategy for many common diagnostic prob-
lems encountered in family medicine.

BASIC IMAGING TESTS AVAILABLE

TO THE CLINICIAN
Standard Radiographic X-Rays and
Contrast Material
An electric tube generating electrons from a heated fil-
ament and accelerating them toward a rotating anode
produces traditional x-rays. The x-rays generated by
this process are passed through the body and are dif- Figure 14-2 Soft tissue radiograph of neck with lateral
view. Note good visibility of hyoid bone, thyroid carti-
ferentially absorbed by various densities of tissue. A lage, and trachea.
detector such as x-ray film, a fluoroscope, or an ana-
log-to-digital converter records the x-rays remaining
after they pass through tissues. Variations in the types ographs have the advantage of being relatively inex-
of x-ray tubes, films, and patient positioning allow dif- pensive and portable and are used occasionally for
ferent special images such as mammograms and soft applications at the bedside. The cost of standard radi-
tissue views (Figs. 14-1 and 14-2). Tomograms are an ographs varies according to the study requested.
application of standard x-rays in which the x-ray Examinations such as an upper gastrointestinal series,
source and the detector are rotated to blur tissue above a barium enema, or an intravenous pyelogram cost
and below the desired level of examination. This about 2.5 to 3 times that of a standard chest radi-
allows better visualization of a specific structure on ograph. Standard radiographs are best for detection of
one plane when overlying tissues or items on a differ- bone (Figs. 14-3 and 14-4), air, soft tissue, and fat den-
ent plane in standard radiographs obscures it. sities, with more-dense tissues appearing lighter
Fluoroscopy is performed by using continuous x-rays (bone) and less-dense tissues darker (air) (Fig. 14-5).
to evaluate a moving process, such as in tube place- Radiographs are limited by their two-dimensional
ment or in evaluation of peristalsis. Standard radi- representation of a three-dimensional structure and in
their ability to detect small differences in tissue density
with superimposition of surrounding structures.
Table 14-1 outlines further details on cost of specific
standard diagnostic radiology imaging.

The Selection of Contrast Material

Contrast agents are used to define structures that
frequently are inadequately visualized on standard
imaging. They can be introduced intravascularly or
intraluminally to define fully the structure in ques-
tion (Fig. 14-6). When ordering imaging studies, the
family physician is required to weigh the value and
risk of an examination requiring contrast and may
even need to decide what type of contrast material
to recommend. High-osmolarity ionic contrast
material is a water-soluble material containing
iodine. It is frequently used in imaging of the uri-
Figure 14-1 Soft tissue radiograph of neck from ante- nary tract and in angiography. Contrast material
rior to posterior view. also is used in enhanced CT applications, such as
171
 Chapter 14 Selecting Radiographic Tests

examinations of the head, chest, and abdomen.

When used with CT, contrast material can deter-
mine the vascularity of a region and the outline of a
hollow viscus. When receiving ionic contrast mate-
rial, up to 5% of patients may experience a mild
reaction and feel a sense of altered taste, heat, nau-
sea, tachycardia, or flushing. Hives and wheezing are
not uncommon side effects. Although fatal reactions
occur in fewer than one per 100,000 doses (Eisenberg
and Margulis, 1996), serious adverse reactions such
as anaphylaxis, cardiovascular collapse, laryn-
gospasm, or bronchospasm can occur in about one
patient in 500 to 1000 doses (American College of
Radiology [ACR], 1991 ● B). The cause of adverse
reactions is unknown but may be related to the high
osmolarity of the solution or to true anaphylactic
reactions. Many of the adverse reactions may be
avoided by the use of low-osmolarity, non-ionic
contrast materials. However, these newer non-ionic
contrast agents are expensive and in some cases may
double the cost of a procedure. In addition, tradi-
tional contrast material must be used with great
caution in patients with reduced renal perfusion
caused by hypovolemia, advanced congestive heart
failure or vascular disease, and baseline preexisting
Figure 14 -3 Anteroposterior view of the elbow with renal disease (serum creatinine >1.5 mg). Contrast
standard radiograph. agents can cause potentially irreversible kidney

Figure 14-4 Two lateral views of the elbow with standard radiographs.

172
 Chapter 14 Selecting Radiographic Tests

Figure 14-5 Radiograph of pelvis showing fracture of

left pubic ramus and bowel gas, stool, and surgical clips
overlying the lumbar spine.

failure in these high-risk patients. The following

approaches have been advocated to manage poten-
tial adverse reactions to contrast material.
Acute renal failure can be a serious complication
with the use of radiographic contrast agents, particu-
larly for those with impaired renal function before the
examination. A serum creatinine greater than 1.5 or a
creatinine clearance less than 60 mL/min identifies a
patient at higher risk for radiocontrast-induced
nephropathy. The best prevention for renal dysfunc-
tion is use of an alternate noncontrast imaging modal-
ity such as MRI. If a contrast test is still required, the
provider should order use of lower-dose non-ionic Figure 14-6 Angiogram of aorta with visible aorta and
contrast (Rudnik et al., 1995● A), should adequately branching vessels.

Table 14-1 Approximate Costs of Diagnostic Radiology Imaging

Diagnostic Radiology Imaging CPT Code Cost * Medicare MPFS†

Chest radiography, 2v. 71020 $90 $38.09

Abdomen, 1v. 74000 $75 $31.48
Lumbar spine, 2v. 72100 $125 $40.45
Pelvis, 1v. 72170 $85 $31.10
Hand, 2v. 73120 $70 $29.08
Ankle, 2v. 73600 $70 $29.08
Barium enema 74270 $250 $110.27
Enteroclysis 74251 $225 $107.30
Intravenous pyelogram 74400 $250 $98.27
Mammogram 76091 $180 $101.66
Dexascan 76075 $200 $148.49
Coronary angiogram 93508 $1700 $785.44
Cerebral angiogram 75671 $1400 $626.50
Pulmonary angiogram 75743 $1400 $625.49

V, views
*
Approximate relative charge based on average of survey of current charges at two hospital systems in Seattle,
Washington, 2004.
†
2004 maximum payment for Healthcare Common Procedure Code for locality 0083602, King County, Washington,
Medicare Physician Fee Schedule. Available at www.cms.hhs.gov/physicians/mpfsapp/display.asp. Accessed 10/8/2004.
173
 Chapter 14 Selecting Radiographic Tests

hydrate the patient before the imaging study

(Solomon et al., 1994● A ), and should consider use of
acetylcysteine prophylactically (Alonso et al., 2004● A ).
One successful method to reduce the risk of radiocon-
trast nephropathy is to hydrate the patient by using
0.45% saline at 1 mL/kg/hr for 12 hours before the
procedure and to give 600 mg of acetylcysteine twice a
day on the day before and day of the imaging proce-
dure (Tepel et al., 2000● A ). Care also should be taken
with patients taking medications that can lead to
metabolic acidosis, such as metformin or topiramate.
Ideally, metformin should be withheld for 48 hours
before and after an intravascular contrast procedure
(ACR, 1997● C ).
Prophylactic medication has provided good pro-
tection from anaphylaxis when a possibility of an
allergic reaction to ionic contrast material exists. The
Figure 14-7 Transverse or axial image from computed
following prophylactic regimen may be used to tomography of abdomen. Note liver is to the left, and
reduce a reaction: 50 mg prednisone orally, 13, 7, and spleen is to the right, as if viewed from patient’s feet.
1 hour before the study, and 50 mg diphenhydramine Note kidneys without contrast toward spine at bottom
1 hour before the study. This regimen does not, how- and small and large intestine in center. Aorta without
ever, protect against direct radiocontrast toxicity to contrast is just anterior to spine.
the kidney. The American College of Radiology
(2001a● C ) recommends the use of non-ionic contrast
material in patients with a history of a previous trast, the image artifacts occurring with patient
adverse reaction to contrast material, asthma or prior movement, and the increased exposure to radiation
serious allergic reaction, renal insufficiency, known in generating the multiple images. Although CT
cardiac dysfunction, generalized debilitation, or on scans offer much more detail, because of the com-
recommendation by the radiologist. In addition, oth- plexity of the examination and the cost of the
ers have recommended that the following patients equipment, CT scans are more expensive than stan-
also be considered for non-ionic contrast material: dard radiographs, and they are not portable. CT
children age 2 years or younger; patients with sickle scans are generally in the cost range of 7 to 10 times
cell disease; patients with renal failure; patients with that of a standard chest radiograph.
major trauma including hypotension, shock, neuro- CT scans may be obtained with or without con-
trauma, or spinal precautions; and patients requiring trast and performed with or without angiography.
angiography. Over the past decade, CT has been modified to
improve image quality and usefulness. A standard
CT moves the patient on its table through the scan-
Computed Tomography
ner in a stepwise fashion. Helical (spiral) CT allows
In CT, x-ray beams are aimed through the patient the patient to move through the scanner continu-
from many different angles. Instead of striking film, ously and rapidly, in one patient breath. This allows
radiation detectors identify the x-rays, and the near elimination of movement artifact, identification
results are recorded as digital information in a com- of much smaller lesions, less scan time, and use of
puter. The computer produces images that may be lower doses of contrast material. Multidetector CT
manipulated in many ways and recorded on film. (MDCT) provides multiple rows of x-ray detectors,
Standard CT images are axial cross sections allowing even shorter scan times, increased resolu-
through the body and are viewed as if oriented at tion, and thinner slices for more specific detail, par-
the foot of the patient looking toward the head ticularly with angiography (Chen et al., 2004). These
(Fig. 14-7). For standard studies, axial images are CT scanners can obtain images in less than 1 second
generated every 5 to 10 mm throughout the body. and allow visualization of the vascular system
However, images may be obtained every 1 to 3 mm with injection of intravenous contrast material
for some specialized studies. The main advantage of without catheterization. They also provide a large
CT scans is the ability to obtain cross-sectional number of scan planes that can be used to recreate
images through the body without the visual super- three-dimensional images. The ability to obtain
imposition of other structures. They also are able to three-dimensional images has revolutionized
detect much smaller differences in tissue density CT angiography and allowed visualization of arte-
than are standard radiographs. Disadvantages are rial, capillary, and venous vascular phases in an
the frequent need to use ionic or non-ionic con- organ. Its use also has been expanded to provide CT

174
 Chapter 14 Selecting Radiographic Tests

colonography (virtual colonoscopy) that allows a before MRI to assess for any ferrous metal object as
patient to forgo the need for sedation for a needed. Although MRI is expensive, it is particularly
colonoscopy but, obviously, does not allow directed useful in evaluating soft tissue around bony struc-
tissue biopsy. Table 14-2 defines costs associated with tures that normally interfere with image clarity on a
CT scanning. CT scan. MRI is especially helpful in imaging the cen-
tral nervous system for masses and other abnormali-
Magnetic Resonance Imaging ties of the brain, spinal cord, and nerve roots (Figs.
14-8 and 14-9). MRI also is useful for evaluating the
MRI produces images by subjecting the body to a musculoskeletal system, including the joints and
very strong magnetic field and then exposing the spine, and is being used to evaluate the pelvis,
body to pulses of radiofrequency energy. These retroperitoneum, mediastinum, and large vessels.
radiofrequency pulses cause randomly oriented Two types of weighted images are available on MRI to
hydrogen nuclei to realign in the body and then assist in better visualization of tissue densities. The
return to their original neutral position, releasing T1-weighted images show fluids as a dark image on
energy sensed by the scanner. The MRI computer is the film and fatty tissue as a white or bright image,
able to recreate a picture in any sagittal, coronal, or whereas the T2-weighted images show fluids as a light
axial plane. Because the magnetic field of an MRI color and fats as dark (Figs. 14-10 and 14-11). Bones
scanner is so strong, it can potentially dislodge tradi- are not well visualized on MRI, and what is actually
tional nerve stimulators, pacemakers, internal defib- imaged is the fat present in the marrow. These
rillators, and some very specific mechanical heart weighted images allow better image definition and
valves, making these devices absolute contraindica- evaluation of tissue density (i.e., solid, cystic, or fatty
tions to MRI scan. Patients with any ferrous metal in lesions). Advantages of MRI are its increased contrast
their body, such as intraorbital metallic fragments, resolution and lack of radiation exposure for the
should not receive MRI scans. In patients with surgi- scan. The cost of an MRI study may be in the range of
cal clips, such as cerebral aneurysm clips, MRIs are 8 to 12 times that of a standard chest radiograph.
contraindicated as well. Titanium wires, most Contrast agents are available with MRI as well.
mechanical heart valves, and most orthopedic hard- The most frequently used contrast agent is gadolin-
ware are made from nonferrous metals, allowing MRI ium dimeglumine. Significantly fewer adverse reac-
scanning to proceed. A plane radiograph can be used tions to gadolinium are found in comparison with

Table 14-2 Approximate Costs of Computed Tomography and

Magnetic Resonance Imaging
CPT Code Cost* Medicare MPFS†

Computed Tomography
Head without contrast 70450 $550 $247.07
With contrast 70460 $650 $301.27
Chest without contrast 71250 $800 $313.78
With contrast 71260 $950 $367.46
Abdomen without contrast 74150 $750 $304.34
With contrast 74160 $850 $359.55

Magnetic Resonance Imaging

Head, without contrast 70551 $1150 $557.39
With contrast 70552 $1350 $669.06
With and without 70553 $1950 $1189.42
Knee 73721 $1200 $543.56
Lumbosacral spine 72158 $2200 $1189.72
MRA head, without contrast 70544 $1300 $542.17
With contrast 70545 $1400 $542.17
With and without 70546 $2000 $1036.15

MRA, magnetic resonance angiography.

*
Approximate relative charge based on average of survey of current charges at two hospital systems in Seattle,
Washington.
†
2004 maximum payment for HCPC for locality 0083602, King County, Washington, Medicare Physician Fee
Schedule. Available at www.cms.hhs.gov/physicians/mpfsapp/display.asp. Accessed 10/8/2004.

175
 Chapter 14 Selecting Radiographic Tests

Figure 14-10 Axial brain magnetic resonance imaging

with T1-weighted image, with fluids appearing dark on
the film. Note patient’s left temporal lobe (to reader’s
right) with prior craniotomy and cerebral defect.

Figure 14-8 Magnetic resonance imaging of brain in

axial view. Note right posterior horn of lateral ventricle
(on the reader’s left in picture) has an abnormality in the
surrounding brain parenchyma.

Figure 14-11 Axial brain magnetic resonance imaging

with T2-weighted image, with fluids now appearing
lighter on the film. Note enhancement of left temporal
Figure 14-9 Magnetic resonance imaging of brain in lobe region with cerebrospinal fluid after recovery from
sagittal view. craniotomy.

176
 Chapter 14 Selecting Radiographic Tests

those to standard radiographic contrast, but these pancreas. Because US is very portable, many applica-
include dizziness, nausea, vomiting, headache, and tions may be done at the bedside.
paresthesias. The gadolinium may add $200 to $300 US has been found to be particularly useful in
to the cost of the imaging study. evaluation of structures such as the heart in echocar-
MR angiography (MRA) is a technique of study- diography or the gallbladder in an abdominal study.
ing the blood vessels with or without the need for Doppler US is a technique used to assess organ per-
intravenous contrast. Short scan times, as quick as fusion and blood flow. Color flow Doppler assigns a
one breath hold, have allowed this technique to different color for faster- or slower-flowing fluids
replace various types of traditional angiography. that permits evaluation of arterial and venous blood
Imaging techniques such as fast spin echo, fast gradi- flow to specific sites. This can be used in obstetric US
ent echo, diffusion imaging, perfusion imaging, and of umbilical cord blood flow or to assess vascularity
echo planar imaging with MRI have provided many of some abdominal or pelvic masses. It is particularly
new uses for these scanners. These techniques are useful in cardiac applications with echocardiography
now being used in the evaluation and treatment of and in identifying ischemic processes, such as testic-
strokes. Another application is magnetic resonance ular torsion.
cholangiopancreatography (MRCP), which allows Transluminal US or sonography has been
noncontrast evaluation of the biliary system in recently refined to provide methods for evaluation
patients unable to tolerate standard or endoscopic of structures around any hollow lumen. This tech-
contrast evaluations (ACR, 2001a● C ). nique can evaluate the heart with transesophageal
Most MRI machines are designed as long tubes echocardiography, the prostate with a transrectal
open at both ends. Standard scans take several min- ultrasound probe, pelvic structures with transvagi-
utes to complete and require the patient to remain nal ultrasound and hysterosonography, and masses
motionless. Newer open MRI machines are now or tumors of the gastrointestinal tract with endolu-
available for patients prone to claustrophobia or who minal probes. Intravascular catheters have recently
may have problems with traditional MRI machines. been developed to assess vascular stenoses and
Recently introduced echo planar machines have plaque formation in vessels. Three-dimensional US
reduced the imaging time to less than 1 second, thus has improved with computer digitalization. This
reducing the artifacts of breathing movement and process is used to define structures and volumes in
allowing imaging of the heart, lungs, and abdomen. abdominal US and, more important, in definition of
Costs of some selected MRI and MRA scans are out- fetal congenital anomalies in obstetric ultrasound.
lined in Table 14-2. The cost of a standard US examination is in the
range of 2 to 3 times that of a standard chest
Ultrasound radiograph, although some examinations such as
echocardiography may cost nearly twice that.
US creates images by using high-frequency sound Selected US costs are outlined in Table 14-3.
waves generated by a hand-held transducer. When
the transducer is passed over a thin layer of gel on the
Nuclear Imaging
surface of the body, it captures the returning sound
waves or echoes that reflect off of the structures Nuclear imaging uses gamma rays emitted from iso-
being imaged. The waves returning are transformed topes that are administered to the patient by the oral
into a picture by a computer. To improve images, gel or intravenous route. The isotopes, such as 99mtech-
is used between the transducer and patient’s skin to netium, are bound to different metabolically active
eliminate any air pocket that would normally reflect chemicals that determine the biodistribution of the
nearly all of the sound waves. Once produced by the compound in different tissues. The gamma rays are
transducer, US waves spread out from the transducer then counted and displayed as a picture by a gamma
into the body and are reflected back at different fre- camera and computer. Nuclear imaging is particu-
quencies by varying tissue planes. The returning sig- larly useful in determining the functional physio-
nals diminish as they pass through tissue, making US logic status of certain organs or tissues instead of
a difficult imaging modality for deeper structures. giving a simple pictorial representation. Applications
Because US delivers no ionizing radiation, it is that assess the function of the heart, thyroid, lung,
thought to be comparatively safe and has been gallbladder, kidneys, and skeleton are particularly
widely used in applications related to pregnancy, common. Although the function can be assessed, the
such as imaging of the fetus and pelvic structures. detail of structures is less defined than with other
However, US has limitations, especially because it techniques.
cannot penetrate bone and gas. Bowel gas can inter- Improved definition of specific tissues is possi-
fere with the examination. The technique works ble with single-photon emission CT (SPECT) scans.
poorly when imaging structures in the lung, brain, SPECT scans use a rotating gamma camera to
and, frequently, the central retroperitoneum and improve images by focusing on a thin slice of tissue

177
 Chapter 14 Selecting Radiographic Tests

Table 14-3 Approximate Costs of Nuclear Medicine and Ultrasound Imaging

CPT Code Cost* Medicare MPFS†

Nuclear Medicine
Bone scan, total body 78306 $550 $228.47
Myocardial perfusion 78460 $475 $147.03
Pulmonary, ventilation/perfusion 78596 $600 $369.40
HIDA scan 78223 $450 $201.36
MUGA scan 78473 $850 $430.98
Ultrasound
Abdomen, total 76700 $300 $127.60
Obstetrical, <14 wk 76801 $150 $142.87
>14 wk 76805 $285 $142.87
Echocardiogram, TTE 93307 $450 $216.35
TEE 93312 $575 $282.35
Stress echocardiogram 93350 $370 $156.14

HIDA, hepatobiliary iminodiacetic acid; MUGA, multigated acquisition; TEE, transesophageal echocardiography;
TTE, transthoracic echocardiography; CPT, current procedural terminology.
*
Approximate relative charge based on average of survey of current charges at two hospital systems in Seattle,
Washington.
†
2004 maximum payment for HCPC for locality 0083602, King County, Washington, Medicare Physician Fee
Schedule. Available at www.cms.hhs.gov/physicians/mpfsapp/display.asp. Accessed 10/8/2004.

and blurring the surrounding tissues in a way similar to allow rapid reference to recommended studies.
to standard tomograms. This technique has Alternative choices are given in cases in which certain
increased the resolution and sensitivity of the exam- tests may not be widely available or are particularly
ination but is nearly double the cost of the standard expensive. It should be understood that as the cost of
nuclear imaging technique. certain procedures change and certain studies
Positron emission tomography (PET) scans take become more widely available, these recommended
advantage of binding positron-emitting isotopes to approaches would change. In some cases, a more
metabolically active compounds (such as nitrogen, expensive test is recommended first, because the test
oxygen, carbon, or glucose) to assess their uptake in is so sensitive or specific that it may save the added
specific tissues. This technique can been used to expense of doing less-focused tests first. Because of
identify more metabolically active tumors and the the limited scope of this chapter, only selected prob-
uptake or release of specific compounds during activi- lems that either represent diagnostic controversy or
ties in the brain. Because the radionuclides are pro- are thought to be most common in family medicine
duced by a cyclotron and are short lived, PET is are addressed. Many resources are available to the
extremely expensive and is available at relatively few reader for other disease entities or symptom com-
large medical centers only. The cost may be reduced plexes, some of which are outlined in the references.
with the recent development of upgraded gamma The tables in this article give an approximate
camera-based scanners. Most nuclear imaging tech- comparison of the charges for various imaging stud-
niques deliver less radiation to the patient than do ies and procedures as a reference. Also given is the
standard x-ray techniques because multiple pictures Medicare Physician Fee Schedule for payment on these
can be taken with a single isotope injection. The cost procedures in one locale.
of most nuclear imaging studies is in the range of 5
to 9 times that of a standard chest radiograph. Some Neurologic System
particular nuclear medicine testing costs are listed in
Table 14-3. With a few exceptions, as noted later, MR and CT are
the most useful examinations with which to study
the central nervous system.
SELECTED DIAGNOSTIC STRATEGIES
FOR COMMON CLINICAL PROBLEMS Cranial Trauma
Skull trauma can be easily assessed with standard
For a family physician, diagnostic imaging strategies radiographs, although CT scan may be helpful in
are complex and rapidly changing. An outline of sug- delineating an acute fracture from cranial suture
gested imaging options is helpful to a busy provider lines or defining a small intranasal or intraorbital

178
 Chapter 14 Selecting Radiographic Tests

fracture. In head trauma and in suspected intracranial as a tumor or an abscess. MRI may be useful if CT
or subarachnoid hemorrhage, head CT without con- does not fully explain the clinical findings, or when a
trast is the best imaging method. MRI is generally inap- posterior fossa or brainstem infarction is suspected.
propriate for the initial examination in head trauma. Fast imaging MRI is now being implemented in the
MRI is practical when symptoms remain unexplained. evaluation of evolving stroke symptoms and is able
It may be useful in subacute or chronic conditions or in to detect smaller regional blood-flow changes. In ini-
brainstem contusions in which posterior fossa bone tial evaluation, MRI has had significant difficulty
structures preclude clear CT imaging. successfully identifying hemorrhage accurately, so
usually it is maintained as a secondary imaging
Transient Ischemic Attack modality. If an aneurysm is suspected, one must keep
Frequently, no acute imaging is necessary with a in mind that MRA or CT angiography is less precise
transient ischemic attack (TIA), which is defined as if lesions are smaller than 5 mm. Standard angiogra-
neurologic changes lasting less than 24 hours. US phy is much more exact and may be performed when
and Doppler are primarily used to evaluate the surgery is being considered for carotid or vertebral
carotid arterial system and, frequently, the vertebral artery disease or when other vascular abnormalities
and intracranial arterial system if adequate views can are suspected or noted on CT or MRI (ACR, 2000● C).
be obtained either around or through bone. If a sig- Standard angiography is vital at some medical cen-
nificant arterial plaque or occlusion is identified with ters in the initial evaluation of a patient within the
US that may require carotid endarterectomy, angiog- first 2 to 4 hours of an evolving acute stroke. An
raphy is frequently requested for preoperative con- interventional radiologist places an angiographic
formation of anatomy (Fig. 14-12). New procedures catheter for the immediate identification of the vas-
performed by some interventional radiologists cular supply. This allows the infusion of thrombolyt-
include cranial arterial stenting with the aid of direct ics for reversal of an acute infarction, placement of a
angiography. For those patients found with a carotid vascular stent, or introduction of a coil for emboliza-
bruit on examination, US Doppler offers the only tion of an aneurysm.
cost-effective method to screen for significant steno-
sis. Patients who have contraindications for an Back Pain and Suspected Lumbosacral Disk
angiography, such as renal disease, can undergo an Herniation with Nerve Root Compression
MRA on either the carotid or vertebral arterial sys- More than 80% of patients with acute back pain
tems, as indicated. respond to conservative therapy and do not require
radiologic imaging initially. If conservative therapy is
Stroke not successful within 4 to 6 weeks or an initial risk is
CT without contrast is used immediately to identify present of nonmuscular causes for the back pain,
hemorrhagic strokes and can distinguish ischemic imaging is appropriate. Initial images should be con-
strokes after 12 to 24 hours. CT also can exclude sidered in significant traumatic injuries, immunosup-
several problems that appear similar to a stroke, such pression, unexplained weight loss, unexplained fever,
use of intravenous drugs, prolonged use of corticos-
teroids, osteoporosis, and in those older than 70 years.
Plain lumbosacral spine films have low sensitivity and
specificity but may provide a rational starting point to
rule out such abnormalities as fracture or metastases
and can provide a correlation with further studies
when they are needed (Figs. 14-13 and 14-14). If clini-
cally indicated, more extensive five-view radiographic
imaging can be obtained to assess neuroforamina, facet
structure, and pedicle stability. If a fracture is not
clearly seen but is clinically suspected, CT may be help-
ful in evaluating the bony structures. SPECT scanning
may be rarely needed in specific instances to visualize
small fractures that are then seen as metabolically
active or to identify an inflamed facet joint before
injection. SPECT also is used to assess localized verte-
bral pain after a spinal fusion because of anatomic
changes interfering with other modalities. Total-body
nuclear medicine bone scans are completed when dis-
tant bone metastases in cancer are suspected. When
disk herniation, nerve root compression, or both are
Figure 14-12 Brain angiogram of middle cerebral artery. suspected, MRI is the preferred imaging modality

179
 Chapter 14 Selecting Radiographic Tests

Figure 14-13 Standard anterior to posterior radiograph

of lumbosacral spine. Note abdominal bowel gas overly-
ing spine.

(Fig. 14-15). Random use of MRI or CT in back-pain

patients is discouraged, as it may identify lumbosacral
spine abnormalities that are frequently present in
asymptomatic individuals and may be unrelated to the
current medical concern (ACR, 1999c ● C ). Controversy Figure 14 -14 Standard lateral radiograph of lum-
exists over whether CT or MRI is the study of choice bosacral spine. Note loss of normal lordotic curve.
for suspected disk herniation and nerve compression.
MRI is preferred by many because of its ability to
obtain views in multiple planes and because it shows careful history and physical examination. A CT with
excellent anatomic detail and avoids ionizing radiation. contrast should be considered when focal disease is
CT also is useful for detecting herniated disks, but it is suspected from the history or physical examination,
limited to certain views by its one-plane imaging abili- when the pattern of the headaches changes signifi-
ties. Its imaging is improved with use of a myelogram cantly, or if further screening history or tests suggest
(placement of contrast in the spinal fluid space) to dif- the presence of an intracranial process such as cancer.
ferentiate tissue planes and nerve root outlets. Concerns for focal disease include aphasia, memory
Myelography also is used preoperatively, in occasional impairment, or focal sensory, motor, or coordination
cases, to define further a herniated intervertebral disk deficits. Headaches of sudden onset and described as
or nerve root compression. CT is the study of choice the worst headache of a patient’s life suggest a poten-
for bone abnormalities such as suspected spinal steno- tial aneurysmal bleed that is best evaluated initially
sis, osteophyte impingement, degenerative disease of with noncontrast CT. Lumbar puncture for red blood
the facets, and spondylolysis in adults. Nuclear bone cell detection is used in some suspected cases only
scans with SPECT are now being used in children sus- after a normal CT is obtained. Angiography can be
pected of having spondylolysis because of its lower used if an aneurysm or hemorrhage is identified to
dose of radiation and its relatively high specificity in define the anatomy clearly for surgery or even for
children. direct embolization (ACR, 1999i ● C ).

Headache Infections
The majority of headaches seen by the family physi- The diagnosis of meningitis is determined with
cian may be diagnosed with reasonable accuracy by a a lumbar puncture examination. Generally before the

180
 Chapter 14 Selecting Radiographic Tests

ularly useful in evaluating for bone changes. If plain

views reveal no fracture, and focal pain is present,
flexion and extension views may be considered or a
CT may be done to clarify the diagnosis. If no focal
pain or bone injury is seen, yet suspicions remain
regarding cord trauma or a myelopathy, then MR
should be considered as the next step to evaluate
clearly the soft tissue structures and spinal cord.

Cerebral Tumors or Metastases

CT with contrast will visualize most cerebral metas-
tases. MRI with contrast is even more sensitive and is
used to diagnose or monitor primary brain tumors
(Figs. 14-16 and 14-17). If symptoms or findings sug-
gest a posterior fossa mass or small anterior cerebral
mass, MRI can be particularly helpful. As neurosurgi-
cal techniques have improved, so have some imaging
techniques that map the exact extent of neoplastic
lesions. Functional MRI scans that track regional
blood flow with specific motor activity and standard
angiography are sometimes used to assist in specific
surgical and radiologic procedures. Although quite
expensive and of limited availability, PET scan can be
used to identify tumor recurrence in patients who
have complex structural anatomic changes after ini-
tial surgical resection.

Figure 14 -15 Normal sagittal magnetic resonance

imaging view of lumbosacral spine in T1-weighted
image.

lumbar puncture, a CT scan is performed to evaluate

for space-occupying lesions or midline shift. These
findings indicate increased risk of high intracranial
pressure that can potentially result in brainstem her-
niation with a lumbar puncture. CT must be done
within the first 30 minutes and should not delay the
start of antibiotics when bacterial meningitis is sus-
pected (Losh, 2004). MRI is the imaging method of
choice for other intracranial infections. Its enhanced
visualization of soft tissues allows identification of
abscesses, cerebritis, subdural infections, and human
immunodeficiency virus–related changes or second-
ary infections.

Spinal Injuries
A plain lateral film should be taken during the initial
assessment to assess spinal stability at any level. If no
fracture is seen, then further plain film views
(oblique, anteroposterior [AP], open-mouth views) Figure 14-16 Magnetic resonance imaging of brain
are obtained. If a fracture is suspected but not defi- with T1-weighted image of film in Figure 14-8. Note con-
nitely seen, CT may be obtained because it is partic- trast enhancement of right posterior lateral ventricle.

181
 Chapter 14 Selecting Radiographic Tests

Figure 14-18 Coronal view of fetal brain from an

echoencephalogram through one of the fontanelles.

Figure 14-17 Magnetic resonance imaging of brain

with T2-weighted image of film in Figure 14-8. Note con-
trast enhancement of right posterior lateral ventricle.

Specific Pediatric Applications

Because of the noncalcified anterior and posterior
fontanelles in newborns and young infants, US is an
imaging modality used to assess intracranial struc-
tures and not available to older children or adults
(Figs. 14-18 and 14-19). This modality can be used to
assess for intracranial hemorrhage, hydrocephalus,
or mass in the first 4 to 8 months of life with no radi-
ation exposure. It may be done at the bedside and
Figure 14 -19 Sagittal view of fetal brain from an
rarely requires sedation. echoencephalogram.

Cardiovascular System and Respiratory

System pericardial effusion, which can mimic myocardial
ischemic pain. If the initial resting ECG shows no
Angina Pectoris and Suspected Coronary abnormalities that preclude valid exercise stress test-
Artery Disease ing, such as a left bundle branch block or ST-seg-
In a nonemergency situation, a resting electrocardio- ment changes, exercise stress testing is appropriate.
gram (ECG) should be obtained as the first step in For approximate costs of stress testing, see Table 14-4.
the evaluation of chest pain of suspected cardiac ori- Controversy exists over whether to do an exercise
gin, along with serologic cardiac markers, such as stress test or to proceed directly to noninvasive imag-
CK-MB and troponin. A chest radiograph may be ing studies. Most patients with good exercise capac-
beneficial to rule out other causes of chest pain, such ity and a normal exercise ECG may avoid further
as pneumothorax, pulmonary embolism, rib frac- more-expensive testing. An abnormal or equivocal
ture, ascending aortic aneurysm, aortic dissection, or exercise stress test is more likely to be a true reflec-
congestive heart failure with pulmonary edema. tion of disease in those patients at highest risk for
Transthoracic echocardiogram can be used to evaluate coronary artery disease. However, these high-risk
for causes of other chest pains, such as pericarditis or patients are the ones most likely to require further

182
 Chapter 14 Selecting Radiographic Tests

urements of the cardiac chamber and ejection frac-

Table 14-4 Approximate Costs of
tion. The cost of coronary angiography is in the
Selected Nonradiology Tests
range of $2000 to $4000 when all costs are totaled.
Medicare A form of CT termed electron beam tomogra-
CPT Code Cost* MPFS† phy (EBT) is being used at some centers to assess cal-
cium deposition around coronary arteries as an
Cardiac indirect and noninvasive method of assessing risk of
stress test 93015 $225 $1000
coronary events (ACR, 1999b ● C ). Ultrafast cine CT
ERCP, alone 43260 $113.36 $328.04
scanners are now able to produce images of the coro-
ERCP, endoscopic retrograde cholangiopancreato- nary arteries after a peripheral injection of contrast
graphy. material. It is thought that these technologies may
*
Approximate relative charge based on average of begin to supplant some of the currently available
survey of current charges at two hospital systems
in Seattle, Washington.
imaging techniques in the evaluation of coronary
†
2004 maximum payment for HCPC for locality artery disease.
0083602, King County, Washington, Medicare
Physician Fee Schedule. Available at www.cms.hhs. Congestive Heart Failure
gov/physicians/mpfsapp/display.asp. Accessed Certainly if ischemia is the primary cause of conges-
10/8/2004.
tive heart failure (CHF), the evaluations outlined
earlier for ischemic heart disease should be the initial
evaluation. If, conversely, CHF is caused by nonis-
diagnostic studies, and it can be argued that with them, chemic disease, echocardiography (ECHO) becomes
the most effective approach is to proceed directly to the most dependable mode of assessment after a
noninvasive diagnostic studies. standard chest radiograph. ECHO provides assess-
Noninvasive imaging studies include stress ment of valvular function and dysfunction, pericar-
echocardiography as the first choice. Poorly perfused dial effusion, chamber size, myocardial muscle mass
myocardial tissue does not contract effectively when and function, and an estimate of ejection fraction
exercised. Wall-motion abnormalities can be and pulmonary artery pressures. It also appraises
detected by echocardiography done within a minute both systolic and diastolic function of the heart,
of exercise completion. The test requires the patient guiding the selection of appropriate medications or
to be free of advanced chronic obstructive pul- treatments. Systolic failure is characterized by a
monary disease (COPD) or massive obesity and to decrease in contractility, with the heart usually
be able to achieve 85% to 90% of the maximal heart dilated and the ejection fraction less than 40%.
rate during exercise. In patients who cannot exercise, Diastolic failure, conversely, is associated with a nor-
the heart may be stressed to obtain similar results by mal or slightly hypertrophic heart and a normal
administering one of the vasodilators, dipyridamole ejection fraction. ECHO assesses chamber size and
or adenosine, or the sympathomimetic agent, dobu- thickness to guide therapy for either a hypertro-
tamine. If stress echocardiography is unavailable or phic or dilated cardiomyopathy, if present. Echo-
the patient has significant COPD, nuclear medicine cardiography is usually sufficient to estimate the
myocardial imaging studies should be considered. cardiac ejection fraction. If a more precise measure-
The thallium stress test is based on the failure of ment of ejection fraction is needed, consideration
areas of ischemic myocardium to take up the thallium should be given to a nuclear ventriculogram dis-
radiopharmaceutical during exercise. 201Thallium played as a multigated acquisition (MUGA) study. A
has been largely replaced by another radiopharma- MUGA study is a series of images created by a com-
ceutical, 99mtechnetium sestimibi. SPECT imaging puter as [99mTc]-labeled red blood cells flow through
is used to yield highly sophisticated images. The the heart after their intravenous injection.
sensitivities of SPECT nuclear imaging and stress Echocardiography is useful in cases of car-
echocardiography are about the same. Stress echo- diomyopathy, cardiac tumors, congenital heart dis-
cardiography is generally less expensive (about $400) ease, cor pulmonale, endocarditis, valvular heart
than nuclear imaging (about $650). disease, cardiac tamponade, and pericardial effusion.
When intervention is planned, it is necessary to In general, most standard ECHO examinations are
proceed to coronary angiography. Coronary angiog- done through the anterior chest, or transthoracically.
raphy yields the most information about the coro- For more accurate visualization of the posterior
nary artery anatomy and the exact location and heart and left atrium, a transesophageal ECHO
degree of stenosis. This can guide either acute or sub- (TEE) is performed. A TEE is frequently used to
acute angioplasty of vessels, coronary artery stenting, assess for an atrial appendage thrombosis in the set-
and coronary artery bypass graft surgery. Contrast ting of an embolic stroke or peripheral vascular
injected into the ventricle allows study of the con- occlusion with atrial fibrillation. TEE also can be
tractility of the heart and, in addition, direct meas- used for identification of other left atrial pathology,

183
 Chapter 14 Selecting Radiographic Tests

such as a myxoma or tumor, or for the assessment of

a mediastinal mass. Echocardiography generally
costs more than $400.

Pulmonary Embolus
Chest pain, dyspnea, tachypnea, or hemoptysis raises
the clinical suspicion for pulmonary embolus and,
therefore, the question of whether anticoagulation is
necessary. The physician is often faced with the
dilemma of determining whether a ventilation/perfu-
sion (V/Q) scan should be done on an emergency
basis. If the symptoms are suggestive of pulmonary
embolus, or the patient has risk factors such as pro-
longed bed rest, recent surgery, myocardial infarction
or heart failure, an indwelling venous catheter, or
venous thrombosis of the pelvis or proximal lower
extremities, then the first step should be a plain chest
radiograph (Figs. 14-20 and 14-21). The chest radi-
ograph will usually be nonspecific or normal but is
important in excluding other chest pathology and is
helpful in interpreting the V/Q scan if baseline radio-
logic abnormalities exist. A nuclear V/Q scan consists
of two parts. The perfusion portion is accomplished
by intravenously administering technetium-labeled
macroaggregated albumin, which lodges in the vas-
cular bed of the lungs and is then scanned. In the Figure 14-21 Standard lateral radiograph of chest. Note
curvature of diaphragm and heart in anterior chest.
ventilation portion of the study, the patient breathes
radioactive-labeled xenon gas for a scan that deter-
mines the portion of the lung being ventilated. If the
V/Q scan is normal, showing good perfusion, it vir- defects match, in the absence of other parenchymal
tually eliminates pulmonary embolus from the diag- disease, the scan will be read as “low probability.”
nosis. Areas of lung with poor alveolar ventilation Clinical judgment will be required regarding antico-
also have resultant vasospasm. Therefore the two agulation, because about an 80% chance exists that
areas of decreased ventilation and perfusion uptake no embolus is present. “Indeterminant” scans are
should “match.” When perfusion and ventilation reported with multiple areas of poor perfusion and
ventilation, making interpretation difficult, or when
the V/Q deficit is associated with a lung lesion of
undetermined etiology. The risk of embolus in inde-
terminant scans may range between 30% and 70%. If
the scan shows normal ventilation of a segment, but
with a perfusion deficit, then the scan is read as
“highly probable,” with enough certainty that, in the
absence of other contraindications, the patient
should be given anticoagulation. A V/Q scan costs
about $600.
With the advent of rapid-scan CT machines,
CT of the chest with contrast is frequently used in
patients with baseline chest radiograph abnormal-
ities, as seen in pulmonary fibrosis, sarcoidosis,
mass lesions, and other cardiopulmonary disease.
These patients have a high likelihood of an abnor-
mal ventilation scan, which frequently leads to
indeterminant V/Q scans. Even with rapid-scan
techniques, some patients with pulmonary decom-
pensation are unable to hold their breath for the
needed 20 to 30 seconds. In these cases, pulmonary
Figure 14-20 Standard radiograph of chest in pos- angiography is an option if clinical suspicion
teroanterior view. remains.

184
 Chapter 14 Selecting Radiographic Tests

Pulmonary angiography is reserved for those the chest radiograph in selected cases of hemoptysis
cases in which a high clinical suspicion of pulmonary or suspected bronchogenic carcinoma. CT may be
embolus is present in the setting of a nondiagnostic needed if symptoms persist despite negative findings
or indeterminant V/Q scan or CT scan. Pulmonary on bronchoscopy. MRI is acquired only to help stage
angiography is very sensitive and specific. It costs some lung cancers and mediastinal masses that are
about $1500 and is associated with a mortality rate of suspected of central vascular involvement. A barium
between 0.5% and 1% (Grossman et al., 1995b ● C ). swallow may be indicated if esophageal pathology is
Duplex Doppler compression examination of the suspected in the posterior mediastinum, and a thy-
lower extremities is used as an adjunct in the evalua- roid nuclear scan may be indicated in the evaluation
tion of the patient with suspected pulmonary embo- of a superior mediastinal mass.
lus to determine the location of the embolism
source, but it is not used to diagnose the lung com- Aneurysms
ponent. If further definition of a suspected lower- US is the first choice when evaluating for a suspected
extremity deep venous thrombosis is need or the US abdominal aortic aneurysm. CT with contrast
is equivocal, contrast venography with standard radi- should be considered with suspicion of a retroperi-
ographs may be used (ACR, 1999h ● C ). toneal hematoma secondary to a leaking aneurysm.
Ultrasound with color Doppler is the initial assess-
Other Chest Pathology ment for peripheral aneurysms, although CT or MRI
Aortic dissection is best diagnosed by first obtaining with contrast may be required for subclavian artery
a chest radiograph and then proceeding to CT with aneurysms.
and without contrast (ACR, 1999a ● C ). If the patient
cannot be given contrast, MRI should be considered. Sinusitis
In general, an initial plain radiograph and rarely fol- Acute sinusitis requires no form of imaging study in
lowing it with CT, when needed, is appropriate for its regular clinical presentation. If sinusitis persists
the first two steps in many diagnoses related to the after initial clinical treatment, or if mechanical
chest (Fig. 14-22). This approach has been used with obstruction of the sinus passages is suspected, imag-
diseases such as lung abscesses, persistent atelectasis, ing becomes appropriate. Traditionally, sinus radi-
asbestosis, blunt chest trauma, bronchiectasis, bron- ographs have been used to evaluate causes of
chogenic carcinoma, bronchopleural fistula, emphy- obstructive sinusitis with a Waters’ view (frontal view
sema with recurrent pneumothoraces, empyema, angled upward) and a lateral view. These can show a
pulmonary metastases, anterior and middle medi- solid mass or an air/fluid level indicating obstruction.
astinal masses, some cases of pneumonia, sarcoido- Any life-threatening complication of acute sinusitis
sis, Wegener’s granulomatosis, pneumothorax, and or chronic sinusitis lasting longer than 3 months war-
solitary lung nodules. US can be used to evaluate rants further evaluation, and CT is the preferred
pleural effusions, particularly for thoracentesis when method (Fig. 14-23). Imaging with CT defines the
needed, and any soft tissue abnormality of the chest nasal bone structure, sinus ostia, fluid accumulation,
wall. Fiberoptic bronchoscopy may be useful after mucosal reaction, and any obstructing polyp, tumor,
or cyst. Frequently, a CT is ordered before endoscopic
sinus surgery to define anatomic structures. If
intracranial complications of sinusitis are suspected,
MRI best defines the areas and their extent.

Gastrointestinal System
Cholelithiasis
US has replaced the oral cholecystogram as the study
of choice for the detection of gallstones in the pres-
ence of appropriate symptoms. Gallstones appear as
very echogenic foci with an intense acoustic shadow
and are easily seen within the gallbladder or biliary
system. The sensitivity of this test approaches 100%
when the examination is done by an experienced
technician. CT of the abdomen can visualize stones,
but not optimally. When the US is indeterminant and
stones are suspected in the biliary tree with elevated
Figure 14-22 Transverse or axial view of computed
tomography of the chest. Note the lungs laterally and appropriate liver-function tests, cholangiography
heart and great vessels centrally. Aorta is just anterior to should be performed with endoscopic retrograde
spine. cholangiopancreatography (ERCP) or MRI (MRCP).

185
 Chapter 14 Selecting Radiographic Tests

has a more consistent accuracy of 85%, but with a

higher cost for the scan, and frequently it takes up to
4 hours to complete the test (ACR, 1999e ● C ).
Abdominal US costs about $250, and HIDA is
slightly more expensive at $400.

Biliary Tract Obstruction

An approach similar to that in cholecystitis is used in
these cases. US will reveal dilated biliary and hepatic
ducts with a specificity of 71% to 96% and sensitivity
of 55% to 95%, depending on technique, although
occasionally they can be normal early in the course of
the obstruction. HIDA scan is useful if obstruction is
highly suspected but the ducts appear normal on US.
CT may be necessary when the cause of the obstruc-
tion and ductile dilatation is not apparent or is
revealed by US and has a specificity of 90% to 94%
and sensitivity of 74% to 96% (ACR, 1999f ● C ). CT
can be helpful in locating tumors in the head of the
pancreas, as US cannot frequently visualize this area
with accuracy. MRI has no advantage over CT in this
indication. ERCP may be necessary to define further
the anatomy or location of the obstruction. For
Figure 14-23 Coronal view of sinus computed tomog-
approximate costs of ERCP, see Table 14-4. This pro-
raphy scan visualizing the maxillary and ethmoid sinuses. cedure involves cannulation of the duct with the use
of an endoscope. Contrast material may be injected
into the common bile duct, and sometimes an
obstructing stone can be removed with a balloon
Acute Cholecystitis catheter or sphincterotomy of the sphincter of Oddi.
An abdominal US examination is particularly useful MRCP depicts three-dimensional anatomy of the bil-
for confirmation of the diagnosis of acute cholecys- iary system and is used primarily for a patient who
titis or if the diagnosis is even somewhat uncertain. cannot tolerate ERCP or for whom it fails.
An US study can localize the gallbladder and allow Occasionally, percutaneous transhepatic cholangiog-
the ultrasonographer to confirm the area of pain (a raphy (PTC) is necessary as well. This procedure
sonographic Murphy’s sign). It will identify stones, involves a US-guided injection of an intrahepatic bil-
gallbladder wall thickening, and edematous fluid iary duct with contrast material through a thin needle
around the gallbladder. The finding of gallstones to outline the biliary tree distal to the injection site.
plus either a positive Murphy’s sign or gallbladder With this technique, a stent can be placed simultane-
wall thickening is highly suggestive of acute chole- ously to bypass the obstruction.
cystitis. If only one of these findings is present, and
the diagnosis is uncertain, a nuclear [99mTc]-hepato- Appendicitis
biliary iminodiacetic acid (HIDA) scan may be done. Most of the time, the diagnosis of appendicitis is made
This radioactive-labeled substance is rapidly excreted with reasonable certainty on clinical and laboratory
from the liver into the biliary system. An injection of examination and without imaging studies. However,
intravenous morphine is used to constrict the when the diagnosis remains clinically uncertain, imag-
sphincter of Oddi and aid in the concentration of the ing studies are of assistance in establishing the diagno-
HIDA in the gallbladder. HIDA is useful to deter- sis. Groups of people that may have atypical abdominal
mine whether the gallbladder is functional and pain or uncertain findings include the elderly, infants
whether the cystic duct is obstructed. If the gallblad- and young children, women in pregnancy or of child-
der does not fill with HIDA, acute obstructive chole- bearing age, and cases of suspected appendiceal rup-
cystitis is highly likely. If the cystic duct is open, the ture. Abdominal plain radiographic films are helpful in
likelihood of obstructive cholecystitis is virtually elim- ruling out other pathology, such as small bowel
inated. Rare cases of acalculous cholecystitis are possi- obstruction, a mass effect, or perforation of a viscus
ble, especially after cardiopulmonary bypass surgery; with intra-abdominal air. However, an appendicolith
however, the combination of HIDA and ultrasound is can be seen only about 10% of the time. The next step
usually sufficient to make an appropriate clinical diag- is to decide between US and CT. CT is the best choice
nosis. US has a variable accuracy of 64% to 88% in in patients other than pregnant women, infants, and
acute cholecystitis. Conversely, HIDA scintigraphy young children. It is especially useful when appendiceal

186
 Chapter 14 Selecting Radiographic Tests

rupture is suspected. CT is often able to detect solids. This is especially important if the patient has
an abnormal appendix or an appendicolith with sur- dysphagia or suspected aspiration from a stroke or
rounding inflammatory changes. US should be other neurologic problem. Endoscopy is usually
ordered as an alternative in pregnant women or in required next with evidence of any strictures, ulcera-
infants or young children (ACR, 1999d● C ). US is less tions, tumors, or webs to allow direct visualization,
sensitive than CT at detecting a perforated appendix, biopsy, or treatment (ACR, 2001d● C ).
and technical problems with loops of bowel, obesity,
and retrocecal appendix location may hamper the Small Bowel Obstruction
examination. Plain films of the abdomen (supine, upright, and
decubitus) looking for air/fluid levels or evidence of
Esophageal Dysfunction air-filled small bowel loops with decreased colonic
A barium swallow with fluoroscopy is a reasonable gas are the initial evaluation for small bowel obstruc-
first step in the management of most cases of dys- tion (SBO). Barium studies are considered next.
phagia (Fig. 14-24). It costs about one-fourth the They are contraindicated with evidence of free air in
cost of endoscopy. This examination can be tailored the abdomen. If an obstruction is suspected in the
to the specific type of dysphagia symptoms by giving distal small bowel or colon, one should proceed to a
various thicknesses of barium or barium-coated barium enema before an upper gastrointestinal
(UGI) barium series (Fig. 14-25). This order is
important because barium may be difficult to evacu-
ate when it is proximal to the obstructing lesion.
Partial and intermittent small bowel obstructions
can sometimes be better detected by a technique
called enteroclysis. With this technique, a bolus of
barium and methylcellulose is injected directly into
the jejunum via an oral tube placed under fluoro-
scopic guidance. CT may have a role in the diagnosis
of small bowel obstruction, but it should probably be
reserved for those cases in which the barium studies
are inconclusive or an extraintestinal mass is sus-
pected (ACR, 1999g ● C ).

Figure 14-25 Upper gastrointestinal series with small

Figure 14-24 Barium esophagogram done to evaluate bowel follow-through (UGI/SBFT). Note stomach and
the swallowing mechanisms. small bowel with barium contrast agent.

187
 Chapter 14 Selecting Radiographic Tests

Acute Gastrointestinal Bleeding A minority of nodules not yielding diagnostic mate-

Endoscopy is indicated for the evaluation of acute rial on a biopsy may have repeated FNAB with US
gastrointestinal bleeding, as both visualization and guidance as necessary. A nuclear thyroid scan is
treatment can occur simultaneously in 95% of cases reserved for situations in which an FNAB is unavail-
(ACR, 2002● C ). However, if endoscopy cannot locate able, the FNAB yields inconclusive results, or the
the bleeding source, a [99mTc]-red blood cell study patient is hyperthyroid. If a nuclear medicine thyroid
may serve to document active bleeding, if 0.05 to 0.1 scan is necessary, it will yield one of several results
mL/min or more of blood flow is present, before (Fig. 14-26). If the scan reveals a solitary nonfunc-
considering an angiogram. If active bleeding of more tioning “cold” nodule, the risk of malignancy is
than 0.5 to 1 mL/min is present, the angiogram is between 15% and 40%. Although a US examination
very good at localizing duodenal or stomach bleed- may be able to differentiate between cystic and solid
ing but is rarely helpful in detecting bleeding from lesions, some malignant lesions may have cystic com-
esophageal varices (Grossman et al., 1995a ● C). ponents, and US cannot rule out malignancy with
Angiography also can be used therapeutically by certainty. A functioning or “hot” nodule or nodules,
allowing embolization of a vessel or injection of conversely, can generally be assumed to be benign.
vasoconstrictive agents. Although multiple cold nodules are usually benign
adenomas or cysts, malignancy cannot be ruled out,
Pancreatic Lesions and a tissue diagnosis should be obtained. A tissue
A radiograph of the acute abdomen in acute pancre- diagnosis also must be obtained for irregular cold
atitis can show a paralytic ileus of the small bowel areas. They may represent a malignancy or may rep-
overlying the pancreas and can be misinterpreted as resent benign lesions such as scars or an atypical ade-
an SBO. US is the initial choice in the evaluation of noma. If thyroid cancer is diagnosed, CT or MRI is
the jaundiced patient with an unknown cause. obtained to assess for cervical or thoracic metastasis
However, CT may be the initial study in the non- as well as for preoperative surgical planning. If papil-
jaundiced patient. CT has better resolution of the lary thyroid cancer is diagnosed, [131I]-radionuclide
retroperitoneal structures and can define pancreatic scanning is performed to assess for metastases, as it is
edema, mass, tumor, abscess, or bleeding. the only thyroid tumor that actively incorporates
iodine (Grossman et al., 1995c ● C ).
Hepatomegaly or Hepatosplenomegaly
A nuclear liver and spleen scan can document Thyroid Gland Enlargement
enlargement of the liver or spleen. However, CT may The recommended approach to a diffusely enlarged
be needed if the etiology of the enlargement is in thyroid gland is a nuclear medicine thyroid scan
question. US is more cost effective with documenta- with [99mTc]-pertechnetate. When the results reveal
tion of splenomegaly alone. an enlarged gland with multiple increased- and
decreased-function areas, the diagnosis is usually a
Hepatic Metastases multinodular goiter. A gland with partial replacement
CT with contrast is generally the study of choice for by multiple cysts, poorly functioning normal tissue,
hepatic metastases. If contrast material is contraindi- and fibrosis characterizes this condition. If a hard,
cated, or clinical suspicion continues despite a normal growing, or dominant cold nodule is found in a thy-
CT, an MRI is indicated. If the MRI is unavailable, an roid gland with multinodular goiter, it should be
alternative is a nuclear liver and spleen scan with diagnosed by tissue biopsy to rule out cancer. A dif-
SPECT. Extrahepatic metastases may be best defined fusely enlarged homogeneous gland with increased
with either CT or MRI with contrast. uptake is suggestive of Graves’ disease, although it
may rarely represent an organification defect in
Endocrine System which iodine is trapped in the gland but not con-
verted to thyroid hormone. An enlarged homoge-
Thyroid Nodule neous gland with normal uptake may represent early
The dilemma for the practitioner when a central Graves’ disease, a stage of Hashimoto’s or subacute
lower neck nodule is identified is determining whether thyroiditis, a multinodular goiter of fine consistency,
the nodule actually arises from the thyroid gland. US or a normal variant. A large gland with poor uptake
of the thyroid gland region may be helpful in locating probably represents subacute thyroiditis and does
the nodule to confirm its location. If the nodule arises not require further imaging.
from the thyroid, the question becomes whether the
nodule is benign or malignant. The best test in euthy- Other Endocrine Abnormalities
roid patients is fine-needle aspiration biopsy (FNAB) Parathyroid adenomas may be visualized by using a
of the thyroid nodule. This test may be done without technetium sestamibi scan (MIBI) with SPECT. CT is
a radiologic imaging study. It yields usable material the most common approach to adrenal masses. The
about 85% of the time and has 95% accuracy. CT must be done with very thin slices because most

188
 Chapter 14 Selecting Radiographic Tests

Figure 14 -26 Nuclear medicine thyroid scan showing uptake of the radioactive tracer.

adrenal tumors are smaller than 2 cm in diameter. CT repeated radiographic film done 10 to 14 days later
is usually the first step for adrenal adenomas, aldos- may show resorption along the fracture line or a
teronomas, and pheochromocytomas. However, periosteal reaction at the site of a fracture. In cases
[131I]iodocholesterol scans, [131I]metaiodobenzyl- that cannot wait for this approach, either CT or MRI
guanidine (MIBG) scans, and adrenal vein sampling should be ordered. CT can be used in most cases
are available if the CT results are incongruous with and is less expensive; however, MRI is preferred in
the clinical findings or if further characterization of a elderly patients with a clinically suspected fracture of
nodule is necessary. the femoral neck despite normal plain films. When
the clinical diagnosis remains unclear, a nuclear
bone scan detecting more metabolically active bone
Skeletal System
repair may be helpful in confirming the diagnosis of
Fractures a fracture. Bone scans may be used to detect a stress
Plain radiographic films can detect the majority of fracture because the plain radiographic films are
fractures adequately. Because fractures can occur in often normal. Common areas for stress fractures
different planes of the bone, it is vitally important to include the tibia, fibula, and feet in runners or other
obtain at least two views of the area suspected of athletes. Although the uptake of radionuclide can
fracture (Figs. 14-27 through 14-30). In a few excep- result from a number of conditions such as inflam-
tions, plain films are not diagnostic. When initial radi- mation, trauma, neoplasm, or arthritis, these condi-
ographs are negative, and a high clinical suspicion tions are rarely confused when searching for a stress
remains of a long-bone fracture or fracture of a bone fracture of high clinical suspicion. A stress fracture is
such as the navicular (scaphoid) bone in the hand, a essentially ruled out by a negative bone scan.

189
 Chapter 14 Selecting Radiographic Tests

Figure 14-27 Standard three-view series of films to evaluate for fractures. Note fracture of proximal radial aspect of
first proximal phalanx.

Figure 14-28 Standard anteroposterior radiograph of knee. Figure 14-29 Standard lateral radiograph of knee.

190
 Chapter 14 Selecting Radiographic Tests

of absorptiometry imaging is in the range of $150

to $250.

Knee Injury with Meniscal Tear

When the diagnosis of a meniscal injury is supported
by history and physical findings after a knee injury, it
is reasonable to first consider plain radiographic
films of the knee. Although the plain knee radi-
ographs do not show the knee cartilage directly, they
are useful as a first step to evaluate for joint effusion
and other potential knee pathology such as an asso-
ciated fracture. If a meniscal tear is suspected, and it
is not responding to conservative therapy or is inter-
fering significantly with the patient’s activity, arthro-
scopic surgery is considered. The family physician
should discuss the approach to this problem with the
intended arthroscopic surgeon to determine whether
MRI would be indicated in the particular patient. If
Figure 14 -30 Standard sunrise-view radiograph of the symptoms are suggestive enough that surgery is
patella on top of distal femur at the knee. likely, it may be most cost effective to proceed
directly to arthroscopic surgery, costing around
$3000. An MRI is useful to determine the exact loca-
Osteoporosis tion and severity of meniscal and ligamentous
Plain radiographic films are useful only late in the injuries to the knee if further definition of the injury
course of osteoporosis because at least 30% of the is needed. It can be done at less cost (about $1000)
bone density must be lost before the loss is apparent than arthroscopy and is noninvasive. MRI may be
on the standard radiograph. Therefore x-ray absorp- useful in identifying meniscal tears or cruciate liga-
tiometry techniques were developed to detect this ment tears that are in locations difficult to visualize
problem in its earlier stages and to follow up the with the arthroscope, as well as injuries to the artic-
progress of therapy. Among the more widely available ular cartilage or underlying bone associated with
techniques are both dual-photon absorptiometry these knee injuries (Figs. 14-31 and 14-32). However,
(DPA) and the faster and more reliable dual x-ray if arthroscopic surgery is ultimately required, MRI
absorptiometry (DEXA). DEXA is generally preferred can add significantly to the total expense. MRI has
because of its low precision error, its low radiation, largely replaced arthrography as the imaging study
and its ability to measure at multiple skeletal sites. for the evaluation of meniscal tears.
These techniques measure the absorption of
x-rays or gamma rays through selected bones of the Urinary and Reproductive Systems
body, such as the hip or lumber spine. All pre- and
postmenopausal women, men with testosterone defi- Obstructive Uropathy including Renal
ciency, persons with primary hyperparathyroidism, and Ureteral Stones
persons with long-term use of corticosteroids, and A plain radiographic kidney, ureter, and bladder
those with vertebral or other suggestive bone fractures (KUB) film of the abdomen should be the first imag-
should discuss ways to prevent osteoporosis with their ing study when evaluating for renal or ureteral stones
family physician. For the majority of patients, the or other causes of obstructive uropathy. Nearly 80%
decision on how and whether to treat is a clinical deci- of stones incorporate calcium into their structure at
sion based on the patient’s risk factors. Bone-density some point and are, therefore, radiopaque and easily
measurement should be obtained when the results seen. When it is available, a noncontrast spiral (heli-
would influence the physician’s therapeutic recom- cal) CT may used to locate the stone because it is
mendations or the patient’s compliance, or when it is faster and requires no contrast agent, when com-
necessary to monitor a patient’s therapeutic progress. pared with an intravenous pyelogram (IVP). An IVP
If a DEXA scanner is not available, a quantitative CT may be considered next, in place of a CT or when CT
scan can be done by any CT scanner, but it is much is not available, in patients who are producing ade-
more expensive, has a higher radiation dose, and is not quate amounts of urine and are free of significant
mobile for easy screening of patients. Newer quantita- renal disease or impairment. A renal US examination
tive US is available for osteoporosis screening because should take the place of the IVP if the patient is
of its low cost, portability, and lack of radiation. anuric, has severe renal disease, or is suspected to
Unfortunately, the US technique is not sufficient to have obstruction from outside the urinary tract itself.
monitor treatment success (ACR, 2001e ● C ). The cost The US examination is useful to define renal pelvis

191
 Chapter 14 Selecting Radiographic Tests

grams or a voiding cystourethrogram may be needed

if the cause and location of the obstruction remain
obscure (ACR, 2001b ● C ).

Renal Failure
The renal US examination is the best initial imaging
method and has several other applications in addi-
tion to the detection of stones and obstructive
uropathy. It is the main imaging method in the eval-
uation of renal failure, especially when obstruction is
a possible cause (ACR, 2001f ● C ). It also can assess
renal atrophy resulting from various causes. Duplex
US is frequently used to assess the renal vasculature
as a cause of secondary hypertension, which occurs
in fewer than 5% of patients. A nuclear medicine
captopril renal study also can be used to assess for
renovascular causes of hypertension. The captopril
causes temporary restriction of the affected renal
artery and, therefore, a decrease in perfusion and
deposition of the radionuclide (ACR, 2003● C ).

Renal Mass
US is one of the first imaging studies to consider when
evaluating a renal mass. If the mass is cystic, the
Figure 14-31 Normal magnetic resonance imaging of workup often ends at that point, as frequently this rep-
knee. Note anterior cruciate ligament traversing from resents a benign cyst. CT may be necessary when the
superior tibia anteriorly to posterior femur superiorly. mass is indeterminant or of solid character. CT or MRI
is used to assess a renal mass preoperatively to evaluate
for renal capsule extension and metastasis. When per-
cutaneous image-guided needle aspiration or biopsy is
needed, renal US is used for needle guidance.

Testicular Torsion and Other Scrotal Lesions

When it is available on an emergency basis, color
Doppler US examination of the scrotum is the pre-
ferred method to evaluate a patient for possible tor-
sion of the testicle in acute-onset scrotal pain
(Fig. 14-33). Because it is important to operate within

Figure 14-32 Magnetic resonance imaging of knee

with anterior cruciate ligament tear noted in center of
knee beginning at tibia and not attaching to posterior
aspect of femur. Area of tear shows moderate to severe
edema of ligament.

and calyceal enlargement, often reveals both

radiopaque and radiolucent stones if larger than 5
mm, and examines the kidney structures, regardless Figure 14-33 Ultrasound of scrotal contents with view
of their function. Antegrade and retrograde pyelo- of testicle.

192
 Chapter 14 Selecting Radiographic Tests

hours of an acute testicular torsion, and because the

clinical examination is frequently inconclusive, emer-
gency imaging is necessary. An acceptable alternative
method of imaging when Doppler is unavailable is a
testicular nuclear medicine scan. The scan does an
excellent job of differentiating between decreased flow
found in testicular torsion and increased flow found in
epididymitis (ACR, 2001c ● C ). US imaging also is use-
ful in the diagnosis of painful swelling arising from
trauma and in differentiating mass lesions of the scro-
tum. US can be used to identify or locate a testicle in
cryptorchidism. Staging of any testicular tumors can
be done with abdominal and pelvic CT with contrast.

Prostate Carcinoma
If a nodule is palpated on examination, or if an
unexplained high prostate-specific antigen (PSA) is
obtained, biopsy is necessary and is usually done
under US guidance. Transrectal US is the approach
of choice to evaluate the prostate and guide transrec-
tal biopsy. MRI is beginning to have an important
role in the evaluation of prostate cancer staging,
because it evaluates local pelvic nodes or local spread
more effectively than CT or US. Nuclear bone scan
can be used to assess for distant bone metastases.

Gynecology
Breast Figure 14-34 Mammogram of breast.
The diagnostic approach to a breast lump is
addressed in Chapter 10. Screening for breast cancer
is an important issue related to diagnostic imaging
and the role of family physicians in health mainte-
nance. The incidence of breast cancer increased to
115 in 100,000 women in 1997, and justifiable public
concern exists over this health problem. Breast cancer
is the most common cancer diagnosed in women and
accounts for approximately one third of all newly
diagnosed cancers in women. The risk of developing
breast cancer is age dependent. For example, the
probability of acquiring breast cancer is about 1:72
for a woman in her 40s, about 1:36 for a woman in
her 50s, and about 1:29 for a woman in her 70s.
Screening mammography (Fig. 14-34) has been
shown to reduce the breast cancer (Fig. 14-35) mor-
tality rate about 30% for women older than 50 years,
although less evidence is found for a benefit at
younger than 50 years. For this reason, a lack of con-
sensus exists over when mammography screening
should begin for the average-risk woman. The risk of
radiation exposure with screening mammography
has been judged to be negligible for women older
than 40 years when mammographers use low-dose
equipment and adhere to high quality-control stan-
dards. One of the problems with screening mammog-
raphy is its relatively low positive predictive value of
2% to 22% and the need for further diagnostic evalu- Figure 14-35 Mammogram of breast showing density
ation, meaning that it results in a large number of in upper central aspect evident by small marker placed.

193
 Chapter 14 Selecting Radiographic Tests

biopsies for benign findings. Specificity of a single

mammogram is 94% to 97%, whereas sensitivity is
77% to 95%. For this reason, the physician must
never be falsely assured about a palpable breast lump
that is followed by a negative mammogram. A tissue
diagnosis of a breast lump must be obtained regard-
less of the result of the mammogram. All women
between ages 50 and 70 years should have an annual
breast examination and mammography at least every
2 years. For average-risk women between ages 40 and
50 years, who desire mammography, it should be
made available yearly despite lack of strong evidence
of its clinical efficacy and should be available every 1
to 2 years for those older than 70 years who desire it.
High-risk women should have annual mammogra-
phy starting at age 35 years, or 5 years before the age
at which their first-degree relative acquired cancer.
US is routinely used in younger women with denser
breasts or in those with probable cystic disease, as it is
able to discern fluid phases in a cyst better than does
mammography. US should not be used to assess a Figure 14 -37 Obstetrical ultrasound of fetus. Note
solid mass. Recent advances have begun to use MRI as transverse view of fetal face.
an imaging modality for breast evaluation when an
abnormal potential cancerous mass is found on rou-
tine mammography screening (U.S. Preventive
Services Task Force, 2002● C ) (Fig. 14-36).

Ectopic Pregnancy and Adnexal Masses

US examination is the preferred imaging study when
evaluating a pregnancy (Figs. 14-37 and 14-38) or

Figure 14-38 Obstetrical ultrasound of fetus. Note axial

view of fetal head and measurement of cranial diameter.

adnexal mass. Imaging studies must always be pre-

ceded by a clinical physical examination to deter-
mine that the patient is in a stable condition and is
able to proceed with the diagnostic evaluation. In
most cases, enough time is found to obtain a serum
β-human chorionic gonadotropin (β-hCG), which
will help determine whether an ectopic or intrauter-
ine pregnancy needs to be considered. When the
β-hCG is more than 1800 IU/L, either abdominal
US or transvaginal US may be used to confirm an
intrauterine pregnancy. Transvaginal US is superior
to the abdominal US in detecting an ectopic preg-
nancy and is usually able to diagnose an intrauterine
Figure 14 -36 Magnetic resonance imaging of left
pregnancy when the β-hCG is more than 1000 IU/L.
breast. Note enhancing lesion of upper outer quadrant, β-hCG levels less than 1000 will warrant careful
consistent with breast cancer. serial monitoring if the transvaginal US fails to

194
 Chapter 14 Selecting Radiographic Tests

detect an intrauterine pregnancy and detects no

other explainable pathology. Transvaginal US also
may be useful when evaluating a suspected adnexal
mass if equivocal findings or technical problems
with the abdominal US occur (Tulandi, 2004 ● C ).
A color flow Doppler US of the ovarian vessels is
used to evaluate an acute ovarian pain suggestive of
ovarian torsion. Obstruction of fallopian tubes can
be assessed with a hysterosalpingogram when needed
to assess infertility or chronic salpingitis (Fig. 14-39).
Many adnexal masses are nonspecific in their
appearance on US and appear to have both cystic
and solid components. When this is the case in post-
menopausal women, or in premenopausal women
without evidence for infection, a biopsy should be
obtained to rule out malignancy. CT may be helpful
in the staging process of ovarian cancer.

Material Available on Student Consult

Review Questions and Answers about Selecting
Figure 14-39 Hysterosalpingogram. Note exiting dye at Radiographic Tests
ends of patent fallopian tubes.

REFERENCES

Alonso A, Lau J, Bertrand L, Weintraub A, et al. Prevention American College of Radiology (ACR). Imaging Strategies
of radiocontrast nephropathy with N-acetylcysteine in in the Initial Evaluation of the Jaundiced Patient, ACR
patients with chronic kidney disease: A meta-analysis of Appropriateness Criteria, 1999f. Available at www.acr.
randomized, controlled trials. Am J Kidney Dis 2004; org/dyna/?doc=departments/appropriateness_crit-
43:1–9.● A eria/text.html. Accessed 9/23/2004.● C
American College of Radiology (ACR). Manual on American College of Radiology (ACR). The Patient with
Iodinated Contrast Media. Reston, VA, ACR, 1991.● B Suspected Small Bowel Obstruction: Imaging
American College of Radiology (ACR). Metformin Strategies, ACR Appropriateness Criteria, 1999g.
(Glucophage) Therapy and the Risk of Lactic Acidosis Available at www.acr.org/dyna/?doc=departments/appr
[Bulletin]. Reston, VA, ACR, 1997.● C opriateness_criteria/text.html. Accessed 9/23/2004.●C
American College of Radiology (ACR). Acute Chest Pain: American College of Radiology (ACR). Suspected Lower
Suspected Aortic Dissection, ACR Appropriateness Extremity Deep Venous Thrombosis, ACR Appropria-
Criteria, 1999a. Available at www.acr.org/dyna/?doc=de teness Criteria, 1999h. Available at www.acr.org/dyna/?
partments/appropriateness_criteria/text.html. Accessed doc=departments/appropriateness_criteria/text.html.
9/23/2004.● C Accessed 9/23/2004.● C
American College of Radiology (ACR). Acute Chest Pain: American College of Radiology (ACR). Atraumatic
Suspected Myocardial Infarction, ACR Appropriateness Isolated Headache: When to Image? ACR
Criteria, 1999b. Available at www.acr.org/dyna/?doc=de Appropriateness Criteria, 1999i. Available at www.acr.
partments/appropriateness_criteria/text.html. Accessed org/dyna/?doc=departments/appropriateness_criteria/
9/23/2004.● C text.html. Accessed 9/23/2004.● C
American College of Radiology (ACR). Acute Low Back Pain: American College of Radiology (ACR). Cerebrovascular
Radiculopathy. ACR Appropriateness Criteria, 1999c. Disease, ACR Appropriateness Criteria, 2000. Available at
Available at www.acr.org/dyna/?doc=departments/ www.acr.org/dyna/?doc=departments/appropriateness_
appropriateness_criteria/text.html. Accessed 9/23/2004.●
C criteria/text.html. Accessed 9/23/2004.●
C
American College of Radiology (ACR). Evaluation of American College of Radiology (ACR). ACR Practice
Acute Right Lower Quadrant Pain, ACR Appropriate- Guideline for the Use of Intravascular Contrast
ness Criteria, 1999d. Available at www.acr.org/dyna/? Material. Reston, VA, ACR, 2001a.● C
doc=departments/appropriateness_criteria/text.html. American College of Radiology (ACR). Acute Onset Flank
Accessed 9/23/2004.● C Pain, Suspicion of Stone Disease, ACR Appropriateness
American College of Radiology (ACR). Evaluation of Criteria, 2001b. Available at www.acr.org/dyna/?doc=de
Patients with Acute Right Upper Quadrant Pain, ACR partments/appropriateness_criteria/text.html. Accessed
Appropriateness Criteria, 1999e. Available at www. 9/23/2004.● C
acr.org/dyna/?doc=departments/appropriateness_ American College of Radiology (ACR). Acute Onset of
criteria/text.html. Accessed 9/23/2004.● C Scrotal Pain: ACR Appropriateness Criteria, 2001c.

195
 Chapter 14 Selecting Radiographic Tests

Available at www.acr.org/dyna/?doc=departments/appr Grossman ZD, Katz DS, Santelli ED, et al. Pulmonary
opriateness_criteria/text.html. Accessed 9/23/2004.● C embolism. In: Cost-Effective Diagnostic Imaging: The
American College of Radiology (ACR). Imaging Clinician’s Guide, 3rd ed. St. Louis, CV Mosby, 1995b,
Recommendations for Patients with Dysphagia, ACR pp 179–187.● C
Appropriateness Criteria, 2001d. Available at www. Grossman ZD, Katz DS, Santelli ED, et al. Thyroid nod-
acr.org/dyna/?doc=departments/appropriateness_ ule/thyroid enlargement. In: Cost-Effective Diagnostic
criteria/text.html. Accessed 9/23/2004.● C Imaging: The Clinician’s Guide, 3rd ed. St. Louis, CV
American College of Radiology (ACR). Osteoporosis and Mosby, 1995c, pp 394–403.● C
Bone Mineral Density, ACR Appropriateness Criteria, Losh DP. Central nervous system infections. Infect Dis Clin
2001e. Available at www.acr.org/dyna/?doc=departments/ Fam Pract 2004;61:41.
appropriateness_criteria/text.html. Accessed 9/23/2004.●
C Mettler FA, Guiberteau MJ, Voss CM, Urbina CE. Primary
American College of Radiology (ACR). Radiologic Care Radiology. Philadelphia, WB Saunders, 2000.
Investigation of Causes of Renal Failure, ACR Appro- Rudnick MR, Goldfarb S, Wexler L, et al. Nephrotoxicity of
priateness Criteria, 2001f. Available at www.acr.org/ ionic and nonionic contrast media in 1196 patients:
dyna/?doc=departments/appropriateness_criteria/text. A randomized trial. Kidney Int 1995;47:254.● A
html. Accessed 9/23/2004.● C Solomon R, Werner C, Mann D, et al. Effects of saline,
American College of Radiology (ACR). Hematemesis, ACR mannitol, and furosemide on acute decreases in renal
Appropriateness Criteria, 2002. Available at function induced by radiocontrast agents. N Engl J Med
www.acr.org/ac_pda. Accessed 9/23/2004.● C 1994;331:1416.● A
American College of Radiology (ACR). Radiologic Investi- Tepel M, Van der Giet M, Schwarzfeld C, et al. Prevention
gation of Patients with Renovascular Hypertension, of radiographic-contrast-agent-induced reductions in
ACR Appropriateness Criteria, 2003. Available at www.acr. renal function by acetylcysteine. N Engl J Med
org/dyna/?doc=departments/appropriateness_criteria/ 2000;343:180–184.● A
text.html. Accessed 9/23/2004.● C Tulandi T. Clinical Manifestations and Diagnosis of Ectopic
Chen MYM, Pope TL, Ott DJ. Basic Radiology. New York, Pregnancy, Up To Date, 2004. Available at www.upto
Lange Medical Books/McGraw-Hill, 2004, pp 6–7. dateonline.com. Accessed 10/10/2004.● C
Eisenberg, RL, Margulis, AR. Radiology Pocket Reference: U.S. Preventive Services Task Force. Screening for Breast
What to Order When. Philadelphia, Lippincott-Raven, Cancer: Recommendations and Rationale. Rockville,
1996, p 441. Md: Agency for Healthcare Research and Quality,
Grossman ZD, Katz DS, Santelli ED, et al. Acute gastroin- 2002. Available at www.ahrq.gov/clinic/3rduspstf/
testinal bleeding in the adult. In: Cost-Effective breastcancer/brcanrr.htm.● C
Diagnostic Imaging: The Clinician’s Guide, 3rd ed. St.
Louis, CV Mosby, 1995a, pp 63–69.● C

196
C h a p t e r

15 Nasal Congestion in a
15-Month-Old Girl (Immunizations)
Richard D. Clover

immunization record is as follows: hepatitis B vac-

KEY POINTS cine (Hep B) at 2 days of age; diphtheria and tetanus
toxoids and acellular pertussis vaccine (DTaP),
1. Simultaneously administer as many indicated Haemophilus influenzae type b vaccine (Hib), Hep B,
vaccines as possible. pneumococcal conjugate vaccine (PCV), and inacti-
2. Remind parents when vaccinations are due, and vated poliovirus vaccine (IPV) at 8 weeks of age;
send recall notices to parents whose children DaTP, Hib, PCV, and IPV at 4 months of age; and
are overdue for vaccinations. DTaP, Hib, PCV, IPV, and Hep B at 6 months of age.
3. Influenza vaccine is now recommended for all
children at 6 to 23 months of age. Family History
4. Children with mild, acute illnesses with or with- Kristin’s father, a physician, is in good health at age
out fever can be vaccinated. 28. Her mother, a teacher, is in good health. Her
5. Low-grade fever by itself is not a contraindica- maternal grandmother died at age 32 from lym-
tion to immunization. phoma. Her other grandparents are in their fifties
6. Children with HIV infection should receive all with no major medical problems.
routine inactivated vaccines.
7. Current antimicrobial therapy is not a con- Objective
traindication to immunization.
8. Recent exposure to infectious disease is not a Physical Examination
contraindication to immunization. Kristin’s vital signs include a temperature of 37.3˚C
(99.1˚F), a respiratory rate of 20, a heart rate of 100,
and a weight of 25 pounds. She is generally alert and
active, although obviously nasally congested. Her
tympanic membranes are normal. She has clear rhi-
INITIAL VISIT norrhea, and her throat is mildly injected but with-
out exudate. Her neck is supple, with no cervical
Subjective lymphadenopathy. Lung, heart, and abdominal
examinations are within normal limits. Findings on
Patient Identification and Presenting the neurologic examination are appropriate for her
Problem age. Her skin is without rashes.
Kristin C. is a 15-month-old girl who presents in
October with a runny nose. Her mother states that Assessment
Kristin was in her usual good health until approxi-
mately 3 days ago, when she developed a runny nose, Working Diagnosis
nasal congestion, and a low-grade fever. Yesterday The working diagnosis is an upper respiratory tract
Kristin’s fever resolved, but her nasal congestion has infection, probably viral in origin. This visit is also an
persisted. Because Kristin has a history of ear infec- opportune time to check on her immunization sta-
tions, Mrs. C. is concerned that she may have another tus, which needs updating. Kristin has had DTaP × 3,
ear infection. Mrs. C. states that Kristin has not had Hib × 3, Hep B × 3, PCV × 3, and IPV × 3; she
a cough, difficulty breathing, vomiting or diarrhea. therefore needs measles-mumps-rubella vaccine
(MMR), varicella vaccine, and her fourth dose of
Medical History DTaP, Hib, and PCV vaccines. In addition, since it is
Kristin was born after a term gestation to a 27-year- October, she will need her first influenza vaccine.
old white woman. The pregnancy and delivery were
uneventful. Kristin has been treated successfully with Differential Diagnosis
amoxicillin three times previously for otitis media. The differential diagnosis includes allergic rhinitis
Her growth and development have been normal. Her and a nonviral respiratory tract infection. Allergic

199
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

rhinitis is usually associated with clear rhinorrhea, a The leading reasons for delayed or missing
more chronic history, and no fever. In this case, the immunizations are failure of simultaneous adminis-
acute onset and initial fever make an infectious etiol- tration, invalid contraindications, missed opportuni-
ogy more likely. ties, missed appointments, and parental concerns
A nonviral respiratory infection, although possi- including vaccine safety and religious beliefs. In
ble, is also unlikely. Although multiple organisms may order to raise the vaccination levels, Standards for
produce a respiratory infection, the improving course Pediatric Immunization Practice were recommended
of this illness (i.e., resolved fever) makes a self-limited by the National Vaccine Advisory Committee and
viral infection the most probable etiology. approved by the U.S. Public Health Service. These
standards address many of the factors that have been
Plan identified as contributing to underimmunization of
children. Following are some of the standards:
Diagnostic
No diagnostic tests are appropriate at this time. Vaccination services are readily available.
Vaccinations are coordinated with other health care
Therapeutic services and provided in a medical home when
Kristin is administered the following vaccines: DTaP, possible.
Hib, PCV, MMR, varicella, and influenza. She also Barriers to vaccination are identified and minimized.
receives symptomatic treatment for rhinorrhea (a Patient costs are minimized.
saline nasal spray). Health care professionals review the vaccination and
health status of patients at every encounter to
Patient Education determine which vaccines are indicated.
Mrs. C. is advised that Kristin’s symptoms should Health care professionals assess for and follow only
continue to improve. She is also informed of the medically accepted contraindications.
potential side effects and adverse reactions to each of Parents or guardians and patients are educated about
the vaccines and is given the appropriate vaccine the benefits and risks of vaccination in a culturally
information handouts. Acetaminophen may be given appropriate manner and in easy-to-understand
to Kristin for the fever and discomfort that accom- language.
pany immunizations. Health care professionals follow appropriate proce-
dures for vaccine storage and handling.
Disposition Up-to-date, written vaccination protocols are accessi-
Mrs. C. is asked to bring Kristin back in 4 weeks for ble at all locations where vaccines are administered.
the child’s second influenza vaccine if her condition People who administer vaccines and staff who man-
deteriorates. age or support vaccine administration are knowl-
edgeable and receive ongoing education.
Health care professionals simultaneously administer
DISCUSSION as many indicated vaccine doses as possible.
Vaccination records for patients are accurate, com-
Immunization programs have reduced the incidence of plete, and easily accessible.
many childhood infections. Through these initiatives, Health care professionals report adverse events after
global eradication of smallpox has been accomplished, vaccination promptly and accurately to the
and polio has been eliminated from the Western hemi- Vaccine Adverse Events Reporting System
sphere. Significant reductions in the incidence of other (VAERS) and are aware of a separate program, the
vaccine-preventable diseases have been accomplished. Vaccine Injury Compensation Program (VICP).
Varicella, hepatitis B, and hepatitis A have recently been All personnel who have contact with patients are
added to the list of vaccine-preventable diseases. The appropriately vaccinated.
reemergence of measles in the years 1989 to 1992 Systems are used to remind parents or guardians,
reminds us of the importance of these programs. patients, and health care professionals when vacci-
Several factors are involved in children and nations are due and to recall those who are
adults not receiving age-appropriate vaccines. These overdue.
factors include patient, provider, and system issues. Office- or clinic-based patient record reviews and
Although this discussion addresses certain indica- vaccination coverage assessments are performed
tions, contraindications, and compliance issues as annually.
they exist at the time of this book’s publication, Health care professionals practice community-based
providers should refer to the published recommenda- approaches.
tions of the Advisory Committee on Immunization
Practices (ACIP) for a more detailed discussion and The frequent changes in the immunization
up-to-date recommendations. schedules have produced uncertainties in providers.

200
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

Figure 15-1 summarizes the recommendations and Contraindications

schedules as published for July through December,
2004 (recommendations may change, and providers Providers’ knowledge of relative and absolute con-
should seek current recommendations from appro- traindications is variable. Some of the most common
priate agencies). This schedule includes a recent invalid contraindications are mild illness, such as a
change in the recommendations. Influenza vaccine is low-grade fever, upper respiratory infection, colds,
now recommended for all children aged 6 to 23 otitis media, or mild diarrhea. Children with mild
months. If this year’s administration of trivalent acute illnesses can and should be vaccinated. Several
inactivated influenza vaccine is the child’s first vacci- large studies have shown that young children with
nation, a second dose is administered at least 4 weeks upper respiratory tract infection, otitis media, diar-
later. In addition, family members of children aged 0 rhea, and/or fever respond as well to measles vaccine
to 6 months old should be vaccinated. as those without these conditions. Low-grade fever
In special circumstances, the provider will need to by itself is not a contraindication to immunization.
alter the recommended schedule. In immunocompro- Other invalid contraindications to vaccination
mised individuals, killed or inactivated vaccines do not include concurrent antibiotic therapy, disease expo-
represent a danger and generally should be adminis- sure or convalescence, pregnancy in the household,
tered as recommended for healthy children. Steroid and breast-feeding of an infant.
therapy usually does not contraindicate administration Nonspecific allergies and nonsevere allergies are
of live virus vaccines (MMR, varicella vaccine) when frequent invalid contraindications. Infants and chil-
such therapy is short term (<2 weeks), of low to mod- dren with nonspecific allergies, duck or feather
erate dose, provided in maintenance physiologic doses, allergy, allergy to penicillin, relatives with allergies,
or administered topically, by aerosol, or by intra-artic- and children taking allergy shots can be immunized.
ular, bursal, or tendon injection. A dose of prednisone Children with egg allergies can be vaccinated with
equal to or greater than 2 mg/kg of body weight or MMR vaccine. Table 15-1 summarizes the true and
20 mg/day should raise concern about the safety of invalid contraindications.
immunization with live virus vaccines. Physicians
should wait at least 3 months after discontinuation of Accelerated Schedules
therapy before administering a live virus vaccine to
patients who have received high-dose, systemic steroids A common problem for providers is determining
for 2 weeks or longer. what vaccinations a child needs when the child is
Children with HIV infection should receive all behind schedule. Table 15-2 is the recommended
routine inactivated vaccines. In general, live vaccines accelerated immunization schedule for infants at least
should be avoided, with the following exceptions: 4 months of age and children younger than 7 years of
MMR can be given to children with HIV infection age who start the series late or who are more than
with no to moderate immunosuppression, and vari- 1 month behind in the immunization schedule (i.e.,
cella can be administered to HIV-infected children children for whom compliance with scheduled return
with no immunosuppression. Children with severe, visits cannot be assured). Table 15-3 is the recom-
non-HIV-related immunocompromise should receive mended immunization schedule for children older
all routine inactivated vaccinations as scheduled. It is than 7 years who were not vaccinated at the recom-
recommended that children with HIV or who are mended time in early infancy.
severely immunocompromised receive both pneumo-
coccal and influenza vaccines. Varicella virus vaccine Material Available on Student Consult
should not be given to individuals who may be
Review Questions and Answers about Immuni-
immunocompromised from cancer except for chil-
zations
dren with acute lymphocytic leukemia in remission.

201
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

RECOMMENDED CHILDHOOD AND ADOLESCENT IMMUNIZATION SCHEDULE1

UNITED STATES, JULY-DECEMBER 2004

Catch-up Vaccination

Birth 1 mo 2 mo 4 mo 6 mo 12 mo 15 mo 18 mo 24 mo 4–6 y 11–12 y 13–18 y

HepB #1 only if mother HBcAg ()

Hepatitis B2

Diphtheria, tetanus,
pertussis3

Haemophilus Hib4 Hib

influenzae Type b4

Inactivated poliovirus

Measles, Mumps,
Rubella5

Varicella6

Pneumococcal

Influenza8
Vaccines below this line are for selected populations
Hepatitis A9 HepA series

1. Indicates the recommended ages for routine administration of currently licensed 4. Haemophilus influenzae type b(Hib) conjugate vaccine. Three Hib conjugate
childhood vaccines, as of April 1, 2004, for children through age 18 years. Any dose vaccines are licensed for infant use. If PRP-OMP (PedvaxHIB© or ComVax© [Merck])
not given at the recommended age should be given at any subsequent visit when is administered at ages 2 and 4 months, a dose at age 6 months is not required.
indicated and feasible. Indicates age groups that warrant special effort to admister DTaP/Hib combination products should not be used for primary vaccination in infants
those vaccines not given previously. Additional vaccines may be licensed and at ages 2,4, or 6 months but can be used as boosters after any Hib vaccine. The final
recommended during the year. Licensed combination vaccines may be used dose in the series should be given at age ≥12 months.
whenever any components of the combination are indicated and the vaccine's other 5. Measles, mumps, and rubella vaccine (MMR). The second dose of MMR is
components are not contraindicated. Providers should consult the manufacturer's recommended routinely at age 4-6 years but may be administered during any visit,
package inserts for detailed recommendations. Clinically significant adverse events provided at least 4 weeks have elapsed since the first dose and both doses are
that follow vaccination should be reported to the Vaccine Adverse Event Reporting administered beginning at or after age 12 months. Those who have not received the
System (VAERS). Guidance about how to obtain and complete a VAERS form is second dose previously should complete the schedule by the visit at age 11-12 years.
available at http://www.vaers.org/ or by telephone, 800-822-7967. 6. Varicella vaccine (VAR). Varicella vaccine is recommended at any visit at or after
2. Hepatitis B vaccine (HepB). All infants should recive the first dose of HepB vaccine age 12 months for susceptible children (i.e., those who lack a reliable history of
soon after birth and before hospital discharge: the first dose also may be given by age chickenpox). Susceptible persons aged ≥13 years should receive 2 doses given at
2 months if the infant’s mother is HBsAg-negative. Only monovalent HeB vaccine can least 4 weeks apart.
be used for the birth dose. Monovalent of combination vaccine containing HepB may 7. Pneumococcal vaccine. The heptavalent pneumococcal conjugate vaccine (PCV) is
be used to complete the series; 4 doses of vaccine may be administered when a birth recommended for all children aged 2–23 months and for certain children aged 24-59
dose is given. The second dose should be given at least 4 weeks after the first dose months. The final dose in the series should be given at age ≥12 months.
except for combination vaccines, which cannot be administered before age 6 weeks. Pneumococcal polysaccharide vaccine (PPV) is recommended in addition to PCV for
The third dose should be given at least 16 weeks after the first dose and at least 8 certain high-risk groups. See MMWR 2000;49(No. RR-9):1-35.
weeks after the second dose. The last dose in the vaccination series (third or fourth 8. Influenza vaccine. Influenza vaccine is recommended annually for children aged ≥5
dose) should not be administered before age 24 weeks. Infants born to HBsAg- months with certain risk factors (including but not limited to asthma, cardiac disease,
positive mothers should receive HepB vaccine and 0.5 mL hepatitis B immune sickle cell disease, HIV, and diabetes), health care workers, and other persons
globulin (HBIG) within 12 hours of birth at separate sites. The second dose is (including household members) in dose contact with persons in groups at high risk
recommended at age 1-2 months. The last dose in the vaccination series should not (see MMWR 2004;53;[RR][in press]) and can be administered to all others wishing to
be administered before age 24 weeks. These infants should be tested for HBsAg and obtain immunity. In addition, healthy children aged 6-23 months and close contacts of
anti-HBs at age 9-15 months. Infants born to mothers whose HBsAg status is healthy children aged 0-23 months are recommended to receive influenza vaccine,
unknown should receive the first dose of the HepB vaccine series within 12 hours of because children in this age group are at substantially increased risk for influenza
birth. Maternal blood should be drawn as soon as possible to determine the mother's related hospitalizations. For healthy persons aged 5–49 years, the intranasally
HBsAG status; if the HBsAg test is positive, the infant should receive HBIG as soon administered live, attenuated influenza vaccine (LAIV) is an acceptable alternative to
as possible (no later than age 1 week). The second dose is recommended at age 1–2 the intramuscular trivalent inactivated influenza vaccine (TIV). See MMWR
months. The last dose in the vaccination series should not be administered before age 2003;52(No.RR-13):1-8. Children receiving TIV should be administered a dosage
24 weeks. appropriate for their age (0.25 mL if 6-35 months or 0.5 mL if ≥3 years). Children aged
3. Diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP). The fourth ≤8 years who are receiving influenza vaccine for the first time should receive 2 doses
dose of DTaP may be administered at age 12 months provided that 6 months have (separated by at least 4 weeks for TIV and at least 6 weeks for LAIV).
elapsed since the third dose and the child is unlikely to return at age 15-18 months. 9. Hepatitis A vaccine. Hapatitis A vaccine is recommended for children and
The final dose in the series should be given at age ≥4 years. Tetanus and diphtheria adolescents in selected states and regions and for certain high-risk groups. Consult
toxoids (Td) are recommended at age 11-12 years if at least 5 years have elapsed your local public health authority and MMWR 1 999;48(No.RR-12):1–37. Children and
since the last dose of tetanus and diphtheria toxoid-containing vaccine. Subsequent adolescents in these states, regions, and high-risk groups who have not been
routine Td boosters are recommended every 10 years. immunized against hepatitis A can begin the hepatitis A vaccination series during any
visit. The 2 doses in the series should be administered at least 6 months apart.

Additional information about vaccines, including precautions and contraindications for vaccination and vaccine shortages is available at http://www.cdc.gov/nip or from the National
Immunization Information Hotline, 800-232-2522 (English) or 800-232-0233 (Spanish). Approved by the Advisory Committee on Immunization Practices
(http://www.cdc.gov/nip/acip), the American Academy of Pediatrics (http:www.aap.org), and the American Academy of Family Physicians (http://www.aafp.org).

Figure 15-1 Recommended childhood and adolescent immunization schedule—United States, July–December, 2004.
(From Advisory Committee in Immunization Practices (ACIP). Recommended Childhood and Adolescent Immunization
Schedule—United States, July–December 2004. MMWR Morb Mortal Wkly Rep 2004;53:Q1–Q3.)

202
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

Table 15-1 Guide to Contraindications* and Precautions† to Commonly Used Vaccines,

by Vaccine
True Contraindications Untrue (Vaccines Can Be
Vaccine and Precautions# Administered)

General for all vaccines, Contraindications Mild acute illness with or without
including diphtheria and Serious allergic reaction (e.g., fever
tetanus toxoids and acellular anaphylaxis) after a previous Mild to moderate local reaction
pertussis vaccine (DTaP); vaccine dose (i.e., swelling, redness,
pediatric diphtheria-tetanus Serious allergic reaction (e.g., soreness); low-grade or
toxoid (DT); adult tetanus- anaphylaxis) to a vaccine moderate fever after previous
diphtheria toxoid (Td); component dose
inactivated poliovirus vaccine Precautions Lack of previous physical
(IPV); measles-mumps-rubella Moderate or severe acute illness examination in well-appearing
vaccine (MMR); Haemophilus with or without fever person
influenzae type b vaccine (Hib); Current antimicrobial therapy
hepatitis A vaccine, hepatitis Convalescent phase of illness
B vaccine; varicella vaccine; Premature birth (hepatitis B
pneumococcal conjugate vaccine is an exception in
vaccine (PCV); influenza certain circumstances)+
vaccine; and pneumococcal Recent exposure to an infectious
polysaccharie vaccine (PPV) disease
History of penicillin allergy, other
nonvaccine allergies, relative
with allergies, receiving allergen
extract immunotherapy

DTaP Contraindications Temperature of <40.5˚C, fussiness

Severe allergic reaction after a or mild drowsiness after a
previous dose or to a vaccine previous dose of diphtheria
component toxoid-tetanus toxoid-pertussis
Encephalopathy (e.g., coma, vaccine DTP or DTaP
decreased level of consciousness; Family history of seizures∧
prolonged seizures) within Family history of sudden infant
7 days of administration of death syndrome
previous dose of DTP or DTaP Family history of an adverse event
Progressive neurologic disorder, after DTP or DTaP
including infantile spasms, administration
uncontrolled epilepsy, Stable neurologic conditions (e.g.,
progressive encephalopathy; cerebral palsy, well-controlled
defer DTaP until neurologic convulsions, developmental
status clarified and stabilized. delay)
Precautions
Fever of >40.5˚C ≤48 hours after
vaccination with a previous
dose of DTP or DTaP
Collapse or shock-like state (i.e.,
hypotonic hyporesponsive
episode) ≤48 hours after
receiving a previous dose of
DTP or DTaP
Seizure ≤3 days of receiving a
previous dose of DTP/DTaP∧
Persistent, inconsolable crying
lasting ≥3 hours ≤48 hours after
receiving a previous dose of
DTP or DTaP
Moderate or severe acute illness
with or without fever

Continued

203
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

Table 15-1 Guide to Contraindications* and Precautions† to Commonly Used Vaccines,

by Vaccine (Continued)
True Contraindications Untrue (Vaccines Can Be
Vaccine and Precautions# Administered)

DT, Td Contraindications
Severe allergic reaction after a
previous dose or to a vaccine
component
Precautions
Guillain-Barré syndrome ≤6
weeks after previous dose of
tetanus toxoid-containing vaccine
Moderate or severe acute illness
with or without a fever

IPV Contraindications
Severe allergic reaction to previous
dose or vaccine component
Precautions
Pregnancy
Moderate or severe acute illness
with or without fever

MMR@ Contraindications
Severe allergic reaction to previous Positive tuberculin skin test
dose or vaccine component Simultaneous TB skin testing++
Pregnancy Breast-feeding
Known severe immunodeficiency Pregnancy of recipient’s mother or
(e.g., hematologic and solid other close or household
tumors; congenital immuno- contact
deficiency; long-term Recipient is child-bearing-age
immunosuppressive therapy## female
or severely symptomatic human Immunodeficient family member
immunodeficiency virus [HIV] or household contact
infection)
Precautions
Recent (≤11 months) receipt of Asymptomatic or mildly
antibody-containing blood symptomatic HIV infection
product (specific interval Allergy to eggs
depends on product)$$
History of thrombocytopenia or
thrombocytopenic purpura
Moderate or severe acute illness
with or without fever

Hib Contraindications
Severe allergic reaction to previous
dose or vaccine component
Age <6 weeks
Precautions
Moderate or severe acute illness
with or without fever

Hepatitis B Contraindications Pregnancy

Severe allergic reaction to previous Autoimmune disease (e.g.,
dose or vaccine component systemic lupus erythematosus or
Precautions rheumatoid arthritis)
Infant weighing < 2000 g
Moderate or severe acute illness
with or without fever

204
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

Table 15-1 Guide to Contraindications* and Precautions† to Commonly Used Vaccines,

by Vaccine (Continued)
True Contraindications Untrue (Vaccines Can Be
Vaccine and Precautions# Administered)

Hepatitis A Contraindications
Severe allergic reaction to previous
dose or vaccine component
Precautions
Pregnancy
Moderate or severe acute illness
with or without fever

Varicella@ Contraindications Pregnancy of recipient’s mother or

Severe allergic reaction to previous other close or household
dose or vaccine component contact
Substantial supression of Immunodeficient family member
cellular immunity or household contact
Pregnancy Asymptomatic or mildly
Precautions symptomatic HIV infection
Recent (≤11 months) receipt of Humoral immunodeficiency (e.g.,
antibody-containing blood product agammaglobulinema)
(specific interval depends on
product)$$
Moderate or severe acute illness
with or without fever

PCV Contraindications
Severe allergic reaction to previous
dose or vaccine component
Precautions
Moderate or severe acute illness
with or without fever

Influenza Contraindications Nonsevere (e.g., contact) allergy

Severe allergic reaction to previous to latex or thimerosal
dose or vaccine component, Concurrent administration of
including egg protein coumadin or aminophyaline
Precautions
Moderate or severe acute illness
with or without fever

PPV Contraindications
Severe allergic reaction to previous
dose or vaccine component
Precautions
Moderate or severe acute illness
with or without fever
*
Contraindications: A contraindication is a condition in a recipient that increases the risk for a serious adverse
reaction. A vaccine will not be administered when a contraindication is present. Consult the MMWR article,
“General Recommendations on Immunizations” for a full definition including examples.
†
Precautions: A precaution is a condition in a recipient that might increase the risk for a serious adverse reaction
or that might compromise the ability of the vaccine to produce immunity. Injury could result, or a person
might experience a more severe reaction to the vaccine than would have otherwise been expected; however,
the risk for this happening is less than expected with a contraindication. Under normal circumstances,
vaccinations should be deferred when a precaution is present. However, a vaccination might be indicated in
the presence of a precaution because the benefit of protection from the vaccine outweighs the risk for an
adverse reaction. Consult the MMWR article, “General Recommendations on Immunizations” for a full
definition including examples.
Continued

205
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

#
Events or conditions listed as precautions should be reviewed carefully. Benefits and risks of administering a
specific vaccine to a person under these circumstances should be considered. If the risk from the vaccine is
believed to outweigh the benefit, the vaccine should not be administered. If the benefit of vaccination is
believed to outweigh the risk, vaccine should be administered. Whether and when to administer DTaP to
children with proven or suspected underlying neurologic disorders should be decided on a case-by-case basis.
+
Hepatitis B vaccination should be deferred for infants weighing <2000 grams if the mother is documented to be
hepatitis B surface antigen (HbsAg)-negative at the time of infant’s birth. Vaccination can commence at
chronological age 1 month. For infants born to HbsAg-positive women, hepatitis B immunoglobulin and
hepatitis B vaccine should be administered at or soon after birth regardless of weight. See MMWR article,
“General Recommendations on Immunizations” text for details.
∧
Acetaminophen or other appropriate antipyretic can be administered to children with a personal or family
history of seizures at the time of DTaP vaccination and every 4–6 hours for 24 hours thereafter to reduce the
possibility of postvaccination fever (Source: American Academy of Pediatrics. Active immunization. In Pickering
LK, ed: 2000 Red Book: Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Villege, IL,
American Academy of Pediatrics, 2000).
@
MMR and varicella vaccines can be administered on the same day. If not administered on the same day, these
vaccines should be separated by ≥28 days.
##
Substantially immunosuppressive steroid dose is considered to be >2 weeks of daily receipt of 20 mg or 2 mg/kg
body weight of prednisone or equivalent.
++
Measles vaccination can suppress tuberculin reactivity temporarily. Measles-containing vaccine can be
administered on the same day as tuberculin skin testing. If testing cannot be performed until after the day of
MMR vaccination, the test should be postponed for >4 weeks after the vaccination. If an urgent need exists to
skin test, do so with the understanding that reactivity might be reduced by the vaccine.
$$
See text for details.
∧∧
If a vaccinee experiences a presumed vaccine-related rash 7–25 days after vaccination, avoid direct contact
with immunocompromised persons for the duration of the rash.
From General Recommendations on Immunizations of the Advisory Committee on Immunization Practices (ACIP).
MMWR Morb Mortal Wkly Rep 2002;51(RR02):1–36.

206
 Table 15-2 Schedule of Accelerated Immunizations for Children under Age 7
Minimum Interval between Doses

Dose 1
(Minimum Age) Dose 1 to Dose 2 Dose 2 to Dose 3 Dose 3 to Dose 4 Dose 4 to Dose 5

DTaP (6 wk) 4 wk 4 wk 6 mo 6 mo1

2
IPV (6 wk) 4 wk 4 wk 4 wk
Hep B3 (birth) 4 wk 8 wk (and 16 wk after 1st dose)
MMR (12 mo) 4 wk4
Var (12 mo) 4 wk: if 1st dose given at 4 wk6: if current age
age < 12 mo < 12 mo
Hib5 (6 wk) 8 wk (as final dose): if 1st dose 8 wk (as final dose)6: if current 8 wk (as final dose): this dose
given at age 12–14 mo age ≥ 12 mo and 2nd dose only necessary for children
given at age <15 mo age 12 mo–5 y who
received 3 doses before
age 12 mo
No further doses needed: if 1st No further doses needed: if previous
dose given at age ≥ 15 mo dose given at age ≥ 15 mo
4 wk: if 1st dose given at age 4 wk: if current age < 12 mo
< 12 mo and current age
≤ 24 mo
PCV 7 (6 wk) 8 wk (as final dose): if 1st dose 8 wk (as final dose): if current 8 wk (as final dose): this dose
given at age ≥ 12 mo or age ≥ 12 mo only necessary for children
current age 24–59 mo age 12 mo–5 y who received
3 does before age 12 mo
No further doses needed: for No further doses needed: for
healthy children if 1st dose healthy children if previous
given at age ≥ 24 mo dose given at age ≥ 24 mo

Notes
1
DTaP: The fifth dose is not necessary if the fourth dose was given after the fourth birthday.
2
IPV: For children who received an all-IPV or all-oral poliovirus (OPV) series, a fourth dose is not necessary if third dose was given at age ≥ 4 years. If both OPV and
IPV were given as part of a series, a total of 4 doses should be given, regardless of the child’s current age.
3
HepB: All children and adolescents who have not been immunized against hepatitis B should begin the HepB immunization series during any visit. Providers should
make special efforts to immunize children who were born in, or whose parents were born in, areas of the world where hepatitis B virus infection is moderately or
highly endemic.
4
MMR: The second dose of MMR is recommended routinely at age 4–6 years but may be given earlier if desired.
5
Hib: Vaccine is not generally recommended for children age ≥ 5 years.
6
Hib: If current age of child is < 12 months and the first 2 doses were PRP-OMP (PedvaxHIB or ComVax [Merck]), the third (and final) dose should be given at age
12–15 months and at least 8 weeks after the second dose.
7
PCV: Vaccine is not generally recommended for children age ≥ 5 years.
From Advisory Committee on Immunization Practices (ACIP). Recommended Childhood and Adolescent Immunization Schedule—United States, July–December 2004.
MMWR Morb Mortal Wkly Rep 2004;53(16);Q1–Q3.

207
 Chapter 15 Nasal Congestion in a 15-Month-Old Girl (Immunizations)

Table 15-3 Schedule of Accelerated Immunizations for Children over Age 7

Minimum Interval between Doses

Dose 1 to Dose 2 Dose 2 to Dose 3 Dose 3 to Booster Dose

Td1: 6 mo: if 1st dose given at age

< 12 mo and current age < 11 y
Td: 4 wk Td: 6 mo 5 y: if 1st dose given at age ≥ 12
mo and 3rd dose given at age
< 7 y and current age ≥ 11 y
10 y: if 3rd dose given at age ≥ 7 y
IPV2: 4 wk IPV2: 4 wk IPV2,4
Hep B: 4 wk Hep B: 8 wk (and 16 wk
after 1st dose)
MMR: 4 wk
VAR3: 4 wk

Notes
1
Td: For children age 7–10 years, the interval between the third and booster dose is determined by the age
when the first dose was given. For adolescents age 11–18 years, the interval is determined by the age when
the third dose was given.
2
IPV: Vaccine is not generally recommended for persons age ≥ 18 years.
3
Varicella: Give 2-dose series to all susceptible adolescents age ≥ 13 years.
4
IPV: For children who received an all-IPV or all-oral poliovirus (OPV) series, a fourth dose is not necessary if
third dose was given at age ≥ 4 years. If both OPV and IPV were given as part of a series, a total of 4 doses
should be given, regardless of the child’s current age
Reporting Adverse Reactions: report adverse reactions to vaccines through the federal Vaccine Adverse Event
Reporting System. For information on reporting reactions following immunization, please visit www.vaers.org
or call the 24-hour national toll-free information line 800–822–7967.
Disease Reporting: report suspected cases of vaccine-preventable diseases to your state or local health
department. For additional information about vaccines, including precautions and contraindications for
immunization and vaccine shortages, please visit the National Immunization Program Web site at
www.cdc.gov/nip or call the National Immunization Information Hotline at 800–232–2522 (English) or
800–232–0233 (Spanish).
From Advisory Committee on Immunization Practices (ACIP). Recommended Childhood and Adolescent
Immunization Schedule––United States, July–December 2004. MMWR Morb Mortal Wkly Rep
2004;53(16);Q1–Q3.

SUGGESTED READINGS
Advisory Committee on Immunization Practices (ACIP). Advisory Committee on Immunization Practices (ACIP).
General Recommendations on Immunization. Recom- Standards for Child and Adolescent Immunization
mendations of the Advisory Committee on Immuni- Practices. Pediatrics 2003;112:958–963.
zation Practices. MMWR Morb Mortal Wkly Rep Advisory Committee on Immunization Practices (ACIP).
2002;51(RR02):1–36. Standards for Adult Immunization Practices. Am J Prev
Advisory Committee on Immunization Practices (ACIP). Med 2003;25:144–150.
Recommended Childhood and Adolescent Immuni-
zation Schedule—United States, July–December 2004.
MMWR Morb Mortal Wkly Rep 2004;53:Q1–Q3.

208
 C h a p t e r

16 Worsening Low Back Pain

(Metastatic Cancer Pain Management)
Frederick Lambert

pressure-like pain that radiates around her hip to

KEY POINTS her left groin (10 of 10 on a numeric analog scale).
Initially, she is prescribed a higher dose of naprosyn in
1. Attempt to characterize chronic pain as noci- combination with a mild opioid agent, hydrocodone
ceptive or neuropathic based on clinical history. with acetaminophen (Vicodin). Her pain does not
2. Believe the patient, as he is or she is the best respond to this regimen, and a magnetic resonance
source of how much pain he or she is currently imaging (MRI) scan is ordered, which reveals multiple
experiencing. metastatic lesions in her lower thoracic and lumbar
3. Use the World Health Organization three-step spine. She is admitted to the hospital for further pain
analgesic ladder to help guide therapy. management, and her pain is quickly controlled with
4. Nonopioid medications all have a ceiling to intravenous morphine administered by means of
their analgesic effects, and they have potentially patient-controlled analgesia (a PCA pump).
serious adverse effects. On discharge, she is prescribed a strong opioid,
5. Opioids do not have a ceiling effect to their sustained-release oxycodone (Oxycontin), 40 mg
analgesia, and short-acting oral opioid agents orally twice daily, in addition to her naproxen, and
can be titrated rapidly to achieve pain control. short-acting oxycodone with acetaminophen
6. Side effects from opioids are usually manage- (Percocet) for breakthrough pain. She also begins
able. Constipation from opioids must be treated radiation therapy for her spinal metastases. After
aggressively, and the risk of respiratory depres- 3 weeks, her pain remains uncontrolled on this regi-
sion from opioids is overestimated. men, and a second strong opioid, transdermal fen-
7. Opioids do not cause the psychological depend- tanyl (Duragesic patch) is added. After titration of
ence involved in addiction, and addiction is rare the fentanyl, her pain is finally well controlled. Five
when opioids are used appropriately for pain months later, herpes zoster (shingles) of her left L3
management. and L4 dermatomes develops, resulting in burning
8. Tricyclic antidepressants and anticonvulsant left groin pain. Sciatica of her left leg also develops,
medications such as gabapentin (Neurontin) are with shooting electrical pains down to her left foot
indicated for neuropathic pain. as well as numbness and tingling of her left leg. Both
of these conditions respond to the addition of
amitriptyline and gabapentin (Neurontin).
CLINICAL SCENARIO
M.W. is a 61-year-old woman who is on disability DISCUSSION
as a result of chronic low back pain secondary to
osteoarthritis of her lumbar spine. Her pain is Each year, approximately 25 million Americans
usually well controlled with naproxen (Naprosyn). experience acute pain due to injury or surgery, and
Two years earlier, she was diagnosed with colon another 50 million have chronic pain. About one of
cancer, which was treated with surgical resection every three Americans will seek medical attention for
followed by 1 year of adjuvant chemotherapy with severe chronic pain at some point during their life-
5-fluorouracil. times. Cancer is one cause of chronic pain, but there
She has had worsening low back pain for the last are several other nonmalignant causes of chronic
3 weeks. Her pain consists of severe throbbing, pain. Such painful conditions include osteoarthritis,

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

209
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

chronic low back pain, fibromylagia, spinal cord Based on history, chronic pain can generally be
injury, peripheral neuropathy, neuralgia, and chronic classified as either nociceptive or neuropathic in origin.
regional pain syndromes. Furthermore, the Joint Nociceptive pain is presumed to involve direct stimula-
Commission of Accreditation of Healthcare tion of intact pain fibers (nociceptors) with transmis-
Organizations (JCAHO) equates pain to “the fifth sion of electrical signals along normally functioning
vital sign” and mandates that physicians and hospi- nerves. Nociceptive pain is usually sharp, aching, or
tals screen for the presence and assess the nature and throbbing. Somatic pain (i.e., from skin, soft tissue,
intensity of pain in all patients. muscle, and bone) is usually easy for patients to local-
Despite such mandates, despite the prevalence ize, whereas visceral nociceptive pain (for example,
of chronic pain, and despite the availability of from the gastrointestinal tract, genitourinary tract, or
effective treatments and medications for pain, many lungs) is more achy and harder to localize. Neuropathic
patients with chronic pain remain undertreated. This pain, conversely, is caused by aberrant signal process-
is in part due to fears and misconceptions related to ing either in the peripheral or central nervous system,
the prescribing of opioid medications for pain. For sometimes as a result of previous nerve injury. Such
instance, many physicians, as well as patients, fear pain is usually burning, shooting, stabbing, tingling, or
that using medications such as morphine for chronic electrical and may be accompanied by paresthesias.
pain will cause addiction. Addiction is characterized Although both types of pain usually respond to opi-
by a psychological dependence on drugs and usually oids, adjuvant analgesics (such as tricyclic antidepres-
includes behaviors such as compulsive drug use sants and gabapentin) are often required to achieve
(even when patients are pain free) and continued adequate relief of neuropathic pain.
drug use despite harm. If prudent dosing guidelines When treating chronic pain, whether from can-
are followed, addiction is quite rare in patients who cer or from nonmalignant illness, it is important to
are receiving opioid medicines for pain control. prescribe effective medication and to achieve ade-
Like any other chronic symptom, pain requires quate pain control as quickly as possible. To this end,
adequate assessment in every patient. This includes in 1986 the World Health Organization developed
the usual historic parameters of location, severity, the three-step analgesic ladder (Fig. 16-2). It pro-
quality, associated symptoms, and aggravating or vides a simple and well-tested approach to the
mitigating factors. Proper assessment of pain also rational selection, administration, and titration of
includes the impact of the pain on the patient’s activ- many analgesics.
ities of daily living and his or her quality of life, as Management can begin at the corresponding step
well as evaluating the impact of the patient’s pain in depending on the severity of the patient’s pain. For
the personal context of psychological, social, and instance, patients with mild pain (1 to 3 of 10 on a
spiritual issues. Several instruments are available to numeric analog scale) can usually be started with
help patients quantify the location and severity of medications from step 1. Patients with moderate pain
pain as well as its impact on their lives. Pain scales are (4 to 6 of 10) usually enter the ladder at step 2, whereas
available for children or patients who cannot com- those with severe pain (7 to 10 of 10) usually require
municate verbally: scales such as the Wong-Baker medications from step 3. Adjuvant analgesics that are
Faces Scale can be used with patients as young as used to enhance the effects of pain medication, such as
3 years of age (Fig. 16-1). tricyclic antidepressants, can be used at any stage.

Faces Pain Rating Scale

0 1 2 3 4 5
No Hurt Hurts Hurts Hurts Hurts Hurts
Little Bit Little More Even More Whole Lot Worst

Consists of six cartoon faces ranging from a smilling face

for "no pain" to a tearful face "worst pain."

Recommended Age: Chilren as young as 3 years

Figure 16-1 The Wong-Baker Faces Scale. (From Wong D, Baker C. Pain in children: Comparison of assessment scales.
Pediatr Nurs 14(1): 9–17, 1988.)

210
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

Op
ioid
to s for m e.g., morphine, oxycodone
e o fentanyl
±N vere derat 3
on p e
±A –opioain
dju id
van

P in
ai c
t

n re
or

pe a
rs sin
Op

is g
e.g., codeine

tin
to mioid f

g
o or
±N derat mild
on e 2
±A –opiopain e.g., aspirin,
dju id paracetamol
van
P r in
ai c

t
n re

or an NSAID
o

pe a
rs sin

±N
is g
tin
on
g
±A –opio 1
dju id
van
t
P
ai
n

Figure 16-2 The World Health Organization analgesic ladder.

It is important to note that every patient’s ditional NSAIDs in relieving pain. In addition, ques-
response to pain is different, so medication regimens tions are emerging about the cardiovascular safety of
must be individualized based on specific patient COX-2 inhibitors, prompted by the recent with-
complaints and individual pain scores. Remember, drawal of rofecoxib (Vioxx) from the global drug
the patient is his or her own best judge of how much market.
pain he or she is currently experiencing—not the Step 2 analgesics generally include lower-potency
doctor, and not the family. It is not necessary for opioids such as codeine, hydrocodone, oxycodone,
patients to traverse each step of the pain ladder and tramadol (Table 16-2). In the United States, these
sequentially; for example, a patient with severe pain medications are usually available in combination with
may need to be prescribed step 3 opioids right away. a step 1 analgesic. Examples include acetaminophen
Step 1 analgesics (Table 16-1) include medica- with codeine (Tylenol 3), acetaminophen with
tions such as aspirin, acetaminophen, and non- hydrocodone (Vicodin), acetaminophen with tra-
steroidal anti-inflammatory drugs (NSAIDs). All of madol (Ultracet), and hydrocodone with ibuprofen
these medications have ceiling effects to their analge- (Vicoprofen). Acetaminophen with short-acting oxy-
sia: a maximal dose above which no further analgesia codone (Percocet) is generally the most potent of the
can be expected or obtained. These medications are step 2 analgesics. These medications are a natural sec-
good for mild pain, such as the well-controlled ond step in the treatment of pain that is not respond-
osteoarthritis that the patient in our clinical scenario ing to nonopioid analgesics. They also are a good first
initially has. Acetaminophen use is limited primarily choice in patients who are having mild to moderate
by hepatotoxicity, with the maximum safe dose being acute pain after injuries or surgery. These medications
4 g (4000 mg) in 24 hours. Alcohol use and preexist- are usually dosed every 4 to 6 hours, and although
ing liver disease can magnify this risk, even with they do have opioid-related side effects such as consti-
lower doses. NSAIDs also are limited by side effects, pation and sedation, the maximal dose is usually lim-
most notably gastric ulceration, renal insufficiency, ited by side effects of the nonopioid component.
hemorrhage, elevations in blood pressure, and fluid When patients have severe pain or pain that
retention. Although selective cyclo-oxygenase does not respond completely to step 1 or 2 analgesics,
(COX)-2 inhibitors may offer theoretical advantages high-potency opioids (step 3 medications) are gener-
in preventing gastric ulcers, they otherwise have the ally indicated. This group of medications includes
same serious side-effect profile as do nonselective morphine, hydromorphone (Dilaudid), fentanyl,
NSAIDS, and they are no more efficacious than tra- and methadone (see Table 16-2). Oxycodone in
211
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

Table 16-1 Step 1 Analgesics Commonly Used in the United States

Dosage Forms Recommended
Generic Name Trade Name(s) Available Usual Dosing Maximum Dosing

Acetaminophen Various, Tylenol Tabs: 325, 500 mg 325–650 mg po, 650 mg po, pr
Plain and Extra Elixir: 80 mg/mL pr q4h routinely q4h (4 g/24 h)
Strength are Supp: 325, 650 mg or prn
examples

NSAIDs and ASA

Acetylsalicylic acid Various, Aspirin is Caplets, tabs: 325, 325–650 mg po, 650 mg po, pr
(ASA) (salicylic an example 500 mg pr q4h routinely q4h (5 g/24 h)
acid derivative) Children’s tab: 80 mg or pm
Coated tabs: 325,
500 mg
Elixir: 80 mg/mls
Supp: 325, 650 mg
Celecoxib (CO-2 Celebrex Cap: 100, 200 mg 100–200 mg 200 mg po bid
selective) po bid
Choline magnesium Trilisate Tabs: 500, 750, 1000 mg 1–1.5 g po q12h or 1.5 g po q8h (4.5
trisalicylate Salicylate 0.5–1.0 g po q8h g/24 h)
(salicylic acid Elixir: 500 mg/5 mL
derivative)
Diclofenac (acetic Various, Cataflam, IR tabs: 50 mg IR: 50–75 mg po, 50 mg IR po q6h
acid derivative) Voltaren are SR tabs: 25, 50, 75, pr q6–8h or SR or 75 mg SR po
examples 100 mg (with 200 75–100 mg po q8h (225 mg/24 h
μg misoprostol: q8–12h
Arthrotec 50, 75 mg)
Diflunisal (salicylic Various, Dolobid is Tabs: 250, 500 mg 250–500 mg 500 mg po q8h
acid derivative) an example po q8–12h (1.5 g/24 h)
Etodolac (acetic Various, Lodine is IR tabs: 200, 300, 200–500 mg 400 mg po q8h
acid derivative) an example 400, 500 mg po q6–12h SR: 1200 mg q d
SR tabs: 400, 500,
600 mg
Flurbiprofen Various, Ansaid is Tabs: 50, 100 mg 50–100 mg po 200–300 mg/24 h
(propionic acid an example q12h
derivative)
Ibuprofen Various, Motrin is Tabs: 200, 400, 600, 200–800 mg 800 mg po q6h
(propionic acid an example 800 mg po q6–8h (3.2 g/24 h)
derivative) Elixir: 100 mg/5 mL
Indomethacin Various, Indocin is IR tabs: 25, 50 mg 25–75 mg po 50 mg po q6h
(indole) an example SR tabs: 75 mg q8–12h or 75 mg (200 mg/24 h)
Supp: 50 mg elixir, SR po q12–24h
25 mg/5 mL
Ketoprofen Various, Orudis is Cap: 25, 50, 75 mg 150–200 mg po/ 75 mg po q6h
(propionic acid an example SR tabs: 100, 150, 24 h (300 mg/24 h)
derivative) 200 mg IR: q6–8h
or SR: q12–24h
Ketorolac (acetic Various, Toradol is Tab: 10 mg 10 mg po qid or 40 mg po/24 h or
acid derivative) an example Inj: 15, 30 mg/mL 60 mg IM, IV 120 mg IM,
loading dose, IV/24 h for ≤5
then 10–30 mg days
IM, IV q6h
Nabumetone Various, Relafen is Tabs: 500, 750 mg 1–2 g po q12–24h 1 g po q12h (2
an example g/24 h)
Naproxen Various, Naprosyn is IR tabs: 250, 375, 250–500 mg po 500 mg po q8h
(propionic acid an example 500 mg q8–12h (1.5 g/24 h)
derivative) SR tabs: 375, 500 mg
Piroxicam (oxicam) Various, Feldene is Caps: 10, 20 mg 10–20 mg po 20 mg po q12h
an example q12–24h (40 mg/24 h)

212
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

Table 16-1 Step 1 Analgesics Commonly Used in the United States (Continued)
Dosage Forms Recommended
Generic Name Trade Name(s) Available Usual Dosing Maximum Dosing

Salsalate (salicylic Various, Disalcid is Tabs: 500, 750 mg 1000–1500 mg 3000 mg/d
acid derivative) an example po bid
Sulindac (indole) Various, Clinoril is Tabs: 150, 200 mg 150 mg po q12h 200 mg po q12h
an example (400 mg/24 h)

See individual opioids for combination medications.

IR, Immediate release; SR, sustained release; ↑, upper dose limited only by need and adverse effects. NSAID,
nonsteroidal anti-inflammatory drug; ASA, acetylsalicylic acid.
From Emmanuel LL, von Gunten CF, Ferris FD, eds. Module 4: “Pain Management,” the Education for Physicians
on End-of-Life Care (EPEC) Curriculum. The Robert Wood Johnson Foundation, 1999.

Table 16-2 Step 2 and 3 Analgesics Commonly Used in the United States
Dosage Forms Recommended
Generic Name Trade Name(s) Available Usual Dosing Maximum Dosing

Codeine (alone) Various IR tabs: 15, 30, 15–60 mg po, SC, 600 mg/24 hr
(methylmorphine, 60 mg IM q4h routinely/
naturally occurring Elixir: 15 mg/5 mL q1h pm
opioid metabolized Inj: 30, 60 mg/mL
into morphine)
Codeine + Various, Tylenol 3, Tabs: 30, 60 mg 1–2 tabs po q4h Limited to 12
acetaminophen 4 are examples codeine + 325 mg routinely or prn tabs/24 h by
combinations acetaminophen acetaminophen
(may include
caffeine, butalbital)
Fentanyl Various, Duragesic, Patch: 25, 50, 75, Patch: 25–↑ μg/h Limited only by
Actiq, Sublimaze 100 μg/hr q72h need and
are examples Lozenge: 200, 400, 600, Lozenge:200 μg adverse effects
800, 1200, 1600 μg q1h prn
Inj: 50 μg/mL
Hydrocodone + Various, Vicoden, Tabs: 2.5/500, 5/500, 1–2 tabs po q4–6h Limited to 4 g
acetaminophen Lortab, Norco are 7.5/500, 7.5/750, routinely or prn acetaminophen
examples 10/325, 10/500, 10/660 in 24 hr
Elixir: 7.5/500 in
15 mL
Hydrocodone + Vicoprofen Tab: 7.5/200 1–2 tabs po q4–6h Limited to 2400
ibuprofen routinely or prn mg ibuprofen in
24 hr
Hydromorphone Various, Dilaudid is Tabs: 1, 2, 4, 8 mg 1–↑ mg: po q4h Limited only by
an example Elixir: 1 mg/mL routinely/q1h prn, need and
Inj: 2, 10 mg/mL SC, IM q3h adverse effects
Powder: 250 mg/vial routinely/q 30
min pm, or SC,
IV q1h via infusion
+ breakthrough
q 30 min pm
Levorphanol Levo-Dromeran Tab: 2 mg 2–↑ mg po q6–8h Limited only by
inj: 2 mg/mL need and
adverse effects
Meperidine Various, Demerol is Tabs: 50, 100 mg 50–150 mg po, IM, 150 mg q3–4h,
(pethidine, an example Inj:50, 75, SC, IV q4h pm 900–1200 mg/
synthetic opioid 100 mg/mL NOT RECOM- 24 hr
not related to Syrup: 50 mg/5 mL MENDED FOR
morphine, useful CHRONIC DOSING
for rigors) Active metabolite
normeperidine
may produce
adverse effects

Continued
213
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

Table 16-2 Step 2 and 3 Analgesics Commonly Used in the United States (Continued)
Dosage Forms Recommended
Generic Name Trade Name(s) Available Usual Dosing Maximum Dosing

Methadone Various Dolophine Tabs: 5, 10, 40 mg 5 mg po q8h Limited only by

is an example Elixir: 10 mg/mL Titrate dose q need and
3–5 days due to adverse effects
delayed clearance
Morphine, IR Various IR tabs: 5, 15 mg 1–↑ mg: po, pr q4h Limited only by
Elixir: 1, 2, 20 mg/mL routinely/q1h need and
Supps: 5, 10, 20, prn, adverse effects
30 mg SC, IM q3h
Inj: 1, 2, 10, 15, 25, routinely/q 30
50 mg/mL min prn, or SC,
IV q1h via
infusion + break
through q 30 min
prn
Morphine, SR Capsule: Kadian Kadian capsules: 20, 10–↑ mg: po, pr Limited only by
Tabs: Ora-Morph- 50, 100 mg (q12– q8–24h routinely need and
SR, MS-Contin 24h) only (depending adverse effects
MS-Contin on product).
tabs: 15, 30, 60, Provide break-
100, 200 mg (q8– through doses
12h) using IR
Ora-Morph-SR morphine q1h
tabs: 15, 30, 60, prn
100 mg (q8–12h)
(Kadian capsules may
be opened and
pellets mixed with
fluids or soft food)
Oxycodone (alone) IR: Various SR: IR tabs: 5, 10 mg 5–↑ mg IR po, pr Limited only by
Oxycontin SR tabs: 10, 20, 40, q4h routinely, need and
80 mg q1h pm or 10–↑ adverse effects
Elixir: 20 mg/mL mg SR po q12h
Oxycodone + Various, Percocet is 5 mg oxycodone + 1–2 tabs po q4h Limited to 12
Acetaminophen an example 325 mg acetamino- routinely or tabs/24 hr by
combinations phen (may include prn acetaminophen
caffeine)
Oxycodone + ASA Various Percodan is 5 mg oxycodone + 1–2 tabs po q4h Limited to 12
combinations an example 325 mg ASA (may routinely or prn tabs/24 hr by
include caffeine) ASA
Tramadol Ultram Tab: 50 mg 1–2 tabs po q6h 2 tabs po q6h

IR, Immediate release; SR, sustained release; ↑, upper dose limited only by need and adverse effects.
From Emmanuel LL, von Gunten CF, Ferris FD, eds. Step 2 and 3: “Pain Management,” the Education for
Physicians on End-of-Life Care (EPEC) Curriculum. The Robert Wood Johnson Foundation, 1999.

doses greater than 5 to 10 mg also is used for severe signs of toxicity such as delirium, excessive sedation,
pain. Many opioid medications have similar phar- and seizures. All of these medications (with the
macologic properties and follow first-order kinetics. exception of methadone and fentanyl) have effective
This means that they are eliminated from the body in half-lives of approximately 3 to 4 hours, and there-
a direct and predictable way, irrespective of dose. fore steady-state concentrations are usually attained
These medications are first conjugated in the liver, within a day. This allows relatively rapid titration of
and then the metabolites are almost exclusively elim- opioids on a daily basis to achieve pain control, espe-
inated in the urine by the kidneys. As a result, these cially in the inpatient setting.
medications (especially morphine) can quickly accu- In general, patients who are in severe pain are
mulate in patients with oliguria and renal failure, started with a moderate dose of a short-acting step 2
and such patients must be watched very carefully for or step 3 opioid every 4 hours. If pain is not con-

214
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

trolled within 24 hours, then the dose of the opioid unique pharmacokinetics of the fentanyl patch,
can be increased by 25% to 50% (or even more for patients need to be counseled that when starting the
severe pain). Unlike NSAIDs, no ceiling effect is patch or increasing the dose of fentanyl, the full
found in opioid analgesia, and the dose can be raised effect of the medicine will not peak until 24 hours
until either adequate analgesia is achieved or side later. Once a steady state is reached, the duration of
effects become limiting. Frequently, titration of pain pain relief from the fentanyl patch is approximately
medications in the inpatient setting requires use of 72 hours in most patients.
parenteral narcotics (intravenous or intramuscular); Several currently available opioids should not be
but once adequate pain relief is achieved, one can used as pain medications. Meperidine (Demerol) has
easily convert to oral narcotics by using an equianal- significant adverse effects, such as tremors, dysphoria,
gesic dosing table. Table 16-3 provides an example. myoclonus, and seizures, especially when given in
If a patient continues to require frequent dosing repeated doses. An active effort is under way in many
of short-acting opioids, or if a patient has chronic hospitals to remove meperidine from their formula-
pain that is stable, consideration should be given to ries. Propoxyphene (Darvocet), when compared with
administering oral sustained-release formulations of other available step 2 analgesics, produces relatively
opioids such as morphine (MS Contin) and oxy- little analgesia, and its use is generally not recom-
codone (Oxycontin). These formulations generally mended by most pain-management specialists. Mixed
provide a baseline level of analgesia for 8 to 12 hours opioid agonists-antagonists, such as pentazocine
and may result in improved patient compliance and (Talwin), butorphanol (Stadol), and nalbuphine
decreased dosing of short-acting or breakthrough (Nubain) also should not be used for the management
medications. However, they should not be used for of chronic pain. Not only do these medications have
initial dose titration in patients with severe pain. side effects, but they also have ceiling effects to their
Patients should be informed that sustained-release analgesia, and they can produce acute withdrawal in
medications such as MS Contin and Oxycontin must patients who are already taking other opioids for pain.
be swallowed whole and cannot be broken, crushed, Opioid medications do have many common side
or chewed. Oxycontin in particular can be lethal if it effects, including constipation, dry mouth, sedation,
is not taken properly, and it has a very high abuse sweats, and nausea and vomiting. Patients must be
potential, so proper patient selection is important. educated that such side effects are not allergic reac-
Another option in patients with severe pain is tions, and true allergies to opioids are uncommon.
transdermal fentanyl (Duragesic). Because of the Patients sometimes do experience urticaria or pruritis
with opioids, which can usually be treated with either
sedating or nonsedating antihistamines. Pharmaco-
logic tolerance to side effects (except constipation)
Table 16-3 Equianalgesic Doses of develops in most patients within a relatively short
Opioid Analgesics period. Constipation due to opioids is almost universal
and should be anticipated and treated aggressively.
Oral/Rectal Parenteral Usually stool softeners such as docusate (Colace) are
Dose (mg) Analgesic Dose (mg)
ineffective by themselves, and often they must be com-
100 Codeine 60 bined with either stimulant laxatives such as senna
— Fentanyl 0.1 (Senokot) or bisacodyl (Dulcolax) to produce regular
15 Hydrocodone — bowel movements. Prokinetic medications, such as
4 Hydromorphone 1.5 metoclopromide (Reglan), and osmotic agents, such as
2 Levorphanol 1 prune juice and lactulose, also may be required.
150 Meperidine 50 Sedation from opioids can be troublesome for
10 Methadone 5 some patients and their families, but it usually disap-
15 Morphine 5
pears within several days when tolerance develops. If
10 Oxycodone —
sedation persists, a different opioid can be tried.
When converting to or from transdermal fentanyl Other serious side effects from opioids are actually
patches, published data suggest that a 25-μg rare. Delirium, with hallucinations, agitation,
patch is equivalent to 45 to 135 mg of oral myoclonic jerks, and seizures, rarely occurs in
morphine/24 hr. However, clinical experience
suggests that most patients will use the lower end patients with normal renal function if opioids are
of the range of morphine doses (i.e., for most administered in a prudent fashion. However, delir-
patients, 25 μg is about equivalent to 45 to 60 mg ium should be a concern in patients who have renal
of oral morphine/24 hr). failure, oliguria, sepsis, and dehydration, and in
Adapted from Emanuel LL, von Gunten CF, Ferris FD,
eds. The EPEC Curriculum. Available at
patients who may be near the end of life.
www.epeconline.net. Accessed 1/24/2006;Levy The risk of respiratory depression from opioids
MH. Pharmacologic treatment of cancer pain. N when they are used for pain management is grossly
Engl J Med 1996;335:1124–1132. exaggerated. In patients who are receiving opioids

215
 Chapter 16 Worsening Low Back Pain (Metastatic Cancer Pain Management)

for pain, respiratory depression does not occur sud- patients. Gabapentin (Neurontin) has become a
denly in the absence of overdose, and somnolence potent treatment for many types of neuropathic pain,
always precedes respiratory depression. Thus PCA including postherpetic neuralgia and pain that is
and even continuous morphine intravenous drips shooting or stabbing. Sometimes a combination of a
can be safely used in most patients, provided they are tricyclic and gabapentin must be used for complex
closely monitored for sedation. neuropathic pain, as illustrated by the patient in
Both patients with cancer and those with non- our scenario. If gabapentin is not successful, other
malignant chronic pain may require escalating doses anticonvulsant medications such as carbamazepine
of opioids as their pain or disease progresses. If opi- (Tegretol) and valproic acid can be tried.
oids must be discontinued because of side effects, Finally, many nonpharmacologic modalities can
they should be tapered slowly to prevent withdrawal be useful for patients whose pain is not entirely
symptoms such as tachycardia, diaphoresis, nausea, responsive to traditional medications. Such modali-
vomiting, diarrhea, abdominal pain, and hallucina- ties include physical therapy, acupuncture, transcu-
tions. If withdrawal symptoms do occur, they can taneous electrical nerve stimulation (TENS units),
usually be managed with clonidine or low doses of relaxation therapy, guided imagery, art and music
benzodiazepines. Once again, patients and families therapy, and biofeedback, among others. Like med-
should be educated that tolerance and signs of ical therapy, such interventions must be tailored
physiologic dependence (as evidenced by withdrawal according to the individual patient’s plan of care.
symptoms) are not evidence of addiction to opioids. In conclusion, as family doctors begin to
They should be reassured that opioids by themselves encounter increasing numbers of patients with
do not cause psychological dependence or craving, chronic pain, we as a specialty will need to feel more
and that addiction is an extremely rare outcome of comfortable prescribing medications to relieve pain
pain management without a history of substance and suffering. This chapter has illustrated that potent
abuse. Even most patients with prior substance abuse pain medications are in our armamentarium, and
can be given opioids safely for chronic pain, but they the World Health Organization analgesic ladder is a
may need to adhere to strict dosing protocols, and useful tool in helping us guide our therapy. If physi-
contracting may be required. cians prescribe opioids in a prudent and rational
Several medications can be used as adjuvant manner, and patients are monitored carefully for
medications to enhance analgesia and as primary side effects, then we can begin to make a profound
treatments for neuropathic pain. Low-dose tricyclic impact on patients who are currently not receiving
antidepressants, in doses of 10 to 25 mg at night, adequate treatment for their chronic pain.
are a good first choice. Amitriptyline (Elavil) is the
most extensively studied of the tricyclics and can be
especially useful in patients with insomnia. It also
has more anticholinergic and cardiac toxicity than Material Available on Student Consult
other medications in its class, and desipramine
Review Questions and Answers about Metastatic
(Norpramin) and nortriptyline (Pamelor) may be Cancer Pain Management
safer and better tolerated, especially in elderly

SUGGESTED READINGS
Berry PH, Chapman CR, Covington RC, et al., eds. Pain: Emanuel LL, von Gunten CF, Ferris FD, eds. Pain manage-
Current Understanding of Assessment, Management, ment. In The Education for Physicians on End-
and Treatments. Monograph produced jointly by the of-life Care (EPEC) Curriculum. The EPEC Project,
National Pharmaceutical Corporation, and by the The Robert Wood Johnson Foundation, 1999. Available
Joint Commission on Accreditation of Healthcare at www.epeconline.net Accessed 1/18/2006.●C
Organizations, 2001. Available at www.jcaho.org and Levy MH. Pharmacologic treatment of cancer pain. N Engl
www.npcnow.org. Accessed 1/18/2006.●C J Med 1996;335:1124–1132. ●B

216
 C h a p t e r

17 Sore Throat
(Acute Pharyngitis)
Roberto Cardarelli

during the prenatal and delivery course. She is up to

KEY POINTS date with all her immunizations. She has been in the
60th percentile for weight and height all her life. She
1. The most common etiologic agent of acute takes no medications. She has had two episodes of
pharyngitis is a virus. streptococcal pharyngitis in the last 4 years, the last
2. The drug of choice for treating group A episode being 1.5 years ago. She did require tympa-
β-hemolytic streptococcus is penicillin V. nostomy tubes when she was 2 years old because of
3. The most important parts of the diagnostic recurrent middle ear infections.
workup for pharyngitis are a thorough history
and an accurate physical examination. Surgical Tympanostomy tubes at age 2.
4. The heterophil antibody test misses a third of
infectious mononucleosis cases in the first week Family History
of the disease. Both of Leanne’s parents are in good health. Her
5. All patients first seen with pharyngitis should maternal grandmother died at age 62 of breast can-
receive appropriate analgesics, antipyretics, and cer. The rest of her relatives are alive and well.
supportive care.
Social History
Leanne is in 8th grade and is on the honor roll. She
plays volleyball and is a member of a traveling soccer
OFFICE VISIT team. She has never attempted cigarettes or illicit
drugs. She tasted a wine cooler once at her friend’s
Subjective house but never tried any other alcoholic beverage
since. Her father smokes outside the house, and he
Patient Identification and Presenting avoids smoking in the car. She gets along well with
Problem her two older brothers, who are 15 and 17 years old.
Leanne, a 13-year-old girl, complains of a sore throat
and fever, which started abruptly while at her family’s Review of Systems
lake house yesterday. She admits to a decreased Aside from that mentioned earlier, she denies
appetite due to feeling mildly nauseated without vom- abdominal pain, discolored urine, dizziness, nasal
iting or diarrhea. Leanne states that she feels “worn congestion, sinus pressure, or skin rashes. A dry
out” with a slight headache. Her throat is what both- cough developed since this morning.
ers her the most, even swallowing her own saliva. She
also admits that her ears ache. She denies being Objective
around anyone who is sick but privately admits that
she kissed a boy in her class for the first time last week. Vital Signs
Height, 59 in
Medical History Weight, 104 pounds
Allergies No known drug allergies. Temperature, 101.3˚F
Blood pressure, 98/68
Medical Leanne is the youngest and the only girl of Pulse, 96 (regular) beats per minute
three children. Her mother had no complications Respiratory rate, 14 respirations per minute

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

217
 Chapter 17 Sore Throat (Acute Pharyngitis)

Physical Examination 5. She is instructed to return to clinic if she does

General Leanne is a slightly tired-appearing young not improve, if a rash develops, if dark urine is
girl in no acute distress and appropriately dressed. noticed, or if symptoms worsen.

Skin Normal skin turgor and pigmentation. No

rashes are appreciated. DISCUSSION
Head, Eyes, Ears, Nose, and Throat Normocephalic. Pharyngitis is one of the most common medical con-
Eyes are anicteric, and the conjunctivae are clear. Her ditions encountered in ambulatory care offices. It
tympanic membranes are without erythema or fluid accounts for little more than 1% of all office visits in
levels. Nasal mucosa is slightly swollen, and the primary care offices (Cherry et al., 2003). The ulti-
oropharynx shows swollen and erythematous tonsils mate decision that must be made by physicians is
with exudates. Several petechiae are appreciated on whether antibiotics are indicated. A delicate balance
the upper palate and uvula. No sinus tenderness is exists between overprescribing antibiotics, appro-
present. priately ordering diagnostic tests, and preventing
complications from untreated pharyngitis. This is
Neck The thyroid is not palpable. Bilateral promi- accomplished by a taking a good history, completing
nent and tender anterior cervical lymph nodes are an accurate physical examination, and appropriately
palpated. No posterior cervical, pre- or postauricular ordering diagnostic tests.
lymph nodes are appreciated.
Differential Diagnosis
Chest Lungs are clear to auscultation bilaterally.
The numerous causes of pharyngitis are listed in Table
Heart Regular rate and rhythm. No murmurs are 17-1 (Bisno et al., 2002● C ; Kazzi, 2005● B ; Vincent et al.,
appreciated. Pulses are +2 throughout. 2004● B ). Most cases are seen in the late fall/early winter
and early spring (Gerber, 1998● B ). Our discussion
Abdomen Flat, normal bowel sounds, soft and focuses on the infectious causes of pharyngitis, prima-
nontender. No masses are appreciated. No hepato- rily viral and bacterial agents, with an emphasis on
splenomegaly is noted. group A β-hemolytic streptococcus (GABHS).
Viral pharyngitis is the most common type of
pharyngitis (Bisno et al., 2002● C ; Gerber, 1998● B ),
Assessment
with adenovirus and Epstein-Barr virus being two of
Working Diagnosis the more common viral agents. The latter is known
The working diagnosis is acute pharyngitis. to cause infectious mononucleosis (Mono), with
Differential etiology includes group A β-hemolytic signs and symptoms of fever, fatigue and malaise,
streptococcus, viral not otherwise specified (NOS), tonsillar exudates, pharyngitis, posterior cervical
infectious mononucleosis. lymphadenopathy, and occasionally hepatosple-
nomegaly. If patients with Mono are given an anti-
biotic, in 90% of them, a classic maculopapular rash
Plan
will develop (Peter and Ray, 1998● B ). Patients who are
Diagnostic diagnosed with Mono should be instructed to rest
A rapid streptococcal antigen test is ordered and and to avoid any vigorous activities that may place
returns positive. No other tests are ordered. them at increased risk for splenic rupture. Other
viral causes of pharyngitis, such as adenovirus, are
Treatment commonly accompanied by typical symptoms such
1. Leanne is given penicillin V, 500 mg, to take by as rhinorrhea, conjunctivitis, low-grade fever, and
mouth every 8 hours for 10 days, because she malaise (Bisno et al., 2002● C ). Atypical symptoms can
refused the intramuscular injection. include abdominal pain, nausea with or without
2. Over-the-counter analgesics are recommended vomiting, and diarrhea (Middleton, 1996● B ).
for fever and pain. Analgesic throat spray also is Approximately 15% to 30% of pharyngitis cases
mentioned for her consideration. in children are attributable to GABHS, whereas only
3. She is instructed to drink plenty of fluids and to 5% to 15% of adult cases are caused by the bacterium
gargle with warm salt water for symptomatic relief. (Bisno, 2001● C ; Bisno et al., 2002 ● C ; Snow et al.,
4. She is given a school absence note and 2001● C ). The objective in treating GABHS infection is
instructed to avoid sharing utensils and cups to improve symptoms, decrease the spread of disease,
with others. She should take the antibiotic for at and prevent, although rare, life-threatening compli-
least 24 hours before coming into contact with cations, such as rheumatic fever, acute glomeru-
others. lonephritis, and peritonsillar abscesses (Bisno et al.,

218
 Chapter 17 Sore Throat (Acute Pharyngitis)

Table 17-1 Causes of Sore Throat

Infectious Noninfectious
Viruses Gastroesophageal reflux
Adenovirus Neoplasm
Epstein-Barr virus Foreign body
Rhinovirus Dry air
Influenza A and B virus Chemical injury
Coxsackievirus A/B Postnasal drip/allergies
Herpes simplex Smoking
Cytomegalovirus Recent endotracheal intubation
Human immunodeficiency virus Ludwig angina
Bacteria Thyroiditis
Group A β-hemolytic streptococci Retropharyngeal abscess
Group C, G, and F streptococci
Neisseria gonorrhoeae
Corynebacterium diphtheriae
Mycoplasma pneumoniae
Chlamydia pneumoniae
Arcanobacterium haemolyticus
Candidiasis
Epiglottitis
Croup
Peritonsillar abscess/cellulitis

Data from Bisno AL, Gerber MA, Gwaltney JM, et al. Practice guidelines for the diagnosis and management of
group A streptococcal pharyngitis. Clin Infect Dis 2002;35:113–125; Cooper RJ, Hoffman JR, Bartlett JG, et al.
Principles of appropriate antibiotic use for acute pharyngitis in adults: Background. Ann Interm Med 2001;
134:509–517; Kazzi AA, Wills J. Pharyngitis. eMed J. Available at www.emedicine.com/emerg/topic419.htm.
Accessed 8/28/2005.

2002● C ). The most common signs and symptoms of with more than 10% lymphocytes helps support the
GABHS infection include severe pharyngitis with diagnosis (Brigden et al., 1999● A ). The heterophil
tonsillar exudates, anterior cervical lymphadenopa- antibody test (Monospot test) misses one third of the
thy, fever, and palatine petechiae. If untreated, cases in the first week of the disease, but the sensitiv-
GABHS pharyngitis can last for about 7 to 10 days ity increases to 80% by the second week (Brigden
and individuals can be infectious for up to 1 week et al., 1999●
A ). Testing for immunoglobulin M (IgM)
after the acute phase (Ebell et al., 2000● B ; Gerber, antibodies against the Epstein-Barr virus can be used
1998● B ). With treatment, symptoms are shortened by in uncertain circumstances.
1 to 2 days, and the infectious period is reduced to 24
hours (Ebell et al., 2000 ● B ; Snow et al., 2001●C; Group A b-Hemolytic Streptococcus
Vincent et al., 2004● B ). Treatment also prevents most Clinical decision rules have been developed to
complications, although this is unclear for periton- help in accurately diagnosing GABHS pharyngitis
sillar abscesses (Bisno et al., 2002● C ; Snow et al., because no single element in the history or exami-
2001● C ; Vincent et al., 2004● B ). nation is sensitive or specific enough to diagnose or
rule out streptococcal pharyngitis (Gerber, 1998● B ).
Others have supported such an approach (Cooper
Diagnostic Workup
et al., 2001●
C). McIsaac and colleagues (2000●B) devel-
A thorough history and accurate physical examina- oped a scored approach by using five criteria: age,
tion will allow the practitioner to refine his or her dif- tonsillar swelling or exudate, anterior cervical
ferential diagnosis in a matter of minutes. Refractory lymphadenopathy, absence of cough, and fever
cases of sore throat with negative cultures may lead higher than 100.4˚F (Table 17-2). Based on the
the practitioner to consider noninfectious causes, score, patients are placed in the low-, intermediate-,
such as gastroesophageal reflux disease or neoplasm. or high-risk group. Patients in the low-risk group
should not receive treatment and should have no
Infectious Mononucleosis further testing. Those in the high-risk group should
As already discussed, the presenting signs and symp- be given empiric antibiotics, and a throat culture or
toms will help make the diagnosis of Mono. Many rapid streptococcal antigen test or both may be con-
times, the typical presentation of Mono requires no sidered. Patients in the intermediate group should
further testing (Brigden et al., 1999●
A ). A blood count have further testing with the rapid streptococcal

219
 Chapter 17 Sore Throat (Acute Pharyngitis)

antigen test or throat culture or both. All refractory

Table 17-2 Sore Throat Score
cases should have a throat culture performed. It is
Give 1 point for each: advocated that children with a negative rapid strep-
The patient is younger than 15 years tococcal antigen test should have the result con-
Tonsillar swelling or exudates firmed by a throat culture (Bisno et al., 2002● C ). A
Tender anterior cervical lymphadenopathy negative rapid streptococcal antigen test does not
Temperature >100.4˚F require confirmation by a throat culture in adults
Absence of cough (Bisno et al., 2002 ●
C ). The rapid streptococcal anti-
Subtract 1 point if:
gen test has an approximate sensitivity of 95% and
The patient is older than 45 years
specificity of 97% (Vincent et al., 2004● B ). The throat

Scoring culture has an approximate sensitivity of 97% and

−1 to 0 Low risk: Antibiotic therapy, rapid specificity of 99%, depending on the technique and
strep test, and throat culture are medium used (Vincent et al., 2004● B ).
not indicated.
1 to 3 Intermediate risk: Perform rapid
strep test and treat accordingly. If
Therapy
rapid strep test is negative, All patients initially seen with pharyngitis should
consider throat culture for children. receive appropriate analgesics, antipyretics, and
4 to 5 High risk: Empiric antibiotics. Rapid
supportive care, such as gargling with warm salt
strep test and/or culture is optional.
water (Snow et al., 2001● C ). Precautions should be

Data from Bisno AL, Gerber MA, Gwaltney JM, et al. discussed with all patients, especially those with
Practice guidelines for the diagnosis and infectious mononucleosis, about the risk of splenic
management of group A streptococcal rupture. Duration of symptoms should be discussed
pharyngitis. Clin Infect Dis 2002;35:113–125; Ebell to give patients a realistic expectation of when the
MH, Smith MA, Barry HC, et al. The rational
clinical examination: Does this patient have strep symptoms will improve.
throat? JAMA 2000;284:2912–2918; Snow V, Appropriate antibiotic choices for treating
Mottur-Pilson C, Cooper RJ, Hoffman JR. Principles GABHS should have a narrow spectrum of action
of appropriate antibiotic use for acute pharyngitis that includes GABHS. Options for treatment are
in adults. Ann Intern Med 2001;134:506–508; and
Vincent MT, Celestin N, Hussain AN. Pharyngitis.
shown in Table 17-3 (Bisno at al., 2002● C ; Cooper

Am Fam Physician 2004;69:1465–1470; McIssac WJ, et al., 2001● C ; Hayes and Williamson, 2001● B ; Kazzi,
Goel V, To T, Low DE. The validity of a sore throat 2005● B ). Penicillin is the preferred antibiotic when it
score in family practice. CMAJ 2000;163:811–815.

Table 17-3 Antibiotic Choices for Group A β-Hemolytic Streptococcus

Antibiotic Pediatric Dose Adult Dose Frequency Duration

Penicillin V 250 mg 500 mg Three times daily 10 days

Benzathine 600,000 units 1,200,000 units One IM injection —
penicillin
Amoxicillin 13.3 mg/kg/dose 500 mg Three times daily 10 days
Ampicillin 12.5 mg/kg/dose 500 mg Four times daily 10 days
Amoxicillin-clavulanate 20 mg/kg/dose 875 mg Two times daily 10 days
potassium
Erythromycin 10 mg/kg/dose 400 mg Four times daily 10 days
ethylsuccinate
Azithromycin 12 mg/kg/dose 500 mg on
day 1 and
250 mg on
days 2–5 Once daily 5 days
Cephalexin 6.25–12.5 mg/kg/dose 250 mg Four times daily 10 days

IM, intramuscular.
Data from Bisno AL, Gerber MA, Gwaltney JM, et al. Practice guidelines for the diagnosis and management of
group A streptococcal pharyngitis. Clin Infect Dis 2002;35:113–125; Cooper RJ, Hoffman JR, Bartlett JG, et al.
Principles of appropriate antibiotic use for acute pharyngitis in adults: Background. Ann Intern Med
2001;134:509–517; Hayes CS, Williamson H. Management of group A beta-hemolytic streptococcal pharyngitis.
Am Fam Physician 2001;63:1557–1564; and Kazzi AA, Wills J. Pharyngitis. eMed J. Available at
www.emedicine.com/emerg/topic419.htm. Accessed 8/28/2005.

220
 Chapter 17 Sore Throat (Acute Pharyngitis)

is indicated (Cooper et al., 2001● C ). Erythromycin tant to remember that avoiding the indiscriminate
should be considered in someone with a penicillin use of antibiotics will help avoid antimicrobial resist-
allergy (Cooper et al., 2001●
C ). Penicillin can be given ance and limit the risks of allergic reactions.
in two ways; orally with penicillin V, 250 to 500 mg,
three or four times per day for 10 days, or intramus-
cularly with benzathine penicillin, 1.2 million units
(adults) in one dose. Material Available on Student Consult
Patients can follow-up as necessary and should Review Questions and Answers about Acute
be instructed to return immediately to the clinic if Pharyngitis.
symptoms worsen or are not improving. It is impor-

REFERENCES
Bisno AL. Acute pharyngitis. N Engl J Med 2001;344: Gerber MA. Diagnosis of group A streptococcal pharyngi-
205–211.● B tis. Pediatr Ann 1998;27:269–273.●
B
Bisno AL, Gerber MA, Gwaltney JM, et al. Practice guidelines Hayes CS, Williamson H. Management of group A beta-
for the diagnosis and management of group A strepto- hemolytic streptococcal pharyngitis. Am Fam Physician
coccal pharyngitis. Clin Infect Dis 2002;35:113–125.●C 2001;63:1557–1564.● B
Brigden ML, Au S, Thompson S, et al. Infectious mononu- Kazzi AA, Wills J. Pharyngitis. eMed J. Available at
cleosis in an outpatient population: Diagnostic utility www.emedicine.com/emerg/topic419.htm. Accessed
of 2 automated hematology analyzers and the sensitiv- 8/28/2005.
ity and specificity of Hoagland’s criteria in heterophile- McIsaac WJ, Goel V, To T, Low DE. The validity of a sore
positive patients. Arch Pathol Lab Med 1999;123: throat score in family practice. CMAJ 2000;163:
875–881.● A 811–815.● B
Cherry DK, Burt CW, Woodwell DA. National Ambulatory Middleton DB. Pharyngitis. Prim Care 1996;23:719–739.● B
Medical Care Survey: 2001 Summary. Adv Data 2003; Peter J, Ray CG. Infectious mononucleosis. Pediatr Rev
337:1–44. 1998;19:276–279.● B
Cooper RJ, Hoffman JR, Bartlett JG, et al. Principles Snow V, Mottur-Pilson C, Cooper RJ, Hoffman JR.
of appropriate antibiotic use for acute pharyngitis Principles of appropriate antibiotic use for acute
in adults: Background. Ann Intern Med 2001;134: pharyngitis in adults. Ann Intern Med 2001;134:
509–517.● C 506–508.● C
Ebell MH, Smith MA, Barry HC, et al. The rational clinical Vincent MT, Celestin N, Hussain AN. Pharyngitis. Am Fam
examination: Does this patient have strep throat? Physician 2004;69:1465–1470.● B
JAMA 2000;284:2912–2918.● B

221
 C h a p t e r

18 Nasal Congestion
(Allergic Rhinitis)
David Q. Hutcheson-Tipton

Medical History
KEY POINTS Alice was diagnosed with eczema as a baby but has
had no further skin problems. She had a tonsillec-
1. Allergic rhinitis is common. It exacts a heavy toll tomy at age 5 years and an extraction of her wisdom
in lost work and school days. teeth as a teenager but no other surgeries. She had a
2. Diagnosis is usually based on clinical picture normal spontaneous vaginal delivery of one child.
but, if in doubt, can be clarified by radioaller-
gosorbent test or skin testing. Family History
3. The cornerstone of treatment is avoidance Her brother, 25 years old, had asthma as a child. In a
(at least minimization) of allergens. maternal aunt, breast cancer developed at age 60
4. Medicinal treatment may involve intranasal years. She is not aware of any family history of aller-
steroids, oral antihistamines, and deconges- gies or eczema. Besides her brother, no other family
tants, among others. members have had asthma.

Social History
Alice works as a local convenience store manager. She
INITIAL VISIT lives in a two-bedroom apartment with her 12-year-
old daughter and a kitten given to them about a
Subjective month ago by a co-worker. She does not use tobacco
in any form, drinks one to two alcoholic beverages
Patient Identification and Presenting weekly, and denies use of recreational drugs. She
Problem runs several miles most evenings with a friend.
Alice is a 36-year-old woman with complaints of
nasal congestion and a frequent need to blow her Review of Systems
nose. Alice denies fever, chills, night sweats, unintended
weight loss, nausea, vomiting, diarrhea, and consti-
Present Illness pation. She denies a change in her senses of smell and
Alice relates that her rhinorrhea and nasal conges- taste or any dyspnea, wheezing, chest pain, or chest
tion had a gradual onset 3 weeks ago. At the time, tightness. She denies sore throat and heartburn. She
she thought she was catching a cold, but the symp- also denies feelings of increased or decreased energy,
toms lasted longer than her usual cold. They have hair or skin changes, or changes in bowel habits. On
neither improved nor worsened during that time. questioning, she admits that her nose has been rather
She has had no fever, malaise, or general achiness. itchy lately. She denies that her eyes have been either
Neither has she had a sore throat, more than rare itchy or watery.
cough, or headache. She denies using an over-the-
counter intranasal decongestant. She tried diphen- Objective
hydramine (Benadryl), and although it relieved her
symptoms some, she found herself too drowsy when Physical Examination
taking it, even if she took it only once a day before General Alice is a pleasant, well-developed, well-
bedtime. nourished woman who appears her stated age. She

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

222
 Chapter 18 Nasal Congestion (Allergic Rhinitis)

often rubs her nose with the side of her hand and but skin testing for allergies is negative. Intranasal
occasionally clears her throat during the office visit. steroids are quite helpful.
3. Acute rhinosinusitis often is first seen with rhinor-
Vital Signs Blood pressure, 122/84; heart rate, 75; rhea and nasal congestion as prominent symp-
respirations, 14 per minute; temperature, 98.4˚F; toms. Most often, sinusitis is a complication of
height, 5 feet 8 inches; weight, 130 pounds; peak expi- allergic rhinitis or a viral respiratory infection (or
ratory flow rate, 540. both) and has as cardinal symptoms headache,
sore throat, and cough. The latter two symptoms
Head, Eyes, Ears, Nose, and Throat Her external are often worse at night, as the sinuses drain best
auditory canals are clear. Both tympanic membranes when the body is in a supine position. Antibiotics
are slightly retracted but without erythema: They are the cornerstone of therapy.
move easily to pneumatic otoscopy. Her oropharynx 4. Vasomotor or idiopathic rhinitis occurs without
is cobblestoned without visible exudate. Her nasal any eosinophilia. Allergic skin testing is negative.
turbinates are boggy and somewhat pale. Some Ipratropium bromide (Atrovent), the 0.03% solu-
watery discharge is visible on the walls of her nares. tion, is helpful, as at times are intranasal steroids,
No sinus tenderness to palpation is noted. Her neck is oral decongestants, regular nasal saline washes, or
supple and without palpable lymphadenopathy or a combination of these.
thyromegaly. 5. Hormonal rhinitis. Hypothyroidism can cause rhi-
norrhea: This etiology should always be consid-
Lungs Both lungs are clear to auscultation, with ered with an atypical presentation. Rhinitis also is
good air movement. quite common in late pregnancy and, if particu-
larly bothersome, can be treated with oral decon-
Heart Her heart has a regular rate and rhythm with- gestants (these should generally be avoided in the
out adventitious sounds. first trimester). Some women, at certain times in
the menstrual or life cycles (or both), have hor-
Skin Her skin appears and feels normal except for monal rhinitis (Howarth, 2003● C ).
some mild dryness in the antecubital areas of her arms. 6. Rhinitis medicamentosa is a problem that occurs
with overuse of over-the-counter intranasal
Assessment decongestants, the most popular being oxymetaz-
oline. Such agents are extremely effective and can
Working Diagnosis have a place in the treatment of various forms of
Allergic rhinitis. rhinitis. Patients should be warned against using
them for more than 3 days at a time, however,
Differential Diagnosis as rebound congestion can be worse than the
1. Infectious rhinitis is generally viral in origin, from original.
an upper respiratory tract infection. It is often 7. Other etiologies include sinus polyps, other
accompanied by rhinorrhea and nasal conges- anatomic problems such as septal deviation, and
tion. Many people—patients, even some physi- complications of certain head and neck surgeries
cians—believe that yellow nasal discharge (American Academy of Allergy, Asthma and
(so-called purulent rhinitis) is invariably a sign Immunology, 2005● C ).
of a sinus infection. Many people during the
course of the common cold have at least one day Plan
of this symptom; should a computed tomogra-
phy (CT) scan of their sinuses be obtained at that Diagnostic
time, it might even show radiologic sinusitis (i.e., No laboratory, radiologic, or other diagnostic evalu-
opacification of one or more of the paranasal ation is needed at this time. A medication trial with
sinuses). This does not mean they need good response will be helpful. Alice should also
antibiotics: The vast majority will pass quickly notice any increase in symptoms on exposure to sus-
through this phase and get better. Should the pected offending allergens—in her case, her cat.
purulence last more than several days, however,
the diagnosis of rhinosinusitis likely to be Therapeutic
responsive to antibiotic therapy should be Several options are discussed with her, and the
strongly considered (American Academy of patient chooses a trial of an intranasal steroid once
Allergy, Asthma, and Immunology, 2005● C ). daily. Adverse effects are discussed.
2. Eosinophilic nonallergic rhinitis is a year-round
(perennial) rhinitis; congestion is the predomi- Patient Education
nant symptom. A nasal smear shows numerous Alice is encouraged to try to identify and avoid, as
eosinophils (as it does with allergic rhinitis [AR]), much as possible, triggers for her symptoms. The

223
 Chapter 18 Nasal Congestion (Allergic Rhinitis)

temporal relation of having a cat in her residence ticular times of year when specific airborne allergens
with subsequent onset of her symptoms cannot be (aero-allergens) are present (such as tree pollen in the
overlooked: It strongly suggests that her leading (or spring, grass pollen in midsummer, and weeds in
sole) allergen is cat dander. Animal dander contains autumn). In perennial AR, the patient is allergic to one
many allergenic proteins in and on the skin of the or more stimuli that are always present (airborne par-
animal, which is sloughed off on a continual basis. In ticles from dust mites, decomposed cockroaches, ani-
the case of cats, who groom themselves so fastidi- mal dander). Both types can coexist. Allergic rhinitis of
ously, a protein in their saliva adheres to their skin either variety also results in a hypersensitivity of the
and becomes airborne. The protein is among the nasal mucosa to many nonspecific stimuli such as
most allergenic known. smoke, smells, and changes in temperature or humid-
Because a good chance exists that Alice is aller- ity. Symptoms then occur on exposure to these stimuli.
gic to her new kitten, she is advised to bathe it Details of the history are exceedingly important
weekly, a measure that reduces the quantity of dan- in diagnosing AR (American Academy of Allergy,
der that becomes airborne. She should also keep the Asthma and Immunology, 2005● C ). Rhinorrhea,
animal out of her bedroom. sneezing fits, pruritus of the nose and eyes, nasal
congestion, and a sensation of “sinus pressure” are
Disposition common. It is a strong clue if symptoms worsen on
The patient is instructed to return to or phone the the patient’s encounter with specific allergens—
clinic should her symptoms worsen or fail to when she or he is around a dog, for instance—or at
improve within the next week to 10 days. An certain times of the year.
appointment in a month is made to review the effec- The physician begins the physical examination
tiveness of the steroid. the moment he or she walks into the room. The
patient with AR may sniffle, rub or blow the nose
frequently, and clear the throat or sneeze or both.
DISCUSSION Specific examination of the head, eyes, ears, nose,
and throat, of course, yields the most information.
Allergic rhinitis (AR) is an inflammation of the nasal When AR is active, tympanic membranes are often
mucosa and is caused by several chemicals, including retracted (from swelling of pharyngeal tissues where
leukotrienes and histamine, the latter mediated by the eustachian tubes drain). Eyes can be injected or
immunoglobulin E (IgE) released from the degranu- watery or both if allergic conjunctivitis is present.
lation of mast cells (Howarth, 2003 ● C). It is basically Sometimes periorbital edema with a bluish hue is
the body trying to reject harmless airborne sub- seen, causing the so-called allergic shiners. Nasal
stances (e.g., pollen, mold, animal dander) that it mucosa may be swollen. Turbinates may be pale and
should ignore. boggy, with clear drainage. The oropharynx is often
AR is extremely common, affecting approxi- injected and sometimes “cobblestoned” from post-
mately 40 million people in the United States. Its nasal drip. The neck is supple but may have some
importance is often underestimated by the general (reactive) shotty lymphadenopathy. Lungs should be
public as well as by physicians. It has significant mor- evaluated for signs of possible asthma (e.g., wheez-
bidity, yearly causing millions of days of school and ing). Skin can be observed by vision and palpation
work to be lost (American Academy of Allergy, for dryness or lichenification, which can occur with
Asthma and Immunology, 2005● C ). atopic dermatitis.
Alone or with allergic conjunctivitis—a dual Most frequently for the family physician, the
presentation is common—AR is one of the three diagnosis of AR is a clinical one, based on presenta-
common atopic (allergic) disorders, the other two tion and examination. If the symptom cluster
being atopic dermatitis (eczema) and asthma. The responds to appropriate treatment for allergies, no
tendency to atopy is strongly heritable, making a need exists for further assessment (American
family (or personal) history of any one or a combi- Academy of Allergy, Asthma and Immunology,
nation of these problems extremely relevant (such a 2005● C ). An argument can be made (and is at times
history is not by any means essential to diagnosing by allergists) for universal testing of patients with AR
this problem). An atopic diathesis can evolve into signs and symptoms. This is usually not necessary,
actual symptoms at any time in the life cycle, though, for a family physician. If doubt remains
although it is usually before adulthood. Symptoms about the etiology of rhinitis, allergic testing can be
also can vanish for a while—the patient “grows out done. A simple, rapid test is to obtain a specimen
of ” the disease or moves to an area with different of nasal secretions and apply Hansel’s stain. If
allergens—only to return. eosinophils are present, the differential diagnosis is
Traditionally, AR has been categorized into two narrowed to either AR or nonallergic eosinophilic
types: seasonal and perennial. In the seasonal variety, rhinitis. Polymorphonuclear lymphocytes point to
popularly called “hay fever,” symptoms appear at par- an infectious etiology.

224
 Chapter 18 Nasal Congestion (Allergic Rhinitis)

A more frequently used and still quite expedient consequences, including motor vehicle collisions
and relatively inexpensive form of testing is the (Casale et al., 2003 ●
C ).
radio-allergosorbent test (RAST), in which circulat- “Second-generation” antihistamines are much
ing antibodies to substances are detected. Although preferred now. Both fexofenadine (Allegra), either 60
RASTs will often demonstrate reactivity to, say, cer- mg twice daily or 180 mg daily for adults, and lorata-
tain pollens or molds, if the tests are negative, aller- dine (Claritin)—10 mg daily for adults and children
gies are not ruled out. Allergists usually perform skin 6 years old and older—are nonsedating (the only
testing, which is more accurate. Here the clinician antihistamines approved by the Federal Aviation
applies solutions containing small amounts of Administration for pilots). Cetirizine (Zyrtec) is
substances that represent classes of allergens (e.g., sedating to some. Its usual dose is 5 to 10 mg daily for
pollen, mold, trees) to small breaks in the skin cre- adults and children 6 and older; 2.5 mg daily for
ated by small needle pricks. When a patient is aller- children age 2 to 5 years.
gic to a substance, the skin at the application site Decongestants are often used to treat the con-
swells and develops an area of surrounding redness gestion that often accompanies AR (American
(the so-called wheal and flare effect). Academy of Allergy, Asthma and Immunology,
Minimizing, preferably eliminating, exposure to 2005 ●C ). The most common one is pseudoephedrine
identified or suspected allergens is the cornerstone of (Sudafed), the adult dose of which is 60 mg every
AR treatment. Washing a pet weekly and keeping it 6 hours. It also comes in a slow-release 12-hour ver-
out of the bedroom will help reduce exposure. Many sion (120 mg) that often causes less-pronounced
people with perennial AR are allergic to decomposing sympathomimetic effects such as restlessness, dry
dust mites that live in bedding. Covering pillow and mouth, and palpitations. Pseudoephedrine is avail-
mattress with plastic or tightly woven cloth, as well as able in numerous preparations in combination with
washing all bedding and bed clothes at least weekly in various antihistamines.
hot water, will reduce exposure to this common aller- Another decongestant used is topical: oxymeta-
gen. If pollens are offenders, keeping windows closed zoline (Afrin). The usual dose is two sprays in each
and using a HEPA filter can help. Likewise with mold nostril, twice daily. As mentioned earlier, patients
from the outside; indoor mold can be reduced by should not use these for more than 3 to at most 5
dehumidification and minimization of carpeting. days, or they risk rebound congestion.
Several medicinal options exist. Intranasal Other treatments are available but much less
steroids are recommended as first-line medication by frequently used. They include intranasal antihista-
the International Board for the Treatment of Allergic mines, cromolyn sodium and ipratropium; nasal
Rhinitis (Ledgerwood and Johnson, 2002). Several saline; and montelukast (Singulair) (can be particu-
versions are available. They are all used once or twice larly useful when congestion is a targeted symptom).
daily. Although many patients will have some relief A short course of oral corticosteroids is rarely given
sooner, it is important to warn that the maximal (prednisome 50 mg daily for 5 to 10 days) to relieve
effectiveness is usually not reached for 2 to 3 weeks. severe symptoms rapidly.
Most common side effects are local: sneezing, epis- Finally, for selected patients, allergic immuno-
taxis, or bad taste. Pretreatment with nasal saline therapy (AIT)—so-called allergy shots—may be
may help attenuate these. appropriate. AIT requires quite a time commitment
The most popular type of medications are oral (usually 3 to 5 years). It works approximately two
antihistamines. The “first-generation” antihistamines— thirds of the time. Although a few family physicians
those like hydroxyzine (Atarax) and diphen- do this (along with prior diagnostic skin testing) in
hydramine (Benadryl)—are not used nearly as their offices, this therapy is usually considered in
frequently as before. Although they are inexpensive consultation with and administered by an allergy
in comparison to their successors, their side-effect specialist.
profile is high. Sedation is a particularly bothersome
effect, with growing evidence that even when these Material Available on Student Consult
medications are taken at bedtime, daytime attention
Review Questions and Answers about Allergic
may be impaired, leading to decreased performance
Rhinitis
in school or work or both, as well as more serious

REFERENCES
American Academy of Allergy, Asthma and Immunology. Casale TB, Blaiss MP, Gelfand E, et al. First do no harm:
The Allergy Report: Science-Based Findings on the Managing antihistamine impairment in patients
Diagnosis and Treatment of Allergic Disorders. with allergic rhinitis. J Allergy Clin Immunol 2003;
Available at www.theallergyreport.org. Accessed 111:S835–S842. ●C
9/9/2005.●
C

225
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

Howarth PH. Allergic and nonallergic rhinitis. In Scadding GK. Corticosteroids in the treatment of pediatric
Adkinson NF, Yunginger JW, Busse WW, et al. (eds): allergic rhinitis. J Clin Allergy Immunol 2001;108
Middleton’s Allergy: Principles and Practice, 6th ed. (1 Suppl):S59–S64. ● C
Philadelphia, Mosby, 2003, pp 1391–1393. ●C
Ledgerwood GL, Johnson RL. Allergy. In Rakel R (ed):
Textbook of Family Practice, 6th ed. Philadelphia, WB
Saunders, 2002, pp 473–493.

C h a p t e r

19 Fever and Fussiness in a

22-Month-Old Child
(Acute Otitis Media)
John G. O’Handley

INITIAL VISIT
KEY POINTS

1. Ear pain has many causes. Subjective

2. A definite diagnosis of acute otitis media Patient Identification and Presenting
(AOM) requires (1) a history of sudden onset,
Problem
(2) evidence of inflammation, and (3) evidence
Hannah R. is a 22-month-old child with a 2-day his-
of middle ear effusion (MEE).
tory of fever, fussiness, crying, and decreased
3 The age of the patient and the severity of the
appetite. The child has also been pulling at her left
disease dictate the use of antimicrobials and
ear, and when asked by her mother if it hurt, Hannah
length of treatment of AOM.
nodded in the affirmative. Three days previously,
4. It can take as long as 3 months for MEE to
Hannah had a runny nose.
gradually resolve.
5. MEE may be monitored without treatment Present Illness
in patients not at risk for speech or hearing Hannah’s mother phoned the office this morning
problems. after a night of very little sleep for both mother and
6. Antibiotics, decongestants, and antihistamines daughter. She has been giving the child liquid aceta-
do not accelerate MEE resolution. minophen every 4 hours, but the fever and fussiness
7. Referral to an otolaryngologist for pressure- returned before the medication was due again.
equalization tubes should be accompanied by Hannah has eaten some juice and milk but has not
documentation of hearing loss and length of eaten solid food for 2 days. The family had been at a
time MEE has persisted. family reunion 6 days earlier, and some of the chil-
dren there had been sick with colds.

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

226
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

Howarth PH. Allergic and nonallergic rhinitis. In Scadding GK. Corticosteroids in the treatment of pediatric
Adkinson NF, Yunginger JW, Busse WW, et al. (eds): allergic rhinitis. J Clin Allergy Immunol 2001;108
Middleton’s Allergy: Principles and Practice, 6th ed. (1 Suppl):S59–S64. ● C
Philadelphia, Mosby, 2003, pp 1391–1393. ●C
Ledgerwood GL, Johnson RL. Allergy. In Rakel R (ed):
Textbook of Family Practice, 6th ed. Philadelphia, WB
Saunders, 2002, pp 473–493.

C h a p t e r

19 Fever and Fussiness in a

22-Month-Old Child
(Acute Otitis Media)
John G. O’Handley

INITIAL VISIT
KEY POINTS

1. Ear pain has many causes. Subjective

2. A definite diagnosis of acute otitis media Patient Identification and Presenting
(AOM) requires (1) a history of sudden onset,
Problem
(2) evidence of inflammation, and (3) evidence
Hannah R. is a 22-month-old child with a 2-day his-
of middle ear effusion (MEE).
tory of fever, fussiness, crying, and decreased
3 The age of the patient and the severity of the
appetite. The child has also been pulling at her left
disease dictate the use of antimicrobials and
ear, and when asked by her mother if it hurt, Hannah
length of treatment of AOM.
nodded in the affirmative. Three days previously,
4. It can take as long as 3 months for MEE to
Hannah had a runny nose.
gradually resolve.
5. MEE may be monitored without treatment Present Illness
in patients not at risk for speech or hearing Hannah’s mother phoned the office this morning
problems. after a night of very little sleep for both mother and
6. Antibiotics, decongestants, and antihistamines daughter. She has been giving the child liquid aceta-
do not accelerate MEE resolution. minophen every 4 hours, but the fever and fussiness
7. Referral to an otolaryngologist for pressure- returned before the medication was due again.
equalization tubes should be accompanied by Hannah has eaten some juice and milk but has not
documentation of hearing loss and length of eaten solid food for 2 days. The family had been at a
time MEE has persisted. family reunion 6 days earlier, and some of the chil-
dren there had been sick with colds.

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

226
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

Medical History available tools have been used. In one study the
Hannah is the product of a term vaginal delivery and prevalence of true AOM by AAP/AAFP criteria was
has received all her appropriate immunizations. She only 70% among clinicians in a variety of settings
has had colds in the past but has never been given any (Rosenfeld, 2002● A ). In the presence of an uncertain
antibiotics. Developmental milestones are normal. diagnosis, the physician must base his decision for
treatment on knowledge of the patient and the relia-
Social History bility of the patient’s family to return for follow-up.
Hannah is the only child of her parents, Katie and
Brendan R. Neither parent smokes. The child does Differential Diagnosis
not attend day care. Because middle ear inflammation and effusion cause
pressure in a closed space, ear pain is invariably pres-
Review of Systems ent (Table 19-1). It is not always easy to distinguish
Respiratory, gastrointestinal, genitourinary, and different types of ear pain, especially when the
integumentary system reviews are noncontributory. patient does not speak. Therefore, the clinician must
separate the possible sources of ear pain. Sources of
pain from the external ear include otitis externa or
Objective
swimmer’s ear. These are identified by pulling back
Physical Examination on the external ear or applying pressure over the tra-
Hannah appears to be alert and well nourished. She gus. A foreign body in the external ear can also cause
clings to her mother in the examination room and pain, and this is diagnosed by direct visualization of
cries when put on the examination table. Her height the canal. Ear pain can also be caused by furunculo-
is 34 inches, and her weight is 28 pounds, which puts sis of the external canal, which is diagnosed by direct
her in the 75th percentile. Her temperature is visualization. Inflammation of the TM itself without
102.2˚F. Her cheeks are flushed, but no rash is MEE can be the cause of pain and is referred to as
observed on any part of her body. The right ear canal myringitis or tympanitis. In addition, a choles-
is impacted with cerumen, but the left tympanic teatoma, although slow growing, can eventually lead
membrane (TM) is erythematous and bulging into to ear pain.
the canal. The nose is illed with yellowish-white Pain arising from the middle ear is not always
mucus, but the mouth is moist and the throat is clear. AOM. Barotrauma can be diagnosed from a recent
The neck is supple with some shotty jugulodigastric history of deep-sea diving or airplane travel. Acute
nodes present. The lungs are clear to auscultation, eustachian tube obstruction also can lead to pain and
and the heart is regular in rate and rhythm. The will eventually result in MEE. Acute mastoiditis and
abdomen is soft except when the child cries, and no extradural abscess, although rare in the antibiotic
masses are palpated. era, must be considered when the origin of the ear
pain remains uncertain. Table 19-1 also lists the
Assessment
Working Diagnosis
The working diagnosis is acute otitis media (AOM) Table 19-1 Differential Diagnosis of Ear
following an upper respiratory infection. Three crite- Pain
ria are needed to make a diagnosis of AOM: (1) signs
and symptoms with an abrupt onset, (2) the presence Referred from
of a middle ear effusion (MEE), and (3) signs or External Ear Middle Ear Elsewhere
symptoms of middle ear inflammation (American
Otitis externa Acute otitis Sinusitis
Academy of Pediatrics/American Academy of Family (OE) media Pharyngitis/
Practice [AAP/AAFP], 2004● C ). MEE is present with
Foreign body Barotrauma tonsillitis
decreased mobility of the TM, bulging of the TM, an Trauma Acute TMJ syndrome
air/fluid level visible behind the TM, or pus draining Furunculosis eustachian Tonsillar cancer
from the middle ear space. Middle ear inflammation Impacted tube Trigeminal
is noted by erythema of the TM or ear pain that dis- cerumen obstruction neuralgia
rupts sleep or normal activities. The erythema of Tympanitis/ Acute Elongated
AOM must be distinguished from the erythema myringitis mastoiditis styloid process
caused by crying. The latter does not cause bulging Cholesteatoma Extradural (Eagle’s
of the TM. Tympanometry can be used to detect abscess syndrome)
Dental abscess
MEE when the physician is unsure of the presence of
Cervical disk
MEE. Pneumatic otoscopy can also aid in the diag- disease
nosis of MEE. Often the diagnosis in infants and
young children remains unconfirmed, even after all TMJ, temporomandibular joint.

227
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

causes of ear pain referred from other areas of the be changed. In the case of uncertain diagnosis when the
head and neck; these sources of pain must be patient is being observed without antimicrobial therapy,
included in the differential diagnosis when faced continuation of symptoms or fever would necessitate
with ear pain in the presence of a normal ear exam. adding antimicrobial therapy. It is important to deter-
mine whether the patient’s caregiver is reliable and can
Plan afford the prescribed medication. Instructing the care-
giver to call the office in 2 to 3 days, regardless of initial
Diagnostic treatment or subsequent outcome, will improve the like-
Direct visualization of the left ear reveals a bulging lihood of proper follow-up. Resolution of MEE can take
erythematous TM. The condition of the TM, the his- up to 3 months, so scheduling a return visit sooner than
tory of acute onset after an upper viral infection, and 4 weeks is not cost effective.
a fever of 102.2˚F fulfill the three criteria necessary to
make a diagnosis of AOM: (1) history of sudden Disposition
onset, (2) MEE (bulging TM), and (3) signs or symp- Hannah’s parents are asked to call back in 2 days to
toms of middle ear inflammation (redness and fever) assess the therapy and to make an appointment in
(Table 19-2). There is no need for tympanometry or 6 weeks to have Hannah evaluated for MEE.
pneumatic otoscopy in this case. There is no need to
remove the cerumen in the right canal to observe the
right TM because it would not alter the therapy. DISCUSSION
Therapeutic Diagnosis
The management of pain in a patient, although often
Each patient is different in presentation of illness and
looked on as peripheral, must be addressed. The
response to therapy and must be treated individually.
parents must be instructed to give acetaminophen
However, a subcommittee on management of otitis
or ibuprofen for mild to moderate pain because
media of the American Academies of Pediatrics and
this is strongly recommended and evidence based
Family Practice (AAP/AAFP, 2004● C ) examined an
(AAP/AAFP, 2004● C ). Topical benzocaine (Auralgan,
extensive body of literature and recommended
Americaine Otic) can provide additional, but brief, guidelines that can assist clinicians in their decision-
relief and can be administered to the affected ear, 2–4 making process. The first recommendation is to
drops three or four times daily as needed. With a cer- establish the diagnosis of AOM. Acute onset, pres-
tain diagnosis of AOM in a child 6 months to 2 years, ence of MEE either by visualizing a bulging TM,
use of an antibacterial agent is recommended. In a otorrhea, or an air/fluid level behind the TM or using
child who is not penicillin allergic, the first-line tympanometry or pneumatic otoscopy; and signs
choice of antimicrobial is amoxicillin in a dose of 80 and symptoms of middle ear inflammation by red-
to 90 mg/kg/day divided two or three times daily. The ness of the TM or distinct otalgia are the require-
higher dose of amoxicillin improves the cure rate, ments for a certain diagnosis.
especially in light of increasing Streptococcus pneumo-
niae resistance to penicillin in younger age groups.
Treatment
Patient Education In an effort to decrease the cost and side effects of
It is important to inform the patient’s caregiver to report medicine and to diminish the emergence of resistant
any pain or fever that continues after 2 to 3 days. bacteria, a 2- to 3-day period of observation is recom-
Persistent pain and fever could indicate that the organ- mended in children older than 2 years if the three
ism is resistant to the chosen antibiotic, which must then criteria are not satisfied. In that same age group,
antimicrobial treatment may be withheld if the
child has a temperature less than 102.2˚F and only
mild pain (Table 19-3). The choice of antimicrobial is
Table 19-2 Definition of Acute Otitis based on many factors including the severity of the ill-
Media ness, the age of the patient, penicillin allergy, and local
1. Acute onset of signs and symptoms experience with resistant organisms. The three main
2. The presence of middle ear effusion organisms at which antimicrobial therapy is aimed are
3. Signs or symptoms of middle ear inflammation Streptococcus pneumoniae, Haemophilus influenzae,
and Moraxella catarrhalis. The incidence of these
Adapted from American Academy of Pediatrics, pathogens in AOM is 25% to 50% for S. pneumoniae,
American Acedemy of Family Physicians. Sub-
committee on Management of Acute Otitis
15% to 30% for nontypeable H. influenzae, 3% to 20%
Media. Diagnosis and management of acute for M. catarrhalis, and 5% to 22% for viruses. By age
otitis media. Pediatrics 2004;113:1451–1465. 12 months, 70% of children are colonized by at least

228
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

H. influenzae and M. catarrhalis, respectively (Sinus

Table 19-3 Criteria for Initial Treatment and Allergy Health Partnership, 2000● C ). Risk factors
or Observation of Acute affecting the resistance of bacteria to antimicrobials
Otitis Media in Children are attending day care, receiving antimicrobials within
Age Certain Dx Uncertain Dx the previous 30 days, and age younger than 2 years.
When the child is penicillin allergic, other
<6 mo Antibiotics Antiobiotics therapies must be used, depending on whether the
6 mo to 2 yr Antibiotics Antibiotics if reaction was type 1 (urticaria or anaphylaxis) or
severe illness;
non-type 1 (Table 19-4). If the child is vomiting, cef-
otherwise,
observe triaxone can be given in a dose of 50 mg/kg/day (up
>2 yr Antibiotics if Observe to 1 g IM), for 3 consecutive days.
severe; When symptoms and signs persist after an initial
otherwise, treatment with amoxicillin, amoxicillin/clavulanate
observe (Augmentin ES-600) in a dose of 90 mg/kg/day of
the amoxicillin component divided every 12 hours
From American Academy of Pediatrics, American (Table 19-5). If the child had severe AOM and was
Acedemy of Family Physicians. Subcommittee on
Management of Acute Otitis Media. Diagnosis first treated with amoxicillin/clavulanate but that
and management of acute otitis media. Pediatrics therapy failed, then either ceftriaxone in the previ-
2004;113:1451–1465. ously mentioned dose or clindamycin in a dose of 8
to 25 mg/kg/day in three or four doses for 5 to 10
days may be given orally.
one of these three pathogens. During viral upper res- The duration of treatment also has been studied
piratory infections, colonization with these organisms from an evidence-based perspective, and for children
increases dramatically (Sinus and Allergy Health 6 years and older with mild to moderate disease, a 5-
Partnership, 2000● C ). Amoxicillin is still the first choice to 7-day course is appropriate. For children 5 years or
to treat these pathogens, with a dose of 80 to 90 mg/ younger or for any child with severe disease, as
kg/day in two or three doses per day. With severe AOM defined earlier, a 10-day course is advised.
(temperature greater than 102.2˚F or moderate to There is no evidence supporting the use of com-
severe otalgia), amoxicillin/clavulanate (Augmentin plementary or alternative medicine for treatment of
ES-600) in a dose of 90 mg/kg/day of the amoxicillin AOM (AAP/AAFP, 2004● C ).

component in two divided doses is recommended.

About 29% of S. pneumoniae are not susceptible to
Risk Factors
penicillin because of alteration of penicillin-binding
proteins. The mechanism of resistance in H. influenzae A number of risk factors in the etiology of AOM can
and M. catarrhalis is β-lactamase production, and cur- be altered, reducing the chance of illness (Table 19-6).
rently resistance rates are running 40% and 98% for Breastfeeding children during the first 6 months of

Table 19-4 Antimicrobial Therapy in Pediatric Penicillin-allergic Patients

Drug Dosage

Non–type 1 Reaction
Cefdinir (Omnicef) 14 mg/kg/day (to a maximum of 600 mg/day) in one or
two doses
Cefpodoxime (Vantin) 10 mg/kg/day (to a maximum of 400 mg/day) every 12 hr
Cefuroxime (Ceftin) 30 mg/kg/day (to a maximum of 100 mg/day) in two doses

Type 1 Reaction (Urticaria or Anaphylaxis)

Azithromycin (Zithromax) 10 mg/kg/day on day 1 and then 5 mg/kg/day for 4 days
in a single dose or 10 mg/kg/day every 24 hr for 3 days
Clarithromycin (Biaxin) 15 mg/kg/day in two doses for 5 to 10 days
Erythromycin/sulfasoxazole (Pediazole) 50 mg/kg/day in three to four doses for 5 to 10 days
Sulfamethoxazole/trimethoprim (Bactrim) 5 ml susp./10kg (up to 20 mL) per dose po bid for 5 to
10 days
Ceftriaxone (Rocephin) 50 mg/kg/day (up to 1 g) for 3 consecutive days, IM or,
if vomiting, IV
Clindamycin (Cleocin) 8–25 mg/kg/day in three or four doses for 5 to 10 days

229
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

language, or learning problems and to intervene even

Table 19-5 Treatment after Initial Failure before 3 months. Such children include those with
Treatment after Initial Failure on Amoxicillin Down syndrome, autism, visual impairment, cleft
Amoxicillin/ clavulanate (Augmentin ES-600): palate, developmental delays, and permanent hear-
90 mg/kg/day of amoxicillin in two doses for ing loss independent of MEE. Management of these
5 to 10 days at-risk children includes speech and language evalu-
ation and hearing tests. Interventions include hear-
Treatment after Failure on Amoxicillin/ ing aids, tympanostomy tube insertion, and repeated
Clavulanate
Ceftriaxone (Rocephin): 50 mg/kg/day up to 1 g IM
hearing testing after the resolution of MEE. Little
in a single dose for 3 consecutive days harm occurs in watchful waiting for children not at
Clindamycin (Cleocin): 8–25 mg/kg/day in three or risk for speech, language, or learning problems. In
four doses for 5 to 10 days the past, physicians have used antihistamines and
decongestants, antimicrobials, and corticosteroids.
But current evidence strongly suggests that these
treatments are not efficacious in the long run and are
Table 19-6 Preventable Risk Factors for certainly not recommended for routine management
Acute Otitis Media (Williamson, 2002● C ). The tendency to “do some-

Day care attendance

thing” must be avoided in healthy children with per-
Bottle feeding for the first 6 mo of life sistent MEE. Despite modest short-term benefits
Supine bottle feeding (“bottle propping”) from antimicrobials in persistent MEE, long-term
Pacifier use in the second 6 mo of life benefits have not been proven (Williamson, 2002● C ).
Passive tobacco smoke The side effects of antimicrobials also warrant avoid-
ance of this therapy in healthy children with persist-
ent MEE. Children not at risk may be monitored at
3-month intervals with hearing tests to determine
Table 19-7 Non preventable Risk Factors the effect of MEE (AAFP/AAO-HNS/AAP, 2004● C ). If
for AOM the hearing test shows 40 dB or more loss in the
Premature birth affected ear, immediate referral to an otolaryngolo-
Native American/Inuit ethnicity gist is recommended. If the decibel loss is between
Genetic predisposition 21 and 39 (mild hearing loss), the physician has the
Male gender option of surgery referral or continuing to monitor
Siblings in the household the patient at 3- to 6-month intervals. The choice is
Low socioeconomic status determined on an individual basis and in concert
with a full discussion of the options with the
patient’s parents. A hearing loss of 20 dB or less may
life helps prevent early episodes of AOM. Altering require repeated hearing evaluation and assessment
day-care attendance patterns in infancy and early for MEE in 3 to 6 months. If the clinician believes the
childhood can decrease the number of respiratory child needs a referral to an otolaryngologist, he or
infections and significantly reduce the incidence of she should document the episode of AOM and the
recurrent AOM. It is not as clear whether avoiding length of time that the MEE has persisted. The results
pacifier use, “bottle propping,” and passive tobacco of hearing tests also must be communicated to the
smoke also decrease the incidence of AOM, but some referral physician. Explaining to the parents that
evidence supports these measures. The benefit of many alternatives exist for the management of per-
pneumococcal conjugate vaccines in preventing sistent MEE and that surgery is not necessarily the
AOM is small, but some studies have shown a 6% desired outcome will help facilitate the referral from
reduction in the incidence of AOM. Risk factors that the parents’ perspective as well. Persistent MEE in
cannot be altered are listed in Table 19-7. children younger than 3 years without risk factors
does not require immediate insertion of PE tubes
because developmental outcomes do not differ when
Natural History of MEE
the procedure is postponed for 6 months (Paradise,
MEE resolves slowly after the middle ear fluid 2001● A ). For children at risk (Table 19-8), surgical
becomes sterile. Antimicrobials will eliminate bacte- intervention may occur earlier to prevent the seque-
ria in the middle ear in 2 to 3 days. By 2 weeks, 30% lae of persistent MEE. When PE tubes become the
to 40% of MEE will be resolved, and by 1 month, recommended procedure, adenoidectomy should
60% of MEE will be cleared. Even at 3 months, it is not be performed unless nasal obstruction from the
possible to have 10% to 25% of patients with MEE adenoids or chronic adenoiditis is seen. Twenty per-
(AAFP/AAO-HNS/AAP, 2004● C ). It is important for cent to 50% of children will have recurrence of MEE
the clinician to identify children at risk for speech, after the PE tubes come out, and in those cases

230
 Chapter 19 Fever and Fussiness in a 22-Month-Old Child (Acute Otitis Media)

years the killed and live-attenuated intranasal

Table 19-8 Risk Factors for influenza vaccines in children older than 2 years have
Developmental Difficulties been shown to reduce the incidence of AOM by 30%
in Children with Persistent during the cold season. With further research the diag-
Middle Ear Effusion nosis and treatment of AOM will continue to evolve.
Permanent hearing loss independent of OME More antimicrobials are prescribed for AOM
Suspected or diagnosed speech and language than for any other childhood infection in the United
delay or disorder States. In 2000 the total number of office visits for
Autism–spectrum disorder and other pervasive otitis media was 16 million, and for these visits 13
developmental disorders million prescriptions were written. In the United
Syndromes (e.g., Down) or craniofacial disorders States, infants in the first year of life average 1.2
that include cognitive, speech, and language
delays
episodes of AOM and 1.1 episodes in the second
Blindness or uncorrectable visual impairment year of life (Baumer, 2004). The direct and indirect
Cleft palate with or without associated syndrome costs of this infection approach $3 billion per year. A
Developmental delay large percentage of these visits are to family physi-
cians, so it is important that physicians feel confi-
OME, Otitis media with effusion. dent diagnosing and treating this common problem.
Adapted from American Academy of Family
Physicians, American Academy of Otolaryngology- The guidelines given here are meant to help the
Head and Neck Surgery, American Academy of practitioner choose a course of action when he or
Pediatrics. Subcommittee on Otitis Media with she is unsure of how to proceed. Part of the impetus
Effusion. Otitis media with effusion. Pediatrics for these guidelines has been the emergence of
2004;113:1412–1429.
resistant strains of organisms causing AOM, making
judicious and proper use of antimicrobials impor-
adenoidectomy plus myringotomy with or without tant for society in general. As practitioners benefit-
PE tube placement should be used. In the case of a ing from experience in our own practice and
child with cleft palate and recurrent MEE, ade- information provided to us, we can continue to offer
noidectomy is not recommended. On average, the PE medical care that is grounded in evidence-based
tubes remain in position for 12 to 14 months and knowledge and affords our patients the latest in
provide ventilation to the middle ear during that medical advances.
time.

Material Available on Student Consult

Conclusion
Review Questions and Answers about Acute Otitis
In addition to the decreased incidence of AOM from
Media
the use of pneumococcal conjugate vaccines, in recent

REFERENCES
American Academy of Family Physicians, American Academy Paradise JL, Feldman HM, Campbell TF, et al. Effect of
of Otolaryngology-Head and Neck Surgery, American early or delayed insertion of tympanostomy tubes for
Academy of Pediatrics (AAFP/AAO-HNS/AAP). Sub- persistent otitis media on developmental outcomes at
committee on Otitis Media with Effusion. Otitis media the age of three years. N Engl J Med 2001;344:
with effusion. Pediatrics 2004;113:1412–1429.●
C 1179–1187.● A
American Academy of Pediatrics, American Academy of Rosenfeld RM. Diagnostic certainty for acute otitis media.
Family Physicians. Subcommittee on Management of Int J Pediatr Otorhinolaryngol 2002;64:89–95.● A
Acute Otitis Media. Diagnosis and management of Sinus and Allergy Health Partnership. Antibacterial treat-
acute otitis media. Pediatrics 2004;113:1451–1465.●C ment guidelines for acute bacterial rhinosinusitis.
Baumer JH. Comparison of two otitis media guidelines. Otolaryngol Head Neck Surg 2000;123:525–531.● C
Arch Dis Child Educ Pract Ed. 2004;89:ep76–ep78. Williamson I. Otitis media with effusion. Clin Evid
Dowell SF, Marcy SM, Phillips WR, Gerber MA, Schwartz B. 2002;7:469–476.● C
Otitis media: Principles of judicious use of antimicro-
bial agents. Pediatrics 1998;101:165–171.●A

231
 C h a p t e r

20 Hiccups

Stephen G. Cook

Surgical History
KEY POINTS Alice had two children by cesarean section. She also
had a laparoscopic cholecystectomy 3 years before
1. More than 100 causes of hiccups have been presentation.
identified.
2. Patients who present with hiccups should be Family History
evaluated thoroughly for underlying pathology. Her father died of myocardial infarction at age 54.
3. No treatment method has proven to be effec- Her mother is alive at 81 but has diabetes and hyper-
tive by evidence-based criteria. tension. Two brothers also have hypertension but are
4. Treatment should address the underlying cause in otherwise good health.
when one can be identified.
Social History
She smokes two packs of cigarettes per day. She
drinks a few glasses of wine several times a week. She
INITIAL VISIT lives with her husband of 31 years, who is also a
smoker.
Subjective
Review of Systems
Patient Identification and Presenting She reports a chronic cough that is the worst in the
Problem morning and seems to have worsened in the past
Alice B. is a 56-year-old African-American woman year. She says she has lost 10 pounds in the past
who complains of continuous hiccups for the past 2 months. She has had no recent acute illnesses and
6 weeks. She states they have been unremitting, mak- feels generally well.
ing it difficult for her to sleep at night and interrupt-
ing meals as well because of their frequency. She Objective
has ried a number of home remedies suggested by
friends and family, including drinking water with her Physical Examination
head upside down, holding her breath, and having Alice is a very pleasant woman who appears some-
friends surprise her by popping a paper bag loudly, what older than her stated age.
but none of these have been successful.
Vital Signs Her temperature is 36.9˚C (98.5˚F),
Medical History blood pressure is 142/86, pulse is 100 and regular,
Alice has mild hypertension, for which she takes respiratory rate is 16, weight is 135 pounds, and
atenolol daily. She has been a two-pack-per-day height is 67 inches.
smoker since age 15, although she states that she is
trying to cut back. Chronic obstructive pulmonary Skin Leathery skin with deep creases and wrinkles
disease was diagnosed 5 years ago, and she uses a around her eyes and mouth but warm and well
steroid inhaler daily as well as ipratropium and perfused.
albuterol inhalers when breathing difficulties
worsen. She had a negative treadmill test 1 year ago Head, Eyes, Ears, Nose, and Throat Tympanic mem-
after an episode of chest pain and has never had a branes are unremarkable. Teeth are yellow stained
heart attack. but without significant caries; tongue is mildly

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

232
 Chapter 20 Hiccups

yellow stained as well. No other abnormalities of Technically, hiccups are an involuntary spasmodic
oropharynx or nares. contraction of the diaphragm followed by sudden
closure of the glottis, which causes the characteristic
Neck No thyromegaly; shotty nontender adenopathy hiccup sound. The hiccup reflex arc consists of the
in posterior and anterior cervical chains. vagus and phrenic nerves, as well as the sympathetic
chain arising from T6-12. Irritation of the phrenic
or vagus nerves anywhere along their course is
Lungs Hiccups noted with a frequency of one per thought to result in spasm of the diaphragm and
5 to 10 seconds. Distant breath sounds with faint external intercostal muscles (Schiff et al., 2002).
end-expiratory wheezes but no rales or rhonchi. The However, central nervous system abnormalities, tox-
expiratory phase is notably prolonged, with an inspi- ins, drugs, and metabolic disorders can lead to hic-
ratory:expiratory ratio of 1:3. cups as well, possibly by removing inhibitory
control of an inspiratory nucleus in the brain
Heart Regular rate and rhythm; no murmurs, gallops (Moretti et al., 2004● B).
or rubs. More than 100 causes of hiccups have been
identified, most of which are gastrointestinal (Box
Abdomen Nondistended abdomen with minimal 20-1). Gastroesophageal reflux disease is perhaps the
amount of subcutaneous fat. Normal bowel sounds. most frequently identifiable cause. A full medication
No masses or hepatosplenomegaly. No tenderness to list is essential in working up this problem. In fact,
palpation or percussion. many of the same drugs used to treat hiccups can
also cause them. Hiccups have also been described as
a complication following surgery, including laparo-
Neurologic Alert, pleasant female in no apparent scopic procedures such as Nissen fundoplication. Of
distress. Speaks in full sentences except as inter- the more sinister possible causes, head/neck and
rupted by her hiccups. chest or mediastinal masses may impinge on the
phrenic or vagus nerves. Appropriate imaging stud-
Extremities Yellow-stained fingers; thinly muscled ies to look for these should be used (Smith and
arms and legs with normal distal pulses. Busracamwongs, 2003● B).

Plan
Assessment
Diagnostic
Working Diagnosis Alice is classified as having intractable hiccups. Her
Hiccups are an extremely common malady, affecting medications (atenolol, inhaled steroids, ipratropium,
all ages from newborns to the very elderly. The med- and albuterol) are unlikely to be causal. She has a his-
ical term for hiccups is singultus, although it is prob- tory of laparoscopic abdominal surgery, but Alice’s
ably best to refer to this common disorder by its hiccups arose long after surgery. While her physical
common name. While quite annoying, they most examination does not immediately reveal a cause,
often are a benign and self-limited problem. Patients she has a number of physical signs consistent with
normally do not present for medical attention for her long-term tobacco use; therefore, further evalua-
hiccups unless the occurrence is quite prolonged. tion of her chest and lungs is indicated.
“Acute hiccups” are episodes up to 48 hours in A complete metabolic panel is normal. A chest
duration. “Persistent hiccups” are defined as those radiograph reveals that Alice has a mass obscuring
lasting longer than 2 days. Episodes lasting longer the right hilum. She is referred for bronchoscopy and
than 1 month are termed “intractable hiccups” biopsy, which reveals squamous cell carcinoma aris-
(Viera and Sullivan, 2001● B). Although hiccups ing from the right mainstem bronchus.
themselves are benign, prolonged cases of hiccups
have been associated with other morbidity including Therapeutic
weight loss, exhaustion, insomnia, anxiety, and even As hiccups are predominantly a symptom rather
suicide (Schiff et al., 2002); cases of aspiration pneu- than an illness in themselves, therapy is first directed
monia and respiratory arrest have been described toward treating an underlying cause if one can be
(Moretti et al., 2004 ● B). Because intractable hiccups identified. Due to the size of the tumor at the time of
can be an indication of severe underlying disease, presentation, Alice is referred to oncology, where she
patients presenting with this complaint should be is scheduled to begin chemotherapy and radiation
evaluated thoroughly. treatment to shrink the tumor.
Despite their prevalence, understanding of both Treatment options for the hiccups themselves are
the cause and purpose of hiccups remains limited. numerous, but it should be noted that no treatment

233
 Chapter 20 Hiccups

Box 20-1 Partial List of Causes of Hiccups

Gastrointestinal Causes Central Nervous System Diseases

Gastroesophageal reflux disease Stroke
Gastric distention or insufflation Arteriovenous malformation
Esophageal or small bowel obstruction Cerebral contusion or hematoma
Excessive food or alcohol intake Temporal arteritis
Sudden change in gastric temperature Encephalitis or meningitis
Aerophagia Neurosyphilis
Multiple sclerosis
Tumor Masses, Benign or Malignant Hydrocephalus
Head/neck tumors, including goiter
Infectious Diseases
Mediastinal masses
Lung/chest masses Psychogenic Causes
Other Causes
Metabolic Causes
Laparoscopic surgery
Diabetes mellitus
Laryngeal mask airway insertion
Hyponatremia
Foreign body in external ear canal
Hypocalcemia
Epidural steroid injection
Addison’s disease
Uremia
Idiopathic Causes
Medications/Toxins
Neuroleptics
Corticosteroids
Benzodiazepines
Alcohol
Tobacco use

method has been proven effective by evidence-based success (Viera and Sullivan, 2001●
B ). These include a
criteria, and no one treatment has been shown to be wide range of drug classes:
better than another. The literature is rife with thera- 1. Neuroleptics such as haloperidol (Haldol) or
pies ranging from drug treatments to acupuncture chlorpromazine (Thorazine)
(Schiff et al., 2002). One case report even indicates 2. Anticonvulsants including phenytoin (Dilantin),
sexual intercourse may be a treatment for chronic gabapentin (Neurontin), and valproate
intractable hiccups (Peleg and Peleg, 2000). (Depakote)
Most patients have tried a wide range of home 3. Gastrointestinal motility drugs like metoclo-
remedies before presentation. Most home remedies pramide (Reglan)
seem to work by either stimulating the nasophar- 4. Antihypertensives, especially nifedipine (Procardia)
ynx or by disrupting the normal respiratory cycle: 5. Muscle relaxants such as baclofen (Lioresal)
Drinking ice water, breath holding, and being
spooked all are part of the popular repertoire, as Case reports of other medications being used
are a variety of Valsalva maneuvers. Others, like include lidocaine by IV infusion or nebulizer,
breathing in and out of a paper bag, seem to work atropine, and methylphenidate (Ritalin) (Moretti
in part because hiccups decrease as CO2 rises. Still et al., 2004●
B). In the most severe cases, surgical man-
others, like drinking out of the far side of a glass, agement such as phrenic nerve interruption or the
are based on little but folklore (Viera and Sullivan, placement of diaphragmatic pacemakers has been
2001● B ). used. (Viera and Sullivan, 2001● B).
Once the patient presents for assistance, some
simple in-office efforts, such as elevating the uvula Patient Education
with a cotton-tipped applicator or stimulating the Again, information should primarily attend to the
nasopharynx with a rubber catheter, may be success- underlying cause if one is identified. If medications
ful. If these fail, numerous medications have been are used to treat hiccups, patients should be aware of
used to treat hiccups, all with varying degrees of the potential side effects of the agent being

234
 Chapter 20 Hiccups

employed. For instance, if neuroleptic drugs are tumor surrounding her bronchus. Thus, treatment
used, patients should be aware of normal concerns options are limited while the tumor continues to
for extrapyramidal side effects. affect the nerves. It is possible that if chemotherapy
and radiation are successful in shrinking her
tumor, her hiccups might be alleviated. If they per-
FOLLOW-UP VISIT sist, surgical ligation of the phrenic nerve may be
considered.
Subjective
Alice returns to clinic after her first week of Plan
chemotherapy. She continues to report persistent
Alice says she is desperate to get rid of her hiccups.
hiccups. She has lost an additional 5 pounds and still
She is started on gabapentin (Neurontin), 400 mg
is unable to sleep through the night. She says that she
orally three times per day for 3 days, then reduced
thinks the hiccups are worse than the effects of
to 400 mg orally once daily, based on case reports
chemotherapy.
of success with this in neurologic patients
(Moretti et al., 2004●B ). She understands that this
Objective treatment is not based on proven efficacy by nor-
mal standards and is informed of possible side
Alice appears visibly more fatigued, with dark circles
effects.
under her eyes. Aside from her weight decreasing to
130 pounds, her examination is unchanged.

Assessment Material Available on Student Consult

Alice’s hiccups are most likely caused by direct Review Questions and Answers about Hiccups
irritation of the phrenic and vagus nerves by the

REFERENCES
Moretti R, Torre P, Antonello RM, Ukmar M, Cazzato G, Schiff E, River Y, Oliven A, Odeh M. Acupuncture therapy
Bava A. Gabapentin as a drug therapy of intractable for persistent hiccups. Am J Med Sci 2002;323:166–168.
hiccup because of vascular lesion: A three-year follow Smith HS, Busracamwongs A. Management of hiccups in
up. Neurologist 2004;10:102–106.● B the palliative care population. Am J Hospice Palliative
Peleg R, Peleg A. Case report: Sexual intercourse as poten- Care 2003;20:149–154.● B
tial treatment for intractable hiccups. Can Fam Viera A, Sullivan SA. Remedies for prolonged hiccups. Am
Physician 2000;46:1631–1632. Fam Physician 2001;63:1684–1685.● B

235
 C h a p t e r

21 Fever without Source in

Children (Fever)
Jennifer E. Lochner

went home from the hospital on day 2 of life. This is

KEY POINTS the first health problem that she has encountered in
her life. She has not yet had any vaccinations and is
1. Although most infants and young children with exclusively breast-fed.
fever without source have a self-limited viral
infection, a significant minority have a serious Family History
bacterial infection (SBI) as the cause of their Zoe has no siblings. Her father has hypothyroidism,
illness. and her mother has no medical problems.
2. Guidelines exist to help guide choice of evalua-
tion and management of febrile children.
Social Hstory
3. It is the physician’s task, in collaboration with
Zoe lives at home with her parents and two pet cats.
the child’s parents, to determine a child’s risk of
No one in the home smokes. She is cared for by her
an SBI and move forward with an evaluation
parents and is not in day care. There are no ill contacts.
that balances the goal of not missing an SBI
with the goal of not subjecting children to inva-
sive testing unless it is necessary. Review of Systems
4. Where this balance lies depends on individual Zoe’s father has not noted any apparent difficulties
physician, patient, and parental factors that with breathing. Zoe frequently spits up a small amount
interact in complex ways. Communication is key of breast milk after eating; this is unchanged from
to finding this balance and achieving everyone’s usual. There is no bilious vomiting or diarrhea.
desired outcome of healthy children.
Objective
Physical Examination
INITIAL VISIT General Zoe is an alert and interactive infant who is
fussy with examination but easily consolable by her
Subjective father.
Patient Identification and Presenting
Vital Signs Her blood pressure is 86/42, pulse is 110,
Problem
respiratory rate is 32, rectal temperature is 38.6˚C
Zoe W. is a 5-week-old infant brought in by her
(101.5˚F), and weight is 5.1 kg (11.2 pounds).
father for evaluation of fever. He first noted that
she felt “warm” a few hours ago. He took her
temperature with a tympanic thermometer and Head, Eyes, Ears, Nose, and Throat Her anterior
found it to be 38.2˚C (100.7˚F). Dad reports that fontanelle is soft and open, and her pupils are equal,
she seems somewhat more fussy than usual but oth- round, and reactive to light; there is no nasal dis-
erwise is acting normally (eating well with the usual charge. Her posterior pharynx has no redness or
number of wet and dirty diapers per day). He has exudate.
noted no cough, nasal congestion, or rash.
Neck There is no cervical lymphadenopathy.
Medical History
Zoe was the product of an uncomplicated pregnancy Heart The heart has a regular rate and rhythm with-
and spontaneous vaginal delivery at 39 weeks. She out murmur.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

236
 Chapter 21 Fever without Source in Children (Fever)

Lungs The lungs are clear to auscultation bilaterally. These studies showed variable utility of guidelines
such as the Rochester criteria (Table 21-1) in identi-
Abdomen Soft; bowel sounds are present. The abdomen fying which febrile young infants are at lowest risk
is nontender and nondistended with no mass. of SBI. The percentage of infants classified in the
lowest risk group who were eventually found to have
Extremities Extremities are warm, with capillary an SBI varied from 0.4% to 6.4% (Baker and Bell,
refill less than 2 seconds at the fingers and toes. 1999● B ; Chiu et al., 1994● B ; Ferrera et al., 1997● B;
Kadish et al., 2000● B ). Because of this variability and
Neurology Zoe moves all four extremities. the potentially serious risk in missing an SBI, there is
general agreement that all febrile infants age 28 days
Skin No rash is noted. and younger should have a full evaluation for SBI
including admission to the hospital for cerebrospinal
Assessment fluid, blood, and urine cultures, with coverage with
parenteral antibiotics while awaiting culture results
Working Diagnosis (Baraff et al., 1993●C ). This is true regardless of how
Fever without source in a 5-week-old infant. well the infant may appear, whether the infant meets
all the low-risk criteria, and whether the infant has
signs and symptoms of a less serious source of infec-
DISCUSSION tion (e.g., upper respiratory infection, otitis media).
A slight variation in this recommendation comes
Evaluation of Infants and Children from Jaskiewicz et al. (1994● B ) who, based on the

Younger than 36 Months of Age with results of their study, propose this evaluation, but
Fever without Source with careful inpatient observation without par-
enteral antibiotics while awaiting culture results for
Fever is defined as a rectal temperature of 38˚C infants age 28 days and younger who meet all the
(100.4˚F) or higher. Other methods of measuring Rochester criteria for low risk of SBI. These options
temperature (oral, axillary, tympanic) are not accu- are included in Figure 21-1.
rate measures of core body temperature and there- Older infants (28 to 90 days old) are the next
fore are considered not to be sufficiently reliable to group considered. In this age group, the Rochester
assess for fever in infants and children. Fever without criteria discussed previously have also been used to
source refers to an acute febrile illness in which the identify infants at low risk of SBI. With fewer reports
etiology of the fever is not apparent after a careful of infants meeting low-risk criteria being found to
history and physical examination. have an SBI (and those eventually found to have an
With an SBI constituting a low percentage of the SBI subsequently doing well after an initial delay in
causes of fever in infants and children, many other treatment), options exist as to the management of
causes are more likely. Viruses are by far the most this group of patients (Baraff et al., 1993● C ). Parent
likely culprit. Some viruses are easily identified by and physician level of concern and acceptability of
their clinical syndrome (e.g., varicella), but most have risk guide the approach to evaluation rather than a
nonspecific syndromes and some appear only to cause strict set of guidelines. An aggressive strategy identi-
fever. Self-limited febrile illnesses that have no source cal to that described for infants 28 days and younger
identified are presumed to have been viral in nature. (admission to the hospital for cerebrospinal fluid,
The main goal of evaluation of infants and young blood, and urine cultures, with coverage with par-
children with fever is to distinguish those with mild enteral antibiotics while awaiting culture results) can
self-limiting illness from those with SBIs (meningitis, also reasonably be used in infants 28 to 90 days old.
sepsis, bone and joint infection, urinary tract infec- Alternatively, if a patient meets all the Rochester cri-
tion, pneumonia, enteritis). This is more difficult than teria described in Table 21-1, less aggressive strategies
in older children and adults due to the failure of clin- may be used. The first option is blood, urine, and
ical signs and symptoms alone in reliably differentiat- cerebrospinal fluid cultures with parenteral antibi-
ing these two groups (Baker et al., 1990● B ). Younger otics but with outpatient rather than inpatient fol-
children also have a higher incidence of SBI than their low-up. A second option is urine culture only with
older counterparts. It is these two principles that form no empirical antibiotics, also with close outpatient
the underlying basis for the guidelines that follow. follow-up. The physician must feel comfortable
The youngest classification of febrile infants with the parent’s ability to adhere to the close moni-
includes those age 28 days and younger. They appear toring and follow-up needed before a less aggressive
to be at highest risk of SBI with studies showing that strategy for management is chosen. Infants who do
7% to 16% of febrile infants in this age category to not meet low-risk criteria should be evaluated
have an SBI (Baker and Bell, 1999 ● B ; Chiu et al., aggressively with hospital admission, cultures, and
1994 ● B ; Ferrera et al., 1997 ●
B ; Kadish et al., 2000●B ). empirical antibiotics while awaiting culture results.

237
 Chapter 21 Fever without Source in Children (Fever)

Nontoxic young infant with fever

Previously healthy, nontoxic young infant (<3 months of age)
with a temperature of 38⬚C without source

>28 days of age ≤28 days of age

Admit infant to hospital for

blood and urine cultures,
lumbar puncture, and
parenterally administered
antibiotics.
Consider low-risk criteria (see Table 21-1):
Previously healthy Alternatively, if the risk of
Generally well apperance serious bacterial infection is
No focal infection on exam low (see Table 21-1), consider
WBC 5000–15,000 per mm3 admission and observation
Absolute band count of <1500 per mm3 without antibiotic therapy
Normal urine microscopy pending culture results.
If diarrhea, <5 WBCs per high-power
field on microscopic examination of
stool

Infant does not meet low- Infant meets low-risk criteria.

risk criteria

Admit infant to hospital for

blood and urine cultures, Option 1: Blood and urine culteres, lumbar Option 2: Urine culture
lumbar puncture, and puncture, parenterally administered antibiotics. and careful observation
parenterally administered
antibiotics.
Re-evaluate infant within 24 hours

Figure 21-1 Algorithm for the management of nontoxic young infants with a temperature of 38˚C (100.4˚F) without
source. (Modified with permission from Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the management
of infants and children 0 to 36 months of age with fever without source. Pediatrics 1993;92:1–12.)

Remember also that included in the Rochester crite- parts of developing significant sequelae including
ria are the results of evaluations including white sepsis and meningitis. Children with higher fevers
blood cell count (WBC) and urinalysis, so none of and higher WBCs are at higher risk. Although these
these recommendations include decision making facts help guide decision making, controversy exists
based on clinical appearance alone. See Figure 21-1 over the optimal management of these children. In
for an algorithm of the above. evaluating fever without source in this age group,
temperature is the first factor used in deciding fur-
Evaluation of Children Age 3 Months ther evaluation. In children with a temperature
lower than 39˚C (102.2˚F) and no focus of infection
to 3 Years with Fever without Source
identified on a careful physical examination, no ini-
Children age 3 months to 3 years with fever without tial tests or antibiotics are indicated if the child
source are at lower risk than their younger counter- appears well. If fever persists or the child has

238
 Chapter 21 Fever without Source in Children (Fever)

sample results in a negative culture, this is considered

Table 21-1 Rochester Criteria for
adequate in ruling out a urinary tract infection
Identifying Febrile Infants at
(American College of Emergency Physicians Clinical
Low Risk of Serious Bacterial
Policies Committee: American College of Emergency
Infection
Physicians Clinical Policies Subcommittee on
Infant appears generally well Pediatric Fever, 2003●B).
Infant has been previously healthy
Born at term (≥37 weeks’ gestation) Urinalysis Versus Urine Culture
No perinatal antimicrobial therapy For children younger than 2 years old, urinalysis has
No treatment for unexplained not been shown to be sensitive enough to rule out
hyperbilirubinemia urinary tract infection. As many as 10% to 50% of
No previous antimicrobial therapy
patients eventually shown to have a urinary tract infec-
No previous hospitalization
No chronic or underlying illness
tion (by urine culture) had a negative urinalysis. Urine
Not hospitalized longer than mother microscopy also has inadequate sensitivity in ruling
Infant has no evidence of skin, soft-tissue, bone, out urinary tract infection (American College of
joint, or ear infection Emergency Physicians Clinical Policies Committee:
Infant has these laboratory values American College of Emergency Physicians Clinical
White blood cell count 5000–15,000/mm3 Policies Subcommittee on Pediatric Fever, 2003● B). For
Absolute band count ≤1500/mm3 this reason urine culture is necessary to determine
≤10 white blood cells per high-power field on whether a child younger than age 2 years has a urinary
microscopic examination of the urine tract infection.
≤5 white blood cells per high-power field on
microscopic examination of stool in infant
with diarrhea
Utility of a Chest Radiograph
In the absence of signs or symptoms of respiratory
infection, it is highly unlikely that a chest radiograph
will be abnormal in children younger than 3 months
worsening symptoms, re-evaluation is necessary. of age (Bramson et al., 1993● B ). It has been reported
With temperatures higher than 39˚C (102.2˚F), in children older than 3 months, however, that a
options for evaluation are more complicated and are small but significant percentage of children without
outlined in Figure 21-2 (Luszczak, 2001). Urinary respiratory signs or symptoms but with tempera-
tract infections are a significant cause of fever with- tures higher than 39˚C (102.2˚F) and a WBC count
out source in this age group, and urine culture is of more than 20,000 have occult pneumonia as the
recommended in male infants younger than 6 source of their illness (Bachur et al., 1999● B ). A chest
months old and female infants younger than 2 years radiograph should be considered in this group of
old because these are the highest risk groups for uri- patients but is not necessary in the evaluation of chil-
nary tract infections. In making the decision as to dren younger than 3 months who do not have signs
whether blood cultures and/or empirical antibiotics or symptoms of respiratory illness.
are indicated, the WBC count may be of assistance.
It remains an option to obtain blood cultures and Other Issues
empirically treat all children aged 3 months to Toxic Appearance Toxic-appearing infants and chil-
3 years with fever higher than 39˚C (102.2˚F) with dren are those who appear lethargic and have signs of
parenteral antibiotics. Another option is to use the poor perfusion, hypoventilation, hyperventilation,
cutoff of a WBC of less than 15,000 to identify chil- or cyanosis. They constitute a separate category and
dren at lower risk of SBI in whom it is reasonable to warrant immediate and intensive evaluation and
not obtain these studies. Both groups of children either treatment aimed at an identifiable cause of ill-
require close follow-up (within 24 to 48 hours) to ness or empirical antibiotic therapy while awaiting
identify any localizing signs of infection or clinical culture results.
deterioration (Baraff et al., 1993●C ).
Children with Chronic Illnesses Another category of
Issues in Diagnostic Evaluation of children not addressed thus far are those with known
Children with Fever chronic illnesses (e.g., congenital heart disease, cystic
fibrosis, human immunodeficiency virus disease).
Method of Obtaining Urine Such children are at much higher risk of SBI and com-
Urethral catheterization and suprapubic aspiration plications from infections and therefore warrant
are the best methods for obtaining urine for use in aggressive evaluation and treatment of febrile illnesses.
evaluation of the infant or child with fever. Bag col-
lection of urine results in an unacceptably high false- Persistent Fever In some cases, a fever may persist
positive rate on urine culture. If, however, a bag urine without a source being identified. Fever of unknown

239
 Chapter 21 Fever without Source in Children (Fever)

Nontoxic infant or young child with fever

Previously healthy, nontoxic infant or child (3 months to 3 years of age)
with a fever without source

Temperature ≥39⬚C Temperature <39⬚C

Careful physical
examination to identify
1993 practice guideline (Baraff et al.): Recent recommendations: potential focal infection
Urine culture in males <6 months Urine culture in all infants
old and females <2 years old and children <2 years of age No tests or antibiotics if
who are prescribed empiric infant or young child
Chest radiograph if there is dyspnea, antibiotics looks well and no
tachypnea, rales, or decreased breath bacterial source is
sounds Consider chest radiograph if identified
infant or child is
Stool culture if blood and mucus in asymptomatic and has a Antipyretics as needed
the stool or there are >5 WBCs per WBC > 20,000 per mm3
high-power field on microscopic Follow-up: re-evaluation
examination of the stool if fever persists more than
48 hours or condition
Blood culture: deteriorates
Option 1: all children with a
temperature >39⬚C
Option 2: all children with a
temperature >39⬚C and a WBC count
>15,000
Empiric antibiotic therapy (e.g.,
ceftriaxone 50 mg per kg IM or IV):
Option 1: all children with a
temperature >39⬚C
Option 2: all children with a
temperature >39⬚C and WBC count
>15,000

Follow-up: within 24-48 hours

Figure 21-2 Algorithm for the management of nontoxic infants and young children with fever without source.
(Modified with permission from Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the management of infants
and children 0 to 36 months of age with fever without source. Pediatrics 1993;92:1–12.)

origin is a specific term referring to a fever whose Effect of Newer Vaccines on the Risk of Serious
source has not been identified after 3 weeks of Bacterial Infection in Children Until recently, the
evaluation in the outpatient setting or 1 week of eval- types of bacteria most commonly identified in chil-
uation in the inpatient setting. Although infections dren with SBI included Streptococcus pneumoniae and
remain high on the list of possible diagnoses in these Haemophilus influenzae type B (Hib). It has already
patients, it is important to remember that fever can been demonstrated that since the introduction of the
be caused by illnesses other than infections. Rheu- vaccine against H. influenzae type B, the rates of SBI
matologic diseases, neoplasms, inflammatory disease, cause by this pathogen have significantly declined
and diseases of hypersensitivity such as drug fevers (Black and Shinefield, 1992●B ). It remains to be seen
are important considerations. The evaluation for the extent to which the same may be true of invasive
such diseases may appropriately include serum bio- pneumococcal disease as more and more children are
chemical analysis, imaging such as computed tomog- vaccinated with the conjugated pneumococcal vac-
raphy or magnetic resonance imaging, and biopsy of cine active against seven of the most pathogenic
any potentially abnormal areas identified. serotypes of S. pneumoniae. If the overall rates of SBI

240
 Chapter 21 Fever without Source in Children (Fever)

decline as expected in response to this vaccine, the Follow-up

preceding recommendations for the evaluation of
children with fever could significantly change. In the clinic the next day, Zoe’s father reported that
she had continued to look well, and that she was eat-
ing, urinating, defecating, and breathing normally.
Plan Her temperature taken at the clinic was 38.1˚C
Based on historical and clinical information, Zoe (100.6˚F) rectally; the rest of her examination
appeared to be at low risk of an SBI. To complete the remained unremarkable. Urine culture returned
assessment as to whether she met the low-risk showing no growth. Again, close parental monitor-
Rochester criteria, a WBC count and urinalysis were ing was discussed, and she returned home with
performed. Results included a WBC count of 11,300, instructions for the father to call the clinic the next
an absolute band count of 300, and a normal urinal- day to report how she was doing. By the next day, she
ysis with fewer than five white blood cells per high- remained well and axillary temperature had come
power field. With this information, Zoe’s father and down to 37.2˚C (99.0˚F). She continued to remain
physician came to the decision that her risk of seri- well and afebrile thereafter with no source for her
ous infection was low, and both preferred to avoid fever having been identified.
further invasive testing with lumbar puncture. Zoe’s
father agreed to carefully observe her for any further
signs of illness and to bring her back for evaluation Material Available on Student Consult
the next day. Zoe’s urine was sent for culture in the Review Questions and Answers about Fever
meantime.

REFERENCES
American College of Emergency Physicians Clinical Pediatric Vaccine Study Group. Pediatr Infect Dis J
Policies Committee: American College of Emergency 1992;11:610–613.● B
Physicians Clinical Policies Subcommittee on Pediatric Bramson RT, Meyer TL, Silbiger ML, et al. The futility of
Fever. Clinical policy for children younger than three the chest radiograph in the febrile infant without respi-
years presenting to the emergency department with ratory symptoms. Pediatrics 1993;92:524–526.● B
fever. Ann Emerg Med 2003;42:530–545. ● C Chiu CH, Lin TY, Bullard MJ. Application of criteria
Bachur R, Perry H, Harper MB. Occult pneumonias: identifying febrile outpatient neonates at low risk for
Empiric chest radiographs in febrile children with bacterial infections. Pediatr Infect Dis J 1994;13:
leukocytosis. Ann Emerg Med 1999;33:166–173.● B 946–949.● B
Baker MD, Anver JR, Bell LM. Failure of infant observation Ferrera PC, Bartfield JM, Snyder HS. Neonatal fever:
scales in detecting serious illness in 4- to 8-week-old Utility of the Rochester criteria in determining low risk
infants. Pediatrics 1990;85:1040–1043.● B for serious bacterial infection. Am J Emerg Med
Baker MD, Bell LM. Unpredictability of serious bacterial 1997;15:299–302.● B
illness in febrile infants from birth to 1 month of age. Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile
Arch Pediatr Adolesc Med 1999;153:508–511.● B infants at low risk for serious bacterial infection—an
Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for appraisal of the Rochester criteria and implications for
the management of infants and children 0 to 36 management. Febrile Infant Collaborative Study
months of age with fever without source. Pediatrics Group. Pediatrics 1994;94:390–396.● B
1993;92:1–12.● C Kadish HA, Loveridge B, Tobey J, et al. Applying outpatient
Black SB, Shinefield HR. Immunization with oligosaccha- protocols in infants 1–28 days of age: Can the threshold
ride conjugate Haemophilus influenzae type B (HbOC) be lowered? Clin Pediatr 2000;39:81–88.● B
vaccine on a large health maintenance organization popu- Luszczak M. Evaluation and management of infants and
lation: Extended follow-up and impact on Haemophilus young children with fever. Am Fam Physician 2001;
influenzae disease epidemiology. The Kaiser Permanente 64:1219–1226.● C

241
 C h a p t e r

22 Cough (Possible Asthma)

Frank J. Domino and Robert A. Baldor

tions are up to date. He takes no medications except

KEY POINTS for a daily multivitamin. He has no known drug
allergies.
1. Chronic cough (cough lasting longer than
4 weeks) is common. Family History
2. Cough in the first hour after eating or that is His mother and father are healthy, although his
worse while supine may reflect gastro- father smokes cigarettes. K.M. has a 15-year-old
esophageal reflux. sister who is healthy and without any medical
3. A single wheeze pitch with discrete starting and problems.
stopping points and cough should encourage
evaluation for foreign body aspiration or tra- Personal and Social History
cheomalacia. K.M. lives with his parents, his sister, and a cat. He plays
4. For some asthmatics, cough is the most promi- soccer and does well in school (getting As and Bs).
nent symptom of their illness.
5. Tuberculosis may be subtle in children; tuber- Review of Systems
culin skin testing should be considered if the General: healthy male, born by spontaneous vaginal
child is at high risk of exposure. delivery at 39 weeks without complications; has
made all developmental and growth milestones
without difficulty. Head, eyes, ears, nose, and throat:
2 to 3 months of slight “itchy” eyes and sneezing in
INITIAL VISIT the mornings and at night but less so at school.
Respiratory: cough is dry and nonproductive; no
Subjective shortness of breath recognized. Dermatologic: last
winter had “blotches” after showers and sporting
Patient Identification and Presenting activities. Other systems benign.
Problem
K.M. is a 9-year-old boy who presents to your office
for follow-up of a cough. Objective
Physical Examination
Present Illness General K.M. is a well-appearing male in no acute
Three weeks ago K.M. came to your office for a distress.
cough that had persisted for over a month. Your
associate examined him but could not make a defin- Vital Signs Temperature is 37.2˚C (99.0˚F), respira-
itive diagnosis. He treated him with erythromycin tory rate is 12, blood pressure is 96/55, and pulse is 88.
empirically for “bronchitis.” K.M.’s mom now
reports that he continues to cough intermittently, Head, Eyes, Ears, Nose, and Throat Tympanic
especially at night. membranes are clear; nasal turbinates are bulging
and erythematous. Oropharynx is slightly red-
Medical and Surgical History dened and injected; no postnasal drip.
K.M. has been very healthy in general. He has not
had any hospitalizations or surgery. His immuniza- Neck No lymphadenopathy.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

242
 Chapter 22 Cough (Possible Asthma)

Lungs Positive breath sounds in all fields; no rales 5. Increased cough receptor sensitivity. Some children
or rhonchi. appear to have increased cough receptor sensitiv-
ity. The etiology of this hypersensitivity may be
Abdomen Positive bowel sounds, soft, nontender, viral illness or other exposures.
no hepatosplenomegaly. 6. Habit cough. Psychogenic (habit) cough is a com-
mon type of chronic cough in children and adoles-
Extremities No clubbing, cyanosis, or edema. cents. The cough is a barking or honking sound
after a short inhalation. It may develop following
Assessment an upper respiratory infection. It is typically absent
at night and when the child is otherwise engaged.
Working Diagnosis Its presence can result in significant secondary gain
Chronic cough. Cough lasting longer than 4 weeks is for the child, as it often results in multiple physi-
common, with an estimated prevalence of 5% to 7% cian visits and disrupts the school classroom. The
in preschoolers and 12% to 15% in older children. It cough may worsen when attention is paid to it in
is more common in boys than in girls up to 11 years the doctor’s office. Habit cough is a diagnosis of
of age and may be less common in developing coun- exclusion and can be related to Tourette’s syn-
tries than in affluent countries (Bush, 2002●
C ; Chang drome or tic disorders (Tan et al., 2004● C ).
and Powell, 1998● C ; Chung and Chang, 2002● C ).
When history and physical examination do not
Differential Diagnosis provide a single diagnosis, then two or more of the
The differential diganosis for a chronic cough listed causes in combination may be the etiology.
includes cough-variant asthma, gastroesophageal Alternatively, functional disorders (including habit
reflux disease (GERD), allergic rhinitis, chronic cough and tic) should be considered.
sinusitis, cough receptor hypersensitivity, chronic
pulmonary infection, cardiac disease, cystic fibrosis, Plan
functional disorders, and some combination of these
diagnoses (Bush, 2002● C ). Diagnostic
The diagnosis is often made on the basis of history
1. Cough-variant asthma. For some asthmatics, cough and examination. Additional testing may be of value,
is the most prominent symptom of their illness. but sensitivities are low in pediatric populations, and
Individuals with cough-variant asthma typically if the cough does not appear to be of serious etiology,
have atopy and reversible obstruction. Initial further testing may lead to unnecessary exposures
empirical treatment of these children includes and false securities. Pulmonary function tests can be
bronchodilators with appropriate holding chamber considered. When performed optimally, spirometry
(spacer) or oral theophylline (National Institutes of may show signs of obstruction when obstructive
Health et al., 2004 ● C ). Some literature exists that the disorders and restriction in interstitial or chest wall
use of oral steroids in combination with inhaled restrictive processes are present. This test measures
beta agonists does not provide benefit in relieving FEV1 (forced expiratory volume in 1 second) and
cough (Chung and Chang, 2002 ● C ). forced vital capacity and, when the result is positive,
2. GERD. Little is known about the prevalence and can help make the diagnosis (Faniran et al., 1999 ● A ).
natural history of GERD in children and adoles- False results may occur if the child exerts a subopti-
cents. Children at increased risk of GERD include mal effort; this will result in a restrictive picture.
those with neuromuscular disorders such as mus- FEV1 less than 80% implies an obstructive pat-
cular dystrophy, cerebral palsy, cystic fibrosis, and tern. Following a positive test or when a test is nor-
Down syndrome. Children with GERD may be at mal but asthma is suspected, a bronchodilator can
increased risk of developing respiratory compli- be given. Should the patient have a greater than 12%
cations, including aspiration pneumonia. improvement in FEV1, reversible obstructive disor-
3. Allergic rhinitis. This syndrome is characterized by ders like asthma can be diagnosed. However, a lack of
paroxysms of sneezing, rhinorrhea, nasal obstruc- a response to a bronchodilator does not rule out an
tion, and itching of the eyes, nose, and palate. It is fre- obstructive disorder.
quently associated with postnasal drip, cough, Bronchoprovocation is the most sensitive
irritability, and fatigue. It can be further classified as method for determining reactive obstruction. It can
seasonal if symptoms typically occur at a particular be accomplished by using methacholine, cold air, or
time of the year or perennial if they occur year round. exercise, as these may induce acute bronchospasm;
4. Chronic sinusitis. This is typically uncommon in bronchoprovocation may be contraindicated in
pediatric populations. Its presence should alert some age groups.
the physician to consider cystic fibrosis or nasal Peak expiratory flow rate is easy to measure but
polyps. Rarely, fungal elements may play a role. is very dependent on the patient’s abilities. Thus its

243
 Chapter 22 Cough (Possible Asthma)

role is to monitor an asthmatic’s status over time medical history should include an account of the
rather than to make the diagnosis of asthma. pregnancy, labor, and delivery, as well as the neonatal
In younger children with chronic cough, aspiration course. Low-birth-weight and/or premature neonates
of a foreign body should be considered. In such cases are at risk of developing atopic sensitization and
a chest radiograph should be ordered. If a history of asthma. Neonates who are small for gestational age
aspiration is likely, a computed tomography scan may be may have congenital infection. In addition, prematu-
needed. Finally, because the presentation of tuberculosis rity and neonatal respiratory distress syndromes are
may be subtle in children, tuberculin skin testing should precursors for bronchopulmonary dysplasia, which
be considered if the child is at high risk of exposure. in turn may predispose to chronic lung disease.
Additional historical features may help lead to a
Therapeutic diagnosis. Chronic paroxysmal cough triggered by
Empirical therapy for asthma (albuterol inhaler), exercise, cold air, sleep, or allergens is often seen in
allergic rhinitis (steroid inhaler), sinusitis (antibiotic, patients with asthma. Cough due to asthma typically
steroid inhaler), or GERD (raising head of bed, not occurs following exposure to characteristic asthma
eating 2 hours before bedtime) can be implemented triggers (i.e., allergens, smoke, exercise, cold air),
when history and/or physical examination suggest and typically worsens during sleep (Bush, 2002● C ;
that these will be helpful. Stein et al., 1999 ● B ; National Institutes of Health
When no clear diagnosis is discerned, a trial of et al., 2004● C ).
over-the-counter cough or cold medicine can be con- A chronic productive (or wet) cough suggests a
sidered, but there are no data supporing the effective- suppurative process and may require further inves-
ness of these medicines for cough. Often the physician tigation to exclude bronchiectasis, cystic fibrosis,
can do little other than reassure the patient and pro- active infection, immune deficiency, or congenital
vide close follow-up. If secondary gain or psychol- malformation.
ogical stress plays a role, cognitive-behavioral therapy Cough that appears in the first hour after eating
may be tried. For psychogenic cough, successful ther- or that is worse when the patient is supine may
apies include hypnosis, suggestion, and biofeedback. reflect GERD. Although cough due to postnasal drip
is also typically worse during changes of position, in
Patient Education this case the patient is more likely to complain of a
In the case of a chronic cough without other worri- tickle in the back of the throat, and this maybe
some signs, the patient should be reassured that the accompanied by a nasal discharge.
condition is not serious but may improve with care- Barking or a brassy cough suggests a process in
ful attention to potentially aggravating environmen- the trachea or more proximal airways, such as airway
tal factors (Schwartz, 2004● C ; Smith et al., 2000●
C ). In malacia, laryngotracheobronchitis, and foreign body.
this case, K.M. is exhibiting allergic symptomatology, Psychogenic cough is present during the day,
and his father is advised to quit smoking or at least to disappears at night, and is typically the worst and
smoke outside the home. In addition, K.M. is advised most disruptive during school classes. Cough that
to limit his exposure to cats, and the cat should not is honking (“Canada goose–like”) and disappears at
be allowed to sleep in his room. If medication is pre- night suggests a psychogenic or habitual cough.
scribed, correct instructions in its use must be given, A careful history should be obtained for current
and the patient must be encouraged to have patience illness in family members or close contacts; such
with medications (inhaled nasal steroids, for exam- individuals with cough, weight loss, and night sweats
ple) that may take several doses to take effect. should arouse suspicion of tuberculosis. Family his-
tory of atopy or asthma increases the risk in off-
Disposition spring and suggests a diagnosis of either allergic
K.M. is started on a steroid nasal inhaler, beclo- rhinitis or asthma in the child with chronic cough.
methasone (42 μg/spray), one spray in each nostril It is also important to obtain a information on
twice daily. He is advised to use the inhaler faithfully who lives in the home with the child and the travel
over the next 10 days and to return to the office for histories of these people. Indoor exposures also play
reassessment in 2 weeks. Depending on his response a role. Wood-burning and gas stoves can cause respi-
to this empirical therapy, further testing/treatment ratory symptoms. Second-hand or active exposure to
will be considered at that time. smoke from tobacco, marijuana, cocaine, or other
substances can result in chronic cough. Contact with
pets can lead to allergy or asthma-induced cough.
DISCUSSION Ascertaining whether there has been a
response to previous treatments may discern the
Chronic cough in children can have many etiologies, cause of chronic cough. Response to antihist-
but the diagnosis can often be made with attention amines suggests rhinitis and postnasal drip,
to a careful history and physical examination. The whereas response to an empirical trial of inhaled

244
 Chapter 22 Cough (Possible Asthma)

bronchodilators may suggest asthma. Previous ■ Murmurs, abnormal heart sounds, abnormal pulses
response to medications, and in particular antibi- ■
Hepato- and/or splenomegaly, abdominal masses
otics, must be interpreted with special caution, as ■ Edema, cyanosis, and/or clubbing of the digits
many causes of cough are self-limiting, and cessa-
The character of a wheeze may give some clue to
tion of symptoms may have been coincidental
its etiology. Wheezing with different pitches, associ-
(Schroeder and Fahey, 2002● A).
ated with cough, is typical of asthma. In children
Finally, when performing the physical examina- with this type of wheeze and atopic symptoms
tion, close attention should be paid to the following (rhinitis, conjunctivitis, and/or eczema), asthma is
signs: the likely cause of the cough (Bush, 2002●C ; National
■ Delayed growth or developmental milestone Institutes of Health et al., 2004●
C ).
attainment A single wheeze pitch with discrete starting and
■
Extremes of weight (wasting or obesity) stopping points and cough should encourage evalu-
■ “Shiners” (bluish discolorations under the eyes), ation for foreign body aspiration or tracheomalacia.
swollen nasal turbinates, nasal polyps, allergic
nasal crease, scarred tympanic membranes, halito-
sis, tonsillar hypertrophy, pharyngeal cobbleston-
ing, high arched or cleft palate, hoarseness Material Available on Student Consult
■
Respiratory rate, retractions, accessory muscle use,
Review Questions and Answers about Possible
abnormal breath sounds (reduced intensity, Asthma
wheezing, stridor, crackles)

REFERENCES
Bush A. Paediatric problems of cough. Pulm Pharmacol Smith KR, Samet JM, Romieu I, Bruce N. Indoor air pollu-
Ther 2002;15:309–315.● C tion in developing countries and acute lower respira-
Chang AB, Powell CV. Non-specific cough in children: tory infections in children. Thorax 2000;55:518–532.● C
Diagnosis and treatment. Hosp Med 1998;59:680–684.● C Stein RT, Holberg CJ, Sherrill D, et al. Influence of parental
Chung KF, Chang AB. Therapy for cough: Active agents. smoking on respiratory symptoms during the first
Pulm Pharmacol Ther 2002;15:335–338.● C decade of life: The Tucson Children’s Respiratory
Faniran AO, Peat JK, Woolcock AJ. Measuring persistent Study. Am J Epidemiol 1999;149:1030–1037.● B
cough in children in epidemiological studies: Develop- Tan H, Buyukavci M, Arik A. Tourette’s syndrome mani-
ment of a questionnaire and assessment of prevalence in fests as chronic persistent cough. Yonsei Med J
two countries. Chest 1999;115:434–439.● A 2004;45:145–149.● C
Schroeder K, Fahey T. Should we advise parents to admin- National Institutes of Health, National Heart, Lung and
ister over the counter cough medicines for acute cough? Blood Institute. National Asthma Education and
Systematic review of randomised controlled trials. Arch Prevention Program. Guidelines for the Diagnosis and
Dis Child 2002;86:170–179.● A Management of Asthma––Update on Selected Topics
Schwartz J. Air pollution and children’s health. Pediatrics 2002 and Expert Panel Report 2 (1997). Available at
2004;113:1037–1043.● C www.nhlbi.nih.gov/guidelines/asthma/index.htm.
Accessed 9/15/2004.● C

245
 C h a p t e r

23 Insomnia

Venita W. Morell

such as driving. She does occasionally nap. She

KEY POINTS denies restless leg sensation or any discomfort or dis-
traction that seems to interfere with her ability to fall
1. Insomnia is a symptom that can be caused by asleep. She has a history of depression but denies any
many disease states or environmental condi- exacerbation of her depressive symptoms at present.
tions. To best treat the insomnia complaint, find She snores occasionally.
the cause and target treatment to that specific
cause. Medical History
2. The evaluation of a patient complaining of Janet contracted human immunodeficiency virus
insomnia relies primarily on the excellent 8 years ago through sexual contact. She elected to take
history and physical examination. Laboratory highly active antiretroviral therapy 2 years ago when
testing and other evaluation are often testing of her viral load showed an increase in the
unnecessary. amount of virus in her blood and showed that her CD4
3. Polysomnography should be reserved for counts had begun to decline. She has been on the same
patients refractory to treatment, patients sus- highly active antiretroviral therapy regimen for 2 years.
pected of having a sleep-related breathing or She has chronic depression, which has been well
limb movement disorder, or those with chronic controlled with medication. No other medical or
insomnia without a diagnosable medical, neu- surgical history is noted.
rologic, or psychiatric cause.
Family History
Janet is an only child. Both parents smoke cigarettes
and are suspected alcohol abusers.
INITIAL VISIT
Social History
Subjective Janet is single and sexually abstinent. She works
full time as a clerk in a convenience store. She
Present Illness smokes one pack of cigarettes per day and occasion-
Janet B., a 30-year-old white woman with asympto- ally marijuana. She drinks two to four beers per day.
matic human immunodeficiency virus infection on Caffeine is consumed in soda and iced tea in as many
highly active antiretroviral therapy, is in the clinic for as six drinks per day. She has no known allergies to
her 3-month checkup. She recently had a change of medicine.
social situation and is now living in her parents’ Her current medications are efavirenz (Sustiva)
home and working during the day. She complains of 600 mg at bedtime, a lamivudine/zidovudine combi-
insomnia and requests sleeping pills. Before this nation (Combivir) twice daily, fluoxetine (Prozac)
change, she slept 5 hours during the day, worked at 20 mg once daily, and a multiple vitamin daily.
night, and was not bothered by sleep-related issues.
Now, she tries to go to bed with the rest of the house-
Objective
hold at about 9 PM but remains awake until after
midnight. Once she falls asleep, she does not wake Physical Examination
until 6 AM. She has always experienced episodes at Janet is a well-developed, well-nourished, alert, white
work when she feels sleepy but denies falling asleep woman in no distress. She smells strongly of tobacco
easily during the day or while performing activities smoke. Her vital signs are all within normal limits.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

246
 Chapter 23 Insomnia

Her head and neck examination shows no abnor- ■ Sleep state misperception (normal sleep pattern in
mality of the airway or thyroid, and no lymph- a patient who perceives insomnia)
adenopathy is noted. Her lungs are clear. Her cardiac ■ Inadequate sleep hygiene (poor habits to promote
examination is unremarkable. Her extremities show sleep)
no edema. Her abdomen is benign. A detailed neuro- ■ Insufficient sleep syndrome (chronic accumulated
logic examination is unremarkable. Her mood is lack of enough time in sleep)
normal and her affect is normally reactive. Her ■ Altitude insomnia (accompanying other symp-
thought is normal. toms at altitudes of more than 4000 m)
■ Restless legs syndrome (urge to move legs often
Assessment accompanied by uncomfortable sensations that
worsen at rest) (Consensus Recommendation from
Differential Diagnosis an Expert Panel, 2004● A)
Insomnia is a symptom, not a disease. Insomnia can ■
Periodic limb movement disorder (intermittent
be caused by many different disease states or can be limb flexion)
the perception of impaired sleep in the absence of any ■ Central sleep apnea syndrome (usually associated
disease state or true sleep problem (Mahowald et al., with daytime sleepiness)
1997● C ). The patient with insomnia may describe ■ Circadian rhythm disorders (normal function dur-
inadequate quantity or quality of sleep. Like Janet, ing waking hours and normal sleep but shifting of
patients complaining of insomnia may have difficulty the normal sleep period)
initiating sleep. They may also have difficulty main-
taining the sleep state, or they may wake frequently or Janet’s insomnia may have multiple causes. She
early. Patients may complain of daytime sleepiness or is noted to snore, but without excessive daytime
may wake feeling unrefreshed. sleepiness, sleep apnea is unlikely. She suffers from
Documenting the specifics of the sleep problem depression, but this problem seems to be well con-
and the duration of the problem helps generate the trolled and does not seem to be a contributor to her
differential diagnosis of insomnia. For example, insomnia complaint. Her normal physical examina-
acute insomnia of less than 3 weeks’ duration may tion and history do not indicate any uncontrolled
have different causes than more chronic symptoms. medical illness that would interfere with her sleep.
Common causes of transient insomnia include the She does take a prescription medication, efavirenz,
following (Graeber, 1994): which is known to interfere with sleep, but she has
taken this medication since long before her insomnia
■ Uncomfortable sleep environment (noise, light,
complaint arose. She does ingest alcohol on a daily
temperature, unfamiliar surroundings)
basis; chronic alcohol ingestion may be interfering
■ Change in sleep/wake cycle (shift change)
with her sleep patterns. Her sleep hygiene, especially
■ Mental stress (worry about work, school, or family
related to the use of stimulants such as tobacco and
dysfunction)
caffeine, can be improved. Janet may also have some
■ Acute illness
degree of sleep state misrepresentation. She does not
■ Central nervous system stimulants (caffeine or
decongestants) complain of daytime sleepiness or seem impaired by
■ Jet lag the lack of restorative sleep. The insomnia complaint
did not occur until she needed to adjust her routine
Janet’s symptoms have been present for longer to fit the patterns of a new household and define her
than 3 weeks, and thus the differential diagnosis sleep to new norms.
must consider causes of chronic insomnia
(Chokroverty, 2004●
A). These include the following:

Plan
■
Medical disorders (the nocturnal dyspnea associ-
ated with congestive cardiomyopathy) Testing and Consultation
■ Medications (efavirenz for human immunodefi- Patients presenting with insomnia complaints should
ciency virus treatment or theophylline for asthma) have a complete history and physical examination
■ Chronic illicit drug or alcohol use performed. The history should include specifics of
■ Psychiatric disorders (anxiety may cause delayed any drug use that may affect sleep, any chronic alco-
or disrupted sleep, psychosis may cause extreme hol use, psychiatric problems, family history of sleep
sleep disruption, and depression typically causes problems, and any medical or neurologic problems.
early morning awakening but sometimes may Because insomnia is primarily a clinical diagnosis,
cause delayed sleep) there are no laboratory evaluations that are routinely
■ Primary sleep disorders (idiopathic/childhood- recommended for evaluation of patients with this
onset insomnia or psychophysiologic insomnia as complaint. However, there are several studies that
a developed response after stress) may be helpful.

247
 Chapter 23 Insomnia

Completion of a sleep log is often helpful in ■ Avoid the use of stimulants in pre-bedtime hours
obtaining detailed information about the time a (including caffeine, nicotine, and over-the-counter
patient attempts to sleep and the time he or she actu- medications such as decongestants).
ally spends asleep. The patient should also record ■ Get regular exercise, but do not perform vigorous
comments about any related issues, such as perceived exercise in the hours before bedtime.
impediments to sleep, changes in daily routine, or ■ Provide a comfortable sleep environment (temper-
daytime naps. The sleep log helps clarify the history ature, lighting, bedding, noise, lack of hunger,
for the clinician and can also clarify insomnia issues empty bladder, use of minor analgesics for pain).
for the patient. ■ Avoid alcohol near bedtime.
Multiple sleep latency testing can also be helpful. ■
Reduce stress and worry overall, and deal with dis-
This informal assessment of daytime sleepiness can be tracting worries before bedtime.
accomplished by asking the patient to attempt to nap ■ Maintain a regular schedule for sleep and waking,
in a dark room four or five times during the day for as even on weekends.
long as 20 minutes. If sleep occurs within that time, ■ Create a bedtime routine.
especially if it occurs within only minutes and on all ■ Do not nap during the day.
occasions, pathologic daytime sleepiness is suspected
and diagnoses that lead to insufficient restorative sleep In addition to these generally recognized sleep
are highly suspect. Without excessive daytime sleepi- hygiene principles, Bootzin’s stimulus control tech-
ness, the diagnosis of sleep apnea syndrome or insuf- nique discusses the use of the bedroom for sleep and
ficient sleep syndrome, for example, is unlikely. sex exclusively. If the patient cannot sleep within a
Actigraphy and polysomnography are also avail- reasonable amount of time, he or she is instructed to
able for evaluation of insomnia complaints. In acti- leave the bedroom and to return when sleepy.
graphy, sensors are used to detect movement, and Eventually, the bed comes to be associated with sleep
patients are assumed to be in a sleep state when in the patient’s mind.
movement is absent and awake when movement is Various forms of relaxation therapies have
documented. When used in correlation with a sleep helped patients with insomnia fall asleep. Techniques
log, actigraphy can be useful in diagnosing causes of such as progressive muscle relaxation, biofeedback,
insomnia or in helping patients identify sleep state and deep breathing can be quickly taught by the office
misperception. practitioner. Additionally, sleep restriction therapy,
Polysomnography is generally done in a sleep which involves the time allotted for sleep each pro-
laboratory, although there are home tests available gressive day, has been successfully used to help
with less elaborate sensor readings. A combination of address insomnia (Lacks and Morin, 1993).
sensors records respiratory air flow, heart rate, mus- The main treatment of insomnia is nonpharma-
cle activity, brain wave activity, and other activity. In cologic, but careful use of hypnotic medication may
sleep laboratories, the patient is also observed or also be indicated. Pharmacologic treatment of
videotaped. The electroencephalographic recording insomnia should be used only after nonpharmaco-
of waves associated with the sleep state can be corre- logic treatment options have been instituted.
lated with other sensor readings and used to diag- Although hypnotic medications are very effective
nose the cause of sleep disruption. The American short-term treatments for insomnia, they do not
Sleep Disorders Association Standards of Practice work well for the treatment of chronic insomnia. In
Committee Guidelines do not suggest polysomno- addition, hypnotic medications may be contraindi-
graphic testing for the routine evaluation of insom- cated in pregnant patients because of concerns about
nia. These guidelines suggest polysomnography may their effects on the developing fetus and in some
be helpful when (1) a sleep-related breathing or limb patients with compromised renal, hepatic, or pul-
movement disorder is suspected; (2) chronic insom- monary function.
nia without medical, neurologic, or psychiatric cause Benzodiazepines are among the most commonly
is present; or (3) a treatment-refractory insomnia used hypnotic medications. These may cause amne-
exists (Committee of the American Sleep Disorders sia, rebound insomnia, daytime somnolence, and
Association, 1995● A , 1997●
A). exacerbation of anxiety disorders. When used long
In some areas, expert consultation with a phy- term, dependence on and tolerance to the medica-
sician specializing in sleep disorders may also be tions develop. As a result, dosage must be increa-
available. sed to maintain hypnotic effects in the patient, and
withdrawal symptoms occur when the medication is
discontinued. Benzodiazepines should be used with
Treatment
caution when used to treat chronic insomnia.
All patients should be asked to pay attention to their Zolpidem (Ambien) and zaleplon (Sonata) do not
sleep hygiene. Here are commonsense sleep hygiene have a benzodiazepine structure but act through
measures to discuss: the benzodiazepine receptor. Other nonbenzodiazepine

248
 Chapter 23 Insomnia

hypnotics that have been used for insomnia include firming the absence of excessive daytime sleepiness.
antidepressants with sedative side effects, such as the tri- These results reassure her that she does not have a
cyclics, and sedating antihistamines. These medications serious insomnia problem and support the diagnosis
may cause daytime sleepiness as well as other side effect of sleep state misrepresentation. We discuss sleep
problems. Their effect as hypnotic agents is transient, as hygiene relevant to her case. She succeeds in elimi-
tolerance to the side effect develops, making them nating her evening naps, cutting down her alcohol
ineffective for use in treating chronic insomnia. intake, and avoiding caffeine after lunchtime. She
It is best to identify and treat a specific disease also is told to get up from the bed if unable to sleep
state that may be the cause of insomnia symptoms, within 20 minutes, to go to the family room to read,
while avoiding the use of general hypnotic medica- and to return to bed when sleepy. She is encouraged
tion. For example, patients with restless legs syn- to stop smoking and increase aerobic exercise, but
drome benefit greatly from targeted treatment for she is not receptive to these changes. We instruct
that illness. Patients with sleep apnea will show Janet in the technique of progressive muscle relax-
improvement in their daytime sleepiness if their ation while lying in bed attempting to sleep. Finally,
nighttime ventilation is improved. Likewise, the sleep she is given a small quantity of zolpidem to use as
of patients with depression improves with treatment often as twice weekly when all conservative measures
of underlying psychiatric disease. fail to help her fall asleep by midnight. After a
month, she reports using the zolpidem only once,
and states she is rarely troubled by difficulty falling
FOLLOW-UP asleep. We will continue to address tobacco cessation
and exercise with her in the future.
Janet completes a sleep log and participates in a mul-
tiple sleep latency test. This demonstrates she is
sleeping about 7 hours a night and napping 30 min- Material Available on Student Consult
utes to an hour during the evening. She does not fall
Review Questions and Answers about Insomina
asleep during most of her nap opportunities, con-

REFERENCES
Chokroverty S. Epidemiology and causes of insomnia. Lacks P, Morin CM. Recent advances in the assessment and
Available at www.uptodate.com, 2004. ● A treatment of insomnia. J Consult Clin Psychol
Consensus Recommendation from an Expert Panel. 1993;60:586–594.
Restless legs syndrome: Diagnosis and treatment strate- Practice parameters for the use of polysomnography in the
gies for the primary care provider. 2004;5.●
A evaluation of insomnia. Standards of Practice Committee
Graeber RC. Jet lag and sleep disruption. In Kryger MH, of the American Sleep Disorders Association. Sleep
Roth T, Dement WC, eds. Principles and Practice of Sleep 1995;18:55–57.● A
Medicine. Philadelphia, WB Saunders, 1994, p 463. Practice parameters for the indications for polysomnogra-
Mahowald MW, Chokroverty S, Kader G, Schenck CH. phy and related procedures. Polysomnography Task
Sleep disorders. Continuum. A Program of the Force, American Sleep Disorders Association Standards
American Academy of Neurology, 1997, p 48.● C of Practice Committee. Sleep 1997;20:406–422.● A

249
 C h a p t e r

24 Pruritus (Atopic Dermatitis)

Jennifer E. Lochner

Social History
KEY POINTS Steven lives with his parents and siblings. He is a jun-
ior in high school and denies using tobacco, alcohol,
1. Itch is a nociceptive sensation with some and illicit drugs.
similarities to pain.
2. Dermatologic conditions commonly cause itch, Review of Systems
but systemic illness may cause itch as well. Steven reports feeling otherwise well and specifically
3. Treatment of itch may be general in nature denies headache, shortness of breath, chest dis-
or specific to the source condition. comfort, abdominal pain, and bladder or bowel
symptoms.

Objective
INITIAL VISIT
Physical Examination
Subjective Steven is an alert male who is actively scratching his
arms but is otherwise in no apparent distress. His
Patient Identification and Presenting blood pressure is 126/68, pulse is 62, temperature is
Problem 37.1˚C (98.8˚F), respiration is 16, height is 5 feet 10
Steven J. is a 17-year-old young man who presents to inches, and weight is 180 pounds. Skin examination
the clinic with intractable itching. He states that he shows thick, red, dry patches over the flexor surfaces
has had “eczema” since childhood and that his cur- of his wrists, elbows, knees, and ankles. No pustules
rent symptoms seem to be related to a flare of his or papules are noted.
eczema. He reports red, dry patches over various
parts of his body with intense itching. It seems to get Assessment
worse the more he scratches it, but the itching is so
intense that he simply cannot avoid scratching. He Working Diagnosis
has tried moisturizing creams, which he thinks help Itch caused by atopic dermatitis.
relieve some of the dryness, but the itching persists.
He has also tried over-the-counter hydrocortisone
1% cream (which has worked for his eczema in the DISCUSSION
past) with minimal relief.
Itch, also called pruritus, is most easily defined as an
Medical History unpleasant sensation that evokes the desire to
In addition to the eczema reported, Steven has sea- scratch. It is similar to pain in that it is a modality of
sonal allergies that are controlled with over-the- nociception with a reflex response. With pain, the
counter antihistamines. He reports no other medical reflex is to withdraw from the source, whereas with
illnesses or surgeries. itch, the reflex is to scratch the source.
Itch has been found to be mediated by C fibers
Family History that transmit signals via the spinothalamic tract
Steven’s mother has a similar history of seasonal aller- to the cerebral cortex. No single mechanism exists to
gies. His father and two siblings are alive and well. trigger these signals, and in fact several different

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

250
 Chapter 24 Pruritus (Atopic Dermatitis)

neurotransmitters have been implicated in the gener- diseases including asthma and allergic rhinitis.
ation of itch. Histamine is well known for its involve- Common locations of the rash in atopic dermatitis
ment in allergy-associated pruritus. Other substances include the flexor surfaces of the elbows, wrists,
that appear to be involved in various types of itch knees, and ankles. Acutely, skin appears swollen and
include serotonin, substance P, and opioids. red in poorly defined areas. When present more
Categories of itch have been proposed based on chronically, skin tends to thicken from the persistent
their differing origins. It is possible for itch in a sin- scratching. Dryness can lead to painful fissures.
gle clinical entity to be explained by more than one
type of itch. The classic example of this is atopic der- Xerosis
matitis in which it appears that both prurioceptive Xerosis refers to dry skin. As a source of itch, it is
and neurogenic itch are involved. most common in older adults and affects the lower
legs, back, flank, abdomen, and waist. Scratching the
Prurioceptive Itch dry skin results in red plaques with fissures.

Prurioceptive itch originates in the skin. Inflam- Allergic Contact Dermatitis

mation or other skin damage is the source; C nerve An itchy rash can develop in response to contact with
fibers transmit the itch message. Common examples particular substances in susceptible people. Poison
of this type of itch include the itch of dry skin and ivy is a common cause of such a rash. The rash is typ-
insect bites. ically erythematous with overlying vesicles and
sharply demarcated borders.
Neuropathic Itch
Scabies
Neuropathic itch originates in the afferent nerve Scabies can be easily diagnosed when it presents with
pathway of itch. Diseases that can affect this pathway the typical burrows in web spaces of the fingers.
and induce itch include postherpetic neuralgia and Other times it presents less specifically with red pru-
multiple sclerosis. ritic papules. Itch can be intense both before treat-
ment and as long as a week afterward due to the
Neurogenic Itch continued presence of organisms in the skin.

Neurogenic itch originates centrally but without evi- Psoriasis

dence of damage in the nervous system pathway. Skin findings in psoriasis include papules and
Chemicals such as opioids, whether endogenous or plaques covered with a silvery scale. Some types of
exogenous, induce itch via this mechanism. psoriasis include pustules as well. Distribution can
be isolated to a particular body part or generalized.
Psychogenic Itch Commonly affected areas include the elbows, knees,
scalp, and intertriginous areas.
Psychogenic itch is associated with psychologic A more complete list of dermatologic causes of
abnormalities such as delusional states and obsessive pruritus can be found in Table 24-1.
compulsive disorders (Yosipovitch et al., 2003).
Systemic Causes of Itch
Differential Diagnosis of Itch
When no clear dermatologic source of itch is appar-
In most cases of itch, a clinically apparent dermato- ent, systemic sources of itch should be considered.
logic condition is the source. Additionally, when appropriate treatment for a der-
matologic source of itch (such as xerosis) does not
Common Dermatologic Conditions result in abatement of symptoms, systemic disease
Associated with Itch should be considered as an additional source of itch.

Atopic Dermatitis Cholestasis and Liver Disease

It is still not clear whether the itch precedes or fol- The specific details of the pathogenesis of itch in
lows the rash seen in atopic dermatitis (also known cholestasis are not understood; there may be more
as atopic eczema or simply eczema). It is clear that no than one contributing factor. It has been suggested
matter what the initial inciting event is, a vicious that impaired secretion of bile leads to an accumula-
cycle of itch and scratch follows in which the damage tion of some pruritogenic substance. Levels of bile
induced by scratching makes the itch worse and salts themselves, however, appear not to be correlated
induces further scratching. Atopic dermatitis often with the level of itch. Significant evidence exists
has its onset in childhood and may persist into that endogenous opioids play a role in pruritus
adulthood. It is often associated with other atopic in cholestasis, and many treatments aimed at

251
 Chapter 24 Pruritus (Atopic Dermatitis)

Table 24-1 Dermatologic Causes of Pruritus

Diagnosis Features

Allergic contact Sharply demarcated erythematous lesion with dermatitis overlying vesicles;
reaction within 2–7 days of exposure
Atopic dermatitis “Itch that rashes (when scratched)” in patients with atopic conditions (e.g.,
allergic rhinitis, asthma); involvement of flexor wrists and ankles as well as
antecubital and popliteal fossae
Bullous pemphigoid Initially pruritic urticarial lesions, often in intertriginous areas; formation of
tense blisters after urticaria
Cutaneous T-cell Oval eczematous patch on skin with no sun exposure (e.g., buttocks); possible
lymphoma (mycosis presentation as new eczematous dermatitis in older adults; possible
fungoides) presentation as erythroderma (exfoliative dermatitis)
Dermatitis herpetiformis Rare vesicular dermatitis affecting lumbosacral spine, elbows, or knees
Folliculitis Pruritus out of proportion to appearance of dermatitis; papules and pustules
at follicular sites on chest, back, or thigh
Lichen planus Lesions often located on the flexor wrists, the “6 Ps”: pruritus, polygonal,
planar, purple papules, and plaques
Pediculosis (lice Occiput of school-age children; genitalia in adults (sexually transmitted
infestation) disease)
Psoriasis Plaques on extensor extremities, low back, palms, soles, and scalp
Scabies Burrows in hand web spaces, axillae, and genitalia; hyperkeratotic plaques,
pruritic papules, or scales; face and scalp affected in children but not in
adults
Sunburn Possible photosensitizing cause (e.g., nonsteroidal anti-inflammatory drugs,
cosmetics)
Xerotic eczema Intense itching in elderly patients (often during winter months in northern
climates); involvement of back, flank, abdomen, waist, and distal
extremities
Reprinted with permission from Moses S. Pruritus. Am Fam Physician 2003;68:1135–1142, 1145–1146.

antagonizing the opioid receptor appear to have some human immunodeficiency virus itself can cause itch
benefit. Diseases that involve cholestasis include pri- because itch has been found in patients with human
mary biliary sclerosis, primary sclerosing cholangitis, immunodeficiency virus but no other infection or
and cholestasis of pregnancy. condition known to be associated with itch.
Some liver diseases classified as primarily non-
holestatic have been associated with itch as well. Medication Effect
Patients with alcoholic cirrhosis, viral hepatitis, and Opioids are the medications most clearly known to
autoimmune hepatitis have been found to have pru- induce itch. Epidural and spinal anesthesia have the
ritus with varying frequency. Again, the pathogenesis highest incidence of associated itch with an inci-
is not well understood in these cases, and manage- dence of 30% to 100% (Szarvas et al., 2003), but itch
ment should be the same as in cholestasis. is also a well-known side effect of intravenous and
intramuscular administration. The exact route by
Uremia which opioids exert this pruritogenic effect is not
Itch has been reported in 25% to 85% of patients known. Evidence of the involvement of serotonin
with renal failure but appears to be becoming less in the pathway includes the fact that ondansetron, a
prevalent due to improved dialysis techniques. The 5-HT3 antagonist, has been shown to relieve itch
exact reason for itch in uremia is not completely A ).
after intrathecal morphine (Yeh et al., 2000●
understood, but accumulation of endogenous opi- Other systemic causes of itch are described in
oids has been proposed as a contributing factor. Table 24-2.

Human Immunodeficiency Virus Disease Pregnancy-Related Causes

Many diseases associated with itch, both dermatologic Pruritus has been reported in 3% to 14% of all preg-
(e.g., scabies, xerosis) and nondermatologic (chronic nancies (Sherard and Atkinson, 2001). The causes
renal or liver disease), are associated with human unique to pregnancy are discussed in the following
immunodeficiency virus disease. It also appears that sections.

252
 Chapter 24 Pruritus (Atopic Dermatitis)

Table 24-2 Systemic Causes of Pruritus

Cause Features

Cholestasis Intense itching (hands, feet, pressure sites) that becomes worse at night;
reactive hyperpigmentation that spares the middle of the back (butterfly-
shaped dermatitis)
Chronic renal failure Severe paroxysms of generalized itching, worse in summer
Delusions of parasitosis Focal erosions on exposed areas of arms and legs
Hodgkin’s lymphoma Prolonged generalized pruritus often preceding diagnosis
Human immunodeficiency A common presenting symptom resulting from secondary causes (eczema,
virus infection drug reaction, eosinophilic folliculitis, seborrhea)
Hyperthyroidism Warm, moist skin; possibly pretibial edema; associated conditions:
onycholysis, hyperpigmentation, vitiligo
Iron deficiency anemia Signs in addition to pruritus: glossitis, angular cheilitis
Malignant carcinoid Intermittent head and neck flushing with explosive diarrhea
Multiple myeloma In elderly patients: bone pain, headache, cachexia, anemia, renal failure
Neurodermatitis or Bouts of intense itching that may awaken patients from sound sleep;
neurotic excoriations involvement of scalp, neck, wrist, extensor elbow, outer leg, ankle, and
perineum
Parasitic infections Usually in returning travelers or immigrants
Filariasis Tropical parasite responsible for lymphedema
Schistosomiasis Freshwater exposure in Africa, the Mediterranean area, or South America
Onchocerciasis Transmitted by black fly in Africa or Latin America
Trichinosis Ingestion of undercooked pork, bear, wild bear, or walrus meat
Parvovirus B19 infection “Slapped cheek” appearance in children; arthritis in some adults
Peripheral neuropathy
Brachioradial pruritus Involvement of lateral arm in white patients who have traveled to the
tropics
Herpes zoster Pruritus accompanying painful prodrome 2 days before appearance of rash
Notalgia paresthetica Pruritus in middle of back with hyperpigmented patch
Polycythemia rubra vera Pricking-type itch persisting for hours after hot shower or bath
Scleroderma Nonpitting extremity edema, erythema, and intense pruritus; edema phase
with pruritus occurring before fibrosis of skin
Urticaria Response to allergen, cold, heat, exercise, sunlight, or direct pressure
Weight loss (rapid) in Signs in addition to pruritus: hair loss, fine lanugo hair on back and cheeks,
eating disorders yellow skin discoloration, petechiae

Reprinted with permission from Moses S. Pruritus. Am Fam Physician 2003;68:1135–1142, 1145–1146.

Pruritic Urticarial Papules and Plaques of Herpes Gestationis Occurring in approximately one
Pregnancy Most commonly, this disorder presents in 50,000 pregnancies, herpes gestationis is uncom-
with erythematous urticarial plaques and papules. mon. It presents with an intensely pruritic urticarial
Other variations have been observed, however, lesion on the trunk in the second or third trimester.
including vesicles and target lesions. Lesions tend to It then spreads to the rest of the body, sparing only
first appear within abdominal striae and then spread the face, palms, soles, and mucous membranes.
to the rest of the trunk and extremities. Pruritic Most cases spontaneously remit in the late third
urticarial papules and plaques of pregnancy are most trimester, although it may flare at delivery or in the
common in primigravidas, with most cases begin- postpartum period. Flares have also been reported
ning in the third trimester and resolving after deliv- with the use of oral contraceptives postpartum and
ery, although it is possible for this condition to first with menses. Diagnosis can be confirmed with skin
appear in the immediate postpartum period. The biopsy showing C3 complement in a linear band
increased incidence in twin pregnancies and along the basement membrane. Treatment is with
increased maternal weight gain suggest that the systemic corticosteroids. Controversy exists as to
physical stretching of the skin plays an etiologic role. whether the fetus is at risk with this disease. Initial
Treatment involves topical steroids and antihista- reports showed no fetal risks, but subsequent stud-
mines. Prognosis is excellent with no fetal risks iden- ies have shown an increased risk of stillbirth, pre-
tified. The condition is unlikely to recur with maturity, and low birth weight (Sherard and
subsequent pregnancies. Atkinson, 2001). With these data, third trimester

253
 Chapter 24 Pruritus (Atopic Dermatitis)

fetal monitoring is recommended, including non- Intrahepatic Cholestasis of Pregnancy The dermati-
stress tests and amniotic fluid volume evaluations. tis in this disorder is from scratching. Pruritus may or
Herpes gestationis is likely to recur in subsequent may not be accompanied by jaundice. It most typically
pregnancies. develops in the third trimester with the itch most

Evaluation of pruritus

Are skin lesions present?

Yes No

Is the presentation reassuring?

Acute onset over several days
Localized pruritus
Pruritus limited to exposed skin
Recent travel
Is the dermatitis typical Possible occupational exposure
for benign disease? Review does not suggest systemic cause

Yes No No Yes

Treat the Diagnostic testing: Two week trial of nonspecific

underlying cause Skin scrapings (KOH prep, mineral pruritus management (Table 24-3)
oil smear) – dermatophytes or
scabies mites
Skin biopsy – mastocytosis,
mycosis fungoides, or bullous
pemphigoid Was the trial effective?
Skin culture – bacterial, viral, or
fungal infection

Yes Is testing diagnostic? No Yes

Treat No Limited laboratory testing: Symptomatic

underlying Thyroid–stimulating hormone level treatment as
cause Serum bilirubin and alkaline phosphatase needed
levels
Serum creatinine and blood urea nitrogen
levels
Complete blood count
Consider human immunodeficiency virus
test and chest radiograph

Figure 24-1 Algorithm for the evaluation of pruritus. (Adapted from Moses S. Pruritus. Am Fam Physician 2003;68:
1135–1142, 1145–1146.)

254
 Chapter 24 Pruritus (Atopic Dermatitis)

prominent on the palms, soles, and trunk. In cholesta- the liver (in cholestasis) or lymph nodes (in human
sis of pregnancy, laboratory studies rather than skin immunodeficiency virus disease), for example.
biopsy findings are diagnostic. Bile acids (cholic acid, Some historical features of pruritus are more
deoxycholic acid, and chenodeoxycholic acid), direct associated with a nonsystemic source of itch and are
bilirubin, and aspartate aminotransferase are all ele- therefore more benign in nature. Acute onset, localized
vated. As with many other disorders related to preg- symptoms, limitation of itch to exposed skin, presence
nancy, the signs and symptoms disappear within 1 to 2 of itch in family members, occupational exposure, and
weeks of delivery. Cholestasis of pregnancy commonly recent travel are all reassuring findings and may allow
recurs with subsequent pregnancies. Most worrisome a trial of nonspecific treatment rather than an exhaus-
with cholestasis of pregnancy is the increase in perina- tive search for systemic illness. Figure 24-1 is an algo-
tal morbidity including prematurity and stillbirth. For rithm for a systematic approach to evaluating pruritus.
this reason, fetal surveillance is warranted with delivery
as soon as fetal lung maturity is established.
Treatment of Itch

Evaluation of Itch Treatment of itch may be specifically directed toward

the etiology of itch or it may be nonspecific in nature.
Because the majority of causes of itch are due to der- Nonspecific treatment includes many therapies that
matologic disease, a thorough history and physical have not been evaluated in clinical trials but have been
examination will yield a diagnosis in most cases. around for decades and have stood the test of time
Exposure history is important in suspected contact (Table 24-3). Treatment aimed at prurioceptive itch
dermatitis or itch due to infectious agents such as includes capsaicin cream, topical doxepin, and topical
scabies. Skin examination is often diagnostic and aspirin. Neurogenic itch tends to respond more to
may need to include microscopic examination of treatments aimed at blocking the opioid pathways
scrapings or skin biopsy if clinical appearance cannot including naltrexone, naloxone, and nalmefene.
rule out more serious skin disease such as cutaneous Neuropathic itch is difficult to treat; anecdotal evi-
T-cell lymphoma. The physical examination should dence supports the use of lidocaine and gabapentin,
not be limited to the skin, however, especially if the medications more commonly known in their treat-
skin examination is found to be normal. Systemic ment of neuropathic pain. In inflammatory condi-
causes of itch may have physical findings involving tions, topical steroids are often a mainstay of therapy. It

Table 24-3 Nonspecific Management of Pruritus

Use skin lubricants liberally: petrolatum or lubricant cream at bedtime; alcohol-free, hypoallergenic lotions
frequently during the day.
Decrease frequency of bathing and limit bathing to brief exposure to tepid water; after bathing, briefly
pat skin dry and immediately apply skin lubricant.
Use mild, unscented, hypo-allergenic soap two to three times per week; limit daily use of soap to groin and
axillae (spare legs, arms, and torso).
Humidify dry indoor environment, especially in winter.
Choose clothing that does not irritate the skin (preferably made of doubly rinsed cotton or silk); avoid
clothing made of wool, smooth-textured cotton, or heat-retaining material (synthetic fabrics); when
washing sheets, add bath oil (e.g., Alpha Keri) to rinse cycle.
Avoid use of vasodilators (caffeine, alcohol, spices, hot water) and excessive sweating.
Avoid use of provocative topical medications, such as corticosteroids, for prolonged periods (risk of skin
atrophy) and topical anesthetics and antihistamines (may sensitize exposed skin and increase risk of
allergic contact dermatitis).
Prevent complications of scratching by keeping fingernails short and clean and by rubbing skin with the
palms of the hands if urge to scratch is irresistible.

Treatments
Standard topical antipruritic agents: menthol and camphor (e.g., Sarna lotion), oatmeal baths (e.g.,
Aveeno), pramoxine (e.g., PrameGel), calamine lotion (Caladryl; use only on weeping lesions, not on
dry skin), doxepin 5% cream (Zonalon).
Topical antipruritic agents for refractory pruritus (e.g., severe atopic dermatitis): Burrow’s solution (wet
dressings), Unna’s boot, tar emulsion.
Systemic antipruritic agents (used in allergic and urticarial disease): doxepin (Sinequan), 10–25 mg at
bedtime; hydroxyzine (Atarax), 25–100 mg at bedtime; nonsedating antihistamines (e.g., fexofenadine
[Allegra]).
Reprinted with permission from Moses S. Pruritus. Am Fam Physician 2003;68:1135–1142, 1145–1146.

255
 Chapter 24 Pruritus (Atopic Dermatitis)

Table 24-4 Specific Management of Pruritic Conditions

Condition Management

Cholestasis Cholestyramine (Questran), 4–6 g orally 30 min before meals

Ursodiol acid (Actigall), 13–15 mg/kg/day orally
Ondansetron (Zofran), 4–8 mg IV, then 4 mg orally every 8 hr
Opiate receptor antagonist such as nalmefene (Revex), 20 mg orally twice daily
Rifampin (Rifadin), 300 mg orally twice daily
Bile duct stenting for extrahepatic cholestasis
Bright-light therapy

Neurotic excoriation Pimozide (Orap) orally for delusions of parasitosis

Selective serotonin reuptake inhibitor (e.g., fluvoxamine [Luvox], fluoxetine
[Prozac], paroxetine [Paxil])

Notalgia paresthetica Capsaicin 0.025% cream (Zostrix) applied to localized areas four to six times
daily for several weeks

Polycythemia vera Aspirin, 500 mg orally every 8–24 hr

Paroxetine (Paxil), 10–20 mg/day orally
Interferon alfa, 3–35 million IU/wk

Spinal opioid-induced Ondansetron, 8 mg IV, concurrent with opioid

pruritus Nalbuphine (Nubain), 5 mg IV, concurrent with opioid

Uremia Ultraviolet B phototherapy twice weekly for 1 mo

Activated charcoal, 6 g/day orally
Capsaicin 0.025% cream applied to localized areas four to six times daily for
several weeks

IV, intravenously.
Reprinted with permission from Moses S. Pruritis. Am Fam Physician 2003;68:1135–1142, 1145–1146.

is important to remember that corticosteroids do not the disease. If these basic measures fail to control the
directly relieve itch and should not be used in pruritic disease, topical corticosteroids are a good choice for
conditions that are not inflammatory in nature. In sys- treatment because of the inflammatory nature of
temic illness, treatment of the underlying condition atopic dermatitis. It is important to use the lowest
often relieves itch. Options for the management of spe- effective potency and dose to minimize the chances of
cific pruritic conditions are listed in Table 24-4. side effects such as thinned skin. Alternatives to corti-
costeroids are the topical immunosuppressant med-
Plan ications tacrolimus and pimecrolimus. Again, these
medications are aimed at treating the inflammatory
Diagnostic cause of atopic dermatitis and have no direct antipru-
Based on the typical history and physical examina- ritic effect. Steven was instructed in the importance of
tion findings, atopic dermatitis is likely to be the moisturizing his skin and avoiding irritants. He was
cause of Steven’s itching, and therefore no further prescribed triamcinolone 0.1% ointment, a moderate
diagnostic tests are indicated at this time. If symp- potency topical corticosteroid.
toms persist despite appropriate treatment, skin
biopsy could be performed to provide additional Disposition
diagnostic information. Steven was advised to follow up in 2 to 3 weeks if his
symptoms were not controlled with these treatment
Therapeutic recommendations or if he had any concerning side
Before initiating drug treatment for atopic dermatitis, effects or new symptoms.
less intensive management strategies may be tried.
Moisturizing is extremely important because dry skin Material Available on Student Consult
is a significant contributor to itch in atopic dermatitis.
Review Questions and Answers about Atopic
Nonspecific therapies for itch such as avoiding skin
Dermatitis
irritants and heat may aid in the prevention of flares of

256
 Chapter 25 Dizziness (Vestibular Neuritis)

REFERENCES

Moses S. Pruritus. Am Fam Physician 2003;68:1135–1142, Yeh HM, Chen LK, Lin CJ, et al. Prophylactic intravenous
1145–1146. ondansetron reduces the incidence of intrathecal mor-
Sherard GB, Atkinson SM. Pruritic dermatological conditions phine-induced pruritus in patients undergoing
in pregnancy. Obstet Gynecol Surv 2001;56: 427–432. cesarean delivery. Anesth Analg 2000;91:172–175.●A
Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet
pruritus: A review. J Clin Anesth 2003;15:234–239. 2003;361:690–694.

C h a p t e r

25 Dizziness (Vestibular Neuritis)

Jeanne M. Ferrante

states that he began to feel ill 1 week ago with fatigue,

KEY POINTS slight sore throat, nasal congestion, and dry cough.
This morning he awoke with severe dizziness,
1. The majority of dizziness cases are self-limited described as “the room spinning” associated with
and benign. nausea, vomiting, and generalized weakness. Any
2. The history and physical examination are most movement of his head makes his symptoms worse.
important in the workup of dizziness. He has been feeling dizzy and nauseated all day and
3. Dizziness can be classified into vertigo, presyn- has not been able to keep anything down. This is the
cope, dysequilibrium, and nonspecific light- first time that he has experienced these symptoms.
headedness. He denies recent head or neck trauma, barotrauma,
4. Laboratory tests are of little value in most headache, hearing loss, discharge from the ears,
patients complaining of dizziness. tinnitus, or fullness in his ears. There is no blurry
5. Patients with cerebrovascular risk factors or vision, double vision, difficulty swallowing, changes
neurologic deficits should undergo magnetic in his speech, or weakness or numbness in his face,
resonance imaging of the posterior fossa. arms, or legs.
6. Holter monitoring and echocardiogram may be
indicated in patients with palpitations, underlying
Medical History
heart disease, or an abnormal cardiac examination.
Tom has had no major medical illnesses or surgery.
He has no history of recurrent ear infections. He
does not take any medications and has not been on
antibiotics recently.
INITIAL VISIT
Family History
Subjective Tom has no siblings. His parents are alive and well.
Patient Identification and Presenting
Problem Social History
Tom W. is a 41-year-old white man who presents for Tom is married and works as a mechanic. He has
the first time with a complaint of dizziness. Tom smoked one pack of cigarettes per day for 25 years.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

257
 Chapter 25 Dizziness (Vestibular Neuritis)

REFERENCES

Moses S. Pruritus. Am Fam Physician 2003;68:1135–1142, Yeh HM, Chen LK, Lin CJ, et al. Prophylactic intravenous
1145–1146. ondansetron reduces the incidence of intrathecal mor-
Sherard GB, Atkinson SM. Pruritic dermatological conditions phine-induced pruritus in patients undergoing
in pregnancy. Obstet Gynecol Surv 2001;56: 427–432. cesarean delivery. Anesth Analg 2000;91:172–175.●A
Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet
pruritus: A review. J Clin Anesth 2003;15:234–239. 2003;361:690–694.

C h a p t e r

25 Dizziness (Vestibular Neuritis)

Jeanne M. Ferrante

states that he began to feel ill 1 week ago with fatigue,

KEY POINTS slight sore throat, nasal congestion, and dry cough.
This morning he awoke with severe dizziness,
1. The majority of dizziness cases are self-limited described as “the room spinning” associated with
and benign. nausea, vomiting, and generalized weakness. Any
2. The history and physical examination are most movement of his head makes his symptoms worse.
important in the workup of dizziness. He has been feeling dizzy and nauseated all day and
3. Dizziness can be classified into vertigo, presyn- has not been able to keep anything down. This is the
cope, dysequilibrium, and nonspecific light- first time that he has experienced these symptoms.
headedness. He denies recent head or neck trauma, barotrauma,
4. Laboratory tests are of little value in most headache, hearing loss, discharge from the ears,
patients complaining of dizziness. tinnitus, or fullness in his ears. There is no blurry
5. Patients with cerebrovascular risk factors or vision, double vision, difficulty swallowing, changes
neurologic deficits should undergo magnetic in his speech, or weakness or numbness in his face,
resonance imaging of the posterior fossa. arms, or legs.
6. Holter monitoring and echocardiogram may be
indicated in patients with palpitations, underlying
Medical History
heart disease, or an abnormal cardiac examination.
Tom has had no major medical illnesses or surgery.
He has no history of recurrent ear infections. He
does not take any medications and has not been on
antibiotics recently.
INITIAL VISIT
Family History
Subjective Tom has no siblings. His parents are alive and well.
Patient Identification and Presenting
Problem Social History
Tom W. is a 41-year-old white man who presents for Tom is married and works as a mechanic. He has
the first time with a complaint of dizziness. Tom smoked one pack of cigarettes per day for 25 years.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

257
 Chapter 25 Dizziness (Vestibular Neuritis)

He drinks alcohol rarely on weekends. He denies vertigo include lesions of the vestibular nerve,
illicit drug use. labyrinth, or both (Froehling et al., 1994 ●B ). Central
vertigo is caused by disorders of the lower brain
Review of Systems stem or cerebellum. Patients with brain stem disease
The patient denies headache, neck pain, shortness of have symptoms typical of vertebrobasilar insuffi-
breath, chest pains, palpitations, depression, anxiety, ciency, such as diplopia, dysarthria, dysphagia,
fainting, and falling. paresthesia, and changes in sensory and motor func-
tion. Patients with cerebellar disease may have trun-
cal ataxia and difficulty with rapid alternating
Objective movements and finger-to-nose testing. Tom had
none of the history or physical findings of central
Physical Examination vertigo. The result of the Dix-Hallpike maneuver
General Tom is a well-developed, well-nourished also helps to point to a peripheral cause of the ver-
alert white man lying on the table in mild to mod- tigo. The Dix-Hallpike maneuver (also referred to as
erate distress. the Nylen-Barany maneuver) is a head hanging
maneuver that helps to distinguish peripheral ver-
Vital Signs His height is 5 feet 10 inches, weight is 165 tigo from central causes of vertigo (Hoffman et al.,
pounds, temperature is 37.3˚C (99.1˚F), respiratory rate 1999 ●B ). The Dix-Hallpike maneuver is performed
is 20, blood pressure is 138/88, and pulse is 90. There is with the patient initially sitting on the examination
no orthostatic change in blood pressure or pulse. table. Quickly the patient is brought into the lying
position by the examiner with the patient’s head
Head, Eyes, Ears, Nose, and Throat His head is with- turned approximately 30 degrees to one side and
out lesions or signs of trauma. His external ear canals slightly hyperextended over the end of the table
and tympanic membranes are clear bilaterally; hear- (Fig. 25-1). The patient should be given clear
ing is intact by testing with tuning forks. His conjunc- instructions to keep his or her eyes open. The
tivae are pink; pupils are equal, round, and reactive to patient is then observed for symptoms of nausea
light and accommodation; extraocular muscles intact and vertigo and signs of nystagmus. This maneuver
with horizontal nystagmus with a rotational compo- is then repeated with the head turned to the oppo-
nent (fast phase) toward the left. His nose is clear; the site side. If the symptoms are reproduced and
maxillary and frontal sinuses are nontender to percus- nystagmus occurs after a brief latency period (3 to
sion. He has poor dentition. His oropharynx is clear. 20 seconds) but resolves in less than 1 minute, then
the dizziness is more likely to have a periphera cause.
Neck It is supple, with no bruits and no lymph- If there are mild or no symptoms, and nystagmus
adenopathy. The thyroid is normal. is present immediately and persists for longer than
1 minute, then a central cause of vertigo should be
Lungs The lungs are clear to auscultation. suspected.
Vestibular neuritis, the most common cause of
Heart He has normal sinus rhythm without mur- vertigo seen in primary care offices (Sloane et al.,
murs, rubs, or gallops. 2001● B), is thought to be due to inflammation of the
vestibular nerve from either an acute viral infection
Neurologic He is oriented to person, place, and time. or reactivation of dormant herpes simplex virus
He has a normal but slowed gait. Cranial nerves II type 1. It is characterized by the acute onset of
through XII are intact. Deep tendon reflexes are 2+ in severe persistent vertigo (made worse by head
upper and lower extremities bilaterally. Strength is 5 movement), nausea, and vomiting, in the absence of
of 5 in all extremities. Sensorium is intact to light hearing loss or tinnitus. When there is cochlear
touch and pinprick. Cerebellum is intact to finger- involvement (tinnitus, hearing loss), then the disor-
to-nose pointing and rapid alternating movements. der is termed labyrinthitis (Hoffman et al., 1999● B ).
Romberg test shows falling toward the right. Dix- An upper respiratory tract infection precedes 50%
Hallpike maneuver is positive on the right for nys- of cases. Tom developed acute persistent symptoms,
tagmus and vertigo after a latency of approximately and he had a recent upper respiratory tract infec-
3 seconds. This lasted for less than 1 minute. tion. He has no hearing loss or tinnitus and no signs
of a central cause of the vertigo. Tom’s history and
Assessment physical findings make vestibular neuritis the most
likely diagnosis.
Working Diagnosis
The working diagnosis is peripheral vertigo caused Differential Diagnoses
by acute vestibular neuritis. Vertigo can be caused by Other common causes of peripheral vertigo include
peripheral or central disorders. Peripheral causes of benign paroxysmal positional vertigo and Meniere’s

258
 Chapter 25 Dizziness (Vestibular Neuritis)

Figure 25-1 The Dix-Hallpike maneuver. (From Reilly BM. Practical Strategies in Outpatient Medicine, 2nd ed.
Philadelphia, WB Saunders, 1991.)

disease. Benign paroxysmal positional vertigo is the Plan

most common cause of vertigo in referral settings
(Sloane et al., 2001● B ). Patients usually have sudden Diagnostic
intermittent episodes of vertigo initiated by position Because Tom does not have symptoms and signs of a
change or head turning only. The episodes last less more severe cause of vertigo, no tests are indicated at
than 1 minute, and there is no hearing loss. In most this time. If the symptoms do not resolve after 6 weeks
cases, it is idiopathic and results from accumulation or if hearing loss or tinnitus develops, then audiome-
of free-floating debris in the endolymph of the pos- try and vestibular assessment (including calorics with
terior semicircular canal. A precipitating factor may or without electronystagmography) may be indicated.
be a recent middle ear infection, vestibular neuritis,
Therapeutic
head trauma, or ear surgery. Peak occurrence is
The patient was given meclizine 25 mg three to four
between ages 50 and 70. Ménière’s disease is caused
times daily for the dizziness and nausea.
by an abnormal collection of endolymphatic fluid
in the inner ear. It is defined by a classic triad of Patient Education
episodic vertigo, low-frequency sensorineural hear- The patient is educated on the benign course of
ing loss, and tinnitus (Froehling et al., 1994● B ). Ear
vestibular neuritis and that it gradually resolves over
fullness may also be present. Patients are usually 2 days to 6 weeks. He is instructed to move slowly
between the ages of 30 and 60 years at the onset. initially and to take the meclizine as needed for
These patients have clusters of vertiginous exacerba- symptoms. Once the nausea and vomiting subside,
tions coinciding with increased hearing loss and habituation exercises (deliberately repeating the head
intensity of tinnitus. During periods of remission, maneuvers that elicit the vertigo) may lessen the dura-
episodes of vestibular dysfunction and even hearing tion and severity. He is also advised to stop smoking.
loss and tinnitus may significantly resolve for weeks
or months. Other rare causes of peripheral vertigo Disposition
are associated with hearing loss and include The patient is instructed to make a second appoint-
perilymphatic fistula (history of pressure changes ment in 6 weeks or sooner if his symptoms are not
such as diving or air flight, worsened with strain- relieved by the meclizine or if he develops hearing
ing), cholesteatoma (complication of chronic otitis loss, tinnitus, or other neurologic symptoms.
media with conductive hearing loss and ear
drainage), temporal bone trauma, ototoxicity (from
aminoglycoside antibiotics), and Ramsay Hunt syn- DISCUSSION
drome (from herpes zoster infection with ear pain,
facial palsy, and vesicles in the ear canal) (Froehling Dizziness is prevalent in the community, ranging
et al., 1994 ●B ). from 1.8% in young adults to more than 30% in the

259
 Chapter 25 Dizziness (Vestibular Neuritis)

elderly (Sloane et al., 2001● B). Dizziness can be caused tion difficulties. Acoustic neuroma is a benign tumor
by a disturbance in any of a number of balance con- that usually causes progressive unilateral high-frequency
trol systems, including the visual pathways, the hearing loss, tinnitus, and imbalance (particularly in the
vestibular apparatus, the cardiovascular system, and dark). Vertigo occurs in less than 20% of patients. The
the proprioceptive tracts of the central nervous sys- lesion is in the cerebellopontine angle and will also
tem. Dizziness is a general and vague term that means affect, when advanced, other cranial nerves (i.e., fifth
different things to different people. History taking is and seventh). Vascular diseases include vertebrobasilar
most important to clarify what the patient means by transient ischemic attacks, cerebellar or brain stem
dizziness. Dizziness can be classified into four main strokes, and vertebrobasilar migraines. Neurologic dis-
categories: vertigo, presyncope, dysequilibrium, and orders include complex partial seizures and multiple
nonspecific lightheadedness (Table 25-1). Vertigo is sclerosis. Complex partial seizures may present with an
an illusion of movement, as if the patient or the room aura of dizziness, vertigo, or unsteadiness. In multiple
is spinning. Vertigo can be peripheral (discussed pre- sclerosis,vertigo can present initially in 5% of patients and
viously) or central in origin. Central vertigo is rare ultimately in as many as 50% of patients. Symp-
and can be caused by neoplastic, vascular, or neuro- toms are usually episodic and associated with a wide
logic disorders of the lower brain stem or cerebellum variety of other neurologic symptoms.
(Froehling et al., 1994● B ). In patients with posterior In presyncope, patients describe the feeling of
fossa tumors, vestibular dysfunction is usually slow in almost fainting or the world going gray and out
onset due to the slow growth of typical neoplasms. of focus, especially when they stand. This can be
These patients usually have imbalance and coordina- caused by orthostatic hypotension due to decreased

Table 25-1 Classification of Dizziness

Vertigo Presyncope
Peripheral Postural symptoms with or without orthostatic hypotension
Vestibular neuritis Medications
Labyrinthitis Anemia
Benign paroxysmal positional vertigo Infections
Ménière’s disease Dehydration
Perilymphatic fistula Metabolic diseases (electrolyte disturbance, diabetes, thyroid)
Cholesteatoma Cardiac disease
Temporal bone trauma Aortic stenosis
Ototoxicity from medications Mitral regurgitation
Ramsay Hunt syndrome Hypertrophic cardiomyopathy
Central Arrhythmias
Posterior fossa tumors Heart blocks
Acoustic neuroma
Vertebrobasilar transient ischemic Nonspecific Lightheadedness
attack Depression
Brain stem or cerebellar strokes Anxiety
Vertebrobasilar migraines Panic attacks
Complex partial seizures Somatization disorder
Multiple sclerosis Substance abuse

Dysequilibrium
Multiple sensory deficits
Decreased vision
Peripheral neuropathy
Diabetes mellitus
Alcoholism
Medications
Anticonvulsants
Benzodiazepines
Neuroleptics
Antidepressants
Neurologic disorders

260
 Chapter 25 Dizziness (Vestibular Neuritis)

baroreceptor responsiveness, medications (antihy- spontaneous nystagmus. Visual acuity should be tested
pertensives, antidepressants), anemia, dehydration, in patients with dysequilibrium. The neck examination
metabolic diseases (e.g., diabetes mellitus, thyroid includes checking for bruits and thyroid abnormalities.
diseases), or cardiovascular disorders. Structural The cardiovascular examination is important to check
cardiac disease (e.g., aortic stenosis, mitral regurgi- for size of the heart, murmurs, and arrhythmias. The
tation, and hypertrophic cardiomyopathy), arrhyth- neurologic examination should focus on the cranial
mias, and heart blocks may also cause dizziness nerves (eye movements, facial strength and sensation,
associated with near-syncope or syncope. hearing), strength, gait observation, Romberg testing,
Dysequilibrium is a sensation of unsteadiness and cerebellar functions. If the dizziness is described
and imbalance when standing or walking and resolves as vertigo, then the Dix-Hallpike maneuver should
at rest. The patient feels a lack of coordination and a be performed. If a psychogenic cause is suspected, an
sense of impending falls. This is commonly seen in often recommended test is to have the patient hyper-
the elderly. The cause is usually multifactorial includ- ventilate for 3 minutes in an attempt to reproduce
ing multiple sensory deficits (e.g., decreased visual symptoms. This test, however, has poor specificity
acuity and peripheral neuropathy with impaired (Kroenke et al., 1992● B ). Laboratory tests are of little
proprioception), medications affecting the central value in most patients complaining of dizziness
nervous system (e.g., anticonvulsants, benzodi- (Hoffman et al., 1999● B). Patients who appear to have
azepines, neuroleptics, and antidepressants), or other fatigue or metabolic abnormalities can be screened
neurologic disorders (Sloane et al., 2001● B ). with a standard biochemical profile and complete
Patients with nonspecific lightheadedness are usu- blood count. Thyroid function tests may be indicated
ally vague in their description, sometimes feeling sen- if thyroid disease is suspected. A rapid plasma reagin
sations of floating, feeling apart or far away from the or Venereal Disease Research Laboratories (VDRL)
environment, fatigue, or tightness or fullness in the test may be useful in patients suspected of Ménière’s
head. Patients may also complain of headache, numb- disease because secondary or early tertiary syphilis
ness or tingling around the mouth or in the hands, or may present with symptoms identical to those seen in
abdominal pain. These patients tend to have psychi- Ménière’s disease. An electrocardiogram can docu-
atric disorders including depression, anxiety, panic ment cardiac abnormalities if they are suspected based
attacks, somatization disorder, and substance abuse. on the history and physical examination. When the
Once the character of the dizziness is deter- history, physical examination, and laboratory studies
mined, it is helpful to find out how long it has persisted rule out organic disease, psychogenic factors should be
and whether it occurs in attacks. In addition, the addressed.
physician should ask about what provokes or wors- Advanced diagnostic tests are helpful if more
ens the dizziness (standing up, head turning or severe causes of dizziness are suspected based on the
rolling over in bed, coughing or straining, stress or history and physical examination. In patients with
emotional upset), and what was happening when the chronic peripheral vertigo or vertigo associated with
dizziness began (e.g., loud noise, blow to the head, hearing loss, audiometric testing and vestibular
flulike symptoms, or a cold beforehand). Inquiring assessment by the audiologist are indicated. Patients
about general health problems such as high blood with cerebrovascular risk factors or neurologic
pressure, diabetes, heart disease, thyroid disease, deficits such as dysarthria or numbness should
migraine headaches, seizure disorder, anxiety, and undergo magnetic resonance imaging of the posterior
depression is also helpful. Medications and drug use fossa. Tests such as Holter monitoring and echocar-
should always be noted. A system review is important diogram may be indicated in patients with palpita-
to identify symptoms that are related to the dizziness tions, underlying heart disease, or an abnormal
including generalized weakness; loss of consciousness; cardiac examination. Treatment of dizziness depends
headaches; nausea; vomiting; diplopia; blurry vision; on the suspected underlying cause. Acute vertigo and
dysarthria; dysphagia; hearing loss; discharge from the associated vegetative symptoms can be treated symp-
ears; tinnitus or fullness in the ears; numbness or tin- tomatically with the antihistamines meclizine or
gling in the face, around the mouth, or in the hands or dimenhydrinate in doses of 25 to 50 mg three or four
feet; chest pain; and a pounding or rapid heartbeat. times daily. In severe cases, diazepam, which decreases
The physical examination can help to narrow the brain stem response to vestibular stimuli, in doses
differential diagnosis. Vital signs, especially postural of 2.5 to 5.0 mg three times daily can be used.
changes in blood pressure, should be obtained to check Methylprednisolone, starting at 100 mg/day and
for orthostatic hypotension. A head, eyes, ears, nose, tapering to 10 mg over 3 weeks was shown in a recent
and throat examination should focus on the ears, eyes, randomized controlled trial to reduce long-term
and sinuses. Spontaneous nystagmus can usually be vestibular dysfunction in vestibular neuritis (Strupp
observed in vertiginous patients. However, in periph- et al., 2004●A). Benign paroxysmal positional vertigo
eral vestibular disorders, visual fixation can suppress can be effectively treated by a canalith repositioning

261
 Chapter 25 Dizziness (Vestibular Neuritis)

1. Have the patient lie down quickly onto her back. procedure, such as the Epley maneuver, which takes
the patient through a series of head positions (Hilton
and Pinder, 2004● A) (Fig. 25-2). This returns debris
from the semicircular canal into the utricle, where its
movement does not cause vertigo. Ménière’s disease is
treated with salt restriction, diuretics, or both. The
more serious causes of peripheral vertigo are best han-
dled by otolaryngologic specialists. Corrective surgical
procedures may sometimes be helpful. Patients with
dysequilibrium are usually managed supportively.
Adjustment of medications may be necessary, and
steps to improve function in the elderly (e.g., treatment
of cataracts, physical therapy for gait and balance train-
ing, use of walkers) can help to prevent secondary dis-
ability, isolation, depression, and falls. Cardiovascular
and neurologic disorders are treated accordingly.
Nonspecific lightheadedness can be managed by
reassurance and addressing the specific psychiatric
disorder.
In summary, dizziness can be caused by a distur-
bance in any of a number of balance control systems.
The history and physical examination are most
important in the workup for dizziness. Dizziness in
2. First, turn the patient's head to primary care very rarely represents a life-threatening
the symptomatic side at a 45⬚
angle for 30–60 seconds. problem. Because the majority of cases are self-
limited and benign, conservative management strate-
3. Then turn the head to the opposite gies, including observation and supportive treatment,
side for 30–60 seconds. are often appropriate.
4. Finally, roll the head facing 45⬚
downward on the same side.
Return the patient to a sitting
position.
Material Available on Student Consult
Figure 25-2 Epley maneuver for benign paroxysmal posi-
tional vertigo. (From Strickland C, Russell R, Hoekzema G. Review Questions and Answers about Vestibular
What is the best way to manage benign paroxysmal Neuritis
positional vertigo? J Fam Pract 2003;52:971–973.)

REFERENCES
Froehling DA, Silverstein, MD, Mohr DN, Beatty CW. Does Reilly BM. Practical Strategies in Outpatient Medicine, 2nd
this dizzy patient have a serious form of vertigo? JAMA ed. Philadelphia, WB Saunders, 1991.
1994;271:385–388. ● B Sloane PD, Coeytaux RR, Beck RS, Dallara J. Dizziness:
Hilton M, Pinder D. The Epley (canalith repositioning) State of the science. Ann Intern Med 2001;134:
manoeuvre for benign paroxysmal positional vertigo 823–832.● B
(Cochrane Review). The Cochrane Library. Vol. 3. Strickland C, Russell R, Hoekzema G. What is the best way
Chichester, UK, John Wiley & Sons, 2004.● A to manage benign paroxysmal positional vertigo? J Fam
Hoffman RM, Einstadter D, Kroenke K. Evaluating dizzi- Pract 2003;52:971–973.
ness. Am J Med 1999;107:468–478.● B Strupp M, Zingler VC, Arbusow V, et al. Methyl-
Kroenke K, Lucas CA, Rosenberg ML, et al. Causes of prednisolone, valacyclovir, or the combination for
persistent dizziness. A prospective study of 100 patients in vestibular neuritis. N Engl J Med 2004;351: 354–361.●A
ambulatory care. Arch Intern Med 1992;117: 898–904.● B

262
 C h a p t e r

26 Ringing in Ears (Tinnitus)

David M. Barclay III

a consequence. Lately he has started to feel depressed

KEY POINTS and apathetic about the future.

1. Subjective tinnitus is the most prevalent type Medical History

and is commonly referred to as idiopathic (sub- John has had no major medical illnesses or surgeries.
jective idiopathic tinnitus). He has no history of head trauma or recurrent ear
2. Hyperacusis, the abnormally intense amplifica- infections. Aside from an occasional acetaminophen,
tion of sound within the auditory pathways, he does not take any medications. He has experi-
may accompany tinnitus. enced brief episodes of ringing in his ears, lasting
3. A complete audiologic evaluation should be from seconds to minutes, from the time he was a
performed on all patients with tinnitus. teenager. He has also experienced brief episodes of
4. The primary goal of tinnitus retraining therapy hearing his pulse in his ears.
(TRT) is to induce habituation to reactions so
that patients are still aware of the tinnitus but Family History
are not bothered or distressed by it. John’s father is 78, and aside from hypertension he is
well. His mother is 74 and a breast cancer survivor.
He has a brother and a sister, both of whom are in
good health.

INITIAL VISIT Social History

John has been married for 20 years and has no children.
Subjective He is the headmaster of a boarding school. He eats a
regular diet and enjoys bicycling and swimming. He
Patient Identification and Presenting drinks socially and does not smoke or use illegal drugs.
Problem
John B. is a 45-year-old white man who presents with Review of Systems
a complaint of ringing in his ears. John does not experience headaches, neck pain,
shortness of breath, chest pains, palpitations, abdom-
History of Present Illness inal pains, or musculoskeletal problems. He has been
John states that about 3 months ago he began to hear feeling depressed for the past couple of weeks and
a persistent, high-pitched ringing in both ears. The has difficulty falling asleep.
ringing has progressed into a constant, unrelenting
sound that alternates between a high-pitched teaket- Objective
tle and the roar of a jet turbine. John has noticed that
lack of sleep, stress, and caffeine make the sound Physical Examination
louder. He has also become very sensitive to loud General John is a well-developed, well-nourished,
noises and sometimes is unable to tolerate everyday alert white man in mild distress.
sounds, such as the car radio at a normal volume. He
has not noticed any hearing loss, aural fullness, or Vital Signs His height is 5 feet 9 inches, weight is 155
vertigo. Falling asleep has become difficult, and his pounds, temperature is 36.9˚C (98.4˚F), respiratory
ability to concentrate during the day has suffered as rate is 18, blood pressure is 130/85, and pulse is 80.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

263
 Chapter 26 Ringing in Ears (Tinnitus)

Head, Eyes, Ears, Nose, and Throat His head is nor- idiopathic tinnitus). Subjective tinnitus is one of the
mocephalic and atraumatic, his external ear canals three symptoms that constitute Ménière’s disease. It
and tympanic membranes are clear bilaterally, his has many forms, varying from a benign sound that is
hearing is grossly intact, and the Webber and Rinne heard only occasionally to a constant roar that is heard
tests are normal. His conjunctivae are pink and the 24 hours per day and is accompanied by hyperacusis
pupils equal, round, and reactive to light and accom- and distortion of sounds. This type of tinnitus disturbs
modation; extraocular movements are intact without sleep and the ability to concentrate on intellectual work.
nystagmus. His nose is clear; the maxillary and It may be accompanied by phonophobia, affective
frontal sinuses are nontender. He has good dentition, disorders such as depression, and even suicide.
and the oropharynx is clear. Hyperacusis, the abnormally intense amplifica-
tion of sound within the auditory pathways, may
Neck His neck is supple, with no lymphadenopathy, accompany tinnitus. In this condition, the neuronal
thyromegaly, or jugular venous distention. activity evoked by a given sound is significantly
higher than that in a normal individual. Patients
Lungs His lungs are clear to auscultation. frequently experience physical discomfort in the
presence of sounds that are perceived as normal to
Heart The heart has a normal sinus rhythm without others. The secondary activation of the limbic and
murmurs, rubs, or gallops. autonomic pathways, as well as the baseline level of
activation within these systems, is normal.
Neurologic Examination Misophonia (from the Greek miso, “hate”), a
He is alert and oriented to person, place, and time; cra- strong aversion to sounds, can also develop. This
nial nerves II through XII are intact. Webber and Rinne originates from the abnormal activation of the
tests are normal. Reflexes are 2+ throughout, motor limbic and autonomic nervous systems in the
strength is 5 out of 5 throughout, sensory examination presence of a normally functioning auditory system.
is intact to light touch and pinprick, cerebellar function Misophonia is a conditioned response that depends
is intact, and the Romberg test is normal. significantly on the patient’s past experiences and the
context in which the sound occurs.
Assessment Conditions associated with tinnitus are listed in
Table 26-1.
Working Diagnosis
John’s history and physical examination are most
Plan
consistent with a diagnosis of subjective tinnitus.
Diagnostic
Differential Diagnosis The initial workup of tinnitus should include a
Tinnitus is classified as either subjective or objective. self-assessment of the severity of the tinnitus,
Objective tinnitus can be heard by the examiner and an audiologic examination, and possibly a radio-
is caused by an acoustic source in the body. Objective graphic evaluation and laboratory tests. A number of
tinnitus has also been referred to as vibratory tinni- self-assessment scales have been developed to meas-
tus or extrinsic tinnitus and may be heard by auscul- ure the intensity of the tinnitus. These scales deter-
tation of the ear and surrounding vessels. It is mine the functional, physical, and psychological
differentiated into pulsatile and nonpulsatile tinni- consequences of the tinnitus and the coping skills of
tus. Nonpulsatile tinnitus is further divided into the patient. One such scale, the Tinnitus Handicap
mild and severe types. Mild nonpulsatile tinnitus is Inventory, developed in 1996, is a self-report instru-
heard by the patient only when in a quiet environ- ment that has been validated to quantify the impact
ment and is usually not distressing. Severe pulsatile
tinnitus is present all the time and often degrades the
patient’s quality of life (Heller, 2003).
Table 26-1 Conditions Associated with
Pulsatile tinnitus is classified as vascular or
Tinnitus
nonvascular. Nonvascular tinnitus is usually caused
by myoclonus of the tensor tympani, stapedius Ménière’s disease
muscle, or palatal musculature. Arterial causes of Presbycusis
pulsatile tinnitus include hypertension, arterio- Otitis
venous malformations, and atherosclerosis of the Otosclerosis
carotid arteries. Venous causes include benign Ototoxicity
intracranial hypertension, jugular bulb abnormali- Vestibular schwannoma
ties, and hydrocephalus (Sismantis, 1998). Autoimmune hearing loss
Hormonal changes of pregnancy
Subjective tinnitus is the most prevalent type
Menopause
and is commonly referred to as idiopathic (subjective

264
 Chapter 26 Ringing in Ears (Tinnitus)

of tinnitus on daily living. It consists of 25 questions

Table 26-2 Medications and Substances
divided into three subscales: (1) functional, (2) emo-
That May Cause Tinnitus
tional, and (3) catastrophic (Newman et al., 1996 ● B ).
The only other scale that has been validated and shown Analgesics
to have good intertest reliability with the Tinnitus Aspirin
Handicap Inventory is the Tinnitus Questionnaire Nonsteroidal anti-inflammatory drugs
(Heller, 2003).
It is important to determine whether the tinni- Antibiotics
tus is unilateral or bilateral and hearing loss is pres- Aminoglycosides
ent. The Webber and Rinne tests may be used as Chloramphenicol
Erythromycin
an initial in-office evaluation of hearing. Magnetic Tetracycline
resonance imaging should be considered in patients Vancomycin
with unilateral tinnitus and sensorineural hearing
loss and in those with asymmetrical hearing loss Chemotherapeutics
suspicious for an acoustic neuroma. Patients who Bleomycin (Blenoxane)
cannot undergo magnetic resonance imaging can Cisplatin
have a computed tomography scan of the posterior Mechlorethamine (Mustargen)
fossae with enhancement. Computed tomography of Methotrexate
the temporal bones should be obtained in patients Vincristine
suspected of hereditary hearing loss, Paget’s disease,
Loop Diuretics
otosclerosis, and trauma (Schaber, 2003). Furosemide
A complete audiologic evaluation should be Bumetanide (Bumax)
performed on all patients. This testing establishes Ethacrynic acid (Edecrine)
a baseline for the future and helps guide more
advanced audiologic testing. Pure tone testing pri- Others
marily evaluates the function of the peripheral por- Chloroquine (Aralen)
tion of the hearing apparatus. Tympanometry may Heavy metals: mercury, lead
identify previously undetected middle ear effusion, Heterocyclic antidepressants
stiffness of the tympanic membrane, or myoclonus Quinine
of the tensor tympani, stapedius muscle, or palatal From Brechtelsbauer D. Adult hearing loss. Prim
musculature. Speech reception thresholds and Care 1990;17:249–266; Schleuning AJ 2nd.
speech discrimination scores usually reflect pathol- Management of the patient with tinnitus.
ogy of the central nervous system. Other audiologic Med Clin North Am 1991;75:1225–1237; Weber P,
Klein A. Hearing loss. Med Clin North Am
tests may include loudness matching (estimates the 1999;83:125–137.
loudness of a pure tone necessary to extinguish the
tinnitus), pitch masking (correlates the frequency
of the tinnitus with a variety of stimuli), minimal
masking level (determines the amount of sound nec-
essary to mask the tinnitus), and residual inhibition
Table 26-3 Treatment Modalities Used
(determines the tone, pitch, and intensity necessary
for Tinnitus
to bring about decreased or absent tinnitus). These
tests help evaluate the potential effectiveness of Counseling
masking therapy (Schaber, 2003). Medications (antidepressants, anticonvulsants,
Laboratory testing including a complete blood anxiolytics, local anesthetics, vasodilators)
count, lipid profile, chemistry panel, and thyroid Surgery
function studies should be obtained in patients who Masking techniques
may have medical abnormalities. Further testing may Psychological approaches
be indicated by the history and physical examination Biofeedback
Acupuncture
(Schaber, 2003).
Hyperbaric oxygen chamber therapy
Medications and other substances that may Temporomandibular joint therapy
cause tinnitus are listed in Table 26-2. Tinnitus retraining therapy

Therapeutic From Brechtelsbauer D. Adult hearing loss. Prim

Several modalities have been used to treat tinnitus Care 1990;17:249–266.
(Table 26-3) TRT is based on the neuropsychological
model of tinnitus and decreased sound tolerance. It
works by inducing a sustained habituation to tinni-
tus and/or external sounds. This habituation is

265
 Chapter 26 Ringing in Ears (Tinnitus)

achieved through a modification of the neural con- The phenomenon of neural plasticity and the
nections linking the limbic and autonomic nervous neurophysiologic model of tinnitus have been used
systems. TRT does not “cure” tinnitus, but it can to explain how tinnitus affects the nonauditory areas
provide relief from symptoms for many patients, of the brain and provide the basis for the role of
particularly those who suffer from hyperacusis TRT in treating many forms of tinnitus. Neural
and misophonia (Jastreboff and Jastreboff, 2003). plasticity occurs in all parts of the central nervous
system and is caused by several factors including
deprivation of input, abnormal input, or injury.
DISCUSSION “Good” plasticity occurs when the functions of the
injured structure are transferred to other parts of
The overall prevalence of tinnitus in the United the central nervous system. “Bad” plasticity results
States is approximately 3% and varies by age with a when hyperactivity or hypersensitivity of particular
prevalence of 1% in those younger than 45 and 9% neurons is transferred to other parts of the central
in individuals older than 65 (Adams et al., 1999● C ). nervous system by activating dormant synapses or
Approximately 80% of tinnitus cases are associated forming new ones. It has been hypothesized that this
with hearing loss. When tinnitus occurs after insults rewiring is responsible not only for tinnitus but also
to the ear, such as exposure to loud noise or ototoxic for the symptoms associated with it, such as hypera-
pharmacologic agents, then these factors are taken to cusis, misophonia, and affective symptoms includ-
be the cause of the tinnitus. More often, however, a ing depression. These changes may be transient,
cause cannot be identified, leading to the diagnosis persistent, or permanent, but most are reversible if
of subjective tinnitus. suitable stimuli are applied (Moller, 2003).
There are many theories and hypotheses regard- The neurophysiologic model of tinnitus and
ing the mechanisms behind subjective tinnitus. The decreased sound tolerance assumes the following
theory of discordant damage or dysfunction between four postulates: (1) in addition to the auditory
the outer hair cells and the inner hair cells of the system, the limbic and the autonomic systems are
inner ear is favored by recent research. According to involved in processing tinnitus-related and sound-
this theory, the perception of tinnitus is a positive invoked neuronal activity, (2) the behavior-induced
phenomenon occurring within the auditory system. problems of tinnitus are largely related to sustained
This explanation accounts for a number of observa- overactivation of the sympathetic part of the auto-
tions about tinnitus, including the fact that 20% of nomic nervous system, (3) functional connections
patients with tinnitus have normal hearing and only are developed between different parts of the brain in
73% of deaf patients experience tinnitus (Kaltenbach much the same way that conditioned reflexes are
et al., 2002; Jastreboff, 1990). (Fig. 26-1), (4) it is possible to ameliorate the nega-

Auditory and Other Cortical Areas

Perception and Evaluation (Consciousness, Memory, Attention)

Auditory
subconscious Limbic system Reactions
Detection/Processing

Auditory periphery Autonomic nervous system

Tinnitus source

Familiar, significant sound

Figure 26-1 A block diagram of the neurophysiologic model of tinnitus and decreased sound tolerance. Note multi-
ple functional connections between involved systems crucial in the development of conditioned reflex arcs. (Adapted
from Jastreboff P, Jastreboff M. Tinnitus retraining therapy for patients with tinnitus and decreased sound tolerance.
Otalaryngol Clin North Am 2003;36:321–336.)

266
 Chapter 26 Ringing in Ears (Tinnitus)

tive impact of tinnitus and decreased sound toler- of treatment, should be avoided because suppression
ance by inducing and sustaining habituation (TRT) of tinnitus removes the signal that needs to be
(Jastreboff and Jastreboff, 2003). habituated.
The plasticity of the brain must be preserved TRT invokes two types of habituation: habitua-
for TRT to be effective. This means that benzodi- tion of reaction (Fig. 26-2) and habituation of
azepines, frequently prescribed to treat tinnitus, are perception (Fig. 26-3). The primary goal of TRT is to
contraindicated in patients undergoing TRT because induce habituation to reactions and, thereby,
they impair brain plasticity and reduce the ability the weakening and elimination of the connections
to learn. Tinnitus masking, also a traditional form between the auditory system and the limbic and

Auditory and Other Cortical Areas

Perception and Evaluation (Consciousness, Memory, Attention)

Auditory
subconscious Limbic system HER
Detection/Processing
HAR

Auditory periphery Autonomic nervous system

Tinnitus source

Familiar sound

Figure 26-2 Habituation of reaction reflects lack of activation of the autonomic nervous system by the tinnitus-
related neuronal activity or activity evoked by external sounds.

Auditory and Other Cortical Areas

(Consciousness, Memory, Attention)

HP

Auditory
subconscious Limbic system HER
Detection/Processing
HAR

Auditory periphery Autonomic nervous system

Tinnitus source

Familiar, significant sound

Figure 26-3 Habituation of perception reflects lack of activation of the high auditory cortical centers.

267
 Chapter 26 Ringing in Ears (Tinnitus)

autonomic systems. When this is achieved, patients

Material Available on Student Consult
are still aware of the tinnitus but they are not both-
ered or distressed by it. Habituation of perception is Review Questions and Answers about Tinnitus
likely to occur when habituation of reaction is suffi-
ciently complete. The result is that patients are aware
of their tinnitus a small percentage of the time.

PATIENT INFORMATION RESOURCES

American Tinnitus Association American Academy of Otolaryngology––Head and
Phone: 800-634-8978 Neck Surgery
Web: http://www.ata.org Phone: 703-836-4444
Web: http://www.ata.org
American Academy of Audiology
Phone: 800-222-2336
Web: http://www.audiology.org

REFERENCES
Adams PF, Henderson GE, Marano MA. Current estimates and its relation to outer hair cell loss: Relevance to tin-
from the National Health Interview Survey, 1996. nitus. J Neurophysiol 2002;88:699–714.
National Center for Health Statistics. Vital Health Stat Moller A. Pathophysiology of tinnitus. Otolaryngol Clin
1999;10:81–103.● C North Am 2003;36:249–266.
Brechtelsbauer D. Adult hearing loss. Prim Care Newman C, Jacobson G, Spitzer J. Development of the
1990;17:249–266. Tinnitus Handicap Inventory. Arch Otolaryngol Head
Heller A. Classification and epidemiology of tinnitus. Neck Surg 1996;122:143–148.● B
Otolaryngol Clin North Am 2003;36:239–248. Schaber M. Medical evaluation of tinnitus. Otolaryngol
Jastreboff PJ. Phantom auditory perception (tinnitus): Clin North Am 2003;36:287–292.
Mechanisms of generation and perception. Neurosci Schleuning AJ 2nd. Management of the patient with tinni-
Res 1990;8:221–254. tus. Med Clin North Am 1991;75:1225–1237.
Jastreboff P, Jastreboff M. Tinnitus retraining therapy for Sismanis A. Pulsitile tinnitus: A 15-year experience. Am J
patients with tinnitus and decreased sound tolerance. Otol 1998;19(abstract):472–477.
Otolaryngol Clin North Am 2003;36:321–336. Weber P, Klein A. Hearing loss. Med Clin North Am
Kaltenbach JA, Rachel JD, Mathog TA, et al. Cisplatin- 1999;83:125–137.
induced hyperactivity in the dorsal cochlear nucleus

268
 C h a p t e r

27 Giardiasis

John W. Tipton

weight loss of 5 pounds even though he had

KEY POINTS resumed a normal diet. The diarrhea sometimes
wakes him at night and seems a little worse after
1. Giardiasis is a common cause of chronic diar- eating but might occur at any time. The abdominal
rhea in the United States. It is spread by the cramping continues, and he notices a lot of stom-
fecal-oral route. ach rumblings and flatus. Appetite is normal. There
2. Sources of infection are ubiquitous. is no food intolerance, nausea, jaundice, melena,
3. Chronic and intermittent diarrhea without or hematochezia. He remembers a similar illness
blood in the stools is a hallmark of giardiasis. about 3 months ago that resolved after 3 to 4 weeks.
Weight loss is common. Fever and leukocytosis This time, when his symptoms persisted, Bob
are uncommon. sought medical care.
4. Laboratory tests can easily diagnose giardiasis
even though stool examinations are frequently Medical History
negative at first. Enzyme-linked immunosorbent Bob has had no serious medical or surgical prob-
assay tests are highly sensitive and highly spe- lems. He does not take any medications and has not
cific. Leukocytosis and white blood cells on taken any antibiotics recently. He has no history of
stool stain are infrequent. bowel problems other than occasional viral gastro-
5. Metronidazole is the most commonly used enteritis as a child.
treatment, but alternative drugs are available.
Tinidazole and/or nitazoxanide may become Family History
preferred over metronidazole. Bob has two younger brothers in good health. Both
parents are alive and well except that his mother has
essential hypertension.

INITIAL VISIT Social History

Bob has been divorced for 3 years and works as a
Subjective pharmacist. He has never smoked and only occasion-
ally drinks alcohol at social gatherings. He denies
Patient Identification and Presenting illicit drug use. He is an avid camper and backpacker.
Problem His last backpacking trip was 4 months ago. He has
Bob is a 29-year-old white man who presents for the had no recent travel out of the United States.
first time with a complaint of diarrhea.
Review of Systems
Present Illness He denies chills, fever, dysphagia, nausea, vomiting,
Bob states that approximately 3 weeks ago, he was abdominal pain other than the cramping, back
awakened with the sudden onset of watery, profuse pain, urinary frequency, dysuria, and depression or
diarrhea accompanied by abdominal cramps. He anxiety.
initially thought this was due to something he ate or
a virus and treated it by pushing fluids and avoiding Objective
solid foods. In about 3 days, he improved some but
continues to have five to seven loose, semisolid Physical Examination
stools daily. He noted the onset of fatigue after Bob is a well-developed, well-nourished white man
about a week. As the diarrhea continued, he noted a seated on the examination table in no distress. His

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

269
 Chapter 27 Giardiasis

vital signs are as follows: height, 5 feet 10 inches; Plan

weight, 165 pounds (last recorded weight, 173
pounds); blood pressure, 110/76; temperature, Diagnostic
98.8˚F (37.1˚C); pulse, 72 with regular rate and The physician thought that infectious diarrhea was
rhythm; respiratory rate, 14. There is no orthosta- most likely considering the abrupt onset and rela-
tic change in blood pressure or pulse. Skin color is tively normal physical examination. The clinician
normal. Head, eyes, ears, nose, and throat are nor- initiated a series of diagnostic studies designed to
mal without any sclericterus. Neck, lungs, and confirm this suspicion.
heart are normal. The abdomen is flat. Bowel Laboratory examination showed the following:
sounds are hyperactive. There are no masses, and normal complete blood count, metabolic panel, and
the liver and spleen are normal. There is mild ten- amylase. Stool examination showed no white blood
derness to deep palpation in the mid-abdomen but cells, blood, ova, or parasites. Stool culture was
no guarding and no rebound tenderness. The rec- negative for pathogens. Repeat examination of the
tal examination showed an empty rectal vault with stool for ova and parasites was positive for Giardia
no tenderness. lamblia.

Therapeutic
Assessment The patient was treated with metronidazole (Flagyl)
Working Diagnosis 250 mg three times per day for 5 days. His symptoms
The working diagnosis is infectious diarrhea, probably of diarrhea and abdominal cramps resolved slowly
bacterial or parasitic. The acute onset is compatible over about 2 weeks.
with infectious diarrhea. There is no history of bowel
or other disease associated with diarrhea. Irritable Patient Education
bowel disease is not considered because of the noctur- Avoidance of lactose-containing foods seemed to
nal diarrhea and lack of psychological stressors. diminish his symptoms. He was instructed on the
contagious nature of his illness and proper hygienic
Differential Diagnosis measures to prevent future infection. The source of
The initial differential diagnosis included infectious his infection was not clear but was surmised to be
diarrhea from bacteria, viruses, or parasites; malab- contaminated water or food. He already was aware of
sorption syndrome; inflammatory bowel disease; proper sanitizing methods for water he drinks on
irritable bowel disease; and chronic diarrhea from backpacking and camping trips.
metabolic or other disease.
Disposition
1. Infectious diarrhea may be caused by a variety of He regained his weight over 2 months and continued
bacteria, viruses, and parasites. The diarrhea is in good health over the immediate follow-up period.
most commonly caused by toxic effects of exotox- He was instructed to return if diarrhea became a
ins, osmotic effects, and changes in normal gut problem again.
flora. Viral diarrheas are usually self-limited and
short-lived. There is no history of antibiotic use
that could lead to Clostridium difficile colitis. DISCUSSION
2. Malabsorption syndromes normally cause diarrhea
because of changes in the gut contents that cause Giardiasis is an acute diarrhea caused by G. lamblia
increased osmotic load and water secretion (synonyms: Giardia intestinalis, Giardia duodenalis).
and/or reduced water resorption. G. lamblia is a protozoal pathogen that is fairly com-
3. Inflammatory bowel diseases such Crohn’s disease mon in all parts of the world including the United
and regional enteritis cause inflammatory States. In the United States, it is estimated to cause
changes in the bowel leading to a wide range of approximately 2.5 million infections per year
diarrhea and intestinal problems from perfora- (Anonymous, 2000● C ). Although it is popularly
tion to obstruction. thought to be primarily associated with travelers’
4. Irritable bowel disease is a functional chronic dis- diarrhea and drinking contaminated water from
ease poorly understood but generally related to mountain streams, in reality, it is a common cause of
stress and dietary factors that tend to cause early diarrhea in all states and many venues. The parasite
morning diarrhea and alternations between diar- exists in two forms: cyst and trophozoite. The cyst is
rhea and constipation. the infectious form and the trophozoite is responsi-
Chronic diarrhea has a very long list of possible ble for symptoms and reproduction within the gut.
causes but is not likely in this patient because of The parasite stays in the trophozoite form in the
the acute, recent onset. However, it is possible that small intestine and only changes back to its conta-
his previous episode of diarrhea is related to this illness. gious encysted form in the large intestine. Chronic

270
 Chapter 27 Giardiasis

infection and shedding of the parasite is possible may lead to malabsorption states, vitamin deficien-
(Gardner, 2001● B). The infectious cyst may survive in cies, and failure to thrive in children, or weight loss
the environment for several weeks. It is spread by in adults.
person-to-person contact and ingestion of fecally
contaminated water or food. It is resistant to cold but
Differential Diagnosis
destroyed by cooking or boiling, so contaminated
food must be raw or be contaminated after cooking. In acute diarrheas, infectious diarrhea must be con-
It is resistant to usual levels of chlorination but can sidered. Bacterial causes are Salmonella, Shigella,
be removed from water supplies by filtration. Deep Yersinia, Campylobacter, pathogenic Escherichia coli,
well water is usually free of the parasite, but surface and C. difficile. Viruses are common but usually self-
water may be contaminated. It may persist in cold limited over short time periods. The two common
(Syed, 2003● B). Domestic or wild animals, including parasitic causes of diarrhea in the United States
mammals, birds, and reptiles, may be a reservoir of are Giardia and Cryptosporidium parvum (Verweij,
the infection. Person-to-person spread is seen in day 2004 ●B). Entamoeba histolytica is common in much
care centers, nursing homes, and other sites where of the developing world but is rare in the United
fecal-oral contamination is likely. Increased risk for States. Malabsorption and inflammatory bowel dis-
disease is seen in infants, young children, travelers, ease may need to be considered. Other causes of
and the immunocompromised (Leder, 2004 ● B). chronic diarrhea are legion. Primary differential
Giardiasis is especially common in areas of the world points for giardiasis are sudden onset, length of ill-
where poor sanitation is prevalent, with infec- ness usually longer than 2 weeks, and weight loss.
tion becoming widespread or universal as early as Chronic, intermittent diarrhea also highly favors
3 months of age in highly endemic areas. However, Giardia. Fever and elevated white blood cell counts
persons living in areas where infection is more com- are not common (Nash, 2001● B).
mon may build up immunity to infection and have
symptom-free carrier states (Gardner, 2001● B).
Laboratory Diagnosis
The parasite can be found in stool specimens. The
Pathology
trophozoite may be found in stools if the diarrhea is
The infection starts after oral ingestion of the infec- profuse, but the cyst is more commonly found.
tious cyst. The incubation period ranges from 1 to 3 Testing for Giardia is historically done by searching
weeks. After ingestion of the infectious cyst, the stool samples for the parasite. This may be diagnostic
organism changes to its trophozoite form and for other pathogens as well. There is a high false-
attaches itself to the small intestine wall. Several the- negative rate on examination of only one stool spec-
ories have been advanced to explain symptoms. imen, but the positive rate becomes high (>90%)
There may be microscopic changes in the small intes- after examining three specimens. Immunoassays and
tine villi, and some damage may be done to the villus fluorescent antibodies have been used more recently.
or its brush border leading to malabsorption, but They have high sensitivity and high specificity, are
this is not constant. There does not appear to be a inexpensive, and are relatively easy to perform
significant inflammatory component. A significant (Aldeen, 1998 ●B). White blood cells are usually not
number of infected persons may remain asympto- seen in stool samples. Blood chemistries are usually
matic (Gardner, 2001● B ). The difference between normal, except with extraintestinal complications
symptomatic and asymptomatic states also is not such as hepatic or pancreatic involvement. Upper
apparent. gastrointestinal series will usually be normal, except
The symptoms of giardiasis are highly variable, possibly for nonspecific findings such as swelling.
from asymptomatic to cases of fulminate diarrhea Duodenal aspirates may show the parasite but are no
and dehydration. The infected person may become longer used except in difficult to diagnose cases.
chronically infected and remain asymptomatic and Chronic cases may show signs of malabsorption of
continue to shed infectious cysts. The importance to various nutrients: vitamin B12, protein, and fats.
the individual of this state is unknown. Symptomatic
persons tend to have an acute onset of diarrhea, Treatment
which is primarily watery at first and associated with
abdominal cramping and flatulence. Chronic or The most commonly used treatment is metronida-
intermittent symptoms are highly suggestive of giar- zole 250 mg three times daily for 5 to 7 days. In the
diasis (Nash, 2001● B). Other symptoms are increased case of relapse or incomplete remission, a repeat
borborygmi, flatulence, and symptoms of malab- course of metronidazole at a higher dose can be
sorption. Upper gastrointestinal symptoms such as given. Side effects are a bitter metallic taste, dyspep-
nausea and vomiting may be significant. Fever and sia, and disulfiram-like reactions when taken with
bloody diarrhea are uncommon. Chronic infections alcohol (Gardner, 2001● B). Alternate antibiotics are

271
 Chapter 27 Giardiasis

available. Tinidazole (Tindamax) is highly effective diagnosis in the United States (Syed, 2003 ● B).
as a single 2-g dose (50 mg/kg, maximum 2 g for Resolution of all symptoms may be slow because the
children) and is well tolerated. It is newly available malabsorption may take several weeks to resolve.
in the United States but has been widely used in Lactose-containing foods may need to be avoided
other parts of the world (Anonymous, 2004 ● B; for 3 to 4 weeks as the brush border recovers.
Nash, 2001● B). Nitazoxanide (Alinia) is another Treatment of asymptomatic individuals is con-
newly available drug that is dosed over a short inter- troversial and should be individualized. Certainly
val. It appears to have higher levels of effectiveness workers in day care or treatment centers such as
when compared with metronidazole. The dose for nursing homes should be treated. A person who is
adults is 500 mg twice daily for 3 days. Smaller doses likely to be a source of infection for people at high
are recommended for children (Ali, 2003 ● B). risk such as the immunocompromised should be
Paromomycin (Humatin), an unabsorbed amino- seriously considered for treatment. Asymptomatic
glycoside, may be used when absorption is undesir- persons who are likely to be reinfected, such as those
able such as in early pregnancy. The usual dose is 25 living in highly endemic areas, probably receive no
to 35 mg/kg/day in three divided doses for 7 days. benefit from treatment (Gilman, 1988 ● B).
The use of metronidazole during pregnancy still has
some controversy associated with it. Metronidazole Follow-up
has been shown to have teratogenic effects in rats
but not in humans. Treatment during pregnancy If symptoms resolve readily, no further follow-up is
may be postponed until after the first trimester if indicated. There is no need to retest for cure.
symptoms are mild and malabsorption is not a Diarrhea may resolve slowly because of the persist-
problem, allowing for more safety. Furazolidone ence of malabsorption syndromes such as lactose
(Furoxone), a nitrofuran, is available in liquid form intolerance. It may be necessary to avoid lactose-
and generally more acceptable to children but has containing foods for several weeks. If symptoms per-
to be dosed four times daily for 7 to 10 days. Nausea sist, retesting for the causative organism may be
and vomiting are the most common side effects necessary. Alternatively, empirical retreatment is an
of furazolidone. Hemolysis due to glucose-6- acceptable alternative. True failure of antibiotic ther-
phosphate dehydrogenase deficiency and other side apy indicates the need for repeating the same antibi-
effects of nitrofurans can occur. The cure rate with otic at a higher dose, switching to an alternate
paromomycin and furazolidone may not be as high antibiotic, or combination antibiotic therapy. In the
as with metronidazole. Quinacrine was widely used face of persistent symptoms, testing for concurrent
in the past but for years has been difficult to obtain disease states may be needed.
in the United States. However, resistant cases may
benefit from combination therapy with quinacrine
and metronidazole. Albendazole (Albenza) has been
used to treat giardiasis but is not approved by the Material Available on Student Consult
U.S. Food and Drug Administration for this indica- Review Questions and Answers about Giardiasis
tion and has not been extensively tested for this

REFERENCES
Adagu IS. In vitro activity of nitazoxanide and related Gilman RH. Rapid reinfection by Giardia lamblia after
compounds against isolates of Giardia intestinalis, treatment in a hyperendemic Third World community.
Entamoeba histolytica, and Trichomonas vaginalis. Lancet 1988;1:343–345. ●B
J Antimicrob Chemother 2002;49:103–111.● B Leder K. Giardiasis. Up to Date, 2004. Available at
Aldeen WE. Comparison of nine commercially available www.uptodate.com.● B
enzyme-linked immunosorbent assays for detection of Nash TE. Treatment of Giardia lamblia infections. Pediatr
Giardia lamblia in fecal specimens. J Clin Microbiol Infect Dis J 2001;20:193–195. ●
B
1998;36:1338–1340. ●B Syed AA. Giardia intestinalis. Curr Opin Infect Dis
Ali SA. Giardia intestinalis. Curr Opin Infect Dis 2003;16:453–460. ● B
2003;16:453–460. ●
B Verweij JJ. Simultaneous detection of Entamoeba histolyt-
Anonymous. Giardiasis surveillance United States. ica, Giardia lamblia, and Cryptosporidium parvum in
MMWR Morb Mortal Wkly Rep 2000;49. ● C fecal samples by using multiplex real-time PCR. J Clin
Anonymous. Drugs for parasitic infections. Med Lett Microbiol 2004;42:1220–1223. ● B
2004;Aug:1–12. ●
B
Gardner TB. Treatment of giardiasis. Clin Microbiol Rev
2001;14:114–128. ●
B

272
 C h a p t e r

28 Vesicular Rash (Varicella)

David L. Gaspar

noted more lesions on her face and arms despite

KEY POINTS staying indoors away from any apparent exposure
to mosquitoes or other insects. Some of the original
1. Adults should be offered acyclovir treatment red lesions on her neck now have small blisters
due to their higher risk of complications from in the center of the red spots. The rash itches, and
varicella. some of the scratched blisters have broken and
2. Patients with varicella are infectious from 2 days are starting to heal by scabbing over. She took over-
before the rash appears until all the lesions the-counter diphenhydramine last evening, and it
have scabbed over. helped her symptoms of itching. She feels warm
3. The classic appearance of varicella lesions is a and tired and has some muscle aches at the present
“dew drop on a rose petal.” time.
4. Options for postexposure prophylaxis include
varicella zoster immune globulin (VZIG) within Medical and Surgical History
72 hours of exposure and varicella vaccine up Linda has been very healthy in general. She had a ski
to 5 days after exposure. injury 5 years ago and underwent a successful right
5. Susceptible pregnant women exposed to vari- anterior cruciate reconstruction. She has otherwise
cella should be offered VZIG and not given the not been hospitalized. Her immunizations are up to
vaccine. date except for the need for a second dose of varicella
6. Almost all patients with a confirmed history of vaccine. She takes folic acid tablets and is on a generic
chicken pox will turn out to be immune on norethindrone and ethinyl estradiol oral contraceptive
serologic testing as will as many as 75% of for contraception.
adults without a varicella history.
Family History
Her mother has had major depression but no other
health issues. Her father has had prostate cancer
INITIAL VISIT treated with radiotherapy. She has two brothers who
are alive and well.
Subjective
Personal and Social History
Patient Identification and Presenting She has been married for 2 years. She and her hus-
Problem band wish to start a family soon. She came in for
Linda J. is a 28-year-old patient presenting with some preconception counseling 2 months ago where
vesicular lesions over her face and arms. Linda will she was advised to begin folate supplementation. She
soon begin to work at Hillhaven Nursing Home. As is a licensed practical nurse but has not worked in
part of her pre-employment assessment, her immu- her field for the past 5 years.
nizations were reviewed, and it was found she did
not have a history of having had chicken pox. She Review of Systems
had a varicella titer done that indicated she had no She complains of a few “canker sores” in her
immunity to varicella. She received her first dose of mouth. She has no cough or headache. Her last
varicella vaccine 10 days ago. normal menstrual period was 2 weeks ago. A full
Yesterday she noted what she thought were review of systems revealed no other significant
mosquito bites on her face. By this morning, she symptoms.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

273
 Chapter 28 Vesicular Rash (Varicella)

Objective ■ Individuals who develop more than 50 lesions 7 to

42 days after vaccination
Physical Examination ■ Individuals who develop certain serious adverse
She looks mildly ill. Her temperature is 37.0˚C experiences after vaccination including pneumo-
(98.6˚F), blood pressure is 104/76, pulse is 72, and res- nia, pneumonitis, cerebritis (encephalitis), cerebel-
piratory rate is 18. There are obvious vesicular lesions litis (cerebellar ataxia), and aseptic meningitis
on her face, upper trunk, and arms. There are also ■ Individuals who develop herpes zoster after
small erythematous macules without vesicles and some vaccination
crusted lesions on an erythematous base. Many of the ■ Suspected cases of secondary transmission of the
lesions have a “drop of dew on a rose petal” appear- vaccine virus
ance. The palms and soles of the feet are spared. There ■ Pregnant women who inadvertently receive vari-
are a few shallow ulcers on the hard palate. Overall cella vaccine or who have been exposed to a vacci-
more than 50 lesions are counted. Her chest is clear, nee and who develop a varicella rash
the heart examination is normal, and her abdominal
examination is benign except for a few crusted lesions. Therapeutic
There is no abdominal tenderness or organomegaly. Linda’s physician prescribes acyclovir, an antiviral
agent, 800 mg orally five times daily for 7 days. As an
Assessment adult, Linda is at risk of having a more serious illness
and is more likely to have complications if this is a
Working Diagnosis coincidental natural disease. Acyclovir has been stud-
Linda appears to have varicella, or chicken pox. The ied the most in varicella and is recommended for the
clinical syndrome has appeared after her varicella following groups at high risk of developing compli-
immunization. It is unclear whether this is due to cations from varicella (CDC, 2005● C ):
coincidental natural infection or occurred as a result
of the vaccine.
■ Healthy, nonpregnant persons 13 years and older
■
Children older than 12 months with chronic cuta-
neous or pulmonary disorder and those receiving
Differential Diagnosis long-term salicylate therapy
The differential diagnosis of varicella can be difficult ■
Consider in children receiving short, intermittent, or
early in the illness. It may appear more localized early aerosolized courses of corticosteroids
in the disease, and the various stages in the evolution
of varicella lesions may not always be evident. For maximum benefit, oral acyclovir therapy
Because of this, individual lesions may take on the should be initiated within the first 24 hours after
appearance of other skin conditions including rash onset, and Linda meets this criterion (Chen
herpes simplex infection, impetigo, coxsackievirus et al., 2002) There is no good evidence that treatment
infection, papular urticaria, insect bites, scabies, der- with antiviral agents reduces complications of
matitis herpetiformis, a drug rash, rickettsialpox, or varicella in healthy children between the ages of
contact dermatitis (Chen et al., 2002). Despite world- 12 months and 12 years. Treatment in this age group
wide eradication, smallpox is back in the differential has been shown only to reduce the number of days
diagnosis of varicella in this age of fear over biologic of fever and the maximal number of skin lesions
terrorism. As the illness evolves, the distribution of (Klassen et al., 2004● B ).

lesions, the variety in their stages of development,

and the rash’s time course help to differentiate vari- Patient Education
cella from the other conditions. Linda was prescribed calamine lotion to use topi-
cally for symptomatic relief. She was told she could
continue to use the diphenhydramine as long as
Plan she was not going to be driving and if she did not
have to be mentally alert. A second-generation non-
Diagnostic sedating antihistamine, over-the-counter lorata-
The diagnosis is clinical. In apparent naturally occur- dine 10 mg once daily was recommended as an
ring varicella infections, no testing is necessary. In alternative. She is sure that her husband has had
this case, Linda has developed a varicella rash after chicken pox. This makes it unlikely but not impos-
immunization. The Centers for Disease Control and sible for him to develop the illness again (Hall et al.,
Prevention (CDC) (2005● C ) recommends strain iden-
2002 ● B ).
tification testing as part of its adverse reaction sur- Linda was scheduled to start work in 2 days.
veillance. It offer’s this testing free of charge. The Varicella is highly contagious, and she was told to not
physician phones the CDC to make arrangements for report to work and stay away from susceptible indi-
the assay. The situations in which the CDC recom- viduals until the scabs on her lesions had crusted
mends strain identification include over. She was advised that she should expect new

274
 Chapter 28 Vesicular Rash (Varicella)

crops of vesicles to appear and crust over during the leads to reactivation and the clinical syndrome of
next 2 to 3 days. herpes zoster or shingles in 15% to 20% of patients
Should she develop new symptoms, such as a (National Advisory Committee on Immunization,
cough, become ill, or have a new fever develop, she 2004● C ).
should be seen to assess the possibility of a secondary In adults, varicella is generally associated with a
bacterial infection or complication. greater number of skin lesions, more systemic com-
She asks whether her aunt who stopped into the plaints, and a 20-fold greater risk of serious complica-
house for 2 to 3 minutes to pick up a book needs to tions compared with children. Although adults make
be seen or treated by her doctor. Although 90% of up only 1.5% of all cases of primary varicella, adults
susceptible individuals with significant exposure will account for 17% of hospitalizations for the disease.
develop the disease, the aunt was not significantly Of mothers who develop varicella in the imme-
exposed to Linda. “Significant exposure” is defined as diate antepartum period (5 days before and up to
15 minutes of face-to-face contact or 60 minutes of 2 days after delivery), 17% to 30% of newborns will
exposure in a room (Watson et al., 2000● B ). Linda’s develop severe varicella with a mortality rate of 20%
physician might reassure Linda that her aunt prob- to 30% as a result of the intrauterine transmission of
ably had chicken pox as a child and is probably varicella-zoster virus before the transfer of protective
immune. If the aunt is concerned, she should by all maternal antibodies. In addition, if a mother is
means see her own family physician. infected in the first two trimesters, congenital vari-
cella syndrome (limb atrophy and scarring of the skin
Disposition of the extremity) may occur in the infant. It occurs in
Linda was asked to call her physician’s office in 3 to 4 0.4% of births when the mother was infected in the
days to report her progress. She will need clearance first trimester and 2% when infected from 12 to 20
to return to work and the physician asks her to weeks’ gestation (Enders et al., 1994● B ; Harger et al.,
return in 6 days, as most lesions will have crusted 7 2002● B ).
days after the first appearance of the rash. Should
this not be the case, she should call the office for Vaccination
advice, as it is important that she avoid exposing
other patients in the office to varicella. The main thrust of managing this disease is immu-
nization. At present, a live attenuated virus vaccine is
available. Since the advent of varicella immunization,
DISCUSSION there has been a dramatic decrease in the incidence of
the disease and the morbidity and mortality attached
to the disease. Vaccination programs have reduced the
Varicella is a common disease that affects primarily
number of cases by 71% to 84% and have reduced
children. It is caused by varicella-zoster virus, a DNA
varicella-related hospitalizations and deaths (Seward
virus. Varicella-zoster virus is acquired from patients
et al., 2002● B ). A single dose of vaccine is recom-
with primary varicella or herpes zoster through
mended for children from 12 months of age to 12
either direct contact with infected vesicular fluid or
years, and a two-dose regimen is recommended for
inhalation of aerosolized respiratory secretions. The
individuals 13 years and older. Adults who are good
disease has an incubation period of 11 to 22 days.
candidates for immunization include health care
In children, there may be few prodromal symptoms,
workers, individuals such as teachers who are at higher
whereas adults may experience myalgias, fever, and
risk of coming in contact with children with the dis-
general malaise. The vesicles appear in crops over 2
ease, and susceptible contacts of immunocompro-
to 5 days. Vesicles appear only to then ulcerate and
mised individuals (Varicella Vaccines: WHO Position
scab over. At any one time, lesions at various stages
Paper, 1998● C). Almost all patients with a reliable his-
may be seen. The lesions may commonly affect the
tory of varicella have protective antibodies on serologic
oral mucosa, and mild liver involvement may occur.
testing. Even in those without this history but who are
The most common complications are secondary bac-
diagnosed clinically with varicella, serology is positive
terial skin infections in children and pneumonia in
in approximately 75% of patients. Because of this, even
adults (Varicella Vaccines: WHO Position Paper,
though Linda gave no history of chicken pox during
1998 ●C ). Varicella is a risk factor for invasive group A
her pre-employment screening visit, she underwent
Streptococcus infection (CDC, 1997● B). Other compli-
cations can affect almost any organ system and testing to establish susceptibility.
include otitis media, bacteremia, osteomyelitis, septic The following examples represent contraindica-
arthritis, encephalitis, cerebellar ataxia, Reye’s syn- tions to varicella immunization (Varicella Vaccines:
drome, and thrombocytopenia. Following the dis- WHO Position Paper, 1998 ● C ):

ease, virus persists in sensory nerve ganglia where ■ Persons who are allergic to any component of the
reactivation is prevented by intact cell-mediated vaccine
immunity. A failure of this immunity later in life ■ Persons with cellular immunodeficiencies

275
 Chapter 28 Vesicular Rash (Varicella)

■ Persons taking large doses of corticosteroids Intravenous acyclovir is used in ill patients and those
(>2 mg/kg of body weight or >20 mg/day of pred- who are immunosuppressed.
nisone or its equivalent) The varicella vaccine can attenuate or prevent
■ Persons with a moderate or severe concurrent clinical varicella when administered as postexposure
illness prophylaxis. The vaccine may be administered as
■ Women who are pregnant long as 5 days after exposure but is generally ineffec-
■ Persons who have received blood products (such as tive when administered more than 5 days after expo-
whole blood or immunoglobulin) during the pre- sure (Watson et al., 2000 ● B).
vious 5 months (reduces vaccine efficacy) Varicella-zoster immune globulin (VZIG) is
■
Persons with a family history of congenital here- indicated for susceptible high-risk persons exposed to
ditary immunodeficiency in first-degree relatives varicella. VZIG is most effective when administered
unless they are known to be immunocompetent within 96 hours of exposure. High-risk individuals
■
Because of the association between aspirin use and include those with leukemia or lymphoma, congenital
Reye’s syndrome after varicella, children should or acquired immunodeficiency, immunosuppressive
avoid salicylates for 6 weeks after vaccination therapy, the newborn of a mother who had the onset
of varicella 5 days or less before delivery or within 48
Common side effects of vaccination include pain hours after delivery, the premature infant >28 weeks’
and swelling at the site of injection. In addition, 3% gestation whose mother lacks a history of varicella, and
to 5% of vaccinees will have a rash in the area of the the premature infant <28 weeks’ gestation or <1000 g
injection and 3% to 5% will have a generalized vari- (CDC, 2005● C ).
cella-like rash. When occurring within 12 weeks of VZIG has been shown to attenuate the disease
immunization, the majority of these rashes are found to in pregnant women and is used in pregnant
be natural wild virus infections occurring coinciden- women exposed to varicella. It should be noted the
tally with the immunization (Wise et al., 2000● B ). vaccine should not be used in pregnant wonen.
Although the risk of spread from a vaccine-induced Approximately one third of the pregnant women
case is very small, especially if the rash is covered, one in a registry set up to gather data on the effect of
cannot be sure that the rash is not due to natural varicella vaccine in pregnancy were given it rather
disease. Linda was isolated from susceptibles, kept than VZIG because of product confusion (Shields
home from work, and treated with acyclovir because of et al., 2001●B ).
this uncertainty. Special assays are needed to dif- In summary, varicella is a common childhood
ferentiate natural infection from vaccine-induced disease that is becoming less common because of
disease. Although the vaccine is highly effective, a break- effective immunization programs. The disease is rel-
through varicella rate of 3% to 4% per year is expected atively mild and self-limited in children but associ-
after vaccination. When this occurs the disease tends to ated with much more morbidity and mortality in
be milder and more short-lived (National Advisory adults. All children and high-risk adults without evi-
Committee on Immunization, 2004 ● C ). dence of immunity should be immunized.

Postexposure Treatment Material Available on Student Consult

Oral acyclovir can be used in patients at high risk
Review Questions and Answers about Varicella
of developing complications, as listed previously.

REFERENCES
Centers for Disease Control and Prevention. Outbreak of Hall S, Maupin T, Seward J, et al. Second varicella infec-
invasive group A Streptococcus associated with varicella tions: Are they more common than previously thought?
in a childcare center—Boston, Massachusetts, 1997. Pediatrics 2002;109:1068–1073. ● B
MMWR Morb Mortal Wkly Rep 1997;46: 944–948. ● B Harger JH, Ernest JM, Thurnau GR, et al. Frequency of
Centers for Disease Control and Prevention. Available at: congenital varicella syndrome in a prospective cohort
www.cdc.gov/nip/vaccine/varicella/faqs-clinic- of 347 pregnant women. Obstet Gynecol 2002;100:
vaccine.htm#10-serious-adverse. Accessed 3/6/2005. ● C 260–265. ● B
Chen TM, George S, Woodruff CA, et al. Clinical manifes- Klassen TP, Belseck EM, Wiebe N, et al. Acyclovir for treat-
tations of varicella-zoster virus infection. Dermatol ing varicella in otherwise healthy children and adoles-
Clin 2002;20:267–282. ● C cents (Cochrane Review). The Cochrane Library, Vol. 2.
Enders G, Miller E, Cradock-Watson J, et al. Consequences Chichester, UK, John Wiley & Sons, 2004. ● B
of varicella and herpes zoster in pregnancy: Prospective National Advisory Committee on Immunization. Update
study of 1739 cases. Lancet 1994;343:1548–1551. ● B on varicella. Can Commun Dis Rep 2004;30:1–28. ● C

276
 Chapter 29 Fever and Cough (Influenza)

Seward JF, Watson BM, Peterson CL, et al. Varicella disease Watson B, Seward J, Yang A, et al. Postexposure effectiveness
after introduction of varicella vaccine in the United of varicella vaccine. Pediatrics 2000;105: 85–88.●B
States, 1995–2000. JAMA 2002;287:606–611. ● B Wise RP, Salive ME, Braun MM, et al. Post-licensure
Shields KE, Galil K, Seward J, et al. Varicella vaccine expo- safety surveillance for varicella. JAMA 2000;284:
sure during pregnancy: Data from the first 5 years 1271–1279.● B
of the pregnancy registry. Obstet Gynecol 2001;98: Varicella vaccines: WHO position paper. Wkly Epidemiol
14–19.● B Rec 1998;73:241–248.● C

C h a p t e r

29 Fever and Cough (Influenza)

Marguerite R. Duane

Joe reports that he had felt fine throughout the day

KEY POINTS yesterday until after dinner when he began to feel
feverish. He developed a dry cough and some chest
1. Influenza is a serious infectious disease that discomfort, which he attributed to the coughing
afflicts thousands of people each year. spells. This morning he woke up with a severe
2. Annual vaccination is the best way to prevent headache and states he felt like he had “been run over
infection and minimize the effect of influenza. by a Mack truck.” He said he did not even have the
3. Clinical diagnosis is difficult due to the lack of energy to come to the doctor, but his wife insisted.
specificity and sensitivity of symptoms, but The patient reports that his youngest daughter was ill
awareness of the prevalence of influenza in the earlier in the week with a “cold.”
community can aid in diagnosis.
4. Rapid viral tests allow early confirmation of the
Medical History
illness, but only viral cultures provide specific
Joe has a history of high blood pressure for which he
information regarding the influenza strains in
takes hydrochlorothiazide 25 mg once daily. He had
circulation, which is used to formulate vaccine
a hernia repair in his early 30s. Otherwise, he has had
for the next year.
no other major illnesses, surgeries, or hospitalizations.
5. Antiviral agents have been shown to reduce the
He has never received a Pneumovax or influenza
duration of influenza illness when given within
vaccine.
36 to 48 hours of symptom onset and to pre-
vent influenza illness when used for prophylaxis.
Family History
Joe’s father is 81 years old. He has high blood pres-
sure and chronic obstructive pulmonary disease.
INITIAL VISIT His mother is 78 years old and has a history of high
blood pressure. Joe has two older sisters and a
younger sister, one of whom has thyroid disease and
Subjective
another who has asthma.
Patient Identification and Presenting
Problem Social History
Joe is a 52-year-old white man who presents with com- Joe works full time at a print shop. He and his wife
plaints of sudden onset of fever and cough last evening. have five children, four of whom still live at home.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

277
 Chapter 29 Fever and Cough (Influenza)

Seward JF, Watson BM, Peterson CL, et al. Varicella disease Watson B, Seward J, Yang A, et al. Postexposure effectiveness
after introduction of varicella vaccine in the United of varicella vaccine. Pediatrics 2000;105: 85–88.●B
States, 1995–2000. JAMA 2002;287:606–611. ● B Wise RP, Salive ME, Braun MM, et al. Post-licensure
Shields KE, Galil K, Seward J, et al. Varicella vaccine expo- safety surveillance for varicella. JAMA 2000;284:
sure during pregnancy: Data from the first 5 years 1271–1279.● B
of the pregnancy registry. Obstet Gynecol 2001;98: Varicella vaccines: WHO position paper. Wkly Epidemiol
14–19.● B Rec 1998;73:241–248.● C

C h a p t e r

29 Fever and Cough (Influenza)

Marguerite R. Duane

Joe reports that he had felt fine throughout the day

KEY POINTS yesterday until after dinner when he began to feel
feverish. He developed a dry cough and some chest
1. Influenza is a serious infectious disease that discomfort, which he attributed to the coughing
afflicts thousands of people each year. spells. This morning he woke up with a severe
2. Annual vaccination is the best way to prevent headache and states he felt like he had “been run over
infection and minimize the effect of influenza. by a Mack truck.” He said he did not even have the
3. Clinical diagnosis is difficult due to the lack of energy to come to the doctor, but his wife insisted.
specificity and sensitivity of symptoms, but The patient reports that his youngest daughter was ill
awareness of the prevalence of influenza in the earlier in the week with a “cold.”
community can aid in diagnosis.
4. Rapid viral tests allow early confirmation of the
Medical History
illness, but only viral cultures provide specific
Joe has a history of high blood pressure for which he
information regarding the influenza strains in
takes hydrochlorothiazide 25 mg once daily. He had
circulation, which is used to formulate vaccine
a hernia repair in his early 30s. Otherwise, he has had
for the next year.
no other major illnesses, surgeries, or hospitalizations.
5. Antiviral agents have been shown to reduce the
He has never received a Pneumovax or influenza
duration of influenza illness when given within
vaccine.
36 to 48 hours of symptom onset and to pre-
vent influenza illness when used for prophylaxis.
Family History
Joe’s father is 81 years old. He has high blood pres-
sure and chronic obstructive pulmonary disease.
INITIAL VISIT His mother is 78 years old and has a history of high
blood pressure. Joe has two older sisters and a
younger sister, one of whom has thyroid disease and
Subjective
another who has asthma.
Patient Identification and Presenting
Problem Social History
Joe is a 52-year-old white man who presents with com- Joe works full time at a print shop. He and his wife
plaints of sudden onset of fever and cough last evening. have five children, four of whom still live at home.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

277
 Chapter 29 Fever and Cough (Influenza)

Formerly, he smoked a pack of cigarettes per day for and other upper respiratory infections. In older
about 25 years, but he quit 3 years ago. He drinks a children and adults such as Joe, the differential
glass of beer or wine occasionally. diagnosis includes viral upper respiratory infections
(such as parainfluenza, respiratory syncytial virus,
Review of Systems adenovirus, and enterovirus), mononucleosis, pneu-
In general, the patient reports feeling very fatigued mococcal pneumonia, and streptococcal pharyngitis.
and weak. He has not had much of an appetite today.
He also complains of a mild sore throat but denies a
Plan
runny nose or nasal congestion. In addition to the
headache, Joe complains of generalized body aches. Diagnostic
He denies chest pain, but he still has some chest Joe’s clinical presentation is highly consistent with
discomfort. He denies shortness of breath. Further influenza. Review of weekly influenza surveillance
review of symptoms is negative. data from the Centers for Disease Control and
Prevention shows more than 95% of influenza cases
Objective in the area are due to influenza A. Given the high
probability that the patient has influenza as well as
Physical Examination the prevalence of influenza in the community, fur-
General Joe is a moderately ill-appearing man in no ther diagnostic testing is not indicated, as it would
acute respiratory distress. He is 5 feet 7 inches tall not be cost-effective (Hueston and Benich, 2004● B ).
and weighs 160 pounds; his temperature is 38.4˚C
(101.2˚F), blood pressure is 140/85, respiratory rate Therapeutic
is 22, and pulse is 96. The patient is treated empirically with rimantadine
100 mg twice daily for 5 days.
Head, Eyes, Ears, Nose, and Throat His head is nor-
mocephalic with no trauma. The pupils are equal, Patient Education
round, and reactive to light; the conjunctivae are The patient is informed that treatment will likely
slightly injected. There is mild erythema of the shorten the duration of his illness by about 1 day. He
nose but no drainage; the oropharynx has slightly dry is educated about the highly contagious nature of the
mucous membranes, mild erythema, but no exudates. illness and is encouraged to limit contact with people
The neck is supple with no lymphadenopathy. who are at high risk of serious complications if they
develop influenza (Table 29-1).
Heart Heart rate and rhythm are regular with no
murmurs.
DISCUSSION
Lungs There are decreased breath sounds at the
bases, but otherwise the lungs are clear to ausculta- Influenza is a significant public health issue, with
tion bilaterally. approximately 10% to 20% of the U.S. population
developing the illness each year. Between 1969 and
Abdomen The abdomen is soft, mildly tender, and 1995, influenza accounted for an average of 114,000
nondistended. The skin is warm and clammy. hospitalizations each year, and between 1990 and
1999, it accounted for an average of 36,000 deaths
Assessment per year (Prevention and Control of Influenza:
Recommendations of the Advisory Committee on
Working Diagnosis Immunization Practices [ACIP], 2004 ● C ). The rate
The working diagnosis is influenza given the abrupt of infection is highest among children, but the rate
onset and constellation of symptoms. of serious illness and death is highest among indi-
viduals older than 65 years of age and in individuals
Differential Diagnosis with chronic medical conditions that place them at
The differential diagnosis of fever and cough varies increased risk of complications.
based on the patient’s age and presenting symptoms. Influenza epidemics occur during the winter
Sepsis must be considered in neonates with the months and may be caused by the influenza A or B
sudden onset of fever and associated nonspecific viruses. Influenza A is divided into subtypes based
symptoms. The presence of nasal discharge suggests a on two surface antigens, hemagglutinin and neu-
viral respiratory tract infection such as respiratory raminidase. Both influenza A and B viruses are
syncytial virus. The differential diagnosis in younger further divided based on antigenic characteristics.
children includes bronchiolitis, bronchitis, laryn- Changes in these antigens result in new variants of
gotracheitis, pneumonia, streptococcal pharyngitis, the influenza virus, a process known as antigenic

278
 Chapter 29 Fever and Cough (Influenza)

Table 29-1 Individuals at Increased Risk of Complications from Influenza

Individuals 65 years and older
Residents of nursing homes and chronic care facilities
Individuals who have chronic medical conditions, such as asthma, heart disease, diabetes, renal
dysfunction, or immunosuppression due to disease or medications
Individuals 6 months to 18 years of age who receive long-term aspirin therapy, as they may be at
increased risk of Reye’s syndrome after influenza infection
Women in their second or third trimester of pregnancy during the influenza season
Young children between 6 and 23 months of age

drift. Because infection or vaccination with one virus may persist for more than 2 weeks (Prevention and
type may not provide protection against an antigenic Control of Influenza: Recommendations of the ACIP,
variant of the same type, a major influenza epidemic 2004● C ).
may be caused by influenza virus types not included Uncomplicated influenza infection is character-
in that year’s vaccine. ized by the abrupt onset and severe nature of a
constellation of symptoms. Constitutional symp-
Prevention toms may include fever, chills, headaches, myalgias,
fatigue, weakness, malaise, and anorexia. Respiratory
Administration of the influenza vaccine is an essen- symptoms commonly include a dry cough and
tial component in the prevention of the disease chest discomfort and may also include a stuffy nose,
and its complications. In the United States, an in- sneezing, and sore throat. Because the respiratory
activated influenza vaccine and a live, attenuated symptoms may be caused by many other respiratory
influenza vaccine are available each year. The in- pathogens, including the common cold, the diagnosis
activated vaccine is approved for all individuals may be difficult to make.
6 months of age and older. The live, attenuated The diagnosis of influenza is also complicated
vaccine is approved only for healthy individuals by the poor sensitivity of clinical findings and the
between the ages of 5 and 49. The vaccine contains poor specificity of clinical diagnosis. During an epi-
at least three viral strains that are expected to be demic, studies among adults show fever and cough to
present during the influenza season. The vaccine be 63% to 78% sensitive for influenza. The classic
is more effective when the vaccine and epidemic triad of fever, cough, and myalgias is only 77% to
strains are well matched and when persons at high 85% sensitive and 55% to 71% specific (Prevention
risk receive the vaccine before the influenza virus and Control of Influenza: Recommendations of
has widely circulated. the ACIP, 2004 ● C ). The predictive value of these
The Centers for Disease Control and Prevention symptoms depends on the level of influenza activity;
recommends that individuals who are at increased therefore, awareness of influenza in the community
risk of complications from influenza receive the can improve identification of the illness. The Centers
vaccine (see Table 29-1) (Prevention and Control of for Disease Control and Prevention maintains
Influenza: Recommendations of the ACIP, 2004 ● C ). weekly influenza surveillance data that may be
Additionally, health care workers and other individ- obtained at its Web site (www.cdc.gov/flu).
uals in close contact with persons at increased risk of In addition to surveillance information, labo-
complications should receive the vaccine to reduce ratory testing can help in the diagnosis of influenza.
transmission rates and subsequent complications. As with any diagnostic test, the sensitivity and
specificity may vary based on the type of test used,
the type of specimen tested, and the laboratory
Diagnosis
where the test is performed. Viral culture is the
Influenza is extremely contagious because the virus most accurate method for identifying specific viral
is spread from person to person via respiratory strains and subtypes. However, results are not avail-
secretions. Individuals with influenza are contagious able for 2 to 10 days, which makes it impractical
beginning approximately 1 day before the onset of to use to determine whether treatment should be
symptoms until approximately 5 days into the ill- initiated.
ness. Children can spread the illness for more than Rapid viral tests are available for use in outpa-
10 days after the illness begins. Symptoms typically tient settings, give results in less than 30 minutes, and
last for 1 to 5 days, although cough and malaise on average cost between $12 and $24 (Montalto,

279
 Chapter 29 Fever and Cough (Influenza)

2003 ● B). These tests vary based on the type of (Fagan and Moeller, 2004 ● A ). When used for pro-
influenza viruses that they can detect, the types of phylaxis, these drugs have been shown to prevent
specimens that can be used, and the complexity 70% to 90% of illnesses from influenza (Couch,
involved in performing the test. Some tests detect 2000● B ; Prevention and Control of Influenza:
only influenza A viruses; other tests detect both Recommendations of the ACIP, 2004 ● C ). Because
influenza A and B viruses but do not distinguish these drugs are renally cleared, caution should be
between the two; finally, others detect both viruses used when administering them in older patients and
and distinguish between influenza A and B. The tests in patients with renal disease. Amantadine should
also vary in terms of their sensitivity and specificity also be used with caution in older patients and in
with sensitivities ranging from 51% to 96% and patients with seizure disorders due to the central
specificities ranging from 52% to 100% (Prevention nervous system side effects (Montalto et al., 2000● B).
and Control of Influenza: Recommendations of the Zanamivir and oseltamivir are neuraminidase
ACIP, 2004● C ). Because the sensitivity of these tests, inhibitors that are effective against influenza A and B.
or their ability to rule out influenza, is lower than for Both have been shown to reduce the duration of
viral culture, physicians may consider further testing symptoms by 1 to 1.5 days as compared with placebo
if confirmation of a negative test is important. (Couch, 2000 ● B ; Fagan and Moeller, 2004 ● A). Like
amantadine and rimantadine, zanamivir must be
given within 48 hours of symptom onset, but
Management
oseltamivir must be given within 36 hours. Although
A rapid, accurate diagnosis is essential to initiate studies show both drugs are approximately 80%
antiviral treatment in a timely fashion. There are four effective in preventing influenza illness, only
antiviral agents effective against influenza, but each is oseltamivir has been approved for prophylaxis
effective only when given within 36 to 48 hours after (Prevention and Control of Influenza: Recom-
onset of symptoms. The four agents, amantadine, mendations of the ACIP, 2004● C ).Because zanamivir
rimantadine, zanamivir, and oseltamivir, differ with is administered via inhalation, caution should be
respect to their antiviral action, age limit for use, used in patients with underlying airway disease due
route of administration, adverse effects, drug interac- to the risk of bronchospasm and a decline in lung
tions, and cost (Table 29-2) (Montalto et al., 2000● B ). function.
All four drugs are classified as pregnancy category C. Several important decision points occur in the
In addition to these antiviral agents, patients should evaluation and management of patients with sus-
receive symptomatic treatment, as they would with pected influenza. Does their clinical presentation sug-
other viral infections. gest a high probability of infection with influenza?
Amantadine and rimantadine are effective Should a rapid viral test be performed to confirm
against influenza A. Systematic reviews show these the diagnosis? If influenza infection is strongly sus-
agents reduce the duration of symptoms by approxi- pected or confirmed, which medication should be
mately 1 day compared with placebo, if they are prescribed? In a cost-benefit analysis of patients at
administered with 48 hours of symptom onset high risk of influenza-related complications, rapid

Table 29-2 Comparison of Antiviral Agents Used to Treat Influenza

Amantadine Rimantadine Zanamivir Oseltamivir
Characteristics (Symmetrel) (Flumadine) (Relenza) (Tamiflu)

Antiviral action A A A+B A+B

Prophylaxis Yes Yes No Yes
Age limit for use ≥1 yr ≥18 yr for treatment ≥7 yr ≥18 yr
≥1 yr for prophylaxis
Route Oral Oral Inhalation Oral
Adverse effects Central nervous Gastrointestinal: Nasal/throat Nausea,
system: insomnia, dyspepsia, irritation, vomiting
anxiety, depression; nausea, cough;
gastrointestinal vomiting bronchospasm
effects in asthmatics
Cost for a 5-day $14 $22 $57 $67
course*
*
Average wholesale cost based on Red Book, Montvale, NJ: Medical Economics Data, 2004.
A, influenza A; B, influenza B.

280
 Chapter 29 Fever and Cough (Influenza)

viral testing was not as cost-effective as empirical diagnosis is difficult due to the lack of specificity
treatment alone with amantadine or rimantadine and sensitivity of symptoms, but awareness of the
even when the probability of influenza infection was prevalence of influenza in the community can aid
as low as 10%. Even though neuraminidase inhibi- in diagnosis. Rapid viral tests allow early confirma-
tors are more expensive, rapid viral testing is not as tion of the illness, but only viral cultures provide
cost-effective as empirical treatment with these agents specific information regarding the influenza strains
until the prevalence of infection falls between 30% and in circulation, which is used to formulate vaccine
40% (Hueston and Benich, 2004 ● B). Therefore, from a for the next year. Antiviral agents have been shown
cost-benefit perspective, rapid viral testing has a to reduce the duration of influenza illness when
limited role in patients at high risk of complications given within 36 to 48 hours of symptom onset
from influenza. In deciding which medication to and to prevent influenza illness when used for
prescribe, consideration should be given to cost, prophylaxis.
side effect profile, patient’s age, and prevalence of
influenza A.
In summary, influenza is a serious infectious
disease that afflicts thousands of people each year. Material Available on Student Consult
Annual vaccination is the best way to prevent infec- Review Questions and Answers about Influenza
tion and minimize the effect of influenza. Clinical

REFERENCES
Couch RB. Prevention and treatment of influenza. N Engl Montalto NJ. An office based approach to influenza:
J Med 2000;343:1778–1785.● B Clinical diagnosis and laboratory testing. Am Fam
Fagan HB, Moeller AH. What is the best antiviral agent Physician 2003;67:111–117.● B
for influenza infection? Am Fam Physician 2004;70: Montalto NJ, Gum KD, Ashley JV. Updated treatment for
1331–1333.● A influenza A and B. Am Fam Physician 2000;
Hueston WJ, Benich JJ. A cost benefit analysis of testing for 62:2467–2476.●B
influenza A in high risk adults. Ann Fam Med Prevention and control of influenza: Recommendations of
2004;2:33–40.●B the Advisory Committee on Immunization Practices
Kingston BJ, Wright CV. Influenza in the nursing home. (ACIP). MMWR Morb Mortal Wkly Rep 2004;53:
Am Fam Physician 2002;65:75–78.● B 1–40.●C

281
 C h a p t e r

30 Sinus Congestion (Sinusitis)

John W. Ely

gets a sinus infection in the fall and wonders whether

KEY POINTS she might be allergic to fall weeds but has never had
skin testing. In the past, she has obtained relief with
1. It is difficult to distinguish bacterial sinusitis antibiotics for similar symptoms. She believes that
from the common cold based on clinical find- she has another sinus infection and is asking for a
ings. However, radiographs and sinus aspiration course of antibiotics.
are rarely indicated in the primary care setting.
2. Clinical findings that favor sinusitis include Medical History
purulent nasal discharge, unilateral maxillary Kathy had a tonsillectomy at age 5. She had two
tooth or face pain, worsening of symptoms uncomplicated vaginal deliveries at age 21 and 23.
after initial improvement, and duration of illness She takes no other medications and has no known
greater than 7 days. medication allergies.
3. Most patients can be treated with amoxicillin
500 to 1000 mg three times daily. Alternatives Family History
include trimethoprim/sulfamethoxazole and Kathy has two sisters, who are alive and well. Her
doxycycline. For patients with severe symptoms, mother has hypertension and “allergies.” Her father
an antibiotic with coverage for resistant bacte- has no health problems that she is aware of.
ria, such as amoxicillin/clavulanate, cefpo-
doxime, cefdinir, or levofloxacin, should be used. Social History
4. Fluoroquinolones should be avoided in patients Kathy is a nonsmoker and drinks alcohol rarely. She
younger than age 18 years and doxycycline in teaches kindergarten and is married to a restaurant
patients younger than age 8 years. Both should manager. She has two children and lives on an
be avoided in pregnancy. acreage with her husband.

Review of Systems
Kathy denies dyspnea, chest pain, nausea, or vomit-
INITIAL VISIT ing. She has had no visual disturbance or other neu-
rologic symptoms.
Subjective
Objective
Patient Identification and Presenting Problem
Kathy V. is a 28-year-old kindergarten teacher who Physical Examination
complains of sinus congestion. She was well until a
week ago when she developed nasal congestion, mild General Kathy is alert but appears moderately ill and
sore throat, fatigue, and headache. She denied cough has obvious nasal congestion.
or fever. Initially, her nasal discharge was clear, but
in the past 2 days, it has turned yellowish green. Vital Signs Her temperature is 37.6˚C (99.7˚F), pulse
She complains of pain and fullness in both cheeks, is 84, respiratory rate is 18, and blood pressure is
especially when she bends forward. She tried over- 130/84.
the-counter decongestants, and these were somewhat
helpful but did not provide complete relief. She Eyes, Ears, Nose, and Throat Her pupils are 3 mm,
denies pain in her maxillary teeth. She says she often equal, and reactive to light. Her external auditory

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

282
 Chapter 30 Sinus Congestion (Sinusitis)

canals and tympanic membranes are normal. Her associated with a purulent discharge or with systemic
nasal mucus is clear bilaterally, turbinates are swollen symptoms. It can usually be distinguished from aller-
bilaterally, and she cannot breathe through her left gic rhinitis by the absence of itching.
nostril at all. The nasal mucosa is pink. Maxillary Rhinitis medicamentosa results from overuse of
sinuses are mildly tender to palpation (but probably topical nasal decongestants. Patients generally admit
within normal limits). There is no inflammation in to daily use of nose sprays and complain that they
her mouth and throat. cannot function during the day or sleep at night if
they stop treatment. The condition is chronic and not
Neck Her neck is supple with no lymph node typically associated with other respiratory symptoms.
enlargement.
Plan
Lungs Her lungs are clear to percussion and auscul-
tation. Diagnostic
Transillumination of the maxillary sinuses seems
Heart Her heart rhythm is regular with a grade somewhat reduced bilaterally. However, the amount
II/VI systolic ejection murmur along the left sternal of transillumination varies depending on the exact
border. placement of the light, and interpretation is judged
unreliable. Because this is the patient’s initial presen-
Abdomen Her abdomen is nontender with no tation for this illness, further diagnostic tests, such as
organomegaly or masses. computed tomography and sinus aspiration, are not
indicated.
Extremities There is no edema.
Therapeutic
Assessment Kathy is treated with amoxicillin 1 g three times daily
for 10 days. She was advised that she could continue
Working Diagnosis her over-the-counter decongestant if it seemed to
Acute bacterial sinusitis. help her symptoms.

Differential Diagnosis Patient Education

The differential diagnosis includes other causes of The physician explains that Kathy probably has
nasal congestion. a viral infection, but because of her symptoms
The common cold, caused by common respira- and the length of her illness, there is a moderate
tory viruses (e.g., rhinoviruses, parainfluenza virus, chance of bacterial sinusitis. Although sympto-
influenza virus), is difficult to distinguish from matic treatment alone is an option, the patient
bacterial sinusitis (Gwaltney et al., 1994● B ; Hickner is convinced that she will not improve without
et al., 2001● B ; Williams and Simel, 1993 ● B ). Colds antibiotics. She is instructed to return if she fails to
tend to produce milder symptoms and a shorter improve over the next 3 to 4 days or if her symp-
course of illness (usually less than 7 to 10 days). toms worsen.
The mucus is likely to be clear, and fever in adults is
unusual. However, there is a large overlap with the
clinical findings of bacterial sinusitis, as discussed DISCUSSION
later in this chapter (Williams and Simel, 1993● B).
Allergic rhinitis is more likely to be associated
Introduction
with itching (itchy eyes, itchy throat, itchy nose) and
with a history of atopic disease and seasonal exacer- How can bacterial sinusitis be distinguished from the
bation of symptoms. Patients often have paroxysms common cold? This is one of the great unanswered
of sneezing and may have other evidence of atopic questions in primary care and one that most family
diseases, such as asthma or eczema. Physical find- physicians grapple with every day. Sinus aspiration
ings, such as hyperlinear palms, Dennie Morgan is onsidered the gold standard for diagnosis, but it
lines (increased number of creases below the eyes), is not a reasonable option for most patients. Sinus
and dry skin, increase the likelihood of atopy as computed tomography scans are expensive and, even
an explanation for nasal symptoms. However, bac- if abnormal, do not assume the diagnosis of bacter-
terial sinusitis can be a complication of allergic ial sinusitis because viral sinusitis can cause identical
rhinitis. findings (Gwaltney et al., 1994 ● B ). Therefore, bacter-
Vasomotor rhinitis (idiopathic rhinitis) is char- ial sinusitis is generally diagnosed by history and
acterized by congestion and rhinorrhea triggered by physical examination findings, such as length of ill-
nonspecific irritants such as odors and temperature ness (>7 days), colored nasal discharge, maxillary
changes. It is a chronic condition that is not pain, and so on. When the patient has all the

283
 Chapter 30 Sinus Congestion (Sinusitis)

symptoms and signs of sinusitis, the likelihood of a abnormalities were used as the gold standard: colored
bacterial infection is high. When none of the signs nasal discharge by history, colored nasal discharge by
and symptoms are present, the likelihood is low. physical examination, maxillary tooth pain, failure to
Most patients fall between these extremes and thus respond to decongestants, and abnormal transillumi-
have an intermediate probability of sinusitis. The nation. If all five findings were present, the patient
question then becomes at what probability should had a high likelihood of having sinusitis, and, if none
antibiotics be prescribed. For example, if the patient were present, the patient had a low likelihood. Most
has a 20% chance of bacterial sinusitis, is that high patients fell between these extremes and had inter-
enough to justify antibiotic treatment? mediate probabilities. To transilluminate the maxil-
In practice, the decision to treat with antibiotics lary sinuses, a fiberoptic light (such as an otoscope
depends as much on “soft” variables, such as patient without the disposable tip) is placed on the upper
wishes, physician beliefs, and community customs, cheek at the infraorbital rim. The procedure must be
as it does on the patient’s clinical findings. Recent carried out in a completely dark room. With the
reviews and clinical guidelines have provided excel- patient’s mouth open, the physician will observe a red
lent summaries of the evidence on diagnosis and glow on the hard palate if the sinus is normal. Fluid or
treatment of acute sinusitis (Anonymous, 1999● B; mucosal thickening will produce various degrees
Gwaltney, 2004● C ; Hickner et al., 2001● B ; Piccirillo, of reduction in the glow. Unfortunately, the procedure
2004● C ). Unfortunately, the lack of reliable methods is not very reliable because it depends on exact light
for distinguishing between common colds and bacte- placement, degree of dark accommodation, and inten-
rial sinusitis has hindered the ability of these groups sity of the light source.
to provide definitive advice. The guidelines have Since 1976, seven studies have attempted to cor-
little to say about the real-world dilemmas faced by relate clinical findings with more objective evidence
practicing physicians who must balance the demands of sinusitis (Axelsson and Runze, 1976 ● B ; Berg and
of patients with concerns about the overuse of Carenfelt, 1988● B ; Hansen et al., 1995● B ; Lindbaek
antibiotics. Physicians who are pressured by patients et al., 1996b● B ; van Buchem et al., 1995 ● B ; van Duijn
for antibiotics cannot say with much conviction et al., 1992● B ; Williams et al., 1992 ●
B ). Based on these
that antibiotics are not needed because they have no studies, Hickner and colleagues (2001● B ) recommend
practical tools for ruling out bacterial infection. Over withholding antibiotics for at least 7 days of typical
the past 30 years, only a handful of studies have cold symptoms because bacterial sinusitis occurs in
attempted to correlate clinical findings with more only 20% of patients within the first 7 days. Other
definitive evidence of sinusitis (Axelsson and symptoms found to favor sinusitis include purulent
Runze, 1976● B ; Berg and Carenfelt, 1988● B ; Hansen nasal discharge, unilateral maxillary tooth or face
et al., 1995● B ; Lindbaek et al., 1996 b● B ; van Buchem pain, and worsening of symptoms after initial
et al., 1995●B ; van Duijn et al., 1992● B ; Williams et al., improvement. Current guidelines favor these find-
1992● B). ings together with the 7-day waiting period as the
most clinically useful method for identifying
Epidemiology patients who should be treated with antibiotics
(Anonymous, 1999● B ; Anonymous, 2001● C ; Hickner
Only 2% of common colds are complicated by bac- et al., 2001● B ).
terial sinusitis. The maxillary sinuses are most fre- The most accurate method for identifying bac-
quently involved. The organisms most likely to cause terial sinusitis is to aspirate the involved sinus, but
acute sinusitis are Streptococcus pneumoniae and this procedure is too invasive for routine use. It
Haemophilus influenzae (Gwaltney, 2004 ● C ). In should be reserved for research studies and in
chronic sinusitis, Staphylococcus aureus and gram- selected patients who are suspected of intracranial
negative rods are the predominant organisms, extension of their infection. Sinus computed tomog-
although anaerobes and fungi are frequently isol- raphy scanning has generally replaced plain films
ated also. because of its improved accuracy and similar cost.
Risk factors for bacterial sinusitis include a preced- However, imaging is not recommended for most
ing viral upper respiratory infection, history of nasal patients because it is expensive and does not distin-
allergies, deviated nasal septum, nasal polyps, and guish between viral and bacterial sinusitis (Gwaltney
swimming. Less common risk factors include cystic et al., 1994● B). It may be indicated for patients whose
fibrosis, disorders of ciliary function, and immunodefi- symptoms fail to respond to antibiotics or who have
ciency (e.g., human immunodeficiency virus infection). recurrent infections. In such patients, a normal com-
puted tomography scan is particularly helpful in
avoiding repeated courses of antibiotics. Computed
Diagnosis
tomography is also recommended in patients sus-
B) found five clinical findings that
Williams et al. (1992● pected of having intracranial or intraorbital compli-
independently predicted sinusitis, when radiographic cations, but these are rare complications.

284
 Chapter 30 Sinus Congestion (Sinusitis)

Table 30-1 Recommendations for Managing Patients with Sinusitis and Strength of
Evidence for Those Recommendations
Strength of
Recommendation Recommendation

The diagnosis of bacterial sinusitis should generally be based on clinical findings B

such as purulent nasal discharge, maxillary pain, and duration of illness >7 days.
Most patients with bacterial sinusitis should be treated with amoxicillin. In patients B
allergic to penicillin, doxycycline or trimethoprim/sulfamethoxazole can be used.
In patients who are likely to have resistant bacteria (day care workers, patients
who have recently taken antibiotics), azithromycin, levofloxacin, or high-dose
amoxicillin/clavulanate should be used.
Radiographs should not be routinely performed to diagnose acute sinusitis. B
They may be indicated in patients with recurrent infection or those who fail to
respond to treatment. Sinus computed tomography scanning has generally
replaced plain films.
Decongestant/antihistamine combinations and analgesics can be offered for B
symptomatic treatment.
B, Recommendation based on inconsistent or limited-quality, patient-oriented evidence.

course of a broader spectrum antibiotic. A computed

Treatment
tomography scan should be obtained after one or
The efficacy of antibiotics for acute sinusitis is two failed antibiotic courses (depending on severity
controversial with some studies showing benefit of symptoms), and referral to an otolaryngologist
and others failing to show benefit (Axelsson et al., should be made if the sinuses are opacified.
1970 ● B ; Gananca and Trabulsi, 1973● B ; Lindbaek In patients who request antibiotics for symptoms
et al., 1996a● B ; Stalman et al., 1997●
B ; van Buchem that are most consistent with a viral infection, a com-
et al., 1997● B ). Once the decision is made to treat with promise measure has been suggested: Couchman and
antibiotics, current guidelines favor narrow-spec- colleagues (2000● B) advised patients with common res-
trum antibiotics such as amoxicillin (adult dose 1.0 g piratory symptoms to fill prescriptions for antibiotics
three times daily for 10 days), trimethoprim/sul- only if their symptoms worsened or did not improve
famethoxazole (one double-strength [160 mg/800 after a specified number of days (which was deter-
mg] tablet twice daily), or doxycycline (100 mg twice mined individually by the physician). In their study,
daily). Narrow-spectrum antibiotics, such as amoxi- only 50.2% of patients filled their prescriptions.
cillin, are justified in patients with mild to moderate Symptomatic treatment with decongestant/
symptoms or in those who have only a moderate antihistamine preparations is commonly prescribed,
likelihood of bacterial infection. However, because of although evidence to support efficacy has been
the increasing prevalence of resistant S. pneumoniae inconsistent. Topical decongestants can also be pre-
and H. influenzae in many communities, patients scribed, but the patient should be warned not to use
with more severe symptoms should receive broader them for more than 4 days due to the risk of induc-
spectrum antibiotics, such as amoxicillin/clavulanate ing rebound congestion or rhinitis medicamentosa.
(2000 mg/125 mg every 12 hours), cefpodoxime (200 Patients with acute sinusitis often have severe facial
mg every 12 hours), cefdinir (600 mg once daily), or pain, and analgesics should be offered in such cases.
levofloxacin (750 mg once daily). Fluoroquinolones
should be avoided in patients younger than age 18 Summary
years, and doxycycline should be avoided in patients
younger than age 8 years. Both should generally be Sinusitis should be suspected in adults who have nasal
avoided in pregnancy. congestion lasting longer than 7 days, especially when
The duration of treatment varies. One study accompanied by unilateral maxillary pain or purulent
found that 3 days of trimethoprim/sulfamethoxazole nasal discharge. In general, symptoms lasting less than
was just as effective as 10 days’ treatment (Williams 7 days can be attributed to a viral common cold unless
et al., 1995● A). However, most physicians continue to symptoms are severe or there is a fever. Once the diag-
treat for 10 days. Otolaryngologists often treat much nosis is made, patients should be treated with antibi-
longer (2 to 4 weeks), but they see a referral popula- otics for 10 days. For most patients, amoxicillin 500 to
tion, which includes patients who have failed shorter 1000 mg three times daily is a reasonable choice.
treatment courses. Patients who fail to respond to 10 Alternatives include trimethoprim/sulfamethoxazole
days of a first-line antibiotic should receive a longer and doxycycline. For patients with severe symptoms,

285
 Chapter 30 Sinus Congestion (Sinusitis)

an antibiotic with coverage for resistant bacteria, such

Material Available on Student Consult
as amoxicillin/clavulanate, cefpodoxime, cefdinir,
or levofloxacin, should be used. The main recommen- Review Questions and Answers about Sinusitis
dations for managing patients with sinusitis are sum-
marized in Table 30-1.

REFERENCES
Anonymous. Diagnosis and treatment of acute bacterial amoxycillin in treatment of acute sinus infections in
rhinosinusitis: Summary, evidence report/technology adults. BMJ 1996a;313:325–329.● B
assessment. No. 9. Rockville, MD, Agency for Health Lindbaek M, Hjortdahl P, Johnsen UL. Use of symptoms,
Care Policy and Research, 1999. (AHCPR publication signs, and blood tests to diagnose acute sinus infections
no. 99-E015.) Available at www.ahrq.gov/clinic/ in primary care: Comparison with computed tomogra-
epcsums/sinussum.htm. Accessed 8/28/2004.● B phy. Fam Med 1996b;28:183–188.● B
Anonymous. Clinical practice guideline: Management of Piccirillo JF. Acute bacterial sinusitis. N Engl J Med
sinusitis. Pediatrics 2001;108:798–808.●C 2004;351:902–910.● C
Axelsson A, Chidekel N, Grebelius N, Jensen C. Treatment of Stalman W, van Essen GA, van der Graaf Y, de Melker RA.
acute maxillary sinusitis: A comparison of four different The end of antibiotic treatment in adults with acute
methods. Acta Otolaryngol 1970;70:71–76.● B sinusitis-like complaints in general practice? A placebo-
Axelsson A, Runze U. Symptoms and signs of acute maxil- controlled double-blind randomized doxycycline trial.
lary sinusitis. ORL J Otorhinolaryngol Relat Spec Br J Gen Pract 1997;47:794–799.● B
1976;38:298–308.● B van Buchem FL, Knottnerus JA, Schrijnemaekers VJ,
Berg O, Carenfelt C. Analysis of symptoms and clinical Peeters MR. Primary-care-based randomised placebo-
signs in the maxillary sinus empyema. Acta Otolaryngol controlled trial of antibiotic treatment in acute maxil-
1988;105:343–349.● B lary sinusitis. Lancet 1997;349:683–687.● B
Couchman GR, Rascoe TG, Forjuoh SN. Back-up antibi- van Buchem L, Peeters M, Beaumont J, Knottnerus JA.
otic prescriptions for common respiratory symptoms. Acute maxillary sinusitis in general practice: The rela-
J Fam Pract 2000;49:907–913.● B tion between clinical picture and objective findings. Eur
Gananca M, Trabulsi LR. The therapeutic effects of J Gen Pract 1995;1:155–160.● B
cyclacillin in acute sinusitis: In vitro and in vivo van Duijn NP, Brouwer HJ, Lamberts H. Use of symptoms
correlations in a placebo-controlled study. Curr Med and signs to diagnose maxillary sinusitis in general
Res Opin 1973;1:362–368.● B practice: Comparison with ultrasonography. BMJ
Gwaltney JM Jr. Acute Sinusitis and Rhinosinusitis, 2004. 1992;305:684–687.● B
Up to Date.com. Accessed 8/21/2004.● C Williams JW, Hollerman DR, Samsa GP, Simel DL.
Gwaltney JM, Phillips CD, Miller RD, Riker DK. Randomized controlled trial of 3 vs 10 days of
Computed tomographic study of the common cold. trimethoprim/sulfamethoxazole for acute maxillary
N Engl J Med 1994;330:25–30.● B sinusitis. JAMA 1995;273:1015–1021.● A
Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute Williams JW, Simel DL. Does this patient have sinusitis?
maxillary sinusitis in a general practice population. Diagnosing acute sinusitis by history and physical
BMJ 1995;311:233–236.● B examination. JAMA 1993;270:1242–1246.● B
Hickner JM, Bartlett JG, Besser RE, Gonzales R, . Hoffman Williams JW Jr, Simel DL, Roberts L, Samsa GP. Clinical
JR, Sande MA. Principles of appropriate antibiotic use evaluation for sinusitis. Making the diagnosis by his-
for acute rhinosinusitis in adults: Background. Ann tory and physical examination. Ann Intern Med
Intern Med 2001;134:498–505.● B 1992;117:705–710.● B
Lindbaek M, Hjortdahl P, Johnsen UL. Randomised, dou-
ble blind, placebo controlled trial of penicillin V and

286
 C h a p t e r

31 Productive Cough
(Acute Bronchitis)
Bruce Barrett

KEY POINTS

1. Acute bronchitis is a very common diagnosis 6. There is very little RCT-based evidence for or against
and is usually caused by viral infection. the effectiveness of antitussive treatments.
2. Other causes of acute cough, such as pneumo- However, limited use may be supported, especially
nia, gastroesophageal reflux disease, and when the cough is interfering with sleep.
allergy, should be considered. 7. Nonsteroidal anti-inflammatory drugs are effec-
3. The best available evidence suggests that antibi- tive for pain, but significant toxicity risks raise the
otics may reduce symptoms and illness duration need for caution.
slightly. Costs and side effects make the bene- 8. Over-the-counter cold formulas containing
fit-harm trade off tenuous at best. decongestants and/or antihistamines are not
4. Neither age nor smoking status has been linked appropriate treatments for acute bronchitis but
to antibiotic effectiveness. may be helpful if nasal congestion or drainage is
5. Only doxycycline, erythromycin, and trimetho- present.
prim/sulfamethoxazole have been tested in pos- 9. Mucolytics and expectorants have not been ade-
itively reported randomized, controlled trials quately assessed for acute bronchitis, but evi-
(RCTs); hence, these are the only antibiotics that dence from common cold and chronic bronchitis
should be considered. suggests possible effectiveness.

INITIAL VISIT pain, shortness of breath, and vomiting. She may

have had some increased dyspnea on exertion, espe-
Subjective cially in the beginning of the illness. She denies sen-
sations of maxillary pain or postnasal drip. Her sore
Patient Identification and Presenting throat has resolved. This acute illness has caused her
Problem to reduce smoking to “a few cigarettes a day.” She
Jane Doe is a 58-year-old woman who presents notes that “I really should quit that stuff.” She has
at your clinic with productive cough of 10 days’ been using an over-the-counter combination cold
duration. Jane first felt ill 2 weeks ago on the first of formula, which she believes has helped manage the
October. She remembers feeling a scratchy throat, cough, although it does make her “a bit groggy.”
which progressed to sore throat, general malaise, and
cough. The cough has been bothersome both during Medical History
the day and at night. It has kept her awake and has You have known Jane since she first came to you
awakened her out of sleep. During the past week, she about 4 years ago with chest pain. Previously, she
has coughed up phlegm. At first, it was clear to white. had neglected her health care for many years. That
Now it is green or brown. There has been no blood. original chest pain was burning in quality, bothered
She felt alternately “slightly feverish” and “chilly” her most when she felt stressed, and was diagnosed
during the first few days of this illness but denies empirically as reflux esophagitis when it responded
high temperatures and has not felt feverish for the to antacids. Her heartburn is now well controlled
past several days. She denies nasal symptoms, chest with lifestyle modifications and ranitidine (Zantac),

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

287
 Chapter 31 Productive Cough (Acute Bronchitis)

150 mg once or twice daily. Routine health screen- reflex and no signs of middle ear fluid. Posterior
ings revealed tobacco use (one pack per day for 30 pharynx is somewhat erythematous but is without
years) and hyperlipidemia, which is now well con- exudates, swelling, or signs of postnasal drainage.
trolled on a statin. She also takes a daily aspirin for There is no tenderness to maxillary percussion.
heart attack and stroke prevention. Her blood pres- There are two small, smooth, mobile, and nontender
sure has ranged from normal to borderline. Random lymph nodes palpable in the anterior chain on the
blood glucose screening was normal. She has had two left side of her neck. Posterior auscultation of the
urinary tract infections since coming to you, both lungs reveals neither rales nor rhonchi. Inspiratory
of which resolved with fluids and short courses of effort is good, with full and symmetrical chest wall
antibiotics. With motivational counseling, she expansion. Heart sounds are normal.
reduced her cigarette consumption to less than half a
pack per day, has improved her diet, and walks a Laboratory Examinations
brisk mile several days per week. Mammograms, You consider a chest radiograph, peak flow, complete
Pap smears, and a screening sigmoidoscopy have all blood count, C-reactive protein, and/or testing for
been negative. Jane received all recommended child- streptococcal pharyngitis or pertussis but decide to
hood immunizations but has declined influenza order no tests.
vaccination. She remembers receiving antibiotics
for acute coughing illnesses several years before Assessment
meeting you.
Working Diagnosis
Family History Although you have not seen Jane before with this
Jane’s father died of a heart attack at age 64. He was specific constellation of symptoms, you presump-
a smoker. Jane’s mother is alive and well at 77 but was tively diagnose acute bronchitis, most likely caused
diagnosed with type 2 diabetes and hypertension in by recent and perhaps ongoing upper airway viral
her 60s. Jane’s grandparents died in their 70s and 80s infection with mid-airway inflammatory sequelae.
of unknown causes. She has a brother and two sisters Chronic exposure to tobacco smoke and possibly to
but is unaware of any major health issues. other airborne pollutants is likely an underlying con-
tributory factor.
Social History
Jane is married with three adult children. She Differential Diagnosis
works as an office manager. She attributes daily The list of possible causes of acute coughing illness
work stress and relationship stress as the primary includes asthma, bronchiectasis, cancer, chemical
obstacles to smoking cessation. Her husband nags bronchitis, chronic obstructive pulmonary disease,
her to quit smoking. She denies physical or sexual drugs (e.g., angiotensin-converting enzyme inhi-
abuse. bitor), eosinophilic bronchitis, gastroesophageal
reflux disease, interstitial lung disease, pneumonia,
Review of Systems and sinusitis. Infectious viral respiratory pathogens
In addition to the acute symptoms mentioned, Jane include adenovirus, coronavirus, enterovirus,
has occasional mild heartburn, generally well con- influenza, parainfluenza, respiratory syncytial
trolled with antacids or ranitidine. She denies any virus, and rhinovirus. Each of these classes of virus
chest pain or pressure with exercise. She also denies has many subtypes; hence, there are several hun-
weight loss and feels that her general health, energy, dred specific viral strains that can lead to upper
and quality of life have improved slightly over the respiratory infection with cough. You know that
past 3 years. She is not aware of any significant occu- influenza and respiratory syncytial virus are con-
pational or environmental exposures but does live in fined to the months November through April in
a city that has occasional ozone alerts. your locale and thus are not in today’s differential
diagnosis. Last year, your state experienced an epi-
Objective demic of pertussis, which was eventually controlled
with an aggressive test-and-treat strategy. This year,
Physical Examination your state public health department has reported
Jane is 5 feet 10 inches and 180 pounds (body mass only rare cases. Sinusitis is excluded by lack of fever,
index = 25.8). Her blood pressure today is 128/86 face pain, maxillary tenderness, or purulent dis-
mm Hg, her heart rate is 68 beats per minute, and charge in nasal passageways or posterior pharynx.
her temperature is 37˚C (98.6˚F) by ear thermome- There is no history of occupational or environmen-
ter. Her respiratory rate is about 20 breaths per tal exposure. The history of esophageal reflux sug-
minute. Her mucous membranes (ocular, nasal, and gests a possible contribution, but the symptoms are
oral) are moist, without any abnormal signs. much more specific for acute infectious bronchitis,
Tympanic membranes are clear, with normal light presumed viral.

288
 Chapter 31 Productive Cough (Acute Bronchitis)

Plan mention that more than a million Americans have

kicked the habit and that you believe that she can too.
Diagnostic
Acute bronchitis, presumed viral, is a very common Follow-up Visit
clinical diagnosis (Gonzales, 2000). There are no sen- You see Jane again for smoking cessation counseling
sitive or specific supporting tests. The main diagnos- and follow-up after an upper endoscopy performed
tic job of the clinician is to rule out other causes. Jane by a gastroenterologist colleague, which showed a
has neither paroxysmal nor whooping cough and has small hiatal hernia but no specific lesions or signs of
no known exposure risk factors. Therefore, you esophageal inflammation. Although smoking cessa-
decide not to do the uncomfortable nasopharyngeal tion is initially unsuccessful, after several attempts
swab required for pertussis polymerase chain reac- over a few years, Jane eventually kicks the habit. In the
tion testing. With normal vital signs and lung sounds meantime, she has two other occurrences of acute
and with the lack of chest pain or pressure, persistent bronchitis, both of which she treats at home with flu-
fever, and shortness of breath, you decide the pretest ids, rest, and over-the-counter cough suppressants.
probability of pneumonia is too low to order a chest
radiograph. You are aware of recent research showing
that C-reactive protein might be useful in the DISCUSSION
absence of a chest radiograph (Almirall et al.,
2004● B ; Flanders et al., 2004● B ; Garcia et al., 2003●
B)
Acute bronchitis is a very common result of upper
but also know it to be too nonspecific to be helpful in respiratory infection. Although bacterial and chemi-
this case. You do note the history of heartburn cal causes are known, the vast majority of cases of
responsive to H2 blockers and discuss the possibility acute bronchitis stem from viral agents. There are no
that esophageal reflux disease may have contributed known effective treatments for acute bronchitis.
to Jane’s symptoms. Together you decide to schedule Whether a cough is productive and the color of the
an upper endoscopy sometime in the next month phlegm are not predictive of etiologic agent (virus vs.
or two. bacteria) or response to therapy. Systematic reviews
of RCTs of antibiotics suggest small but statistically
Therapeutic significant benefits of antibiotics over placebo in
After careful consideration and a detailed discuss- terms of persistence and severity of cough
ion of risks and benefits, you suggest conservative (Anonymous, 1998● A ; Becker et al., 1999● A ; Bent
treatment: drinking lots of fluids, rest, and cough et al., 2000● A ; Fahey et al., 1998● A ; NHS Centre for
medicine. Jane will try an over-the-counter dex- Reviews and Dissemination, 2004 ● A ; Orr et al.,
tromethorphan-guaifenesin combination cough 1993● A ; Smucny et al., 2004a ● A). Combining all evalu-
syrup. If that is unsuccessful, and especially if the able data, weighted mean differences suggest an
cough keeps her awake at night, she will fill your pre- approximate half day reduction in the duration of
scription for a codeine-guaifenesin cough syrup. She cough (Smucny et al., 2004a ● A). Of the nine published
will avoid cold formulas with antihistamines or RCTs, three are “positive” in that they report statisti-
decongestants, as she has neither allergic symptoms cally significant benefits of doxycycline (Verheij et al.,
nor nasal congestion and these agents have side effect 1994● A) and erythromycin (Dunlay et al., 1987● A;
risks as well as being an expense. King et al., 1996● A) compared with placebo. Although
the other six trials testing doxycycline (Scherl et al.,
Patient Education 1987● A ; Stott and West, 1976● A ; Williamson, 1984● A),
You specifically ask Jane whether she wants or erythromycin (Brickfield et al., 1986● A ; Hueston,
expects an antibiotic prescription. She says she would 1994● A), and trimethoprim/sulfamethoxazole (Franks
take any medicine that you think would be helpful and Gleiner, 1984● A) failed to find substantial benefit,
and asks your opinion. You discuss the fact that most primary outcomes trended toward benefit, and
antibiotics may be slightly better than placebo in a few secondary outcomes reached statistical signifi-
relieving the symptom severity and duration of acute cance. It should be noted that the number of unpub-
bronchitis. However, you also note the risk of side lished RCTs is unknown. However, it is suspected that
effects and touch on the societal problem of antibi- several negative trials conducted by drug companies
otic resistance. You offer a “delayed fill” antibiotic remain unpublished. Because positive trials are more
prescription, but Jane declines. You also provide reas- likely to be published than negative trials and because
surance that the symptoms will go away and give her internal biases tend to favor treatment over placebo,
a few specific signs that would require a return visit actual benefits may be less.
(hemoptysis, shortness of breath or difficulty breath- There are no RCTs that specifically address the
ing, chest pain or pressure, persistent fever, cough question of whether antibiotics are useful for
lasting more than 6 weeks). You gently discuss the tobacco smokers with acute bronchitis. However,
association between smoking and bronchitis and Linder and Sim (2002● A) reviewed the nine trials

289
 Chapter 31 Productive Cough (Acute Bronchitis)

noted above (774 participants), looking specifically Although some evidence supports use (Hueston,
at the 276 smokers included. There were no statisti- 1994 ● A), the weight of evidence currently suggests
cally significant differences between smokers and that beta agonists are not very helpful in this
nonsmokers. However, trends actually suggested that setting (Anonymous, 2002b ● A ; Smucny et al.,
antibiotics were less effective for smokers than non- 2004b ● A ).
smokers. This is a secondary analysis (“data dredg- Expectorants and mucolytics have not been ade-
ing”); hence, conclusions are tentative but certainly quately assessed in the setting of acute bronchitis.
do not support the widespread practice of justifying However, evidence from trials for common cold and in
antibiotic prescriptions with smoking status. the setting of chronic lung disease suggests possible
Although it may be reasonable to prescribe benefits and little harm (Anonymous, 2002a ● A;
antibiotics for some patients with acute bronchitis Schroeder and Fahey, 2004● A ; Smith and Feldman,
(e.g., if early pneumonia is suspected or if there is 1993● A). Neither antihistamines nor decongestants
underlying chronic lung disease), most experts rec- have been shown to be helpful for bronchitis, and both
ommend against this practice (Anonymous, 1997● A; carry risks. Antihistamines can cause drowsiness,
Gonzales et al., 2001a,b● C ) because societal harms which may lead to a motor vehicle accident. Decon-
(antibiotic resistance) and individual adverse effects gestants are contraindicated in the settings of hyper-
may outweigh potential benefits. Side effects of tension and heart disease. For children, there is no
antibiotics, such as nausea, diarrhea, vaginal candidi- evidence of any benefit of any over-the-counter medi-
asis, and allergic reaction, occur frequently with cine for colds or bronchitis and reasonable evidence of
most antibiotics. When using antibiotics for acute potential harm (Anonymous, 2002a● A ; Gunn et al.,
bronchitis, the number needed to treat (Walter, 2001; Schroeder and Fahey, 2004● A ). Nonsteroidal
2001) and the number needed to harm are similar anti-inflammatory drugs may help if pain is present.
and in the range of 10 to 20 (Anonymous, 1998 ● A; However, the widespread use of nonsteroidal anti-
Becker et al., 1999 ●; Bent et al., 2000●; Fahey et al.,
A A inflammatory drugs is associated with major morbid-
1998● A ; NHS Centre for Reviews and Dissemination, ity and mortality, with more than 10,000 Americans
2004● A). Nevertheless, approximately half of patients dying each year, mostly from gastrointestinal bleeding,
diagnosed with acute bronchitis receive a prescrip- but also from congestive heart failure and renal failure
tion for an antibiotic (Cantrell et al., 2002● B ; Walter, (Fries, 1991● B ; Heerdink et al., 1998● B ; Page and Henry,
2001; Stone et al., 2000 ● B ). This unfortunate situa- 2000; Wolfe et al., 1999 ● B ). Although the effectiveness
tion is due both to patient demand and to physicians’ of nonsteroidal anti-inflammatory drugs appears sim-
beliefs and prescribing habits. Education, in the form ilar, risks vary, with ibuprofen being among the safest.
of a pamphlet or physician advice, significantly Acetaminophen, not a nonsteroidal anti-inflammatory
reduces the desire for antibiotics (Macfarlane et al., drug, is even safer.
2002 ● A). Some evidence suggests that writing a There is a broad body of robust evidence that
delayed prescription may reduce antibiotic use tobacco smoking cessation can be facilitated through
(Arroll et al., 2004 ●
A ). a variety of physician-assisted modalities (Lancaster
Unfortunately, there is very little reliable evi- et al., 2004● A ; Park et al., 2004● A ; Silagy and Stead,
dence regarding the effectiveness of cough treat- 2004● A ; Stead et al., 2004● A ). In addition to nico-
ments. Systematic reviews of RCTs have concluded tine replacement, bupropion (Zyban), clonidine
that there is neither good evidence for nor good (Catapres), and nortriptyline (Pamelor) have all
evidence against the effectiveness of antitussives been shown to be useful in supporting smoking ces-
(Anonymous, 2002 a ● A ; Schroeder and Fahey, sation (Gourlay et al., 2004● A ; Hughes et al., 2004● A;
2004● A ; Smith and Feldman, 1993● A). However, Silagy et al., 2004● A). Although no specific evidence
with the definite possibility of specific effectiveness links acute illness with readiness to quit, it makes
(Parvez, 1998 ● A) and with evidence suggesting that good sense that the occasion of an episode of acute
the placebo effect for cough treatments is substan- bronchitis might provide opportunity and incentive
tial (Eccles, 2002; Lee et al., 1992 ● B ), the use of to support active attempts at tobacco cessation or at
over-the-counter dextromethorphan-containing least to “plant the seed.” The fact that Jane’s father
formulations and/or limited use of prescription smoked and died of a heart attack at age 64 might
codeine or hydrocodone may be reasonable. also be diplomatically used as a motivational tool.
Although benzonatate (Tessalon) has been
approved as a prescription cough medicine, there is
Summary
virtually no evidence for or against its effective-
ness. Furthermore, the number and quality of Acute bronchitis is the most common diagnosis
RCTs on beta agonist (e.g., albuterol inhaler) used when a patient presents with prolonged acute cough.
in the setting of acute bronchitis are limited. There are no specific methods for diagnosing bron-

290
 Chapter 31 Productive Cough (Acute Bronchitis)

chitis or for distinguishing bronchitis from upper inhalers may help those with wheezing or a history of
respiratory infection with cough. The first job of the asthma. Supportive home treatments, such as fluids,
clinician is to rule out other causes, such as pneumo- rest, and avoidance of stressors, make good sense but
nia, asthma, bacterial sinusitis, and gastroesophageal are largely unsupported by evidence. Unless symp-
reflux disease. Once the diagnosis of acute infectious toms dramatically worsen, most patients with acute
bronchitis is reached, the clinician’s task turns to bronchitis do not need a return visit.
supporting the patient, in terms of both reassurance
and selection of therapy. In most cases, antibiotics
should be avoided. Until and unless better evidence
emerges, the use of over-the-counter and prescrip- Material Available on Student Consult
tion antitussives can be cautiously supported in
Review Questions and Answers about Acute
adults. Decongestants should be avoided, especially if
Bronchitis
hypertension or heart disease is present. Beta-agonist

REFERENCES
Almirall J, Bolibar I, Toran P, et al. Contribution of C-reac- Franks P, Gleiner JA. The treatment of acute bronchitis
tive protein to the diagnosis and assessment of severity with trimethoprim and sulfamethoxazole. J Fam Pract
of community-acquired pneumonia. Chest 2004;125: 1984;19:185–190.● A
1335–1342.● B Fries JF. NSAID gastropathy: The second most deadly
Anonymous. Antibiotics are ineffective for acute bronchi- rheumatic disease? Epidemiology and risk appraisal.
tis. ACP J Club 1997;126:39.● A J Rheumatol Suppl 1991;28:6–10.● B
Anonymous. Review: Antibiotics do not resolve acute Garcia VE, Martinez JA, Mensa J, et al. C-reactive protein
cough. Evid Based Med 1998;3:183.● A levels in community-acquired pneumonia. Eur Respir J
Anonymous. Lack of evidence exists for effectiveness of 2003;21: 702–705.● B
over-the-counter cough preparations for children with Gonzales R. Uncomplicated acute bronchitis. Ann Intern
URTI. ACP J Club 2002a;137:106.● A Med 2000;133:981–991.
Anonymous. Beta2-agonists are ineffective but increase Gonzales R, Bartlett JG, Besser RE, et al. Principles of
adverse effects in acute bronchitis without underlying appropriate antibiotic use for treatment of uncompli-
pulmonary disease. ACP J Club 2002b;137:72.● A cated acute bronchitis: Background. Ann Intern Med
Arroll B, Elley R, Goodyear-Smith F, Kenealy T, Kerse N. 2001a;134:521–529.● C
Delayed prescriptions for reducing antibiotic use in Gonzales R, Malone DC, Maselli JH, Sande MA. Excessive
acute respiratory infections. Cochrane Database Syst antibiotic use for acute respiratory infections in the
Rev 2004.● A United States. Clin Infect Dis 2001b;33:757–762. ●B
Becker L, Glazier R, McIsaac WJ, Smucny J. Antibiotics for Gourlay SG, Stead LF, Benowitz NL. Clonidine for smok-
acute bronchitis. The Cochrane Library. Vol. 4, 1999.● A ing cessation. Cochrane Database Syst Rev 2004;3.● A
Bent S, Saint S, Vittinghoff E, Grady D. Antibiotics in acute Gunn VL, Taha SH, Liebelt EL, Serwint JR. Toxicity of
bronchitis: A meta-analysis. Am J Med 2000;107: over-the-counter cough and cold medications.
62–67.● A Pediatrics 2001;108:52–56.
Brickfield FX, Carter WH, Johnson RE. Erythromycin in Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP,
the treatment of acute bronchitis in a community prac- Stricker BH, Bakker A. NSAIDs associated with
tice. J Fam Pract 1986;23:119–122.● A increased risk of congestive heart failure in elderly
Cantrell R, Young AF, Martin BC. Antibiotic prescribing in patients taking diuretics. Arch Intern Med 1998;158:
ambulatory care settings for adults with colds, upper 1108–1112.● B
respiratory tract infections, and bronchitis. Clin Ther Hueston WJ. Albuterol delivered by metered-dose inhaler to
2002;24:170–182.● B treat acute bronchitis. J Fam Pract 1994;39:437–440.●A
Dunlay J, Reinhardt R, Roi LD. A placebo-controlled, dou- Hughes JR, Stead LF, Lancaster T. Antidepressants for
ble-blind trial of erythromycin in adults with acute smoking cessation. Cochrane Database Syst Rev
bronchitis. J Fam Pract 1987;25:137–141.● A 2004.● A
Eccles R. The powerful placebo in cough studies? Pulm King DE, Williams WC, Bishop L, Shechter A. Effectiveness
Pharmacol Ther 2002;15:303–308. of erythromycin in the treatment of acute bronchitis.
Fahey T, Stocks N, Thomas T. Quantitative systematic J Fam Pract 1996;42:601–605.● A
review of randomized controlled trials comparing Lancaster T, Silagy C, Fowler G. Training health profes-
antibiotic with placebo for acute cough in adults. BMJ sionals in smoking cessation. Cochrane Database Syst
1998;316:906–910.● A Rev 2004.● A
Flanders SA, Stein J, Shochat G, et al. Performance of a Lee PCL, Jawad MS, Hull JD, West WHL, Porter K, Eccles
bedside C-reactive protein test in the diagnosis of com- R. The effect of placebo treatment on cough associated
munity-acquired pneumonia in adults with acute with common cold. Br J Clin Pharmacol 1992;
cough. Am J Med 2004;116:529–535.● B 51:373. ●B

291
 Chapter 31 Productive Cough (Acute Bronchitis)

Linder JA, Sim I. Antibiotic treatment of acute bronchitis Silagy C, Stead LF. Physician advice for smoking cessation.
in smokers: A systematic review. J Gen Intern Med Cochrane Database Syst Rev 2004;3.● A
2002;17:230–234.● A Smith MBH, Feldman W. Over-the-counter cold medica-
Macfarlane J, Holmes W, Gard P, Thornhill D, Macfarlane R, tions: A critical review of clinical trials between 1950
Hubbard R. Reducing antibiotic use for acute bronchitis and 1991. JAMA 1993;269:2258–2263.● A
in primary care: Blinded, randomised controlled trial of Smucny J, Fahey T, Becker L, Glazier R. Antibiotics
patient information leaflet. BMJ 2002;324: 91–94.●
A for acute bronchitis. Cochrane Database Syst Rev
NHS Centre for Reviews and Dissemination. Quantitative 2004a;3.● A
systematic review of randomised controlled trials com- Smucny J, Flynn C, Becker L, Glazier R. Beta2-agonists
paring antibiotic with placebo for acute cough in for acute bronchitis. Cochrane Database Syst Rev
adults. Database of Abstracts of Reviews of Effective- 2004b;3.● A
ness 2004;3.●A Stead LF, Lancaster T, Perera R. Telephone counselling
Orr PH, Scherer K, Macdonald A, Moffatt MEK. for smoking cessation. Cochrane Database Syst Rev
Randomized placebo-controlled trials of antibiotics for 2004;3. ●A
acute bronchitis: A critical review of the literature. Stone S, Gonzales R, Maselli J, Lowenstein SR. Antibiotic
J Fam Pract 1993;36:507–512.● A prescribing for patients with colds, upper respiratory
Page J, Henry D. Consumption of NSAIDs and the devel- tract infections, and bronchitis: A national study of
opment of congestive heart failure in elderly patients: hospital-based emergency departments. Ann Emerg
An underrecognized public health problem. Arch Med 2000;36:320–327.● B
Intern Med 2000;160:777–784. Stott NC, West RR. Randomised controlled trial of antibi-
Park EW, Schultz JK, Tudiver F, Campbell T, Becker L. otics in patients with cough and purulent sputum. BMJ
Enhancing partner support to improve smoking cessa- 1976;2:556–559.● A
tion. Cochrane Database Syst Rev 2004;3.● A Verheij TJ, Hermans J, Mulder JD. Effects of doxycycline in
Parvez L. Objective evaluation of the pharmacodynamic patients with acute cough and purulent sputum: A
response of 30 and 60 mg of dextromethorphan in double blind placebo controlled trial. Br J Gen Pract
acute cough. Eur Respir J 1998;12:413S.●A 1994;44:400–404.● A
Scherl ER, Riegler SL, Cooper JK. Doxycycline in acutse Walter SD. Number needed to treat (NNT): Estimation
bronchitis: A randomized double-blind trial. J Ky Med of a measure of clinical benefit. Stat Med 2001;20:
Assoc 1987;85:539–541.● A 3947–3962.
Schroeder K, Fahey T. Over-the-counter medications for Williamson HA Jr. A randomized, controlled trial of doxy-
acute cough in children and adults in ambulatory set- cycline in the treatment of acute bronchitis. J Fam Pract
tings. Cochrane Database Syst Rev 2004;2.● A 1984;19:481–486.● A
Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal tox-
replacement therapy for smoking cessation. Cochrane icity of nonsteroidal antiinflammatory drugs. N Engl J
Database Syst Rev 2004;3.● A Med 1999;340:1888–1899.● B

292
 C h a p t e r

32 Diagnosis and Management of

an Acute Exacerbation (Chronic
Obstructive Pulmonary Disease)
Keith B. Holten

Medical History
KEY POINTS John has been healthy and denies any treatment for
medical illnesses. He has never been treated for res-
1. Initial evaluation of a patient with chronic piratory illnesses. He has no surgical history. He is
obstructive pulmonary disease (COPD) not taking medications, except for one aspirin per
presenting to the emergency department day because he heard it was “good for circulation.”
includes a chest radiograph and an arterial He denies any medication allergies.
blood gas test.
2. Treatment for an acute exacerbation includes Family History
inhaled short-acting bronchodilators, oxygen for His parents are living and both have type 2 diabetes.
hypoxia, antibiotics, and corticosteroids. He has two siblings, both older brothers. There is no
Mucolytics, chest physiotherapy, and methyl- family history of chronic lung disease.
xanthines are not effective.
3. The ongoing management of COPD can be Health Habits
staged, based on the forced expiratory volume His cigarette smoking does increase when he is under
in 1 second (FEV1) and patient symptoms. stress. He denies alcohol or drug use. He does not
exercise.

Social History
INITIAL VISIT He lives with his wife, who is also a cigarette smoker.
He is an insurance executive and has a sedentary
Subjective job. He has not had any occupational respiratory
exposures.
Patient Identification and Presenting
Problem Review of Systems
John F. is a 42-year-old white man who presents to He has morning cough and dyspnea with exertion
the emergency department with shortness of breath. but denies hemoptysis, weight loss, or chronic spu-
For 1 week, he has noticed a low-grade fever 37.9˚C tum production.
(100.2˚F), a cough producing green sputum, and
worsening dyspnea with exertion. He denies any Objective
pleuritic chest pain, nausea, diaphoresis, chills, or
fatigue. There have not been any exposures to ill- Physical Examination
ness, including tuberculosis. He has a 2-year history General John is a well-nourished, alert white man in
of worsening dyspnea with exertion, which he no acute distress.
attributes to being “out of condition.” He notices
when walking up stairs that he has to rest to “get his Vital Signs His height is 5 feet 10 inches, weight is
breath.” He has smoked two packs of unfiltered ciga- 210 pounds, temperature is 38.3˚C (100.9˚F), respi-
rettes per day since he was 16 years old. He has tried ratory rate is 24, blood pressure is 136/80, and pulse
to reduce the amount but has been unable to do so. is 90.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

293
 Chapter 32 Diagnosis and Management of an Acute Exacerbation (Chronic Obstructive Pulmonary Disease)

Head, Eyes, Ears, Nose, and Throat John’s head is Assessment

without lesions or trauma; his pupils are equal,
round, and reactive to light; and his ear canals and Working Diagnosis
tympanic membranes are normal. His mouth and COPD with acute exacerbation. An alternate term
throat are normal. is acute bronchitis in a patient with COPD. This
patient’s symptoms indicate airway inflammation
Neck There is no cervical adenopathy and no jugular and infection resulting in wheezing, fever, worsen-
venous distention; the thyroid is nonpalpable. ing dyspnea, and purulent sputum production. The
features of this illness are typical for a patient with
Chest The anteroposterior chest wall diameter is COPD (Global Initiative for Chronic Obstructive
increased; there is no chest wall tenderness. Lung Disease [GOLD], 2001● B ): onset in mid-life,
significant smoking history, and dyspnea during
Lungs There are decreased breath sounds diffusely, exertion.
scattered ronchi that clear with coughing, and expi-
ratory wheezes. Differential Diagnosis (Table 32-1)
Asthma is an inflammatory airway disease with
Heart The heart rate and rhythm are regular with no largely reversible air flow. It more commonly occurs
gallops, rubs, or murmurs. early in life and symptoms vary from day to day.
Family history is common.
Abdomen The abdomen is benign. Congestive heart failure is more commonly seen
in the elderly and is characterized by fine basilar crack-
Lower Extremities Posterior tibial and dorsalis pedis les on physical examination. A chest radiograph reveals
pulses are present bilaterally and are strong. There is pulmonary edema and cardiomegaly. Pulmonary
no edema. function tests do not demonstrate obstruction.
Bronchiectasis is typically associated with large
Neurologic Cranial nerves II to XII are intact. There amounts of purulent sputum and coarse crackles on
are no strength deficits. physical examination. Chest radiograph or computed

Table 32-1 Differential Diagnosis of COPD with Acute Exacerbation

Diagnosis Prominent Features

Asthma Early life onset

Positive family history
Allergies
Reversible obstruction
Congestive heart failure Older adults
Basilar crackles
Cardiomegaly
Pulmonary edema on chest radiograph
Bronchiectasis Large volumes of purulent sputum
Bacterial pathogen
Bronchial dilation and thickening on chest radiograph
Pulmonary tuberculosis All ages
Infiltrate, nodular lesions on chest radiograph
High local prevalence
Obliterative bronchiolitis Younger age
Nonsmokers
History of rheumatoid arthritis or occupational exposure
Hypodense areas on expiratory chest computed tomography
Diffuse panbronchiolitis Males
Nonsmokers
Chronic sinusitis
Computed tomography chest centrolobular nodular opacities and
hyperinflation

Adapted from Global Initiative for Chronic Obstructive Lung Disease (GOLD), World Health Organization (WHO),
National Heart, Lung, and Blood Institute (NHLBI). Global Strategy for the Diagnosis, Management, and
Prevention of Chronic Obstructive Pulmonary Disease, Bethesda, MD, GOLD, WHO, NHLBI, 2001.

294
 Chapter 32 Diagnosis and Management of an Acute Exacerbation (Chronic Obstructive Pulmonary Disease)

tomography shows bronchial wall thickening and tion, and his dyspnea has improved. He has not
bronchial dilation. smoked since his admission to the hospital. More
Pulmonary tuberculosis is seen where there is a detailed questioning reveals no history suspicious for
high local prevalence or in immunocompromised obstructive sleep apnea (daytime sleepiness, loud
patients. A chest radiograph shows an infiltrate or snoring, choking during sleep, or observed apnea
nodular lesion. Onset is at any age. during sleep).
Obliterative bronchiolitis is usually seen in non-
smokers at a younger age. It is more common in
Objective
rheumatoid arthritis or after inhaling environmental
fumes. His respiratory rate is 14 at rest. His lungs are clear
Diffuse panbronchiolitis is mostly seen in male with no crackles or wheezes. Oxygen saturation is
nonsmokers. There is a high association with chronic 94% by pulse oximetry.
sinusitis. A chest radiograph shows diffuse small cen-
trolobular densities.
Assessment

Plan COPD with an acute exacerbation is resolving. His

examination is consistent with infection that cleared
Diagnostic with treatment.
A chest radiograph is obtained. There is bronchial
wall thickening but no evidence of an infiltrate, car-
Plan
diomegaly, or pleural effusion. An arterial blood gas
shows a low pH (7.32), hypercarbia (PCO2= 50), and Pulmonary function studies are ordered to be done
hypoxia (PO2 = 72). A complete blood count and in a few weeks. Those tests show FEV1 greater than
electrolytes are normal. 50% with no change after bronchodilators, consis-
tent with mild COPD. He is counseled to avoid risk
Therapeutic factors (smoking and airborne pollutants) and
The patient is admitted to the hospital. Oxygen ther- advised to get the flu vaccine yearly. He is pre-
apy at 4 L via nasal cannula is initiated, and a repeat scribed a short-acting inhaled anticholinergic
arterial blood gas test confirms correction of the bronchodilator for use when needed. Follow-up
hypoxia and no change in the hypercarbia. An inhaled every 3 months is scheduled.
anticholinergic bronchodilator (ipratropium) is
begun, given every 4 hours, and a corticosteroid
(methylprednisolone 60 mg every 8 hours intra- DISCUSSION
venously) is initiated. Antibiotics (amoxicillin 500 mg
orally three times daily) are given, and because of Acute Exacerbation of Chronic Obstructive
slow progress, after 24 hours an inhaled β2-agonist Pulmonary Disease
bronchodilator (albuterol) is added and given every 4
hours. A nutrition screen is negative for malnutrition. Evaluation of Acute Exacerbation
Influenza and pneumococcal vaccines are adminis- Physical findings are rarely diagnostic in COPD
tered. After another 48 hours, the patient is discharged (GOLD, 2001● C ). Findings of increased anteroposte-
from the hospital; he is afebrile with a normal arterial rior chest wall diameter, crackles, and wheezing sup-
blood gas and significant improvement in dyspnea. port the diagnosis. Chest radiograph findings can be
helpful (Snow et al., 2001● B ), especially for patients
Patient Education presenting to the emergency department with acute
Smoking cessation and exercise are reviewed. COPD symptoms. It has been shown that 23% of
patients have a change in their management based
Disposition on a chest radiograph. There is not good evidence
An office follow-up visit is arranged for 1 week. to support a chest radiograph for patients seen in
Completion of a 7-day course of antibiotics is the office setting. The chest radiograph can help to
recommended. differentiate between pneumonia, congestive heart
failure, and other differential diagnoses. Indirect
findings of bullae, scarring, and bronchial wall thick-
FOLLOW-UP VISIT ening can suggest underlying COPD. Heart enlarge-
ment, fluid in the minor fissure, or pulmonary
edema can support a diagnosis of congestive heart
Subjective
failure. Arterial blood gas analysis is helpful (Snow
John F. returns to the office for his follow-up visit A ) in assessing severity of the exacerba-
et al., 2001●
1 week later. He is free of cough and sputum produc- tion. The presence of hypercarbia, when associated

295
 Chapter 32 Diagnosis and Management of an Acute Exacerbation (Chronic Obstructive Pulmonary Disease)

with hypoxia and a low pH, indicates increased risk ate exacerbation. The approach for these patients
of respiratory failure. Spirometry is not helpful to includes a chest radiograph, inhaled bronchodila-
diagnose an exacerbation of COPD or to assess the tors, systemic corticosteroids, oxygen as needed, and
severity acutely (Snow et al., 2001●
A ). There is little positive-pressure ventilation as needed.
evidence that additional laboratory testing, electro- For patients meeting three of the first-level
cardiography, or echocardiography is useful (Snow criteria (increase in dyspnea, increase in sputum
et al., 2001●
C ). volume, and increase in sputum purulence), a severe
exacerbation is diagnosed. The management
Management of Acute Exacerbation includes all of the above plus antibiotics.
Oxygen therapy is beneficial to patients with hypoxia
(Bach et al., 2001● B ). Inhaled short-acting Long-term Management of Chronic
β2-agonists and anticholinergic bronchodilators Obstructive Pulmonary Disease
improve symptoms (Bach et al., 2001● A ) in patients Existing medications for COPD are not shown to
acutely ill with COPD. Anticholinergic bronchodila- alter the decreasing lung function that occurs over
tors have fewer side effects and should be used as time. A stepped approach in which treatment is
first-line therapy. A second bronchodilator should increased based on severity of illness (FEV1) can
be added if there is slow progress. Systemic improve symptoms and the health status of sufferers
corticosteroids reduce dyspnea and have been shown (Bach et al., 2001● B ; GOLD, 2001● B ; Veterans Health
to reduce the relapse rate (Bach et al., 2001● A ). This Administration [VHA], 1999 ● A● B) (Table 32-2). The
therapy should include 3 days of intravenous most important aspect of this care is monitoring
methylprednisolone, followed by oral prednisone, disease progression and development of complica-
for a total of 2 weeks. Antibiotics are beneficial tions, pharmacotherapy, exacerbation history, and
(Snow et al., 2001● A ), but narrow-spectrum agents comorbidities (GOLD, 2001● B ). A few key areas are
(amoxicillin, trimethoprim/sulfamethoxazole, tetra- considered in the remainder of this section.
cycline) should be first-line agents. No evidence is Smoking cessation interventions using brief
available to determine optimal length of antibiotic strategies (ask, advise, assess, assist, and arrange)
treatment, but generally 7 days of treatment is pro- coupled with medications can be very effective
vided. Noninvasive positive-pressure ventilation (GOLD, 2001 ● A). Patient education and pulmonary
(NPPV) decreases the risk involved in invasive mecha- rehabilitation, although they do not improve lung
nical ventilation (Bach et al., 2001● A). Parenteral function, do improve health status by improving
methylxanthines and sympathomimetics are not as coping skills (GOLD, 2001● B ). Inhaled corticos-
effective (Snow et al., 2001● B ) and have potential seri- teroids should be prescribed only for those with
ous cardiovascular side effects. Mucolytics and chest proven spirometric response and FEV1 less than
physiotherapy are not effective (Snow et al., 2001● C ). 50% (GOLD, 2001● B ). Systemic corticosteroids
The empirical use of diuretics has not been studied should be avoided due to an unfavorable benefit-
adequately (Bach et al., 2001● C ). risk ratio (GOLD, 2001● A). Long-term oxygen ther-
An algorithm for the management of acute apy to maintain oxygen saturation at more than
exacerbations of COPD was developed by the 90% prolongs life (VHA, 1999● A ). Influenza vac-
American College of Physicians based on the work cine should be administered yearly (VHA 1999 ● A).
of Snow et al. (2001 ● C ) (Fig. 32-1). This algorithm Pneumococcal vaccine should be considered
determines the management based on the presence (VHA, 1999 ● B ). All patients with COPD should
or absence of three criteria: increase in dyspnea, have nutrition screening (Harmon-Weiss, 2002● C ).
increase in sputum volume, and increase in sputum A reasonable weight (>90% ideal) should be main-
purulence. If at least one of these is present, a second tained. If food intake is inadequate, nutrition sup-
level of criteria is applied: upper respiratory infec- plements should be given. Surgical management
tion in past 5 days, fever without apparent cause, (bullectomy, lung volume reduction therapy, and
increased wheezing, increased cough, and a 20% lung transplantation) is still investigational and
increase of heart rate or respiratory rate over base- may be considered for carefully selected patients
line. If one of these second-level criteria is present, (GOLD, 2001● C ).
the patient is diagnosed with a mild exacerbation. It
is recommended that these patients have a chest
radiograph and be treated with bronchodilators
only. Material Available on Student Consult
Patients meeting two of the criteria (increase in
Review Questions and Answers about Chronic
dyspnea, increase in sputum volume, or increase in Obstructive Pulmonary Disease
sputum purulence) are considered to have a moder-

296
 Chapter 32 Diagnosis and Management of an Acute Exacerbation (Chronic Obstructive Pulmonary Disease)

COPD Guideline Algorithm

Stable COPD Further considerations for diagnosis:

patient There is no evidence for using the following
for diagnosis or as indicators of severity of
acute exacerbation of COPD (AECOPD):
1. Acute spirometry
Increase in 2. Acute PEFR
symptoms from 3. Pulse oximetry
baseline

Patient presents at
ER or hospital

Further considerations for management:

The following are not useful in the management
MD examines patient for three
of acute exacerbation of COPD (AECOPD):
diagnostic criteria for acute
1. Methylxanthine bronchodilator
exacerbation of COPD:
2. Chest physiotherapy
1. Increase in dyspnea
3. Mucolytics
2. Increase in sputum volume
4. Inhaled steroids
3. Increase in sputum purulence

No None of 3
Criteria present? diagnostic criteria Consider other
present diagnosis

Yes
One diagnostic criterion with at least one
of the following:
One 1. URI in the past 5 days
One or more only 2. Fever without apparent cause No Consider other
criteria present? 3. Increased wheezing diagnosis
4. Increased cough
Two or more 5. 20% increase in heart rate or respiratory rate
over baseline
Two or more Two only
diagnostic criteria Yes
present? Yes. Treat for mild
exacerbation of
Three COPD
Three criteria: Two criteria only:
treat for severe treat for moderate
exacerbation exacerbation

Management:
1. Chest X-ray Management:
2. Inhaled bronchodilators1 1. Chest X-ray
3. Systemic corticosteroids2 2. Inhaled bronchodilators1
4. Antibiotics4 3. Systemic corticosteroids2 Management:
5. O2 PRN 4. O2 PRN 1. Chest X-ray
6. NPPV PRN3 5. NPPV PRN3 2. Inhaled bronchodilators1

Figure 32-1 Management of acute exacerbations of chronic obstructive pulmonary disease. COPD, chronic obstructive
pulmonary disease; NPPV, noninvasive positive-pressure ventilation; PEFR, peak expiratory flow rate; PRN, as needed.
(Developed by American College of Physicians from Snow V, Lascher S, Mottur-Pilson C. Evidence base for manage-
ment of acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 2001;134:595–599.)
1
Use anticholinergic bronchodilators first, once at maximum dose, then add β2-agonist bronchodilators.
2
Dosing regimen used in the SCOPE trial: 3 days intravenous methylprednisolone, 125 mg every 6 hours followed by
oral prednisone, taper to complete the 2 week course (60 mg/day on days 4–7, 40 mg/day on days 8–11, and 20 mg/day
on days 12–15).
3
Noninvasive positive-pressure ventilation should be administered under the supervision of a trained physician.
4
Use narrow-spectrum antibiotics; the agents favored in the trials were amoxicillin and trimethoprin-sulfamethoxa-
zole, and tetracycline.

297
 Chapter 32 Diagnosis and Management of an Acute Exacerbation (Chronic Obstructive Pulmonary Disease)

Table 32-2 Approach to Management of Chronic Obstructive Pulmonary Disease

Stage FEV1 Management

All All Avoidance of tobacco smoke, occupational dusts and chemicals, indoor and
outdoor pollutants
Influenza and pneumococcal vaccines
Mild ≥50% Short-acting inhaled bronchodilator when needed
Moderate 35%–49% Regular inhaled bronchodilator(s)
Pulmonary rehabilitation
Inhaled glucocorticosteroids if frequent recurrences and lung response
Severe <35% Regular treatment with inhaled bronchodilators
Inhaled glucocorticosteroids if frequent recurrences and lung response
Treat complications
Pulmonary rehabilitation
Long-term oxygen therapy if respiratory failure
Consider surgical treatment

Data from Bach PB, Brown C, Gelfand SE, McCrory DC. Management of acute exacerbations of chronic
obstructive pulmonary disease: A summary and appraisal of published evidence. Ann Intern Med
2001;134:600–620; Global Initiative for Chronic Obstructive Lung Disease (GOLD), World Health Organization
(WHO), National Heart, Lung, and Blood Institute (NHLBI). Global Strategy for the Diagnosis, Management,
and Prevention of Chronic Obstructive Pulmonary Disease. Bethesda, MD, GOLD, WHO, NHLBI, 2001; Veterans
Health Administration. Clinical Practice Guideline for the Management of Chronic Obstructive Pulmonary
Disease. Version 1.1a. Washington, DC, Department of Veterans Affairs (U.S.), Veterans Health Administration,
1999.

REFERENCES
Bach PB, Brown C, Gelfand SE, McCrory DC. Harmon-Weiss S. Chronic Obstructive Pulmonary Disease.
Management of acute exacerbations of chronic Nutrition Management for Older Adults. Washington,
obstructive pulmonary disease: A summary and DC, Nutrition Screening Initiative, 2002.●
C
appraisal of published evidence. Ann Intern Med Snow V, Lascher S, Mottur-Pilson C. Evidence base
2001;134:600–620.● A ●
B ●
C for management of acute exacerbations of chronic
Global Initiative for Chronic Obstructive Lung Disease obstructive pulmonary disease. Ann Intern Med
(GOLD), World Health Organization (WHO), 2001;134:595–599.● A ●
B ●
C
National Heart, Lung, and Blood Institute (NHLBI). Veterans Health Administration (VHA). Clinical Practice
Global Strategy for the Diagnosis, Management, and Guideline for the Management of Chronic Obstructive
Prevention of Chronic Obstructive Pulmonary Pulmonary Disease. Version 1.1a. Washington, DC,
Disease. Bethesda, MD, GOLD, WHO, NHLBI, Department of Veterans Affairs (U.S.), Veterans Health
2001.●
A ● B ●C Administration, 1999.●A ●
B

298
 C h a p t e r

33 Dyspnea and Confusion

(Pulmonary Embolism)
Dino William Ramzi

because of her right hemiparesis and decondition-

KEY POINTS ing. Maria was started on megestrol to help her
regain the weight she had lost during the hospitaliza-
1. Clinical assessment and search for risk factors tion. One week later, Maria developed progressive
are paramount as a starting point in the evalua- confusion over several days. This morning, she was
tion of pulmonary embolism (PE). found to be frankly delirious and breathing rapidly.
2. A well-validated clinical prediction rule provides
a reliable estimate of the pretest probability Medical History
of PE. Maria’s health problems include longstanding hyper-
3. A D-dimer assay can be used as a negative pre- tension and congestive heart failure controlled on a
diction tool to reduce the need for further stud- loop diuretic and a β-blocker as well as bullous
ies to rule out thromboembolic disease. D-Dimer emphysema associated with a 30 pack-year smoking
cannot under any circumstances confirm the history.
presence of deep venous thrombosis (DVT)
or PE. Family History
4. Helical computed tomography (CT) scanning Maria’s father died suddenly when Maria was a child.
detects large, centrally located emboli but may The cause of death was never clear. One of her broth-
miss small peripherally located ones. ers has had problems with recurrent DVT and had a
5. Ventilation-perfusion (VQ) scanning is still the Greenfield filter placed. Maria has one daughter who
standard investigation for PE. is healthy. Maria suffered a series of miscarriages and
never had another child.

Social History
INITIAL VISIT Maria drinks socially and smoked regularly for 30
years. She quit smoking 10 years ago when her doc-
Subjective tor told her she had emphysema. She lived with her
Patient Identification and Presenting Problem husband until she was hospitalized this past year.
Maria V. is a 72-year-old Hispanic woman who is
readmitted to the hospital from a skilled nursing Review of Systems
facility with dyspnea and confusion. Maria was well Nursing home records indicate that Maria developed
until 4 weeks earlier when she underwent a chole- some lower extremity swelling over the past several
cystectomy for biliary colic. An incidental Dukes B days. She has been afebrile and has not been coughing.
carcinoma was resected by hemicolectomy. Her post-
operative course was stormy, complicated by pancre- Objective
atitis and a cerebrovascular accident. After a long
hospitalization, she was discharged to a skilled nurs- Physical Examination
ing facility for rehabilitation. Maria is a frail elderly woman in restraints, disori-
Maria has been doing well since arriving at the ented to time, place, and person. Her vital signs are as
rehabilitation wing of the skilled nursing facility. follows: blood pressure 140/85, pulse 104, respiratory
Ambulation and gait training have been difficult rate 24. Her oxygen saturation by pulse oximetry was

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

299
 Chapter 33 Dyspnea and Confusion (Pulmonary Embolism)

initially 80%, rising to 97% on an FiO2 of 0.4. She is

afebrile. Her head and neck examination is normal. Table 33-1 Wells Clinical Prediction Rule
There is no jugular venous distention. Her lung for PE
examination is normal; she has a fixed split S2. The Clinical Feature Points
abdomen is soft, not distended, and not tender.
There is no lymphadenopathy. Her right leg shows Clinical symptoms 3
trace edema at mid-shin, but her left leg is signifi- of DVT
cantly more swollen. Her left leg measures 32 cm at a Other diagnosis less 3
point 10 cm below the tibial tubercle as compared to likely than PE
28 cm for her right leg. Heart rate >100 beats 1.5
per minute
Immobilization or surgery 1.5
Assessment within past 4 weeks
Working Diagnosis Previous DVT or PE 1.5
The rapid development of dyspnea and hypoxia with Hemoptysis 1
asymmetrical leg swelling in a patient with multiple Malignancy 1
risk factors for the development of thromboembolic Total points
disease suggests DVT and PE.
Risk score interpretation (probability of DVT): >6
Differential Diagnosis points: high risk (78.4%); 2 to 6 points: moderate
risk (27.8%); <2 points: low risk (3.4%).
The differential diagnosis of acute dyspnea includes DVT, deep venous thrombosis; PE, pulmonary
chronic obstructive pulmonary disease exacerbation, embolism.
pneumonia, pneumothorax, pulmonary edema, Adapted with permission from Wells PS, Anderson
myocardial infarction, pericarditis, and arrhythmia, DR, Rodger M, et al. Derivation of a simple clinical
model to categorize patients’ probability of
among others. pulmonary embolism: Increasing the model utility
with the SimpliRED D-dimer. Thromb Haemost
2000;83:418.
Plan
Diagnostic
A careful clinical history and examination are the
first steps in the assessment of a suspected PE, with Treatment
careful attention to risk factors for thromboem- Immediate anticoagulation with unfractionated intra-
bolism. Chest radiograph, electrocardiography, and venous (IV) heparin is the treatment of choice. Maria
arterial blood gas all provide important clinical will be switched to an oral anticoagulation regimen as
information. soon as she is stable and will remain on warfarin for at
The use of a clinical decision rule such as the least 6 months. The option of continuing anticoagula-
Wells rule for PE (Table 33-1) is strongly recom- tion beyond 6 months depends on the identification
mended. The Wells rule estimates a pretest probability of risk factors. Maria has multiple risk factors, which
of PE, which guides interpretation of further testing. may continue to influence her risk of thrombosis. One
Maria is clearly high risk, given her recent history of immediately remediable risk factor is megestrol, an
surgery and clinical findings consistent with DVT. estrogenic medication, which should be discontinued.
A negative D-dimer is useful only in low-risk patients
and cannot be relied on in high-risk situations. Patient Education
VQ scanning has been the standard first-line Maria should be instructed about symptoms of DVT.
investigation for many decades. The role of helical Any new or additional lower extremity swelling or
CT scanning is evolving and is commonly used as an sudden onset of chest pain and dyspnea constitutes
alternative to VQ scanning. The Institute for Clinical an urgent need for consultation. Maintaining her
Improvement has developed an evidence-based algo- mobility and function will be important for prevent-
rithm that uses either CT or VQ approaches to the ing future DVT. Additionally, she should be made
diagnosis of PE (Fig. 33-1). aware that warfarin interacts with many medications
Investigations often include a Doppler ultra- and foods. Maria should avoid foods that contain
sound of the legs in search of a potential source of high amounts of vitamin K, such as green leafy veg-
embolism. Unfortunately, PEs are frequently docu- etables, cauliflower, and legumes, among others.
mented in which no evidence of an embolic source
is ever found. A negative compression ultrasound is Disposition
helpful in situations in which a thoracic CT is nega- Maria is returned to the nursing home once her
tive or a VQ scan is low or intermediate probability international normalized ratio (INR) of prothrom-
(see Fig. 33-1). bin clotting time has reached 2.0. She is requested to

300
 Chapter 33 Dyspnea and Confusion (Pulmonary Embolism)

Pulmonary Embolism

Clinical signs and symptoms of PE

Estimate clinical pretest probability of PE

Choose lung imaging study

CT pulmonary angiography Ventilation-perfusion lung scan

Positive Negative
High-probability scan Normal scan

Diagnosis: PE Compression ultra- Low- or intermediate-

sound examination probability scan Clinical pretest Follow-up for
of lower extremities (nondiagnostic) probability other diagnosis

Treat

Negative Positive Low Intermediate

or high

Clinical pretest probability Diagnosis: VTE Angiography

Diagnosis: PE

Treat
Treat
Low Intermediate High Negative Positive

D-dimer test or serial Angiography Follow-up for Diagnosis: PE

ultrasound examination other diagnosis

Treat

Negative Positive

Follow-up for other diagnosis Diagnosis: PE

Treat

Figure 33-1 Institute for Clinical Systems Improvement evidence-based treatment algorithm for CT or VQ approaches
to diagnosing pulmonary embolism (PE). (From Institute for Clinical Systems Improvement. Healthcare guidelines.
Venous thromboembolism. Available at www.icsi.org/knowledge/detail.asp?catID=29&itemID=202. Accessed
10/11/2004.)

301
 Chapter 33 Dyspnea and Confusion (Pulmonary Embolism)

return weekly to monitor her ratio until stable and investigations. The oldest, best validated, and most
then at least monthly for periodic monitoring. widely used clinical decision rule for pulmonary
embolism is the one developed by Wells and col-
leagues (see Table 33-1).
DISCUSSION Imaging technology is the backbone of investiga-
tion for PE. The definitive study to determine or refute
Diagnosis
the presence of a PE is pulmonary angiography.
PE is a potentially fatal condition that often presents However, it is a dye-based and relatively invasive test
suddenly, with or without evidence of prior DVT. that carries risk. VQ scanning has been the standard
Patients with potential thromboembolic disease first-line investigation for many decades. The
must first be evaluated for predisposing risk factors Prospective Investigation of Pulmonary Embolism
(Box 33-1). The majority of patients with PE have at Diagnosis (PIOPED) study provided landmark evi-
least one risk factor, and 50% are hospitalized or at dence of the usefulness of the VQ scan. The pretest
nursing facilities. None of the clinical findings asso- probability of PE is a subjective physician determina-
ciated with DVT or PE are specific enough to be tion, not a standardized set of criteria. The VQ test itself
entirely reliable. For example, a fixed split S2 may is most useful in combination with a formalized deci-
well reflect the presence of a PE, but it may also be sion rule. Unfortunately, VQ scanning is difficult to
present in pulmonary hypertension in the context of interpret in the presence of other pulmonary pathol-
chronic obstructive pulmonary disease. Likewise, the ogy, such as chronic obstructive pulmonary disease.
classic electrocardiographic signs of PE such as right Results from VQ scanning frequently do not provide
axis shift, P pulmonale, or right bundle branch block definitive evidence of the presence or absence of a PE.
are present in the minority of cases. Nonspecific Over the past several years, increased interest
changes are common but do not guide the diagnosis. and reliance on helical CT scanning has distracted
Chest radiograph is most commonly normal but on clinicians from the essential diagnosis. Helical
rare occasions demonstrates evidence of embolism CT scanning is technology in rapid evolution.
or infarction. Arterial blood gas analysis is helpful in Resolution is progressing to the point that some
the management of hypoxemia but is not sufficiently machines can currently discern emboli in segmental
specific to have any diagnostic use. arteries but may still miss emboli in smaller, more
The use of clinical decision rules can effectively distal vessels. In time, helical CT angiography may
estimate the probability of PE based on a formal and replace traditional angiography as the gold standard
standardized set of criteria. Numerous decision rules for assessing PE. However, data to validate the use of
have been elaborated for use in PE. The pretest prob- the technology in real-world clinical settings are still
ability of PE guides the interpretation of subsequent sparse in comparison to VQ. PIOPED II is currently

Box 33-1 Risk Factors for Thromboembolic Disease

Increasing age Fibrinogen abnormality

Prolonged immobility Plasminogen abnormality
Surgery Plasminogen activator abnormality
Major trauma Protein C deficiency
Fractures Protein S deficiency
Malignancy Resistance to activated protein C
Pregnancy Hyperhomocystinemia
Estrogenic medications Thrombocytosis
Oral contraceptive pills Heparin-associated thrombocytopenia
Hormone therapy Indwelling central catheters
Tamoxifen (Nolvadex) Hyperlipidemias
Diseases that alter blood viscosity Congestive heart failure
Polycythemia Obesity
Sickle cell disease Varicose veins
Multiple myeloma Venography
Inherited thrombophilia Chronic venous insufficiency
Lupus anticoagulant Venous stasis
Antithrombin III deficiency

302
 Chapter 33 Dyspnea and Confusion (Pulmonary Embolism)

under way and should soon provide valuable infor-

mation about the true role of the current generation Table 33-2 Initiation of Warfarin
of CT scanners in diagnosing PE. Therapy at 5 mg per Day
In recent years, refinements in D-dimer testing Warfarin Dose
have spurred interest in the use of this simple blood Day INR (mg/day)
test in the diagnosis of thromboembolic disease. For
example, a D-dimer in combination with low clinical 1 5
probability effectively rules out the possibility of a 2 5
DVT. However, the same cannot necessarily be 3 <1.5 10
said for PE, in which the use of D-dimer is more lim- 1.5–1.9 5
ited. The D-dimer is a nonspecific marker that rises 2.0–2.9 2.5
>3.0 0
with any inflammatory condition. Thus, an elevated
D-dimer has no utility when pneumonia is in the 4 <1.5 10
1.5–1.9 7.5
differential or in hospitalized patients in whom it is
2.0–2.9 5
simply not sufficiently specific. The D-dimer may be >3.0 0
useful in circumstances in which imaging has been
5 <2.0 10
indeterminate and there is a low clinical probability
2.0–2.9 5
of PE. One study suggests that CT scanning in com-
>3.0 0
bination with D-dimer is as cost-effective as VQ
6 <1.5 10
scanning, in which a negative D-dimer helps reas-
1.5–1.9 7.5
sure the clinician. It should be noted that the use of 2.0–2.9 5
D-dimer in thromboembolic disease applies only to
>3.0 0
second-generation D-dimer tests, which are more
reliable but not universally used by hospitals and INR, international normalized ratio.
laboratories. Adapted with permission from Crowther MA,
Harrison L, Hirsh J. Reply. Warfarin: Less may be
better. Ann Intern Med 1997;127:333.
Treatment
For patients who are hemodynamically stable, the tion. Nearly 50% of episodes of DVT and PE are
treatment of PE is supportive and includes the associated with some form of inherited or acquired
administration of oxygen and IV fluids in addition to thrombophilia. Patients with thrombophilias may
anticoagulation. Fibrinolytics, pulmonary artery require indefinite anticoagulation.
catheterization, and possibly surgical embolectomy When there is no clinical reason for a patient to
may be required in patients who are hemodynami- develop thromboembolic disease or when there is a
cally compromised. strong family history, then the possibility of an
Unfractionated intravenous heparin is the stan- inherited thrombophilia is heightened and a hema-
dard method of anticoagulation for patients with PE, tologic investigation may be considered. Multiple
although low-molecular-weight heparin is also safe miscarriages may also be a clue to an underlying
and effective. Enoxaparin and tinzaparin are the only thrombophilia. Table 33-3 presents one author’s
low-molecular-weight heparins currently approved approach to the investigation of thrombophilias in
for use in PE. It is not yet definitively known whether patients with PE. However, it should be noted that
the use of low-molecular-weight heparin reduces this approach is not validated or evidence based. It
length of hospitalization for PE. does not appear that investigation for thrombophil-
Once the patient is fully anticoagulated with ias reliably predicts future recurrence but may be
heparin, the use of warfarin follows. A nomogram for useful in patients with a strong family history.
initiation of warfarin at a dose of 5 mg is presented in All patients who may be immobilized for a pro-
Table 33-2. A similar nomogram exists for the use of a longed period of time should be considered candidates
10-mg dose. Occasionally, anticoagulation does not for anticoagulation in prophylactic doses. Elderly
prevent clot or embolus recurrence. In these cases, the patients undergoing surgical procedures, especially
use of an inferior vena cava filter provides some short- orthopedic procedures, are at high risk. Young patients
term benefit. Survival at 2 years does not appear to be with major trauma or acute spinal cord injury are also
affected by the use of an inferior vena cava filter. at significant risk. Many critically ill and general medi-
cine patients have risk factors associated with age and
Prevention immobility, which are underrecognized.
Subcutaneously administered heparin is a simple
The usual duration of warfarin anticoagulation fol- method of prophylaxis for venous thromboem-
lowing PE is at least 6 months. Patients with PE who bolism. Low-molecular-weight heparin is at least
have ongoing risk factors need ongoing anticoagula- as effective and possibly associated with fewer

303
 Chapter 33 Dyspnea and Confusion (Pulmonary Embolism)

Table 33-3 Risk-Specific Investigations for Thrombophilias

Risk of Having a
Clinical Characteristics Thrombophilia Investigations

First episode of venous thromboembolic Low None

disease with known risk factors for
thromboembolism and no family
history of thromboembolism*
Age older than 50 years, idiopathic Moderate Resistance to activated protein C
first episode of venous thromboembolic with a clotting assay that dilutes
disease, and no family history of patient plasma in factor V–deficient
thromboembolism* plasma or genetic test for factor
V Leiden mutation
Genetic test for prothrombin
G20210A mutation
Clotting assay for lupus
anticoagulant
ELISA for antiphospholipid
antibodies
Plasma homocysteine level
Idiopathic venous thromboembolic High All of the above and antithrombin
disease before age 50 years assay (heparin cofactor assay)
Recurrent thrombosis Protein C assay
Protein S assay
Family history of thromboembolism*
*
Family history is defined as venous thromboembolic disease occurring in a first-degree relative before the age of
50 years.
ELISA, enzyme-linked immunosorbant assay.
Adapted with permission from Ramzi DW, Leeper KV. DVT and pulmonary embolism: Part I: Diagnosis. Am Fam
Physician 2004;69:2829–2836; Ramzi DW, Leeper KV. DVT and pulmonary embolism: Part II: Treatment and
prevention. Am Fam Physician 2004;69:2841–2848.

adverse events in most surgical settings. Intermittent

Material Available on Student Consult
pneumatic leg compression is useful as an adjunct or
in patients who have contraindications to anticoagu- Review Questions and Answers about Pulmonary
lation. Elastic compression stockings must be truly Embolism
graded to deliver pressure of 30 to 40 mm Hg and are
useful only in low-risk patients.

SUGGESTED READING
Agnelli G, Prandoni P, Becattini C, et al. Extended oral with pulmonary embolism. American-Canadian
anticoagulant therapy after a first episode of pul- Thrombosis Study Group. Arch Intern Med
monary embolism. Ann Intern Med 2003;139:19–25.● A 2000;160:229–236.● A
American College of Emergency Physicians (ACEP) Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic ther-
Clinical Policies Committee. ACEP Clinical Policies apy for venous thromboembolic disease. Chest
Subcommittee on Suspected Lower-Extremity Deep 2001;119(1 Suppl):176S–193S.● B
Venous Thrombosis. Clinical policy: Critical issues in Institute for Clinical Systems Improvement. Healthcare
the evaluation and management of adult patients guidelines. Venous thromboembolism. Available at
presenting with suspected lower-extremity deep www.icsi.org/knowledge/detail.asp?catID=29&itemID
venous thrombosis. Ann Emerg Med 2003;42: =202. Accessed 12/11/2004.●B
124–135. ●B Kovacs MJ, Rodger M, Anderson DR, et al. Comparison of
Bauer KA. The thrombophilias: Well-defined risk factors 10-mg and 5-mg warfarin initiation nomograms
with uncertain therapeutic implications. Ann Intern together with low-molecular-weight heparin for outpa-
Med 2001;135:367–373.● C tient treatment of acute venous thromboembolism:
Hull RD, Raskob GE, Brant RF, et al. Low-molecular- A randomized, double-blind, controlled trial. Ann
weight heparin vs heparin in the treatment of patients Intern Med 2003;138:714–719.● A

304
 Chapter 34 Episodic Chest Pain (Angina Pectoris)

Ramzi DW, Leeper KV. DVT and pulmonary embo- with the SimpliRED D-dimer. Thromb Haemost
lism: Part I: Diagnosis. Am Fam Physician 2004; 2000;83:416–420.●A
69:2829–2836.● B Wells PS, Anderson DR, Rodger M, et al. Excluding pul-
Ramzi DW, Leeper KV. DVT and pulmonary embolism: monary embolism at the bedside without diagnostic
Part II: Treatment and prevention. Am Fam Physician imaging: Management of patients with suspected pul-
2004;69:2841–2848.● B monary embolism presenting to the emergency depart-
Wells PS, Anderson DR, Rodger M, et al. Derivation of a ment by using a simple clinical model and D-dimer.
simple clinical model to categorize patients’ probability Ann Intern Med 2001;135:98–107.●A
of pulmonary embolism: Increasing the model utility

C h a p t e r

34 Episodic Chest Pain

(Angina Pectoris)
Ruth Falik

INITIAL VISIT
KEY POINTS
Subjective
1. Electrocardiographic stress testing can be done
in patients who are stable and able to exercise Patient Identification and Presenting
to evaluate for coronary artery disease. It is a Problem
provocative test and should be done only when Richard H. is a 42-year-old white man who presents
trained personnel are available. with a 2-month history of episodic chest discomfort
2. Exercise testing should not be done in patients occurring with exertion. Richard describes his dis-
with recent myocardial infarction (less than 48 comfort as tightness in the central part of his chest
to 72 hours), infective uncontrolled hyperten- that sometimes involves his left arm. These episodes
sion, severe aortic stenosis, or a history of resolve with rest and do not last longer than 5 min-
exercise-provoked ventricular tachycardia or utes. He has had two episodes in the past week and is
syncope, resting angina, decompensated heart concerned. He denies cough, shortness of breath,
failure, acute myocarditis or pericarditis, or sig- and pain with inspiration. There is no association
nificant electrolyte abnormality. with eating or history of recent trauma.
3. The presence of left bundle branch block, left
ventricular hypertrophy with more than 1 mm
Medical History
ST depression, pre-excitation syndromes, or use
Richard has no history of diabetes or hypertension.
of digoxin precludes accurate interpretation of
His lipid status is unknown. He has had an appen-
electrocardiographic changes and requires an
dectomy. He is on no medications.
imaging stress test to evaluate for coronary
artery disease.
4. In patients unable to exercise, pharmacologic Family History
agents (e.g., dipyridamole, adenosine, dobuta- Richard’s father had a myocardial infarction at age
mine) can be used to assess for evidence of 41 and died at age 49. His mother is alive and
provocable ischemia. being treated for hypertension. His two sisters are
well.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

305
 Chapter 34 Episodic Chest Pain (Angina Pectoris)

Ramzi DW, Leeper KV. DVT and pulmonary embo- with the SimpliRED D-dimer. Thromb Haemost
lism: Part I: Diagnosis. Am Fam Physician 2004; 2000;83:416–420.●A
69:2829–2836.● B Wells PS, Anderson DR, Rodger M, et al. Excluding pul-
Ramzi DW, Leeper KV. DVT and pulmonary embolism: monary embolism at the bedside without diagnostic
Part II: Treatment and prevention. Am Fam Physician imaging: Management of patients with suspected pul-
2004;69:2841–2848.● B monary embolism presenting to the emergency depart-
Wells PS, Anderson DR, Rodger M, et al. Derivation of a ment by using a simple clinical model and D-dimer.
simple clinical model to categorize patients’ probability Ann Intern Med 2001;135:98–107.●A
of pulmonary embolism: Increasing the model utility

C h a p t e r

34 Episodic Chest Pain

(Angina Pectoris)
Ruth Falik

INITIAL VISIT
KEY POINTS
Subjective
1. Electrocardiographic stress testing can be done
in patients who are stable and able to exercise Patient Identification and Presenting
to evaluate for coronary artery disease. It is a Problem
provocative test and should be done only when Richard H. is a 42-year-old white man who presents
trained personnel are available. with a 2-month history of episodic chest discomfort
2. Exercise testing should not be done in patients occurring with exertion. Richard describes his dis-
with recent myocardial infarction (less than 48 comfort as tightness in the central part of his chest
to 72 hours), infective uncontrolled hyperten- that sometimes involves his left arm. These episodes
sion, severe aortic stenosis, or a history of resolve with rest and do not last longer than 5 min-
exercise-provoked ventricular tachycardia or utes. He has had two episodes in the past week and is
syncope, resting angina, decompensated heart concerned. He denies cough, shortness of breath,
failure, acute myocarditis or pericarditis, or sig- and pain with inspiration. There is no association
nificant electrolyte abnormality. with eating or history of recent trauma.
3. The presence of left bundle branch block, left
ventricular hypertrophy with more than 1 mm
Medical History
ST depression, pre-excitation syndromes, or use
Richard has no history of diabetes or hypertension.
of digoxin precludes accurate interpretation of
His lipid status is unknown. He has had an appen-
electrocardiographic changes and requires an
dectomy. He is on no medications.
imaging stress test to evaluate for coronary
artery disease.
4. In patients unable to exercise, pharmacologic Family History
agents (e.g., dipyridamole, adenosine, dobuta- Richard’s father had a myocardial infarction at age
mine) can be used to assess for evidence of 41 and died at age 49. His mother is alive and
provocable ischemia. being treated for hypertension. His two sisters are
well.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

305
 Chapter 34 Episodic Chest Pain (Angina Pectoris)

Social History
Table 34-1 Differential Diagnosis
Richard is married and works in sales. He has
of Chest Pain
smoked two packs of cigarettes per day since he was
in his late teens. He has one or two beers per day. He Cardiac
denies illicit drug use. He has been trying to lose Coronary artery disease
weight by walking but finds that he develops symp- Aortic stenosis
toms when he tries to increase his pace. Hypertrophic cardiomyopathy
Mitral valve prolapse
Pericarditis
Review of Systems
Syndrome X
The patient denies palpitations, lightheadedness, Aortic dissection
shortness of breath, and neck or back pain. His
appetite is unchanged, and he denies change in bowel Gastrointestinal
or bladder habits. Esophageal spasm
Esophageal reflux
Mallory-Weiss tear
Objective Biliary disease
Physical Examination Peptic ulcer
Gastritis
General Richard is a well-developed overweight
Pancreatitis
man in no distress.
Neurologic
Vital Signs He is 6 feet tall and weighs 235 pounds; Cervical disk disease
his temperature is 37.1˚C (98.8˚F), respiratory rate is Herpes zoster
12, blood pressure is 146/90 in the right arm and
142/88 in the left arm, and pulse is 72. Psychiatric
Panic attacks
Head, Eyes, Ears, Nose, and Throat Head is without
Pulmonary
signs of trauma; eyes, ears, nose, and throat are unre-
Pulmonary embolus
markable. Pneumothorax
Pneumonia
Neck The trachea is midline, neck is supple, jugular Pleurodynia
venous pulsations are of normal contour and vol- Pulmonary hypertension
ume, and no bruits are heard.
Musculoskeletal
Chest The chest is resonant to percussion; ausculta- Costochondritis
tion is clear without rales, wheezes, or rubs. Intercostal muscle spasm
Bicipital tendinitis
Heart The rhythm is regular with normal S1 and S2,
with no murmurs, rubs, or gallops heard.
pulmonary embolism, aortic dissection, and pneumo-
Abdomen The abdomen is soft and nontender with thorax) to benign (esophageal reflux or spasm, anxi-
bowel sounds in all four quadrants. ety, and costochondritis). The physician needs to
eliminate those conditions that place the patient in
Extremities There is no cyanosis, clubbing, or immediate jeopardy. This can be accomplished by a
edema; pulses are full and equal throughout. complete and focused history and physical examina-
tion, as well as readily available blood, electrocardio-
Neurologic Examination A nonfocal motor and graphic, and imaging tests.
sensory examination was done, with a normal gait
and intact cranial nerve assessment. Differential Diagnosis
Angina pectoris occurs when the blood supply to the
Assessment myocardium is not sufficient to meet metabolic
demand. The mismatch can be precipitated by an
Working Diagnosis increase in demand (physical exertion, emotional
The working diagnosis is angina pectoris, but the stress, fever) or by a decrease in supply (obstruction
differential diagnosis for chest discomfort is large; to coronary flow resulting from atherosclerotic
it includes conditions affecting organs of the tho- plaque, anemia, hypoxemia) or a combination of the
rax and abdomen (Table 34-1). These conditions two. The pain of angina pectoris is most frequently
vary from life threatening (myocardial ischemia, described as discomfort that is deep and visceral. The

306
 Chapter 34 Episodic Chest Pain (Angina Pectoris)

location is usually retrosternal and cannot be local- Plan

ized to a small area. It may radiate to the neck, jaw,
one or both arms, and the shoulders. This reflects the Diagnostic
common origin in the posterior horn of the spinal An electrocardiogram (ECG) is essential. The pres-
cord of sensory neurons to the heart, neck, shoul- ence of electrocardiographic abnormalities consis-
ders, and arms. Pain is typically brought on by tent with acute or chronic ischemia would provide
increased physical activity or emotional excitement, evidence that this patient is having chest pain that
or after eating a heavy meal. Anginal pain lasts 2 to is due to atherosclerotic blockages of the coronary
10 minutes and is relieved with rest or sublingual arteries, but the absence of such changes does not
nitroglycerin. exclude such pathology. Richard, who does not have
Other cardiac causes of chest pain similar to chest pain at this time and has a normal ECG, is a
angina pectoris (a term specific to chest pain due to good candidate for outpatient evaluation. This
coronary atherosclerosis) include hypertrophic car- should include chest radiograph, fasting lipids (to
diomyopathy, aortic stenosis, and mitral valve pro- stratify risk), complete blood count, and basic meta-
lapse; however, these cardiac lesions are associated bolic profile. Only Richard’s lipid profile is abnor-
with a systolic murmur and other characteristic find- mal: Total cholesterol is 246 mg/dL, low-density
ings. Syndrome X causes chest pain and electrocardio- lipoprotein is 149 mg/dL, and high-density lipopro-
graphic changes, but on angiography, patients have tein is 32 mg/dL. A Bruce protocol electrocardio-
normal coronary arteries and an excellent prognosis. graphic stress test is positive at 6 minutes (2.0 mm ST
Pericarditis causes chest pain that lasts hours to segment depression) at a heart rate of 150 beats per
days, is positional (worse lying down, better sitting minute, confirming that Richard’s chest discomfort
up), and has distinct electrocardiographic findings as is angina.
well as a pericardial rub.
Aortic dissection, a potentially catastrophic cause Therapeutics
of chest pain, results from a tear in the subintimal Richard is started on a β-blocker, lipid-lowering
wall of the aorta or from rupture of the vasa vasorum drug, and aspirin without side effects. He is able to
within the aortic media. Trauma to the aorta from a stop smoking cigarettes, although he complains of
motor vehicle accident or from invasive procedures, mild anxiety. He has an episode of exertional chest
e.g., cardiac catheterization, can also cause aortic dis- discomfort while on medications. The recurrence of
section. Inherited connective tissue diseases such as symptoms coupled with his relative youth, his pos-
Marfan’s and Ehlers-Danlos syndromes are associated itive cardiovascular risk profile (positive family
with cystic medial degeneration and dissection of the history, hyperlipidemia, and many pack-years of
large vessels. Acute dissection causes a sudden onset cigarette smoking), and strongly positive electro-
of severe chest pain, whereas angina tends to have a cardiographic stress test warrants a myocardial per-
less abrupt onset. fusion imaging study. It reveals a large area of
Pulmonary embolism when associated with anterior, septal, and apical ischemia. A cardiac
chest pain is most likely due to distention of the pul- catheterization is recommended. This study reveals
monary artery or infarction of a segment of the lung a 90% stenosis of the proximal left anterior
adjacent to the pleura. The pain is typically pleuritic descending artery that is successfully stented at the
and often lateral. There is often tachycardia and dysp- time of catheterization.
nea. When present, characteristic electrocardio-
graphic changes (new-onset atrial fibrillation, an Patient Education
S wave in lead I, a Q wave in lead III, and an inverted Richard is encouraged to walk 30 minutes every day
T wave in lead III) are helpful in the diagnosis. and to eat a low-fat diet.
Pneumothorax also presents with the sudden
onset of pleuritic chest pain and dyspnea and can FOLLOW-UP VISIT
readily be diagnosed with a chest radiograph, as can
pneumonia. Subjective
Gastrointestinal conditions such as esophageal
reflux, spasm, or obstruction cause chest pain that Richard is encouraged by a 15-pound weight loss over
can be visceral and located in the mid-chest. These the next 3 months and notes that he is less anxious
conditions can have associations with time of day, than previously, but he still misses cigarette smoking.
body position, or type of food ingested.
Neuromusculoskeletal conditions are the most Objective
common causes of anterior chest pain and can usu-
ally be diagnosed by the history (pain is sharp and Richard is now able to walk 2 miles every day in 30
fleeting) and the physical examination findings minutes without chest pain or shortness of breath.
(reproducible pain). He has had no further episodes of chest pain since

307
 Chapter 34 Episodic Chest Pain (Angina Pectoris)

his coronary artery stent placement. His physical Contraindications to exercise stress testing
examination is notable for a blood pressure of include rest angina within 48 to 72 hours, unstable
115/72 and pulse of 62. He is tolerating his medica- rhythm, severe aortic stenosis, acute myocarditis,
tions without adverse effects. uncontrolled heart failure, and active infective endo-
carditis.
Laboratory Tests Major indications to perform a stress myocar-
At 3 months on a low-fat diet and a lipid-lowering dial perfusion imaging study during exercise or
medication, Richard has a total cholesterol of 205 pharmacologic stress include the following:
mg/dL, low-density lipoprotein of 112 mg/dL, and ■
Diagnosis of coronary artery disease in the patient
high-density lipoprotein of 38 mg/dL. Liver function
with a positive electrocardiographic stress test
testing is normal. His ECG remains entirely normal.
without symptoms during the test or a negative
electrocardiographic stress test but with symptoms
Plan suggestive of ischemia
■ The presence of resting electrocardiographic
Richard is encouraged to continue with his dietary
abnormalities such as left bundle branch block or
modifications and weight loss regimen. He will con-
left ventricular hypertrophy, or use of drugs such
tinue to take a β-blocker and aspirin. The dose of his
as digoxin, all of which alter the repolarization
lipid-lowering medication is increased to try to fur-
phase of the ECG and preclude accurate interpre-
ther reduce his low-density lipoprotein.
tation of an electrocardiographic stress test
■ Need to determine the functional significance of
coronary artery disease
DISCUSSION
When a patient is unable to exercise due to con-
Electrocardiographic stress testing remains the most comitant medical conditions, e.g., peripheral vascular
widely used test for the diagnosis of coronary artery disease, morbid obesity, neurologic disease, poor
disease (Gibbons et al., 1997 ● C ). It involves the motivation, or anti-angina medication (β-blocker or
recording of a 12-lead ECG before, during, and after calcium channel blocker therapy), pharmacologic
exercise, most commonly on a treadmill. The test stress testing is done in conjunction with imaging
consists, of a standardized incremental increase in techniques (Lee et al., 2001). Intravenous dipyri-
the workload while symptoms, ECG, and blood pres- damole (Persantine) or adenosine is used in place of
sure are monitored. The test is stopped on complaint exercise. Dipyridamole blocks the uptake of adenosine
of chest discomfort, significant dyspnea, lighthead- by red blood cells and endothelium, resulting in an
edness, severe fatigue, ST segment depression of increase in endogenous adenosine, which in turn leads
more than 2 mm, a drop in systolic blood pressure of to relaxation of vascular smooth muscle and arteriolar
more than 10 mm Hg, or the development of ven- vasodilation. The patient should be in a fasting state,
tricular tachyarrhythmia. having received no xanthine medications (e.g., theo-
A test is considered positive if chest discomfort phylline) during the previous 36 hours and no
develops during testing, ST segment depression is caffeine-containing beverages in the preceding 24
flat and more than 1 mm below baseline (i.e., the PR hours. Dipyridamole is contraindicated in patients
segment) with a duration longer than 0.08 seconds. with reactive airways. Adenosine is a powerful vaso-
Upsloping or junctional ST segment changes are not dilator and is the mediator of dipyridamole’s vasodi-
considered to be diagnostic of ischemia, nor are T- lating action. Adenosine infusion reaches maximal
wave abnormalities, conduction disturbances, or effect at 2 minutes and is active for only 2 to 3 minutes
ventricular arrhythmias that occur during the test. If postinfusion. Patient preparation and contraindica-
the target heart rate is not achieved, defined as 85% tions are the same as for dipyridamole.
of the maximal predicted heart rate for age and gen- Dobutamine is a powerful sympathomimetic
der, then an otherwise negative test is considered to drug with β1-, β2-, and α1-adrenoreceptor agonist
be nondiagnostic. If blood pressure drops during effects resulting predominantly in inotropic effects.
testing, the test is considered positive because the Myocardial contractility is increased, as is systolic
normal response to graded exercise is a progressive blood pressure. At higher doses, dobutamine causes
increase in heart rate and blood pressure. The devel- an increase in heart rate. These effects increase
opment of chest pain and/or severe (>2 mV) ST myocardial oxygen requirements and in the presence
segment depression at a low workload (early in the of coronary artery disease may provoke ischemia.
test protocol) or the persistence of ST segment Vasodilator protocols using dipyridamole or adeno-
depression for more than 5 minutes after the termi- sine are shorter and have a lower incidence of side
nation of exercise is considered strongly positive and effects and complications.
increases the specificity of the test for coronary Two-dimensional echocardiography can assess
artery disease. both global and regional wall motion abnormalities

308
 Chapter 34 Episodic Chest Pain (Angina Pectoris)

of the left ventricle due to myocardial infarction or

Table 34-2 Stress Myocardial Perfusion
persistent ischemia. Stress (exercise or dobutamine)
Imaging Versus Stress
echocardiography may provoke akinesis or dyskine-
Echocardiography
sis not present at rest. Stress echocardiography, like
stress myocardial perfusion imaging, is more sensi- Advantages of stress myocardial perfusion
tive than exercise electrocardiography in the diagno- imaging
sis of coronary artery disease (Garber and Solomon, Greater sensitivity, especially for single-vessel
1999) (Table 34-2). coronary artery disease involving the left
Coronary arteriography is indicated in patients circumflex
with angina or evidence of ischemia on noninvasive Larger published database
testing who have evidence of ventricular dysfunc- Higher technical success rate
tion. Patients who are at high risk of sustaining coro-
Advantages of stress echocardiography
nary events based on signs of severe ischemia on Greater specificity
noninvasive testing should also undergo coronary Provides more information of cardiac anatomy
arteriography (Blumenthal et al., 2000). Other indi- and function
cations for coronary arteriography include patients Lower cost
with chronic stable angina pectoris who are severely
symptomatic despite medical therapy and who are
being considered for revascularization, i.e., percuta- artery bypass grafting. The disadvantages of percuta-
neous coronary intervention with stenting or coro- neous coronary intervention include a high incidence
nary artery bypass grafting. Coronary arteriography of incomplete revascularization, restenosis, and
is recommended for patients who present diagnostic unknown effect on outcomes in patients with severe
difficulties and in whom there is a need to confirm or left ventricular dysfunction.
eliminate the diagnosis of coronary artery disease.
Coronary artery catheterization offers the
option of revascularization if the vessel proves suit- Material Available on Student Consult
able, as was the case in this patient. It has the advan-
Review Questions and Answers about Angina
tage of being less invasive and requiring a shorter Pectoris
hospitalization and hence lower cost than coronary

REFERENCES
Blumenthal RS, Cohn G, Schulman SP. Medical therapy A report of the American College of Cardiology/
versus coronary angioplasty in stable coronary artery American Heart Association Task Force on Practice
disease: A critical review of the literature. J Am Coll Guidelines (Committee on Exercise Testing).
Cardiol 2000;36:668–673. Circulation 1997;96:345–354.●
C
Garber AM, Solomon NA. Cost-effectiveness of alternative Lee TH, Boucher CA. Noninvasive tests in patients with
test strategies for the diagnosis of coronary artery dis- stable coronary artery disease. N Engl J Med
ease. Ann Intern Med 1999;130:719–728. 2001;344:1840–1845.
Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA
guidelines for exercise testing: Executive summary:

309
 C h a p t e r

35 Palpitations (Atrial Fibrillation)

Ruth Falik

The patient specifically denies binge drinking or

KEY POINTS stimulant drug use.

1. Rate control with chronic anticoagulation is the Medical History

recommended strategy for the majority of Howard has a 35-year history of hypertension, which
patients with atrial fibrillation. Rhythm control is has been treated with hydrochlorothiazide. He has
not superior. no history of rheumatic fever or recent viral illness.
2. Patients who are at moderate or high risk of There are no known drug allergies.
stroke should receive long-term anticoagulation
with adjusted-dose warfarin. The international Family History
normalized ratio (INR) goal is 2 to 3. Howard has two older sisters. Both have hyperten-
3. To achieve adequate rate control during exer- sion and one (age 66) recently had coronary artery
cise as well as at rest, use β-blockers (atenolol bypass grafting for triple vessel coronary disease. His
or metoprolol) or nondihydropyridine calcium parents are dead; the causes are unknown, but they
channel blockers (diltiazem or verapamil). survived into their 70s.
Digoxin is effective only for rate control at rest.
4. There is an inverse relationship between the Health Habits
duration of atrial fibrillation and the ability to Howard has never smoked cigarettes. He drinks one
cardiovert to sinus rhythm—the longer the or two glasses of wine once or twice a week. He
duration of the dysrhythmia, the less likely denies illicit drug use. Howard plays golf most
cardioversion. A similar inverse relationship weekends.
exists between left atrial size and successful
cardioversion to sinus rhythm. Social History
Howard lives with his wife of 49 years. He is a retired
engineer. His three daughters live out of state.

Review of Systems
INITIAL VISIT
The patient denies a history of heart murmur, joint
disease, or neurologic disorder. He denies anxiety,
Subjective
diarrhea, loss of consciousness, or lightheadedness.
Patient Identification and Presenting Problem
Howard L. is a 77-year-old man who presents with Objective
palpitations and complains of not feeling “right” for
the past several days. He is unsure when this feeling Physical Examination
began, but he states that last weekend he could not General Howard is a well-developed, well-nourished
play his usual 18 holes of golf. He denies chest pain alert male sitting up on the examination table in no
or discomfort but is aware of an irregular beating in apparent distress.
his chest, particularly at night before falling asleep.
He has no shortness of breath and continues to sleep Vital Signs He is 6 feet 3 inches tall and weighs 200
on two firm pillows. He denies cough or fever. He has pounds. His temperature is 37˚C (98.6˚F), respira-
not noted heat intolerance, tremor, or weight loss. tory rate is 16 and unlabored, blood pressure is

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

310
 Chapter 35 Palpitations (Atrial Fibrillation)

148/86, and pulse is irregularly irregular with a ven-

tricular response of up to 160 beats per minute. Box 35-1 Irregularly Irregular Rhythms

Head, Eyes, Ears, Nose, and Throat All are unre- Atrial fibrillation
markable except for male pattern baldness. Multifocal atrial tachycardia
Atrial flutter with variable block
Neck The thyroid is of normal size and texture. Sinus rhythm with frequent ectopy

Cardiac There is no jugular venous distention, heart

sounds are crisp and irregularly irregular, and no
murmurs or gallops are heard. Differential Diagnosis (Box 35-1)
Frequent premature atrial depolarizations can cause
Chest The chest is clear to auscultation. an irregularly irregular rhythm, but P waves are pres-
ent on the electrocardiogram. Multifocal atrial
Abdomen The abdomen is soft and nontender with tachycardia is also an irregularly irregular rhythm
no evidence of hepatic enlargement. with at least three different P wave morphologies and
PR intervals, most typically seen in patients with
Extremities There is no edema. chronic hypoxemic lung disease. Atrial flutter with
variable atrioventricular nodal block may be per-
Laboratory Findings ceived as having an irregular ventricular rate, but the
Complete blood count, partial thromboplastin time, electrocardiogram shows discrete undulations of the
prothrombin time, urinalysis, blood chemistry, and baseline (e.g., “sawtooth” pattern) and, most com-
thyroid function studies are normal. monly, a ventricular rate of approximately 150 beats
per minute as a result of a 2:1 block at the atrioven-
Chest Radiograph A normal cardiac size is seen; tricular node. The diagnosis of atrial fibrillation can
there is no evidence of pulmonary infiltrate. be made by correct interpretation of the electrocar-
diogram.
Electrocardiogram There is atrial fibrillation with a
ventricular response of 130 and nonspecific ST-T
changes. Plan

Echocardiographic and Doppler Studies There is Diagnostic

concentric left ventricular hypertrophy with an ejec- The cardiac conditions most typically seen with
tion fraction of 55% and no evidence of mitral valve atrial fibrillation are rheumatic mitral valve disease,
disease. The left atrial size is 46 mm. coronary artery disease, atrial septal defect, conges-
tive heart failure, pericarditis, and hypertension.
These cardiac conditions can be evaluated with a
Assessment thorough history, physical examination, and echo-
cardiogram. The noncardiac associations for atrial
Working Diagnosis fibrillation are hyperthyroidism, hypoxic condi-
The working diagnosis is atrial fibrillation. Atrial fib- tions (pneumonia, pulmonary embolus), surgery
rillation is characterized by disorganized atrial elec- (particularly cardiac, which causes pericardial
trical and mechanical activity that is manifested by inflammation), and alcohol excess. The noncardiac
the absence of P waves on the electrocardiogram and associations can be evaluated by simple laboratory
an irregularly irregular ventricular rate. It may be tests and chest radiograph (spiral computed
seen in normal individuals during acute alcoholic tomography scan if the clinical situation is suspi-
intoxication or it may be the presenting finding in cious for pulmonary embolus).
thyrotoxicosis. Because left ventricular function and the size
There are three major classes of atrial fibrilla- of the left atrium on transthoracic echocardiography
tion: paroxysmal atrial fibrillation, in which the are independent predictors of thromboembolism,
episodes are self-terminating, usually lasting less a strategy of performing transthoracic echocardiogra-
than 24 hours but no more than 7 days; persistent phy on all individuals with newly diagnosed atrial fib-
atrial fibrillation, which fails to self-terminate, lasts rillation is reasonable. Left atrial size also is a predictor
for more than 7 days, and requires cardioversion— of the patient’s ability to cardiovert to and maintain
if atrial fibrillation recurs postcardioversion, it is sinus rhythm; a left atrial size greater than 45 mm cor-
considered recurrent—and permanent atrial fibril- relates with a poor likelihood to convert to and main-
lation which lasts longer than 1 year and cardiover- tain sinus rhythm. Transesophageal echocardiography
sion either has not been attempted or has failed. is used to identify features correlating with an

311
 Chapter 35 Palpitations (Atrial Fibrillation)

increased risk of thromboembolism: the presence of not associated with rheumatic heart disease or valvu-
left atrial thrombus, left atrial appendage size, left lar abnormalities affects approximately 4% of per-
atrial appendage peak velocities, echocardiographic sons older than 60 years. The prevalence of this most
“smoke,” left ventricular dysfunction, left ventricular common arrhythmia in adults increases with age: it
hypertrophy, and complex aortic plaque. Transeso- increases from less than 1% in persons younger than
phageal echocardiography is recommended when 60 years to more than 8% in those older than 80
immediate cardioversion is considered and the dura- years. The age-adjusted incidence for women is
tion of the arrhythmia is uncertain but likely to be approximately half that for men.
longer than 48 hours, as is the case in this patient. In addition to compromised cardiac hemody-
namics, the patient’s cardiac arrhythmia predisposes
Therapeutic him to thromboembolism. Compared with age-
The immediate therapeutic goals in this clinically matched controls, the relative risk for stroke is
stable patient are to provide ventricular rate control increased two- to sevenfold in patients with non-
and to initiate anticoagulation. Rate control should rheumatic atrial fibrillation, and the absolute risk for
improve hemodynamics and provide symptom stroke is between 1% and 5% per year, depending on
relief, whereas anticoagulation diminishes the risk of B ).
associated clinical characteristics (Gage et al., 2001●
thromboembolic complications. Had Howard pre- The CHADS2 score for risk of stroke (Table 35-1) is
sented with hemodynamic compromise (e.g., symp- calculated by adding 1 point each for recent congestive
tomatic low blood pressure or heart failure), heart failure (i.e., active within the preceding 14 weeks
immediate intervention with intravenous heparin or documented by echo), hypertension (systolic
and cardioversion, which can be pharmacologic or and/or diastolic), age (at least 75 years), and diabetes
electrical, would have been warranted. mellitus, and adding 2 points for a history of stroke or
Because Howard has no evidence of acute transient ischemic attack.
decompensation and the duration of the arrhythmia Because this patient is not experiencing chest
is likely to be longer than 48 hours, he is started on pain, hypotension, or dyspnea, acute cardioversion is
metoprolol (50 mg orally every 12 hours) for rate not indicated. The initial aim in treating this patient is
control. He is instructed on the self-administration to slow the ventricular rate and to start anticoagula-
of low-molecular-weight heparin and started on oral tion. This patient is without evidence of significant
warfarin, 5 mg per day. These agents are adminis- compromise, so this can be done in the outpatient set-
tered in the outpatient setting with laboratory mon- ting with close clinical follow-up. The choice of agent
itoring of the prothrombin time international for rate control is based on the Agency for Healthcare
normalized ratio. At day 4 his international normal- Research and Quality–funded evidence report
ized ratio is 2 (goal: 2 to 3), and low-molecular-
weight heparin therapy is stopped. His ventricular
rate is in the 80s. He feels much better since starting
the β-blocker, but he is concerned about the risk of
Table 35-1 Risk for Stroke using the
long-term anticoagulation. After discussing the risks
CHADS2 Criteria
and benefits of attempting cardioversion versus
maintaining rate control and anticoagulation, CHADS2 Score Risk Level
Howard chooses to attempt pharmacologic car-
0 Low
dioversion in 3 weeks and will be electively admitted
1 Low
to the cardiology inpatient service at that time. He is 2 Moderate
aware that even if cardioversion is successful, he will 3 Moderate
have to remain on warfarin for an additional 4 4 High
weeks. If he cannot maintain sinus rhythm, then 5 High
anticoagulation will be indefinite. He is scheduled 6 High
for a recheck of his prothrombin time international
normalized ratio in 1 week. The CHADS2 score is calculated by adding a point
each for congestive heart failure, hypertension,
age > 74, and diabetes mellitus, and adding 2
points for prior stroke or transient ischemic
DISCUSSION attack. Moderate- and high-risk patients should
receive anticoagulation with warfarin.
The patient’s symptoms reflect decreased cardiac
output due to loss of the atrial kick as well as Modified from Snow V, Weiss KB, Le Fevre M, et al.
decreased ventricular filling due to a shortened car- Management of newly detected atrial fibrillation:
A clinical practice guideline from the American
diac cycle. The normal echocardiogram excludes Academy of Family Physicians and the American
mitral valve stenosis as well as a depressed left ven- College of Physicians. Ann Intern Med 2003;139:
tricular ejection fraction. Indeed, atrial fibrillation 1009–1017.

312
 Chapter 35 Palpitations (Atrial Fibrillation)

reviewing 48 trials assessing 17 different agents for Management trial compared rhythm control and rate
rate control in atrial fibrillation (McNamara et al., control (Wyse et al., 2002● A). In this multicenter, ran-
2003● A). Studies comparing digoxin with placebo were domized controlled trial, anticoagulation was recom-
inconsistent, particularly during exercise. The nondi- mended in both arms. More than 4000 patients were
hydropyridine calcium channel blockers diltiazem enrolled, and the average age was 70 years. Sixty-one
and verapamil were more effective than placebo or percent of patients were men, 89% were white, 71%
digoxin in controlling ventricular rate during exercise had hypertension, and 38% had coronary artery dis-
as well as at rest. β-Blockers atenolol and metoprolol ease. After patients were randomly assigned to the
were also found to control both resting and exertional rhythm-control or rate-control group, physicians
heart rate. The Joint Panel of the American Academy chose from a list of pharmacologic and nonpharma-
of Family Physicians and the American College of cologic therapies. Anticoagulation was continued
Physicians recommends atenolol, metoprolol, dilti- indefinitely for the rate-control arm but could be dis-
azem, and verapamil for rate control in patients with continued at 4 weeks or later after conversion to sinus
atrial fibrillation. Digoxin is effective only for rate con- rhythm. The mortality rate at 5 years was essentially
trol at rest and therefore should be used only as a the same in both groups. There was no difference
second-line agent for rate control in atrial fibrillation. between the groups in terms of stroke. Analyses of
Digoxin may be useful in patients with concomitant other secondary endpoints, including quality of life
heart failure. and functional status, did not show a statistical differ-
The Joint Panel has reviewed the role of ence between treatment groups. Of note, there were
echocardiography in the acute conversion of atrial more hospitalizations in the rhythm-control group
fibrillation. It based its recommendation on the (Van Gelder et al., 2002● A).
Assessment of Cardioversion Using Transesophageal These data were supported by a smaller study,
Echocardiography study that randomly assigned the Rate Control versus Electrical Cardioversion
patients either to a transesophageal echocardiogra- for Persistent Atrial Fibrillation study. In this
phy–guided strategy with short-term precardiover- randomized controlled trial, 522 patients were ran-
sion and 4-week postcardioversion anticoagulation domly assigned to aggressive rhythm control or
or to “conventional therapy” (3 weeks of pre- rate control only. Mean age was 68 years. Sixty-four
cardioversion anticoagulation and 4 weeks postcar- percent were men, 49% had hypertension, and 27%
dioversion anticoagulation). The primary endpoints had coronary artery disease. Endpoints includ-
were stroke, transient ischemic attack, and peripheral ing death, heart failure, thromboembolic compli-
embolism. There was no difference between patients cations, and bleeding showed no advantage to
undergoing transesophageal echocardiography and rhythm control. However, the study found rate
those undergoing conventional therapy. More bleed- control may be superior to rhythm control for
ing occurred in the conventional therapy group. The woman and patients with hypertension. Of note, at
transesophageal echocardiography–guided group study’s end, only 39% of the rhythm control group
had a shorter time to cardioversion and a higher ini- was still in sinus rhythm.
tial success rate, but at 8 weeks, there was no differ- The Joint Panel of the American Academy of
ence between the groups in the number of patients Family Physicians and the American College of
still in sinus rhythm. The Joint Panel recommends Physicians recommends rate control with chronic -
that for patients who elect to undergo cardioversion, anticoagulation for the majority of patients with atrial
both the transesophageal echocardiography–guided fibrillation. It also recommends patients with atrial
approach with short-term previous anticoagulation fibrillation receive chronic anticoagulation with
followed by early acute cardioversion (in the absence adjusted-dose warfarin, unless they are at low risk of
of intracardiac thrombus) with postcardioversion stroke (see Table 35-1) or have a specific contraindica-
anticoagulation and the delayed cardioversion with tion to the use of warfarin (e.g., thrombocytopenia,
pre- and post-anticoagulation management strate- recent trauma or surgery, alcoholism).
gies are appropriate (Klein et al., 2001● A).
The decision to pursue sinus rhythm rather than
settle for rate control with long-term anticoagulation
in the above case was the patient’s choice. There is Material Available on Student Consult
no evidence that rhythm control is superior to rate
Review Questions and Answers about Atrial
control with chronic anticoagulation. The Atrial
Fibrillation
Fibrillation Follow-up Investigation of Rhythm

313
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

REFERENCES
Gage BF, Waterman AD, Shannon W, Boechler M, Rich of pharmacologic therapy, electrical cardioversion,
MW, Radford MJ. Validation of clinical classification and echocardiography. Ann Intern Med 2003;139:
schemes for predicting stroke: Results of the National 1018–1033.● A
Registry of Atrial Fibrillation. JAMA 2001;285: Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison
2864–2870.● B of rate control and rhythm control in patients with
Klein AL, Grimm RA, Murray RD, et al. Use of trans- recurrent persistent atrial fibrillation. N Engl J Med
esophageal echocardiography to guide cardioversion in 2002;347:1834–1840.● A
patients with atrial fibrillation. N Engl J Med 2001; Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of
344:1411–1420.● A rate control and rhythm control in patients with atrial
McNamara RI, Tamariz LJ, Segal JS, Bass EB. Management fibrillation. N Engl J Med 2002;347:1825–1833.● A
of atrial fibrillation: Review of the evidence for the role

C h a p t e r

36 Dyspnea on Exertion
(Congestive Heart Failure)
Kara L. Cadwallader

KEY POINTS

1. The incidence and prevalence of heart failure inhibitor and a β-blocker should be used in
are increasing over time. all patients, unless there is a contraindication.
2. Heart failure has a very high associated morbid- Spironolactone should be used in patients
ity and mortality once symptomatic. who have symptoms at rest or have had them
3. Although heart failure can be difficult to diag- in the past 6 months. Diuretics and digoxin
nose, the absence of dyspnea on exertion or should be reserved for management of
the presence of a normal electrocardiogram symptoms.
(ECG) makes it very unlikely. 7. Treatment of comorbid hypertension, dia-
4. The strongest predictors of heart failure on clin- betes, coronary artery disease, myocardial
ical examination are a laterally displaced point infarction, and tobacco and alcohol use can
of maximal impulse and a gallop. decrease both the risk of development as well
5. Although laboratory test results, ECG, and as the progression of heart failure. Treat
chest radiograph are useful, a two-dimensional aggressively!
echocardiogram is the gold standard of diagno- 8. Close clinic and telephone follow-up, multidisci-
sis and should be performed in all patients in plinary team management, patient education,
whom heart failure is suspected. and patient self-monitoring of blood pressure,
6. When left ventricular (LV) dysfunction is pres- weight, and symptoms have been shown to be
ent, an angiotensin-converting enzyme (ACE) effective.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

314
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

REFERENCES
Gage BF, Waterman AD, Shannon W, Boechler M, Rich of pharmacologic therapy, electrical cardioversion,
MW, Radford MJ. Validation of clinical classification and echocardiography. Ann Intern Med 2003;139:
schemes for predicting stroke: Results of the National 1018–1033.● A
Registry of Atrial Fibrillation. JAMA 2001;285: Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison
2864–2870.● B of rate control and rhythm control in patients with
Klein AL, Grimm RA, Murray RD, et al. Use of trans- recurrent persistent atrial fibrillation. N Engl J Med
esophageal echocardiography to guide cardioversion in 2002;347:1834–1840.● A
patients with atrial fibrillation. N Engl J Med 2001; Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of
344:1411–1420.● A rate control and rhythm control in patients with atrial
McNamara RI, Tamariz LJ, Segal JS, Bass EB. Management fibrillation. N Engl J Med 2002;347:1825–1833.● A
of atrial fibrillation: Review of the evidence for the role

C h a p t e r

36 Dyspnea on Exertion
(Congestive Heart Failure)
Kara L. Cadwallader

KEY POINTS

1. The incidence and prevalence of heart failure inhibitor and a β-blocker should be used in
are increasing over time. all patients, unless there is a contraindication.
2. Heart failure has a very high associated morbid- Spironolactone should be used in patients
ity and mortality once symptomatic. who have symptoms at rest or have had them
3. Although heart failure can be difficult to diag- in the past 6 months. Diuretics and digoxin
nose, the absence of dyspnea on exertion or should be reserved for management of
the presence of a normal electrocardiogram symptoms.
(ECG) makes it very unlikely. 7. Treatment of comorbid hypertension, dia-
4. The strongest predictors of heart failure on clin- betes, coronary artery disease, myocardial
ical examination are a laterally displaced point infarction, and tobacco and alcohol use can
of maximal impulse and a gallop. decrease both the risk of development as well
5. Although laboratory test results, ECG, and as the progression of heart failure. Treat
chest radiograph are useful, a two-dimensional aggressively!
echocardiogram is the gold standard of diagno- 8. Close clinic and telephone follow-up, multidisci-
sis and should be performed in all patients in plinary team management, patient education,
whom heart failure is suspected. and patient self-monitoring of blood pressure,
6. When left ventricular (LV) dysfunction is pres- weight, and symptoms have been shown to be
ent, an angiotensin-converting enzyme (ACE) effective.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

314
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

INITIAL VISIT Social History

Mr. T. is a retired auto mechanic. He is remarried to
Subjective a retired nurse. He loves World War II memorabilia
and hockey.
Patient Identification and Presenting Problem
Mr. Clarence T. is a 64-year-old African-American Review of Systems
man who presents to the clinic complaining of Mr. T. admits to a dry cough but denies frothy spu-
increasing dyspnea on exertion. Over the past 6 tum or hemoptysis. He has noted lightheadedness
months, he has noticed generalized weakness and when he stands suddenly but denies syncope. He
fatigue, intermittent nausea and anorexia, and denies changes in skin or hair, diarrhea, jaundice,
increased swelling in his legs. Despite decreased food and abdominal pain. He denies palpitations, exer-
intake, he reports significant weight gain. He occa- tional chest pain, pleurisy, and orthopnea.
sionally awakens in the middle of the night “gasping
for air” and has had episodes of pain in his chest,
mostly very early in the morning. While he used to Objective
play and run with his grandchildren, he notes that he Physical Examination
can no longer “keep up” and has to stop frequently to Mr. T. is a well-developed man who appears slightly
“catch his breath.” He believes that his fatigue is due anxious but is speaking in full sentences and is in no
to frequent awakenings from sleep to urinate. He has acute distress. His blood pressure is 190/95, respira-
noticed some new constipation but no blood in his tory rate is 26 (without Cheyne-Stokes respiration),
stools. About 6 months ago, he drove across the coun- heart rate is 105 and regular, oxygen saturation is
try to visit relatives in Mississippi and noted some leg 91%, and temperature is 37.2˚C (98.9˚F). His sclerae
swelling at that time. He has increased his use of ipra- are anicteric, and his mouth is slightly dry without
tropium (Atrovent) and albuterol inhalers, which he lesions or evidence of bleeding. Chest examination
was given for “smoking too much,” but reports little reveals bibasilar rales, end-expiratory wheezes, and a
improvement. He has been intermittently compliant prolonged expiratory phase. There is no dullness to
with medication for hypertension. percussion, egophony, or increased work of breath-
ing. Examination of the neck reveals significant
Medical History jugular venous distention, a normal carotid
Mr. T. was diagnosed with hypertension at age 45. He upstroke, and no bruits. Cardiac examination
has mild osteoarthritis in his knees and hips and was reveals a grade II/VI systolic ejection murmur that
recently started on naproxen sodium (Naprosyn) for radiates into the axilla, an S3 gallop, and a laterally
pain relief. He is overweight but is unsure whether he displaced, diffuse point of maximal impulse.
has been tested for diabetes. He has no history of Abdominal examination is positive for mild
childhood asthma or recurrent pulmonary infections. hepatomegaly and right upper quadrant tenderness
He had a cholecystectomy 1 year ago and had a pro- but negative for a fluid wave, rebound, or guarding.
longed recovery due to “problems with breathing.” His extremities have 2+ pitting edema bilaterally,
but no cyanosis or clubbing in the hands or feet. His
Medications skin is not clammy or diaphoretic, and his hair
Naprosyn, nifedipine appears normal in distribution. His neurologic
examination is nonfocal.
Family History
Mr. T.’s father died of end-stage renal disease as a com- Assessment
plication of diabetes in his early 40s. His mother had
“hardening of the arteries” and died from a heart Working Diagnosis
attack in her mid-60s. He has a sister with a “clotting The patient’s symptoms and physical examination
disorder” who is on life-long warfarin (Coumadin). He are most consistent with congestive heart failure
has three children who are healthy. There is no family (CHF). However, various pulmonary etiologies for
history of thyroid disease or cancer of the colon. his dyspnea are also possible.

Health Habits Differential Diagnosis

Mr. T. began smoking at age 21 when he joined the A pulmonary embolism (PE) is a life-threatening
army. He quit 2 months ago. He has a glass of bour- potential cause of dyspnea in this patient. In the
bon each evening and sometimes drinks more on the acute setting, PEs may present with chest pain (usu-
weekends. He has never used illicit drugs. He drinks ally pleuritic), cough, hemoptysis, dyspnea, anxiety,
two cups of coffee in the morning. He used to walk and occasionally syncope. Physical findings may
his dog to the post office (0.5 miles) each morning include tachycardia, fever, tachypnea, pulmonary
but has stopped due to dyspnea. rales, and lower extremity edema, usually unilateral.

315
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

However, chronic, recurrent PEs may present with A chest radiograph is obtained, which reveals
more subtle symptoms of intermittent dyspnea, cardiomegaly, cephalization of the pulmonary ves-
tachycardia, and pleurisy. Most emboli result from sels, and bilateral pleural effusions. An ECG reveals
clots in the deep veins of the lower extremities. Risk sinus tachycardia, left atrial enlargement, LV hyper-
factors in Mr. T. include a history of prolonged inac- trophy (LVH), Q waves in leads II and III, and aVF
tivity, a family history of hypercoagulability, obesity, consistent with an old inferior myocardial infarc-
and probable concomitant CHF. tion. There is no evidence of current ischemia or
Coronary artery disease (CAD) or an acute coro- infarction.
nary syndrome may also present with dyspnea. Acute At this point, Mr. T. meets the Modified
myocardial infarctions usually manifest with chest Framingham Clinical Criteria for diagnosis of CHF
pain but may present painlessly with symptoms of (Table 36-1). Given the suggestive clinical scenario,
acute heart failure. CAD may be silent or present with a Doppler echocardiogram is ordered to rule out
intermittent chest pain, usually on exertion. Any etiologies such as valvular disease, pericarditis, and
patient presenting with symptoms of CHF needs to be wall motion abnormalities and to assess ventricular
evaluated for CAD, as it is a common etiology of CHF. function.
Mr. T. has multiple risk factors for CAD, including
uncontrolled hypertension, obesity, family history, Therapeutic
smoking, male gender, and African-American race. The patient is admitted to the hospital and placed on
Chronic obstructive pulmonary disease oxygen and a cardiac monitor. An intravenous (IV)
(COPD) is often difficult to distinguish from CHF. line is started, and IV furosemide (Lasix) is initiated
Exacerbations usually present with many similar with a urine output goal of more than 500 mL in
symptoms such as anxiety, cough, dyspnea, fatigue, 2 hours. Nitroglycerin and morphine are written to
orthopnea, tachypnea, tachycardia, and chest pain. be given if there is a recurrence of chest pain. A baby
Hypoxia is common but may also be seen with CHF. aspirin is initiated, given the findings of a previous
Mr. T’s major risk factor for COPD is his long history myocardial infarction on the initial ECG. The
of tobacco use. Naprosyn that Mr. T. had been taking is discontinued
Thyroid disease may be confused with CHF or due to its deleterious effects on heart failure. The
may contribute to its development. Symptoms of nifedipine is also discontinued, and a β-blocker is
hyperthyroidism include anxiety, diaphoresis, tachy- chosen instead for its benefits in patients with systolic
cardia, fatigue, weight changes, and skin changes. heart failure as well as patients with a previous
Symptoms of hypothyroidism also include weakness, myocardial infarction. A low dose is chosen given
fatigue, and weight changes as well as constipation,
dry skin, and edema.
Other causes of increased extracellular fluid that
should be considered in a patient with dyspnea, Table 36-1 Modified Framingham
jugular venous distention, and peripheral edema are Clinical Criteria for CHF
anemia, renal failure, and liver failure. Diagnosis
Major Criteria Minor Criteria
Plan
Paroxysmal nocturnal Bilateral peripheral
Diagnostic dyspnea edema
The following initial laboratory tests are performed: a Orthopnea Nocturnal cough
complete blood count to rule out anemia and infec- Elevated jugular venous Dyspnea with
tion; electrolytes, blood urea nitrogen and serum cre- distention ordinary exertion
atinine to assess renal function and establish a Pulmonary rales Hepatomegaly
baseline for potential future use of diuretic and ACE Presence of S3 Pleural effusions
inhibitor therapies; liver function tests to assess for Cardiomegaly on chest Tachycardia (>120
hepatic congestion; thyroid-stimulating hormone to radiograph beats/min)
Pulmonary edema on Weight loss >4.5 kg
rule out concomitant thyroid disease; brain natri-
chest radiograph over 5 days (when
uretic peptide (BNP) to help distinguish CHF from Weight loss (≥4.5 kg over weight loss may be
pulmonary disease; troponin and creatine kinase– 5 days in response to due to other
myocardial bound (CKMB) levels drawn serially to treatment of CHF) conditions besides
rule out ongoing myocardial ischemia or infarction; treatment of the
and iron studies to rule out hemochromatosis. Other CHF)
laboratory tests to consider if the history is suggestive
Diagnosis requires two major and two minor
might be an antinuclear antibody (ANA), viral serolo- criteria; minor criteria cannot be attributable to
gies and antimyosin antibody (myocarditis), and other causes.
laboratory tests to rule out pheochromocytosis. CHF, congestive heart failure.

316
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

Mr. T.’s probable comorbid COPD and the possibility tolic dysfunction is greater than 50%. CHF becomes
of an exacerbation caused by the β-blocker. A low clinically apparent when the heart is no longer able
dose of an ACE inhibitor is also initiated for control to meet the metabolic needs of the body. Millions of
of hypertension and for treatment of CHF. Mr. T. feels Americans are affected by this clinical syndrome; it is
much better a few hours after he undergoes a brisk a common cause of hospitalization in patients older
diuresis. His electrolytes, magnesium, blood urea than age 65 (Mair and Lloyd-Williams, 2002 ● C ).
nitrogen, and creatinine are carefully monitored. Morbidity and mortality from CHF are high, with
patients at increased risk of sudden death, throm-
Patient Education boembolism, arrhythmias, and renal insufficiency.
A nutrition consult is obtained, and Mr. T. is coun- Many diseases place patients at an increased risk
seled regarding a low-sodium diet and avoidance of a of developing CHF. The most common are CAD,
high intake of free water. He is also counseled regard- hypertension, idiopathic dilated cardiomyopathy, and
ing weight loss, exercise, and continued tobacco valvular disease. Other less common causes of car-
cessation. He is advised to avoid potentially exacer- diomyopathies that can lead to heart failure include
bating medications such as nonsteroidal anti- diabetes, alcohol, hypertrophy, infiltrative processes
inflammatory drugs (including high-dose aspirin), such as sarcoidosis and amyloidosis, and infection,
corticosteroids, carbenoxolone, urinary alkalinizers, usually viral. Women with CHF are more likely than
tricyclics, and calcium channel blockers (except men to have isolated diastolic dysfunction. Common
amlodipine and felodipine). He is enrolled in a mul- etiologies for this include hypertension with LVH,
tidisciplinary outpatient disease management pro- ischemia, aortic stenosis, and both restrictive and
gram that includes frequent weight, blood pressure, hypertrophic cardiomyopathies. There are two stag-
and medication checks. ing systems commonly used to grade the severity of
CHF (Tables 36-2 and 36-3). These are helpful for
Screening for Modifiable Risk Factors both research and clinical purposes.
Mr. T. is counseled about other conditions that may The diagnosis of CHF in its early stages can be
contribute to heart disease, and he agrees to labora- difficult, as signs and symptoms are neither sensitive
tory screening for diabetes (fasting glucose) and dys- nor specific. The presence of dyspnea on exertion has
lipidemia (total cholesterol, low- and high-density almost 100% sensitivity and thus its absence virtually
lipoproteins, and triglycerides). rules out CHF (Mair and Lloyd-Williams, 2002● C ).
Weakness and fatigue due to low cardiac output are
Disposition common but nonspecific. Orthopnea and paroxys-
Serial cardiac enzymes are negative, and Mr. T.’s lab- mal nocturnal dyspnea are fairly specific if present
oratory test results and echocardiogram confirm the but may also seen with pulmonary diseases.
diagnosis of CHF due to LV systolic dysfunction. He Gastrointestinal symptoms can confuse the clinician.
is also diagnosed with concomitant mitral regurgita- Many patients with CHF have nausea due to hepatic
tion, dyslipidemia, and glucose intolerance. He is dis-
charged to his home once a dry weight is achieved,
his blood pressure is controlled, and he is free of dysp-
nea. He is sent home on Lasix, an ACE inhibitor, a Table 36-2 American College of
β-blocker, a baby aspirin, and Tylenol for his arthri- Cardiology/American Heart
tis. An outpatient cardiology referral is made for fur- Association Heart Failure
ther workup of probable CAD, and he eventually Staging
undergoes cardiac catheterization. In addition, an
appointment is made for pulmonary function testing Stage Description
to assist with the diagnosis and optimal management
of his comorbid COPD. A High risk to develop heart
failure; no current
symptoms; no structural
heart disease
DISCUSSION B No symptoms, but heart
disease with left
CHF is a clinical syndrome that results when the ven- ventricular dysfunction is
tricle’s ability to eject and/or fill with blood is present.
impaired. Systolic dysfunction refers to decreased C Previous or ongoing
ejection of blood from the ventricle or an ejection symptoms of heart
fraction of less than 40% (Chavey et al., 2001a● A● B). failure
Diastolic dysfunction refers to abnormal relaxation D Severe symptoms, advanced
heart disease, refractory
and thus filling of the ventricle leading to increased
heart failure
filling pressures. The ejection fraction in pure dias-

317
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

systolic failure. Other helpful findings of volume

Table 36-3 New York Heart Association
overload include pleural effusions, Kerley B lines, and
Classification of Heart Failure
cephalization. Radiography is also helpful to evaluate
Class Description for other diagnoses such as pneumonia and COPD.
Finally, the ECG is almost always abnormal if signifi-
1 No limitations: ordinary cant LV dysfunction exists. Thus, a normal ECG has a
physical activity does 98% negative predictive value for CHF. Common
not cause symptoms. electrocardiographic findings that are helpful include
2 Mild limitations; no
dysrhythmias (atrial fibrillation, ventricular tachycar-
symptoms at rest.
Ordinary physical dias), evidence of ischemia, left atrial enlargement,
activity causes symptoms LVH, and left bundle branch block.
such as dyspnea, fatigue, The acute stabilization of patients with CHF
and angina. requires oxygen, cardiac monitoring, and IV access.
3 Marked limitation; no Patients with evidence of volume overload (Mr. T.)
symptoms at rest. need diuresis. If overload is mild, furosemide is used.
Activities such as getting If moderate to severe, higher dose Lasix and nitro-
dressed cause symptoms. glycerin and/or nesiritide may be required. Patients
4 Severe limitations; symptoms with evidence of low cardiac output (azotemia,
at rest; any activity
altered mental status, cool extremities, poor response
worsens symptoms
to diuretics) often require dobutamine for its
inotropic effects. Dopamine and other vasopressors
may be needed for severely hypotensive patients.
congestion and anorexia due to bowel edema and These patients require intensive care unit monitor-
poor splanchnic circulation. Dependent edema is a ing, cardiology consultation, and probable place-
common finding in CHF and many other disease ment of pulmonary artery catheters.
states. Once patients are stabilized, they should be
The physical examination can be very helpful in started on both an ACE inhibitor and a β-blocker
diagnosis. The presence of an S3 and/or S4 gallop on if there is not a contraindication (Chavey et al.,
cardiac examination is strongly predictive of heart 2001b ● A●B). ACE inhibitors have been shown to
failure (Mair and Lloyd-Williams, 2002● C ). An abnor- decrease mortality as well as future hospitalizations
mal apical impulse has high specificity for a decreased and ischemic events in patients with systolic dys-
ejection fraction. Elevated jugular venous distention function. β-Blockers have also been shown to
also strongly predicts heart failure and is indicative of decrease mortality and hospitalizations. Patients
right ventricular failure. Pulmonary findings can be often need to be maintained on diuretics to achieve a
misleading, as many patients with chronic heart fail- euvolemic state (Chavey et al., 2001b● A●B). In the set-
ure will not have rales or wheezing. Similarly, depend- ting of LV systolic dysfunction, digoxin has been
ent edema is not present until there is greater than 5 L shown to decrease hospitalizations but not overall
of extracellular fluid and frequently does not corre- mortality in CHF (Chavey et al., 2001b● A●B). It should
late with the severity of symptoms. be used as add-on therapy for patients already on an
Laboratory work similar to that done for Mr. T. ACE inhibitor and diuretic. Spironolactone decreases
is helpful to rule out many disease states that may mortality for patients with New York Heart
cause heart failure. The relatively newly available BNP Association class 4 CHF and requires careful moni-
is one of the few laboratory tests that helps to confirm toring of potassium and serum creatinine (Chavey
the diagnosis of CHF. Using a BNP cutoff value of 100 et al., 2001b● A●B). Anticoagulation should be used
pg/mL gives a sensitivity of 90% and specificity of only in the setting of atrial fibrillation or other indi-
76% for CHF. Other potential causes of increased cations for anticoagulation, but not for CHF alone.
BNP levels that must be considered include myocar- Calcium channel blockers are not effective and
dial infarction, hypertension, ventricular hypertro- should be discontinued if not used for another indi-
phy, cardiomyopathies, renal failure, cirrhosis, cation (Chavey et al., 2001b● A● B ; McConaghy and
hyperaldosteronism and Cushing’s syndrome, and Smith, 2002 ● A). Nutritional supplements such as
primary pulmonary hypertension. Thus, while an ele- taurine, carnitine, coenzyme Q10, and antioxidants
vated BNP is helpful, it is not in itself diagnostic. have not been shown to be effective and may be
The gold standard for making the diagnosis of harmful. Effective nondrug interventions include
CHF is two-dimensional echocardiography (Mair exercise, a low-salt diet, multidisciplinary clinical
and Lloyd-Williams, 2002● C ). All patients in whom manage-ment, and implantable defibrillators
CHF is suspected should thus have an echo. A chest (McKelvie, 2004● A ; McConaghy and Smith, 2002● A).
radiograph is also useful. Cardiomegaly is the most Prevention involves behavior modification and
common associated finding and is indicative of diagnosis and treatment of conditions that lead to

318
 Chapter 36 Dyspnea on Exertion (Congestive Heart Failure)

heart disease. Patients should be counseled to avoid Patients with heart failure require regular clinical fol-
tobacco, excessive alcohol, and cocaine and to exercise low-up and may also benefit from home nursing
regularly. Conditions such as diabetes, hypertension, management and frequent telephone monitoring.
dyslipidemia, thyroid disease, anemia, CAD, COPD,
thiamine deficiency, and human immunodeficiency
virus should be diagnosed and treated aggressively. Material Available on Student Consult
Common medications such as nonsteroidal anti-
Review Questions and Answers about Congestive
inflammatory drugs, corticosteroids, and tricyclics Heart Failure
may exacerbate heart failure and should be avoided.

REFERENCES
Chavey WE, Blaum CS, Bleske BE, Van Harrison R, McKelvie R. Heart failure. Available at www.clinical-
Kesterson S, Nicklas JM. Guideline for the management evidence.com/ceweb/conditions/cvd/0204/0204.jsp.
of heart failure caused by systolic dysfunction: Part I: Accessed 10/10/2005.
Guideline development, etiology and diagnosis. Am Mair FS, Lloyd-Williams F. Evaluation of suspected left
Fam Physician 2001a;64:769–774.● A●B ventricular systolic dysfunction. J Fam Pract
Chavey WE, Blaum CS, Bleske BE, Van Harrison R, Kesterson 2002;51:466–471.● C
S, Nicklas JM. Guideline for the management of heart fail- McConaghy JR, Smith SR. Outpatient treatment of heart
ure caused by systolic dysfunction: Part II: Treatment. Am failure. J Fam Pract 2002;51:519–525.●
A
Fam Physician 2001b; 64:1045–1054. ● A● B

SUGGESTED READINGS
DiDomenico RJ. Guidelines for acute decompensated Pharmacologic Management of Heart Failure and Left
heart failure treatment. Ann Pharmacother 2004;38: Ventricular Systolic Dysfunction: Effect in Female,
649–669. Black and Diabetic Patients and Cost-effectiveness.
Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines AHRQ report, publication No. 03-E044. July 2003.●
A
for the evaluation and management of chronic heart
failure in the adult. Bethesda, MD, American College of
Cardiology Foundation, 2001.● C

319
 C h a p t e r

37 High Blood Pressure (Hypertension)

Roberto Cardarelli

herbal medications or being exposed to any

KEY POINTS known chemicals.

1. The most important component of hyperten- Medical History

sion management is accurate and appropriate Mr. Smith has no allergies. He wears glasses only for
measurement of blood pressure. reading. He never had a pneumococcal or influenza
2. Hypertension is defined as a systolic blood pres- immunization. He reports an unremarkable childhood
sure (SBP) of greater than 140 mm Hg or a except for having chicken pox and believes he received
diastolic blood pressure (DBP) of greater than all his childhood immunizations. His tetanus status is
90 mm Hg. regularly monitored and updated by his employer. He
3. All patients with hypertension should be educated has never been hospitalized and has never had surgery.
about the benefits of lifestyle modifications.
4. The initial medication of choice for the treat- Family History
ment of stage 1 hypertension is thiazide-type Mr. Smith is an only child and reports that his father
medications. died of a heart attack at the age of 43. His mother is
5. Each clinic visit should emphasize tobacco ces- still living and is in good health, except for mild glau-
sation and medication compliance, in addition coma. He does not recall any other family members
to lifestyle modifications. having medical conditions.

Social History
Mr. Smith is widowed and has one daughter, who is
INTIAL VISIT currently in nursing school. He has been doing
construction work for 35 years and is still doing
Subjective heavy manual labor. He has smoked one and a half
packs of cigarettes since the age of 22 and admits to
Patient Identification and Presenting having three or four beers on weekends. He denies
Problem any illicit drug use and does not have a regular exer-
Mr. Smith, a 62-year-old white man, presents to cise regimen.
the office accompanied by his daughter, who is
concerned about a blood pressure reading that Objective
they noticed while she was practicing using a
sphygmomanometer on him for her nursing Physical Examination
school examination. Mr. Smith states that he has Vital Signs Mr. Smith’s height is 68 inches, his weight
not seen a physician since he was a teenager. He is 208 pounds, his body mass index is 31.6, and his
denies shortness of breath, chest pain at rest or temperature is 37˚C (98.6˚F). His initial blood pres-
with exertion, orthopnea, peripheral edema, sure in his left arm (sitting) is 168/78 mm Hg and,
paroxysmal nocturnal dyspnea, headaches, and repeated after 10 minutes, is 164/76 mm Hg. His ini-
urinary or visual complaints. He reports that he is tial blood pressure in his right arm (sitting) is 166/80
physically active with construction work and has mm Hg and, repeated after 10 minutes, is 168/78 mm
no issues with fatigue. He plans to retire in 3 years. Hg. His pulse is 76 (regular) beats per minute, and his
Mr. Smith denies taking any over-the-counter or respiratory rate is 12 respirations per minute.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

320
 Chapter 37 High Blood Pressure (Hypertension)

General Mr. Smith is a heavyset man in no acute dis- return visit since he is feeling well. He still is not
tress who is appropriately dressed and who appears interested in giving up his smoking habit. The blood
slightly older than his stated age. pressure record shows an systolic blood pressure
(SBP) range of 148 to 178 mm Hg and a diastolic
Skin His skin turgor and pigmentation are normal, blood pressure (DBP) range of 64 to 88 mm Hg.
and no lesions are appreciated. A review of symptoms remained negative, and the
physical examination is unchanged. His vital signs
Head, Eyes, Ears, Nose, and Throat Mr. Smith’s head are normal except for a blood pressure reading of
is normocephalic. His eyes are anicteric. A fundus- 174/86 mm Hg. His diagnosis (stage 2 hypertension)
copic examination is normal. The pupils are equally and options for management are discussed, as is the
reactive to light and accommodation. The nasal need for an electrocardiogram and laboratory tests.
mucosa is normal, and the oropharynx is clear. The risks and benefits of the treatment options are
further discussed, and Mr. Smith states that he is
Neck The thyroid is not palpable and no bruits are against starting a medication at this time. He agrees
appreciated. No jugular venous distention is noted. to regular blood pressure monitoring and to follow-
ing a diet and exercise plan with the help of a nutri-
Chest The lungs are clear to auscultation bilaterally. tionist. He is reminded again about the detrimental
effects of smoking to his overall health. Signs and
Heart The rate and rhythm are regular with no extra symptoms that would require immediate attention
heart sounds. The point of maximal impulse is aus- are discussed. A follow-up visit is scheduled for 4 to
cultated slightly lateral of the mid-clavicular line. 6 weeks to review the laboratory results; he is advised
Carotid, abdominal, and femoral bruits are not to make an appointment sooner if there are any sig-
appreciated. Pulses are +2 throughout. nificant abnormalities.

Abdomen The abdomen is slightly obese, soft, and

nontender, with normal bowel sounds. No masses
DISCUSSION
are appreciated. No hepatosplenomegaly is noted.
Diagnosis
Neurologic No focal deficits or findings are found.
The most important component of hypertension
Assessment management is accurate and appropriate measure-
ment of blood pressure. To appropriately measure
1. Elevated blood pressure without a definitive diag- the blood pressure, the patient should sit in a chair
nosis of hypertension in a quiet room for 5 minutes with his feet flat on
2. Tobacco use the floor, his back supported, and his arms relaxed
and supported at the level of the heart (World
Plan Hypertension League, 2004). The size of the cuff
Mr. Smith is informed about his current condition bladder should be at least 80% of the size of the
and told that another elevated blood pressure read- patient’s arm. Two measurements should be made on
ing at a separate clinic visit would give him a diag- each arm, averaged, and the readings shared with the
nosis of high blood pressure. Diet and exercise patient. Before establishing a diagnosis of hyper-
handouts are given to him and their contents dis- tension, many clinicians prefer to have at least two
cussed. Limiting salt intake is also discussed. He is separate measurements at different visits and also
advised to check his blood pressure daily or every self-monitored blood pressure readings that the
other day at various times of the day for 2 weeks and patient provides. There is insufficient research to
to bring the readings to his next appointment. know whether self-monitored blood pressure read-
Mr. Smith is strongly advised to quit smoking. ings predict clinical outcomes (Powers, 2003● B ). Yet

He does not express interest in quitting, so a handout they may improve patient adherence and are useful
demonstrating the adverse health effects of smoking in determining response to medication. High blood
is given. He is told that help was available once he is pressure is established when two readings have an
interested in quitting. SBP greater than or equal to 140 mm Hg or a DBP
A return appointment is scheduled for 2 weeks. greater than or equal to 90 mm Hg (Chobanian et al.,
2003● C ).

FOLLOW-UP VISIT Blood Pressure Classification

Mr. Smith returns with his daughter 2 weeks later. He Blood pressure classification has changed based on
remains asymptomatic and is irritable about the the Seventh Report of the Joint National Committee

321
 Chapter 37 High Blood Pressure (Hypertension)

on Prevention, Detection, Evaluation, and Treatment patients with atherosclerotic disease, renal disease,
of High Blood Pressure (JNC-7) (Chobanian et al., and/or diabetes.
2003●C ). The categories include normal (SBP ≤ 120
mm Hg and DBP ≤ 80 mm Hg), prehypertension
Therapy
(SBP 120–139 mm Hg or DBP 80–89 mm Hg), stage
1 hypertension (SBP 140–159 mm Hg or DBP 90–99 Lifestyle modifications are a preventive and thera-
mm Hg), and stage 2 hypertension (SBP ≥ 160 mm peutic modality in the treatment of hypertension.
Hg or DBP ≥ 100 mm Hg). It was found that patients They should be recommended to all patients without
with prehypertension were twice as likely to develop contraindications, including those at risk of devel-
hypertension compared with those with lower blood oping high blood pressure (prehypertension). A
pressures (Vasan et al., 2001●
B ). 3-month trial of lifestyle changes may be offered ini-
tially for some patients before starting a medication.
Workup Combined lifestyle changes have a cumulative effect.
For example, improvements in diet and exercise
Once high blood pressure has been diagnosed, the decrease blood pressure better than either one alone.
patient’s lifestyle, cardiovascular risk factors, Weight reduction, such as using the Dietary
concomitant disorders, and the presence of target Approaches to Stop Hypertension eating plan, can
organ damage need to be assessed (Chobanian et al., decrease blood pressure with the same magnitude of
2003● C ). In addition to hypertension, major cardio- some single drug therapies (Sacks et al., 2001● A). One
vascular risk factors include age, diabetes mellitus, study found that restricted salt intake reduces blood
decreased renal function, family history of prema- pressure but not death or cardiovascular morbidity
ture heart disease (men younger than age 55 and (Hooper et al., 2003● A).
women younger than age 65), obesity, tobacco use, Many clinical trials have shown how different
and physical inactivity. Target organ damage to assess classes of antihypertensive medications do an excellent
includes chest pain, history of myocardial infarction, job in reducing morbidity and mortality associated
heart failure, left ventricular hypertrophy, stroke, with hypertension. Table 37-1 is a simple list of the dif-
chronic kidney disease, peripheral arterial disease, ferent classes of hypertensive medications. Most of the
and eye disease. In addition, causes of high blood research available on antihypertensive medications has
pressure need to be evaluated, including sleep apnea, been on the thiazide-type class. The most recognized
medication or illicit drug use, kidney disease, pri- study is the Antihypertensive and Lipid Lowering
mary aldosteronism, renovascular disease, chronic Treatment to Prevent Heart Attack Trial (ALLHAT,
steroid therapy, Cushing’s syndrome, pheochromo- 2002● A). Based on favorable outcomes and affordabil-
cytoma, coarctation of the aorta, and thyroid or ity, thiazide-type medications remain the initial med-
parathyroid disease. This is accomplished by the ication of choice for hypertension. Another study
medical history, a physical examination, and appro- found angiotensin-converting enzyme inhibitors have
priate diagnostic tests. The components of the phys- more favorable outcomes compared with diuretics
ical examination should emphasize evaluating the (Wing et al., 2003● A). Choice of medication is also
endocrine, cardiovascular, pulmonary, neurologic,
integument, and gastrointestinal systems. The sug-
gested laboratory and diagnostic procedures include
a complete metabolic panel, fasting lipid profile, uri- Table 37-1 Classes of Antihypertensive
nalysis or spot urinary albumin/creatinine ratio, Medications
hematocrit, and electrocardiogram. More extensive
testing is not usually warranted unless blood pres- Alpha agonists
sure control is not achieved with appropriate α1
medication (details can be found below) (Chobanian Central α2
Aldosterone receptor blockers
et al., 2003● C ).
Angiotensin-converting enzyme inhibitors
Angiotensin receptor blockers
Treatment Goals β-Blockers
Calcium channels blockers
Cardiovascular morbidity and mortality associated Dihydropyridines
with hypertension are reduced with treatment (Neal Nondihydropyridines
et al., 2000●
A). Focus should be placed on reducing Combined α-blockers and β-blockers
SBP, since a decrease in DBP normally follows. In Direct vasodilators
addition, treating isolated SBP has been found to Diuretics
prevent major cardiovascular events (Ferrucci et al., Loop
Potassium sparing
2001● A). The target blood pressure is lower than
Thiazide
140/90 mm Hg or lower than 130/80 mm Hg for

322
 Chapter 37 High Blood Pressure (Hypertension)

dependent on concomitant conditions. β-Blockers are may dictate the frequency of follow-up, such as dia-
preferred for patients with a history of ischemic heart betes. The patient’s electrolytes—especially potas-
disease and stable angina, although calcium channel sium—and renal function need to be monitored on
blockers can be used (Chobanian et al., 2003● C ). a regular basis. At each visit, lifestyle modifications,
Angiotensin-converting enzyme inhibitors and tobacco cessation, and compliance with taking med-
β-blockers are preferred in patients with heart failure. ications should be encouraged. Smoking cessation
Patients with diabetes are normally started with in patients with coronary heart disease reduces the
an angiotensin-converting enzyme inhibitor or risk of all-cause mortality and nonfatal myocardial
angiotensin receptor blocker because both medications infarction (Critchley and Capewell, 2003● A). Further,
have cardiovascular benefits and slow the progression side effects, such as muscle cramping due to diuretics
of diabetic nephropathy (Chobanian et al., 2003● C ). or impotence due to β-blockers, should be assessed.
The JNC-7 report provides detailed information on Aspirin therapy should be started once blood pres-
medications that should be considered based on a sure is controlled, and other cardiovascular risk fac-
patient’s medical condition (Chobanian et al., 2003● C ). tors, such as weight and cholesterol levels, should be
As time progresses, most patients will require vigorously managed.
two or more medications. If the blood pressure at the
time of diagnosis averages 20/10 mm Hg or greater
above goal, the clinician should consider starting
with two medications. However, it is important to CONCLUSION
consider and discuss the risks and benefits with each
Mr. Smith eventually agrees to start a thiazide-type
patient before starting two medications. Blood pres-
medication after he fails to achieve his blood pressure
sure reductions are additive when drugs are com-
goal with lifestyle modifications. He continues to
bined; however, the adverse effects may not be (Law
remain asymptomatic, and all his blood work is nor-
et al., 2003●
A).
mal, including his cholesterol. He has cut back to a
half a pack of cigarettes per day with the help of his
Follow-up daughter’s persistence. He is encouraged to continue
an exercise and diet regimen because of the beneficial
The management of hypertension requires regular
health effects. After the medication is titrated over
surveillance with frequent follow-up visits. Initial
several visits, his blood pressure becomes well con-
monthly intervals are recommended until the blood
trolled, with an average reading of 132/82 mm Hg.
pressure is controlled. More frequent visits should be
After receiving the rationale for each step of his man-
considered in patients with poorly controlled blood
agement plan, Mr. Smith has come to accept the need
pressure or other comorbid conditions. In addition,
to manage his hypertension and to adhere to the
some patients become confused about the options
required 6-month follow-up appointments.
associated with their diagnosis. Aids such as videos
and pamphlets have been shown to reduce decisional
conflict in patients who are newly diagnosed with
hypertension (Montgomery et al., 2003 ● A). Well- Material Available on Student Consult
controlled patients without other comorbid condi-
Review Questions and Answers about Hyper-
tions can follow up approximately every 6 months
tension.
(Birtwhistle et al., 2005●
A). Other medical conditions

REFERENCES
ALLHAT Officers and Coordinators for the ALLHAT detection, evaluation, and treatment of high blood
Collaborative Research Group. Major outcomes in pressure. Hypertension 2003;42:1206–1252.● C
high-risk hypertensive patients randomized to Critchley JA, Capewell S. Mortality risk reduction associ-
angiotensin-converting enzyme inhibitor or calcium ated with smoking cessation in patients with coronary
channel blocker vs. diuretic: The Antihypertensive and heart disease: A systematic review. JAMA 2003;290:
Lipid-Lowering Treatment to Prevent Heart Attack 86–97.● A
Trial (ALLHAT). JAMA 2002;288:2981–2997.● A Ferrucci L, Furberg CD, Penninx BW, et al. Treatment of
Birtwhistle RV, Godwin MS, Delva MD, et al. Randomised isolated systolic hypertension is most effective in older
equivalence trial comparing three month and six patients with high-risk profile. Circulation 2001;
month follow up of patients with hypertension by fam- 104:1923–1926.● A
ily practitioners. BMJ 2005;328:204.●
A Hooper L, Bartlett C, Davey Smith G, et al. Reduced dietary
Chobanian AV, Bakris GL, Black HR, et al. Seventh report salt for prevention of cardiovascular disease. Cochrane
of the Joint National Committee on the prevention, Database Syst Rev 2003;1:CD003656.● A

323
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose Sacks FM, Svetkey LP, Vollmer WM, et al. Effects of blood
combination treatment with blood pressure lowering pressure of reduced sodium and the Dietary
drugs: Analysis of 354 randomized trials. BMJ Approaches to Stop Hypertension (DASH) diet. DASH-
2003;326:1427–1437.● A Sodium Collaborative Research Group. N Engl J Med
Montgomery AA, Fahey T, Peters TJ. A factorial randomized 2001;344:3–10.●A
controlled trial of decision analysis and an information Vasan RS, Larson MG, Leip EP, et al. Assessment of fre-
video plus leaflet for newly diagnosed hypertensive quency of progression to hypertension in nonhyperten-
patients. Br J Gen Pract 2003;53:446–453.● A sive participants in the Framingham Heart Study:
Neal B, MacMahon S, Chapman N. Effects of ACE A cohort study. Lancet 2001;358:1682–1686.● B
inhibitors, calcium antagonists, and other blood- Wing LM, Reid CM, Ryan P, et al. A comparison of out-
pressure-lowering drugs: Results of prospectively come with angiotensin-converting enzyme inhibitors
designed overviews of randomized trials. Blood and diuretics for hypertension in the elderly. N Engl
Pressure Lowering Treatment Trialists’ Collaboration. J Med 2003;348:583–592.● A
Lancet 2000;356:1955–1964.● A World Hypertension League. Measuring your blood pres-
Powers DV. Review: Ambulatory blood pressure monitoring sure. Available at www.mco.edu/org/whl/bloodpre.
predicts clinical outcomes. Evid Based Med 2003; 8:20.●B html. Accessed August 13, 2004.

C h a p t e r

38 Abdominal Pain and Loose Bowel

Movements (Hypercholesterolemia)
Michael Crouch

KEY POINTS

1. More than one half of U.S. adults have 3. With appropriate support, some patients with
unhealthy levels of low-density lipoprotein (LDL) unhealthy baseline dietary patterns can make
cholesterol, triglycerides, and/or high-density enough long-term modifications to their dietary
lipoprotein (HDL) cholesterol that place them at intake, exercise habits, and weight status to satis-
increased risk of coronary heart disease (CHD) factorily improve their lipid levels and lower their
and stroke—the causes of more than one half CHD risk. Lifestyle change success usually requires
of all adult U.S. deaths. Hypercholesterolemic repeated, detailed patient education, accompanied
individuals who use tobacco, have strong family by long-term monitoring and encouragement by
histories, or have diabetes or metabolic syn- the primary health care provider.
drome are at highest risk of heart attack and 4. A given amount of dietary change produces as
stroke. much lipid improvement as it is ever going to
2. LDL cholesterol tends to be 10 to 15 mg/dL provide after 4 weeks of sustained dietary
higher when fasting than when in the post- change; more prolonged dietary change does not
prandial state. (LDL goes up as triglycerides go yield additional benefit unless it is accompanied
down and vice versa.) This should be kept in by significant sustained weight loss in an over-
mind when reviewing lipid results for individuals weight individual.
screened with nonfasting lipids for reasons of 5. Numerous randomized controlled trials have
convenience and expedience. shown statin (3-hydroxy-3-methylglutaryl

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

324
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose Sacks FM, Svetkey LP, Vollmer WM, et al. Effects of blood
combination treatment with blood pressure lowering pressure of reduced sodium and the Dietary
drugs: Analysis of 354 randomized trials. BMJ Approaches to Stop Hypertension (DASH) diet. DASH-
2003;326:1427–1437.● A Sodium Collaborative Research Group. N Engl J Med
Montgomery AA, Fahey T, Peters TJ. A factorial randomized 2001;344:3–10.●A
controlled trial of decision analysis and an information Vasan RS, Larson MG, Leip EP, et al. Assessment of fre-
video plus leaflet for newly diagnosed hypertensive quency of progression to hypertension in nonhyperten-
patients. Br J Gen Pract 2003;53:446–453.● A sive participants in the Framingham Heart Study:
Neal B, MacMahon S, Chapman N. Effects of ACE A cohort study. Lancet 2001;358:1682–1686.● B
inhibitors, calcium antagonists, and other blood- Wing LM, Reid CM, Ryan P, et al. A comparison of out-
pressure-lowering drugs: Results of prospectively come with angiotensin-converting enzyme inhibitors
designed overviews of randomized trials. Blood and diuretics for hypertension in the elderly. N Engl
Pressure Lowering Treatment Trialists’ Collaboration. J Med 2003;348:583–592.● A
Lancet 2000;356:1955–1964.● A World Hypertension League. Measuring your blood pres-
Powers DV. Review: Ambulatory blood pressure monitoring sure. Available at www.mco.edu/org/whl/bloodpre.
predicts clinical outcomes. Evid Based Med 2003; 8:20.●B html. Accessed August 13, 2004.

C h a p t e r

38 Abdominal Pain and Loose Bowel

Movements (Hypercholesterolemia)
Michael Crouch

KEY POINTS

1. More than one half of U.S. adults have 3. With appropriate support, some patients with
unhealthy levels of low-density lipoprotein (LDL) unhealthy baseline dietary patterns can make
cholesterol, triglycerides, and/or high-density enough long-term modifications to their dietary
lipoprotein (HDL) cholesterol that place them at intake, exercise habits, and weight status to satis-
increased risk of coronary heart disease (CHD) factorily improve their lipid levels and lower their
and stroke—the causes of more than one half CHD risk. Lifestyle change success usually requires
of all adult U.S. deaths. Hypercholesterolemic repeated, detailed patient education, accompanied
individuals who use tobacco, have strong family by long-term monitoring and encouragement by
histories, or have diabetes or metabolic syn- the primary health care provider.
drome are at highest risk of heart attack and 4. A given amount of dietary change produces as
stroke. much lipid improvement as it is ever going to
2. LDL cholesterol tends to be 10 to 15 mg/dL provide after 4 weeks of sustained dietary
higher when fasting than when in the post- change; more prolonged dietary change does not
prandial state. (LDL goes up as triglycerides go yield additional benefit unless it is accompanied
down and vice versa.) This should be kept in by significant sustained weight loss in an over-
mind when reviewing lipid results for individuals weight individual.
screened with nonfasting lipids for reasons of 5. Numerous randomized controlled trials have
convenience and expedience. shown statin (3-hydroxy-3-methylglutaryl

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

324
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

KEY POINTS (Continued)

coenzyme A reductase inhibitor) therapy to be averaged approximately 60% at 1 year and less
the most effective way to treat hypercholes- than 40% at 3 years after initiation of therapy.
terolemia; it lowers CHD event and stroke risk 7. Many patients decline or discontinue statin therapy
by approximately 30% to 40% in individuals because of procrastination, financial difficulties and
with mild, moderate, or severe LDL cholesterol priorities, exaggerated concerns about potential or
elevations whose estimated 10-year risk of CHD perceived adverse statin side effects, minimization or
is moderately high (10% to 20%) or high denial of their CHD risk level, preference for avoid-
(>20%). ing chronic prescription medication, or the belief
6. Despite the overwhelming evidence of statin that statin therapy is “not natural.”
benefit and safety, more than one half of the 8. Improving acceptance, persistence, and adher-
persons who are considered appropriate candi- ence for statin therapy often requires just as
dates for statin therapy have never started tak- much, if not more, attitude assessment and
ing a statin. The persistence rate for statin patient education as dietary change, including
therapy in community practice in 2003 provider monitoring and encouragement.

INITIAL VISIT often associated with unusually forceful and rapid

heartbeat. The episodes typically occur at rest, after
Subjective he has been experiencing abdominal pain for an
hour or more. The symptoms are relieved by his get-
Patient Identification and Presenting Problem ting up and moving around restlessly.
Gary A. is a 24-year-old white freshman medical stu-
dent being seen for a preschool physical examination. Medical History
Although his general health has been quite good in Gary has had no surgery, accidents, serious injuries,
the past, Gary has been experiencing abdominal pain, or hospitalizations. He has no known medication
loose bowel movements, chest discomfort, and palpi- allergies. He takes no medications on a regular basis
tations intermittently for approximately 2 weeks. and denies using laxatives or stool softeners.

Present Illness Family History

Gary began experiencing cramping periumbilical pain, Gary’s father, a dairy farmer, died suddenly at age 48,
and loose bowel movements after a farewell weekend presumably of a heart attack. His mother is in good
with college friends, just before moving to University health at age 58. His only brother has hypercholes-
City to begin medical school. The abdominal pain terolemia. His only sister has had no serious health
originally began while he was packing his belongings in problems. His paternal grandfather died of colon
his car. The most severe episode occurred midway cancer at age 45. His other three grandparents died of
through the first day of orientation week and was quite unknown causes past the age of 80. He admits to
uncomfortable (8 on a scale of 10). Each episode lasts worrying quite a bit about the possibility of his hav-
30 to 45 minutes. The pain occurrs at all different times ing inherited a predisposition to heart disease from
of the day but does not awaken him from sleep. The his father. He is also worried about getting colon
pain is unrelated to mealtime or physical activity. cancer like his grandfather did.
Neither antacids nor bismuth subsalicylate (Pepto-
Bismol) produces prompt pain relief, but a dose of Health Habits
bismuth subsalicylate seems to normalize his bowel Gary does not smoke. He drinks small amounts of
movements for approximately 12 hours. His bowel alcohol on rare occasions and denies using any illicit
movements are brown (except for being black the day drugs. He always wears seat belts when driving his
after taking Pepto-Bismol), with a quite loose but not car. For the past 5 years he has always used latex con-
liquid consistency. The stool contains small amounts of doms when having intercourse. He exercises regu-
mucus at times, without visible blood. larly, usually running approximately 3 to 4 miles at
Gary began experiencing bilateral chest discom- least three times per week. He has avoided eating red
fort and palpitations sometime after the onset of the meat, pork, and whole milk dairy products for 2
abdominal pain. He has had episodes lasting 5 to 10 years, after reading that they could increase one’s risk
minutes, occurring two to three times per week, and of heart disease and cancer.

325
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Social History This inherited condition is the most common

Gary is single. He has been seeing one girlfriend reg- cause of severe hypercholesterolemia. As is often
ularly for 2 years and is sexually active exclusively the case, Gary’s family history was a huge clue to
with her. They are planning to marry after his second his problem (Myers et al., 1990●B ; Silberberg et al.,
year in medical school. He describes his relationships 1998● B ). Although unlikely, secondary causes of
with his girlfriend, mother, and siblings as close and hypercholesterolemia should be kept in mind.
supportive. He is unsure that he will be able to com-
pete well academically in medical school and is con- Differential Diagnosis
cerned about how he will handle the heavy academic Gary’s symptoms and findings suggest several other
load and mental stress that he has heard about. He plausible possibilities.
made excellent grades in college while being active in 1. Hypertriglyceridemia is a distinct possibility.
intramural sports and social life. Triglycerides are transported in the blood mainly in
very low-density lipoprotein particles, which also
Review of Systems contain some cholesterol. For this reason, elevated
Gary has had no change in his appetite, weight, triglyceride levels raise the total cholesterol level.
energy, or general mood. He has experienced no nau- Triglyceride elevation of more than 150 mg/dL (1.7
sea or vomiting. He has felt somewhat jittery and mmol/L) is associated with a lesser degree of risk of
restless while sitting in lectures for the past few days. heart disease than LDL cholesterol elevation.
He has also had uncharacteristic difficulty getting to 2. Metabolic syndrome (varied combinations of
sleep recently. He denies having thoughts of immi- central obesity, elevated triglycerides, low HDL
nent life-threatening illness or death. cholesterol, insulin resistance with glucose intol-
erance, thrombogenic state, and proinflammatory
Objective state) is unlikely because of Greg’s slenderness
and high physical activity level. The prevalence of
Physical Examination obesity and metabolic syndrome has risen alarm-
Vital signs are all within normal limits, including ingly in the past several decades (to an estimated
blood pressure of 110/70, heart rate of 92, weight of 47 million Americans in 2000), and it is a major
160 pounds, and height of 70 inches. Affect is normal contributor to the development of CHD and
except for looking mildly nervous. The physical stroke (Ford and Giles, 2003● C ).
examination is notable only for cool clammy hands, 3. Hypothyroidism is unlikely because of the mild
moist axillae, mild diffuse tenderness of the tachycardia, but it is a cause of secondary hyper-
abdomen, and questionably diminished deep tendon cholesterolemia worth keeping in mind. Patients
reflexes. The thyroid gland and Achilles tendons are with hypothyroidism usually present with fatigue
normal on inspection and palpation. Peripheral and lethargy, but some can be completely asymp-
pulses are all normal. tomatic, especially elderly people.
4. Generalized anxiety disorder is not an appropri-
Laboratory Tests ate diagnosis at this point because of the short
A multitest executive profile drawn 2 days before duration of symptoms.
Gary’s office visit is notable only for a total choles- 5. Somatization disorder is not an appropriate diag-
terol level of 300 mg/dL (7.7 mmol/L). The panel nosis at this point because of the relatively limited
includes normal liver and renal function test results, scope and duration of somatic symptoms. If this
but does not include cholesterol subfractions or episode is not handled well, however, the patient
triglyceride levels. may gradually become more preoccupied with
somatic symptoms.
Assessment 6. Panic disorder is unlikely because of the lack of
intense acute fear of imminent personal catastro-
Working Diagnoses phe. If the patient were biologically predisposed
Two likely diagnoses best explain the patient’s symp- to panic disorder (despite a lack of suggestive
toms and findings. family history in this case), sustained or severely
1. Adjustment disorder with anxious mood, expressed heightened concerns could eventually be
as situational anxiety, mild sleep disorder, symp- expressed as panic attacks.
toms of autonomic overactivity, and irritable bowel 7. Hypochondriasis with cardiac and cancer neuroses
syndrome. should be kept in mind as a plausible possibility,
2. Familial heterozygous hypercholesterolemia (type given the patient’s family history and current symp-
IIa in the Frederickson classification), based on the toms. If he does not already have this disorder, he
suggestive family history and the very high total may well be vulnerable to developing an exagger-
cholesterol value despite a heart healthy lifestyle. ated fear of heart disease as he approaches the age at

326
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

which his father died. Some degree of fear is 4. More extensive cardiovascular testing (e.g., tread-
rational, given his lipid disorder and family history. mill stress test with or without contrast agent
scanning, coronary artery calcium score by elec-
Some other serious diagnoses are even less likely.
tron beam computed tomography) does not
1. Acute pancreatitis resulting from severe hyper- appear to be indicated at this time, but chest pain
triglyceridemia is unlikely because of the rela- more typical for angina pectoris would prompt
tively brief duration and mild severity of the pain diagnostic testing.
episodes and the patient’s slenderness, regular
aerobic exercise, low alcohol intake, and nondia- Therapeutic Treatment Plan
betic status. 1. The physician advises long-term adherence to a
2. Hyperalphalipoproteinemia is unlikely, especially in diet low in saturated fat and cholesterol and high in
a male. Patients with this condition have a very high water-soluble fiber (e.g., oat bran). He asks Gary to
level of HDL cholesterol (>90 mg/dL or 2.3 keep a 3-day food diary, recording everything he
mmol/L and as high as 150 mg/dL or 3.9 mmol/L). eats and drinks for 72 hours, noting serving sizes
High levels of HDL cholesterol are usually associ- and method of preparation. Because Gary’s choles-
ated with low risk of atherosclerosis. In some cases, terol is severely elevated, he is urged to follow the
however, small dense HDL particles do not function National Cholesterol Education Program
normally in transporting peripheral cholesterol to Therapeutic Lifestyle Changes dietary guidelines
the liver; such particles are proinflammatory and (formerly known as Step 2 Diet) (National
atherogenic, and the patient can be at risk of CHD Cholesterol Education Program, 2001● A). If his
despite having a high HDL cholesterol level. cholesterol were not so high, the Heart Healthy
3. Angina pectoris caused by atherosclerotic coronary Diet (formerly called Step 1) would be appropriate.
artery disease is highly unlikely in such a young 2. Gary is advised to continue his current aerobic
adult. Patients with homozygous familial hypercho- exercise routine throughout medical school and
lesterolemia develop heart disease early in life, but residency training as much as possible. Exercise
if he had the homozygous form, he probably would may help his anxiety and lipids.
have already experienced one or more atheroscle- 3. Lipid-altering medication is strongly advisable if
rotic events (stroke or myocardial infarction). the lipid profile results show the anticipated severe
4. Coronary vasospasm causing atypical angina is LDL cholesterol elevation that is characteristic of
rare in this age group, especially in men. familial heterozygous hypercholesterolemia.
4. The physician recommends the daily use of relax-
PLAN ation techniques to help reduce the adverse effects
of stress and to help Gary deal with acute and
Diagnostic Laboratory and Special Tests chronic anxiety.
1. Fasting lipoprotein analysis (lipid profile) is the
most appropriate initial test. Measurement of total Patient Education
cholesterol, HDL cholesterol, and triglyceride lev- 1. The physician presents and discusses both work-
els, and a calculated estimate of LDL cholesterol ing diagnoses and answers Gary’s questions.
allow verification and categorization of common 2. The physician normalizes Gary’s anxiety as an
lipid disorders. A repeat fasting lipid profile is entering medical student and predicts that a good
advisable several weeks later to examine short-term adjustment is likely. His anxiety is reframed as a
variation and establish pretreatment baseline val- useful signal of stress and as an energy-mobilizing
ues for LDL cholesterol level. LDL cholesterol tends catalyst for change.
to be 10 to 15 mg/dL higher when fasting than 3. The physician briefly explains and demonstrates
when in the postprandial state. (LDL cholesterol the relaxation techniques of deep breathing, pro-
increases as triglycerides decrease and vice versa.) gressive muscle relaxation, and visual imagery.
Clinicians should keep this in mind when review- 4. Gary’s cholesterol elevation is provisionally char-
ing results for individuals screened with nonfasting acterized as severe, pending confirmation of
lipids for reasons of convenience and expedience severely elevated LDL cholesterol and a normal
(Weiss et al., 2003●C ). thyroid-stimulating hormone level.
2. Thyroid-stimulating hormone level is the most 5. The strong role of cholesterol elevation as a causal
cost-effective test for excluding hypothyroidism, a risk factor for heart disease is discussed.
treatable secondary cause of high cholesterol level. 6. Dietary modification is emphasized as the corner-
3. Electrocardiography, although very unlikely to stone for hypercholesterolemia treatment. The
show abnormalities, may provide useful reassur- physician gives Gary an educational pamphlet
ance to the patient if the reading is normal. containing details of the recommended dietary
Neither the patient nor the physician thought that changes and asks him to study it and write down
electrocardiography was necessary at this point. any questions that he has before the next visit.

327
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

7. The physician explains that regular aerobic and 30s, respectively, and that both had high choles-
exercise usually improves stress coping, sometimes terol. He has already encouraged his sister and fiancée
lowers LDL cholesterol modestly, usually increases to undergo cholesterol screening. He has increased his
HDL cholesterol by 5 to 15 mg/dL, and often dra- intake of water-soluble fiber with oatmeal for break-
matically lowers elevated triglyceride levels. fasts and oat bran muffins for lunches. Gary has done
8. The physician briefly discusses the pros and some research on the Internet, and he asks about the
cons of 3-hydroxy-3-methylglutaryl coenzyme A advisability of taking fish oil capsules or red yeast rice.
reductase inhibitor (statin) therapy and gives
Gary a statin decision aid to study before the next
Objective
visit.
9. Gary is urged to encourage his sister and fiancée The patient looks less nervous than on the first visit.
to have their cholesterol checked if they have not His heart rate is 72 (compared with 90 on the previous
already done so. visit). His 3-day food diary shows a very low intake of
foods high in saturated fat and cholesterol, congruent
Disposition with Therapeutic Lifestyle Change dietary guidelines.
Gary is asked to return to the laboratory in 4 weeks A fasting lipoprotein analysis done the day of his
for blood tests and to the office in 5 weeks for a first visit shows a total cholesterol of 310 mg/dL (8.0
follow-up visit. No referral is required at this point. mmol/L), HDL cholesterol of 40 mg/dL (1.0 mmol/L),
triglycerides of 100 mg/dL (1.13 mmol/L), and an esti-
FOLLOW-UP VISIT mated LDL cholesterol of 250 mg/dL (6.5 mmol/L).
The thyroid-stimulating hormone result is 2.0, within
Subjective normal limits. A repeat lipid profile done 4 weeks after
his first visit shows a total cholesterol of 302 mg/dL (7.8
Gary returns for follow-up 5 weeks after his initial mmol/L), HDL cholesterol of 44 mg/dL (1.1 mmol/L),
visit. He is feeling much better. He attributes his triglycerides of 60 mg/dL (0.68 mmol/L), and an esti-
improvement mainly to relief from worry about his mated LDL cholesterol of 246 mg/dL (6.4 mmol/L).
symptoms’ indicating some serious underlying illness
such as heart disease or cancer. His abdominal pain,
Assement
chest discomfort, and palpitations have resolved. He
is still having occasional loose bowel movements but Familial heterozygous hypercholesterolemia with
is not concerned about them. Gary is anxious to dis- severely elevated total and LDL cholesterol
cuss his lipid profile results. In the intervening (Fig. 38-1). He also has borderline low HDL cho-
month, he has discovered that a paternal aunt and a lesterol. The average HDL cholesterol for males is
paternal uncle developed heart disease in their 50s 45 mg/dL (1.15 mmol/L), and for females, the

More
NCEP* LDL Cholesterol Ranges Descriptive
Terms Terms

Very Extremely promotive for Extremely

High atherosclerosis elevated
190 190
Highly promotive for Severely
High
atherosclerosis elevated
LDL-C 160 160
Borderline Moderately conducive to Moderately
High atherosclerosis elevated
130 130
Above Mildy conducive to Mildly
Optimal atherosclerosis elevated
100 100
Near Usually preventive for
atherosclerosis Healthy
Optimal
70 70
Optimal preventive range for
Optimal Ideal
atherosclerosis

*NCEP, National Cholesterol Education Program, Adult Treatment Panel III

Figure 38-1 Prognostic range for low-density lipoprotein cholesterol (LDL-C).

328
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

average is 55 mg/dL (1.42 mmol/L). Despite his

being young and having only two other risk factors Table 38-1 Other Risk Factors for
(male gender and borderline low HDL cholesterol; Coronary Heart Disease
Table 38-1), Gary’s risk of atherosclerotic cardio- Factors cited by National Cholesterol Education
vascular disease events over the next 10 years is Program (NCEP) Adult Treatment Panel (ATP) III
high because of his particular genetic dyslipidemia Male gender
(Marks et al., 2003 ● C ). His LDL cholesterol level Cigarette smoking
greatly exceeds the recommended cut point for Diabetes mellitus
considering drug therapy regardless of other risk Hypertension
Low high-density lipoprotein cholesterol
factor status (Table 38-2). Obesity
Adjustment disorder with anxious mood of Personal history of atherosclerotic disease
mild severity; is responding well to reassurance and Family history of lipid disorder
education about stress-coping strategies. Family history of atherosclerotic disease
(especially men age <55 and women <65)
Plan
Other Coronary Heart Disease Risk Factors (not
Diagnostic Laboratory and Special Tests cited by NCEP ATP III)
1. A repeat lipid profile should be obtained to mon- C-reactive protein elevation
itor treatment response approximately 4 to 6 Homocysteine elevation
weeks after each change in the regimen is made. Lip (a) elevation
Once a regimen has achieved satisfactory results, Apolipoprotein B elevation
a lipid profile should be repeated every 6 to 12 Low apolipoprotein A-I level
months to monitor the ongoing response. Postmenopausal status for females
2. Numerous more sophisticated tests are becoming Lipoprotein-associated phospholipase-2 elevation
(PLAC test)
available for measuring other independent risk Small dense low-density and high-density
factors for CHD. Although none are indicated for lipoprotein particles
this very high risk patient, they can be helpful to Proinflammatory high-density lipoprotein
refine 10-year CHD risk estimates for selected Coronary-prone (type A) behavior or personality
patients with marginal low-intermediate or Old age (risk increases with increasing age)
intermediate-high risk levels based on the major
risk factors. Abnormal values for any of them
indicate increased risk of CHD events.
a. C-reactive protein is a moderate, independent
CHD predictor when it persists in the moder- b. Lp(a) lipoprotein is a relatively uncommon
ately elevated range (3 to 10 mg/L). Higher independent predictor of CHD.
values (>10 mg/L) are occasionally seen in c. Homocysteine is a relatively uncommon CHD
asymptomatic persons and in chronic illness, risk predictor; high levels predict risk.
but severe C-reactive protein elevation usually d. Apolipoprotein B is the main protein in LDL;
indicates the presence of an acute or subacute high levels predict risk.
infection or inflammatory condition (Pearson, e. Apolipoprotein A is the main protein in HDL;
2004). low levels predict risk.

Table 38-2 LDL Cholesterol Cut Points Recommended for Considering Drug Therapy by
the National Cholesterol Education Program Adult Treatment Panel III
10-Year Estimated LDL Level (mg/dL [mMol/L])
Risk Category Risk for CHD for Considering Drug Therapy

CHD or CHD risk equivalent >20% ≥100 mg/dL (2.6 mMol/L)

(diabetes, stroke) (70–100 mg/dL or 1.8–2.6
mMol/L: drug optional)
2+ risk factors 10–20% ≥130 mg/dL (3.35 mMol/L)
<10% >160 mg/dL (4.2 mMol/L)
0–1 risk factor (not diabetes) Usually <10% >190 mg/dL (4.9 mMol/L)
(160–189 mg/dL or 4.2–4.9
mMol/L:drug optional)

CHD, Coronary heart disease; LDL, low-density lipoprotein.

329
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

f. LDL and HDL particle size and number include Benecol, Take Control, and Smart Balance
predict CHD. Small dense particles are athero- Omega Plus.
genic. 5. Omega-3 fatty acids supplementation (fish oil rich
g. Lipoprotein-associated phospholipase A2, in eicosapentaenoic acid and docosahexaenoic
measured by the phospholipase-associated acid): two to three capsules per day if not eating fish
complex (PLAC) test, predicts CHD events regularly (reduces triglycerides but can increase
when elevated. LDL cholesterol). Gary is cautioned that intake of
h. Proinflammatory HDL is an abnormal HDL more than 3 g/day may increase stroke risk.
type that is atherogenic, not protective.
i. Interleukin-6 is another indicator of inflamma- Other dietary supplements were not recom-
tion that correlates with C-reactive protein. mended because they have been less studied.
j. Serum amyloid A (SAA) predicts CHD risk 1. Linolenic acid supplementation is converted to
when elevated. eicosapentaenoic acid in the body.
k. Two identified serum adhesion molecules 2. Garlic has produced mixed results in clinical trials.
predict CHD risk-soluble intercellular adhe- It sometimes lowers LDL cholesterol 10% to 15%.
sion molecule and soluble vascular cell 3. Fenugreek, 50 to 100 g/day, can lower LDL 20% to
adhesion molecule. 35%. Its safety is not established.
4. Gugulipids, 25 mg, three times per day, can
Therapeutic Treatment Plan reduce LDL by 15% to 35%. Its safety is not
The physician again advises close adherence to a life- established.
long Therapeutic Lifestyle Change dietary pattern by 5. Red yeast rice contains nine natural statin com-
restricting foods high in saturated fat and cholesterol. pounds. It lowers LDL 15% to 30%, but its safety
Whole milk dairy products and fatty cuts of beef and is not established. Red yeast rice products con-
pork are the main sources of saturated fat for the aver- taining statins were removed from the U.S. mar-
age person. The physician recommends using nonhy- ket in 2000.
drogenated corn, safflower, soybean, olive, or flaxseed 6. Flavonoids contain antioxidants from green and
oil in cooking and avoiding oils high in saturated fat black teas, grape juice, and wine. Lipid effects and
(coconut and palm) and trans fat (most commercial safety are not established.
fried foods). The goal is to restrict saturated fat to less
Gary is encouraged to bring his fiancée along to
than 7% of daily caloric intake, with total fat provid-
the next visit for a more detailed discussion of food
ing a maximum of 25% to 35% of caloric intake, and
selection and preparation. A referral to a dietitian is
less than 200 mg/day of dietary cholesterol, less than
offered for more detailed dietary education.
2400 mg/day of sodium, and just enough calories to
Lipid altering medication is strongly recom-
maintain a healthy weight. Carbohydrates are to pro-
mended to lower LDL cholesterol at least to below 100
vide 50% to 60% of total calories, mainly in the form
mg/dL (2.6 mmol/L) and ideally below 70 mg/dL (1.8
of slowly digested starches (whole wheat bread, brown
mmol/L), in accordance with National Cholesterol
rice), with minimal intake of sugars and white
Education Program Adult Treatment Panel guideline
starches. The recommended goal for fiber intake is 20
recommendations (Table 38-3) (Grundy et al., 2004● A)
to 30 g/day (preferably mostly viscous soluble fiber
and American Heart Association Evidence-Based
from such foods as oat bran, whole grain bread and
Guidelines for Cardiovascular Disease Prevention
cereal, brown rice, apples, pears, prunes, beans, peas,
(Table 38-4) (Mosca et al., 2004● A ). Gary is advised to
Brussels sprouts, broccoli, and cauliflower). Protein
keep his LDL cholesterol lowered lifelong. Pros and
intake is best limited to 15% of total calories; long-
cons of lipid drugs in general and specific drugs are
term high-protein intake may harm the kidneys.
discussed. Because his LDL cholesterol is so high and
Additional dietary recommendations are made
his family history so concerning, immediate drug
to maximize LDL cholesterol lowering (Hu and
therapy is recommended.
Willett, 2002● A ; Jenkins et al., 2003●B ):
The statin (3-hydroxy-3-methylglutaryl coenzyme
1. Cold water fish: two servings per week (salmon, A reductase inhibitor) atorvastatin is recommended
mackerel, sardine, herring, bluefish) (AHA, 2002●
A ). as the medication most likely to produce good results
Gary is cautioned to limit swordfish to once per with monotherapy because of its superior efficacy
month because of its high mercury content. (40% to 50% reduction of LDL cholesterol compared
2. Nuts with healthy fat ratios (almonds, peanuts, with 25% to 35% with most other “statins”) and
pecans, walnuts): one 2-oz serving per day. excellent results in multiple clinical trials (Colhoun
3. Soy products (tofu, soy burgers/dogs/milk): two et al., 2004●B ; Koren et al., 2004●
B ). Gary has checked
servings per day in lieu of animal protein. with his health insurance plan and found that ator-
4. Plant sterol/stanol product as margarine/butter vastatin is one of the preferred medications on the
substitute: two to three servings per day; brands second lowest tier of his plan’s formulary and that he

330
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Patient Education
Table 38-3 LDL Cholesterol Treatment
The physician discusses the general pros and cons of
Goals Recommended by the
the over-the-counter and prescription medications
National Cholesterol
for lowering LDL cholesterol. He also elicits Gary’s
Education Program Adult
preferences and priorities related to taking prescrip-
Treatment Panel III
tion drugs. (Gary states a preference for not taking
Treatment Goal for LDL long-term prescription drugs but a willingness to
Cholesterol, mg/dL waive that preference in this instance in favor of
(mmol/L) reducing his risk of heart attack and stroke.) The
physician discusses statins’ generally excellent safety
Known CAD or <100 (<2.6) Optional goal
diabetes is <70 (<1.8)
record (Ballantyne, 2003 ● B ). Three potential side

No known CAD effects are discussed: (1) mild elevation of the liver
10-year risk <100 (<2.6) Optional goal enzyme alanine aminotransferase, which occurs in
>20% is <70 (<2.6) approximately 10% of patients and is virtually always
10-year risk <130 (<3.35) Unlikely to benign; (2) muscle discomfort or weakness (occurs in
10–20% occur approximately 10% of patients); and (3) the only seri-
10-year risk ≥2 risk factors: <2 risk factors: ous potential side effect, rhabdomyolysis (rare, occur-
<10% <160 (<4.2) <190 (<4.9) ring in approximately one in 10,000 to 100,000
Optional goal patients) (Graham et al., 2004 ● B ). The physician
is <160 (<4.2)
answers Gary’s questions and then strongly recom-
CAD, Coronary artery disease; LDL, low-density mends statin therapy. Gary agrees to start on statin
lipoprotein. therapy right away. He says that he had minimal
reservations about potential side effects compared
with potential benefits. The physician emphasizes the
can get a month’s supply for a $20 copayment (com- noncurative nature of statin therapy and the need to
pared to the $95 retail cost [Table 38-5]). A newer continue taking a statin long-term to minimize CHD
statin, rosuvastatin, is mentioned as an option to con- risk (unless a better treatment comes along).
sider if atorvastatin results are not satisfactory. At the The physician discusses the genetic inheritance
time of this visit, rosuvastatin’s superior efficacy (50% pattern of familial hypercholesterolemia and the
to 60% reduction of LDL chole1sterol) is offset by its reproductive implications of the patient’s marrying
short time on the market and controversy about its someone who also has familial hypercholes-
safety (Jones et al., 2003●B ). terolemia. He suggests that Greg watch for new
Niacin is presented as an inexpensive ($10 to developments from human genome research that
$20 per month) over-the-counter choice for adjunc- might pertain to his cholesterol problem.
tive treatment. Sustained release niacin (Slo-Niacin) The dietary information is discussed and Greg’s
gives good results at 1 to 2 g/day. The usual side nutrition questions are answered. The physician
effects of flushing and itching can be minimized by stresses the importance of maintaining a healthy diet
taking one aspirin one to three times daily, but many long term to help the medication do a good job.
patients do not tolerate niacin well. Liver toxicity
should be watched for, especially during the first few Disposition
months, by monitoring the liver enzyme alanine The patient is asked to return to the laboratory in
aminotransferase periodically. Patients with diabetes 6 weeks for a fasting lipid profile and alanine amino-
mellitus or prediabetes or who are at increased risk transferase and to schedule an office visit for 7 weeks
of diabetes should be periodically screened for glu- to discuss his response to treatment.
cose intolerance (fasting or random glucose).
Ezetemibe was presented as a useful adjunctive
drug to add to a statin instead of increasing statin DISCUSSION
dose, if the usual therapeutic dose does not produce
satisfactory results (Table 38-6) (Gagne et al., 2002● B ). Gary’s symptoms are quite common expressions of
Cholestyramine and colestipol are presented as anxiety related to difficulty coping with stress at home,
costly adjunctive treatment options for use at a low school, or work. Most patients in this situation respond
to medium dose to avoid the constipation caused by well to simple reassurance, normalization, and
a high dose. empathic support, coupled with developing an effec-
Relaxation techniques are discussed. The physi- tive repertoire of strategies for preventing and coping
cian explains deep breathing, progressive muscle with stress and anxiety. Gary’s anxiety appears to stem
relaxation, and visual imagery in more detail, partly from irrational fear about acute heart disease
encourages Gary to try them, and lends Gary an and a more rational fear of eventually having heart dis-
audiotape with relaxation instructions. ease. Discussing and treating his major risk factor for

331
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Table 38-4 American Heart Association Evidence-based Guidelines for Cardiovascular

Disease Prevention (2002)
Class of Level of Generalizability
Measure Description Evidence Evidence to Women

Lifestyle Interventions
Cigarette Consistently encourage women I B 1
smoking not to smoke and to avoid
environmental tobacco
Physical activity Consistently encourage women I B 1
to accumulate a minimum of
30 min of moderate-intensity
physical activity (e.g., brisk
walking) on most, and prefer-
ably all, days of the week
Heart healthy Consistently encourage an I B 1
diet overall healthy eating pattern
that includes intake of a
variety of fruits, vegetables,
grains, low-fat or nonfat
dairy products, fish, legumes,
and sources of protein low in
saturated fat (e.g., poultry,
lean meats, plant sources)
Limit saturated fat intake to
<10% of calories, limit
cholesterol intake to <300
mg/d, and limit intake of
trans fatty acids
Weight Consistently encourage weight I B 1
maintenance/ maintenance/reduction through
reduction an appropriate balance of
physical activity, caloric intake,
and formal behavioral
programs when indicated to
maintain/achieve a body mass
index between 18.5 and 24.9
kg/m2 and a waist
circumference <35 in.
Psychosocial Women with cardiovascular IIa B 2
factors disease (CVD) should be
evaluated for depression and
referred/treated when indicated
Omega-3 fatty As an adjunct to diet, omega-3 IIb B 2
acids fatty acid supplementation
may be considered in high-
risk* women
Folic acid As an adjunct to diet, folic acid IIb B 2
supplementation may be
considered in high-risk*
women (except after
revascularization procedure)
if a higher than normal level
of homocysteine has been
detected
Cardiac Women with a recent acute I B 2
rehabilitation coronary syndrome or coronary
intervention, new-onset or
chronic angina should
participate in a comprehensive

332
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Table 38-4 American Heart Association Evidence-based Guidelines for Cardiovascular

Disease Prevention (2002) (Continued)
Class of Level of Generalizability
Measure Description Evidence Evidence to Women

risk-reduction regimen, such

as cardiac rehabilitation or a
physician-guided, home- or
community-based program

Major Risk Factor Interventions

Blood pressure: Encourage an optimal blood I B 1
lifestyle pressure of <120/80 mm Hg
through lifestyle approaches
Blood pressure: Pharmacotherapy is indicated I A 1
drugs when blood pressure is ≥140/
90 mm Hg or an even lower
blood pressure in the setting
of blood pressure–related
target-organ damage or
diabetes. Thiazide diuretics
should be part of the drug
regimen for most patients
unless contraindicated
Lipids, Optimal levels of lipids and I B 1
lipoproteins lipoproteins in women are
low-density lipoprotein
cholesterol (LDL-C) <100 mg/dL,
high-density lipoprotein
cholesterol (HDL-C) > 50 mg/dL,
triglycerides <150 mg/dL, and
non–HDL-C (total cholesterol
minus HDL cholesterol) <130
mg/dL and should be
encouraged through lifestyle
approaches
Lipids: diet In high-risk* women or when I B 1
therapy LDL-C is elevated, saturated fat
intake should be reduced to <7%
of calories and cholesterol to
<200 mg/days, and trans fatty
acid intake should be reduced
Lipids: Initiate LDL-C–lowering therapy I A 1
pharmacotherapy, (preferably a statin)
high risk* simultaneously with lifestyle
therapy in high-risk women
with LDL-C ≥100 mg/dL
Initiate statin therapy in high- I B 1
risk women with an LDL-C
<100 mg/dL unless
contraindicated
Initiate niacin† or fibrate therapy I B 1
when HDL-C is low or non–
HDL-C elevated in high-risk
women
Lipids: Initiate LDL-C–lowering therapy I A 1
pharmacotherapy, (preferably a statin) if LDL-C
intermediate risk‡ level is ≥130 mg/dL on
lifestyle therapy or
Continued

333
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Table 38-4 American Heart Association Evidence-based Guidelines for Cardiovascular

Disease Prevention (2002) (Continued)
Class of Level of Generalizability
Measure Description Evidence Evidence to Women

Initiate LDL-C–lowering therapy I B 1

with niacin† or fibrate therapy
when HDL-C is low or non–
HDL-C elevated after LDL-C
goal is reached
Lipids: Consider LDL-C–lowering therapy IIa B 1
pharmacotherapy, in low-risk women with 0 or 1
lower risk§ risk factor when LDL-C level is
>190 mg/dL or if multiple risk
factors are present when LDL-C
is >160 mg/dL or
Consider niacin† or fibrate IIa B 1
therapy when HDL-C is low or
non-HDL-C elevated after
LDL-C goal is reached
Diabetes Lifestyle and pharmacotherapy I B 1
should be used to achieve
near-normal glycosylated
hemoglobin (HbA1C) (<7%) in
women with diabetes

Preventive Drug Interventions

Aspirin, high risk* Aspirin therapy (75–162 mg) or I A 1
clopidogrel if patient is
intolerant to aspirin, should
be used in high-risk women
unless contraindicated
Aspirin, Consider aspirin therapy IIa B 2
intermediate (75–162 mg) in intermediate-
risk‡ risk women as long as blood
pressure is controlled and bene-
fit is likely to outweigh risk
of gastrointestinal side effects
β-Blockers Should be used indefinitely in I A 1
all women who have had a
myocardial infarction or who
have chronic ischemic syndromes
unless contraindicated
Angiotensin- Should be used (unless I A 1
converting contraindicated) in high-risk*
enzyme (ACE) women
inhibitors
Angiotensin- Should be used in high-risk* I B 1
receptor women with clinical evidence
blockers of heart failure or an ejection
fraction <40% who are
intolerant to ACE inhibitors

Atrial Fibrillation/Stroke Prevention

Warfarin Among women with chronic or I A 1
paroxysmal atrial fibrillation,
warfarin should be used to
maintain the international
normalized ratio at 2.0–3.0

334
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Table 38-4 American Heart Association Evidence-based Guidelines for Cardiovascular

Disease Prevention (2002) (Continued)
Class of Level of Generaliz-ability
Measure Description Evidence Evidence to Women

unless they are considered to

be at low risk of stroke (<1%/yr)
or high risk of bleeding
Aspirin 325 mg should be used in I A 1
women with chronic or
paroxysmal atrial fibrillation
with a contraindication to
warfarin or at low risk of
stroke (<1%/yr).

Class III Interventions

Hormone therapy Combined estrogen plus III A —
progestin hormone therapy
should not be initiated to
prevent CVD in postmenopausal
women
Combined estrogen plus III C —
progestin hormone therapy
should not be continued to
prevent CVD in postmeno-
pausal women
Other forms of menopausal III C —
hormone therapy (e.g.,
unopposed estrogen) should
not be initiated or continued
to prevent CVD in postmeno-
pausal women pending the
results of ongoing trials
Antioxidant Antioxidant vitamin supplements III A 1
supplements should not be used to prevent
CVD pending the results of
ongoing trials
Aspirin, Routine use of aspirin in lower III B 2
lower risk§ risk women is not recom-
mended pending the results
of ongoing trials
*
High risk is defined as coronary heart disease (CHD) or risk equivalent or a 10-year absolute CHD risk >20%.
†
Dietary supplement niacin must not be used as a substitute for prescription niacin, and over-the-counter niacin
should only be used if approved and monitored by a physician.
‡
Intermediate risk is defined as a 10-year absolute CHD risk of 10% to 20%.
§
Lower risk is defined as a 10-year absolute CHD risk <10%.
Strength of Recommendations: classification––class I, intervention is useful and effective; class IIa, weight of
evidence/opinion is in favor of usefulness/efficacy; class IIb, usefulness/efficacy is less well established by
evidence/opinion; class III; intervention is not useful/effective and may be harmful; level of evidence—
A, sufficient evidence from multiple randomized trials; B, limited evidence from single randomized trial or
other nonrandomized studies; C, based on expert opinion, case studies, or standard of care; Generalizability
Index—1, very likely that results generalize to women; 2, somewhat likely that results generalize to women;
3, unlikely that results generalize to women; 0, unable to project whether results generalize to women.

heart disease could greatly reduce his anxiety, if the half of all adult U.S. deaths. Hypercholesterolemic
treatment is successful and well tolerated. If treatment individuals who use tobacco, have strong family his-
does not go well, however, his anxiety could escalate. tories, or have diabetes or metabolic syndrome are at
More than one half of U.S. adults have highest risk of heart attack and stroke.
unhealthy levels of LDL cholesterol, triglycerides, Gary’s lipid disorder, familial heterozygous
and/or HDL cholesterol that place them at increased (Type IIa) hypercholesterolemia, is generally asymp-
risk of CHD and stroke, the causes of more than one tomatic until atherosclerotic lesions progress to a

335
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Table 38-5 Retail Cost of Therapeutic Equivalent Doses of HMG-CoA Reductase Inhibitors
(Statins) as Monotherapy or Combination Therapy
Medication Trade Name Dose Monthly Retail Cost

OTC Niacin Slo-Niacin 1000–2000 mg $10–20

Lovastatin Generic 10 mg $20

Lovastatin Generic 20 mg $26
Lovastatin Generic 40 mg $32
Fluvastatin Lescol 20 mg $64
Fluvastatin Lescol 40 mg $64
Simvastatin Zocor 10 mg $79
Pravastin Pravachol 20 mg $101
Lovastatin + OTC niacin Generic + Slo-Niacin 20 mg, 500 mg $36

Lovastatin-niacin Advicor 20–500 mg $75

Lovastatin Altoprev 40 mg ER $75
Fluvastatin Lescol 80 mg XL $77
Atorvastatin Lipitor 10 mg $78
Rosuvastatin Crestor 5 mg $94
Pravastatin Pravachol 40 mg $103
Simvastin Zocor 20 mg $125
Lovastatin + OTC niacin Generic + Slo-Niacin 40 mg + 1000 mg $42

Lovastatin Altoprev 60 mg ER $78

Rosuvastatin Crestor 10 mg $94
Lovastatin-niacin Advicor 20–1000 $95
Atorvastatin Lipitor 20 mg $108
Simvastatin Zocor 40 mg $125
Pravastatin Pravachol 80 mg $138
Lovastatin + OTC niacin Generic + Slo-Niacin 40 mg + 2000 mg $52

Simvastatin-ezetemibe Vytorin* 10–10 mg $90*

Rosuvastatin Crestor 20 mg $94
Simvastatin-ezetemibe Vytorin* 20–10 mg $106*
Atorvastatin Lipitor 40 mg $108
Simvastatin Zocor 80 mg $125
Fluvastatin + ezetemibe Lescol + Zetia 80 mg XL, 10 mg $156
Rosuvastatin Crestor 40 mg $94

Rosuvastatin + OTC niacin Crestor + Slo-Niacin 5 mg, 1000 mg $104

Atorvastatin Lipitor 80 mg $108
Simvastatin-ezetemibe Vytorin* 40–10 mg $113*
Simvastatin-ezetemibe Vytorin* 80–10 mg $113*
Atorvastatin + ezetemibe Lipitor + Zetia 10 mg, 10 mg $157
Rosuvastatin + ezetemibe Crestor + Zetia 5 mg, 10 mg $173
Rosuvastatin + OTC niacin Crestor + Slo-Niacin 10 or 20 mg, 2000 mg $114

Atorvastatin + OTC niacin Lipitor + Slo-Niacin 20 or 40 mg, 2000 mg $128

Rosuvastatin + ezetemibe Crestor + Zetia 10 mg, 10 mg $173
Rosuvastatin + ezetemibe Crestor + Zetia 20 mg, 10 mg $173
Atorvastatin + ezetemibe Lipitor + Zetia 20 mg, 10 mg $187
Atorvastatin + ezetemibe Lipitor + Zetia 40 mg, 10 mg $187
Rosuvastatin + OTC niacin Crestor + Slo-Niacin 40 mg, 2000 mg $114

Atorvastatin + OTC niacin Lipitor + Slo-Niacin 80 mg, 200 mg $128

Rosuvastatin + ezetemibe Crestor + Zetia 40 mg, 10 mg $173
Atorvastatin + ezetemibe Lipitor + Zetia 80 mg, 10 mg $187
*
Based on retail price quotes from community pharmacies, December 20, 2004, survey, Houston, TX, for whole
tablets of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), except for Vytorin
prices, which, because Vytorin was not on local pharmacy Web sites, are from a Canadian Internet pharmacy
www.abconlinepharmacy.com&/ns/customer/home.php?cat=27&page=4.
ER, extended release; OTC, over-the-counter.

336
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Table 38-6 Cost-effective Medication Regimens for Treating Elevated LDL Cholesterol
LDL-C Treatment Goal

Baseline LDL-C (mg/dL) <130 mg/dL <100 mg/dL

100–159 Lovastatin, generic, one 10- or Lovastatin, generic, one 20-mg,

20-mg tab, qd, $20–26/mo or plus OTC niacin (Slo-Niacin), one
fluvastatin (Lescol), one half 40- 500 mg, qd, $36/mo or
mg tab, qd, $32/mo or simvastatin simvastatin (Zocor), one half
(Zocor), one half 10-mg or one half 40-mg tab, qd, $65/mo or
20-mg tab, qd, $40-65 mo or lovastatin (Altoprev), one 40-mg
lovastatin-niacin (Advicor), one ER tab, qd, $75/mo or lovastatin-
20-500-mg tab, qd, $75/mo niacin (Advicor), one 20–500-mg
tab, qd, $75/mo or fluvastatin
(Lescol XL), one 80-mg ER tab,
qd, $77/mo or atorvastatin
(Lipitor), one 10-mg tab, qd,
$78/mo or rosuvastatin (Crestor),
one 5-mg tab, qd, $94/mo
160–189 Lovastatin, generic, one 20-mg, qd, Lovastatin (generic), one 40-mg,
plus OTC niacin (Slo-Niacin), one plus OTC niacin (Slo Niacin), one
500-mg, qd, $36/mo or simvastatin to two 500-mg, bid, $42-52/mo
(Zocor), one half 40-mg tab, qd, $65/ or simvastatin (Zocor), one half
mo or lovastatin (Altoprev), one to one 80 mg tab, qd,
40-mg ER tab, qd, $75/mo or $65–125/mo or lovastatin
lovastatin-niacin (Advicor), one 20– (Altoprev), one 60-mg ER tab,
500-mg tab, qd, $75/mo or fluvastatin qd, $78/mo or rosuvastatin
(Lescol XL), one 80-mg ER tab, qd, (Crestor), one 10-mg tab, qd,
$77/mo or atorvastatin (Lipitor), one $94/mo or lovastatin-niacin
10-mg tab, qd, $78/mo or rosuvastatin (Advicor), one 20–1000-mg tab,
(Crestor), one 5-mg tab, qd, $94/mo qd, $95/mo or atorvastatin
(Lipitor), one 20-mg tab, qd,
$108/mo
≥190 Lovastatin (generic), one 40-mg plus Rosuvastatin (Crestor), one 20- or
OTC niacin (Slo-Niacin), one or two 40-mg tab, qd, $94/mo or
500-mg, qd, $42-52/mo or simvastatin atorvastatin (Lipitor), one 40- or
(Zocor), one half to one 80-mg tab, 80-mg tab, qd, $108/mo or
qd, $65-130/mo or lovastatin (Altoprev), rosuvastatin (Crestor), one 20- or
one 60-mg ER tab, qd, $78/mo or 40-mg tab, qd, plus OTC niacin
rosuvastatin (Crestor), one 10-mg tab, (Slo Niacin), four 500-mg, qd,
qd, $94/mo or lovastatin-niacin (Advicor), $114/mo or simvastatin (Zocor),
one 20–1000-mg tab, qd, $95/mo or one 80-mg tab, qd, $125/mo or
atorvastatin, one 20-mg tab Lipitor, atorvastatin (Lipitor), one 40- or
$108/mo 80-mg tab, qd, plus OTC niacin
(Slo Niacin), two 500-mg, bid,
$128/mo or simvastatin (Zocor),
one half 40- or 80-mg tab, qd,
plus ezetemibe (Zetia), one
10-mg tab, qd, $144/mo or
atorvastatin (Lipitor), one 10-mg
tab, qd, plus ezetemibe (Zetia),
one 10-mg tab, qd, $157/mo or
rosuvastatin (Crestor), one 5-mg
tab, qd, plus ezetemibe (Zetia),
one 10-mg tab, qd, $173/mo

ER, extended release; LDL-C, low-density lipoprotein cholesterol; OTC, over-the-counter.

337
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

critical extent or until a plaque ruptures and triggers Multiple large randomized clinical trials have
formation of a coronary thrombus. This usually established that lowering elevated LDL cholesterol with
occurs after the age of 30. For persons with this dis- statin medication is the most cost-effective way to sub-
order, the average age of developing clinical heart stantially lower the risk of CHD events (myocardial
disease is 42 for men and 52 for women. Although infarction and CHD death) in both men and women
the likelihood of Gary’s having symptomatic coro- and in the elderly (who are at higher risk of a CHD
nary artery disease now is quite low, he most likely event) (National Cholesterol Education Program,
already has some degree of coronary atherosclerosis. 2001● A ). While patients with severe LDL elevation
His concern about developing early heart disease in (>190 mg/dL) and/or low HDL cholesterol (<40
his 30s or 40s is well founded. The severity of choles- mg/dL) are most likely to benefit from treatment,
terol elevation might be exacerbated by the stress of statins have also shown primary prevention benefit in
beginning medical school and ambivalence about his individuals with moderate LDL cholesterol elevation
ability to succeed academically and cope well with (130 to 189 mg/dL) and secondary prevention benefit
the demands of his chosen profession. It would be in high-risk individuals with LDL cholesterol levels
important to clarify that his long-term LDL choles- above 100 mg/dL. For elderly patients, the estimated
terol range is the important determinant of progno- potential benefit of treatment (enhanced quality of life
sis, not any particular LDL cholesterol level. for more of the remaining life span) must be weighed
Familial heterozygous (Type IIa) hypercholes- for each individual against the expense and possible
terolemia is not uncommon, with a prevalence of adverse effects of medications being considered.
approximately one in 400 in the general population. The National Cholesterol Education Program
Mild and moderate degrees of hypercholesterolemia Adult Treatment Panel guidelines for lifestyle change
are extremely common. More than 50% of American and drug therapy (see Fig. 38-1) (Grundy et al., 2004 ● A)
adults have levels of LDL cholesterol high enough to and the American Heart Association Guidelines for
promote coronary atherosclerosis, especially in the Primary Prevention of Cardiovascular Disease and
presence of other identified risk factors. More than Stroke (see Table 38-4) (Mosca et al., 2004● A ) are based
one half of patients who experience myocardial on the evidence from these studies. Many patients pre-
infarctions have total cholesterol values between 200 fer to delay starting lipid-lowering medication until
and 239 mg/dL (5.2 to 6.1 mmol/L) and LDL choles- persistently elevated values on several lipid profiles con-
terol levels below the National Cholesterol Education vince them that they cannot obtain satisfactory results
Program cut point for defining high LDL cholesterol with dietary change, regular exercise, and sustained
(160 mg/dL [4.1 mmol/L]). Individuals with diabetes, weight loss. Despite the overwhelming evidence of
hypertension, or tobacco abuse (cigarette smokers statin benefit and safety, more than one half of the per-
and users of oral tobacco) are at especially high risk if sons who are considered appropriate candidates for
their LDL cholesterol levels are even mildly elevated statin therapy have never started taking a statin. Worse,
(100 to 159 mg/dL or 2.6 mmol/L) and/or their HDL the persistence rate for statin therapy in community
cholesterol levels are below average. After menopause, practice in 2003 averaged approximately 60% at 1 year
women’s risk of CHD rapidly catches up to men’s. and less than 40% at 3 years after initiation of therapy
When starting a program of dietary change to (Ellis et al., 2004● A ). The main patient obstacles to statin
lower LDL cholesterol, it can be very helpful to ask acceptance and persistence are (1) misunderstanding or
patients to bring in their spouse, children, and other denying the seriousness of their risk of CHD, (2) failing
key family members for a family conference to to appreciate the noncurative nature of statin therapy,
discuss the rationale and details of a heart healthy (3) being distrustful of statins because of their “not
diet. Teaching patients and spouses how to interpret being natural,” (4) worrying inordinately about poten-
the information on food labels is an important tial or perceived adverse side effects of statins, (5) wish-
component of patient education. Figuring out ways ing to avoid acknowledging and accepting their physical
to deal with ethnic food preferences and customs is frailty and mortality, and (6) the added short-term
an important need for some families. health care costs entailed with statin therapy (LaRosa
Patients who have an average American intake of and LaRosa, 2000● C ; Morris and Schulz, 2003● C ). The
saturated fat and cholesterol usually respond to per- impact of cost on compliance can be minimized by
sistent dietary modification by lowering their total careful selection of statin and by having patients split
and LDL cholesterol levels by approximately 10% to pills into halves to save money (see Table 38-6)
30% of the baseline value. Patients who already have (Crouch, 2001● A ). The risk of serious adverse side effects
a low intake of saturated fat do not respond well to from statin therapy can be minimized by instructing
dietary modification because they have so little room patients about medications to avoid while on a statin
for change. Cholesterol lowering medication usually (Table 38-7) and by monitoring patients’ other medica-
lowers the LDL cholesterol an additional 25% to 60% tions closely and avoiding or using great caution when
below the level achieved by dietary modification, prescribing medications that tend to raise statin blood
depending on the medication and dose. levels when taken concomitantly.

338
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

mize or postpone the development of atherosclerosis

Table 38-7 Drugs and Other Substances in adulthood (AHA, 1997). Although many clini-
That Interact with Statins* cians are reluctant to use lipid-altering drugs in chil-
Grapefruit juice dren, medication should be considered if a child has
Niacin, also called nicotinic acid (Slo-Niacin, severely elevated LDL cholesterol that does not
Niacor, Niaspan, Nico-400, Niadelay, Endur- respond well to dietary modification.
Acin) Triglyceride elevation increases the risk of
Gemfibrozil (Lopid) heart disease in female patients, especially those
Femfibrate (Tricor) with diabetes. Patients with mild triglyceride eleva-
Itraconazole (Sporonox)
Amlodopine (Norvasc)
tions often benefit from restriction of carbohy-
Diltiazem (Cardizem, Cartia, Dilacor, Diltia, drates and alcohol, weight loss, exercise, and
Tiazac) improved control of diabetes. Severe or persistent
Verapamil (Calan, Covera, Isoptin, Verelan) hypertriglyceridemia should be treated with niacin,
Amiodarone (Cordarone) fenofibrate, or gemfibrozil, and/or a statin. The goal
Cimetidine (Tagamet) of treatment is to reduce the triglyceride level to
Erythromycin (EES, E-Mycin, Eryc, PCE, Ery-Tab) below 150.
Clarithromycin (Biaxin) Low HDL cholesterol is a powerful independent
Clindamycin (Cleocin) risk factor, even if LDL cholesterol is only mildly ele-
Cyclosporine vated (100 to 159 mg/dL). Although National
Indinavir (Crixivan)
Nelfinavir (Viracept)
Cholesterol Education Program guidelines have not
Ritonavir (Norvir) yet recommended medical management for low
Saquinavir (Invirase) HDL cholesterol per se, the results of the Helsinki
Tacrolimus (Prograf) study suggest that treating low HDL cholesterol is at
least as beneficial as lowering elevated LDL choles-
*
Some statins (atorvastatin, simvastatin, and terol. Hygienic approaches, including regular aerobic
lovastatin, but not pravastatin, rosuvastatin, or
fluvastatin) interact with other drugs metabolized exercise, weight loss, and smoking cessation, tend to
by the cytochrome P-450 3A4 liver enzyme system. raise HDL cholesterol by 5 to 15 mg/dL, as does
treatment with niacin, gemfibrozil, or fenofibrate.
Statins sometimes elevate HDL cholesterol slightly.
Studies continue to show that physicians have not
done well managing dyslipidemia in accordance with The Prevention Challenge
treatment guidelines (Eaton and Stamp, 2002 ● C;
McBride et al., 1998● C ). The main physician obstacles The prognosis for patients with lipid problems can
to prescribing statin therapy are (1) unfamiliarity with be greatly improved by lasting lifestyle changes, long-
the details of lipid guidelines, (2) complexity of the rec- term lipid-lowering medication, and diligent follow-
ommendations for lipid assessment and treatment, (3) up care. Creative solutions are needed to improve the
skepticism about guideline validity and insufficient level of acceptance and trust in the efficacy and safety
familiarity with the outcomes of statin clinical trials, of statin therapy among both patients and physi-
(4) logistical difficulties with applying the guidelines in cians, so that more of the statins’ preventive potential
a busy primary care practice, (5) time pressure, and (6) can be realized.
inadequate reimbursement for time spent doing
patient education (Powell-Cope et al., 2004● C ).
Guidelines are also available for diagnosing and Material Available on Student Consult
managing hypercholesterolemia in children. Dietary
Review Questions and Answers about Hyper-
prevention should ideally begin relatively early in life
cholesterolemia
in all individuals at increased risk of CHD to mini-

RESOURCES
American Heart Association. Available at www.american- MAC OS version). Available at http://hp2010.nhlbihin.
heart.org net/atpiii/riskcalc.htm
National Cholesterol Education Program. Available at Third Report of Expert Panel on Detection, Evaluation,
www.nhlbi.nih.gov/about/ncep/index.htm and Treatment of High Blood Cholesterol in Adults
Therapeutic Lifestyle Change diet. Available at www. (Adult Treatment Panel III) Executive Summary.
nlhbi.nih.gov/cgi-bin/chd/step2intro.cgi Available at www.nhlbi.nih.gov/guidelines/cholesterol/
10-Year CHD Risk Estimate Calculator. Available at atp_iii.htm
www.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof Implications of Recent Clinical Trials for the National
10-Year CHD Risk Estimate Calculator (downloadable Cholesterol Education Program Adult Treatment Panel
Excel 95 and 2000 spreadsheet versions for Palm or III Guidelines. Circulation 2004 July 13;110:227–239.

339
 Chapter 38 Abdominal Pain and Loose Bowel Movements (Hypercholesterolemia)

Available at www.nhlbi.nih.gov/guidelines/cholesterol/ NCEP ATP III: X. Adherence. Available at www.nhlbi.nih.

atp3upd04.htm gov/guidelines/cholesterol/chap_9.pdf
HeartAge (online alternative way of expressing CHD risk).
All resources accessed November 29, 2005
Available at www.heartage.com.

REFERENCES
AHA Compliance Action Program. Available at tatin, simvastatin, and pravastatin across doses (STEL-
www.americanheart.org/CAP/patient/con_quiz.html, LAR Trial). Am J Cardiol 2003;92:152–160.● B
www.americanheart.org/CAP/pro/prof_pledge.html, Koren MJ, Hunninghake DB. Clinical outcomes in man-
www.americanheart.org/CAP/pro/prof_quiz.html aged-care patients with coronary heart disease treated
American Heart Association (AHA). Nutrition and aggressively in lipid-lowering disease management clin-
Children. A Statement for Healthcare Professionals ics. The ALLIANCE Study. J Am Coll Cardiol 2004;
from the Nutrition Committee, 1997. 44:1772–1779.● B
AHA Scientific Statement: Fish consumption, fish oil, LaRosa JH, LaRosa JC. Enhancing drug compliance in cho-
omega-3 fatty acids and cardiovascular disease, #71- lesterol-lowering treatment. Arch Fam Med 2000;
0241. Circulation 2002;106:2747–2757.● A 9:1169–1175.● C
Ballantyne CM. Current and future aims of lipid-lowering Marks D, Thorogood M, Neil HA, Humphries SE. A review
therapy: Changing paradigms and lessons from the on the diagnosis, natural history, and treatment of
Heart Protection Study on standards of efficacy and familial hypercholesterolaemia. Atherosclerosis 2003;
safety. Am J Cardiol 2003;92:3K–9K.● B 168:1–14.● C
Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary McBride P, Schrott HG, Plane MB, Underbakke G, Brown
prevention of cardiovascular disease with atorvastatin in RL. Primary care practice adherence to national choles-
type 2 diabetes in the Collaborative Atorvastatin Diabetes terol education program guidelines for patients with
Study (CARDS): Multicentre randomized placebo-con- coronary heart disease. Arch Intern Med 1998;
trolled trial. Lancet 2004; 364:685–696.●B 158:1238–1244.● C
Crouch MA. Effective use of statins to prevent coronary heart Morris LS, Schulz RM. Medication compliance: The
disease. Am Fam Physician 2001;63:309–320, 323–324.● C patient’s perspective. Clin Ther 1993;15:593–606.● C
Eaton CB, Stamp MJ. National Cholesterol Education Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-based
Program (NCEP): The Adult Treatment Panel III guidelines for cardiovascular disease prevention in
Guidelines. Practice patterns related to the Adult women. Circulation 2004;109:672–693.● A
Treatment Panel III guidelines in primary care. Am Myers RH, Kiely DK, Cupples LA, Kannel WB. Parental
J Cardiol 2002;90:687.● C history is an independent risk factor for coronary
Ellis JJ, Erickson SR, Stevenson JG, et al. Suboptimal statin artery disease: The Framingham Study. Am Heart
adherence and discontinuation in primary and second- J 1990;120:963–969.● B
ary prevention populations. J Gen Intern Med National Cholesterol Education Program, Adult Treatment
2004;19:638–645.● A Panel III. Summary of the third report of the National
Ford ES, Giles WH. A comparison of the prevalence of the Cholesterol Education Program (NCEP) Expert Panel
metabolic syndrome using two proposed definitions. on Detection, Evaluation, and Treatment of High Blood
Diabetes Care 2003;26:575–581.● C Cholesterol in Adults (Adult Treatment Panel III).
Gagne C, Bays HE, Weiss SR, et al. Efficacy and safety of JAMA 2001;285:2486–2497.● A
ezetimibe added to ongoing statin therapy for treat- Pearson TA, Mensah GA, Hong Y, Smith SC. CDC/AHA
ment of patients with primary hypercholesterolemia. workshop on markers of inflammation and cardiovas-
Am J Cardiol 2002;90:1084–1091.● B cular disease: Application to clinical and public health
Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospi- practice: Overview. Circulation 2004;110:e543–e544.
talized rhabdomyolysis in patients treated with lipid- Powell-Cope GM, Luther S, Neugaard B, Nelson VJ.
lowering drugs. JAMA 2004;292:2585–2590.● C Provider-perceived barriers and facilitators for
Grundy SM, Cleeman JI, Merz NB, et al. Implications of ischaemic heart disease (IHD) guideline adherence.
recent clinical trials for the National Cholesterol J Eval Clin Pract 2004;10:227–239.● C
Education Program Adult Treatment Panel III Silberberg JS, Wlodarczyk J, Fryer J, Robertson R, Hensley
Guidelines. Circulation 2004;110:227–239.● A MJ. Risk associated with various definitions of family
Hu FB, Willett WC. Optimal Diets for prevention of coro- history of coronary heart disease. The Newcastle Family
nary heart disease. JAMA 2002;288:2569–2578.● A History Study II. Am J Epidemiol 1998;147:
Jenkins DJA, Kendall CWC, Marchie A, et al. Effects of a 1133–1139.● B
dietary portfolio of cholesterol-lowering foods vs lovas- Weiss R, Harder M, Rowe J. The relationship between non-
tatin on serum lipids and C-reactive protein. JAMA fasting and fasting lipid measurements in patients with
2003;290:502–510.● B or without type 2 diabetes mellitus receiving treatment
Jones PH, Davidson MH, Stein EA, et al. Comparison of with 3-hydroxy-3-methylglutaryl-coenzyme A reduc-
the efficacy and safety of rosuvastatin versus atorvas- tase inhibitors. Clin Ther 2003;25:1490–1497.● C

340
 C h a p t e r

39 Bilateral Leg Pain

(Peripheral Arterial Disease)
Kalyanakrishnan Ramakrishnan

discomfort in both calves and right thigh after walk-

KEY POINTS ing two blocks. The pain is relieved after a minute or
two of rest. Other symptoms include charley horses,
1. Clinical presentation of peripheral arterial dis- occasional tingling and numbness in his right foot,
ease (PAD) ranges from asymptomatic stenosis and fatigue in the legs on walking around the house
to intermittent claudication (IC) and critical limb or on standing for 15 minutes. He has no nocturnal
ischemia (CLI). pain or rest pain. He denies any change in color of
2. Many patients with PAD are asymptomatic (less the legs or any sores, chest pain, shortness of breath,
than 50% of patients with an abnormal dizziness, numbness in his upper limbs, or transient
ankle/brachial index [ABI] have claudication). loss of vision. He also denies any abdominal dis-
Individuals with even asymptomatic PAD have a comfort after meals, anorexia, weight loss, or erectile
reduced functional capacity, a lower quality of dysfunction.
life, a sixfold increase in cardiovascular morbid-
ity and mortality, carotid artery stenosis, and Medical History
cognitive dysfunction. Medical history is significant for hypertension,
3. Smoking, diabetes mellitus, and hypertension non–insulin-dependent diabetes mellitus, and hyper-
have the greatest association with and an addi- cholesterolemia. His comorbid illnesses are well con-
tive effect on the risk of PAD. trolled on metoprolol (Lopressor) 50 mg twice daily,
4. The ABI (normal ≥ 1) is a simple, painless, lisinopril (Zestril) 20 mg daily, atorvastatin (Lipitor)
highly reproducible test performed to document 20 mg daily, and metformin (Glucophage) 1000 mg
PAD, and values less than 0.9 correlate well twice daily. Three years ago, he was admitted with an
with 50% or greater stenosis of one or more episode of congestive heart failure, thought to be
major lower limb arteries. ischemic in origin. Since then, however, his cardiores-
5. Treatment aims to relieve lower extremity symp- piratory status had been stable. He had also under-
toms, increase functional walking capacity and gone a cholecystectomy and an appendectomy in the
quality of life, prevent progression of disease early 1980s.
and ulcer formation, and preserve the limb.
Lifestyle changes and medications result in Social History
improvement in most patients. He has a 40-pack-year smoking history. He denies any
6. Revascularization (endovascular or surgical) is alcohol or drug use. He professes to “eat whatever he
reserved for short-distance IC, rest pain (CLI), wants.” He enjoyed walking 2 miles every day until his
nonhealing ulcers, or threatened limb loss. leg cramps prevented this continued activity.

Family History
Both his parents had died of myocardial infarction.
INITIAL VISIT
Subjective Objective
Patient Identification and Presenting Physical Examination
Problem On physical examination, his pulse is 70 beats per
John B. is a 60-year-old man who presents with a minute and regular, blood pressure is 140/90, and
history of bilateral leg pain described as a cramping weight is 220 pounds. There are no carotid bruits

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

341
 Chapter 39 Bilateral Leg Pain (Peripheral Arterial Disease)

or jugular venous distention. Cardiorespiratory noticed in the lower limbs. In cauda equina
examination shows no evidence of congestive heart syndrome (central disk herniation), saddle anes-
failure. Abdominal examination is negative for thesia and bladder or bowel incontinence may be
organomegaly, palpable aortic aneurysm, and renal present.
bruits. On examination of his lower extremities, the 3. Osteoarthritis of the hips and knees causes discom-
right femoral pulse is weak with a bruit. No distal fort in the area of the buttock, groin, thigh, or knee,
pulses are palpable on the right. The left femoral typically worse with movement and alleviated by
pulse is normal; popliteal and pedal pulses are absent rest. Severe osteoarthritis may present with rest
on the left. Power, sensations, and reflexes are normal pain or nocturnal pain. Morning stiffness lasting
in both lower limbs. No areas of skin breakdown are less than 30 minutes is common. Knee instability
noticed. or buckling while descending stairs or stepping off
curbs may be noticed. The pain is usually localized
Assessment to the affected joint and may be elicited by palpa-
tion and range-of-motion maneuvers. Crepitation
Working Diagnosis or effusion may be present in the knee.
Intermittent claudication due to right common iliac 4. Skeletal muscle disorders such as myositis can cause
artery stenosis and bilateral superficial femoral exertional leg pain. Muscle tenderness, abnormal
artery occlusion. neuromuscular examination findings, elevated
skeletal muscle enzymes, and a normal pulse exam-
Differential Diagnosis (Table 39-1) ination should distinguish myositis from PAD.
1. Intermittent claudication. This is defined as repro- 5. Chronic venous insufficiency due to deep vein
ducible lower limb discomfort during exercise, thrombosis may cause exertional leg pain (venous
relieved within minutes by rest or reduction in claudication) due to the rapid increase in venous
walking pace. It is the most common symptom of pressure and congestion due to exercise-induced
mild to moderate atherosclerotic PAD and affects hyperemia and outflow obstruction. This is seen
3% to 5% of adults (five million people) in the most commonly following iliofemoral venous
United States. Claudication most frequently local- thrombosis without adequate collateralization.
izes to the calf muscles due to their relatively greater Patients often experience aching sensations at rest
metabolic demand, and the superficial femoral and bursting cramps on ambulation. They may
arteries are a common site of atherosclerosis. also have peripheral edema, venous stasis pig-
Buttock or thigh claudication may result from ath- mentation, varicosities, ulcers, or lipoder-
erosclerotic narrowing of the aortoiliac segment. matosclerosis (induration and scarring of the
Patients may quantify their exercise capacity in lower leg leading to a champagne-bottle defor-
walking distance or time to the onset of claudica- mity). The discomfort is relieved by frequent leg
tion (claudication distance) (Brook et al., 2002● B). elevation, avoiding prolonged standing or sitting,
2. Lumbosacral radiculopathy due to degenerative and wearing graduated compression stockings.
joint disease, spinal stenosis, and herniated inter- 6. Chronic compartment syndrome seen in young
vertebral disks cause pain in the buttock, hip, well-conditioned athletes may present as agoniz-
thigh, calf, and/or foot with walking, often after ing pain, tense swelling, paresthesias, or weakness
very short distances, or even with standing (neu- of the calf or feet brought on by exercise or pas-
rogenic pseudoclaudication). Fatigue, numbness, sive stretching of the muscles post-exercise and
or paresthesias in the legs and feet may also be relieved by rest and elevation. Muscle swelling
present. The pain is made worse on lying prone or and increased osmotic pressure in an unyielding
extension of the spine and is relieved by sitting or compartment result in decreased blood flow and
bending forward. Sensorimotor deficits may be acute myoneural ischemia. Foot drop may be

Table 39-1 Differential Diagnosis of Claudication

Vascular Musculoskeletal Neurologic

Atherosclerosis Herniated disk Lumbosacral

Thrombosis Spinal canal stenosis radiculopathy
Embolism Osteoarthritis of hips or knees Myositis
Thromboangiitis obliterans Baker’s cysts Compartment syndrome
Arterial entrapment Ligament/tendon injury
Venous insufficiency
From Lesho EP, Manngold J, Gey DC. Management of peripheral arterial disease. Am Fam Physician
2004;69:525–532.

342
 Chapter 39 Bilateral Leg Pain (Peripheral Arterial Disease)

present. The anterior compartment of the leg is to worsening rest pain in his left lower limb.
most commonly involved (45%), followed closely Unfortunately, the graft clotted, and he subsequently
by the deep posterior compartment (40%). required a left above-knee amputation for spreading
7. Popliteal artery entrapment is a rare cause of exer- gangrene. He still continues to smoke, takes his med-
cise-induced leg pain in young men. An abnormal ications indifferently, is not motivated to use his
relationship between the popliteal artery and the prosthesis, and is wheelchair bound.
surrounding myofascial structures in the popliteal
fossa results in entrapment and arterial insuffi-
ciency in the affected limb, causing leg symptoms DISCUSSION
with exertion.
8. Buerger’s disease (thromboangiitis obliterans) PAD results from chronic narrowing of the distal
occurs predominantly in young men of age 20 to 40 abdominal aorta or iliac or lower extremity arteries.
who smoke. It involves small- and medium-sized Most lesions in the lower limbs develop in the poste-
arteries and superficial veins of the extremities in a rior aspects of the proximal portions of the major
segmental pattern. Patients notice coldness, numb- arteries, bifurcation sites, or specific areas of high
ness, tingling, or burning of the involved extremity. atherogenesis (distal superficial femoral artery at the
Intermittent claudication of the foot or leg, rest Hunter’s canal) (Levy, 2002● B). An area of stenosis
pain, ulceration, or gangrene may occur. becomes hemodynamically significant at rest when
the arterial diameter is reduced by greater than 80%.
Plan The clinical presentation of PAD ranges from
asymptomatic stenosis to IC and CLI. Eight to 12
Diagnostic Testing million people in the United States have PAD; its
John B. had normal blood counts and liver and kid- prevalence increases with age and affects 12% to 17%
ney function tests. His total cholesterol was reported of those older than age 50 and almost 20% of people
as 240 mg/dL, and low-density lipoprotein level was older than age 70. Many patients with PAD are
148 mg/dL. Segmental pressure measurements asymptomatic. Less than half of patients with an
showed a sharp drop in the right thigh and both legs abnormal ABI have IC.
and feet. The ABI measured 0.65 in the right thigh, Individuals with PAD have a reduced functional
0.95 in the left thigh, and 0.5 in both legs and feet. An capacity, lower quality of life, an extremely high risk
arteriogram showed some insignificant plaques in (sixfold) of cardiovascular morbidity and mortality,
the aorta and both common iliac arteries, a 3-cm carotid artery stenosis, and cognitive dysfunction
occlusion of the right external iliac artery, bilateral (Criqui et al., 1992●A).
superficial femoral artery occlusions, normal Risk factors for PAD include smoking, diabetes
popliteals, and three-vessel runoff in both legs. mellitus, and hypertension (Table 39-2). Others
include advancing age, family history, hyperlipi-
Treatment demia, renal dysfunction, previous myocardial
John B. was started on aspirin 81 mg/day and cilosta- infarction, heart failure or stroke, elevated homocys-
zol (Pletal) 100 mg twice daily. He was advised to teine and C-reactive protein levels, and previous
enter a smoking cessation program and to exercise on
a treadmill 30 minutes daily at least three times per
week or until claudication limited his exercise. He was
also counseled about “eating right.” Tight control of Table 39-2 Risk Factors for Peripheral
his sugars was recommended, and the doses of both Arterial Disease
the blood pressure and cholesterol medications were
adjusted to aim for a target blood pressure of 130/80 Smoking
and a low-density lipoprotein level lower than 100 Diabetes mellitus
mg/dL (Regensteiner and Hiatt, 2002● B). Hypertension (systolic blood pressure)
Previous myocardial infarction, stroke, heart
failure
Chronic renal insufficiency
FOLLOW-UP VISIT Positive family history
Chronic infections
When seen 6 weeks later, John B. was still smoking a Age (~75 yr)
pack daily. His claudication distance was decreasing, Fibrinogen level
although he had not experienced any rest pain. African-American race
Angioplasty was therefore advised, and he under- Hyperhomocysteinemia
went an uneventful angioplasty and stenting of the From Regensteiner JG, Hiatt WR. Treatment of
right external iliac artery. Three months later, he peripheral arterial disease. Clin Cornerstone
underwent a femoropopliteal bypass on the left due 2002;4:26–40.

343
 Chapter 39 Bilateral Leg Pain (Peripheral Arterial Disease)

infections (pneumonia, chronic bronchitis, peptic reduced or absent; bruits may be present over
ulcer, and periodontal infections). PAD has a higher stenotic vessels (carotid, femoral, iliac).
prevalence in African Americans. The distribution of The ABI (normal ≥ 1) is a simple, painless,
PAD is similar for men and women, although its fre- highly reproducible test performed with a handheld,
quency is much higher in women with diabetes mel- continuous-wave Doppler probe that compares the
litus. Smoking, diabetes mellitus, and hypertension blood pressure obtained in the dorsalis pedis or
have an additive effect on the risk of PAD. posterior tibial artery (whichever is higher) with
Most patients with PAD are asymptomatic. the higher of the two brachial artery pressures
Apart from IC (described previously), patients may (Fig. 39-1). Resting ABI values less than 0.9 correlate
present with persistent rest pain, nonhealing ulcers, well with 50% or greater stenosis of one or more
or gangrene. Leriche syndrome refers to bilateral major lower limb arteries. An ABI of 0.71 to 0.9 indi-
lower limb claudication and impotence due to aor- cates mild PAD, 0.41 to 0.70, moderate PAD, and ABI
toiliac occlusion. On examination, trophic changes less than 0.40 indicates severe PAD (Belch et al., 2003
(dry skin, thickened nails, and loss of hair and sub- ●B ). The ABI may be high if the vessels are calcified
cutaneous fat), ulcers, or gangrene may be noticed in and incompressible (as in diabetes mellitus and renal
the lower limbs. Ischemic ulcers are usually located failure) and does not define the site of the lesion or
on the plantar surface of the foot, over the first and differentiate between stenosis and total occlusion.
fifth metatarsal heads. Peripheral pulses may be The ABI may be repeated after exercise (treadmill or

• Lower limb discomfort on exertion

• High-risk patient (elderly, history of hypertension,
diabetes mellitus, smoking, renal dysfunction,
hyperlipidemia)
• Abnormal peripheral pulses

Ankle-brachial index (ABI)

ABI >1.30 ABI 0.9–1.30 ABI <0.9

Normal, incompressible ABI after

vessel (diabetes, renal exercise testing
failure) (treadmill, heel
raise)

Duplex scan
PVR Normal ABI decreased
Toe-brachial index

Abnormal Peripheral vascular

Normal−−no PVD, disease
consider
pseudoclaudication,
venous claudication,
compartment
syndrome etc.

Figure 39-1 Evaluation of peripheral arterial disease. PVD, peripheral vascular disease; PVR, peripheral vascular resist-
ance. (From Hiatt WR. Medical treatment for peripheral arterial disease and intermittent claudication. N Engl J Med
2001;344:1608–1621.)

344
 Chapter 39 Bilateral Leg Pain (Peripheral Arterial Disease)

heel raise) in symptomatic patients with a normal limb (Brook et al., 2002● B). Smoking cessation slows
ABI at rest (Pellerito, 2001● B). the progression of IC to CLI, reduces the need for
Measurement of segmental lower limb pressures revascularization, and improves graft patency (Hiatt,
helps to localize the site of the PAD. A decrease in pres- 2001● B). Diabetics should maintain glycohemoglobin
sure between two consecutive levels (thigh, leg, or foot) levels below 7% (Table 39-3). Blood pressure should be
of greater than 30 mm Hg suggests proximal arterial maintained at 130/80 to minimize cardiovascular mor-
occlusive disease (Jaff, 2002● B ). Ultrasound duplex bidity and mortality. Low-density lipoprotein choles-
scanning detects arterial wall thickness, degree of terol levels should be reduced to lower than 100 mg/dL.
stenosis, and changes in flow velocity and has higher Exercise programs improve oxygen consumption,
sensitivity in detecting lesions in the more proximal skeletal muscle metabolism, and endothelial vasodila-
arteries (iliac and superficial femoral). Peak systolic tor function and reduce blood viscosity and ischemia
velocity determination and Doppler waveform analy- (Regensteiner and Hiatt, 2002● B). Sessions should last
ses also help localize and quantify PAD. Significant longer than 30 minutes and be carried out at least three
PAD shows elevated peak systolic velocity, marked times every week. Ideally the patient should walk until
spectral broadening, and loss of diastolic reversal near-maximal pain is reached in each session, and the
(Pellerito, 2001● B ). Transcutaneous measurement of program should last at least 6 months. Aspirin, in doses
oxygen tension denotes adequacy of tissue perfusion. between 81 and 325 mg/day, or clopidogrel 75 mg/day
Values greater than 40 mm Hg predict healing of foot should be commenced (Fig. 39-2). Cilostazol, a phos-
ulcers or primary forefoot amputations; values less phodiesterase 3 inhibitor, at 100 mg twice daily relieves
than 10 mm Hg are associated with failure to heal. IC, improves walking time and distance, and enhances
Angiography is useful in defining the anatomy of the of quality of life. Common side effects include
aorta, iliac arteries and their branches, and the periph- headache, loose stools, and dizziness. It should not be
eral arteries. Magnetic resonance angiography is a cost- administered to patients with heart failure of any
effective, noninvasive alternative, as accurate and severity or when the ejection fraction is less than 40%.
reliable as conventional angiography in imaging inflow Ticlopidine, another antiplatelet agent, is associated
vessels and grading stenosis severity. Using gadolinium with serious hematologic side effects that preclude its
minimizes contrast nephrotoxicity and enhances the use. Pentoxifylline (Trental), at a dose of 400 mg three
accuracy of imaging. times daily with meals, or naftidrofuryl (a serotonin
The goals of treatment include relief of lower antagonist) 100 to 200 mg three times daily are other
extremity symptoms, increasing functional walking options. Adequate pain control in CLI often requires
capacity and quality of life, preventing the progression narcotics. Feet are evaluated periodically to minimize
of disease and ulcer formation, and preservation of the trauma, and ulcers should be kept clean, infections

Table 39-3 Nonoperative Management Strategies for Peripheral Arterial Disease

Risk Factor Goal Treatment

Smoking Cessation Counseling; nicotine patch, gum,

spray; bupropion
Hypertension SBP ≤ 130/80 ACE inhibitors, β-blocker (if CAD,
no rest pain or CLI)
Diabetes mellitus Glycohemoglobin < 7.0% Oral hypoglycemics, insulin,
exercise, diet
Hyperlipidemia LDL < 100 mg/dL Statins ± niacin or fibric acid
derivatives
Platelet aggregation Antiplatelet therapy Aspirin 81–325 mg/day
Cilostazol 100 mg twice daily
Clopidogrel 75 mg/day
Pentoxyfilline 400 mg three times
daily
Naftidrofuryl 100–200 mg three
times daily
Lack of exercise Exercise therapy 30-min sessions at least three
times per week until near-
maximal pain is reached for 6 mo
ACE, angiotensin-converting enzyme; CAD, coronary artery disease; CLI, critical limb ischemia; LDL, low-density
lipoprotein; SBP, systolic blood pressure.
From Regensteiner JG, Hiatt WR. Treatment of peripheral arterial disease. Clin Correstone 2002;4:26–40.

345
 Chapter 39 Bilateral Leg Pain (Peripheral Arterial Disease)

Peripheral arterial disease

Risk factors Claudication severity Rest pain, gangrene, non-

present assessed by history, healing ulcer (CLI)
examination, ABI

– Exercise
– Smoking cessation Improvement on
– BP 130/80 risk factor No improvement
– LDL–C< 100 mg/dL modification, or worsening
– HbA1C≤ 7.0 exercise, disease (CLI)
– Antiplatelet agents (Aspirin, medications
Cilostazol, Clopidogrel)

Continue conservative
treatment
Localization of
obstruction (duplex
ultrasound, MRA,
angiography)

Correctable lesion Uncorrectable lesion

(multilevel disease, poor
run-off)
Co-morbid illness,
immobile elderly patient
Analgesics
Treat intercurrent
infection
Angioplasty ± stent
Bypass grafting Analgesics, Antiplatelet
Endarterectomy agents
Skin grafting Treat intercurrent
infection
Consider amputation

Figure 39-2 Treatment of peripheral arterial disease. ABI, ankle/brachial index; BP, blood pressure; CLI, critical limb
ischemia; HbA1C, hemoglobin A1c; LDL-C, low-density lipoprotein cholesterol; MRA, magnetic resonance angiography.
(From Hiatt WR. Medical treatment for peripheral arterial disease and intermittent claudication. N Engl J Med
2001;344:1608–1621.)

treated, and ongoing pressure minimized (Rajagopalan benefits most patients (85%) with threatened limb loss
and Grossman, 2002● B ). (see Fig. 39-2). Continuing antiplatelet agents or oral
Revascularization (endovascular or surgical) is anticoagulants postoperatively maximizes the patency
reserved for short-distance IC, rest pain (CLI), non- of the reconstructed vessel or the bypass. The absence
healing ulcers, or threatened limb loss (Brook et al., of patent distal vessels with a low ABI (<0.3) in the set-
2002● B). Patients who exercise regularly derive the most ting of CLI makes amputation inevitable (Rajagopalan
benefit. Angioplasty with or without stenting for lower and Grossman, 2002● B).
extremity ischemia is appropriate for short common
iliac or femoropopliteal artery stenoses or occlusions.
Surgical endarterectomy or bypass (aortoiliac, femoro- Material Available on Student Consult
popliteal) is indicated in the presence of long-segment
Review Questions and Answers about Peripheral
stenosis or occlusion, associated aneurysmal dilatation
Arterial Disease
of the vessel, or lesions causing distal embolization and

346
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

REFERENCES
Belch JJF, Topol EJ, Agnelli G, et al. Critical issues in Jaff MR. Lower extremity arterial disease: Diagnostic
peripheral arterial disease detection and management: aspects. Cardiol Clin 2002;20:491–500.● B
A call to action. Arch Intern Med 2003;163: Lesho EP, Manngold J, Gey DC. Management of periph-
884–892.● B eral arterial disease. Am Fam Physician 2004;
Brook RD, Weder AB, Grossman PM, Rajagopalan S. 69:525–532.● B
Management of intermittent claudication. Cardiol Clin Levy PJ. Epidemiology and pathophysiology of peripheral
2002;20:521–534.● B arterial disease. Clin Cornerstone 2002;4:1–15.●B
Criqui MH, Langer RD, Fronek A, et al. Mortality over a Pellerito JS. Current approach to peripheral arterial sonog-
period of 10 years in patients with peripheral arterial raphy. Radiol Clin North Am 2001;39:553–567.● B
disease. N Engl J Med 1992;326:381–386.● A Rajagopalan S, Grossman PM. Management of chronic
Hiatt WR. Medical treatment for peripheral arterial disease critical limb ischemia. Cardiol Clin 2002;20:535–545.● B
and intermittent claudication. N Engl J Med Regensteiner JG, Hiatt WR. Treatment of peripheral arte-
2001;344:1608–1621.● B rial disease. Clin Cornerstone 2002;4:26–40.●B

C h a p t e r

40 Leg Pain and Swelling

(Venous Thrombosis)
Jennifer DeVoe

KEY POINTS

1. Patients with deep vein thrombosis (DVT) days of a therapeutic International Normalized
(and/or pulmonary embolism [PE]) should be Ratio (INR). (In a few cases, such as massive PE or
treated urgently with low-molecular-weight severe iliofemoral thrombosis, continue heparin
(LMW) heparin, unfractionated intravenous therapy for approximately 10 days.)
heparin, or adjusted-dose subcutaneous 4. While the patient is taking warfarin, the INR
heparin. target range should be 2.0 to 3.0. In some cases
2. Continue treatment with chosen heparin prod- in which warfarin is contraindicated or not
uct for at least 5 days. Check a platelet count tolerated, LMW heparin or adjusted-dose
between day 3 and day 5 of therapy to monitor unfractionated heparin can be continued.
for heparin-induced thrombocytopenia. If the 5. The use of thrombolytic agents requires further
patient remains on heparin, check another investigation.
platelet count between days 7 and 10, and 6. Consider inferior vena caval filter placement in
another at day 14. Stop the heparin product if some individuals who are unable to take long-
the patient experiences a precipitate or sus- term anticoagulant therapy or in patients with
tained decrease in the platelet count, or if the recurrent thromboembolism despite adequate
platelet count is less than 100,000/μL. anticoagulation.
3. Overlap oral anticoagulation with the chosen 7. If a first thromboembolic event is due to a
heparin product for at least 4 to 5 days. Warfarin reversible or time-limited factor, continue antico-
can usually be initiated simultaneously with the agulation therapy for at least 3 months. Until
heparin. The heparin product can be discontin- recently, a first idiopathic event was usually
ued on day 5 or 6 after at least two consecutive treated for 3 to 6 months. Several trials now

Continued

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

347
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

REFERENCES
Belch JJF, Topol EJ, Agnelli G, et al. Critical issues in Jaff MR. Lower extremity arterial disease: Diagnostic
peripheral arterial disease detection and management: aspects. Cardiol Clin 2002;20:491–500.● B
A call to action. Arch Intern Med 2003;163: Lesho EP, Manngold J, Gey DC. Management of periph-
884–892.● B eral arterial disease. Am Fam Physician 2004;
Brook RD, Weder AB, Grossman PM, Rajagopalan S. 69:525–532.● B
Management of intermittent claudication. Cardiol Clin Levy PJ. Epidemiology and pathophysiology of peripheral
2002;20:521–534.● B arterial disease. Clin Cornerstone 2002;4:1–15.●B
Criqui MH, Langer RD, Fronek A, et al. Mortality over a Pellerito JS. Current approach to peripheral arterial sonog-
period of 10 years in patients with peripheral arterial raphy. Radiol Clin North Am 2001;39:553–567.● B
disease. N Engl J Med 1992;326:381–386.● A Rajagopalan S, Grossman PM. Management of chronic
Hiatt WR. Medical treatment for peripheral arterial disease critical limb ischemia. Cardiol Clin 2002;20:535–545.● B
and intermittent claudication. N Engl J Med Regensteiner JG, Hiatt WR. Treatment of peripheral arte-
2001;344:1608–1621.● B rial disease. Clin Cornerstone 2002;4:26–40.●B

C h a p t e r

40 Leg Pain and Swelling

(Venous Thrombosis)
Jennifer DeVoe

KEY POINTS

1. Patients with deep vein thrombosis (DVT) days of a therapeutic International Normalized
(and/or pulmonary embolism [PE]) should be Ratio (INR). (In a few cases, such as massive PE or
treated urgently with low-molecular-weight severe iliofemoral thrombosis, continue heparin
(LMW) heparin, unfractionated intravenous therapy for approximately 10 days.)
heparin, or adjusted-dose subcutaneous 4. While the patient is taking warfarin, the INR
heparin. target range should be 2.0 to 3.0. In some cases
2. Continue treatment with chosen heparin prod- in which warfarin is contraindicated or not
uct for at least 5 days. Check a platelet count tolerated, LMW heparin or adjusted-dose
between day 3 and day 5 of therapy to monitor unfractionated heparin can be continued.
for heparin-induced thrombocytopenia. If the 5. The use of thrombolytic agents requires further
patient remains on heparin, check another investigation.
platelet count between days 7 and 10, and 6. Consider inferior vena caval filter placement in
another at day 14. Stop the heparin product if some individuals who are unable to take long-
the patient experiences a precipitate or sus- term anticoagulant therapy or in patients with
tained decrease in the platelet count, or if the recurrent thromboembolism despite adequate
platelet count is less than 100,000/μL. anticoagulation.
3. Overlap oral anticoagulation with the chosen 7. If a first thromboembolic event is due to a
heparin product for at least 4 to 5 days. Warfarin reversible or time-limited factor, continue antico-
can usually be initiated simultaneously with the agulation therapy for at least 3 months. Until
heparin. The heparin product can be discontin- recently, a first idiopathic event was usually
ued on day 5 or 6 after at least two consecutive treated for 3 to 6 months. Several trials now

Continued

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

347
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

KEY POINTS (Continued)

suggest that prolonged anticoagulation is benefi- with three or more episodes or earlier in some
cial in patients with a first idiopathic thromboem- patients with confirmed thrombophilias who
bolic event (Kearon et al., 2003 ● A ; Ridker et al., have had massive or unusual clots.
2003 ● A ; Schulman et al., 2003 ● A ). No clear guid- 9. Use caution in treating cancer patients with
ance has yet emerged as to the optimal length of anticoagulant therapy, which is associated
time for anticoagulation, but suggested length with both benefit and a high rate of
has been extended to 6 to 12 months in most complications.
recent writings. However, treatment decisions 10. In patients who will be at risk for developing a
must still take into account the unique factors clot (e.g., surgery, prolonged immobilization),
present in each individual case. remember to consider primary prophylaxis with
8. Prolonged anticoagulation, for at least 12 either anticoagulant medications or physical
months, also appears to be beneficial in second methods (e.g., intermittent pneumatic
cases (Ridker et al., 2003 ● A ). Indefinite compression) that are effective for
anticoagulation is recommended for patients preventing DVT.

INITIAL VISIT She also has osteoporosis and hypercholesteremia.

She denies any history of blood clots or stroke.
Subjective
Surgical History
Patient Identification and Presenting Problem Mrs. B. had a total abdominal hysterectomy at age 58
Mrs. Val B. is a 70-year-old woman who is seen in the years.
clinic with left leg pain and swelling.
Medications
Present Illness She is using ipratropium + albuterol (Combivent)
Val reports that she started noticing swelling in her metered-dose inhaler, fluticasone + salmeterol
left leg 2 nights ago. She initially thought it was due (Advair Diskus), albuterol (Ventolin) nebulizer as
to standing on her feet for several hours while volun- needed, isosorbide mononitrate (Imdur), aspirin,
teering at the fair. Despite elevating her feet and stay- atorvastatin (Lipitor), lisinopril (Zestril), alen-
ing off her leg yesterday, she noticed that the swelling dronate (Fosamax), and esomeprazole (Nexium).
persisted and that her leg was more painful. It is now
warmer than her right leg and seems to be showing Habits
some discoloration. She has not taken any recent air- She has smoked two packs of cigarettes per day for
plane flights or experienced a long period of immo- the past 50 years.
bilization. She has never used hormone replacement
therapy. She denies acute shortness of breath or Family History
hemoptysis; however, she has had dyspnea on exer- Val’s father had coronary artery disease and died
tion over the past 4 months, especially while going of a myocardial infarction at age 72 years, and her
up one flight of stairs. She also reports a chronic two younger brothers have coronary artery disease.
cough productive of clear sputum. She has a 100- Her mother died of colon cancer at age 65 years. Her
pack-year smoking history and is currently trying daughter and son currently have no health problems.
to quit. No family history is known of blood clots or stroke.

Medical History Social History

Her history is significant for coronary artery disease, Mrs. B. was born and raised in Washington State
and she is status post myocardial infarction and stent and is a retired dairy farmer. She recently moved into
placement in the left anterior descending artery in town to be closer to her daughter. Her husband is
1999. She has occasional angina and palpitations currently dying of lung cancer.
with exertion, relieved with nitroglycerin. She also
has chronic obstructive pulmonary disease, managed Review of Systems
with daily inhalers, occasional nebulizer treatments, Mrs. B. has had occasional nausea, vomiting, and
and steroid bursts; however, she does not require diarrhea over the past 7 months since her husband’s
supplemental oxygen. Her gastroesophageal reflux cancer diagnosis. She reports a 5-pound weight
disease responds well to a proton-pump inhibitor. loss over that same time period. The patient also

348
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

reports frequent postnasal drip and sinus conges- and a normal urinalysis. Her coagulation studies
tion. She denies fevers, chills, headaches, bladder (including prothrombin time, activated partial throm-
changes, arthralgias, or myalgias. boplastin time, and D-dimer) are all normal, except an
elevated D-dimer of 1500 ng/mL by enzyme-linked
immunosorbent assay. Chest radiograph shows no ele-
Objective
vation of the hemidiaphragm, infiltrate, or effusion;
Physical Examination lung parenchyma is consistent with severe emphysema.
General Mrs. B. is a well-nourished, well-developed
woman sitting comfortably in the chair, breathing Recent Studies
comfortably, and in no acute distress, speaking in Pulmonary-function tests 6 months ago: FEV1 of
full sentences. She has notable kyphosis. 1.01, 52% of predicted value; FVC, 2.32, 93% of
predicted value, with a ratio of 4.3. After bron-
Vital Signs chodilators, FEV1 increased to 1.13, 58% predicted
Blood pressure, 110/70 value, and FVC, to 2.58, or 103% of predicted value.
Heart rate, 90 Mammogram 6 months ago: negative. Colonoscopy
Respirations, 16 2 years ago: negative.
Height, 61 inches
Weight, 99 pounds Assessment
O2 saturation, 96% on room air
Working Diagnosis
Head, Eyes, Ears, Nose, and Throat Pupils are equal, Ipsilateral lower extremity edema, possibly due to
round, and reactive to light and accommodation. deep vein thrombosis (DVT).
Extraocular movements are intact. Sclerae are nonin-
jected and anicteric. Tympanic membranes are clear Differential Diagnosis
bilaterally. Nares and oropharynx are mildly erythe- A wide differential diagnosis exists for lower extrem-
matous with no exudate. ity edema associated with warmth, redness, and pain
(Landaw, 2004 ● A ). Table 40-1 outlines some of the
Lungs Good breath sounds are present bilaterally. most common causes.
She has a prolonged expiratory phase and an occa-
sional wheeze. Plan
Cardiovascular Regular rate and rhythm are noted When evaluating a patient with possible DVT, a
without audible murmur. pretest probability scoring system can be a helpful
guide in the diagnostic process. A score devised by
Abdomen Bowel sounds are normoactive. The Wells and colleagues is commonly used (Wells et al.,
abdomen is soft and nondistended, with no ascites or 1997 ●B ; Wells et al., 2003 ●
A). Table 40-2 summarizes
hepatosplenomegaly. the features of this pretest probability score and how
it applies to Mrs. B.
Genitourinary No pelvic masses are palpated.
Diagnostic
Rectal No rectal masses are palpated; stool is light In this case, Mrs. B. has a pretest probability score of
brown and guaiac negative. 4, indicating a high clinical probability of DVT, so
Doppler compression ultrasonography of the lower
Extremities No clubbing or cyanosis is seen. extremities is immediately performed. Her ultra-
Ipsilateral calf swelling is noted (left calf circumfer- sound reveals a large DVT in the left lower extremity.
ence measures 4 cm larger than the right calf), with Although she does not have acute respiratory symp-
mild erythema and warmth. A 3+ pitting edema is toms, she does have concerning dyspnea on exertion
found up to the left tibial tuberosity, with no edema and a positive D-dimer. It is important to rule out a
in the right leg. Tenderness appears on deep palpa- pulmonary embolism. A helical computed tomogra-
tion of the left calf muscles, with no palpable cord. phy (CT) scan is negative for pulmonary embolism or
Equivocal Homan’s sign is noted. The legs are warm evidence of malignancy but confirms significant
and well perfused, with symmetrical 2+ distal arterial emphysema. Because she is older than 50 years with
pulses. No skin vesicles or open sores are seen. an idiopathic first episode of venous thrombosis and
no family history, she is considered to be “weakly
Initial Laboratory and Radiology thrombophilic” and will be advised to undergo a
Examination limited screening for inherited hypercoagulable con-
Mrs. B.’s initial laboratory evaluation includes a ditions including activated protein C resistance, pro-
normal complete blood count, normal serum thrombin mutation, antiphospholipid antibodies,
chemistries including liver- and renal-function tests, and plasma homocysteine. If a DVT had developed

349
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

Table 40-1 Differential Diagnosis for Table 40-2 Wells Revised Model for
Unilateral Lower Extremity Determining Pretest
Edema Probability of Deep Vein
Thrombosis (DVT)
1. Popliteal (Baker’s) cyst. A popliteal cyst usually
causes calf symptoms when it is leaking or has Does Mrs. B.
ruptured. Leg swelling can occur when the Have This
popliteal vein is compressed and may Clinical Clinical
ultimately result in a DVT. Feature Score* Feature?
2. Knee injury. Pain, inflammation, and swelling
of the calf can accompany knee joint Active cancer
pathology. (treatment within
3. Drug-induced edema. Some drugs, such as past 6 months or
calcium channel blockers, cause leg swelling. current palliative
Although the edema is usually bilateral, it can treatment) 1 No
be asymmetric, especially when there is Paralysis, paresis,
underlying venous pathology. or recent plaster
4. Calf muscle pull or tear. Calf muscle injuries immobilization of
are frequently sustained during unusual the lower extremity 1 No
physical activity. Ecchymosis may be present as Recently bedridden
a sign of bleeding within muscle for more than 3 days
compartments of the affected leg. or major surgery within
5. Superficial thrombophlebitis. It is common to the past 12 weeks 1 No
find a palpable, tender cord in superficial vein Localized tenderness
phlebitis. along the distribution
6. Venous valvular insufficiency. Chronic venous of the deep venous
insufficiency can cause unilateral leg edema, system 1 Yes
especially when there is a past history of DVT Entire leg swollen 1 Yes
in the affected extremity. Calf swollen to more
7. Lymphedema. Lymphedema also causes than 3 cm larger than
chronic edema of the extremities and can be the asymptomatic side
unilateral in some cases. (measured 10 cm below
8. Cellulitis. Cellulitis is commonly associated tibial tuberosity) 1 Yes
with edema, warmth, pain, and discoloration. Pitting edema confined
to the symptomatic leg 1 Yes
From Landaw SA. Approach to the diagnosis and Collateral superficial
therapy of suspected deep vein thrombosis: veins (nonvaricose) 1 No
UpToDate. Available at www.uptodate.com, last
Previously documented
revised May 14, 2004. Accessed October 5, 2004.
deep-vein thrombosis 1 No
Alternative diagnosis at
before age 50 years, if she had a recurrent DVT or a least as likely as deep-
family history of thromboembolic disease or both, vein thrombosis −2 No
additional tests would be recommended to check for Mrs. B.’s Score* 4
deficiencies of antithrombin, protein C, and protein S *
A score greater than or equal to 2 indicates a high
(Bauer, 2001● B ). Although her cancer screening tests probability of DVT; a score less than 2 indicates
have recently been negative and her chest CT scan did that DVT is unlikely.
not show evidence of malignancy, any DVT recur- Data from Wells PS, Anderson DR, Rodger M, et al.
Evaluation of D-dimer in the diagnosis of
rence will warrant a further malignancy workup. suspected deep vein thrombosis. N Engl J Med
2003;349:1227–1235.
Therapeutic
Mrs. B. is started on low-molecular-weight heparin
subcutaneous injections (1 mg/kg twice daily) and (3) to prevent DVT recurrence. Mrs. B. is told that a
warfarin (Coumadin) oral therapy (5 mg daily, orally). recent evidence-based guideline recommends that
Her heparin will be discontinued after approximately she remain on anticoagulation therapy for 6 to 12
5 days, when her International Normalized Ratio months (Hyers et al., 2001 ● A). She is counseled
(INR) of prothrombin clotting time exceeds 2.0. regarding smoking cessation.

Patient Education Disposition

Mrs. B. is instructed about the three primary goals of Mrs. B. will make regular visits to the anticoagulation
treatment for DVTs: (1) to stop clot propagation in clinic for warfarin dosing to keep her INR between 2.0
the leg, (2) to stop embolic disease to the lungs, and and 3.0. A visiting nurse will administer her low-

350
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

molecular-weight heparin twice-daily injections for at predictive value of 94% (95% confidence interval,
least 5 days. She will have a follow-up physician visit in 87% to 98%) (Cogo et al., 1998 ● B ). If an initial ultra-
2 to 3 days. She is instructed to return immediately if sound study is negative and the clinical suspicion of
signs or symptoms of pulmonary embolism develop, DVT is high, a repeat study should be obtained 5 to
such as acute shortness of breath, tachypnea, tachycar- 7 days later. If results from the second study are
dia, distended neck veins, or hemoptysis. equivocal, venography can be used.
Several algorithms have been developed to diag-
nose DVT accurately by using a clinical pretest
DISCUSSION probability and noninvasive imaging. Recently, algo-
rithms have been revised to include D-dimer labora-
DVT falls within the spectrum of venous throm- tory analysis, when available and reliable. D-Dimer
boembolic disease, which includes both DVT and is a degradation product of cross-linked fibrin that
pulmonary embolism (PE). In people younger than is detectable at levels greater than 500 ng/mL of
60 years, the annual incidence of venous thrombo- fibrinogen equivalent units in nearly all patients
embolism is 117 cases per 100,000 persons. By age 85 with venous thromboembolism. A positive D-dimer
years, the incidence may be as high as 900 cases per cannot establish the diagnosis of venous throm-
100,000 (Ramzi and Leeper, 2004a ● A ). Improved boembolism because it is nonspecific and com-
diagnostic strategies and treatment guidelines have monly elevated in many patients hospitalized for
contributed to a significant decrease in mortality other conditions. The highly sensitive D-dimer test is
from venous thromboembolic disease in the past 10 useful to rule-out DVT because of its high negative
to 20 years (Ramzi and Leeper, 2004b ●A). When faced predictive value in cases in which DVT is unlikely. A
with a patient who has a suspected DVT or PE or recent systematic review assessed the sensitivity,
both, clinicians must consider the best approaches to specificity, likelihood ratios, and variability among
diagnosis, evaluation, and treatment. D-dimer assays (Stein et al., 2004● A ). Enzyme-linked
immunosorbent assays (ELISA) and quantitative
Diagnosis rapid ELISA are the most clinically useful because
they have the highest sensitivities (0.96 for both)
In diagnosing DVT, a careful history and physical and negative likelihood ratios (0.12 and 0.09,
examination must first be performed. Several com- respectively) for excluding DVT. A negative quanti-
mon risk factors should be addressed when taking a tative rapid ELISA result is as diagnostically useful
history, including recent surgery or immobilization, as a negative duplex ultrasound for excluding DVT,
previous history of DVT, malignancy, stroke, estro- especially in patients with a low pretest probability.
gen therapy, lower extremity trauma, pregnancy or In contrast, whole-blood agglutination and quanti-
postpartum state, and obesity. Classic symptoms of tative and semi-quantitative latex agglutination
DVT include swelling, pain, and discoloration in the assays had lower sensitivities.
involved extremity. Physical examination may reveal Two additional noninvasive studies have shown
a palpable cord (reflecting a thrombosed vein), promise: magnetic resonance venography and lower
ipsilateral edema, erythema, warmth, superficial extremity CT scans; however, these diagnostic stud-
venous dilation, or a combination of these (Ramzi ies are still under active investigation. Figure 40-1
and Leeper, 2004a ● A). Examination maneuvers, such outlines a summary of one common diagnostic
as Homan’s sign, can be done but are not highly algorithm.
sensitive or specific. Because of the inaccuracies of
physical examination, at least one imaging study is
Evaluation
generally indicated to confirm or exclude the diag-
nosis (Hirsh and Lee, 2002). Once a diagnosis of DVT is made and treatment is
Contrast venography is the “gold standard” for initiated, the second step is to conduct an evaluation
the diagnosis of DVT (Hull et al., 1981● B ). However, of possible causes. The thrombophilic state that leads
venography is usually not the initial diagnostic study to a DVT can be inherited or acquired. In some
performed because of patient discomfort and diffi- acquired cases, the etiology can be easily identified,
culty in obtaining an adequate study. In one study such as immobilization after surgery or long airplane
comparing venography with noninvasive studies, trips. Other acquired causes, such as malignancy and
venography could not be performed in 20% of cases the inherited conditions usually require further
because of contraindications or technical factors investigation. An extensive evaluation for malig-
(Heijboer et al., 1992 ●B ). Although several combina- nancy should be undertaken if a patient has a recur-
tions of noninvasive studies are acceptable, Doppler rent thrombosis or has abnormal clinical findings. In
ultrasonography is usually the first-line noninvasive selected subsets of patients in whom no obvious
diagnostic procedure for patients with suspected acquired cause is evident, a screen for hereditary
DVT. Compression ultrasonography has a positive thrombophilias should be performed. The likelihood

351
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

Suspect DVT

High clinical pretest probability–DVT likely Low clinical pretest probability–DVT unlikely

Consider starting with D-dimer test first

Doppler ultrasound (if available and reliable)
Or, skip to ultrasound

Ultrasound positive for DVT Ultrasound negative for DVT D-Dimer positive D-Dimer negative
Diagnosis of DVT confirmed DVT ruled out
Begin treatment

D-Dimer test Doppler ultrasound

(if available and reliable)
Otherwise, skip to repeat ultrasound

D-Dimer positive D-Dimer negative Ultrasound positive for DVT Ultrasound negative for DVT
repeat ultrasound in 1 week DVT ruled out Diagnosis of DVT confirmed DVT ruled out
Begin treatment (Consider repeat ultrasound if
D-dimer not available)

Repeat ultrasound positive for DVT Repeat ultrasound negative for DVT
Diagnosis of DVT confirmed DVT ruled out
Begin treatment (consider venography in rare cases)

Figure 40-1 New suggested diagnostic algorithm for patients with suspected deep vein thrombosis, by using a
D-dimer laboratory test. DVT, deep vein thrombosis.

of identifying a coagulation abnormality in appro- thromboembolism before age 50 years. A “weakly”

priate screening has been estimated to be as high as thrombophilic patient has no family history and a first
30% to 40% (Bauer and Lip, 2004● A). thrombophilic event after age 50 years. In both strong
No consensus exists on thrombophilia screening and weak patients, screening tests should be done for
guidelines; however, most recommendations are based activated protein C resistance, prothrombin mutation,
on the prevalence of inherited causes of hypercoagu- antiphospholipid antibodies, and plasma homocys-
lability and the patient’s history. If an acquired cause is teine. Additional tests for deficiencies of antithrom-
identified, it is usually not necessary to screen unless bin, protein C, and protein S are recommended only
the thrombosis occurs in association with oral contra- for individuals who fall into the strongly throm-
ceptive use or pregnancy; in unusual vascular beds bophilic category (Bauer, 2001 ● B).
such as portal, hepatic, mesenteric, or cerebral or in Once screening tests have been chosen, it is
patients with a history of warfarin-induced skin important to be aware of timing considerations. Acute
necrosis (Bauer and Lip, 2004● A). A “strongly” throm- thrombosis, comorbid illness, and anticoagulant
bophilic patient has a first idiopathic venous throm- therapy can affect the results; therefore confirmative
bosis before age 50 years, a history of recurrent testing should be done at least 2 weeks after comple-
thromboses, or at least one first-degree relative with tion of anticoagulant therapy.

352
 Chapter 40 Leg Pain and Swelling (Venous Thrombosis)

Treatment thromboembolic event have been revised (Hirsh

et al., 2003).
Most treatment protocols follow evidence-based rec-
ommendations that were put forth at the Sixth
American College of Chest Physicians Consensus
Conference on Antithrombotic Therapy and pub- Material Available on Student Consult
lished in January 2001 (Lip and Hull, 2004 ●A). Since
Review Questions and Answers about Venous
the publication of these recommendations, guide-
Thrombosis
lines for the patient with a first idiopathic venous

REFERENCES
Bauer KA, Lip GYH. Evaluation of the patient with Landaw SA. Approach to the diagnosis and therapy of sus-
established venous thrombosis. Available at www.upto- pected deep vein thrombosis: UpToDate. Available at
date.com, last revised May 14, 2004. Accessed October 5, www.uptodate.com, last revised May 14, 2004. Accessed
2004.●A October 5, 2004.●A
Bauer KA. The thrombophilias: Well-defined risk factors Lip GYH, Hull RD. Treatment of deep vein thrombosis:
with uncertain therapeutic implications. Ann Intern UpToDate. Available at www.uptodate.com, last revised
Med 2001;135:367–373.● B May 13, 2004. Accessed October 5, 2004.● A
Cogo A, Lensing AW, Koopman MM, et al. Compression Ramzi DW, Leeper KV. DVT and pulmonary embolism:
ultrasonography for diagnostic management of patients Part I: Diagnosis. Am Fam Physician 2004a;69:2829–
with clinically suspected deep venous thrombosis: 2836.●A
Prospective cohort study. BMJ 1998;316:17–20.● B Ramzi DW, Leeper KV. DVT and pulmonary embolism:
Heijboer H, Cogo A, Buller HR, Prandoni P, ten Cate JW. Part II: Treatment and prevention. Am Fam Physician
Detection of deep vein thrombosis with impedance 2004b;69:2841–2848.● A
plethysmography and real-time compression ultra- Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term,
sonography in hospitalized patients. Arch Intern Med low-intensity warfarin therapy for the prevention of
1992;152:1901–1903.● B recurrent venous thromboembolism. N Engl J Med
Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart 2003;348:1425–1434.● A
Association/American College of Cardiology Founda- Schulman S, Wahlander K, Lundstrom T, Clason SB,
tion guide to warfarin therapy. J Am Coll Cardiol Eriksson H. Secondary prevention of venous throm-
2003;41:1633–1652. boembolism with the oral direct thrombin inhibitor
Hirsh J, Lee AY. How we diagnose and treat deep vein ximelagatran. N Engl J Med 2003;349:1713–1721.● A
thrombosis. Blood 2002;99:3102–3110. Stein PD, Hull RD, Patel KC, et al. D-Dimer for the exclu-
Hull RD, Hirsh J, Sackett DL, et al. Clinical validity of a sion of acute venous thrombosis and pulmonary
negative venogram in patients with clinically suspected embolism: A systematic review. Ann Intern Med
venous thrombosis. Circulation 1981;64:622–625.● B 2004;140:589–602.● A
Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic ther- Wells PS, Anderson DR, Bormanis J, et al. Value of assess-
apy for venous thromboembolic disease. Chest ment of pretest probability of deep-vein thrombosis
2001;119:176S–193S.● A in clinical management. Lancet 1997;350:
Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of 1795–1798.● B
low-intensity warfarin therapy with conventional- Wells PS, Anderson DR, Rodger M, et al. Evaluation of
intensity warfarin therapy for long-term prevention of D-dimer in the diagnosis of suspected deep vein throm-
recurrent venous thromboembolism. N Engl J Med bosis. N Engl J Med 2003;349:1227–1235.● A
2003;349:631–639.● A

353
 C h a p t e r

41 Tiredness (Anemia)

Paul Paulman

Medical History
KEY POINTS Operations Abdominal hysterectomy 4 years ago for
postmenopausal bleeding, no endometrial hyperpla-
1. Anemia should be considered not a primary sia or malignancies were found.
diagnosis, but a marker for other disease
processes. Allergies No medication or seasonal allergies are
2. The most common symptoms of anemia are present.
dyspnea with exertion, weakness, headache,
lethargy, and palpitation. Illnesses Hyperlipidemia, postmenopausal bleeding,
3. Most causes of anemia can be determined in a mild arthritis in both knees.
primary care office through history, physical
examination, and judicious use of standard lab- Hospitalizations She had two normal vaginal deliv-
oratory tests. eries and a hysterectomy.

Medications She is taking atorvastatin (Lipitor),

10 mg/day, glucocosamine and chondroitin sulfate,
aspirin (81 mg/day), and over-the-counter vitamins
INITIAL VISIT with iron.

Subjective Family and Social History

Sandy is a vice president in charge of operations at
Patient Identification and Presenting a local telemarketing firm. She is married, with two
Problem children and two grandchildren. She does not
Sandy is a 64-year-old white American woman who smoke or use illicit drugs and drinks less than one
appears for an office visit with the complaint of “just alcoholic beverage per day on average. She exercises
feeling tired.” 30 minutes aerobically per day. Sandy’s parents
were first-generation immigrants from Sweden.
Present Illness The family history is positive for thyroid disease
Sandy has been fatigued for more than 12 months (mother) and colon cancer (father). No family his-
with gradual worsening. Her husband states that she tory is known of anemia, depression, sleep disor-
“looks pale.” She has had no depressive symptoms ders, collagen vascular disease, breast cancer, or
and no symptoms to suggest a sleep disorder. She arthritis.
has had no wheezing or chest pain but does become
dyspneic after climbing two flights of stairs. No Review of Systems
changes have occurred in her diet; she eats a “stan- Sandy denies any blood loss, pain, nausea, vomiting,
dard American diet.” She has no history of thyroid fever, chills, or diarrhea. She has not had any heat or
disease and no nausea, vomiting, or diarrhea. She cold intolerance. She has had no cough or headache
has had no blood loss and no fevers, chills, or joint and has not been exposed to tuberculosis or other
pain. infectious diseases. No one else at her workplace has

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

354
 Chapter 41 Tiredness (Anemia)

experienced similar symptoms. She has not used shows a hemoglobin of 5.3 g/dL with macrocyctic
new herbal or over-the-counter preparations. She indices, a white blood cell (WBC) level of 7200/μL,
has had no changes in her sleep patterns and has not and adequate platelets. A thyroid-stimulating hor-
experienced any emotional trauma or family dis- mone, complete metabolic profile including elec-
cord. She denies loss of appetite or feelings of trolytes, B12 level, red blood cell (RBC) and serum
sadness. folate levels, and intrinsic factor antibody assay are
pending.
Objective
Assessment
Physical Examination
Vital Signs Working Diagnosis
Height, 66 inches Macrocytic anemia. Given Sandy’s age, symptom
Weight, 148 pounds complex, including the gradual onset of symp-
Blood pressure, 126/62 mm Hg toms, the hemoglobin level, and her ethnic back-
Pulse, 102 and regular ground, pernicious anemia (B12 deficiency) must
Temperature, 98.2˚F (36.8˚C) (oral) be considered.
Respirations, 16 per minute, unlabored
Differential Diagnosis
General Alert, very pleasant and cooperative, well 1. Alcoholism. Alcohol has direct toxic effects on
oriented. bone marrow and can decrease red cell folic acid,
leading to a macrocytic anemia. Sandy has no his-
Integument Marked pallor, no rashes. tory of excessive or problematic alcohol intake.
2. Medications. Several medications, most notably anti-
Lymph No adenopathy. convulsants, antineoplastics, oral contraceptives,
and sulfa-derived medications, can cause macro-
Head, Eyes, Ears, Nose, and Throat Palpebral con- cytic anemia. None of Sandy’s medications have
junctivae are pale; otherwise no abnormalities. been closely associated with macrocytic anemia.
3. Thyroid disorders. Hypothyroidism causes a
decrease in red cell production and can affect
Neck Trachea midline, thyroid not palpable, carotids
release of erythropoietin from the kidneys. Sandy
full.
has no symptoms to suggest a thyroid disorder.
4. Liver disease. Hepatic dysfunction also can affect
Lungs Clear. erythropoietin release, as well as disrupting iron
metabolism. Sandy has no symptoms of liver
Heart Tachycardia; regular and rhythmic with no disease.
murmurs or rubs. 5. Bone marrow disorders. Primary bone marrow
disorders, including marrow replacement and
Breasts No masses, tenderness, or nipple discharge. malignancies, can cause a macrocytic anemia. The
presence of a normal WBC and platelet count
Neurologic Mild decrease in vibratory sense in both makes a bone marrow disorder unlikely.
lower extremities. 6. Folic acid deficiency. Because of the relatively low
level of folic acid reserves in the human body (4 to
Abdomen Soft, normoactive bowel sounds, with no 5 months’ supply), folic acid deficiency is a
masses, tenderness, or organomegaly. common cause of macrocytic anemia. Folic acid
deficiency can occur because of increased require-
ment (pregnancy, malignancy, hemodialysis, or
Pelvic Normal external genitalia, vagina normal, decreased absorption or intake of folic acid [e.g.,
cervix and uterus surgically absent, adnexa not pal- malabsorptive syndromes, alcoholism, or eating
pable, no masses. Stool test negative for blood. disorder]). Sandy has no symptoms suggestive of
conditions causing folic acid deficiency.
Extremities Loss of color in palmar creases with no
clubbing, cyanosis, or edema.
Plan and Treatment
Laboratory Tests Sandy is hospitalized for monitored transfusion of 2
Office laboratory hemoglobin level is 5.4 g/dL. A stat units of packed red blood cells after blood has been
complete blood count (CBC) run at the hospital drawn for diagnostic studies.

355
 Chapter 41 Tiredness (Anemia)

Patient Education
Table 41-1 Normal Hemoglobin Values
Causes of macrocytic anemia and risks and benefits
of transfusion were discussed with Sandy. Age Male Female

Newborn 15.0–21 g/dL 15.0–21.0 g/dL

Disposition
3 months 9.5–12.5 g/dL 9.5–12.5 g/dL
Sandy was discharged to home the following morn- 1 year to
ing with a hemoglobin of 8.8 g/dL and was asked to puberty 11.0–13.5 g/dL 11.0–13.5 g/dL
return to the office in 3 days for laboratory results Adults 13.5–17.5 mg/dL 11.5–15.5 g/dL
and further treatment. She is instructed in home
fecal occult blood testing and given three test cards.

(microcytic, normocytic, or macrocytic) and can be

FOLLOW-UP VISIT caused by decreased RBC production, increased RBC
destruction, an increase in plasma volume (Table
Subjective 41-2), or a combination of causes. Anemia should
not be considered a primary diagnosis, but rather a
Sandy returns to the office in 3 days and reports that sign of nutritional deficiency (e.g., iron, folate, B12)
she feels much better. Her exercise tolerance has or other pathologic processes (e.g., microcytic ane-
improved. She experienced no problems with the mia is often seen in elderly patients with colon can-
transfusion. cer). The signs and symptoms seen in anemia are
caused by decreased delivery of oxygen to peripheral
Objective tissues, or by the deficiency of the nutrient causing
the anemia.
Sandy’s tachycardia (heart rate, 72 beats/min) and
her pallor have improved. No other major changes
in her physical examination were found. Her hemo- Signs and Symptoms of Anemia
globin is 8.6 g/dL; her thyroid stimulating hormone Mild anemia may cause few or no symptoms. The
(TSH) is 2.1 in mIU/L (normal range, 0.4 to 5.0 most common symptoms of anemia are dyspnea
mIU/L); her metabolic profile is normal, serum folic with exertion, weakness, headache, lethargy, and pal-
acid level is 10 μg/L (normal range, 5.0 to 25 μg/L), pitations. Older patients may experience angina pec-
red blood cell folic acid level is 310 μg/L (normal toris, heart failure, claudication, confusion, or retinal
range, 166 to 690 μg/L), B12 level is 35 mg/L (normal hemorrhage. Physical signs include pallor of the skin
range, 200 to 800 mg/L), intrinsic factor antibody or mucous membranes, tachycardia, systolic heart
assay is positive (normal value, negative). All three
fecal occult blood tests are negative.

Assessment
Table 41-2 Common Causes of Anemia
Sandy has pernicious anemia (vitamin B12 de-
Increased
ficiency). Decreased RBC Increased RBC Plasma
Production Destruction Volume
Plan
Iron deficiency Hemolytic Pregnancy
After discussing treatment options, Sandy chose (microcytic) anemias (normocytic)
weekly intramuscular injections of 1000 μg of vita- Sideroblastic (normocytic)
min B12 for 4 weeks, followed by 1000 μg of vitamin (microcytic)
Thalassemias
B12 orally every day. She will return to the office in 2
(microcytic)
weeks for hemoglobin and vitamin B12 levels. Lead poisoning
(microcytic)
Anemia of chronic
DISCUSSION disorders
(normocytic or
Anemia is a common problem seen in primary care microcytic)
practices, and the most common cause of anemia is Vitamin B12 or
iron deficiency. Anemia is an absolute or relative folate deficiency
reduction of hemoglobin or red blood cells (RBCs). (macrocytic)
Bone marrow
Normal hemoglobin values are listed by age and gen-
failure (normocytic)
der in Table 41-1. Anemias are classified by RBC size

356
 Chapter 41 Tiredness (Anemia)

murmur, jaundice, or loss of color of the palmar flex- poisoning include pallor, abdominal pains, irritability
ion creases (if the hemoglobin level is 7 g/dL or less). followed by lethargy, anorexia, ataxia, slurred speech,
The severity of signs and symptoms of anemia and convulsions. Laboratory findings include
depends on the degree and rapidity of onset of the basophilic stippling of RBCs, elevated lead level, and
anemia and the age and the general medical condi- elevated free erythrocyte protoporphyrin level. The
tion of the patient. Sandy exhibited weakness, dysp- treatment of lead poisoning consists of removing the
nea on exertion, skin pallor, loss of color of palmar source of exposure and removal of lead through chela-
creases, and tachycardia as manifestation of her ane- tion when clinically indicated. Because lead poisoning
mia. Her neurologic findings in her lower extremities is very widespread, screening is recommended for any
are likely due to her B12 deficiency. child at risk for lead exposure and for any child who
demonstrates cognitive, language, or learning deficits.
Causes of Anemia
Anemia of Chronic Disorders A number of chronic
Anemia Due to Decreased Production of infections, connective tissue diseases, renal failure,
RBCs and malignancies can cause a microcytic hypo-
Sideroblastic Anemia Sideroblastic anemia is char- chromic anemia by blocking erythropoietin
acterized by hypochromic RBCs, increased marrow response, decreasing RBC life span, and decreasing
iron, and ringed sideroblasts in the bone marrow. iron release from macrophages. The characteristics
Ringed sideroblasts are abnormal erythroblasts with of anemia of chronic disorders include mild anemia
iron granules surrounding the nucleus. Sideroblastic (hemoglobin level rarely less than 9.0 g/dL),
anemia can be hereditary, caused by a defect in heme decreased serum iron and total iron-binding capac-
synthesis, or acquired from bone marrow dysfunc- ity levels, and normal or increased ferritin level.
tion or replacement. Some patients with hereditary Treatment of the anemia usually depends on treat-
sideroblastic anemia respond to pyridoxine therapy. ment of the underlying cause. Erythropoietin has
Folic acid therapy also is recommended. In acquired been successfully used in some cases of anemia of
sideroblastic anemia, treatment is aimed at correct- chronic disorders (Krantz, 1994 ●A ).
ing the cause of the bone marrow failure. For some
patients, the only treatment is repeated blood trans- B12 and Folate Deficiency Deficiencies of both vita-
fusions, sometimes resulting in iron overload requir- min B12 and folate can cause a macrocytic anemia.
ing chelation therapy. Erythropoietin has been used The most common cause of B12 deficiency is malab-
in some cases of sideroblastic anemia. sorption (including that due to pernicious anemia).
The most common causes of folate deficiency
Thalassemia The thalassemias (alpha and beta) are include dietary deficiency, malabsorption, excessive
a group of genetic disorders characterized by a folate demand, and drugs (including alcohol and
reduced rate of production of α- or β-globin chains. chemotherapeutic agents). The diagnosis can be
The severity of the disease is dependent on the made through blood levels of vitamin B12 or folate or
number of genes affected. Thalassemia is seen most both, and replacement therapy can be instituted.
commonly in patients from the “thalassemia belt” Vitamin B12 is usually replaced by the parenteral
(southern Europe, northern Africa, the Middle East, route (500 to 1000 μg/month), because malabsorp-
Indian subcontinent, and Southeast Asia, including tion is the leading cause of vitamin B12 deficiency.
Indonesia). Patients with thalassemia are first seen Oral B12, given at dose of 1000 μg/day, has been suc-
with microcytic hypochromic RBCs with or without cessfully used to treat pernicious anemia (Oh and
anemia, depending on the severity of the genetic Brown, 2003 ● A ). Folate can usually be replaced via
defect. Hemoglobin electrophoresis is usually the oral route (5 mg/day). Signs and symptoms
required to make the diagnosis. Treatment depends include mild jaundice, glossitis, angular stomatitis,
on the severity of the illness and is aimed at main- and peripheral sensory neuropathy. Folate deficiency
taining the hemoglobin at 10 g/dL or more. does not cause neurologic symptoms. Laboratory
Treatment modalities include regular blood transfu- findings include macrocytic RBCs, hypersegmented
sions (with iron chelation if iron overload occurs), neutrophils, and elevated bilirubin level.
folic acid supplementation, splenectomy if hemolysis The intrinsic factor antibody assay is often posi-
is a problem, and bone marrow transplantation in tive in pernicious anemia; this assay has decreased
very severe cases (Schrier, 1994 ●
A). the need to perform the Schilling test to diagnose
pernicious anemia (Davenport, 1996 ● A ). In patients
Lead Poisoning Lead causes a microcytic hypo- with vitamin B12 deficiency, both vitamin B12 and
chromic anemia by inhibiting heme and globin syn- serum folate levels can be low. A low RBC folate level
thesis. Children are at highest risk for lead poisoning is a more precise indicator (less than 150 μg/dL) of
from various sources including ingestion of lead- chronic folate deficiency than is a serum folate level
containing paint chips. Signs and symptoms of lead (Schrier, 2005).

357
 Chapter 41 Tiredness (Anemia)

Bone Marrow Failure Replacement or an intrinsic Initial Evaluation of Anemia in the Office
defect of bone marrow usually is the cause of nor-
mocytic anemia. Treatment is aimed at correcting A cause for most cases of anemia can be determined
the cause of the marrow replacement or defect, if by a thorough history and physical examination and
possible, or maintaining an acceptable hemoglobin judicious use of the clinical laboratory. Patients with
level via transfusion. anemia from suspected underproduction of RBCs
should be screened for gastrointestinal blood loss;
iron studies are indicated if RBC indices are micro-
Anemia Due to Increased RBC Destruction cytic. Vitamin B12 and folate levels should be
A number of intrinsic and acquired illnesses obtained in patients with macrocytic RBC indices,
including splenomegaly, hemoglobinopathies with or without anemia. Bone marrow examination
(e.g., sickle cell disease), infections, drug effects, may be helpful in some patients with anemia from
collagen vascular diseases, and tumors can cause RBC underproduction, especially those for whom
an increase in RBC destruction. Laboratory find- standard treatment protocols fail. If hemolysis is sus-
ings include an elevated reticulocyte count, abnor- pected, a reticulocyte count, haptoglobin level, and
mal RBC morphology, increased unconjugated examination of the peripheral blood smear for
bilirubin level, decreased haptoglobin level, and abnormal cell forms are reasonable screening tests.
increased plasma hemoglobin level. Treatment is Lead screening is recommended for children with
aimed at correcting the cause of hemolysis or at microcytic anemia. Other tests are indicated based
maintaining an acceptable hemoglobin level on the history and results of screening laboratory
through transfusion. evaluations. Further testing may be indicated to eval-
uate uncommon causes of anemia.
Anemia Due to Increased Plasma Volume
A relative anemia due to hemodilution from
increased plasma volume can be seen in various Material Available on Student Consult
conditions including pregnancy. This disease Review Questions and Answers about Anemia
responds to treatment of the underlying condition.

REFERENCES
Davenport, J. Macrocytic anemia. Am Fam Physician Schrier SL. Thalassemia: Pathophysiology of red cell
1996;53:155–162.● A changes. Annu Rev Med 1994;45:211–218.● A
Krantz SB. Pathogenesis and treatment of the anemia of Schrier SL. Diagnosis and treatment of vitamin B12 and folic
chronic diseases. Am J Med Sci 1994; 307:353–359.●
A acid deficiency. Available at www.uptodate.com/
Oh RC, Brown DL. Vitamin B12 deficiency. Am Fam physicians/hematology_toclist.asp, Accessed 9/14/2005.
Physician 2003;67:979–986.●A

SUGGESTED READINGS
Brill JR, Baumgardner DJ. Normocytic anemia. Am Fam Hoffman R, Benz E, Shattell S, eds. Hematology: Basic
Physician 2000;62:2255–2264. Principles and Practice. New York: Churchill-
Centers for Disease Control and Prevention. Recommenda- Livingstone, 2000.
tion to prevent and control iron deficiency in the United
States. Min Recomm Rep 1998;47:1–29.

358
 C h a p t e r

42 Right Upper Quadrant

Abdominal Pain (Cholelithiasis)
Joel J. Heidelbaugh

been evaluated in the office of her family physician

KEY POINTS and by other providers over the past few months for
similar complaints, which were thought to be “the
1. Gallstones are extremely common in our soci- stomach flu,” “reflux disease,” and “all in my head,”
ety, with a 35% lifetime prevalence for women, according to the patient.
compared with a 20% lifetime prevalence for
men. Present Illness
2. Cholesterol stones are the most common form Sherrie states that this episode of RUQ abdominal
of gallstones in the Western world. pain began to develop 2 days ago after she consumed
3. Observational studies on the natural history of beef tacos, nachos, hot salsa, and a caffeinated bever-
asymptomatic gallstones report a complication age. She has experienced similar pain numerous times
rate of 1% to 2% per year. in the past, and it has always resolved on its own over
4. Because the incidence of the development of several days to weeks, or with antacids. At a previous
biliary complications as the presenting com- visit, she was advised to try Prilosec (omeprazole) on
plaint of gallstone disease is rare (0 to 5.5%), demand for symptomatic relief and has seen only a
the recommendation is for expectant manage- slight improvement of her symptoms after this treat-
ment of asymptomatic gallstones. ment. In this instance, the RUQ abdominal pain
5. Transabdominal ultrasonography is the gold gradually progressed to 10/10, is radiating to her right
standard for diagnosing gallstones in most shoulder, and she has become nauseated with several
patients. episodes of nonbloody, nonbilious emesis yesterday.
6. Laparoscopic cholecystectomy is the gold stan- Sherrie is uncertain whether she has been febrile at
dard for the treatment of acute cholelithiasis. home. She complains that her pain becomes more
7. Laparoscopic cholecystectomy and endoscopic severe when she takes a deep breath.
stone extraction via either pre- or postoperative
endoscopic retrograde cholangiopancreatogra- Medical History
phy together make up the gold standard for Sherrie has a medical history significant for a mixed
treatment of choledocholithiasis. anxiety/depression disorder since her teenage years
and post-traumatic stress disorder (PTSD) resulting
from a domestic assault by her boyfriend, the father of
INITIAL VISIT her two children, several months ago. She is currently
under the care of both a psychiatrist and a psycholo-
Subjective gist. Sherrie has had two normal spontaneous vaginal
deliveries at term without any complications, and no
Patient Identification and Presenting surgical history other than vaginal laceration repairs
Problem subsequent to her deliveries. Currently, she takes
Sherrie M. is a 29-year-old African-American with Ortho-Novum 7/7/7 daily for contraception, as well as
the complaint of right upper quadrant (RUQ) clonazepam (Klonopin), 0.5 mg twice daily; bupropion
abdominal pain that occasionally radiates to her (Wellbutrin), 100 mg twice daily; and paroxetine
right shoulder, as well as episodic nausea. She has (Paxil), 40 mg daily for her psychiatric disorders.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

359
 Chapter 42 Right Upper Quadrant Abdominal Pain (Cholelithiasis)

Family History Lungs Clear to auscultation bilaterally without

Sherrie is unaware of her father’s medical history, as wheezes, rales, or rhonchi.
he has only rarely been involved in her life. Her
mother has hypertension, has poorly controlled type Heart Regular rate and rhythm, S1, S2, no murmurs,
2 non–insulin-requiring diabetes mellitus, and is rubs, or gallops.
morbidly obese. Sherrie has two younger sisters who
are alive and well without any significant medical Abdomen Obese, soft, with marked tenderness dur-
problems. ing deep inspiration along the ninth right costal
margin in the midclavicular line (a positive
Social History Murphy’s sign). The liver percusses to approxi-
Sherrie has 2 boys, ages 4 years and 19 months. She mately 10 cm below the last rib in the midclavicular
works part-time as a cashier at a fast-food restaurant. line. Although the abdominal examination is diffi-
She has smoked approximately 1/2 pack of cigarettes cult because of the patient’s body habitus, the
per day since she was age 15 years, denies any current abdomen was felt to be nondistended, with positive
alcohol or illicit drug use, but has consumed alcohol on bowel sounds, no hepatosplenomegaly, bruits,
occasion in the past. Her boyfriend, the father of her masses, ascites, or fluid wave. Abdominal and
two children, is now in jail on account of spousal abuse. inguinal hernias appeared to be absent. Pelvic exam-
ination was deferred.
Review of Systems
Extremities Warm and well perfused, without
Sherrie admits sporadic nausea and nonbloody, non-
cyanosis, clubbing, or edema.
bilious emesis, but denies diarrhea or constipation;
bloody, dark, or tarry stools; abdominal trauma; Neuromuscular Cranial nerves II to XII are grossly
headache; chest pain; palpitations; syncope; cough; or intact, with no focal deficits on strength and sensory
any genitourinary symptoms. Her last normal men- testing.
strual period was 1 week ago. She admits occasional
anorexia secondary to epigastric and RUQ pain after Rectal Guaiac negative, no masses, fissures, fistulae,
eating hot, spicy, and fatty foods, and does not think or hemorrhoids.
that she has lost any weight recently. Sherrie denies
any other constitutional symptoms or other recent Skin No significant lesions.
illness. She denies taking any nonsteroidal anti-
inflammatory drugs or aspirin in the recent past. Laboratory Studies
A complete blood count revealed 12,200/mm3 white
Objective blood cells, with a differential of 67% neutrophils,
24% leukocytes, and 9% monocytes. Serum amylase
Physical Examination is 42 IU/L; lipase is 17 IU/dL; alkaline phosphatase is
General Sherrie is an obese woman sitting on the 93 IU/L; alanine aminotransferase (ALT) is 39 IU/L;
examination table in mild distress. aspartate aminotransferase (AST) is 26 IU/L; and
total bilirubin is 0.5 mg/dL. Serum chemistries were
Vital Signs otherwise normal. A urinalysis and a urine preg-
Height, 5 feet 3 inches tall nancy test were normal.
Weight, 254 pounds
Body mass index, 45 Radiographic Studies
Temperature, 37.6˚C (99.6˚F) An abdominal ultrasound revealed multiple hyper-
Blood pressure, 139/87 echoic, mobile gallstones and a moderate amount of
Pulse, 88 and regular gallbladder sludge. A positive sonographic Murphy’s
Respiratory rate, 18 sign was noted. The common bile duct (CBD) meas-
ured 0.5 mm in diameter (within normal limits), with
Head, Eyes, Ears, Nose, and Throat Head is normo- no evidence of gallbladder wall thickening or peric-
cephalic, atraumatic; pupils are equally round and holecystic fluid. The remainder of the ultrasound
reactive to light; extraocular movements are full; evaluation was within normal limits. A cholescintigra-
sclerae are anicteric; external auditory canals and phy (HIDA) scan was negative for CBD obstruction.
tympanic membranes are clear bilaterally; orophar-
ynx is without significant lesions; dentition is good.
Assessment
Neck Supple, with full range of motion and no cer- Working Diagnosis
vical lymphadenopathy, jugular venous distention, The working diagnosis for Sherrie is acute calculous
thyromegaly, or carotid bruits. cholecystitis.

360
 Chapter 42 Right Upper Quadrant Abdominal Pain (Cholelithiasis)

Differential Diagnosis (Box 42-1) 3. Perforated peptic ulcer. A perforated gastric or

1. Dyspepsia. This term is used to describe a constella- duodenal ulcer often is first seen with epigastric
tion of symptoms including heartburn, regurgita- or upper quadrant abdominal pain or both with
tion, reflux, and epigastric abdominal pain. Patients radiation to the back or upper extremities, nau-
may describe this term as “gas,”“bloating,”“frequent sea, and vomiting. Most patients with this syn-
belching,” and “stomach pain.” Dyspepsia can be drome will have a gradually worsening case of
associated with numerous gastrointestinal (GI) dis- epigastric abdominal pain that may become unre-
orders, including gastric or duodenal ulcers or both, lenting, leading to generalized peritonitis, abdom-
gastroesophageal reflux disease, upper GI malig- inal rigidity, the disappearance of bowel sounds,
nancies, pancreatitis, hiatal hernia, cholelithiasis, and the increased probability of cardiovascular
choledocholithiasis, as well as psychiatric disorders collapse and sepsis. If the suspicion for a perfo-
including anxiety and depression, medication side rated ulcer is high, then plain film radiographs
effects, acute myocardial infarction, and angina. should be obtained to evaluate for the presence of
2. Choledocholithiasis. CBD stones are found in up free air under the diaphragm. Prompt surgical
to 10% of patients with symptomatic cholelithia- evaluation should be obtained, and the patient
sis, yet routine ultrasonography may miss up to should be hemodynamically stabilized.
one third of stones present in the CBD as a result 4. Acute appendicitis. The diagnosis of appendicitis is
of overlying loops of bowel (Avunduk, 2002● B). usually made on a clinical basis, considering the
CBD stones can be either primary (those that combination of the patient’s presenting physical
develop in the duct itself) or secondary (those signs and symptoms. Often this includes a sudden
that originate in the gallbladder and migrate). onset of epigastric or periumbilical pain that will
Approximately 95% of patients with cholesterol eventually migrate to the right lower quadrant
gallstones also have stones in the CBD (Avunduk, (RLQ). The characteristic findings in a patient with
2002● B). If these stones are discovered after a acute appendicitis include a low-grade fever, leuko-
cholecystectomy, they may have been overlooked cytosis, and tenderness over McBurney’s point (the
(retained) or may have formed after the surgery junction of the middle and outer thirds of the line
(recurrent). Bile stasis associated with partial from the umbilicus to the anterior superior iliac
obstruction or marked dilation of the duct may spine). Rovsing’s sign (pain sensed in the RLQ after
promote choledocholithiasis. Patients with chole- deep palpation in the left lower quadrant), the
docholithiasis often appear similar to patients psoas sign (worsening of pain with extension of the
with cholelithiasis, but they may also have con- ipsilateral hip joint, which stretches the iliopsoas
comitant obstructive jaundice, cholangitis, pan- muscle), the obturator sign (pain produced by
creatitis, hemobilia, or a combination of these. internal rotation of the ipsilateral flexed thigh), or

Box 42-1 Differential Diagnosis of Cholelithiasis

Gastrointestinal Psychiatric
Acute acalculous cholecystitis Anxiety
Appendicitis Major depressive disorder
Choledocholithiasis Panic disorder
Dyspepsia Post-traumatic stress disorder
Gastroesophageal reflux disease (GERD)
Gastrointestinal malignancy Pulmonary
Hiatal hernia
Pleurisy
Hepatitis (acute)
Pneumonia
Intestinal ischemia
Pneumothorax
Intestinal obstruction/ileus
Peptic ulcer disease
Renal
Perforated peptic ulcer
Pancreatitis Pyelonephritis
Renal colic
Cardiovascular
Other
Acute myocardial infarction
Angina (unstable) Abdominal muscle strain
Ruptured aortic aneurysm Abdominal trauma

361
 Chapter 42 Right Upper Quadrant Abdominal Pain (Cholelithiasis)

a combination of these may suggest irritation or for these conditions and make an expedient referral
rupture of the appendix and peritonitis. Atypical for radiographic and surgical evaluations.
presentations of appendicitis are exceedingly com- 7. Acute acalculous cholecystitis. A severe form of
mon, especially in obese patients, as not all appen- gallbladder inflammation, this condition occurs
dicitis appears with RLQ pain. Plain radiographs, in the absence of gallstones. Most patients who
abdominal/pelvic ultrasonography, computerized experience this condition are elderly or debili-
tomography (CT), or a combination of these may tated as a result of comorbid disease or trauma, in
be useful in locating an appendicolith, abscess, the intensive care unit, in the postoperative
regional inflammation, or signs of perforation. period, receiving total parenteral nutrition or a
5. Pancreatitis. This condition, in both its acute and combination of these. With this condition, a high
chronic forms, usually is first seen with epigastric incidence is seen of gallbladder necrosis, gan-
or upper quadrant abdominal pain or both that grene, perforation of the gallbladder, sepsis, and
may radiate to the midthoracic area of the back, potentially death (Avunduk, 2002● B).
chest, flanks, and lower abdomen, and is associ- 8. Anxiety/depression/post-traumatic stress disorder.
ated with nausea, vomiting, anorexia, and abdom- Many patients with any or a combination of these
inal distention secondary to ileus. Leukocytosis disorders have a variety of vague systemic com-
and elevations in serum amylase, lipase, glucose, plaints, with one of the more common complaints
and lactate dehydrogenase are common, depend- being episodic “stomach pain.” This complaint is
ing on the time of the clinical presentation. frequently associated with nausea, vomiting,
6. Intestinal obstruction/gallstone ileus. Mechanical anorexia, and dyspepsia, and it may wax and wane
obstruction may occur in the setting of a large gall- with the patient’s psychological symptoms.
stone that has traveled into the small bowel (usually
the ileum) by way of a cholecystenteric fistula. The Plan
Mirrizzi syndrome occurs when a gallstone becomes
impacted in the cystic duct and may obstruct the Diagnostic
common hepatic duct either from direct obstruc- Risk factors for cholelithiasis are presented in Box
tion or from inflammatory changes around the duct 42-2. When a physician encounters a patient with
itself (Avunduk, 2002 ●B). A high level of suspicion abdominal pain, the first step in diagnostic planning
should prompt the clinician to evaluate the patient is to determine the severity of the pain and the

Box 42-2 Risk Factors for the Development of Cholelithiasis

Age: incidence increases with age in both Ileal disease, bypass, or resection: Crohn’s dis-
women and men ease or surgical resection of distal small bowel
Cystic fibrosis with pancreatic insufficiency: leads to the impairment of bile acid reabsorp-
largely due to malabsorption of bile salts tion
Diabetes mellitus: due to increased biliary cho- Medications: ceftriaxone, clofibrate, estro-
lesterol secretion and obesity, if applicable gens, octreotide, progestogens
Diet: high in calories, refined carbohydrates, Obesity: bile in people who are obese is more
polyunsaturated fats, and cholesterol lithogenic
Dyslipidemia: decreased low-density lipopro- Pregnancy: the increase of estrogens and
teins with increased hepatic uptake, increased progesterone leads to impaired gallbladder
serum triglycerides, decreased serum high- emptying
density lipoproteins Rapid weight loss: cholesterol is mobilized from
Family history: prevalence varies in different peripheral adipose tissue and is secreted into
populations (i.e., >75% of Pima Indian women bile, leading to cholesterol supersaturation
have gallstones by age 30 yr) Spinal cord injury: depending on level of injury
Gender: 2 to 3 times higher risk in women (i.e., thoracic), may lead to gallbladder stasis
Genetic predisposition: greater in Native Total parenteral nutrition: promotes gallblad-
American Pima Indians, Chileans, Scand- der sludge and stasis
inavians, those with apolipoprotein E4/E4 alleles Truncal vagotomy: may decrease gallbladder
motility

Adapted from Avunduk C. Gallstones. In Avunduk C (ed): Manual of Gastroenterology, Diagnosis and Therapy, 3rd
ed. Philadelphia, Lippincott Williams & Wilkins, 2002, pp 340–350.

362
 Chapter 42 Right Upper Quadrant Abdominal Pain (Cholelithiasis)

potential for complications from underlying pathol- tivity and specificity in detecting these stones.
ogy. The physician must then determine whether the Magnetic resonance cholangiopancreatography is
patient warrants an emergency workup with labora- another noninvasive modality for identifying gall-
tory tests, radiographic imaging, expectant manage- stones and CBD stones, but it often has a lower sensi-
ment, or a prompt surgical evaluation (Table 42-1). tivity and specificity as compared with ultrasound and
Serum bilirubin, alkaline phosphatase, amylase, is more costly (Horton and Bilhartz, 2002● A).
alanine aminotransferase, and aspartate aminotrans-
ferase may be elevated in patients with acute cholecys- Therapeutic
titis, and the patient may exhibit a leukocytosis with a Both surgical and nonsurgical approaches exist for
left shift with or without the presence of ascending the patient with symptomatic cholelithiasis. The
cholangitis. The evaluation of gallstones via abdomi- laparoscopic cholecystectomy is the recommended
nal ultrasonography is currently the best screening treatment of choice for long-term management of
modality, with sensitivity and specificity above 90% symptomatic biliary colic. When it is suspected that
(Horton and Bilhartz,2002 ● A). A CT scan of the upper the operation may be complicated, or if the patient is
abdomen is more sensitive than conventional plain morbidly obese, the open form of the procedure is
film radiography, yet it may miss a significant amount often preferred, yet the complication rate is higher.
of cholesterol gallstones and biliary sludge readily seen Nonsurgical treatments include pain relief with
on ultrasonography. Biliary scintigraphy (HIDA scan) narcotic analgesics, excluding morphine and its
uses technetium-99m–labeled derivatives of excreted derivatives (which may precipitate spasm of the
bile acids to determine CBD obstruction. This test is sphincter of Oddi and worsen symptoms), extracor-
generally reserved for those patients for whom a defin- poreal shockwave lithotripsy, and gallstone dissolu-
itive diagnosis cannot be reached after routine abdom- tion via oral bile acid therapy and contact solvents
inal ultrasonography. False-positive scans may occur such as methyl-tert-butyl ether (Ransohoff and
in patients with chronic cholecystitis, and false-nega- Gracie, 1993 ●
B).
tive scans may occur in cases of acute acalculous chole-
cystitis (Horton and Bilhartz, 2002● B). Disposition
Endoscopic retrograde cholangiopancreatogra- The plan for Sherrie was to undergo a surgical eval-
phy (ERCP) with sphincterotomy is useful in identify- uation for a laparoscopic cholecystectomy. Within 1
ing and treating CBD stones but is invasive, expensive, week after her surgery, she is to return to our office
and often fraught with complications, including iatro- for postsurgical evaluation.
genic pancreatitis. Endoscopic ultrasonography is a
noninvasive method for evaluating CBD stones that is Patient Education
becoming more widely used and has excellent sensi- Sherrie was educated on the importance of proper
dietary modifications, including the minimization
of saturated fats and foods high in cholesterol.
Table 42-1 Comparison of Diagnostic Our office provided a referral to a dietitian to assist
Methods for Cholelithiasis Sherrie in making the proper modifications in her
and Choledocholithiasis diet. In addition, she was instructed on an exercise
program to follow after she is fully recovered from
Modality Sensitivity (%) Specificity (%)
her surgery in an attempt to reach an ideal weight.
Abdominal Smoking cessation and the avoidance of alcohol were
radiographs*† <50 <50 also strongly encouraged.
Abdominal CT*† 60–70 60–70
Ultrasonography* 90–95 98
Ultrasonography† 25–58 68–91 FOLLOW-UP VISIT
HIDA scan† 85–90 80–90
MRCP† 70–100 80–100 Sherrie underwent an uncomplicated laparoscopic
EUS† 94–100 >90
cholecystectomy 1 week before her follow-up visit.
*
Cholelithiasis.
She admits complete symptom relief, except for one
†
Choledocholithiasis.
episode of postprandial nausea in the postoperative
CT, computed tomography; HIDA scan, biliary
period. She plans to meet with a dietitian and to
scintigraphy using dimethylphenylcarbamyl commence an exercise program to foster weight loss.
methyliminodiacetic acid (HIDA); MRCP, magnetic
resonance cholangiopancreatography; EUS,
endoscopic ultrasonography. DISCUSSION
Adapted from Avunduk C. Gallstones. In Avunduk C
(ed): Manual of Gastroenterology, Diagnosis and
Therapy, 3rd ed. Philadelphia, Lippincott Williams Gallstones are extremely common among both young
& Wilkins, 2002, pp 340–350. and older patients, in both male and female patients,

363
 Chapter 42 Right Upper Quadrant Abdominal Pain (Cholelithiasis)

and affect approximately 20% of all Americans.

Population-based studies indicate that the prevalence
for women between the ages of 20 and 55 years ranges
from 5% to 20% and increases to 25% to 30% after the
age of 50 years. It has been estimated that by the age
of 75 years, gallstones will develop in up to 35% of
women and 20% of men, either symptomatically or
asymptomatically (Attili et al., 1995 ● C ). The preva-
lence of gallstones for men is approximately one-third
to one-half that for women in any given age group.
Gallstones are formed from the precipitation
of the insoluble bile constituents cholesterol, poly-
merized bilirubin, bile pigments, calcium salts, and Figure 42-2 Gallbladder with black-pigment gallstones.
(Courtesy of Dr. Henry D. Appelman, Professor of
proteins. They are classified into cholesterol, black Pathology, University of Michigan Medical School, Ann
pigment, and brown pigment stones. Cholesterol Arbor, Michigan.)
stones are the most commonly occurring gallstones
in the Western world; black pigment stones generally
occur in patients with chronic hemolytic disorders,
and brown pigment stones, which are more common
in Asia, are associated with impaction of the biliary
tract (Avunduk, 2002 ● C ) (Figs. 42-1 to 42-5).
Results from observational studies on the natu-
ral history of asymptomatic gallstones suggest that
serious complications develop in 1% to 2% of
cases per year and that this rate decreases over time
(Kragg et al., 1995 ● B). The Rome Group for the
Epidemiology and Prevention of Cholelithiasis
(GREPCO) study found that the overall cumulative
probability of developing biliary colic over time was
11.9% at 2 years, 16.5% at 4 years, and 25.8% at 10 Figure 42-3 Gallbladder with multiple cholesterol gall-
years, with a cumulative probability of 3% of devel- stones. (Courtesy of Dr. Henry D. Appelman, Professor of
oping complications at 10 years (GREPCO, 1984● B ). Pathology, University of Michigan Medical School, Ann
Arbor, Michigan.)
The incidence of the development of biliary compli-
cations as the presenting complaint of gallstone dis-
ease is rare, ranging from none to 5.5% (GREPCO,
1984 ●B). Based on these data, evidence from well-
designed cohort and case-controlled studies is sum-
marized by GREPCO to weigh in favor of expectant
treatment of asymptomatic gallstones.

Figure 42-4 Gallbladder with multiple cholesterol gall-

stones. (Courtesy of Dr. Henry D. Appelman, Professor of
Pathology, University of Michigan Medical School, Ann
Arbor, Michigan.)

In the approach to the patient with symptomatic

Figure 42-1 Gallbladder hydrops with black-pigment
gallstone obstructing the cystic duct. (Courtesy of Dr. gallstones, the clinician must entertain and effectively
Henry D. Appelman, Professor of Pathology, University rule out other potential causes of RUQ localized
of Michigan Medical School, Ann Arbor, Michigan.) abdominal pain, distinguishing biliary from nonbiliary

364
 Chapter 42 Right Upper Quadrant Abdominal Pain (Cholelithiasis)

should be strongly encouraged (Abraham et al.,

2001● B).
Numerous randomized controlled trials have
confirmed the adoption of laparoscopic cholecys-
tectomy as the gold standard for the treatment of
gallstone disease over the open procedure. The
most serious complication of this procedure is
CBD injury, occurring in approximately 0.1% to
0.2% of cases, and it is directly related to the sur-
geon’s skill and experience, anatomic variation,
and local inflammatory conditions. The main
advantages of this procedure include the avoidance
of a large abdominal incision through the skin and
Figure 42-5 Cholesterol gallstone (Courtesy of Dr. muscles of the RUQ, and a decrease in hospital
Henry D. Appelman, Professor of Pathology, University stay, convalescence, and postoperative pain
of Michigan Medical School, Ann Arbor, Michigan.) (Abraham et al., 2001● B; Ransohoff and Gracie,
1993 ●B).
etiologies as the primary source of pain and disease. Randomized trials have examined the treat-
For example, it is often a challenge to differentiate ment options for choledocholithiasis and have
between dyspepsia and biliary colic. Population-based shown that the treatment of choice is laparoscopic
studies have failed to show any significant difference in cholecystectomy and pre- or postoperative endo-
the prevalence of patients with dyspepsia with and scopic stone extraction via ERCP. Open chole-
without gallstones (Abraham et al., 2001● B). One meta- cystectomy and CBD exploration, usually via an
analysis found that heartburn, flatulence, regurgita- intraoperative cholangiogram, are reserved for
tion, and fatty food intolerance were not associated patients with contraindications to the laparoscopic
with gallstones, but that epigastric pain, nausea, and procedure, or who require abdominal exploration.
vomiting were associated with a higher odds ratio of In approximately 2% of patients, a residual CBD
having gallstones (Kragg et al., 1995●A). stone is demonstrated on postoperative cholan-
Patients suspected to have biliary disease giograms. In these rare cases, the stones may be
should undergo a targeted workup, and those with extracted by ERCP with sphincterotomy or dis-
nonbiliary symptoms should not be treated for gall- solved via MBTE infusion (Abraham et al., 2001● B;
stones. Cohort studies have suggested that patients Ransohoff and Gracie, 1993● B).
with both biliary and nonbiliary symptoms should
be given realistic expectations for the management
of their complaints, specifically regarding the level Material Available on Student Consult
of anticipated symptomatic improvement, and con- Review Questions and Answers about Cholelithiasis
tinued follow-up with their primary care provider

REFERENCES
Abraham NS, Romagnuolo J, Barkun A. Gallstone disease. In Liver Disease: Pathophysiology/Diagnosis/ Management,
Irvine EJ, Hunt RH (eds): Evidence-Based Gastroenterology. 7th ed. Philadelphia, Elsevier, 2002, pp 1065–1086.
Hamilton, Canada, Decker, 2001, pp 360–376. ● A● B●C ●
A●B●
C
Attili AF, DeSantis A, Capri R, et al. The natural history of Kragg N, Thijs C, Knipschild P. Dyspepsia: How noisy are
gallstones: The GREPCO experience. Hepatology gallstones? A meta-analysis of biliary pain, dyspeptic
1995;21:656–659.● A● B●C symptoms, and food intolerance. Scand J Gastroenterol
Avunduk C. Gallstones. In Avunduk C (ed): Manual of 1995;30:411–421.● A
Gastroenterology, Diagnosis and Therapy, 3rd ed. Ransohoff DF, Gracie WF. Treatment of gallstones. Ann
Philadelphia, Lippincott Williams & Wilkins, 2002, pp Intern Med 1993;119:606–619.● A● B● C
340–350.● B●C Rome Group for the Epidemiology and Prevention of
Horton JD, Bilhartz LE. Gallstone disease and its compli- Cholelithiasis (GREPCO). Prevalence of gallstone dis-
cations. In Feldman M, Friedman L, Sleisenger M ease in an adult female population. Am J Epidemiol
(eds): Sleisenger and Fordtran’s Gastrointestinal and 1984;119:796–805.● B●
C

365
 C h a p t e r

43 Cramping Abdominal Pain

(Irritable Bowel Syndrome)
Scott E. Moser

Present Illness
KEY POINTS Susan describes her pain as “crampy” and occasion-
ally like a “sharp knife.” It is so severe that it doubles
1. In patients without alarm features, a diagnosis her over. It most often strikes in the right upper
of irritable bowel syndrome (IBS) can be made quadrant but also can be in other parts of the
reliably, based on standard clinical criteria with- abdomen; no radiation to the back occurs. The pain
out many special tests. usually occurs a few minutes to a few hours after
2. Key symptoms of IBS include (1) abdominal meals and is worse if she eats “too much,” although
pain, (2) pain relief with a bowel movement, (3) no specific relation to fatty or spicy foods is noted.
more frequent stools with pain, (4) looser stools Antacids have had no effect. Susan gets the most
with pain, (5) mucus in stools, (6) feeling of relief from a bowel movement but often has to try
incomplete evacuation, and (7) bloating or several times before she senses she has fully evacu-
abdominal distention. ated her stool. Her bowels have never moved very
3. Alarm features include (1) age older than 50 years, regularly. Sometimes she has two or three bowel
(2) persistent diarrhea, (3) significant weight loss, movements per day, and other times she goes 2 to 3
(4) fever, (5) blood in stools, (6) anemia, (7) abnor- days between bowel movements. During flare-ups of
mal physical findings or blood studies, (8) family the pain, she often has multiple, thin, small-volume
history of irritable bowel disorders or cancer, and “diarrhea” stools accompanied by mucus but no
(9) failure to respond to initial IBS treatment. blood. She is nauseated with the abdominal cramps
4. Best outcomes usually require a multimodal but has not vomited. She cannot remember the
approach that involves medication, dietary cramps ever waking her at night but notes that they
modification, and psychosocial interventions. often come at the most inopportune times at her job,
5. Dietary fiber is a primary treatment; all patients such as before and during important presentations.
should be encouraged to ingest at least 25 g/day. She has not noticed any relation to her menstrual
6. For symptom relief in women, the following have cycle, which has a regular 28- to 30-day pattern. She
Food and Drug Administration approval: alos- wears loose-fitting dresses to work because slacks feel
etron, a 5HT4-receptor antagonist, for diarrhea- tight, especially when the abdominal pain starts.
predominant IBS; and tegaserod, a 5HT4-receptor
agonist, for constipation-predominant IBS.
Medical History
Susan is G2P1AB1, with one vaginal delivery and one
early miscarriage. She has had no other surgery,
medications, or allergies.
INITIAL VISIT
Subjective Family History
Susan’s 63-year-old father is 4 years status post par-
Patient Identification and Presenting tial colectomy for colon cancer and doing well with-
Problem out evidence of recurrence. Her mother and siblings
Susan M. is a 41-year-old woman who complains of have no serious illnesses. Susan has been divorced for
intermittent abdominal cramps that have been wors- 5 years and has a 16-year-old daughter who lives with
ening over the past several months. her and who has no medical problems.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

366
 Chapter 43 Cramping Abdominal Pain (Irritable Bowel Syndrome)

Social History other ethnic groups. The symptoms of cramp-

Susan is a loan officer at a bank, a job she enjoys but ing, flatulence, bloating, and diarrhea are very
finds very stressful. She does not smoke. She has a glass similar to those of IBS. Milk products are com-
of wine several times per year on special occasions. She mon enough in processed foods that patients
denies sexual intercourse since her divorce, noting that may not make the association with their symp-
she endured years of verbal abuse and occasional phys- toms for themselves. A lactose tolerance test or
ical abuse before leaving her ex-husband. lactose breath hydrogen test can make the diag-
nosis in cases in which the dietary history is
Review of Systems suggestive.
Susan has obtained Pap tests every 2 to 3 years with 4. Colon cancer. A change in bowel pattern can be a
no abnormal findings. She is actively trying to lose sign of colon cancer, although abdominal pain is
weight through a nonspecific low-calorie diet. She rare. Minimal evaluation should include a rectal
feels fatigued and is tired of dealing with her pain but examination and appropriate screening based on
denies feeling depressed. Her knees ache when she age and family history.
tries to exercise, but she denies other joint or muscle 5. Thyroid disease. In cases with a marked predom-
pain. She denies any urinary symptoms. inance of either diarrhea or constipation, a thy-
roid-stimulating hormone level can make the
diagnosis.
Objective
6. Celiac disease. Gluten-sensitive enteropathy may
Physical Examination have an incidence as high as about 1 in 200
Susan is a somewhat anxious, moderately overweight patients of northern European extraction. This
woman with normal vital signs. Her general physical autoimmune disease is characterized by vari-
examination, including pelvic, is normal except for able levels of diarrhea and malabsorption that
the abdomen. The abdomen appears distended, and improve after complete discontinuation of
borborygmus is noted without aid of a stethoscope. dietary gluten. Screening for this condition with
She is moderately tender to palpation in all quad- specific autoantibody studies should be consid-
rants with some voluntary guarding but no rebound. ered in patients with diarrhea-predominant
She has no masses or hepatosplenomegaly. symptoms.
7. Infectious bowel disease. Parasitic infestations are
Laboratory Tests characterized by diarrhea-predominant symp-
Complete blood count, serum electrolytes, and liver toms without nighttime relief, usually accompa-
function tests are normal. A gallbladder ultrasound nied by weight loss, and may have other features
is normal. of inflammation such as hematochezia or fever.
8. Inflammatory bowel disease. Ulcerative colitis
and Crohn’s disease would have features similar
Assessment
to those described for infectious bowel disease
Working Diagnosis and may exhibit the systemic findings associated
Irritable bowel syndrome (IBS), mixed constipation with these conditions.
and diarrhea type. 9. Somatization. Psychosocial factors frequently
play an important role in IBS and could be the
Differential Diagnosis primary issue in treatment. More than half of
1. Cholelithiasis. The pain of IBS can be in any part women with chronic abdominal or pelvic pain
of the abdomen, and it is often global, but it is have a significant history of physical or sexual
most frequently in the lower abdomen. The right abuse.
upper quadrant location of some of Susan’s pain, 10. Medications. Susan’s history does not suggest a
along with her age and weight, are suggestive medication as the etiology of her symptoms,
enough of gallbladder disease to warrant a nonur- but it is important to remember that many
gent ultrasound at presentation. commonly prescribed drugs cause IBS-like
2. Isolated constipation. If the “diarrhea” represents symptoms. Examples include diarrhea from
small-volume discharge leaking around an selective serotonin reuptake inhibitors (SSRIs),
obstipating stool, she may have isolated constipa- gastrointestinal distress from tetracycline and
tion. The distinction is clinically important in erythromycin, and constipation from calcium
that isolated constipation should have a more channel blockers.
aggressive “clean-out phase” than IBS with consti- 11. Dietary indiscretion. Irregular eating patterns can
pation symptoms. cause or exacerbate IBS symptoms. The Institute
3. Lactose intolerance. The prevalence of lactose of Medicine report on dietary recommendations
intolerance is 7% to 20% in adults of northern published in 2002 encouraged men to consume
European extraction and much higher among 38 g of total dietary fiber per day and women to

367
 Chapter 43 Cramping Abdominal Pain (Irritable Bowel Syndrome)

consume 25 g. Median intake in the United States years and often dates back to childhood. It is charac-
at the time of the report was 12 to 18 g/day, with terized by periodic exacerbations of chronic abdom-
many people taking in less than 10 g/day. inal pain accompanied by altered bowel habits and
bloating in the absence of an organic cause.
Plan Considerable overlap of IBS is found with fibromyal-
gia, interstitial cystitis, and chronic fatigue syn-
Diagnostic drome, suggesting a possible unifying explanation of
Even though Susan has classic IBS symptoms, she is muscle hypersensitivity. Recent evidence suggests
older than 40 years with a family history of colon can- that small-intestinal bacterial overgrowth might
cer, so she is scheduled for colonoscopy. She is given a serve as an explanation that meets this unifying prin-
pain diary to elicit relations with foods, stressors, or ciple (Lin, 2004). Psychiatric comorbidity is very
other activities that may not be apparent to her now. common, with 94% of IBS patients exhibiting
Because she has no weight loss and her diarrhea seems depression, anxiety, a somatoform disorder, or a
to be of small volume, no further tests are ordered. combination of these.
Because no specific biologic marker is known
Therapeutic for IBS, several authors have attempted to standard-
Susan is offered psychotherapy regarding her history ize the criteria to make the diagnosis clinically
of abuse, but she declines. She is started on psyllium, (Table 43-1). The predictive value of Manning’s cri-
1 Tbsp per day, and given a prescription for teria depends on the number of criteria met and the
hyoscyamine, 0.125-mg tablets, one by mouth every patient’s age and gender (Table 43-2). In the
4 hours as needed for cramps. absence of alarm features, a presumptive diagnosis
of IBS can be made on the basis of these clinical
Patient Education criteria, avoiding extensive diagnostic testing.
Susan is instructed regarding the current recommen- Alarm features include (1) age older than 50 years,
dations for dietary fiber intake and given a patient (2) persistent diarrhea, (3) significant weight loss,
guide listing fiber contents of common foods. She (4) fever, (5) blood in stools, (6) anemia, (7) abnor-
is given reassurance about the likelihood that her mal physical findings or blood studies, (8) family
symptoms represent a medically benign although history of irritable bowel disorders or cancer, and
often uncomfortable problem. She is instructed (9) failure to respond to initial IBS treatment.
about the importance of colon cancer screening, Screening for these alarm features can be accom-
given her family history. plished with the history and physical examination
followed by a complete blood count, routine blood
chemistries, and stool Hemoccult. Patients with
FOLLOW-UP VISIT chronic diarrhea should be considered for addi-
tional evaluation as outlined earlier for celiac dis-
Susan’s colonoscopy was normal. She made a discov- ease, thyroid disease, lactose intolerance, and
ery as she reviewed the dietary fiber list: her diet was parasitic infection. Patients with persistent consti-
extremely low in fiber. She ate lots of tossed salads, pation should undergo screening for hypothy-
thinking they were high in “roughage.” She learned roidism and further evaluation if initial treatment
that lettuce and other salad ingredients are poor of constipation fails. Screening for colon cancer is
sources of fiber compared with legumes, whole as per guidelines for the general population. A his-
grains, and many other fruits and vegetables. She tory of physical or sexual abuse is common in
noted some improvement in bowel regularity and patients with IBS, and exploration of this possibil-
cramps with the medications, but her symptoms are ity should be a routine part of the evaluation.
still interfering with her job. She indicates a readiness Treatment goals include (1) establishment of an
to talk with a counselor regarding her job stress and effective therapeutic relationship, (2) patient under-
history of abuse. standing of and reassurance regarding IBS, (3) con-
trol of predominant symptoms, and (4) identification
and reduction of precipitating or exacerbating factors
DISCUSSION with the overall goal of return to a comfortable daily
routine. Anticholinergics (dicyclomine, hyoscyamine,
IBS is the most commonly diagnosed gastrointestinal and others) can control spasmodic pain and are
condition and the second highest cause of work available in both immediate-release formulations for
absenteeism (behind the common cold). Its preva- acute pain relief and long-acting preparations for
lence in North America is 10% to 15% of the popu- prolonged or recurrent pain relief. Tricyclic anti-
lation, with a female predominance of 2:1. IBS depressants also are useful for chronic control of
accounts for as many as 25% to 50% of referrals to frequent or severe pain, probably because of their
gastroenterologists. Onset is usually before age 35 anticholinergic and antidepressant activity.

368
 Chapter 43 Cramping Abdominal Pain (Irritable Bowel Syndrome)

Table 43-1 Symptom-based Criteria for Irritable Bowel Syndrome

Symptom-
based Positive Predictive
Criteria Symptoms Sensitivity (%) Specificity (%) Value (%)

Manning Abdominal pain 42–90 70–100 74

Pain relief with
bowel movement
More frequent stools
with pain
Looser stools with pain
Mucus in stools
Feeling of incomplete
evacuation
Rome I >3 mo of continuous
or recurrent abdominal
pain relieved with
defecation or associated
with change in stool
consistency 65–84 100 69–100
Plus: >2 of the following
on 25% of days
Altered stool frequency
Altered stool form
Altered stool passage
Passage of mucus
Bloating or abdominal
distention
Rome II Abdominal discomfort
or pain for ≥12 wk (not
necessarily consecutive)
in the preceeding 12 mo
and having two of the
three following features: 49–65* 100* 69–100*
Relieved with defecation
Onset associated with
a change in frequency
of stool
Onset associated with
a change in form
(appearance) of stool
Supportive symptoms:
Fewer than three bowel
movements per wk
More than three bowel
movements per day
Hard or lumpy stools
*
Found to have sensitivity and specificity similar to Rome I.
From Holten KB. Irritable bowel syndrome: Minimize testing, let symptoms guide treatment. J Family Pract
2003;52:942–950.

Additional treatment of IBS is based on mixed. Cathartics are useful for acute constipation
whether the predominant symptom is constipa- but should be used with caution in IBS patients
tion, diarrhea, or alternating constipation and because they can precipitate diarrhea. Tegaserod, a
diarrhea. Dietary-fiber supplements (bran, psyl- 5HT4-receptor agonist, is the only agent approved
lium, methylcellulose, polycarbophil) to increase specifically for treating constipation-predominant
total daily fiber intake above 25 g/day are main- IBS (Holten, 2003). The approval is for use in
stays of IBS therapy. Dietary fiber helps with con- women only; severe diarrhea and ischemic colitis
stipation, but evidence that it reduces pain is are serious potential side effects.

369
 Chapter 43 Cramping Abdominal Pain (Irritable Bowel Syndrome)

and ischemic colitis. Loperamide is effective for con-

Table 43-2 Predicted Percentage
trol of diarrhea but is no more effective than placebo
Probability of Irritable Bowel
at relieving global symptoms of IBS.
Syndrome as a Function of
Other medications, including the SSRIs, pepper-
Age, Gender, and Number of
mint oil, lactobacillus, pancreatic enzymes, and gin-
Manning Criteria Present
ger, are commonly used for IBS but have minimal
Predicted Probability of evidence to support their effectiveness. Narcotics
IBS vs. Those Without should be used with extreme caution if at all because
Number of At age At age At age
of precipitation of constipation and potential
Manning 20 yr 40 yr 60 yr habituation.
Criteria (1–6) Psychological approaches seem of greatest ben-
efit in patients who relate exacerbations of their IBS
Men to specific stressors, demonstrate associated anxiety
Any 2 51 38 26 or depression, have relatively short duration of
Any 4 72 61 48 symptoms, or have intermittent symptoms rather
All 6 87 80 70
than chronic pain (American Gastroenterological
Women
Association, 2002● C ).

Any 2 64 51 38 IBS is usually considered a problem that can be

Any 4 82 73 61 very distressing but is medically benign. However,
All 6 92 87 80 recent evidence suggests that IBS is an independent
risk factor for ischemic colitis. Excluding patients
From Talley NJ, Phillips SF, Melton LJ, Mulvihill C, taking alosetron or tegaserod, patients with IBS were
Wiltgen C, Zinsmetster AR. Diagnosing value of
Manning Criteria in irritable bowel syndrome. Gut
more than 3 times as likely to develop ischemic coli-
1990;31:77–81. tis as the general population in two large studies
(Cash, 2004).

For diarrhea-predominant IBS, alosetron, a Material Available on Student Consult

5HT4-receptor antagonist, has been demonstrated to
Review Questions and Answers about Irritable
be effective in women (Holten, 2003). Its use is
Bowel Syndrome
restricted because of potential severe constipation

REFERENCES
American Gastroenterologic Association. Medical position Lin HC. Small intestinal bacterial overgrowth: A frame-
statement: Irritable bowel syndrome. Gastroenterology work for understanding irritable bowel syndrome.
2002;123:2105–2107.● C JAMA 2004;292:852–859.
Cash BR, Chey WD. A clinical and safety update on seroton- Talley NJ, Phillips SF, Melton LJ, Mulvihill C, Wiltgen C,
ergic agents for the treatment of irritable bowel syndrome Zinsmeister AR. Diagnosing value of the Manning crite-
and chronic constipation. Express Report, a supplement ria in irritable bowel syndrome. Gut 1990;31:77–81.●
B
to Family Practice Recertification, September 2004.
Holten KB. Irritable bowel syndrome: Minimize testing, let
symptoms guide treatment. J Family Pract 2003;
52:942–950.

370
 C h a p t e r

44 Heartburn (Gastroesophageal
Reflux Disease)
Brian S. Bacak

KEY POINTS

1. Heartburn is the most common symptom of anemia, vomiting, odynophagia, or onset

gastroesophageal reflux disease (GERD). of GERD symptoms after the age of
2. Heartburn and acid regurgitation symptoms 50 years suggests complicated GERD or an
(belching, exacerbation by spicy and fatty underlying pathology that needs further
foods, sour taste) are highly specific but poorly investigation.
sensitive for the diagnosis of GERD. 8. For uncomplicated GERD, initial medical
3. GERD can be diagnosed based on history; for therapy with either a proton-pump
uncomplicated GERD, diagnostic imaging is not inhibitor or an H2RA is preferred over
necessary. endoscopy.
4. Dyspepsia refers to episodic midepigastric pain 9. Patients with documented esophagitis on endo-
that can be accompanied by esophageal reflux scopy should be continued on maintenance
symptoms, nausea, and bloating. medical therapy after resolution of their symp-
5. The differential diagnosis for dyspepsia includes toms.
GERD. 10. Lifestyle modifications are an important
6. Peptic ulcer disease, biliary tract disorders, medica- component of GERD management.
tion side effects, underlying malignancies, pancre- 11. Complications from GERD include Barrett’s
atic disease, and cardiac ischemia can present esophagus, esophageal strictures, bleeding, and
with symptoms similar to those of GERD. adenocarcinoma.
7. The presence of dysphagia, unexplained weight 12. No role for Helicobacter pylori testing exists in
loss, early satiety, gastrointestinal bleeding, the management of GERD.

INITIAL VISIT Medical History

Bob has hypertension. He takes hydrochlorothiazide,
Subjective 25 mg by mouth once a day. He is not diabetic. He
has had no surgeries.
Patient Identification and Presenting
Problem Family History
Bob R. is a 38-year-old white man who complains Bob has one sister, who is 40 years old and in good
of heartburn and is seeking relief. Bob complains health. No family history of heart disease or colorec-
of heartburn and belching. The pain is burning, tal disease, peptic ulcer disease, or other gastroin-
episodic, and occurs at night and in the early morn- testinal disorders is known.
ing. The pain has been present for the past 4 to 6
months. It occurs after he eats spicy food. He com- Social History
plains of an acidic taste associated with the belching. Bob works as a dispatcher for a trucking company.
He initially had some relief with over-the-counter He is married, with two children in junior high. Bob
antacid medications, but now the burning sensation is an ex-smoker. He stopped smoking 4 months ago,
occurs more frequently. and as part of his management strategy, he has been

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

371
 Chapter 44 Heartburn (Gastroesophageal Reflux Disease)

sucking on peppermint candies. He drinks four beers with spicy foods suggest acid regurgitation. Together,
a week and denies illicit substance use. He is on an these symptoms suggest a working diagnosis of
exercise program that involves walking through the gastroesophageal reflux disease (GERD) and are
hills near his house for 1 hour, 3 nights a week. highly suggestive of and specific for GERD (Klauser,
1990●B ).
Review of Systems
Bob feels at his baseline. He denies any recent Differential Diagnosis
increases in stress and says that he does not feel The differential diagnosis for Bob’s symptoms falls
depressed. He denies nausea, difficulty swallowing, within the larger category of dyspepsia. Episodic,
or changes in his appetite or bowel habits. The pain epigastric pain accompanied by heartburn, regurgi-
is not colicky, is nonradiating, and is unchanged by tation, and other symptoms is known as dyspepsia
exertion. He denies shortness of breath, diarrhea, and can be caused by several different pathologic
vomiting, and diaphoresis. processes. After investigation, a majority of patients
will not have a specific pathologic process identified
Objective and will be diagnosed with nonulcer or “functional”
dyspepsia (Bazaldua, 1999 ● C ). The remaining causes
Physical Examination include GERD and other structural conditions.
General Bob is an overweight man in no acute Peptic ulcer disease occurs in up to 25% of per-
distress. sons with dyspepsia. A prior diagnosis of a peptic
ulcer greatly increases the likelihood of a recurrence.
Vital Signs Other risk factors for peptic ulcer disease include a
Height, 5 feet 9 inches family history of ulcers, current cigarette smoking,
Weight, 200 pounds and a history of nonsteroidal anti-inflammatory
Body mass index, 29.5 drug (NSAID) use. Orthostatic symptoms, anemia,
Blood pressure, 132/82 and the presence of blood in the stool suggest a pep-
Pulse, 76 tic ulcer with accompanying blood loss.
Respiratory rate, 14 An underlying malignancy such as gastric can-
Temperature, 37.1˚C (98.8˚F) cer, esophageal cancer, or pancreatic or abdominal
No orthostatic change is found in blood pressure or cancer rarely is first seen as dyspepsia without
pulse. accompanying “warning symptoms” (Box 44-1).
Underlying malignancies are more common in
Head, Eyes, Ears, Nose, and Throat Anicteric sclerae, the elderly and typically have a shorter presenting
no conjunctival pallor; oropharynx shows no tonsil- history (Bazaldua, 1999 ● C ).
lar erythema or oral lesions; dentition notable for Biliary tract disease can cause dyspepsia. Gall-
moderate erosions with loss of enamel and exposed stones produce pain located in the right upper quad-
dentin. rant that is episodic, severe, and temporally related to

Cardiovascular Heart sounds have a regular rate and

rhythm, with no murmur, gallop, or rub; no carotid,
abdominal, or femoral bruits. Box 44-1 Warning Signs and Symptoms
of Dyspepsia and GERD That
Lungs Clear to auscultation with good air movement. Suggest Complicated Disease
or More Serious Underlying
Abdomen With minimal midepigastric tenderness to
Process
palpation; no hepatomegaly or splenomegaly; no
Murphy’s sign, ascites, or overlying skin changes. Dysphagia
Unexplained weight loss
Rectal Normal tone, no masses; stool testing negative
History of gastrointestinal bleeding
for occult blood.
Early satiety
Iron-deficiency anemia
Skin No jaundice. Vomiting
Odynophagia (sharp substernal pain on
Assessment swallowing)
Initial onset of heartburn-like symptoms after
Working Diagnosis age 50 years
Bob’s sensation of midsternal burning in his chest is History of immunocompromised state
referred to as heartburn. His complaints of frequent Anorexia
belching, an acidic taste, and symptom exacerbation

372
 Chapter 44 Heartburn (Gastroesophageal Reflux Disease)

the ingestion of a high-fat meal. Biliary disease is fre-

quently accompanied by acholic stools, dark-colored Box 44-2 Lifestyle Modifications That
urine, and jaundice and is associated with a positive ASSIST ME in the
Murphy’s sign on physical examination. Management of GERD
Medication-induced dyspepsia can be associated
with multiple agents. Dyspepsia is classically associated Avoid medications that can make reflux worse
with the use of NSAID agents, which can cause Slim down (modest weight reduction)
mucosal injury to the esophagus and stomach lining. Smaller meal portions
Dyspepsia also has been attributed to alendronate, oral Ingest less alcohol
iron, and macrolide antibiotics such as erythromycin. Sit up after eating (avoid recumbency for
Certain herbal medications also cause dyspepsia 2–4 hr after eating)
(Bazaldua, 1999 ● C ). Tobacco cessation
Ischemic heart disease can appear as dyspepsia.
Most typically, patients characterize the pain of Meals: acidic and spicy foods such as caffeine,
heart disease as radiating substernal chest pressure, chocolate, alcohol, mints, garlic, and tomato-
rather than the burning, nonradiating pain of based items should be avoided
esophageal reflux disease. Ischemic symptoms Elevate the head of the bed 6 to 8 inches
should be considered more likely in anyone with a
history of multiple cardiac risk factors (Bazaldua,
1999● C ). Diagnostic testing and risk stratification
FOLLOW-UP VISIT
can aid in distinguishing between cardiac and non-
cardiac causes of dyspepsia.
Subjective
After 7 weeks, Bob telephones for an appointment
Plan because of continued heartburn. On evaluation, Bob
Diagnostic states that the ranitidine has helped, but that he still
Bob’s symptom history is highly suggestive of and has midsternal burning and belching in the morning.
specific for GERD. His physical examination findings He is abstinent from smoking and has improved his
of dental erosions and dentin exposure support diet. However, he has not attempted to raise the head
prolonged oral exposure to acidic stomach acids of his bed, and he admits to eating snacks occasion-
(Bazaldua, 1999 ●C ). Bob denies any of the warning ally within 1 hour before his usual bedtime.
signs and symptoms that might suggest a more seri-
ous underlying process. Objective
Given Bob’s symptom complex, no further test-
ing is necessary to assign the working diagnosis of Bob’s blood pressure is 128/82 mm Hg, his pulse
GERD (Heidelbaugh, 2003● B). is 80, and he has normal respirations. He is afebrile.
His weight is 197 pounds. Abdominal examination
Therapeutic reveals no epigastric tenderness to palpation and no
Bob is started on a histamine H2-receptor antagonist masses. His conjunctivae and skin show no pallor,
(H2RA), ranitidine (Zantac), 150 mg by mouth on a icterus, or jaundice.
twice-daily basis.
Assessment
Patient Education Bob has GERD with poor initial response to a trial of
Bob is given information on lifestyle modification an H2RA. He has been partially compliant with the
that he should attempt to follow, along with his med- recommended lifestyle modifications. He has no new
ication (Box 44-2). He is counseled specifically on his complaints and has no apparent warning signs or
diet, and he is given a patient handout with instruc- symptoms of more serious underlying disease.
tions for elevating the head of his bed by 4 to 6 inches
by using blocks placed under the bed supports. His
Plan
use of peppermint candies may be exacerbating his
symptoms; he is instructed to switch to a nonmint Diagnostic
candy such as root beer or lemon drops. No current indications exist for imaging, endoscopy,
or 24-hour pH monitoring.
Disposition
Bob is instructed to make a follow-up appointment Therapeutic
in 2 months and to call if any new symptoms or Bob is asked to discontinue the ranitidine and to
problems arise. begin an 8-week trial of a proton-pump inhibitor

373
 Chapter 44 Heartburn (Gastroesophageal Reflux Disease)

(PPI). Bob will begin rabeprazole (Aciphex), 20 mg clinically without additional testing. In the presence
by mouth, 30 to 60 minutes before his first meal of of warning signs, upper endoscopy is recommended.
the day, as part of an 8-week trial. He will continue It allows direct visualization of the esophageal
with the lifestyle modifications previously suggested. mucosa (Eisen, 2001● C ). If extraesophageal manifes-
tations of GERD, such as cough, asthma, laryngitis,
Disposition and hoarseness, are suspected, ambulatory 24-hour
Bob is asked to schedule an appointment at the con- pH monitoring can be helpful to confirm GERD.
clusion of his 8-week PPI trial. At that time, further Ambulatory monitoring also can be helpful in
treatment will be dictated by his response to the PPI. patients who fail to respond to initial treatment with
a PPI. A negative pH study does not preclude the
diagnosis of GERD. Barium contrast radiology can
be useful if other causes of dyspepsia are sought,
DISCUSSION such as peptic ulcers, malignancy, or esophageal
strictures, but it has no role in the initial evaluation
Epidemiology of uncomplicated GERD (Eisen, 2001● C ). Esophageal
GERD is a very common entity in family medicine, and motility testing also has no role in the diagnosis of
it is the most common upper gastrointestinal disorder GERD, unless achalasia or dysmotility disorders are
in the Western world. Among the adult population suspected. It is useful in the preoperative evaluation
of the United States, 20% experience heartburn and for antireflux surgery (Eisen, 2001● C ).
symptoms of GERD at least once per week, with almost Historically the diagnosis of GERD was thought
half experiencing symptoms on a monthly basis. to require the presence of documented mucosal
Patients with GERD consistently report low quality-of- abnormalities on endoscopy. Often, endoscopy in
life scores (Heidelbaugh and Nostrant, 2004●
B ). symptomatic individuals fails to show visible
mucosal damage. This subset of GERD is known as
nonerosive reflux disease (NERD). It is managed
Pathophysiology
similarly to traditional GERD. Patients with NERD
The development of GERD has been associated with may show abnormal pH testing, or they may show
the presence of hiatal hernias, abnormal lower- normal pH monitoring along with normal
esophageal sphincter pressures, delayed gastric emp- endoscopy. This variant is referred to as functional
tying, and gastric acid–secretion abnormalities. As heartburn (Modlin, 2004 ● B ).
the medical understanding of GERD has evolved, the-
ories behind the pathophysiology have changed. Therapy
Currently, up to 80% of episodes of GERD are
thought to be associated with transient lower- Bob’s initial treatment plan parallels the most com-
esophageal sphincter relaxation (TLESR) episodes monly advocated approach for GERD. Several stud-
(Modlin, 2004● B). Hiatal hernias are associated with ies have shown that antacid therapy is more effective
TLESR episodes, as is gastric distention. Sphincter than placebo in the relief of GERD symptoms.
relaxations allow the reflux of acidic stomach con- Treatment with oral sucralfate (Carafate) has not
tents into the esophagus. The presence of acid in been shown to be more beneficial than that with
contact with the esophageal mucosa causes irritation placebo (Heidelbaugh, 2004● B).
and inflammation. Damage to this stratified squa- Lifestyle modifications are an important part
mous epithelium can be accelerated by prolonged of therapy (see Box 44-2). Weight loss is often
acid-contact time resulting from sphincteric relax- advocated, although the reduction of symptoms
ation, delayed gastric emptying with subsequent shown in clinical trials with weight loss has not
reflux, or ineffectual esophageal motility. A direct cor- been associated with a corresponding decrease in
relation exists between the exposure of the esophagus pH testing. Certain foods, such as chocolate, coffee,
to acid and the severity of GERD. Heartburn and peppermint, and alcohol, are thought to transiently
regurgitation symptoms are highly specific for the decrease lower esophageal sphincter pressure and
presence of GERD. However, GERD with esophageal should be reduced or eliminated from the diet
mucosal injury can often be documented in persons (Eisen, 2001● A).
without the presence of symptoms, and poor correla- Initial treatment with an H2RA or a PPI is indi-
tion is found between the presence or absence of a cated. As in Bob’s case, treatment with an H2RA can
hiatal hernia and GERD (Modlin, 2004● B). be initiated as part of step-up therapy. Currently
four H2RA medications are available (Box 44-3).
They are considered equally efficacious. To initiate
Diagnosis
therapy, the chosen H2RA is begun at the standard
In the absence of warning signs or alarm symptoms prescription dosage for an 8-week trial. H2RA
(see Box 44-1), the diagnosis of GERD can be made medications have been shown to be more effective

374
 Chapter 44 Heartburn (Gastroesophageal Reflux Disease)

Box 44-3 Histamine H2-Receptor Box 44-4 Proton Pump Inhibitors

Antagonists (H2RAs) (PPIs)

Cimetidine (Tagamet) Lansoprazole (Prevacid)

Famotidine (Pepcid) Omeprazole (Prilosec)
Nizatidine (Axid) Pantoprazole (Protonix)
Ranitidine (Zantac) Rabeprazole (Aciphex)
Esomeprazole (Nexium)

than placebo in the control of symptoms for GERD the outcome of surgery is inferior to medical
and in esophageal healing times for documented management. Endoscopic treatments that seek to
esophagitis. Tachyphylaxis with the H2RAs during increase lower-esophageal sphincter tone should be
prolonged use can occur (Eisen, 2001● A). As in Bob’s considered experimental and not pursued as treat-
treatment plan, failure to improve after a trial of a ment options (Modlin, 2004● C ).
H2RA then prompts a change to a once-daily dosage
of a PPI.
Step-down therapy for GERD involves initial Complications
treatment with a PPI medication (Box 44-4). The Complications associated with GERD include
PPI of choice is started at the standard daily dose and esophageal strictures, bleeding, Barrett’s esophagus,
prescribed for an 8-week trial. In comparisons with and adenocarcinoma. Barrett’s esophagus is caused
placebos, PPI medications are shown to be markedly by prolonged exposure to gastric acid and is charac-
more effective in symptom relief and healing of terized by a transformation of the normal squamous
esophagitis. They also have proved to be superior to epithelium to metaplastic columnar epithelium. This
treatment with antacids and H2RA medications. All markedly increases the risk of esophageal adenocar-
PPIs have been considered equally efficacious, cinoma over the general population. For this reason,
although the newest PPI, esomeprazole, has shown screening endoscopy is recommended every 5 to 10
faster healing rates of documented esophagitis when years for persons with long-term GERD symptoms
compared to other PPIs. Its benefit in symptom (Eisen, 2001● C ).
reduction in GERD is less clear. Long-term therapy
with a PPI does not appear to increase the incidence
of malignancies or interfere with vitamin absorp- Other
tion. Step-down therapy may be more cost effec- There is no role for Helicobacter pylori testing in
tive than step-up therapy, but studies have yielded patients with GERD unless a coexisting peptic ulcer is
conflicting results. At the end of the 8-week trial, the present. Helicobacter pylori infection is implicated in
PPI can then be dosed on an as-needed basis, or the development of peptic ulcers and is a primary risk
the patient can be changed to a daily or as-needed factor for gastric cancer. Its role in GERD, however, is
H2RA. Patients who have documented esophagitis less clear. Some studies have shown an association
on endoscopy should be monitored for healing and between therapy for H. pylori and an increased occur-
should remain on maintenance therapy to prevent rence of refractory GERD (Cremonini, 2003 ● A).
recurrence (Eisen, 2001● A).
Refractory GERD exists when symptoms are not
controlled by initial medical management or when Summary
symptom relapse occurs after initial control. Endoscopy GERD is a common problem in the general popu-
should be performed in these patients to evaluate for lation. Uncomplicated GERD can be managed
esophagitis. Monitoring with pH testing will typi- medically, by using either PPI or H2RA agents in
cally show evidence of acid reflux. These patients are an initial trial. After initial treatment, patients should
offered additional options to include medical man- be maintained on the lowest dose of the chosen agent
agement or laparoscopic fundoplication. Antireflux to prevent relapse. The presence of alarm symptoms
surgery can be offered to those patients who have nor- or refractory GERD dictates further investigation to
mal gastric emptying, normal esophageal manometry, include endoscopy or pH monitoring.
and have had a partial response to acid-suppression
therapy. It also may be useful in those patients with a
coexistent hiatal hernia. When compared with PPI Material Available on Student Consult
therapy, antireflux surgery performed by experi-
Review Questions and Answers for Gastroeso-
enced surgeons has long-term success rates that
phageal Reflux Disease
equal or exceed medical therapy. In other settings,

375
 Chapter 45 Pancreatitis (Acute Pancreatitis)

REFERENCES
Bazaldua OV, Schneider FV. Evaluation and management Heidelbaugh JJ, Nostrant TT. Medical and surgical man-
of dyspepsia. Am Fam Physician 1999;60:1773–1787.● C agement of gastroesophageal reflux disease. Clin Fam
Cremonini F. Meta-analysis: The relationship between Pract 2004;6:547–568.●
B
Helicobacter pylori infection and gastro-oesophageal reflux Klauser AG, Schindlbeck NE, Muller-Lissner SA, et al.
disease. Aliment Pharmacol Ther 2003;18:279–289.● A Symptoms in gastro-oesophageal reflux disease. Lancet
Eisen GM. An evidence-based approach to gastro- 1990;335:205–208.● B
esophageal reflux disease: Evidence-based. Gastro- Modlin IM, Moss SF, Kidd M, et al. Gastroesophageal
enterology 2001;2:160–168.● C reflux disease: Then and now. J Clin Gastroenterol
Heidelbaugh JJ, Nostrant TT, Kim C, et al. Management of 2004;38:390–402.●B
gastroesophageal reflux disease. Am Fam Physician
2003;68:1311–1321.● B

C h a p t e r

45 Pancreatitis (Acute Pancreatitis)

Leslie Brott

INITIAL VISIT
KEY POINTS
Subjective
1. The diagnosis of pancreatitis is based on clinical
presentation, supported by elevated levels of Patient Identification and Presenting
lipase and/or amylase and, in some cases, radi- Problem
ographic evaluation of the pancreas. Mike V. is a 55-year-old man who presents with a
2. The severity of pancreatitis can be assessed 24-hour history of abdominal pain. Mike is an other-
early using staging systems such as APACHE wise healthy man who developed epigastric pain yes-
(Acute Physiology, Age and Chronic Health terday. The constant, dull pain radiates into his back
Evaluation) II and multiple organ system failure and worsens with deep breathing. He feels more com-
scales. Patients with severe pancreatitis should fortable sitting up, as lying flat accentuates the pain.
be monitored in the intensive care unit. Those He has nausea but denies vomiting and is, in fact, able
with mild pancreatitis can usually be managed to eat small amounts. His last normal bowel move-
in the general medical ward. ment was yesterday, before the onset of his pain. He
3. The mainstays of treatment include fluid resus- took ibuprofen once yesterday for his pain, but it pro-
citation and pain management. vided no relief. He has had no fever or chills. There
4. The most common causes of acute pancreati- has been neither heartburn nor urinary complaints.
tis are gallbladder disease and ethanol He drinks three or more alcohol drinks daily and has
ingestion. for many years. He has never had abdominal surgery.
5. Early complications of acute pancreatitis include
pancreatic necrosis and secondary infection. Medical History
Late complications include pancreatic pseudo- Mike has no known chronic medical problems. He
cyst and abscess. has had two orthopedic surgeries. He is on no
chronic medications and has no drug allergies.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

376
 Chapter 45 Pancreatitis (Acute Pancreatitis)

REFERENCES
Bazaldua OV, Schneider FV. Evaluation and management Heidelbaugh JJ, Nostrant TT. Medical and surgical man-
of dyspepsia. Am Fam Physician 1999;60:1773–1787.● C agement of gastroesophageal reflux disease. Clin Fam
Cremonini F. Meta-analysis: The relationship between Pract 2004;6:547–568.●
B
Helicobacter pylori infection and gastro-oesophageal reflux Klauser AG, Schindlbeck NE, Muller-Lissner SA, et al.
disease. Aliment Pharmacol Ther 2003;18:279–289.● A Symptoms in gastro-oesophageal reflux disease. Lancet
Eisen GM. An evidence-based approach to gastro- 1990;335:205–208.● B
esophageal reflux disease: Evidence-based. Gastro- Modlin IM, Moss SF, Kidd M, et al. Gastroesophageal
enterology 2001;2:160–168.● C reflux disease: Then and now. J Clin Gastroenterol
Heidelbaugh JJ, Nostrant TT, Kim C, et al. Management of 2004;38:390–402.●B
gastroesophageal reflux disease. Am Fam Physician
2003;68:1311–1321.● B

C h a p t e r

45 Pancreatitis (Acute Pancreatitis)

Leslie Brott

INITIAL VISIT
KEY POINTS
Subjective
1. The diagnosis of pancreatitis is based on clinical
presentation, supported by elevated levels of Patient Identification and Presenting
lipase and/or amylase and, in some cases, radi- Problem
ographic evaluation of the pancreas. Mike V. is a 55-year-old man who presents with a
2. The severity of pancreatitis can be assessed 24-hour history of abdominal pain. Mike is an other-
early using staging systems such as APACHE wise healthy man who developed epigastric pain yes-
(Acute Physiology, Age and Chronic Health terday. The constant, dull pain radiates into his back
Evaluation) II and multiple organ system failure and worsens with deep breathing. He feels more com-
scales. Patients with severe pancreatitis should fortable sitting up, as lying flat accentuates the pain.
be monitored in the intensive care unit. Those He has nausea but denies vomiting and is, in fact, able
with mild pancreatitis can usually be managed to eat small amounts. His last normal bowel move-
in the general medical ward. ment was yesterday, before the onset of his pain. He
3. The mainstays of treatment include fluid resus- took ibuprofen once yesterday for his pain, but it pro-
citation and pain management. vided no relief. He has had no fever or chills. There
4. The most common causes of acute pancreati- has been neither heartburn nor urinary complaints.
tis are gallbladder disease and ethanol He drinks three or more alcohol drinks daily and has
ingestion. for many years. He has never had abdominal surgery.
5. Early complications of acute pancreatitis include
pancreatic necrosis and secondary infection. Medical History
Late complications include pancreatic pseudo- Mike has no known chronic medical problems. He
cyst and abscess. has had two orthopedic surgeries. He is on no
chronic medications and has no drug allergies.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

376
 Chapter 45 Pancreatitis (Acute Pancreatitis)

Family History Laboratory Data

There is no family history of pancreatitis. The patient The patient’s complete blood count is remarkable
believes that his mother has had gallbladder problems. for an elevated white count of 17,300 with 92%
neutrophils and 1% bands. Hemoglobin, hemat-
Social History ocrit, and platelets are normal. The complete meta-
Mike has a female significant other. He works in bolic panel is within normal limits including serum
computer operations for an insurance company in transaminases. His amylase is 2182 U/L (normal 25
town. He does not smoke and denies current or past to 125 U/L), and lipase is 7200 U/L (normal 10 to
use of illicit drugs. 140 U/L).

Review of Systems Radiographic Studies

The patient denies dizziness, cough, shortness of Plain films of the abdomen show a nonspecific
breath, chest pain, and palpitations. He has not expe- abdominal gas pattern. There are no abnormal air-
rienced easy bleeding or bruising or bloody stools. fluid levels, calcifications, or distended bowels. The
He has never had seizures or signs of delirium chest radiograph is normal as well.
tremens when abstaining from alcohol.
Assessment
Objective
Working Diagnosis
Physical Examination Acute pancreatitis, most likely due to gallstones or
General Mike is a well-developed man sitting hunched alcohol.
over on the examination table. He is alert and conver-
sant but in moderate distress. He weighs 196 pounds
Differential Diagnosis
(stable over the past 2 years) and is 6 feet tall.
Other causes of acute upper abdominal pain include
the following:
Vital Signs His blood pressure is 112/78, heart rate is
82, and temperature is 37.1˚C (98.7˚F). 1. Peptic ulcer disease with perforation presents with
an abrupt onset of epigastric pain versus pancre-
Head, Eyes, Ears, Nose, and Throat His pupils are atitis in which the pain may be more gradual,
equal, round, and reactive to light. Tympanic mem- reaching peak severity in 10 to 20 minutes. The
branes are normal. The oropharynx is without patient with a perforated ulcer will experience
erythema or exudates. There is good dentition. initial nausea and vomiting, but this will resolve
quickly. Movement does not relieve the pain,
Neck The neck is supple with no lymphadenopathy. whereas in pancreatitis, the fetal or sitting posi-
tions seem to lessen the intensity of the pain.
Heart The rate and rhythm are regular with no mur- 2. Biliary colic and acute cholecystitis cause a very
murs. similar epigastric pain as pancreatitis, but it is of
shorter duration, lasting hours rather than days.
Lungs The lungs are clear bilaterally, but breathing is The pain will wax and wane as opposed to the
shallow. constant, unremitting pain of pancreatitis.
3. Mesenteric ischemia and infarction occur more
Back The back is straight. There is a well-healed ver- often in elderly patients who have a history of car-
tical lumbar incision. Bilateral costovertebral angle diovascular disease. These patients’ sudden onset
tenderness is found. of abdominal pain is accompanied by nausea,
vomiting, and bloody diarrhea.
Abdomen There are hypoactive bowel sounds. The 4. Intestinal obstruction presents as cyclic pain
abdomen is distended and diffusely tender but with associated vomiting. There is abdominal
more exquisitely in the epigastrium. There is no distention with hyperactive, high-pitched bowel
hepatosplenomegaly or masses and no rebound or sounds.
involuntary guarding. 5. An inferior myocardial infarction can present with
epigastric pain. However, the pain usually radiates
Genitourinary He has normal male genitalia with into the chest, jaw, and left upper extremity.
no hernia. Patients classically have diaphoresis, nausea,
and shortness of breath, and cardiac risk fac-
Rectal There is normal tone; stool is brown and tors can often be identified (family history,
guaiac negative. The prostate is of normal size. tobacco use, hyperlipidemia, hypertension).
Electrocardiographic and cardiac enzyme eleva-
Extremities There is no clubbing, cyanosis, or edema. tions differentiate it from pancreatitis.

377
 Chapter 45 Pancreatitis (Acute Pancreatitis)

6. A patient with a dissecting aortic aneurysm suffers feeding is started. This is tolerated well, and Mike is
the abrupt onset of severe, tearing chest and/or discharged home.
abdominal pain. His or her vital signs are often
remarkable for hypotension. Chest radiographs Patient Education
may show a widened mediastinum, cardiomegaly Mike is taught that alcohol use is the most likely
from heart failure, or pericardial effusion or pos- cause of his pancreatitis. He is advised to abstain
sibly a left pleural effusion. from further alcohol use, as it may cause recurrent
7. Ruptured ectopic pregnancy is included in the dif- episodes of pancreatitis. He is offered information
ferential, although obviously is not a considera- on alcohol rehabilitation. In the weeks following dis-
tion in our patient. As many as one half of women charge, he is to monitor for a return of epigastric
with a ruptured ectopic pregnancy will present pain, which may indicate a late complication of acute
with diffuse abdominal pain. They will often have pancreatitis such as formation of a pseudocyst.
other signs of early pregnancy as well, including
breast tenderness and nausea. Approximately Disposition
75% will have vaginal bleeding. A positive preg- The patient is to follow up at the clinic in 1 week fol-
nancy test will often differentiate these patients lowing discharge, sooner if pain, fever, nausea, or
from those with acute pancreatitis. vomiting develops.

Plan
DISCUSSION
Diagnostic
Based on history, physical examination and labora- Acute pancreatitis can cause significant morbidity
tory studies (particularly the high levels of amylase and mortality. Its incidence is increasing worldwide
and lipase), Mike is diagnosed with acute pancreati- for unclear reasons. It is important for family physi-
tis. Identifying the cause of his pancreatitis is cians to identify pancreatitis early and treat it appro-
important in preventing recurrent episodes. The priately to avoid serious sequelae. It is estimated that
two most common causes of pancreatitis are gall- 40% of all cases of pancreatitis are missed, only to be
stones, which cause more than half the cases, and found at autopsy.
alcohol, constituting approximately 30% of the Acute pancreatitis can be divided into mild and
cases. Laboratory studies and ultrasound scans are severe disease. Mild pancreatitis accounts for 80%
commonly used to differentiate the two. In gall- of all cases and is defined as interstitial edema of
stone pancreatitis, the serum alanine aminotrans- the pancreas with minimal distal organ involvement.
ferase and aspartate aminotransferase are generally Severe pancreatitis is distinguished by pancreatic
elevated. In alcoholic pancreatitis, it is thought that necrosis with possible infection and multiorgan fail-
a serum lipase/amylase ratio of greater than 2.0 ure. The inappropriate activation of trypsin, a pan-
occurs, although this is not particularly specific. A creatic enzyme, is the pathophysiologic basis for
transabdominal ultrasound scan was performed in acute pancreatitis. When the resultant inflammation
our patient immediately after diagnosis. No gall- is localized to the pancreas, mild disease results. If
stones or common duct stones were identified nor the inflammation extends into the space surround-
was there evidence of biliary tract obstruction. ing the pancreas, a systemic inflammatory response
With the negative results of the ultrasound scan, the ensues, resulting in severe disease.
high serum lipase/amylase ratio, and a history of
significant alcohol use, our patient is diagnosed
Clinical Presentation
with alcoholic pancreatitis.
The patient with acute pancreatitis presents with the
Therapeutic acute onset of severe upper abdominal pain, which is
Mike is admitted as an inpatient to our community characterized as boring and steady. Approximately
hospital. He is started on intravenous fluids and is half the patients will experience radiation of the pain
kept NPO. His pain is initially treated with meperi- in a bandlike pattern to the back. Ninety percent
dine, but due to inadequate pain relief, he is placed experience nausea and vomiting. On examination,
on a patient-controlled anesthetic device with the patient with mild pancreatitis will have abdomi-
hydromorphone. His pain gradually resolves over nal tenderness but rarely guarding; bowel sounds will
the next 4 or 5 days. He suffers no systemic compli- be diminished. Those with severe pancreatitis will
cations of pancreatitis and is hemodynamically sta- appear toxic and will exhibit abdominal guarding
ble throughout his hospitalization. He is monitored and distention. They are more likely to have tachy-
closely for evidence of alcohol withdrawal using cardia, hypotension, and fever.
the Clinical Institute Withdrawal Assessment There are two examination findings that are
for Alcohol scale. Once his pain has resolved, oral described classically as indicative of pancreatitis:

378
 Chapter 45 Pancreatitis (Acute Pancreatitis)

Cullen’s sign (ecchymosis of the periumbilical area) A more valuable imaging test for the diagnosis
and Grey Turner’s sign (ecchymosis of the flank). and staging of pancreatitis is contrast-enhanced
These signs are quite rare (less than 1% of all cases) computed tomography (CT). CT gauges the severity
and are not specific for pancreatitis. of the pancreatitis as well as excludes other intra-
abdominal pathology and should be used in patients
Laboratory Studies whose diagnosis is in question, who present with
severe symptoms, or who have evidence of infection
Several laboratory studies are helpful in diagnosing (fever, persistent leukocytosis). CT is helpful in stag-
pancreatitis and identifying the etiology, but none ing the severity of pancreatitis and, in fact, forms the
are diagnostic in isolation. An elevated white blood basis of one of the staging systems (see later).
cell count and elevated serum glucose level are com-
mon. Liver enzymes may be elevated, especially in
Prognosis
gallstone pancreatitis.
Serum amylase and lipase are key laboratory Identifying the patient with acute pancreatitis is
indices in the evaluation of pancreatitis. Amylase is much easier than predicting the prognosis of the
produced by both the pancreas and salivary glands. disease. Much work has been done over the years to
Although there are assays that differentiate the two, a develop systems to stage acute pancreatitis to predict
total serum amylase can be obtained quickly and severity and mortality. Approximately 20% of patients
cheaply and is helpful in the diagnosis of pancreati- with pancreatitis are graded as severe, and the mortal-
tis. After the onset of pancreatic inflammation, the ity rate can be as high as 10%. Staging systems attempt
amylase rises within 6 to 12 hours and will remain to identify early those patients who are most likely to
elevated for 3 to 5 days in mild cases. However, develop severe pancreatitis.
serum amylase is not completely sensitive nor One of the first staging systems reported was
specific. There are many nonpancreatic causes of an that of Ranson. Eleven criteria are used to predict
elevated amylase. Therefore, it is used as one element the severity of disease (Box 45-1). The criteria are
in the diagnosis of pancreatitis. divided into signs at admission and at 48 hours.
Another element is the lipase level. Lipase is pro- Traditionally, if fewer than three signs are noted,
duced almost entirely by the pancreas. Its sensitivity mortality is less than 1%. Mortality rises to 100%
and specificity, however, are similar to amylase. Like if more than six signs are found. Unfortunately, the
amylase, it rises early in the course of pancreatitis but system is neither very sensitive (57% to 85%) nor
stays elevated as long as 14 days. Opinions differ on specific (68% to 85%), and it takes 48 hours to
the value of either the lipase or amylase level. Some complete staging. It is valuable, however, in exclud-
experts argue that taken together, they differentiate ing severe disease, as its negative predictive value is
pancreatitis from other acute abdominal processes, approximately 90%.
particularly if their values are three times normal. Two newer staging systems, the APACHE II and
There are additional laboratory markers that multiple organ system failure scale, are improve-
are in development as markers for pancreatitis. ments over Ranson’s criteria. Unlike Ranson’s, they
C-reactive protein is readily available and is valuable can be used at admission and then on a daily basis
in determining prognosis, if not diagnosis. Serum to assess progression of disease. APACHE II uses
levels of trypsin and elastase also have value in
detecting pancreatitis but are not readily available to
most hospitals and clinics.
Box 45-1 Ranson’s Criteria
Radiographic Studies
At initial presentation:
Radiographic studies are used in the workup of pan- ■
Older than 55 years
creatitis to determine both its etiology and progno- ■ White blood cell count >16,000/mm3

sis. Plain films of the abdomen are often normal, ■ Low-density lipoprotein >350 IU/L

thus excluding other causes of intra-abdominal pain. ■

Aspartate aminotransferase >250 IU/L
A transabdominal ultrasound scan is useful early in ■ Glucose >200 mg/dL

the diagnosis of pancreatitis to identify gallstones, At 48 hours:

biliary duct dilation, common duct stones, and ■
Decrease of hematocrit >10%
ascites. It should be performed within 24 hours of ■ Increase in blood, urea, nitrogen >5 mg/dL

presentation. One pitfall of ultrasonography, how- ■ Serum calcium <8 mg/dL

ever, is that the pancreas is often not well visualized ■

Arterial PO2 <60 mm Hg
because as much as 35% of the time, it is obscured by ■ Base deficit >4 mEq/L

bowel gas. Nevertheless, it is useful in differentiating ■ Fluid sequestration >600 mL

gallstone from alcoholic pancreatitis.

379
 Chapter 45 Pancreatitis (Acute Pancreatitis)

age, presence of chronic disease and 12 physiologic ished, oral feedings may begin with small amounts of
parameters including vital signs (i.e., temperature, noncaloric liquid. Their diet is advanced as tolerated.
heart rate, respiratory rate) and laboratory values
(i.e., serum sodium, creatinine, hematocrit, arterial Complications
pH) to determine a severity score. The multiple organ
system failure system assesses the cardiovascular, The complications of pancreatitis usually occur within
pulmonary, renal, neurologic, hepatic, and gastro- 2 weeks of the onset of symptoms. Seventy percent to
intestinal systems separately to stage pancreatitis. 80% of all deaths from acute pancreatitis are attributed
Any significant abnormality in a system qualifies as a to secondary infection of the pancreas. Necrosis of the
point, and severity is based on total points obtained pancreas can lead to multiorgan failure including acute
on a daily basis. renal failure, hypovolemia and circulatory shock, sep-
CT is the basis of yet another system of staging sis, and acute respiratory distress syndrome.
pancreatitis. Using a 5-point severity scale based on Beyond the acute period, late-presenting compli-
the pancreas’ appearance on CT, along with the cations of pancreatitis include pancreatic pseudocysts
percentage of pancreatic necrosis, the Computed and abscesses. Patients will often present weeks after
Tomography Severity Index predicts morbidity and their initial episode with new complaints of abdomi-
mortality. This scale reflects the importance of CT in nal pain. Abdominal CT will identify these findings.
the management of pancreatitis.
Causes
Management The majority of cases of acute pancreatitis are due to
two main causes: gallbladder disease, accounting for
Management of pancreatitis is dependent on the
more than 50% of all cases, and alcohol use, implicated
severity of disease. Almost all patients need to be
in approximately 30% of all cases. Other less com-
admitted to the hospital. Those with severe disease or
mon causes include hereditary pancreatitis, hyper-
poor prognostic indicators should be monitored in
triglyceridemia (>1000 mg/dL), hypercalcemia/
the intensive care unit. All patients need fluid resus-
hyperparathyroidism, infection (viral or bacterial),
citation and bowel rest. Cardiac, renal, and pul-
medications, iatrogenic (e.g., endoscopic retrograde
monary status should be monitored closely. Pain
cholangiopancreatography), α1-antitrypsin defi-
control is best with meperidine or hydromorphone.
ciency, anatomic abnormalities, pregnancy, and
An antiemetic is also usually necessary. There is no
trauma, among others.
evidence that proton pump inhibitors, H2 blockers, or
antibiotics are routinely necessary. Nasogastric tubes
are needed only if an ileus is present and decompres- Material Available on Student Consult
sion is needed, but they are not routinely used.
Review Questions and Answers about Acute
Patients with mild cases can be expected to
Pancreatitis
improve in 3 to 7 days. Once their pain has dimin-

SUGGESTED READINGS
Balthazar E. Staging of acute pancreatitis. Radiol Clin Feldman M, Friedman L, Sleisenger M, eds. Sleisenger and
North Am 2002;40:1199–1209. Fordtran’s Gastrointestinal and Liver Disease, 7th ed.
Munoz A, Katerndahl D. Diagnosis and management of Philadelphia, Elsevier, 2002, pp 913–941.
acute pancreatitis. Am Fam Physician 2000;62:164–174.
Orbuch M. Optimizing outcomes in acute pancreatitis.
Clin Fam Pract 2004;6:607.

380
 C h a p t e r

46 Swollen Foreskin
(Diabetes Mellitus Type 2)
Cheng-Chieh Chuang

KEY POINTS

1. Diabetes mellitus type 2 usually does not produce insulin resistance, and postprandial hyper-
symptoms for years before the diagnosis is made. glycemia reflects the insulin deficiency.
Screening all people 45 years and older, and 6. Secretagogues (sulfonylureas, meglitanide,
those younger than 45 with risk factors, is rec- d-phenylalanine derivative) work primarily to
ommended. enhance the body’s production of insulin in
2. Screening can be done using the fasting glucose response to glucose intake.
or 2-hour postprandial blood glucose level tested 7. Insulin sensitizers (biguanide, thiazolidinediones)
using 75 g of anhydrous glucose. treat insulin resistance.
3. The management of diabetes mellitus type 2 has 8. Insulin is the most potent of all medications.
three major components: nutrition, physical activ- The goal of using insulin is to duplicate the nat-
ity, and medication. The goals are to lower the ural physiologic insulin and glucose level, in
blood glucose level and decrease hemoglobin which basal insulin supplies half of the body’s
A1C to less than 7%. needs and insulin secreted in response to meals
4. Medical nutrition therapy is a concept that incor- supplies the rest.
porates nutrition and physical activity. It includes 9. Individuals with type 2 diabetes tend to have
carbohydrate counting, calorie restriction, lipid disorders and hypertension.
weight reduction, and exercise. Medical nutrition 10. Diabetes is considered a coronary heart disease
therapy may decrease the hemoglobin A1C by risk equivalent. Aspirin should be considered for
1% to 2%. all individuals with diabetes mellitus type 2.
5. There are two main defects in glucose metabo- 11. Potential microvascular complications from dia-
lism in diabetes, insulin resistance and insulin betes mellitus type 2 include nephropathy,
deficiency. A high fasting glucose level reflects retinopathy, and neuropathy.

INITIAL VISIT History of Present Illness

Mr. M. was in his usual state of health until 3 to
Subjective 4 weeks ago, when he began experiencing increasing
discomfort and then pain while retracting his fore-
Patient Identification and Presenting skin to urinate or have sex. He reports no dysuria, no
Problem urethral discharge, no history of sexually transmitted
David M. is a 37-year-old white man of Portuguese disease, no increase in urinary frequency, and no
descent who says with some embarrassment that he changes in foreskin color. This is the first time in his
is here for a second opinion. He saw a urologist life he has had a problem with his foreskin.
1 week ago because of difficulty retracting his fore-
skin for the past 3 to 4 weeks. The urologist suggested
circumcision. Not satisfied with this proposal, Mr. Medical History
M. decided to see a primary care physician. Mr. M. states that he has been in excellent health.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

381
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

Family History Assessment

Mr. M.’s parents have diabetes mellitus type 2 and
hypertension. His father had a heart attack at age 53. Working Diagnosis
His mother also takes thyroid medication. He has no The working diagnosis is Candida balanitis, most likely
siblings. associated with hyperglycemia of diabetes mellitus.

Social History Differential Diagnosis

Mr. M. has been married for the past 15 years and Nonketotic hyperglycemia can be due to diabetes
works as a truck driver. He reports a monogamous mellitus type 2. It can also be caused by acute pain
sexual relationship with his wife since marriage. He from trauma, myocardial ischemia or infarction,
has never had sex with another woman or man. He other critical illnesses, steroid use or Cushing’s dis-
has two healthy teenage children. He does not smoke, ease, hypothyroidism, and hemochromatosis.
but drinks one glass of red wine with his dinner. He
denies any illicit drug use. He feels that loading and Plan
unloading cargos for his truck is enough exercise for
him. On average, he watches 4 hours of television Mr. M. chooses to take one dose of oral fluconazole,
a day. He notes that in his early 20s he used to lift 150 mg, for the balanitis. The high glucose level comes
weights and play soccer, but after marriage he as a shock to Mr. M. He maintains that it is impossible
stopped these activities. for him to have diabetes as his parents do, because he
feels great except for the foreskin problem. He is to
Review of Systems return in 1 week after the test results are ready.
The review of systems is negative other than for the
complaints already noted. Specifically, Mr. M. FIRST FOLLOW-UP VISIT
reports no fatigue, no malaise, no polydypsia, no
polyuria, no nocturia, no recurrent infection, no Subjective
visual changes, no dental problems, no numbness or
At his 1-week visit Mr. M. is happy that the candidi-
paresthesia anywhere, and no abnormal nodes, espe-
asis has cleared. He is somewhat distraught, however,
cially in his groin.
because he used his parents’ glucometer a day before
returning to the office and found his fasting glucose
Objective concentration to be 165 mg/dL. He is very anxious
about the full blood test results.
Mr. M. is obese and pleasant. His blood pressure is
150/90, pulse is 80 and regular, weight is 258
pounds, height is 5 feet 8 inches, and body mass Objective
index (BMI) is 39.3. Genital examination reveals an
His blood pressure is 145/95 and his pulse is 85.
edematous foreskin, which on slight retraction dis-
The results of the blood tests are within normal
closes a white, cheesy discharge. No inguinal lym-
range except for a fasting glucose concentration of
phadenopathy is palpable bilaterally. The rest of the
154 mg/dL, a hemoglobin A1C value of 11.4%, a
genital examination is negative. Normal saline and
total cholesterol concentration of 250 mg/dL, an
KOH slide of the discharge shows elongated pseudo-
HDL concentration of of 44 mg/dL, an LDL con-
hyphae and budding spores. An office fingerstick
centration of 169 mg/dL, and a triglyceride concen-
blood test shows a glucose concentration of 250
tration of 256 mg/dL. A spot urine test shows no
mg/dL. Urinalysis of a clean catch urine specimen
microalbuminuria. He has no thyromegaly. Results
shows a high glucose concentration but is otherwise
of the cardiac examination, external genitals exam-
negative, including for ketones. The specimen is sent
ination, bilateral foot examination, and neurologic
for culture, gonorrheal, and chlamydial studies. Mr.
examination, including the monofilament test, are
M. declines HIV and syphilis testing, saying that he
all normal. The electrocardiogram is also normal.
has no risk factor for them. He is asked to return for
fasting blood tests for glucose, hemoglobin A1C, a
lipid panel (total cholesterol, high-density lipopro- Assessment
tein [HDL] level, low-density lipoprotein [LDL]
level, and triglycerides), a complete blood cell count, The physician’s assessment is diabetes mellitus type 2,
determination of electrolyte, blood urea nitrogen, presumptive hypertension, and dyslipidemia.
creatinine, and thyroid-stimulating hormone levels,
and liver function tests. A spot urine is also ordered Plan
to check for microalbuminuria. He is instructed not
to drink alcoholic beverages for 3 days before the A long discussion with Mr. M. about lifestyle
blood tests. modification (medical nutrition therapy), including

382
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

increasing physical activities and sensible nutrition, Symptoms

ensues. Mr. M. insists that he does not want any med-
ication at present and that he will try lifestyle modifica- Classic symptoms of diabetes mellitus type 2 include
tion first. Because he enjoys watching television, which fatigue, polydypsia, polyuria, unexplained weight
helps relax him after a full day’s work, the physician loss, and blurred vision. Because the majority of
suggests he obtain a stationary bicycle to use while those with undiagnosed diabetes mellitus type 2 are
watching television. A few other exercises that can be without symptoms, screening individuals at high risk
done in front of the television are also explored. He is is recommended.
referred for a dilated diabetic eye examination. He is
also referred to a nutritionist for detailed meal and food Screening
planning needed for medical nutrition therapy, and
to a diabetic nurse for further education on diabetes In contrast to the current recommendation by the
and the use of a glucometer. The physician suggests that U.S. Preventive Services Task Force, which recom-
his wife also attend the meeting with the nutritionist mends screening only those who have hypertension
because she cooks for the family. Because Mr. M. takes or hyperlipidemia, the American Diabetes Asso-
a glass of wine with his evening meal, he is instructed to ciation and the U.S. Department of Health and
be on the watch for hypoglycemia and always to drink Human Services recommend screening all people 45
with food. The possible effect of alcohol on his blood years and older, and those younger than 45 with the
pressure is discussed. He is to return in 2 weeks and following risk factors: obesity, a family history of dia-
bring with him daily fasting glucose readings. betes, member of a high-risk ethnic group (African
American, Latino, Native American), polycystic ovary
disease, hypertension, or dyslipidemia. Other risk
SUBSEQUENT FOLLOW-UP VISITS factors include acanthosis nigricans, associated with
insulin resistance, components of metabolic syndrome
At his return visit in 2 weeks’ time, Mr. M.’s fasting (central obesity, hypertension, dyslipidemia), and pre-
glucose readings show a gradual decrease during that existing cardiovascular disease (American Diabetes
period, with last 2 days’ readings in the 110s. In addi- Association Expert Committee, 2004● C ).

tion to working out on the stationary bicycle, Mr. M. Screening can be done using fasting glucose
has joined one of his old buddies in weight training. or 2-hour postprandial blood glucose using 75 g of
Three months after his initial visit Mr. M. has anhydrous glucose. The latter test may be abnormal
lost 18 pounds, and his hemoglobin A1C value has before the first one, but the convenience of the fast-
come down to 6.5%. His home blood pressure read- ing glucose test makes it the more practical method.
ings range from 110-140/70-85. His lipid profile has With either method, a second, confirmatory test is
also improved to within normal limits, although his needed before the diagnosis can be made.
blood pressure is still in the high normal range. Mr.
M is still not interested in any medication. Management
At his 6-month visit Mr. M. has lost an additional
15 pounds, for a total of 33 pounds since his first visit. Once diabetes mellitus type 2 has been diagnosed,
His blood pressure numbers at home range from management has three major components: nutrition,
110–130/70–85. His hemoglobin A1C value is 6.1%. physical activity, and medical management. The goals
Mr. M. continues to do well until 3 years after are to lower the glucose concentration and to decrease
diagnosis, when his hemoglobin A1c value hovers in the hemoglobin A1C value to less than 7%, thereby
the low 7s with medical nutrition therapy alone. minimizing or preventing the microvascular and
Medication therapy with metformin is started. macrovascular complications of diabetes. Each per-
His blood pressure also has increased slightly to centage point reduction in A1C corresponds to a 30
110–140/70–90, and an ACE inhibitor is started. His mg/dL reduction in fasting glucose levels (Table 46-1).
lipid panel is still within normal limits. Patient education and an emphasis on the
patient’s own involvement in disease management
are crucial. In addition, the patient may need sup-
DISCUSSION port to deal with the anger and frustration of living
with a chronic condition. The primary care physi-
Up to half of patients with diabetes mellitus type 2 cian’s main functions are to facilitate these efforts
are diagnosed after complications develop. Unlike and to coordinate care among a formal or informal
most of these individuals, who present with cardio- team consisting of a dietician, an ophthalmologist
vascular complications, Mr. M. presented with or optometrist, and other specialists, such as an exer-
candidiasis. It is possible that the candidiasis con- cise physiologist, podiatrist, nephrologist, cardio-
tributed further to the hyperglycemia, which would logist, and psychologist or psychiatrist, depending
explain the initial hemoglobin A1c value of 11.4%. on the severity of the illness and the associated

383
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

Carbohydrate Counting Carbohydrate counting

Table 46-1 Hemoglobin A1C Level and involves counting carbohydrate intake, focusing more
Corresponding Average on the total amount of carbohydrate than on the type
Glucose Value of food. The convention now is that one carbohydrate
Hemoglobin Average Blood Glucose choice is equal to 15 g of carbohydrates (Table 46-4).
A1C* (%) Level (mg/dL) Individuals plan their total daily personal carbohy-
drate needs with the help of a dietician. The goal is to
4 60 have an even intake throughout the day of carbo-
5 90
hydrates coming from starchy foods, meat and meat
6 120
7 150 substitutes, and fats. Although the emphasis in carbo-
8 180 hydrate counting is on total carbohydrate intake,
9 210 discrimination among food sources is ultimately nec-
10 240 essary, as calories from other nutrients such as fats
11 270 will affect calorie restriction and weight reduction.
12 300
13 330 Fat Reduction Reduction of fat intake is part of calorie
*
Glycosylated hemoglobin, also known as %A1C, is a
restriction. Distinguishing among different types of fats
measure of average blood glucose level over the is also important. Saturated fat increases LDL concen-
preceding 8 to 12 weeks. trations and total cholesterol levels. Polyunsaturated
fats that contain omega-3 fatty acids decrease LDL lev-
els, increase HDL levels, and decrease triglyceride levels.
complications. Negotiating with patients changes Monounsaturated fats such as canola and olive oils
in lifestyle, diet, exercise, and tobacco cessation is decrease LDL concentrations and protect HDL choles-
important and necessary. Resources available to help terol. Trans fats (partially hydrogenated vegetable oils),
patient and physician are listed in Box 46-1. used in most restaurants and confectioneries, increase
Table 46-2 lists items important in the manage- LDL concentrations and lower HDL concentrations,
ment of diabetes mellitus type 2. and now are recognized as detrimental to health.

Medical Nutrition Therapy Physical Activities

Medical nutrition therapy is a concept that incorpo- Exercise, or adequate physical activy, is not only impor-
rates nutrition and physical activity. It includes car- tant for glucose control; it also confers many other
bohydrate counting, calorie restriction, weight health benefits, such as increasing HDL, weight reduc-
reduction, and exercise (Franz, 2004● A ●B●C ). The rec- tion, and enhancing the sense of well-being. Exercise at
ommended macronutrient intake central to medical least once every 2 to 3 days is needed for these benefits
nutrition therapy is listed in Table 46-3. to appear. Cumulative exercise, such as three 10-minute
Medical nutrition therapy may decrease the hemo- sessions, may be as beneficial as one 30-minute session.
globin A1C value by 1% to 2%. It improves insulin
resistance and may control the hypertension and dys- Weight Reduction Insulin resistance typically starts
lipidemia associated with diabetes mellitus type 2. It is at a BMI of 27. The ideal goal for weight reduction is
reasonable to attempt a trial of medical nutrition ther- a BMI of less than 25. However, it may not be possi-
apy without medication in patients with hemoglobin ble to achieve this ideal, for a variety of reasons. If the
values at or below 8.5%, and in individuals who, like patient agrees that weight loss is a goal, a gradual loss
Mr. M., insist on no medication initially and who are of about 10% of current weight, or 20 pounds, at the
not at immediate risk of severe hyperglycemia. rate of 1/2 to 1 pound a week, may be reasonable.

Medical Management
Medical management for diabetes mellitus type 2 not
Box 46-1 Patient Education Resources only aims to contain hyperglycemia, it also involves
preventing and controlling comorbid conditions
American Diabetes Association (hypertension, dyslipidemia) and diabetic complica-
800-232-6733 tions (neuropathy, retinopathy, nephropathy, and
www.diabetes.org cardiovascular disease).
National Diabetes Information Clearinghouse
301-654-3327 Containing Hyperglycemia There are two main
www.niddk.nihgov/health/diabetes/ndic.htm defects in glucose metabolism in diabetes, insulin
resistance and insulin deficiency. A high fasting glucose
National Diabetes Education Program
concentration reflects insulin resistance, and postpran-
www.ndep.nih.gov
dial hyperglycemia reflects insulin deficiency. The U.K.

384
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

Table 46-2 Taking Care of Patients with Diabetes Mellitus Type 2

Interval Goal

Physical and Emotional Assessment

Blood pressure Every visit Target goal < 130/80
Weight Every visit BMI < 27, or 10% less
than the original weight
Foot examination
Visual inspection Every visit
Pedal pulses, neurologic
examination Yearly
Dilated eye examination Upon diagnosis and every year
Screening for depression At least yearly
Dental examination At least twice yearly
Prophylaxis 2–4 x per year

Laboratory Studies
Hemoglobin A1C Every 3 months <7%
1–2 x per year if stable
Microalbuminuria (albumin/ At diagnosis
creatinine ratio) Every year till proteinuria is
documented
Blood lipid At diagnosis and yearly Triglyceride < 200 mg/dL
HDL > 45 (men), >55
(women)
LDL < 100 mg/dL

Self-Management Training
Assess knowledge of diabetes, Initially and yearly
medications, self-monitoring,
complications, and problem-
solving skills
Self-glucose monitoring As needed
Medical nutrition therapy Ongoing
Physical activity Ongoing
Weight management Ongoing

Interventions
Medication As needed A1C < 7%
Aspirin therapy Unless contraindicated 81 mg/day to 325 mg/day
Smoking cessation Encourage at every visit
Immunization Influenza yearly
Pneumococcal at diagnosis if not
done already

Prospective Diabetes Study (1995 ● A ) suggested that at meglitanide, d-phenylalanine derivative) that function
the time of diagnosis, individuals with type 2 diabetes primarily to enhance the body’s production of insulin
have about half of their beta-cell function remaining, in response to glucose intake. These drugs may induce
as the real onset of the diabetes occurred around 10 to hypoglycemia. Others are insulin sensitizers (bigu-
11 years earlier. Six years after diagnosis, beta-cell func- anide, thiazolidinediones) that treat insulin resistance
tion decreases further to about a quarter of its original and in general do not induce hypoglycemia. There is
function. Therefore, after some time with medical also a third class of agents, a-glucosidase inhibitors,
nutrition therapy, it is often necessary to start medica- which delay carbohydrate absorption.
tion to achieve good glycemic control. The major action, efficacy, indication, and side
effects of each class of oral agent are listed in Table
Oral Glucose-Lowering Agents There are several 46-5. Metformin, a secretagogue, or a thiazodine-
classes of oral glucose-lowering agents (Lebovitz, dione is often used for initial monotherapy for dia-
2001● A ●
B ). Some are secretagogues (sulfonylureas, betes mellitus type 2.

385
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

superior and cause less hypoglycemia. An individual’s

Table 46-3 Macronutrient Composition response to the medication may take place within days.
Recommended for Medical The most important side effect is hypoglycemia.
Nutrition Therapy Other side effects include weight gain and gastroin-
Recommended testinal symptoms. Sulfonylureas need to be used
Nutrient Intake with caution in the presence of renal disease.
Carbohydrate 50–60% of total calories Other Secretagogues Meglitinide and nateglinide
Protein Ca. 15% of total calories
Total fat 25–35% of total calories
are rapid-acting secretagogues with a short duration
Saturated fat <7% of total calories of action. Either is taken with meals. They do not
Polyunsaturated fat Up to 10% of total have a renal contraindication.
calories
Monounsaturated fat Up to 20% of total Biguanides Biguanides targets fasting glucose. They
calories reduce hepatic glucose production and improve
Trans fatty acids Minimum insulin action to increase glucose uptake at the
Cholesterol <200 mg/day muscle level.
Fiber 20–30 g/day Metformin is the only biguanide used in the
United States. It may reduce A1C values by up to
2.2%. It also reduce weight and reduce cholesterol and
About half of individuals with diabetes mellitus triglyceride concentrations. It is the only oral agent
type 2 need another agent added after 3 years of shown thus far to reduce cardiovascular complications.
monotherapy. Two-drug therapy should also be con- Meformin is indicated for a BMI greater than 27,
sidered for patients whose A1C value is above 8% after an A1C value less than 9%, and a blood glucose con-
medical nutrition therapy. The addition of a second centration of 160 to 250 mg/dL. Care should be taken
agent may decrease A1C by 1% to 2%. There is no in patients with renal disease and liver disease, exces-
evidence that any one combination is better than sive alcohol intake, metabolic acidosis, and active
another. The addition of a third agent may further cardiac or pulmonary disease. Meformin should be
decrease A1C by about 1% to 1.5%. Insulin may be stopped before contrast dye use or surgery. The most
considered for A1C values above 8% on two agents. common side effects are gastrointestinal distress and
a metallic taste.
Sulfonylurea Sulfonylurea stimulates beta cells to
secrete more insulin in response to elevated glucose Thiazolidinediones Rosiglitazone and pioglitazone
levels. It is used in patients with a BMI less than 27, an are the thiazolidinediones used in the United States.
A1C value less than 9%, and/or a postprandial glucose They enhance insulin-sensitizing effect on muscles,
level of 200 to 300 mg/dL. Second-generation sulfony- adipose tissue, and liver cells. They may also increase
lureas are better tolerated and are preferred. About HDL concentrations, decrease blood pressure,
85% of the clinical effectiveness of glyburide and glip- decrease inflammation (CRP), and effect better fat
izide is achieved with half the recommended maximal distribution. Hemoglobin A1C may be reduced by
dose. Once daily preparations appears to be clinically up to 2.6% with a thiazolidinedione.

Table 46-4 Food Servings Equivalent to 15 g of Carbohydrate

1 small apple (4 oz) 1 cup milk
1
⁄4 large bagel (1oz) 1
⁄2 cup orange juice
1 small banana (4 oz) 1
⁄3 cup cooked pasta
1 biscuit 1 medium peach (4 oz)
1 slice of bread 1
⁄2 cup peas
2-inch-square unfrosted cake 1
⁄2 cup pinto beans or kidney beans
3
⁄4 cup ready-to-eat cereal 3 cups popped popcorn
1
⁄2 cup cooked cereal 1
⁄2 cup mashed potato
2 small cookies (2/3 oz) 15–20 potato chips (3/4 oz)
1
⁄2 cup corn 3
⁄4 oz pretzels
6 saltine crackers 1
⁄3 cup rice
1
⁄2 cup canned fruit 1 tablespoon sugar
1
⁄2 hamburger bun 1
⁄2 cup sweet potato
1
⁄2 cup light ice cream 2 taco shells (6-inch size)
1 tablespoon jam 1 tortilla (6-inch size)

386
 Table 46-5 The Effect of Various Treatments on the Reduction of Hemoglobin A1C Values
Medical Nutrition Thiazolidinedione
Treatment Therapy Sulfonylurea Biguanide Inhibitor α-Glucosidase Insulin

Reduction in 1%–2% Up to 2.3% Up to 2.2% Up to 2.6% 0.5%–1% Unlimited

hemoglobin A1C
Action Secretagogue Insulin sensitizer Insulin sensitizer
Monotherapy A1C < 8.5% BMI < 27, A1C < 9% BMI = 27, A1C < 9% BMI > 27, A1C < 9% A1C < 8%
indication
Major side effect Hypoglycemia Metabolic acidosis, Weight gain, edema Gastrointestinal Hypoglycemia,
gastrointestinal symptoms weight gain
symptoms
Caution Hypoglycemia, renal Stop before contrast Congestive heart Renal or hepatic
disease dye use; renal or failure; monitor disease
hepatic disease, liver function
cardiac or pulmonary
disease

387
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

In general, thiazolidinedione is indicated for New Agents Injectable glucose lowering agents from
insulin resistance, a BMI greater than 27, an A1C two new classes were approved by the U.S. Food and
value less than 9%, a glucose concentration of Drug Administration (FDA) in 2005 for treatment
160 to 250 mg/dL, and metabolic syndrome. Liver of type 2 diabetes. Exenatide (Byetta) is an incretin
function should be monitored regularly, and thia- mimetic that stimulates insulin secretion, slows
zolidinedione should be discontinued if the ala- gastric emptying, and reduces hunger. Pramlintide
nine transaminase level is more than 2.5 times (Symlin) is a synthetic amylin, which along with
normal. It also should not be used in individuals insulin, is secreted by the pancreas to reduce post-
with New York Heart Association functional status prandial glucose.
class II to IV. Inhaled insulin may also receive FDA approval
The side effects of thiazolidinediones include soon. It was approved in the European Union in
volume expansion leading to weight gain, edema, 2005.
and a mild reduction in hemoglobin values. Another class of glucose lowering agent, gli-
tazars, is under investigation. It improves blood
a-Glucosidase Inhibitors This class includes acar- glucose like the thiazolidinediones and improves
bose (Precose) and miglitol (Glyset). They target lipids like a fibrate. The first glitazar is muragli-
postprandial glucose by delaying the absorption of tazar, which is pending FDA approval but has raised
disaccharides and complex carbohydrates, and to a some safety concerns regarding the cardiovascular
lesser degree lactose. If acarbose or miglitol is used in system.
combination with sulfonylureas or insulin, then
hypoglycemia can be managed with glucose or milk. Complications and Comorbid Conditions
a-Glucosidase inhibitors are less potent than
sulfonylureas or biguanides, with the usual A1C Macrovascular Complications, Dyslipidemia,
reduction of 0.5% to 1%. They are indicated for and Hypertension
insulin resistance or deficiency, an A1C value less Individuals with diabetes mellitus type 2 tend to have
than 8%, and a postprandial glucose concentration lipid disorders and hypertension (National Chol-
of 180 to 225 mg/dL. They need to be used with cau- esterol Education Program Expert Panel, 2001● A ●
B;
tion in patients with liver or renal disease. The most Stratton et al., 2000● A ). The lipid disorders include
common side effects are diarrhea and flatulence. hypertriglyceridemia, low HDL concentration, and
an increase in atherogenic small, dense LDL parti-
Insulin Insulin has the greatest blood sugar lower- cles. The management goals are to achieve HDL
ing potency of all medications. The goal of using concentrations above 40 mg/dL, triglyceride levels
insulin is to duplicate the natural physiologic insulin below150 mg/dL, and LDL concentrations below
and glucose level, in which basal insulin supplies 100 mg/dL (< 70 for individuals with high cardiac
half of the body’s needs while insulin secreted in risks). There are several classes of medication for
response to meals fills the rest. The insulin regimen these goals. Statins lower LDL concentrations.
should start simple and advance as needed (Mayfield Fibrate increases HDL concentrations and lowers
et al., 2004● C ). triglyceride levels. Combinations of these two alone
Insulin is usually divided into two major types. or with niacin, nicotinic acid, thiazolidinedione, and
Background insulin includes NPH, lente, ultralente, ezetimebe are also used.
and glargine. Glargine is preferred as it provides the The aim of blood pressure control is to achieve
most consistent results. It can be given at bedtime a systolic blood pressure of less than 130 mm Hg
or in the morning to accommodate the patient’s and a diastolic blood pressure of less than 80 mm
lifestyle. Bolus insulin includes regular, Aspart, and Hg, according to the American Diabetes Association
Lispro. Aspart or Lispro is preferred as they provide (2003● C) and the National Kidney Foundation
more flexibility. (2004● C ), or a diastolic blood pressure of less than
There are several ways in which insulin may con- 85, according to the Joint National Committee VII
tribute to the management of diabetes mellitus type 2. (2003 ●C ). ACE inhibitors or thiazide diuretics are
It can be used briefly for 2 to 3 months upon diagno- usually the first choice for those with no nephropa-
sis to stabilize the hyperglycemia before transitioning thy. For individuals with nephropathy, ACE
to an oral agent. Patients taking several combination inhibitors are preferred if tolerated. Angiotensin-
oral agents may want to switch to a combination of receptor blockers are used if ACE inhibitors are not
an oral agent and long-acting glargine, or just combi- tolerated.
nations of short-acting and long-acting insulins in According to the National Cholesterol Education
place of oral agents. Program Expert Panel on Detection, Evaluation and
Common side effects of insulin are hypo- Treatment of High Blood Cholesterol in Adults
glycemia, local skin reactions, weight gain, systemic (2001● A ●B ) (Adult Treatment Panel III), diabetes is
allergic reactions, and lipodystrophy. considered a coronary heart disease risk equivalent.

388
 Chapter 46 Swollen Foreskin (Diabetes Mellitus Type 2)

Aspirin should be considered for all individuals with Preventing and Forestalling
diabetes mellitus type 2. the Development of Diabetes Mellitus

Preventing Microvascular Complications Lifestyle changes such as sensible nutrition and phys-
Potential microvascular complications from dia- ical activity as discussed in medical nutrition therapy
betes mellitus type 2 include nephropathy, retinopa- can prevent and forestall diabetes. Identifying and
thy, and neuropathy. An annual microalbuminuria educating individuals at risk are important. Met-
screen with spot urine (albumin/creatinine ratio) is formin, thaizoidinediones, and antihypertensives
used for monitoring early signs of nephropathy. An such as ACE inhibitors and ARBs may prevent the
ACE inhibitor is often used for prevention and treat- complex interaction among diabetes, hyperlipi-
ment for nephropathy. An annual dilated eye exam- demia, and hypertension.
ination screens for and prevents diabetic retinopathy.
Screening for peripheral neuropathy entails a com-
prehensive foot examination, including inspection Material Available on Student Consult
of skin and nails, palpation for pedal pulses, and
Review Questions and Answers about Diabetes
checking for reflexes, light touch sensation, and Mellitus Type 2
vibration.

REFERENCES
American Diebetes Association. Clinical practice recom- Executive summary of the third report of the National
mendations 2003. Diabetes Care 2003;26(Suppl 1): Cholesterol Education Program (NCEP) Expert Panel
S1–S156.● A ●B ●C on Detection, Evaluation and Treatment of High Blood
American Diabetes Association Expert Committee. Cholesterol in Adults (Adult Treatment Panel III).
Diagnosis and classification of diabetes mellitus. JAMA 2001;285:2486-2497.● A ●B
Diabetes Care 2004;27(Suppl 1):S5–S10.● C National Kidney Foundation. Kidney Disease Outcome
Franz MJ, Bantle JP, et al. Nutrition principles and recom- Quality Initiative (K/DOQI). K/DOQI clinical practice
mendations in diabetes. Diabetes Care 2004;27(Suppl 1): guidelines on hypertension and antihypertensive agents
S36–S46.● A●B ●CJ in chronic kidney disease. 2004. Available at www.
Joint National Committee on Prevention, Detection, kidney.org/professionals/kdoqi/guidelines_bp/index.
Evaluation, and Treatment of High Blood Pressure. The htm. Accessed 1/6/2006.
seventh report. JAMA 2003;289:2560–2571.● C Stratton IM, Adler AI, et al. Association of glycemia with
Lebovitz HE. Oral therapies for diabetic hyperglycemia. macrovascular and microvascular complications of
Endocrinol Metab Clin North Am 2001;30:909-933.● A ●B type 2 diabetes (UKPDS 35): Prospective observational
Mayfield JA, White RD, et al: Insulin therapy for type 2 dia- study. BMJ 2000;321:405–412.● A
betes: Rescue, augmentation, and replacement of beta- U.K. Prospective Diabetes Study 16. Overview of 6 years’
cell function. Am Fam Physician 2004;70:489–500.● C therapy of type 2 diabetes: A progressive disease.
National Cholesterol Education Program Expert Panel on U.K. Prospective Diabetes Study Group. Diabetes
Detection, Evaluation and Treatment of High Blood 1995;44:1249–1258 [erratum in Diabetes 1996;
Cholesterol in Adults (Adult Treatment Panel III): 45:1655].●A

SUGGESTED READINGS
Diabetes Coalition of California, California Diabetes Thiedke CC. From page to practice: Improving care of type
Prevention and Control Program. Basic Guidelines for 2 diabetes. American Academy of Family Physicians
Diabetic Care. Sacramento, California Diabetes Monograph, April, 2004.
Prevention and Control Program, Department of
Health Services, 2003.●
A ●
B ●
C

389
 C h a p t e r

47 Obesity and Elevated Blood

Pressure (Metabolic Syndrome)
Anna Mies Richie

Family History
KEY POINTS Both parents are living. Her mother is obese, has type
2 non–insulin-dependent diabetes, hypertension,
1. The combination of visceral adiposity, poor and high cholesterol. Her father has hypertension.
nutrition, inactivity, and a genetic predisposition She has two younger sisters, both alive and well.
leads to insulin resistance. There is no family history of breast or colon cancer.
2. Type 2 diabetes is a two-hit disorder: insulin Her two children are healthy.
resistance and beta cell toxicity.
3. Waist circumference is measured at the iliac
Health Habits
crest, with the patient gently exhaling.
Suzanne denies using tobacco products, alcohol, or
4. In certain populations, waist circumference may
illicit drugs. She has had no exercise routine for more
be a more sensitive measure of relative disease
than 5 years.
risk than body mass index (BMI).
5. Successful management of the patient with
metabolic syndrome should focus on weight Social History
reduction and modification of the patient’s Suzanne lives with her husband and two children.
lifestyle. She enjoys singing in the church choir and reading.

Review of Systems
A 12-point review of systems is negative except for an
8-pound weight gain in the past year. The patient
INITIAL VISIT admits to only 1 day per week or less of physical
activity. The patient also states she has been eating
Subjective more fast food for lunch and eating out more for
dinner due to time constraints and increased stress
Patient Identification and Presenting from a new job. Nighttime snacking is common.
Problem Fruits and vegetables are consumed only once or
Suzanne S. is a 36-year-old white woman who pre- twice daily.
sents to the clinic for her annual physical and Pap
examination. She has no concerns or problems to
discuss. Her last Pap was 1 year before. Objective
Physical Examination
Medical History Suzanne is a pleasant woman who appears her
Suzanne has no major medical illnesses. A tubal liga- stated age. Her blood pressure is 138/88 (recheck
tion is her only surgery. She has had two normal 136/88), pulse is 78 and regular, weight is 190
spontaneous vaginal deliveries 4 and 7 years ago. pounds, and height is 5 feet 5 inches. BMI is 32, and
During the last pregnancy, Suzanne had gestational waist circumference is 37 inches. The physical
diabetes that was controlled with diet. On her 6 week examination is normal except for abdominal
postpartum visit, her blood sugar was normal. obesity. A Pap smear is done.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

390
 Chapter 47 Obesity and Elevated Blood Pressure (Metabolic Syndrome)

Assessment and behavioral modification. The risks of developing

hypertension, diabetes mellitus, heart disease, and
Working Diagnosis stroke were discussed. A follow-up visit in 1 month
Obesity, elevated blood pressure, hypothyroidism, was recommended for a blood pressure and weight
metabolic syndrome. check. Periodic cholesterol and glucose assessment
will be made; further action will depend on the
amount of weight loss.
Plan
Diagnostic
Fasting plasma cholesterol, high-density lipoprotein DISCUSSION
(HDL), low-density lipoprotein (LDL), triglycerides,
fasting glucose, liver, kidney, and thyroid function Metabolic syndrome is the product of primary
studies (aspartate aminotransferase, alanine amino- insulin resistance of tissues and secondary defects of
transferase, creatinine, blood urea nitrogen, and free fatty acid (FFA), carbohydrate, and lipoprotein
thyroid-stimulating hormone) were performed. metabolism. The constellation of increased abdomi-
nal obesity, elevated triglycerides, hyperglycemia,
Patient Education and elevated blood pressure is related to the underly-
The 8-pound weight gain since last year and the ing insulin resistance. This ultimately predisposes to
28-pound weight gain since her first child 7 years the development of diabetes mellitus type 2, dyslipi-
ago were discussed. A physical activity prescrip- demia, hypertension, and cardiovascular disease
tion, including 30 minutes of activity at least 3 days (CVD). Metabolic syndrome provides a common
per week, was given; both cardiovascular and clustering of these diseases (Fig. 47-1).
resistance training were recommended. Increasing The relationship between these findings has
fruits and vegetables and decreasing portion sizes been described throughout the 20th century (Table
were recommended. 47-1). In 2001, the National Cholesterol Education
Program Adult Treatment Panel (ATP) III published
guidelines defining metabolic syndrome (Table
FOLLOW-UP VISIT 47-2). Although the new guidelines are specific, the
disease itself should be understood as a progression
Subjective of vague and complex interactions between the ele-
Suzanne returned in 2 weeks to follow up on her vated FFAs and target organs.
laboratory test results. She reports that she has Assessing U.S. Census 2000 data, approximately
started improving her diet and has walked several 47 million adults in the United States manifest
times since the last patient encounter, although metabolic syndrome. The prevalence of metabolic
finding time to work out routinely is still difficult. syndrome is also high among obese children and
adolescents. Factors associated with increased
expression of metabolic syndrome include excess
Objective
caloric and carbohydrate consumption, visceral
Her blood pressure is 138/86, pulse is 70 and regular, obesity, physical inactivity, advancing age, family
and weight is 188 pounds. BMI and waist circumfer- history, and medications (some atypical antipsy-
ence have not changed (32 and 37, respectively). chotics).

Laboratory Tests
The results of the lipid panel were triglycerides, 180
mg/dL; HDL cholesterol, 40 mg/dL; LDL cholesterol,
130 mg/dL; fasting glucose, 116 mg/dL; thyroid- Diabetes
stimulating hormone 1.2 μIU/mL (normal). Liver mellitus Type 2
function studies and creatinine were also normal.

Assessment
Metabolic
Metabolic syndrome is most likely due to visceral obe- syndrome
sity, inactivity, excess caloric consumption, and age.

Dyslipidemia Hypertension
Plan
A strict weight loss program was recommended con-
centrating on the triad of nutrition, physical activity, Figure 47-1 The clustering of metabolic syndrome.

391
 Chapter 47 Obesity and Elevated Blood Pressure (Metabolic Syndrome)

Table 47-1 Recognition of Insulin Table 47-2 NCEP ATP III Diagnostic
Resistance throughout the Factors for Metabolic
Past Century Syndrome in Adults
1923 Kylin Described clustering Risk Factor Defining Level
of hypertension,
hyperglycemia, and Abdominal obesity
gout (waist circumference)
1936 Himsworth Recognized class of Men >102 cm (>40 inches)
diabetes related to Women >88 cm (>35 inches)
a lack of an Triglycerides ≥150 mg/dL (1.69 mmol/L)
“insulin-sensitizing” HDL cholesterol
factor Men <40 mg/dL (1.04 mmol/L)
1947 Vague Recognized the high Women <50 mg/dL (1.29 mmol/L)
risk of “android” Blood pressure ≥130/85 mm Hg
(upper body) Fasting glucose ≥110 mg/dL (6.1 mmol/L)
obesity compared
with “gynoid” Diagnosis is established when three or more risk
(gluteofemoral) factors are present.
obesity HDL, high-density lipoprotein; NCEP ATP III, National
1988 Reaven Syndrome X Cholesterol Education Program Adult Treatment
(hyperinsulinemia, Panel III.
high blood pressure, From Executive Summary of the Third Report of the
National Cholesterol Education Program (NCEP)
elevated
Expert Panel on Detection, Evaluation, and
triglycerides, low Treatment of High Blood Cholesterol in Adults
HDL) (Adult Treatment Panel III). JAMA 2001;285:
1989 Kaplan The Deadly Quartet— 2486–2497.
Recognized the
relationship of
syndrome X with insulin resistance, increased adrenergic receptors,
upper body obesity impaired insulin-mediated antilipolysis, and increased
1999 World Health Hypertension, catecholamine-mediated lipolysis. These differences
Organization dyslipidemia, increase the FFAs in circulation.
obesity, elevated The increase in FFAs contributes to insulin
fasting insulin,
resistance and vice versa. FFAs impair the insulin
microalbuminuria
2001 NCEP ATP III Waist circumference,
mediated glucose transport at muscle tissue and also
HDL, triglycerides, cause beta-cell lipotoxicity in the pancreas resulting
blood pressure, ultimately in hyperglycemia. As the peripheral tissues
fasting glucose (see become more resistant to insulin, glucose disposal
Table 47-2) declines and the FFA level continues to increase. As
the FFA level and insulin resistance increase, hepatic
HDL, high-density lipoprotein; NCEP ATP III, National
Cholesterol Education Program Adult Treatment
glucose and lipoprotein production increase, con-
Panel III. tributing to the hyperglycemia and dyslipidemia
(Fig. 47-2).
One study of women of similar body fat used
In the United States, Mexican Americans have magnetic resonance imaging to characterize them by
the highest age-adjusted prevalence of metabolic percentage of visceral adiposity. Women with larger
syndrome (31.9%). The prevalence in whites is the amounts of visceral adipose tissue had higher levels
same in both men and women (24%). However, of fasting insulin and triglycerides and lower levels of
African-American women and Mexican-American HDL cholesterol.
women have a much higher prevalence than men of
the same ethnic background.
Pathophysiology of Insulin Resistance

Visceral Adiposity and Free Fatty Acids Under normal conditions, plasma insulin regulates
the release of FFAs from adipocytes, glucose dis-
Visceral adipose tissue may be categorized as an posal in skeletal muscle, and glucose and lipid
endocrine organ because of its regulation and metabolism in the liver. A variety of theories are
production of hormones. It appears that visceral thought to underlie the defects in insulin-stimu-
adipose tissue differs significantly from other adi- lated glucose transport in the peripheral tissue and
pose tissue because of the larger cell size, greater liver (Box 47-1).

392
 Chapter 47 Obesity and Elevated Blood Pressure (Metabolic Syndrome)

Pancreas: Muscle:
↓Insulin ↓Glucose
secretion uptake

Hyperglycemia

Adipose: Liver:
↑ Lipolysis ↑ Glucose
production

Figure 47-2 The progression from visceral adiposity to metabolic syndrome.

In the earliest phases, most of the insulin resist- insulin resistance and the clinical diagnosis of dia-
ance appears to be concentrated in the peripheral betes mellitus type 2. The progression of abnormal
tissue (adipose and skeletal muscle), the site respon- glucose begins with postprandial hyperglycemia
sible for approximately 70% to 90% of glucose dis- from peripheral tissue resistance and develops to
posal following a carbohydrate load. Loss of insulin fasting hyperglycemia. Fasting hyperglycemia is
sensitivity in the liver is believed to be a later stage of more closely associated with hepatic resistance.
insulin resistance. The liver is an important site for In an effort to improve the peripheral and
glucose clearance, storage, gluconeogenesis, insulin hepatic resistance, release of insulin from the
clearance, and lipid metabolism. pancreas progressively increases. As long as the beta-
cell function is adequate, the patient will be normo-
glycemic from compensatory hyperinsulinemia.
Diabetes Mellitus
Once the beta-cell function is inadequate, there is a
The combination of visceral adiposity, poor nutri- relative insulin deficiency resulting in diabetes melli-
tion, inactivity, and a genetic predisposition leads to tus (fasting glucose >126 mg/dL) (Fig. 47-3).

Box 47-1 Possible Theories and Mechanisms for Insulin Resistance

1. The hormone resistin, secreted from inositol 3 kinase (Pl3K) activity, leading to
adipocytes, has been shown to impair glu- decreased glucose transport into muscle.
cose tolerance. 6. Chronic hyperglycemia causing interfer-
2. The “thrifty genotype” hypothesis proposes ence or toxicity to the insulin-stimulated
that evolving from a harsh environment and glucose transport.
unstable food supply causes efficient fat 7. Tumor necrosis factor (TNF) may be overex-
storage, leading to weight gain, thus predis- pressed in the muscle and adipose tissue
posing a person to metabolic syndrome. and is negatively correlated with insulin
3. Defects in the genes that code for: glyco- stimulated glucose metabolism.
gen synthase, hexokinase, the insulin 8. Alterations in the hypothalamic–pituitary-
receptor substrate (IRS) isomer, glucose adrenal axis, possibly in diurnal cortisol
transporter 4 (GLUT 4), tumor necrosis fac- kinetics in response to stress.
tor α, and/or peroxisome proliferators acti- 9. Receptor knockout models suggest the
vated receptor (the target of the diabetic liver may have a greater role in whole-body
drug class thiazolidinediones). insulin sensitivity.
4. There may be a link between insulin resist- 10. Defects in the β3-adrenergic receptor have
ance and leptin resistance, a protein been associated with increased lipolysis in
encoded by the obese gene in adipocytes visceral fat tissue and features of metabolic
that is thought to signal a decrease in syndrome.
ingestive behavior. 11. Low birth weight predisposes to increased
5. Chronic elevations of free fatty acids have risk of diabetes.
been shown to inhibit the phosphatidyl-

393
 Chapter 47 Obesity and Elevated Blood Pressure (Metabolic Syndrome)

terol, and small LDL particles define atherogenic

dyslipidemia, a characteristic feature associated with
metabolic syndrome. This lipid profile is related to
the overproduction, impaired clearance, and abnor-
mal regulation of the lipoprotein particle and com-
position (variation in the amount of cholesterol
Subcutaneous
carried per particle).
Triglyceride and very low density lipoprotein
Retroperitoneal particle production increases in response to
Visceral
increased FFA delivery to hepatic tissue. Normally,
very low density lipoprotein particles are cleared
by lipoprotein lipase. Increased levels of FFAs,
apolipoprotein C-III, and decreased physical activity
Figure 47-3 Etiology of type 2 diabetes mellitus: insulin
resistance and diminished insulin secretion.
impair lipoprotein lipase and result in insulin resist-
ance. The makeup of the LDL and HDL particles
may also become triglyceride enriched and choles-
Therefore, type 2 diabetes is a two-hit disorder:
terol depleted, making them less stable in the pres-
insulin resistance and beta-cell toxicity. Because insulin
ence of insulin resistance.
resistance is related to three areas (adipose, skeletal,
and hepatic tissue) and beta-cell toxicity occurs in the
pancreas, the development of hyperglycemia has been Hypertension
referred to as the “dyshormonious quartet” (Fig. 47-4).
Because resistance to insulin-mediated glucose dis-
posal and compensatory hyperinsulinemia are com-
Dyslipidemia mon in patients with hypertension, the possibility has
Elevated serum triglycerides, decreased HDL choles- been raised that insulin resistance causes hyperten-
terol, normal to minimally increased LDL choles- sion. There may be a relationship between eating,
especially carbohydrate and fat consumption, and
increased sympathetic activity. Obesity-related
Visceral adiposity hypertension may also be a byproduct of mechanisms
to restore energy balance and stabilize body weight.

Increased lipolysis Waist Circumference

Glucose Measurement of the waist circumference with a tape

measure can be used to assess visceral adiposity
Increased free fatty acids (Fig. 47-5) and risk of CVD. The measurement should
be at the iliac crest, not at the belt line, with the patient
gently exhaling. Men are more apt to develop the clas-
X sic “apple” shape, whereas women tend to have lower
body obesity or the “pear” shape. This body fat distri-
bution may be influenced by androgens, cortico-
steroids, and growth hormones. Women with
Muscle tissue Hepatic tissue polycystic ovarian syndrome are also more likely to
develop the characteristic visceral obesity.
In certain populations, such as Asian Amer-
icans and older women of normal weight, waist
• Increased: free fatty Increased: circumference may be a more sensitive measure of
acid oxidation • Free fatty acid oxidation relative disease risk than BMI. For patients with
• Decreased: glucose • Triglyceride synthesis a BMI between 25 and 34.9 kg/m2, a high waist
utilization • VLDL Secretion
• Gluconeogenesis
circumference increases the risk of type 2 diabetes
mellitus, dyslipidemia, hypertension, and CVD.
However, with a BMI greater than 35 kg/m2, waist
circumference may not be as significant to the risk of
Hyperglycemia and dyslipidemia morbidity and mortality (Table 47-3).
(Metabolic syndrome) The National Institutes of Health (NIH) devel-
oped evidence-based waist circumference cutoff points
Figure 47-4 The dyshormonious quartet. VLDL, very that assist with identifying those at increased health
low density protein. risk. Those with high waist circumference values are

394
 Chapter 47 Obesity and Elevated Blood Pressure (Metabolic Syndrome)

Inactivity + Visceral + Genetic

poor diet adiposity predisposition

Insulin
resistance
Compensatory hyperinsulinemia Relative insulin deficiency
“normoglycemia” hyperglycemia

Adequate Inadequate
beta cell function beta cell function

Metabolic syndrome Metabolic syndrome

without diabetes mellitus with Type 2 diabetes mellitus

Figure 47-5 Location of visceral adipose tissue.

more likely to have hypertension, diabetes, dyslipi- 60 years without known CVD, cancer, or diabetes
demia, and metabolic syndrome compared with those were followed for an average of 11.4 years to deter-
with normal waist circumference values. Many associ- mine CVD, coronary heart disease (CHD) death, and
ations remained significant after adjusting for con- all-cause mortality among those with and without
founding variables (age, race, poverty, physical activity, defined metabolic syndrome. After adjustment for
smoking, and alcohol intake) in normal weight, over- conventional cardiovascular risk factors, CHD death
weight, and obese women and overweight men. In this was 2.9- to 4.2-fold higher for subjects with ATP
study, the adverse effects of a high waist circumference III defined metabolic syndrome. Data from the
were more apparent in women than men. Framingham Heart Study reported that the presence
of metabolic syndrome alone predicts approximately
25% of all new-onset CVD. The 4S (Scandinavian
Cardiovascular Disease
Simvastatin Survival Study) and the Air Force/
Individuals with metabolic syndrome are at Texas Coronary Atherosclerosis Prevention Study
increased risk of CVD and overall mortality. In the (AFCAPS/TexCAPS) both showed that patients with
Kuoppio Ischemic Heart Disease Risk Factor Study, a metabolic syndrome showed an increased risk of
prospective cohort of 1209 Finnish men of age 42 to major coronary events.

Table 47-3 Classification of Overweight and Obesity by BMI, Waist Circumference, and
Associated Disease Risk

Disease Risk (Relative to Normal

Weight and Waist Circumference)

Men: ≤40 inches (102 cm) Men: >40 inches (102 cm)
Classification BMI (kg/m2) Women: ≤35 inches (88 cm) Women: >35 inches (88 cm)

Underweight <18.5 — —
Normal 18.5–24.9 — Increased
Overweight 25.0–29.9 Increased High
Obesity 30.0–34.9 High Very high
Morbid obesity 35.0–39.9 Very high Very high
Supermorbid obesity ≥40 Extremely high Extremely high

BMI, body mass index.

Adapted from National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation,
and Treatment of Overweight and Obesity in Adults. Available at www.nhlbi.nih.gov/guidelines/obesity/
ob_home.htm. Accessed 1/24/2006.

395
 Chapter 47 Obesity and Elevated Blood Pressure (Metabolic Syndrome)

Besides dyslipidemia and elevated blood pres- Exercise can also increase insulin sensitivity in mus-
sure, there may be many other factors involved that cle cells by increasing the mitochondrial oxidation.
independently increase the risk of CVD. For exam-
ple, increased levels of asymmetric dimethylarginine
Pharmacotherapy
are associated with endothelial dysfunction and
increased risk of CVD. There is a significant relation- Beyond lifestyle changes, aggressive pharmacologic
ship between insulin resistance and plasma concen- treatment is frequently necessary. Because of the high
tration of dimethylarginine. risk of CVD, all patients with metabolic syndrome,
It is believed that long before diabetes becomes unless there is a contraindication, should be pre-
manifest, the clustering of metabolic abnormalities scribed aspirin for antiplatelet therapy. Frequently,
seems to exert an additive effect on the atherosclerotic medications are needed for hyperlipidemia, glycemic
process. The relationship between diabetes and CVD control, hypertension, and weight loss.
is so profound that approximately 75% of people with It is important to remember that, although a
diabetes will die of CVD complications. Also, those number of medications may lower blood sugar, lower
with diabetes have the same risk of a cardiovascular blood pressure, or improve lipids, the overall goal is
event as do people with already established CHD. to decrease mortality. For example, if the medication
has been shown to increase HDL but has not been
Management of Metabolic Syndrome shown to decrease mortality, then treatment with this
medication would be treating a disease, not the
Successful management of the patient with metabolic patient. For example, estrogen therapy has been
syndrome should focus on weight reduction and shown to favor lipid profiles; however, the current
modification of the patient’s lifestyle (diet, physical evidence suggests estrogen therapy may lead to an
activity). Behavior modification techniques may increase in cardiovascular events. Generally, patient-
include self-monitoring, stimulus control, cognitive oriented medical practice is the goal over disease-ori-
restructuring, stress management, and social support. ented medicine. This may require some difficult
From the Nurses Health Study, almost 90,000 decision making and analysis of the evidence.
women were followed to examine the association of
lifestyle and CHD. Adherence to lifestyle guidelines
Conclusion
involving diet, exercise, and abstinence from smok-
ing was associated with a very low risk of CHD, CHD remains the leading cause of death among men
more than 80% lower than that in the rest of the and women in the United States. Much effort has
population. focused on the pharmacologic management of
Physical activity is an important predictor of hypertension, hyperlipidemia, CHD, and congestive
weight maintenance. Several studies suggest that heart disease. These treatments are of proven benefit
physically activity, even in obese patients, may sub- but costly and are secondary and tertiary prevention.
stantially reduce the risk of cardiovascular events Addressing a healthy BMI early in a disease process
and all-cause mortality. by promoting healthy lifestyle practices is important
Exercise has been shown to improve lipoprotein in stopping the disease process of metabolic syn-
production and concentration. Using conventional drome that ultimately will lead to the diseases associ-
lipid analysis, exercise may not show a significant ated with CVD.
change in the lipid profile. However, using nuclear
magnetic resonance spectroscopy, exercise can be Material Available on Student Consult
shown to positively affect the concentration and size
Review Questions and Answers about Metabolic
of LDL, HDL, and very low density lipoprotein, mak- Syndrome
ing these particles more stable and less atherogenic.

SUGGESTED READINGS
Depres JP, Lemieux I, Prud’homme D. Treatment of obe- Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular mor-
sity: Need to focus on high risk abdominally obese bidity and mortality associated with the metabolic syn-
patients. BMJ 2001;322:716–720. drome. Diabetes Care 2001;24:683–689.● B
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic Janssen I. Body mass index, waist circumference, and
syndrome among US adults: Findings from the Third health risk. Arch Intern Med 2002;162:2074–2079.● B
National Health and Nutrition Examination Survey. Lakka H, Laaksonen DE, Lakka TA, et al. The metabolic
JAMA 2002;287:356–359. syndrome and total and cardiovascular disease
Ginsberg HN. New perspectives on atherogenesis: Role of mortality in middle aged men. JAMA 2002;288:
abnormal triglyceride-rich lipoprotein metabolism. 2709–2716.● B
Circulation 2002;106:2137–2142.

396
 Chapter 48 Abdominal Obesity (Metabolic Syndrome)

Report of the Expert Committee on the Diagnosis and no. 01-3670). Washington, DC, Government Printing
Classification of Diabetes Mellitus. Diabetes Care Office, 2001.●
C
2003;26(Suppl 1):S5–S20.● C Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of
The Sixth Report of the Joint National Committee on Preven- type 2 diabetes mellitus by changes in lifestyle among
tion, Detection, Evaluation, and Treatment of High Blood subjects with impaired glucose tolerance. N Engl J Med
Pressure. NIH/NHLBL (NIH publication no. 98-4080). 2001;344:1343–1350.● A
Washington, DC, Government Printing Office, 1997.● C Weiss, R, Dziura J, Burgert T, et al. Obesity and the meta-
Third Report of the National Cholesterol Education bolic syndrome in children and adolescents. N Engl J
Program Panel. Executive Summary (NIH publication Med 2004;350:2362–2374.● B

C h a p t e r

48 Abdominal Obesity
(Metabolic Syndrome)
Darwin Deen

health screening at his job a few months ago, he was

KEY POINTS told that his blood pressure was elevated. The read-
ing was 138/90. At the time, he was advised to see his
1. Metabolic syndrome (MES) is associated with personal physician to have his blood pressure
insulin resistance and predicts risk of diabetes rechecked, but he was feeling fine and forgot about
mellitus and myocardial infarction. it. Eric reports a 10- to 15-pound weight gain over
2. MES is associated with an atherogenic dyslipi- the past 2 years––since he got married and his wife
demia and a prothrombotic state. had their daughter. On further questioning, he
3. Polycystic ovary syndrome and nonalcoholic admits that his pants waist size has increased from
steatohepatitis are also associated with insulin 36 to 40 inches and that his wife has commented on
resistance. his “beer belly.” He also feels that his physical activ-
4. Exercise and a weight reduction diet reduce ity level has declined since the birth of his 8-month-
insulin resistance. old daughter.
5. Assessment of and attention to stage of behav-
ior change will help physicians be more effective
Medical History
at stimulating behavior change in their patients.
Eric denies any significant medical history. He had
asthma as a child but has had no problems related to
his breathing since he was about 14 years old. He has
occasional eczema for which he uses hydrocortisone
INITIAL VISIT cream as needed. He reports some seasonal allergy
symptoms.
Subjective
Patient Identification and Presenting Family History
Problem Eric is an only child. His father died suddenly at the
Eric V. is a 37-year-old man who presents at his age of 62 (he thinks he was told his father had a heart
wife’s urging for a physical examination. Eric denies attack). His mother is 77 and has had diabetes for
any current complaints but reports that during a approximately 15 years ago.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

397
 Chapter 48 Abdominal Obesity (Metabolic Syndrome)

Report of the Expert Committee on the Diagnosis and no. 01-3670). Washington, DC, Government Printing
Classification of Diabetes Mellitus. Diabetes Care Office, 2001.●
C
2003;26(Suppl 1):S5–S20.● C Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of
The Sixth Report of the Joint National Committee on Preven- type 2 diabetes mellitus by changes in lifestyle among
tion, Detection, Evaluation, and Treatment of High Blood subjects with impaired glucose tolerance. N Engl J Med
Pressure. NIH/NHLBL (NIH publication no. 98-4080). 2001;344:1343–1350.● A
Washington, DC, Government Printing Office, 1997.● C Weiss, R, Dziura J, Burgert T, et al. Obesity and the meta-
Third Report of the National Cholesterol Education bolic syndrome in children and adolescents. N Engl J
Program Panel. Executive Summary (NIH publication Med 2004;350:2362–2374.● B

C h a p t e r

48 Abdominal Obesity
(Metabolic Syndrome)
Darwin Deen

health screening at his job a few months ago, he was

KEY POINTS told that his blood pressure was elevated. The read-
ing was 138/90. At the time, he was advised to see his
1. Metabolic syndrome (MES) is associated with personal physician to have his blood pressure
insulin resistance and predicts risk of diabetes rechecked, but he was feeling fine and forgot about
mellitus and myocardial infarction. it. Eric reports a 10- to 15-pound weight gain over
2. MES is associated with an atherogenic dyslipi- the past 2 years––since he got married and his wife
demia and a prothrombotic state. had their daughter. On further questioning, he
3. Polycystic ovary syndrome and nonalcoholic admits that his pants waist size has increased from
steatohepatitis are also associated with insulin 36 to 40 inches and that his wife has commented on
resistance. his “beer belly.” He also feels that his physical activ-
4. Exercise and a weight reduction diet reduce ity level has declined since the birth of his 8-month-
insulin resistance. old daughter.
5. Assessment of and attention to stage of behav-
ior change will help physicians be more effective
Medical History
at stimulating behavior change in their patients.
Eric denies any significant medical history. He had
asthma as a child but has had no problems related to
his breathing since he was about 14 years old. He has
occasional eczema for which he uses hydrocortisone
INITIAL VISIT cream as needed. He reports some seasonal allergy
symptoms.
Subjective
Patient Identification and Presenting Family History
Problem Eric is an only child. His father died suddenly at the
Eric V. is a 37-year-old man who presents at his age of 62 (he thinks he was told his father had a heart
wife’s urging for a physical examination. Eric denies attack). His mother is 77 and has had diabetes for
any current complaints but reports that during a approximately 15 years ago.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

397
 Chapter 48 Abdominal Obesity (Metabolic Syndrome)

Social and Occupational History

Eric is married and has one child. He works as a
police officer. He smoked as a teen but stopped more
than 10 years ago. He drinks one to two beers nightly
(12-oz. cans) and more on social occasions when he
and his wife get together with coworkers. He has
never used recreational drugs.

Review of Systems
Eric denies headache, blurry vision, chest pain, or
shortness of breath. He has no polyuria or polydipsia.

Objective
Physical Examination
Eric is a well-developed overweight but not obese-
Figure 48-1 Brown, velvety plaques in the axilla of a
appearing young man with a mildly protruding patient with acanthosis nigricans. (From Levine NL,
abdomen. He sits on the examination table in Baron JB. Acanthosis nigricans. E-medicine, July 2002.
no apparent distress. He is 70 inches tall and Available at www.emedicine.com/derm/topic1.htm.)
weighs 216 pounds. His blood pressure is 135/88,
and his resting pulse is 80. There is no significant
difference in his blood pressure when he is stand-
ing or lying down or between his right and left
arms. On inspection of his skin, some hyperpig-
mentation around his neck and under his axillae
consistent with acanthosis nigricans is noted
(Figs. 48-1 and 48-2). His head, ears, eyes, nose,
and throat examination is entirely within normal
limits. His neck is supple with no palpable thyroid
gland. His heart sounds are normal, and his PMI is
not displaced. His lungs are clear bilaterally, and
his abdominal examination reveals no masses or
palpable organomegaly. When he is both sitting
and standing, his subcutaneous abdominal fat Figure 48-2 Syndromes associated with acanthosis
flows over his belt in front and on both sides. His nigricans. (From Department of Dermatology, University
extremities and peripheral pulses are unremark- of Iowa College of Medicine. Available at www.tray.der-
able. There is no palpable adenopathy. His matology.uiowa.edu/AcanNigr01.htm.)
neurologic examination is normal. His waist
circumference measures 41 inches. His body mass
index is calculated at 31.
insulin resistance. Dominant mode of inheritance
(also called hereditary benign acanthosis nigricans).
2. Malignant acanthosis nigricans. Lesions are
Assessment occasionally associated with an underlying malig-
Working Diagnosis nancy.
Based on his blood pressure and waist circumfer- 3. Drug-induced acanthosis nigricans. Drugs that
ence, you suspect that Eric has metabolic syndrome produce or aggravate insulin resistance have been
(MES) (Table 48-1). You discuss with him the associated with acanthosis nigricans, for example,
possibility that his weight and specifically his niacin, oral contraceptive, methyltestosterone,
abdominal obesity are putting him at risk of future atypical antipsychotics.
diabetes and heart disease and ask him to return in 4. Acanthosis nigricans associated with insulin resist-
1 week for fasting blood sugar and lipid profile ance type A. A rare inherited form of severe
measurements. insulin resistance associated with hyperandro-
genism in females. Cause unknown. Diabetes
invariably develops.
Differential Diagnosis for Acanthosis 5. Acanthosis nigricans associated with insulin resist-
Nigricans ance type B. A rare inherited form of severe
1. Pseudoacanthosis nigricans. Same clinical appear- insulin resistance abnormality characterized by
ance as acanthosis nigricans but no underlying insulin antireceptor autoantibodies.

398
 Chapter 48 Abdominal Obesity (Metabolic Syndrome)

Treatment Panel III, the methodology for this test is

Table 48-1 Adult Treatment Panel III
poorly standardized. In addition, it adds little to
Criteria for Metabolic
making the diagnosis of MES.
Syndrome
You go over the results of these laboratory tests
Component Criteria (Any Three) with Eric, who is upset at how high his triglycerides
are and does not understand how his blood work can
Abdominal/central Waist circumference: be so abnormal when he feels fine. You explain to
obesity >102 cm (40 inches) him that this is a risk assessment and indicates a
in men, >88 cm (35 metabolic abnormality that will take years to have an
inches) in women
effect on how he feels and that the good news is that
Hypertriglyceridemia ≥150 mg/dL
Low HDL cholesterol <40 mg/dL (<1.036 because he is aware of the problem, he has an oppor-
mmol/L) for men, <50 tunity to do something about it before it causes any
mg/dL (<1.295 permanent damage.
mmol/L) for women You take a 24-hour recall of activity and diet
High blood pressure ≥130/85 mm Hg or from him and learn the following information.
documented use of Breakfast is usually a cup of coffee and a bagel with
antihypertensive cream cheese or butter or a croissant with jelly. He
therapy frequently has a snack consisting of a muffin or
High fasting glucose ≥110 mg/dL (≥6.1 donut and another cup of coffee before lunch. He
mmol/L)
uses whole milk and sugar in his coffee. Lunch is two
HDL, high-density lipoprotein. slices of pepperoni pizza or fast food and a large
Adapted from National Cholesterol Education Panel. soda. He eats dinner at home with his wife, who
Adult treatment panel III report. Available at often makes fried chicken or steak or occasionally
www.nhlbi.gov/guidelines/cholesterol/index.htm.
Accessed 8/28/2002.
fish. He likes rice or potatoes as a side dish and
usually has a vegetable or salad. He is sedentary on
Eric is not certain how to respond to the infor- most days of the week but plays softball with his
mation that you have given him but promises to coworkers on weekends in the spring and summer.
return for the requested blood work and to read Although he enjoys this leisure time activity, he
the information in the educational handout that admits that he is not in the kind of shape that he
you have provided (www.aafp.org/afp/20040615/ used to be in and that it takes him a few weeks each
2887ph.html). spring to get back to being able to run the bases
without getting seriously short of breath. You ask
him “stages of change” questions (Box 48-1) to
FOLLOW-UP VISITS assess his readiness to make lifestyle changes. He
seems more ready to change his exercise habits than
Two weeks later he returns for the results of his lab- his diet.
oratory work:

Laboratory Test Result (mg/dL) DISCUSSION

Fasting glucose 100
Total cholesterol 237 Metabolic Syndrome
Triglycerides 467 MES has been called by a variety of names, including
High-density lipoprotein 31 syndrome X and insulin resistance syndrome. This
Alanine aminotransferase, Within normal cluster of risk factors is responsible for much of the
aspartate aminotransferase, limits excess cardiovascular disease morbidity among over-
total and direct bilirubin weight and obese patients and those with type 2 dia-
Complete blood count Within normal betes mellitus (DM) (Vega, 2001● B). The National
limits Cholesterol Education Program’s Adult Treatment
Panel III report (2002● C ) identified MES as an inde-
Low-density lipoprotein is not calculated because pendent risk factor for cardiovascular disease and
his triglyceride level is too high. His non–high-density considers it an indication for intensive lifestyle mod-
cholesterol level is calculated at 206. ification; this conclusion is based on numerous non-
Although MES is a reflection of insulin resist- intervention trials.
ance, which can be measured using a ratio of fasting Although definitions have varied, the major
insulin to glucose, you have decided not to draw a characteristics of MES include insulin resistance,
fasting insulin level because, according to the abdominal obesity, elevated blood pressure, and
National Cholesterol Education Program’s Adult lipid abnormalities including elevated triglycerides

399
 Chapter 48 Abdominal Obesity (Metabolic Syndrome)

resistance has the potential to successfully address

Box 48-1 Assessing Readiness to MES. Expending more calories through exercise and
Change consuming fewer calories by eating less are the most
obvious and most successful interventions. The type
Stage of change can be determined using the
of exercise or the specific type of diet is of secondary
following series of questions:
importance. Starting slowly and gradually increasing
1. Have you ever changed or tried to change
exercise duration and intensity are associated with
the way you eat to lose weight or improve
greater long-term compliance with an exercise regi-
your health?
men. Any diet that leads patients to consume fewer
If “no,” skip to question 4.
calories will be effective, but saturated fat intake and
If “yes,” proceed to question 2.
simple carbohydrate intake deserve specific atten-
2. Are you currently following a dietary plan to
tion. Although pharmacotherapy needs to be consid-
lose weight or for other health related rea-
ered for some components, all patients diagnosed
sons?
with MES should be encouraged to attempt to
If “no,” skip to question 4.
change their diet and exercise habits as primary
If “yes,” proceed to question 3.
therapy. There is no question that weight loss
3. How long have you been following this
improves most (if not all) aspects of MES as well as
plan?
reduces obesity-related morbidity and mortality
If less than a month, the patient is in action
(Williamson et al., 1999● B). Unfortunately, most
stage.
patients find weight loss very difficult to achieve. The
If longer than 6 months, the patient is in
good news is that dietary changes and increased
maintenance stage.
exercise levels can be effective therapy, even in the
4. During the past month, have you thought
absence of weight loss.
about dietary changes you could make to
lose weight or improve your health?
If “yes,” the patient is in contemplation Behavior Change
stage. If the plan is specific and will be
The transtheoretical model of behavior change is
implemented within a month, then the
well suited to assessing a patient’s motivation and
patient is in preparation stage.
readiness to make lifestyle changes to reduce obesity,
If no, the patient is in precontemplation
diabetes, and cardiovascular-related risks. According
stage.
to the transtheoretical model, the stages that individ-
uals go through are precontemplation (not consid-
ering making a change in the target behavior),
and low high-density lipoprotein levels (Deen, contemplation (considering the pros and cons of
2004● B ). MES is also associated with a proinflamma- making a behavior change), preparation (planning
tory/prothrombotic state that may include coagula- steps to make a change), action (actually changing
tion abnormalities, elevated uric acid levels, the targeted behavior), maintenance (making the
microalbuminuria, and a shift toward small dense changed behavior habitual), and relapse (when a for-
low-density lipoprotein particles. The proinflamma- merly altered behavior pattern returns). Appropriate
tory state characterized by elevated levels of C-reac- provider responses to a patient depend on the stage
tive protein has been recognized as a stronger that the patient is in (Table 48-2).
predictor of sudden cardiac death than elevated
lipid levels (Albert et al., 2002●B). The coagulation
abnormalities include endothelial dysfunction, PLAN
hyperfibrinogenemia, increased platelet aggrega-
tion, and increased levels of plasminogen activator Eric is started on an angiotensin-converting enzyme
inhibitor 1. Insulin resistance has been implicated in inhibitor medication that will lower his blood pres-
the polycystic ovarian syndrome and nonalcoholic sure while not interfering with other aspects of his
steatohepatitis. Using the definition of the Adult lifestyle (he sits for many hours in a patrol car daily
Treatment Panel III of MES, a review of data from and is concerned about the impact of a diuretic). You
the Third National Health and Nutrition Exam- counsel him about diet and exercise and discuss glu-
ination Survey estimated that 22% of U.S. adults (24% cose-sensitizing medication. You assure him that
after age adjustment) have MES. exercise and dieting for weight loss is more effective
At this time no randomized controlled trials than medication (Diabetes Prevention Program
aimed specifically at treating MES have been pub- Research Group, 2002● A). You review his goals with
lished. Therefore, current treatment for MES consists him, and he seems to understand that there is no
of aggressive management of the individual compo- “quick fix” to this problem and that improvement is
nents of the syndrome. Anything that reduces insulin up to him. You reassure him that while it will not be

400
 Chapter 48 Abdominal Obesity (Metabolic Syndrome)

ter the day after he walks (better sleep, more energy),

Table 48-2 Stage-Specific Interventions
and he is motivated to try to find the time to walk on
Clinician’s Motivational the other days. His wife and daughter usually walk
Client Stage Tasks with him, so they spend family time together. He has
switched his milk to 2% and will try changing to 1%
Precontemplation Raise doubt: increase in a few more weeks. He is avoiding his second break-
the client’s perception fast in the morning and has started bringing a piece of
of the risks and
fruit with him for a snack. If he is really hungry, he has
problems of current
behavior an energy bar or a handful of nuts. He no longer has
Contemplation Tip the balance: discuss pizza or fast food for lunch, opting instead for a brown
reasons to change, bag lunch of a turkey sandwich with light mayonnaise,
risks of not changing; lettuce, and tomato, as well as yogurt and a few baby
strengthen the carrots. His wife has stopped frying foods in oil for
client’s self-efficacy dinner, and they are eating broiled or sautéed chicken
for change breast or fish one to two nights per week. You con-
Determination Help determine the gratulate him on the many positive changes that he
(preparation) best course of action has made and assure him that if he keeps up like this,
Action Help patient take steps
he will begin to see changes in his weight and waist cir-
toward change, build
multiple small steps cumference. You also challenge him to try to reduce
Maintenance Help patient to identify his beer consumption to three to four cans per week
and use strategies to rather than the same quantity per day. He denies any
prevent relapse problems with his antihypertension medication, and
Relapse Help patient renew the his blood pressure is 135/85.
process, avoid being Eric returns in 2 months. He and his wife have
judgmental continued seeing the dietitian, and he reports that he
enjoys a number of new recipes using whole grains
easy, he does not have to be “perfect,” that you are that his wife has found. He has continued his walking
confident that he can succeed, and that you will be regimen and has increased his pace when his wife and
there to help him in any way that you can. He makes daughter are not along. He drinks beer only on Friday
an appointment for his wife and himself to see a die- and Saturday nights, and he has noticed that his pants
titian in their community for dietary advice, and he are looser. He weighs 210 pounds, and his waist cir-
promises to begin your exercise prescription by cumference is 39 inches. You ask him about his plans
walking daily for 25 to 30 minutes. for the future, and he says that he wants to start run-
ning as soon as he feels up to it and that he would like
to get off the medication for his blood pressure if he
NEXT FOLLOW-UP VISIT can. You assure him that his goal is achievable.
Eric returns in 1 month. He is disappointed because
he has not lost any weight, but he reports that he and
his wife have tried a number of the suggestions made Material Available on Student Consult
by the dietitian and that most of them have been quite Review Questions and Answers about Metabolic
positive. He has started walking more, and although Syndrome
he usually walks only 3 to 4 days a week, he feels bet-

REFERENCES
Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM. Vega GL. Obesity, metabolic syndrome, and cardiovascular
Prospective study of C-reactive protein, homocysteine, disease. Am Heart J 2001;142:1108–1116.● B
and plasma lipid levels as predictors of sudden cardiac National Cholesterol Education Project. Adult treatment
death. Circulation 2002;105:2595–2599.● B panel III report. Available at www.nhlbi.nih.gov/guide-
Deen D. Metabolic syndrome: A time for action. Am Fam lines/cholesterol/index.htm. Accessed 8/28/2002.●C
Physician 2004;69:2875–2882.● B Williamson DF, Pamuk E, Thun M, Flanders D, Byers T,
Diabetes Prevention Program Research Group. Reduc- Heath C. Prospective study of intentional weight loss
tion in the incidence of type 2 diabetes with lifestyle and mortality in overweight white men aged 40–64
intervention or metformin. N Engl J Med 2002;346: years. Am J Epidemiol 1999;149:491–503.● B
393–403.● A
Levine NL, Baron JB. Acanthosis nigricans. E-medicine,
July 2002. Available at www.emedicine.com/derm/
topic1.htm. Accessed 1/8/2006.

401
 C h a p t e r

49 Irregular Menstruation
and Fatigue (Cushing’s Syndrome)
David M. Barclay III

tion, she feels tired all the time and finds it difficult
KEY POINTS to go about her usual daily routine. Activities that
used to excite her, such as her passion for kickboxing,
1. Most women who present with Cushing’s syn- no longer interest her, and even if she had the energy
drome also have clinical features of polycystic to box, excessive bruising has prevented her from
ovary syndrome, suggesting that Cushing’s syn- participating in the sport. She believes that her lack
drome should be ruled out in these patients. of activity is responsible for the 15-pound weight
2. Cushing’s syndrome may be diagnosed using gain she has experienced over the past year.
24-hour urinary free cortisol (UFC) in combina-
tion with an overnight 1 mg dexamethasone Medical History
suppression test (DST). Other than one or two urinary tract infections as a
3. Hypertension, abdominal obesity, glucose intol- teenager, Katie’s health has been excellent until
erance, and psychological disturbances are recently. Two months ago she went to the emergency
common presenting symptoms of Cushing’s department with unbearable lower abdominal pain
syndrome. and was diagnosed with a kidney stone. She was
4. Metabolic syndrome shares many features in given antibiotics and pain medication and the stone
common with Cushing’s syndrome. passed on its own 3 days later.
5. Primary care providers should treat the second-
ary conditions associated with hypercortisolism Family History
while a definitive treatment is pursued. Katie’s mother is 68 years old and has arthritis. Her
father is 74 years old. He has hypertension and dia-
betes. She has two sisters and one brother, who are in
good health as far as she knows.
INITIAL VISIT
Social History
Subjective Katie has been married for 5 years and has no children.
She works as a guidance counselor at the local high
Patient Identification and Presenting school. She eats a regular diet and until recently
Problem enjoyed running, swimming, and kickboxing. She
Katie B. is a 29-year-old white woman who presents drinks socially and does not smoke or use illegal drugs.
as a new patient complaining of irregular menses.
Review of Systems
History of Present Illness Katie has gained 15 pounds in the past year with no
Katie had her first period at the age of 14, and until noticeable change in eating habits. Constipation has
about a year ago, they came regularly every 28 days, also become a problem. She feels slow and lethargic
lasted 4 to 5 days, and had an “average” flow. She is a on most days, and she describes her mood as “blue.”
gravida 0, para 0. Katie is sexually active with her She does not consider herself depressed but admits
husband only. He had a vasectomy so she is sure she that many activities that used to be enjoyable are no
is not pregnant. During the past year, her periods longer interesting. She has no trouble falling asleep,
have become less frequent, occurring every 6 to 8 but getting up in the morning is very difficult. She
weeks, and her last period was 3 months ago. In addi- has noticed that she bruises easily and often notices

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

402
 Chapter 49 Irregular Menstruation and Fatigue (Cushing’s Syndrome)

new bruises during her morning shower. She has had

no headaches, shortness of breath, chest pains, Table 49-1 Features of Cushing’s
abdominal pains, or muscle aches. Syndrome and Metabolic
Syndrome X

Objective Cushing’s Metabolic

Syndrome Syndrome X
Physical Examination Hypertension Hypertension
General Katie appears anxious and alert. Her arms and Diabetes/insulin Diabetes/insulin
legs appear thin while her trunk appears mildly obese. resistance resistance
Dyslipidemia Dyslipidemia
Osteoporosis PCOS/hyperandro-
Vital Signs Her height is 5 feet 4 inches, weight is 138 PCOS/hyperandro- genism
pounds, temperature is 37.2˚C (98.9˚F), respiratory rate genism Oligomenorrhea/
is 18, blood pressure is 150/97 mm Hg, and pulse is 84. Oligomenorrhea/ hypogonadism
hypogonadism Abdominal
Head, Eyes, Ears, Nose, and Throat Katie’s face Myopathy/ obesity
appears rounded (moon face); external ear canals cutaneous wasting Nodular adrenal
and tympanic membranes are clear bilaterally; hear- Abdominal obesity disease
ing is grossly intact; conjunctivae are pink; pupils are Kidney stones
equal, round, and reactive to light and accommoda- Neuropsychiatric
tion; extraocular movements are intact without nys- problems
Nodular adrenal disease
tagmus; nose is clear; maxillary and frontal sinuses
are nontender; mouth has good dentition; and the PCOS, polycystic ovary syndrome.
oropharynx is clear.

Neck A prominent hump (buffalo hump) is present out in these patients. In addition, several characteris-
on her posterior neck; there is no lymphadenopathy, tics of the metabolic syndrome are shared with
thyromegaly, or jugular venous distention. Cushing’s syndrome (Table 49-1), presumably because
of the hyperactivity of the hypothalamic-pituitary-
Lungs The lungs are clear to auscultation. adrenal axis found in both. The differential diagnosis
of Cushing’s syndrome is found in Box 49-1.
Heart There is normal sinus rhythm without mur-
murs, rubs, or gallops.

Neurologic Katie is alert and oriented to person, Box 49-1 Differential Diagnosis
place, and time; cranial nerves II through XII are of Cushing’s Syndrome
intact; reflexes are 2+ throughout; motor strength is
5/5 throughout; however, the proximal musculature Metabolic syndrome X
of all extremities appears atrophied relative to the Obesity
distal musculature. The sensory examination is Chronic alcoholism
intact to light touch and pinprick; cerebellar func- Depression
tion is intact. Iatrogenic Cushing’s syndrome
Subclinical hypercortisolism
Skin Sun-exposed areas are darkly tanned. There are Acute illness
purple striae on the medial and proximal thighs and
lower abdomen.
Plan
Assessment
Diagnostic
Working Diagnosis The first step in Katie’s workup is to establish a diagno-
The presence of mild hypertension, moon face, a buf- sis of Cushing’s syndrome. Several diagnostic tests have
falo hump on the posterior neck, proximal muscle been used over the years, and no single test has proven
wasting, striae, oligomenorrhea, neuropsychiatric fully capable of distinguishing all cases of Cushing’s
problems, and a history of nephrolithiasis are all find- syndrome from normal and obese individuals.
ings that warrant an evaluation for the presence of The 24-hour urinary free cortisol (UFC) gives an
hypercortisolism or overt Cushing’s syndrome. Most integrated index of the amount of free (unbound)
women who present with Cushing’s syndrome also cortisol in the blood during this period and is consid-
have clinical features of polycystic ovary syndrome, ered by most experts to be the most useful initial test
suggesting that Cushing’s syndrome should be ruled at this time. Urinary cortisol levels, unlike plasma

403
 Chapter 49 Irregular Menstruation and Fatigue (Cushing’s Syndrome)

cortisol levels that measure total cortisol, both for 48 hours with measurement of urine steroids).
unbound and bound, are not influenced by factors This test has been shown to have a sensitivity of 79%,
that affect corticosteroid-binding globulin. Because a specificity of 74%, and a diagnostic accuracy of 71%
some individuals have intermittent hypercortisolism, in patients with mild Cushing’s syndrome. Factors
if the initial test is normal and there is a high index of that can cause an apparent lack of suppression for any
suspicion, as many as three 24-hour urine collections DST include decreased intestinal absorption of
should be performed. Urinary creatinine should also dexamethasone, drugs that enhance hepatic metabo-
be measured to verify the adequacy of the urine col- lism of dexamethasone (carbamazepine, phenytoin,
lection. If the glomerular filtration rate is less than 30 barbiturates, rifampin, meprobamate, amino-
mL/min, the UFC level may be falsely decreased. In glutethimide, methaqualone), elevated concentrations
children, the UFC level should be corrected by divid- of corticosteroid-binding globulin (exogenous estro-
ing the body surface area by 1.72 m2. gen therapy, pregnancy), and pseudo-Cushing’s con-
The most widely available measurement of UFC ditions. Any cortisol assay used for this test must have
is by immunoassays (e.g., radioimmunoassay, a sensitivity of at least 1 μg/dL.
immunometric assays). These assays may be influ- Late-night salivary cortisol testing appears to be
enced by various metabolites of cortisol and some a promising first-line screening test for Cushing’s
synthetic glucocorticoids. The reference range for syndrome in the future. Cortisol concentrations in
UFC depends on the type of assay used. The intro- saliva are independent of salivary flow rate and are
duction of high-performance liquid chromato- highly correlated with free plasma cortisol. Late-
graphy allows the separation of various urinary night (11 PM) salivary cortisol is a simple way to
glucocorticoids and metabolites; however, some screen for Cushing’s syndrome and has been found
substances such as carbamazepine and digoxin can to have a high diagnostic sensitivity and specificity.
coelute with cortisol and cause false elevations of the Larger studies of this technique and more widely
UFC. Although this technology is more sensitive and available commercial assays may make it an alterna-
specific, it is more expensive and is not widely avail- tive first-line screening test in the future.
able. The recent addition of mass spectrometry Katie undergoes a 24-hour UFC, and the result
combined with high-performance liquid chro- is positive with a level of 150 μg/dL. An overnight
matography may overcome these problems in the 1-mg DST is also abnormal at 7.2 μg/dL.
future. UFC levels in excess of four times normal are
considered diagnostic for Cushing’s syndrome.
Milder elevations may be seen in conditions such as
depression, chronic anxiety, and alcoholism and in FOLLOW-UP VISIT
normal pregnant women. UFC may not identify
Subjective
early or subclinical cases of Cushing’s syndrome and
is often used in conjunction with other tests. Katie returns for her follow-up visit 2 weeks later.
A low-dose dexamethasone suppression test She reports no change in her symptoms, and having
(DST) has been used to evaluate patients with sus- done an Internet search on Cushing’s syndrome, she
pected Cushing’s syndrome for more than four is not surprised to learn that her tests were diagnos-
decades. The overnight low-dose DST consists of a tic for the condition.
1-mg oral dose of dexamethasone taken between 11 PM
and 12 AM, followed by a fasting plasma cortisol meas- Objective
urement between 8:00 and 9:00 AM the following
morning. The old cutoff value for this test of 5 μg/dL Her blood pressure is 160/97 mm Hg, and her pulse
has recently been reduced to 1.8 μg/dL, greatly enhanc- is 86. The rest of her examination is unchanged.
ing the sensitivity of this test for mild hypercortisolism.
The specificity of the 1.8 μg/dL cutoff is limited due to Assessment
the misclassification of patients with increased corti-
costeroid-binding globulin, acute and chronic illness, Cushing’s syndrome is established.
pseudo-Cushing’s syndrome (e.g., alcoholism), and the
otherwise healthy individual who fails to suppress Plan
cortisol to this level. Another increasingly recognized
problem is the suppression of steroids by dexametha- The next step in Katie’s workup is to establish the
sone in patients with proven Cushing’s syndrome. cause of her disease. Figure 49-1 outlines a straight-
Some experts believe that the low sensitivity and speci- forward approach to the differential diagnosis of
ficity of this test do not justify its continued use. Cushing’s syndrome.
The classic 2-day DST is another way to perform An endocrinologist experienced in the diagnosis
this test (dexamethasone 0.5 mg is given every 6 hours and management of Cushing’s syndrome should be

404
 Chapter 49 Irregular Menstruation and Fatigue (Cushing’s Syndrome)

Cushing’s syndrome
suspected
Cushing’s syndrome
excluded
24-hr urine free cortisol level (Repeat testing if
↑ Filtered load of cortisol Normal results
high index of suspicion)

and/or

11 PM salivary cortisol level

Disrupted circadian rhythm Equivocal results Dexamethasone CRH test

and/or

Low-dose dexamethasone
suppression test Abnormal results
Alternated negative feedback
Cushing’s syndrome
established

Figure 49-1 Differential diagnosis of Cushing’s syndrome. (Reproduced with permission from Ruff HR, Findling FW. A
physiologic approach to diagnosis of Cushing’s syndrome. Ann Inter Med 2003;138:980–991.)

consulted to manage her disease at this point. In the accompanied by organ damage, particularly cardiac
meantime, she should be placed on antihypertensive hypertrophy. It is thought that the concentric remod-
medication to control her blood pressure and have eling of the left ventricle seen in some patients may be
an evaluation for insulin resistance/diabetes with an due to prolonged exposure to excess circulating corti-
oral glucose tolerance test while a definitive cure for sol. Hypertension is treated using conventional med-
her disease is pursued. ications (thiazides, calcium channel blockers, and
angiotensin-converting enzyme inhibitors). In most
patients, successful treatment of Cushing’s syndrome
DISCUSSION eliminates hypertension, but in some it persists, likely
secondary to microvascular remodeling and/or
The mortality rate for patients with Cushing’s syn- underlying essential hypertension.
drome is four times higher than that of age- and
gender-matched controls, largely due to the complica- Impaired Glucose Tolerance/Diabetes
tions caused by glucocorticoid excess. The primary
goal of management is therefore to properly identify It is estimated that approximately 20% to 50% of
the condition and eliminate the hypercortisolism. patients with Cushing’s syndrome have overt dia-
betes, and 30% to 60% have some degree of glucose
intolerance. These estimates may actually be low, as
Obesity the oral glucose tolerance test is not often performed
Excess glucocorticoids bring about a redistribution in patients with Cushing’s syndrome.
of body fat from peripheral to more central parts
of the body, primarily the abdominal region. Hyperlipidemia
Abdominal obesity (visceral obesity) is now recog-
nized as an independent risk factor for increased The insulin resistance induced by hypercortisolism
mortality and is one of the four key components of also contributes to the development of lipid abnor-
the metabolic syndrome (abdominal obesity, hyper- malities. Very-low-density lipoproteins and low-
tension, insulin resistance/diabetes, hyperlipidemia). density lipoproteins are elevated, leading to an
elevation of total triglycerides and cholesterol,
whereas high-density lipoproteins are not affected.
Hypertension
Hypertension is present in 70% to 80% of patients Gonadal Axis
with Cushing’s syndrome and may be the presenting
sign. Although patients with Cushing’s syndrome Females with Cushing’s syndrome may display several
usually have mild hypertension, it may be severe and of the characteristics of polycystic ovary disease,

405
 Chapter 49 Irregular Menstruation and Fatigue (Cushing’s Syndrome)

including oligomenorrhea or amenorrhea and the altered metabolism at the level of the osteoblasts and
effects of hyperandrogenism (acne, hirsutism, metabolic osteoclasts. This places patients with Cushing’s
syndrome). Hyperprolactinemia may also be present. syndrome at increased risk of fracture and the
Males usually develop features of hypogonadotropic complications thereof, including back pain from
hypogonadism. Restoration of the gonadal axis in vertebral fractures, kyphosis, height loss, and
men and premenopausal women is variable, and thus nonvertebral fractures. Deficits in bone mineraliza-
patients should be evaluated 3 months after successful tion are partially reversible to varying degrees in any
cure. If gonadal function has not returned, steroid given patient with the reversal of hypercortisolism.
replacement may be considered. Some patients may require pharmacologic interven-
tion to improve bone density both before and after
Thyroid Axis cure of the disease.

Thyroid function is suppressed by hypercortisolism

through inhibition of thyrotropin-releasing hormone Nephrolithiasis
and thyroid-stimulating hormone and decreased Patients with Cushing’s syndrome have an increased
conversion of thyroxine to triiodothyronine. After sur- prevalence of nephrolithiasis compared with the
gical cure of Cushing’s syndrome, hypothyroidism may general population. The reason for this is not com-
persist for at least 3 months. Patients with persistently pletely clear but it probably is because of the syner-
subnormal free thyroxine levels should receive replace- gistic effect of various hypercortisolism-dependent
ment therapy titrated according to the free thyroxine, hemodynamic and metabolic abnormalities, parti-
not the thyroid-stimulating hormone. Occasionally, cularly excessive uric acid excretion and systemic
curing Cushing’s syndrome may unmask a preexisting arterial hypertension.
primary autoimmune thyroid disease presenting as
either hypothyroidism or hyperthyroidism.
Somatotropic Axis
Psychological Disturbances and Hypercortisolism reduces the secretion of growth
Cognitive Disturbances hormone and the response of growth hormone to
various stimuli. This may lead to growth retardation
Fifty percent to 80% of patients with Cushing’s syn- in children due to inhibition of the epiphyseal carti-
drome meet Diagnostic and Statistical Manual of lage. Children’s growth curve should be monitored
Mental Disorders IV criteria for major depression. after reversal of hypercortisolism, and children
Other symptoms including mania, anxiety, and should be treated with growth hormone in selected
suicidal ideations may also be present. Patients with cases.
hypercortisolism also have impaired cognitive func-
tion, often specific to the medial temporal lobe declar-
ative memory system, associated with reversible Hyperpigmentation
apparent loss of brain volume. One year after surgical Hyperpigmentation is seen in Cushing’s syndrome
cure, the loss of brain volume and mood disorders usu- that is secondary to adrenocorticotropic hormone–
ally improve, but there is no change in cognitive func- producing pituitary tumors. Adrenocorticotropic
tion. Many patients, however, have residual symptoms hormone is a precursor of melanocyte-stimulating-
and may need continued psychological and pharmaco- hormone and, as such, stimulates the production of
logic support. melanin by melanocytes. Increased skin pigmenta-
tion, especially in the creases, pressure areas, new
Coagulopathy scars, and nipples, is common. Patients may present
simply with a complaint of “getting darker.”
Hypercortisolism stimulates the synthesis of several
clotting factors by the liver, creating a hypercoagula-
ble state and predisposing patients to thrombo-
embolic events. Material Available on Student Consult
Review Questions and Answers about
Osteoporosis Cushing’s Syndrome

Glucocorticoids inhibit bone mineralization at

many levels, from decreased calcium absorption to

406
 Chapter 50 Fatigue (Hypothyroidism)

SUGGESTED READINGS
Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and com- Cushing’s syndrome. J Clin Endocrinol Metab 2004;
plications of Cushing’s syndrome: A consensus state- 89:122–126.●B
ment. J Clin Endocrinol Metab 2003;88:5593–5602.● C Papanicolaou D, Mullen N, Kyrou I, Nieman L. Nighttime
Findling JW, Raff H. Diagnosis and differential diagnosis salivary cortisol: A useful test for the diagnosis of
of Cushing’s syndrome. Endocrinol Metab Clin North Cushing’s syndrome. J Clin Endocrinol Metab 2002;
Am 2001;30:729–747. 87:4515–4521.● B
Findling J, Raff H, Aron D. The low-dose dexamethasone
suppression test: A reevaluation in patients with

C h a p t e r

50 Fatigue (Hypothyroidism)

Sarah Ellen Lesko

Present Illness
KEY POINTS Christine describes a slowly increasing sensation of
tiredness that has progressed over at least 2 months.
1. Think of hypothyroidism when encountering She finds it difficult to get up to go to work and has
unexplained constitutional symptoms or hyper- little energy once there. Her sleep has been normal.
lipidemia, especially in an older woman. She has noticed a weight gain of about 5 pounds,
2. Do not screen everyone for thyroid disease; although she denies any change in eating habits. Her
keep your eye out for future recommendations. bowel movements are less frequent and harder than
3. Be patient when treating hypothyroidism; do not usual. She has decreased the distance of her daily
expect rapid correction of thyroid-stimulating walks due to new leg cramps, and she feels like she
hormone (TSH) level. needs to “bundle up” more. Her menstrual periods,
4. Approach subclinical hypothyroidism with a previously light and somewhat irregular, have
watchful waiting approach; for a detailed become heavier and longer. Her mood is “okay,”
risk/benefit discussion with your educated although she is more worried than usual. She has
patients, discuss the evidence found at normal enjoyment of her favorite activities. She has
www.ahrq.gov/clinic/3rduspstf/thyroid/thyrrs.htm. tried taking ginkgo supplements for the past month
but has had no relief.

Medical History
Christine has been coming to the clinic regularly
INITIAL VISIT for 15 years. She had mildly elevated cholesterol 3
years ago (total cholesterol 221, high-density
Subjective lipoprotein 55, low-density lipoprotein 148, triglyc-
erides 90), which she attempted to manage with
Patient Identification and Presenting diet. Her last mammogram 9 months ago was nor-
Problem mal; her last Pap smear 21⁄2 years ago was normal
Christine G. is a 53-year-old white woman who pre- with the exception of yeast. She had three negative
sents to her regular clinic complaining of fatigue. fecal occult blood tests 9 months ago as well but has

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

407
 Chapter 50 Fatigue (Hypothyroidism)

SUGGESTED READINGS
Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and com- Cushing’s syndrome. J Clin Endocrinol Metab 2004;
plications of Cushing’s syndrome: A consensus state- 89:122–126.●B
ment. J Clin Endocrinol Metab 2003;88:5593–5602.● C Papanicolaou D, Mullen N, Kyrou I, Nieman L. Nighttime
Findling JW, Raff H. Diagnosis and differential diagnosis salivary cortisol: A useful test for the diagnosis of
of Cushing’s syndrome. Endocrinol Metab Clin North Cushing’s syndrome. J Clin Endocrinol Metab 2002;
Am 2001;30:729–747. 87:4515–4521.● B
Findling J, Raff H, Aron D. The low-dose dexamethasone
suppression test: A reevaluation in patients with

C h a p t e r

50 Fatigue (Hypothyroidism)

Sarah Ellen Lesko

Present Illness
KEY POINTS Christine describes a slowly increasing sensation of
tiredness that has progressed over at least 2 months.
1. Think of hypothyroidism when encountering She finds it difficult to get up to go to work and has
unexplained constitutional symptoms or hyper- little energy once there. Her sleep has been normal.
lipidemia, especially in an older woman. She has noticed a weight gain of about 5 pounds,
2. Do not screen everyone for thyroid disease; although she denies any change in eating habits. Her
keep your eye out for future recommendations. bowel movements are less frequent and harder than
3. Be patient when treating hypothyroidism; do not usual. She has decreased the distance of her daily
expect rapid correction of thyroid-stimulating walks due to new leg cramps, and she feels like she
hormone (TSH) level. needs to “bundle up” more. Her menstrual periods,
4. Approach subclinical hypothyroidism with a previously light and somewhat irregular, have
watchful waiting approach; for a detailed become heavier and longer. Her mood is “okay,”
risk/benefit discussion with your educated although she is more worried than usual. She has
patients, discuss the evidence found at normal enjoyment of her favorite activities. She has
www.ahrq.gov/clinic/3rduspstf/thyroid/thyrrs.htm. tried taking ginkgo supplements for the past month
but has had no relief.

Medical History
Christine has been coming to the clinic regularly
INITIAL VISIT for 15 years. She had mildly elevated cholesterol 3
years ago (total cholesterol 221, high-density
Subjective lipoprotein 55, low-density lipoprotein 148, triglyc-
erides 90), which she attempted to manage with
Patient Identification and Presenting diet. Her last mammogram 9 months ago was nor-
Problem mal; her last Pap smear 21⁄2 years ago was normal
Christine G. is a 53-year-old white woman who pre- with the exception of yeast. She had three negative
sents to her regular clinic complaining of fatigue. fecal occult blood tests 9 months ago as well but has

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

407
 Chapter 50 Fatigue (Hypothyroidism)

not yet had a flexible sigmoidoscopy. Surgical his- Neck Her neck is supple, with no lymphadenopathy;
tory is notable only for a tonsillectomy/adenoidec- her thyroid is smooth and mobile without
tomy at age 3. nodularity.

Family History Heart Her heart rate is 60, with a regular rhythm, no
Mrs. G.’s father died at age 78 in a motor vehicle acci- murmurs, rubs, or gallops.
dent; her mother, who has mild to moderate
Alzheimer’s dementia, lives in an assisted-living facil- Lungs The lungs are clear to auscultation.
ity. Mrs. G.’s two older sisters are well; they experi-
enced menopause at ages 58 and 56. A brother died Extremities There are no cords, clubbing, or edema.
in infancy due to a congenital heart defect. Mrs. G.’s
two children are well. Skin There are no rashes; her hands feel slightly rough.

Social History Neurologic Cranial nerves II through XII are grossly

Mrs. G. is an elected state official with a demanding intact; patellar and ankle reflexes are present with a
work and social schedule. She is married and has two slightly prolonged relaxation phase; gait is normal.
children in college. She is a nonsmoker and drinks
one to two glasses of wine daily. Laboratory Studies
A laboratory test is sent after the visit.
Review of Systems
Mrs. G. denies shortness of breath, chest pain, dizzi-
Assessment
ness, visual changes, voice changes, galactorrhea,
recent viral infection, fever, radiation exposure, snor- Working Diagnosis
ing, headaches, nausea, and vomiting. Fatigue, possibly secondary to hypothyroidism.
Fatigue is a common presenting complaint (account-
Objective ing for 10% to 20% of primary care visits), as it is a
common final pathway of a host of problems. It can
Physical Examination be very difficult to identify the cause of fatigue.
General Christine is a well-groomed woman who Medical causes may account for only 10% of fatigue
looks her stated age. Blood pressure is 120/90 mm complaints. History can help sort out the broad dif-
Hg, pulse is 60 and regular, weight is 160 pounds ferential diagnosis (Table 50-1). Fatigue that lasts
(previous weight 9 months ago was 152 pounds), more than 6 months or varies in severity is more
and height is 5 feet 4 inches. likely to be functional. Fatigue that is worse in the
morning is often psychiatric. The history should
Head, Eyes, Ears, Nose, and Throat Her pupils are focus on evaluating the timing, severity, and symp-
equally round and reactive to light; extraocular toms associated with fatigue as well as a detailed
movements are intact; and conjunctivae are pink. sleep and drug history.

Table 50-1 Differential Diagnosis of Fatigue as Presenting Complaint

in the Primary Care Office
Psychological Depression, anxiety, eating disorder, substance abuse,
somatization, seasonal affective disorder
Pharmacologic Check side effect profiles; many antihypertensives and sleeping
aids
Endocrine Hypothyroidism, diabetes, hypoadrenal states
Reproductive Pregnancy
Neoplastic All types
Hematologic Anemia
Infection Chronic infection, Lyme disease
Cardiopulmonary Heart failure, mitral regurgitation or stenosis, chronic lung
disease
Connective tissue disease Polymyalgia rheumatica, rheumatoid arthritis, sarcoidosis
Disturbed sleep Sleep apnea
Renal Renal insufficiency or failure
Gastrointestinal Liver disease
Neurologic Multiple sclerosis

408
 Chapter 50 Fatigue (Hypothyroidism)

Table 50-2 Symptoms and Signs of Hypothyroidism Present at Time of Diagnosis

Coarse skin/dry skin/coarse hair Possible statistical significance*
Bradycardia Possible statistical significance*
Abnormal or delayed relaxation of ankle reflexes Possible statistical significance*
Hoarse voice/deep voice Possible statistical significance*
Cold sensitivity
Fatigue
Puffy eyes Possible statistical significance*
Weight gain
Irregular menses/heavy menses
Muscle cramps/weak muscles Possible statistical significance*
Slow thinking/poor memory/math difficulty
Decreased hearing
Diastolic hypertension
Pretibial edema
Carpal tunnel syndrome
Depression/dementia
Constipation
*
In one or more studies, shown to be present more frequently in patients with hypothyroidism than in a control
population.

Hypothyroidism can be similarly elusive to edema, severe obstructive sleep apnea, and, ultimately,
pinpoint. Presenting symptoms for hypothyroid- coma. Side effects of untreated hypothyroidism
ism may include a large variety of complaints (Table include all the previously mentioned symptoms as
50-2), only a few of which have been found to be well as hypercholesterolemia (increased low-density
possibly statistically significant for biochemical lipoprotein and decreased high-density lipoprotein
hypothyroidism. Physical examination also has a poor due to decreased catabolism of very low density
diagnostic accuracy for hypothyroidism. No single sign lipoprotein and intermediate density lipoprotein), nor-
effectively rules hypothyroidism in or out, although a mocytic anemia, and pernicious anemia.
combination of coarse skin, bradycardia, and delayed Causes of hypothyroidism can be separated
ankle reflex may increase the likelihood of biochemical into primary hypothyroidism (impaired thyroid
hypothyroidism. However, due to the poor prognosis function), which accounts for 95% of patients with
of untreated disease, clinicians need to test at-risk hypothyroidism (Table 50-3), and secondary hypo-
patients. If it is not caught and treated, hypothyroidism thyroidism (impaired hypothalamic-pituitary func-
can progress to myxedema with lethargy, generalized tion). Secondary hypothyroidism is the result of

Table 50-3 Causes of Primary Hypothyroidism

Type of Hypothyroidism Expected Prognosis/Course

Hashimoto’s thyroiditis: immune mediated; Transient hyperthyroidism followed by

antimicrosomal antibodies are a marker hypothyroidism; majority of cases are mild
and do not require thyroid hormone
replacement
Postpartum thyroiditis; variant of Hashimoto’s Usually resolves over 2–3 mo
Radiation-induced hypothyroidism Usually requires hormone replacement
Subacute thyroiditis: follows viral upper Resolves over weeks to months
respiratory infection
Subtotal thyroidectomy Transient hypothyroidism; becomes permanent
in half of cases
Drugs: lithium (5% clinically hypothyroid), Medication dependent
propylthiouracil, methimazole
Iodide excess: impairs thyroxine synthesis/release Correct excess
Iodide deficiency: inhibits thyroxine synthesis Correct deficiency
Infiltrative disease: hemochromatosis, amyloidosis, Address underlying disease
scleroderma

409
 Chapter 50 Fatigue (Hypothyroidism)

injury to the thyrotropic cells, most often by pitu- although not yet back to baseline. Her bowel habits
itary adenoma. In cases of secondary hypothy- have returned to normal and her fatigue level has
roidism, the TSH will be low. improved significantly. She had mild insomnia
Key points of Mrs. G.’s history include weight the first week that she took the levothyroxine. She
gain, inability to tolerate cold, menorrhagia, constipa- had one menstrual period that was still heavier
tion, and muscle cramps. Key components of her than usual. She has experienced no chest pain or
physical examination are borderline bradycardia, doc- palpitations.
umented weight gain, delayed relaxation phase of
reflexes, and rough skin on her hands. A past signifi-
cant laboratory test is her abnormal lipid profile. Objective
Given this combination of symptoms and physical Her pulse is 75 and regular, blood pressure is 125/80,
findings, a measurement of TSH is warranted. The cli- and weight is 156 pounds. Her gait and reflexes are
nician could consider checking a hematocrit as well. normal.

Plan Laboratory Testing

Diagnostic Repeat TSH is 10.2 mIU/L; free thyroxine is
TSH alone is the recommended screening tool to 1.29 ng/dL.
detect hypothyroidism. It has a sensitivity of 89% to
95% and a specificity of 90% to 96%. TSH and thy-
roid hormone (thyroxine) concentrations are related Assessment
by inverse log. Therefore, a 50% decrease in free thy- Mrs. G. has had a good initial response to treatment
roxine concentration causes a 90-fold increase in with thyroid replacement hormone. Her subjective
TSH concentration. For this reason, TSH is the much complaints have improved, her weight is down, her
more sensitive detector of primary hypothyroidism. reflexes are normal, and her pulse has returned to
Mrs. G.’s TSH result returns at 22.4 mIU/L (normal normal.
for this laboratory, 0.50 to 5.10 mIU/L). A free thy-
roxine measurement, added on by automatic clinical
laboratory algorithm when TSH is high, is low-nor- Plan
mal at 0.85 ng/dL. Mrs. G. has overt hypothyroidism The advisability of maintaining the current dose
and needs thyroid hormone replacement. of levothyroxine and rechecking the TSH in 6
weeks—due to the common lag of TSH returning
Therapeutic
to normal—is discussed with Mrs. G. The option
Mrs. G. is prescribed a starting dose of 50 μg levothy-
of increasing the dose by 25 μg/day is also dis-
roxine (Synthroid) per day (usual starting dose 25 to
cussed, with the risk of overtreatment and future
50 μg in elderly patients or those with comorbidities,
need to decrease her levothyroxine dose. The patient
100 μg in young patients). This dose may be
prefers to increase her dose and is scheduled for
increased by 25 to 50 μg every 4 to 8 weeks to a typ-
repeat TSH, fasting cholesterol, and follow-up visit
ical dose of 1.7 μg/kg body weight/day. (In this
in 6 weeks.
patient, 100 to 125 μg/day).

Patient Education
Mrs. G. is educated on the expected course of treatment DISCUSSION
(likely permanent) and symptom resolution (should
improve within 3 to 4 weeks and resolve within 3 Hypothyroidism, although not difficult to diagnose
months). She is warned about the potential unmasking once the laboratory test is ordered, presents many
of silent coronary artery disease as well as other possi- dilemmas in clinical practice. The prevalence of
ble side effects of the medication. The etiology of her hypothyroidism in the general population increases
hypothyroidism is likely Hashimoto’s thyroiditis; it is with age and disproportionately affects women.
not necessary to definitively test for the causative factor, Prevalence in women 60 and older approaches 5%.
as it will not affect treatment decisions. The core clinical question often becomes: Whom to
test? Referencing the nonspecific symptom informa-
tion given above, the physician is clearly asked to
FOLLOW-UP VISIT invoke the art of medicine. The U.S. Preventive
Services Task Force states, “Clinicians should remain
Subjective alert for subtle or nonspecific symptoms of thyroid
dysfunction when examining such patients, and
Mrs. G. returns for re-evaluation 5 weeks after her maintain a low threshold for diagnostic evaluation of
original visit. She reports that she is feeling better thyroid function.”

410
 Chapter 50 Fatigue (Hypothyroidism)

Table 50-4 Recommendations Regarding Thyroid Screening

U.S. Preventive Services Task Force Insufficient evidence to recommend for or against
routine screening in adults (yield of screening may
be greater in postpartum women, patients with
trisomy 21, and the elderly)
American Academy of Family Physicians Recommends against routine screening in
asymptomatic patients younger than 60
Canadian Task Force on the Periodic No screening; have a high index of suspicion for
Health Examination nonspecific symptoms in perimenopausal and
postmenopausal women
American College of Physicians Screen women older than 50 with one or more
symptoms that could be caused by thyroid disease
American College of Obstetricians Apply knowledge of the symptoms for postpartum
and Gynecologists thyroid dysfunction; test as indicated
American Association of Clinical Screen all women of childbearing age before
Endocrinologists pregnancy or during the first trimester
American Thyroid Association Measure thyroid function in all adults beginning at
age 35 and every 5 years thereafter

Screening ical hypothyroidism shows that approximately 20%

of these patients will develop clinically symptomatic
By definition, screening tests are performed on hypothyroidism within 5 years. Patients with high
asymptomatic populations. Because the symptoms titers of antithyroid antibodies are at greatest risk
of hypothyroidism can be vague or multifactorial, (implicating Hashimoto’s thyroiditis). However,
several groups have studied the utility of generalized there is no evidence to recommend treatment of
screening for thyroid dysfunction. Principles of a subclinical hypothyroidism to prevent overt
good screening test include good detection rate (sen- hypothyroidism. “The USPSTF estimates that in a
sitivity) of the screening test (with an acceptable reference population of 1,000 women screened,
false-positive rate) as well as evidence that treatment 3 cases of overt hypothyroidism would be prevented
improves clinically important outcomes. TSH testing in 5 years, but 40 people would have taken medica-
can detect asymptomatic thyroid disease; however, tion for 5 years without a clear benefit.” Subclinical
the U.S. Preventive Services Task Force recently con- hypothyroidism does not appear to be associated
cluded that there is insufficient evidence to establish with an abnormal lipid panel when adjusted for
the benefits versus harms of treatment for screening- confounding factors. Treatment of patients with
detected hypothyroidism. Current recommendations subclinical hypothyroidism with thyroid hormone
for population-based screening for thyroid disease replacement, hypothesized to improve lipid profiles,
are listed in Table 50-4. myocardial function, adverse cardiac endpoints,
and neuropsychiatric function, has not proved to be
Subclinical Hypothyroidism clinically beneficial. In addition, there are potential
harms of overtreatment, including osteoporosis,
Invariably, even when applying the best clinical palpitations, and worsening coronary artery disease.
algorithms, the clinician will have to analyze inde- Therefore, although each case should be approached
terminate results. This occurs in thyroid function on an individual basis, subclinical hypothyroi-
testing when the TSH result returns in the mildly dism should in general be followed by laboratory test-
elevated range (generally 5 to 10 mIU/L) with a nor- ing but not treated with thyroid replacement hormone.
mal free thyroxine and with no clearly attributable
symptoms of hypothyroidism. This is termed sub-
clinical hypothyroidism and has a prevalence of 7%
in women (approaching 20% in women older than Material Available on Student Consult
age 60) and 2.5% in men. Of patients with an abnor- Review Questions and Answers about Hypo-
mally high TSH, approximately 75% will have values thyroidism
lower than 10 mIU/L. The clinical course of subclin-

411
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

SUGGESTED READINGS
Agency for Healthcare Research and Quality: Screening roidism: A cross-sectional, double-blind study. J
Thyroid Disease: Recommendation Statement, January, Postgrad Med 2004;50:7–10.●
B
2004. Available at www.ahrq.gov/clinic/3rduspstf/ Sharpe M, Wilks D. Fatigue: Clinical review. BMJ
thyroid/thyrrs.htm. Accessed 9/1/2004.● A 2002;325:480–483.
Canaris Gay J, Steiner JF, Ridgway EC. Do traditional Surks MI, Ortiz E, Daniels GH, et al. Subclinical thy-
symptoms of hypothyroidism correlate with biochemi- roid disease: Scientific review and guidelines
cal disease? J Gen Intern Med 1997;12: 544–550.● B for diagnosis and management. JAMA 2004;291:
Hueston WJ, Pearson WS. Subclinical hypothyroidism and 228–238.● A
the risk of hypercholesterolemia. Ann Fam Med U.S. Preventive Services Task Force. Screening for
2004;2:351–355.● B thyroid disease. In Guide to Clinical Preventive
Indra R, Patil SS, Joshi R, Pai M, Kalantri SP. Accuracy of Services, 2nd ed. Baltimore, Williams & Wilkins,
physical examination in the diagnosis of hypothy- 1996, p 209.●
A

C h a p t e r

51 Unexplained Weight Loss

(Hyperthyroidism)
Barbara A. Majeroni

KEY POINTS

1. Hyperthyroidism should be considered in the 6. A single measurement of low serum TSH in indi-
differential of unexplained weight loss. Check a viduals age 60 years or older has been associated
thyroid-stimulating hormone (TSH) level. with increased mortality, particularly due to circu-
2. The most common cause of hyperthyroidism is latory and cardiovascular disease.
Graves’ disease. 7. A study of cancer incidence in patients treated
3. A very low or undetectable TSH is the hallmark with iodine 131 found significant decreases in
of thyrotoxicosis. the incidence of cancers of the pancreas,
4. In the pregnant patient, iodine 131 is con- bronchus, trachea, bladder, and lymphatic and
traindicated. Propylthiouracil is generally the hematopoietic systems. Although a threefold
preferred treatment. In severe cases, subtotal increase in the risk of thyroid cancer was found,
thyroidectomy can be performed in the second the absolute risk remained small.
trimester. 8. TSH should be measured in elderly patients with
5. Because lean body mass declines with age, systolic hypertension, a widened pulse pressure,
weight loss in the elderly may be of greater recent-onset angina, atrial fibrillation, or an exacer-
clinical significance. bation of underlying ischemic heart disease.

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

412
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

SUGGESTED READINGS
Agency for Healthcare Research and Quality: Screening roidism: A cross-sectional, double-blind study. J
Thyroid Disease: Recommendation Statement, January, Postgrad Med 2004;50:7–10.●
B
2004. Available at www.ahrq.gov/clinic/3rduspstf/ Sharpe M, Wilks D. Fatigue: Clinical review. BMJ
thyroid/thyrrs.htm. Accessed 9/1/2004.● A 2002;325:480–483.
Canaris Gay J, Steiner JF, Ridgway EC. Do traditional Surks MI, Ortiz E, Daniels GH, et al. Subclinical thy-
symptoms of hypothyroidism correlate with biochemi- roid disease: Scientific review and guidelines
cal disease? J Gen Intern Med 1997;12: 544–550.● B for diagnosis and management. JAMA 2004;291:
Hueston WJ, Pearson WS. Subclinical hypothyroidism and 228–238.● A
the risk of hypercholesterolemia. Ann Fam Med U.S. Preventive Services Task Force. Screening for
2004;2:351–355.● B thyroid disease. In Guide to Clinical Preventive
Indra R, Patil SS, Joshi R, Pai M, Kalantri SP. Accuracy of Services, 2nd ed. Baltimore, Williams & Wilkins,
physical examination in the diagnosis of hypothy- 1996, p 209.●
A

C h a p t e r

51 Unexplained Weight Loss

(Hyperthyroidism)
Barbara A. Majeroni

KEY POINTS

1. Hyperthyroidism should be considered in the 6. A single measurement of low serum TSH in indi-
differential of unexplained weight loss. Check a viduals age 60 years or older has been associated
thyroid-stimulating hormone (TSH) level. with increased mortality, particularly due to circu-
2. The most common cause of hyperthyroidism is latory and cardiovascular disease.
Graves’ disease. 7. A study of cancer incidence in patients treated
3. A very low or undetectable TSH is the hallmark with iodine 131 found significant decreases in
of thyrotoxicosis. the incidence of cancers of the pancreas,
4. In the pregnant patient, iodine 131 is con- bronchus, trachea, bladder, and lymphatic and
traindicated. Propylthiouracil is generally the hematopoietic systems. Although a threefold
preferred treatment. In severe cases, subtotal increase in the risk of thyroid cancer was found,
thyroidectomy can be performed in the second the absolute risk remained small.
trimester. 8. TSH should be measured in elderly patients with
5. Because lean body mass declines with age, systolic hypertension, a widened pulse pressure,
weight loss in the elderly may be of greater recent-onset angina, atrial fibrillation, or an exacer-
clinical significance. bation of underlying ischemic heart disease.

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

412
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

INITIAL VISIT active, biking or swimming several times a week. Her

husband is her only sexual partner, and she feels sure
Subjective that he does not see anyone else.
Patient Identification and Presenting Review of Systems
Problem She has no headaches, visual disturbances, hearing
Mrs. P. is a 53-year-old married white woman who problems, or dizziness. She denies chest pain, but
was in her usual state of good health until about admits to occasional palpitations, not necessarily
6 months ago. At that time, she noticed that she was associated with activity. No shortness of breath,
losing weight. She began to pay more attention to her cough, or sputum; no abdominal pain, diarrhea, or
eating habits and believes she has a good appetite constipation; and no blood in stools is reported. She
and eats a well-rounded diet, but she has continued has soft bowel movements 2 or 3 times a day. She has
to lose weight. By her scale at home, she has lost had no vaginal bleeding or discharge. She notes some
30 pounds over the past 6 months. She initially vaginal dryness and complains of excessive sweating,
attributed the problem to nervousness and stress at which she attributes to hot flashes. No rashes or skin
work, where she is in a supervisory position at a changes, and no jaundice or pruritis is found. She
nursing home, but the problem has continued denies feeling hopeless or suicidal, but states she has
despite her efforts to delegate more at work. Now she felt very tense and anxious lately. She has had no hal-
is experiencing excessive fatigue and difficulty sleep- lucinations or delusions.
ing, as well as continued weight loss. Her sister was
recently diagnosed with breast cancer, and she wor-
ries that this might be the problem, although she has Objective
not noted any changes on her monthly breast self- Physical Examination
examination. Mrs. P. is well groomed, pleasant, and cooperative.
She appears tense and worried. Her height is 68
Medical History inches; weight, 120 pounds. Weight at last visit,
Mrs. P. has been in good health. She had a tubal 1 year ago, was 158 pounds. Blood pressure is 128/80;
ligation at age 32 years and cholecystectomy at age pulse, 100; respirations, 16; oral temperature, 37.6˚C
48 years. Her two pregnancies resulted in normal (99.7˚F). Hair is normal. Head is normocephalic.
spontaneous vaginal deliveries. She stopped men- Her eyes are normal in configuration. Sclerae are
struating 2 years ago. No history of diabetes, heart clear, extraocular movements are intact. Pupils are
disease, hypertension, cancer, gastrointestinal equally round and reactive to light and accommoda-
(GI), or psychiatric illness is known. She has no tion; fundi show no hemorrhages or vascular
known allergies. Her only medication is an over- changes. Tympanic membranes are clear. Pharynx
the-counter multiple vitamin and mineral supple- is clear. Teeth are in good condition. No lym-
ment, which she started about 4 months ago. Her phadenopathy is appreciated; thyroid is diffusely
last Pap test was 5 years ago. She has never had a enlarged, with no nodules or tenderness. Heart is
mammogram. regular with normal S1 and S2 and no murmur.
Lungs are clear to examination. Breasts are sym-
Family History metrical, with no masses, skin changes, or nipple
Mrs. P.’s father died at age 76 years of prostate cancer. discharge, and with no axillary adenopathy.
Her mother is living and well at age 74 years. One Her abdomen is soft and nontender with no organo-
older sister had surgery for breast cancer. Another megaly. Bowel sounds are active in all quadrants.
sister and brother are well. No family history of heart On pelvic examination, the vaginal mucosa is
disease, respiratory disease, renal, hematologic, GI, atrophic; no skin lesions are present. The cervix has
or endocrine disease is known. Her children and no lesions or discharge. Pap smear is taken from the
grandchildren have no medical problems. cervix. No masses or tenderness of the uterus or
adnexae are found. Rectal examination: normal
Social History tone, no lesions, heme-negative, soft brown stool.
Mrs. P. lives with her husband, who works as a com- Extremities: No edema, clubbing, or cyanosis.
puter consultant. One daughter lives upstairs. The Hands are warm and moist. Distal pulses are
other is married and lives with her husband and two normal. Neurologic examination reveals no focal
children about an hour away. Mrs. P. has never abnormalities except for a symmetrical fine tremor
smoked and denies any past or present use of alcohol of the hands. Deep tendon reflexes are brisk and
or illicit drugs. She enjoys her work as a nursing symmetrical. Cranial nerves II through XII are
supervisor and is able to take some time off occa- intact. Gait and station are normal. No deficits are
sionally to travel with her husband to various cities observed in strength or sensation. Memory, thought
in the United States. She has always been physically processes, and speech patterns are normal.

413
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

Assessment
Box 51-1 Differential Diagnosis of
Unexplained weight loss results from either Involuntary Weight Loss
decreased intake (or absorption) or increased output
(or metabolism) of caloric energy. A loss of more Reduced Intake
than 5% of total body weight within a 6- to
12-month period suggests underlying pathology, Social isolation
especially when progressive. Low body weight and Financial limitations
weight loss are powerful indicators of morbidity and Problems with dentition
mortality (Bouras et al., 2001). Inability to obtain food, mobility,
transportation restrictions
Alcohol or drug abuse
Differential Diagnosis (Box 51-1) Drugs that alter appetite, cause nausea, or
1. Decreased intake. Common causes of weight loss affect taste
that result from social isolation, problems with
finances, problems with dentition, inability to Psychiatric Disorders
shop, or loneliness are unlikely in this woman, Anorexia nervosa
who has a job and family support. She is taking Depression, anxiety, bereavement
no drugs that would be likely to cause nausea or Dementia
anorexia, and no suspicion of alcoholism exists. Psychosis
2. Psychiatric disorders. Because of her age and the
history of good appetite, the diagnosis of anorexia Cancer
nervosa is unlikely. Loss of appetite due to mood Gastrointestinal tact is most common site
disorders occurs in depression and in bipolar dis- for occult tumors
order. Psychotic patients may stop eating because Hepatobiliary
of delusions, such as fear of being poisoned. This Hematologic
patient has been worried and is concerned about Lung
her sister, but she denies feeling sad or hopeless and Breast
continues to take pleasure in activities such as trav- Genitourinary
eling with her husband. She does not fulfill criteria Ovarian
for a diagnosis of depression. Prostate
3. Cancer. Malignancies account for about one third
of all patients with unintentional weight loss, Infection
which may be the presenting complaint. In a Tuberculosis
woman of this age, common cancers would Fungal disease
include lung, breast, and GI cancers. Because the Amebic abscess
patient never smoked, lung cancer is less likely, Subacute bacterial endocarditis
although not impossible. The absence of cough or Human immunodeficiency virus
sputum production is reassuring. A first-degree
relative with breast cancer increases her risk for Endocrine/Metabolic Diseases
this. A mammogram is indicated despite a normal Diabetes mellitus
examination. A single heme-negative stool does Hyperthyroidism
not rule out colon cancer, and if no other cause is Apathetic hypothyroidism
found for the weight loss, further GI workup with
an upper GI endoscopy and colonoscopy would Gastrointestinal Disorders
be considered. Peptic ulcer disease
4. Gastrointestinal disorders. GI disorders are the Gastroesophageal reflux
most common nonmalignant organic causes Pancreatitis
identified in patients with unintentional weight Sprue
loss. Upper tract disorders such as reflux, gastri- Short bowel syndrome
tis, and peptic ulcer disease may result in Inflammatory bowel disease
reduced intake. Decreased absorption of calo-
ries can occur with chronic pancreatitis, short- Chronic Illnesses
bowel syndrome, sprue, inflammatory bowel Congestive heart failure
disease, or parasitic infection. Mrs. P. has no Renal or hepatic disease
symptoms to suggest an intestinal disorder. If Connective tissue disease
no cause for her weight loss is found in her ini- Pulmonary disease
tial evaluation, further GI evaluation will be
considered. Idiopathic (25%)

414
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

5. Infection. Chronic infectious processes such as

subacute bacterial endocarditis, tuberculosis, or Box 51-2 Evaluation for Unexplained
acquired immunodeficiency syndrome (AIDS) can Weight Loss
result in weight loss. This patient has no lifestyle
risk factors for AIDS. Because she works in a health Complete history and physical
care facility, she has an annual purified protein Labs: Complete blood count, electrolytes,
derivative (PPD) skin test, and all have been nega- blood urea nitrogen, creatinine, glucose, free
tive. No physical signs of infection are noted. thyroxine, thyroid-stimulating hormone, liver
6. Endocrine diseases. Diabetes mellitus causes weight function tests, amylase, urinalysis
loss, initially due to osmotic diuresis, and in insulin- Stool hemoccult ×3.
dependent forms, due to caloric wastage. Weight loss Further studies based on symptoms: chest radi-
in diabetes is frequently associated with increased ograph, upper gastrointestinal studies, bar-
food intake. Increased metabolism resulting in ium enema, or colonoscopy
weight loss can be caused by hyperthyroidism. Signs If these do not reveal a cause, and social factors
and symptoms are variable and may be subtle. This have been corrected, close follow-up is rec-
patient’s symptoms of nervousness, weight loss, pal- ommended rather than extensive undirected
pitations, increased sweating, and fatigue could be testing.
secondary to hyperthyroidism, even in the absence
of exophthalmos and heat intolerance. Although it is
more commonly associated with weight gain, suggesting chronic malnutrition. T4 was elevated
patients with hypothyroidism sometimes initially at 19.5 μg/100 mL (251.5 nmol/L), and TSH was
have apathy and weight loss. This is more common 0.03 mU/L. Mammogram and Pap test were normal.
in patients older than 65 years.
7. Chronic disease. In addition to cancer, other
chronic disease can result in increased metabolic Diagnosis
demands and decreased caloric intake, resulting The combination of low TSH with an elevated T4 is
in weight loss. Some examples are congestive diagnostic of hyperthyroidism. This is consistent with
heart failure, renal failure, cirrhosis, and chronic the patient’s symptoms of weight loss with nervous-
obstructive pulmonary disease. In some neuro- ness, palpitations, fatigue, and sweating, and the
logic diseases, functional limitations reduce physical findings of enlarged thyroid and a higher-
caloric intake. This patient’s physical examination than-expected heart rate. A radioactive iodine-
does not point to any of these. uptake scan was ordered.
8. Idiopathic. In approximately 25% of patients
evaluated for weight loss, the problem remains
unexplained despite extensive evaluation and DISCUSSION
prolonged follow-up.
Most common in white women, hyperthyroidism
Plan affects up to 2% of women and 0.2% of men.
Prevalence increases with age and is highest in
Because the cause of Mrs. P.’s weight loss has not been patients older than 80 years. In this age group, the
clearly defined by the history and physical, further female predominance becomes less marked (1:2
evaluation is indicated (Box 51-2). Laboratory values compared with 1:8 in younger groups) (Flynn et al.,
ordered included a complete blood count (CBC), glu- 2004● B ). Although signs and symptoms are variable,
cose, electrolytes, blood urea nitrogen (BUN), creati- the most common signs of thyrotoxicosis include
nine, amylase, liver enzymes, albumin, free thyroxine resting tachycardia, atrial fibrillation in the elderly,
(T4), and thyroid-stimulating hormone (TSH). thyroid gland enlargement, tremor, exophthalmos,
A mammogram was scheduled. Further testing will lid lag, warm moist skin, and muscle weakness. More
be determined based on these results. than 50% of patients exhibit some of the common
symptoms, which include nervousness, increased
FOLLOW-UP sweating, heat intolerance, palpitations, dyspnea,
fatigue, weight loss, diarrhea, polyuria, oligomenor-
Laboratory Tests rhea, loss of libido, and eye complaints.
Sinus tachycardia is the most common rhythm
A normal CBC made infection unlikely. A fasting glu- disturbance in patients with hyperthyroidism (Klein
cose of 100 ruled out diabetes. Normal electrolytes, and Ojamaa, 2001● B ). Atrial fibrillation occurs in 5%
BUN, and creatinine suggested normal renal function. to 15% of patients with hyperthyroidism and may be
Amylase and liver enzymes were also within normal the presenting problem. The risk of atrial fibrillation
range. Albumin was 2.5 g/100 mL (0.385 mmol/L), or atrial flutter is higher in men than in women and

415
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

increases with age (Frost et al., 2004●B ). Treatment of

the hyperthyroidism alone reverts atrial fibrillation Box 51-3 Causes of Thyrotoxicosis
to sinus rhythm in fewer than half of the cases.
Hyperthyroidism is associated with a risk of worsen- Graves’ disease (most common)
ing of existing heart disease but can also, by itself, Iatrogenic (overtreated hypothyroidism)
cause cardiac disease. Excess thyroid hormone causes Thyroiditis
palpitations with some degree of exercise intolerance Hashimoto’s (autoimmune) thyroiditis,
and a widened pulse pressure. In patients with subacute thyroiditis, silent thyroiditis,
hyperthyroidism, cardiac output is increased because postpartum thyroiditis
of a decrease in systemic vascular resistance, an Toxic multinodular goiter
increase in resting heart rate, increased left ventricu- Toxic adenoma
lar contractility, and increased blood volume. In Factitious hyperthyroidism (patient taking
older patients with heart disease, the increased work- excess thyroid hormone)
load that results from hyperthyroidism may further Excess exogenous iodine
impair cardiac function. Rare causes
More than 50% of thyrotoxic men report sexual TSH-secreting pituitary adenoma
dysfunction associated with decreased libido, which is Trophoblastic tumor
improved after 6 months of treatment for hyperthy- Struma ovarii
roidism. Thirty percent of hyperthyroid patients in Thyroid cancer
this study had lower-than-normal semen volumes and Activating mutation of the TSH receptor
sperm densities than did controls. Sperm motility also Thyroid hormone–resistance syndrome
was significantly lower. After treatment, sperm density TSH, thyroid-stimulating hormone.
and motility improved (Krassas et al., 2002● B ).

Testing
RAIU may be reduced when T4 is high and
Measurement of serum thyrotropin (TSH) by using increased when T4 is low, in a patchy nonhomoge-
at least a second-generation assay (detection limit, neous pattern. The RAIU also is reduced, at times
approximately 0.05 mIU/L) is the most sensitive test to zero, in patients with hyperthyroidism due to
for screening for hyperthyroidism, a normal result excess iodine (Jod-Basedow disease). These
virtually excluding hyperthyroidism, except in the patients have goiter, but no image on thyroid scan.
rare instance in which it is due to thyrotropin hyper- Trophoblastic tumors are rare, but they can cause
secretion (Woeber, 2000). An undetectable value is a low TSH because of tumor secretion of excess
the hallmark of hyperthyroidism. Confirmation is by β-human chorionic gonadotropin, which interacts
measuring the free thyroxine (T4). If the free T4 is with TSH receptors in the thyroid. Another rare
normal and suspicion is high for thyrotoxicosis, cause of hyperthyroidism is struma ovarii, in
a serum free triiodothyronine (T3) should also be which thyroid nests in the ovary become hyper-
measured to rule out T3 thyrotoxicosis. plastic and produce thyroxine. If no other cause for
Misleading laboratory results may occur. Drugs the hyperthyroidism is found, focusing the gamma
such as glucocorticoids, levodopa, and dopamine can camera on the ovaries at the thyroid scan will
cause a low TSH in patients who are euthyroid. reveal increased radioactive iodine uptake in this
Estrogen in pregnancy, hormone replacement ther- condition.
apy, or oral contraceptives may cause an increased
T4, but free T4 will be normal, and the patient is Results
euthyroid. Causes of thyrotoxicosis are summarized
in Box 51-3. Mrs. P.’s thyroid scan showed diffuse increased
The usual pattern in hyperthyroidism is a high uptake, suggestive of Graves’ disease. Although the
free T4 with a low TSH. A thyroid scan with classic triad of Graves’ disease includes hyper-
radioactive iodine (RAIU) can help differentiate thyroidism with diffuse thyroid enlargement, oph-
the causes of hyperthyroidism. Factitious or iatro- thalmopathy, and dermopathy, the three major
genic hyperthyroidism can be differentiated by the manifestations need not appear together, and some
RAIU, which is suppressed to less than 5% in the patients exhibit only one of the three.
presence of excess exogenous thyroid hormone.
In endogenous disease, the RAIU is elevated. In Treatment
toxic adenoma or toxic multinodular goiter, the
radioisotope is concentrated in one or more areas, Hospitalization is required only in the case of serious
whereas in Graves’ disease, diffuse uptake may arrhythmias, congestive heart failure, or impending
occur throughout the gland. In thyroiditis, the thyroid storm. Mrs. P. can be treated as an outpatient.

416
 Chapter 51 Unexplained Weight Loss (Hyperthyroidism)

Symptoms of nervousness and palpitations may be Follow-up

controlled with a β-blocker while awaiting definitive
treatment. In acute thyroiditis, symptomatic treat- After her treatment with radioactive iodine, Mrs. P.
ment may be used alone in anticipation of sponta- will be monitored by her family doctor, who will
neous remission. Graves’ disease may be treated with watch carefully for signs of hypothyroidism and
propylthiouracil, methimazole, or carbimazole (not monitor her T4 and TSH to determine whether she
available in the United States) in the hope of remis- has obtained a euthyroid state. The β-blocker
sion or to achieve a euthyroid state before ablative will be tapered as symptoms permit. Health-
treatment with radioactive iodine (Pearce and maintenance issues that will continue to be
Braverman, 2004). In the case of Mrs. P., the history addressed include the advisability of annual mam-
suggested a long duration of hyperthyroidism. mograms, regular Pap tests, and consideration of
Definitive treatment with iodine 131 was adminis- calcium supplementation.
tered. The patient was informed before the treatment
that in as many as 40% to 70% of patients treated Material Available on Student Consult
with this modality, hypothyroidism will develop
Review Questions and Answers about Hyper-
within 10 years, requiring life-long hormone replace- thyroidism
ment therapy.

REFERENCES
Bouras EP, Lang SM, Scalapio JS. Rational approach to Krassas GE, Pontikides N, Deligianni V, Miras K.
patients with unintentional weight loss. Mayo Clinic A prospective, controlled study of the impact of hyper-
Proc 2001;76:923–929. thyroidism on reproductive function in males. J Clin
Flynn RWV, MacDonald TM, Morris AD, et al. The thyroid Endocrinol Metab 2002;87:3667–3671.● B
epidemiology, audit, and research study: Thyroid dys- Pearce EN, Braverman LE. Hyperthyroidism: Advantages
function in the general population. J Clin Endocrinol and disadvantages of medical therapy. Surg Clin North
Metab 2004;89:3879–3884.● B Am 2004;84:833–847.
Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and the Woeber KA. Update on the management of hyperthy-
risk of atrial fibrillation or flutter: A population based roidism and hypothyroidism. Arch Intern Med 2000;
study. Arch Intern Med 2004;164:1675–1678.● B 1060:1067–1071.
Klein I, Ojamaa K. Mechanisms of disease: Thyroid hor-
mones and the cardiovascular system. N Engl J Med
2001;344:501–509.● B

417
 C h a p t e r

52 Dysuria and Urinary Frequency

(Urinary Tract Infection)
Kurt Kurowski

Medical History
KEY POINTS She had an appendectomy at age 15 years. The only
medication she takes is Ortho Evra patch for birth
1. Recurrence of urinary tract infection (UTI) symp- control.
toms shortly after finishing 3-day antibiotic
courses suggests that the original infection was Family History
actually pyelonephritis. No history of urinary tract abnormalities is known
2. Avoid 3-day antibiotic courses for cystitis in chil- in her parents or her two siblings. Her maternal
dren, as they are only about 60% effective. grandmother has diabetes mellitus.
3. Altered vaginal flora is the basis for most UTIs.
4. Fluoroquinolones allow a reduction of the treat- Social History
ment course for pyelonephritis to 7 days. She was married for 2 years and has no children. She
has been divorced for the past 3 years and is currently
living with her boyfriend of 8 months. She is a recep-
tionist in a primary care medical office. She tries to
INITIAL VISIT avoid eating meat, as she is opposed to the killing of
animals, but she does consume milk and cheese. She
Subjective does not smoke but has two to three glasses of wine
each week.
Patient Identification and Presenting
Problem Review of Systems
Amber L. is a 30-year-old white woman who com- The patient denies any nausea, vomiting, fever, or
plains of frequency and burning on urination. chills.

Present Illness
The patient states that she began to notice dysuria and Objective
frequency of urination yesterday but without urgency Physical Examination
or hematuria. She has no vaginal discharge or dyspare- General The patient appears in no distress, but she
unia. She also denies noticing any fever or back pain. did have to make a quick trip to the bathroom to uri-
She has had two episodes of similar symptoms in the nate just before you came into the room.
past 6 months. She was told on these previous episodes
that she had a bladder infection and was given 3-day Vital Signs
courses of antibiotics with resolution of her symptoms. Temperature, 37.3˚C (99.2˚F)
Her last episode was 1 month ago. Before the past Blood pressure, 128/80
6 months, she had only two urinary tract infections Pulse, 86 and regular
(UTIs), and neither of these was during childhood. She Respiratory rate, 16
has not had any recent instrumentation of her urinary Height, 5 feet 6 inches
tract and has not been hospitalized. Weight, 120 pounds
Her last menstrual period was 1 week ago. She
has no history of vaginal spermicide use or immuno- Head, Eyes, Ears, Nose, and Throat Pharynx reveals
compromise. a moist mucosa.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

418
 Chapter 52 Dysuria and Urinary Frequency (Urinary Tract Infection)

Abdomen Her abdomen has active bowel sounds and

Table 52-2 Bacterial Prevalence in
is scaphoid, with suprapubic tenderness to deep pal-
Complicated Urinary Tract
pation but no guarding or rebound. No palpable
Infection
masses in the abdomen or palpable kidneys are found.
Bacteria Prevalence (%)
Back No dimpling or skin defects overlie the spine,
and no costovertebral angle tenderness is seen. Escherichia coli 30
Proteus species 13
Pelvic On pelvic examination, no external vaginal Enterobacter species 3
Staphylococcus epidermidis 12
lesions are found. A scant amount of yellowish white
Staphylococcus aureus 4
discharge is present in the vagina. The cervix appears Enterococcus species 16
smooth, with no cervical motion tenderness. The Pseudomonas species 5
fundus is smooth and nontender, and no adnexal Others (Serratia, Streptococci, 17
masses are appreciated. Actineobacter, and Citrobacter
species)
Neurologic Motor strength and sensation to pain
and touch are normal in both legs. and those with diabetes mellitus or tract abnormal-
ities have an increased risk of pyelonephritis with
Assessment UTIs, even if the hallmark symptoms are not
present.
Working Diagnosis 2. Interstitial cystitis. This patient is in the age range and
The working diagnosis is recurrent cystitis. of the gender in which interstitial cystitis predomi-
Recurrent cystitis is defined as three or more UTIs in nates. Previous UTIs also are considered to be a risk
the course of 1 year (or two episodes in 6 months). factor for interstitial cystitis. However, the asympto-
Although she has had multiple recent infections, she matic periods in her recent history strongly speak
has an uncomplicated infection. Complicated infec- against this diagnosis. Patients with interstitial cysti-
tions are more likely to be caused by resistant organ- tis typically have severe combinations of dysuria,
isms and occur when the urinary tract is abnormal frequency, and suprapubic pain, which vary from
or when the infection occurs in an environment day to day but are usually disabling in severity.
where resistant organisms are more likely to be pres- 3. Relapsing cystitis. Reinfections are much more
ent, such as hospitals, nursing homes, Foley common than relapsing infections, even when
catheters, etc. (Tables 52-1 and 52-2). symptoms recur shortly after previous episodes.
A relapsing infection is caused by the same organism
Differential Diagnosis because it was not eradicated with the first treatment
1. Pyelonephritis. The hallmarks of pyelonephritis are and typically occurs within 2 weeks of treatment. In
high fever, chills, back or flank pain, and nausea and contrast to reinfection, an abnormality in the uri-
vomiting. Of these, the single best predictor of nary tract is common when a UTI relapses.
pyelonephritis is a temperature greater than 38.9˚C 4. Bladder cancer. Risk factors for bladder carcinoma
(102˚F). However, the presence or absence of these are cigarette smoking and exposure to industrial
clinical indicators is not always reliable, and the mis- dyes or solvents. Bladder cancer is more common
labeling of cystitis as pyelonephritis and vice versa in men. Most patients have at least intermittent
occurs in about 30% of patients. Pregnant women hematuria, either gross or microscopic, but some
have pyuria, and occasional patients are initially
seen with urinary frequency and urgency. Urine
Table 52-1 Bacterial Prevalence in cytology has been useful in the diagnosis of higher-
Uncomplicated Urinary Tract stage and more undifferentiated tumors, in which
Infection sensitivity approaches 90%, but ultimate diagnosis
and staging of bladder carcinoma is by cystoscopy
Bacteria Prevalence (%) and transurethral resection.
Escherichia coli ≥80 5. Vaginitis. Bacterial vaginitis is most commonly
Staphylococcus 10–15 (20% in caused by altered vaginal flora but also can be caused
saprophyticus college-aged by the direct introduction of organisms. Candida
population) and Trichomonas vaginitis are more inflammatory
Proteus species 3 than bacterial vaginosis and therefore more likely to
Klebsiella species 3 produce dysuria. Among noninfectious etiologies,
Enterobacter species 1.5 atrophic vaginitis in postmenopausal women and
Citrobacter species 0.8 chemical vaginitis from vaginal products and
Enterococcus species 0.5
scented toilet paper must be considered.

419
 Chapter 52 Dysuria and Urinary Frequency (Urinary Tract Infection)

6. Viral cystitis. Adenovirus type II is a recognized the cause is a UTI or one of the other causes listed
cause, most typically producing a spontaneously in the differential diagnosis section. The second
resolving hemorrhagic cystitis in children. goal, if the diagnosis is UTI, is differentiation
7. Chemical cystitis. Cyclophosphamide is the most between upper or lower tract infection and compli-
common cause. Initial symptoms are similar to cated or uncomplicated infection.
those of bacterial cystitis, but microscopic and Cystitis is an extremely common infection in
gross hematuria can develop, particularly with women, with 40% of women experiencing at least
prolonged courses and higher doses. one episode in their lifetimes. It is rare in men unless
8. Radiation cystitis. This should be suspected as the at least partial obstruction or some other anatomic
cause in any patient with a previous history of abnormality occurs in their urinary tract. Male
radiation to nearby structures (prostate, uterus) infants who have not been circumcised also have
who has cystitis symptoms but no evidence of an 8 times higher relative risk. In some men, the
infection on culture. infection is acquired through intercourse. If present,
9. Urethral diverticulum. During physical examina- the triad of symptoms of dysuria, frequency, and
tion, milking of the urethra will reveal a palpable urgency is particularly predictive of cystitis. The
mass, and pus will be seen at the urethral meatus. dysuria of cystitis is sensed as more internal than is
that of vaginitis. Associated hematuria is common.
Plan Many UTIs are associated with intercourse, with
symptoms developing approximately 24 hours later.
Diagnostic Vaginal spermicides kill protective lactobacilli but are
Because Ms. L. has symptoms suggestive of an not bactericidal against Escherichia coli and thus are
uncomplicated cystitis, a urinalysis (dipstick would risk factors. In smaller children or infants who cannot
be adequate) is the only test indicated. Despite a his- describe dysuria, the presence of an otherwise unex-
tory suggestive of recurrent infections, no history plained fever is the most typical presentation. Visible
suggests a complicated infection or pyelonephritis, discomfort with urination, falling off height curves
both of which would warrant urine cultures with with chronic infection, and nausea, vomiting, or
sensitivity. A complete blood count (CBC) with dif- diarrhea can suggest UTI in these age groups.
ferential and blood cultures (blood cultures are pos- Infectious vaginitis is associated with a vaginal dis-
itive in about 20% of cases of pyelonephritis) would charge, and the dysuria is described as more external.
be appropriate only if the patient appeared septic. Risk factors such as recent antibiotic use, sexual activity,
Urine Gram stains are appropriate to guide initial and diabetes mellitus should be elicited. Dyspareunia is
antibiotic choices in patients with urosepsis but are frequently present with vaginitis. Atrophic vaginitis is a
not necessary for uncomplicated cystitis. consideration in any postmenopausal woman com-
plaining of dysuria. Previous vaginal dryness and dys-
Therapeutic pareunia are typically present, and frequently systemic
The patient is given nitrofurantoin sustained release, features such as hot flashes are found.
100 mg twice daily for 3 days, for the acute infection Urethritis is the most common cause of dysuria
and then 50 mg after intercourse for prophylaxis. in young adult men, but it is usually asymptomatic in
women. Men often notice a urethral discharge and
Patient Education can have urethral pruritus.
The patient is instructed to urinate after intercourse Painless hematuria (gross or microscopic), espe-
and to avoid vaginal spermicides. She is to stop the cially in patients with risk factors, suggests bladder
nitrofurantoin and contact the office if any fever, carcinoma. However, bladder carcinoma is not an
cough, or skin reactions develop. The beneficial role initial concern if symptoms of infection are found
of daily cranberry juice also is discussed. with the hematuria.
Interstitial cystitis should be suspected with
Disposition chronic symptoms. Often severe, they can include
The patient is sent home. She is instructed to make an any combination of dysuria, urgency, frequency, and
appointment in 6 months, at which time a trial off the suprapubic pain that cannot be otherwise explained
prophylactic antibiotic is planned, even if it has sup- by infection or the other presented differential diag-
pressed repeated infections. She will return sooner if noses for dysuria.
UTI symptoms appear despite receiving prophylaxis. Pyelonephritis is suggested when back/flank pain,
nausea and vomiting, or high fever is reported.
Although low-grade temperature elevations can be
DISCUSSION seen with cystitis, a fever of greater than 38.9˚C (102˚F)
has been shown to be the best indicator. Pyelonephritis
Two basic goals exist in the approach to a patient also is more likely (even if these other features are
with dysuria. The first goal is to determine whether not present) if the patient has had previous episodes

420
 Chapter 52 Dysuria and Urinary Frequency (Urinary Tract Infection)

of pyelonephritis, has an abnormal urinary tract, is in uncomplicated cystitis, as the sensitivity (about
pregnant, or has delayed (for longer than 1 week) 88%) and specificity of a positive leukocyte esterase
getting treatment for the cystitis. In about 20% of are slightly poorer than those in adults (American
pyelonephritis cases, no cystitis symptoms are present. Academy of Pediatrics, 1999● A). Blood cultures are
Even with use of these criteria, however, about one positive in about 20% of pyelonephritis cases. They
third of cystitis cases and one third of pyelonephritis should be obtained in suspected urosepsis and can be
cases are misclassified. Because of this, any woman obtained in any patient hospitalized for pyelonephri-
who notices a quick return of symptoms, even though tis. Although a CBC is appropriate for patients in
these symptoms initially improved on a 3- or even urosepsis, elevated white blood cell counts and sedi-
7-day antibiotic course, should be assumed to have mentation rates are not adequately specific to be
pyelonephritis and given a 14-day course of antibiotics useful in the differentiation of pyelonephritis from
after urine culture. cystitis. Imaging studies are not needed in the vast
The physical examination needed in assessing a majority of cases. Indications for urgent imaging
patient with possible UTI is focused, but important. are symptoms that suggest ureteral obstruction in
Vital signs, especially temperature and blood pres- association with the UTI. Other situations in which
sure, should be obtained. Cystitis patients are typi- imaging is appropriate are to assess for perinephric
cally afebrile, but some have a low-grade temperature abscess in patients who remain febrile after 3 days
elevation (less than 38.9˚C [102˚F]). Patients with of treatment with an appropriate antibiotic, and to
interstitial cystitis, chemical or radiation cystitis, or rule out vesico-ureteral reflux in children (especially
viral cystitis or urethritis are afebrile. Costovertebral preschoolers) in whom voiding cystourethrograms
angle tenderness should be evaluated for evidence of (VCUGs) are indicated (Hoberman et al., 2003● B ).
pyelonephritis. About 20% of patients with UTIs will See Box 52-1 for VCUG indications.
have suprapubic tenderness. In UTIs, this tenderness Treatment choices for uncomplicated cystitis in
is mild to moderate and not associated with guarding nonpregnant women include 3-day courses of
or rebound. The remainder of the abdomen should trimethoprim-sulfa-DS, twice daily, or nitrofuran-
be palpated for evidence of hydronephrosis or other toin, 100 mg four times daily, or an oral first-genera-
tract abnormalities (e.g., polycystic kidneys). tion cephalosporin or amoxicillin with clavulanate
Pelvic examination can be omitted if symptoms (500/125 mg twice daily). Oral fluoroquinolones
of UTI are obvious and supported by urinalysis should be reserved for high local trimethoprim-sulfa
results. Lower back inspection for dimples or hairy resistance (greater than 20%) (Gupta et al., 1999 ● B ).
patches and motor and sensory examinations of the Fosfomycin in a single 3-g dose is another option but
lower extremities are appropriate for recurrent infec- is less effective than the 3-day courses. Children,
tions in which spina bifida or neurogenic bladder men, and pregnant women should receive 7-day
may be predisposing to infection. Prostate examina- antibiotic courses, and sensitivity should be con-
tion is indicated in men with suspected UTI, as pro- firmed with culture (Keren and Chan, 2002 ● A).
statitis can occur with dysuria, and prostatic urethral Fluoroquinolones and tetracyclines are contra-
obstruction from benign prostatic hypertrophy or indicated in children and during pregnancy.
localized adenocarcinoma of the prostate is a major Trimethoprim-sulfa has particular safety concerns in
predisposing factor to UTI development. pregnancy. Pyelonephritis is treated with the same
A dipstick urinalysis is an inexpensive and antibiotics (except for fosfomycin) for 14-day
useful test in assessing for possible UTIs. In non- courses, but if a fluoroquinolone is chosen, this
pregnant adults, the sensitivity of urine leukocyte can be reduced to 7 days (Talan et al., 2000 ● A).
esterase is greater than 90% for a UTI. Urinary
nitrite is only about 30% sensitive (although this
improves to 60% if the first void of the morning is Box 52-1 Indications for Voiding
used) but is a highly specific test for UTI. White
Cystourethrograms in Urinary
blood cell casts on a microscopic urinalysis are
highly specific for pyelonephritis, but sensitivity is Tract Infections
poor. The presence of bacteriuria on Gram stain is Children
very specific for UTI but is not sensitive (especially Any UTI in boy
for infections with colony counts of less than 105). One UTI in girl younger than 5 years or two
Gram-positive cocci on Gram stain can give pre- or more infections in girl younger than 5 yr
sumptive clues as to enterococci to guide empirical Adults or children
antibiotic therapy in urosepsis. Urine culture is not Symptom of flank pain that occurs only with
necessary in uncomplicated cystitis in nonpregnant micturition
adult women. Urine culture should be obtained if Otherwise unexplained renal scarring or
pyelonephritis is suspected or if the UTI is compli- poor renal growth
cated. Urine cultures are indicated in children, even

421
 Chapter 52 Dysuria and Urinary Frequency (Urinary Tract Infection)

Table 52-3 Antibiotic Choices for Table 52-4 Prophylactic Antibiotics for
Complicated Urinary Tract Recurrent Urinary Tract
Infection Infection
Antibiotic Comments Antibiotic Dose

Ampicillin and Ampicillin, 1g IV Daily Administration

gentamicin q6h; gentamicin, Trimethoprim-sulfa 1 single-strength
1 mg/kg IV q8h (Bactrim) (400 mg/80 mg)
Piperacillin and 3.375 g IV q6h or tab each day
tazobactam (Zosyn) 4.5 g IV q8h Nitrofurantoin
Ticarcillin and (Furadantin) 50–100 mg qhs
clavulanate (Timentin) 3.1 g IV q6h
Meropenem (Merrem IV) 1 g IV q8h Postcoital Administration
Fluoroquinolone Ciprofloxin (Cipro), Trimethoprim-sulfa One double-
400 mg IV or PO strength (800
twice daily, mg/160 mg) tab
or gatifloxacin after coitus
(Tequin), 400 mg Nitrofurantoin One 100-mg tablet
q day, or after coitus
levofloxacin
(Levaquin), 500
mg q day, or
ofloxacin (Floxin), vaginal estrogens (Raz and Stamm, 1993● A); however,

400 mg PO twice this decrease does not occur with oral estrogens
daily (Brown et al., 2001● A). Cranberry products have been
shown to reduce the incidence of UTIs in women
(Jepson et al., 2004● A). If such factors are not present
or if recurrences continue, daily or intermittent
Complicated infections require 2 weeks of therapy.
antibiotics, as in Table 52-4, can be used. The need for
See Table 52-3 for options. Perinephric abscesses
continued prophylaxis should be assessed at 6 to 12
require surgical or percutaneous drainage as well as
months, as spontaneous resolution is common.
antibiotics. Treatment for recurrent UTIs should first
try to correct factors that may be adversely affecting
vaginal flora. Alternative contraceptive methods Material Available on Student Consult
should be used if the patient is using a spermicide.
Review Questions and Answers about Urinary
Postmenopausal women increase their vaginal lacto- Tract Infection
bacilli and decrease their frequency of UTIs with

REFERENCES
American Academy of Pediatrics: Committee on Quality febrile urinary tract infection in young children. N Engl
Improvement and Subcommittee on Urinary Tract J Med 2003;348:195–202.● B
Infection Practice Parameter. The diagnosis, treatment, Jepson RG, Mihaljevic L, Craig J. Cranberries for prevent-
and evaluation of the initial urinary tract infection in ing urinary tract infections. Cochrane Database Syst
febrile infants and young children. Pediatrics Rev 2004;CD001321.● A
1999;103:843–852.● A Keren R, Chan E. A meta-analysis of randomized, con-
Brown JS, Vittinghoff E, Kanaya AM, et al., for the Heart trolled trials comparing short- and long-course anti-
and Estrogen/Progestin Replacement Study Group. biotic therapy for urinary tract infections in children.
Urinary tract infections in postmenopausal women: Pediatrics 2002;109:e70.● A
Effect of hormone therapy and risk factors. Obstet Raz R, Stamm WE. A controlled study of intravaginal estriol
Gynecol 2001;98:1045–1052.● A in postmenopausal women with recurrent urinary tract
Gupta K, Scholes D, Stamm WE. Increasing prevalence of infections. N Engl J Med 1993;329:753–756.● A
antimicrobial resistance among uropathogens causing Talan DA, Stamm WE, Hooton TM, et al. Comparison
acute uncomplicated cystitis in women. JAMA of ciprofloxacin (7 days) and trimethoprim-sul-
1999;281:736–738.● B famethoxazole (14 days) for acute uncomplicated
Hoberman A, Charron M, Hickey RW, Baskin M, pyelonephritis in women: A randomized trial. JAMA
Kearney DH, Wald ER. Imaging studies after a first 2000;283:1583–1590.● A

422
 C h a p t e r

53 Bedwetting (Childhood
Nocturnal Enuresis)
Jennifer DeVoe

KEY POINTS

1. Reassurance that enuresis will spontaneously discontinuation and because they are associated
resolve is usually the best approach in children with fewer adverse effects.
younger than 7 years. 4. Desmopressin acetate (DDAVP) is an effective
2. Once the child is old enough to be partially short-term alternative to the enuresis alarm in
responsible for treatment, motivation and sim- patients who are unresponsive to the alarm. It
ple behavior therapies are usually the first line also may be used as an adjunct to the alarm and
of treatment (including reinforcement for as a short-term solution for camp attendance or
dry nights, bladder-training exercises, fluid sleepovers.
management, or a combination of these 5. Tricyclic antidepressants (TCAs) are an effective
therapies). short-term therapy for nocturnal enuresis.
3. Enuresis alarms or pharmacologic therapy or However, TCAs have a high relapse rate and
both should be considered in children who potentially severe adverse effects.
have failed to improve after 3 to 6 months of 6. A primary care provider can effectively manage
behavioral interventions. In systematic reviews, nocturnal enuresis. On occasion, children with
enuresis alarms are superior to pharmacologic refractory nocturnal enuresis may benefit from
therapy because their effects are sustained after referral to a pediatric urologist.

INITIAL VISIT Family History

Bob is the youngest of four children. He has two sis-
Subjective ters and one brother. His father reports that all three
of his siblings had problems with nocturnal enuresis
Patient Identification and Presenting Problem but with only occasional frequency. Bob’s father also
Bob L. is a 9-year-old boy who reports nighttime wet the bed regularly until age 8.
enuresis. He is accompanied by his father, who reports
that Bob has been wetting his bed since he was an Social History
infant. Bob is currently wetting nearly every night and Bob’s parents are getting divorced, and Bob recently
has never had a period of dryness. He denies daytime started seeing a counselor.
wetting. He has not complained of polydypsia,
polyuria, dysuria, hematuria, or urinary urgency. His Review of Systems
parents have tried limiting his evening fluid intake and Bob denies insomnia, abdominal pains, headaches,
waking him at night to urinate. Despite these meas- constipation, diarrhea, or encopresis.
ures, he is still wetting the bed on most nights.
Objective
Medical History
Bob has no history of bladder infections or diabetes Physical Examination
mellitus. He has had no hospitalizations and takes no General Bob is a well-nourished 9-year-old boy
medications. who appears to be healthy.

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

423
 Chapter 53 Bedwetting (Childhood Nocturnal Enuresis)

Vital Signs children with monosymptomatic nocturnal enure-

Blood pressure, 106/70 sis have this form (Gonzalez, 2004● A ).
Heart rate, 84 ■ Secondary enuresis. Approximately 20% of children
Respirations, 16 with monosymptomatic nocturnal enuresis have
Height, 52.5 inches had a period of dryness, usually for at least
Weight, 95.1 pounds 6 months, before the onset of wetting begins; these
children have secondary enuresis. Secondary
Head, Eyes, Ears, Nose, and Throat Tympanic mem- enuresis is often associated with an unusually
branes are clear. Pupils are equal, round, and reactive stressful event (e.g., parental divorce, birth of a
to light. Mucous membranes are moist with no ery- sibling, death of a family member) at a time of
thema in the pharynx. vulnerability in a child’s life (Gonzalez, 2004●A).
However, the exact cause of secondary enuresis
Neck No lymphadenopathy or thyromegaly. remains unknown.
A small percentage of children who have night-
Cardiovascular Heart sounds are regular with no
time wetting also have significant daytime problems.
murmurs; 2+ distal pulses.
The daytime symptoms usually include urgency,
frequency, and occasionally daytime incontinence
Lungs Clear to auscultation bilaterally.
(diurnal enuresis). Urologic and neurologic disor-
ders (e.g., detrusor instability, recurrent urinary tract
Abdomen Soft and nontender with no masses.
infection, spinal dysraphism) are more common
among children with diurnal symptoms than in
Genitourinary He has a circumcised penis; both
those with isolated nocturnal enuresis. In addition,
testes are descended. No evidence of wetness is seen
some children also have troublesome encopresis
in undergarments; Tanner stage II; no hernias.
(incontinence of stool). Patients who have nocturnal
enuresis with daytime symptoms are described as
Back No clefts or tufts of hair, no scoliosis.
having complex or complicated enuresis (also called
dysfunctional voiding), whereas those who have
Extremities Warm and well perfused with no edema.
associated bowel symptoms are often described as
having dysfunctional elimination syndrome (Feng
Musculoskeletal Gait and physical mobility are
and Churchill, 2001● B ).
within normal range.

Neurologic Normal strength, sensation, and deep Epidemiology

tendon reflexes throughout. The prevalence of monosymptomatic nocturnal
enuresis slowly declines with age, as outlined in
Skin Mild facial acne. Table 53-1 (Gonzales, 2003 ● B ; Howe and Walker,
1992● A). The disorder is twice as common among

Laboratory Examination boys as among girls and resolves spontaneously in

Urinalysis is negative for blood, glucose, ketones, most children (Forsythe and Redmond, 1974 ● B ;

leukocyte esterase, and nitrites. Basic metabolic Klackenberg, 1981● B ). The longer the enuresis per-

panel is normal. sists, the lower the probability that it will resolve
spontaneously (Bakker et al., 2002● B ; Forsythe and
Redmond, 1974● B ; Klackenberg, 1981● B ).
Assessment
Working Diagnosis
Bob is diagnosed with primary monosymptomatic Table 53-1 Prevalence of Nocturnal
nocturnal enuresis. Urinary incontinence at night Enuresis in Children, by Age
is a common problem in children. Fifteen percent
Prevalence of Nocturnal
of 5-year-old children remain incompletely conti- Enuresis among All
nent of urine. Most of these children have isolated Child’s Age (yr) Children (%)
nocturnal enuresis (monosymptomatic nocturnal
enuresis). Monosymptomatic nocturnal enuresis 5 16
is usually divided into primary and secondary 6 13
forms. 7 10
8 7
■ Primary enuresis. Children who have never 10 5
achieved a satisfactory period of nighttime dryness 12 to 14 2–3
have primary enuresis. An estimated 80% of ≥15 1–2

424
 Chapter 53 Bedwetting (Childhood Nocturnal Enuresis)

Differential Diagnosis and Possible is told that enuretic episodes occur at random
Causes for Nocturnal Enuresis throughout the night and can occur in all stages of
When presented with a child who is bedwetting, the sleep. In most cases, enuresis occurs during
clinician should consider diagnoses other than non–rapid eye movement (REM) sleep (mainly in
enuresis. In some cases, further evaluation and treat- the early part of the sleep cycle), but some children
ment are required to determine the exact diagnosis. wet during phases of early awakening.
See Box 53-1 for a list of alternative diagnoses
(Gonzalez, 2003● A ).
Therapeutic
Nocturnal childhood enuresis may be caused by After a discussion of various approaches to treat-
several different factors. In any given child, several of ment, the patient and his father agree first to try
these factors may occur simultaneously. Maturational some nonpharmacologic interventions. Bob and his
delay, genetics, small bladder capacity, decreased father make a plan for a stepwise approach to these
nocturnal secretion of antidiuretic hormone, detru- therapies, described in succeeding sections and out-
sor instability, sleep disorders, and psychological lined in Figure 53-1.
problems have been considered as major contributors
to nocturnal enuresis (Gonzales, 2003● A). No consen- 1. Motivational therapy. Bob agrees to keep a record of
sus exists about the exact combination of causes or progress, and his father will give him awards for
the validity of an exact relation between each cause periods of dryness, with larger awards for longer
and childhood nocturnal enuresis. dry periods. Motivational therapy is a good first-
line therapy for primary nocturnal enuresis, partic-
ularly in younger children (Cendron, 1999● A). In a
Plan and Discussion Cochrane systematic review, children using reward
Diagnostic systems (e.g., star charts) had significantly fewer wet
Because Bob does not have daytime symptoms of uri- nights, higher cure rates, and lower relapse rates
nary incontinence, no urologic imaging studies (renal compared with those of controls (Glazener and
sonogram or voiding cystourethrogram) are indi- Evans, 2004● A ).
cated at this time. His neurologic examination is nor- 2. Bladder-retention training. Bob will try holding
mal, so neuroimaging (usually magnetic resonance his urine for successively longer intervals (“as
imaging of the spine) also is not recommended. long as possible”) after first sensing the urge to
void. His father will record his volume of voided
Patient Education urine once per week to evaluate success. The tar-
Bob is given information about how to manage his get volume is 11 ounces, based on the calculated
fluid intake. Normal bladder capacity (in ounces) bladder capacity for Bob’s age. In Cochrane sys-
can be estimated by adding 2 to a child’s age in years, tematic reviews of simple behavioral and physical
up to age 10. Thus Bob is given a visual demonstra- interventions for nocturnal enuresis in children,
tion of 11 ounces of liquid. His father asks about the not enough evidence was available to evaluate
times when Bob is most likely to wet the bed, and he bladder retention used either in isolation or in
addition to other interventions (Glazener and
Evans, 2004● A ). Nonetheless, a trial of this simple
behavioral method is recommended before use of
Box 53-1 Differential Diagnosis for alarms and pharmacologic agents, which may be
Childhood Nocturnal Enuresis more demanding and have adverse effects (Jalkut
et al., 2001● B ; Koff, 1983●B ).

Unrecognized underlying medical disorders (e.g., 3. Fluid management. A review of Bob’s previous
sickle cell disease, seizures, hyperthyroidism) diary showed that he was drinking a dispropor-
Encopresis or constipation tionate amount of fluid in the evening hours, so
Dysfunctional voiding (usually associated with he will try to drink 40% of his total daily fluid in
daytime symptoms) the morning (7 AM to 12 PM), 40% in the afternoon
Urinary tract infection (12 PM to 5 PM), and only 20% in the evening (after
Chronic renal failure 5 PM). In addition, he agrees to drink only non-
Spinal dysraphism caffeinated beverages in the evening (Jalkut et al.,
Upper airway obstruction 2001● B ). This fluid-management program permits

Pinworms Bob to drink as much as he wants throughout the

Chronic renal failure day. Encouraging fluid intake in the morning and
Diabetes mellitus afternoon reduces the need for significant intake
Diabetes insipidus later in the day. It also increases daytime urinary
Psychogenic polydipsia flow and may assist in bladder training to increase
functional bladder capacity (Jalkut et al., 2001● B ).

425
 Chapter 53 Bedwetting (Childhood Nocturnal Enuresis)

First-line nonpharmacologic
interventions for childhood nocturnal
enuresis:
• Motivational therapy
Using first-line • Bladder-retention training
therapies in • Fluid management
combination • Dry-bed training (if above
with alarm may three approaches do not
further lower work)
relapse rate
after If first-line not
discontinuation working after
of therapy. 3 months

Enuresis alarms Pharmacologic therapy (DDAVP or TCAs)

• Put child in charge of alarm; alarm Can be used in • For occasional use, such as sleepovers
works by conditioning combination and summer camp, or regular use
• Lower relapse rates after • Higher relapse rates after
discontinuation compared with discontinuation compared with
medications alarms.

Figure 53-1 Stepwise approach to the management of childhood nocturnal enuresis. DDAVP, desmopressin acetate;
TCAs, tricyclic antidepressants.

4. Dry-bed training. If motivational therapy, bladder three approaches (motivational therapy, bladder-
training, and fluid management do not work for retention training, and fluid management). They
Bob, his family will try intensive dry-bed training have started dry-bed training; however, Bob’s contin-
and may consider purchasing an alarm. During ued enuretic episodes are starting to cause major
the first night, Bob will be awakened frequently embarrassment, and Bob has become more with-
and taken to the toilet. Even if an accident occurs drawn. He refused to go to summer camp and had a
before the time of awakening, Bob must still prac- miserable summer. He continues to deny polydypsia,
tice getting up and going to the toilet. On subse- polyuria, dysuria, hematuria, or urinary urgency.
quent nights, Bob will be awakened once, at They have not yet tried an enuresis alarm, but they
progressively earlier times, and taken to the toilet. request a trial of medications for the bedwetting.
5. Enuresis alarms. Because an alarm costs between $40
and $90, Bob and his father will not immediately Objective
buy one. They are aware, however, that conditioning
therapy with an enuresis alarm is the most effective Physical Examination
means of controlling nocturnal enuresis (Glazener General Bob, a well-nourished, healthy-appearing
et al., 2004●A ; Moffatt et al., 1993●
A ). The alarm 9-year-old boy, is more withdrawn, avoids eye contact,
works through conditioning: the patient learns to and offers minimal verbal responses to examiner ques-
wake or inhibit bladder contraction in response to tions. He is responsive and interactive with his father.
the neurologic conditions present before wetting.
Vital Signs
Disposition Blood pressure, 110/72
Bob and his father understand that nonpharmaco- Heart rate, 80
logic therapies should be tried for approximately 3 to Respirations, 16
6 months. They will return for a follow-up visit after Height, 53.0 inches
3 months. Weight, 97.1 pounds
The remainder of the physical and laboratory
FOLLOW-UP VISIT examinations is unchanged from the previous visit.

Subjective Assessment
Bob and his father return 3 months later. His father The assessment is primary monosymptomatic
reports that Bob continues to wet his bed nearly nocturnal enuresis unresponsive to nonpharma-
every night, despite trying a combination of the first cologic therapies. Bob and his father consider the

426
 Chapter 53 Bedwetting (Childhood Nocturnal Enuresis)

continued enuresis to be a “big problem” and are ■ Compared with placebo, DDAVP (20-μg nasal
eager to try other interventions (see Fig. 53-1 for spray) reduced bedwetting by 1.34 nights per week
a stepwise approach to the management of noc- (95% confidence interval, 1.11 to 1.57) (Glazener
turnal enuresis in children). and Evans, 2002 ● A).
■ Compared with placebo, children treated with
Plan DDAVP (20-μg nasal spray) were more likely to be
dry for 14 nights (RR, 1.19; 95% confidence inter-
Therapeutic Interventions val, 1.10 to 1.27) (Glazener and Evans, 2002● A).
Bob and his father agree to buy an enuresis alarm for ■ DDAVP and TCA appear to be equally effective
nightly use. Bob will be in charge of the alarm. Each (Glazener and Evans, 2002 ● A).
night before he goes to sleep, he will test the alarm; ■ Although alarms appear to be less immediately
with the sound (or vibration) in mind, he will imag- effective than DDAVP, alarms are more effective in
ine in detail, for 1 to 2 minutes, the sequence of events preventing relapse. Alarms also are more effective
that should occur when the alarm sounds (or vibrates) than TCAs during and after treatment. Relapse can
during sleep. In one Cochrane systematic review, occur after the alarm unit is discontinued. However,
approximately two thirds of children using alarms the relapse rate after discontinuation of therapy is
became dry for 14 consecutive nights (compared with much lower with alarms than with DDAVP (RR,
children with no alarm, relative risk (RR) for failure, 0.11; 95% confidence interval, 0.02 to 0.78) or TCAs
0.36; 95% confidence interval, 0.31 to 0.43) (Glazener (Glazener et al., 2003b●A ; Glazener et al., 2004●A).
et al., 2003a● A ). Forty-five percent of children who ■ The combination of alarm therapy with a complex
continued to use the alarm remained dry after treat- behavioral intervention, such as dry-bed training
ment, compared with only 1% in the no-treatment or full-spectrum home training, may further
group (Glazener et al., 2003a● A). Bob also requests a decrease the relapse rate (Glazener et al., 2004● A).
medication to help him stay dry during sleepovers and
summer camp. This pharmacologic intervention is Many other drugs, including phenmetrazine,
sought because Bob is getting older and experiencing oxybutinin, indomethacin, amphetamine sulfate,
social pressures and self-esteem problems linked to ephedrine, atropine, furosemide, and diclofenac have
the enuresis. He is counseled about desmopressin been tried. A systematic review of randomized trials
acetate (DDAVP), with a starting dose of 0.2 mg per of drugs other than TCAs and DDAVP in the treat-
night, increasing to 0.6 mg over a 2-week trial period. ment of nocturnal enuresis found that although
He is warned about relapse if the medication is indomethacin and diclofenac were better than
stopped and is strongly encouraged first to try consis- placebo, none of the drugs was better than DDAVP
tent alarm therapy, which has been shown to be the (Glazener et al., 2003c●
A).
most effective long-term treatment.
Summary
Patient Education Regarding Alarms
and Medications to Treat Childhood Childhood nocturnal enuresis is common and has a
Nocturnal Enuresis high spontaneous resolution rate. Evidence supports
Bob and his father are educated about the pitfalls in a genetic link between parents who had childhood
treatment of childhood enuresis and the latest evi- enuresis and their children. Most treatment should be
dence. Most of the efforts surrounding childhood delayed until the child is at least age 7. Simple behav-
enuresis have focused on finding a treatment with ioral methods are usually tried first, but more active
long-term benefits. Two medications have been prom- intervention should be recommended as the child
ising in the short term: tricyclic antidepressants and gets older, because social pressures increase, and self-
DDAVP. Tricyclic antidepressants (TCAs) have been esteem is affected. In Cochrane systematic literature
used to treat enuresis since 1960. TCAs decrease the reviews, arousal alarm systems are the most effective
amount of time spent in REM sleep, stimulate vaso- long-term therapy. Fluid management and bladder
pressin secretion, and relax the detrusor muscle. training may be helpful supplemental approaches.
DDAVP, in tablet and intranasal forms, was approved Pharmacologic agents can be effective in the short
as a treatment option for nocturnal enuresis in 1990. term, especially for children who want to participate
Twenty-five percent of patients achieve total dryness by in age-specific social activities, such as camping or
using DDAVP, whereas another 50% show a significant sleepovers with friends. Refer to the Key Points in the
decrease in nighttime wetting (Moffatt et al., 1993● A ). treatment of childhood nocturnal enuresis.
However, discontinuation of medications is associated
with high rates of relapse (60% to 70%) (Wille, 1986 Material Available on Student Consult
●A). Cochrane systematic reviews comparing DDAVP
with TCAs or alarms in the treatment of nocturnal Review Questions and Answers about Childhood
Nocturnal Enuresis
enuresis showed the following:

427
 Chapter 53 Bedwetting (Childhood Nocturnal Enuresis)

REFERENCES
Bakker E, van Sprundel M, van der Auwera JC, van Gool JD. Glazener C, Evans J, Peto R. Complex behavioural and edu-
Voiding habits and wetting in a population of 4,332 cational interventions for nocturnal enuresis in chil-
Belgian schoolchildren aged between 10 and 14 years. dren. Cochrane Database Syst Rev 2004;CD004668. ● A
Scand J Urol Nephrol 2002;36:354–362.● B Gonzales ET. Approach to the child with nocturnal enure-
Cendron M. Primary nocturnal enuresis: Current. Am Fam sis. Available at www.uptodate.com, last revised
Physician 1999;59:1205–1214, 1219–1220.● A September 2, 2003. Accessed 9/29/2004.● A
Feng WC, Churchill BM. Dysfunctional elimination syn- Gonzales ET. Management of nocturnal enuresis in chil-
drome in children without obvious spinal cord dis- dren. Available at www.uptodate.com, last revised
eases. Pediatr Clin North Am 2001;48:1489–1504.● B March 4, 2004. Accessed 9/29/2004.● A
Forsythe WI, Redmond A. Enuresis and spontaneous cure Howe AC, Walker CE. Behavioral management of toilet
rate: Study of 1129 enuretics. Arch Dis Child 1974;49: training, enuresis, and encopresis. Pediatr Clin North
259–263.● B Am 1992;39:413–432.● B
Glazener C, Evans J. Desmopressin for nocturnal enuresis in Jalkut MW, Lerman SE, Churchill BM. Enuresis. Pediatr
children. Cochrane Database Syst Rev 2002;CD002112.● A Clin North Am 2001;48:1461–1488.● B
Glazener C, Evans J. Simple behavioural and physical inter- Klackenberg G. Nocturnal enuresis in a longitudinal per-
ventions for nocturnal enuresis in children. Cochrane spective: A primary problem of maturity and/or a sec-
Database Syst Rev 2004;CD003637.● A ondary environmental reaction? Acta Paediatr Scand
Glazener C, Evans J, Peto R. Alarm interventions for noc- 1981;70:453–457.● B
turnal enuresis in children. Cochrane Database Syst Rev Koff SA. Estimating bladder capacity in children. Urology
2003a;CD002911.● A 1983;21:248.●B
Glazener C, Evans J, Peto R. Tricyclic and related drugs for Moffatt ME, Harlos S, Kirshen AJ, Burd L. Desmopressin
nocturnal enuresis in children. Cochrane Database Syst acetate and nocturnal enuresis: How much do we
Rev 2003b;CD002117.● A know? Pediatrics 1993;92:420–425.● A
Glazener C, Evans J, Peto R. Drugs for nocturnal enuresis Wille S. Comparison of desmopressin and enuresis alarm
in children (other than desmopressin and tricyclics). for nocturnal enuresis. Arch Dis Child 1986;61:
Cochrane Database Syst Rev 2003c;CD002238.● A 30–33.●A

428
 C h a p t e r

54 Nausea, Vomiting, and Lethargy

(Acute Renal Failure)
Kurt A. Lindberg

or abdominal pain. The symptoms worsened over

KEY POINTS the subsequent week to the point at which she is
unable to hold down any fluids, is lightheaded and
1. Acute renal failure (ARF) is caused by prerenal, weak, and is beginning to slur words and wax and
intrarenal, and postrenal etiologies. wane in her cognition.
2. Differentiating between prerenal and intrarenal
pathology can usually be done by relying on a Medical History
careful history supplemented by evaluating The patient has adult-onset diabetes, which is usually
serum and urine laboratory values. controlled well with oral medication. Her husband
3. Postrenal causes of renal failure are readily ruled reports that her sugars have been running in the 100s
out by using a Foley catheter and renal ultra- through the past 2 days. She has hypertension that
sound. has been well controlled and chronic renal insuffi-
4. Prerenal ARF is caused by decreased perfusion ciency with a baseline creatinine of 1.8 mg/dL.
of the glomerulus.
5. The most common cause of intrarenal failure is Medications
acute tubular necrosis (ATN). She takes glipizide (Glucotrol), 10 mg twice a day;
6. Prerenal ARF and ischemic ATN represent two pravastatin (Pravachol), 20 mg daily; lisinopril
ends of a continuum. The more severe the (Zestril), 40 mg daily; hydrochlorothiazide, 25 mg
decrease of glomerular perfusion, the more pro- daily; and now ibuprofen, 800 mg 3 times a day as
longed the recovery will be. needed. She has no known medical allergies.
7. Treatment of renal failure focuses on reversing
the underlying cause and managing fluid and Family History
electrolyte abnormalities. Mary’s father died at age 70 of complications of dia-
betes, and her mother died at age 74 of a stroke and
congestive heart failure (CHF). She has one sister,
who has diabetes and early heart disease. Her three
adult children are healthy.
INITIAL VISIT
Social History
Subjective
Mary was divorced and has recently remarried. She
Patient Identification and Presenting Problem has been a one-pack-a-day smoker for more than 40
Mary D. is a 58-year-old woman complaining of years. She does not drink alcohol or use drugs. She
nausea, vomiting, and lethargy. She was in her usual has had no exposure to anyone with a similar illness.
state of health until about 2 weeks ago, when she
slipped on some ice and twisted her left knee. She Review of Systems
went to the emergency room, where she had normal As stated, she has had no fever or upper respiratory
radiographs and was determined to have a strained symptoms. She reports no shortness of breath,
knee. She was given ibuprofen, 800 mg, to use for the cough, or sputum production. She has had no chest
discomfort and discharged home. Approximately pain or palpitations. She has had two loose stools in
2 days later, she began having gradually worsening the past several days but no signs of melena or blood.
nausea. This was not associated with fever, diarrhea, Her urine has been normal in color and has been

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

429
 Chapter 54 Nausea, Vomiting, and Lethargy (Acute Renal Failure)

slightly decreased from her usual output. She has had Differential Diagnosis
no dysuria or urinary frequency, no peripheral 1. Dehydration due to emesis. Mary may have
swelling or skin changes, and no changes in her joints gastroenteritis, acute cholecystitis, or another
or muscles. According to her husband, she has been primary cause of nausea and vomiting, causing
intermittently uncoordinated during the past several hypovolemia. This state of decreased intravascu-
days, having difficulty walking, speaking, and lar volume may have decreased perfusion of the
remembering where she is or what is happening kidneys, leading to accumulation of waste prod-
around her. At other times, she seems quite clear. She ucts (e.g., BUN and Cr).
has had no localized numbness or weakness. 2. Ibuprofen effect. The recent addition of ibuprofen,
a nonsteroidal anti-inflammatory drug (NSAID),
Objective seemed to coincide with the patient’s onset of
symptoms. NSAIDs can cause gastrointestinal
Physical Examination side effects, which can result in nausea and
Mary is a middle-aged obese woman who is lethargic hypovolemia such as that described earlier.
with no signs of acute distress. She is 5 feet 8 inches tall NSAIDs can have a direct effect on decreasing
and weighs 225 pounds (down about 10 pounds from glomerular filtration rate (prerenal). NSAIDs also
her last visit a month ago). Her temperature is 36.6˚C can cause allergic interstitial nephritis
(97.8˚F); respiratory rate, 14; pulse, 115; and blood (intrarenal) (Albright, 2001● B ).
pressure, 98/50 while reclined. She is unable to co- 3. Other medication effect. The patient is taking an
operate with a standing blood pressure. Her head angiotensin-converting enzyme inhibitor (ACE-I)
examination is normal, with somewhat dry mucous medication, lisinopril, which has been known to
membranes and no oral lesions. Her neck is supple reduce glomerular filtration rate (GFR) and cause
with no jugular venous distention, lymphadenopathy, renal failure. Similarly, hydrochlorothiazide may
or thyromegaly. Lungs are clear to auscultation bilat- have caused dehydration, leading to decreased
erally. Her heart is tachycardic but regular with no renal perfusion. However, these two medications
murmur. Abdomen is diffusely tender, worse in the have been present over a long period and are less
epigastrium, with normal bowel sounds. She has no likely to be at fault for her current presentation.
abdominal mass or organomegaly. Peripheral exami- 4. New intrinsic renal disease. Although statistically
nation reveals no edema and no rashes. She has no less common, intrinsic renal disease is still a con-
joint pain or swelling. Neurologically she has difficulty sideration. With this degree of prerenal azotemia,
maintaining eye contact, is somewhat confused, but is a component of acute tubular necrosis (ATN) may
able to answer simple questions appropriately. She is be present. It is the most common intrarenal cause
unable to stand or ambulate and has been brought to of acute renal failure (ARF) (Brady et al., 2004● A ).
the examination room in a wheelchair. Cranial nerves 5. Postrenal obstruction. The etiologies that result in
are intact, and symmetrical strength and sensation are postrenal obstruction (Box 54-1) are usually sim-
noted in her periphery. ply diagnosed and remedied and should always
be a consideration. The relatively normal urine
Laboratory Tests production in this patient’s history makes this an
Blood chemistries obtained this morning show the unlikely possibility.
following values.
Sodium: 133 mmol/L (normal [nl], 136 to 144) Plan
Potassium: 5.5 mmol/L (nl, 3.6 to 5.1)
Chloride: 104 mmol/L (nl, 101 to 111) Therapeutic
Carbon dioxide: 17 mmol/L (nl, 22 to 32) Mary is admitted to the hospital for control of her
Blood urea nitrogen (BUN): 88 mg/dL (nl, 7 to 19) vomiting, evaluation of the etiology of the renal fail-
Creatinine (Cr): 3.5 mg/dL (nl, 0.4 to 1.0) ure, and hydration. Her examination is most sugges-
BUN/Cr ratio: 25.1 tive of hypovolemia at this time, and correcting this
condition may result in resolution of her renal failure
A complete blood count is within normal limits.
and symptoms. Care should be taken, however, to
A urinalysis shows urine concentration of 1.020 with
avoid overcorrection of her dehydrated state. If her
no sediment, a few ketones, and no other abnormal-
kidneys are sufficiently damaged, they may be unable
ities. Urine electrolytes are pending.
to manage a significant fluid bolus, and hypervolemia
may ensue. Judicious use of normal saline or lactated
Assessment Ringer’s solution is appropriate.
Any medications that result in decreased renal per-
Working Diagnosis fusion should be discontinued until the etiology of her
Acute renal failure, predominantly prerenal but may condition can be better ascertained and her condition
have components of intrinsic renal disease. improved. Because hydrochlorothiazide, lisinopril, and

430
 Chapter 54 Nausea, Vomiting, and Lethargy (Acute Renal Failure)

Box 54-1 Etiologies of Acute Renal Failure

Prerenal Vasculitis
Scleroderma
Loss of intravascular volume
Hemolytic-uremic syndrome, T TP, or DIC
Fluid loss (vomiting, diarrhea, overdiuresis,
Toxemia of pregnancy
skin losses)
Diseases of renal tubules
Hemorrhage
Acute tubular necrosis (ATN)
Third spacing (congestive heart failure, pan-
Ischemic (usually the result of the condi-
creatitis, hypoalbuminemia)
tions listed in PRERENAL)
Ineffective cardiac output (congestive heart
Toxic (e.g., caused by antibiotics, IV con-
failure)
trast, myoglobin, or hemoglobin de-
Hypotension
position)
Antihypertensive medications or anesthesia
Obstruction of tubules (e.g., uric acid, cal-
Sepsis
cium oxalate, light chains)
Cardiogenic shock
Diseases of interstitium
Loss of glomerular pressure
Infection (bacterial pyelonephritis, fungal, or
NSAID medications
viral)
ACE inhibitors
Allergic interstitial nephritis
Renal vasoconstriction (e.g., with use of
Infiltration (e.g., lymphoma, leukemia, sar-
norepinephrine, ergotamine,
coidosis, allograft rejection)
hypercalcemia)

Intrarenal Postrenal
Diseases of large vessels Ureteral (tumors, calculi, clot, sloughed papil-
Thrombosis of renal arteries or veins lae, retroperitoneal fibrosis)
Atheroembolism or thromboembolism Bladder (prostate enlargement/cancer, bladder
Arterial dissection tumor, neurogenic, clotted blood)
Diseases of glomerulus/small blood vessels Urethral (stricture, tumor, malfunctioning
Acute or rapidly progressive glomerulone- catheter)
phritis

ACE, acute tubular necrosis; DIC, disseminated intravascular coagulation; NSAID, nonsteroidal anti-inflammatory drug;
TTP, thrombotic thrombocytopenic purpura.

ibuprofen are all problematic, they should be stopped. ultrasound should be ordered to assess the presence
If the patient’s blood pressure or pain becomes uncon- of postrenal obstruction and to assess the general
trolled, other medications that do not affect the kidney’s appearance of her kidneys. Shrunken, hardened kid-
performance should be used instead. neys would suggest a chronic loss of renal function,
The placement of a Foley catheter is useful to rule whereas enlarged or inflamed kidneys would suggest
out some causes of postrenal obstruction and to mon- an acute etiology. It is rare that any more invasive
itor closely the patient’s fluid status and renal function. testing would be required, such as a renal biopsy.
Mary does not have a significant electrolyte
problem at this time. Close observation of her elec-
trolytes will be necessary as fluid resuscitation, pH, DISCUSSION
and renal function evolve.
ARF is defined as a significant decline in GFR over a
Diagnostic course of hours to weeks, which results in the accu-
This patient has already had some of the basic inves- mulation of nitrogenous waste products (e.g., BUN
tigations that must take place when one suspects and Cr). No absolute criteria exist for what consti-
renal failure. These are a urinalysis, complete blood tutes “a significant decline” in the GFR, nor does the
count, serum electrolytes, BUN, and Cr. Urine elec- increase of BUN and serum Cr levels always indicate
trolytes will provide more insight into whether she the severity of this decline. Some commonly used
has predominantly a prerenal or intrarenal pathol- objective standards are an increase in serum Cr of 0.5
ogy. Mary’s decreased serum carbon dioxide suggests mg/dL, an increase of 50% over the baseline Cr level,
some acute acidosis. Obtaining an arterial blood gas or a decline in the Cr clearance of at least 25%
would be more definitive in assessing her acid/base (Albright, 2001● B ). In patients for whom no baseline
condition, if it is thought to be appropriate. A renal laboratory values are available, ARF is difficult to

431
 Chapter 54 Nausea, Vomiting, and Lethargy (Acute Renal Failure)

differentiate from chronic renal failure. ARF is most “effective” circulation to the kidneys (e.g., CHF). This
common in the inpatient setting, where the majority depleted state results in a direct decrease of GFR with
of the research on this topic has been performed. It resultant increases in waste products. This condition
has been estimated that in hospitalized patients, the is often referred to as prerenal azotemia. In these situ-
mortality of ARF is 20% to 70%, depending on the ations, reinstituting adequate vascular perfusion will
specific population tested and the criteria for ARF result in an immediate return to normal GFR and
used (Singri et al., 2003● B ). It also has been estimated a gradual return to baseline BUN and Cr. Adequate
that up to 30% of patients with ARF will require vascular perfusion is accomplished by the addition of
some form of long-term dialysis (Albright, 2001● B ). fluids in the case of hypovolemia, but it may require
ARF is rarely diagnosed without the assistance diuresis in the case of volume overload (e.g., CHF).
of laboratory testing of BUN and Cr. This is prima- Lack of flow across the glomerulus also may
rily because the symptoms of ARF are nonspecific. occur when the kidney’s own methods to preserve
An absence or significant reduction of urine output GFR are inhibited. For example, NSAID medications
(less than 400 mL/day) may herald the condition. inhibit the production of prostaglandins, which are
However, approximately half of ARF presentations responsible for maintaining dilation of the afferent
involve normal or even increased urine flow. (incoming) arteriole in the glomerular complex
Patients with ARF will frequently have symptoms of (refer to Fig. 54-1). When this happens, the amount
fatigue, nausea, pruritus, shortness of breath, of pressure producing a flow of filtrate across the
edema, flank pain, confusion, and so forth. The glomerulus is diminished (i.e., decreased GFR).
clinical examination may reveal signs of hypov- Conversely, ACE inhibitors block angiotensin II
olemia or hypervolemia, hypertension or hypoten- (a vasoconstrictor) at the efferent arteriole. This too
sion, mental status changes, a distended bladder, or results in decreased pressure and flow across the
skin changes due to an underlying systemic cause glomerulus (Albright, 2001● B ).
(e.g., vasculitis, lupus, or scleroderma). A routine When the blood flow into the kidneys is reduced
urinalysis may appear normal or may be filled with for a long enough period or to a large enough degree,
sediment. Because of this wide variety of presenting damage to the cells that line the tubules will occur.
signs and symptoms, the condition of ARF becomes These cells have a high metabolic activity rate, which
evident only on review of screening blood work makes them prone to anoxic stress. Damage of the
(Singri et al., 2003 ● B ). tubules due to ischemia, or similar damage due to
Once the condition of ARF is recognized, a nephrotoxins, is referred to as ATN. This intrarenal
determination of its most likely etiology will help to pathology is the most common cause of ARF in the
guide therapy. The causes of ARF are best considered inpatient setting and is a significantly more severe
by the site of pathology in relation to the nephron problem than is prerenal azotemia. In ATN, the dam-
(Fig. 54-1). Prerenal causes of ARF are those affecting aged cells must regenerate before normal function of
the amount or pressure of blood flow across the the kidneys may return. This may take days to weeks
glomerulus. Intrarenal etiologies are those that affect to occur, even if normal perfusion of the kidneys has
the function of the nephron itself (e.g., the small returned. No treatment is available to speed this
blood vessels, glomerulus, tubules, or interstitium). process (Brady et al., 2004● A ).
Postrenal causes are primarily obstruction of the The transition from mildly decreased blood flow
urine flow away from the nephron. The most fre- causing prerenal azotemia to severely limited flow
quent etiologies of ARF based on this classification resulting in ATN represents a continuum. The worse
are presented in Box 54-1. the ischemic insult, the worse the tubular damage,
Although a thorough history and physical are and the longer the recovery. Some tubules may be so
usually adequate to determine the likely cause of ARF, severely damaged that the patient’s kidneys may
some laboratory testing may be useful to help delin- never fully recover function.
eate prerenal versus intrarenal causes (Table 54-1). Damage to other parts of the nephron also will
Some of the most common causes of postrenal result in ARF with intrarenal indices. Malfunction of
obstruction may be diagnosed (and corrected) by the the glomerulus is often caused by inflammation,
placement of a Foley catheter into the bladder. This which appears with abnormal urine sediment or
procedure is an excellent first step in the evaluation signs of a systemic disease. Such urine abnormalities
and treatment of ARF. Most other causes of postrenal may include severe proteinuria (nephrotic category)
obstruction may be assessed by using a renal ultra- or hemoglobinuria (erythrocytes and red cell casts;
sound (Albright, 2001● B ). nephritic category). Systemic diseases that may occur
Prerenal causes of ARF predominate in the out- with glomerulonephritis are lupus, hepatitis, vasculi-
patient setting, accounting for approximately 70% of tis, and pulmonary renal syndromes. If glomeru-
cases (Singri et al., 2003 ● B ). Frequently, such a patient lonephritis is suspected, specialized renal biopsies
has a condition of quantitative loss of intravascular and serologic assays (antinuclear antibody, anti-
volume (e.g., hemorrhage or dehydration) or loss of double stranded [ds] DNA, etc.) will usually identify

432
 Chapter 54 Nausea, Vomiting, and Lethargy (Acute Renal Failure)

Afferent arteriole Efferent arteriole

PRERENAL

Glomerulus

INTRARENAL Tubular cells

Interstitium

POSTRENAL

Figure 54-1 The nephron and locations of pathology in acute renal failure.

the underlying cause. These causes are important in have a high index of suspicion in considering this as a
that they are frequently reversible with immunosup- possibility.
pressive therapy (Albright, 2001● B ). Sometimes the exact etiology of a patient’s ARF
Damage to the interstitium of the nephron result- is not initially apparent. Regardless of the ability to
ing in ARF may be caused by infection (pyelonephri- identify or reverse the etiology of renal pathology,
tis) or inflammation due to an allergic response from the most important therapy to provide for a patient
medications. The hallmark of allergic interstitial with ARF is the maintenance of fluid balance,
nephritis is the presence of eosinophils in the blood or acid/base balance, and serum electrolytes. As has
urine and a rash. Frequently, one or more of these already been discussed, a patient who has hypov-
signs may be absent. Thus the practitioner should olemia should receive intravenous fluids (i.e., normal
433
 Chapter 54 Nausea, Vomiting, and Lethargy (Acute Renal Failure)

Table 54-1 Laboratory Values Box 54-2 Indications for Hemodialysis

Differentiating Prerenal
versus Intrarenal Causes Severe derangements in electrolyte concentra-
of Acute Renal Failure tion (potassium or sodium)
Volume overload unable to be corrected by
Prerenal Intrarenal
diuretics
Serum BUN/ >20 10–20 Severe acid base imbalance
creatinine Florid symptoms of uremia (pericarditis,
ratio encephalopathy, bleeding, nausea)
Urine specific >1.020 ~1.010 Very elevated blood urea nitrogen (approx.
gravity BUN, >100)
Urine osmolality >350 ~300
(mOsm/kg) Bun, blood urea nitrogen.
Urinary Na <10 >20
concentration
(mEq/L)
*
FeNa (%) <1 >1
Hyperkalemia is another common problem in
Urine sediment Hyaline casts Granular patients with ARF. If the level of potassium is very
casts, red high and resulting in significant electrocardio-
cells or casts, graphic changes, the patient should be treated with
white cells or calcium gluconate or calcium chloride to stabilize
casts, cardiac function. Temporary shifts of potassium out
eosinophils, of the serum and into cells can be accomplished with
etc. intravenous insulin, which requires concomitant
*
The “fractional excretion of sodium” (FeNa) is one dextrose administration. Total body potassium may
of the most sensitive tests to differentiate these be reduced with the use of furosemide (Lasix) if suf-
two conditions. ficient urine is being produced. Sodium polystyrene
FeNa = ([urine sodium] × [plasma creatinine])/([urine sulfonate (Kayexalate) can be used to bind potassium
creatinine] × [plasma sodium]) × 100
BUN, blood urea nitrogen.
enterically. This may be given orally or as an enema.
Recent studies have suggested, however, that colonic
necrosis may occur in patients who are severely ill if
saline or lactated Ringer’s solution) to maximize per- they are treated with this medication (Albright,
fusion of the kidneys. Diuretics should be used in 2001● B ). Thus it should be used with some amount of

increasing doses to treat a patient with significant caution. As listed in Box 54-2, uncontrolled hyper-
hypervolemia. Failure of these medications to stabi- kalemia is an indication for dialysis.
lize patients with signs of fluid overload is an indica-
tion for hemodialysis (Box 54-2). In patients who
appear to be euvolemic, the use of diuretics or “renal
dose” dopamine to increase urine production is not Material Available on Student Consult
recommended because neither has been shown to
Review Questions and Answers about Acute Renal
make a difference in clinical outcomes (Brady et al.,
Failure
2004● A).

REFERENCES
Albright RC Jr. Acute renal failure: A practical update. The Kidney, 7th ed. Philadelphia, Saunders, 2004, pp
Mayo Clin Proc 2001;76:67–74.● B 1215–1292.●A
Brady HR, Clarkson MR, Lieberthal W. Acute renal failure. Singri N, Ahya S, Levin ML. Acute renal failure. JAMA
In Brenner BM, Rector FC (eds): Brenner and Rector’s 2003;289:747–751.●B

434
 C h a p t e r

55 Multiple Allergies
(Allergic Rhinitis Asthma)
Greg L. Ledgerwood

asthma and required a nebulizer at least daily until

KEY POINTS around age 11, when she says her breathing problems
“just got better.” As a child, she thinks she tried “every
1. Remember to include the diagnosis of asthma medication under the sun” to treat her asthma. She
in a differential when it presents in an atypical carried a hand-held inhaler from that time on and
fashion, such as a postinfectious cough. continues to do so today. She uses this medicine at
2. Gastroesophageal reflux disease is a frequent least daily, more so since the weather has turned cold.
companion in asthmatics. She was seen by an allergist at age 17 and was skin
3. Classify asthma in the correct severity category. tested. She states that she was positive to “everything,”
4. Use inhaled corticosteroid (ICS) therapy in all particularly molds and dust mites. She received
patients, including women who are pregnant. allergy shots for 21/2 years and thought that they
5. Obta in consultation for any patient with helped her eye and nasal allergies. She stopped
asthma that becomes difficult to control or who immunotherapy when she went to college because it
becomes pregnant. was “too much of a hassle.”
6. Remember that ICSs are the preferred first-line She uses over-the-counter allergy medications
therapy for children of all ages. during the spring and fall but states that certain ones
7. Perform pulmonary-function tests. make her very sleepy. She was given a prescription
8. Review patient medications, albuterol use, and allergy medication in the past, but her insurance
proper metered-dose inhaler use, and re- would not cover it; it was very expensive. She remem-
evaluate the patient’s current asthma-severity bers getting a chest radiograph when she started col-
classification with each visit. lege but does not believe she has ever had a
“breathing” test.
Her first child, a boy, seems to “catch” every infec-
tion in the community, even though she breast-fed
INITIAL VISIT until he was 12 months old; he also wheezes when ill.
Emily is concerned that any future children might have
Subjective the same problem. She worries about this and the fact
that her health seems to be getting worse. Before her
Patient Identification and Presenting Problem first pregnancy, Emily worked as a news producer for
Emily C. is a 26-year-old married woman with the local television station. She now only does volun-
a history of allergic rhinitis and asthma for her teer work at her son’s preschool. She believes that she
“entire” life. She also complains of dry, itchy skin. had fewer problems when she was working. Her
She has one child and is contemplating another husband has had “mild hay fever” since his teenage
pregnancy. Since a sinus infection 3 weeks ago, she years. Tobacco smoke really bothers her, as do some
awakens nightly with shortness of breath and cough- other odors such as certain perfumes and cleaning
ing. Using her inhaler allows her to return to sleep. solutions.
They have recently moved into a newer home.
Present Illness The previous owners had dogs and cats that stayed
Emily has had respiratory problems “as long as [she] indoors during the winter months. Although she
can remember.” She was told by her mother that at believes the home is basically clean, when the forced-
age 2, she was admitted to a hospital because of her air furnace is running, she notices worsening

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

435
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

“allergy” problems and also thinks she uses her unteering at her son’s preschool. She denies any signif-
inhaler more. Neither Emily nor her husband was icant stress in her life, except that she is becoming more
raised with pets in the home, but they have been discouraged about her health. She wonders whether
entertaining the idea of getting a cat for their young she will have to quit exercising because of her asthma.
son. She wonders if this will be a problem.
Emily does not use any medications other than Review of Systems
her albuterol inhaler on a regular basis. She was given Emily has not experienced a change in appetite or
an inhaled steroid before her first pregnancy, but she weight. Energy levels and sleep patterns have become
stopped using this when she became pregnant a problem recently. She denies headaches or visual
because she had heard about steroids and their “bad” changes. She has had problems with “heartburn” since
effects. She occasionally takes aspirin for headaches her teenage years. The rest of her review of systems is
but prefers acetaminophen (Tylenol). She denies any noncontributory except for a problem with dry, itchy
drug allergies, although she will not take penicillin skin on her face, arms, and behind her knees.
because her mother was “allergic” to it, and she
believes she might be as well.
Objective
She thinks she had fewer problems during her
pregnancy. Over the past several months, she has Physical Examination
experienced more allergy and asthma problems. She Emily is a pleasant, well-developed white woman
does not believe that they are well controlled. who is alert, cooperative, and gives a good and very
Contemplating another pregnancy, she is worried complete medical history.
about how her asthma and any medications she
might need will affect it. She also is afraid that her Vital Signs
children will become asthmatic. Blood pressure, 112/60, left arm, sitting
Pulse, 68 and regular
Medical History Respiration rate, 15, with a prolonged expiratory phase
Emily had her tonsils removed at age 6 because of
snoring and difficulty swallowing. Her ear infections, Head, Eyes, Ears, Nose, and Throat Nose shows
which had been frequent, seemed to become less of boggy inferior turbinates with clear rhinorrhea bilat-
a problem after this. She thinks she had a “pneumo- erally. Tympanic membranes show peripheral scarring
nia shot” in the past; however, she thinks it did not without acute changes. Scleral membranes demon-
work because she had pneumonia while she was in strate mild injection.
college. Other than her respiratory problems, she is
in good health. She has used “birth control pills” in Chest Chest wall looks normal, and the chest is cur-
the past. She denies experiencing any drug allergies. rently clear to percussion and auscultation.

Family History Heart Cardiac sounds are normal.

Emily has two brothers, one with “mild” asthma.
Both parents are alive without significant health Abdomen Abdomen is currently unremarkable.
problems except that her mother also has asthma
and, unfortunately, smokes. Emily’s mother does Skin Skin is dry, with mild excoriations at the
require oxygen at bedtime. Her paternal grand- popliteal areas bilaterally.
mother had diabetes before she died.
Laboratory Tests
Health Habits A complete blood count (CBC) shows a white count
Neither she nor her husband smokes. She has an of 6300 with 9% eosinophils and 3% basophils. Nasal
occasional alcoholic beverage, mostly wine with cytology shows only neutrophils. Induced sputum
a meal. She did not consume any alcohol when preg- cytology demonstrates mild to moderate eosinophils.
nant. She stays very active and exercises at least Pulmonary-function tests done without a bron-
3 times per week, either jogging or cycling. She chodilator reveal a decrease of her forced expiratory
always uses her albuterol inhaler before running or volume (FEV1) to 75% of predicted, a normal forced
bicycling. If she forgets, she “runs out of air” very vital capacity (FVC), and a reduced forced expiratory
quickly. She enjoys gardening and sewing. flow (FEF) of 25/75, only 60% of predicted.

Social History
Assessment
Emily has been happily married for the past 5 years.
Before her first pregnancy, she worked with the local Working Diagnosis
television station in news production. After her first 1. Allergic rhinosinusitis. This is supported by his-
child, she became a stay-at-home mom, recently vol- tory and physical findings.

436
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

2. Asthma of moderate severity. This probably has a Objective

significant allergic component.
3. Atopic dermatitis Physical Examination
4. Gastroesophageal reflux disease The data reveal a normal examination. Repeated
spirometry shows her FEV1 to be 94% of predicted,
Differential Diagnosis and her FEF of 25/75 is 90% of predicted. This is
1. Respiratory distress associated with gastro- approximately 3 hours after her prescribed inhaled
esophageal reflux and frequent aspiration steroid/long-acting β-agonist use.
2. “Cardiac” asthma
3. Congenital bronchiectasis Assessment
4. Pulmonary embolism, chronic and recurrent
5. Psychosocial adjustment disorder The patient has become stable.
6. Contact dermatitis
7. Vasomotor rhinitis Plan
1. Discuss the importance of continued regular use
Plan of medication, even with pregnancy.
Therapeutic/Patient Education 2. Review proper use of inhalers.
1. Discuss asthma and allergic rhinitis and factors 3. Update influenza vaccination if indicated.
that cause and influence these diseases. 4. Review peak expiratory flow values, and reinforce
2. Explain severity levels of asthma and how these the importance of instituting the action plan when
determine the appropriate medication use. needed. See physician if action plan is instituted.
3. Prescribe a low-dose inhaled steroid with a long- 5. Suggest follow-up visit to discuss potential med-
acting β-agonist. ication reduction in 4 to 6 months.
4. Continue short-acting β-agonist; ask patient to 6. Continue to track frequency of albuterol use.
track frequency of use. 7. See sooner if conception occurs to discuss therapy
5. Consider using an intranasal steroid for upper and for an obstetrics/gynecology consult.
airway allergic disease.
6. Discuss dust and dander control in the home
and the possibility that animal exposure in the DISCUSSION
home might contribute to increased difficulty
now and in the future. Asthma is a reversible obstructive airway disorder of
7. Review correct use of metered-dose inhalers the tracheobronchial tree characterized by paroxysmal
with a spacer; discuss and demonstrate use of episodes of respiratory distress, often interspersed
a peak flow meter, how to record the personal with periods of apparent well-being (Ledgerwood,
best, and how these values relate to the action 2002● C ). Physiologic changes include smooth muscle
plan that also has been developed. spasm, mucus plugging, edema, inflammation of the
8. Prescribe low-potency steroid ointment for bronchial wall, and potential thickening of the base-
atopic dermatitis. ment membrane or smooth muscle or both, so-called
9. Update influenza vaccination if needed, and sug- remodeling. The history often provides the diagnosis.
gest pneumococcal vaccine booster every 7 to 10 Asthma should be considered in any person with
years. unexplained episodes of dyspnea, cough, recurrent
10. Follow-up visit recommended in 4 to 6 weeks. “colds,” or bronchitis. Specific diagnostic studies are
occasionally helpful. Often a chest radiograph is nor-
mal, except in acute episodes, in which hyperinflation
is seen. Serum immunoglobulin E (IgE) levels and
FIRST FOLLOW-UP VISIT CBCs also can be normal, except in allergic patients, in
whom IgE levels can be elevated and WBC differen-
Subjective
tials show elevated eosinophils and perhaps basophils.
Emily returns after making the medication changes Baseline pulmonary-function tests (PFTs) are man-
recommended. She also spent time cleaning her dated. These can be normal as well, but serve as a
home, paying particular attention to the heating and baseline for future events. Differences between
cooling system and her bedroom and that of her obstructive/restrictive diseases, however, can be deter-
child. After several days, her awakening at night mined. Methacholine challenge should be used only
stopped, and her need for rescue albuterol almost by providers experienced with this procedure.
disappeared. She believes this is the best she has felt In the past several years, much has been learned
in a very long time. She wonders if she will have to about the relation of environment and genetics and
use these medications for the “rest of my life.” how these two elements interact in any given

437
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

asthmatic patient (Taussig et al., 2003● A). Information up/step-down” approach is still recommended, with a
from the National Heart, Lung, and Blood Institute re-evaluation every 1 to 6 months, depending on con-
(NHLBI), under the guidance of the National trol. A parent (especially the mother) who has asthma
Institutes of Health and the National Asthma presents the greatest risk of asthma developing in any
Education and Prevention Program (NAEPP), used offspring. Other issues that may contribute to the
both evidence-based information and scientific data potential future diagnosis of asthma include male
(ranked according to level of scientific validity) to gender, parental smoking, atopic dermatitis, allergic
change previous recommendations pertaining to rhinitis, wheezing apart from colds, sensitization to
therapy for both acute and chronic asthma. These Alternaria sp., obesity in prepubertal girls, and fre-
were published in the autumn of 2002 (NAEPP quent lower respiratory tract infections before age 3
Expert Panel Report, 2002● C ). These principles have (Fig. 55-1). Of the early childhood infections, only
been used to stratify asthma severity in both children respiratory syncytial virus has been associated with the
and adults, based not only on objective data (PFTs) development of asthma. Recent data suggest that rhi-
but also on symptoms: albuterol use, nocturnal awak- novirus sp. might also be involved in both children
enings, and so forth (Tables 55-1 and 55-2). From and adults (Jacoby, 2002● B ).
these recommendations, different therapeutic inter- The NAEPP expert panel states that the use of
ventions have evolved. These are significantly differ- antibiotics during acute flares is not associated with
ent from previous treatment modalities, particularly outcome improvement unless substantial evidence of
in the case of children. Long-term management of bacterial involvement exists. It is therefore recom-
asthma dictates that the correct level of severity be mended that these agents not be used routinely.
recognized: mild intermittent, mild persistent, mod- Action plans continue to be valuable, but primarily in
erate persistent, and severe persistent. Goals of patient education, and the 1997 NHLBI recommenda-
asthma therapy now include minimal or no chronic tions remain unchanged (Gibson and Powell, 2004● A).
symptoms day or night; minimal or no exacerbations; Adult asthma therapy parallels that of children
no limitations on activities (no school/work missed); (see Table 55-2). The only really significant difference is
minimal use of short-acting β-agonists (fewer than being able to obtain more objective information,
once per day, fewer than one canister per month); specifically PFTs. It is recommended that PFTs be done
minimal or no adverse effects from medications with an initial evaluation and at any time medication
(Table 55-3) (NAEPP Expert Panel Report, 2002● C ). changes occur or control is of concern (both before
The Tucson Children’s Respiratory Study and after use of small-volume nebulization of
(Taussig et al., 2003● A ) has helped define not only albuterol). It is impractical to do PFTs on children,
those children at risk for asthma but also those who with perhaps the exception of peak flow readings. Even
potentially are subject to permanent decline in lung then, children younger than 5 present a challenge. It is
function without proper intervention (see Table 55-1). important to observe the correct use of metered-dose
Inhaled corticosteroid (ICS) therapy has been shown inhalers, whether they are aerosol driven or the dry-
to be the only medication to prevent relapse and powder type. Use of spacer devices is recommended on
improve quality of life (NAEEP Expert Panel Report, all propellant units. In several years, chlorofluorocar-
2002● C ). With data showing no adverse effects on the bon propellant devices will be unavailable.
hypothalamic-pituitary-adrenal axis, growth, bone The NAEPP database has been developed in
mineral density, or subcapsular cataracts, ICSs are such a way that updated recommendations will be
now considered the first line of therapy in the treat- made by using computer data banking. These excel-
ment of asthma for children younger than 5 years lent scientific databases will allow a more rapid
(Childhood Asthma Management Program Research response to evolving studies dealing with asthma.
Group, 2000 ● A ; NAEPP Expert Panel Report, 2002● C ). Issues that must be addressed concerning control
Inhaled sodium cromolyn also can be used but is not include the following.
the preferred drug. Leukotriene inhibitors also are
indicated in the treatment of asthma, but data sup- 1. How does β2-receptor genetics influence therapy?
porting these as first-line therapy are not as plentiful. 2. What objective laboratory information can be
Because low-dose ICS therapy is still preferred in all used in a practical fashion? (Nitrous oxide–exha-
patients, especially children, the issue of how to deal lation concentration measurement is expensive.)
with the loss of asthma control also has been updated. 3. Will sputum eosinophils and CD8 lymphocytes
Excellent evidenced-based data demonstrate that identification be anything but a research tool
adding a long-acting β-agonist to low-dose ICS ther- (both cell types are associated with control when
apy allows control to be achieved without increasing decreased or absent) (Childhood Asthma Man-
the risk of side effects sometimes seen in high-dose agement Program Research Group, 2000● A )?
ICS therapy (Nelson et al., 2000● A ). With the newer 4. What is the role of viral infections as they pertain
ICS products, the difference between high- and low- to initiation/exacerbation of asthma (Nelson et al.,
dose ICSs should be reviewed (Table 55-4). The “step- 2000● A )?

Text continued on page 444

438
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

Table 55-1 Stepwise Approach for Managing Infants and Young Children
(5 Years of Age and Younger) with Acute or Chronic Asthma
Classify Severity: Clinical Features before Medications Required to Maintain
Treatment or Adequate Control Long-Term Control

Symptoms/Day
Symptoms/Night Daily Medications

Step 4: Severe Continual ■ Preferred treatments:

persistent Frequent – High-dose inhaled corticosteroids
and
– Long-acting inhaled beta2-agonists
and, if needed,
– Corticosteroid tablets or syrup long term (2 mg/kg/day,
generally do not exceed 60 mg per day). (Make
repeat attempts to reduce systemic corticosteroids
and maintain control with high-dose inhaled
corticosteroids.)
Step 3: Moderate Daily ■ Preferred treatments:
persistent >1 night/week – Low-dose inhaled corticosteroids and long-acting
inhaled beta2-agonists
or
– Medium-dose inhaled corticosteroids
■
Alternative treatment:
– Low-dose inhaled corticosteroids and either
leukotriene receptor antagonist or theophylline
If needed (particularly in patients with recurring severe
exacerbations):
■ Preferred treatment:

– Medium-dose inhaled corticosteroids and long-

acting beta2-agonists
■ Alternative treatment:

– Medium-dose inhaled corticosteroids and either

leukotriene receptor antagonist or theophylline
Step 2: Mild > 2/week but < 1 x/day ■ Preferred treatment:
persistent > 2 nights/month – Low-dose inhaled corticosteroid (with
nebulizer or MDI with holding chamber with or
without face mask or DPI)
■
Alternative treatment (listed alphabetically):
– Cromolyn (nebulizer is preferred or MDI with
holding chamber) or leukotriene receptor
antagonist
Step 1: Mild ≤ 2 days/week ■ No daily medication needed.
intermittent ≤ 2 nights/month

Quick Relief: ■ Bronchodilator as needed for symptoms. Intensity of treatment will depend upon
All patients severity of exacerbation.
– Preferred treatment: Short-acting inhaled beta2-agonists by nebulizer or face
mask and space/holding chamber
– Alternative treatment: Oral beta2-agonist
■ With viral respiratory infection
– Bronchodilator q 4–6 hours up to 24 hours (longer with physician consult); in
general, repeat no more than once every 6 weeks
– Consider systemic corticosteroid if exacerbation is severe or patient has history
of previous severe exacerbations
■
Use of short-acting beta2-agonists >2 times a week in intermittent asthma (daily,
or increasing use in persistent asthma) may indicate the need to initiate (increase)
long-term control therapy

Continued

439
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

Table 55-1 Stepwise Approach for Managing Infants and Young Children (5 Years of Age
and Younger) with Acute or Chronic Asthma (Continued)
Step down
Review treatment every 1 to 6 months; a gradual stepwise reduction in treatment may be
possible.
Step up
If control is not maintained, consider step up. First, review patient medication technique,
adherence, and environmental control.

Goals of Therapy: Asthma Control

■ Minimal or no chronic symptoms day or night
■ Minimal or no exacerbations

■ No limitations on activities; no school/parent’s work missed

■ Minimal use of short-acting inhaled beta -agonist (< 1x per day, <1 canister/month)
2
■ Minimal or no adverse effects from medications

Notes
The stepwise approach is intended to assist, not replace, the clinical decisionmaking required to meet individual
patient needs.
Classify severity: assign patient to most severe step in which any feature occurs.
There are very few studies on asthma therapy for infants.
Gain control as quickly as possible (a course of short systemic corticosteroids may be required); then step down
to the least medication necessary to maintain control.
Provide parent education on asthma management and controlling environmental factors that make asthma
worse (e.g., allergies and irritants).
Consultation with an asthma specialist is recommended for patients with moderate or severe persistent asthma.
Consider consultation for patients with mild persistent asthma.
DPI, dry powder inhaler; MDI, metered-dose inhaler.
Adapted from National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the
Diagnosis and Management of Asthma: Update on Selected Topics. Bethesda, MD, National Institutes of
Health. NIH Publication No. 02-5075, 2002.

Table 55-2 Stepwise Approach for Managing Asthma in Adults and Children Older Than
5 Years of Age: Treatment
Classify Severity: Clinical Features before Medications Required to Maintain
Treatment or Adequate Control Long-Term Control

Symptoms/Day PEF or FEV1

Symptoms/Night PEF Variability Daily Medications

Step 4: Severe Continual ≤ 60% ■

Preferred treatment:
persistent Frequent > 30% – High-dose inhaled corticosteroids
and
– Long-acting inhaled beta2-agonists
and, if needed,
– Corticosteroid tablets or syrup long
term (2 mg/kg/day, generally do not
exceed 60 mg per day). (Make repeat
attempts to reduce systemic
corticosteroids and maintain control
with high-dose inhaled corticosteroids.)
Step 3: Daily > 60% − < 80% ■ Preferred treatment:
Moderate >1 night/week > 30% – Low-to-medium dose inhaled
corticosteroids and long-acting
inhaled beta2-agonists
Persistent ■ Alternative treatment (listed
alphabetically):
– Increase inhaled corticosteroids
within medium-dose range
or
– Low-to-medium dose inhaled
corticosteroids and either leukotriene
modifier or theophylline

440
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

Table 55-2 Stepwise Approach for Managing Asthma in Adults and Children Older Than
5 Years of Age: Treatment (Continued)
If needed (particularly in patients with
recurring severe exacerbations):
■ Preferred treatment:

– Increase inhaled corticosteroids within

medium-dose range and add long-
acting inhaled beta2-agonists
■ Alternative treatment:

– Increase inhaled corticosteroids within

medium-dose range and add either
leukotriene modifier or theophylline
Step 2: Mild >2/week but < 1x/day ≥ 80% ■ Preferred treatment:

persistent > 2 nights/month 20%–30% – Low-dose inhaled corticosteroids

■ Alternative treatment (listed

alphabetically): cromolyn, leukotriene

modifier, nedocromil, or sustained
release theophylline to serum
concentration of 5–15 mcg/mL
Step 1: Mild ≤ 2 days/week ≥ 80% ■ No daily medication needed

intermittent ≤ 2 nights/month < 20% ■

Severe exacerbations may occur,
separated by long periods of normal
lung function and no symptoms.
A course of systemic corticosteroids is
recommended.

Quick Relief: ■
Short-acting bronchodilator: 2–4 puffs short-acting inhaled beta2-agonists as needed for
All patients symptoms.
■ Intensity of treatment will depend on severity of exacerbation; up to 3 treatments at

20-minute intervals or a single nebulizer treatment as needed. Course of systemic

corticosteroids may be needed.
■ Use of short-acting beta -agonists >2 times a week in intermittent asthma (daily, or
2
increasing use in persistent asthma) may indicate the need to initiate (increase) long-
term control therapy.
Step down
Review treatment every 1 to 6 months; a gradual stepwise reduction in treatment may be
possible.

Step up
If control is not maintained, consider step up. First, review patient medication technique,
adherence, and environmental control.

Goals of Therapy: Asthma Control

■ Minimal or no chronic symptoms day or night

■ Minimal or no exacerbations

■
No limitations on activities; no school/work missed
■ Maintain (near) normal pulmonary function

■ Minimal use of short-acting inhaled beta -agonist (< 1x per day, < 1 canister/month)
2
■
Minimal or no adverse effects from medications

Notes
The stepwise approach is meant to assist, not replace, the clinical decisionmaking required to meet individual
patient needs.
Classify severity: assign patient to most severe step in which any feature occurs (PEF is % of personal best; FEV1 is
% predicted).
Gain control as quickly as possible (consider a short course of systemic corticosteroids); then step down to the
least medication necessary to maintain control.
Provide education on self-management and controlling environmental factors that make asthma worse (e.g.,
allergens and irritants).
Refer to an asthma specialist if there are difficulties controlling asthma or if step 4 care is required. Referral may
be considered if step 3 care is required.
FEV1, forced expiratory volume; PEF, peak expiratory flow.
Adapted from National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the
Diagnosis and Management of Asthma: Update on Selected Topics. Bethesda, MD, National Institutes of
Health. NIH Publication No. 02-5075, 2002.

441
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

Table 55-3 Usual Dosages for Long-Term-Control Medications

Medication Dosage Form Adult Dose Child Dose

Inhaled Corticosteroids (See Table 55-4)

Systemic Corticosteroids (Applies to all three corticosteroids)
Methylprednisolone 2, 4, 8, 16, 32 mg ■ 7.5–60 mg daily in a ■ 0.25–2 mg/kg daily in

tablets single dose in AM or single dose in AM or

qod as needed for qod as needed for
control control
Prednisolone 5 mg tablets, ■
Short-course “burst” ■
Short-course “burst”:
5 mg/5 cc, to achieve control: 1–2 mg/kg/day,
15 mg/5 cc 40–60 mg per day as maximum 60 mg/day
single or two divided for 3–10 days
doses for 3–10 days
Prednisone 1, 2.5, 5, 10, 20, 50 mg
tablets; 5 mg/cc,
5 mg/5 cc
Long-Acting Inhaled Beta2-Agonists (Should not be used for symptom relief or for exacerbations. Use
with inhaled corticosteroids.)
Salmeterol MDI 21 mcg/puff 2 puffs q 12 hours 1–2 puffs q 12 hours
DPI 50 mcg/blister 1 blister q 12 hours 1 blister q 12 hours
Formoterol DPI 12 mcg/single-use 1 capsule q 12 hours 1 capsule q 12 hours
capsule
Combined Medication
Fluticasone/ DPI 100, 250, or 1 inhalation bid; dose 1 inhalation bid; dose
Salmeterol 500 mcg/50 mcg depends on severity of depends on severity of
asthma asthma
Cromolyn and Nedocromil
Cromolyn MDI 1 mg/puff 2–4 puffs tid–qid 1–2 puffs tid–qid
Nebulizer 20 mg/ampule 1 ampule tid–qid 1 ampule tid–qid
Nedocromil MDI 1.75 mg/puff 2–4 puffs bid–qid 1–2 puffs bid–qid
Leukotriene Modifiers
Montelukast 4 or 5 mg chewable 10 mg qhs 4 mg qhs (2–5 yrs)
tablet, 10 mg tablet 5 mg qhs (6–14 yrs)
10 mg qhs (> 14 yrs)
Zafirlukast 10 or 20 mg tablet 40 mg daily (20 mg 20 mg daily (7–11 yrs)
tablet bid) (10 mg tablet bid)
Zileuton 300 or 600 mg tablet 2,400 mg daily (give
tablets qid)
Methylxanthines (Serum monitoring is important [serum concentration of 5–15 mcg/mL at steady state]).
Theophylline Liquids, sustained-release Starting dose 10 mg/kg/ Starting dose 10 mg/kg/
tablets, and capsules day up to 300 mg max; day; usual max:
usual max 800 mg/day ■ <1 year of age: 0.2
(age in weeks) + 5
= mg/kg/day
■
≥1 year of age: 16
mg/kg/day

DPI, dry powder inhaler; MDI, metered-dose inhaler.

Adapted from National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the
Diagnosis and Management of Asthma: Update on Selected Topics. Bethesda, MD, National Institutes of
Health. NIH Publication No. 02-5075, 2002.

442
 Table 55-4 Estimated Comparative Daily Dosages for Inhaled Corticosteroids
Low Daily Dose Medium Daily Dose High Daily Dose
* *
Drug Adult Child Adult Child Adult Child*

Beclomethasone CFC: 42 or 168–504 mcg 84–336 mcg 504–840 mcg 336–672 mcg >840 mcg >672 mcg
84 mcg/puff
Beclomethasone HFA: 40 or 80–240 mcg 80–160 mcg 240–480 mcg 160–320 mcg >480 mcg >320 mcg
80 mcg/puff
Budesonide DPI: 200 mcg/ 200–600 mcg 200–400 mcg 600–1,200 mcg 400–800 mcg >1,200 mcg >800 mcg
inhalation
Inhalation suspension for 0.5 mg 1.0 mg 2.0 mg
nebulization (child dose)
Flunisolide: 250 mcg/puff 500–1,000 mcg 500–750 mcg 1,000–2,000 mcg 1,000–1,250 mcg >2,000 mcg >1,250 mcg
Fluticasone 88–264 mcg 88–176 mcg 264–660 mcg 176–440 mcg >660 mcg >440 mcg
MDI: 44, 110, or 220 mcg/puff
DPI: 50, 100, or 250 mcg/inhalation 100–300 mcg 100–200 mcg 300–600 mcg 200–400 mcg >600 mcg >400 mcg
Triamcinolone acetonide: 100 mcg/ 400–1,000 mcg 400–800 mcg 1,000–2,000 mcg 800–1,200 mcg >2,000 mcg >1,200 mcg
puff
*
Children ≤12 years of age
CFC, chlorofluorocarbons; DPI, dry powder inhaler; HFA, hydrofluoroalkane.
Adapted from National Asthma Education and Prevention Program Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma: Update on
Selected Topics. Bethesda, MD, National Institutes of Health. NIH Publication No. 02-5075, 2002.

443
 Chapter 55 Multiple Allergies (Allergic Rhinitis Asthma)

5. Can immunoregulation be manipulated to

Transient Non-atopic Asthma
wheezers wheezers change the lymphocytic immune response from a
Wheezing prevalence

TH2 (allergic) to a TH1 (nonallergic) response?

The advances in detecting and treating asthma
in the past several years are dramatic. Omalizumab, a
murine-derived anti-IgE antibody, has shown excel-
lent promise in treating the most severe forms of
allergic asthma (Spector, 2004● A ). The goals of the
NAEPP expert panel seem likely to be achieved with
aggressive applications of knowledge already
0 3 6 11 obtained. We hope that future discoveries relating to
Age in years
genetics and environment will lead to complete
Figure 55-1 Hypothetical peak prevalence by age for understanding of factors that currently are obstacles
the three different wheezing phenotypes. The preva- to asthma control.
lence for each age interval should be the area under the
curve. This does not imply that the groups are exclusive.
(Modified from Figure 2 in Stein RT, Holberg CJ, Morgan Material Available on Student Consult
WJ, et al. Peak flow variability, methacholine respon-
siveness and atopy as markers for detecting different Review Questions and Answers about Allergic
wheezing phenotypes in childhood. Thorax 1997;52: Rhinitis Asthma
946–952.)

REFERENCES
Childhood Asthma Management Program Research Group. Nelson HS, Busse WW, Kerwin E, et al. Fluticasone propi-
Long-term effects of budesonide or nedocromil in chil- onate/salmeterol combination provides more effective
dren with asthma. N Engl J Med 2000;343:1054–1063.● A asthma control than low-dose inhaled corticosteroid
Gibson PG, Powell H. Written action plans for asthma: An plus montelukast. J Allergy Clin Immunol 2000;
evidence-based review of the components. Thorax 106:1088–1095.● A
2004;59:87–88.●A Spector S. Omalizumab: Efficacy in allergic disease.
Jacoby DB. Virus-induced asthma attacks. JAMA 2002;287: Panminerva Med 2004;46:141–148.● A
755–761.●B Stein RT, Holberg CJ, Morgan WJ, et al. Peak flow variabil-
Ledgerwood GL. Allergy. In Rakel RE (ed): Textbook of ity, methacholine responsiveness and atopy as markers
Family Practice, 6th ed. Philadelphia, WB Saunders, for detecting different wheezing phenotypes in child-
2002, pp 473–493.●C hood. Thorax 1997;52:946–952.
NAEPP Expert Panel Report. Guidelines for the Diagnosis Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan
and Management of Asthma: Update on Selected WJ, Martinez FD. Tucson Children’s Respiratory Study:
Topics. Bethesda, MD, National Institutes of Health. 1980 to present. J Allergy Clin Immunol 2003;
NIH Publication No. 02-5075, 2002.● C 111:661–676.● A

444
 C h a p t e r

56 Widespread Pruritic Rash

(Adverse Drug Reaction)
Rahul Gupta

KEY POINTS

1. Types of Adverse Drug Reaction (ADR) c. Anaphylactoid reactions after contrast

A. Type A: Nonimmunologic (75% to 80%)— media
Predictable 2. Diagnostic Tests for ADRs
i. Side effects A. Comprehensive history and physical exami-
ii. Toxicity nation
iii. Drug-drug interactions B. Discontinuation of drug and reassessment
iv. Overdoses C. Complete blood count, chemistry
B. Type B: Immunologic or nonimmunologic D. Drug levels (if indicated)
(20% to 25%)—Unpredictable E. Drug-specific skin tests (if indicated)
i. Immune mediated 3. Treatment of ADRs
a. Type I to IV hypersensitivity reaction A. Discontinue the offending drug
b. Morbilliform rash B. Administer epinephrine for anaphylaxis
c. Stevens-Johnson syndrome (SJS), toxic C. Administer antihistamines and/or corticos-
epidermal necrolysis (TEN) teroids, supportive care
d. Drug-induced lupus D. Treat SJS/TEN as burn injury
e. Anticonvulsant hypersensitivity syn- E. Note that corticosteroids are controversial in
drome SJS, contraindicated in TEN
ii. Nonimmune mediated F. Avoid using chemically similar compounds
a. Idiosyncratic reactions: Hemolytic ane- G. Desensitization if the drug must be used
mia in patients with glucose- again (only for type 1 reaction)
6-phosphate dehydrogenase H. Provide patient education
deficiency treated with primaquine I. Keep risk factors for ADR in mind
b. Drug intolerance

INITIAL VISIT both arms. Furthermore, Kathy states that the rash
now involves her whole body, including her palms and
Subjective the soles of her feet. Her scalp is pruritic as well.
Patient Identification and Presenting Problem
Kathy W. is a 47-year-old white woman and home- Medical History
maker who complains of a skin lesion. Kathy was doing Kathy has had hypertension for the past 20 years. She
well until 4 weeks ago, when she noticed a rash over her was diagnosed with elevated cholesterol and
chest and face. The rash began as being diffusely red, osteoarthritis 4 years ago. Recently her physician
raised, and pruritic. She applied hydrocortisone cream notified her that she has developed stage I chronic
to the lesion for several days. Instead of resolving, the kidney disease from long-standing hypertension.
rash spread to her trunk, back, and face and across About 4 weeks ago her physician discontinued

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

445
 Chapter 56 Widespread Pruritic Rash (Adverse Drug Reaction)

celecoxib (Celebrex) and started her on sulindac

(Clinoril). She observed that the rash and pruritus
started at that time, but she has not discontinued any
of her medications.

Family History
Kathy’s father was an electrician and died from his
first heart attack at age 51. Her mother is 70 years old
and has coronary artery disease, osteoarthritis, and
hypertension.

Social History
The patient does not smoke or drink alcohol. She
denies any illicit drug use. She has been happily mar-
ried for the past 20 years. Kathy and her husband
both walk 2 miles each day and follow a heart-
healthy diet. She does not remember any such skin
problem in the past. She enjoys outdoor activities
such as gardening and fishing.

Medications
Kathy takes metoprolol (Lopressor), aspirin, and
sulindac (Clinoril). She also uses acetaminophen
(Tylenol) occasionally.

Review of Systems
Kathy can recall no recent changes in the use of skin
or hair products. She has not changed her detergent.
Because of the rash she has stopped wearing jewelry
and wears only cotton clothing. She reports no
changes in weight or sleep patterns. She denies any
fever, shortness of breath, cough, palpitations, chest
pain, or anxiety.

Objective
Physical Examination
General Kathy is a healthy-appearing, well-devel-
oped white woman. She is observed to be somewhat
uncomfortable due to intense pruritus. She is nicely
dressed and has tanned skin. She is wearing no
makeup.

Vital Signs Kathy is afebrile. Vital signs are within

normal limits.

Skin Her skin displays facial erythema with mac- Figure 56-1 Symmetrical, intensely pruritic papules
ules and papules along with some exfoliation. throughout the trunk with confluent erythema in sev-
There are no erosions of the mucous membranes. eral craps (A and B). Some weeping is also noted.
C, Similar lesions cover the upper back.
Symmetrically arranged, intensely pruritic papules
with confluent erythema are noted diffusely
throughout the trunk, back, and on all four
extremities. There are several crops, ranging from
fresh lesions to old healing ones (Fig. 56-1). Chest Breath sounds are normal. Both heart sounds
Purulent discharge and weeping are also observed are normal, without murmurs or clicks.
from some lesions on the lower extremities.
Minimal bilateral axillary lymphadenopathy is also Abdomen Scaphoid and soft without tenderness.
noted. Bowel sounds are normal.

446
 Chapter 56 Widespread Pruritic Rash (Adverse Drug Reaction)

Laboratory Tests with silvery scales. Commonly affected areas

None were done at this visit. The patient had her include elbows, knees, scalp, and hands. Patients
cholesterol level and chemistry profile done a week often complain of pruritus. Several variants of
before her visit. Her cholesterol level was 225 mg/dL. classic psoriasis are described including guttate,
Her aspartate transaminase and alanine transami- pustular, and erythrodermic types. Joint and nail
nase levels were twice the normal range. involvement, such as pitting of nails, can be seen in
25% to 50% of patients with psoriasis. Although
the cause of psoriasis remains unknown, some
Assessment
drugs such as lithium, β-blockers, and NSAIDs
Differential Diagnosis have been known to induce or aggravate the con-
The cause of this generalized pruritic, erythema- dition. Psoriasis may develop in an area of previ-
tous and papular-type rash with what seems to be a ous trauma, a process known as the Koebner
secondary bacterial infection can be established by phenomenon. Treatment of psoriasis involves top-
Kathy’s history. She notes that it all really began ical therapies such as corticosteroids, calcipotriene
when she started taking sulindac approximately 4 (vitamin D3 analog), anthralin, tazarotene
weeks ago. Such a pattern is consistent with drug (retinoid), coal tar preparations, and keratolytics.
eruption associated with nonsteroidal anti-inflam- Natural sunlight, phototherapy, and systemic
matory drugs (NSAIDs), which has progressed treatments such as sulfasalazine, methotrexate,
because the patient did not discontinue the offend- cyclosporine, and oral retinoids have been demon-
ing agent. The patient’s condition could be con- strated efficacious. The application of biologic
fused with atopic dermatitis, psoriasis, and contact therapies currently in use for other diseases such
dermatitis. as rheumatoid arthritis and Crohn’s disease is
currently being evaluated.
1. Drug eruption with secondary bacterial infection. 4. Contact dermatitis. This is an inflammatory
NSAIDs such as sulindac may cause cutaneous response of the skin to an allergen or irritant. It
drug eruption, which may be associated with or accounts for 4% to 7% of dermatology referrals. In
followed by secondary bacterial infection. One the United States, 90% of worker’s compensation
percent to 5% of people using NSAIDs may claims in dermatology are for contact dermatitis.
develop a drug eruption. The common serious Allergic contact dermatitis results from direct skin
and distinctive drug reaction patterns of the skin contact with a substance that the body recognizes
are described in the Discussion section. as foreign. This is a delayed type of hypersensitivity
2. Atopic dermatitis. This is a chronic inflammatory reaction in contrast to irritant contact dermatitis,
dermatosis that is considered familial, and which is a nonimmunologic-type reaction result-
patients commonly exhibit additional symptoms ing from direct insult to the tissues. As an example,
of atopic disorders such as allergic rhinitis or poison ivy exposure leads to allergic contact der-
asthma. Altogether the atopic disorders affect 8% matitis. Both types of contact dermatitis are local-
to 25% of the total population worldwide. ized to the area of contact with the offending agent.
Therefore, the diagnosis is based on a personal Treatment requires avoidance of the inciting agent.
and family history of atopy, pruritus, and physical Symptomatic treatments range from topical corti-
eczema. This disorder commences at age 5 to 7 costeroids, calamine lotion, and cold compresses to
years. Examination reveals recurrent excoriated, systemic corticosteroids, depending on the severity
scaling papules and plaques with erythema, and of the reaction and the site on the body.
intense pruritus located commonly at flexural
areas such as the antecubital and popliteal fossa.
Secondary bacterial infection can occur. The
Plan
approach to treatment includes skin hydration,
topical corticosteroids, and the elimination of Diagnostic
precipitating irritants. Current evidence suggests No testing is required at this time.
that immunomodulators that work by blocking
T-cell activation such as tacrolimus 0.1% oint- Therapeutic
ment or pimecrolimus 1% cream when applied 1. Discontinue the offending agent (sulindac).
twice daily may be advantageous compared to 2. Start hydroxyzine HCl (Atarax) 25 mg four times
corticosteroids because they do not induce sys- daily by mouth. Hydroxyzine antagonizes H1
temic immunosuppression or cutaneous atrophy. receptors in the periphery and reduces the hista-
3. Psoriasis. This condition affects 1% to 2% of the mine activity.
U.S. population. It is a chronic inflammatory dis- 3. Start topical corticosteroids such as triamci-
order characterized by symmetric, erythematous, nolone acetonide (Aristocort), which decrease
sharply demarcated papules and rounded plaques inflammation by suppressing migration of poly-

447
 Chapter 56 Widespread Pruritic Rash (Adverse Drug Reaction)

morphonuclear leukocytes and reversing capillary Plan

permeability.
4. Administer cephalexin (Keflex) 500 mg twice The patient is started on atorvastatin 10 mg daily.
daily for 1 week. She is advised to follow up in 3 months for repeat
5. Provide patient education and prevention. Have liver function tests.
patient avoid NSAIDs. Provide a list to the patient
and advise him or her to use hypoallergenic soap
and detergents. DISCUSSION

FOLLOW-UP VISIT About 10% to 20% of hospitalized patients and 2%

to 5% of outpatients develop adverse effects while
taking medications. Epidemiologic studies indicate
Subjective that a small group of frequently used drugs accounts
Kathy returned 1 month later and was ecstatic about for the majority of ADRs, and therefore familiarity
the improvement in her rash and pruritus. She has not with some of these drugs as well as the type of
used any NSAIDs but continues her other medica- adverse reactions is imperative in clinical practice
tions. She states that because the diet and exercise trial (Table 56-1 and Box 56-1).
recommended previously has not helped with her
cholesterol levels, she would like to initiate therapy. Definition and Classification
Also, a repeat chemistry done 2 days ago, including
liver function tests, is normal. The term adverse drug reaction incorporates all the
adverse events related to drug administration. The
World Health Organization defines an ADR as any
Objective
noxious, unintended, and undesired effect of a drug
Kathy’s skin examination reveals mostly healing and that occurs at doses used for prevention, diagnosis,
dry skin lesions. There is minimal scaling and ery- or treatment. Drug hypersensitivity is defined as an
thema. No significant desquamation is noted. The immune-mediated response to a drug formulation in
rest of the examination is normal. a sensitized patient. Drug allergy is a response medi-

Table 56-1 Adverse Drug Reactions to Commonly Used Drugs

Drug Adverse Reaction or Effect

β-Lactam antibiotics Hypersensitivity reactions such as urticaria, anaphylaxis,

serum sickness, neutropenia, interstitial nephritis,
pseudomembranous colitis
Sulfonamides Skin rash including exfoliation, nausea, diarrhea,
neutropenia, thrombocytopenia, and renal failure
Nonsteroidal anti-inflammatory drugs Skin rash, nausea, diarrhea, epigastric discomfort,
gastritis, hepatitis, headache, neutropenia, and
thrombocytopenia
Aspirin Urticaria, angioedema, nausea, gastritis, tinnitus,
prolonged bleeding time, and dizziness
Acetaminophen Hepatic necrosis and neutropenia
Warfarin Fatal or nonfatal hemorrhage from any tissue or organ,
skin necrosis, nausea, and hepatitis
Digoxin Anorexia, nausea, vomiting, diarrhea, visual
disturbance, cardiac arrhythmias, headache, and
dizziness
Loop diuretics Hypovolemia, hypokalemia, hyperuricemia,
hyponatremia, hyperglycemia, and ototoxicity
Prednisone Fluid retention, hypertension, proximal muscle
weakness, peptic ulcer, pancreatitis, osteoporosis,
skin atrophy, adrenal suppression, hyperglycemia,
hyperlipidemia, psychosis, cataracts, glaucoma, and
hirsutism
β-Blockers Fatigue, bradycardia, bronchospasm, depression, and
impotence

448
 Chapter 56 Widespread Pruritic Rash (Adverse Drug Reaction)

mechanism alone. Examples include fixed drug

Box 56-1 Drugs That Rarely Cause eruption, maculopapular rash, erythema multi-
Rashes forme, exfoliative dermatitis, vasculitis, and specific
drug hypersensitivity syndromes.
Acetaminophen Although it is not possible to determine which
Antihistamines: diphenhydramine individual will develop a drug reaction, some risk fac-
Atropine tors have been identified that appear to contribute to
Benzodiazepines such reactions (Box 56-2). These risk factors have
Digoxin been divided into those related to the patient and
Insulin those related to the drug. Patient-related factors that
Prednisone may increase the likelihood of a drug hypersensitivity
Propanolol reaction include older age, family history of drug
Theophylline allergy, personal history of drug reaction to a chemi-
Thyroid hormones cally related compound, concurrent illness, female
Spironolactone gender, slow acetylator type, and history of atopy.
Although atopy has no effect on induction of a drug-
specific IgE response, it is associated with increased
risk of serious reactions once an IgE response has
ated by drug-specific immunoglobulin E (IgE) been generated. A large molecular weight and multi-
antibodies. valency are the most important drug-related factors
ADRs are broadly divided into two categories. to influence the development of a drug hypersensitiv-
Type A reactions are common, nonimmunologic, ity reaction. Smaller molecular weight compounds
and predictable and may include toxicity, overdoses, may also become immunogenic by their ability to
side effects, and drug interactions. Approximately covalently link to carrier proteins such as albumin.
75% to 80% of ADRs fall into this category. Type B
reactions account for the remaining 20% to 25% of
Diagnosis
ADRs. These are unpredictable, often are not mani-
fest until after a drug is marketed, and may be Most allergic reactions have dermatologic manifesta-
immune mediated. Examples in this category include tions with or without other immunologic features.
drug intolerance, idiosyncratic reactions, and allergic Maculopapular or morbilliform eruption is the most
or hypersensitivity (immunologic) reactions. Immune- common dermatologic drug-induced reaction.
mediated reactions account for 5% to 10% of all The actual pathogenesis is unclear, although a
drug reactions and constitute true drug hypersensi- T cell–mediated process is likely, as there is a 2-day to
tivity, including IgE-mediated drug allergies. 2-week delay in onset. The erythematous, maculo-
The Gell and Coombs classification system sep- papular rash commences over the trunk and soon
arates drug hypersensitivity reactions into four types spreads to the extremities. It is usually symmetrical,
depending on the mechanism, time of onset, and confluent, and spares the palms and soles. Urticaria
clinical manifestations (Table 56-2). However, some is usually an IgE-mediated (type I) reaction, occur-
allergic reactions may not be associated with a single ring minutes to hours after drug exposure and may

Table 56-2 Gell and Coombs Classification of Drug Hypersensitivity Reactions

Reaction Type Mechanism Clinical Characteristics Time of Onset

Type I Drug–IgE complex Urticaria, angioedema, Minutes to hours after

mediated bronchospasm, hypotension, drug exposure
nausea, vomiting, diarrhea
Type II Direct cytotoxic: Hemolytic anemia, neutropenia, Variable
drug-specific IgG or thrombocytopenia
IgM antibodies
mediated
Type III Drug–antibody immune Serum sickness, fever, rash, 1–3 wk after drug
complex deposition arthralgias, urticaria, vasculitis, exposure
on tissues lymphadenopathy
Type IV Delayed, T-cell mediated Allergic contact dermatitis 24–72 hr after topical
drug exposure

Ig, immunoglobulin.

449
 Chapter 56 Widespread Pruritic Rash (Adverse Drug Reaction)

and atypical lymphocytes. The rash may change to

Box 56-2 Risk Factors for Development an exfoliative type. Varying organ system involve-
of Drug Reactions ment may include liver, kidney, intestinal tract,
lungs, and bone marrow.
Patient-Related Factors No further diagnostic workup is usually
Older age required for an ADR because the condition is prima-
Female rily a clinical diagnosis. A skin or patch test is a use-
Personal history of atopy ful diagnostic procedure to confirm suspected type I
Personal or family history of previous drug hypersensitivity reaction. A positive test in the pres-
allergy ence of antigen-specific IgE is supportive of the diag-
Use of β-blockers nosis. A skin biopsy may help establish a diagnosis by
Concurrent illness (liver disease, renal disease, showing both superficial and deep perivascular
human immunodeficiency virus, Epstein-Barr inflammatory cell infiltrates. Eosinophils may be
infection, cytomegalovirus infection, systemic present as well. Laboratory evaluation may reveal
lupus erythematosus eosinophilia, atypical lymphocytes, neutropenia,
Slow acetylator phenotype nephritis, vasculitis, hemolytic anemia, and hepatitis.

Drug-Related Factors Management

Large molecular weight and multivalent com- The first step in management is obtaining a good his-
pound tory because this will usually suggest the culprit
Topical, intravenous, or intramuscular route drug. A physical examination should be able to fur-
Frequent, short courses of therapy ther confirm the type of rash and to rule out features
of anaphylaxis such as hypotension, upper airway
edema, and acute urticaria. Other serious drug reac-
also be observed in immune complex disease (type tions can be suggested by the presence of fever,
III). Allergic contact dermatitis is an example of lymphadenopathy, arthralgias, and bronchospasm.
delayed hypersensitivity (type IV). It presents as a Treatment requires discontinuing the offending
papulovesicular eruption caused by a medication agent. If the patient is on multiple drugs, reduce the
applied topically to the skin. TEN, SJS, and erythema number to as few as possible and re-evaluate.
multiforme describe severe erythematous, polymor- Further therapy for drug hypersensitivity is mostly
phic eruptions associated with urticaria, vesicles, and supportive and symptomatic. Topical corticos-
epidermal detachment. Mucous membranes are teroids and oral antihistamines may help. Systemic
commonly involved. In TEN, full-thickness epider- corticosteroids may help speed recovery in severe
mal necrosis involves more than 30% of the body cases. TEN and SJS frequently require hospitaliza-
surface area. Drugs such as penicillins and sulfon- tion and intensive therapy. Use of corticosteroids in
amides cause approximately 65% of TEN cases, and SJS is controversial because it has been found to be
the mortality rate is 40%. SJS presents as widespread helpful in some studies but has been shown to delay
erythematous or purpuric macules and targetoid healing in others. Corticosteroids are contraindi-
lesions. The same drugs may be involved as well cated in TEN, which should be treated similar to a
as infections such as mycoplasma and viruses such as burn injury.
herpes. As the rate of epidermal detachment in SJS
is much less compared with TEN, the mortality rate
is also much lower, approximately 5%. Drug rash Material Available on Student Consult
with eosinophilia and systemic symptoms syndrome
Review Questions and Answers about Adverse
is a discrete drug reaction distinguished by a morbil-
Drug Reaction
liform rash, fever, lymphadenopathy, eosinophilia,

SUGGESTED READINGS
Demoly P. Classification and epidemiology of hypersensi- Joint Task Force on Practice Parameters, the American
tivity drug reactions. Immunol Allergy Clin North Am Academy of Allergy, Asthma and Immunology, and the
2004;24:345–356.● B Joint Council of Allergy, Asthma and Immunology.
Gruchalla RS. Drug allergy. J Allergy Clin Immunol Executive summary of disease management of drug
2003;111(2 Suppl):S548–S559.● B hypersensitivity: A practice parameter. Ann Allergy
Habif TP. Clinical Dermatology, 4th ed. St. Louis, Mosby, Asthma Immunol 1999;83:665–700.● C
2004.● C

450
 Chapter 57 Acne (Acne Vulgaris)

Schmader KE, Hanlon JT, Pieper CF, et al. Effects of geri- Volcheck GW. Clinical evaluation and management of
atric evaluation and management on adverse drug reac- drug hypersensitivity. Immunol and Allergy Clin North
tions and suboptimal prescribing in the frail elderly. Am 2004;24:357–371.● A
Am J Med 2004;116:394–401.● A

C h a p t e r

57 Acne (Acne Vulgaris)

Scott Kinkade

in the past for minor illnesses and injuries. Today

KEY POINTS she is seeing you for “worsening acne.” Sara states that
she has had “mild acne” for several years. When it
1. Acne is common and distressing to patients but has become noticeable, usually around the time of
can almost always be well controlled. her menses, she has applied an over-the-counter
2. The pathogenesis of acne starts with andro- benzoyl peroxide 5% cream. She says that this first
genic stimulation of the pilosebaceous unit semester of college has been stressful and has caused
causing increased sebum and hyperkeratiniza- her acne to worsen significantly. She attributes the
tion that leads to follicular plugging and a condition to increased stress from tests, too much
comedone. Propionibacterium acnes then prolif- greasy food in the dormitory cafeteria, not washing
erates within the comedone and releases her face often enough, and not getting enough sleep.
inflammatory mediators and chemoattractants. She has been using the benzoyl peroxide product
3. Topical retinoids are an excellent cornerstone daily for several months but does not feel that it is
for all facets of acne therapy. controlling the acne.
4. Patients should be reassessed after a minimum
of 6 to 8 weeks to give the medications ade-
Medical History
quate time to work.
Sara has had no surgeries, hospitalizations, or signif-
5. Patient education should be targeted toward
icant medical illnesses. Her immunizations are up to
dispelling acne myths, instructions on how to
date.
use the medications, expected side effects, and
expected efficacy.
Family History
Family history is noncontributory. Specifically, no
one has had severe, scarring acne.

INITIAL VISIT Health Habits

Sara does not take any medicines. She does not smoke
Subjective or use alcohol. She exercises a few times per week.
Patient Identification and Presenting
Problem Social History
Sara is an 18-year-old young woman home from col- Sara is a freshman in college. She is making good
lege on Christmas break. You have seen her a few times grades and has a strong peer network.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

451
 Chapter 57 Acne (Acne Vulgaris)

Schmader KE, Hanlon JT, Pieper CF, et al. Effects of geri- Volcheck GW. Clinical evaluation and management of
atric evaluation and management on adverse drug reac- drug hypersensitivity. Immunol and Allergy Clin North
tions and suboptimal prescribing in the frail elderly. Am 2004;24:357–371.● A
Am J Med 2004;116:394–401.● A

C h a p t e r

57 Acne (Acne Vulgaris)

Scott Kinkade

in the past for minor illnesses and injuries. Today

KEY POINTS she is seeing you for “worsening acne.” Sara states that
she has had “mild acne” for several years. When it
1. Acne is common and distressing to patients but has become noticeable, usually around the time of
can almost always be well controlled. her menses, she has applied an over-the-counter
2. The pathogenesis of acne starts with andro- benzoyl peroxide 5% cream. She says that this first
genic stimulation of the pilosebaceous unit semester of college has been stressful and has caused
causing increased sebum and hyperkeratiniza- her acne to worsen significantly. She attributes the
tion that leads to follicular plugging and a condition to increased stress from tests, too much
comedone. Propionibacterium acnes then prolif- greasy food in the dormitory cafeteria, not washing
erates within the comedone and releases her face often enough, and not getting enough sleep.
inflammatory mediators and chemoattractants. She has been using the benzoyl peroxide product
3. Topical retinoids are an excellent cornerstone daily for several months but does not feel that it is
for all facets of acne therapy. controlling the acne.
4. Patients should be reassessed after a minimum
of 6 to 8 weeks to give the medications ade-
Medical History
quate time to work.
Sara has had no surgeries, hospitalizations, or signif-
5. Patient education should be targeted toward
icant medical illnesses. Her immunizations are up to
dispelling acne myths, instructions on how to
date.
use the medications, expected side effects, and
expected efficacy.
Family History
Family history is noncontributory. Specifically, no
one has had severe, scarring acne.

INITIAL VISIT Health Habits

Sara does not take any medicines. She does not smoke
Subjective or use alcohol. She exercises a few times per week.
Patient Identification and Presenting
Problem Social History
Sara is an 18-year-old young woman home from col- Sara is a freshman in college. She is making good
lege on Christmas break. You have seen her a few times grades and has a strong peer network.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

451
 Chapter 57 Acne (Acne Vulgaris)

Review of Systems Plan

Sara reports no excessive fatigue except when she stays
up late studying. Her mood is good, and she does not Therapeutic
feel depressed. Her menstrual cycles have been regular. Given that Sara has tried benzoyl peroxide 5% cream,
She denies any polydipsia, polyuria, or polyphagia. it would be reasonable to step up the therapy target-
ing various components of the pathogenesis of acne.
Her benzoyl peroxide is mainly an antibiotic,
Objective although it has some comedolytic activity. Adding
another or different antibiotic and a more powerful
Physical Examination
comedolytic would be helpful. Sara is given a prescrip-
Vital Signs Sara’s vital signs are normal. Her weight
tion for tretinoin (Retin-A) 0.025% cream and tetracy-
is 128 pounds, and her height is 67 inches.
cline 500 mg to be taken twice daily on an empty
stomach. She is given extensive counseling on the
General She is an alert white female who appears pathogenesis and treatment options for acne as well as
comfortable. expectations of therapy.

Skin The hair pattern is normal with no signs of vir- Patient Education
ilization. She has 30 to 40 scattered inflamed papules Patients can have significant emotional distress from
and pustules and a few noninflamed comedones (all their acne and, at times, are pessimistic about the
<4 mm) on the chin, cheeks, and forehead. There are ability to treat it, given past failures. Patients should
three to four excoriated lesions on the upper back understand that although acne is a chronic disease, it
and none on the chest. There are no nodules or cysts, can almost always be well controlled. Many of the
and there is no evidence of scarring or changes in the medications have side effects and must be used as
pigmentation. directed. If the side effects can be anticipated, com-
pliance increases. Finally, therapies should be given
sufficient time to work before re-evaluation. When
Assessment starting a new therapy, the minimum time needed
before assessing efficacy is 6 to 8 weeks.
Working Diagnosis
Sara can be told that stress (such as around the
Acne vulgaris.
time of examinations) can exacerbate acne. Many
women also experience premenstrual flares of their
Differential Diagnosis
acne. Research on various diets has not shown a link
Rosacea usually begins after age 30. It can appear very
between consumption of greasy foods or chocolate and
similar to acne vulgaris. Patients typically have facial
acne. Tetracycline must be taken on an empty stomach
flushing and can have telangiectasias. These features
to be effective. It can cause some gastrointestinal upset
help distinguish it from acne.
and photosensitivity and can stain the teeth of children
Folliculitis is distinguished by small perifollicular
younger than age 12. It cannot be given to pregnant
pustules that more commonly affect the trunk and
women. Retin-A can cause irritation, transient worsen-
extremities in addition to the chest, back, and face. One
ing of acne, and photosensitivity. It should be applied
variant, gram-negative folliculitis, occurs in patients on
at night, with a pea-sized dose spread evenly over the
long-term antibiotics. The pustules are usually concen-
face. If it is too irritating, a smaller dose can be used, or
trated around the nares and central face.
it can be used every other night. Because many patients
Steroid acne, mechanical acne, pomade acne, and
get frustrated with tretinoin when their face gets
acne cosmetica are variants of acne that are distin-
irritated or when their acne worsens, it is not uncom-
guished mainly by the history.
mon for patients to stop using it after a week.
Steroid acne occurs after systemic or prolonged
Encouragement and patient education are essential
topical corticosteroid therapy. There are numerous
components of patient therapy and can help patients
small papules and pustules on the face in the case of
overcome side effects of medications.
topical steroids or on the trunk and upper arms in
the case of systemic steroids.
Mechanical acne is due to trauma and occlusion DISCUSSION
from things such as a phone receiver, bra straps, or a
chin strap on a helmet. Acne affects almost 80% of adolescents and young
Pomade acne results from hair oils and usually adults. It can be well controlled in almost all cases.
occurs along the hairline. It is more common in Because some adolescents may feel ashamed about
black males and females. their acne or may feel resigned to the fact that it is
Acne cosmetica is due to greasy, occlusive cos- incurable, the doctor may need to encourage patients
metics and moisturizers. It is most common in to try acne medications. An excellent approach is
females. during well-child, sports, or school physical exami-

452
 Chapter 57 Acne (Acne Vulgaris)

Table 57-1 Treatment Based on Pathophysiologic Target

Decrease
Hyperkeratinization
Decrease Androgen- and Follicular Decrease
Mediated Sebum Plugging (Comedone Propionibacterium Decrease
Medication Production Formation) acnes Bacteria Inflammation

Topical Therapies
Topical retinoids — ++ — (+)
Benzoyl peroxide — + ++ —
Topical erythro-
mycin or
clindamycin — (+) ++ +
Azelaic acid — + + +
Salicylic acid — + — —

Systemic Therapies
Oral antibiotics — − ++ (+)
Oral contraceptives + (+) — —
Oral corticosteroids + — — +
Isotretinoin ++ + + ++

++, Strong activity, +, moderate activity, (+), weak activity.

nations. The provider can note the presence of acne, Therapy is guided by the severity of the acne and
ask the patient whether he or she would like to try to by targeting different components of the pathogene-
control it, and then have the patient come in for an sis of acne lesions (Tables 57-1 and 57-2). Mild acne
appointment dedicated to formulation and discus- can be comedonal, inflammatory, or mixed. In mild
sion of an acne treatment plan. acne there are no cysts or scarring and usually fewer
The precursor lesion of acne is the microcome- than 20 lesions. Moderate acne is easily visible, usu-
done, which forms in the pilosebaceous unit. ally with more than 20 lesions or covering about half
Androgens stimulate the sebaceous gland and cause of the face, with no scarring or cysts. Severe acne
increased sebum production. In acne, the keratino- involves more than half of the face, has a cystic com-
cytes within the follicle hyperproliferate and clump ponent, or causes scarring.
together, plugging the follicle. The resulting micro- For purely comedonal acne or mild cases, a topical
comedone matures into either an open comedone retinoid is the preferred therapy. Alternatives or addi-
(blackhead) or closed comedone (whitehead). With the tional therapy include topical antibiotics such as ben-
retained sebum and relatively anaerobic environment, zoyl peroxide, clindamycin, erythromycin, azelaic acid,
the bacteria Propionibacterium acnes flourish. The or a benzoyl peroxide/topical antibiotic combination.
sebum and the P. acnes generate inflammatory media- Careful instruction in the use of topical retinoids
tors and cause an inflammatory lesion to develop. is required to increase patient compliance and achieve

Table 57-2 Treatment Based on Severity

Acne Classification Initial Treatments If Inadequate Response

Mild comedonal Topical retinoid Add topical antibiotic or BPO

Mild inflammatory Topical antibiotic (BPO, clindamycin, Add topical retinoid or topical
erythromycin, azelaic acid, antibiotic
and BPO/Abx) or topical retinoid
Moderate inflammatory Topical retinoid ± oral antibiotic or Oral antibiotic; oral
BPO or topical BPO/Abx contraceptive for females;
increase strength of retinoid or
change type; consider referral
to dermatologist
Severe Oral antibiotic and topical retinoid Refer to dermatologist;
± oral contraceptive for females isotretinoin
± BPO/Abx

BPO, benzoyl peroxide; BPO/Abx, topical product containing benzoyl peroxide and either erythromycin or
clindamcyin.
453
 Chapter 57 Acne (Acne Vulgaris)

the best outcome. For patients who are sensitive to daily and can be taken with foods. It can cause photo-
topical retinoids, there are several strategies that can sensitivity but less than with tetracycline. It should not
be tried, based on the following. First, the creams are be used in children or in pregnancy. Minocycline
less drying and irritating than gels or solution. Second, (Minocin) is the most expensive but also probably the
the lowest possible formulation can be used. Third, most effective because it is very lipophilic and concen-
tretinoin is available in alternate vehicles, a microsphere trates in the sebaceous glands. The usual starting dose is
(Retin-A Micro) and a polyolprepolymer (Avita), which 50 to 100 mg twice daily, and it can be taken with food.
are less irritating. Fourth, adapalene (Differin) is usu- There are fewer gastrointestinal problems and less pho-
ally less irritating than tretinoin or tazarotene. Finally, totoxicity than with the other tetracycline derivatives.
these can be used sparingly or every other day until Minocycline has some severe but rare side effects,
tolerated or applied and washed off after a short time. including central nervous system disturbances
Benzoyl peroxide is inactivated by topical (headache, vertigo, and pseudotumor cerebri), blue-
retinoids, so they should not be used together. gray discoloration of the skin and oral mucosa, autoim-
Typically, the topical retinoid is used at night and the mune hepatitis, and drug-induced lupus.
benzoyl peroxide is used in the morning. Benzoyl per- Combination oral contraceptives are an option
oxide is unique in that it does not induce resistance in for females, particularly when contraception is
P. acnes, unlike the other oral and topical antibiotics. desired. They suppress ovarian and peripheral andro-
Side effects of benzoyl peroxide include facial irrita- gen metabolism and increase sex hormone–binding
tion and bleaching of clothes, towels, and bed linens. globulin, resulting in a net reduction in free testos-
Topical antibiotics include erythromycin and terone. Several oral contraceptives, including those
clindamycin (Cleocin T). They are available as solu- containing the progestins norethindrone, desogestrel,
tions, lotions, ointments, and gels. In addition, they norgestimate, and drospirenone, have been studied
are available as combination products with either and found to be effective.
benzoyl peroxide or tretinoin. Combination prod- Products containing the progestins norgestrel,
ucts can increase patient compliance, decrease bacte- levonorgestrel, and norethindrone are not as effica-
rial resistance, and enhance penetration. Side effects cious because of their androgenic effects.
of topical antibiotics are predominantly due to local Isotretinoin (Accutane) is a powerful and effec-
irritation. There have been a few reports of systemic tive medicine for controlling acne and may cause
side effects from topical antibiotics. remission. It is indicated for severe nodular acne unre-
Azelaic acid (Azelex) is not as potent an antibiotic sponsive to conventional therapy. It should also be
as benzoyl peroxide, erythromycin, or clindamycin, but considered for scarring acne and other moderate to
it does not induce resistance in P. acnes. It also has mild severe acne cases that do not respond well to conven-
comedolytic, anti-inflammatory, and hypopigmenting tional treatments. Because of severe side effects,
properties. The ability to decrease some postinflamma- including teratogenicity and possible increases in
tory hyperpigmentation from acne lesions is unique to depression and suicide, it should be prescribed only by
azelaic acid. Salicylic acid is available over the counter physicians experienced with the use of the drug. In
in various acne washes and creams. It is a mild kera- addition, the manufacturer requires prescribers to be
tolytic. Side effects to azelaic acid and salicylic acid are enrolled in a special program that outlines specific
primarily due to local irritation. protocols for use. Common but less severe side effects
Moderate acne and severe acne require systemic include dry skin and mucous membranes, hyperlipi-
therapy. Topical preparations can still be used, but demia, myalgias, arthralgias, and headaches.
an oral antibiotic, oral contraceptive, or isotretinoin Patients should be reassessed after at least 6 to 8
is required. Oral tetracyclines (tetracycline, doxycycline, weeks of therapy and encouraged to continue ther-
and minocycline) are first-line therapies. Erythro- apy, even if their acne seems to transiently worsen at
mycin leads to higher rates of resistant P. acnes and the beginning. Maintenance of acne therapy is best
trimethoprim-sulfamethoxazole (Bactrim), while effec- managed with a topical retinoid or benzoyl peroxide.
tive, has a higher rate of severe side effects. Oral antibi- Continuous, long-term use of topical or oral antibi-
otics are used at full strength for 6 to 8 weeks or until otics leads to resistance and treatment failures. In the
there is an improvement in the acne. They can then be case of worsening acne while on an antibiotic, one
decreased to maintenance doses but should not be used should consider gram-negative folliculitis, or, more
longer than needed due to bacterial resistance. A typical commonly, antibiotic resistance.
course of antibiotics is 6 to 9 months. Tetracycline is the
least expensive but must be taken 1 to 2 hours before
meals, which decreases patient compliance. A usual
starting dose is 500 mg twice daily. It is contraindicated Material Available on Student Consult
in children younger than age 12 and in pregnancy and
Review Questions and Answers about Acne
can cause photosensitivity and gastrointestinal upset.
Vulgaris
Doxycycline is usually started at a dose of 100 mg twice

454
 Chapter 58 Genital Warts (Condyloma Acuminata)

SUGGESTED READINGS

Feldman S, Careccia RE, Barham KL. Diagnosis and treat- Katsambas AD, Stefanaki C, Cunliffe WJ. Guidelines for
ment of acne. Am Fam Physician 2004;69: treating acne. Clin Dermatol 2004;22:439–444.●
C
2123–2130.●CC Krautheim A, Gollnick HP. Acne: Topical treatment. Clin
Gollnick H, Cunliffe W, Berson D, et al. Management of Dermatol 2004;22:398–407.● C
acne: A report from a Global Alliance to Improve Rigopoulos D, Ioannides D, Kalogeromitros D,
Outcomes in Acne. J Am Acad Dermatol 2003;49: Katsambas AD. Comparison of topical retinoids in the
S1–S37.●
C treatment of acne. Clin Dermatol 2004;22:408–411.● C
Haider A, Shaw JC. Treatment of acne vulgaris. JAMA Smolinski KN, Yan AC. Acne update: 2004. Curr Opin
2004;92:726–735.● A Pediatr 2004;16:385–391.●C
Katsambas A, Papakonstantinou A. Acne: Systemic treat- Thiboutot D. Acne: Hormonal concepts and therapy. Clin
ment. Clin Dermatol 2004;22:412–418.● C Dermatol 2004;22:419–428.● C

C h a p t e r

58 Genital Warts
(Condyloma Acuminata)
Richard P. Usatine and Heidi Chumley

KEY POINTS

1. Condyloma acuminata (genital warts) are 5. When choosing which treatments to

caused by human papillomavirus (HPV) and are prescribe, the physician should consider the
sexually transmitted. size, keratinization, location and number of
2. The differential diagnosis for condyloma acumi- genital warts, patient preferences, treat-
nata includes condyloma lata, molluscum con- ment costs, convenience, and adverse
tagiosum, and pearly penile papules. effects.
3. Any person with genital warts should be tested 6. Treatment of genital warts improves symptoms
for sexually transmitted diseases including from the warts and induces wart-free periods but
syphilis and human immunodeficiency virus does not necessarily prevent transmission of HPV
(HIV). Women with genital warts should have to a partner.
Pap smear screening. 7. While condom use may not prevent transfer of
4. Genital warts may be treated by the application the HPV, it does prevent the occurrence of genital
of topical medications such as imiquimod or warts in partners of persons with HPV and does
podofilox or by the destruction of wart tissue reduce the transmission of other sexually trans-
with cryotherapy, electrotherapy, or surgery. mitted diseases (STDs).

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

455
 Chapter 58 Genital Warts (Condyloma Acuminata)

SUGGESTED READINGS

Feldman S, Careccia RE, Barham KL. Diagnosis and treat- Katsambas AD, Stefanaki C, Cunliffe WJ. Guidelines for
ment of acne. Am Fam Physician 2004;69: treating acne. Clin Dermatol 2004;22:439–444.●
C
2123–2130.●CC Krautheim A, Gollnick HP. Acne: Topical treatment. Clin
Gollnick H, Cunliffe W, Berson D, et al. Management of Dermatol 2004;22:398–407.● C
acne: A report from a Global Alliance to Improve Rigopoulos D, Ioannides D, Kalogeromitros D,
Outcomes in Acne. J Am Acad Dermatol 2003;49: Katsambas AD. Comparison of topical retinoids in the
S1–S37.●
C treatment of acne. Clin Dermatol 2004;22:408–411.● C
Haider A, Shaw JC. Treatment of acne vulgaris. JAMA Smolinski KN, Yan AC. Acne update: 2004. Curr Opin
2004;92:726–735.● A Pediatr 2004;16:385–391.●C
Katsambas A, Papakonstantinou A. Acne: Systemic treat- Thiboutot D. Acne: Hormonal concepts and therapy. Clin
ment. Clin Dermatol 2004;22:412–418.● C Dermatol 2004;22:419–428.● C

C h a p t e r

58 Genital Warts
(Condyloma Acuminata)
Richard P. Usatine and Heidi Chumley

KEY POINTS

1. Condyloma acuminata (genital warts) are 5. When choosing which treatments to

caused by human papillomavirus (HPV) and are prescribe, the physician should consider the
sexually transmitted. size, keratinization, location and number of
2. The differential diagnosis for condyloma acumi- genital warts, patient preferences, treat-
nata includes condyloma lata, molluscum con- ment costs, convenience, and adverse
tagiosum, and pearly penile papules. effects.
3. Any person with genital warts should be tested 6. Treatment of genital warts improves symptoms
for sexually transmitted diseases including from the warts and induces wart-free periods but
syphilis and human immunodeficiency virus does not necessarily prevent transmission of HPV
(HIV). Women with genital warts should have to a partner.
Pap smear screening. 7. While condom use may not prevent transfer of
4. Genital warts may be treated by the application the HPV, it does prevent the occurrence of genital
of topical medications such as imiquimod or warts in partners of persons with HPV and does
podofilox or by the destruction of wart tissue reduce the transmission of other sexually trans-
with cryotherapy, electrotherapy, or surgery. mitted diseases (STDs).

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

455
 Chapter 58 Genital Warts (Condyloma Acuminata)

INITIAL VISIT Family History

Both parents are alive and well. A full family history
Subjective is not essential for this particular case.
Patient Identification and Presenting Problem
Fred B. is a 32-year-old white man who presents Health Habits
for the first time concerned that he may have Fred generally lives a healthy lifestyle and denies drug
warts on his penis (Figs. 58-1 and 58-2). He and tobacco use. He likes to have wine with dinner
believes that the warts started about 4 months when he goes out but does this less than twice a
ago. He has been married for 2 years. He denies week.
having sexual relationships outside of his mar-
riage and believes his wife is also not having sex Social History
with anyone else. Fred admits to having other sex- Fred is married and has no children.
ual partners before meeting his wife but does not
understand how he could have contracted this Review of Systems
now. He denies fevers, urethral discharge, and burning on
urination.
Medical History
Fred denies any history of STDs and had a negative Objective
HIV test before he got married. The patient has no
other symptoms and no chronic illnesses. Physical Examination
The patient has no fever or lymphadenopathy. A gen-
ital examination (see Fig. 58-1) reveals skin-colored
verrucous lesions at the base of the penis. A close-up
photograph of one of the lesions on the shaft of the
penis clearly shows the cauliflower look of condy-
loma acuminata (see Fig. 58-2).

Assessment
Working Diagnosis
These large verrucous lesions are most likely
condyloma acuminata. These are caused by the
HPV and are sexually transmitted. It is possible to
contract HPV and not develop warts until much
later.

Differential Diagnosis
Figure 58-1 Condyloma acuminata at the base of the Other causes of genital lesions that may be confused
penis.
with condyloma acuminata include:

1. Condyloma lata. Lata means flat, and this type of

flat wart occurs in secondary syphilis. Condyloma
lata are teeming with spirochetes, and a dark-field
microscopy can be used to visualize the
Treponema pallidum. These lesions are much less
common than condyloma acuminata and can be
distinguished with a markedly positive Venereal
Disease Research Laboratories (VDRL) test or
rapid plasmin reagin test.
2. Molluscum contagiosum. The papules of mollus-
cum contagiosum are smooth and pearly with
central umbilication. They look stuck on the sur-
face and range from 1 to 5 mm. The papules can
be found anywhere on the body except for the
scalp and can vary from a few isolated papules to
Figure 58-2 Close-up of a genital wart on the shaft of many widespread lesions. Molluscum contagio-
the penis. sum is caused by three different DNA poxviruses

456
 Chapter 58 Genital Warts (Condyloma Acuminata)

There are no data to support the use of type-specific

HPV nucleic acid tests in the routine diagnosis or
management of visible genital warts (Centers for
Disease Control and Prevention, 2002●C ).

Therapeutic
The primary goal of treating visible genital warts is
the removal of symptomatic warts ( Centers for
Disease Control and Prevention, 2002● C ). Treatment
can induce wart-free periods. Available therapies for
genital warts may reduce, but probably will not erad-
icate, infectivity (Centers for Disease Control and
Prevention, 2002● C ). There is no evidence that sug-
gests that one single treatment is ideal for all patients
or all warts. The natural history of genital warts is
Figure 58-3 Pearly penile papules on the corona of the
glans and genital warts on the shaft.
benign, and the types of HPV that cause external
genital warts (HPV 6 and 11) are not associated with
cancer.
and is spread through person-to-person contact, The Centers for Disease Control and Prevention
autoinoculation, or contact with fomites. In 2002 treatment guidelines for STDs recommend the
adults, these lesions may be sexually transmitted following options:
and found in the genital area.
3. Pearly penile papules. Figure 58-3 shows a patient Patient-Applied Treatments (See Table 58-1 for
with pearly penile papules on the corona of the Cost Data)
glans and genital warts on the shaft of the penis. Podofilox 0.5% solution or gel (Condylox). Patients
The pearly penile papules are a variation of the should apply podofilox solution with a cotton swab
normal male anatomy. The main reason to rec- or podofilox gel with a finger to visible genital warts
ognize these papules is to reassure worried men twice daily for 3 days, followed by 4 days of no ther-
that they are normal and to avoid removing apy. This cycle may be repeated, as necessary, for up
them with unnecessary invasive treatments to four cycles. The health care provider should apply
(Usatine, 2004). the initial treatment to demonstrate the application
technique and identify the warts to be treated.
Plan Imiquimod 5% cream (Aldara). Patients should
Diagnostic apply imiquimod cream once daily at bedtime, three
Since Fred likely has one type of STD, he should be times weekly for up to 16 weeks. The treatment area
tested for syphilis and HIV regardless of other risk should be washed with soap and water 6 to 10 hours
factors (Centers for Disease Control and Prevention, after the application.
2002●C ). In this case, testing for syphilis with either a
rapid plasmin reagin or VDRL test will be helpful to Provider-Administered Treatments
rule out condyloma lata. These specific condyloma Cryotherapy. Cryotherapy is applied with liquid
lesions do not resemble molluscum contagiosum and nitrogen, a chemical refrigerant, or a cryoprobe using
do not need to be biopsied to establish the diagnosis. CO2 or nitrous oxide gas (Usatine, 1998). Providers

Table 58-1 Self-Administered Medications for Human Papillomavirus

Medication Method Cost

Podofilox 0.5% solution or Apply twice daily for 3 days, Generic topical solution, 3 mL, $90.85
gel (podophyllotoxin) then off 4 days. May repeat Condylox gel, 3.5 g (1 tube), $164
cycle total of 4 times. Condylox solution, 3.5 mL, $121
Imiquimod 5% cream Apply once daily 3 times/wk. 12 packets for $159 (for 4 wk of
Wash off after 6–10 hr. therapy if one packet is used per
May use up to 16 wk. application; using a packet for
more than 1 day is possible)

Prices from ePocrates. Available at www.epocrates.com. Accessed 10/30/2005.

457
 Chapter 58 Genital Warts (Condyloma Acuminata)

should freeze each lesion for about 5 to 15 seconds Trichloroacetic acid (TCA) (Tri-chlor). A small
with 2-mm margins, as HPV is present in normal- amount should be applied only to the warts and
appearing tissue surrounding each lesion (Usatine, allowed to dry, at which time a white “frosting” devel-
1998). Freeze time is the amount of time that the ops. This treatment can be repeated weekly, if neces-
lesion remains frozen and not the amount of time the sary. Figure 58-5 shows the white frosting that is visible
cryogen is applied. These times will vary depending on penile warts right after treatment with topical TCA.
on the cryogen, the delivery method, the size of the
lesion, and the patient’s tolerance. The coldest cryo- Surgical removal. Surgical removal is achieved by
gen is liquid nitrogen; it is delivered most efficiently tangential scissor excision (snip excision), curettage,
with a cryogun. Other cryogens include nitrous oxide or electrosurgery. These methods usually require
and chemical refrigerants. Fewer complications will local anesthetic unless the lesion is tiny or on a tiny
occur with shorter freeze times, and the freeze times base. When using electrosurgery, the physician
can always be increased at the next visit if needed. No should use a smoke evacuator and surgical mask to
current evidence indicates that double freeze/thaw avoid inhaling smoke with viral particles.
cycles are superior to a single freeze and thaw. When choosing the type of therapy for each
Providers can repeat applications every 1 to 2 weeks. patient, it is helpful to note that the soft nonkera-
Cryosurgery is ideal for isolated lesions on the penile tinized warts respond well to the various forms of
shaft or on the vulva (Usatine, 1998). Figure 58-4 podophyllin and trichloroacetic acid, while the more
shows the genital wart in Figure 58-2 undergoing keratinized lesions respond better to physical ablative
treatment with liquid nitrogen in a cryogun. methods such as cryotherapy, excision, and electro-
For patients with multiple lesions that make up cautery. Imiquimod appears to work well for both
a considerable extent of the surface area of the penis types of lesions but is more effective for the nonkera-
or the vulva, patient-administered topically applied tinized warts. The softer nonkeratinized warts are
medications are better tolerated than cryotherapy. often found on the softer mucosa around the anus,
under the foreskin, and around the female introitus.
Podophyllin resin 10% to 25% (Podifin) in a com- The firmer, more keratinized warts are often found on
pound tincture of benzoin. A small amount should more keratinized skin such as on the shaft of the penis.
be applied to each wart and allowed to air dry. The
treatment can be repeated weekly, if necessary. To Patient Education
avoid the possibility of complications associated with Patient education should include information about
systemic absorption and toxicity, some specialists transmission and outcomes.
recommend that application be limited to <0.5 mL
of podophyllin or an area smaller than 10 cm2 of ●
Advise patients that genital warts are transmitted
warts per session. Some specialists suggest that the sexually and encourage testing for other STDs,
preparation should be thoroughly washed 1 to 4 including cervical cytology screening in women.
hours after application to reduce local irritation. ●
Reassure women that the risk of cervical cancer is
Avoid using podophyllin during pregnancy. low even with genital warts and that yearly Pap
smears can detect early changes that can be treated
before cancer develops.

Figure 58-4 Genital wart undergoing treatment with Figure 58-5 White frosting on penile warts right after
liquid nitrogen in a cryogun. treatment with topical trichloroacetic acid.

458
 Chapter 58 Genital Warts (Condyloma Acuminata)

● Encourage patients to use condoms, particularly if and, for men, being uncircumcised (Svare et al., 2002● B).
the patient is not in a monogamous relationship. The most important risk factor for oncogenic HPV
Condoms may reduce the risk of a partner devel- types is lifetime number of partners. Risk factors for the
oping warts but probably do not reduce transmis- nononcogenic HPV types include number of partners
sion of HPV. in the past year and ever having genital warts (Svare
● Clarify that HPV has a long latency period and that et al., 2002● B). Fortunately, a vaccine that targets onco-
the development of genital warts in only one part- genic HPV subtypes 16 and 18 has shown promise in
ner does not indicate sexual contact outside that decreasing infection and cervical dysplasia in women
relationship. and is in late clinical trials (Harper et al., 2004●
A).
●
Encourage current partners and recent partners to Genital HPV infection or genital warts are not
be assessed for genital warts and advised about nationally reportable diseases. Therefore, comprehen-
STDs and their prevention. sive surveillance data are not available for HPV infec-
●
Reassure patients that these warts typically resolve, tions. If age-specific incidence estimates for cervical
although it may take up to 6 months, and recur- HPV infection among women reflect the HPV inci-
rences may occur (von Krogh et al., 2001● C ). dence rates among men, then approximately 6.2 mil-
lion new HPV infections occurred in the year 2000
among Americans age 15 to 44; of these infections,
Disposition 74% (4.6 million) occurred among 15- to 24-year-old
The treatment options were discussed with the persons (Myers, 2000; Weinstock et al., 2004).
patient. A process of shared decision making was used There is no single first-line treatment option for
to come up with the treatment plan. The patient genital warts, in part because each therapy has less
decided to have cryotherapy performed in the office than optimal cure and recurrence rates. The treat-
and was given a prescription for imiquimod cream to ment guidelines from the Centers for Disease
be used on any remaining warts. The patient tolerated Control and Prevention are based on a limited num-
the cryotherapy with an acceptable level of temporary ber of clinical trials. One double-blind, randomized,
discomfort. His HIV and rapid plasmin reagin tests multicenter, vehicle-controlled study demonstrated
were negative. While still using the imiquimod cream, that 0.5% podofilox gel was significantly better than
he returned with his wife to discuss the implications vehicle gel for successfully eliminating and reducing
of his infection for her. Her physical examination and the number and size of anogenital warts. In the
Pap smear were normal. After long discussions and intent-to-treat population, 37% treated with pod-
much reassurance, they both understood that he was ofilox gel had complete clearing of the treated areas
probably infected before their marriage. compared with 2% who had clearing of warts with
the vehicle gel after 4 weeks (Tyring et al., 1998● A)
(P < 0.001, number needed to treat = 3).
DISCUSSION Imiquimod has been shown to be effective in
many studies, including three randomized controlled
HPV causes many types of warts in humans, includ- trials in which clearance rates were 37% to 52% after
ing common warts (verruca vulgaris), flat warts (ver- 8 to 16 weeks of treatment (Maw, 2004). One study
ruca plana), plantars warts, and genital warts found that clearance rates were twofold higher in
(condyloma acuminata). The common and flat warts women than in men (72% and 33%, respectively)
found on hands, feet, and other locations can be a (Sauder et al., 2003● A). This is probably because gen-
cosmetic and functional nuisance. These warts are ital warts in females are less keratinized than the
most often treated with cryotherapy and topical most commonly found warts on the penile shaft in
acids. Genital warts can be physically and psycholog- males. Similarly, clearance rates with imiquimod
ically distressing; however, the most deadly conse- seem to be higher in uncircumcised men (62%) than
quence of HPV infection is cervical cancer. The in circumcised men (33%), probably due to the
detection and treatment of cervical dysplasia and degree of keratinization (Maw, 2004). However,
cancer involve using the Pap smear, the colposcope, uncircumcised men are at higher risk of acquiring
and treatment with surgical means when indicated. genital warts and other STDs independent of other
HPV can be divided into high-risk (oncogenic) sexual risk factors (Svare et al., 2002● B ).
and low-risk (nononcogenic) types. High-risk HPV Recurrence rates for sole therapy with
(such as HPV 16 and 18) may actually lead to cancers imiquimod (9% to 19%) are substantially lower than
of the cervix, vulva, vagina, anus, or penis. Low-risk for most other genital wart treatments including
HPV (such as HPV 6 and 11) can cause genital warts podophyllin (Maw, 2004). Imiquimod may even be
and may cause abnormal Pap results without causing effective in reducing wart recurrence rates when used
cancer. as an adjunct to surgical treatment (Maw, 2004).
The most important predictors of any HPV infec- Figure 58-6 shows condyloma acuminata around
tion are lifetime number of sexual partners, young age, the anus of a 2-year-old girl. The mother had common

459
 Chapter 58 Genital Warts (Condyloma Acuminata)

In summary, genital warts bring up complicated

social and personal issues that need to be addressed
with the patients and their partners. Medical or sur-
gical treatment should be determined using
informed consent and shared decision making.
When choosing which treatments to prescribe for
patients, the clinician should consider the size, kera-
tinization, location and number of genital warts,
patient preferences, treatment costs, convenience,
and adverse effects. Most treatments take months to
work. If one treatment does not work, other options
should be considered.

Figure 58-6 Condyloma acuminata around the anus of a

Material Available on Student Consult
2-year-old girl.
Review Questions and Answers about Condyloma
Acuminata
warts (verruca vulgaris) on her fingers and believed
that these warts were the result of her diapering her
child. Genital warts in children should prompt investi-
gation for child abuse, as was done in this case.

REFERENCES
Centers for Disease Control and Prevention. 2002 Sexually dees at a Danish STD clinic. Sex Transm Infect
transmitted diseases treatment guidelines. MMWR 2002;78:215–218.● B
Recomm Rep 2002;51:1–80.● C Tyring S, Edwards L, Cherry LK, et al. Safety and efficacy of
Harper DM, Franco EL, Wheeler C, et al. Efficacy of a biva- 0.5% podofilox gel in the treatment of anogenital
lent L1 virus-like particle vaccine in prevention of warts. Arch Dermatol 1998;134:33–38.● A
infection with human papillomavirus types 16 and 18 in Usatine RP. Pearly penile lesions. J Fam Pract 2004;53:
young women: A randomised controlled trial. Lancet 885–888.
2004;364:1757–1795.● A Usatine R. Cryosurgery. In Usatine R, Moy R, Tobinick E,
Maw R. Critical appraisal of commonly used treatment for Siegel D, (eds): Skin Surgery: A Practical Guide. St.
genital warts. Int J STD AIDS 2004;15:357–364. Louis, Mosby-Year Book, 1998, pp 137–164.
Myers ER. Mathematical model for the natural history of von Krogh G, Lacey CJ, Gross G, Barrasso R, Schneider A.
human papillomavirus infection and cervical carcino- European Course on HPV Associated Pathology
genesis. Am J Epidemiol 2000;151:1158–1171. (ECHPV), European Branch of the International
Sauder DN, Skinner RB, Fox TL, Owens ML. Topical Union against Sexually Transmitted Infection and the
imiquimod 5% cream as an effective treatment for European Office of the World Health Organization.
external genital and perianal warts in different European guideline for the management of anogenital
patient populations. Sex Transm Dis 2003;30: warts. Int J STD AIDS 2001;12(Suppl 3):40–47.● C
124–128.● A Weinstock H, Berman S, Cates W. Sexually transmitted dis-
Svare EI, Kjaer SK, Worm AM, Osterlind A, Meijer CJ, van eases among American youth: Incidence and preva-
den Brule AJ. Risk factors for genital HPV DNA in men lence estimates, 2000. Perspect Sex Reprod Health
resemble those found in women: A study of male atten- 2004;36:6–10.

460
 C h a p t e r

59 Pigmented Thumbnail (Nail Lentigo)

Robert S. Fawcett

medical problems. She knows of no cancers in the

KEY POINTS family, although one sister had a breast biopsy for
what turned out to be benign disease. Several chil-
1. Longitudinal melanocytic bands are almost dren and grandchildren are alive and well.
ubiquitous in dark-skinned adults, which makes
the diagnosis of malignant melanoma of the Social History
nail problematic in those individuals. The patient does not drink or smoke. She lives with
2. Risk factors making biopsy of a new band her husband and stays active caring for a number of
necessary include the usual ABCDE criteria for grandchildren.
melanoma as well as Hutchinson’s sign (skin
involvement at the proximal or distal nail fold); Review of Systems
family history of dysplastic nevi or melanoma; There is nothing of significance to the case. The patient
single nail involvement, particularly of the complains of some aches in her knees and back for
thumb or index finger; sudden change in which she takes occasional acetaminophen and
appearance; association with trauma; nail dys- ibuprofen with some relief. She takes milk of magnesia
plasia; or onset after age 60. for occasional constipation. She denies taking other
3. Biopsy of possible melanoma is done by remov- over-the-counter medications or herbal supplements.
ing the nail and excising the skin involved with
the pigmentation, being sure to include the
most proximal area, and warning the patient in Objective
advance of the likelihood of resultant nail Physical Examination
dysplasia. Jadyra G. is a healthy-appearing, moderately obese
Hispanic woman in no distress. Her blood pressure is
140/75, pulse is 76 and regular, temperature is 36.9˚C
(98.4˚F), and respiratory rate is 16. The examination
INITIAL VISIT is unremarkable aside from the right thumb. There
she has pigmentation on the radial two thirds of the
Subjective thumbnail, with a 4-mm darkly banded area to
Patient Identification and Presenting Problem the radial side (Figs. 59-1 and 59-2). The pigmenta-
Jadyra G. is a 65-year-old Hispanic woman who tion extends onto the proximal nail fold and epony-
presents to the office complaining of an expanding chium (Hutchinson’s sign) and into the distal nail
streak on her right thumb. The streak itself has been fold beneath the free edge of the nail. Nail dystrophy
present for about 10 years but has recently gotten is manifest by slight thickening over the most darkly
broader. Jadyra also notes that the notching of the pigmented area and by notching at the free edge of
distal nail plate is new. the nail plate. No inflammation is seen, and scraping
the surface of the nail plate with a no. 15 blade does
Medical History not affect the coloration of the nail. No other nails
The patient has hypertension that is well controlled show pigmented bands.
with hydrochlorothiazide and an angiotensin-con-
verting enzyme inhibitor. She is moderately over- Assessment
weight but not diabetic. There is no history of cancer,
heart disease, or skin problems. Working Diagnosis
Rule out subungual melanoma.
Family History
The patient’s mother died of a stroke at age 72. Her Differential Diagnosis
father died in an accident at age 35. The woman has 1. Melanoma is relatively rare in darkly pigmented
three brothers and two sisters with whom she has lit- individuals, but approximately half of the
tle contact, but she is not aware that any have chronic melanomas that do occur are in the nail bed, and
461
 Chapter 59 Pigmented Thumbnail (Nail Lentigo)

3. Acanthosis nigricans can cause some variable

brown discoloration of the nail plate, but this
patient does not have the velvety, thickened,
darkly pigmented skin in the axilla or neck that
suggests that condition.
4. Adrenal insufficiency can cause longitudinal
brown lines. This patient feels well, however,
and her blood pressure is slightly elevated. She
does not have any overall increase in pigmen-
tation.
5. Drugs. Adriamycin, bleomycin, hydroxyurea, and
minocycline can all cause brown discoloration,
although all nails would likely be affected.
6. Lentigo. Brown pigmentation from lentigo sim-
plex can affect the nail, just as it can other sun-
Figure 59-1 Dysplasia of the nail (see notching of the exposed areas. Lentigo maligna and lentigo
distal plate), broadness of the pigmented band (>3 mm), maligna melanoma are also possible, however,
and Hutchinson’s sign (extension of pigment onto proxi- and need to be ruled out through biopsy.
mal nail fold) make malignancy more likely. (Reproduced
with permission from Fawcett RS, Linford S, Stulberg DL.
7. Nevus. Nevi can occur on the nail bed, as they can
Nail abnormalities: Clues to systemic disease. Am Fam anywhere else, and may give a streaked appear-
Physician 2004;69:1422. Copyright © 2004 American Aca- ance as the nail grows distally. It would be
demy of Family Physicians. All Rights Reserved.) unusual, however, for nevi to appear de novo in
this age group without a potential for malignancy.
Biopsy would be warranted here as well.

Plan
After visual inspection with both the naked eye and
10× magnification, noting the extension of the lesion
onto not only the proximal but also the distal nail
fold, the patient is referred to a dermatologist for
biopsy. The dermatologist removes the nail and
biopsies the nail bed. Because the patient is otherwise
healthy, no additional workup is thought to be
immediately indicated.

Disposition
The biopsy is returned with a diagnosis of lentigo.
The patient is reassured regarding the benignity of
Figure 59-2 Extension of the pigmented area to the dis- this diagnosis but educated regarding the necessity of
tal nail fold makes malignancy more likely. (Reproduced
with permission from Fawcett RS, Linford S, Stulberg DL.
self-evaluation for any changes in the lesion.
Nail abnormalities: Clues to systemic disease. Am Fam Arrangements are made to see the patient back in the
Physician 2004;69:1422. Copyright © 2004 American family doctor’s office in 6 months.
Academy of Family Physicians. All Rights Reserved.) At the return visit, the nail has completely regrown,
although with a prominent longitudinal depression in
the area of the previous procedure. Pigmentary streak-
most of those are on the index finger or thumb. ing remains, although it is considerably narrower and
Melanoma of the nail is usually seen in older indi- lighter than at the previous visit. Continued surveil-
viduals in the sixth or seventh decade of life. Nail lance and 6-month follow-up are recommended
dystrophy and single nail involvement as well as
Hutchinson’s sign and the recent change in the
lesion all make this the diagnosis to consider most DISCUSSION
strongly and, because of the consequences of
missing it, to rule out. Nails are laid down by the nail matrix at the proximal
2. Longitudinal melanonychia is almost universally seen end of the nail bed. As the nail plate is formed, it
in older darkly pigmented individuals. It is totally moves distally, and the more distal cells of the nail
benign and usually affects several fingers or toes. matrix lay down additional layers to the undersurface

462
 Chapter 59 Pigmented Thumbnail (Nail Lentigo)

of the plate. If the cells of the nail matrix are more pig-
mented than surrounding cells, the keratin that they Box 59-1 Risk Factors for Melanoma
lay down on the underside of the nail plate might well in a Nail with Longitudinal
retain some of that pigment, giving rise to a longitudi- Pigmented Striation
nal striation in the nail. In fact, such lines are quite
common among more highly pigmented individuals. 1. Sudden change in appearance of band
One may observe them in 77% of African Americans (wider, darker, blurred border)
older than the age of 20. They usually involve multiple 2. Single nail involvement (especially thumb,
nails, although the color variations may be subtle. index finger, or great toe)
The chief problem with such stripes is in distin- 3. Pigmentation of skin of nail fold or proximal
guishing them from malignant melanoma, which nail bed (Hutchinson’s sign)
can also give rise to pigmented longitudinal bands. 4. New pigmentation in older individual (60s
There are a number of factors that may increase the and 70s)
likelihood of malignancy in a patient with these 5. Association with history of digital trauma
bands. They are outlined in Box 59-1. 6. Family history of melanoma or dysplastic
Nevi and lentigo can cause similar changes. The nevi
latter is thought to represent actinic change, often 7. Abnormal nail structure (destruction or dis-
stemming from significant sun exposure in childhood. ruption of nail plate)
Again, the problem is in distinguishing benign from Adapted from Fawcett RS, Linford S, Stulberg DL.
malignant lesions, which can arise from either lesion. Nail abnormalities: Clees to systemic disease. Am
The evaluating physician should think of the Fam Physician 2004;69:1417–1424.
usual ABCDE risk factors for melanoma in these sit-
uations as well (as adapted from the article by Levit
et al. in the Suggested Reading list). Asymmetry is
applicable in that a single nail being affected not to disrupt the extensor tendon. Procedures involv-
increases risk. Border irregularities and color varie- ing the proximal nail bed should be oriented with the
gation could apply to blurring and indistinct mar- long axis across the finger; those involving the lateral or
gins of the streak. Diameter could apply to width of distal region should be longitudinal.
the band greater than 3 to 4 mm or a widening band, Other causes for longitudinal stria should also
and enlargement might be viewed as extending onto be ruled out. Temporary staining can occur with
the skin at the distal nail fold or the proximal nail tobacco and podophyllin. Shelling walnuts can also
bed and eponychium (Hutchinson’s sign). result in dark brown stains over the nails. Staining
If melanoma is suspected, biopsy should be per- may be differentiated from pigmentation by simply
formed. Simple punch biopsy including the nail plate scraping the nail. More generalized brown nail dis-
can be done if the band is 3 mm or narrower, with good coloration may be seen with long-term hydroxyurea
cosmetic result. If a wider band is present, the nail plate administration and with hyperthyroidism.
should be removed, and an elliptical or punch biopsy
can then be performed over the area of pigmentation.
Such a biopsy is likely to result in permanent dysplasia
of the nail plate when it regrows, so one should consider Material Available on Student Consult
referring the patient for the procedure. The physician
Review Questions and Answers about Nail Lentigo
performing the biopsy must also exercise caution so as

SUGGESTED READINGS
Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: Levit EK, Kagan MH, Scher RK, Grossman M, Altman E.
Clues to systemic disease. Am Fam Physician 2004;69: The ABC rule for clinical detection of sub-ungual
1417–1424. melanoma. J Am Acad Dermatol 2000:42:269–274.
Habif TP. Nail diseases. In Clinical Dermatology: A Color Mayeaux EJ. Nail disorders. Primary Care 2000;27:
Guide to Diagnosis and Therapy. Philadelphia, Mosby, 333–350.
2004, pp 864–868.

463
 C h a p t e r

60 Rash and Fever (Rocky Mountain

Spotted Fever)
Walter D. Leventhal

vascular, or abdominal infection, and there is no

KEY POINTS hepatosplenomegaly. A diagnosis of a viral syndrome
is made. A complete blood count shows a hemoglobin
1. A high degree of suspicion in any patient who of 11.3 g/dL and a white blood cell count of
develops an unusual flu-like illness with minimal 9500/mm3: 65% polymorphonuclear leukocytes, 30%
respiratory symptoms during the spring and lymphocytes, and 5% monocytes. Platelets are noted
summer months. to be 90,000/mm3. The patient mentions the tick bite
2. A history of tick bite or environmental exposure again, but only supportive therapy is prescribed.
to ticks. Within 36 hours, Kathy’s condition has wors-
3. A willingness to begin doxycycline, especially ened and her musculoskeletal pain has increased.
in the absence of confirmatory laboratory The fever has persisted, and she has developed a red-
evidence. dish purple macular rash on her forearms and legs.
4. A maculopapular rash on the forearms and/or Overnight, Kathy’s level of consciousness has dimin-
ankle areas in a patient with fever and severe ished to the point that she does not respond to ver-
headache during the summer months. bal stimuli. The rash has developed into purpura,
some parts of which are palpable, spreading centrally
to involve her thighs and trunk.
INITIAL VISIT Kathy is immediately admitted to an intensive
care unit with a presumptive diagnosis of sepsis of
Subjective uncertain cause. Her platelet count now is
9000/mm3, and her white blood cell count has risen
Patient Identification and Presenting to 26,500/mm3. Cultures are drawn, and intravenous
Problem chloramphenicol and gentamicin are administered.
Kathy T. is a 33-year-old white woman from Chicago She has begun to have seizures and has developed
who presents to her family physician in May with a renal and hepatic failure. The patient became
1- to 2-day history of flu-like illness: headache, myal- hypotensive, and all resuscitative efforts failed. She
gia, nausea, and a temperature that has ranged died within 24 hours after admission.
between 37.8˚C and 38.3˚C (100˚F and 101˚F). About An autopsy has determined her death to be due
10 days earlier, she and her husband had gone to to disseminated intravascular coagulation, probably
their mountain cabin in North Carolina to clear out caused by rickettsial disease or meningococce-
the underbrush. While there she found a tick on her mia. Cultures for meningococcus are negative and
abdomen one evening, and she removed it. Kathy is complement fixation titers and indirect fluorescent
examined briefly, and antipyretics and antiemetics antibodies are negative for Rickettsia infection, but
are prescribed. Over the next several days, her condi- the diagnosis is later confirmed as Rickettsia by
tion changes, with development of swollen cervical immunofluorescent staining of skin biopsies.
glands and continued nausea and vomiting.

DIFFERENTIAL DIAGNOSIS
SECOND VISIT
The combination of fever and rash presents the prac-
Kathy returns to her physician 3 days later. Exami- titioner with a difficult and common problem.
nation fails to show any signs of pulmonary, cardio- Although many conditions may present initially with

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

464
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

fever and rash, one can subdivide these by consider- The preceding differential diagnosis does not
ing their potential severity, for example, life threaten- include many other minor conditions associated
ing or minor. with fever and rash often found in children––that is,
Life-threatening conditions associated with the viral exanthems associated with measles, chicken
fever and rash include: pox, roseola, rubella, and fifth disease (erythema
infectiosum). One should also consider in this cate-
1. Rocky Mountain spotted fever. See diagnosis of gory the rashes associated with drug reactions, which
Kathy’s case in Discussion section. also may be associated with fever (Table 60-1).
2. Meningococcemia. Meningococcemia tends to
occur in late winter and early spring and often in
crowded conditions, e.g., barracks or schools. The DISCUSSION
patient may present with petechiae initially on the
trunk and extremities, but in fulminating cases, This case illustrates many of the characteristics of
petechiae can spread visibly over several hours. Rocky Mountain spotted fever. Unfortunately, it also
Shock and disseminated intravascular coagula- demonstrates the rapid course of the infection from
tion are associated clinical manifestations. the time of first exposure to the tick to prodrome and
Diagnosis is confirmed by Gram stain of skin ultimately to fulminating multi-organ failure and
lesions, blood cultures, and spinal fluid examina- shock when not recognized and treated (American
tion. A chronic form of meningococcemia associ- Academy of Pediatrics, 2003● C ).
ated with rash has also been described. The patient lived in Chicago but had vacationed
3. Disseminated gonococcemia. There is a much in North Carolina, and this particular area typifies
higher incidence in women. The rash consists of the most common area of cases reported, that is, the
pustules on an erythematous base, usually over south Atlantic, southeastern, and south central
the extremities. It is often associated with migra- states. The name Rocky Mountain spotted fever is
tory polyarthralgia, arthritis, and pelvic inflam- misleading because even though the condition has
matory disease. Diagnosis can be confirmed by a been reported in every state, after the Carolinas and
Gram stain of the lesions as well as culture and Tennessee, Oklahoma is the state with the most other
sensitivity of the blood, joint fluid, or cervical cases reported (Gubler et al., 1994● C ). A clue to the
secretions. etiology is that the majority of these cases appear
4. Toxic shock syndrome. Toxic shock syndrome between April and late September (that is, the spring
occurs predominantly in women, with the rash and summer), which is when ticks are most preva-
preceded by a flu-like illness and diarrhea associ- lent. This is also the time when people are active out-
ated with mucus. The rash is macular, giving a doors and therefore more prone to exposure. The
sunburned appearance. It occurs over the whole main vector for this condition is the American dog
body but is seen mainly on the hands and feet. tick, which transmits the offending organism,
The clinical presentation is that of multisystem Rickettsia rickettsii.
involvement. The diagnosis is confirmed by his- After the tick has bitten its human host, organ-
tory, physical examination, and isolation of a isms are usually disseminated through the blood-
toxin-producing strain of Staphylococcus aureus. stream during the first 6 to 12 hours, when the tick is
5. Bacterial endocarditis. Bacterial endocarditis is still attached to the host. Attachment by the tick to
often associated with a history of valvular heart the host is usually painless, and the tick is often dis-
disease, prosthetic valves, and recent dental or covered only accidentally at the end of the day when
surgical procedures. The rash is petechial and the patient undresses.
associated with Osler’s nodes and Janeway’s This patient also showed the initial symptoms of
lesions. The rash is found in the palate and upper a flu-like illness, fever, headache, myalgia, and some-
chest and may be present on the palms, fingers, times vomiting within 4 to 20 days after being bitten.
soles, and toes. A heart murmur, splenomegaly, Usually the rash occurs on the fourth to the sixth
hematuria, and metastatic abscesses may be pres- day after the patient first complains of the systemic
ent. Diagnosis is by echocardiography and serial symptom; it begins on the wrist and ankles. It can
blood cultures. then involve the palms and soles and later becomes
6. Lyme disease. Lyme disease is caused by exposure to more generalized. Initially, the rash is erythematous
ticks in endemic areas––the Northeast, Midwest, or and macular but can become petechial if untreated
West––in the summer. The rash classically mani- (Habif, 2004● C ). The rash is difficult to see in African
fests as erythema migrans, often on the thigh, Americans. It is also important to note that the rash
groin, or axillae. Clinically, the patient presents does not develop in approximately 15% of cases. The
with a flu-like syndrome, later developing central infection is then referred to as Rocky Mountain spot-
nervous system, cardiac, or joint involvement. The less fever. The spotless type of rash appears to be
diagnosis is confirmed by history and serology. more common in adults.

465
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

Table 60-1 Some Major Diseases Associated with Fever and Rash
Morphology Distribution Diagnostic
Disease of Rash of Rash Method Treatment

Ecthyma gangre- Erythematous to Especially in axillae Blood culture; Admit to hospital;

nosum and purpuric macules, and anogenital biopsy with aminoglycoside
Pseudomonas hemorrhagic regions tissue culture plus an
septicemia vesicles, bullae, antipseudomonal
nodules, painless penicillin or
ulcers with central antipseudomonal
necrotic, black cephalosporin
eschar (e.g., ceftazidime
or cefepime)
Meningococcemia Petechiae, macules, Generalized; Blood culture Admit to hospital;
and purpura papules, purpura especially on penicillin G or
fulminans (may become lower extremities; third-generation
ecchymotic) neck and face cephalosporin
usually spared (e.g., ceftriaxone)
Vibrio vulnificus Large, hemorrhagic Especially on Blood and Admit to hospital;
infection bullae are charac- lower wound doxycycline plus
teristic; also extremities cultures ceftazidime;
cellulitis, débridement
lymphangitis often necessary
Staphylococcal Scarlatiniform rash Generalized Clinical Admit to hospital;
toxic shock (diffuse erythema), assessment appropriate
syndrome strawberry tongue; of diagnostic antibiotic (e.g.,
desquamation late criteria nafcillin);
in course supportive care
Staphylococcal Diffuse, ill-defined Generalized; Blood cultures Admit to hospital;
scalded skin erythema with especially in antistaphylococcal
syndrome fine sandpaper perineal and antibiotics (e.g.,
appearance; periumbilical nafcillin)
peeling of skin; regions (in
Nikolsky’s sign neonates) and
present extremities (in
older children)
Streptococcal Localized area of Localized or Clinical assessment; Admit to hospital;
toxic shock cellulitis or necro- generalized blood cultures; penicillin G plus
syndrome tizing fasciitis; some culture of local clindamycin
times generalized primary lesion if
erythema as well present; CT scan
to evaluate for
necrotizing
fasciitis
Disseminated Erythematous Trunk and Blood and tissue Admit to hospital;
candidiasis papules and extremities cultures amphotericin B
nodules or fluconazole
Stevens-Johnson Macules, plaques, Generalized Fulfillment of Admit to hospital;
syndrome target lesions (both clinical and supportive care;
typical and atypical), histopathologic discontinuation of
vesicles, bullae, criteria unnecessary
erosions and blisters drugs; antibiotic
of mucous mem- therapy for
branes Mycoplasma
pneumoniae if
indicated
Toxic epidermal Macules, target Generalized; Fulfillment of Same as for
necrolysis lesions, large bullae, especially on clinical and Stevens-Johnson
severe mucosal trunk and proxi- histopathologic syndrome
erosions mal extremities criteria

466
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

Table 60-1 Some Major Diseases Associated with Fever and Rash (Continued)
Morphology Distribution Diagnostic
Disease of Rash of Rash Method Treatment

Infective Petechiae, purpura, Petechiae and Blood cultures; Admit to hospital;

endocarditis Osler’s nodes, purpura on heels, echocardio- appropriate
Janeway’s lesions, shoulders, legs, graphy; antibiotic therapy
splinter oral mucosa, con- clinical
hemorrhages junctivae; Osler’s presentation
nodes on digits
(especially pulps of
fingers and toes);
Janeway’s lesions
on palms and
soles; splinter
hemorrhages
on nail plates
Scarlet fever Diffuse erythema Generalized, with Clinical assessment; Penicillin
(usually with punctate sparing of area throat culture;
Streptococcus elevations (“sand around mouth blood cultures
pyogenes paper skin”); linear (“circumoral
[group A striations (Pastia’s pallor”)
strepto- lines) of confluent
coccus]) petechiae (which
can be demon-
strated on arms
by applying a
tourniquet)
North American Inflammatory Face and extremities Blood culture; Itraconazole or
blastomycosis papules and biopsy with amphotericin B
nodules with crusts; tissue culture
hyperkeratotic
plaques with
central ulceration
Histoplasmosis Ulcers, papules, Generalized Blood cultures; Itraconazole or
plaques, purpura, biopsy and amphotericin B
abscesses, nodules, tissue cultures
mucosal ulcerations
Coccidioidomy- Papules, nodules, Head Blood cultures; Fluconazole or
cosis plaques, ulcers, biopsy and amphotericin B
papulopustules tissue cultures
Cryptococcosis Papules, plaques, Head and neck Blood and tissue Amphotericin B
nodules, palpable cultures
purpura, cellulitis,
pyoderma
gangrenosum–like
ulcers
Rocky Macules, papules; Wrists and ankles Fourfold increase Doxycycline
Mountain later becomes initially, then in antibody
spotted fever petechial palms and soles; titers between
finally, centripetal acute and
spread to face, convalescent
trunk, and more phases
proximal aspects
of extremities
Primary HIV Macules, papules, Face, trunk HIV-1 RNA testing See Chapter 17
infection mucocutaneous and HIV
ulcers, palatal antibody testing
papules (ELISA)

Continued

467
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

Table 60-1 Some Major Diseases Associated with Fever and Rash (Continued)
Morphology Distribution Diagnostic
Disease of Rash of Rash Method Treatment

Leptospirosis Macules, papules, Trunk Four-fold increase Doxycycline or

urticaria (wheals), in antibody titers penicillin G
purpura between acute
and convalescent
phases
Disseminated Macules, papules, Distal extremities, Blood cultures; Ceftriaxone
gonococcal vesicles, and typically near an biopsy with
infection petechiae initially, involved joint tissue cultures;
which may evolve cultures of
into hemorrhagic urethra, cervix,
vesicopustules rectum, and
pharynx
Lyme disease Macules, papules, Trunk, lower Serologic tests Doxycycline
erythema chronica extremities; 4–6 wk after
migrans classically a single onset
lesion but
multiple lesions
can be present
Typhoid fever Slightly raised pink Trunk, anteriorly Blood cultures; Ciprofloxacin,
(Salmonella macules that and urine and stool trimethoprim-sul-
typhi) blanch on posteriorly cultures; smear famethoxazole, or
pressure (rose (typically in crops and culture of third-generation
spots) of about 10–20 rose spots cephalosporin
lesions) (ceftriaxone or
cefotaxime)
Mycoplasma Maculopapular or Variable Fourfold increase Doxycycline or a
pneumoniae morbilliform rash in antibody macrolide antibio-
infection most common; a titers between tic (erythromycin,
variety of rashes acute and azithromycin, or
can be seen, includ- convalescent clarithromycin)
ing urticaria, ery- phases, or
thema multiforme demonstration
(including Stevens- of high
Johnson syndrome), IgM antibody
erythema nodosum, titer
and papulovesicular
lesions
Rat-bite fever Maculopapular, Begins on Inoculation of Penicillin G
caused by later becoming abdomen; blood or wound
Spirillum petechial progresses aspirate into mice
minus to extremities; or guinea pigs;
may involve darkfield exami-
palms and nation of bite,
soles rash, or aspirate
from lymph
node; RPR (VDRL)
often false
positive (50%)
Rat-bite fever Maculopapular or Most extensive on Blood, wound, or Penicillin G
caused by petechial extremities; joint fluid
Streptobacillus typically around cultures; sero-
moniliformis joints; may logic tests may be
become helpful (fourfold
generalized increase in
antibody titers
between acute
and convalescent
phases)

468
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

Table 60-1 Some Major Diseases Associated with Fever and Rash (Continued)
Morphology Distribution Diagnostic
Disease of Rash of Rash Method Treatment

Epidemic typhus Macules, papules, Axillary folds, Fourfold increase Doxycycline

petechiae trunk, extremities in antibody
(characteristically titers between
the face, palms, acute and
and soles convalescent
are spared) phases
Murine typhus Macules, papules, Begins on inner Fourfold increase Doxycycline
morbilliform rash surfaces of arms in antibody
and axillae; titers between
quickly becomes acute and
generalized, convalescent
involving phases
especially the
trunk (limited
involvement of
face, palms, and
soles)
Acute rheumatic Macules, erythema Erythema margina- Fulfillment of Benzathine
fever marginatum, tum on trunk, Jones’ criteria penicillin G
subcutaneous extremities;
nodules subcutaneous
nodules on
extensor surfaces
near joints
Secondary Macules, papules, Usually generalized, RPR (VDRL) is Benzathine
syphilis mucous patches, with involvement nearly always penicillin G
condylomata lata; of palms and positive in secon-
rash is sometimes soles; sometimes dary syphilis (in
pustular confined to contrast to other
palms and soles stages of
or to face syphilis);
confirmed by
FTA-ABS
(or MHA-TP)
assays; dark-field
microscopy
Herpes zoster Grouped vesicles on Shingles has Tzanck smear or Acyclovir
(shingles and an erythematous dermatomal direct
disseminated base; hemorrhagic distribution; fluorescent
herpes zoster) bullae; in disseminated antibody test
disseminated herpes zoster
form, large ulcers is generalized
and plaques
Babesiosis Petechiae, purpura, Generalized Giemsa-stained Clindamycin
ecchymoses blood smear or and
indirect immuno- quinine
fluorescence
Ehrlichiosis Usually, macules and Trunk Fourfold increase Doxycycline
papules; may be in antibody titers
petechial; diffuse between acute
erythema and convalescent
sometimes phases; indirect
seen immunofluo-
rescence

Continued

469
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

Table 60-1 Some Major Diseases Associated with Fever and Rash (Continued)
Morphology Distribution Diagnostic
Disease of Rash of Rash Method Treatment
Kawasaki disease Erythema (most often, Generalized, Clinical criteria Aspirin; IV
raised, deep red, especially on with exclusion immune
plaquelike erup- trunk and of other globulin
tion; sometimes extremities; etiologies
morbilliform); accentuation in
swelling of perineal area
hands and feet;
involvement of
mucous membranes
(dry, fissured lips,
strawberry tongue;
oropharyngeal
erythema;
conjunctival
suffusion; later,
desquamation)

CT, computed tomography; ELISA, enzyme-linked immunosorbent assay; FTA-ABS, fluorescent treponemal antibody,
absorbed; HIV, human immunodeficiency virus; IgM, Immunoglobulin M; IV, intravenous; MHA-TP,
microhemagglutination–Treponema pallidum; RPR, rapid plasma reagin; VDRL, Venereal Disease Research Laboratory.
From Longshore S, Camisa C. Fever with rash and other skin lesions. In Bryan CS (ed): Infectious Diseases in Primary Care.
Philadelphia, WB Saunders, 2002, pp 181–184.

The fact that systemic symptoms frequently indirect immunofluorescence, complement fixation,
develop before the rash appears is important in con- indirect hemagglutination, or latex agglutination
sidering preventive and early treatment modalities. (Centers for Disease Control and Prevention, 2004● C ).
Rocky Mountain spotted fever should be suspected in In practical terms, the decision to treat the
any patient who presents with a flu-like illness with patient suspected of having Rocky Mountain spot-
headache and who has been in the endemic areas, espe- ted fever should not await the result of a laboratory
cially during the summer. The physician should be par- test. Only on the very rarest of occasions is culture
ticularly suspicious when the patient reports removing from blood or tissue obtained. Complement fixation
a tick. Unfortunately, in the case presented, despite the and microagglutination tests are specific for the
fact that the history of the tick bite was given repeat- disease but lack sensitivity, especially when the
edly, it was ignored, with deadly consequences. The patient has received antibiotic treatment. In the case
overall mortality for an untreated individual may be as described, confirmation of the diagnosis was
high as 30% (Braunwald et al., 2002● C ; Habif, 2004●C ). obtained by immunofluorescent staining of the skin
The mortality is usually higher for individuals who are biopsy specimen.
40 years or older and for African Americans. Most of Treatment in the early phases of the suspected ill-
the delays in initiating appropriate treatment result ness is very effective. Drugs of choice are tetracycline
from failure to recognize the significance of the history and doxycycline. Doxycycline is given in the following
of a tick bite in an endemic area. recommended doses: 100 mg twice daily for adults
The diagnosis must rely on a high degree of sus- and children weighing more than 100 pounds (45 kg)
picion and on familiarity with the clinical presenta- and 2.2 mg/kg twice daily for children weighing less
tion and the epidemiologic criteria for the area. This than 100 pounds. Duration is 7 to 10 days, and in the
case also illustrates the importance of a physician’s severely compromised, the dose may be given par-
asking about and paying attention to a patient’s his- enterally. Tetracycline would still be a reasonable alter-
tory of travel and insect bites, especially when a native. Chloramphenicol is no longer considered
patient presents with a flu-like illness in the summer. appropriate (American Academy of Pediatrics, 2003● C;
When this patient presented to her physician with a Centers for Disease Control and Prevention, 2004● C ).
flu-like illness, thrombocytopenia was noted, but no Given the widespread range of illnesses that can
intervention was initiated. result from tickborne diseases, including Lyme dis-
Laboratory diagnosis is usually confirmed sero- ease, relapsing fever, ehrlichiosis, tularemia, tick fever,
logically with fourfold increases or decreases in anti- and babesiosis, this case also provides an opportunity
body titer between acute and convalescent sera by to consider the control of all tickborne infections.

470
 Chapter 60 Rash and Fever (Rocky Mountain Spotted Fever)

Physicians and local communities should be the longer the tick remains attached, the higher
aware of the prevalence of tickborne infections in the inoculum will be.
their areas. The onset of spring each year should pro- 6. Tick removal should also be taught with an empha-
vide a reminder to everyone to promulgate precau- sis on removing all the mouth parts with curved
tions through the summer. Some specific suggestions forceps or tweezers and avoidance of squeezing tick
include the following (Gubler et al., 1994● C ): body parts. A simple plastic tool called Ticked Off
is now available. It consists of a small plastic spoon-
1. Widespread education, especially in endemic shaped instrument with a V shaped notch cut into
areas by all the media from early spring through the distal part of the spoon. If the mouth parts are
summer. placed in the notch, the tick and all its body parts
2. The avoidance of known tick-infested areas. may be removed with careful pressure and traction
3. Use of protective clothing to cover the arms, legs, (Gubler et al., 1994● C ).
and other exposed areas.
4. Permethrin spray to decrease tick attachment may This case of Rocky Mountain spotted fever
be employed, and tick repellents containing embodies many of the basic principles of modern
diethyltoluamide may also be used to limit expo- family medicine, namely the prevention of a serious
sure to ticks. Great care especially with children illness, the ability to make an early and accurate diag-
should be employed in using diethyltoluamide- nosis and provide effective treatment, and the oppor-
containing repellents. tunity to educate our patients and communities.
5. Regular body checks for tick attachment by peo-
ple who have been possibly exposed in endemic
areas should be performed. Adults should inspect Material Available on Student Consult
themselves and their children’s bodies regularly
Review Questions and Answers about Rocky
for potential tick exposure. The more frequently Mountain Spotted Fever
this is done, the better. It is generally thought that

REFERENCES
American Academy of Pediatrics. 2003 Redbook: Report of Habif T. Clinical Dermatology, 4th ed. St. Louis: Mosby-
the Committee on Infectious Diseases, 26th ed. Elk Grove, Year Book, 2004.● C
IL, American Academy of Pediatrics, 2003, pp 532–534.● C Longshore S, Camisa C. Fever with rash and other skin
Braunwald E, Fauci A, Kasper D, Hauser S, Longo D, lesions: Infectious Diseases in Primary Care. In Bryan CS
Jameson JL. Harrison’s Principles of Internal Medicine. (ed): Philadelphia, WB Saunders, 2002, pp 181–184.● C
Companion Handbook, 15th ed. New York, McGraw- Centers for Disease Control and Prevention. Fatal cases of
Hill, 2002, pp 465–474.● C Rocky Mountain spotted fever in family clusters––Three
Gubler D, Koster F, Legters L, et al. A field guide to animal- states, 2003. MMWR Morb Mortal Wkly Rep
borne infections. Patient Care 1994;28:23–44.● C 2004;53:407–410. Reprinted in JAMA 2004;292:31–33.● C

471
 C h a p t e r

61 Red Area on Left Temple

(Basal Cell Carcinoma)
Mark Andrews

crusting, or drainage is noted. There is no immediate

KEY POINTS family history of similar skin problems.

1. The timed spot freeze technique in cryosurgery is Medical History

useful in the treatment of basal cell carcinoma Mrs. S. has a history of hypertension, for which she is
because it allows standardization of the amount taking lisinopril. She is also taking ibuprofen to man-
of freezing applied to a target lesion, which helps age the symptoms of degenerative joint disease in her
prevent complications and maximize results. knees. She has no history of significant dermatologic
2. Continuous freezing at one location for more problems or recurrent skin infections. She has not
then 30 seconds after an adequate freeze ball taken antibiotics recently. She states she has not been
has formed around the lesion being treated can using new cosmetics or soaps. There is no history of
result in disruption of the collagen matrix of the major previous surgery.
skin with possible scarring.
3. In respect to the “four Cs” of dermatologic Family History
cancer therapy—cure rate, cost, convenience, Mrs. S. has one sister who has multiple health prob-
and cosmetic result—no other technique offers lems but no history of chronic skin problems. Her
so high a cure rate (95% to 98%) at a reason- parents died a number of years ago and their health
able cost, without needles, in a convenient problems are not well known.
physician office setting, and with generally
good cosmetic results.

INITIAL VISIT
Subjective
Patient Identification and Presenting
Problem
Jane S. is a 76-year-old white woman who presents
with a complaint of a puffy red area on her left tem-
ple, noted for the past several months, that seems to
be slowly growing (Fig. 61-1).

Present Illness
Mrs. S. states that the lesion arose gradually as a
small red spot and later became a little larger and ele- Figure 61-1 The timed spot freeze technique demon-
vated. She denies similar rashes, trauma to the area, strated on a superficial nodular basal cell carcinoma on
or previous insect bites. No associated pruritus, pain, the left temple. The lesion is approximately 10 mm.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

472
 Chapter 61 Red Area on Left Temple (Basal Cell Carcinoma)

Social History
Mrs. S. is widowed and has been retired from the Table 61-1 Efficacy of Cryosurgery
accounting field for more than 15 years. She has no Lesion Cure Rate (%)
smoking history and denies alcohol use. There is no
history of illicit drug use. Viral warts (hands) 75
Dermatofibroma 90
Actinic keratosis 99
Review of Systems Bowen’s disease >95
The patient denies fever, chills, pruritus, cough or Basal cell carcinoma >95
cold symptoms, or rash in other body areas. She has Squamous cell carcinoma >95
had no sore throat or localized facial pain.
Modified from Dawber R. Cryosurgery. In Lask G,
Moy R (eds): Principles and Techniques of
Objective Cutaneous Surgery. New York, McGraw-Hill, 1996.

Physical Examination
Mrs. S. is a well-developed, well-nourished, alert solution (Drysol). A Polysporin dressing is applied after
woman. She is not in distress. Her height is 5 feet the procedure. The various options for management of
1 inch, and her weight is 145 pounds. Her tempera- the presumed basal skin cancer are discussed.
ture is 37˚C (98.6˚F), respiratory rate is 16, blood
pressure is 148/84, and pulse is 80. A focused skin Patient Education
examination reveals an approximately round, 1-cm, Mrs. S. is informed of the various treatment options
slightly raised red nodule on the left temple. There is and allowed to select among the reasonable alterna-
no similar skin lesion identified elsewhere. The area tives. Primary excision might be considered first, but
in question is well demarcated and without ulcera- this would require excising an elliptical area approxi-
tion, crusting, or bleeding. On examination with a mately 1.5 to 2 cm by 5 to 6 cm, which is a consider-
hand lens, the tissue is opalescent, with increased able size excision on the temple region for a neoplasm
vascularity and some vessel tortuosity. The area is of fairly low aggressiveness. There is also the option of
nontender, but the raised tissue is firm and palpable. performing electrodesiccation and curettage under
local anesthesia, and finally the option of cryosurgery,
Assessment which offers some compelling advantages, including
lack of prep time and expensive supplies, no need for
Working Diagnosis injection anesthesia, and minimal postprocedural
The working diagnosis, based on clinical appearance infection risk, wound care, or need for suture removal.
and the patient’s history, is an early primary nodular Cure rates are about 97% in experienced hands com-
basal cell carcinoma. Other possibilities in the differ- pared with 98% for primary excision and 99% for
ential diagnosis, although much less likely, include a Mohs’ technique (which is not strictly indicated for
squamous cell carcinoma or—least possible—an small primary basal cell lesions that are well demar-
inflamed seborrheic keratosis. cated and not in areas that are difficult to treat; it is
Seborrheic keratoses tend to have a rougher, more aggressive and costly than needed) (Graham,
gritty surface without inflammation and a more 1994● C , 2001●C ; Kuflik and Gage, 1991●B ) (Table 61-1).
stuck-on appearance with darker pigmentation. On
close observation, small, clear pseudocysts can often
be seen in the body of the lesion.
Squamous cell cancer, on the other hand, is often FOLLOW-UP VISIT
more distorted on the surface and has a greater ten-
dency to ulcerate and crust and invade tissue, except for Subjective
the in situ form (Bowen’s disease), which is indolent Mrs. S. returns for definitive treatment and is con-
and flat and often appears like a chronic fungal or sidering cryosurgical intervention if needed. The
eczematous red patch, occasionally with some crusting. shave biopsy site has healed well, without evidence
of secondary bacterial infection or significant
irritation.
Plan
Diagnostic Objective
The current working diagnostic possibilities are dis-
cussed with Mrs. S. She agrees to undergo a shave Physical Examination
biopsy under local lidocaine anesthesia, with the biopsy Her vital signs are stable and the biopsy site is heal-
performed using a sterilized razor blade and postproce- ing nicely. The minimal crusting is removed easily,
dural hemostasis achieved with aluminum chloride and no ulceration or bleeding is noted.

473
 Chapter 61 Red Area on Left Temple (Basal Cell Carcinoma)

Box 61-1 Skin Care after Cryosurgery

1. Wash skin as usual every day.
2. Do not pull the scab off; do not pull the blis-
ter roof off.
3. Twice a day, clean with mild soap and tap
water. Pat dry and put a thin layer of
Polysporin antibiotic ointment on it.
4. If it is oozing a little, you may put a bandage
over it.
5. If it stays really sore, is red all around or
draining pus—or if things just don’t seem
right—call your doctor.

obtained. The perimeter of the basal cell cancer is out-

lined with a surgical marking pen, and then 5 mm fur-
ther out a perimeter is also marked for delineating the
outer border of the eventual freeze halo (Fig. 61-2).
The liquid nitrogen spray is then begun using a timed
spot freeze technique with the gun 1 cm away from the
center of the lesion. The spray is continuously admin-
Figure 61-2 The lesion with an appropriate margin of istered until the freeze zone extends to the outer
normal skin outlined, about 5 additional millimeters. marked margin of the halo zone, and then the spray is
pulsed to maintain the freeze area for 30 seconds
Laboratory Tests (Fig. 61-3). The freezing is then stopped and the area is
Her biopsy result reveals histologic changes consistent allowed to completely thaw over 3 to 4 minutes. The
with a nodular basal cell carcinoma, with the tumor process is repeated once for a total of two complete
extending to the bottom of the shave specimen. freeze-thaw cycles (Graham, 2001● C ; Kuflik and Gage,
1991● B ). The treatment at this point is complete.
Follow-up care instructions are given to the patient
Assessment (Box 61-1). Cosmesis with cryosurgery is quite satis-
Mrs. S. has a small, localized, superficial but nodular- factory compared with the cosmetic effect remaining
type basal cell carcinoma of the left temple area. after other treatment modalities (Fig. 61-4). Common
side effects are hypopigmentation (more of a concern
in darker pigmented individuals), hair loss, and slightly
Plan
Therapeutic
The cryosurgery option for management is again dis-
cussed with the patient, and informed consent is

Figure 61-4 Follow-up image of treatment site healing

Figure 61-3 Freezing with the cryogun. at 5 months.

474
 Chapter 61 Red Area on Left Temple (Basal Cell Carcinoma)

Table 61-2 Contraindications to Cryosurgery

Absolute Contraindications
Proven sensitivity or adverse reaction to cryosurgery
Melanoma
Areas of compromised circulation
Sclerosing basal cell or recurrent basal cell/squamous cell carcinoma, particularly in high-risk areas
(temples, nasolabial groove)
Patient nonacceptance of potential pigment changes
Lesions in which tissue pathology is required (In these situations biopsy specimens should be obtained
before cryosurgery treatment is undertaken)

Relative Contraindications
Cold intolerance
Raynaud’s disease
Multiple myeloma
Cryoglobulinemia
Collagen and autoimmune diseases
Cold urticaria
Concurrent treatment with immunosuppressive drugs
Pyoderma gangrenosum

Modified from Andrews M. Cryosurgery for common skin conditions. Am Fam Physician 2004;69:2365–2372.

slower initial healing due to the local inflammation Cryosurgery has proved competitive with other
resulting from the freezing process (Heidenheim and techniques in the management of skin cancers such
Jemec, 1991). Scarring is a rare complication of as basal cell and squamous cell carcinomas. It is also
cryosurgery unless continuous freezing at one location commonly used in the treatment of premalignant
is maintained for more then 30 seconds after an ade- lesions and in situ malignancies such as actinic
quate freeze ball has formed around the target area;
longer freezing can result in disruption of the collagen
matrix of the skin and possible scarring (Andrews,
2004 ●C ). Table 61-2 lists contraindications to Table 61-3 Complications and Side
cryosurgery and Table 61-3 lists common side effects. Effects of Cryosurgery
Acute
DISCUSSION Pain
Edema
Blister formation
Although family physicians are not routinely trained
Bleeding (at the freeze site)
in the cryotherapy management of skin cancers, the Syncope (rare––vasovagal)
principles and techniques involved are not complex Headache (after treatment of facial lesions)
or difficult to master. Workshops are offered at a
number of national meetings that will assist clini- Delayed
cians in developing the basic skills needed to begin Infection (rare)
selectively treating more superficial cutaneous Bleeding
malignancies as their experience develops. Excess granulation tissue (rare)
Achieving an adequate, usually 3- to 5-mm, halo
of frozen tissue around a lesion and utilizing a repeat Protracted––Temporary
Hyperpigmentation
freeze-thaw cycle for deeper tumors should yield a cure
Milia
rate of 97% to 99% in appropriately selected tumors Hypertrophic scars
(Graham, 2001● C ; Graham and Clark, 1990● C ). The sur-
Altered sensation
geon’s preoccupation with always obtaining clear tissue
margins with malignant lesions has pervaded training Protracted––Permanent
programs but is not borne out as definitely superior in Hypopigmentation
light of the similar low recurrence rates achieved with Hair and hair follicle loss
cryosurgical techniques. This may be partially attribut- Atrophy (rare)
able to patient selection, but it could also reflect the Modified from Andrews M. Cryosurgery for common
immunologic activation that occurs with inflamma- skin conditions. Am Fam Physician 2004;69:
tion arising from the freezing itself. 2365–2372.

475
 Chapter 61 Red Area on Left Temple (Basal Cell Carcinoma)

keratosis, lentigo maligna, Bowen’s disease, keratoa- 2001● C ; Dawber et al., 1997). Tumors of the ear or nose
canthoma, and actinic cheilitis (Andrews, 2004● C; overlying cartilage or bone respond well, with excel-
Graham, 1994● C ). lent healing. Sclerosing or morpheaform basal cell car-
cinomas, because of their ill-defined margins, should
probably not be treated with cryosurgery. Neither
Tumor Selection
should larger lesions of the scalp and nasolabial folds.
Well-defined or well-demarcated basal cell or squa- Many clinicians avoid cryosurgical treatment of
mous cell carcinomas less than 1 to 2 cm in size and tumors in the lower extremities, particularly in the
3 mm in depth respond most favorably to cryosurgi- elderly, because of issues of delayed healing and higher
cal intervention (Graham, 2001● C ). Superficial spread- rates of wound infections (Dawber et al., 1997).
ing and smaller noduloulcerative basal cell cancer
subtypes are some of the most readily amenable to
treatment with this modality. Squamous cell carci-
noma in situ (Bowen’s disease) and squamous cell car- Material Available on Student Consult
cinoma arising in hypertrophic actinic keratosis,
Review Questions and Answers about Basal
which are less aggressive variants of this type of skin Cell Carcinoma
cancer, are particularly ideal for cryosurgery (Cooper,

REFERENCES
Andrews M. Cryosurgery for common skin conditions. Am Graham G. Cryosurgery in the management of cutaneous
Fam Physician 2004;69:2365–2372.● C malignancies. Clin Dermatol 2001;19:321–327.● C
Cooper C. Cryotherapy in general practice. Practitioner Graham G, Clark L. Statistical analysis in cryosurgery of
2001;245:954–956.● C skin cancer. Clin Dermatol 1990;8:101–107.● C
Dawber R, Cryosurgery. In Lask G, Moy R (eds): Principles Heidenheim M, Jemec GBE. Side effects of cryosurgery.
and Techniques of Cutaneous Surgery. New York, J Am Acad Dermatol 1991;4:653.
McGraw-Hill, 1996. Kuflik EG, Gage AA. The five-year cure rate achieved by
Dawber R, Colver G, Jackson A. Equipment and techniques. cryosurgery for skin cancer. J Am Acad Dermatol 1991;
In Cutaneous Cryosurgery: Principles and Clinical 24:1002–1004.● B
Practice. London, Martin Dunitz, 1997, pp 28–36.
Graham G. Cryosurgery for benign, premalignant, and
malignant Lesions. In Wheeland R (ed): Cutaneous
Surgery. Philadelphia, WB Saunders, 1994.●C

SUGGESTED READINGS
Dawber RPR. Cryosurgery: Complications and contraindi- Usatine R, Moy R. Cryosurgical technique. In Skin Surgery:
cations. Clin Dermatol 1991;8:96–100.●
C A Practical Guide. St. Louis, Mosby, 1998, pp 137–164.●
C
Kuflik EG. Cryosurgery updated. J Am Acad Dermatol Zacarian SA. Cryogenics, the cryolesion and the pathogen-
1994;31:25–44.●B esis of cryonecrosis. In Zacarian SA (ed): Cryosurgery
Luba M, Scott B, Andrew M, Stulberg D. Common benign for Skin Cancer and Cutaneous Disorders. St. Louis,
skin tumors. Am Fam Physician 2003;67:729–738. Mosby, 1985, pp 1–30.● B

476
 C h a p t e r

62 Thorn in Bottom of Foot

(Plantar Wart)
Daniel L. Stulberg

to remove the remaining portion of the thorn but

KEY POINTS was unable to identify or extract any more material.
She now presents to the office to have the area evalu-
1. Warts are an outward sign of an underlying ated and the thorn removed.
viral infection.
2. Warts can be very difficult to treat and have fre- Medical History
quent recurrences. Wendy reports that she is in good health. She had her
3. Wart expression varies based on the host’s appendix removed at age 12 and had a tubal ligation
immune defenses, and treatment can be even after the birth of her fourth child. She reports that
more difficult with a compromised host. she had routine childhood illnesses but no hospital-
4. Less invasive treatments are most prudent, as in izations other than for childbirth.
most patients the warts will eventually sponta-
neously resolve albeit slowly and unpredictably. Family History
5. Topical salicylic acid preparations have the best Wendy’s parents are both alive and in good health.
evidence for effect in the treatment of warts. Her maternal grandfather had a long history of type
2 diabetes and died of a myocardial infarction at the
age of 72. Her paternal grandmother is a survivor of
postmenopausal breast cancer.
INITIAL VISIT
Health Habits
Subjective Wendy is a nonsmoker and drinks no alcohol. She
walks regularly for exercise but notes that this has
Patient Identification and Presenting become difficult due to the pain in her foot.
Problem
Wendy R. is a 32-year-old woman who presents with Medications
the chief concern of a thorn in the bottom of her foot. Wendy takes multivitamins.

Present Illness Social History

Wendy reports that approximately 4 weeks ago she Wendy is married and a full-time homemaker with
had been pruning Pyracantha bushes in her yard. four school-age children. She is very active in her
The following day she went outside barefooted and community.
stepped on a thorn from the trimmed branches.
With some difficulty, she used a razor blade, needle, Review of Systems
and tweezers to remove what she thought was the Wendy reports that she has not purchased any new
whole thorn from the bottom of her right foot. Two shoes in the past 6 months, and her shoes are in good
weeks later, after the initial inflammation and pain condition. She denies arthritis, arthralgias, or history
had subsided, she noticed that the area of the wound of foot fractures. She gets dry skin in the winter, which
had thickened skin and was not returning to a nor- responds to moisturizers. The only other skin concern
mal appearance. She again attempted home surgery she has had was warts when she was in grade school.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

477
 Chapter 62 Thorn in Bottom of Foot (Plantar Wart)

Objective Plan
Physical Examination Diagnostic
Wendy’s vital signs are all within normal limits. She The physical examination and the paring down of the
is alert and appropriately and neatly dressed. lesion as noted above make the diagnosis. No viral
Examination of her skin reveals several benign- cultures, biopsy, or other laboratory testing is indi-
appearing moles on the trunk. Both of her heels have cated.
some thickening overlying the Achilles tendons. The
plantar surface of her right foot is notable for a raised Therapeutic
7-mm lesion just lateral to the fifth metatarsal head. Multiple treatment modalities are available for the
There is slight irregularity and peeling of the epider- destruction of warts. Treatment decisions are based on
mis at that site with diminished normal skin lines. It patient age, location, extent, pain tolerance, risk of scar-
is firm to the touch, with no erythema, warmth, fluc- ring, inconvenience, and patient’s desires. Cryotherapy
tuance, or drainage. Direct pressure causes moderate can lead to blistering, which could increase the patient’s
discomfort. There are no other skin lesions of note. discomfort when walking. After a thorough discussion
of the options, Wendy chose over-the-counter topical
Laboratory Tests salicylic acid applied at bedtime after soaking the lesion
No radiographic or laboratory testing is done at the for 10 minutes. The soaking facilitates penetration of
time of visit. A no. 15 blade scalpel is used to shave the salicylic acid. Peeling away the dead skin can also aid
down the thickened lesion, revealing multiple pin- in the local tissue destruction.
point bleeding spots.
Patient Education
Assessment Warts are the outward sign of a viral infection by the
human papillomavirus (HPV). The virus can be
Working Diagnosis passed from person to person via direct contact or
Plantar wart, based on the location, symptoms, and from contact with a contaminated surface. After infec-
clinical appearance. There is no evidence of bacterial tion, the virus lives inside the body and can cause char-
infection or remaining foreign body to justify a acteristic thickening of the skin, resulting in a wart.
wound exploration. Over-the-counter salicylic acid liquids or
patches are reasonably effective for destroying the
Differential Diagnosis wart but will not take away the viral infection.
1. Foreign body reaction due to retained thorn. The Therefore, warts can recur later in life in the same or
history pointed the patient in this direction, different areas. Over-the-counter topical treatment
but clinical examination failed to support this usually takes weeks to months to work.
diagnosis. The inflammatory nature of wood Warts will often go away without treatment,
leads to erythema, fluctuance, and even purulent explaining why so many odd “folk remedies” are
drainage subacutely when it is retained as a for- reported to work.
eign body. The body’s immune system plays a major role in
2. Granuloma or cyst due to a foreign body. This whether people have warts. That is why people with
would be a similar possibility but would more human immunodeficiency virus or those taking
likely present later and with deeper findings. immunosuppressant drugs often develop warts and
3. Callus. In response to excessive pressure, recur- have a hard time getting rid of them.
rent friction, or poorly fitting shoes, the normal Physicians can use many different procedures to
response is to develop a very thickened epider- destroy warts but there is always the chance of recur-
mis in the affected area. Factors incongruous rence.
with this diagnosis are the diminished normal
skin lines and the pinpoint bleeding spots Disposition
revealed on paring the lesion. Wendy was advised to follow up at the clinic if the
4. Corn. As the result of an underlying bony promi- wart did not clear up in 2 to 3 months with daily
nence, there can be excessive callous response application of salicylic acid or if she desired more
and even erosions. This patient has no signifi- aggressive treatment.
cant bony abnormalities.
5. Skin cancer. Squamous cell cancers can some- FOLLOW-UP VISIT
times develop in warts or appear verrucous. This
lesion was not present long enough to suggest Subjective
malignancy; however, if it does not respond to
therapy as anticipated, then a biopsy would be Wendy is seen 2 months after her initial visit. She
prudent. reports using the salicylic acid daily for 1 month

478
 Chapter 62 Thorn in Bottom of Foot (Plantar Wart)

with mild improvement but no resolution of her bly higher, as cells can be infected asymptomatically
wart. She then became discouraged and stopped and the latency period between infection and the dis-
treatment. She states that the wart is back to its play of disease can be as long as 6 months. In general,
previous size and is causing increasing pain with warts are rarely present in infancy, have a peak inci-
walking. dence in the teen years, and then become less com-
mon with age.
Objective Warts are benign neoplasms of the epidermis
caused by the HPV. The virus is a double-stranded
Examination of Wendy’s foot again shows a thick- DNA virus that infects the keratinocytes, causing
ened, firm epidermal lesion without any evidence of hyperproliferation and mass effect. The mass is con-
bacterial infection. She has no other significant skin fined to the epidermis, although it may appear to
lesions and no indications of other systemic illnesses. invade the dermis because of downward displacement
(Habif, 2004●C ). The category of warts is often further

Assessment subdivided into common warts, filiform warts, flat

warts, and plantar warts. More than 80 types of HPV
Plantar wart with no significant improvement. have been characterized (Gibbs, 2004● B ). Most often,
HPV types 1 and 2 are responsible for common and
Plan plantar warts. HPV types 2, 4, and 27 have also been
implicated in common warts (Gibbs, 2004● B ).
Diagnostic
Since her examination and history indicate no risk
Common Warts (Verruca Vulgaris)
factors or indications of an immune system problem,
no laboratory testing is indicated. Common warts typically present as flesh-colored
papules, starting out as small, pin-sized papules rep-
Therapeutic resenting discrete hyperkeratosis. They gradually
Multiple treatment options are discussed with evolve over a period of weeks to months to rough
Wendy, including cryotherapy, curettage with elec- gray, brown, or black dome-shaped, solitary nodules
trodesiccation, injection with bleomycin, application or clusters, often with black dots on their surface
of duct tape, laser destruction, or local injection with (Fig. 62-1). These black dots are thrombosed capil-
Candida albicans antigen. Wendy chooses to have her laries. Warts also obscure normal skin lines, which is
wart injected with Candida albicans antigen, which is an important diagnostic feature (Habif, 2001● C)
based on the theory that it will induce an immune (Fig. 62-2).
system reaction locally to the antigen. The warty
tissue gets caught up in the associated immune Treatment
response and is gradually destroyed. Two thirds of common warts resolve spontaneously
within a 2-year period. Nongenital warts in the
Patient Education immunocompetent person are usually harmless and
Treating warts can be a very frustrating and time- medically require no treatment unless associated
consuming process. Multiple treatments may be with pain or disfigurement, which is rare. Still,
tried before the wart resolves either from the treat- patients often seek treatment because of the social
ment or spontaneously. Many warts will disappear
on their own within 1 to 2 years.

Disposition
Wendy is advised to follow up in 2 to 3 months if the
wart persists, sooner if there are any signs of infec-
tion, increased pain, or other complaints.

DISCUSSION
Wendy’s diagnosis of plantar wart is common in
family medicine. Prevalence studies have yielded
conflicting results, but most data suggest that at any
given time approximately 5% of the population has
warts, with estimates of occurrence in the school-age
population reaching as high as 24% (Allen, 2000● B ).
The incidence of true infectivity with HPV is proba- Figure 62-1 Wart with thrombosed capillaries.

479
 Chapter 62 Thorn in Bottom of Foot (Plantar Wart)

A clinical trial comparing the local application

of duct tape with cryotherapy in the treatment of
common warts suggested that occlusion with duct
tape for 6 of 7 days for as long as 8 weeks was as effec-
tive or more effective in the short-term cure of the
common wart (Focht, 2002● B).
Other treatments for common warts that are pos-
sibly effective include the daily application of mild cor-
ticosteroid cream under an occlusive dressing,
electrosurgery after local anesthesia, and, in adults, oral
vitamin A 50,000 U/day for no longer than 3 months
(contraindicated in pregnancy) (Sauer, 1996● C ).

Flat Warts (Verruca Plana)

These typically present as pink, light brown, or yel-
low papules that are relatively flat in appearance and
Figure 62-2 Wart displacing normal skin lines. typically do not exceed 3 to 4 mm in diameter. They
sometimes occur in clusters of 20 to 30 or more and
most often are found on the dorsum of the hand, the
stigma associated with warts and find themselves forehead, and the beard area.
having to choose from a wide selection of over-the-
counter or physician-recommended treatment Treatment
options (Gibbs, 2004● B). Groups of flat warts can sometimes be successfully
First-line treatments for the common wart treated with tretinoin cream 0.025% to 0.1%. This is
include topical salicylic acid and cryotherapy with the preferred method when treating facial warts
liquid nitrogen. Wendy opted for topical salicylic because of its low risk of scarring. Isolated lesions
acid as her first treatment choice. Therapy with can be treated by cryotherapy.
topical solutions containing salicylic acid is clearly
superior to treatment with placebo (Gibbs, 2004● B ).
Plantar Warts (Verruca Plantaris)
Typically, a 17% over-the-counter solution is
applied daily until the wart disappears. This requires Plantar warts occur on the soles of the foot along pres-
not only diligence but patience, as it can take weeks sure points such as the heel or the metatarsal heads
to months, even with consistent application. (Fig. 62-3). Paring back the epidermal hypertrophy of a
Efficacy is enhanced by paring the superficial layers plantar wart produces a surface studded with black dots
of the wart with a scalpel, pumice stone, or sand- (thrombosed capillaries) that bleed with deeper
paper (emery board) as well as occlusion by a debridement (Fig. 62-4), whereas paring a simple callus
nonpermeable membrane. The 40% films or plaster or corn often produces a pale, translucent central core.
(Duofilm, Mediplast) are cut to the exact size of the
wart and then left in place for 48 to 72 hours. They Treatment
are applied weekly until the wart disappears. Treatment of plantar warts is not necessary unless the
Efficacy is again improved by paring the wart before warts are painful and result in disability. Wendy initially
treatment and between applications of the topical underwent treatment with salicylic acid. Additional
patches. The films can be used on common warts treatment options could include cryotherapy or blunt
and are particularly effective on solitary plantar dissection, which is often used by podiatrists. However,
warts (Barone, 2000● C ). when choosing a treatment option for plantar warts,
Cryotherapy with liquid nitrogen is also a com- physicians should seek therapies that limit any scarring
mon treatment method. Liquid nitrogen can be or inflammation to reduce subsequent disability.
applied to the surface of a wart through direct appli- Wendy next chose local injection with Candida
cation with a cotton-tipped swab or through a spray albicans antigen into the base of her wart (Fig. 62-5).
nozzle mechanism. The goal is a 10- to 15-second It is theorized that local injection of 1:1000 Candida
freeze with a “freeze halo” extending beyond the albicans antigen (the author uses Candin for dermal
margin of the wart by 2 mm. It is less desirable for skin testing, 0.1 mL mixed with 0.9 mL of 1:1,000,000
treatment of periungual warts because postproce- lidocaine, injecting 0.5 mL per wart up to two warts
dure swelling under the nail can be quite painful. It per session and then repeatedly stabs the wart with the
also must be used with caution in the treatment of injecting needle) stimulates a local immune response
plantar warts because the subsequent blistering and resulting in resolution of warts. An unpublished dou-
swelling can make ambulation extremely painful. ble-blind, placebo-controlled trial in 1999 suggested a

480
 Chapter 62 Thorn in Bottom of Foot (Plantar Wart)

Figure 62-5 Injection of plantar wart with Candida albi-

cans antigen mixed with lidocaine.

superior response to antigen when compared with

placebo. Possible complications include potential risk
of stimulating an immunologic response to normal
gastrointestinal tract floral organisms and the poten-
tial risk of triggering a Candida hypersensitivity syn-
drome (Allen, 2000● B ).
Other less common or more invasive treatment
options are sometimes used by other specialties.
Figure 62-3 Plantar wart. Treatment of warts is varied and requires
much patience as well as persistence. Topical, sur-
gical, and oral therapies have all been used with
varying degrees of success. The right treatment
plan for any one patient depends on the partner-
ship between physician and patient in reaching a
common goal. In the vast majority of cases, warts
will resolve spontaneously over the course of
months to years, but achieving earlier resolution
can be even more satisfying for the patient as well
as his or her physician.

Material Available on Student Consult

Review Questions and Answers about Plantar
Warts
Figure 62-4 Thrombosed capillaries after paring.

REFERENCES
Allen AL. What’s new in human papillomavirus infection. Focht DR. The efficacy of duct tape vs cryotherapy in the
Curr Opin Pediatr 2000;12:365–369.● B treatment of verruca vulgaris (the common wart). Arch
Barone EJ. Skin Disorders: The Academy Collection Quick Pediatr Adolesc Med 2002;156:971–974.● B
Reference Guides for Family Physicians. New York, Gibbs S. Local treatment for cutaneous warts (review).
Lippincott Williams & Wilkins, 2000.●C Cochrane Database Syst Rev 2004;3.● B

481
 Chapter 63 Changing Nevus (Melanoma)

Habif TP. Skin Disease: Diagnosis and Treatment. St. Louis: Stulberg DL, Hutchinson AG. Molluscum contagiosum
Mosby, 2001.● C and warts. Am Fam Physician 2003;67:1233–1240.●
C
Habif TP. Clinical Dermatology: A Color Guide to Diagnosis Verbov J. How to manage warts. Arch Dis Child 1999;
and Therapy, 4th ed. St. Louis, Mosby, 2004.●
C 80:97–99.●
C
Sauer GC. Manual of Skin Diseases, 7th ed. New York,
Lippincott–Raven, 1996.● C

C h a p t e r

63 Changing Nevus (Melanoma)

Cheng-Chieh Chuang

KEY POINTS

1. Early detection of curable primary melanoma enlargement (greater than 6 mm), and eleva-
can be lifesaving for patients, and as a result, tion. These elements are usually referred to as
gratifying to physicians. the “ABCDE” rule of melanoma. Recent change
2. Personal risk factors for melanoma include in a mole in these areas should prompt atten-
light complexion, inability to tan, blond or red tion. Bleeding is a late sign of melanoma and
hair, blue eyes, presence of many pigmented usually portends a poor prognosis.
lesions, and immunocompromised status. The 7. There are several benign lesions that may
presence of many clinically atypical moles, a resemble melanoma. Among these are nevi,
prior history of melanoma, or a family history seborrheic keratoses, angiomas, and dermatofi-
of melanoma confers the greatest risk. bromas. All suspicious lesions should be excised
3. Familial atypical mole syndrome is an autoso- with narrow margins.
mal dominant syndrome characterized by mul- 8. Melanoma is generally classified, on the
tiple nevi and atypical nevi, with significant basis of the tumor’s microscopic anatomy,
risk for development of melanoma. as superficial spreading melanoma, nodular
4. Increased exposure to ultraviolet radiation melanoma, lentigo maligna melanoma, and
(UVA and UVB) is a major environmental con- acral-lentiginous melanoma. There are two
tributor to the risk of developing melanoma. types of local growth in a melanoma: radial
5. About half of melanomas develop de novo, and vertical.
the others from an existing lesion. Although 9. Breslow’s depth of invasion number is the thick-
nevi can be precursors to melanomas, they ness in millimeters from the top of the granular
more often indicate an increased risk; the cell layer or base of superficial ulceration to the
greater the number of nevi, the greater the deepest part of the tumor, and is the most
risk for melanoma. important prognostic variable.
6. Early signs of melanoma include asymmetry, 10. The presence of histologic ulceration places the
border irregularity, color variation, diameter tumor in a later stage.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

482
 Chapter 63 Changing Nevus (Melanoma)

Habif TP. Skin Disease: Diagnosis and Treatment. St. Louis: Stulberg DL, Hutchinson AG. Molluscum contagiosum
Mosby, 2001.● C and warts. Am Fam Physician 2003;67:1233–1240.●
C
Habif TP. Clinical Dermatology: A Color Guide to Diagnosis Verbov J. How to manage warts. Arch Dis Child 1999;
and Therapy, 4th ed. St. Louis, Mosby, 2004.●
C 80:97–99.●
C
Sauer GC. Manual of Skin Diseases, 7th ed. New York,
Lippincott–Raven, 1996.● C

C h a p t e r

63 Changing Nevus (Melanoma)

Cheng-Chieh Chuang

KEY POINTS

1. Early detection of curable primary melanoma enlargement (greater than 6 mm), and eleva-
can be lifesaving for patients, and as a result, tion. These elements are usually referred to as
gratifying to physicians. the “ABCDE” rule of melanoma. Recent change
2. Personal risk factors for melanoma include in a mole in these areas should prompt atten-
light complexion, inability to tan, blond or red tion. Bleeding is a late sign of melanoma and
hair, blue eyes, presence of many pigmented usually portends a poor prognosis.
lesions, and immunocompromised status. The 7. There are several benign lesions that may
presence of many clinically atypical moles, a resemble melanoma. Among these are nevi,
prior history of melanoma, or a family history seborrheic keratoses, angiomas, and dermatofi-
of melanoma confers the greatest risk. bromas. All suspicious lesions should be excised
3. Familial atypical mole syndrome is an autoso- with narrow margins.
mal dominant syndrome characterized by mul- 8. Melanoma is generally classified, on the
tiple nevi and atypical nevi, with significant basis of the tumor’s microscopic anatomy,
risk for development of melanoma. as superficial spreading melanoma, nodular
4. Increased exposure to ultraviolet radiation melanoma, lentigo maligna melanoma, and
(UVA and UVB) is a major environmental con- acral-lentiginous melanoma. There are two
tributor to the risk of developing melanoma. types of local growth in a melanoma: radial
5. About half of melanomas develop de novo, and vertical.
the others from an existing lesion. Although 9. Breslow’s depth of invasion number is the thick-
nevi can be precursors to melanomas, they ness in millimeters from the top of the granular
more often indicate an increased risk; the cell layer or base of superficial ulceration to the
greater the number of nevi, the greater the deepest part of the tumor, and is the most
risk for melanoma. important prognostic variable.
6. Early signs of melanoma include asymmetry, 10. The presence of histologic ulceration places the
border irregularity, color variation, diameter tumor in a later stage.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

482
 Chapter 63 Changing Nevus (Melanoma)

INITIAL VISIT Assessment

The diagnostic assessment is atypical nevus or
Subjective melanoma with recent changes.
History of Present Illness This patient possibly has familial atypical nevi
Ms. M. is a 40-year-old sales representative whose syndrome. She has many nevi, several of which are
sister, while applying sunscreen for her on the beach, atypical. Her family history of skin cancer (though
noticed a mole that had changed in color. type unknown) and increasing numbers of nevi
Ms. M. and her sister have spent summers by the since adolescence also point to this possibility.
ocean every year since childhood. They use a lot of
sunscreen with an SPF of 30 because their skin burns Plan
very easily. Ms. M. has always had moles, especially
on her back, since her teenage years. Other than this The mole is excised with a narrow margin and sent
finding, the review of systems is negative. for pathologic examination.

Family History
Both parents had skin cancer, although the types are FOLLOW-UP VISIT
unknown.
The pathology report suggests superficial spreading
Medical History melanoma with Breslow’s thickness of 0.6 mm with-
The patient’s medical history is negative. out ulceration. The margin is reported to be free of
tumor cells.
A second excision with the margin of 1 cm is
Objective
performed, with the pathologist reporting margins
Physical Examination free of tumor cells.
The patient has blond hair and blue eyes. She has The patient’s answers to a review of systems
multiple lentigines on sun-exposed areas. There are focusing on symptoms in Table 63-1 are negative. A
many nevi ranging from 2 to 7 mm on her body, full physical exam does not suggest any signs of
mostly on her upper trunk. There are at least 40 nevi metastasis (Johnson et al., 2000● C ).
on her back alone, 4 of which appear atypical, With the information that Ms. M.’s mother also
including the lesion in question. The mole in ques- has a history of melanoma, it was possible to make a
tion is on the right upper back near the axilla. It is clinical diagnosis of familial atypical nevi syndrome
asymmetric in shape, slightly raised, about 7 mm in for Ms. M.
diameter, with an irregular border and variation of Ms. M. is instructed on self-examination of her
dark pigmentation within. There is neither ulcera- skin using the ABCDE rule (Table 63-2). She is
tion nor bleeding. No axillary lymphadenopathy is advised that she should never sunbathe and never do
found. outdoor work without appropriate clothing and

Table 63-1 Review of Systems for Visceral Melanoma Metastases

Constitutional Hepatic Paralysis Skin
Weight loss Abdominal pain Local weakness Color change
Fatigue Jaundice Easy bruising
Malaise Musculoskeletal New pigmented
Fever Neurologic Bone pain skin lesion(s)
Decreased appetite Headache Nonhealing/bleeding
Weakness Focal CNS symptoms Gastrointestinal skin lesion(s)
Balance problems Cramping
Respiratory Memory disturbance Anorexia Lymphatics
Cough Visual disturbances Abdominal pain Lumps
Chest pain Blackouts Vomiting “Swollen glands”
Hemoptysis Depression Bleeding
Dyspnea Seizures Constipation
Pneumonia Numbness Nausea
Pleurisy Mood swings
CNS, central nervous system.
Adapted from Johnson TM, Chang A, Redman B, et al. Management of melanoma with a multidisciplinary
melanoma clinic model. J Am Acad Dermatol 2000;42:820–826.

483
 Chapter 63 Changing Nevus (Melanoma)

Table 63-2 ABCDE Rule of Melanoma Table 63-3 Risk Factors for Developing
Screening Cutaneous Melanoma
Asymmetry in shape Risk Factor Risk Ratio
Border irregularity
Color haphazardly displayed Personal history of atypical 35
Diameter enlargement in recent time (>6 mm) moles, family history of
Elevation of the lesion melanoma, and more
than 75 to 100 moles
Any of these may be a sign of melanoma. Often it is Previous nonmelanoma 17
not possible to distinguish between an atypical skin cancer
nevus and a melanoma until after biopsy. Congenital nevus >20 cm 5–15
History of melanoma 9–10
Family history of 8
melanoma in first-
sunscreen with an SPF of greater than 30. degree relatives
Photographs of her skin are taken for future com- Immunosuppression 6–8
parison. She is to be followed every 3 months for 3 2–9 atypical nevi without
years. Thereafter she is to be seen every 6 months. family history 4.9–7.3
51–100 nevi 3–5
Ms. M.’s family is advised of their increased risk
26–50 nevi 1.8–4.4
of melanoma, need for everyday sun protection, the Chronic tanning 5.4
ABCDE rule of screening (see Table 63-2), and regu- with UVA, treatment with
lar screening exams with a physician. Specifically, PUVA
those family members found to have atypical nevi Up to three repeated 1.7–3.8
are to be checked every 6 months and those without blistering sunburns
atypical nevi every year. Freckling 3
Fair skin, inability to tan 2.6
One atypical nevus 2.3
DISCUSSION Red or blond hair 2.2
PUVA, oral methoxalen and UVA.
Melanoma is a malignant proliferation of melano- Adapted from Robinson JK. Early detection and
cytes that has the potential to metastasize to any treatment of melanoma. Dermatol Nurs 2000;
organ. Melanomas may originate in skin, eyes, ears, 12:397–402, 441–442.
gastrointestinal tract, leptomeninges, and oral and
genital mucous membranes. This chapter focuses on of melanoma, or a family history of melanoma con-
cutaneous melanoma. Table 63-3 lists risk factors for fers the greatest risk.
developing cutaneous melanomas. Increased exposure to ultraviolet radiation (UVA
In the United States melanoma ranks fifth in inci- and UVB) is a major environmental contributor to
dence of all cancers among men and seventh among the development of melanoma. Intermittent sun
women. It is the most common cancer in women 20 to exposure and severe sunburns, especially during
29 years of age, and it occurs 20 times more com- childhood, are considered more dangerous than
monly in whites than in African Americans. chronic exposure. Certain sunscreens block UVB, the
Individuals at a high risk for melanoma should cause of sunburn, but are not as effective against
be counseled in the primary care setting with UVA, which has also been shown to promote
respect to preventive measures, self-examination, melanoma. Sunscreens such as zinc oxide, titanium
and regular medical surveillance. Because the prog- dioxide, benzophenones, oxybenzones, sulisoben-
nosis of melanoma is related to the depth of the zone, and avobenzone (Parsol 1789), block both UVA
lesion, and examination of the skin is easily and UVB, and are thus more effective at preventing
performed, early detection of curable primary the development of melanoma.
melanoma can be lifesaving for patients, and as a Some studies suggest that PUVA (oral methox-
result, gratifying to physicians. alen and UVA) treatment for various skin conditions
including psoriasis confers risk for the development
Risk Factors of melanoma. Tanning beds emit UVA, and therefore
their use can be a risk factor.
Personal risk factors for melanoma include light
complexion, inability to tan, blond or red hair, blue
Origin
eyes, presence of numerous nevi, and immunocom-
promised status (Rhodes et al., 1987● A● B ). The pres- Roughly half of melanomas develop de novo, the oth-
ence of many clinically atypical moles, a prior history ers from existing lesions such as benign nevi, atypical

484
 Chapter 63 Changing Nevus (Melanoma)

nevi, or congenital nevi. Although nevi can be pre-

cursors to melanomas, they more often are markers Table 63-4 Differences between Atypical
for an increased risk. The greater the number of nevi Nevi and Common Nevi
present, the greater the risk for melanoma. Atypical Common
Characteristics Nevi Nevi
Identification Distribution Back most Sun-
common exposed
Early signs of melanoma include asymmetry, border Extremities areas
irregularity, color variation, diameter enlargement, Sun-protected Most
and elevation. These elements are usually referred to areas above
as the ABCDE rule of melanoma (see Table 63-2). Female breasts, the waist
Recent change in a mole in these areas should prompt scalp, buttocks,
attention. Bleeding is a late sign of melanoma and groin
usually portends a poor prognosis. Age at onset Appear as normal Absent at
Examination can be done by simple visual nevi at age 2–6 birth,
observation, magnification with a 10× ocular hand years appear
lens, or with a dermatoscope. at age
2–6 years
New nevi Grow in
Benign Lesions That Resemble Melanomas appear uniform
There are several benign lesions that may resemble throughout manner
melanoma: nevi, seborrheic keratoses, angiomas, and life through-
dermatofibromas. A biopsy should be performed on out life
Several
all suspicious lesions. may
appear at
Nevi puberty
Nevi are classified as acquired (benign), congenital,
and atypical. Table 63-4 lists the differences between Size Usually >5 mm Usually
<6 mm
benign and atypical nevi.
Shape Irregular Round and
Acquired Nevi Acquired nevi, also known as benign symmetric
nevi, usually appear after 6 months of age (Color Plates Color Variable within Uniform
63-1 to 63-8). Most are less than 5 mm in diameter. a single lesion within a
They may be junctional, compound, or dermal nevi. single
A junctional nevus is located at the dermoepi- lesion
dermal junction and tends to be flat. When some
nevus cells of a junctional nevus migrate to the der-
mis, the nevus becomes a compound nevus. Dermal
nevi are the result of complete migration of nevus usually larger than 5 mm, irregularly pigmented and/
cells into the dermis and tend to be elevated. or irregularly shaped, and tend to appear in puberty
Shave excision, or simple excision with suture or later rather than in childhood. In contrast to com-
closure, can be done for nevi that do not appear sus- mon nevi (acquired or congenital), atypical nevi
picious. Small dark spots within nevi may be continue to develop after the fourth decade. They
melanoma. Biopsy with excision should be per- may appear on the scalp, buttocks, and breasts, in
formed on all suspicious-appearing nevi. addition to sun-exposed areas.
Atypical nevi are a risk factor for melanoma and
Congenital Nevi Congenital nevi are present at birth can be precursor lesions to melanomas. At present
(Color Plates 63-9 to 63-11). The malignant poten- there are no data available on the effect of prophy-
tial of congenital nevi may be dependent on the lactic removal on decreasing risk for melanoma.
depth of penetration of the nevus cells into the der- Familial atypical mole/nevi syndrome is an
mis and subcutaneous tissues. Cells of larger nevi autosomal dominant syndrome characterized by
tend to penetrate deeper and are thus more prone to multiple nevi and atypical nevi, with significant risk
become malignant. for development of melanoma.
Table 63-4 lists general differences between
Atypical Nevi Atypical nevi are also known as dys- common nevi and atypical nevi.
plastic nevi, or atypical moles (Naeyaert and
Brochez, 2003●A●B ) (Color Plates 63-12 to 63-17). Other Melanocytic Lesions Halo nevus is a com-
They may be familial or sporadic. Atypical nevi are pound or dermal nevus with a white border. The

485
 Chapter 63 Changing Nevus (Melanoma)

average age of onset is 15 years. Lymphocytic compression with two fingers produces a retraction
involvement is associated with the depigmentation or “dimple” (retraction or dimple sign). Treatment
and development of the halo. A symmetric halo sur- can be either by cryotherapy or excision.
rounding a typical nevus rarely requires removal
except for cosmetic reasons (Color Plate 63-18). Freckles
Spitz nevus is most common in children. Freckles are also known as ephelides. They are asso-
Though known as benign juvenile melanoma, it ciated with sun exposure and fade without it. They
should be removed for microscopic examination, also decrease with age. The tendency to have freckles
because the clinical and histologic appearances are is an autosomal dominant trait. Treatment and pre-
similar to melanoma (Color Plate 63-19). vention are with sunscreen.
Labial melanotic macules are brown macules on
the lower lip most commonly found in women. Lentigines
Similar lesions can occur in the vulvar region and Lentigines, also known as liver spots, range from 2 to
glans penis, and are more common in dark-skinned 20 mm in diameter (Color Plate 63-28). They occur
persons. They are benign if not atypical in appear- in sun-exposed areas and increase with age. Lenti-
ance. Cryotherapy or laser surgery may be performed gines are the predominant component of photo-
for cosmetic reasons. aging in people of Chinese and Japanese descents.
Cryotherapy, topical retinoids, tazarotine cream,
Seborrheic Keratoses and/or hydroquinone can be used for treatment.
Seborrheic keratosis is the most common of the benign
epithelial tumors (Color Plates 63-20 and 63-21). It
Classification of Melanomas
tends to appear after the age of 30 and is hereditary.
Lesions start as macules and become more pigmented, Based on the microscopic anatomy of the tumor,
taking on a “stuck-on” appearance in the form of a melanoma is generally classified as superficial spread-
plaque. Later on the surface becomes “warty.” Horn ing melanoma, nodular melanoma, lentigo maligna
cysts on the surface are plugged follicles and are virtu- melanoma, and acral-lentiginous melanoma. There
ally pathognomonic of the lesion. Treatment for non- are two types of local growth in a melanoma: radial
suspicious lesions is with electrocautery or cryotherapy. and vertical. Radial growth confines the neoplastic
melanocytes in the basal layer of the epidermis, and
Angiomas the tumor for the most part spreads horizontally
Cherry angiomas usually appear in the third decade along the plane of the skin. The lesion usually pre-
of life and increase in number (Color Plates 63-22 sents as a macule or a patch. The melanocytes in the
and 63-23). They are made up of many moderately vertical growth phase invade deeper than the basal
dilated capillaries. Apart from cosmetic concerns, layer of the epidermis into the dermis and/or the sub-
they are of no clinical consequence. Sometimes they cutaneous layer, and the lesion more often presents as
can mimic melanoma in appearance. Treatment is by a papule or a nodule than as a macule. Vertical growth
electrocoagulation or laser coagulation for small in general confers much greater risk for metastasis.
lesions, excision for large ones. Table 63-5 lists the distinguishing characteristics of
the different melanomas.
Dermatofibromas
Dermatofibromas are common button-like dermal Superficial Spreading Melanoma
nodules of variable colors appearing mostly on the Superficial spreading melanoma constitutes 70% of
extremities (Color Plates 63-24 to 63-27). Pigmented melanomas (Color Plate 63-29). Although it can
versions may be confused with melanoma. Lateral occur anywhere, the most common site is on the

Table 63-5 Types of Melanomas

Superficial Lentigo Maligna
Spreading Nodular Melanoma Acral-Lentiginous

Percentage of all 70% 15% to 20% 4% to 15% 30% to 75% in

melanomas nonwhites
2% to 8% in
whites
Location Trunk in both Trunk and legs Head, neck, and Palms, soles, under
sexes, legs in trunk (sun-exposed nail plates
women areas)

486
 Chapter 63 Changing Nevus (Melanoma)

upper back of both sexes and the legs of women. It is important prognostic factor, this number is essential
characterized by irregular radial growth and usually for the evaluation and management of melanoma
is larger than 6 mm in diameter. It often begins as a (Negin et al., 2003●A●B)
flat or elevated brown lesion and evolves into black, The presence of histologic ulceration is the sec-
blue, red, or white colors. ond most important prognostic factor. It places the
tumor in a later stage.
Nodular Melanoma Clark levels, which indicate the anatomic depth
Nodular melanoma occurs most often in the fifth of tumor invasion, do not seem to provide as good a
and sixth decades of life (Color Plate 63-30). The fre- correlation with prognosis as Breslow’s thickness,
quency of nodular melanomas is 15% to 20%, and though they may help differentiate between 1a and
men have twice the risk of women for developing 1b in staging (Kim et al., 2002).
this type of melanoma. It is dome-shaped and grows
rapidly in weeks or months. The nodular appearance Excision after Biopsy
derives from its rapid vertical growth. The entire lesion of the melanoma must be excised
and confirmed by histologic verification. The margin
Lentigo Maligna Melanoma of resection is based on the depth of the tumor
Lentigo maligna melanoma occurs most often in the (Breslow’s number), as listed in Table 63-6. The mar-
sixth and seventh decades of life and makes up 4% to gins for excision for lesions on the face and digits
15% of melanomas (Color Plate 63-31). It occurs on may have to be compromised.
exposed areas, especially the face.
A precursor for this melanoma, melanotic Metastatic Staging
freckle of Hutchinson (also known as lentigo Melanoma tends to metastasize to the lungs, liver,
maligna), is confined to radial growth, may last for and brain.
years, and may never evolve into the vertical growth Sentinel lymph node micrometastasis is consid-
phase to become lentigo maligna melanoma. ered by some to be an important factor for recurrence
Acral-Lentiginous Melanoma and a powerful predictor of survival (Brady and Coit,
Acral-lentiginous melanoma occurs on the palms, 1997● A ). The sentinel lymph node is the first node in

soles, terminal phalanges, and mucous membranes the lymphatic chain that drains the lesion. Biopsy is
(Color Plates 63-32 to 63-35). It accounts for 30% to considered for melanomas with Breslow’s thickness
75% of melanomas in African Americans, Asians, between 1 and 4 mm (Balch et al., 1996● A ). Radio-
’

and Hispanics. In whites, 2% to 8% of melanomas graphic mapping (lymphoscintigraphy) is used pre-

are of this type. The foot is the most common site for operatively to identify the sentinel lymph node.
nonwhites. Periungual spread of pigmentation from Sentinel lymph node biopsy is not indicated if there is
melanoma to the proximal and lateral nail fold is clinically evident notal metastasis. In this case, nodal
called Hutchinson’s sign. dissection is indicated.
Table 63-7 lists the tumor-node-metastasis
Management (TNM) staging system for cutaneous melanoma as
classified by the American Joint Committee on Cancer
Initial Biopsy (Balch et al., 2001●A● B ). Survival rates for melanoma
All suspicious lesions should be excised with narrow TNM and staging categories are listed in Table 63-8.
margins (1–3 mm of normal skin). A wider margin In the TNM system, the T category reflects the
may impede later identification of sentinel node(s). Breslow’s thickness, not the Clark level. The N cate-
When the suspicion is low, when the lesion is too gory reflects the number of metastatic lymph nodes
large, or when it is impractical to perform excision, a discovered either microscopically by sentinel node
punch biopsy through the thickest and darkest part biopsy or macroscopically by physical examination.
of the lesion is done. Repeat biopsy is needed if the
specimen is inadequate for accurate histologic stag-
ing. Incisional biopsy does not affect survival (Bong
et al., 2002●
B ). Table 63-6 Surgical Margins for
Shave biopsy often does not permit Breslow’s Cutaneous Melanoma
depth of invasion measurement and, therefore, is
Tumor Thickness Excision Margins
usually not recommended.
In situ 0.5 cm
Prognostic Factors <2 mm 1 cm
Breslow’s depth of invasion number is the thickness ≥2 mm 2 cm
in millimeters from the top of the granular cell layer From Sober AJ, Chuang Y, Duric M, Guidelines of
or base of superficial ulceration to the deepest part of care for primary cutaneous melanoma. J Am Acad
the tumor. Because tumor thickness is the most Dermatol 2001;45:579–586.

487
 Chapter 63 Changing Nevus (Melanoma)

Table 63-7 Melanoma Tumor-Node-Metastasis Classification

T Classification Thickness (Breslow) Ulceration Status
T1 ≤1.0 mm a: Without ulceration and level
II/III
b: With ulceration or level IV/V
T2 1.01–2.0 mm a: Without ulceration
b: With ulceration
T3 2.01–4.0 mm a: Without ulceration
b: With ulceration
T4 >4.0 mm a: Without ulceration
b: With ulceration

N Classification No. of Metastatic Nodes Nodal Metastatic Mass

N1 One node a: Micrometastasis*
b: Macrometastasis†
N2 Two to three nodes a: Micrometastasis*
b: Macrometastasis†
c: In-transit metastasis(es)/
satellite(s) without metastatic
node(s)
N3 Four or more metastatic nodes,
or matted nodes, or in-transit
metastasis(es)/satellite(s) with
metastatic node(s)

M Classification Site Serum Lactate Dehydrogenase

M1a Distant skin, subcutaneous, or Normal
nodal metastases
M1b Lung metastases Normal
M1c All other visceral metastases Normal
Any distant metastasis Elevated
*
Micrometastases are diagnosed after sentinel or elective lymphadenectomy.
†Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic
lymphadenectomy or when nodal metastasis shows gross extracapsular extension.
From Balch CM, Buzaid AC, Soong SJ. Final version of the American Joint Committee on Cancer staging system
for cutaneous melanoma. J Clin Oncol 2001;19:3635–3648. © 2001 American Society for Clinical Oncology.

The M category represents distant metastasis and the thickness number and the presence of nodal involve-
presence of elevated serum lactate dehydrogenase. ment, guided by a review of systems and a complete
Ulceration in general places the melanoma in a physical examination with attention to the skin,
higher stage. lymph nodes, liver, and spleen, direct the need for lab-
Melanoma in situ is also known as stage 0 oratory tests and imaging studies.
melanoma and is a very early stage in the disease in Individuals with a history of melanoma should be
which the tumor is confined strictly in the epidermis able to perform a self-examination of skin and lymph
in the radial growth phase. It is considered to have nodes. Photographing the skin may be useful. At least
very low potential for disease recurrence or spread to an annual exam with the physician is needed, and the
lymph nodes. follow-up interval depends on Breslow’s thickness.

Initial Diagnostic Workup and Follow-up Medical Treatment

Table 63-9 provides guidelines for initial workup and Besides surgery, chemotherapy is usually not effec-
follow-up visits. tive for melanoma. Interferon alfa-2b (IntronA) was
For lesions less than 4 mm in thickness with neg- approved adjuvent treatment to surgery in patients
ative nodal involvement, chest radiography and blood with high risk of systemic recurrence. Several vac-
work for initial staging or routine follow-up have lim- cine and biologic modifiers are under investigation
ited value for asymptomatic patients but may allevi- for their use in the treatment of metastatic
ate the patient’s anxiety. In general, the Breslow’s melanoma.

488
 Table 63-8 Survival Rates for Melanoma Tumor-Node-Metastasis and Staging Categories
Survival ± Standard Error
Pathologic Thickness No. + Nodal Distant No. of
Stage TNM (mm) Ulceration Nodes Size Metastasis Patients 1-Year 2-Year 5-Year 10-Year

IA T1a 1 No 0 — — 4,510 99.7 ± 0.1 99.0 ± 0.2 95.3 ± 0.4 87.9 ± 1.0
IB T1b 1 Yes or 0 — — 1,380 99.8 ± 0.1 98.7 ± 0.3 90.9 ± 1.0 83.1 ± 1.5
level IV, V
T2a 1.01–2.0 No 0 — — 3,285 99.5 ± 0.1 97.3 ± 0.3 89.0 ± 0.7 79.2 ± 1.1
IIA T2b 1.01–2.0 Yes 0 — — 958 98.2 ± 0.5 92.9 ± 0.9 77.4 ± 1.7 64.4 ± 2.2
T3a 2.01–4.0 No 0 — — 1,717 98.7 ± 0.3 94.3 ± 0.6 78.7 ± 1.2 63.8 ± 1.7
IIB T3b 2.01–4.0 Yes 0 — — 1,523 95.1 ± 0.6 84.8 ± 1.0 63.0 ± 1.5 50.8 ± 1.7
T4a >4.0 No 0 — — 563 94.8 ± 1.0 88.6 ± 1.5 67.4 ± 2.4 53.9 ± 3.3
IIC T4b >4.0 Yes 0 — — 978 89.9 ± 1.0 70.7 ± 1.6 45.1 ± 1.9 32.3 ± 2.1
IIIA N1a Any No One Micro — 252 95.9 ± 1.3 88.0 ± 2.3 69.5 ± 3.7 63.0 ± 4.4
N2a Any No Two to Micro — 130 93.0 ± 2.4 82.7 ± 3.8 63.3 ± 5.6 56.9 ± 6.8
three
IIIB N1a Any Yes One Micro — 217 93.3 ± 1.8 75.0 ± 3.2 52.8 ± 4.1 37.8 ± 4.8
N2a Any Yes Two to Micro — 111 92.0 ± 2.7 81.0 ± 4.1 49.6 ± 5.7 35.9 ± 7.2
three
N1b Any No One Macro — 122 88.5 ± 2.9 78.5 ± 3.7 59.0 ± 4.8 47.7 ± 5.8
N2b Any No Two to Macro — 93 76.8 ± 4.4 65.6 ± 5.0 46.3 ± 5.5 39.2 ± 5.8
three
IIIC N1b Any Yes One Macro — 98 77.9 ± 4.3 54.2 ± 5.2 29.0 ± 5.1 24.4 ± 5.3
N2b Any Yes Two to Macro — 109 74.3 ± 4.3 44.1 ± 4.9 24.0 ± 4.4 15.0 ± 3.9
three
N3 Any Any Four Micro/ — 396 71.0 ± 2.4 49.8 ± 2.7 26.7 ± 2.5 18.4 ± 2.5
macro
IV M1a Any Any Any Any Skin, SQ 179 59.3 ± 3.7 36.7 ± 3.6 18.8 ± 3.0 15.7 ± 2.9
M1b Any Any Any Any Lung 186 57.0 ± 3.7 23.1 ± 3.2 6.7 ± 2.0 2.5 ± 1.5

M1c Any Any Any Any Other visceral 793 40.6 ± 1.8 23.6 ± 1.5 9.5 ± 1.1 6.0 ± 0.9
Total 17,600

SQ, squamous cell carcinoma.

From Balch CM, Buzaid AC, Soong SJ. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol
2001;19:3635–3648. © 2001 American Society for Clinical Oncology.

489
 Chapter 63 Changing Nevus (Melanoma)

Table 63-9 Follow-up Guidelines for Cutaneous Melanoma

History and
Breslow Depth (mm) Physical Exam Radiography/Laboratory

Stage IA Every 6 months for 2 years No

Every 12 months thereafter
Stage I/II Every 4–6 months for 3 years Initial: CXR, optional CBC,
Every 12 months thereafter LFTs
Follow-up: yearly CXR,
optional CBC, LDH
Stage III/IV Every 3–4 months for 3 years Initial: CXR, CT scans; CBC,
Every 12 months thereafter LFTs
Follow-up: every 6–12
months CXR and LFTs
CBC, complete blood count; CXR, chest radiogram; LDH, lactate dehydrogenase; LFTs, liver function tests (lactate
dehydrogenase [LDH], aspartate aminotransferase [AST], alanine aminotransferase [ALT], and alkaline
phosphatase).
Adapted from Robinson JK. Early detection and treatment of melanoma. Dermatol Nurs 2000;12:397–402,
441–442.

Prevention
Material Available on Student Consult
Prevention of melanoma may include avoiding
Review Questions and Answers about Melanoma
excessive exposure to sun and using sunblocks effec-
tive against UVA as well as UVB. Frequent regular
screening of individuals at high risk to detect early
curable lesions is essential.

REFERENCES
Balch CM, Buzaid AC, Soong SJ, et al. Final version of the Kim CJ, Reintgen DS, Balch CM. The new melanoma stag-
American Joint Committee on Cancer staging system for ing system. Cancer Control 2002;9:9–15.
cutaneous melanoma. J Clin Oncol 2001;19:3635–3648.●A●B Naeyaert JM, Brochez L. Clinical practice. Dysplastic nevi.
Balch CM, Soong SJ, Bartolucci AA, et al. Efficacy of an N Engl J Med 2003;349:2233–2240.● A●
B
elective regional lymph node dissection of 1 to 4 mm Negin BP, Riedel E, Oliveira SA, et al. Symptoms and signs
thick melanomas for patients 60 years of age and of primary melanoma: Important indicators of Breslow
younger. Ann Surg 1996;224:255–263.● A depth. Cancer 2003;98:344–348.● A● B
Bong JL, Herd RM, Hunter JA, et al. Incisional biopsy and Rhodes AR, Weinstock MA, Fitzpatrick TB, et al. Risk
melanoma prognosis. J Am Acad Dermatol 2002; factors for cutaneous melanoma. JAMA 1987;258:
46:690–694.● B
3146–3154.● A●B
Brady MS, Coit DG. Sentinel lymph node evaluation on Robinson JK. Early detection and treatment of melanoma.
melanoma. Arch Dermatol 1997;133:1014–1020.● A
Dermatol Nurs 2000;397–402,441–442.● A●
B
Habif TP. Clinical Dermatology: A Color Guide to Diagnosis Sober AJ, Chuang TY, Duric M, et al. Guidelines of care
and Therapy. St. Louis, Mosby, 2004, pp 773–813.●C
for primary cutaneous melanoma. J Am Acad
Johnson TM, Chang A, Redman B, et al. Management of Dermatol 2001;45:579–586.● A ● B● C
melanoma with a multidisciplinary melanoma clinic
model. J Am Acad Dermatol 2000;42:820–826.● C

SUGGESTED READINGS

Stulberg DL, Clark N, Tovey D. Common hyperpigmenta- Tsao H, Atkins MB, Sober AJ. Management of cutaneous
tion disorders in adults: Part I and Part II. Am Fam melanoma. N Engl J Med 2004;351:998–1012.●
A● B
Physician 2003;68:1955–1968.● C

490
 Color Plate 63-5 Dermal nevus. Flesh colored and
dome shaped.

Color Plate 63-1 Junction nevus. The lesion is slightly

raised, dark, and uniform.

Color Plate 63-6 Dermal nevus. Warty (verrucous) sur-

face.

Color Plate 63-2 Compound nevus. The surface is cov-

ered with uniform brown-black dots.

Color Plate 63-7 Dermal nevus. Polypoid.

Color Plate 63-3 Dermal nevus. Flesh-colored with

surface vessels; resembles basal cell carcinoma.

Color Plate 63-8 Dermal nevus. Pedunculated with a

Color Plate 63-4 Dermal nevus. Dome shaped. soft, flabby, wrinkled surface.

Color Plates 63-1 through 63-35 from Habif TP: Clinical Dermatology: A Color Guide to Diagnosis and Therapy, 4th ed. Philadelphia,
Mosby, 2004, with permission.
Color Plate 63-9 A small congenital nevus has a uni- Color Plate 63-12 Atypical mole. Macular, variable
form cobblestone surface and is covered with hair. pigmentation, ill-defined borders.

Color Plate 63-13 Atypical mole. Macular, complex

pigmentation, notched border.
Color Plate 63-10 Medium-sized congenital nevus.
Pigmentation is variable and nonuniform, but a biopsy
showed all such areas were benign.

Color Plate 63-14 Atypical mole. Macular, variable

pigmentation, fades at border.

Color Plate 63-11 Medium-sized congenital nevus.

The border is irregular and appears notched, but that
characteristic is maintained in a uniform manner
around the entire border.
Color Plate 63-15 Atypical mole. Papular, large lesion.

Color Plate 63-18 Halo nevus. A sharply defined,

white halo surrounds this compound nevus.

Color Plate 63-16 Atypical mole. Macular, papular,

variable pigmentation, irregular border.

Color Plate 63-19 Benign juvenile melanoma (Spitz

nevus). A reddish, dome-shaped nodule that generally
Color Plate 63-17 Atypical mole. “Fried egg pattern,” appears in children.
raised with dark center, macular periphery, pigmenta-
tion fades at border.
 Irregular or smooth surface; Epidermis thickens;
marked papillomatosis causes an immature keratinocytes
irregular surface that retains keratin accumulate

Horn cysts (horn pearls)

Focal keratination occurs

to produce horn cysts

Melanocytes
Melanocytes proliferate and
transfer melanin; color of lesion
deepens from brown to black

Color Plate 63-20 Seborrheic keratosis. Cross-section shows embedded horn cysts.

A B

Color Plate 63-21 Seborrheic keratosis. Lesions are very common on the back; an individual may have numerous
lesions on the sun-exposed back and none on the buttocks.
 Color Plate 63-22 Cherry angioma. Multiple small, red
papules commonly occur on the trunk.

A B
Color Plate 63-23 Angiokeratomas (Fordyce). Multiple red-to-purple papules consisting of multiple small blood
vessels.
Color Plate 63-24 Dermatofibroma. Early lesions have Color Plate 63-27 Retraction sign. Dermatofibromas
a well-defined border with an irregular red surface. retract beneath the skin during attempts to compress
Brown pigmentation may occur at the periphery after and elevate them.
months or years. Pigmentation may extend onto the
lesion but almost never reaches the center. Patients
often suspect melanoma at this stage.

Color Plate 63-25 Dermatofibroma. A typical lesion

on the lower leg that is slightly elevated, round, and
hyperpigmented, with a scaling surface.

Color Plate 63-26 Dermatofibroma. Dermoscopy

reveals a white lacy center surrounded by a uniform B
network.
Color Plate 63-28 Lentigo (liver spots). Brown mac-
ules that appear in chronically sun-exposed areas.
 SUPERFICIAL SPREADING MELANOMA

Initial phase (months to years)

1. Flat, not palpable Brown, brown-black
2. Color variation slight Slight focal blue
3. Indistinguishable from other early melanomas 0 to 0.6 cm Faint red and white

Radial growth phase (months to 10 years) Colors become

1. Border irregular more pronounced
2. Areas of regression appear with angular notching
3. Thick areas appear at about 2.5 cm—herald
onset of vertical phase Angular notching
0.6 to 2.5 cm

Vertical growth phase (months to years) Highly regressed

1. Numerous patterns, depending on degree area
of growth and regression
2. Tumors palpable
Plaquelike elevation at border
Nodules in center
3. Areas of ulceration and scaling

or

Striking contrast
in colors

Blue-gray
Blue-black
Red and white
A

B C
Color Plate 63-29 Superficial spreading melanomas in all stages of development. The small early lesions have
irregular borders, irregular pigmentation, and small white areas indicating regression. The largest tumors show
an accentuation of all of these features.
D E

F G

H I

J K
Color Plate 63-29 Continued
A B

C D

E F

G H

Color Plate 63-30 Nodular melanoma.

A B

C D

E
F

G
Color Plate 63-31 Lentigo maligna melanoma.
Color Plate 63-32 Acral lentiginous melanoma. A large,
dark, flat lesion.

Color Plate 63-34 Acral lentiginous melanoma.

Periungual spread of pigmentation from a melanoma
to the proximal and lateral nail folds is called
Hutchinson’s sign.

Color Plate 63-33 Acral lentiginous melanoma. The

sudden appearance of a pigmented band at the proxi-
mal nail fold is suggestive of melanoma.

Color Plate 63-35 Acral lentiginous melanoma.

Melanoma involving the entire nail bed.
 C h a p t e r

64 Restless Legs Syndrome

Max Bayard

bosacral spine, and nerve-conduction studies.

KEY POINTS According to the patient, all of these were normal.
She has been treated with quinine for nocturnal leg
1. Although restless legs syndrome (RLS) affects cramps, but that was ineffective. She was told by
approximately 10% of the adult population in another physician that she had fibromyalgia. She was
the United States, the vast majority of RLS suf- given amitriptyline (Elavil), but it did not help her
ferers are undiagnosed. symptoms; it seemed to make them a bit worse.
2. Most cases of RLS are primary, but the condi- Occasionally, when the discomfort was very severe,
tion may be secondary to iron deficiency, preg- she has taken hydrocodone; this has eased the pain
nancy, renal failure, spinal cord injuries, or but not completely relieved it. Three months ago, she
medications. was given clonazepam (Klonopin); although this has
3. If RLS is secondary to an underlying disorder, not completely relieved the symptoms, it has
the symptoms may improve or resolve with improved them significantly and has helped her to
treatment of the disorder. fall asleep at night.
4. The diagnosis of RLS is based entirely on the
patient’s history. Medical History
5. First-line medications for the treatment of RLS Wanda has chronic obstructive pulmonary disease
include dopaminergic agents, dopamine ago- (COPD) but has never required hospitalization. She
nists, and anticonvulsants. has gastroesophageal reflux disease. She is hyperten-
sive and has hyperlipidemia. She had ankle surgery
years ago after a fracture. Her medications include
albuterol metered-dose inhaler, hydrochlorothiazide,
INITIAL VISIT montelukast, fluticasone nasal spray, and omepra-
zole.
Subjective
Family History
History of Present Illness Both parents are dead. Her father died of complica-
Wanda is a 58-year-old woman who complains of tions of COPD. Her mother had diabetes and hyper-
pain in her legs for the past 5 years. The pain is tension. Her two brothers have hypertension but are
described as a “discomfort” or as a “crawling” sensa- otherwise healthy.
tion. She has trouble falling asleep because of the
pain and frequently gets out of bed and walks Social History
around, which affords temporary relief. The pain Wanda has smoked one pack of cigarettes per day
bothers her only in the evenings and is particularly since age 15 years. She denies any alcohol use or
uncomfortable when she lies down to sleep. When abuse of recreational drugs. She does not exercise
she awakens in the morning, her legs feel fine. She regularly. She is not currently employed. In the past,
does not experience cramps when walking. She does she worked in a school cafeteria.
not have any leg weakness. She has reported these
symptoms to several doctors over the last 5-year Review of Systems
period and has been evaluated with ankle/brachial She has not had any weight change. She denies symp-
indices, magnetic resonance imaging of her lum- toms of depression or anxiety. She has not had any

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

491
 Chapter 64 Restless Legs Syndrome

chest pains or gastrointestinal complaints. She Legs Syndrome Study Group (IRLSSG). Wanda’s score
becomes short of breath with exertion secondary to is 24, suggesting moderate severity of symptoms.
her COPD, but this is chronic. She denies any
endocrine diseases. Plan
Wanda is given a prescription for gabapentin
Objective (Neurontin). She is instructed to take 300 mg at sup-
Physical Examination pertime. She is encouraged to work on weight loss
Her weight is 215 pounds, and her height is 5 feet and to begin a mild exercise program 3 or 4 times per
1 inch, with a body mass index of 41. Her blood week. She is encouraged to quit cigarettes. Complete
pressure is 142/86. HEENT, neck, cardiac, lung, and blood count (CBC), basic chemistry panel, and fer-
abdominal examinations are all normal. Straight ritin are ordered. She will follow up in 2 weeks.
leg–raise test is negative bilaterally. She has normal
sensation and reflexes. Dorsalis pedis and posterior
tibial pulses are normal bilaterally. She has no FOLLOW-UP VISIT
edema.
Wanda has had marked improvement in her symp-
toms. Her score on the IRLSSG rating scale is 14.
Differential Diagnosis
Weight is unchanged. She is exercising 20 minutes
1. Restless legs syndrome (RLS) is the most likely eti-
per day 3 times a week. CBC results are as follows:
ology of Wanda’s discomfort. Her symptoms
hemoglobin, 11.4; hematocrit, 35; mean corpuscular
occur in the evening and at night. She experiences
volume, 82; and ferritin is 24. Electrolytes are nor-
improvement with activity. The difficulty describ-
mal. Blood urea nitrogen and creatinine are 14 and
ing the sensation is typical in RLS.
0.8, respectively. She is given a prescription for iron
2. Nocturnal leg cramps are sudden, involuntary
supplementation in light of the relatively low ferritin
muscle contractions that typically occur at night.
level. Plans are to continue iron for 3 months and to
The calf muscles are most often affected. These
reassess symptom severity in 1 month.
cramps may last for seconds or minutes, and
occasionally discomfort persists after the cramps.
The affected muscles feel tight. The patient may DISCUSSION
experience relief by dorsiflexion of the foot or by
walking around. Epidemiology
3. Peripheral neuropathies have a number of possi-
ble etiologies, including trauma, mechanical RLS is a common condition. Its prevalence is approx-
nerve compression, endocrine disorders (such as imately 10% of the adult population, and prevalence
diabetes and thyroid disorders), infectious dis- increases with age (Philips et al., 2000● B ). It is more
eases, toxins, and nutritional disorders. Most common in women than in men, and increasing par-
commonly, neuropathies cause sensory symp- ity appears to increase the likelihood of RLS devel-
toms, including burning, tingling, or numbness. oping (Berger et al., 2004● C ). A recent survey reported
Although the pain may be more noticeable at that 24% of adult patients seen in a primary care
night, it is not typically relieved by activity. office had symptoms consistent with RLS (Nichols
4. Peripheral vascular disease is primarily a result of et al., 2003●C ).
atherosclerosis. Risk factors for peripheral vascu- In spite of the high prevalence of RLS, the condi-
lar disease are the same as those for other athero- tion is underdiagnosed. In a survey of 23,052 patients,
sclerotic diseases, specifically hypertension, 2,223 (9.6%) reported weekly RLS symptoms. A sub-
diabetes, hyperlipidemia, and cigarette use. The group of 551 had symptoms that had a significant
dull, cramping pains of claudication usually negative impact on their lives. Of these, 357 (64.8%)
involve the calf muscles, occur with activity, and had reported their symptoms to a physician, but only
improve with rest. 46 (12.9%) reported being given a diagnosis of RLS
5. Akathisia refers to an internal need to move, but it (Hening et al., 2004). The 2001 Sleep in America Poll
is not necessarily associated with discomfort in reported an RLS prevalence of 13% in the adult pop-
the legs. Symptoms are not worse at night. It is ulation, but only 3% of these had actually been diag-
most commonly a side effect of neuroleptic med- nosed with RLS (National Sleep Foundation, 2001● C ).
ications. RLS is associated with significant morbidity.
Patients with RLS report sleep disturbances and day-
time somnolence. Anxiety and depression are com-
Assessment mon in patients with RLS (Sevim et al., 2004● B ). RLS
Severity of RLS symptoms is quantified based on the patients report that the symptoms have a negative
rating scale developed by the International Restless impact on their quality of life (Hening et al., 2004● B ).

492
 Chapter 64 Restless Legs Syndrome

Although most cases of RLS are primary condi-

tions (i.e.. no known underlying pathologic condi- Box 64-1 Terms Used to Describe
tion), RLS may be secondary to certain medical Restless Legs Syndrome
conditions or medications. Iron deficiency, even in Sensations
the absence of frank anemia, may cause RLS. Ferritin
levels less than 50 μg/L have been associated with Creeping
RLS (Sun et al., 1998● B ). Patients with spinal cord Crawling
injuries have a high incidence of RLS. RLS is com- Itching
mon in pregnancy and usually resolves after delivery. Burning
It is extremely common in patients with end-stage Searing
renal failure. Certain medications may exacerbate Tugging
RLS; these include tricyclic antidepressants, selective Indescribable
serotonin reuptake inhibitors, lithium, dopamine Pulling
antagonists, and caffeine (National Heart, Lung, and Drawing
Blood Institute, 2000●C ). Aching
Like water falling
Like worms or bugs crawling under the skin
Pathophysiology Like electric current
RLS is a neurologic movement disorder of unclear Restless
etiology. It appears to be associated with abnormali- Painful
ties in central nervous system dopamine and iron
function. RLS runs in families, suggesting a genetic
component. Although it is a separate entity from Laboratory tests that may identify secondary causes
periodic limb movements of sleep (PLMSs), the of RLS include a serum ferritin and basic chemistry
majority of patients with RLS also have PLMSs. panel.
Treatments for RLS often improve PLMSs. The diagnosis of RLS is made based on the
patient’s history. Physical examination findings and
Clinical Findings laboratory studies may identify an etiology for the
symptoms or other possible diagnoses, but they are
Patients frequently do not report symptoms of RLS, not part of the criteria for the diagnosis of RLS. The
and when they do, it is frequently not diagnosed cor- criteria are listed in Box 64-2. All four criteria are
rectly. The diagnosis may be complicated by the vari- required for the diagnosis (Walters, 1995● C ).
ety of adjectives used to describe the symptoms of The severity of restless legs symptoms can be
RLS. It is not generally described as painful; more quantified by use of the International Restless Legs
often, it is a discomfort. It may be described as an Syndrome Study Group Rating Scale (Box 64-3).
aching, a crawling, an itching, a tingling, a moving This 10-question survey, which is easily adminis-
(of the skin), or a burning (or a number of other tered, has recently been validated (Walters et al.,
similar adjectives). Patients may say, “I just have to 2003● B ). The survey assesses frequency of RLS symp-
move my legs,” or “I don’t know how to explain it.”
Terms patients use to describe RLS symptoms are
listed in Box 64-1 (National Heart, Lung, and Blood
Institute, 2000● C ). It may be extremely severe, causing Box 64-2 Diagnostic Criteria for Restless
the patient to get out of bed and walk around. This Legs Syndrome (Diagnosis
will relieve symptoms to some degree, but only tem- requires all four)
porarily. Frequently, patients report poor sleep qual-
ity, difficulty falling asleep, and daytime somnolence. 1. A compelling urge to move the limbs, usu-
It is important to ascertain the effect of the symp- ally associated with paresthesias/dysesthe-
toms of RLS on the patient’s life. Some patients have sias
symptoms only rarely, whereas others have symp- 2. Motor restlessness as seen in activities such
toms daily. Some patients’ symptoms are severe, as floor pacing, tossing and turning in bed,
whereas others’ are only mild. The decision to use and rubbing the legs
medications to treat RLS is dependent on the effect 3. Symptoms worse or exclusively present at
RLS symptoms have on the patient’s quality of life. rest (i.e., lying, sitting) with variable and
The physical examination and laboratory evalu- temporary relief by activity, and
ation serve to rule out conditions known to cause 4. Symptoms worse in the evening and at night
RLS and other conditions with similar presentations. Adapted from Walters AS. Toward a better defini-
A neurologic examination and vascular examination tion of restless legs syndrome. Mov Disord
of the lower extremities should be performed. 1995;10:634–642.

493
 Chapter 64 Restless Legs Syndrome

Box 64-3 International Restless Legs Syndrome Study Group Severity Scale Questions
1. Overall, how would you rate the RLS discomfort in your legs or arms?
2. Overall, how would you rate the need to move around because of your RLS symptoms?
3. Overall, how much relief of your RLS arm or leg discomfort do you get from moving around?
4. Overall, how severe is your sleep disturbance from your RLS symptoms?
5. How severe is your tiredness or sleepiness from your RLS symptoms?
6. Overall, how severe is your RLS as a whole?
7. How often do you get RLS symptoms?
8. When you have RLS symptoms, how severe are they on an average day?
9. Overall, how severe is the impact of your RLS symptoms on your ability to carry out your daily
affairs, for example, carrying out a satisfactory family, home, school, or work life?
10. How severe is your mood disturbance from your RLS symptoms—for example, angry, depressed,
sad, anxious, or irritable?

Responses and assigned point values:

For questions 1, 2, 4, 5, 6, 8, 9, and 10, the responses and their values are as follows:
Very severe—4 points
Severe—3 points
Moderate—2 points
Mild—1 point
None—0 points

For question 3, the responses and their values are as follows:

No relief—4 points
Slight relief—3 points
Moderate relief—2 points
Either complete or almost complete relief—1 point
No RLS symptoms—0 points

For question 7, the responses and their values are as follows:

6 to 7 days a week—4 points
4 to 6 days a week—3 points
2 to 3 days a week—2 points
1 day a week or less—1 point
None—0 points

Score:
31–40 Very severe
21–30 Severe
11–20 Moderate
1–10 Mild
Adapted from Walters AS, LeBrocq C, Dhar A, et al. International Restless Legs Syndrome Study Group: Validation
of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med
2003;4:121–132.

toms, severity of symptoms, effectiveness of activity ranging from zero to 40. Higher scores are associated
in alleviating symptoms, effect of RLS on sleep and with more severe or frequent symptoms or both.
daytime somnolence, and the impact RLS has on the
patient’s daily activities and mood. Each question has Treatment
a choice of answers corresponding to scores of zero
(representing no symptoms or effect on quality of Secondary Restless Legs Syndrome
life) to four (representing most frequent or severe Patients with RLS who have RLS secondary to
symptoms). The 10 items are totaled, yielding a score another underlying medical condition or medication

494
 Chapter 64 Restless Legs Syndrome

may improve with treatment of the condition or dis- severe primary RLS in adults. All other medications
continuation of the medication. Patients with RLS are used “off-label” (i.e., they are not specifically indi-
who are iron deficient will likely have improvement cated for the treatment of RLS). Patients with mild or
or resolution of their symptoms with iron supple- infrequent symptoms may not need medical treat-
mentation. Patients with end-stage renal disease may ment. Iron supplementation may improve symptoms
have improvement in their symptoms after renal in patients with iron-deficiency anemia, but it is not
transplant. Removal of a causative medication may beneficial in individuals who are not iron deficient.
also improve or eliminate symptoms. Medications used to treat RLS are listed in Table 64-1.

Lifestyle Dopaminergic Agents Levodopa (with carbidopa or

Little scientific evidence concerns the effectiveness of benserazide) has been used for years to treat the
lifestyle interventions on the symptoms of RLS. symptoms of RLS. It is an effective treatment for mild
Although it is more common in obese individuals to moderate symptoms of RLS and improves symp-
and in individuals with sedentary lifestyles, anec- toms rapidly (Benes et al., 1999 ●
A ). Side effects of lev-
dotal reports exist of both easing and worsening of odopa include gastrointestinal upset, insomnia, and
symptoms with exercise. An exercise program has headaches. Levodopa may also cause augmentation of
been shown to be beneficial in RLS/PLMS patients RLS symptoms. Augmentation refers to exacerbation
with spinal cord injuries, but no published studies of symptoms of RLS during the daytime and at other
concern the effectiveness of exercise in individuals times when medication is withheld. This may limit its
without spinal cord injuries (deMello et al., 2004 ● B ). usefulness for patients requiring long-term daily use.
Some patients may find improvement with decreas-
ing their caffeine, alcohol, or cigarette use. Dopamine Agonists Several dopamine agonists have
been found to treat RLS effectively. Pergolide, an ergo-
Medications tamine dopamine agonist, has been shown to be effec-
Several classes of medications are effective in the tive in the treatment of symptoms of RLS and periodic
treatment of RLS. The mainstays of RLS medical leg movements. The PEARLS Study (Pergolide Euro-
treatment are dopaminergic agents and dopamine pean Australian RLS study) demonstrated long-term
agonists, medications normally prescribed for the efficacy of pergolide (Trenkwalder et al., 2004b● A ).
treatment of Parkinson’s disease. Other classes of Ropinirole and pramipexole are nonergotamine
agents that have been effective in relieving the symp- dopamine agonists. In the TREAT RLS 1 Study, ropini-
toms of RLS include opiates, benzodiazepines, and role was associated with rapid improvement in restless
anticonvulsants. Ropinirole (Requip) has recently legs symptoms, sleep quality, and quality of life com-
received FDA approval for treatment of moderate to pared with placebo (Trenkwalder et al., 2004a● A ).

Table 64-1 Medications Used to Treat Restless Legs Syndrome

Medication Starting Dose Side Effects/Disadvantages

Levodopa/ Carbidopa (Sinemet) 25/100 mg Short half-life. Augmentation.

Side effects include GI upset and
headache
Pergolide (Permax) (ergotamine 0.05 mg Side effects include hypotension.
dopamine agonist) Nausea can be severe.
Non-ergotamine dopamine agonist Side effects include nausea,
Pramipexole (Mirapex) 0.125 mg sleepiness, and orthostatic
Ropinirole (Requip) 0.25 mg hypotension. Should titrate
slowly
Opioids Nightly dose varies by Nausea, constipation. Potential for
choice of opioid abuse
Benzodiazepines Daytime sleepiness. Increased risk
Clonazepam (Klonopin) 0.5 mg of falls at night. Potential for
Temazepam (Restoril) 15 mg abuse
Anticonvulsants Side effects include sedation,
Gabapentin (Neurontin) 300 mg gastrointestinal discomfort.
Long-term studies not yet
available

495
 Chapter 64 Restless Legs Syndrome

Pramipexole was effective in treating the symptoms of improvements in symptoms of RLS and periodic
RLS and remained efficacious for more than 2 years leg movements (Happe et al., 2003● B ). Carbam-
(Silber et al., 2003●
B ). Side effects of the dopamine ago- azepine has also been shown to be more effective
nists included nausea, headache, and orthostatic than placebo in treating restless legs discomfort
hypotension. Reports have been noted of augmenta- (Telstad et al., 1984●
A ).
tion occurring with these medications.
Opioids Oxycodone has been demonstrated to
Benzodiazepines Clonazepam has not been shown improve symptoms of RLS and to decrease periodic
to treat the symptoms of RLS. However, it may be leg movements in a small trial (Walters et al., 1993●
A ).
beneficial in patients with RLS, as the hypnotic Small studies of other opioids have shown improve-
effects of clonazepam promote sleep in spite of the ment in symptoms. Side effects of opioids include
presence of symptoms. Adverse effects of clon- nausea and constipation. Opioids also have a poten-
azepam include daytime somnolence and increased tial for abuse.
risk of falls at night. Benzodiazepines also have the
potential for abuse.
Conclusion
Anticonvulsants Patients who do not respond well RLS is a very common disorder associated with sig-
to dopaminergic agents and dopamine agonists, nificant morbidity. The condition is underdiag-
those who have significant side effects, and those nosed. It may be a primary condition, or it may be
with painful restless legs may respond well to anti- secondary to pregnancy, iron deficiency, spinal cord
convulsants. Slow-release valproic acid had similar injury, end-stage renal disease, or certain medica-
efficacy to slow-release levodopa-benserazide in a tions. Treatment of the underlying condition may
small randomized controlled trial (Eisensehr et al., resolve symptoms of RLS. In patients with no appar-
2004● A ). Gabapentin improved sensory and motor ent underlying cause for RLS, medications may sig-
symptoms in patients with RLS; it also reduced nificantly improve the symptoms and quality of life.
quantity of periodic leg movements during sleep
(Garcia-Borreguero et al., 2002● A ). It is an effective
treatment for RLS symptoms in dialysis patients Material Available on Student Consult
(Thorp et al., 2001● A ). In a head-to-head study
Review Questions and Answers about Restless
comparing gabapentin and ropinirole, both med-
Legs Syndrome
ications were found to have similar significant

REFERENCES
Benes H, Kurella B, Kummer J, Kazenwadel J, Selzer R, restless legs syndrome (RLS) in a primary care pop-
Kohnen R. Rapid onset of action of levodopa in restless ulation: The REST (RLS epidemiology, symptoms,
legs syndrome: A double-blind, randomized, multicen- and treatment) primary care study. Sleep Med
ter, crossover trial. Sleep 1999;22:1073–1081. ●A 2004;5:237–246.● B
Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. National Heart, Lung, and Blood Institute Working Group
Sex and the risk of restless legs syndrome in the general on Restless Legs Syndrome. Restless legs syndrome:
population. Arch Intern Med 2004;164:196–202.● C Detection and management in primary care. Am Fam
deMello MT, Esteves AM, Tufik S. Comparison between Physician 2000;62:108–114.● C
dopaminergic agents and physical exercise as treatment National Sleep Foundation. The 2001 Sleep in America
for periodic limb movements in patients with spinal Poll. Washington, DC: National Sleep Foundation,
cord injury. Spinal Cord 2004;42:218–221. ● B 2001.●C
Eisensehr I, Ehrenberg BL, Rogge Solti S, Noachtar S. Nichols DA, Allen RP, Grauke JH, et al. Restless legs syn-
Treatment of idiopathic restless legs syndrome (RLS) with drome symptoms in primary care. Arch Intern Med
slow-release valproic acid compared with slow-release lev- 2003;163:2323–2329.● C
odopa/benserazid. J Neurol 2004;251:579–583. ● A Philips B, Young T, Finn L, Asher K, Hening WA, Purvis C.
Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Epidemiology of restless legs syndrome in adults. Arch
Masramon X, Hernandez G. Treatment of restless legs Intern Med 2000;160:2137–2141.● B
syndrome with gabapentin: A double-blind, crossover Sevim S, Dogu O, Kaleagasi H, Aral M, Metin O,
study. Neurology 2002;59:1573–1579. ● A Camdeviren H. Correlation of anxiety and depression
Happe S, Sauter C, Klosch G, Saletu B, Zeitlhofer symptoms in patients with restless legs syndrome:
J. Gabapentin versus ropinirole in the treatment of A population based survey. J Neurol Neurosurg
idiopathic restless legs syndrome. Neuropsychobiology Psychiatry 2004;75:226–230.● B
2003;48:82–86.● B Silber MH, Girish M, Izurieta R. Pramipexole in the man-
Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, agement of restless legs syndrome: An extended study.
Ferini-Strambi L. Impact, diagnosis and treatment of Sleep 2003;26:819–821. ●B

496
 Chapter 65 Headache

Sun ER, Chen CA, Ho G, Earley CJ, Allen RP. Iron and the Trenkwalder C, Hundemer HP, Lledo A, et al. Efficacy of
restless legs syndrome. Sleep 1998;21:371–377.●B pergolide in treatment of restless legs syndrome: The
Telstad W, Sorensen O, Larsen S, Lillevold PE, Stensrud P, PEARLS Study. Neurology 2004b;62:1391–1397. ● A
Nyberg-Hansen R. Treatment of the restless legs syn- Walters AS. Toward a better definition of the restless legs
drome with carbamazepine: A double blind study. Br syndrome. Mov Disord 1995;10:634–642.● C
Med J (Clin Res Ed) 1984;288:444–446. ● A Walters AS, Wagner ML, Hening WA, et al. Successful treat-
Thorp ML, Morris CD, Bagby SP. A crossover study of ment of the idiopathic restless legs syndrome in a ran-
gabapentin in treatment of restless legs syndrome domized double-blind trial of oxycodone versus
among hemodialysis patients. Am J Kidney Dis placebo. Sleep 1993;16:327–332. ● A
2001;38:104–108. ● A Walters AS, LeBrocq C, Dhar A, et al. International Restless
Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Legs Syndrome Study Group: Validation of the
Ropinirole in the treatment of restless legs syndrome: International Restless Legs Syndrome Study Group
Results from the TREAT RLS 1 study, a 12 week, ran- rating scale for restless legs syndrome. Sleep Med
domized, placebo controlled study in 10 European 2003;4:121–132.● B
countries. J Neurol Neurosurg Psychiatry 2004a;
75:92–97. ● A

C h a p t e r

65 Headache

Rahul Gupta

left-sided headache developed earlier in the day. The

KEY POINTS pain started around her left eye, gradually spread to
her left temple, and soon involved the complete left
1. To achieve a better quality of life by reducing side of her head. It was throbbing, 10/10 on a pain
the patient’s suffering scale, and associated with nausea. The headache was
2. To reduce the impact of disease on the ability worse with movement and not associated with fever.
to work and function socially She felt somewhat better lying down in the dark. No
3. To avoid medication abuse significant improvement was achieved by taking two
4. To avoid frequent emergency department visits tablets of ibuprofen. As the pain continued, she had
5. To minimize recurrence through education, to take leave from her job, where she works as a bank
avoidance of triggers, and prophylaxis manager, and visit her physician. This is her third
6. To assemble a platform where a long-term rela- visit to the physician’s office in the past 12 months.
tionship of trust with the physician can be fostered On review of her chart, the past two visits have been
very similar to the current one.
Mary is happily married to her husband of the
past 20 years, and the couple have two children. Mary
has a busy life, which she manages well. She started
INITIAL VISIT having headaches at age 22. Earlier she noticed that her
headaches were related to her menstrual cycles, and she
Subjective
would be able to achieve fair control by over-
Patient Identification and Presenting Problem the-counter medications. The headaches became
Mary B., a 47-year-old white woman, complains of somewhat less frequent after she reached menopause
severe headache for the past 6 hours. Mary states that 5 years ago. However, she states that she thought
she was doing well when a sudden onset of severe the headaches would be better when her sons left

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

497
 Chapter 65 Headache

Sun ER, Chen CA, Ho G, Earley CJ, Allen RP. Iron and the Trenkwalder C, Hundemer HP, Lledo A, et al. Efficacy of
restless legs syndrome. Sleep 1998;21:371–377.●B pergolide in treatment of restless legs syndrome: The
Telstad W, Sorensen O, Larsen S, Lillevold PE, Stensrud P, PEARLS Study. Neurology 2004b;62:1391–1397. ● A
Nyberg-Hansen R. Treatment of the restless legs syn- Walters AS. Toward a better definition of the restless legs
drome with carbamazepine: A double blind study. Br syndrome. Mov Disord 1995;10:634–642.● C
Med J (Clin Res Ed) 1984;288:444–446. ● A Walters AS, Wagner ML, Hening WA, et al. Successful treat-
Thorp ML, Morris CD, Bagby SP. A crossover study of ment of the idiopathic restless legs syndrome in a ran-
gabapentin in treatment of restless legs syndrome domized double-blind trial of oxycodone versus
among hemodialysis patients. Am J Kidney Dis placebo. Sleep 1993;16:327–332. ● A
2001;38:104–108. ● A Walters AS, LeBrocq C, Dhar A, et al. International Restless
Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Legs Syndrome Study Group: Validation of the
Ropinirole in the treatment of restless legs syndrome: International Restless Legs Syndrome Study Group
Results from the TREAT RLS 1 study, a 12 week, ran- rating scale for restless legs syndrome. Sleep Med
domized, placebo controlled study in 10 European 2003;4:121–132.● B
countries. J Neurol Neurosurg Psychiatry 2004a;
75:92–97. ● A

C h a p t e r

65 Headache

Rahul Gupta

left-sided headache developed earlier in the day. The

KEY POINTS pain started around her left eye, gradually spread to
her left temple, and soon involved the complete left
1. To achieve a better quality of life by reducing side of her head. It was throbbing, 10/10 on a pain
the patient’s suffering scale, and associated with nausea. The headache was
2. To reduce the impact of disease on the ability worse with movement and not associated with fever.
to work and function socially She felt somewhat better lying down in the dark. No
3. To avoid medication abuse significant improvement was achieved by taking two
4. To avoid frequent emergency department visits tablets of ibuprofen. As the pain continued, she had
5. To minimize recurrence through education, to take leave from her job, where she works as a bank
avoidance of triggers, and prophylaxis manager, and visit her physician. This is her third
6. To assemble a platform where a long-term rela- visit to the physician’s office in the past 12 months.
tionship of trust with the physician can be fostered On review of her chart, the past two visits have been
very similar to the current one.
Mary is happily married to her husband of the
past 20 years, and the couple have two children. Mary
has a busy life, which she manages well. She started
INITIAL VISIT having headaches at age 22. Earlier she noticed that her
headaches were related to her menstrual cycles, and she
Subjective
would be able to achieve fair control by over-
Patient Identification and Presenting Problem the-counter medications. The headaches became
Mary B., a 47-year-old white woman, complains of somewhat less frequent after she reached menopause
severe headache for the past 6 hours. Mary states that 5 years ago. However, she states that she thought
she was doing well when a sudden onset of severe the headaches would be better when her sons left

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

497
 Chapter 65 Headache

home for college 3 years ago, but her life has been more Blood pressure, 130/72 mm Hg
stressful. Her “bad” headaches can occur between once Pulse, 80 beats per minute
a month and once in 3 months, depending on “how Respirations, 14 breaths per minute
stressed” she is. Occasionally, she gets a daily, nagging-
type headache localized to the frontal area of the head, Head and Neck Mary’s pupils are equal and react
which feels like a band. The back of her neck also hurts normally to light; both fundi are normal, as are the
with this type of headache, but the headache is not as ocular muscles and accommodation reflex. She is
severe. This headache is typically relieved with aceta- tender over the left temporal area. The posterior part
minophen or ibuprofen. Her husband works as an of the neck is tender but without any meningeal
executive and is generally supportive. signs. No carotid bruits are heard. No lymph-
adenopathy is noted, and the thyroid gland is nor-
Medical History mal. Her oral cavity is normal as well.
Mary has had no major medical illnesses or surgery.
Apart from her two pregnancies, she has never been Neurologic Mary is oriented to place, time, and per-
hospitalized. She has never had head or other trauma. son. Cranial nerves, deep tendon reflexes, motor, and
She has no allergies. Her husband has voiced concern sensory examinations are normal. Cerebellar func-
in the past that she might be depressed, as he has tions are normal.
occasionally observed her crying for no clear reason,
and she has been sleeping less. She remembers that Chest Breath sounds are normal.
her headaches had improved during both pregnan-
cies. She takes ibuprofen when she has headaches, Heart Both heart sounds are normal without mur-
which is once to twice a week on average. Fifteen murs or clicks.
months ago, she had to go to the local emergency
department for a similar migraine episode. She was Abdomen Scaphoid and soft without tenderness.
treated with intravenous medications, and the com- Normal bowel sounds.
puted tomography scan of brain was normal then.
Extremities Cool and sweaty.
Family History
Mary’s mother had migraines, as did an older sister. Assessment
Her mother died of her first heart attack at age 71.
Her father is alive and well at age 75. Working Diagnosis
The history and presentation confirm the current diag-
Social History nosis of migraine. However, she reports another type
The patient does not smoke or drink alcohol. She of headache that may have developed recently. The fol-
denies any illicit drug abuse. She has learned that lowing headache diagnoses should be considered.
some foods, including ripe bananas, avocados,
1. Migraine without aura.
chocolate, and red wine, cause her headaches to flare
2. Tension-type headache.
up, and does her best to avoid them. She also exer-
3. Substance-withdrawal headache. This type of
cises daily and is absolutely sure that this has helped
headache can be induced by prolonged use of
her control her headaches more effectively.
analgesics. Patients with a predisposition to
headaches often have a pharmacologic tolerance
Review of Systems
to these drugs, and a rebound headache develops
Mary denies any recent weight gain or loss. She
as the medicine is metabolized. The headache
denies any shortness of breath, cough, palpitations,
may be diffuse or pulsating, and the onset occurs
chest pain, or anxiety.
several hours after taking the analgesic.

Objective Mary B.’s overall clinical picture includes fea-

tures of all of these. The current presentation,
Physical Examination physical examination, and the history strongly sug-
Mary is a healthy-appearing, slightly overweight gest an acute episode of migraine without aura.
white woman. A mixed pattern of tension-type and substance-
withdrawal headaches may also exist. She may be
General She lies comfortably in a dark room but depressed, which can be contributing as well.
becomes anxious during questioning.
Plan
Vital Signs
Weight, 180 pounds Diagnostic
Height, 5 feet 7 inches No testing is required at this time.
498
 Chapter 65 Headache

Therapeutic of the eye (Table 65-1 and Fig. 65-1). Danger signs or red
1. Sumatriptan (Imitrex), 50 mg, is administered via and flags may alert the physician and generally suggest
subcutaneous route to the anterior thigh area further evaluation (Box 65-1). A primary headache
after explaining the side-effect profile. The disorder is one that is benign, recurrent, and not
patient’s headache is reduced to 2/10 at 30 min- associated with any underlying pathology (Headache
utes. A prescription for sumatriptan is provided Classification Committee, 1988● C ; Headache Classi-
to the patient with directions and precautions. fication Committee, 2004● C ). Primary headaches con-
2. Counseling is provided to educate the patient on sist of migraine, tension-type headache, and cluster
the pathophysiology of migraine, tension, and headache.
withdrawal headaches. She is advised to discontinue
the regular use of ibuprofen and acetaminophen. Migraine
3. A prophylaxis program is started with
amitriptyline (Elavil), 25 mg at bedtime. This Migraine is an episodic but chronic disorder that con-
should further help her depression and insom- stitutes a common type of headache. The pain is typi-
nia. The side-effect profile including weight cally moderate to severe and unilateral at the outset but
gain is explained. may later become bilateral. Migraine commonly occurs
4. Dietary advice is given on how to avoid all trigger without aura (common migraine); however, an aura
factors. may occur in up to 15% to 25% of the migraineurs
5. Relaxation therapy is advised. An audiotape copy is (classic migraine). The aura can precede the headache
given to the patient. The role of stress in such by up to 1 hour. It includes visual symptoms like flash-
mixed-type headache is explained to the patient, ing lights, zig-zag lines, and a feeling of numbness or
and she agrees to try the therapy at least twice daily. pins-and-needles around lips and hands. Migraine
6. Daily record keeping of the headaches is empha- occurs in women 3 times as commonly as in men.
sized. A model of a typical headache diary is pro- Transformed headache is the term used when the
vided to the patient, and she is counseled to bring combination of tension-type and episodic migraine
her daily record on her next office visit. results in a chronic daily headache that usually
occurs over a long period.
Disposition
The physician and nurse educator discussed these Migraine Management
treatment modalities with the patient. Mary was The comprehensive management is an exigent task
informed of the reasons to withhold analgesics and due to the chronic and episodic nature of the disease.
start a tricyclic antidepressant. She was given several
references on available information for migraines.
A strong physician/patient relationship was empha-
sized, and the patient seemed to understand it. A 2- Table 65-1 Types of Headaches
week follow-up appointment was made. Primary Headache Disorder
Migraine, with or without aura
Tension-type, infrequent, frequent, or chronic
DISCUSSION Cluster and other trigeminal autonomic
cephalgias (TACs)
Introduction and Burden of the Disease
Secondary Headache
Headache is a common clinical challenge encoun- Associated with head and/or neck trauma
tered by physicians in primary care. More than 65% Associated with cranial or vascular disorder, such as
of Americans have a headache at some time in a stroke
given year. In the United States, migraine alone costs Associated with nonvascular intracranial disorder,
employers $13 billion per year because of the missed such as intracranial hypertension and seizures
Associated with a substance (nitrate and alcohol)
workdays and impaired work function (Johnson, or its withdrawal (analgesics, caffeine,
2004●A ; Mannix, 2001● A ).
narcotics, and alcohol)
Associated with infection, such as meningitis and
Making the Diagnosis brain abscess
Associated with metabolic disorder, such as hypoxia,
A comprehensive history, including a headache his- hypercapnia, and hypoglycemia
tory and physical examination, is the initial step. It is Associated with disorder of surrounding
essential to rule out the secondary causes, including structures, including neck, eyes, ears, nose,
uncontrolled hypertension, infections (sinusitis, sinuses,and teeth
dental abscess), stroke, meningitis, brain neoplasm, Associated with psychiatric disorder
Cranial neuralgias
subarachnoid hemorrhage, and refractory disorders

499
 Chapter 65 Headache

Recurrent headache, comprehensive

history, and physical examination

Yes

Yes
Investigate as appropriate Red flags

No No
Yes
Features of migraine History of trauma

No No

Feature of giant Yes Age of onset of the

cell arteritis headache more than 50 years

Yes No
Rebound
Giant cell Use of analgesics Yes Headaches
arteritis regularly > 3 days/week for (others may
headaches be associated)
No
Refractory
Sinusitis−manage Yes Associated sinus Yes errors−manage
accordingly and complaints or refractory accordingly and
re-evaluate disorders of the eye re-evaluate
No

Other
characteristics

Well-defined unilateral severe attacks Throbbing headaches Nonthrobbing Pain associated

for days to months associated with with associated nausea band like dull with chewing
ipsilateral nasal and eye symptoms and vomiting headache with
posterior neck pain

Yes Yes Yes Yes

Cluster headaches Migraine Tension-type Temporoman-

headache dibular joint
disorder

Only during Without aura With aura Associated with

menstruation reversible prolonged
neurologic symptoms
Yes Yes Yes Yes

Menstrual Common Classical Complicated

migraine migraine migraine migraine

Figure 65-1 Differential diagnosis of headaches

Exclusion of a secondary headache etiology is of The goals of migraine management involve not
paramount significance and determines whether any only improving the quality of life by reducing patient
imaging or laboratory tests are required. suffering in recurrent episodes but also avoiding

500
 Chapter 65 Headache

Box 65-1 “Red Flags” in the Diagnosis Box 65-2 Precipitating Factors in
of Headache Migraines

Reflexes, asymmetrical or abnormal Hormonal imbalance, such as during menses,

Exertional, such as onset with sexual activity, pregnancy, and hormonal replacement therapy
coughing, or sneezing Emotional factors
Different or a new headache Accident/Trauma
Fever, stiff neck, rash, weight loss associated Diet: see below
Loss of memory or other neurologic function Alcohol and medicines such as nonsteroidal
such as paralysis antiinflammatory drugs
Age older than 50 years Caffeine
Gait abnormality Hot or cold weather
Severest headaches ever experienced Exertion
Smoking
medication abuse and educating the patient to Migraine Dietary Restrictions
avoid triggers (Silberstein, 2000●
A ; Snow et al., 2002●
C)
(Box 65-2). Dairy products: Aged cheeses (cheddar, Swiss),
To achieve these goals, the comprehensive man- sour cream, chocolates
agement strategy may include the following: Meats: Beef and chicken livers, unrefrigerated
dry fermented sausage, fermented bologna,
1. Acute pharmacologic therapy salami, pepperoni, pickled fish, pickled her-
2. Nonpharmacologic therapy ring, smoked fish, bacon
3. Preventive therapy Beverages: Red wine, caffeinated drinks, chi-
4. Patient education anti, burgundy, beer, ale, sauternes
Fruits: Avocados, overripe bananas
Acute Pharmacologic Therapy Medications used Vegetables: Fava beans, peanuts, snow pea
range from a wide variety of nonspecific analgesics pods, broad bean pods, sauerkraut
to specific agents directed toward rectifying the cause Food additives: Meat tenderizers, food con-
of the migraine. taining monosodium glutamate (MSG) or
Nonsteroidal anti-inflammatory drugs (NSAIDs), brewer’s yeast
such as aspirin, ibuprofen (Motrin, Advil), and
naproxen (Aleve), as well as those in combination with
acetaminophen, aspirin, and caffeine (Excedrin), have Nonpharmacologic Therapy These briefly include
been proven to be superior to placebo in clinical trials biofeedback (self-regulation), cognitive/behavioral
for mild to moderate attacks, if used occasionally. A (stress management) therapy, and relaxation training.
well-controlled study also showed the benefit of acet-
aminophen over placebo. Parenteral antiemetics, such Preventive Therapy Prophylaxis is frequently required
as metoclopramide (Reglan) and prochlorperazine in migraineurs who continue to have frequent attacks
(Compazine) also have been shown to be superior to despite the described management. A variety of pre-
placebo in migraine headaches. ventive medications are available (Table 65-2) includ-
Opioids such as meperidine (Demerol) and ing antidepressants, antihypertensives, and antiseizure
hydrocodone (Lorcet, Lortab) are commonly prescribed medications. Amitriptyline, valproate, propranolol,
for migraines but should be used sparingly. The concern and timolol have been proven most efficacious in clin-
for physical dependence and addiction is real. ical trials. The drug is chosen depending on the
Although ergot products are effective, their use patient’s comorbidity. It is important to understand
has declined because of their significant adverse- that most prophylactic agents take at least 4 to 6 weeks
effect profile and contraindications. before their benefit can be evaluated.
Since the introduction of triptans (Tfelt-Habsen
et al., 2000●A ), migraine management has been revo- Patient Education Patient education is the corner-
lutionized. They have better efficacy because of their stone of migraine management. It is imperative that
specificity for the abnormal mechanisms involved in the patient understand that migraines can be man-
the migraine pathophysiology. Triptans stimulate the aged but not cured. The goal of therapy is to reduce
specific serotonin receptors (5-HT1B/D) found on the migraine frequency and severity to an extent at
the cranial and meningeal vasculature and the which the patient can carry out regular physical
trigeminal afferent nerves. This stimulation restores activity and daily responsibilities with a decent qual-
the neurovascular integrity and rectifies the ongoing ity of life. This is a chronic disorder, and lifestyle
secondary inflammatory reaction. modification plays a great role. Maintaining a

501
 Chapter 65 Headache

Table 65-2 Prophylactic Agents

Antidepressants Tricyclic antidepressants
Nonsedating Protriptyline, desipramine
Sedating Amitriptyline, nortriptyline, imipramine, doxepin
Selective serotonin Fluoxetine, sertraline, paroxetine, fluvoxamine
reuptake inhibitors
Others Trazodone, bupropion, venlafaxine
Antihypertensives β-Blockers Atenolol, nadolol, propranolol, metoprolol, timolol
Calcium channel blockers Verapamil, nifedipine, diltiazem, nimodipine
ACE inhibitors Lisinopril
Alpha agonist Clonidine
Antiseizure Divalproex, gabapentin,
topiramate
Others NSAIDs, MAOIs, methysergide,
cyproheptadine, ergot
derivatives, magnesium

ACE, angiotensin-converting enzyme; MAOI, monoamine oxidase inhibitor; NSAID, nonsteroidal anti-
inflammatory drug.

headache diary to track the pattern of headaches is quent urgent therapy is required. The headaches may
often helpful and frequently helps the patient realize become disabling and long lasting, interfering with
that many factors are associated with headaches. performance on a daily basis. Prophylactic agents are
Education on avoiding the triggers and focusing on similar to those used mostly for migraines. Tricyclic
protective factors is immensely important, as the antidepressants have shown proven benefit.
patient feels more in control of his or her condition. Management of other associated conditions, as men-
Support groups are helpful, as patients realize they tioned, is helpful and should be done in all cases.
are not alone out there.
Cluster Headache
Tension-type Headache
Cluster headache is the least common of the primary
Tension-type headaches can be episodic or headaches and often causes excruciating pain, which
chronic. This is the most common type of
headache, and most of us have had them at some
time in life. Female patients are more frequently Table 65-3 Distinguishing Characteristics
affected. The pain is typically a steady, nonthrob- of Tension-type and Migraine
bing, dull, and bilateral ache, which does not Headaches
worsen with routine physical activity (Table 65-3). Tension-type
Patients commonly describe it as a bandlike con- Headache Migraine
striction around the head and a sensation of heav-
iness and tightening at the back of the head and No aura Aura present in
neck. Nausea and vomiting are absent. Posterior 15%–25% of
neck muscles may be tender as well as contracted. patients
The headaches are commonly associated with sig- Steady tightness or Throbbing and
nificant life stressors and emotional lability but are dull pain pulsating pain
Not aggravated with Aggravated with
usually not disabling. Concomitant depression routine physical activity exertion or physical
may be an ongoing process in these patients and activity
must be evaluated further. Mostly bilateral Mostly begins as
unilateral but may
Treatment become bilateral
The moderate attacks are controlled well with the tra- Mild to moderate pain Moderate to severe
ditional NSAIDs (Krusz, 2004● B). For severe attacks, disabling pain
triptans as well as narcotic analgesics are reserved. Usually not associated Usually associated
Muscle relaxants and osteopathic manipulative ther- with nausea, vomiting, with nausea,
apy also are frequently helpful because of the concomi- or photo/phonophobia vomiting,
photophobia, or
tant neck-muscle contraction associated with this type phonophobia
of headache. Prophylaxis may be warranted when fre-

502
 Chapter 65 Headache

peaks quickly from the onset within 15 minutes and a comprehensive history and physical examination.
lasts up to 4 hours. Pain commences around an orbit, This simple step helps to rule out a secondary
radiates to the rest of the face, and is associated with cause for headache most of the time. The various
lacrimation, facial flushing, conjunctival injection, diagnostic tests can be individualized and per-
and nasal congestion. It affects smoking men in their formed only if needed. Once a primary headache
second or third decade more often than women. The disorder is diagnosed, it becomes relatively simple
headaches tend to occur at the same time of the day to classify the headache type and treat accordingly.
continuously for many days, followed by remission, Often patients will have more than one primary
only to recur later in life in similar clusters. Attacks headache type. As we understand today, consider-
can be triggered by alcohol consumption as well as by able overlap occurs in treatment and prevention
sudden temperature changes when a patient is within strategies of the primary headache disorders. The
a cluster series. During an attack, the patient is rest- physician should use this fact to the advantage of
less, agitated, and can be observed pacing in pain. the patient in the management, rather than ignor-
ing it. Managing the chronic nature of headaches
Treatment requires an ongoing healthy partnership between
Inhalation of 100% oxygen from a tight-fitting mask at the physician and the patient.
a flow rate of 5 to 10 L/min for 10 to 15 minutes dur-
ing an attack is highly effective. Injectible or intranasal
triptans as well as narcotic analgesics and traditional
NSAIDs offer relief when given parenterally. Material Available on Student Consult
Review Questions and Answers about Headache
Summary
For the many individuals who have headaches,
a primary care physician can begin by performing

REFERENCES

Headache Classification Committee of the International Silberstein SD. Practice parameter: Evidence-based guide-
Headache Society. Classification and diagnostic criteria lines for migraine headache (an evidence-based
for headache disorders, cranial neuralgias, and facial review): Report of the Quality Standards Sub-
pain. Cephalgia 1988;8(Suppl 7):1–96.● C committee of the American Academy of Neurology.
Headache Classification Committee of the International Neurology 2000;55:754–762.● A
Headache Society. The International Classification of Snow V, Weiss K, Wall EM, Mottur-Pilson C. AAFP/ACP-
Headache Disorders, 2nd ed. Available at ASIM Pharmacologic management of acute attacks of
http://216.25.100.131/ihscommon/guidelines/pdfs/ migraine and prevention of migraine headache. Ann
ihc_II_main_no_print.pdf. Accessed 10/7/2004.● C Intern Med 2002;137:840–849.● C
Johnson CJ. Headache in women. Prim Care 2004;31: Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in
417–428, viii.●
A migraine: A comparative review of pharmacology,
Krusz JC. Tension-type headaches: What they are and how pharmacokinetics and efficacy. Drugs 2000;60:
to treat them. Prim Care 2004;31:293–311. ●B 1259–1287.● A
Mannix LK. Epidemiology and impact of primary
headache disorders. Med Clin North Am 2001;85:
887–895.● A

503
 C h a p t e r

66 Tremor (Parkinson’s Disease)

Kira Zwygart

is concerned about a slight hand tremor that has

KEY POINTS recently been affecting his tennis game.
John has remained very active throughout his
1. Typical presenting symptoms of Parkinson’s dis- life. He is currently working full time and playing
ease (PD) include a resting tremor, rigidity, and tennis twice a week. He also works out with gym
bradykinesia. equipment. Over the past year, he has noted a slight
2. It is important to consider and rule out other tremor in his left hand and leg. The tremor initially
causes of tremor (such as medications or toxins, began in his left leg and then moved to his left hand.
essential tremor, or kinetic tremors) when mak- It appears worse when sitting and remains constant
ing a diagnosis. unless he gets up and does something. John has
3. Important initial interventions for patients with noted that anxiety appears to worsen the symp-
PD include exercise, physical and/or occupa- toms. He has noted some muscle soreness and stiff-
tional therapy, referral to support groups, and ness in his legs, which he has attributed to “getting
improvement in nutrition. older.” He denies any history of similar symptoms.
4. Treatment with medications should be done on an He has not had any weakness, tingling, headaches,
individual basis according to symptoms and with dizziness, or visual changes. Other than the doxa-
careful consideration of potential side effects. zosin (Cardura), he has not been taking any other
medications. He does admit to four to five glasses of
red wine per week but denies any history of alcohol
abuse. He has not noted that the wine makes his
INITIAL VISIT tremor any better. He has no knowledge of being
exposed to any toxic substances. No family history of
Subjective neurologic problems or tremors is known. He has
not noted any weight change, and his appetite
Patient Identification remains good. John is concerned that the tremor is
John is a 62-year-old married white man. slowly worsening and would like to know if he can
do anything to prevent further worsening.
Chief Complaint
This is a new patient on an initial visit. Medical History
As mentioned previously, John’s medical history is
History of Present Illness significant only for a history of BPH. He denies a his-
John is a 62-year-old man with a history of benign tory of coronary artery disease, diabetes mellitus,
prostatic hypertrophy (BPH) with an elevated tuberculosis, hepatitis, hypertension, or thyroid dis-
prostate specific antigen (PSA), for which he is being ease. He has no drug allergies.
monitored by his urologist. He has had recent biop-
sies for this problem, and the results indicated a Family History
benign process. He is being treated with doxazosin John’s family history is noncontributory. His mother
(Cardura), which has improved his symptoms signif- died at age 86 years of natural causes, and his father
icantly. He feels that his BPH is doing well and is still alive and well at 91 years. He has one brother
appears today for a complete physical examination. who is alive and healthy. No family history of neu-
He has not had a complete physical in some time and rodegenerative illnesses or tremors is known.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

504
 Chapter 66 Tremor (Parkinson’s Disease)

Health Habits noted. At rest, a noticeable tremor is seen in his left

John denies any history of smoking. He drinks four hand and leg. The hand tremor is fine, with a pill-
to five glasses of red wine per week with dinner. He rolling appearance. The tremor disappears with move-
exercises regularly and is a good tennis player. ment, such as picking up a magazine. The hand
tremor is of slow frequency and is best noted when
Social History John is resting his hands on his lap. No rigidity is pres-
John has been married for 42 years. He has worked in ent in the larger joints, but noticeable cogwheeling is
radio broadcasting for some time. seen in his left wrist. John shows no difficulty in aris-
ing from the examining room chair when asked to sit
Review of Systems on the examining table. His gait is appropriate, but he
Other than the complaints already mentioned, John shows decreased arm swing with his left arm. Rapid
is doing well. He denies any recurrent headaches, alternating movements reveal slight bradykinesia on
visual disturbances, or changes in speech or swallow- his left side as compared with his right. Romberg is
ing. He has no complaints of lung, cardiac, or gas- negative. Reflexes are 2+ in all upper and lower
trointestinal disease. His bowel movements are extremities bilaterally, with no Babinski or clonus. The
regular, and he has no history of melena or hema- tremor disappears when he is asked to touch the
tochezia. physician’s fingers.

Laboratory Tests
Objective
Office laboratory analyses ordered with the first visit
Physical Examination included a complete blood cell count, chemistry pro-
Vital Signs John’s height is 67 inches; weight is 157 file, and thyroid-stimulating hormone, all of which
pounds; pulse is 51; and blood pressure is 141/77. were normal.

Head Male pattern alopecia. Assessment

Eyes Full range of motion in all quadrants with no Working Diagnoses
gaze abnormality. 1. Tremor. The differential diagnosis includes vari-
ous causes of tremor. Because the patient’s tremor
Nose and Ears is resting, unilateral, progressive, and associated
Clear. Hearing intact bilaterally. with some rigidity, the diagnosis of idiopathic
Parkinson’s disease (PD) is most likely.
Mouth Good dentition. 2. BPH. Controlled with current medication.
Monitored by a urologist.
Neck Thyroid normal; no bruits, no thyromegaly.
Plan
Lungs Clear to auscultation.
Diagnostic
Heart Sinus bradycardia without murmur. 1. Re-address key symptoms and signs in John’s his-
tory and examination to help rule in or rule out a
Abdomen Soft, nontender, nondistended; no her- diagnosis of PD versus benign tremor.
nias, no organomegaly. 2. Serum chemistry laboratory work to include liver
function tests to evaluate for Wilson’s disease and
Genital/Rectal Normal external male genitalia, uncir- creatinine phosphokinase to evaluate for muscle
cumcised. Testicles descended bilaterally. No masses, disease.
no hernias. Rectal tone normal; 60-g prostate, smooth, 3. Magnetic resonance imaging (MRI) of the brain
symmetrical, without nodules. Hemoccult negative. to evaluate for other neurodegenerative processes,
although MRI is not of benefit for making the
Extremities Muscle tone normal. Full range of diagnosis of PD.
motion in all extremities. No cyanosis, edema, club- 4. Cerebrospinal spinal fluid (CSF) analysis to eval-
bing, or joint deformities. Peripheral pulses 2+ and uate for other neurologic disorders presenting
equal bilaterally. with parkinsonism (optional).

Skin No rash or pigment changes. Therapeutic

A full explanation of the diagnosis and treatment of
Neurologic Oriented to person, place, and time. PD is given to John and his wife. John is begun on
Affect is appropriate. Cranial nerves II through XII selegiline (Eldepryl) at 5 mg twice a day by mouth.
grossly intact. No focal motor or sensory deficit is He is told to take it with breakfast and lunch, to limit

505
 Chapter 66 Tremor (Parkinson’s Disease)

its amphetamine-like stimulation that can interfere ing (ADLs), no further medication is prescribed. John
with sleep, and always to take it with food to limit is encouraged to continue with his work and routine
nausea. exercises and to report any worsening of symptoms.
John and his wife are given the phone number and
Patient Education address of the local PD support group to contact for
John is asked to maintain a symptom diary. He is further education and social support.
advised to bring the symptom diary with him to all
future visits. John also is encouraged to maintain a Disposition
program of exercise and social activity to keep phys-
ically and mentally healthy, yet to balance these activ- John is scheduled to return for office follow-up in
ities with the necessary rest and precautions required 1 month (sooner if any deterioration occurs in his
of patients with this disease. condition).

Disposition
John is asked to complete the diagnostic testing, ini- DISCUSSION
tiate the medication previously discussed, and return
in 4 weeks. The purpose of this case study is to discuss the
differential diagnosis of tremors, particularly PD.
Currently no laboratory or imaging tests are avail-
FOLLOW-UP VISIT able that can make a definitive diagnosis of PD.
Instead, these tests help rule out other neurodegen-
Subjective erative disorders. The diagnosis of PD is purely a
clinical diagnosis and is based largely on the tremor
John has noted no difficulty with the medicine. and other symptoms (including rigidity, bradykine-
Initially some nausea was felt, but this has resolved. sia, and autonomic dysfunction). The type, onset,
His tremor is no worse, and at times it appears better. duration, frequency, and progression of the tremor,
He continues playing tennis twice a week and as well as ameliorating and aggravating factors, are
remains active at work. all important in helping to distinguish between a
parkinsonian tremor and other tremors. To aid in
Objective the diagnosis of a patient with a tremor, the tremor
must first be classified. Classifications can be based
On physical examination, no change is apparent either on a description or on the pathophysiology of
from the previous physical findings. John’s resting the tremor.
tremor is still present, but it is less visible. The elbow
and wrist joint rigidity are still present but slightly
decreased. Tremor Classification
Resting Tremor
Laboratory Tests This type of tremor occurs only at rest. It may
The serum chemistries, including liver function tests worsen when the patient is engaged in mental tasks
and creatinine phosphokinase, were all normal. The or moving an unaffected body part. It disappears
MRI of the brain shows mild cerebral atrophy, not quickly with muscle contraction in target-directed
unusual for his age, and otherwise is normal. CSF movements, so the patient’s performance is rarely
studies were not obtained. affected. Clinically, this type of tremor is associated
with idiopathic PD and secondary parkinsonism.
Assessment Secondary parkinsonism is a term given to condi-
tions that mimic PD clinically but are caused by
1. Idiopathic PD in early stages. John’s history, essen- known agents. These include the following:
tially normal laboratory results, and MRI help Postinfectious. This type of tremor is seen primarily
support this diagnosis. The patient’s daily activi- during the convalescent phase of viral encephalitis.
ties are not yet affected by his symptoms. He is Toxin-induced. This type of tremor is associated with
tolerating selegiline (Eldepryl) well. exposure to carbon monoxide, carbon disulfide,
2. BPH symptoms are stable. manganese, cyanide, methanol, and the synthetic
heroin analogue MPTP (1-methyl-4-phenyl-1,2,3,
Plan 6-tetrahydropyridine).
Drug-induced. This type of tremor is associated with
The selegiline (Eldepryl) is continued at the recom- ingestion of drugs that block dopamine receptors,
mended dose of 5 mg twice a day. Because John’s especially the neuroleptic and antiemetic agents,
symptoms are not affecting his activities of daily liv- as well as metoclopramide (Reglan) and reserpine.

506
 Chapter 66 Tremor (Parkinson’s Disease)

Removal of the offending agent will cause resolu- evoked through goal-oriented movements such as
tion of symptoms within weeks to months. finger-to-nose or heel-to-shin testing. As the
patient’s finger or heel approaches the target, the
Postural Tremors tremor will increase. Kinetic and intention tremors
These tremors are provoked by isometric contraction can develop in patients with heavy-metal poisoning
of the affected body segment (thus considered action (lead, mercury, bismuth, thallium), carbon tetra-
tremors rather than resting tremors). They can be chloride exposure, and metal chelator intoxication.
seen involving almost all body parts (i.e., head, neck,
trunk, upper extremities, and lower extremities). Cerebellar tremor. A cerebellar tremor is generally an
They are the most common type of tremor and intention tremor but also may occur as a postural
include both physiologic and pathologic tremors. tremor. The tremor commonly appears ipsilateral
Physiologic tremors (normal or enhanced). These are to the cerebellar lesion. The most common cause
normal tremors that occur in most individuals. of cerebellar tremor is multiple sclerosis, but
The tremor is continuous, but with an irregular brainstem tumors, strokes, and paraneoplastic
rate. It is usually not visible. The enhanced physi- cerebellar degeneration also can be responsible.
ologic tremor is a more pronounced type. It is Associated symptoms and signs may include gait
provoked by fatigue, anxiety, hypoglycemia, thyro- or speech abnormalities, defects in ocular move-
toxicosis, caffeine, dopaminergic agonists, ments, or difficulty executing rapid alternating
β-adrenergic agonists, valproic acid (Depakene), hand movements. Chronic alcoholism also may
lithium, amiodarone (which also may produce produce this tremor.
ataxia and peripheral neuropathy), and tricyclic Wilson’s disease. This condition involves a defect in
antidepressants. It also may be seen in patients copper metabolism that first appears in the second
withdrawing from alcohol or benzodiazepines. or third decade and causes hepatic disease. It is
Essential tremor. This is the most prevalent patho- treatable with chelating agents and diet. The tremor
logic postural tremor, 20 times more common is either an intention tremor or a “wing-beating”
than Parkinson’s disease. Onset is noted in a movement seen when the patient abducts the arm.
bimodal distribution, and it is seen typically in the
second and the sixth decades. A family history Isometric Tremors
exists in more than 50% of patients with this dis- This tremor occurs with muscle contraction against
order, whereas family history is uncommon with a stationary object. An example would be a tremor
PD. It primarily affects the hands, followed by the while holding a heavy object.
head, the voice, the tongue, the lower extremities,
and the trunk. In severe instances, it can appear as Task-Specific Tremors
a resting tremor. Its progression is slow, and usu- These tremors encompass both primary writing tremor
ally no significant change is noted for years. Often and vocal tremor. They appear only with specific tasks.
patients have noted that alcohol appears to ame- Primary writing tremor appears only with handwriting
liorate the tremor. β-Blockers and primidone also or a few other skilled manual tasks and, in general, is
are effective in treatment. not produced by posture or goal-directed movement.
Tremor with basal ganglia disease. Postural tremor Vocal tremors are apparent only when speaking. Both
also is visible in conditions affecting the basal gan- these types of tremors are similar to essential tremor
glia. Therefore conditions such as Parkinson’s dis- but differ in that they are not always responsive to β-
ease, Wilson’s disease, and dystonia are associated blockers, and no family history is known.
disorders in which this type of tremor is seen.
Tremor with peripheral neuropathy. These are pos- The type of tremor thus guides the physician
tural tremors that occur concomitantly with a toward the appropriate diagnosis. In John’s case, the
peripheral neuropathy, either acquired or heredi- resting, unilateral tremor in a 62-year-old patient
tary. Motor-conduction velocities are slow in these with evidence of rigidity and no other evidence of
patients, and β-blockers have little benefit. neurologic disease is most indicative of PD.
Post-traumatic tremor. This may occur after a severe PD is the second most common neurodegenera-
head injury. tive disorder (Alzheimer’s-type dementia is more
common), affecting between 300,000 and 1 million
Americans. PD usually manifests itself clinically in
Kinetic Tremor patients of age 55 to 65 years, after 75% of the
These tremors are action (kinetic) and goal oriented dopaminergic neurons in the substantia nigra are
(intention). They are usually the most incapacitat- destroyed by mechanisms not fully understood at this
ing, and their appearance may indicate disorders of time. It is a difficult disease to diagnose because many
the cerebellum and related pathways. The tremors of its signs and symptoms are characteristic of several
usually involve proximal muscles. They can be other disease entities. The classic symptoms and signs

507
 Chapter 66 Tremor (Parkinson’s Disease)

of PD include a resting tremor; rigidity, especially of ing in fewer symptoms. A recent meta-analysis of
the upper extremities (which is called “cogwheel rigid- selegiline as compared with placebo or levodopa
ity” if superimposed tremors); bradykinesia or akine- revealed that selegiline was effective in reducing dis-
sia (reduced or lack of muscle movement); and ability and delaying the need for levodopa treatment.
postural reflex impairment causing patients to be Recommended dosing of selegiline is 5 mg twice
unstable and fall. It is important to note that, the diag- a day by mouth. It should be given with food to limit
nosis of PD does not require all four of these symp- nausea, and it is recommended that this medication
toms and signs to be present. Balance problems are be taken with breakfast and lunch to limit its
often absent in early PD. The diagnosis is made clini- amphetamine-like stimulation, which can interfere
cally, because no specific, reliable laboratory or radio- with sleep.
logic studies confirm the diagnosis of PD. However, Amantadine (Symmetrel) can be used for initial
laboratory and radiologic studies are performed in therapy of PD. The therapeutic benefits seem to be
patients with tremor to help rule out other disease derived from its ability to increase dopamine release,
entities. Other, more subtle signs and symptoms of PD block dopamine re-uptake, stimulate dopamine recep-
include drooling due to impairment of swallowing tors, and exert possible peripheral anticholinergic
and increased salivation; hypophonia (a soft, monoto- properties. Studies have demonstrated a modest
nous voice due to the loss of the ability to vary speech improvement in symptoms of tremor, rigidity, and
intensity); micrographia (very small handwriting, bradykinesia. The usual dosage is 100 mg twice a day.
probably a component of bradykinesia); depression Side effects may include edema, rash, and confusion.
(either endogenous or reactive); and autonomic nerv- Alternatively, anticholinergics such as benztropine
ous system dysfunction with orthostatic hypotension. (Cogentin), trihexyphenidyl (Artane), ethopropazine
(Parsidol), and procyclidine (Kemadrin) have been
Treatment used in patients with predominant tremor. Their ben-
efit is based on the balance that exists between acetyl-
The treatment of PD includes not only medications choline and dopamine in the brain. PD patients with
but also patient and family education, as well as a depletion of dopamine have a relative excess of
physical therapy to help keep the patient mobile. acetylcholine. The anticholinergic medications help
Various national PD organizations are available to limit this relative excess influence of acetylcholine.
assist patients and their families in dealing with the These agents are most helpful as early monotherapy
social and physical implications of this illness. in patients younger than 60 years with tremor-pre-
No established guidelines exist for the treatment dominant PD. They also have been somewhat helpful
of PD. Although the benefits of physical and occupa- in reducing bradycardia and rigidity, but because of
tional therapy, good nutrition, and education of their many side effects (including memory impair-
patient and family are universally accepted, the initia- ment, confusion, dry mouth, urinary retention,
tion of medication is debated. Medical treatment is blurred vision, and constipation), they are limited to
therefore highly individualized and symptom based. younger patients with minimal symptoms.
Consideration of treatment options is based on sev- A possible choice for initial treatment in younger
eral factors: neuroprotection, or prevention of patients with PD is a dopamine agonist. Currently
progression of the disease; treatment of motor symp- available agonists include bromocriptine, pergolide,
toms; and treatment of nonmotor symptoms. Of ropinirole, pramipexole, and talipexole. These med-
course, the overall goal of treatment is to extend and ications were initially used as adjunctive therapy to
improve the quality of life and maintain function. levodopa but have recently been added to the list of
The first concern in treating a patient with newly first-line medications. Dopamine agonists have
diagnosed PD is slowing the neuronal degeneration demonstrated improvement in motor symptoms,
and progression of symptoms. Several medications although not to the extent that levodopa has. The
have been proposed to do just that: vitamin E, selegi- agonists are also associated with more side effects
line, coenzyme Q10, and dopamine agonists. Studies (such as nausea, hypotension, edema, hallucinations,
have been performed to evaluate neuroprotection in and sleep attacks), which makes them a poor option
each of these cases, and none has shown irrefutable for elderly patients. The benefit of these drugs over
evidence of slowed disease progression. With that in levodopa is the decreased incidence of dyskinesia.
mind, the first step of treatment will be to improve the Levodopa is still considered the mainstay of treat-
motor symptoms displayed by the patient. Treatment ment for symptoms of PD. It is the most potent of the
options for this goal include selegiline (Eldepryl), current treatment options. It is an acceptable first-line
amantadine, anticholinergics, levodopa, and agent, as it is inexpensive, and patients demonstrate
dopamine agonists (ropinirole and pramipexole). fewer side effects than with dopamine agonists. In
Selegiline is a monoamine oxidase-B inhibitor addition, if patients are started on any of these other
that limits the breakdown of dopamine. This results medications, they will eventually require levodopa as
in a higher level of dopamine at the receptors, result- the disease progresses (generally in 3 to 5 years).

508
 Chapter 66 Tremor (Parkinson’s Disease)

Levodopa is converted in the brain to dopamine, eventually deteriorates. After 5 years of carbidopa/
although it also can be converted to dopamine out- levodopa therapy, in approximately 50% of patients,
side the blood/brain barrier. If significant conversion unstable, fluctuating response patterns to levodopa
of levodopa to dopamine occurs outside the develop. The two most common types of levodopa-
blood/brain barrier, side effects such as nausea can response deterioration that are noted are the wearing-
be a significant problem. Carbidopa was therefore off effect and dyskinesia. The wearing-off effect (often
combined with levodopa, because it is able to block called end-of-dose failure) is characterized by the
effectively much of the conversion of levodopa to symptomatic benefits of each carbidopa/levodopa
dopamine outside the brain. A minimum of 75 mg dose becoming more short lived than in the past,
carbidopa per day is usually necessary to block the lasting only a few hours or less. This type of response
peripheral conversion of levodopa. is thought to be due to progressive loss of dopaminer-
Two formulations of carbidopa/levodopa are gic nigrostriatal neurons. As the disease progresses, the
now available. The older version carbidopa/levodopa remaining nigrostriatal neurons are slowly depleted,
(Sinemet) is a fast-release agent; the newer version, limiting the brain’s capacity to metabolize and store
controlled-release carbidopa/levodopa (Sinemet- dopamine, causing a shorter response to levodopa
CR), provides a slower sustained release of medica- therapy. The initial therapeutic adjustment often
tion. PD patients taking the older, faster-release beneficial in limiting the wearing-off effect is to
preparations are often frustrated with the short increase the frequency of doses, sometimes to as often
duration of action causing motor fluctuations, such as every 2 to 3 hours.
as “wearing off ” and “on-off ” effects. The addition of The other common type of levodopa-response
controlled-release carbidopa/levodopa (Sinemet- deterioration is dyskinesia. Dyskinesias are involun-
CR) provides more stable plasma levodopa levels, tary, nonperiodic hyperkinetic movements. Several
helping to limit dyskinetic motor fluctuations in varied forms of dyskinesia can be noted as complica-
patients with more advanced PD. Dosing intervals tions of levodopa therapy and include peak-dose,
can often be lengthened, although not dramatically, end-of-dose, and biphasic-pattern dyskinesias. Peak-
when PD patients are initiated on this formulation. dose dyskinesia occurs at the peak plasma drug levels
A drawback encountered with this formulation is or time of maximal levodopa effect. Hyperkinetic
that achieving levodopa peak plasma levels is like- movements about 1 hour after the first daily morn-
wise lengthened. Use of the older, faster-acting ing levodopa dose are usually peak-dose dyskinesias.
preparations early in the morning followed by use of This type of dyskinesia can be limited by reducing
the newer, controlled-release formulation has been the levodopa dose. End-of-dose dyskinesia occurs
used as an answer to this therapeutic concern. when the levodopa effect wears off. Hyperkinetic
Another benefit of the controlled-release formula- movements, especially dystonia, before the first daily
tion is its use at bedtime, which appears to improve levodopa dose are usually end-of-dose dyskinesias.
sleep patterns in the majority of PD patients. This This type of dyskinesia is best approached by short-
sustained-release preparation is available at doses of ening the interval between doses.
carbidopa/levodopa, 25/200 mg and 50/200 mg, and Biphasic-pattern dyskinesia occurs as levodopa
is often initially prescribed twice a day but has been plasma levels increase and decline. This pattern is the
used as often as 5 to 6 times a day. least common form of dyskinesia and is more com-
To minimize nausea, it is best to give car- monly associated with chorea-type dyskinesia.
bidopa/levodopa with food. Limiting the protein in Biphasic-pattern dyskinesias are often difficult to
both the breakfast and noontime meals, maximiz- treat but may improve by shortening the dosing
ing protein in the evening meal, and taking car- intervals. In addition to the levodopa dosage and
bidopa/levodopa on an empty stomach after the interval adjustments discussed earlier, the addition of a
first couple of weeks of levodopa therapy are tech- dopaminergic agonist may help stabilize the response
niques that can maximize levodopa absorption in to levodopa therapy in patients with dyskinesia.
the gastrointestinal tract. Nausea also can be lim- Nonmotor symptoms that may require treat-
ited by starting with low doses of carbidopa/lev- ment include autonomic dysfunction (leading to
odopa combinations and building up to therapeutic constipation, urinary symptoms, sexual dysfunction,
doses gently. It is best to maintain a relatively low and orthostatic hypotension), depression, sleep dis-
dose of 200 to 400 mg of levodopa until progressive turbances, hallucinations, and dementia. Careful
disabling symptoms require an increase in dosage attention to these symptoms and consideration of
or dosing frequency. On reaching a daily dose of medication interactions are important in manage-
600 mg of levodopa, the addition of a dopamine ment.
agonist is usually favored over further increases in Surgical treatments of PD have been used in
levodopa. the past but are now being studied again because of
In the majority of PD patients receiving long- the complications of long-term levodopa treat-
term levodopa therapy, the response to therapy ment. The oldest successful surgical procedures

509
 Chapter 66 Tremor (Parkinson’s Disease)

have included thalamotomy and ventral pallido- The other benefit over surgery is that the electrodes
tomy, which improved contralateral tremor and can be relocated for further treatment, and the fre-
dyskinesia. The problem with the surgery is the pos- quency can be altered to decrease adverse effects.
sibility of permanent adverse effects, such as hemor- Fetal tissue transplantation also has been studied,
rhage, infarct, seizures, and speech impairment. but it produced significant dyskinesia. Stem cell
A more recent innovation is deep-brain stimulation. transplantation is currently under discussion, but
Electrodes are placed into the brain, and then high- legal and ethical debates (as well as the poor efficacy
frequency stimulation is performed. This procedure of the fetal tissue transplants) have delayed further
has been studied and performed in the thalamus, study in this area.
subthalamic nucleus, and globus pallidus internus.
The greatest success has been at the latter two sites.
Patients report significant improvement in dyskine- Material Available on Student Consult
sia, tremor, and activities of daily living. The inci-
Review Questions and Answers about Parkinson’s
dence of adverse events is lower (although still Disease
present), because less trauma to the brain occurs.

SUGGESTED READINGS
Bonuccelli U. Comparing dopamine agonists in Minagar A, Kelley R. Movement disorders. Prim Care Clin
Parkinson’s disease. Curr Opin Neurol 2003;16(suppl 1): Office Pract 2004;31:111–127.
S13–S19.● A Samii A, Nutt JG, Ransom BR. Parkinson’s disease. Lancet
Drucker-Colin R, Verdugo-Diaz L. Cell transplantation for 2004;363:1783–1793.● B
Parkinson’s disease: Present status. Cell Mol Neurobiol Shults CW. Treatment of Parkinson’s disease. Arch Neurol
2004;24:301–317.● B 2003;60:1680–1684.● A
Ives NJ, Stowe RL, Marro J, et al. Monoamine oxidase type Sibon I, Fenelon G, Quinn NP, Tison F. Vascular parkin-
B inhibitors in early Parkinson’s disease: Meta-analysis sonism. J Neurol 2004;251:513–524.● B
of 17 randomized trials involving 3525 patients. BMJ Smaga S. Tremor. Am Fam Physician 2003;68:1545–1552.
2004;329:593–596.● A Volkman J. Deep brain stimulation for the treatment of
Jenner P. Dopamine agonists, receptor selectivity and dys- Parkinson’s disease. J Clin Neurophysiol 2004;21:6–17.●
A
kinesia induction in Parkinson’s disease. Curr Opin
Neurol 2003;16(suppl 1):S3–S7.● B

510
 C h a p t e r

67 Clumsiness and Difficulty

Walking (Brain Tumor)
Amber Barnhart

Present Illness
KEY POINTS Shirley presents to the emergency department
accompanied by her husband. Friends had called
1. If unexplained neurologic symptoms occur in a Shirley’s husband earlier in the day because of their
patient with significant risk factors for coronary concern about her writing. Shirley has always been
artery disease, vascular disease of the brain, an accomplished writer and now her e-mails are
stroke, and transient ischemic attack should be filled with grammatical errors, misspellings, and
considered and appropriately evaluated. incomplete sentences. Shirley has recently been fired
2. Other clues to the causes of unexplained neuro- from two housekeeping jobs because of “clumsi-
logic symptoms include ness.” Her husband noticed that she has been unusu-
a. Head injury and subdural hematoma ally quiet the past several weeks, and he thought she
b. Contagious infections and meningitis might be depressed. The couple has just retired and
c. Recent viral infections and encephalitis moved to a new state to be close to their grandchild.
d. Diabetes with hypoglycemia or hyper- Shirley’s husband thought his wife seemed happy
glycemia (or diabetic ketoacidosis) and content with their new life but had noticed this
e. Medication side effects or toxicity change in her recently. Because of all these concerns,
f. Alcohol abuse or illicit drug use he brought her to the emergency department.
3. Headache is the sole initial complaint in less
than 20% of patients with brain tumors. Medical History
4. New-onset seizures, an abnormal neurologic Shirley has a history of type 2 diabetes for the past 10
examination, change in mental function, or loss years. She also has a history of obesity, and with
of consciousness should raise concern about a weight loss, her diabetes has been under good con-
possible brain tumor. trol. In addition, she has coronary artery disease and
5. Brain metastases are commonly from the lung, had a coronary artery stent inserted 2 years ago. She
breast, prostate, and melanomas. takes metoprolol (Lopressor), 100 mg/day; ramipril
6. Appropriate radiographic studies in the evalua- (Altace), 5 mg/day; simvastatin (Zocor), 40 mg/day;
tion of a brain tumor include either computed and aspirin, 325 mg/day.
tomography or magnetic resonance imaging.
The choice depends on the suspected location Family History
of the tumor. Shirley is a twin; she and her twin are the youngest of
10 children. Her parents died of “undetermined
causes” in their 80s. Her siblings are healthy.

INITIAL VISIT Social History

Shirley is married and has worked as a housekeeper
Subjective and babysitter for years. She is very active in her
church, and her husband is a pastor. She has never
Patient Identification and Presenting smoked or used alcohol or drugs.
Problem
Shirley T. is a 58-year-old woman who presents to Review of Systems
the emergency department because of “problems Shirley denies any significant complaints, including
writing.” the problems noticed by her friends and family. She

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

511
 Chapter 67 Clumsiness and Difficulty Walking (Brain Tumor)

denies seizures, dizziness, vision changes, sensation or Differential Diagnosis

motor changes, head pain, ear drainage, or difficulty
swallowing. She denies shortness of breath, chest 1. TIA or stroke. Because of her history of diabetes,
pain, nausea, emesis, diarrhea, or melena. She denies hypertension, and coronary artery disease,
any unusual skin lesions or vaginal bleeding. concerns about possible vascular disease of the
brain would be appropriate. Such vascular disease
could involve the small cerebral vessels with
Objective multi-infarct disease or larger arteries with tran-
Physical Examination sient ischemic attacks or actual stroke. Usually a
General Shirley is a friendly woman who appears her transient ischemic attack or stroke presents with
stated age. She is in no distress. change to the motor and/or sensory components
of the neurologic system rather than the subtle
Vital Signs Height, 5 feet 8 inches tall; weight, 230 higher orders of function as seen in this patient.
pounds; respiratory rate, 20; pulse, 60; blood pres- 2. Non–brain tumor conditions of the brain.
sure, 169/83; temperature, 36.3˚C (97.3˚F). Conditions such as subdural hematomas,
meningitis, and encephalitis need to be consid-
Head, Eyes, Ears, Nose, and Throat Head: No signs of
ered also, but there is no history of trauma to
trauma. Eyes: Pupils equal, reactive to light and
suggest a subdural hematoma. The patient
accommodation; equal ocular movement; normal
is afebrile and has no other symptoms of
without nystagmus. Sclerae and conjunctivae are clear.
meningitis or encephalitis, although those may
Fundus: No signs of papilledema, no arterio- venous
present with subtle symptoms as well.
nicking, no hemorrhages. Ears: Tympanic membrane
3. Diabetes mellitus. The history of diabetes raises
normal bilaterally; canals are clear with no drainage.
concern about the blood glucose, and possible
Neck Neck nodes: All nonpalpable and nontender. early diabetic ketoacidosis should be consid-
Thyroid: Nonpalpable, no masses. ered, but this would be a very unusual presenta-
tion for diabetic ketoacidosis. Hypoglycemia
Lungs Clear without rales, rhonchi, or wheezing. should be considered if the change has been
Cardiovascular Heart: Regular rhythm and rate. Nor- relatively acute in onset and brief, but a history
mal S1 and S2. No murmurs. No carotid or renal bruits. of neurologic change persisting over several
weeks makes this diagnosis very unlikely.
Abdomen Obese. Nontender in all four quadrants 4. Medications. Patient use of medications and in
without masses. Liver and spleen are nonpalpable particular narcotics, sedatives, or sleeping aids
and not enlarged. could result in subtle changes in higher level func-
tion. The medications prescribed for her chronic
Rectal No masses and hemoccult-negative stool. conditions must be evaluated. Metoprolol, rami-
Back No costovertebral angle tenderness on right or left. pril, simvastatin, and aspirin were considered, but
the subtle intellectual function changes that
Breasts Symmetrical without masses. Supraclavicular occurred in this patient have not been reported
and axillary nodes are nontender and nonenlarged. with these medications.
5. Illicit drug or alcohol use. The use of alcohol,
Neurologic Cranial nerves II through XII are intact. illicit drugs, over-the-counter herbs and supple-
Deep tendon reflex: Lower and upper extremities ments, or mind-altering recreational drugs
symmetrical. Sensation: Grossly normal. Strength: should be investigated thoroughly, although this
Normal and symmetrical in face and upper and lower is not relevant in this patient.
extremities. Mental status: Oriented to person, place,
and time. Long- and short-term memory: Grossly
intact. Judgment: Grossly intact. Writing a sentence: Plan
Done correctly to oral command as well as copying. Diagnostic
Because of the importance of a brain tumor, com-
Assessment puted tomography or magnetic resonance imaging
should be ordered immediately. In addition, basic
Working Diagnosis laboratory tests should be performed to exclude
This patient presents with a subtle change in a higher other possibilities given her medical history.
order of function: grammatical errors in writing.
Noting the change in function should direct the Therapeutics
physician to begin a thorough evaluation of the Because the patient has subtle complaints, none of
patient. Of course, brain tumor is high on the list of which is causing her discomfort or anxiety, no
concerns and would be the working diagnosis. change in medications should be made at this time.

512
 Chapter 67 Clumsiness and Difficulty Walking (Brain Tumor)

Patient Education that suggest a brain tumor, the treating physician is

The patient and her family should be advised as to usually obliged to evaluate the entire patient and not
the various diagnostic possibilities given her symp- limit the investigation to the neurologic system.
toms. They should be encouraged to proceed with Fortunately, the clinical features of the patient’s health
the radiographic testing. However, they should also will usually mandate the appropriate evaluation.
be advised that the patient’s symptoms are subtle and Realistic and practical considerations concerning
that it might be difficult to discover the cause of the questions of medical insurance, the cost of appropri-
complaints. ate studies, the patient’s anxiety, and the need for a
relatively early diagnosis and the development of an
Disposition appropriate treatment plan are issues that have to be
A computed tomography scan is arranged for the resolved with the patient in a timely fashion.
patient (after insurance approval) for that afternoon. If a metastatic brain tumor is suspected, the site
Blood tests are obtained as the patient completed the of the primary cancer must be determined from a
clinic visit. The patient and her family are given an thorough history and physical examination as well as
appointment at the clinic for the next day to discuss appropriate comprehensive laboratory and radi-
the results of the tests. ographic studies of multiple organ systems (Fig. 67-1
and Box 67-1). Basic hematologic studies such as a
complete blood count are indicated to evaluate for
DISCUSSION possible anemia or infection. Abnormalities in the
white blood cell or platelet count may indicate lym-
Brain tumors are among the most feared diagnoses phoma. Serum electrolytes should be assessed
for a patient. Some of this fear and concern relates to because electrolyte abnormalities can result in
the perceived inherent importance of the brain for changes in mental status, and some abnormalities
normal function and for life. Laypeople and medical may suggest the primary site such as lung or adrenal
personnel alike are aware of the vital roles of the cancers. Liver function tests are helpful in the investi-
brain. Indeed, there is no simplistic “cut it out and fix gation of possible hepatic metastases or cirrhosis.
it” approach for brain tumors as is possible with other Ammonia levels may be needed if liver enzymes are
tumors. Thus, treatment options are often more normal and yet hepatic disease is suspected, because
restricted, which makes the disease and its manage- elevated ammonia levels with resultant hepatic
ment difficult for both patients and physicians. In encephalopathy often involve changes in mental sta-
addition, simple common complaints by patients can tus. Normal creatinine and blood urea nitrogen levels
actually herald the presence of the tumor. Although eliminate advanced renal failure as a cause of mental
complaints such as headaches, arm weakness, or stum- confusion, but renal cancer may still be a source of
bling often are of no significance, they may indicate brain metastases even with normal creatinine and
the need for further and more extensive evaluation. blood urea nitrogen. A thorough breast examination
Conducting a careful history and physical examina- for both female and male patients is a requirement in
tion is usually necessary to reassure the patient and the search for a primary cancer and may necessitate a
physician that further workup is or is not necessary. mammogram as well. In addition, a digital prostate
The physician takes special note of any unusual fea- examination and a pelvic examination may be neces-
tures of the history or physical. Sloane and colleagues sary in selected patients. Clinical judgment will dictate
(2002) point out that “headache is the sole initial the inclusion of a prostate-specific antigen test in men.
complaint in fewer than 20% of patients with brain Sonograms of the uterus and ovaries, a CA 125 blood
tumor.” The history of new onset seizures, an abnor- level, and a Pap smear may all be indicated in the
mal neurologic examination, a change in mental search for a primary cancer in women. A rectal exami-
function, and loss of consciousness are hallmarks of nation as well as a series of occult blood fecal tests
brain tumors. Occasionally, some brain tumors, would begin the workup for gastrointestinal cancer,
because of their distinctive location or pathology, do which can metastasize to the brain. A chest radiograph
produce specific findings. The schwannomas, for is needed to begin the evaluation of possible lung can-
example, cause unilateral hearing loss. Therefore, per- cer. All these were indicated for Shirley because she
forming a complete neurologic examination is the presented with a subtle form of confusion and with no
foundation for the evaluation of brain tumors. obvious source of a primary cancer after the initial his-
Brain tumors may be primary, such as the tory and physical examination. In general, in the vast
gliomas or meningiomas, or may represent metastatic majority of patients the history and physical examina-
disease from a distant primary malignancy. The inci- tion, and the results of the laboratory studies as well as
dence of primary brain tumors as well as of brain initial radiographs, will direct the physician to the pre-
metastases is increasing. Brain metastases are com- cise primary cancer involved.
mon in lung, breast, and prostate cancers and in If a brain tumor is suspected, a radiographic
melanomas. When a patient presents with symptoms examination is the next step in the investigation. This

513
514
Suggestive
symptoms1

Appropriate radiologic
studies2

Normal
studies Brain mass (lesion)

No brain tumor, other

studies as appropriate

Non brain Primary brain tumor Metastasis from other site

tumor3

Benign Malignant Appropriate medical evaluation4

Treat as
appropriate

Distant metastases
Localized Invasive
(rare)

Treatment dependent on other Prostate Breast Melanoma Lung Other

considerations5

No Surgical Appropriate
Observe Hospice Medical Radiation
treatment excision treatment for
primary cancer

Anti-seizure Chemo- Correct metabolic

medication therapy abnormalities, lower CSF
pressure

Figure 67-1 Suggested approach for the diagnosis and treatment of brain tumors. This is only a suggested approach, and, like any algorithm, it cannot include all possi-
ble variations. Although this stepwise evaluation will be helpful in the majority of patients, clinical judgment is required in selected patients. Note: Superscript numbers
refer to Box 67-1, page 515.
CSF, cerebrospinal fluid.
 Chapter 67 Clumsiness and Difficulty Walking (Brain Tumor)

study, but the suspected location of the tumor dic-

Box 67-1 Suggested Approach for the tates the ordering of the tests, and in many instances
Diagnosis and Treatment of both studies are necessary, as are positron emission
Brain Tumor tomography scans in selected patients. Magnetic res-
onance imaging shows brain structures best with
1. Suggestive of brain tumor fewer artifacts if the tumor is adjacent to bony struc-
a. Mental function changes tures such as the base of the brain. Computed
b. Loss of consciousness tomography is the most sensitive in the parenchyma
c. Personality changes of the brain where calcifications may be present. The
d. Seizures addition of intravenous contrast enhancement may
e. Sensorimotor abnormalities help “highlight” those tumors that have the same
2. Appropriate neurologic studies density as brain parenchyma. Positron emission
a. Computed tomography: most sensitive if tomography (PET) using fluorodeoxyglucose pro-
suspected tumor is in the brain paren- vides a relatively noninvasive method for studying
chyma glucose metabolism in tumors. Several studies show
b. Magnetic resonance imaging: fewer arti- that PETs can assess tumor progression and response
facts if suspected tumor is located near to treatment in gliomas (Padma et al., 2003● B ), glio-
bony structures (e.g., base of the brain) blastoma multiforme (Tralins et al., 2002● B ), and
c. Positron emission tomography: in supratentorial gliomas (Pardo et al., 2004● B ). PET
selected patients will undoubtedly have greater utility in the future
3. Non–brain tumor mass as the specific indications for the study become more
a. Subdural hematoma apparent and as the technology becomes more
b. Abscess widely available and less expensive.
c. Granuloma Management of a brain neoplasm is based on
4. Appropriate medical evaluation for suspec- several factors, certainly including the patient’s and
ted metastatic brain tumors the family’s requests and decisions. The nature of the
a. Complete blood count presenting symptoms, the localization of the tumor
b. Liver function tests within the brain, and the presence or absence of sig-
c. Electrolytes nificant comorbidities such as heart failure, chronic
d. Renal function (creatinine, blood urea pulmonary disease, and end-stage renal or hepatic
nitrogen) disease or the presence of other malignancies or
e. Prostate-specific antigen other illnesses that may limit life expectancy are crit-
f. Mammogram ical factors that must be given consideration as an
g. CA 125 (and/or pelvic sonogram) extensive workup is initiated. The cell type of origin,
h. Chest radiograph usually demonstrated by a brain biopsy, is critical in
i. Hemoccult determining appropriate treatment. The size and
5. Other considerations for appropriate treat- extent of the tumor, the rapidity of change, and
ment of brain tumors whether it is encapsulated or invasive are important
a. Patient/family decisions factors in determining treatment. There are several
b. Location in the brain cell types in the brain. Glial cells are categorized as
c. Symptoms macroglia (astrocytes, oligodendrocytes, ependyma
d. Type of tumor/rapidity of change [derived from neuroectoderm]) or microglia
e. Size and extent of tumor (derived from bone marrow). Each of these cell types
f. Encapsulated versus invasive can result in a different tumor type. Each tumor type
g. Comorbidities requires a specific oncology treatment plan with spe-
i. Age/state of health cific outcome possibilities. Gliomas, for example, are
ii. Chronic obstructive pulmonary the most common primary brain tumors. Tumors
disease/congestive heart failure/other within this type of cell are further divided into astro-
cancers, etc. cytomas (from astrocytes) and oligodendrogliomas
(from oligodendrocytes). Within each of these cell
types tumors also are graded, and each grade
This would be the first order of testing if the physician requires a different management plan. In addition,
believes a primary brain tumor is a likely diagnosis. many brain tumors have a strong propensity to
In addition, other neurologic abnormalities such as a develop malignant components and have mixed cell
subdural hematoma, stroke, and brain abscess would grades. Because of the specific and extensive range of
be eliminated by this testing. There is controversy treatment plans for brain tumors, the family physi-
about whether computed tomography or magnetic cian or primary care doctor will be instrumental in
resonance imaging is the most appropriate initial making the diagnosis, initiating the appropriate

515
 Chapter 67 Clumsiness and Difficulty Walking (Brain Tumor)

workup, establishing whether the brain mass is invasiveness is poor, with survival measured in terms
limited to the brain or represents metastatic disease, of months rather than years, but new rapidly chang-
and starting initial medical management. Other ing developments in the treatment of brain tumors
members of the medical team, including a neurosur- are encouraging. Recent investigational protocols
geon and a radiation therapist or an oncologist, need combining chemotherapy, radiation, and surgery
to be consulted unless the patient or the family administered in varying order have shown some
specifically requests that no aggressive therapy be promising results. In addition, there are new advances
provided. The initial medical management of most in the technology of chemotherapeutic agents for
brain tumors includes the use of corticosteroids, treatment of brain tumors. Gliadel wafers (con-
such as dexamethasone. If a lymphoma with brain trolled-release 1,3-bis-(2-choroethyl)-1-nitrosourea)
metastases is a possibility or the patient is HIV posi- are inserted into the bulk of the tumor, thus bypass-
tive or has AIDS and is immunocompromised, the ing the blood-brain barrier. They hold promise for
use of corticosteroids is more complex. Many tumors the future in the treatment of brain neoplasia.
result in seizures, and the use of diphenylhydantoin Fortunately, science continues to explore options in
or antiseizure medication should be strongly consid- the treatment of a deadly and very intimate disease:
ered. Generally, chemotherapy is not a primary con- brain cancer.
sideration for the treatment of a patient with a brain
tumor because the blood-brain barrier that protects Material Available on Student Consult
the brain in most situations is a deterrent for many
Review Questions and Answers about Brain
chemotherapeutic agents.
Tumor
The prognosis for most malignant brain tumors
regardless of cell type, location, extent, and degree of

REFERENCES
Padma MV, Said S, Jacobs M, et al. Prediction of pathology Tralins KS, Douglas JG, Stelzer KJ, et al. Volumetric analy-
and survival by FDG PET in gliomas. J Neurooncol sis of 18F-FDG PET in glioblastoma multiforme:
2003;64:227–237.● B Prognostic information and possible role in definition
Pardo FS, Aronen HJ, Fitzek M, et al. Correlation of FDG- of target volumes in radiation dose escalation. J Nucl
PET interpretation with survival in a cohort of glioma Med 2002;43:1667–1673.● B
patients. Anticancer Res 2004;24:2359–2365.● B
Sloane PD, Slatt LM, Ebell MH, Jacques LB. Essentials of
Family Medicine, 4th ed. Baltimore, Lippincott Williams
& Wilkins, 2002.

SUGGESTED READINGS
Becker LA, Green LA, Beaufait D, Kirk J, Froom J, Freeman Cady R, Dodick DW. Diagnosis and treatment of migraine.
WL. Detection of intracranial tumors, subarachnoid Mayo Clin Proc 2002;77:255–261.● A
hemorrhages, and subdural hematomas in Primary
care patients: A report from ASPN, part 2. J Fam Pract
1993;37:135–141.● C

516
 C h a p t e r

68 Terminal Illness

Timothy P. Daaleman

tional status, the cardiologist recommends surgical

KEY POINTS replacement of her aortic valve. Mrs. R. declines the
surgery and returns to her family physician for ongo-
1. Palliative care begins once the goals of care ing care, requesting a prognosis.
have been outlined and established. Advance
care planning requires communication skills Medical History
that include open-ended questioning, empathic Mrs. R. has a history of essential hypertension, uri-
listening, and attention to the psychological nary incontinence, macular degeneration, atrial fib-
and social contexts of the patient. rillation, valvular heart disease with mitral valve
2. Regular and standardized assessments of pain replacement, and generalized anxiety disorder with
and symptoms are the foundation for effective depressive symptoms. Her medications include meto-
treatment, and pharmacologic medications prolol (Lopressor), 50 mg twice daily; bumetanide
should be scheduled on a regular basis rather (Bumex), 0.5 mg/day; digoxin, 0.25 mg/day;
than waiting for symptoms to accelerate. amlodipine (Norvasc), 10 mg/day; sertraline (Zoloft),
3. Suffering cuts across psychological, social, and 25 mg/day; and warfarin (Coumadin), 5 mg/day.
spiritual domains, and care providers should
consider using resources, such as hospice and Family History
palliative care services, that can provide care Mrs. R. reports a family history of cerebrovascular
and support in these areas. and atherosclerotic heart disease; however, she states
that her only daughter has no health problems.

Social History
INITIAL VISIT Mrs. R. quit cigarette smoking 20 years ago and does
not drink alcohol. She recently relocated to the area
Subjective to be closer to her daughter, who is her primary care-
giver, and resides in an apartment adjacent to her
Patient Identification and Presenting daughter’s home. Mrs. R. is fully independent in all
Problem of her activities of daily living and travels to her med-
Mrs. R. is an 83-year-old woman seen by her family ical appointments using public transportation. She
physician after an initial consultation with a cardiol- has previously completed an advance directive and
ogist. Mrs. R. was referred for evaluation of valvular has named her daughter as having durable power-
heart disease—she underwent mitral valve replace- of-attorney for health-care decisions.
ment approximately 12 years ago—and for her
chronic rate-controlled atrial fibrillation. She denies Review of Systems
any chest pain; however, she acknowledges some dys- Mrs. R. denies any syncope, orthopnea, peripheral
pnea on exertion, especially when climbing stairs. swelling, or pain. She discloses some remorse over
During her consultation, a two-dimensional echo- her recent relocation and misses her friends and
cardiogram reveals a well-seated prosthetic mitral other family members from her prior place of resi-
valve, but a markedly sclerotic aortic valve with mild dence. She describes a functional relationship with
regurgitation. As a result of this finding, and in con- her daughter and son-in-law, but one that is not
sideration of Mrs. R’s very good health and func- close and intimate.

517
 Chapter 68 Terminal Illness

Objective 2. Coordination of care. Once a care plan has been

established, Mrs. R.’s physician makes several
Physical Examination copies of the advance directive for the medical
The patient is a thin, anxious-appearing woman who is record and Mrs. R.’s family members, and docu-
alert and oriented and appears her stated age. Her ments the discussion and plan within the elec-
weight is 107 pounds, and her vital signs include blood tronic medical record that serves both the
pressure of 175/75, pulse irregular at 62, respiratory rate outpatient family practice clinic and the admitting
of 16, and temperature of 36.2˚C (97.1˚F). Her neck hospital. The physician also contacts Mrs. R.’s
examination is without jugular venous distention, and daughter—who has the durable power of attor-
her lungs were clear to auscultation bilaterally without ney—and reviews and verifies the care plan. The
wheezes, rales, or rhonchi. The cardiovascular exami- physician’s pager number and direct phone line to
nation is remarkable for an irregularly irregular rhythm the clinic are given to Mrs. R. and to her daughter,
with a loud grade 4/6 crescendo/decrescendo murmur and a 6-week follow-up appointment is scheduled.
at her right base, which radiates into neck bilaterally. In 3. Pain and symptom care. Mrs. R. denies any pain
addition, a high-pitched holosystolic murmur is heard but describes some dyspnea on exertion with stair
at the left sternal border and an audible mechanical climbing, but feels that supplemental oxygen is
valve click. Mrs. R.’s abdomen is soft and nontender, unnecessary. A greater concern is her frequent
with no hepatosplenomegaly, and her extremities are tearfulness, difficulty with sleep, and feelings of
without cyanosis, clubbing, or edema. Her interna- loss and distance from some family members that
tional normalized ratio (INR) is reported at 2.6. predated the disclosure of her terminal disease.
She is maintained on sertraline, which has a low
Assessment likelihood of cardiogenic side effects; however,
she declines outpatient psychological therapy,
Working Diagnosis such as cognitive-behavioral therapy and counsel-
The working diagnosis is valvular heart disease and ing (Morrison and Meier, 2003).
chronic atrial fibrillation, which constitutes a pro- 4. Social, spiritual, and bereavement support. Mrs. R.
gressive disease leading to eventual heart failure and and her daughter would clearly benefit from a
subsequently death. Mrs. R. chooses to forego a sur- support group and the involvement of counseling
gical intervention that would potentially prolong her or bereavement services. The patient has previ-
life and has elected a palliative course of care. ously attended activities coordinated through the
area agency on aging, but has no interest in
returning there and considers herself too private
Plan
to allow nonfamily members to be involved in her
Four major areas must be considered in providing care. She comes from a Jewish faith tradition and
palliative care to Mrs. R. as she begins to approach does not draw any inner strength from her beliefs,
the end-of-life: effective communication and estab- practices, or communities of faith. Mrs. R. is
lishment of care goals; coordination of care; pain and offered enrollment in a hospice program but can-
symptom care; and social, spiritual, and bereavement not see the benefit of this service at this time.
support (Morrison and Meier, 2004).

1. Effective communication and establishment of care FOLLOW-UP VISIT

goals. Mrs. R.’s request for a prognosis for her termi-
nal heart disease invites an open-ended discussion Subjective
about the type of care that she wishes to receive and
her overall goals of care. She speaks freely with her Mrs. R returns for an office visit accompanied by her
family physician and has a level of trust that has daughter approximately 3 months after her previous
developed over several months. Mrs. R. is unam- appointment and 1-week after hospitalization for
biguous about the goals of her care, predicated on a upper gastrointestinal bleeding. In the emergency
quality of life that is determined by her ability to department, she had a 1-day history of weakness and
remain independent and highly functional. Her was found to be profoundly anemic with guaiac-
physician reviews the existing advance directive, out- positive stools. Her admission INR was 2.5 (normal
lines several potential clinical scenarios regarding for therapy), and during hospitalization, she received
her disease progression, and they arrive at a care plan vitamin K and fresh frozen plasma before upper
that includes hospitalization for symptom control, endoscopy identified a bleeding site at her distal
but sets limits regarding curative or aggressive treat- esophagus. Mrs. R. received 4 units of packed red
ment (EPEC, 2004). These limits include foregoing blood cells and was started on omeprazole (Prilosec)
resuscitative efforts and transfer to an intensive care and enoxaparin (Lovenox). Her cardiovascular status
unit should her condition in the hospital deteriorate. remained stable, and her weakness improved after

518
 Chapter 68 Terminal Illness

her transfusion. She was discharged to a skilled nurs- lorazepam (Ativan), 0.5 mg, is prescribed at 6- to
ing facility for interim care with an anticipated 8-hour intervals. Low-dose morphine sulfate
return to home. On today’s visit, Mrs. R. complains drops are added to the treatment regimen for per-
of persistent shortness of breath and bilateral lower sistent dyspnea that is refractory to the other
extremity swelling. measures (Doyle et al., 2004).
4. Social, spiritual, and bereavement support. Mrs.
Objective R.’s nursing facility has an existing support group
for family caregivers and a full-time chaplain on
The patient’s weight is 113 pounds, and her vital signs site. Both she and her daughter are open to these
include a blood pressure of 160/72, irregular pulse of services and to the possibility of reconnecting
69, respirations 20, and temperature of 36.2˚C with an area synagogue (National Consensus
(97.1˚F); her room air pulse oximetry is recorded at Project, 2004).
90%. Her neck examination is remarkable for trace
jugular venous distention, and her lungs demonstrate
bibasilar crackles. The cardiovascular examination is DISCUSSION
remarkable for an irregularly irregular rhythm with a
loud grade 4/6 crescendo/decrescendo murmur at her The provision of quality palliative care is an essential
right base, a high-pitched holosystolic murmur at the skill of primary care medicine. Patients consistently
left sternal border, and an audible mechanical valve focus on three domains when asked about end-of-
click. Mrs. R.’s abdomen is soft and nontender with life care issues; pain and symptom management,
no hepatosplenomegaly. Her extremities show +2 communication and goal planning, and attention to
nonpitting edema. psychosocial and spiritual needs (Morrison and
Meier, 2004).
Assessment
Pain and Symptom Management
Mrs. R. shows marked progression and exacerbation
of her chronic heart failure. A primary goal in palliative care is the relief of pain
and other common symptoms, such as nausea and
Plan dyspnea, which contribute to suffering. Regular and
standardized assessments of pain and symptoms are
1. Effective communication and establishment of care the foundation for effective treatment. Table 68-1
goals. Mrs. R.’s physician reviews the clinical outlines some approaches to pain and symptom
impression of worsening heart failure and management in palliative care. The simplest, least
reassesses her understanding of the diagnosis, invasive, and most effective regimen is the one that is
prognosis, and disease course (EPEC, 2004). Both used (Doyle et al, 2004; EPEC, 2004).
disease-modifying and symptom-directed treat- The nature, cause, and temporal component of
ments, involving hospitalization, skilled nursing the pain should be assessed to determine the physi-
care, and hospice, are outlined and considered ologic (e.g., neuropathic or nociceptive) and con-
during a discussion that involves both the patient textual (e.g., psychosocial, spiritual) components
and her daughter. At the end of the discussion, composing the pain (Morrison and Meier, 2003).
Mrs. R. recognizes and accepts that her symptoms Pharmacologic pain medications should be sched-
may be the beginning of a more active phase of uled on regular basis rather than waiting for
dying and directs a care goal of symptom care symptoms to increase. Rescue dosages of imme-
only within the nursing facility. diate-release medications are generally 10% of the
2. Coordination of care. The discussion and care plan 24-hour required opioid dose and should be avail-
are documented within the medical record, and able for breakthrough pain (Doyle et al., 2004;
the advance directive is reviewed and verified. EPEC, 2004). Dosing of both scheduled and rescue
During the office visit, the physician personally medications must be frequently reassessed and
contacts the medical director and director of titrated according to the response to pain.
nursing at Mrs. R.’s skilled care facility to outline Meperidine, because of low potency and the toxic-
and coordinate the care plan: treatment of symp- ity of its metabolite, in addition to antagonist ago-
toms with no hospitalization (Morrison and nists such as pentazocine, nalbuphine, and
Meier, 2004). butorphanol, should be avoided (Doyle et al., 2004;
3. Pain and symptom care. Mrs. R. has persistent dys- EPEC, 2004). In addition, all patients who are tak-
pnea at rest, and her bumetadine is increased to ing opioids should be on a bowel regimen to pre-
1 mg/day, and supplemental oxygen also is vent constipation.
prescribed. She acknowledges that part of her Formal (e.g., nursing) and informal (e.g., fam-
difficulty breathing may be due to anxiety, and ily) caregivers should be directed in their routine

519
 Chapter 68 Terminal Illness

Table 68-1 Pain and Symptom Management in Palliative Care

Symptom Assessment Treatment

Pain Visual pain analogue For mild pain, consider acetaminophen or NSAIDs.
scales For moderate pain, short-acting opioids should
be titrated to pain control For severe pain, use
short-acting opioids until pain is controlled
Begin a long-acting opioid at equal-analgesic
dosage
For neuropathic pain, adjuvant analgesics include
anticonvulsants or low-dose tricyclic
antidepressants
For bone pain, consider NSAIDs, calcitonin, or
bisphosphonates
Constipation Check bowel functioning, Use stool softener with stimulant until effective
and review potential Consider other stimulant classes if refractory
medication side effects
Nausea/Vomiting Check bowel functioning, Promethazine or scopolamine if mild
and review potential If severe, consider haldoperidol, chlorpromazine,
medication side effects metoclopromide, or ondansetron
Dyspnea Think BREATH AIR Treat specific symptoms
Bronchospasm Albuterol, ipratropium, steroids
Rales Diuretics, check IV fluids
Effusions Consider thoracentesis
Airway obstruction Check airway
Thick secretions Nebulized saline, glycopyrrolate, hyoscyamine
Hemoglobin low Consider transfusion
Anxiety Benzodiazepines, relaxation therapy, opioids
Interpersonal issues Counseling
Religious concerns Pastoral care
Anxiety Is there panic, agitation, Supportive counseling, and consider
restlessness, insomnia, or benzodiazepines
excessive worry?
Depression Feelings of anhedonia, Psychotherapy, pharmacologic therapy, or
helplessness, hopelessness, combination
suicidal
Delirium Identify potential reversible Treat underlying causes if possible
causes; is this a terminal Consider atypical antipsychotics
event?

NSAID, nonsteroidal anti-inflammatory drug.

assessments to specific symptoms (e.g., dyspnea, goal requires communication skills that include
constipation) and away from medical parameters open-ended questioning, empathic listening, and
such as vital signs, for patients who have elected pal- attention to the psychological and social contexts of
liative care (Morrison and Meier, 2003). Table 68-1 the patient (Morrison and Meier, 2004). Primary
includes common symptoms found at the end of life, care is an ideal setting to facilitate and formulate
which are assessed both by targeted questions to con- advance care planning because of an emphasis on
scious patients (e.g., “are you depressed?”) and by continuity; however, adequate time must be allo-
recognizing symptoms (e.g., agitation, delirium) in cated for this task.
patients who are unable to respond (Morrison and Physicians should gauge both patient and family
Meier, 2004). understanding of the disease process, prognosis, and
treatment alternatives. Dying patients and their
physicians frequently overestimate survival probabil-
Communication and Goal Planning
ities, which often influence treatment choices
Palliative care begins once the goals of care have (Morrison and Meier, 2003). For some patients, a pri-
been outlined and established. Arriving at a care mary goal may be to prolong life at all costs. However,

520
 Chapter 68 Terminal Illness

most patients approaching death want to have some spiritual domains (National Consensus Project,
quality of life that includes a closer relationship and a 2004). Dying is a time of tremendous stress but also
lessened burden to their families, treatment of their offers important opportunities for growth, intimacy,
pain and other physical symptoms, and retention of a reconciliation, and closure within relationships.
sense of control over their lives. Physicians who care for these patients should be
Advance directives are helpful in documenting attentive to various cues that indicate depression,
and communicating care goals to other providers familial conflict, or spiritual distress and should con-
(e.g., first responders) and family members, once sider resources, such as hospice and palliative care
they are established. These documents verify a plan services, that can provide care and support in these
of care and treatment that the patient has designated. areas (National Consensus Project, 2004).
A durable power of attorney for health care allows a
patient to identify a family member, or other indi-
vidual, to make decisions regarding his or her care,
and it is effective once a patient with a terminal con- Material Available on Student Consult
dition no longer has the capacity to make decisions Review Questions and Answers about Terminal
(Morrison and Meier, 2003). Illness

Psychosocial, Spiritual, and Bereavement

Support
Patients and family members who approach death
have needs that cut across psychological, social, and

REFERENCES
Doyle D, Hanks GW, Cherny NI, Calman K. Oxford Morrison RS, Meier DE. Palliative care. N Engl J Med
Textbook of Palliative Medicine, 3rd ed. Oxford, 2004;350:2582–2590.
England, Oxford University Press, 2004. The National Consensus Project for Quality Palliative Care
EPEC Project home page. Available at www. epec.net/EPEC/ home page. Available at www.nationalconsensuspro-
webpages/index.cfm. Accessed 9/30/2004. ject.org. Accessed 9/30/2004.
Morrison RS, Meier DE. Geriatric Palliative Care. New
York, Oxford University Press, 2003.

521
 C h a p t e r

69 Pain “Everywhere” (Fibromyalgia)

Kurt A. Lindberg

Medical History
KEY POINTS Review of Jennifer’s chart shows that she has a his-
tory of anxiety and depression, which has recently
1. Fibromyalgia is a distinct condition with definable been under good control. She has had an appendec-
findings on history and physical examination. tomy, total abdominal hysterectomy, and cholecys-
2. No signs of significant abnormalities are found tectomy. She carries a diagnosis of irritable bowel
in the peripheral tissues or the serum of syndrome (IBS) and female urethral syndrome.
patients with fibromyalgia.
3. Current theories of pathophysiology of the con- Medications
dition suggest abnormalities in the communica- Jennifer takes fluoxetine (Prozac), 60 mg daily;
tion, processing, and thresholds of pain in the bupropion (Wellbutrin), 150 mg twice daily; cele-
central nervous system. coxib (Celebrex), 100 mg twice daily; and conjugated
4. Treatment of fibromyalgia includes patient edu- estrogens (Premarin), 0.625 mg daily.
cation, getting regular sleep, treating comorbid
conditions, and maintaining regular aerobic Family History
exercise. Jennifer’s father died at age 65 of a sudden heart
5. Few medications have been shown to be help- attack. Her mother was “always in the doctor’s office”
ful for this condition. for various medical problems and died of a stroke at
age 76. She has no siblings and two children, one of
whom has depression and chronic back pain.

INITIAL VISIT Social History

Jennifer has been married for 32 years. She smokes
Subjective half of a pack of cigarettes per day but has been try-
ing to “cut back.” She drinks alcohol occasionally
Patient Identification and Presenting (approximately three to four drinks per week) and
Problem does not use illicit drugs.
Jennifer C., a 55-year-old woman seen in the outpa-
tient clinic, complains of low back pain that has been Review of Systems
gradually worsening during the past 6 months. She Jennifer has felt chilled and clammy but has had no
attributes the pain to a day when she cared for her fever. She has no shortness of breath or cough or sig-
2-year-old grandchild and “overdid it.” Jennifer nificant chest pain. Her chronic IBS causes abdomi-
describes the back pain as a severe, dull ache that nal discomfort, diarrhea, and constipation, but no
radiates into her hips. She complains of paresthesias rectal bleeding, reflux, or nausea. She has her usual
in both lower extremities. She has difficulty falling urinary frequency but no dysuria or other urologic or
asleep at night and wakes frequently because of her gynecologic symptoms. She has had no joint swelling
pain. Over the last several months, the pain seems to or redness but feels as if her hands are “puffy.” She has
have traveled “everywhere.” She now aches in her had no skin, hair, or mucous membrane abnormali-
arms, her hands, and her neck. She feels severely ties. Her mood is low because of her condition, but
fatigued and is unable to do even the most basic she denies feeling as depressed as she has been in the
housework. She cannot even tolerate having some- past. Her appetite is normal, but sleep is disturbed, as
one touch her arm without shrinking in pain. noted in the history. She often feels as if she is “in a

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

522
 Chapter 69 Pain “Everywhere” (Fibromyalgia)

fog” and is forgetful and has trouble concentrating. membrane abnormalities. If signs of systemic
She has no suicidal ideations or anhedonia. inflammation such as sedimentation rate (ESR)
or C-reactive protein are normal, these conditions
Objective can effectively be ruled out as causes of Jennifer’s
complaints. It should be noted that several blood
Physical Examination tests used to diagnose connective tissue disorders
Jennifer is a middle-aged Hispanic woman who (e.g., antinuclear antibody or rheumatoid factor)
appears in no acute distress. She is 5 feet 2 inches tall may be positive in a small number of normal
and weighs 160 pounds. Her temperature is 36.6˚C individuals. For this reason, these tests should not
(97.8˚F), respiratory rate 16, pulse 88, blood pressure be ordered unless the patient’s inflammatory
124/78. Her head examination is normal with no markers, physical examination, or history is con-
mucosal lesions. Her neck is supple with no lym- sistent with one of these disorders. This will avoid
phadenopathy or thyromegaly. Lungs are clear to a patient becoming overly concerned about a con-
auscultation bilaterally. Her heart is regular with no nective tissue disorder because of an elevated
murmur. Her abdomen has normal bowel sounds blood test that has no clinical relevance.
with generalized tenderness but no guarding or 4. Fibromyalgia. Fibromyalgia is a condition of gen-
rebound. Specifically, she has no peripheral edema or eralized pain in muscles, tendons, and skin that
joint swelling or redness. Her skin and hair are nor- has no demonstrable local abnormality. Patients
mal. Her orientation and memory appear to be with fibromyalgia often are initially seen with a
intact. Objective cutaneous numbness is not found. single area of maximal concern in the axial skele-
Her muscle strength is difficult to assess because she ton (spine, hips, or buttocks) and often attribute
seems to collapse because of pain when being tested. the onset to a specific event (Bradley and Alarcon,
Her reflexes are normal. She is limited in spinal flex- 2005● A). This diagnosis seems to fit this patient’s
ion to 45 degrees and is unable to extend backward presentation; however, further testing should be
because of pain in the lumbar musculature. The performed to rule out other conditions before
areas in which she describes pain are primarily the arriving at this diagnosis. If fibromyalgia is sug-
muscles and tendinous regions, not in bones or gested by the patient’s history and examination,
joints. the practitioner should perform a “tender point”
evaluation (Fig. 69-1). No serologic or radiologic
test is available to confirm or rule out fibromyal-
Assessment
gia (Gilliland, 2005● B ).
Working Diagnosis 5. Hypothyroidism. Patients with low levels of thyroid
Low-back pain, diffuse myalgias, and fatigue hormone often experience cold intolerance,
fatigue, and swelling similar to Jennifer’s symp-
Differential Diagnosis toms. Hypothyroidism is common and may be eas-
1. Muscular strain. Jennifer’s history of low-back ily diagnosed through testing of the serum level of
pain beginning after overuse could be consistent thyroid-stimulating hormone (TSH). If the TSH
with a muscular strain. This would not explain level confirms this diagnosis, thyroid-replacement
the widespread discomfort she is experiencing, therapy would reverse any associated symptoms.
however. 6. Inflammatory myopathy (e.g., dermatomyositis).
2. Polymyalgia rheumatica. This is a condition of Inflammation of the muscles usually results in
inflammation causing proximal muscle pains, weakness rather than pain and is ruled out if
usually seen in middle-aged patients. This condi- inflammatory markers and creatinine kinase are
tion responds well to corticosteroids and is normal.
important to identify because of rare sudden 7. Somatoform disorder. This is a group of psychi-
blindness due to an association with temporal atric diagnoses that includes somatization disor-
arteritis. A normal erythrocyte sedimentation rate der, hypochondriasis, conversion disorder, and
(ESR) would make this condition highly unlikely. malingering. This group of disorders requires the
3. Connective tissue disorder (e.g., lupus). The hall- assumption that no physical abnormality is pres-
mark of these disorders is objective signs of joint ent in the patient (First, 2000 ● C ). Because
inflammation, objective skin or mucous mem- fibromyalgia has no readily apparent organic
brane abnormalities, and abnormal serologies abnormalities, many patients with fibromyalgia
(e.g., antinuclear antibody). These conditions receive (formally or informally) one of these
usually respond to immune-modulator medica- labels. However, it will be presented in the
tions and thus are important to consider in Discussion section that fibromyalgia is a distinct
patients with generalized pain. However, this disorder with objective diagnostic criteria and
patient has mostly muscular or tendinous pain with research findings that suggest an organic
and no objective signs of joint, skin, or mucous basis.

523
 Chapter 69 Pain “Everywhere” (Fibromyalgia)

physical therapy, and consideration of imaging stud-

ies if thought appropriate.
If she has abnormally painful responses on ten-
der-point examination and the blood and radiology
testing is normal, a diagnosis of fibromyalgia can be
made. A patient-education brochure on fibromyalgia
is then provided with information about this condi-
tion and how it can be managed (see Discussion).
She is given a prescription for amitriptyline
(Elavil), 25 mg, to take at bedtime to assist with sleep.
Close questioning of her husband reveals that
Jennifer displays no symptoms of sleep apnea. She is
strongly encouraged to institute regular aerobic exer-
cise and specific instructions on how to do so is pro-
vided. Follow-up visits will be made on a regular basis
until Jennifer becomes well accustomed to the diag-
nosis of fibromyalgia and its treatment strategies.

DISCUSSION
The existence of fibromyalgia has been controversial
for decades. Some authors have suggested a distinct
organic pathology, whereas others have repudiated
Figure 69-1 Tender points used in the diagnosis of this claim and insist these patients are somaticizing
fibromyalgia: suboccipital muscle insertion, anterior to
C5–C7 intertransverse process, midpoint of the upper
psychiatric problems. The current predominant
border of trapezius, medial origin of supraspinatus, sec- opinion, however, notes that these patients have a
ond costochondral junction, 2 cm distal to the lateral consistent presentation of their illness, with research
eipcondyle, upper outer quadrant of the buttock, poste- findings suggestive of a complex pathology involving
rior to the trochanteric prominence, medial fat pad peripheral tissues and the central nervous system.
proximal to the knee.
The term fibromyalgia syndrome (FMS) has been
used to incorporate this new understanding (Bradley
9. Worsened depression. Depression is frequently and Alarcon, 2005● A).
coexistent with chronic pain conditions, and it is In 1990 the American College of Rheumatology
always appropriate to consider this in such published its diagnostic criteria for fibromyalgia.
patients. Depression or anxiety does intensify the Musculoskeletal pain must be present on both sides
reporting of pain. Conversely, experiencing of the body, above and below the waist, and in the
chronic pain may lead to depression or anxiety. If axial skeleton. Symptoms must have been present
screening questions reveal that a mood disorder is for at least 3 months. Significant pain should be
present, it should be appropriately treated regard- evidenced in at least 11 of 18 tender points (see Fig.
less of its specific role in Jennifer’s complaints. 69-1) with relatively low-intensity pressure. Patients
with fewer than 11 tender points may still be consid-
Plan ered for this condition outside of the research set-
ting. The tender points are elicited with the examiner
Diagnostic applying enough pressure (approximately 4 kg or
Laboratory testing to rule out these conditions should 9 pounds) with his or her thumb to cause blanching
be obtained. Specifically, a complete blood count with of that thumbnail. A positive response is simply the
differential, chemistry profile, ESR or C-reactive pro- patient’s report of pain. A normal control would
tein, TSH, and creatine kinase are most appropriate. notice only mild pressure with the same maneuver. If
Follow-up testing may include T4 or free T3 levels, malingering or exaggeration is suspected, control
antinuclear antibody (ANA), anti–double-stranded sites, such as the top of the patient’s thumbnail, or
DNA, etc. the dorsal side of the distal forearm, may be palpated.
However, it should be cautioned that patients with a
Therapeutic formal diagnosis of fibromyalgia will have decreased
It is reasonable to address Jennifer’s primary concern thresholds for pain, even in these sites, compared
of back pain as one would do for most muscu- with patients that do not have fibromyalgia (Bradley
loskeletal conditions. This includes anti-inflamma- and Alarcon, 2005● A). The hallmark of FMS is a
tory drugs, a program of stretching, referral to decreased threshold for pain (allodynia) in addition

524
 Chapter 69 Pain “Everywhere” (Fibromyalgia)

to increased skin sensitivity to temperature and

touch (hyperalgesia). Box 69-1 Conditions That Frequently
The pathophysiology of fibromyalgia has been Coexist with Fibromyalgia
difficult to identify. Consensus is building that ini-
tially a peripheral source of painful stimulus (injury, Depression
muscle microtrauma, etc.) sensitizes central nervous Anxiety disorders
pain thresholds and processing. This is evidenced by Post-traumatic stress disorder
documented changes in neurotransmitter levels in Migraine headaches
the blood and cerebrospinal fluid of affected Tension headaches
patients and altered cerebral blood flow in regions of Dysmenorrhea
the brain known to be associated with pain Irritable bowel syndrome
processing. Malfunction of the hypothalamus/ Female urethral syndrome
pituitary/adrenal axis, decreased secretion of growth Paresthesias/dysesthesias
hormone, and altered thyroid function have been Raynaud phenomenon
documented in patients with fibromyalgia. Unfor- Sicca symptoms
tunately, we still have no ability to rule in or rule out Photosensitivity
this condition with objective testing. However, this Chronic pelvic pain
does not refute the growing evidence that Multiple chemical sensitivities
fibromyalgia has at least some organic pathology Obstructive sleep apnea
present (Bradley and Alarcon, 2005● A). Restless leg syndrome
Ninety percent of those with fibromyalgia are Chronic fatigue syndrome
female patients, and the condition seems to become
more common with increasing age. It is estimated that
3.4% of women in the general population and 0.5% of condition and how it can be managed. The physician
men fit the criteria for FMS (Gilliland, 2005 ● B ). should reassure the patient that the symptoms are
Reports from tertiary care centers have noted a high not imaginary, empathize with the patient’s suffer-
prevalence of psychiatric diagnoses and histories of ing, and commit to working with the patient to man-
childhood trauma in their patients with fibromyalgia. age symptoms. Explaining the chronic nature of this
It is still debated whether psychiatric or psychosocial condition is essential. It has been estimated that after
stressors play a role in the development of this condi- 5 years, up to 75% of patients have not had signifi-
tion, or whether they merely contribute to seeking cant improvement of their complaints. Children and
medical attention or result in poor coping skills. Some men seem to have better prognoses.
studies have suggested that the prevalence of psychi- Often coexisting psychiatric problems and per-
atric diagnoses in patients with fibromyalgia who have sonality disorders inhibit patients from adopting dis-
not sought medical attention does not differ from con- ciplined management of the illness. Cognitive
trols (Bradley and Alarcon, 2005● A). behavioral therapy may be helpful to address these
Patients with FMS consistently have difficulty issues, and coexistent mood disorders should be
with sleep. Specifically, deep-sleep deprivation has treated. Fluoxetine and amitriptyline have been
been documented and may in fact contribute to the shown to be superior to placebo in reducing symp-
development of symptoms of pain and the fre- toms of fibromyalgia in addition to their mood-
quently reported compromises in memory and con- altering effects. Treatment of underlying depression
centration. Studies also have shown a high or sleep apnea will help to restore deep-sleep cycles,
correlation between obstructive sleep apnea and which may improve cognitive function and fatigue
fibromyalgia. Therefore sleep testing should be con- somewhat. Other medications that may help with
sidered in patients for whom this seems appropriate. sleep are tricyclic antidepressants, gabapentin, and
Other conditions that frequently coexist in patients cyclobenzaprine. Benzodiazepines have been shown
with fibromyalgia are listed in Box 69-1. to be useful when combined with ibuprofen in
Severe fatigue is one of the most debilitating patients with fibromyalgia and may also assist in
complaints of many fibromyalgia patients. It has been sleep regulation (Bradley and Alarcon, 2005● A).
estimated that 65% to 75% of FMS patients also fit Pain is best treated with regular aerobic exercise
the diagnostic criteria for chronic fatigue syndrome. (Busch et al., 2002●A). This information is often treated
Fibromyalgia patients often notice worsened fatigue with suspicion and antagonism by patients who have
and pain after even minimal physical activity (e.g., experienced exacerbated symptoms after exertion. In
doing laundry or dishes). This leads to physical such cases, it may be helpful to have a physical thera-
deconditioning and a fear of exercise (Busch et al., pist involved who is familiar with fibromyalgia and
2002● A). has access to pool therapy, which has been found to be
The treatment of fibromyalgia begins with particularly effective in treating FMS. Patients should
explaining to the patient what is known about this be encouraged to start with low-impact aerobic exer-

525
 Chapter 69 Pain “Everywhere” (Fibromyalgia)

cise at a low intensity for only 5 minutes per day. the long term (Bradley and Alarcon, 2005● A ; Gilliland,
Achieving a consistent daily routine should be 2005● B ). When addressing a request for pain medica-
stressed. Once a routine is established, the duration tion from a patient with FMS, the physician should
and intensity of the exercise can be increased. attempt to turn the focus away from depending on pills
No pain relievers have been shown to be consis- and onto adopting healthy habits such as maintaining
tently helpful in fibromyalgia patients. Acetaminophen regular exercise, getting regular sleep, and achieving
or nonsteroidal anti-inflammatory medications may emotional balance. Further study is ongoing and may
be helpful for mild cases. Tramadol (Ultram) also may soon provide a more definitive treatment for this often
be of some benefit and has few drawbacks in patients frustrating condition.
who can tolerate it. Frequently patients request opiate
medications, but doctors hesitate to prescribe them.
No strong research is available to help guide this deci- Material Available on Student Consult
sion. Most fibromyalgia experts strongly recommend
Review Questions and Answers about
against starting opiate medications in fibromyalgia
Fibromyalgia
patients because they rarely help reduce symptoms in

REFERENCES
Bradley LA, Alarcon GS. Fibromyalgia. In Koopman WJ, First MB, ed. Diagnostic and Statistical Manual of Mental
Moreland LW (eds): Arthritis and Allied Conditions: Disorders–Revision (DSM-IV-TR). Washington, DC,
A Textbook of Rheumatology, 15th ed. Philadelphia, American Psychiatric Association, 2000.● C
Lippincott Williams & Wilkins, 2005, pp 1869–1910.●A Gilliland BC. Fibromyalgia: Arthritis associated with sys-
Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise temic disease, and other arthritides. In Kasper DL,
for treating fibromyalgia syndrome. Cochrane Braunwald E, Fauci AS, et al. (eds): Harrison’s Prin-
Database Syst Rev 2002;(3):CD003786.● A ciples of Internal Medicine, 16th ed. Chicago, McGraw-
Hill, 2005, pp 2055–2064.●B

526
 C h a p t e r

70 Elbow Pain (Epicondylitis)

Allan V. Abbott

when he tried to play tennis (“that’s when I decided

KEY POINTS it must be tennis elbow”). He states that the pain
usually resolves within seconds or minutes after rest-
1. Epicondylitis results from injury to the musculo- ing the arm but recurs immediately with any heavy
tendinous attachments of extensor carpi radialis use of the right hand.
brevis (lateral) and flexor carpi radialis (medial)
tendons to the epicondyle. Medical History
2. The diagnosis is confirmed on physical examina- John has had an unremarkable medical history with
tion: local tenderness over the lateral or medial no previous major illnesses or hospitalizations. He
epicondyle, elbow pain on resisted wrist exten- has had a few episodes of minor low back pain but
sion (lateral) or flexion (medial), pain worse has never sought medical attention.
with strong hand gripping, entirely normal
elbow range of motion. Family History
3. Treatment: Initially the arm is put at rest. Ice John is an only child. His mother is living and well
applied intermittently to the epicondyle reduces and is under treatment for high blood pressure. His
pain. Immobilization with a wrist splint may father died 2 years ago of a myocardial infarction at
give pain relief. Nonsteroidal anti-inflammatory the age of 75. His father was overweight and seden-
drugs can give temporary relief of pain. Local tary. John has a wife and two children who are in
injection of corticosteroid is reserved for persist- good health.
ent cases. After pain is resolved, stretching and
strengthening exercises are necessary to prevent Health Habits
relapse. John takes pride in his good health. He has never
smoked and only drinks a glass of wine occasionally.
He follows a low-fat diet and has tried to stay thin.
He jogs three mornings each week for about 3 miles
INITIAL VISIT and takes long hikes most weekends. He started play-
ing tennis with a friend about 2 months ago. He takes
Subjective no medications.

Patient Identification and Presenting

Objective
Problem
John N. is a 48-year-old right-handed white man Physical Examination
who works as a college English professor. John com- Vital Signs His weight is 156 pounds, height is 69
plains of pain in his right elbow for the past month inches, blood pressure is 120/70, pulse is 60 and reg-
and thinks that he has tennis elbow. He feels only a ular, and temperature is 37.2˚C (99˚F) orally.
mild ache most of the time, but he describes a sharp
pain that is brought on by certain activities. He is General John is pleasant and well nourished and
uncertain about the onset of the pain and states that appears physically fit. As he describes his elbow pain,
it came on gradually but has been especially bad the he cups and holds his right elbow with his left hand.
past few days, when he was picking up books and Both upper extremities appear muscular and sym-
boxes while moving his office. He also notices the metrical, and there is no apparent deformity,
pain when he grips and carries his briefcase or shakes swelling, or inflammation of either elbow. Passive and
hands, and he noticed it a few days before this visit active range of motion of both hands, wrists, elbows,

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

527
 Chapter 70 Elbow Pain (Epicondylitis)

and shoulders is normal. There is mild tenderness to

palpation over and immediately distal to the lateral Box 70-1 Differential Diagnosis
epicondyle of the right elbow. Otherwise there is for Epicondylitis
no other palpable warmth, tenderness, or deformity.
John demonstrates that it hurts his elbow most Conditions commonly associated with racket
when he makes a fist and extends his right wrist. sports
Indeed, extension of his wrist against resistance Lateral epicondylitis (most common)
causes pain near the lateral epicondyle, especially Medial epicondylitis
when the forearm is pronated. Medial collateral ligament injury
Bony articular injuries
Laboratory Tests Ulnar neuropathy
Radiographs of the elbow are normal. Other conditions
Trauma
Radial neck fractures
Assessment
Distal humerus fractures
Working Diagnosis Neuropathic pain
The most likely diagnosis is lateral epicondylitis, Radial tunnel syndrome
often called tennis elbow. The onset and association Entrapment
of the pain with lifting and with playing tennis as Of posterior interosseous nerve
well as the tenderness over the lateral epicondyle are Of musculocutaneous nerve
typical. Of median nerve
Inflammation
Differential Diagnosis (Box 70-1) Arthritis
In racket sports, the differential diagnosis includes Synovitis
lateral and medial epicondylitis, medial collateral lig- Gouty arthritis
ament injury, bony articular injuries, and ulnar neu- Joint infection
ropathy. Referred pain
Medial epicondylitis, often called golfer’s elbow, Cervical radiculopathy
occurs less often than lateral epicondylitis, but the Shoulder arthritis
symptoms are similar. The pain is localized to the Carpel tunnel syndrome
medial epicondyle at the site of the flexor pronator Angina pectoris
tendon origins. Pain results from resisted wrist flex- Tumor
ion and pronation. Management is similar to lateral Bone cyst
epicondylitis. John has no medial elbow pain or ten-
derness.
Medial collateral ligament injury causes medial nerve compression. Numbness and tingling in the
elbow pain and can overlap with other injuries such fourth and fifth fingers are common symptoms and
as medial epicondylitis. The medial collateral liga- are often associated with medial elbow pain that
ment receives valgus stress in tennis serves and over- radiates into the forearm. Careful palpation of the
head strokes. A tennis player may report medial ulnar nerve where it crosses the elbow and observa-
elbow pain during vigorous overhead serves. tion of the nerve in its groove as the elbow moves
Tenderness may be elicited over the medial collateral through its full range of motion help rule out entrap-
ligament or instability or pain may be produced ment. John has no neurologic findings.
when the examiner applies valgus stress to the elbow Other differential diagnoses that are less com-
in 30 degrees of flexion. mon include the following.
Bony articular injuries can result from excessive Radial tunnel syndrome can closely simulate lat-
articular compression during vigorous and repeated eral epicondylitis. The radial nerve becomes com-
use of the elbow in racket sports. This can lead to pressed in the radial tunnel as it passes laterally
degenerative changes, osteophytes, and loose body around the posterior surface of the humerus and
formation, especially in older adults. Poorly local- pierces the lateral muscular septum. Pain may be
ized pain, stiffness, and limitation of motion are the referred to the lateral epicondyle, and paresthesias
most common findings. John has well-localized pain may occur along the course of the superficial radial
and no limitation of motion as well as normal nerve. Most commonly, pain is elicited when the
radiographs. forearm is forcefully supinated. Tinel’s sign (a distal
Ulnar neuropathy can result from traction or tingling sensation in an extremity when a nerve is
compression of the nerve, direct trauma, and sublux- percussed) may be elicited over the radial head, and
ation. Medial elbow joint instability, degenerative tenderness may be palpated in the extensor muscles
arthritis, and soft-tissue scarring can lead to ulnar more distally than 1 or 2 cm from the lateral

528
 Chapter 70 Elbow Pain (Epicondylitis)

epicondyle (as in lateral epicondylitis). Tenderness sary, the weight should be lifted close to the body,
over the lateral epicondyle, as John has, would not be with the elbow extended and the forearm supinated.
expected. Pain is aggravated most by motions of the hand
Entrapment of the posterior interosseous, mus- and wrist; therefore, many patients find some relief
culocutaneous, or median nerves can lead to elbow with immobilization of the wrist with a Velcro wrist
pain. Entrapment of the posterior interosseus nerve splint. Wrist splinting should be in neutral position
by the supinator muscle can cause elbow pain and and limited in duration to no more than 3 to 4 weeks
weakness of extension of the fifth finger, mimicking if possible (Little, 1984). Tennis elbow bands wrap
the radial tunnel syndrome. Musculocutaneous around the forearm, placing pressure over the attach-
nerve entrapment can result in anterolateral elbow ment of the extensor tendons to the epicondyle.
pain and decreased sensation in the anterior (volar) A tennis elbow band is likely to be helpful if the
forearm. Compression of the median nerve can pro- patient notices a reduction of pain when pressure is
duce pain in the volar forearm that is worse with applied by fingers over the painful area while the
repeated use (pronator syndrome). Pain may be pro- patient performs painful arm movements. However, a
duced by resisting flexion at the third finger proximal systematic review of splints, bands, and other orthotic
interphalangeal joint or by resisting forearm prona- devices did not find clear benefit from any of these
tion. John has none of these findings. devices (Struijs et al., 2001● A). Various physical thera-
Fractures of the radial neck or distal humerus pies may be helpful in some cases, including heat,
can be suspected if the patient has had a fall or other ultrasound, whirlpool, massage, and electrical stimu-
acute trauma. The elbow is swollen and movement is lation.
painful. The diagnosis is confirmed radiographically. Repeated application of ice directly to the
Inflammation associated with arthritis or syn- painful area for 15 minutes every 4 to 6 hours often
ovitis can be suspected in cases of a swollen, painful provides effective local anti-inflammatory treat-
elbow, especially in individuals with inflammation in ment and pain relief. An oral nonsteroidal anti-
other joints. Joint infection should be suspected if inflammatory drug is commonly prescribed and may
the joint is swollen, erythematous, or warm or if the be continued for several weeks. Studies have shown
patient is febrile. nonsteroidal anti-inflammatory drugs to produce
Referred pain from cervical radiculopathy, short-term benefit but more adverse effects than
shoulder arthritis, carpal tunnel syndrome, or angina without nonsteroidal anti-inflammatory drugs (Hay
pectoris can be ruled out through examination of the et al., 1999●A ; Labelle and Guibert, 1997● B).
neck, shoulder, and wrist and careful history taking. Corticosteroid injections should be reserved for
When the history and physical examination are those patients in whom the pain is severe or persist-
inconclusive, radiographic examination will rule out ent, and more conservative treatments are not satis-
rare bone tumors or cysts. factory. Studies of these injections have yielded
conflicting results (Hay et al., 1999● A). Injection can

Plan decrease pain acutely but does not improve outcome

at 1 year (Assendelft et al., 1996● B ; Hay et al., 1999●
A;
Diagnostic Verhaar et al., 1996●B ). Injection should be in the most
The diagnosis of lateral epicondylitis is based entirely tender area and into the subaponeurotic space with
on the history and physical examination. Radiographs approximately 40 mg of methylprednisolone and
of the elbow will be normal in lateral epicondylitis, but lidocaine. Superficial subcutaneous injection and
they may be obtained if other causes of pain are sus- injection into the tendon should be avoided. No more
pected by a decreased elbow range of motion or by than three injections should be performed within
crepitance palpated over the radiohumeral joint. 1 year, and repeat injections should be avoided in ath-
Magnetic resonance imaging is rarely indicated but letes who continue to engage in activities that aggra-
can be used to differentiate epicondylitis from other vate the condition (Smidt et al., 2002● A ). Surgery is
tendon injury, nerve entrapment, or stress fractures rarely indicated but may be considered if all else fails
(Sonin et al., 1996●
B ). and symptoms have persisted for more than 1 year;
however, there have been no controlled trials of effec-
Therapeutic tiveness (Buchbinder et al., 2002● A).
Treatment of epicondylitis begins with patient edu- Rehabilitation is essential to avoid recurrences.
cation. The goals are to allow healing of microrup- Gentle active and passive full range of motion exer-
tures in the tendon, to allow inflammation to resolve, cises are begun with the initial visit and should be
and to improve muscle strength in the forearm. The painless. After the pain has resolved, passive stretch-
patient must avoid or reduce activities that produce ing of the extensor forearm muscles should be per-
extensor stress on the lateral epicondyle. Racket formed. Beginning 3 to 4 weeks after symptoms
sports should be avoided initially. Lifting of heavy resolve, forearm muscle strength should be restored
objects should also be avoided; when lifting is neces- using isometric exercise. Grip exercises are followed

529
 Chapter 70 Elbow Pain (Epicondylitis)

by exercises of wrist extension and flexion and signs and symptoms. John typically had pain relieved
should be continued for at least several months to by rest, and he noticed pain with gripping objects
prevent recurrence. with the involved hand, especially with the right
For an athlete or person who must participate in wrist extended. The pain developed gradually but
the activity that caused the lateral epicondylitis, was exacerbated with heavy repetitive use of his hand
a more formal rehabilitation and physical and occu- and arms. Morning stiffness and aching throughout
pational therapy program may be necessary. A tennis the day are common symptoms.
professional may be consulted to correct the back- On physical examination, tenderness over and
hand technique and to select the correct racket with just distal to the lateral epicondyle and pain on
larger head size, reduced string tension, and soft or extension of the pronated wrist are usually diagnos-
loose grip. tic. If the patient with tennis elbow is asked to hold a
5-pound object such as a book in the affected hand
with the elbow flexed at 90 degrees, there is usually
DISCUSSION little pain with the hand supinated but marked pain
and associated weakness when the hand is pronated.
Tennis elbow has been used to describe pain at or Grip strength is usually decreased. There is normal
near the origin of the extensor carpi radialis brevis elbow range of motion and usually no visible
since 1882. It occurs most commonly in white mid- swelling. The presence of swelling should alert the
dle-aged men and nearly always in the dominant examiner to the possibility of another etiology.
hand. The majority of cases of lateral epicondylitis
do not occur as the result of racket sports but result
from repetitive movements in certain occupations. Prevention
Tennis elbow affects about 50% of recreational ten- The racket sports player who fails to follow a com-
nis players and is related to overuse and poor tech- prehensive conditioning program or who uses poor
nique, especially during the backhand stroke. technique is more likely to develop lateral epi-
The exact etiology is unknown, but tennis elbow condylitis. Strengthening exercises should be done
results from repeated stress on or near the lateral epi- routinely using progressive resistance. Forearm
condyle by the action of the wrist extensor muscles, extensor muscle stretching should be done consis-
especially the extensor carpi radialis brevis, and the tently during the playing season and immediately
carpi radialis longus, extensor carpi ulnaris, and the before sports participation. Proper technique and
brachioradialis. This causes microruptures of collage- equipment are also important.
nous fibers, fibrous tendon degeneration, and an
associated inflammatory response (Pfahler et al.,
1998● B). Lateral epicondylitis rarely results from direct Material Available on Student Consult
local trauma or from systemic connective tissue disease.
Review Questions and Answers about
Lateral epicondylitis is a clinical diagnosis and, Epicondylitis
as in this patient, most cases will present with typical

REFERENCES
Assendelft, WJ, Hay, EM, Adshead, R, Bouter, LM. Smidt N, van der Windt DA, Assendelft WJ, et al.
Corticosteroid injections for lateral epicondylitis: A sys- Corticosteroid injections, physiotherapy, or a wait-
tematic overview. Br J Gen Pract 1996;46:209–216.● B and-see policy for lateral epicondylitis: A randomized
Buchbinder R, Green S, Bell S, et al. Surgery for lateral controlled trial. Lancet 2002;359:657–662.● A
elbow pain (Cochrane Review). Cochrane Database Sonin AG, Tutton SM, Fitzgerald SW, Peduto AJ. MR imag-
Syst Rev 2002.●A ing of the adult elbow. Radiographics 1996;16:
Hay EM, Paterson SM, Lewis M, et al. Pragmatic random- 1323–1336.● B
ized controlled trial of local corticosteroid injection Struijs PA, Smidt N, Arola H, et al. Orthotic devices for
and naproxen for treatment of lateral epicondylitis of tennis elbow (Cochrane Review). Cochrane Database
elbow in primary care. BMJ 1999;319:964–968.● A Syst Rev 2001.●A
Labelle H, Guibert R. Efficacy of diclofenac in lateral epi- Verhaar JA, Walenkamp GH, van Mameren H, et al. Local
condylitis of the elbow also treated with immobiliza- corticosteroid injection versus Cyriax-type physiother-
tion. The University of Montreal Orthopaedic Research apy for tennis elbow. J Bone Joint Surg Br
Group. Arch Fam Med 1997;6:257–262.● B 1996;78:128–132.● B
Little TS. Tennis elbow: To rest or not to rest. Practitioner
1984;228:457–460.
Pfahler M, Jessel C, Steinborn M, Refior HJ. Magnetic res-
onance imaging in lateral epicondylitis of the elbow.
Arch Orthop Trauma Surg 1998;118:121–125.● B

530
 C h a p t e r

71 Ankle Injury (Ankle Sprain)

Trish Palmer

INITIAL VISIT
KEY POINTS
Subjective
1. Grade I to II ankle sprains should respond well
to the PRICE regimen: Patient Identification and Presenting
Protection: bracing or support to protect the Problem
ankle from further injury. Jennifer K. is a 40-year-old woman who presents to the
Rest: limitation of activities that cause pain or clinic reporting a swollen right ankle. She reports that
swelling, relative rest of the ankle; people may the mechanism of injury was rolling the ankle inward
continue to do exercises that do not specifically while playing tennis this morning, while cutting and
involve the ankle to keep up their aerobic fit- pivoting to get at the ball. The swelling about the ankle
ness (e.g., weights, swimming). has slowly increased since then, with some bruising
Ice: 15 minutes every 1 to 2 hours while below the ankle bone. She is able to bear some weight
awake; this has been shown to significantly and walk several steps with a limp. This has never hap-
reduce healing time (use a bucket of ice water, pened previously. She has done nothing so far to treat
plastic bag of ice cubes, or bag of frozen veg- the ankle, including icing, bracing, or medications.
etables).
Compression: use of elastic bandage or pneu- Medical History
matic ankle splint while awake. There is none, including no history of peptic ulcers
Elevation: raise the ankle above the level of the or gastrointestinal side effects to nonsteroidal anti-
heart. inflammatory drugs (NSAIDs).
2. Suspicion of fracture should prompt radi-
ographs of the ankle, foot, or fibula, depending Family History
on the mechanism of injury and area of tender- There is no history of arthritides.
ness; use of Ottawa ankle rules may decrease
the need for radiographs. Social History
3. Continuation of strengthening and propriocep- She drinks two glasses of wine per night, does not
tion exercises after a grade I to II sprain is likely smoke, and exercises four to five times per week.
to decrease the risk of future injury.
4. A red, warm, swollen joint, especially with no Surgical History
history of trauma, is a septic joint until proven There is none, including the right ankle.
otherwise. This finding should prompt urgent
aspiration of the ankle, with urgent determina- Medications/Allergies
tion of the 3 Cs—cell count, culture, and crys- There are none.
tals—to determine whether the cause is
infectious so that appropriate treatment can be Review of Systems
immediately started. The review is negative for constitutional, other muscu-
loskeletal, other skin, eye, and genitourinary symptoms.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

531
 Chapter 71 Ankle Injury (Ankle Sprain)

Objective sider Salter-Harris type (growth plate) fractures

in a person who is still growing (radiographs of
Physical Examination type I may be normal).
Inspection reveals that Ms. K’s right ankle has evi- 4. Red, warm, swollen joint. This is a septic joint until
dent moderate swelling through the talocrural joint, proven otherwise, especially with no history of
with ecchymosis below the lateral malleolus. There is trauma. This finding should prompt urgent aspi-
little erythema or warmth about the joint. Palpation ration of the ankle, with urgent determination of
reveals tenderness of the anterior talofibular liga- the 3 Cs—cell count, culture, and crystals—to
ment (ATFL) but not of the calcaneofibular ligament determine whether the cause is infectious so that
(CFL), posterior talofibular ligament, or deltoid liga- appropriate treatment can be immediately
ment. There is no bony tenderness at the distal lateral started. If the joint is not septic, other diagnoses
malleolus, medial malleolus, fifth metatarsal, navicu- include initial presentation or flare of osteoarthri-
lar, or proximal fibula. Passive and active range of tis, rheumatoid arthritis, gout, or pseudogout.
motion is slightly limited in both inversion and ever- This is a situation in which blood testing may also
sion compared with the unaffected left ankle. be helpful.
Resisted function of the peroneus longus and brevis 5. Complex regional pain syndrome (previously
is symmetric bilaterally but does cause some pain. termed reflex sympathetic dystrophy). Symptoms
The anterior drawer test is negative for laxity and include burning pain, hypersensitivity, allodynia,
positive for pain. Talar tilt testing is negative for both and edema, often arising after a fairly minor
laxity and pain. Squeeze, external rotation, and injury like a sprain or a fracture. The symptoms
Thompson tests are negative. often appear to be much out of proportion to the
injury and do not respond to the typical treat-
Investigations ment regimens for the suspected cause.
No blood work or radiographs were ordered. 6. Osteochondritis dissecans. This is a disorder in
which a fragment of cartilage and subchondral
bone separates from the articular surface, with the
Assessment
patient usually presenting as a teenager, many
Working Diagnosis with a history of trauma or high level of athletic
A first-degree sprain of the lateral right ankle (ATFL activity. Symptoms may include pain, effusion,
stretch) is the most likely diagnosis based on the and mechanical locking sensation. Diagnosis is
mechanism of injury and clinical examination. made by radiograph, with this disorder suspected
because of age and symptoms. It often responds
Differential Diagnosis to modification of activity if found to be a minor
When there is no history of trauma, when examina- lesion; surgery may be necessary for larger lesions.
tion reveals any concerning signs (redness and 7. Peroneal tendon subluxation, Achilles tendon strain
warmth with the swelling), or when the clinical find- or tear. Other structures may be torn or stretched
ings are more than that described above, enlarge the and may mimic a sprained ankle. Specific tests
differential diagnosis to include the following: include eversion against resistance with palpation
of the peroneal tendon moving out of place and
1. Second- or third-degree sprain. Examination reveals the Thompson test, which tests the integrity of
laxity of one or more of the tendons (ATFL, CFL, the Achilles.
posterior talofibular ligament), indicating a partial
to complete tear. A partial to complete tear takes a Plan
longer time to heal, and a complete tear may benefit
from surgery. Diagnostic
2. Syndesmotic sprain. The syndesmosis consists of At this point, the diagnosis is based on the history and
the anterior tibiofibular ligament, posterior clinical examination. If a first-degree sprain is not
tibiofibular ligament, and the distal interosseus improving within 3 to 4 days or if there is persistent
membrane between the tibia and the fibula. pain, swelling, or disability, then the differential diag-
Injury to this structure usually presents with ante- nosis should be expanded to include the diagnoses
rior ankle pain. Examination reveals a positive noted above, and consideration should be given to re-
squeeze test and external rotation stress test. examination of the joint and a possible radiograph.
Expect this injury to take a prolonged time to
heal, from 8 to 10 weeks. Therapeutic
3. Fracture. Any bony tenderness or inability to bear The therapeutic goal is to control pain and to main-
weight must prompt radiographs. Specific bones tain or regain range of motion. PRICE is a mnemonic
to assess include the proximal fibula, navicular, to help remember the principles of physical modali-
fifth metatarsal, distal fibula, and tibia. Also con- ties to limit pain and swelling.

532
 Chapter 71 Ankle Injury (Ankle Sprain)

Protection: bracing or support to protect the ankle the ankle is not improving, or there is an increase in
from further injury pain/swelling after the first 3 days. Advice should be
Rest: limitation of activities that cause pain or given about the PRICE regimen and medication in
swelling, relative rest of the ankle; people may the acute phase and early mobilization progressing to
continue to do exercises that do not specifically proprioception rehabilitation when tolerable. The
involve the ankle to keep up their aerobic fitness expectation is that the injury should improve over
(e.g., weights, swimming) the next 3 to 4 days and not last beyond 1 to 2 weeks.
Ice: 15 minutes every 1 to 2 hours while awake; this The athlete is thought to be ready to return to
has been shown to significantly reduce healing training and competition when a progression through
time (use a bucket of ice water, plastic bag of ice activity is not painful. When the ankle is no longer
cubes, or bag of frozen vegetables) painful with straight-line forward and backward walk-
Compression: use of elastic bandage or pneumatic ing and jogging, the athlete may progress to side-to-
ankle splint while awake side jogging, then figure-of-eight jogging, and then
Elevation: raise the ankle above the level of the heart into cutting and pivoting. Any forward progression
through these steps should be painless; otherwise the
Medications such as acetaminophen and NSAIDs
athlete is not ready to progress to the next step. If all
may be quite helpful in addition to physical modalities
activities are now painless, the athlete may return to
in limiting pain, while NSAIDs may also limit swelling.
previous training and competition.
The use of NSAIDs in the first 24 hours in athletes has
Continuation of strengthening and propriocep-
become somewhat controversial: Some believe that the
tion exercises should be advised to decrease the risk
decrease in swelling speeds recovery; others believe that
of future injury. Also any brace that is used needs to
acute use of NSAIDs may increase swelling by increas-
be tightened after bouts of activity, because braces
ing potential bleeding through platelet inhibition. This
tend to become loose.
only matters in terms of speed of recovery, which
makes it an issue unique to athletes, and has not yet
been studied well (Stanley and Weaver, 1998).
Immobilization may both help and hinder heal-
DISCUSSION
ing. Acute protection of the painful area is appropri-
Ankle sprain is the most common sports and non-
ate and helps to limit swelling and thus pain.
sports injury (as many as 21% of all sports injuries),
Prolonged immobilization leads to muscle atrophy
with 85% of these being lateral sprains (Garrick,
and loss of range of motion. Therefore, it is recom-
1982; Renstrom and Kannus, 1994). The normal
mended to start gentle range-of-motion exercises
anatomy of the ankle is shown in Figure 71-1.
(tracing of the alphabet with the foot) and weight
Inversion is the most common mechanism of injury
bearing as soon as tolerable. Ankle bracing is some-
(Fig. 71-2) because the extension of the distal end of
thing that is to be recommended with care and usu-
the fibula gives the medial ankle stability by providing
ally for short-term treatment. Taping is also effective
bony resistance to eversion. Inversion in a position of
support but is only as good as the person applying
dorsiflexion puts the ATFL at its greatest tension,
the taping and only lasts for about 20 to 40 minutes
placing it in a likely position to sustain injury. The
of activity (Lohrer et al., 1999; Manfroy et al., 1997).
ATFL (laxity tested by anterior drawer test [Fig. 72-3])
Physical therapy has been shown to get people
is the most commonly injured ligament, followed by
back to activity somewhat quicker and is used fre-
the CFL (laxity tested by the inversion stress or talar
quently with athletes for this reason. The treatment
tilt test [Fig. 71-4]) and the posterior talofibular liga-
plan usually consists of regaining range of motion,
ment.
strength, and proprioception. Range-of-motion exer-
Examination should begin with inspection for
cises are the first step. Strengthening of the peroneal
obvious deformity, swelling, and ecchymosis. The
muscles (resisted eversion and inversion), which act
affected ankle should be compared in every facet of
as the dynamic stabilizers of the ankle, is of great
the examination to the unaffected ankle (assuming
importance. Proprioception can be regained through
that ankle is “normal”). Examination of a first-degree
standing on the injured foot with an attempt to hold
sprain will likely show tenderness at the ATFL and/or
the position for longer and longer periods of time,
CFL areas without laxity (a finding of laxity increases
use of a balance board, and progression through a
the grade of the sprain). The amount and area of
series of cutting and pivoting exercises. This may also
ecchymosis often correlate with the amount of treat-
help prevent recurrent ankle sprains.
ment (PRICE/NSAIDs) and not necessarily to the
severity of injury. Pain should not be increased by a
Patient Education squeeze test (compression of the tibia and fibula
together at midshaft, with positive tests producing
The patient needs to be reassessed if there is persist- pain at the distal syndesmosis [Fig. 71-5]) or by an
ent difficulty with ambulation 3 days after the injury, external rotation test (external rotation of the foot

533
 Chapter 71 Ankle Injury (Ankle Sprain)

Inferior extensor
retinaculum

Posterior talofibular Anterior inferior tibiofibular ligament

ligament Anterior talofibular ligament

Lateral talocalcaneal ligament

Calcaneofibular
Interosseous talocalcaneal ligament
ligament
Cervical ligament

A Bifurcate ligament

Superficial deltoid ligament Deep portion deltoid ligament

Tibiocalcaneal ligament Posterior tibiotalar ligament
Tibionavicular ligament
Superficial tibiotalar ligament

B Spring ligament

Posterior inferior
Anterior inferior tibiofibular ligament
tibiofibular ligament Posterior talofibular
Deltoid
Anterior ligament
Deltoid ligament
talofibular ligament
ligament Calcaneofibular
Calcaneofibular ligament
ligament

C Cervical ligament
D
Figure 71-1 Compendium of the foot and ankle ligaments. A, Lateral view of the foot and ankle demonstrating the
anterior talofibular ligament, calcaneofibular ligament, posterior talofibular ligament, anterior inferior tibiofibular
ligament, lateral talocalcaneal ligament, inferior extensor retinaculum, interosseous talocalcaneal ligament, cervical
ligament, and bifurcate ligament. B, Medial view of the foot and ankle demonstrating the superficial deltoid liga-
ment, including the tibionavicular, spring ligament, tibiocalcaneal, and superficial tibiotalar components. C, An ante-
rior view of the ankle and hindfoot demonstrating the deltoid ligament with its superficial and deep components, the
anterior inferior tibiofibular ligament, the cervical ligament, the anterior talofibular ligament, and the calcaneofibu-
lar ligament. D, A posterior view of the ankle and hindfoot demonstrating the deltoid ligament with its superficial
and deep components, the posterior inferior tibiofibular ligament, the posterior talofibular ligament, and the calca-
neofibular ligament. (From DeLee and Drez’s Orthopaedic Sports Medicine, 2nd ed. Philadelphia, Elsevier, 2003.)

534
 Chapter 71 Ankle Injury (Ankle Sprain)

FIGURE 71-2 A, At a position of neutral dorsiflexion, the anterior talofibular ligament (ATFL) is perpendicular to the
axis of the tibia, and the calcaneofibular ligament (CFL) is oriented parallel to the tibia. In this position, the CFL pro-
vides resistance to inversion stress or varus tilt of the talus. B, If, however, the talus is plantar flexed (the most com-
mon position for lateral ankle inversion injuries), then the ATFL is parallel and the CFL is perpendicular to the axis of
the tibia, and the ATFL provides resistance to inversion stress or varus tilt of the talus. (From DeLee and Drez’s
Orthopaedic Sports Medicine, 2nd ed. Philadelphia, Elsevier, 2003.)

FIGURE 71-3 A and B, The anterior drawer test of the ankle. (From DeLee and Drez’s Orthopaedic Sports Medicine,
2nd ed. Philadelphia, Elsevier, 2003.)

with the knee and foot at 90 degrees, causing pain at tendons are evaluated for subluxation by placing the
the distal syndesmosis [Fig. 71-6]). If pain is evoked foot in a dorsiflexed and everted position and having
on these tests, consider a syndesmotic sprain; more the patient resist inversion. If damage is present,
proximal pain may indicate a Maisonneuve or proxi- movement of the peroneal tendon may be observed.
mal fibula fracture. Tenderness at the deltoid (medial) Anterior drawer and talar tilt testing may be falsely
ligament suggests a medial ankle sprain. The peroneal negative in the setting of a lot of swelling.

535
 Chapter 71 Ankle Injury (Ankle Sprain)

FIGURE 71-4 The talar tilt (inversion stress) test of the ankle. (From DeLee and Drez’s Orthopaedic Sports Medicine,
2nd ed. Philadelphia, Elsevier, 2003.)

Ankle sprains are graded I, II, and III depending

on the amount of laxity encountered on examination
in addition to other factors (Table 71-1). Grade I
sprains tend to heal well with little intervention,
whereas grade II injuries may benefit from acute
immobilization (rigid brace or casting), and treat-
ment of grade III injuries is controversial, ranging
from casting to surgery. This type of injury should
probably be referred to an orthopedic surgeon for
consideration of surgical repair, depending on the
patient’s level of function before the injury and the
anticipated timing of demand on the ankle.
With a clear mechanism of injury and ability to
bear weight, the likely diagnosis is an ankle sprain,
which should heal within a limited amount of time.
Lack of memory of a specific mechanism of injury
should make the clinician suspect other diagnoses.
Inability to bear weight should raise the index of sus-
picion for fracture, and skeletal immaturity increases
the risk of an epiphyseal (growth plate) injury. History
of use of anticoagulants may complicate the picture
with an increased risk of bleeding into the injured site.
Bony point tenderness at the proximal fibula,
lateral malleolus, medial malleolus, base of the fifth
metatarsal, or midfoot bones should prompt consid-
eration of radiographs looking for fracture of these
bones. Ottawa ankle rules are used by many to deter-
mine when radiographs of the ankle are indicated
(Box 71-1). These guidelines are not recommended if
FIGURE 71-5 The squeeze test. Syndesmosis injury is the patient is younger than age 18 or older than age
suspected when compression of the midleg produces
pain at the ankle syndesmosis. (From DeLee and Drez’s
65, pregnant, intoxicated at the time of injury, has
Orthopaedic Sports Medicine, 2nd ed. Philadelphia, multiple injuries or a head injury, or has diminished
Elsevier, 2003.) sensation due to a neurologic deficit. Using these

536
 Chapter 71 Ankle Injury (Ankle Sprain)

FIGURE 71-6 The external rotation stress test of the

syndesmosis. (From DeLee and Drez’s Orthopaedic
Sports Medicine, 2nd ed. Philadelphia, Elsevier, 2003.)

Table 71-1 Grading of Lateral Ankle Sprains

Grade I Grade II Grade III
Sign/Symptom (Stretch) (Partial tear) (Complete tear)

Laxity (anterior drawer None (good Slight (soft 10 mm total or 3 mm

test, ATFL) endpoint) endpoint) greater than unaffected
side on stress
radiographs
Laxity (talar tilt or inversion None (good Slight (soft 20–30 degree opening or
stress test, CFL) endpoint) endpoint) 10 degrees greater than
unaffected side on stress
radiographs
Loss of functional ability Minimal Some Great
Pain Minimal, localized Moderate, localized Severe, localized to ATFL,
to ATFL to ATFL, CFL CFL, PTFL
Ecchymosis, swelling None to slight, local Moderate, local Significant, diffuse
Weight-bearing ability Full to partial Difficult without Impossible without
crutches significant pain
Average time to return 11 days 2–6 wk 4–26 wk
to sport
ATFL, anterior talofibular ligament; CFL, calconeofibular ligament; PTFL, posterior talofibular ligament.
Adapted from Wexler RK. The injured ankle. Am Fam Physician 1998;57:474–480; Renstrom PAFH, Kannus P.
Injuries to the foot and ankle. Orthop Sports Med 1994;1705–1767; Gerber JP, Williams GN, Scoville CR, et al.
Persistent disability associated with ankle sprains: A prospective examination of an athletic population. Foot
Ankle Int 1998;19:653–660.

537
 Chapter 71 Ankle Injury (Ankle Sprain)

Special consideration must be given to patients

Box 71-1 Ottawa Ankle Rules who are still growing or have open growth plates.
They may have a Salter-Harris type I fracture of the
Ankle radiograph if pain in malleolar zone and distal fibula and a normal radiograph. A finding of
(one of the following): swelling at this spot and inability to bear weight must
● Bony tenderness at the posterior or distal
lead the clinician to suspect this type of fracture and
edge of the lateral malleolus treat it as such.
● Bony tenderness at the posterior or distal
Suspicion of fracture should prompt radi-
edge of the medial malleolus ographs of the ankle, foot, or fibula, depending on
● Inability to bear weight for four steps (re-
the mechanism of injury and area of tenderness.
gardless of limping) both immediately after Findings to look for on radiograph include evidence
injury and at time of medical evaluation of fracture, widening of the ankle mortise, and
Foot radiograph if pain in midfoot zone and displacement or widening of the growth plate.
(one of the following): Laboratory studies are not indicated for the diagno-
● Bony tenderness at the base of the fifth
sis of an ankle sprain but may be considered if there
metatarsal is no clear mechanism of injury or rheumatologic or
● Bony tenderness at the navicular
infectious causes are suspected (red, warm, swollen
● Inability to bear weight for four steps (re-
joint).
gardless of limping) both immediately after Treatment for ankle sprain in general consists of
injury and at time of medical evaluation the PRICE regimen, with medications to limit pain
Adapted from Wexler RK. The injured ankle. Am and swelling. Once pain and swelling start to
Fam Physician 1998;57:474–480; Stiell IG, McKnight improve, usually within 1 to 2 days with a grade I
RD, Greenberg GH. Implementation of the Ottawa ankle sprain, mobilization should begin to regain
ankle rules. JAMA 1994;271:827–832. strength, range of motion, and proprioception. It is
recommended to continue strengthening and pro-
prioception to prevent future ankle sprains.
guidelines, it is unlikely to miss a clinically significant
fracture, thereby eliminating unneeded radiographs.
Also consider a radiograph if the history or physical Material Available on Student Consult
examination is suspicious for an injury other than an
Review Questions and Answers about Ankle
ankle sprain or an injury diagnosed as an ankle
Sprain
sprain is not improving as expected.

REFERENCES
Casillas MM. Ligament injuries of the foot and ankle. In Manfroy PP, Ashton-Miller JA, Wojtys EM. The effect of
Miller MD, ed. DeLee and Drez’s Orthopaedic Sports exercise, prewrap, and athletic tape on maximal active
Medicine, 2nd ed. Philadelphia, WB Saunders, 2003, pp and passive ankle resistance of ankle inversion. Am J
2323–2348.● C Sports Med 1997;25:156–163.
Garrick JG. Epidemiologic perspective. Clin Sports Med Renstrom PAFH, Kannus P. Injuries to the foot and ankle.
1982;1:13–18. Orthop Sports Med 1994;1705–1767.
Gerber JP, Williams GN, Scoville CR, et al. Persistent dis- Stanley KL, Weaver JE. Pharmacologic management of
ability associated with ankle sprains: A prospective pain and inflammation in athletes. Physician Sports
examination of an atheletic population. Foot Ankle Int Med 1998;17:375–392.
1998;19:653–660. Stiell IG, McKnight RD, Greenberg GH. Implementation
Lohrer H, Alt W, Gollhoffer A. Neuromuscular properties of the Ottawa ankle rules. JAMA 1994;271:827–832.● A
and functional aspects of tape ankles. J Sports Med Wexler, RK. The injured ankle. Am Fam Physician
1999;27:69–75. 1998;57:474–480.● C

SUGGESTED READING
Hockenbury RT, Sammarco GJ. Evaluation and treatment
of ankle sprains: Clinical recommendations for a posi-
tive outcome. Phys Sports Med 2001;29. Available at
www.physsportsmed.com. Accessed 11/22/05.● C

538
C h a p t e r

72 Arm Laceration (Laceration Repair)

Louis A. Kazal, Jr.

KEY POINTS

1. Lidocaine 1% is the drug of choice (~1 mL/2 cm 8. Simple sutures will evert the wound edges if (a)
of wound) for local anesthesia. the needle enters and exits the skin at an identical
2. Minimize pain by injecting slowly through the distance from each edge, (b) the sutures are
opening of the wound and by using a longer deeper than they are wide, and (c) the base of the
needle (1.5 inches) to reduce the number of loop incorporates more dermis than epidermis.
needle jabs. 9. Stitch marks occur when sutures are (a) of too
3. Irrigate with a large syringe (10 to 50 mL) and heavy a gauge, (b) too long, (c) too tight, or (d)
an 18-gauge soft angiocatheter to provide jet left in too long, or (e) when they incorporate
stream turbulence. too much tissue.
4. Debride devitalized tissue whenever possible. 10. Suture removal is performed at approximately 3
5. Most wounds require 4 to 5 mm of undermin- to 5 days for sutures in the face, 7 days for
ing, especially if there has been loss of tissue. sutures in the scalp, 7 to 10 days for sutures on
6. Compression applied for 5 to 10 minutes the the trunk and extremities, and 10 to 14 days
stops bleeding and prevents hematoma forma- for sutures on the back, hands, and feet.
tion. 11. Shaving hair around the wound increases the
7. Gentle approximation of everted skin edges infection rate.
will produce a thinner scar that heals flatly 12. Antiseptics should be kept from entering open
without a ridge. wounds because of their cytotoxic properties.

INITIAL VISIT Medical History

Gus has no history of a bleeding disorder or other
Subjective medical illness. His last tetanus booster was 12 years
ago. There are no known allergies to, or current use
Patient Identification and Presenting of, any medications.
Problem
Gus is a 32-year-old white rancher who drove him- Family History
self to the emergency department (ED) for evalua- Gus’s father died of a myocardial infarction at age 48,
tion of a 4-hour-old laceration of his arm. as did his paternal grandfather at age 55. Gus’s
mother and two sisters are in good health.
Presenting Illness Health Habits
Gus had dressed out a five-point bull elk, and as he Gus does not use a seat belt when driving. He has
hoisted one of the hindquarters onto the bed of his smoked two packs of cigarettes per day for 15 years.
truck, the broken end of the elk’s femur tore He rarely drinks alcohol.
through the skin on the inside of his left arm. He
applied pressure over the wound with a clean folded Social History
bandana, which stopped the bleeding. When Gus Gus is a high school graduate who is currently a suc-
arrived home 3 hours later, he had no intention cessful rancher in western Wyoming. He and his wife
of seeking medical attention, but his wife insisted of 8 years have two healthy children.
that he see their family physician. Once in the
ED, his only concern was to confirm that he did not Review of Systems
need stitches. He had no numbness, weakness, loss Gus last saw a physician 12 years ago after stepping
of function, or any significant pain. on a rusty nail. His cholesterol level has never been

539
 Chapter 72 Arm Laceration (Laceration Repair)

checked. He coughs up yellowish phlegm every lacerations of the body and extremity greater than 6
morning. There is no history of hemoptysis. hours old should not be closed as they are prone to
infection. An exception is sometimes made for lacera-
Objective tions of the head and neck, which have excellent blood
supply and may be repaired up to 12 hours after injury.
Physical Examination Tetanus toxoid is administered in his nondomi-
Gus is alert, cooperative, and in no apparent distress. nant arm. Tetanus prophylaxis is a priority in lacera-
No alcohol is detected on his breath. His blood pres- tion care. If the patient has not been immunized
sure is 140/92, pulse is 80, respirations are 20, and against tetanus, 0.5 mL of toxoid is given. The injec-
temperature is 37˚C (98.6˚F). He weighs 188 pounds tion is repeated in 6 weeks, and repeated again in 6 to
and stands 5 feet 10 inches tall. A pack of cigarettes is 12 months. If the wound is tetanus-prone, 250 units of
in his shirt pocket. tetanus immune globulin (TIG) are also given intra-
Examination of his left arm reveals a 2.5-cm lac- muscularly at the initial visit. If the patient has been
eration of the flexor surface of the midforearm. immunized and the wound is tetanus-prone, a booster
Small portions of the wound edges are jagged. There is recommended when more than 5 years have elapsed
is some dried blood over the wound. There is no since the last dose. For the immunized patient with a
weakness on resistance to flexion of his fingers or clean wound, a tetanus booster is not necessary unless
hand or on pronation of the forearm. His biceps and it has been more than 10 years since the last dose.
brachioradialis reflexes are normal. Distal sensation The physician decides to address Gus’s poor
and circulation are intact. health maintenance record during the laceration
repair.
Laboratory Tests
No tests are ordered.
Procedure
Assessment 1. Two milliliters of 1% Xylocaine without epineph-
Diagnosis rine are injected with a sterile 1.5-inch, 27-gauge
Gus is diagnosed with what appears to be an uncom- needle through the open wound, infiltrating the
plicated 2.5-cm laceration of the left forearm. The surrounding tissue in a fanlike fashion.
full extent of the injury cannot be determined until a. 1% lidocaine HCl (Xylocaine) is the drug of
it is explored. choice as a local anesthetic in laceration repair.
Approximately 1 mL is required for each 2 cm
Other Health Risk Factors of wound. The maximum adult dose with epi-
Gus has a number of other health risk factors. He does nephrine is 7 mg/kg, and without epinephrine
not use a seat belt, which places him at increased risk it is 4.5 mg/kg. Note: Each milliliter of 1%
for traumatic injury or death if he is involved in a Xylocaine contains 10 mg of lidocaine HCl.
motor vehicle accident. Motor vehicle injuries are a b. Aqueous epinephrine combined with lido-
leading cause of years of potential life lost before age caine is useful in closing lacerations of the
75. It is estimated that crash mortality can be reduced scalp and other vascular areas. In tissues with
by 40% to 50% with the use of lap and shoulder belts. less blood supply or in dirty wounds, the rou-
Gus has a 30-pack-year history of smoking ciga- tine use of lidocaine with epinephrine is dis-
rettes (two packs a day for 15 years). Cigarettes are couraged because it decreases blood supply,
the leading preventable cause of death in the United leading to delayed healing and possible infec-
States. He also has an elevated blood pressure read- tion. Its use is contraindicated in the fingers,
ing. However, he is not labeled hypertensive based on toes, penis, nose, and earlobes.
one measurement. This diagnosis typically requires c. Anesthetic solutions should not be injected
two or more blood pressures recorded at separate into rigid fascial compartments because of
times, and then the measurements, including the ini- potential tamponading of neurovascular
tial one, are averaged. bundles. Regional blocks are preferred in
Finally, Gus is mildly obese. His body mass these circumstances after evaluation of sensa-
index (weight in kilograms divided by height in tion and function.
meters squared) is 27. A body mass index of 27 or d. Important cosmetic landmarks should be
greater is associated with an increased risk for obe- marked before injecting, and the least
sity-related diseases. amount of local anesthetic should be used to
avoid distortion and malalignment of the
Plan wound edges.
e. Pain can be minimized by injecting (1) slowly
These findings are reviewed with Gus, who gives oral to avoid rapid distention of the tissue (using
permission to assess and repair his injury. In general, a 27-gauge needle assists in this goal), (2)

540
 Chapter 72 Arm Laceration (Laceration Repair)

through the opening of the wound in a fan-

like fashion rather than repeatedly through
the skin, (3) with a longer needle (1.5 inches),
reducing the number of needle jabs, and (4)
with lidocaine buffered with 8.4% sodium
bicarbonate in a 1:10 solution.
f. Local anesthetic should be infiltrated 1 cm
into the wound margins. (Subcutaneous fat
does not need to be anesthetized.)
g. Nonsterile gloves may be worn while admin-
istering the local anesthetic but sterile gloves
are used during the repair.
h. Small (1 to 2 cm) superficial lacerations
requiring only a couple of sutures or staples
(scalp) may be closed without an anesthetic.
i. A topical anesthetic, LET (lidocaine, epineph-
rine, and tetracaine), is an alternative source
of analgesia for simple open lacerations. (The
use of LET should be avoided on or near
mucous membranes because of potential
lidocaine toxicity or on end-arteriole regions
of the body, such as digits, because of the
vasoconstrictive properties of epinephrine,
which may cause ischemic complications.) Figure 72-1 Wound revision. Jagged wound edges
should be trimmed with tissue scissors or a no. 15 blade
2. After adequate local anesthesia is obtained, the scalpel to produce a wound with even and vertical
wound is irrigated copiously with sterile saline edges. Tangential wound edges, either left as such or
and the skin surrounding the wound is scrubbed made during revision, create a wider, more depressed
with Hibiclens antiseptic. The field is then scar due to retraction. (From Zuber TJ. Wound manage-
ment. In Rakel RE (ed): Saunders Manual of Medical
draped in sterile fashion and illuminated. Practice. Philadelphia, WB Saunders, 1996, p 1008.)
a. Commonly used surgical preps are chlorhex-
idine gluconate (Hibiclens), povidone-iodine
(Betadine), and hydrogen peroxide. Debate a. Depending on the region of the body (i.e., how
exists over which is the best solution because thick the skin is), it may be necessary to use a
each has cytotoxic properties that interfere no. 15 blade scalpel instead of tissue scissors.
with wound healing and local immune b. Debridement of devitalized tissue is essential
response. Regardless, antiseptics should be whenever possible, except when it would
kept from entering open wounds. compromise function or result in greater cos-
b. Irrigation is best accomplished using a large metic deformity than expected if the crushed
syringe (10 to 50 mL) with an 18-gauge soft edges were closed.
angiocatheter providing jet-stream turbulence. c. If large areas of the wound margins are devi-
c. The practice of shaving hair about the wound talized, or if the edges are too jagged, the revi-
is avoided because it may increase the risk of sion may need to be more extensive. When
wound infection. feasible, the tension lines or wrinkles in the
3. There is some oozing of blood, which is easily skin should be followed when revising a
controlled with sterile 4 × 4 antiseptic pads and wound in order to minimize the retractive
pressure. forces on the wound. An ellipse is made with a
4. The wound edges are slightly ragged. The lacer- no. 15 blade scalpel parallel to the lines of ten-
ation extends through the subcutaneous tissue sion (Fig. 72-2). It requires a length to width
and fascia without injury to the underlying mus- ratio of approximately 3:1 in order to avoid an
culature. No debris is seen. Digital examination uneven closure.
using a sterile gloved finger reveals no foreign 6. The new wound edges are bluntly undermined
body or disruption of underlying structures. with tissue scissors (Fig. 72-3).
5. Ample skin is present to permit debridement of a. Most wounds require some degree of under-
the wound without resulting in excessive tension mining, especially if there has been loss of
with closure. The damaged wound edges are tissue.
trimmed with tissue scissors to produce sym- b. Undermining the edges 4 to 5 mm reduces
metrical, freshly squared-off edges with an intact tension on the wound by disrupting the elastic
blood supply (Fig. 72-1). fibers that cause inversion of the skin edges.

541
 Chapter 72 Arm Laceration (Laceration Repair)

8. Hemostasis is achieved with steady compression

of the wound with a sterile 4 × 4 pad for 5 min-
utes. Health maintenance issues are discussed
during this time.
a. Hemostasis usually can be attained in 5 to 10
minutes with compression.
b. Prevention of hematoma formation is critical
for proper wound healing. Hematomas cause
wider scars by increasing wound tension and
by separating the skin edges. Wound edges
also may necrose when capillary ingrowth to
the skin is prevented by hematoma forma-
tion. Additionally, hematomas promote
infection by providing a source of culture
medium for bacteria.
9. The revised laceration is closed in layers, the
deep layer first, using interrupted simple sutures
of 4-0 Vicryl with inverted knots (Fig. 72-4).
Figure 72-2 Elliptical wound revision. Wound edges
with significant traumatic injury need to be revised,
a. Closing all “dead space” is essential. Doing so
location permitting, by making an elliptical excision reduces tension on the healing skin edges,
(ratio of length to width 3:1) of the wound with a no. 15 decreases the chance of hematoma forma-
blade scalpel. (From Zuber TJ. Wound management. In tion, and allows for earlier removal of skin
Rakel RE (ed): Saunders Manual of Medical Practice. sutures.
Philadelphia, WB Saunders, 1996, p 1008.)
b. The size of suture is dependent on the location
of the laceration and degree of tension.
The smaller the number, the thicker and
c. The safest level at which to undermine is just stronger is the suture. For the deep layer, a 2-0
below the dermal-fat junction. Such precau- or 3-0 absorbable suture is used in the extrem-
tion will help avoid injury to deeper blood ities and 4-0 or 5-0 in the face. (Subcutaneous
vessels and nerves. In some lacerations of the sutures are contraindicated in facial skin flaps.)
trunk and extremities, it may be necessary to c. Absorbable sutures such as polyglactic acid
undermine at the fat-fascial level. (Vicryl), polyglycolic acid (Dexon), or
d. The ends of slightly opened tissue scissors chromic catgut swedged on a curved cutting
can be entered between the dermis and fat needle are typically used to close the deep
and the tissue spread apart by gently open- and subcutaneous layers.
ing the scissors. The edge of a scalpel blade d. Knots should be inverted (buried), with the
can also be used to tease open this tissue ends of the suture cut closely.
plane. e. The deeper layers should be approximated so
7. The wound is reirrigated with sterile saline. that the skin edges come together evenly with

A. Limb or Trunk B. Face

Figure 72-3 Undermining. Preparation of a laceration for repair often requires some undermining of the wound
edges. Undermining disrupts elastic fibers that cause inversion of the edges and facilitates placement of deep sutures.
It is performed below the subcutaneous tissue and above the muscle fascia for the limbs and trunk (A) and just
beneath the dermal level in the face (B).

542
 Chapter 72 Arm Laceration (Laceration Repair)

B Figure 72-5 Alternating simple and vertical mattress

sutures. The vertical mattress suture is an excellent tech-
nique to evert wound edges. The increased width of the
Figure 72-4 The inverted knot. Deep sutures should be deep portion of this double-layered suture also provides
tied so that the knots are buried below the layer being added wound support.
closed. This prevents the knots from interfering with the
approximation of wound edges and minimizes tissue
reaction to suture near the skin’s surface. Start under one
edge (A) and end underneath on the opposite side (B).
d. Use the smallest suture possible: 6-0 on the face,
5-0 or 4-0 on the trunk and extremities, and 4-
0 on the back or other areas with thick skin.
little tension. These layers include the der- e. Stitch marks occur when sutures are (1) of
mal-fat and fat-fascial junctions, depending too heavy a gauge, (2) too long (distance
on the depth of the laceration. In this case, from entrance to exit sites), (3) too tight, or
the skin on the inside of Gus’s forearm is (4) left in too long, or (5) when they incor-
thin, and therefore the dermal-fat layer can porate too much tissue.
be approximated with the skin closure as f. The skin layer is usually closed with nonab-
described below. sorbable monofilament suture, either nylon
10. The skin is closed with a combination of alter- (Ethilon or Dermalon) or polypropylene
nating vertical mattress and simple sutures of (Prolene or Surgilene) on a curved needle.
4-0 Ethilon (Fig. 72-5). g. Start the closure at one corner of the wound
a. A major goal in laceration repair is the gentle and work toward the other (unless an
approximation of everted skin edges, which anatomic landmark is present, which is then
allows for matching of the regenerating basal approximated first). The needle should enter
layer of skin to produce a thinner scar that and exit the skin at a distance from the edge
heals flatly without a ridge. equal to the skin’s thickness, usually about
b. Simple sutures will evert the wound edges if 3 to 4 mm. Sutures should be placed at a dis-
(1) the needle enters and exits the skin at tance from each other equal to their length.
identical distances from each edge, (2) they h. Handle the skin as atraumatically as possible
are deeper than they are wide, and (3) the by using skin hooks or by gently grasping the
base of the loop incorporates more tissue fat-dermal junction with tissue forceps held
than its epidermal counterpart (Fig. 72-6). parallel to the plane of the skin.
c. In areas of thin skin or increased tension, a i. Knots are tied with the needle holder by a
vertical mattress suture effectively everts the technique known as the instrument tie. A sur-
wound edges. It is stronger than the simple geon’s knot is made, followed by a second
suture and is often used on extremities. knot that is not squared and is incompletely
Alternating vertical mattress and simple tightened leaving a tiny loop. The third and
sutures is a common practice. This takes some fourth knots are squared. Remember to
of the remaining tension off the larger vertical approximate, not strangulate, the tissue when
mattress sutures, decreasing stitch scarring. tying knots.

543
 Chapter 72 Arm Laceration (Laceration Repair)

j. Cyanoacrylate tissue adhesives, such as

Dermabond, are an alternative to skin sutures
for closure of small superficial wounds requir-
ing 5-0 or smaller suture. This method is a par-
ticularly attractive option in children and can
be used on properly selected lacerations of the
face, extremities, and torso. (The later two heal
better when subcutaneous sutures are placed.)
11. The laceration repair is cleansed and dried.
Benzoin is applied with a cotton swab to the skin
on both sides of the closed laceration and
allowed to dry. Steri-Strips are placed across the
wound, and the drapes are removed. A protec-
tive nonadherent dressing is applied.
a. Repairs are cleansed with either normal
saline or hydrogen peroxide.
b. Steri-Strips are a commonly used type of
A wound closure tape. They are sterile micro-
porous tapes of various widths that add
support to the repair, thus relieving some
tension on the sutures. They are applied on
one side of the laceration up to the skin edge,
drawn across the repair, and then pressed
down on the other side.
c. Tincture of benzoin is a liquid that makes the
skin more adhesive after it dries, allowing the
Steri-Strips to be more effective and helping
them to remain in place longer.
d. Dressings for 24 to 48 hours serve two purposes:
They keep the wound clean and help maintain
a moist environment. The latter can accelerate
epithelialization (sealing the wound), which
protects the wound from gross contamina-
tion. After 48 hours, showering without cover-
B ing the sutured laceration is permitted, but
soaking and scrubbing are to be avoided.

Disposition
Gus is asked to keep the wound clean and dry and to
rest and elevate his arm over the next 24 hours. Signs
of infection (fever, redness, tenderness, increased
local warmth, or purulent discharge) are explained.
If these signs appear, he will need to return earlier
than the scheduled follow-up in 2 days. The dressing
is to be changed after 24 hours and hydrogen perox-
ide used to remove any dried blood from the sutures
(unless wound closure tapes are present).
Gus is educated about the need to use a seat belt
when driving and advised to stop smoking. His
blood pressure will be rechecked at the time of the
C follow-up visit in 48 hours and again when his
sutures are removed. Because of his risk factors for
Figure 72-6 The simple suture. This basic suture will
evert wound edges when placed correctly. Begin by coronary artery disease (cigarette smoking, male sex,
piercing the skin with the needle at a right angle or positive family history, and obesity), a fasting lipid
greater (A), take a bite of tissue that is deeper than it is profile instead of a random screening cholesterol test
wide (B), and exit the skin symmetrically on the opposite will be ordered. Gus is also encouraged to give con-
side of the wound (C).
sideration to a diet and exercise program.

544
 Chapter 72 Arm Laceration (Laceration Repair)

FIRST FOLLOW-UP VISIT At that time, an appropriate diet and exercise plan
will be outlined.
Subjective
Gus returns for follow-up at the scheduled time and
has no concerns about his arm. He is not aware of any
DISCUSSION
fever and has had no pain or paresthesia. He is happy
The schedule for suture removal is approximately 3 to
to report that he stopped smoking cigarettes and has
5 days for the face, 7 days for the scalp, 7 to 10 days for
already started to watch what he eats. His wife says he
the trunk and extremities, and 10 to 14 days for the
wore his seat belt on the way into clinic today.
hands, feet, back, and areas overlying joints. If a
patient returns for suture removal and has a slow-
Objective healing wound with areas that may separate, partial
Gus is afebrile, and his blood pressure is 118/78. suture removal should be considered as an option to
There are no cigarettes in his pocket. The dressing is minimize stitch scarring. Steri-Strips are placed
dry, and no distal edema is noted. His circulation, where sutures were removed, and the remaining
sensation, and function remained normal. The dress- sutures are taken out as soon as possible. An antibi-
ing is removed. The wound is clean and dry without otic ointment such as Bacitracin or Polysporin is
signs of infection. There is no necrosis of the skin applied daily to the wound (on top of the Steri-Strips,
edges or hematoma formation. The wound edges are if necessary). Antibiotic ointments may decrease the
slightly everted and well approximated. risk of infection and prevent scab formation.
Scars require 2 years to fully mature, during which
time they become less erythematous and hypertrophic.
Assessment Progressive collagen turnover results in retraction and
The revised layered repair of the 2.5-cm laceration of produces a softer scar. Any revision should be delayed
Gus’s left forearm is healing well without signs of until this process of remodeling is complete.
infection. Gus’s blood pressure is within normal lim- Scarring in areas of cosmetic significance may
its today, and he has discontinued his cigarette habit. be minimized by daily massage and protection from
the sun. Massaging is started approximately 2 weeks
after laceration repair and recommended daily (20
Plan minutes qid or, more realistically, 5 minutes bid) for
about 3 months (anecdotal information from plastic
Gus will return in 7 days for suture removal. He will
surgeons). Sunblock lotions and shading are used to
continue to keep the wound clean and protect it with
limit sun exposure until the scar is mature. This
an adhesive bandage.
after-laceration care may produce a softer, flatter, and
Gus is congratulated on his cessation of smok-
less noticeable scar.
ing, seat belt use, and attention to diet.
His blood pressure will be recorded by a friend
(nurse) each week for 3 weeks, and he is to return to Material Available on Student Consult
the office with these readings. Review Questions and Answers about Laceration
A blood sample for a lipid profile is drawn, and Repair
the results will be discussed with him at his next visit.

SUGGESTED READINGS
Breitenbach KL, Bergera JJ. Principles and techniques of Moy RL, Lee A, Zalka A. Commonly used suturing tech-
primary wound closure. In Snell GF (ed): Office niques in skin surgery. Am Fam Physician 1991;
Surgery: Primary Care Clin Office Pract. Philadelphia, 44:1625–1634.
WB Saunders, 1986;13:(3):411–431. Norton LW. Trauma. In Hill GJ II (ed): Outpatient Surgery,
Brunds TB, Worthington JM. Using tissue adhesive for 2nd ed. Philadelphia, WB Saunders, 1980, pp 112–114.
wound repair: A practical guide to Dermabond. Am Singer AJ, Hollander JE, Quinn JV. Evaluation and man-
Fam Physician 2000;61:1383–1388. agement of traumatic lacerations. N Engl J Med 1997;-
Dushoff IM. A stich in time. Emerg Med 1973;5:21–43. 337:1142–1147.
Kundu S, Achar S. Principles of office anesthesia: Part II. Zuber TJ. Wound management. In Rakel RE (ed): Saunders
Topical anesthesia. Am Fam Physician 2002;66:99–102. Manual of Medical Practice. Philadelphia, WB
Little DN. Simple and infected lacerations. In Mayhew HE, Saunders, 1996, pp 1007–1008.
Rogers LA (eds): Basic Procedures in Family Practice. Zuber TJ. The mattress sutures: Vertical, horizontal, and
Bethany, CT, Fleschner, 1984, pp 7–12. corner stitch. Am Fam Physician 2002;66:2231–2236.

545
 C h a p t e r

73 Fatigue, Nausea, Breast Tenderness

(Normal Pregnancy)
Randy Wertheimer

nausea, and breast tenderness. She had a positive

KEY POINTS pregnancy test 2 weeks ago and is experiencing
symptoms similar to those that she had 5 years ago
1. Fetal heart tones are audible by Doppler ultra- when she was pregnant for the first time. Rachel
sound at 12 weeks’ gestation and possibly as stopped her birth control pill 3 months ago with the
early as 9 weeks. hope of becoming pregnant within the next year.
2. A urine pregnancy test to detect an elevated She had a normal withdrawal menses at that time
human chorionic gonadotropin level is positive and had a few days of spotting around 8 weeks ago.
by the time of the first missed menstrual period She is unsure of the exact date of her last menstrual
89% of the time. period, as the spotting episode was not typical of her
3. The due date can be predicted from the first menses. She expressed concern about becoming
day of the last menstrual period (if it was nor- pregnant so soon after using the contraceptive pill.
mal) by adding 1 year plus 7 days and then Rachel has been on a multivitamin preparation
subtracting 3 months (total of 280 days or 40 with folic acid as prescribed by her family physician
weeks). since she went off the birth control pill with plans to
4. Ultrasound during pregnancy has not improved become pregnant. She has been immunized against
perinatal morbidity or mortality. It can be used hepatitis B with the full triple vaccine within the past 5
to determine gestational age if the date is years. We know from her previous pregnancy that she is
uncertain. immune to rubella and that her blood type is B nega-
5. All pregnant women should have a urine cul- tive. She remembers having chicken pox as a child. Her
ture at 12 to16 weeks’ gestation to detect last Pap smear 6 months ago was within normal limits,
asymptomatic bacteriuria. and she has had normal Pap smears yearly since age 18.
6. An a-fetoprotein test to screen for neural tube Ben, Rachel’s husband of 3 years, is excited
defects should be obained at 16 to 18 weeks. about this pregnancy according to Rachel. Although
7. Fetal movement (quickening) occurs at 18 to 20 they have no family close by, they have been living in
weeks. the area since college and have a community of close
8. A perineal swab for group B streptococcus is friends. Rachel plans to work part-time as a com-
obtained at 35 to 37 weeks since infection with puter programmer after the baby is born, and her
this organism is a leading cause of neonatal ill- husband will continue to work full-time in his job as
ness and death. an electrical engineer.

Medical History
Menarche at age 13. Menstrual cycle 31 days, 5 days
of flow. Oral contraceptives used 1990 to 1996.
INITIAL VISIT Pregnancy 1990: elective first-trimester termination.
No complications. Rh immune globulin given after
Subjective
procedure. Hospitalizations: None. Allergies: None.
Patient Identification and Presenting
Problem Family History
Rachel is a 23-year-old gravida 2, para 0, ab 1 woman Maternal mother (Rachel’s mother) has hyperten-
who presents with a 4-week history of fatigue, sion and hypercholesterolemia. Paternal father (Ben’s

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

546
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

father) has type 2 diabetes. No family history of con- symptoms of early pregnancy, i.e., fatigue, breast
genital defects or genetic disorders. swelling and tenderness, nausea.
Her physical examination reveals changes in the
Health Habits cervix and the uterus, which are also consistent with
Alcohol intake of one glass of wine a few times per early pregnancy. Her cervix has a bluish hue, know as
week was stopped 3 months ago. History of occa- Chadwick’s sign. She has an enlarged uterus, about
sional marijuana use. No cocaine or other substance the size of a large orange, corresponding to 8 weeks’
use. No smoking. gestation. The physician does not hear a fetal heart-
beat by Doppler ultrasound. Fetal heart tones may be
Review of Systems audible by Doppler as early as 9 weeks’ gestation,
History of occasional headaches. Urinary tract infec- depending in part on the position of the uterus and
tion twice in the past 10 years. No history of the body habitus of the woman. By 12 weeks’ gesta-
pyelonephritis. tion, fetal heart tones are audible by Doppler ultra-
sound in most pregnant women.
Rachel did not need a urine pregnancy test done
Objective in the office because she had a positive test that she
had done at home and physical examination con-
Physical Examination
firmed an intrauterine pregnancy. The commonly
Rachel is a well-appearing, mildly overweight young
performed urine test measures the presence of an ele-
woman. Blood pressure 110/70 mm Hg, pulse
vated level of human chorionic gonadotropin.
76, regular. Height 5 feet 3 inches, weight 140
Normally, nonpregnant women have low circulating
pounds. Skin: no rashes. HEENT: normal. Neck: sup-
levels, 0.02 to 0.08 IU of human chorionic gonado-
ple. No adenopathy. Thyroid normal size. Lungs:
tropin. With early pregnancy, levels double every 1.3
clear. Cardiovascular: S1 normal, S2 normal. No mur-
to 2.3 days and peak at 7 to 10 weeks (100,000 IU).
mur. Breasts: no masses, inverted nipples bilater-
Elevated human chorionic gonadotropin levels are
ally. Abdomen: bowel sounds normoactive. No
generally detected in the urine by 7 to 10 days after
hepatosplenomegaly. No fetal heart tones audible by
conception. By the time menses is missed, 89% of
Doppler scan. Pelvic: external genitalia normal, vagi-
pregnant women have a positive test.
nal vault has scant discharge. Cervix shows bluish
The most commonly used method to ascertain a
discoloration. Chlamydia culture taken. Uterus is
pregnant woman’s due date is the last menstrual
anterior, enlarged, 8 weeks in size (size of large
period (LMP). When a woman can recall with clarity
orange). Ovaries not palpated. No adnexal masses
the first day of her last menstrual period and can
palpated. Diagonal conjugate (distance between
define it as a normal period with regard to regularity
sacral promontory and inferior aspect of symphysis)
and duration, and there has not been a recent use of
13 cm, distance between ischial spines 12 cm, pelvic
birth control pills, then the LMP is a remarkably
side walls concave. Extremities: No edema.
accurate predictor of the due date. However, in this
case, Rachel’s last normal menses was attached to her
Laboratory Tests last cycle of oral contraceptives. The few days of spot-
Urine dipstick test negative for albumin and glucose. ting 4 weeks later may represent the LMP, but it is dif-
ficult to determine with accuracy by this history.
Assessment Women may not ovulate regularly the first few
months after stopping the pill. Her physical examina-
Intrauterine pregnancy. History, physical examina- tion, however, with a uterus the size of an 8-week ges-
tion, and laboratory data all point to an early tation, suggests that this spotting was in fact the LMP.
intrauterine pregnancy. Establishing the due date is If the LMP were believed to be more accurate
the first order of business. In addition, the physician were, one could estimate the due date by using a
needs to identify screening tests to diagnose and treat pregnancy wheel or by applying the Nägele rule. One
prenatal disease. Last, one wants to promote a begins with the first day of the LMP, adds 1 year plus
healthy pregnancy by assessing the woman’s home 7 days and subtracts 3 months. The length of human
and work environment and by promoting a healthy gestation is estimated at 280 days, or 40 weeks count-
lifestyle. ing from the first day of the LMP. This assumes a 28-
day cycle and that the time from ovulation to menses
Discussion was 14 days. In women with longer cycles, as is true
with Rachel who has a 31-day cycle, one should add
Establishing the Due Date a few days to the expected due date.
The diagnosis of pregnancy in this case is relatively Because we are not able to estimate a due date
straightforward. Rachel has had unprotected sex, is with certainty by history and physical examination at
amenorrheic, and is exhibiting many of the frequent this point, it is reasonable to order an ultrasound as

547
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

an additional tool to help establish accurate dating.

First-trimester scans can identify the gestational age Box 73-1 Prenatal Screening Tests
of a pregnancy within 3 to 5 days using the crown-
rump length. This method of measurement is not Initial Prenatal Visit
used after 12 weeks’ gestation because of fetal spine Blood pressure
flexion. Transvaginal scanning uses a higher fre- Hemoglobin or hematocrit
quency transducer, and structures may be seen ear- Antibody screen
lier than in transabdominal screening. Fetal poles Rapid plasma reagin
can be seen as early as 6 weeks transvaginally and 7 to HBsAg (if status unknown)
8 weeks transabdominally. It is important to note Blood group and Rh factor (if status unknown)
that the use of ultrasound is not recommended as a Rubella titer (if status unknown)
routine screening test in pregnancy. Neither early, Varicella titer (if status unknown)
late, nor serial ultrasounds have demonstrated an Urine culture (12–16 wk)
improved perinatal morbidity or mortality (U.S. Chlamydia (if woman < 25 yr of age or high risk)
Preventive Services Task Force, 1996● A). However, it Gonococcal culture (if high risk)
is an appropriate tool to use for gestational age Pap smear (if not done within past 6–12 mo)
assessment in cases of uncertain dates. Hemoglobin electrophoresis (if status unknown
in at-risk racial groups)
Diagnose and Treat Prenatal Disease HIV screen (counsel and offer to all)
Rachel did have adequate preconception care within
the year before pregnancy. During this time, risk assess- 16–18 wk
ment, health promotion, and medical and psychosocial
α-Fetoprotein
intervention were addressed by her family physician.
We know that the greatest sensitivity to the environ-
24–28 wk
ment for the developing fetus occurs during the 17 to
56 days after conception, yet as many as one fourth of Glucose (Glucola) screen
pregnant women fail to initiate care until after the first Antibody (if Rh negative)
trimester. Because healthy women are more likely to Rapid plasma reagin (if high risk)
have healthier babies, the time to treat illness or change
HBsAg, hepatitis B surface antigen; HIV, human
unhealthy behavior is before pregnancy. immunodeficiency virus.
A number of screening tests must now be
ordered as part of the initial prenatal visit. Many of
the tests ordered in the preconception period need
not be repeated. Box 73-1 lists recommended screen- Testing for antibodies is done also during this first
ing laboratory tests during pregnancy. prenatal visit. One needs to know blood type
First the hemoglobin/hematocrit level should be (ABO/Rh) and antibodies for each pregnancy. Because
determined. During pregnancy, the increase in Rachel was pregnant previously, we already know that
plasma volume is disproportionately greater than the she is B negative, and blood type testing need not be
red blood cell mass, causing physiologic dilution and repeated. Antibodies must be checked with each preg-
a normal drop in hematocrit by 3% to 5%. nancy, however. The most prevalent antibody of con-
Therefore, the definition of anemia in pregnancy is cern during pregnancy is the anti-Rh (D) antibody. Rh
different from that in the nonpregnant adult woman. incompatibility occurs when an Rh-negative woman is
For women living at sea level, a hemoglobin of 11 pregnant with an Rh-positive fetus. This occurs in 9%
g/dL in the first and third trimester, and 10.5 g/dL in to 10% of pregnancies. Consequences for the fetus
the second trimester, is acceptable. Although hemo- include hemolytic anemia, hyperbilirubinemia, ker-
globin values well below 10% have been associated nicterus, and intrauterine death due to hydrops fetalis.
with an increased risk of low birth weight, preterm Without preventive measures, 0.7% to 1.8% of Rh-
delivery, and perinatal mortality in numerous longi- negative women become isoimmunized antenatally
tudinal cross-sectional studies, most of these studies and develop Rh (D) antibody through exposure to fetal
did not control for other factors such as smoking and blood; 8% to 15% become isoimmunized at birth; 3%
maternal malnutrition. Whereas a large body of data to 5% become isoimmunized after spontaneous or
suggests that iron supplements improve hematologic therapeutic abortion; and 2.1% to 3.4% become isoim-
indices in hemoglobin levels above 10 g/dL, there is munized after amniocentesis (U.S. Preventive Services
no consistent evidence that iron supplementation Task Force, 2004● A).
actually improves clinical outcomes. Therefore, there Rachel’s rubella status (immune) is already
are no evidence-based outcomes to recommend rou- known, and she also has a positive hepatitis B surface
tine iron supplementation in pregnant women with antibody documented on her chart. If these results
hemoglobin values greater than 10 g/dL. were not known as part of her medical history, they

548
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

would have to be checked at the first prenatal visit. complicated by neural tube defects occur in the
Similarly, there is no need to repeat a normal Pap absence of a positive history. It is recommended that
smear that was done within the past 6 months in a all women planning a pregnancy take a multivitamin
patient with no other known risk factors and with containing folic acid at a dose of 0.4 mg, beginning at
documented yearly normal Pap smears. Rachel is not least 1 month before conception and continuing
at high risk of sexually transmitted diseases. through the first trimester to reduce the risks of
Gonorrhea is more prevalent in specific high-risk neural tube defects. Rachel had been started on folic
groups, i.e., in prostitutes, in women younger than 25 acid when she discontinued her birth control pill
years of age with two or more sexual partners within 3 months ago. Adequate studies have not been com-
the past year, and in women with recurrent episodes of pleted to evaluate whether adequate dietary intake
sexually transmitted diseases. Routine screening for without vitamin supplementation could achieve the
women at high risk is recommended. At this first pre- same results.
natal visit, Rachel is screened for Chlamydia, however. Rachel stopped drinking her usual one glass of
Patient characteristics associated with a higher preva- wine a few times a week when she stopped the birth
lence of infection include a history of a sexually trans- control pill. Her physician supports that decision,
mitted disease, new or multiple sexual partners, although there is no proven association between
inconsistent use of barrier contraceptives, cervical occasional light drinking and adverse birth outcomes.
ectopy, and age younger than 25. Rachel is only 23 years There is a known association between problem drink-
old and thus fits into one of the high-risk categories. ing (two or more drinks per day or binge drinking)
All pregnant women need to be screened for and fetal alcohol syndrome. According to the U.S.
syphilis with a rapid plasma reagin titer, even if they Preventive Services Task Force (2004 ● A), there is
have been tested within the past year (U.S Preventive insufficient evidence to prove or disprove harm from
Services Task Force, 2004● A). The neurologic sequelae occasional light drinking during pregnancy.
for the surviving newborn are devastating, and there Fortunately, Rachel does not smoke cigarettes.
is a 40% fetal or perinatal death rate in pregnancies Tobacco use contributes to low birth weight, placenta
compromised by congenital syphilis. Penicillin is an previa, congenital anomalies, and spontaneous abor-
inexpensive, easily available treatment. tion.
Rachel is advised to have human immunodefi- Rachel is encouraged to exercise regularly, at the
ciency virus testing, as the overall prevalence in her same level that she was exercising before her preg-
community of seropositive newborns has increased nancy, providing she feels up to it. She should not
to greater than 0.1%. The U.S. Preventive Services work to increase her exercise stamina at this time.
Task Force (2004● A) recommends that all pregnant Sexual activity needs to be addressed by the
women from communities in which prevalence of physician early in pregnancy. If the patient does not
seropositive newborns has increased be offered test- ask about it, the physician must feel comfortable
ing as soon as the woman is known to be pregnant. initiating the topic. There is no contraindication to
The probability of vertical transmission varies from sexual intercourse in a normal health woman during
13% to 35%, increasing with the severity of disease her pregnancy.
in the mother, and can be significantly decreased We perform a screening interview to elicit any his-
with adequate antiviral therapy. Pregnancy is not tory of domestic violence, an underdiagnosed prob-
necessarily a contraindication to the use of optimal lem. Rachel was asked whether she had ever been
therapeutic regimens to treat this disease in the emotionally or physically abused by her partner and if
mother as well. Other benefits of early detection she had been hit, slapped, kicked, or otherwise physi-
include Pneumocystis carinii pneumonia prophylaxis, cally hurt by someone within the past year. She was
prevention of vertical transmission associated with surprised by the questions and responded with a
breast-feeding, early treatment of the infant, and clearly negative answer. Surveys from women in urban
early accessing of social service support. clinics state that 7% to 18% of women report physical
Rachel does not need hemoglobin electrophore- abuse or forced sex during pregnancy (Norton et al.,
sis, as she is not a member of one of the ethnic groups 1995● B). Several well-controlled studies suggest detec-
at high risk of a hemoglobinopathy, i.e., women tion rates improve when more than one question per-
of Caribbean, Latin American, Mediterranean, taining to violence is asked in a single interview, and
Southeast Asian, or African descent. with repeated questions on subsequent visits. However,
there are insufficient data to recommend for or against
Promote a Healthy Pregnancy the use of specific screening instruments, as methods
Rachel needs to be counseled on a healthy lifestyle. have not been adequately evaluated to change behav-
She is advised to eat a diet high in calcium (1200 to iors once the problem is identified.
1500 mg/day) with generous amounts of protein, Rachel’s workplace is a computer room at a col-
fruit, and vegetables. She is advised to continue her lege campus. No occupational hazards were discov-
folic acid. Ninety percent to 95% of pregnancies ered in review of her work site.

549
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

Plan occurrence of this condition in pregnancy varies in

studies between 2% and 7%. If untreated, pregnant
1. Ultrasound for dating women are at increased risk of pyelonephritis, with
2. Hematocrit, antibodies, Chlamydia, rapid plasma subsequent preterm delivery and a low birth weight
reagin, human immunodeficiency virus infant. The timing of a urine culture may vary,
3. Continue multivitamins with folic acid although asymptomatic bacteriuria is best detected if
4. Diet, exercise, sexual activity discussed the specimen is taken between 12 and 16 weeks’ ges-
5. Follow-up in 1 month tation. Urine dipstick testing for leukocyte esterase is
not an acceptable alternative screening test in the
pregnant woman. Sensitivity for dipstick testing of
FIRST FOLLOW-UP VISIT urine is only 50%.
The doctor notes that flu season will be starting
Subjective
over the next few weeks and wishes to immunize
Rachel and her husband return 4 weeks later. Ben is Rachel. The Advisory Committee on Immunization
looking forward to hearing the fetal heartbeat today. Practices recommends vaccination of all pregnant
Rachel’s nausea and fatigue have passed. She has women regardless of stage of pregnancy if the ges-
gained weight and is enjoying her pregnancy. She tation overlaps with flu season. (Harper et al.,
plans to keep working as long as possible. 2004● C ).
Ultrasound done 4 weeks ago confirmed an
8-week-old fetus, making her 12 weeks pregnant
today. She is concerned about her 5-pound weight Plan
gain over the past month. She continues to take her Urine culture today.
multivitamins with folate.
Her normal laboratory studies are reviewed. Her 1. Flu vaccine
hematocrit is 35. Antibodies, Chlamydia, and human 2. Follow-up in 1 month
immunodeficiency virus testing are all negative.
SUBSEQUENT FOLLOW-UP VISITS
Objective
Rachel is seen monthly over the next 24 weeks. Her
Well-appearing gravid woman. Blood pressure uterine growth, blood pressure, and weight gain con-
115/70 mm Hg, weight 145 pounds. Fundus palpated tinue to be normal.
just above the symphysis pubis. Fetal heart audible Specific objectives, e.g., screening tests, physical
by Doppler at 150 beats per minute. findings, and anticipatory guidance issues, are high-
Urine is negative for glucose and albumin. lighted at subsequent visits.
1. At 16 weeks. Rachel is screened for poten-
Assessment tial neural tube defects with a maternal serum
α-fetoprotein test. This is recommended for all
Normal pregnancy. Rachel’s due date has been con- women at 16 to 18 weeks’ gestation. False-positive
firmed by ultrasound and she is growing well. results can occur with multiple gestations, fetal
demise, or incorrect gestational age. A test is consid-
Discussion ered abnormal if it is 2.0 to 2.5 times above the
median value for gestational age. A very low α-feto-
A 5-pound weight gain over the past month is protein is suggestive of Down syndrome. Rachel’s
acceptable. Rachel has gained approximately 10 results are normal.
pounds from her pregravid weight, and a total preg- 2. At 20 weeks. Rachel is now at the midpoint of
nancy weight gain of 25 to 35 pounds, or 11 to 16 kg, her pregnancy. Her physician asks her whether she
is desirable in a woman of normal weight. Low has begun to feel movement. “Quickening,” as it is
prepregnant weight and inadequate weight gain are commonly called, occurs at 18 to 20 weeks’ gestation
both contributors to intrauterine growth retarda- in a primipara. It is subtle at first, and Rachel
tion. Conversely, in obese women, perinatal morbid- describes fleeting, faint movements over the past few
ity begins to increase with a weight gain of greater days. On physical examination, the fundus is at the
than 15 pounds (ACOG Technical Bulletin No. 179, umbilicus and measures 20 cm above the upper rim
1993● C ). Extreme obesity increases the risk of gesta- of the symphysis pubis. Over the next 12 to 16 weeks,
tional diabetes, hypertension, macrosomia, shoulder her growth corresponds to a centimeter per week
dystocia, and prolonged dysfunctional labor. (Fig. 73-1).
At 12 weeks’ gestation, Rachel may now be 3. At 24 weeks. Rachel expected to be screened
screened for occult bacteriuria. All pregnant women for gestational diabetes at this visit. At 24 to 28
need to be screened for occult bacteriuria. The weeks, the goal is to identify women with glucose

550
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

Table 73-1 Leopold’s Maneuvers

Maneuver Action Question
9
10 10 First Examine the What fetal
8 fundus part is in
7 the fundus?
Second Palpate the Where is the
6 lateral fetal back?
abdomen
5 Third Palpate the Is the
suprapubic area presenting
4 part
engaged?
3 Fourth Find the cephalic Is the head
(vertex prominence flexed?
only)

are discussed and Rachel is encouraged to attend pre-

Figure 73-1 Fundal growth at various months of gesta- natal classes. In the third trimester, signs of labor are
tons. (From Rakel, Robert E. Textbook of Family Practice, reviewed; birth plans are discussed including specifics
5th edition. Philadelphia, WB Saunders, 1996.) of anesthesia and labor support. Between 35 and 37
weeks, Rachel will be screened for group B strepto-
coccal infection via a single swab run over the skin
from the vaginal introitus to the anus (Box 73-2). The
intolerance and treat them with diet or insulin as vaginal and rectal areas of 10% to 30% of pregnant
needed. A 50-mg glucose drink is given, and the women may be colonized. Group B streptococcus is a
blood sugar is checked 1 hour later. A normal read- leading cause of neonatal illness and death. The risk
ing is below 140 ng/dL. Glycosuria is not an accurate of early-onset group B streptococcal disease in the
predictor of diabetes in the pregnant woman because infant of a colonized mother is one infant per 50
the renal threshold for glucose is lowered. Rachel to 100 colonized mothers. Group B streptococcal
does not fit into the specified high-risk groups, infection can also cause preterm labor, premature
including those who are obese, are age 25 or older, membrane rupture, urinary tract infections,
have a positive family history of diabetes, or are chorioamnionitis, and postpartum endometritis
members of ethnic groups with a high prevalence of (Keenan, 1998● C ). If Rachel’s culture is positive, she
diabetes, i.e., African Americans, Asians, Native will receive antibiotic prophylaxis in labor. Rachel’s
Americans, and Hispanics. Her doctor elects not to
screen her as the 2003 U.S. Preventive Health
Services Task Force report did not find that routine
Box 73-2 High-Risk Markers for
screening reduced important health outcomes for
mothers or their infants, i.e., cesarean delivery, birth Neonatal Invasive Group B
injury, neonatal morbidity or mortality. It does cite Streptococcal Infection
fair to good evidence that screening combined with
Previous infant with invasive group B strepto-
diet and insulin therapy can reduce the rate of fetal
coccal disease
macrosomia in gestational diabetes.
Maternal carrier state, especially if colonization
4. At 28 weeks. Antibodies are repeated at this visit
is heavy
because Rachel is Rh negative. She has negative results
Maternal group B streptococcal bacteriuria
and thus is given an intramuscular injection of 300 mg
Preterm labor or preterm rupture of the mem-
of Rh immune globulin, which should prevent any
branes at an estimated gestational age of
isoimmunization over the third trimester.
<37 wk
5. At 30 weeks and later. Beginning at 30 weeks,
Rupture of the membranes for >18 h
the uterus is examined at each visit using Leopold’s
maneuvers (Table 73-1 and Fig. 73-2) to detect the From Centers for Disease Control and Prevention.
baby’s position. Rachel is seen weekly by her physi- Prevention of perinatal group B streptococcal dis-
cian after 36 weeks’ gestation. ease: A public health persepective. MMWR Morb
Mortal Wkly Rep 1996;45:679; Schuchat A, Wenger
Health education and risk assessment continue JD. Epidemiology of group B streptococcal disease.
at each visit throughout the second and third Risk factors, prevention strageties, and vaccine
trimesters. During the second trimester, signs of labor development. Epidermiol Rev 1994;16:374–402.

551
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

First maneuver Second maneuver

Third maneuver Fourth maneuver

Figure 73-2 Leopold’s maneuvers for determining fetal position. (From Rakel, Robert E. Textbook of Family Practice,
5th edition. Philadelphia, WB Saunders, 1996.)

wishes for a natural childbirth are supported and

documented on her prenatal form. Breast-feeding, Material Available on Student Consult
circumcision, and postpartum contraception are also Review Questions and Answers about Normal
addressed, as are the plans of Ben and Rachel for help Pregnancy
with the newborn (Table 73-2).

552
 Chapter 73 Fatigue, Nausea, Breast Tenderness (Normal Pregnancy)

Table 73-2 U.S. Preventive Services Task Force Recommendations

for Low-Risk Pregnancies
Routine Recommendations/ Strength of Date of
Screening Recommendation Recommendation

Folic acid supplementation (0.4–0.8 mg A 1996

1 mo before conception through
1st trimester)
Rh incompatibility blood screening A 2004
Syphilis screening A 2004
Bacterial vaginosis screening in D 2001
asymptomatic woman
Routine asymptomatic bacteriuria A 2004
screening at 12–16 wk
NTD screening: maternal serum α-fetoprotein B 1996
at 16–18 wk
Gestational diabetes blood screening I 2003
Preeclampsia screening (blood pressure B 1996
measurements)
Routine ultrasound screening in 3rd trimester D 1996
Routine ultrasound screening in 2nd trimester C 1996
Brief education and counseling by M.D. to C 2003
promote breast-feeding
Routine screening for intimate partner violence I 2004
A, Good evidence that (the service) improves important health outcomes; B, at least fair evidence that (the
service) improves important health outcomes and concludes that benefits outweigh harms; C, at least fair
evidence that (the service) can improve health outcomes but concludes that the balance of benefits and harms
is too close to justify a general recommendation; D, at least fair evidence that (the service) is ineffective or that
harms outweigh benefits; I, effective evidence is lacking or of poor quality or conflicting; the balance of
benefits and harms cannot be determined.
NTD, neural tube defect.

REFERENCES
ACOG Technical Bulletin No. 179: Nutrition during U.S. Preventive Services Task Force. Screening for gestational
Pregnancy. Washington, DC, American College of diabetes mellitus. Guide to Clinical Preventive Services,
Obstetricians and Gynecologists, 1993.● C 2nd edition. Washington, DC, U.S. Department of
Harper SA, Fukuda K, Uyeki TM, et al. Prevention and Health and Human Services, Office of Disease
Control of Influenza: Recommendations of the Prevention and Health Promotion, 2003 Available at
Advisory Committee on Immunization Practices http://www.ahrq.gov/clinic/3rduspstf/gdm/gdmrr.pdf.
(ACIP). MMWR Recomm Rep 2004;53:1–40.● C Accessesed 4/14/2006.● A
Keenan C. Prevention of neonatal group B streptococcal U.S. Preventive Services Task Force. Screening for Rh (D)
infection. Am Fam Physician 1998;57:2713–2720.● C incompatibility. Guide to Clinical Preventive Services,
Norton LB, Peipert JF, Zierler S, et al. Battering in preg- 2nd edition. Washington, DC, U.S. Department of
nancy: An assessment of two screening methods. Health and Human Services, Office of Disease
Obstet Gynecol 1995;85:321–325.● B Prevention and Health Promotion, 2004. Available at
U.S. Preventive Services Task Force. Screening ultrasonogra- http://www.ahrq.gov/clinic/3rduspstf/rh/rhrs.pdf.
phy in pregnancy. Guide to Clinical Preventive Services, Accessesed 4/14/2006.● A
2nd edition. Washington, DC, U.S. Department of
Health and Human Services, Office of Disease
Prevention and Health Promotion, 1996. Available at
http://cpmcnet.columbia.edu/texts/gcps/gcps0046.html.
Accessesed 4/14/2006.● A

SUGGESTED READINGS
National Institute of Health. Caring for Our Future: The Connor EM, Sperling RS, Gelber R, et al. Reduction of
Content of Prenatal Care. U.S. Department of Health maternal-infant transmission of HIV-1 with zidovu-
and Human Services, Public Health Service, 1989. NIH dine treatment. N Engl J Med 1994;331:1173–1180.● A
publication no. 90-3182. Rakel RE. Textbook of Family Practice, 5th ed. Philadelphia,
WB Saunders, 1996, pp 528–567.● C

553
 C h a p t e r

74 Short Child
(Constitutional Growth Delay)
Sanford R. Kimmel

few green or yellow vegetables. He plays and keeps up

KEY POINTS with other boys his age.

1. Children with constitutional growth delay (CGD) Medical History

and those with familial short stature (FSS) both Johnny was the product of a full-term, uncomplicated
have normal birth length and weight, with sub- pregnancy. His birth weight was 7 pounds 8 ounces
sequent decline in birth percentiles during the (3.4 kg) and his length was 20 inches (51 cm). A chart
first 2 years of life. However, children with CGD of his growth is presented in Figure 74-1.
have a delayed bone age, whereas those with His developmental milestones include the follow-
FSS usually have a bone age equal to their ing: he smiled at 2 months, sat without support at 6
chronologic age. months, said “dada” specifically at 11 months, walked
2. Consider Turner’s syndrome in any girl with alone at 13 months, and now dresses himself without
short stature. supervision. He speaks in understandable sentences.
3. A comprehensive history and physical examina- Immunizations include diphtheria–tetanus–
tion determines the extent of laboratory testing. acellular pertussis (DTaP), conjugated pneumococ-
4. The decision to initiate growth hormone (GH) cal, and Haemophilus influenzae B vaccines at 2, 4,
therapy requires individualizing the potential 6, and 15 months of age; inactivated polio vaccine
benefits, risks, and costs and is usually done in (IPV) at 2, 4, and 12 months of age; and a
consultation with a pediatric endocrinologist. measles–mumps–rubella (MMR) vaccine at 15
months of age. Johnny also received a hepatitis B vac-
cine at birth and at 2 and 6 months of age.
Johnny has had four to five upper respiratory
infections per year and three lifetime episodes of oti-
INITIAL VISIT tis media. He has not had varicella, been hospital-
ized, or required major surgery.
Subjective
Patient Identification and Presenting Family History
Problem Johnny’s mother is 26 years old and in good health.
Johnny J. is a 5-year-old white boy seen for a prekinder- She is 5 feet 4 inches tall and weighs 140 pounds. His
garten well-child physical examination. Johnny’s 30-year-old father is 5 feet 8 inches tall and weighs
mother notes that he is smaller than other boys his age. 165 pounds. Johnny’s father recalls being smaller
His 3-year-old sister is almost as tall as he is. than his peers as a child and being a “late bloomer.”
Johnny’s 57-year-old paternal grandfather had
Present Illness a heart attack 2 years ago. His other grandparents are
Johnny’s only recent illness has been a cold, which in their 50s and in good health. Johnny’s 3-year-old
was treated with an over-the-counter antihista- sister is 37 inches tall and weighs 33 pounds.
mine–decongestant medicine. His appetite and phys-
ical activity are normal. He is a picky eater who Health Habits
generally has cold cereal and milk for breakfast, mac- Johnny uses a belted child booster seat when travel-
aroni and cheese for lunch, and a hamburger or pizza ing in the car. His parents limit television viewing to
for supper. He likes apples, bananas, and corn but 2 hours per day. He is learning to ride a bicycle.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

554
 Chapter 74 Short Child (Constitutional Growth Delay)

(95%) (95%)
40

(5%) 70
35
40 (5%)
65
(95%)
30
35 60
(95%)
200
25 30 55

Weight (lb)

Weight (lb)
Length (in)
Height (in)

(5%)
20 50
25
150
45
15 20
(5%)
40
15 100
35
10
30
50
5
30
6 12 18 24 30 36 2 5 10 15
Age (mo) Age (y)

Figure 74-1 Growth curves for Johnny J. for length/height (top curve) and weight (lower curve). The 95th and 5th per-
centiles for each parameter are also outlined.

Social History Laboratory Tests

Johnny is currently in nursery school but will be A urinalysis demonstrates a specific gravity of 1.022,
starting kindergarten next year. His mother, who is a pH 6.0, with negative dipstick and microscopic
teacher, reports that he interacts well with other chil- examination.
dren his age. However, she and her husband, who is
an executive, are concerned that his small size may
Assessment
place him at a disadvantage in school.
Working Diagnosis
Review of Systems The most likely diagnosis is constitutional growth
Other than slight rhinorrhea, the review of systems is delay (CGD) in an otherwise well child. Although
unremarkable. Johnny’s height is below the 5th percentile and his
weight is at the 5th percentile, his rate of growth par-
Objective allels the growth curve. His deceleration in growth
occurred before age 2 and was accompanied by
Physical Examination crossing of percentile lines. Since age 2, his linear
Johnny’s height is 38.5 inches, weight is 33 pounds, growth has averaged 4 to 5 cm per year. Johnny’s
blood pressure is 94/58, and pulse is 76 and regular. family history of delayed physical development also
He appears normally proportioned and has no supports this diagnosis (Bareille et al., 1998).
detectable deformities. Examination of the head,
neck, eyes, ears, nose, and throat is normal. The car- Differential Diagnoses
diorespiratory and abdominal examinations are While genetic and environmental factors often cause
also normal. His genitalia are prepubertal (Tanner short stature, almost any serious chronic illness can
stage 1). He follows directions and can balance on have an adverse impact on a child’s growth. Common
one foot for 6 seconds, catch a bounced ball, and causes of short stature are listed in Box 74-1 and
draw a man with a head, eyes, ears, nose, mouth, are discussed later in this chapter (see Discussion
body, arms, and legs. section).

555
 Chapter 74 Short Child (Constitutional Growth Delay)

position. Children 2 years and older should have

Box 74-1 Common or Significant Causes their shoeless standing height measured with a
of Short Stature in Children stadiometer. Using either method, the head
should be positioned so the outer canthus of the
Familial eye is aligned with the external auditory canal and
Constitutional growth delay perpendicular to the measuring surface (Halac
Familial (genetic) short stature and Zimmerman, 2004). Children should wear
minimal clothing when they are weighed at each
Congenital visit, preferably on the same scale. Height and
Down syndrome weight are then plotted on a growth chart devel-
Noonan’s syndrome oped by the National Center for Health Statistics.
Russell-Silver syndrome Height age is the age at which the child’s height
Skeletal dysplasia (dwarfism) intersects the 50th percentile curve on this chart.
Turner’s syndrome 2. A bone-age radiograph of the left hand and wrist
Virilizing congenital adrenal hyperplasia is compared with published age-specific stan-
(tall child, short adult) dards (Miller and Zimmerman, 2004). Children
must be at least 2 years of age for epiphyseal ossi-
Systemic Disorders fication centers to be reliably identified. Bone age
Cancer due to poor nutrition, chemotherapy, films help differentiate familial short stature
or radiotherapy (FSS) from CGD and various endocrinologic dis-
Endocrine disease orders (Table 74-1).
Cushing’s syndrome 3. The child’s lower segment is determined by meas-
Diabetes mellitus (poorly controlled) uring the distance from the top of the symphysis
Growth hormone deficiency, congenital pubis to the floor or surface supporting the feet.
or acquired The upper segment equals this distance sub-
Hypopituitarism tracted from the total height. The upper-to-lower
Hypothyroidism segment ratio decreases from 1.7 at birth to 1.4 at
Heart disease 2 years of age, to 1.0 at age 10 years, and to 0.9 in
Chronic heart failure adults. This ratio is increased in short-limbed
Congenital heart disease dwarfism, chondrodystrophies, gonadal dysgene-
Gastrointestinal disease sis, and Klinefelter syndrome. Vertebral anomalies
Celiac disease decrease the upper-to-lower segment ratio (Halac
Inflammatory bowel disease (Crohn’s dsease) and Zimmerman, 2004).
Malabsorption syndromes 4. A complete blood count with differential may
Immunologic diseases reveal anemia or malignancy. An erythrocyte
Acquired immunodeficiency syndrome sedimentation rate may detect nonspecific
Severe combined immunodeficiency inflammatory disorders such as inflammatory
Pulmonary disease bowel disease or collagen vascular disease.
Asthma (poorly controlled) Endomysial antibodies should also be considered
Cystic fibrosis because celiac disease is increasingly recognized.
Renal disease Stool specimens for fat and ova and parasites may
Chronic renal failure be useful in detecting causes of malabsorption.
Renal tubular acidosis Girls of short stature should have a karyotype
evaluation (Halac and Zimmerman, 2004).
Environmental 5. Serum free thyroxine and thyroid-simulating
Malnutrition hormone determinations should be performed
Psychosocial deprivation because hypothyroidism is easily detected and
Toxin or drug exposure (e.g., lead) treated. Levels of insulin like growth factor 1
(IGF-1) and insulin growth factor binding pro-
tein 3 may estimate growth hormone (GH) func-
Plan tion (Miller and Zimmerman, 2004).
6. Renal and liver function tests, blood glucose, lipid
Diagnostic profile, calcium, phosphorus, and electrolyte
1. Proper evaluation of the growth curve is the most determinations, and a urinalysis are useful in
important consideration. A normal rate of linear ruling out renal or hepatic disease, diabetes, or
growth excludes most organic causes of short hyperlipidemia. Cholesterol level is important in
stature. Children younger than 2 years of age this case because the family history is suspicious
should have their length measured in the supine for early cardiac disease.

556
 Chapter 74 Short Child (Constitutional Growth Delay)

Table 74-1 Causes of Short Stature and Relationship to Bone Age and Growth Rate
Bone Age Bone Age Bone Age
Growth Rate < Chronologic Age = Chronologic Age > Chronologic Age

Initially increased Congenital adrenal

(short adult) hyperplasia
Exogenous androgenic
steroids
Precocious puberty
Normal or slightly Constitutional growth Familial short stature
decreased delay Skeletal dysplasias
Rickets
Decreased Endocrine disorders Chromosomal disorders
Cushing’s syndrome Down syndrome
Growth hormone Turner’s syndrome
deficiency
Chronic systemic disease
Crohn’s disease
Heart failure
Renal failure
Severe malnutrition
Severe psychosocial
deprivation

Therapeutic Disposition
The appropriate preschool immunizations— Johnny is scheduled to return in 6 months for a fol-
varicella vaccine, DTaP booster, IPV, and MMR low-up of his growth parameters. Laboratory results
vaccine—should be given at separate sites. and any subsequent necessary action will be commu-
nicated by telephone.
Patient (Parent) Education
The parents’ concerns are acknowledged. Johnny’s
satisfactory rate of growth despite his small FIRST FOLLOW-UP VISIT
absolute size is then demonstrated on the growth
curve. The parents are told that although some Subjective
children are going to constitute the lower per- Johnny returned 6 months later accompanied by his
centiles of the normal population, the family his- mother. He has been in kindergarten for several
tory suggests that Johnny might be a “late bloomer” months and is adjusting well.
like his father.
Anticipatory guidance should include injury
Objective
prevention issues such as locking up poisons, medi-
cines, dangerous tools, or firearms; teaching children Johnny’s height is now 393⁄4 inches, and his weight is
to follow the proper rules of the road and to wear 35 pounds. His bone-age film of the wrists done
helmets when bicycling or rollerblading; and model- shortly after his first visit approximates 3 years and
ing this behavior. Children should be taught to swim, 6 months. His chemistry panel demonstrates normal
and they should be constantly supervised when in or levels of electrolytes, calcium, phosphorus, total pro-
near the water. The child should know his or her tein, and albumin. His creatinine is normal at 0.6
name, address, and telephone number and to say mg/dL (53 μ mol/L), as is his blood urea nitrogen at
“no” to strangers. Age-appropriate chores should be 7 mg/dL (2.50 mmol/L). His alkaline phosphatase
encouraged at home as well as quality family time. level is normal for his age at 172 U/L. Other liver
Appropriate and consistent limit setting should bal- enzymes are normal. Serum free thyroxine is normal
ance the child’s need for autonomy. Playing well with at 1.4 ng/dL (17.5 pmol/L), and thyroid-stimulating
other children, taking turns, following simple direc- hormone is 3.5 μU/L. Erythrocyte sedimentation
tions, and dressing oneself indicate skills appropriate rate is normal at 4 mm/hour. Serum cholesterol is
for school entry. 156 mg/dL (4.04 mmol/L).

557
 Chapter 74 Short Child (Constitutional Growth Delay)

Assessment DISCUSSION
The delayed bone age consistent with height age and
a normal growth velocity supports the diagnosis of Parents (and grandparents) are greatly interested in
CGD. An elevated alkaline phosphatase is appropri- their child’s growth. They are especially concerned if
ate for a child with active skeletal growth and should he or she is smaller than his or her peers. A careful
be compared to reference values for age. history should include prenatal factors such as nutri-
tion, smoking, and drug use, problems in the perina-
tal period, and the child’s subsequent growth and
Plan development. A family history to detect short stature,
delayed maturation, genetic abnormalities, and
Diagnostic chronic diseases is also necessary. Accurate measure-
Continued monitoring of Johnny’s growth at yearly ments of the child’s height, weight, and head circum-
intervals is essential. No further diagnostic testing is ference should be made. Arm span and upper-
necessary at this time. The serum cholesterol deter- to-lower segment ratio should also be measured if
mination may be repeated in 5 years. indicated, and a careful physical examination should
be performed including assessment for dysmorphic
Therapeutic features. Linear growth in children normally
At this time, Johnny does not seem to be suffering decreases from approximately 10 cm per year at age
any adverse psychological effects such as poor self- 2 to between 5 and 6 cm per year at age 6 until the
image or social isolation. Continued reassurance is pubertal growth spurt (Halac and Zimmerman,
sufficient. If a child is sustaining deleterious psycho- 2004). Growth occurs in spurts rather than continu-
logical effects, then referral to a pediatric endocri- ously. Table 74-2 presents approximate growth
nologist to consider a trial of human GH therapy guidelines for prepubertal children.
may be in order.
Constitutional Growth Delay
Patient Education
Johnny’s mother is reassured that his delayed bone CGD is a variant of normal growth that occurs more
age indicates that he has additional time to catch up frequently in boys who enter puberty and develop
in growth. His family can expect that he will enter later than their peers. Their bone age is correspond-
puberty later and be a “late bloomer” like his father. ingly delayed by 2 or more years and approximately

Table 74-2 Approximate Growth Guidelines for Children

Age Length or Height Weight

Newborn 50 cm (20 inches) average 3.4 kg (7.5 lb) average

Newborn to 3 mo 1 kg/mo (1 oz/day) average weight
gain
3–12 mo Wt (kg) = [age (mo) + 9] ÷ 2
Wt (lb) = age (mo) + 11*
12 mo 75 cm (30 inches) average Triples birth weight
12–24 mo Increases by >10 cm/yr 0.25 kg/mo
>5 yr >5 cm (2 inches)/yr until 2.3 kg (5 lb)/yr until adolescent
adolescent growth spurt growth spurt
Ages 1–6 Wt (kg) = age (yr) × 2 + 8
*
Wt (lb) = age (yr) × 5 + 17

Ages 7–12 Height (cm) = age (yr) × 6 + 77 Wt (kg) = [age (yr) × 7 − 5] ÷ 2

Height (in) = age (yr) × Wt (lb) = age (yr) × 7 + 5*
2.5 + 30* e.g., 4 year old
= 40 inches
Puberty 8–14 cm/yr
*
Adapted from Needleman RD. The first year. In Behrman RE, Kliegman RM, Jenson HB (eds): Nelson Textbook of
Pediatrics, 17th ed. Philadelphia, WB Saunders, 2004, p 31.

558
 Chapter 74 Short Child (Constitutional Growth Delay)

equal to their height age. Review of the growth chart ative dipstick for glucose excludes diabetes mellitus.
demonstrates an average birth size with deceleration Poor growth due to malnutrition may be caused by
in the growth rate during the first 2 years of life. The malabsorption syndromes characterized by loose or
growth rate subsequently returns to normal, but the foul-smelling stools and diminished caloric intake.
child now follows a lower percentile on the growth
curve. The pubertal growth spurt and adolescent
Endocrinologic Causes and Hypothyroidism
development will also be correspondingly delayed.
There is usually a family history of delayed growth Endocrinologic causes of short stature are less com-
and development (Bareille and Stanhope, 1998). mon but are treatable diseases that must be consid-
ered. Most children with endocrine causes of poor
Familial Short Stature linear growth have a normal weight for height age.
Congenital hypothyroidism occurs in 1 in 4000 infants
Children with FSS usually have parents or close rela- and is acquired in 1 in 1250 school-age children. Girls
tives who are short. They often have normal birth acquire hypothyroidism twice as often as boys. Infants
weight and length, but their growth declines during may have prolonged jaundice, sluggishness, feeding
the first 2 to 3 years of life and follows a trajectory difficulties, constipation, cold extremities, slow pulse,
consistent with their genetic potential. Their growth heart murmur, anemia, and developmental delay.
curve is below the 5th percentile but then parallels Older children may have myxedema, cold intolerance,
the normal curve, indicating a normal growth veloc- and significant delay in bone age. Puberty is often
ity (Barielle et al. 1998). Their bone age is approxi- delayed in adolescents, but younger children may
mately equal to their chronologic age but less than demonstrate pseudoprecocious puberty (LaFranchi,
their height age. Untreated children with FSS will 2004). The thyroid-stimulating hormone level is ele-
have a below-normal adult height. vated in primary hypothyroidism, whereas a low free
CGD and FSS are both characterized by a nor- thyroxine and a low thyroid-stimulating hormone
mal growth rate. The mean predicted adult height for suggest pituitary or hypothalamic defects. Thyroid
a boy can be calculated as [father’s height + hormone is necessary for normal GH synthesis, and
(mother’s height + 13 cm)] ÷ 2. If the child is a girl, levels must be assayed before GH studies are done.
the mean predicted adult height is [(father’s height −
13 cm) + mother’s height] ÷ 2 (Rogol, 2004). Ninety-
Cushing’s Syndrome
five percent of the population will attain an adult
height within 3 to 4 inches above or below their pre- Cushing’s syndrome is often caused by the adminis-
dicted height. If the child is growing at a rate that will tration of pharmacologic doses of glucocorticoids
enable him to achieve his predicted adult height, but may be due to a functional adrenocortical tumor
then careful observation of growth parameters is or excess adrenocorticotropic hormone. Young chil-
appropriate. If the child’s growth rate is declining, dren have generalized obesity, but older children
then further investigation is warranted. often have truncal obesity, “moon” facies, “buffalo
hump,” purplish striae, glucose intolerance, and
Malnutrition and Psychosocial Deprivation osteoporosis. Hypertension is present in both age
groups. Children with Cushing’s syndrome demon-
Adverse nutritional or socioeconomic factors should strate excessive weight gain accompanied by growth
always be considered in the evaluation of a child’s retardation (Halac and Zimmerman, 2004).
growth. However, the diagnosis of psychosocial dep-
rivation should not be made until an appropriate
Congenital Adrenal Hyperplasia
nutritional assessment and trial have been conducted
and organic causes excluded. Some chronic illnesses Undetected and untreated congenital adrenal hyperpla-
that can result in poor growth are listed in Box 74-1. sia ultimately leads to short stature as an adult, although
the initial signs are ambiguous genitalia and virilization.
Chronic Systemic Illness Initial growth is accelerated and bone age is advanced
leading to premature closure of the epiphyses.
Chronic systemic illness usually has an adverse effect
on body mass (weight) before linear growth. Failure
Growth Hormone Deficiency
to grow is sometimes the only manifestation of
inflammatory bowel disease or renal disease. A com- Infants with congenital hypopituitarism have normal
plete blood count, erythrocyte sedimentation rate, or less than average birth length and poor linear
electrolytes, and other blood chemistries may be growth that is apparent by 12 months of age.
required if these conditions are suspected. A normal Prolonged neonatal conjugated and unconjugated
urinalysis with a specific gravity greater than 1.020 hyperbilirubinemia is common, and apnea or severe
assists in ruling out diabetes insipidus, whereas a neg- hypoglycemia may occur. Affected boys may have

559
 Chapter 74 Short Child (Constitutional Growth Delay)

micropenises (stretched length less than 2.8 cm [1.1 caused by failure of the epiphyses to close.
inch] in a term infant). Children may appear pudgy, Complete skeletal radiographs may be required in
have immature facies, underdeveloped genitalia, and addition to determination of serum calcium, phos-
secondary sexual characteristics. Fasting hypo- phorus, protein, and alkaline phosphatase to rule
glycemia occurs in 10% to 15% and may also be pres- out hypophosphatasia, vitamin D–resistant and
ent in children with acquired GH deficiency (Parks, vitamin D–dependent rickets. Urine screening for
2004). Acquired causes of GH deficiency include metabolic and storage disorders should also be
trauma, tumors such as craniopharyngioma, and cen- considered.
tral nervous system infections or irradiation. Bone
age is severely delayed in children with long-standing
Growth Hormone Treatment
GH deficiency, regardless of cause.
Children with classic GH deficiency fail to release Most children with CGD will reach their predicted
normal amounts of GH in response to pharmacologic mid-parental height. Some may remain several
stimuli. Emotional deprivation can produce func- inches below their target height. Children with FSS
tional hypopituitarism characterized by inadequate will grow up to be short adults, a fact that some
GH response to provocative stimuli and low levels of families may not accept. Short stature has not been
IGH-1. Coexisting pituitary disorders must be investi- shown to affect acceptance by peers among middle
gated in children with suspected GH deficiency. and high school students (Sandberg et al., 2004 ● B ).
Children with GH neurosecretory dysfunction may However, taller college graduates may earn more
exhibit a normal GH response to the usual provocative money and most presidents have been the taller
tests but demonstrate a marked deficiency of pulsatile candidate. Consequently, there has been greater
secretion of GH over a 24-hour period (Parks, 2004). pressure to give human GH to children who do not
Because of the variation in testing, referral to a pedi- have classic GH deficiency. In addition to proven
atric endocrinologist is in order when GH deficiency GH deficiency, recombinant human GH is now
is suspected. approved in the United States for the treatment of
short stature in children with Turner’s syndrome,
Chromosomal Disorders intrauterine growth retardation, chronic renal
insufficiency, Prader-Willi syndrome, and idio-
Children with chromosomal disorders usually have pathic short stature. Recent evidence suggests
apparent dysmorphic features. Turner’s syndrome recombinant human GH treatment of children with
should always be considered in short girls, especially idiopathic short stature may increase their final
if there is no family history of short stature. predicted height by 5 to 7 cm (Miller and Zim-
Characteristic features include low birth weight, merman, 2004), but treated individuals are still rel-
webbing of the neck, low posterior hairline, broad atively short compared with their peers of normal
chest with widely spaced nipples (shieldlike chest), height (Bryant et al., 2003●
A). In addition, therapy is
cubitus valgus, and lymphedema of the hands and costly ($35,000/inch), and the child must tolerate
feet. If mosaicism is present, short stature may be the daily or thrice-weekly injections. Furthermore, it
only manifestation. Consequently, short girls with has not yet been demonstrated that GH treatment
subnormal growth rates should have banded kary- improves measured quality of life (Radcliffe et al.,
otyping performed. Special growth charts are avail- 2004● A). Long-term GH use is rarely accompanied
able for girls with Turner’s syndrome as well as by adverse effects such as impaired glucose toler-
children with Down syndrome. ance, pseudotumor cerebri, slipped capital femoral
epiphysis, and progression of scoliosis. Children
Skeletal Dysplasias treated with GH also have a theoretical increased
risk of malignancies and some with Prader-Willi
Skeletal dysplasias or osteochondrodysplasias are syndrome have died (Miller and Zimmerman,
usually inherited and cause disproportionate short 2004).
stature. The term dwarfism has been used to refer to
this group of disorders, although there are more
than 200 varieties. Skeletal dysplasias are frequently
characterized by a greater than normal upper-to- Material Available on Student Consult
lower segment ratio (Halac and Zimmerman,
2004). In contrast, children with hypogonadism Review Questions and Answers about Constitu-
tional Growth Delay
have longer extremities and a less than normal ratio

560
 Chapter 75 Behavior Problem in a 2-Year-Old Boy (Autism)

REFERENCES
Bareille P, Craig F, Stanhope R. Familial short stature. In Needleman RD. The first year. In Behrman RE, Kliegman
Finberg L (ed): Saunders Manual of Pediatric Practice. RM, Jenson HB (eds): Nelson Textbook of Pediatrics,
Philadelphia, WB Saunders, 1998, pp 733–734. 17th ed. Philadelphia, WB Saunders, 2004, p 31.
Bareille P, Stanhope R. Constitutional short stature. In Parks JS. Hypopituitarism. In Behrman RE, Kliegman RM,
Finberg L (ed): Saunders Manual of Pediatric Practice. Jenson HB (eds): Nelson Textbook of Pediatrics, 17th
Philadelphia, WB Saunders, 1998, pp 731–733. ed. Philadelphia, WB Saunders, 2004, pp 1847–1853.
Bryant J, Cave C, Milne R. Recombinant growth hormone for Radcliffe DJ, Pliskin JS, Silvers JB, Cuttler L. Growth hor-
idiopathic short stature in children and adolescents. The mone therapy and quality of life in adults and children.
Cochrane Database of Systematic Reviews 2003, Issue 2.Art. Pharmacoeconomics 2004;22:499–524.● A
No.: CD004440. DOI: 10.1002/14651858.CD004440.● A Rogol AD. Diagnostic approach to short stature. UpToDate
Halac I, Zimmerman D. Evaluating short stature in chil- Online. Available at www.utdol.com/application/topic/
dren. Pediatr Ann 2004;33:170–176. print.asp?file= pediendo/2375&type=A&selectedTitle.
LaFranchi S. Hypothyroidism. In Behrman RE, Kliegman Accessed 10/3/2004.
RM, Jenson HB (eds): Nelson Textbook of Pediatrics, 17th Sandberg DE, Bukowski WM, Fung CM, Noll RB. Height
ed. Philadelphia, WB Saunders, 2004, pp 1873–1879. and social adjustment: Are extremes a cause for con-
Miller BS, Zimmerman D. Idiopathic short stature in chil- cern and action? Pediatrics 2004;114:744–750.● B
dren. Pediatr Ann 2004:33:177–181.

C h a p t e r

75 Behavior Problem in a
2-Year-Old Boy (Autism)
Kenneth Lin

INITIAL VISIT
KEY POINTS
Subjective
1. Although autism remains a relatively rare disor-
der, the ability of early interventions to improve Patient Identification and Presenting
its prognosis mandates timely identification in Problem
the office setting. Adam is a 2-year-old boy who is brought to the office
2. Investigations continue into its genetic and by his parents because they are concerned about his
environmental causes, but the measles, mumps, loss of language skills and worsening behavioral
and rubella (MMR) vaccine does not appear to problems.
be one of them.
3. Intensive behavior modification programs seem Present Illness
to improve functioning, but no consensus exists Adam met age-appropriate milestones on the Denver
about which program works best or even if II Developmental Scale until his 9-month checkup,
there is a “best” program for all autistic chil- saying “mama” and “dada,” but then he lost these
dren. words at 15 months and learned no more.
4. Medications are effective for controlling According to Adam’s parents, he makes limited
seizures, tantrums, and comorbid psychiatric eye contact, has a narrow range of interests, and
diagnoses. prefers to play alone. He also engages in unusual
repetitive activities such as rocking, spinning, head

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

561
 Chapter 75 Behavior Problem in a 2-Year-Old Boy (Autism)

REFERENCES
Bareille P, Craig F, Stanhope R. Familial short stature. In Needleman RD. The first year. In Behrman RE, Kliegman
Finberg L (ed): Saunders Manual of Pediatric Practice. RM, Jenson HB (eds): Nelson Textbook of Pediatrics,
Philadelphia, WB Saunders, 1998, pp 733–734. 17th ed. Philadelphia, WB Saunders, 2004, p 31.
Bareille P, Stanhope R. Constitutional short stature. In Parks JS. Hypopituitarism. In Behrman RE, Kliegman RM,
Finberg L (ed): Saunders Manual of Pediatric Practice. Jenson HB (eds): Nelson Textbook of Pediatrics, 17th
Philadelphia, WB Saunders, 1998, pp 731–733. ed. Philadelphia, WB Saunders, 2004, pp 1847–1853.
Bryant J, Cave C, Milne R. Recombinant growth hormone for Radcliffe DJ, Pliskin JS, Silvers JB, Cuttler L. Growth hor-
idiopathic short stature in children and adolescents. The mone therapy and quality of life in adults and children.
Cochrane Database of Systematic Reviews 2003, Issue 2.Art. Pharmacoeconomics 2004;22:499–524.● A
No.: CD004440. DOI: 10.1002/14651858.CD004440.● A Rogol AD. Diagnostic approach to short stature. UpToDate
Halac I, Zimmerman D. Evaluating short stature in chil- Online. Available at www.utdol.com/application/topic/
dren. Pediatr Ann 2004;33:170–176. print.asp?file= pediendo/2375&type=A&selectedTitle.
LaFranchi S. Hypothyroidism. In Behrman RE, Kliegman Accessed 10/3/2004.
RM, Jenson HB (eds): Nelson Textbook of Pediatrics, 17th Sandberg DE, Bukowski WM, Fung CM, Noll RB. Height
ed. Philadelphia, WB Saunders, 2004, pp 1873–1879. and social adjustment: Are extremes a cause for con-
Miller BS, Zimmerman D. Idiopathic short stature in chil- cern and action? Pediatrics 2004;114:744–750.● B
dren. Pediatr Ann 2004:33:177–181.

C h a p t e r

75 Behavior Problem in a
2-Year-Old Boy (Autism)
Kenneth Lin

INITIAL VISIT
KEY POINTS
Subjective
1. Although autism remains a relatively rare disor-
der, the ability of early interventions to improve Patient Identification and Presenting
its prognosis mandates timely identification in Problem
the office setting. Adam is a 2-year-old boy who is brought to the office
2. Investigations continue into its genetic and by his parents because they are concerned about his
environmental causes, but the measles, mumps, loss of language skills and worsening behavioral
and rubella (MMR) vaccine does not appear to problems.
be one of them.
3. Intensive behavior modification programs seem Present Illness
to improve functioning, but no consensus exists Adam met age-appropriate milestones on the Denver
about which program works best or even if II Developmental Scale until his 9-month checkup,
there is a “best” program for all autistic chil- saying “mama” and “dada,” but then he lost these
dren. words at 15 months and learned no more.
4. Medications are effective for controlling According to Adam’s parents, he makes limited
seizures, tantrums, and comorbid psychiatric eye contact, has a narrow range of interests, and
diagnoses. prefers to play alone. He also engages in unusual
repetitive activities such as rocking, spinning, head

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

561
 Chapter 75 Behavior Problem in a 2-Year-Old Boy (Autism)

banging, and toe walking. Certain sounds, such as Head, Eyes, Ears, Nose, and Throat Normo-
the vacuum and lawn mower, cause him great dis- cephalic, atraumatic. Pupils are equal, round, and
tress. He is impulsive and has frequent tantrums that reactive to light. Extraocular movements are intact.
are extremely difficult to manage. Mucous membranes are moist. No deformities of
the ears or prominence of facial features. Palate
Medical History is intact. Oropharynx is without erythema or exudate.
Adam was hospitalized for pneumonia at 10 months
of age and uses twice-daily inhaled budesonide for Neck No lymphadenopathy or thyromegaly.
mild persistent asthma.
Adam has never had significant head trauma Pulmonary Clear to auscultation bilaterally.
and has no history of seizures.
Immunizations are up to date for his age, Cardiovascular Regular rate and rhythm, without
including the first dose of the MMR vaccine at 14 murmurs, rubs, or gallops.
months.
Abdomen Soft, nontender, with normoactive bowel
Birth History sounds. No hepatomegaly or splenomegaly.
Adam was born at term to a primigravida mother by
spontaneous vaginal delivery after an 18-hour labor. Extremities No clubbing, cyanosis, or edema.
The pregnancy was complicated by maternal tobacco
use. Adam’s birth weight was 7 pounds, 2 ounces. Genitourinary Normal male genitalia, testes
Apgar scores were 9 and 9. His newborn nursery descended bilaterally, Tanner stage 1.
course was uneventful. He passed the hearing screen.
There was no neonatal jaundice. Newborn screening Skin No rashes or lesions.
results are not available.
Musculoskeletal Moves all four extremities sym-
Family History metrically. Walks, runs, and climbs on to the exami-
There is no family history of mental retardation, nation table without difficulty. Can stack two blocks.
developmental disorders, or other childhood ill-
nesses except for attention-deficit/hyperactivity dis- Neurologic Cranial nerves II through XII are grossly
order in a maternal cousin. A paternal uncle was intact. Occasionally vocalizes but makes no under-
diagnosed with bipolar disorder in his 20s. standable speech. Does not repeat words or imitate
behaviors of his parents or the examiner. Does
Social History not follow simple directions or respond to requests to
Adam lives with his father, mother, and 7-month-old identify his parents or familiar objects. Exhibits
brother in a single-family home built in 1957. His father no recognition when shown a photograph of himself.
was recently laid off from his job as a machine operator
at a chemical plant, and his mother has not worked out- Assessment
side the home since Adam was born. As a result, the
family now depends on public assistance for income, Working Diagnosis
which both parents say has been “stressful.” Adam’s Autistic spectrum disorder (ASD), most likely autis-
father smokes cigarettes at home. They have no pets. tic disorder with associated mental retardation.

Review of Systems Differential Diagnoses

Adam’s head circumference, height, and weight have A hallmark of ASDs, distinguishing them from condi-
been within normal limits for age at his previous tions such as cerebral palsy caused by prenatal or perina-
well-child visits. The remainder of the review of sys- tal insults, is a period of normal growth and development
tems is otherwise unremarkable. followed by stagnation or regression. Common condi-
tions that may mimic ASDs in their clinical presentation
are lead intoxication, fragile X syndrome, and hearing
Objective
impairments (Simms and Schum, 2000).
Physical Examination
General Adam is a nontoxic-appearing toddler who Plan
is unable to sit still or follow instructions for any part
of the examination. Diagnostic
Adam’s parents and physician complete the Checklist
Vital Signs Temperature 37˚C (98.6˚F) orally, with for Autism in Toddlers, which consists of nine yes/no
height, weight, and head circumference all in the questions for the parents, followed by five questions
Vital Signs 75th percentile for age. for the physician based on observations of the child

562
 Chapter 75 Behavior Problem in a 2-Year-Old Boy (Autism)

at play. The answers are consistent with the working typed patterns of behavior, interests, and activities
diagnosis of autism. (Volkmar and Pauls, 2003). Box 75-1 describes some
The physician orders a lead level, chromosomal common behaviors in autistic children. Although not
analysis, and formal audiology evaluation, all of essential for the diagnosis, autism is associated with
which are normal. mental retardation (75%), epilepsy (35%), behavioral
problems, and depression and anxiety disorders
Therapeutic (Rapin, 1997). Although the skills of “autistic savants”
Adam is referred to an intensive, 40 hours per week were well publicized in the 1988 movie Rain Man and
behavioral modification therapy program with a 2:1 stu- by the protagonist of Oliver Sacks’s An Anthropologist
dent-to-teacher ratio. His parents are given information on Mars, these persons are rarities. In fact, almost
about support groups for parents of autistic children. 50% of autistic children will never develop commu-
nicative speech. Although one-third will eventually
Patient and Parental Education achieve some degree of independent living, fewer
The physician explains to Adam’s parents that autism than 5% are completely self-sufficient as adults.
is a neurodevelopmental disorder, the cause of which is ASDs affect approximately six in 1000 children,
unknown. Although it was originally thought to be with a 4:1 male-to-female ratio (Baird et al., 2003).
secondary to problem parenting (mothers who did not Their prevalence appears to be on the rise; from 1992
demonstrate physical affection), it is now thought to be to 1993 to 2000 to 2001, the U.S. Department of
the result of a complex genetic predisposition triggered Education reported a more than sevenfold increase
by uncertain environmental influences. Nearly half of in the number of autistic children served under the
all children with autism will never develop commu- Individuals with Disabilities Education Act (Vastag,
nicative speech, and fewer than 5% will be completely 2004). Although part of the observed increase may
self-sufficient as adults. Early, intensive behavioral be secondary to increased recognition, the reasons
interventions do appear to improve the prognosis. for the remainder are unknown and have been the
Studies of siblings of autistic children predict that subject of much speculation.
Adam’s younger brother Nathan has a 5% chance of The sharp rise in prevalence of ASDs, along with
being diagnosed with autism in the future. its typical age of diagnosis between the ages of 18
months and 3 years, prompted concerns that some
element of the MMR vaccine, administered between
12 and 15 months of age, could be responsible. These
DISCUSSION concerns received support from a case series by
Wakefield and colleagues published in Lancet in 1998
Definition/Epidemiology
that described 12 patients with gastrointestinal com-
Autism is not a single disease but rather a spectrum of plaints who developed autistic symptoms within 1
behaviorally defined disorders (Table 75-1) distin- month after receiving the MMR vaccine. These inves-
guished by impaired social interactions, impaired tigators hypothesized that a component of the MMR
communication, and restricted, repetitive, or stereo- vaccine causes small intestinal inflammation, increas-
ing gastrointestinal absorption of encephalopathic
proteins, which leads to the development of autism in
these children. Several well-controlled retrospective
Table 75-1 The Autistic Spectrum cohort studies, as well as a recent systematic review,
Disorders
Autistic disorder: “classic” autism
Asperger’s syndrome: social withdrawal without
cognitive or language delays Box 75-1 Behaviors Associated with
Rett’s syndrome: young girls lose previously Autism
acquired motor and cognitive skills between
6 and 18 months Clumsiness
Childhood disintegrative disorder: 2–10 years of Hand flapping, rocking, pacing, spinning
normal development followed by regression Head banging
Pervasive developmental disorder—not otherwise
Inadequate or nonexistent expressive language
specified: milder form of autistic disorder that
does not satisfy Diagnostic and Statistical Inflexibility
Manual of Mental Disorders IV criteria Preference for playing alone
Sensitivity to loud noises
Modified from American Psychiatric Association. Toe walking
Diagnostic and Statistical Manual of Mental
Disorders, 4th ed. Washington, DC, American Data from Rapin I. Clinical crossroads. An 8-year-old
Psychiatric Association, 1995, pp 65–78. boy with autism. JAMA 2001;285:1749–1757.

563
 Chapter 75 Behavior Problem in a 2-Year-Old Boy (Autism)

have since refuted this hypothesis (Madsen et al.,

2002● B ; Makela et al., 2002●B ; Smeeth et al., 2004●
B; Box 75-2 Developmental “Red Flags”
Wilson et al., 2003● B). In April 2004, Wakefield and
No babbling, pointing, or other gestures by 12
colleagues retracted the interpretation of their origi-
months
nal study, admitting that “no causal link was estab-
No single words by 16 months
lished between MMR and autism as the data were
No two-word spontaneous phrases by 24
insufficient” (Murch et al., 2004). In the United
months
States, the National Immunization Safety Review
Loss of previously learned language or social
Committee (2004● C ) subsequently concluded that the
skills at any age
overwhelming evidence “favors rejection of a causal
relationship” between the MMR vaccine and autism. From Prater CD, Zylstra RG. Autism: A medical
primer. Am Fam Physician 2002;66:1667–1674,1680.

Genetics and Neuroanatomy

Autism is in part a genetic disorder. Identical twin
studies have demonstrated that the twin of an autis- (75% to 83%) and specificity (79% to 81%) for ASDs
tic child has a 60% chance of developing autism and (Filipek et al., 2000● C ). Several developmental “red
a 92% chance of developing an ASD. Fraternal twins flags,” listed in Box 75-2, should automatically
and siblings have approximately 50 times the inci- prompt screening.
dence of the general population, as much as 5%. The Checklist for Autism in Toddlers screening
Multiple chromosomal abnormalities have been instrument was published in 1992 and has been val-
linked to autism in studies of affected families, but idated in multiple prospective studies of children
because the most common accounts for only 1% to older than 18 months of age. It does not require spe-
3% of cases, experts believe that there are many cific training and takes 5 to 10 minutes to administer
genetic pathways to autism (Veenstra-Vanderweele and score. Although it is not a diagnostic instrument,
and Cook, 2003). the Checklist for Autism in Toddlers has been shown
If genes predispose a child to autism, then pre- to effectively differentiate children with ASDs from
natal, perinatal, and neonatal factors may serve as children with other types of developmental delays
triggers. In multiple studies, “unfavorable events” (Scambler et al., 2001● B ).
such as maternal tobacco use, contraceptive use at Box 75-3 outlines the expert consensus for further
the time of conception, prolonged second stage of testing of a child with suspected autism (American
labor, and neonatal hyperbilirubinemia have been Academy of Pediatrics Committee on Children with
associated with an increased risk of being diagnosed C ; Filipek et al., 2000●
Disabilities, 2001● C ).
with an ASD (Juul-Dam et al., 2001● B). More sophis-
ticated analyses, however, have cast doubt on the
hypothesis that these associated events actually cause
autism (Zwaigenbaum et al., 2002● B).
Investigators have also sought to understand Box 75-3 Evaluation for Suspected
what brain structures may be abnormal in autistic Autism
children. Some believe that autism results from the
disruption of a “neural network” of distinct brain Recommended
areas that are responsible for social cognition; for Formal audiology evaluation
example, the amygdala is thought to mediate the Lead level
process of facial recognition (Tuchman, 2003). This Chromosomal analysis for fragile X syndrome
theory of “underconnectivity” recently received sup- if mental retardation is present
port from a functional magnetic resonance imaging Not recommended
study sponsored by the National Institute of Child Routine metabolic testing
Health and Human Development of the National Routine neuroimaging
Institutes of Health (Koshino et al., 2005●B ). Routine electroencephalography
Data from Filipek PA, Accardo PJ, Ashwal S, et al.
Diagnosis Practice parameter. Screening and diagnosis
of autism. Report of the Quality Standards Sub-
Although universal screening is not recommended, committee of the American Academy of Neurology
any suspicion of autism should prompt investiga- and the Child Neurology Society. Neurology
tion. The commonly used Denver II Developmental 2000;55:468–479; American Academy of Pediatrics
Committee on Children with Disabilities. The pedia-
Scale fails to reliably detect children with ASDs; in trician’s role in the diagnosis and management of
contrast, the presence of parental concerns about a autistic spectrum disorder in children. Pediatrics
child’s development has both reasonable sensitivity 2001;107:1221–1226.

564
 Chapter 75 Behavior Problem in a 2-Year-Old Boy (Autism)

Management in autistic children (McCracken and the Research

Units on Pediatric Psychopharmacology Autism
Few treatments for autism have proven to be effective. Network, 2002● A).
The best studied are intensive, individualized behavior The limited benefit of proven therapies has
modification programs that reward positive behaviors often led parents of autistic children to turn to
such as appropriate social responses. These range from untested medications or supplements popularized
the classic conditioning techniques pioneered by on the Internet or in the lay press. The perils of this
UCLA’s Lovaas to North Carolina’s school-based approach are well illustrated in the case of secretin, a
TEACCH (Treatment and Education of Autistic and peptide hormone that stimulates pancreatic secre-
Related Communication Handicapped Children). Both tion. A single case report of a 3-year-old child with
programs have documented short-term gains, but long- autism who underwent endoscopy for chronic diar-
term results are not well studied (Rapin, 2001). rhea, received intravenous secretin, and then showed
The treatment plan for autism includes control- dramatic improvements in behavior and language
ling seizures and comorbid psychiatric disorders, skills led to secretin being hailed as a “miracle cure”
including schizophrenia, mood disorders, and atten- for ASDs. However, a subsequent double-blind,
tion-deficit/hyperactivity disorder. As many as 35% placebo-controlled trial of 60 children with ASDs
of patients with autistic disorder develop epilepsy by
found that secretin administration was not associ-
adolescence, with increasing risk corresponding to
ated with improvement in functioning or decreases
increasing degrees of mental retardation. Baseline
in any associated symptoms (seizures, behavioral
electroencephalography and prophylactic antiepilep-
problems, sleep disorders) (Sandler et al., 1999● A).
tic medication are not recommended for autistic
children without a history of seizures. It is uncertain
whether certain medications are more effective than Material Available on Student Consult
others (Tuchman and Rapin, 2002). Atypical
antipsychotic agents such as risperidone have been Review Questions and Answers about Autism
effective in controlling serious behavioral problems

SELECTED AUTISM RESOURCES ONLINE

Centers for Disease Control and Prevention Autism Infor- MEDLINE Plus: Autism: www.nlm.nih.gov/medlineplus/
mation Center: www.cdc.gov/ncbddd/dd/ddautism.htm autism.html
National Institutes of Health, National Institute of Child Autism Society of America: www.autism-society.org
Health and Human Development: www.nichd.nih.gov/ Cure Autism Now: www.cureautismnow.org
autism/

REFERENCES
American Academy of Pediatrics Committee on Children disorder-not otherwise specified, and the general popula-
with Disabilities. The pediatrician’s role in the diagno- tion. Pediatrics 2001;107:767(E63).●B
sis and management of autistic spectrum disorder in Koshino H, Carpenter PA, Minshew NJ, et al. Functional
children. Pediatrics 2001;107:1221–1226.● C connectivity in an fMRI working memory task in high-
American Psychiatric Association. Diagnostic and functioning autism. Neuroimage 2005;24:810–821.● B
Statistical Manual of Mental Disorders, 4th ed. Madsen KM, Hviid A, Vestergaard M, et al. A popula-
Washington, DC, American Psychiatric Association, tion-based study of measles, mumps, and rubella
1995, pp 65–78. vaccination in autism. N Engl J Med 2002;347:
Baird G, Cass H, Slonims V. Diagnosis of autism. BMJ 1477–1482.● B
2003;327:488–493. Makela A, Nuorti JP, Pelota H. Neurologic disorders after
Filipek PA, Accardo PJ, Ashwal S, et al. Practice parameter: MMR vaccination. Pediatrics 2002;110:957–963.● B
Screening and diagnosis of autism: Report of the McCracken JT, the Research Units on Pediatric
Quality Standards Subcommittee of the American Psychopharmacology Autism Network. Risperidone in
Academy of Neurology and the Child Neurology children with autism and serious behavioral problems.
Society. Neurology 2000;55:468–479.● C N Engl J Med 2002;347:314–321.● A
Immunization Safety Review Committee of the Institute of Muhle R, Trentacoste SV, Rapin I. The genetics of autism.
Medicine. Vaccines and autism. Washington, DC, Pediatrics 2004;113:e472–e484.
National Academy of Sciences, 2004. Available at Murch SH, Anthony A, Cassen DH, et al. Retraction of an
http://books.nap.edu/catalog/10997.html. Accessed interpretation. Lancet 2004;363:750.
1/12/06.●C Prater CD, Zylstra RG. Autism: A medical primer. Am Fam
Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, Physician 2002;66:1667–1674,1680.
and neonatal factors in autism, pervasive developmental Rapin I. Autism. N Engl J Med 1997;337:97–104.

565
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

Rapin I. Clinical crossroads: An 8-year-old boy with Vastag B. National autism summit charts a path through a
autism. JAMA 2001;285:1749–1757. scientific, clinical wilderness. JAMA 2004;291:29–31.
Sandler AD, Sutton KA, DeWeese J, et al. Lack of benefit of Veenstra-Vanderweele J, Cook EH. Genetics of childhood
a single dose of synthetic human secretin in the treat- disorders: XLVI. Autism, part 5: Genetics of autism.
ment of autism and pervasive developmental disorder. J Am Acad Child Adolesc Psychiatry 2003;42:116–118.
N Engl J Med 1999;341:1801–1806.● A Volkmar FR, Pauls D. Autism. Lancet 2003;362:1133–1141.
Scambler D, Rogers SJ, Wehner EA. Can the Checklist for Wakefield AJ, Murch SH, Anthony A, et al. Ideal-lymphoid-
Autism in Toddlers differentiate young children with nodular hyperplasia, non-specific colitis, and pervasive
autism from those with developmental delays? J Am developmental disorder in children. Lancet 1998;
Acad Child Adolesc Psychiatry 2001;40:1457–1463.● B 351:637–641.
Simms MD, Schum RL. Preschool children who have atyp- Wilson K, Mills E, Ross C, McGowan J, Jadad A.
ical patterns of development. Pediatr Rev 2000; Association of autistic spectrum disorder and the
21:147–158. measles, mumps, and rubella vaccine: A systematic
Smeeth L, Cook C, Fombonne E, et al. MMR vaccination review of current epidemiological evidence. Arch
and pervasive developmental disorders: A case-control Pediatr Adolesc Med 2003;157:628–634.● B
study. Lancet 2004;364:963–969.●B Zwaigenbaum L, Szatmari P, Jones MB, et al. Pregnancy
Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol and birth complications in autism and liability to the
2002;1:352–358. broader autism phenotype. J Am Acad Child Adolesc
Tuchman R. Autism. Neurol Clin 2003;21:915–932. Psychiatry 2002;41:572–579.● B

C h a p t e r

76 Difficulty Paying Attention

(Attention-Deficit/
Hyperactivity Disorder)
Lloyd A. Darlow

KEY POINTS

1. Not every child with an attentional disorder has examination, including assessments of hearing,
attention-deficit/hyperactivity disorder (AD/HD). vision, and airway patency; (b) mental status
2. Success in treating AD/HD starts with a proper testing; (c) administration of parent-teacher
diagnosis. rating scales for AD/HD and comorbid disorders;
3. Comorbid disorders must be ruled in or out. and (d) administration of a child rating scale for
4. Psycho-educational assessment must be performed depression.
to rule out learning disabilities. 6. The follow-up schedule is monthly until the condi-
5. The initial workup should entail (a) a physical tion is stable, then at least every 3 months.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

566
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

Rapin I. Clinical crossroads: An 8-year-old boy with Vastag B. National autism summit charts a path through a
autism. JAMA 2001;285:1749–1757. scientific, clinical wilderness. JAMA 2004;291:29–31.
Sandler AD, Sutton KA, DeWeese J, et al. Lack of benefit of Veenstra-Vanderweele J, Cook EH. Genetics of childhood
a single dose of synthetic human secretin in the treat- disorders: XLVI. Autism, part 5: Genetics of autism.
ment of autism and pervasive developmental disorder. J Am Acad Child Adolesc Psychiatry 2003;42:116–118.
N Engl J Med 1999;341:1801–1806.● A Volkmar FR, Pauls D. Autism. Lancet 2003;362:1133–1141.
Scambler D, Rogers SJ, Wehner EA. Can the Checklist for Wakefield AJ, Murch SH, Anthony A, et al. Ideal-lymphoid-
Autism in Toddlers differentiate young children with nodular hyperplasia, non-specific colitis, and pervasive
autism from those with developmental delays? J Am developmental disorder in children. Lancet 1998;
Acad Child Adolesc Psychiatry 2001;40:1457–1463.● B 351:637–641.
Simms MD, Schum RL. Preschool children who have atyp- Wilson K, Mills E, Ross C, McGowan J, Jadad A.
ical patterns of development. Pediatr Rev 2000; Association of autistic spectrum disorder and the
21:147–158. measles, mumps, and rubella vaccine: A systematic
Smeeth L, Cook C, Fombonne E, et al. MMR vaccination review of current epidemiological evidence. Arch
and pervasive developmental disorders: A case-control Pediatr Adolesc Med 2003;157:628–634.● B
study. Lancet 2004;364:963–969.●B Zwaigenbaum L, Szatmari P, Jones MB, et al. Pregnancy
Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol and birth complications in autism and liability to the
2002;1:352–358. broader autism phenotype. J Am Acad Child Adolesc
Tuchman R. Autism. Neurol Clin 2003;21:915–932. Psychiatry 2002;41:572–579.● B

C h a p t e r

76 Difficulty Paying Attention

(Attention-Deficit/
Hyperactivity Disorder)
Lloyd A. Darlow

KEY POINTS

1. Not every child with an attentional disorder has examination, including assessments of hearing,
attention-deficit/hyperactivity disorder (AD/HD). vision, and airway patency; (b) mental status
2. Success in treating AD/HD starts with a proper testing; (c) administration of parent-teacher
diagnosis. rating scales for AD/HD and comorbid disorders;
3. Comorbid disorders must be ruled in or out. and (d) administration of a child rating scale for
4. Psycho-educational assessment must be performed depression.
to rule out learning disabilities. 6. The follow-up schedule is monthly until the condi-
5. The initial workup should entail (a) a physical tion is stable, then at least every 3 months.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

566
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

INITIAL VISIT parents have never been told that he was more than a
grade level behind where he should be for his age.
Subjective
Medical History
Patient Identification and Presenting Phillip is the younger of two children. He was born
Problem after a normal pregnancy, with labor complicated by
Phillip is a 12-year-old white male in the sixth grade. premature rupture of the membranes; he was dis-
A teacher at his middle school recommended an charged home with his mother on the third postpar-
assessment. The presenting complaint, offered by tum day. Developmental milestones were achieved
Phillip’s mother, is “difficulty paying attention in uneventfully: his mother reports no delays in speech,
class.” The initial assessment is performed midway language development, motor skills, or toilet train-
through the fall semester. Phillip’s mother is present ing. Phillip has no active medical problems and has
during the interview. never undergone surgery. He is not currently taking
medication and has no known allergies.
History of Present Illness
A problem with Phillip’s attention span was first Family History
noted in kindergarten, when his teacher observed An uncle has a bipolar disorder.
that he had difficulty staying on task. Historically, he
has had more trouble with math and the sciences
Social History
from grades one through five, and homework in
Phillip lives at home with both parents and his older
these subject areas usually takes him longer than
brother. There is no exposure to cigarette smoke in
homework in his other classes. He typically has been
the home. Both parents are college educated. Phillip’s
a B or C student, with higher grades in courses he
father is an engineer and his mother is an adminis-
likes (art, social studies) than in those he does not
trative aide at a local college.
(math, science). His mother notes that he sustained
some injuries early in childhood due to impulse con-
trol, and she continues to worry about his safety: “He Review of Systems
leaps before he looks.” She does not note any specific No problems are noted with snoring. Phillip’s vision
problems with extreme physical hyperactivity, pur- and hearing have been checked recently as part of a
poseless movements, or difficulty sitting in his chair school screening; no abnormalities were found. He
in school or at the dinner table. has no problem with seasonal or perennial allergies.
From time to time, Phillip’s behavior at home He has no exertional dyspnea or chest pain, no
has been an issue, and he can get angry, but his abdominal complaints or weight loss, no joint pains,
mother tends to associate these outbursts with frus- no dizziness, and no fatigue.
tration. For instance, after he had difficulty with a
homework assignment, he kicked a hole in the bath-
Objective
room door. He recently had an altercation at school
during which he said some hurtful words to another Physical Examination
child, but he has never been in trouble for fighting, Phillip is a well-developed, well-nourished white
and he is always remorseful after such episodes. male adolescent in no distress. His blood pressure is
There have never been any instances of vandalism, 108/62, pulse is 82 and regular, and respiratory rate
theft, or cruelty to animals. In general, he has had no is 18, with unlabored breathing. His height is 60
problems complying with requests unless school- inches (60th percentile) and weight is 95 pounds
work is involved, and in these situations he can occa- (61st percentile). On eye examination the pupils are
sionally become outwardly defiant. His mother notes equally reactive to light and accommodation, and
that he helps out a lot at home. Mornings are not a extraocular movements are intact. Visual acuity is
problem for him, nor are weekends or school holi- 20/20 in both eyes without correction. Ear examina-
days; his difficulty seems to be confined to school tion shows clear tympanic membranes and hearing
hours and the after-school homework period. within normal limits to whisper. The nares are
Socially, Phillip has several friends and plays soc- patent. The throat is clear, with a class I airway. The
cer and basketball. He likes to do things with his neck is supple. Lungs are clear to auscultation, with
hands. His parents do not feel that he is worried, good respiratory effort. Heart rate and rhythm are
depressed, or preoccupied, and there are no reported regular, without murmurs. The extremities show no
problems with getting him to sleep, although as a edema, cyanosis, or clubbing. Muscle strength is 5/5;
young child he reportedly had some nightmares. This deep tendon reflexes are 2+ (normal). The neuro-
is the first time he has been evaluated for any educa- logic examination shows entirely nonfocal findings;
tional or behavioral disorder. No academic assess- gross motor function is intact, fine motor control is
ments have been done by his public school, but his adequate.

567
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

Mental Status Examination

1. Attention. Phillip can do forward digit spans to Box 76-1 Attention-Deficit/
four, but transposes the last two digits at five Hyperactivity Disorder:
places. He repeats a phrase (“No ifs, ands, or Comorbid Conditions
buts”) without errors and can execute a four-step
command in correct order. Oppositional-defiant disorder
2. Concentration. Phillip can do a verbal math prob- Conduct disorder
lem (money calculation) without errors and can Childhood depression
do backward digit spans to four places. He spells Anxiety
“world” backward as d-l-o-r-w. Bipolar disorder
3. Short-term memory/four-word recall. Phillip recalls Learning disabilities
four out of four words at 10 minutes, in order.
4. Speech. His articulation and rate are age-appro-
priate.
5. Language. His language is coherent and organized. signs of impairment at home but is having consider-
6. Mood. Phillip’s mood is stable and his affect is able difficulty at school, alternative explanations for
bright; he is cooperative during the evaluation. the attention difficulty should be sought. The physi-
cal examination should include an evaluation of the
Working Diagnosis child’s hearing and vision, as well as the patency of
The working diagnosis is attention-deficit/hyperactiv- the upper airway; sleep disorders, including sleep
ity disorder (AD/HD), probably the inattentive type apnea, will not cause AD/HD but, if not addressed,
rather than the hyperactive/impulsive or combined will make an existing attentional deficit more diffi-
type. Oppositional-defiant disorder seems doubtful. It cult to treat successfully. Some assessment of mental
is also possible that Phillip has a learning disability. status and function should be performed, taking into
account distant and short-term memory and the
ability to follow instructions.
DISCUSSION Comorbid disorders are conditions that can
mimic or masquerade as an attentional deficit and
The prevalence of AD/HD is in the range of 2% to 9% must be ruled in or out during the initial evaluation
in the general population and 3% to 5% of all school- (Box 76-1). The main comorbid disorders to consider
aged children. Although many causative factors have in a workup for AD/HD are oppositional-defiant dis-
been proposed, recent evidence seems to point to order, conduct disorder, depression, anxiety, bipolar
a genetic defect in the process of dopamine transport disorder, and learning disabilities. Thirty-three percent
in the frontal lobes (Dougherty et al., 1999). Media bias of children with AD/HD have one or more comorbid
has led some in the general public to conclude that conditions; “pure” AD/HD (that is, AD/HD without a
AD/HD is a phenomenon of the late 20th century, yet comorbid condition) is seen in only 30% of cases.
the first mention of this condition dates back to the Oppositional-defiant disorder is the most common
pre-Civil War era. Various terms for AD/HD have been comorbidity, with up to 33% of AD/HD patients (60%
used over the years in the medical literature, many of of males and 30% of females) exhibiting this condition
them unfortunate, including brain damage syndrome, (Agency for Healthcare Research and Quality, 1999).
minimal brain disorder, and organic behavior syn- The rating scale has become the staple of the
drome. The first analysis of the effects of psychostimu- diagnostic process for AD/HD and its common
lants on schoolchildren with attentional deficits took comorbid conditions (Box 76-2). The Connors scale
place in 1937 by Charles Bradley, who demonstrated has been the gold standard over the years, but only
that children taking these medications attended and recently has this scale begun to factor in the comorbid
focused better in class and caused fewer disruptions conditions. In reality, it does not matter which scale or
socially. For those who choose to believe that AD/HD combination of scales the physician uses. Any number
is merely a social phenomenon and the result of bad of rating scales can be used, and the choice should be
parenting or relaxed social expectations, it may be
worth the physician’s time to note that the diagnosis
and treatment of AD/HD predate the use of penicillin.
The initial office visit consists of a thorough his- Box 76-2 Rating Scales on the Internet
tory, including identification of who initiated the www.addwarehouse.com
referral of the child to the physician. The diagnostic www.help4adhd.org
criteria set forth in the Diagnostic and Statistical www.addvance.com (for girls)
Manual of Mental Disorders (DSM-IV-TR) mandate www.therapeuticresources.com
that the patient’s symptoms be present in more than www.fpnotebook.com (depression scales)
one clinical setting. If the child shows no significant

568
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

based on factors such as cost, comorbid consideration, The second office visit should begin with a
and ease of interpretation. A separate scale should be review of the rating scales and a discussion of the
given to the parents and one other person, usually in findings, which should enable the physician to make
the school setting, who knows the child well. Both a formal diagnosis. The treatment plan is formu-
inattentive and hyperactive/impulsive types of lated, including recommendations for medication (if
AD/HD require six positive responses out of nine appropriate), further educational testing (if neces-
possible criteria; for oppositional-defiant disorder, sary), writing of 504 Plans or Individualized
four positive responses out of eight are necessary Educational Plans (IEPs), and referrals for counsel-
(American Psychiatric Association, 2000● C ). In addi- ing. The physician should encourage the parents to
tion to the parent/teacher rating scales, the child read about their child’s condition on physician-
should be given a scale that addresses mood disorders. approved, refereed sites (Box 76-4). The patient and
A final piece of information that is of critical parents should make plans to return for follow-up in
necessity, but is often overlooked, is a formal edu- 1 month’s time, at which point the physician should
cational assessment to rule out learning disabilities, request some form of written communication from
to be done by the school the child attends. school regarding the child’s progress. Reviewing
Comorbid learning disorders (Box 76-3) occur in assignments, tests, progress notes and report cards
12% to 30% of children with AD/HD (Agency for are essential for assessing the efficacy of the treat-
Healthcare Research and Quality, 1999). If the stu- ment plan. If necessary, the plan should be modified
dent attends a private school, the public school that at subsequent visits, and the schedule of follow-up
child would have attended must perform this eval- appointments from this point forward should be
uation. If a learning disability is present, the student monthly until the situation is stable, then every
will qualify for academic interventions under the 3 months thereafter.
Individuals with Disabilities Education Act; if no A thorough addressing of AD/HD pharma-
formal learning disability is found, the child with cotherapy can be a textbook chapter unto itself. In
AD/HD may still be eligible for accommodations 2001 the American Academy of Pediatrics (AAP)
under the learning disability category of “Other provided a clinical practice guideline to aid in the
Health Impaired.” A full discussion of the physi- decision-making process (AAP, 2001● C ), but the devel-
cian’s role in the educational process is beyond the opment of new medications and a greater body of
scope of this chapter, but Matthew Cohen’s excel- research have only complicated the issue. Briefly, the
lent article (2004) on this subject should be manda- treatment options for AD/HD can be broken down
tory reading for all physicians who evaluate and into two classes: stimulants and nonstimulants. As a
treat patients for AD/HD. group, the stimulants have been shown to have
greater overall efficacy than the nonstimulants
(Faraone, 2003 ● A). Classic stimulants, such as
methylphenidate and dextroamphetamine, primarily
block the reuptake of dopamine at the postsynaptic
Box 76-3 Common Learning Disorders neuron in the prefrontal cortex and have been shown
to have excellent long-term efficacy (Centre for
Disorders of Developmental Speech
Reviews and Dissemination, 2002). Within the stimu-
and Language
lant group, the medications differ in duration of
Developmental articulation disorder action; short-acting stimulants typically last up to 4
Developmental expressive language disorder hours, intermediate-acting agents are effective for
Developmental receptive language disorder approximately 5 hours, and sustained-release prepa-
rations can improve focus and attention for 6 to 12
Academic Skills Disorders hours. It is common practice to give a child attending
Developmental reading disorder
Developmental writing disorder
Developmental arithmetic disorder
Box 76-4 Resources for Parents on the
Nonverbal Learning Disabilities Internet
Visual-spatial
www.chadd.org (Children and Adults with
Visual motor
Attention-Deficit/Hyperactivity Disorder,
Sensory deficits
CHADD)
Motor deficits
www.ADHD.com
www.additudemag.com (ADDitude magazine)
Central Auditory Processing Deficit
www.ldonline.org (for learning disabilities)

569
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

school a longer-acting preparation to minimize the physician has to provide guidance to the child and
social stigma of having to receive medication daily family in both areas. Counseling may be recom-
from the nurse, as well as to smooth the transitions mended for the child, family, or both. List making
that occur between doses of the shorter-acting should be taught as a means of organizational skill
formulations. However, some students metabolize building. Parents should be instructed to develop
these medications faster than others and may require reasonable expectations and goals for their child, set
a dose of a short-acting preparation when they clearly defined limits, and construct a reward and
get home from school in order to complete their punishment system to help the child attain those
homework in a timely manner. The physician must be goals. This system should be based on privileges
aware of the side effects typical of the class, including rather than monetary rewards. Statistically speaking,
suppression of appetite and insomnia, when recom- three out of four children diagnosed with AD/HD
mending dosing of these medications later in the day. will not take medication for this condition into
For decades, the nonstimulants have been uti- adulthood, and since AD/HD is a lifelong disorder, it
lized for the approximately 20% of patients who, is only through the integration of behavior modifi-
because of existing contraindications, intolerance, or cation into the patient’s daily life that the need for
lack of efficacy, could not take a stimulant. This medication becomes secondary.
group of medications includes tricyclic antidepres- At the conclusion of the first visit, the physician
sants; SSRI antidepressants; a2-receptor agonists; should distribute rating scales (Connors or equiva-
buspirone; bupropion; and the selective norepineph- lent) for parent and teacher to complete; the physi-
rine reuptake inhibitor, atomoxetine. Of the non- cian should also request that these scales be sent to
stimulants, only atomoxetine is currently approved the office before their next appointment. The
by the U.S. Food and Drug Administration (FDA) for Children’s Depres-sion Index should be completed
the treatment of AD/HD in children and adults. The by the patient at home. A written request should be
nonstimulants differ radically from the stimulants in made to the school for a complete psycho-educa-
their mechanism of action, primarily blocking the tional assessment, to be done within 6 calendar
reuptake of neurochemicals other than dopamine, weeks, with a copy of the findings to be sent to the
and they may also last up to 24 hours, double the physician’s office upon completion.
duration of any of the stimulant preparations. For
this reason, persons who require a longer duration of
action, such as a child who has significant difficulty
SECOND OFFICE VISIT
in the morning (before the stimulant takes effect) or
evening (after the stimulant has worn off), may ben-
Interval History
efit from the primary use of a nonstimulant.
It is of critical importance for the physician to Phillip returns to the office in 10 days, accompanied
identify the patient’s core symptoms during the ini- by his mother and father. No change in his history is
tial part of the workup. By clarifying the hours dur- noted since his previous visit.
ing the day when the patient’s function is impaired During this visit the physician reviews the rating
by the attentional deficit, the physician can then scales filled out by Phillip, his parents, teachers, and
decide which pharmacologic approach offers the best the school’s trained evaluator.
chance for a successful outcome. At each successive
visit, these core symptoms should be revisited, with Parental Rating Scale
emphasis placed on whether the symptoms are bet- The rating scales filled out by the parents show six
ter, worse, or the same under the current treatment positive responses out of nine possible for AD/HD,
plan. If a patient has not improved on a given med- inattentive type; one positive response out of nine
ication in a specific class, another medication in that possible for AD/HD, hyperactive/impulsive type; one
same class may be tried (AAP, 2001● C ). However, if a positive response out of eight criteria for opposi-
second trial of medication produces unsatisfactory tional-defiant disorder; and no positive responses on
results, the prudent physician will go back to the criteria for conduct disorder.
beginning and reconsider the diagnosis. Further test-
ing or referral to a psychologist, psychiatrist, or edu- Teacher Rating Scale
cational specialist may reveal a comorbid diagnosis The rating scales filled out by the teacher show eight
that had not previously been considered. positive responses out of nine possible for AD/HD,
Behavioral modifications for AD/HD and its inattentive type; one positive response out of nine
comorbid conditions are an integral part of the treat- possible for AD/HD, hyperactive/impulsive type; two
ment algorithm (National Institute of Mental positive criteria out of eight possible for opposi-
Health, 2000). It should never be only about pills; the tional-defiant disorder; and no positive responses on
approach must consist of “pills and skills,” and the criteria for conduct disorder.

570
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

Children’s Depression Index has been completing his homework on time accord-
The score on this instrument is 2 (low probability of ing to his lists, although his mother notes that he
depression). doesn’t always like to fill out the lists. The medication
effect seems to be lasting about 8 hours. He has done
Psycho-educational Assessment a good enough job completing his homework on time
The psycho-educational assessment has not yet been so that he has been able to do “pretty much whatever
completed by the school. he wants to do” at night. He does not take his med-
ication on weekends. Vital signs show no appreciable
Impression change in pulse, blood pressure, or weight from his
The rating scales imply a diagnosis of AD/HD, inat- first visit. His psycho-educational assessment has
tentive type. Learning disability is a possible comor- been completed, and no learning disabilities were
bid diagnosis. found during the evaluation by the school psycholo-
gist, who found him to be “helpful and friendly,” with
intellectual testing in the superior range.
Plan
1. Medication. Recommend starting a stimulant, Impression
given that Phillip’s difficulties are confined to
school and homework time. He is not in favor of The physician’s impression is AD/HD, inattentive
taking medication at school because of the social type, stable on a long-acting stimulant.
stigma of doing so; therefore, a longer-acting
stimulant is recommended. Phillip and his par- Plan
ents are not in favor of him taking medication on
the weekends, and as long as he has nothing A follow-up visit is scheduled in 1 month.
planned that would require an intense intellectual
or educational effort, this is felt to be an accept- FOURTH OFFICE VISIT
able option. Side effects are discussed, including
but not limited to appetite suppression, stomach Interval History
upset, headache, insomnia, and emotional lability.
2. Behavior modification. Advice is given to Phillip Phillip and his parents return for this visit. He contin-
regarding list making for organization. Reason- ues to do well. He has brought his grades up to a mix
able goals are established: he agrees to make lists of Bs and As and has made the honor roll. He contin-
of things he has to accomplish the following day, ues to experience no side effects from his medication.
including specifically assigning his after-school Vital signs are again unchanged significantly from his
homework hours. Reward–punishment methods prior visits. He has no objections to taking his med-
are discussed for compliance and noncompliance ications. Behavior modification is working well, and
with these goals. Phillip and his parents mutually he likes being rewarded for completing his homework
decided on a points system that he could redeem before his father gets home; this has increased the
each night for extra television or computer game amount of time the family can spend together.
time.
3. School intervention. Phillip’s parents will continue Assessment
to urge the school to complete his educational
testing expediently. His mother will be in touch The assessment is AD/HD, inattentive type, stable on
with his teachers, who will be asked to notify her a long-acting stimulant.
in writing at the end of each week as to how
Phillip is doing in their classes. Plan
4. A follow-up visit is scheduled in 4 weeks’ time.
A follow-up visit is scheduled in 3 months’ time. The
parents are to call if the condition changes or wors-
THIRD OFFICE VISIT ens in any way.

Interval History
SUBSEQUENT VISITS
Phillip returns with his mother. He has had no side
effects from his long-acting stimulant. His teachers Phillip has been followed for 3 years. He continues to
have noted a significant improvement in his ability to take the long-acting stimulant on school days only,
focus on his work, even in math and science; he has and not on weekends or during school holidays or
achieved several good test grades in these subjects. He vacations unless he has an activity that requires him to

571
 Chapter 76 Difficulty Paying Attention (Attention-Deficit/Hyperactivity Disorder)

maximally focus his attention. He experienced a brief for a follow-up visit, at which time an interval history
decrease in the medication’s efficacy in the second is taken, his progress in school is reviewed, his vital
year, and the dose was increased to the next level, with signs are checked, and a medication refill is prescribed.
good improvement in his core symptoms. His weight
and height have continued to increase, with percentile Material Available on Student Consult
ranks in the 80th and 85th range, respectively; no sig-
Review Questions and Answers about Attention-
nificant increases in his blood pressure or pulse have
Deficit/Hyperactivity Disorder
been noted. He returns to the office every 3 months

EVIDENCE-BASED MEDICINE SOURCES

Source: National Institute of Mental Health Summary: The recommendation was made based on a
review of 29 studies with 551 participants, including
URL: www.nimh.nih.gov/events/mtaqa.cfm 8 crossover trials. All studies reported statistically signifi-
Recommendation: The optimal treatment approach for cant improvements after treating with methylphenidate.
children with AD/HD is medication plus behavior modifi- The drug appeared to be well tolerated, with side effects
cation. reported to be dose dependent, and virtually nonexistent at
lower doses.
Summary: The recommendation is based on the findings
of the MTA (Multimodal Treatment Study of Children Source: Agency for Healthcare Research and Quality (for-
with AD/HD) study, which included nearly 600 children merly Agency for Health Care Policy and Research)
ages 7 to 9 years, randomly assigned to one of four treat-
ment groups: (1) medication alone, (2) psychosocial/ URL: www.ahrq.gov/clinic/epcsums/adhdsutr.htm
behavioral treatment alone, (3) a combination of medica- Recommendation: Comorbid conditions must be actively
tion and behavioral modification, or (4) routine commu- considered in the evaluation and treatment processes for
nity care. Long-term combination treatments and any child with a working diagnosis of AD/HD.
management by medication alone were both shown to be
significantly superior to intensive behavior therapy in Summary: The evidence on AD/HD prevalence and diag-
reducing AD/HD symptoms. The combined approach was nosis reported here was gathered from 87 published arti-
also demonstrated to be superior in other areas of func- cles and 10 behavioral scale manuals. The prevalence rates
tioning, including anxiety, academic performance, oppo- for comorbid educational and behavioral disorders with
sitional behavior, parent-child interaction, and social AD/HD are high; up to 33% of children with AD/HD have
skills. The combined approach allowed children to be more than one comorbid condition. The most common
treated with lower doses of medication than were used in comorbid condition is oppositional-defiant disorder
the medication-only group. (ODD), with approximately one-third of children diag-
nosed with AD/HD meeting criteria for this condition.
Source: Centre for Reviews and Dissemination Approximately one-quarter of children diagnosed with
URL: nhscrd.york.ac.uk/online/dare/20013548.htm AD/HD meet some criteria for conduct disorder. In gen-
eral, anxiety is more common than depression in ADHD
Recommendation: Methylphenidate is a safe, long-term children. More than 10% of students with AD/HD also
therapeutic option for treating AD/HD. have a comorbid learning disability.

REFERENCES

American Academy of Pediatrics. Clinical practice guide- Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras
line: Diagnosis and evaluation of the child with atten- BK, Fischman AJ. Dopamine transporter density in
tion-deficit/hyperactivity disorder. Pediatrics 2001;105: patients with attention deficit hyperactivity disorder.
1158–1170.● C Lancet 1999;354:2132–2133.
American Psychiatric Association. Diagnostic and Statistical Faraone SV. Understanding the effect size of AD/HD med-
Manual of Mental Disorders, 4th ed., Text Revision. ications: Implications for clinical care. Medscape
Bethesda, MD, American Psychiatric Press, 2000.● C Psychiatry & Mental Health 2003;8. Available at
Cohen M. Section 504 and IDEA: Limited vs. substantial pro- www.medscape.com/viewarticle/461543. Accessed
tections for children with AD/HD and other disabilities. 3/2/2004.●A
Available at www.chadd.org/pdfs/Section_504_and_
IDEA_by_Matt_Cohen.pdf. Accessed 4/27/2004.

572
 C h a p t e r

77 Third-Trimester Vaginal Bleeding

(Placenta Previa)
Melissa Nothnagle

Objective
KEY POINTS
Physical Examination
Vital Signs Blood pressure, 110/70 mm Hg; pulse,
1. Because of the high rate of blood flow to the
88; temperature, 36.9˚C (98.4˚F).
placenta in the second part of pregnancy, con-
ditions resulting in bleeding can be life threat-
General Appearance Well-appearing pregnant
ening to both the mother and fetus.
woman; somewhat anxious.
2. Vaginal examinations are contraindicated in
patients presenting with third-trimester bleed-
Cardiovascular Regular rate and rhythm, no murmurs.
ing until the placental location is determined
using ultrasound and placenta previa is
Pulmonary Lungs clear to auscultation bilaterally.
excluded.
3. Maternal stabilization should be the first priority
Abdomen Gravid; fundal height, 38 cm. Uterus is
in managing third-trimester bleeding and may
nontender. Leopold’s maneuvers: fetus in vertex
be life preserving for both the mother and fetus.
position; estimated fetal weight, 6.5 pounds.
4. Conservative management of early third-
trimester bleeding to prolong gestation may be
Pelvic Examination Deferred. External examina-
possible depending on the rate of bleeding and
tion shows a small amount of bleeding from the
maternal and fetal stability.
vagina, and the patient has soaked through one san-
itary pad since the onset of the bleeding.

Extremities Warm and well perfused; trace edema

INITIAL EVALUATION to the mid-calf bilaterally.

Subjective External Fetal Monitoring Fetal heart rate baseline

140 beats per minute with several reactive accelera-
Patient Identification and Presenting
tions and no decelerations.
Problem
Elena is a 24-year-old gravida 2 para 1 at 37 1⁄7 weeks’ Tocometry Uterine contractions every 8 to 10
gestation who presents at obstetric triage with vagi- minutes.
nal bleeding for the previous 3 hours. She reports Further history is obtained while intravenous
that she has had no major problems in her pregnancy fluids are started, blood for laboratory tests drawn,
but mentions that she had an ultrasound when she and ultrasound done.
was about 4 months pregnant and was told that her
placenta was over the cervix. At that time her physi-
cian advised her to have a repeat cesarean section History of Present Illness
(which is scheduled for next week), avoid sexual Elena was at home making dinner for her family
intercourse, and come to the hospital immediately if when she felt a leakage of fluid. The amount of
she experienced any bleeding. bleeding is similar to the first day of her period. She
Further history is deferred until maternal hemo- has been having mild contractions for the past
dynamic status has been assessed. 2 days. She denies any recent trauma.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

573
 Chapter 77 Third-Trimester Vaginal Bleeding (Placenta Previa)

Prenatal History is reassuring. Fetal bradycardia, tachycardia, or pro-

Elena reports that she started prenatal care early longed or late decelerations would suggest fetal com-
in pregnancy and denies any complications during promise and warrant expedited delivery.
this pregnancy, including diabetes, vaginal or urinary Based on the patient’s reported ultrasound and
infections, anemia, or high blood pressure. her presentation with painless bleeding, the most
likely diagnosis is placenta previa, meaning that part
Obstetric and Gynecologic History of the placenta has implanted over the internal os of
One previous pregnancy 3 years ago. She delivered a the cervix. The diagnosis of placenta previa is con-
healthy male infant weighing 3270 g at 38 weeks by firmed by localization of the placenta on ultrasound.
cesarean section for breech presentation. She had no Vaginal examinations of patients with third-
bleeding during her first pregnancy. trimester bleeding must be avoided until placenta
Menarche at age 14. No history of infections or previa has been ruled out, as disruption of the pla-
abnormal Pap smears. No miscarriages or abortions. centa can result in large-volume hemorrhage.

Medical History Differential Diagnosis

Hospitalized at age 8 with pneumonia. Migraine 1. Placental abruption refers to premature separa-
headaches that have been rare during her pregnancy. tion of the placenta from the uterus. The most
common symptom of abruption is pain, which
Medications Prenatal vitamins daily, acetaminophen may vary from mild cramping to severe pain.
as needed for headaches. Vaginal bleeding and uterine tenderness may be
present. Fetal distress will be evident with moder-
Family History ate to severe abruption. A history of risk factors
Elena’s mother has type 2 diabetes. Her father has for abruption, including hypertension, trauma,
hypertension. She has two healthy siblings. smoking, and crack cocaine use, should be
sought.
Social History 2. Ruptured vasa previa is a rare event that may
Elena lives with her husband and 3-year-old son. She occur in the presence of a low-lying placenta or
works part time at a hair salon. Her mother, who a velamentous cord insertion, in which umbili-
lives in the apartment upstairs, helps care for her son. cal vessels insert into the membranes rather
Elena does not smoke, drink alcohol, or use drugs. than directly into the placenta. Vessels crossing
She denies domestic violence. This pregnancy was the internal os rupture, usually at the time of
planned. She intends to breast-feed, and she plans rupture of the membranes. Because fetal blood
to use an intrauterine device for postpartum birth is lost, fetal heart monitoring may show a rapid
control. deterioration, and immediate cesarean section
is indicated. Pediatric personnel should be pre-
Review of Systems pared for volume resuscitation of the infant at
No fevers or chills. No lightheadedness. No delivery. Fetal mortality in cases of ruptured
headaches. No vision changes. No abdominal pain or vasa previa approaches 50%. If vasa previa is
back pain. No dysuria. No vaginal itching or dis- suspected in the context of a normal fetal heart
charge. Good fetal movement. Mild swelling of both tracing, the Apt test may be used to rapidly
ankles for several weeks. As noted above, mild con- diagnose fetal blood. A sample of vaginal blood
tractions for several days. is collected and mixed with a small amount of
tap water to lyse the red blood cells. The sample
is centrifuged for 5 minutes, and the pink
Assessment
supernatant is removed and mixed in a 5:1 ratio
Working Diagnosis with 1% sodium hydroxide. Persistent pink
Because of the potential for maternal and fetal mor- color of the resulting mixture indicates fetal
bidity from hemorrhage in pregnancy, the first pri- hemoglobin; adult hemoglobin turns brown
ority in assessing a patient with third-trimester within 2 minutes.
bleeding is not to establish a diagnosis but rather to 3. Other causes of bleeding in the latter part of
assess maternal hemodynamic status and institute pregnancy include lower genital tract lesions such
resuscitative measures if necessary. This patient’s as cervicitis, cervical ectropion, cervical polyps,
vital signs appear normal, and her bleeding appears cervical cancer, or vaginal trauma. The most
mild. Initial vital signs should be interpreted with benign and probably most common cause of
caution, however, as the increased blood volume of bleeding in the third trimester is bleeding from
pregnancy may blunt early signs of shock. After cervical dilation in early labor. This “bloody
ensuring stability of the mother, attention can be show” is generally a small volume of blood with a
turned to the fetus. The fetal heart tracing in this case mucous consistency.

574
 Chapter 77 Third-Trimester Vaginal Bleeding (Placenta Previa)

Plan packed red blood cells should be considered early to

ensure adequate oxygen delivery to the fetus. If evi-
Diagnostic dence of disseminated intravascular coagulation is
Complete blood count, blood type, and antibody observed, platelets and fresh frozen plasma should be
screen are ordered. Vital signs are assessed frequently, administered. Ongoing monitoring of maternal and
and continuous external fetal monitoring is used. No fetal well-being is essential. In the context of mater-
vaginal examinations are performed. An ultrasound nal shock, fetal distress may not be an indication for
is done to determine location of the placenta. delivery. Maternal stabilization results in improved
placental perfusion and oxygen delivery to the fetus.
Therapeutic Often apparent fetal distress will resolve with these
Because of the potential for large-volume hemor- measures, and unnecessary delivery of a preterm
rhage, two large bore IV catheters are placed and fetus and the increased maternal morbidity due to
crystalloid solution infused. Four units of packed red blood loss from emergent surgery can be avoided.
blood cells are cross-matched. After maternal hemodynamic stability has been
established, the cause of bleeding should be investi-
Patient Education gated. History should include an assessment of pain
Elena is informed that close monitoring of her and and any recent trauma. Patients in normal active
her fetus are needed and that an urgent cesarean labor do not have pain between contractions.
delivery may be necessary if there is increased blood Ultrasound should be used to exclude placenta pre-
loss or signs of fetal compromise. via before speculum or digital examinations. Any
Rh-negative woman with antepartum bleeding
Disposition should be treated with a full dose of Rh immune
The patient is hemodynamically stable, and the fetal globulin (Wible-Kant and Beer, 1983● B ).
heart tracing remains reassuring.
Initial laboratory test results are normal except
for hemoglobin of 10.5 and hematocrit of 32. Placenta Previa
Ultrasound shows a single fetus in cephalic presenta- Placenta previa occurs in one of 250 livebirths.
tion. The placenta is anterior and the lower border Current classifications of placenta previa include com-
overlies the internal os. The cervix appears 75% plete, in which the placenta directly overlies the inter-
effaced and 1 cm dilated. Ongoing bleeding is noted. nal os, and marginal, in which the placental border lies
Because Elena is at more than 36 weeks’ gestation, within 2 to 3 cm of the os. Risk factors include previ-
there is low risk of fetal lung immaturity. She gives ous cesarean delivery, previous uterine instrumenta-
consent for a cesarean section and delivers a 3230 g tion, multiparity, advanced maternal age, maternal
baby with Apgar scores of 8 and 9. smoking, and multiple gestation. With access to high-
resolution ultrasonography, most cases of placenta
previa are detected prenatally, and this has greatly
DISCUSSION reduced maternal and fetal mortality from this condi-
tion. However, most placentas that appear to cover the
Third-trimester bleeding occurs in 6% of pregnan- os in the second trimester will have a normal location
cies. Placental abruption and placenta previa account at term. This is likely due to differential growth of the
for as many as half of these cases. Because of the high lower uterine segment and limitations of ultrasound
rate of uterine blood flow during the third trimester to precisely localize the placental border early in preg-
(25% of the cardiac output or 500 mL/min), these nancy. For patients whose second trimester ultra-
conditions are potentially life threatening for both sound shows placenta previa, repeat ultrasound
the mother and fetus. should be scheduled between 24 and 28 weeks to re-
evaluate placental location. Bleeding episodes before
Approach to the Patient this repeat study should be treated presumptively as
placenta previa. Patients with documented placenta
Initial evaluation of third-trimester bleeding should previa after 24 weeks can be managed expectantly but
include a rapid assessment and stabilization of must avoid sexual intercourse and digital examina-
maternal hemodynamic status. Assessment should tion. Early in gestation, cervical cerclage may reduce
begin with basic components of advanced cardiac the incidence of delivery before 34 weeks and of low
life support, including status of the patient’s airway, birth weight (Neilson, 2003● C ).
breathing, and circulation, followed by identification Placenta previa classically presents with painless
of the amount and character of bleeding. Large-bore bleeding at the end of the second trimester or early
IV access should be obtained and volume replace- third trimester. The bleeding may be associated with
ment initiated (if indicated) with crystalloid solution contractions, although pain between contractions
while blood products are ordered. Transfusion of should raise suspicion for placental abruption. Placenta

575
 Chapter 77 Third-Trimester Vaginal Bleeding (Placenta Previa)

previa rarely causes large-volume hemorrhage unless

instrumentation or digital examination is performed. Box 77-1 Classification of Placental
Because most perinatal morbidity from placenta Abruption
previa results from preterm birth, management Grade 1: Small abruption with minimal maternal
depends on gestational age, in light of the severity of or fetal symptoms
bleeding and maternal and fetal well-being. Before Grade 2: Bleeding, contractions, and uterine
term in a stable patient, tocolysis with magnesium sul- tenderness with a live fetus (usually
fate or beta agonists may be considered as a way to with a nonreassuring fetal heart
prolong gestation (Sharma et al., 2004● B ; Towers et al., tracing)
1999● C ). Tocolysis before 34 weeks may also provide a Grade 3: Moderate to severe bleeding with
sufficient time to administer corticosteroids to pro- intrauterine fetal demise, high risk of
maternal coagulopathy
mote fetal lung maturation. Patients should be moni-
tored closely for signs of hemodynamic instability or
disseminated intravascular coagulation. Indications
for delivery include ongoing bleeding, documented fetal distress or ongoing bleeding. Grade 2 abruption
fetal lung maturity, and signs of fetal distress. is more severe and usually requires emergent
At term, cesarean delivery is indicated for ongo- cesarean section unless vaginal delivery is imminent.
ing bleeding or nonreassuring fetal heart tracing after In cases of grade 3 abruption, in which fetal death is
maternal stabilization. In cases of marginal placenta confirmed, expeditious vaginal delivery is preferable
previa, vaginal delivery may be possible because the to operative delivery because of risks from coagu-
fetal head may tamponade the bleeding from the pla- lopathy (Sher and Statland, 1985● C ).
cental border. Vaginal delivery should be attempted
only under conditions of a “double setup” in the Conclusion
operating room, with immediate availability of blood
products and surgical and anesthesia personnel to Third-trimester bleeding involves potentially life-
perform a cesarean section in case of rapid blood loss. threatening conditions for both mother and fetus. In
cases of significant hemorrhage, maternal stabiliza-
tion is always the first priority. No vaginal examina-
Placental Abruption tions should be done until placenta previa has been
Bleeding due to placental abruption is usually associ- ruled out by ultrasound. Management of third-
ated with abdominal or back pain. Although most trimester bleeding depends on severity of bleeding,
patients will present with vaginal bleeding, abrup- maternal and fetal well-being, and length of gesta-
tion may also occur behind the placenta or into the tion. Urgent delivery should be considered if there is
myometrium without vaginal bleeding (concealed or evidence of fetal compromise or fetal maturity. With
occult abruption). Risk of placenta abruption is minor amounts of bleeding from placenta previa or
increased with maternal trauma, cocaine use, hyper- placental abruption before 36 weeks’ gestation, con-
tension, smoking, multiparity, and history of abrup- servative management may be possible. Attempts to
tion. In cases of third-trimester bleeding, if placenta prolong gestation with tocolysis should be made only
previa is not seen on ultrasound and lower genital after careful consideration of maternal and fetal risks
tract lesions or labor have been ruled out, placental and benefits and informed consent of the patient.
abruption is the most likely diagnosis. Any Rh-negative woman with bleeding in pregnancy
Treatment of placental abruption depends on should receive Rh immune globulin.
the degree of placental separation (Box 77-1). Grade
1 abruption is mild and may be managed conserva- Material Available on Student Consult
tively with Pitocin induction at term or tocolysis for
Review Questions and Answers about Placenta
the stable preterm patient. Expeditious delivery, gen- Previa
erally by cesarean section, is indicated for signs of

REFERENCES
Neilson JP. Interventions for suspected placenta praevia. Towers CV, Pircon RA, Heppard M. Is tocolysis safe in the
Cochrane Database Syst Rev 2003(2):CD001998.● A management of third trimester bleeding? Am J Obstet
Sharma A, Suri V, Gupta I. Tocolytic therapy in conserva- Gynecol 1999;180:1572–1578.● C
tive management of symptomatic placenta previa. Int Wible-Kant J, Beer AE. Antepartum Rh immune globulin.
J Gynaecol Obstet 2004;84:109–113.● B Clin Perinatol 1983;10:343–355.●
B
Sher F, Statland BE. Abruptio placentae with coagulopathy:
A rational basis for management. Clin Obstet Gynecol
1985;28:15–23.● C

576
 C h a p t e r

78 Abdominal Pain (Endometriosis)

Kenneth J. Grimm

painful defecation. She denies diarrhea or blood in her

KEY POINTS stool. She has not traveled recently. She has no history
of fever, changes in her appetite, weight loss, upper
1. Endometriosis is found in up to 65% of adoles- abdominal pain, nausea, or vomiting. She has had no
cents with pelvic pain and 30% to 50% of dysuria, hematuria, or increase in urinary frequency.
women undergoing laparoscopy for pelvic pain She has never been sexually active and denies vaginal
or infertility. discharge. The pain is partially relieved by ibuprofen,
2. There is a tenfold increased risk of endometrio- 400 mg, taken every 6 hours.
sis in patients who have a first-degree relative
with endometriosis. Medical History
3. Ultrasound can eliminate other causes of pelvic Amanda is a healthy young woman. She is not taking
pain but a definitive diagnosis can be made any medications, and her only hospitalization was
only by direct visualization, such as with for the surgical correction of an imperforate hymen
laparoscopy. at menarche. Her immunizations are up to date.
4. Treatment of endometriosis includes non-
steroidal anti-inflammatory drugs (NSAIDs), oral Developmental History
contraceptives, progesterone, danazol, Amanda reached all of her developmental milestones
gonadotropin-releasing hormone (GnRH) ago- at the appropriate ages. Menarche was at age 13, and
nists, and surgery (either laparoscopically or by her menses have been regular since, occurring every
hysterectomy). 28 to 30 days and lasting for 6 days with normal flow.

Family History
Amanda’s parents and younger brother are healthy.
She has a maternal aunt with ulcerative colitis. No
INITIAL VISIT
family history of depression is known.
Subjective
Social History
Patient Identification and Presenting Amanda is a well-adjusted, happy teenager. She is in
Problem 12th grade and excels academically. She is looking
Amanda E. is a 17-year-old who complains of forward to studying at a local college next year. She
abdominal pain. has been an avid skier and tennis player, and she has
continued to participate in these activities. She
Present Illness denies smoking, alcohol, or illicit drug use. Her par-
Amanda says the pain began about 9 months ago and ents have no concerns regarding her peer group. No
has been steadily worsening since then. It is located in history of physical or sexual abuse is known.
her lower abdomen, midline. She notes a near-constant
dull ache, but she has worsening cramping pain typi- Review of Systems
cally beginning the day before her menses and lasting Gastrointestinal and genitourinary symptoms as
for 4 to 5 days. She has missed approximately 10 days mentioned, otherwise unremarkable. Her last men-
of school this year because of the pain. When the pain strual period was normal in timing and duration and
is at its worst, she often experiences constipation and began 3 weeks ago.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

577
 Chapter 78 Abdominal Pain (Endometriosis)

Objective adnexa and is significant enough to cause her to miss

school.
Physical Examination
Amanda is a well-appearing adolescent in no distress. Differential Diagnosis
Her temperature is 98.4°F, her pulse is 76, her respira- The differential diagnosis of chronic pelvic pain is
tion rate is 12, her blood pressure is 112/64, her complex and includes both gynecologic and nongy-
weight is 120 pounds, and her height is 5 feet 5 inches. necologic etiologies (Table 78-1). Endometriosis can
She is alert and oriented with a full affect. She displays cause both cyclic and noncyclic pain, especially in
no psychomotor retardation and is appropriately adolescents. The absence of a history of sexual activ-
interactive, with good eye contact throughout the ity rules out pelvic infection and pregnancy compli-
interview and examination. Heart and lung examina- cations. The pattern of her pain makes ovulation an
tions are normal. Abdominal examination shows unlikely etiology. Her pelvic examination is not sug-
normally active bowel sounds. Her abdomen is soft gestive of leiomyomata or an ovarian cyst or neo-
with moderate tenderness, worse in the suprapubic plasm. She denies any voiding symptoms and has no
area and radiating to the right lower quadrant, with anterior tenderness on examination, making a uro-
no guarding or rebound tenderness. No masses are logic etiology unlikely. Her bowel symptoms warrant
appreciable. Pelvic examination reveals normal, considering inflammatory bowel disease in the dif-
Tanner stage 4 external genitalia. The vaginal dis- ferential diagnosis, especially with a family history of
charge is normal, and no blood is seen. The cervix ulcerative colitis. However, with no diarrhea, hema-
appears unremarkable. She has moderate cervical tochezia, or weight loss, this is unlikely to be the
motion tenderness. The uterus is normal size, mid- cause of her symptoms. Gastrointestinal and uro-
line, and retroverted but mobile. Her right adnexal logic symptoms are common in adolescent patients
area is moderately tender with no palpable mass. She with endometriosis. Finally, no history suggests
has no anterior tenderness. Rectovaginal examination physical abuse, and she has no other symptoms of
reveals tender nodularity in the rectovaginal septum. depression. Endometriosis seems to be the most
likely diagnosis.
Impression
Plan
Working Diagnosis
This patient has chronic pelvic pain. Chronic pelvic Diagnostic
pain is defined as pain lasting 6 or more months that A urinalysis, obtained to rule out urinary tract infec-
localizes to the anatomic pelvis (ACOG, 2004●C ). This tion and interstitial cystitis, was normal. A urine
patient has both a cyclic and a noncyclic component pregnancy test was negative. Given the lack of a pal-
that localizes on examination to the uterus and right pable mass on pelvic examination, the yield from an

Table 78-1 Differential Diagnosis of Chronic

Pelvic Pain
Gynecologic Causes Nongynecologic Causes

Endometriosis Urologic disease

Ovulatory pain (mittelschmertz) Interstitial cystitis
Ovarian cyst Urethral syndrome
Gynecologic neoplasia Bladder malignancy
Pelvic inflammatory disease Chronic urinary tract infection
Leiomyomata Gastrointestinal
Adhesions Inflammatory bowel disease
Primary dysmenorrhea Irritable bowel syndrome
Adenomysosis Diverticular disease
Pelvic congestion syndrome Gastrointestinal neoplasia
Chronic ectopic pregnancy Constipation
Musculoskeletal source
Other
Porphyria
Shingles
Depression
History of abuse

578
 Chapter 78 Abdominal Pain (Endometriosis)

ultrasound would be very low. If an adequate pelvic throughout the pelvis (ovaries, fallopian tubes, broad
examination had not been possible, an ultrasound ligament, uterosacral ligaments, bladder) as well as in
would have been important in ruling out various extrapelvic locations (bowel, omentum, kidneys,
pelvic abnormalities as the cause of her pain. abdominal wall, diaphragm, pleura/lung), and even
A definitive diagnosis of endometriosis requires in nasal mucosa and skin.
laparoscopic visualization of the ectopic endometrial The etiology of endometriosis is not known
implants. For this reason, it is widely acceptable to with certainty. Ectopic endometrial tissue can result
treat suspected endometriosis empirically, especially from retrograde menstruation (supported by an
in the adolescent population, when other causes of increased incidence in patients with outflow tract
pelvic pain have been reasonably well ruled out. obstruction, such as in this case), hematologic or
lymphatic spread, or metaplasia of undifferentiated
Therapeutic coelomic cells in the peritoneal cavity. Observational
After discussing the diagnostic and therapeutic data demonstrate an association between endo-
options, Amanda and her parents elect initial metriosis and other autoimmune diseases, suggest-
empiric treatment. Because she has received some ing that a component of immune system alteration
relief from over-the-counter dosing, ibuprofen 800 may allow the ectopic endometrial tissue to grow
milligrams three times per day was prescribed. (Sinaii et al., 2002●B ). Some genetic component to the
disease exists, with up to a tenfold increase risk in
patients with first-degree relatives with endometrio-
FOLLOW-UP VISIT sis (ACOG, 2000● C ).
Although endometriosis is often asymptomatic, it
Subjective can cause significant morbidity related to pain and
After 2 months of treatment, Amanda returns to the infertility. Patients often have deep pelvic pain and
office for re-evaluation. Her symptoms are significantly dyspareunia. The pain is often cyclic, being worse
improved with regular use of ibuprofen. The continu- immediately before or during menses, but the pain
ous pain has mostly resolved, but she continues to have can be noncyclic as well, especially in adolescents.
significant pain beginning just before her menses. She Involvement of the bladder can cause urinary symp-
wishes to try something else for relief of her pain. toms such as dysuria, urgency, and hematuria, and
bowel involvement can result in constipation, painful
defecation, and rectal bleeding. Adolescent patients
Objective
are more likely to have these bowel and bladder symp-
Unchanged from previous examination. toms. The relation between endometriosis and fertility
is complex. Although anatomic alterations from the
Impression scarring of severe endometriosis can clearly lead to
tubal factor infertility, controversy exists over the role
Amanda has had an inadequate response to a trial of milder forms of endometriosis can play in infertility.
a nonsteroidal anti-inflammatory drug (NSAID). The diagnosis of endometriosis is typically a
She desires further treatment but still wishes to avoid clinical one. History and physical examination can
surgery unless it is necessary. suggest the diagnosis, while helping to rule out other
causes of pelvic pain. Ultrasound can be helpful in
Plan eliminating other potential causes for pain, particu-
larly if the physical examination is abnormal or
A trial of low-dose combined oral contraceptive pills limited. It also has a role in the diagnosis of
is prescribed. If this is not effective, Amanda agrees endometriomas (chocolate cysts), blood-filled cystic
to a referral for laparoscopy before more aggressive lesions that may complicate endometriosis.
medical management is started. A definitive diagnosis of endometriosis can be
made only after direct visualization of the lesions in
the operating room. Laparoscopy allows confirma-
DISCUSSION tion of the diagnosis and staging into categories of
minimal, mild, moderate, and severe, based on the
Endometriosis is a common cause of chronic pelvic location and severity of the disease (American Society
pain and infertility. Endometriosis has been reported for Reproductive Medicine, 1997● C ). Interestingly, no
in up to 32% and 48% of women undergoing correlation appears to exist between the amount of
laparoscopy for pelvic pain and infertility, respec- ectopic endometrium found at laparoscopy and the
tively (Sangi-Haghpeykar and Poindexter, 1995● B). In severity of pain that women experience.
adolescents with pelvic pain, the prevalence may be When deciding on treatment for endometriosis, it
as high as 65% (Chatman and Ward, 1982● C ). The is important first to determine the goals of treatment
ectopic endometrial glands and stroma can be found for a particular patient. For some patients, the goal may

579
 Chapter 78 Abdominal Pain (Endometriosis)

be treatment of the pain associated with the disease; for back at the hypothalamic and pituitary level. Its effec-
others, it may be treatment for infertility. The treat- tiveness in reducing endometriosis-associated pain also
ment can include both medical and surgical modali- has been supported by a recent systematic review (Selak
ties, and the approach may be different, depending on et al., 2004 ● A ). Danazol has significant side effects,
which of these problems is being addressed. including menopausal symptoms, acne, hirsutism, liver
If the primary treatment goal is relief of pain, disease, and thromboembolic disease. GnRH agonists
then many medical options can be considered decrease ovarian function by acting at the level of the
(Mahutte and Arici, 2003● C ). NSAIDs are commonly pituitary. Normally, pulsatile secretion of GnRH stimu-
prescribed for various forms of pain, including pelvic lates the pituitary to produce follicle-stimulating hor-
pain. They have a well-established role in the treat- mone and luteinizing hormone. Continuous GnRH
ment of primary dysmenorrhea, a prostaglandin- stimulation has the opposite effect, decreasing pituitary
mediated disease. Whereas they have no direct effect gonadotropin production and creating a sort of “med-
on the pathophysiology of endometriosis, they have ical menopause.” Although they are effective in treating
been extensively used for first-line symptomatic relief endometriosis pain, a recent systematic review found
of pain. They are inexpensive, and most physicians no evidence that they are superior to other medical
are very familiar with their use. Side effects from treatments (Prentice et al., 2000 ● A). Significant side
NSAIDs include gastrointestinal problems (gastritis, effects relating to estrogen deficiency occur, including a
peptic ulcer disease) and a rare incidence of renal fail- decrease in bone mineral density. These can be
ure. Despite the commonness of their use, data sup- improved with the concurrent use of add-back
porting the effectiveness of NSAIDs in endometriosis estrogen/progesterone therapy at levels sufficient to
are relatively scarce. At least one older placebo-con- reduce hormonal withdrawal symptoms, but low-
trolled crossover trial demonstrated a benefit over enough not to stimulate the ectopic endometrial tissue.
placebo (Kauppila and Ronnberg, 1985● A). A systematic It is important to realize that medical treatments,
review of the use of NSAIDs in endometriosis is cur- although effective for pain, have not been shown to
rently under way and is expected to be published some- improve fertility in patients with endometriosis
time in 2005 (Allen et al., 2004● A). (Hughes et al., 2003● A ).
Because of the role of ovarian hormones in sup- The role of surgery in the management of
porting the growth of the endometrium, treatments endometriosis includes definitively diagnosing the
that decrease production of these hormones have disease and both conservative and definitive treat-
been used extensively for endometriosis. These treat- ment options. Conservative treatment involves
ments attempt to mimic either pregnancy or destruction of endometriosis lesions and restoration
menopause, two physiologic states associated with of normal anatomy through lysis of adhesions cre-
improvement in this disease. Options in this category ated by the disease. This is typically accomplished
include oral contraceptive pills, progesterones, dana- laparoscopically. A recent systematic review identi-
zol, and gonadotro-pinreleasing hormone (GnRH) fied only one randomized controlled trial evaluating
agonists. Oral contraceptives have been extensively used the effectiveness of conservative surgery on the pain
to treat the pain associated with endometriosis. A com- of endometriosis (Jacobson, 2001● A). This study
mon strategy is to use continuous low-dose combina- showed a significant decrease in pain 6 months after
tion agents (i.e., no “placebo” week, unlike their normal surgery. Unlike medical therapy, surgery has been
use for birth control.) A systematic review found shown to have some effectiveness against infertility
only one randomized controlled trial supporting their associated with endometriosis (Jacobson, 2002● A ). If
efficacy against pain (Moore et al., 2004● A). Side effects future fertility is not desired, definitive surgery (hys-
include nausea, breast tenderness, hypertension, and terectomy, often with oophorectomy) can be used to
a small risk of thromboembolic disease. Progesterone- treat endometriosis pain that has not adequately
only therapy also has been widely used. Medro- responded to other treatment options. It should be
xyprogesterone can be used either orally (50 to 100 mg noted, however, that even this is not 100% effective
daily), or the depo-formulation can be given intramus- in refractory disease.
cularly (150 mg every 3 months). The effectiveness of
progesterone therapy is supported by a recent system-
atic review (Prentice et al., 2004● A). Side effects include
weight gain, irregular menses or amenorrhea, and a
small risk of thromboembolic disease. Danazol is a Material Available on Student Consult
weak androgen that is used to treat endometriosis by Review Questions and Answers about Endometriosis
decreasing estrogen production through negative feed-

580
 Chapter 78 Abdominal Pain (Endometriosis)

REFERENCES
Allen C, Hopewell S, Prentice A. Non-steroidal Anti- Mahutte N, Arici A. Medical management of endometrio-
inflammatory Drugs for Pain in Women with sis-associated pain. Obstet Gynecol Clin North Am
Endometriosis (Protocol for a Cochrane Review). 2003;30:133–150.● C
Chichester, The Cochrane Library, 2004.● A Moore J, Kennedy S, Prentice A. Modern Combined Oral
American College of Obstetricians and Gynecologists. Contraceptives for Pain Associated with Endometriosis
Medical management of endometriosis: ACOG Practice (Cochrane Review). Chichester, UK, The Cochrane
Bulletin No. 11. Int J Gynecol Obstet 2000;71:183–196.●
C Library, 2004.●A
American College of Obstetricians and Gynecologists. Prentice A, Deary A, Bland E. Progestagens and Anti-prog-
Chronic pelvic pain: ACOG Practice Bulletin No. 51. estagens for Pain Associated with Endometriosis
Obstet Gynecol 2004;103:589–605.● C (Cochrane Review). Chichester, UK, The Cochrane
American Society for Reproductive Medicine Revised clas- Library, 2004.●A
sification of endometriosis, 1996. Fertil Steril Prentice A, Deary EJ, Goldbeck-Wood S, et al.
1997;67:817–821.● C Gonadotropin-releasing Hormone Analogues for Pain
Chatman D, Ward A. Endometriosis in adolescents. Associated with Endometriosis (Cochrane Review).
J Reprod Med 1982;27:156–160.● C Chichester, UK, The Cochrane Library, 2000.● A
Hughes E, Fedorkow D, Collins J, et al. Ovulation Sangi-Haghpeykar H, Poindexter A. Epidemiology of
Suppression for Endometriosis (Cochrane Review). endometriosis among parous women. Obstet Gynecol
Chichester, UK, The Cochrane Library, 2003.● A 1995;85:983–992.● B
Jacobson T, Barlow DH, Garry R, et al. Laparoscopic Selak V, Farquhar C, Prentice A, et al. Danazol for Pelvic
Surgery for Pelvic Pain Associated with Endometriosis Pain Associated with Endometriosis (Cochrane
(Cochrane Review). Chichester, UK, The Cochrane Review). In. Chichester, UK, The Cochrane Library,
Library, 2001.●A 2000.● A
Jacobson T, Baklow DH, Koninckx P, et al. Laparoscopic Sinaii N, Cleary SD, Ballweg ML, et al. High rates of
Surgery for Subfertility Associated with Endometriosis autoimmune and endocrine disorders, fibromyalgia,
(Cochrane Review). Chichester, UK, The Cochrane chronic fatigue syndrome and atopic diseases among
Library, 2002.●A women with endometriosis: A survey analysis. Hum
Kauppila A, Ronnberg L. Naproxen sodium in dysmenorrhea Reprod 2002;17:2715–2724.● B
secondary to endometriosis. Obstet Gynecol 1985;
65:379–383.●A

581
 C h a p t e r

79 Severe Menstrual Cramps

(Primary Dysmenorrhea)
Melissa Nothnagle

bleeding, lasting 4 to 5 days. Marta had her tonsils

KEY POINTS and adenoids removed at age 5. She uses albuterol for
exercise-induced asthma. She is otherwise healthy.
1. Primary dysmenorrhea is extremely common
but underreported and undertreated. Family History
2. Secondary causes of dysmenorrhea can be Marta has two younger brothers. Her mother, who is
excluded by using history and physical examina- with her today, reports mild cramps with her own
tion. menstrual periods. Marta’s maternal grandmother
3. First-line treatment of primary dysmenorrhea had a hysterectomy at age 40 for uterine fibroids.
involves nonsteroidal anti-inflammatory drugs
(NSAIDs), which reduce prostaglandin levels. Social History
4. Combined oral contraceptives and other hor- Marta denies smoking, alcohol, or drug use. She is an
monal contraceptives may be effective in cases honor-roll student in the 10th grade. She has never
in which NSAIDS provide inadequate relief or been sexually active.
when patients desire effective birth control.
Review of Systems
She denies vaginal discharge, weight loss, constipa-
tion, and fever. She denies midcycle pain or bleeding.
INITIAL VISIT
Objective
Subjective
Physical Examination
Patient Identification and Presenting Marta appears well. Her blood pressure is 110/70
Problem mm Hg, pulse is 72 and regular, height is 5 ft
Marta R. is a 16-year-old girl with painful cramps in 3 inches, and weight is 120 pounds. Abdominal
her back and lower abdomen that have occurred with examination: normal bowel sounds, soft, nontender,
her menses for the past 2 years. nondistended. No masses are palpated. Pelvic exam-
ination reveals normal external genitalia, normal
History of Present Illness cervix and vagina. Her uterus is normal size, antev-
For the past 2 years, Marta has experienced severe erted, and nontender. Adnexal examination shows
cramps in her back and lower abdomen during the normal ovaries with no masses or tenderness.
first 2 days of her period. She occasionally has nau-
sea and loose stools when she has the pain. She has Assessment
tried taking ibuprofen, 200 mg every 6 hours, with-
out much relief. Sometimes she misses school Working Diagnosis
because her pain is so severe. Her last period was The most likely diagnosis in this case is primary dys-
2 weeks ago. menorrhea. This syndrome generally appears during
adolescence, within 1 to 2 years of menarche, when
Medical History ovulatory cycles are established. Patients report
Marta states that her periods began when she was 13 sharp, intermittent suprapubic pain that may radiate
years old. They occur every 30 days with moderate to the lower back or the back of the legs. Associated

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

582
 Chapter 79 Severe Menstrual Cramps (Primary Dysmenorrhea)

symptoms may include nausea, vomiting, diarrhea, due to instrumentation, cryotherapy, or surgery
fatigue, or headache. Pain usually begins on the first for cervical dysplasia.
day of menses and peaks in the first or second day 3. Cervical or endometrial polyps. These are benign
of menses, during the heaviest flow. Uterine growths of the endocervical canal or endometrium.
prostaglandins appear to have a causative role in pri- Cervical polyps often have postcoital bleeding and
mary dysmenorrhea. During menstruation, the dis- are visible protruding from the cervix on speculum
integrating endometrial cells release prostaglandins, examination. Endometrial polyps may be diag-
which stimulate myometrial contractions and nosed with ultrasound or hysteroscopy.
ischemia. Higher levels of prostaglandins have been 4. Pelvic inflammatory disease. Pelvic inflammatory
found in the menstrual fluid of women with more disease (PID) is a polymicrobial infection of the
severe dysmenorrhea (Chan, 1978● B). In addition, upper genital tract that usually occurs with lower
nonsteroidal anti-inflammatory drugs (NSAIDs), abdominal pain and fever. Examination findings
which inhibit prostaglandin synthesis, are effective in include purulent cervical discharge, cervical
relieving symptoms of dysmenorrhea. motion tenderness, and adnexal tenderness.
A subacute infection could cause symptoms simi-
Differential Diagnosis lar to dysmenorrhea, but differences in timing of
Secondary dysmenorrhea is defined as painful symptoms, examination findings, and cervical cul-
menses that are associated with an identifiable patho- tures would likely point to infection. Pelvic adhe-
logic condition. Such conditions can often be identi- sions resulting from a previous episode of PID
fied by history and physical examination. Patients may be associated with subsequent dysmenorrhea.
should be asked about age of menarche, onset of 5. Ovarian cysts. Cyclic pain may be associated with
symptoms, and timing of the pain in relation to the functional ovarian cysts or hemorrhagic cysts.
menstrual cycle. Secondary causes of dysmenorrhea However, symptoms are unlikely to occur only
may be suggested by abnormal findings on physical during the initial days of the menses. Pelvic ultra-
examination or poor response to NSAIDS or com- sound is helpful in diagnosing ovarian cysts, but
bined hormonal contraceptives. Secondary dysmen- given the high prevalence of asymptomatic ovar-
orrhea also should be suspected in women who ian cysts, it may be difficult to establish that these
report onset of symptoms after puberty or who have are the cause of a patient’s pain.
associated infertility, irregular menses, or dyspareu- 6. Leiomyomata (uterine fibroids). These benign
nia. Treatment for many causes of secondary dys- tumors of the uterine muscle are uncommon in
menorrhea is surgical, so these patients may need adolescents and may be associated with heavy,
referral to a gynecologist for evaluation. painful menses. Nodularity or enlargement of the
uterus may be noted on bimanual examination.
1. Endometriosis. This condition is characterized by Pelvic ultrasound is useful in confirming this
growth of endometrial tissue outside the uterine diagnosis.
cavity. Cyclic stimulation of the ectopic endome- 7. Adenomyosis. Rarely seen in women younger than
trial tissue causes pelvic pain. Women with 30 years, this condition involves penetration by
endometriosis classically appear with cyclic pelvic endometrial glands and stroma deep into
pain, infertility, and dyspareunia, especially with myometrial tissue. This is associated with
deep penetration. Physical examination findings increased menstrual bleeding and dysmenorrhea.
suggestive of endometriosis include cervical Mild uterine enlargement may be noted on exam-
motion tenderness, uterosacral nodularity, and ination. The diagnosis can be made with mag-
decreased uterine mobility. However, the physical netic resonance imaging or at the time of
examination has low sensitivity and specificity for hysterectomy.
endometriosis. The diagnosis should be suspected 8. Intrauterine devices. Some intrauterine devices are
in patients who report midcycle and perimen- associated with increased volume of menstrual
strual pain, especially those with a history of fer- flow, which may result in higher incidence of dys-
tility problems. The gold standard for diagnosis of menorrhea.
endometriosis is laparoscopy. However, the extent
of the disease at laparoscopy does not correlate
Plan
well with severity of symptoms. Many patients
with a history suggestive of endometriosis will Diagnostic
respond to empirical treatment with combined Because Marta has a history typical of primary dys-
oral contraceptives or gonadotropin-releasing menorrhea and a normal physical examination, no
hormone agonists. further testing is indicated. A poor response to
2. Cervical stenosis. A less-common cause of dys- empirical treatment would suggest a second-
menorrhea than was previously believed, cervical ary cause of dysmenorrhea, warranting further
stenosis may result from infection or from trauma evaluation.

583
 Chapter 79 Severe Menstrual Cramps (Primary Dysmenorrhea)

Therapeutic Plan
The patient is prescribed naproxen, 500 mg, twice
Combined oral contraceptives were recommended
daily. She is encouraged to start the medicine the day
to Marta, given her inadequate response to NSAID
before her anticipated onset of menses and to con-
therapy. In addition to preventing pregnancy, bene-
tinue through the first 3 days of menses.
fits of treatment with combined oral contraceptives
include improvement in acne, menstrual regularity,
Patient Education
reduced risk of anemia, prevention of ovarian cysts,
Marta’s mother is concerned that the cause of
and prevention of PID (Fraser and Kovacs, 2003 ●B ●
C ).
Marta’s severe pain could be associated with future
While taking oral contraceptives, she can continue to
fertility problems. Marta and her mother are
use NSAIDs to relieve any discomfort during her
informed about the high prevalence of primary dys-
menses.
menorrhea among adolescents and the lack of a rela-
tion between dysmenorrhea and future problems
with fertility. She is told that if her pain is not ade-
quately relieved with these higher-dose NSAIDs, DISCUSSION
combined oral contraceptives are an effective second-
Primary dysmenorrhea is the most common gyneco-
line treatment.
logic problem in menstruating women. Reported
prevalence rates are as high as 90% (Jamieson and
Disposition
Steege, 1996● B ). Dysmenorrhea is a major cause of
Marta is instructed to make a follow-up appointment
activity restriction and absence from work and school.
in 2 months to review her response to NSAID therapy.
Further, this problem is underreported as well as under-
treated in primary care.
The diagnosis of primary dysmenorrhea can
FOLLOW-UP VISIT generally be made based on a typical history and a
normal physical examination. Primary dysmenorrhea
Subjective usually is first seen within 2 years of menarche, and
Marta returns for her follow-up visit 2 months later. onset of the pain coincides with the onset of menses
She reports taking naproxen as instructed, starting and resolves after 2 to 3 days. Table 79-1 lists features
the day before her anticipated period. She describes suggestive of primary or secondary dysmenorrhea.
some reduction in pain, although on her first day of Physical examination findings may suggest a
menses this month, the pain was still severe enough secondary cause of dysmenorrhea, although several
that she left school early. She has not had any pain causes of secondary dysmenorrhea such as endo-
between her periods. metriosis or ovarian cysts may not be detectable by
physical examination. Laboratory testing and imag-
ing studies are not needed to make the diagnosis of
Objective primary dysmenorrhea.
Her vital signs are normal.
Treatment of Primary Dysmenorrhea
Assessment
Nonsteroidal Anti-inflammatory Drugs
Marta’s partial response to NSAID therapy is still The efficacy of NSAIDs for primary dysmenorrhea
consistent with the diagnosis of primary dysmenor- has been demonstrated in randomized controlled tri-
rhea. als, although insufficient evidence exists to evaluate

Table 79-1 Features Suggestive of Primary or Secondary Dysmenorrhea

Primary Dysmenorrhea Secondary Dysmenorrhea

Onset in early adolescence Onset after adolescence

Duration of symptoms, 2–3 days Duration of symptoms, >3 days
Onset of pain coincides with menses Pain before menses or midcycle pain
Normal pelvic exam Abnormal findings on pelvic exam
Relief with NSAIDs or OCPs Lack of response to NSAIDs or OCPs
Infertility
Irregular bleeding

NSAID, nonsteroidal anti-inflammatory drug; OCP, oral contraceptive.

584
 Chapter 79 Severe Menstrual Cramps (Primary Dysmenorrhea)

differences in efficacy among various NSAIDs Other hormonal contraceptives also are benefi-
(Marjoribanks et al., 2003●A). Possible adverse effects cial in treating primary dysmenorrhea (Fraser and
of NSAIDs include nausea, epigastric pain, and gas- Kovacs, 2003● B ●C ). Extended-cycle oral contracep-
trointestinal bleeding. Contraindications include his- tives may be helpful for patients with severe dysmen-
tory of peptic ulcer disease or gastrointestinal orrhea. They may reduce the frequency of
bleeding and renal or hepatic insufficiency. menstruation to 4 times per year, in addition to pre-
venting ovulation and reducing menstrual volume.
Combined Oral Contraceptives Specific products are marketed for this purpose, but
The efficacy of combined oral contraceptive pills for any combined oral contraceptive can be prescribed
primary dysmenorrhea has been demonstrated in for extended cycles by instructing patients to use
laboratory and observational studies, as well as a few only the active pills for 3 months, followed by a week
small randomized controlled trials (Davis and of placebo pills. Progestin-only hormonal contracep-
Westhoff, 2001● B ; Hendrix and Alexander, 2002● B ). tives, including progestin-only pills, injectable prog-
No data are available comparing different formula- estins and progestin-releasing intrauterine devices
tions. Treatment with oral contraceptives is ideal for (IUDs), alleviate primary dysmenorrhea through
women with dysmenorrhea who desire effective con- their inhibitory effects on the endometrium. Both
traception, or for those who do not respond ade- injectable progestins and the progestin-releasing
quately to a trial of NSAIDs. IUDs may induce amenorrhea in some users, which
Combined oral contraceptives inhibit ovula- may be of benefit to women with severe menstrual
tion, which reduces stimulation of endometrial tis- symptoms.
sue. As a result, menstrual volume decreases, as
does prostaglandin release. Newer combined hor- In summary, primary dysmenorrhea is a com-
monal delivery systems such as the contraceptive mon but undertreated condition in primary care.
patch and vaginal ring should have similar effects Once secondary causes have been ruled out from the
on the endometrium. Possible adverse effects of history and physical examination, dysmenorrhea is
combined hormonal contraceptives include nausea, usually managed successfully with medications.
breakthrough bleeding, amenorrhea, headache, and
thromboembolic events. Smokers older than 35
years and women with breast cancer, cerebrovascu- Material Available on Student Consult
lar or coronary artery disease, thromboembolic dis-
Review Questions and Answers about Primary
orders, or undiagnosed abnormal vaginal bleeding Dysmenorrhea
should not use combined hormonal contraceptives.

REFERENCES
Chan WY, Hill JC. Determination of menstrual Hendrix SL, Alexander NJ. Primary dysmenorrhea treat-
prostaglandin levels in nondysmenorrheic and dys- ment with a desogestrel-containing low-dose oral con-
menorrheic subjects. Prostaglandins 1978;130:83.●
B traceptive. Contraception 2002;66:393–399.● B
Davis AR, Westhoff CL. Primary dysmenorrhea in adoles- Jamieson DJ, Steege JF. The prevalence of dysmenorrhea, dys-
cent girls and treatment with oral contraceptives. pareunia, pelvic pain, and irritable bowel syndrome in
J Pediatr Adolesc Gynecol 2001;14:3–8.●
B primary care practices. Obstet Gynecol 1996;87:55–58.● B
Fraser IS, Kovacs GT. The efficacy of non-contraceptive Marjoribanks J, Proctor ML, Farquhar C. Nonsteroidal
uses for hormonal contraceptives. Med J Aust anti-inflammatory drugs for primary dysmenorrhoea.
2003;178:621–623.● B ●
C Cochrane Database Syst Rev 2003;CD001751.● A

585
 C h a p t e r

80 Back Pain (Osteoporosis)

Kenneth J. Grimm

KEY POINTS INITIAL VISIT

Subjective
1. Vertebral compression fractures, seen with
new-onset back pain radiating to the anterior Patient Identification and Presenting
abdominal wall (“girdle of pain”), are a com- Problem
mon presentation of osteoporosis. Mrs. M. is a 74-year-old white woman complaining
2. It should be recognized that vertebral com- of back pain.
pression fractures are a sign of generalized
osteoporosis and are associated with a three- Present Illness
fold increase in the risk of hip fractures. Mrs. M. reports that she awoke with pain in her back
3. Risk factors for osteoporosis include age, female approximately 2 weeks ago. She denies fall, trauma,
sex, sex hormone deficiency, family history, being and unusual or new activities. She has had no previ-
white, poor calcium and vitamin D intake, inactiv- ous problems with her back. The pain is midline in
ity, smoking, low body weight, excessive caffeine the upper lumbar area. It does not radiate to either
intake, hyperthyroidism, diabetes, inflammatory leg, but it does extend to her anterior abdomen on
bowel disease, and the use of corticosteroids, both sides. It was initially sharp and severe, signifi-
anxiolytics, anticonvulsants, and neuroleptics. cantly limiting her activities for the first 4 or 5 days.
4. The risk of fracture is increased by conditions Since then it has lessened somewhat, and she now
that increase the general risk of falling. describes it as a constant ache. It has affected her
5. Osteoporosis is a common condition, resulting sleep, and she has been using acetaminophen regu-
in significant morbidity, mortality, and health larly for the past 2 weeks with some relief. She denies
care expenditure. fever, dysuria, hematuria, changes in bowel or blad-
6. Osteoporosis is defined by the World Health der function, or incontinence. She has no lower-
Organization as resulting in a T-score of −2.5 extremity weakness, pain, or numbness. The pain
or less. does not change with position.
7. Osteopenia is defined as resulting in a T-score
of between −1.0 and −2.5. Medical History
8. Screening for osteoporosis with dual-energy Mrs. M. has a long history of asthma, for which she
x-ray absorptiometry should be offered to all has required five hospital admissions since child-
women older than 65 years, and all high-risk hood. Her last admission was 2 years ago. She is seen
women older than 60 years. in the office for an exacerbation of her asthma
9. Adequate calcium and vitamin D intake should approximately twice per year and has required short
be recommended to all women, regardless of courses of oral prednisone every 1 to 2 years. Her
age, to protect against the development of asthma is well controlled with a combination of
osteoporosis. inhaled corticosteroid and long-acting β2-agonist
10. Bisphosphonates have the best evidence that twice daily, with a short-acting β2-agonist as needed
they are effective at preventing fractures and for symptoms approximately once a week. She also
should be used as first-line therapy. Other treat- has a history of Parkinson’s disease, which is treated
ments that have been shown to affect bone with a dopamine agonist. She is otherwise healthy
density include calcitonin, calcium and vitamin and uses no other medications. She had a negative
D, and hormone replacement therapy. mammogram 6 months ago and a normal
colonoscopy within the past 5 years.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

586
 Chapter 80 Back Pain (Osteoporosis)

Family History back pain with no warning symptoms to suggest

Mrs. M.’s father died at age 75 of complications of neurologic compromise or malignancy. She is tender
diabetes. He had asthma as well. Her mother is age 92 over her upper lumbar spine and has lost 2 inches of
and healthy except for obesity. height in the past 2 years.

Social History Working Diagnosis

Mrs. M. has a significant smoking history of 60 pack- Spinal compression fracture secondary to osteoporosis.
years. She was finally convinced to quit after her last
hospitalization 2 years ago. She denies alcohol or Differential Diagnosis
drug use, and she only occasionally drinks caf- Back pain is a common problem, usually resulting
feinated beverages. She lives with her husband of 55 from muscular strain or osteoarthritis of the facet
years in a senior apartment complex. joints. More significant spinal causes of back pain
include disc herniation, spondylolisthesis, spinal
Review of Systems stenosis, infections (osteomyelitis or epidural infec-
She is thin but denies changes in her appetite or tion), and malignancy. In an elderly patient, spinal
weight. She has tremor and difficulty with ambula- stenosis with neurologic compromise and cancer
tion initially in the morning, which improves after must be seriously considered, but Mrs. M. has no
taking her Parkinson’s medication. She has fallen “alarm” symptoms or signs to suggest the presence of
twice in the past 6 months without injury. Aside these more serious causes of back pain.
from her back pain, she denies musculoskeletal com-
plaints. Review of other systems is noncontributory. Plan
Diagnostic
Objective
Plain films of her back show generalized osteopenia
Physical Examination and the presence of a spinal compression fracture of
Mrs. M. appears to be a thin, healthy woman, sitting the L2 vertebral body. Bone mineral density (dual-
in a chair in no distress. She has some clear discom- energy x-ray absorptiometry [DEXA]) scan reveals a
fort when moving about the examination room. Her T-score of −2.8 at the hip and −3.0 in the lumbar
temperature, pulse, and blood pressure are normal. spine. The diagnosis of an osteoporotic spinal com-
Her weight is 98 pounds, which is unchanged from pression fracture is confirmed.
her last visit. Her height is 61 inches, which is
2 inches less than the last recorded height from Therapeutic
2 years ago. Head and neck, cardiovascular, and pul- She is prescribed calcium, vitamin D, and antiresorp-
monary examinations are normal. Abdominal tive therapy with a once-weekly dose of a bisphos-
examination reveals normally active bowel sounds phonate. Additionally, she is started on daily nasal
with no tenderness, organomegaly, or mass. Her calcitonin to help with pain and advised to increase
aorta is easily palpable, nontender, and not enlarged. the dosage of acetaminophen to 1000 mg every
She has normal femoral pulses. Inspection of her 6 hours, if needed. Her Parkinson’s regimen is
back reveals loss of lumbar lordosis and some mild adjusted to decrease her risk of falling.
thoracic kyphosis. She has no muscular atrophy. No
significant tenderness or spasm is noted in the tho- Patient Education
racic or lumbar paraspinal muscles. She has midline The high risk of hip fracture from falling is stressed
tenderness on palpation of the spine at the upper to Mrs. M. She is asked to use a cane, and the use of
lumbar level. Her straight-leg raise shows no sign of hip-protective padding is discussed. Interventions
radiculopathy. Her neurologic examination reveals aimed at decreasing her risk of falling at home, such
minimally increased tone in all extremities, with as removing throw rugs and installing shower han-
mild cogwheel rigidity. She is slow to arise from her dles, are suggested.
chair and has mild difficulty in initiating movement,
but her gait is normal once she has started walking.
She has some difficulty turning to climb onto the DISCUSSION
examination table. Lower-extremity strength, sensa-
tion, and deep tendon reflexes are normal with no Vertebral fractures are the most common manifesta-
Babinski sign. tion of osteoporosis (Genant et al., 1999● B ). This
patient’s pain is typical for spinal compression frac-
ture, with its abrupt onset and its radiation to the
Assessment
anterior abdominal wall (the “girdle of pain”).
Mrs. M is a 72-year-old woman with asthma and Although vertebral fractures can cause significant
Parkinson’s disease with a 2-week history of midline and disabling pain in some patients, their larger

587
 Chapter 80 Back Pain (Osteoporosis)

significance is that they denote a threefold increase in patients with osteoporosis. In our case, Mrs. M.’s
the risk of the more serious osteoporotic hip fracture risk factors for osteoporosis include her age, her
(Black et al., 1999●B ). Failure to diagnose the systemic race, her smoking history, and previous steroid use.
disease of osteoporosis in a patient with a spinal Furthermore, her neurologic condition increases her
compression fracture is common, occurring more risk of falling.
than 60% of the time (Neuner et al., 2003● B ). Screening for osteoporosis can be an effective
Osteoporosis is a disease characterized by strategy for decreasing the morbidity and mortality
decreased bone strength and increased risk of frac- associated with fractures. Screening is generally
ture. Whereas bone strength is affected by both bone considered to be beneficial when the target condi-
density and bone quality, the latter factor, deter- tion is common and carries significant morbidity
mined by the microarchitectural structure, is diffi- or mortality, when a reasonably accurate and
cult to determine. Therefore the World Health affordable screening test is available, and when
Organization defines osteoporosis as a decrease in treatment offers additional benefit when it is initi-
bone mineral density of more than 2.5 standard ated during an early, asymptomatic stage of the dis-
deviations below what would be expected for the ease. Although no studies have directly looked at
average young white woman (a T-score of less than − the effect of screening, it is reasonably clear from
2.5). Approximately 7% of women older than the literature that treatment of patients identified as
50 years meet this definition. A T-score between having high fracture risk can decrease this risk. The
−1.0 and −2.5 is defined as osteopenia, and this United States Preventive Services Task Force has
occurs in 40% of women aged 50 and older (Siris evaluated the evidence related to screening and rec-
et al., 2001 ●
B ). Osteoporosis results in approximately ommended that DEXA at the femoral neck be
1.3 million fractures (Consensus Development offered to all women age 65 and older, and to high-
Conference, 1993● C ) and costs between $10 and $15 risk women between the ages of 60 and 65. Testing
billion every year in the United States (National should not be repeated more often than every 2
Institutes of Health, 2001● C). Common sites for years because of limitations in the precision of bone
osteoporotic fractures include the vertebrae, the mineral density measurements, and no clear data
wrist, and the hip, with the majority of the morbid- exist to suggest at which age screening should be
ity, mortality, and cost resulting from hip fractures. discontinued (United States Preventive Services
Approximately one third of patients with hip frac- Task Force, 2002● B ).
tures are unable to return to independent living, and Strategies for the prevention and treatment of
20% die within the first year (National Institutes of osteoporosis include modification of risk factors for
Health, 2001● C ). bone loss and for falls, increase in physical activity,
Risk factors for osteoporosis can be divided into and the use of pharmacologic agents. If modifiable
those that decrease peak bone mass and those that risk factors exist, these should be addressed. Patients
lead to accelerated bone loss. Peak bone mass is should be advised to stop smoking and to limit caf-
reached by the mid-30s. Genetic factors are the most feine intake. Medical conditions associated with
important determinants of peak bone mass. Gender increased bone loss should be controlled, and the use
is an important factor, as women have lower peak of medications that increase the risk of osteoporosis
bone mineral densities than men. Race also is an should be minimized. The use of external hip pro-
important factor, with African-American women tectors to prevent fracture has been evaluated in sev-
achieving higher peak bone mass than whites. eral studies. A recent systematic review of this
Environmental factors also play a role in determin- literature shows no benefit for the use of these
ing peak bone mass. These factors include calcium devices in community-dwelling elderly patients at
and vitamin D intake, as well as activity level. risk for falls and fractures. The reviewed studies give
Certain diseases, such as celiac disease, cystic fibro- conflicting results regarding the benefit of these
sis, and the female-athlete triad (amenorrhea, dis- devices when used in nursing homes. Finally, com-
ordered eating, and osteoporosis) are risk factors pliance with use of these devices is poor (Parker
for failure to achieve optimal peak bone mass. et al., 2004●A ).
Factors known to accelerate bone loss include age, The effect of exercise on the prevention of osteo-
low levels of sex hormones, smoking, inactivity, low porosis has been evaluated in several studies.
body weight, high caffeine intake, certain medical A Cochrane review of 18 randomized controlled tri-
conditions (hyperthyroidism, diabetes, and inflam- als concluded that aerobic, weight-bearing, and
matory bowel disease), as well as certain medica- resistance exercises can have positive effects on bone
tions (steroids, anxiolytics, anticonvulsants, and mineral density. However, no data exist to show a
neuroleptics) (Cummings et al., 1995● B). Finally, fac- decreased risk of fracture from any form of exercise
tors that increase the risk of falling will result in a (Boniauti et al., 2002● A ).
higher incidence of fractures at any level of bone Pharmacologic agents commonly used for the
density, but this effect is especially important in prevention and treatment of osteoporosis include

588
 Chapter 80 Back Pain (Osteoporosis)

calcium with vitamin D, bisphosphonates, calci- Some evidence exists for the effectiveness of cal-
tonin, and hormone replacement therapy (HRT). citonin in the treatment of osteoporosis (Cranney
Calcium and vitamin D are the most commonly et al., 2002●A). Calcitonin has been shown to increase
used agents for the prevention of osteoporosis. bone mineral density in the wrist and spine. Studies
Although their combined use has been shown to also have shown a strong, but not statistically signif-
increase bone mineral density in several different icant, trend toward increased bone density in the
populations, studies have shown only a modest hip. The evidence for an actual decrease in fracture
trend toward decreasing fracture risk that did not risk is less clear. Some, but not all, studies have
reach statistical significance (Cranney et al., 2002●A ). shown a decrease in the risk of vertebral fractures,
Calcium, 1200 to 1500 mg/day, and vitamin D, 400 but no effect seems to exist on the risk for nonverte-
IU/day, should be recommended for primary pre- bral fractures, including fractures of the hip.
vention of osteoporosis in all women. They are also Therefore, calcitonin is considered a second-line
used as adjuvant to other osteoporosis treatments agent for the prevention and treatment of osteo-
but should not be used alone for the treatment of porosis, usually used for patients for whom more
established osteoporosis. effective bisphosphonates either fail or cannot be
Bisphosphonates have more high-quality evi- tolerated. In addition to preserving bone density,
dence (Cranney et al., 2002● A) supporting their use calcitonin can be used to decrease the pain resulting
in the prevention and treatment of osteoporosis from a vertebral fracture.
than does any other category of drug. The use of bis- Because of the significant decrease in bone min-
phosphonates has been clearly shown to increase eral density in the first 10 years after menopause,
bone mineral density. Their effectiveness for preven- HRT was once recommended as the primary means
tion of fractures also has been shown. Alendronate of preventing osteoporosis and fracture. Initial
has been shown to reduce the risk of both vertebral observational studies demonstrated a 50% reduction
and nonvertebral fractures by approximately half, in vertebral fractures and a 25% to 50% reduction in
whereas risedronate decreases the risk of vertebral hip fractures from HRT (Cranney et al., 2002● A). The
fractures by one third and the risk of nonvertebral Women’s Health Initiative (Rossouw et al., 2002● A),
fractures by one fourth. Bisphosphonates are the the largest prospective clinical trial evaluating the
only agents that have direct evidence for a decrease risks and benefits of HRT, confirmed a 35% reduc-
in the risk of hip fractures in high-risk patients. The tion in the risk of hip fractures. In this population at
magnitude of the effect bisphosphonates have on relatively low risk for fracture, this corresponded to
fracture risk can be expressed by the number of an NNT of approximately 2000 over a 5-year period.
patients who would need to be treated with the However, because the study also showed that HRT
drugs for 2 years to prevent one fracture, also known resulted in an increased risk of cardiovascular disease
as the number needed to treat (NNT). For low-risk and breast cancer, the long-term use of HRT for the
patients, approximately 2000 patients would need to prevention of osteoporosis and fractures is no longer
be treated to prevent one vertebral fracture. For recommended.
high-risk patients (those with a previous fracture, or
those with a bone mineral density less than −2.5),
between 75 and 100 patients would need to be
treated to prevent one vertebral fracture, and 25 to
50 patients would need to be treated to prevent one
nonvertebral fracture. These NNTs are well within Material Available on Student Consult
the range of what is commonly considered accept- Review Questions and Answers about Osteoporosis
able for pharmacologic therapy.

REFERENCES
Black DM, Arden NK, Palermo L, et al. Prevalent vertebral Cranney A, Guyatt G, Griffith L, et al. Summary of meta-
deformities predict hip fractures and new vertebral analyses of therapies for postmenopausal osteoporosis.
deformities but not wrist fractures: Study of Endocr Rev 2002;23:570–578.● A
Osteoporotic Fractures Research Group. J Bone Miner Cummings SR, Nevitt MC, Browner WS, et al. Risk factors
Res 1999;14:821–828.● B for hip fractures in white women: Study of
Bonaiuti D, Shea B, Iovine R, et al. Exercise for preventing Osteoporotic Factures Research Group. N Engl J Med
and treating osteoporosis in postmenopausal women 1995;332:767–773.● B
Cochrane Database Syst Rev 2002;CD000333● A Genant HK, Cooper C, Poor G, et al. Interim report and
Consensus Development Conference. Diagnosis, prophy- recommendations of the World Health Organization
laxis, and treatment of osteoporosis. Am J Med Task Force for Osteoporosis. Osteoporos Int 1999;
1993;94:646–650.● C 10:259–264.● B

589
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

Neuner J, Zimmer J, Hamel M. Diagnosis and treatment of Siris E, Miller P, Barrett-Connor E, et al. Identification and
osteoporosis in patients with vertebral compression fracture outcomes of undiagnosed low bone mineral
fractures. J Am Geriatr Soc 2003;51:483–491.● B density in postmenopausal women: Results from the
National Institutes of Health (NIH). NIH Consensus National Osteoporosis Risk Assessment. JAMA 2001;
Development Panel on osteoporosis prevention, diag- 286:2815–2822.● B
nosis, and treatment. JAMA 2001;285:785–795.● B United States Preventive Services Task Force. Screening for
Parker M, Gillespie L, Gillespie W. Hip protectors for pre- osteoporosis in postmenopausal women: Recom-
venting hip fractures in the elderly. Cochrane Database mendations of the United States Preventive Services
Syst Rev 2004;(3):CD001255.● A Task Force. Ann Intern Med 2002;137:526–528.● B
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and
benefits of estrogen plus progestin in healthy post-
menopausal women. JAMA 2002;288:321–333.● A

C h a p t e r

81 Vaginal Discharge
(Vulvovaginal Candidiasis)
Karl E. Miller

KEY POINTS INITIAL VISIT

1. Vulvovaginal candidiasis usually presents with Subjective

intense pruritus on the external and internal Patient Identification and Presenting Problem
genitalia with a discharge that is thick cottage Mrs. P. is a 45-year-old woman whose main complaint
cheese–like in appearance. is a vaginal discharge for the past 3 weeks. She
2. The treatment for bacterial vaginosis includes describes the discharge as thick, cottage cheese–like
both oral and intravaginal routes, which have material. She also states that she is having severe itch-
similar cure rates. ing on her external genitalia. Her last menstrual
3. The use of fluoroquinolones in the treatment of period was 3 weeks ago and was normal. She does
uncomplicated gonorrhea should be avoided in complain of pain during intercourse but it occurs only
individuals that live in Asia, the Pacific Islands, during initial penetration. She denies any pelvic or
and California. abdominal pain. She also denies any fevers, chills, or
4. Uncomplicated genital chlamydia can be sweats. She currently takes no medications or supple-
treated either with a one-time, 1-g dose of ments and no recent antibiotics. She has been in a
azithromycin or with doxycycline, 100 mg twice monogamous relationship for the last 25 years, and
daily for 7 days. her partner has no symptoms and no known sexual
5. The Centers for Disease Control and Prevention contact outside of their relationship.
recommends empiric treatment for pelvic inflam-
matory disease if the patient has cervical motion Medical History
tenderness or uterine/adnexal tenderness and is She has had no prior medical illnesses or hospitaliza-
at risk for sexually transmitted diseases. tion other than for two pregnancies and a postpar-
tum tubal ligation.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

590
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

Neuner J, Zimmer J, Hamel M. Diagnosis and treatment of Siris E, Miller P, Barrett-Connor E, et al. Identification and
osteoporosis in patients with vertebral compression fracture outcomes of undiagnosed low bone mineral
fractures. J Am Geriatr Soc 2003;51:483–491.● B density in postmenopausal women: Results from the
National Institutes of Health (NIH). NIH Consensus National Osteoporosis Risk Assessment. JAMA 2001;
Development Panel on osteoporosis prevention, diag- 286:2815–2822.● B
nosis, and treatment. JAMA 2001;285:785–795.● B United States Preventive Services Task Force. Screening for
Parker M, Gillespie L, Gillespie W. Hip protectors for pre- osteoporosis in postmenopausal women: Recom-
venting hip fractures in the elderly. Cochrane Database mendations of the United States Preventive Services
Syst Rev 2004;(3):CD001255.● A Task Force. Ann Intern Med 2002;137:526–528.● B
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and
benefits of estrogen plus progestin in healthy post-
menopausal women. JAMA 2002;288:321–333.● A

C h a p t e r

81 Vaginal Discharge
(Vulvovaginal Candidiasis)
Karl E. Miller

KEY POINTS INITIAL VISIT

1. Vulvovaginal candidiasis usually presents with Subjective

intense pruritus on the external and internal Patient Identification and Presenting Problem
genitalia with a discharge that is thick cottage Mrs. P. is a 45-year-old woman whose main complaint
cheese–like in appearance. is a vaginal discharge for the past 3 weeks. She
2. The treatment for bacterial vaginosis includes describes the discharge as thick, cottage cheese–like
both oral and intravaginal routes, which have material. She also states that she is having severe itch-
similar cure rates. ing on her external genitalia. Her last menstrual
3. The use of fluoroquinolones in the treatment of period was 3 weeks ago and was normal. She does
uncomplicated gonorrhea should be avoided in complain of pain during intercourse but it occurs only
individuals that live in Asia, the Pacific Islands, during initial penetration. She denies any pelvic or
and California. abdominal pain. She also denies any fevers, chills, or
4. Uncomplicated genital chlamydia can be sweats. She currently takes no medications or supple-
treated either with a one-time, 1-g dose of ments and no recent antibiotics. She has been in a
azithromycin or with doxycycline, 100 mg twice monogamous relationship for the last 25 years, and
daily for 7 days. her partner has no symptoms and no known sexual
5. The Centers for Disease Control and Prevention contact outside of their relationship.
recommends empiric treatment for pelvic inflam-
matory disease if the patient has cervical motion Medical History
tenderness or uterine/adnexal tenderness and is She has had no prior medical illnesses or hospitaliza-
at risk for sexually transmitted diseases. tion other than for two pregnancies and a postpar-
tum tubal ligation.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

590
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

Family History appearance and is adherent to the vaginal wall.

Mother and father have type 2 diabetes. The discharge usually does not cause any external
symptoms. Other findings include clue cells pres-
Social History ent microscopically, a vaginal pH greater than 4.5,
She has been married for 23 years and works as an and a positive “whiff ” test when potassium
administrative assistant. She denies any alcohol, hydroxide is added to the sample of the discharge.
tobacco, or illicit drug use. 3. Trichomoniasis. This organism causes a thin,
frothy, green-yellow or gray malodorous vaginal
Review of Systems discharge. Dyspareunia or vaginal soreness may
Her only other complaint is increased urine output be present. The cervix has a “strawberry” red
and excessive thirst over the last 6 months. appearance, or some erythema of the vagina or
external genitalia may be seen. The laboratory
findings include a vaginal pH of more than 5.0,
Objective
more than 10 WBCs per high-power field, and
Her height is 5 feet 3 inches; her weight is 180 mobile trichomonads on the wet preparation.
pounds, with a body mass index of 32. She is afebrile, 4. Chlamydia and gonorrhea. Any time a female
and her vital signs are normal. Her abdomen is non- patient has a vaginal discharge during her repro-
tender to palpation with no rebound or guarding, and ductive years, these two infections must be consid-
no masses or organomegaly. Genital examination ered. Risk factors for these infections include being
reveals an inflamed-appearing introitus, some minor younger than 25, history of multiple sexual part-
swelling of the labia, and no lesions. Examination ners, previous sexually transmitted diseases (STDs),
with a speculum finds a normal-appearing cervix and nonbarrier contraception. The discharge is
with no discharge from the os; the posterior vaginal mucopurulent and comes from the cervical os.
vault has a thick, cottage cheese–like discharge with 5. Pelvic inflammatory disease (PID). Because this
no odor. A wet preparation and potassium hydroxide infection can have such a negative long-term
sample are performed. The bimanual examination impact on women, it should be considered in
reveals no tenderness or abnormalities. women in their reproductive years who have vagi-
nal discharge. The history and physical examina-
Laboratory Tests tion were not consistent with what would be
The pH of the discharge is 5.0, with budding yeast expected in patients with PID.
and hyphae noted on the potassium hydroxide
portion of the slide. The wet preparation has epithe-
lial cells present and no white blood cells (WBCs). DISCUSSION
The “whiff ” test is negative.
The accurate diagnosis of vaginal discharge is based
on signs, symptoms, and microscopic examination
Assessment
of the discharge. The presence of pruritus, the odor of
Vaginal discharge: vulvovaginal candidiasis. the discharge, and presence of inflammation provide
information that can assist in establishing the correct
diagnosis. Office microscopy provides the most accu-
Plan
rate laboratory test (Anderson et al., 2004●B ).
The patient requests an oral agent, so fluconazole
(Diflucan), 150 mg, one-time dose is prescribed. Her Vulvovaginal Candidiasis
random blood sugar is 205.
Vulvovaginal candidiasis is one of the most com-
Differential Diagnosis mon causes of vaginitis; Candida albicans is the
1. Vulvovaginal candidiasis. This is the most likely most common etiologic agent, but infections also
diagnosis because the patient has external pruri- can result from C. tropicalis or C. glabrata. This
tus with erythema and swelling of the labia. The form of vaginal discharge usually is first seen with
presence of the characteristic thick, cottage intense pruritus on the external and internal geni-
cheese–like discharge with no odor in the vaginal talia. The discharge characteristics are odorless,
vault also supports this diagnosis. Budding yeast thick, cottage cheese–like appearance. Risk factors
and hyphae on the potassium hydroxide portion for developing vulvovaginal candidiasis include
of the slide, no other abnormalities on the wet recent antibiotic use, oral contraception use, preg-
preparation, and a vaginal pH between 4.5 and nancy, receptive oral sex, diabetes mellitus, or a
5.5 make this the most likely diagnosis. partner with candidiasis.
2. Bacterial vaginosis. The characteristic discharge in Physical examination usually reveals erythema
patients with bacterial vaginosis has an off-white and edema of the vulvovaginal area. The speculum

591
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

examination reveals a normal-appearing cervix with

a thick, cottage cheese–like discharge present in the Box 81-1 Criteria for the Diagnosis of
vaginal vault. The discharge has a pH of 4.5 to 5.5, Bacterial Vaginosis
and the microscopic examination shows budding
yeast or hyphae after applying potassium hydroxide Homogeneous, white noninflammatory vaginal
to the slide. discharge
Some treatment regimens for vulvovaginal Discharge coats vaginal wall
candidiasis are available over the counter. In some Clue cells present on microscopic examination
instances with a potential for resistant infections, Vaginal fluid pH, >4.5
the use of terconazole (Terazol) in a 3- or 7-day Positive “whiff” test
intravaginal course may improve the cure rate. Adapted from Workowski KA, Levine WC. Sexually
Fluconazole (Diflucan), 150 mg orally, in one dose, transmitted diseases treatment guidelines 2002:
is available to treat vulvovaginal candidiasis. Oral Centers for Disease Control and Prevention. MMWR
and vaginal treatments have similar cure rates, with Morb Mortal Wkly Rep 2002;51:1–80.
more side effects with the oral regimens (Watson et
al., 2002●A ).
Complicated vulvovaginal candidiasis is defined Bacterial vaginosis has been shown to cause
as four or more infections during 1 year. In these adverse outcomes in women who are pregnant.
cases, the intravaginal treatment should be expanded These include premature rupture of membranes,
to 10 to 14 days. If oral fluconazole is used, a repeated preterm labor, preterm birth, and postpartum
tablet must be given 3 days after the initial dose. This endometritis. The treatment of bacterial vaginosis
regimen for fluconazole also can be used in women during pregnancy has had inconsistent outcomes.
with severe infections. The CDC currently recommends that women who
Women with recurrent infections of vulvovagi- are at high risk for preterm delivery should be
nal candidiasis must be assessed for underlying treated (Workowski and Levine, 2002● A). Both
causes. This may include a screen for glucose intoler- metronidazole and clindamycin can be used during
ance or for immunocompromise, such as human pregnancy.
immunodeficiency virus testing.
Chlamydia Infection
Bacterial Vaginosis
More than 800,000 new cases of Chlamydia tra-
Bacterial vaginosis develops when the normal flora chomatis infections were reported in 2002. The
of the vagina is replaced with high concentrations of majority of the time, women with Chlamydia infec-
anaerobic bacteria. This is one of the most common
causes of vaginal discharge. Most women will be seen
initially with a malodorous vaginal discharge, but
approximately half will be asymptomatic. Box 81-2 Treatment Recommendations
The Centers for Disease Control and Prevention for Bacterial Vaginosis
(CDC) established criteria for the diagnosis of bacte-
Recommended Regimens
rial vaginosis (Workowski and Levine, 2002 ● A) (Box
81-1). Clue cells are epithelial cells that are coated Metronidazole (Flagy l), 500 mg orally, twice
with bacteria. The “whiff ” test is performed by per day for 7 days
adding 10% potassium hydroxide to the vaginal Metronidazole gel, 0.75%, one applicator
secretion. A positive test is the emission of a fishy intravaginal, once per day for 5 days
odor. Cultures of the vaginal discharge are not Clindamycin (cleocin) cream 2%, one appli-
needed because they are not specific and do not usu- cator intravaginally at bedtime for 7 days
ally assist establishing the diagnosis. A DNA probe
tests for high concentrations of Gardnerella vaginalis. Alternative Regimens
The CDC recommends a different treatment reg- Metronidazole, 2 g orally, in a one-time dose
imen for bacterial vaginosis than that used for vulvo- Clindamycin, 300 mg orally, twice per day for
vaginal candidiasis (Workowski and Levine, 2002● A)
7 days
(Box 81-2). Both oral and intravaginal regimens pro- Clindamycin ovules, 100 g intravaginally once
vide similar cure rates (Hanson et al., 2000● A).
at bedtime for 3 days
Patients taking metronidazole should be advised to
avoid alcohol consumption during treatment and for Adapted from Workowski KA, Levine WC. Sexually
24 hours after completing the course. Clindamycin transmitted diseases treatment guidelines 2002:
cream is oil based and has the potential to weaken Centers for Disease Control and Prevention. MMWR
latex condoms and diaphragms. Morb Mortal Wkly Rep 2002;51:1–80.

592
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

tions have no or minimal symptoms, but in some

cases, the infection will ascend the genitourinary Box 81-3 Treatment Regimens for
tract and cause PID. Uncomplicated Urogenital
If women are symptomatic with C. trachomatis Chlamydia
infections, the most common symptom is a mucoid
vaginal discharge that has little or no odor. In addi- Recommended
tion, they can have vaginal bleeding or spotting, Azithromycin (Zithromax), 1 g orally in a
lower abdominal pain, and irregular or heavy single dose
menses. A rare presentation for this infection is pleu- Doxycycline (Vibramycin), 100 mg, twice per
ritic right upper quadrant abdominal pain with or day for 7 days
without pelvic pain. The cervix will appear inflamed
and will have a yellow or cloudy mucoid discharge Alternative
from the os. The cervix tends be friable and bleeds
easily. Chlamydia infections in the lower genital tract Erythromycin base, 500 mg orally, 4 times per
do not cause vaginitis. day for 7 days
Currently two techniques are available to detect Erythromycin ethylsuccinate, 800 mg orally,
C. trachomatis infections—culture and nonculture. 4 times per day for 7 days
Culture techniques are considered the gold standard Ofloxacin (Floxin), 300 mg, twice per day for
but have been replaced in some instances by the non- 7 days
culture techniques. The new nonculture technique is Levofloxacin (Levaguin), 500 mg, once per day
nucleic acid amplification tests (NAATs). These tests for 7 days
have good sensitivity and specificity when compared Adapted from Workowski KA, Levine WC. Sexually
with cultures. NAAT techniques can be used to diag- transmitted diseases treatment guidelines 2002:
nose urogenital chlamydia by either an endocervical Centers for Disease Control and Prevention. MMWR
or a urine specimen. Morb Mortal Wkly Rep 2002;51:1–80.
Patients who have signs and symptoms sugges-
tive of salpingitis or PID should be evaluated by a
white blood cell count with a differential. In addition, The most common site for gonococcal infec-
a serum pregnancy test and pelvic ultrasound should tions is the endocervix. Symptoms include vaginal
be performed if ectopic pregnancy is a possibility. discharge, dysuria, abnormal vaginal bleeding, or
The current recommended treatment according to pelvic pain. The majority of women have few or no
the CDC for uncomplicated genital chlamydia infec- symptoms. The cervix on examination may appear
tions includes azithromycin or doxycycline (Workowski normal or may be inflamed with a mucopurulent
and Levine, 2002● A ) (Box 81-3). Both regimens are discharge from the os.
acceptable because they have similar cure rates and In addition to infecting the lower genital tract,
adverse effects (Lau and Qureshi, 2004● A). Azithromycin gonorrhea also can develop at other sites, either
has the benefit of being able to provide the patient with through direct or contiguous spread or by dissemi-
the one-time dose in the office. For patients who may nation through the bloodstream. These include
not be able to tolerate either azithromycin or doxycy- anorectal gonorrhea, conjunctivitis, perihepatitis
cline, the CDC has published alternative regimens (Fitz-Hugh-Curtis syndrome), pharyngitis, and
(Workowski and Levine, 2002● A ) (see Box 81-3). PID. Anorectal gonorrhea can result from direct
The CDC currently does not recommend sexual contact or contiguous spread from the
rescreening for chlamydia after completion of an vagina. Patients with this infection can be asympto-
antibiotic course unless the patient has persistent matic, have mild pruritus and mucoid discharge, or
symptoms or is pregnant (Workowski and Levine, have severe proctitis. Pharyngeal gonorrhea is
2002● A ). Because reinfection is a common problem, asymptomatic the majority of the time, but if
the CDC recommends that women with chlamydia symptoms are present, the patient tends to have a
infections should be rescreened 3 to 4 months after mild sore throat. Physical findings usually are an
antibiotic completion. The CDC also recommends erythematous pharynx, but in some cases, an
that women seen within 12 months after treatment exudative pharyngitis with oral ulcers may be seen.
who have not been screened should be reassessed for Gonococcal conjunctivitis develops after direct
chlamydia infection. contact and tends to have copious amounts of
purulent secretions from the eye.
Left untreated, gonococcal infections can
Gonorrhea Infection
develop into a disseminated infection. This occurs
Neisseria gonorrhoeae is one of the more common in two stages, with the first being bacteremic, in
STDs in the United States. The normal incubation which patients will have fever, chills, and typical skin
time between exposure and infection is 3 to 5 days. lesions. The skin lesions develop on the volar aspect

593
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

of the hands and plantar aspect of the feet, initially Hawaii), and in California, the CDC recommends
as small vesicles and then developing into pustules that fluoroquinalones should not be used. A substan-
with a hemorrhagic base and central necrosis. tial increase of fluoroquinalone-resistant N. gonor-
During this stage, patients also will have joint stiff- rhoeae has been seen in men who have sex with men,
ness and pain. The second stage is the septic arthri- so fluoroquinalones should not be used as first-line
tis stage, in which patients have a purulent synovial treatment in these cases (CDC, 2004● A).
effusion more commonly occurring in the knees, Patients with suspected disseminated gonococcal
ankles, and wrist. infections should be hospitalized for their initial par-
There are two different methods for detecting N. enteral treatment. Parenteral antibiotics should be con-
gonorrhoeae—culture and nonculture. The new non- tinued for 24 to 48 hours after clinical improvement
culture technique is NAAT, and in women with uro- begins and then switched to oral regimens for at least 1
genital gonorrhea, NAAT can be performed on either week (Workowski and Levine, 2002● A ) (see Box 81-4).
endocervical or urine specimens.
Treatment recommendations by the CDC for
Pelvic Inflammatory Disease
uncomplicated gonococcal infections of the cervix,
urethra, and rectum include oral and parenteral In women with infections in the lower genital tract, an
options (Workowski and Levine, 2002● A) (Box 81-4). ascending infection may cause acute salpingitis with or
Because of the increase in the incidence of fluoro- without endometritis, also known as PID. Symptoms
quinalone-resistant N. gonorrhoeae in individuals tend to have a subacute onset and usually develop dur-
who live in Asia, the Pacific Islands (including ing menses or the first 2 weeks of the menstrual cycle.
Symptoms may range from none to severe abdominal
pain with high fevers. Other symptoms include dys-
pareunia, prolonged menses, and intramenstrual
bleeding. Women in whom PID develops have signifi-
Box 81-4 Treatment Guidelines for cant increase in the risk for developing infertility.
Uncomplicated Gonococcal The CDC recommends that physicians maintain
Infections a low threshold for diagnosing PID (Workowski and
Levine, 2002● A ). It recommends empiric treatment in
Uncomplicated women at risk for STDs if they have any of the min-
Cefixime (Suprax), 400 mg orally, as a single dose imal criteria (Box 81-5). Additional and specific cri-
Ceftriaxone (Rocephin), 125 mg IM, as a single dose teria to assist physicians in establishing the diagnosis
Ciprofloxacin (Cipro), 500 mg orally, as a single of PID have been published (see Box 81-5).
dose A patient with PID can be treated as an outpa-
Levofloxacin (Levaguin), 250 mg orally, as a tient if the patient does not meet any of the criteria
single dose for hospitalization (Workowski and Levine, 2002● A)

Ofloxacin (Floxin), 500 mg orally, as a single dose (Box 81-6). The options for outpatient treatment
include two regimens that are equally efficacious
Disseminated with regard to cure rates (Table 81-1). If patients
with PID meet any of the criteria for hospitalization,
Recommended parenteral parenteral antibiotic therapy is indicated.
Ceftriaxone, 1 g IM or IV, q24h
Alternative parenteral
Cefotaxime (Claforan), 1 g IV, q8h Trichomoniasis
Ciprofloxacin, 400 mg, q12h The protozoan Trichomonas vaginalis is the etiologic
Ofloxacin, 400 mg IV, q12h agent for trichomoniasis, which is considered an STD.
Levofloxacin, 250 mg IV, daily The incubation period is 3 to 21 days after exposure.
Spectinomycin (Trobicin), 2 gm IM, q12h Women with a history of multiple sex partners or sex-
Oral Regimen: Can be started 24–48 hr after ual activity, or who are currently pregnant or
improvement begins, and ≥1 week of anti- menopausal, are at increased risk for this infection.
microbial therapy must be completed The majority of women with trichomoniasis
Cefixime, 400 mg, twice daily have no symptoms. If symptoms are present, they
Ciprofloxacin, 500 mg, twice daily include a diffuse, malodorous, yellow-green vaginal
Ofloxacin, 400 mg, twice daily discharge, vaginal soreness, and dyspareunia.
Levofloxacin, 500 mg, once daily Because the vaginal pH changes around the time of
Adapted from Workowski KA, Levine WC. Sexually menses, women are at risk for trichomoniasis devel-
transmitted diseases treatment guidelines 2002: oping during that period. The discharge may start
Centers for Disease Control and Prevention. MMWR during or immediately after menses and may be
Morb Mortal Wkly Rep 2002;51:1–80. exacerbated during this time.

594
 Chapter 81 Vaginal Discharge (Vulvovaginal Candidiasis)

Box 81-5 Diagnostic Criteria for Pelvic Box 81-6 Hospitalization Criteria for
Inflammatory Disease Pelvic Inflammatory Disease

Minimum Criteria Unresponsive to oral antimicrobial therapy

Cervical motion tenderness or Pregnancy
Uterine/adnexal tenderness Severe illness (i.e., nausea, vomiting or high
fever)
Additional Criteria Surgical emergencies cannot be excluded
Tubo-ovarian abscess present
Abnormal cervical or vaginal mucopurulent Unable to follow or tolerate outpatient oral
discharge regimen
Documentation of gonorrhea or chlamydia
infection Adapted from Workowski KA, Levine WC. Sexually
Elevated C-reactive protein transmitted diseases treatment guidelines 2002:
Centers for Disease Control and Prevention. MMWR
Elevated erythrocyte sedimentation rate
Morb Mortal Wkly Rep 2002;51:1–80.
Oral temperature >38.3˚C (>101˚F)
White blood cells present on saline
preparation of vaginal secretions Physical findings consistent with trichomoniasis
include a copious vaginal discharge that is yellow-
Specific Criteria green or gray, frothy, and malodorous. The cervix can
be inflamed and have a “strawberry” appearance, red
Endometrial biopsy with evidence of endometritis and inflamed with punctations. The vaginal pH will be
Laproscopic abnormalities consistent with 5 or greater, and on microscopic examination, 10 white
pelvic inflammatory disease blood cells per high-power field will be seen, with
Transvaginal ultrasound or MRI showing mobile trichomonads. Cultures are indicated only
thickened, fluid-filled tubes with or without when the diagnosis of trichomoniasis is uncertain.
free pelvic fluid or tubo-ovarian complex The current CDC treatment recommendation
Adapted from Workowski KA, Levine WC. Sexually is metronidazole, 2 g, in a single dose (Workowski
transmitted diseases treatment guidelines 2002: and Levine, 2002 ● A ). For those who cannot tolerate
Centers for Disease Control and Prevention. MMWR the one-time dose, the alternative is metronidazole,
Morb Mortal Wkly Rep 2002;51:1–80. 500 mg, twice a day for 7 days. Follow-up after treat-
ment is not necessary unless symptoms persist. If the
infection persists or recurs, the recommendation is
to treat with metronidazole, 500 mg twice per day,
for 5 days. Those who experience treatment failure

Table 81-1 PID Treatment Regimens

Parenteral Cefotetan (Cefotan), 2 g IV, q12h
or
Cefoxitin (Mefoxin), 2 g IV, q6h
and
Doxycycline (Vibramycin) 100 mg orally or IV, q12h
Oral Regimen A Ofloxacin (Floxin), 400 mg orally, twice daily
or
Levofloxacin (Levaquin), 500 mg, once daily
with or without
Metronidazole (Flagyl), 500 mg, bid
Oral Regimen B Ceftriaxone (Rocephin), 250 mg IM, in a single dose
or
Cefoxitin (Mefoxin), 2 g IM, plus Probenecid, 1 g orally, in a single dose
and
Doxycycline, 100 mg orally, twice daily
with or without
Metronidazole, 500 mg, twice daily

All oral regimens must be given for 14 days.

Adapted from Workowski KA, Levine WC. Sexually transmitted diseases treatment guidelines 2002: Centers for
Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 2002;51:1–80.

595
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

after this course should be given metronidazole, 2 g

Material Available on Student Consult
orally, once per day for 3 days. Because this is an
STD, it is important to treat the patient’s partner Review Questions and Answers about Vulvovaginal
(Forna, and Gulmezoglu, 2003● A ). Candidiasis

REFERENCES
Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal Lau CY, Qureshi AK. Azithromycin versus doxycycline for
complaints. JAMA 2004;291:1368–1379.● B genital chlamydia infections: A meta-analysis of ran-
Centers for Disease Control and Prevention. Increases in domized clinical trials (structured abstract). In The
fluoroquinalone-resistant Neisseria gonorrhoeae among Cochrane Library, Issue 2, 2004. DARE 2002217.● A
men who have sex with men: United States, 2003, and Watson MC, Grimshaw JM, Bond CM, Mollison J,
revised recommendations for gonorrhea treatment, Ludbrook A. Oral versus intra-vaginal imidazole and
2004. MMWR Morb Mortal Wkly Rep 2004;53: triazole anti-fungal agent for the treatment of uncom-
335–338.● A plicated vulvovaginal candidiasis (thrush): A systematic
Forna F, Gulmezoglu AM. Intervention for treating tri- review. Br J Obstet Gynecol 2002;109:85–95.● A
chomoniasis in women. Cochrane Database Syst Rev Workowski KA, Levine WC. Sexually transmitted diseases
2003;CD000218.● A treatment guidelines 2002: Centers for Disease Control
Hanson JM, McGregor JA, Hillier SL, et al. Metronidazole and Prevention. MMWR Morb Mortal Wkly Rep
for bacterial vaginosis: A comparison of vaginal gel vs. 2002;51:1–80.● A
oral therapy. J Reprod Med 2000;45:889–896.● A

C h a p t e r

82 Lower Abdominal Pain

(Pelvic Inflammatory Disease)
Ann M. Aring

KEY POINTS

1. Failure to isolate a sexually transmitted agent from 3. According to the 2002 guidelines from the
the cervix does not rule out pelvic inflammatory Centers for Disease Control and Prevention,
disease (PID). PID is a polymicrobial infection empirical treatment of PID should be initiated in
whose causative agents may include gram-positive sexually active women if the following mini-
and gram-negative anaerobic organisms, gram- mum criteria are present and no other cause for
positive and gram-negative rods, and cocci, as the illness can be identified: uterine/adnexal
well as sexually transmitted pathogens such as tenderness or cervical motion tenderness.
Chlamydia trachomatis and Neisseria gonorrhoeae. 4. The recommended drug regimens for the treat-
2. A high index of suspicion is essential for diagnos- ment of PID require two or more agents. The
ing PID. No single physical examination finding data are insufficient to recommend
can be used to suggest PID. No individual blood azithromycin in the treatment of PID.
test or combination of blood tests can reliably 5. Fertility is better preserved when patients are
diagnose PID. treated within 48 hours of symptom onset.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

596
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

after this course should be given metronidazole, 2 g

Material Available on Student Consult
orally, once per day for 3 days. Because this is an
STD, it is important to treat the patient’s partner Review Questions and Answers about Vulvovaginal
(Forna, and Gulmezoglu, 2003● A ). Candidiasis

REFERENCES
Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal Lau CY, Qureshi AK. Azithromycin versus doxycycline for
complaints. JAMA 2004;291:1368–1379.● B genital chlamydia infections: A meta-analysis of ran-
Centers for Disease Control and Prevention. Increases in domized clinical trials (structured abstract). In The
fluoroquinalone-resistant Neisseria gonorrhoeae among Cochrane Library, Issue 2, 2004. DARE 2002217.● A
men who have sex with men: United States, 2003, and Watson MC, Grimshaw JM, Bond CM, Mollison J,
revised recommendations for gonorrhea treatment, Ludbrook A. Oral versus intra-vaginal imidazole and
2004. MMWR Morb Mortal Wkly Rep 2004;53: triazole anti-fungal agent for the treatment of uncom-
335–338.● A plicated vulvovaginal candidiasis (thrush): A systematic
Forna F, Gulmezoglu AM. Intervention for treating tri- review. Br J Obstet Gynecol 2002;109:85–95.● A
chomoniasis in women. Cochrane Database Syst Rev Workowski KA, Levine WC. Sexually transmitted diseases
2003;CD000218.● A treatment guidelines 2002: Centers for Disease Control
Hanson JM, McGregor JA, Hillier SL, et al. Metronidazole and Prevention. MMWR Morb Mortal Wkly Rep
for bacterial vaginosis: A comparison of vaginal gel vs. 2002;51:1–80.● A
oral therapy. J Reprod Med 2000;45:889–896.● A

C h a p t e r

82 Lower Abdominal Pain

(Pelvic Inflammatory Disease)
Ann M. Aring

KEY POINTS

1. Failure to isolate a sexually transmitted agent from 3. According to the 2002 guidelines from the
the cervix does not rule out pelvic inflammatory Centers for Disease Control and Prevention,
disease (PID). PID is a polymicrobial infection empirical treatment of PID should be initiated in
whose causative agents may include gram-positive sexually active women if the following mini-
and gram-negative anaerobic organisms, gram- mum criteria are present and no other cause for
positive and gram-negative rods, and cocci, as the illness can be identified: uterine/adnexal
well as sexually transmitted pathogens such as tenderness or cervical motion tenderness.
Chlamydia trachomatis and Neisseria gonorrhoeae. 4. The recommended drug regimens for the treat-
2. A high index of suspicion is essential for diagnos- ment of PID require two or more agents. The
ing PID. No single physical examination finding data are insufficient to recommend
can be used to suggest PID. No individual blood azithromycin in the treatment of PID.
test or combination of blood tests can reliably 5. Fertility is better preserved when patients are
diagnose PID. treated within 48 hours of symptom onset.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

596
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

INITIAL VISIT Objective

Physical Examination
Subjective Ms. W. is a well-developed, thin, older adolescent.
Patient Identification and Presenting Her blood pressure is 124/82, pulse is 72 and regu-
Problem lar, weight is 130 pounds, and height is 5 feet 4
Gabrielle W. is a 19-year-old white teenager who inches. Abdominal examination reveals normal
presents to the clinic reporting lower abdominal pain bowel sounds, mild diffuse lower abdominal tender-
for 1 week. Her last menstrual period occurred ness, no hepatosplenomegaly, no rebound, and no
3 weeks ago. guarding. Gynecologic examination shows Tanner
stage 5 external genitalia with several external geni-
tal warts noted, normal vaginal tissue, and a multi-
Medical History parous cervical os. A mucopurulent discharge is
Ms. W. entered menarche at age 12. Her menses are seen. The cervix is friable and bleeds easily with
regular, with 28- to 30-day cycles. Her age at first manipulation. Her uterus is anteverted and of nor-
intercourse was 15 years. She had her first baby at mal size. She does have cervical motion tenderness.
age 16 years and a second baby at age 18. Cultures Adnexal examination reveals bilateral tenderness.
for Chlamydia were positive during both pregnan- Her rectal examination is normal, with a negative
cies. The infections were treated successfully, with fecal occult blood test.
two documented negative cultures for cure. She
delivered vaginally at term with both pregnancies.
She did not breast-feed or use contraceptives. Her Assessment
surgical history includes the removal of four Working Diagnosis
impacted wisdom teeth last year. She does not have The working diagnosis is pelvic inflammatory dis-
any chronic medical problems and does not take any ease (PID), most likely from a sexually transmitted
prescription medications. disease (STD).

Family History Differential Diagnosis

Ms. W.’s mother has type 2 diabetes mellitus and The differential diagnosis includes appendicitis,
hypertension, and underwent a hysterectomy for cer- ovarian torsion, hemorrhagic or ruptured cyst,
vical cancer. Her father has type 2 diabetes and endometritis, irritable bowel syndrome, ectopic
hypercholesterolemia. She has three sisters and one pregnancy, and PID (Box 82-1).
brother, who are all healthy. There is no family his-
tory of breast cancer or colon cancer. Ms. W.’s chil- Discussion Pelvic inflammatory disease manifests
dren are healthy. with infection and inflammation of the upper female
genital tract, including any combination of
endometritis, salpingitis, tubo-ovarian abscess, and
Health Habits
pelvic peritonitis (Centers for Disease Control and
Ms. W. started smoking at age 14. She currently C ). PID is a common condi-
Prevention [CDC], 2002●
smokes half a pack of cigarettes daily. She also
tion that affects about 8% of women during their
reports weekly marijuana use “to relax.” She drinks
reproductive years (Ness et al., 2002● A). Recent esti-
one to two beers each week. Ms. W. estimates that she
mates from the CDC indicate that approximately
has had more than 30 lifetime sexual partners. She
780,000 cases of acute PID are diagnosed annually
has had three sexual partners within the past month.
in the United States (Beigi and Wisenfeld, 2003● B ).
She does not use condoms.
Several demographic, behavioral, and contraceptive
factors are identified as risk factors for PID (Box 82-2).
Social History
Ms. W. lives with her mother, three younger siblings,
and her own two children. She dropped out of high
school but did earn her GED certificate. She is cur- Box 82-1 Differential Diagnosis of
rently unemployed. She enjoys spending time with Pelvic Inflammatory Disease
her friends and watching television.
Appendicitis
Ectopic pregnancy
Review of Systems
Ovarian torsion
Ms. W. reports pelvic pain, dyspareunia, vaginal dis-
Hemorrhagic or ruptured ovarian cyst
charge, and low-grade fever. She denies abnormal
Endometriosis
vaginal bleeding, dysuria, nausea, vomiting, diar-
Irritable bowel syndrome
rhea, constipation, or back pain.

597
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

treatment (Beigi and Wisenfeld, 2003● B ; Eschenbach

Box 82-2 Risk Factors for Pelvic et al., 1977●
B ).
Inflammatory Disease Menses also may increase the risk of PID since
retrograde flow may spread infection from the uterus
Young age at first intercourse to the fallopian tubes. Classically, gonococcal PID
Multiple sexual partners occurs within a week of the onset of menses
Increased frequency of sexual intercourse (Eschenbach et al., 1977● B ). The relationship between
Prior history of PID PID and douching has also been evaluated, with one
Sexually transmitted infection study showing that twice as many women with PID
No barrier contraceptive use had douched recently (Scholes et al., 1993 ● B).

Adapted from Beigi RH, Wisenfeld HC. Pelvic inflam- The mechanical pressure of douching was postu-
matory disease: New diagnostic criteria and treat- lated to contribute to upper genital tract infections. In
ment. Obstet Gynecol Clin North Am 2003;30: addition, a change in the pH may also contribute to an
777–793. environment that allows an infection to flourish.

Plan
There is considerable overlap between the risk of Diagnostic
acquiring an STD and the risk for PID. Women N. gonorrhoeae and Chlamydia cultures were
younger than age 25 years account for more than obtained. KOH and wet prep slides showed 10 white
75% of all cases of PID and have a 10 times greater blood cells (WBCs) per high power field. No tri-
incidence compared with older women (Peipert chomonas, buds, or hyphae were observed under the
et al., 2000● A). Sexually active adolescents are more microscope. A urine pregnancy test was negative.
than three times more likely to have PID than A complete blood cell (CBC) count, erythrocyte sed-
women of similar activity who are 25 to 29 years old imentation rate (ESR), and C-reactive protein (CRP)
(CDC, 2002● C ). Studies have also shown at least a level were determined. In addition, Ms. W. was
twofold increase in the risk for PID with a history of scheduled for pelvic computed tomography (CT).
prior tubal infection (Beigi and Wisenfeld, 2003● B ).
Physiologically, the risk of infection with PID is Discussion The diagnosis of PID is often difficult to
accelerated in adolescents by the columnar epithe- establish. A high index of suspicion is essential for
lium exposure found in the adolescent cervix and the optimizing patient outcomes. In the past, the CDC
greater permeability of the cervical mucous plug. recommended diagnosis and treatment of women
The risk of acquiring PID from insertion of an who met all three major criteria (lower abdominal
intrauterine device (IUD) occurs primarily in the tenderness, cervical motion tenderness, and bilateral
first 3 months after insertion (Beigi and Wisenfeld, adnexal tenderness) plus one of the minor support-
2003● B ). ing criteria (temperature >38.3˚C [101˚F] orally,
PID is thought to arise from an ascending infec- mucopurulent cervicitis, elevated ESR or CRP level,
tion of the female genital tract. PID is a polymicro- documented cervical infection with C. trachomatis or
bial infection whose causative agents may include N. gonorrhoeae, or the presence of an inflammatory
gram-positive and gram-negative anaerobic organ- mass on pelvic ultrasound) (CDC, 1998● C ). Since
isms, gram-positive and gram-negative rods, and many women with PID have subtle signs and symp-
cocci, as well as sexually transmitted pathogens such toms, the 2002 guidelines are less stringent. The 2002
as C. trachomatis and N. gonorrhoeae. Approximately CDC guidelines state that empirical treatment of PID
two thirds of all proven cases of PID involve either C. should be initiated in sexually active women if the fol-
trachomatis or N. gonorrhoeae (Beigi and Wisen- lowing minimum criteria are present and no other
feld, 2003● B ). Bacterial vaginosis–associated micro- cause for the illness can be identified: uterine/adnexal
flora are also identified in the upper genital tract in tenderness or cervical motion tenderness. A recent
most cases of PID (Beigi and Wisenfeld, 2003● B; study showed that when the CDC’s new criteria for
CDC, 2002● C ). Therefore, PID cannot be ruled out diagnosing PID were used, the prevalence doubled
even if a sexually transmitted organism is not and the incidence tripled (Risser et al., 2004● B ).
isolated. PID is suggested in the patient’s history by lower
Barrier contraception reduces the risk for PID abdominal pain, fever, vaginal discharge, onset of
because it protects against some cervical infections. symptoms after the menstrual cycle, and abnormal
Oral contraceptive users also have a lower risk for vaginal bleeding. No single finding on physical
developing PID. This may be explained by the fact examination can be used to suggest PID. Many labo-
that there is a higher detection rate associated with ratory studies have been evaluated for their useful-
oral contraceptive users and consequently earlier ness in predicting PID. The CDC makes no specific

598
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

recommendation for the use of a specific blood test does not improve as expected. Although computed
in the diagnosis of PID (CDC, 2002● C ). tomography is not specifically mentioned in the
No individual blood test or combination of CDC guidelines, this imaging technique can also
blood tests can reliably diagnose PID (Hall et al., identify pathology consistent with PID.
2004● A). Individual tests do not appear to signifi-
cantly improve diagnostic accuracy (Hall et al., Therapeutic
2004● A). The WBC count is a nonspecific indicator Ms. W. is started on ofloxacin (Floxin), 400 mg orally
of infection and is elevated in less than half of twice a day for 14 days, and metronidazole (Flagyl),
women with PID (Beigi and Wisenfeld, 2003● B ). In 500 mg orally twice a day for 14 days.
addition, the ESR and CRP level have been studied
in PID, with the CRP level having a slightly higher Discussion A high index of suspicion and a low
sensitivity and specificity (Beigi and Wisenfeld, threshold for treatment are important for managing
2003● B ). The absence of WBCs on a vaginal wet patients with PID. The CDC has established treat-
smear has a high negative predictive value (94.5%) ment guidelines for patients that provide broad-
(Beigi and Wisenfeld, 2003● B ; Peipert et al., 2000● A). spectrum coverage. According to the CDC, all
Three or more WBCs per high power field on a vagi- regimens should be effective against N. gonorrhoeae
nal wet smear has a sensitivity of 87% to 91% (Beigi and C. trachomatis, and should also include coverage
and Wisenfeld, 2003● B ; Yudin et al., 2003● B ). The for anerobic organisms and gram-negative rods
combination of WBC count, CRP level, ESR, and (CDC, 2002● C ). Because no single drug meets these
vaginal WBCs can reliably exclude PID if results on requirements, the recommended drug regimens for
all four tests are normal. Combining CRP and ESR the treatment of PID require two or more agents
is helpful in excluding PID (Hall et al., 2004● B ).
The definitive diagnosis of PID requires more
invasive testing with transvaginal ultrasound (US),
endometrial biopsy, or laparoscopy. US features con-
sistent with PID include large, dilated fallopian tubes
or the presence of a tubo-ovarian abscess. Pelvic US Table 82-1 Oral Treatment of Pelvic
has been well studied in PID and is useful for identi- Inflammatory Disease
fying tubal and ovarian pathology. In one study,
Regimen A Regimen B
endovaginal US showing a thickened, fluid-filled fal-
lopian tube with or without free pelvic fluid had a Oflaxacin (Floxacin), Ceftriaxone
sensitivity of 85%, a specificity of 100%, and a pre- 400 mg PO bid for (Rocephin), 250 mg
dictive value above 95% for the diagnosis of 14 days IM in a single dose
endometritis (Boardman et al., 1997● B). Another or or
study reported that endovaginal US had a high speci- Levofloxacine (Levaquin), Cefoxitin (Mefoxin),
ficity (97%) but a low sensitivity (32%) in the diag- 500 mg PO qd for 2 g IM in a single
nosis of upper genital tract infection (Beigi and 14 days dose, and
with or without Probenecid, 1 g PO
Wisenfeld, 2003● B ; Boardman et al., 1997● B ).
Metronidazole (Flagyl), in a single
Endometrial biopsy is helpful for making a diag- 500 mg PO bid for concurrent dose
nosis of PID but has limited clinical use because of a 14 days or
delay in reading and reporting results. One published Other parenteral
study showed that the presence of five or more neu- third-generation
trophils per 400 power field and one or more plasma cephalosporin
cells per 120 power field had a sensitivity of 92% and a (e.g., ceftizoxime
specificity of 87% for the prediction of upper genital [Cefizox] or
tract microbial infection (Beigi and Wisenfeld, 2003● B ). cefotaxime
Clinical diagnosis has a positive predictive value [Claforan])
plus
of 65% to 90% compared with laparoscopy (CDC, Doxycycline
2002● C ; Hall et al., 2004● C ). Most experts agree that
(Vibramycin), 100
laparoscopy is still the gold standard for establishing mg PO bid for 14
the diagnosis of PID (Beigi and Wisenfeld, 2003● B ). days
Findings consistent with PID on laparoscopy include with or without
edema and erythema of the fallopian tubes, purulent Metronidazole, 500
exudate in the fallopian tubes, and peritubal adhe- mg PO bid for 14
sions. Because of cost and surgical risk, laparoscopy days
is not a practical screening tool. However, Adapted from CDC. 2002 guidelines for treatment
laparoscopy is an important technique when the of sexually transmitted diseases. MMWR Morb
diagnosis of PID is in question or when the patient Mortal Wkly Rep 2002;51:48–52.

599
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

Table 82-2 Parenteral Treatment of Objective

Pelvic Inflammatory Disease Physical Examination
Regimen A Regimen B Her blood pressure is 132/85 mm Hg, pulse is 100
and regular, and temperature is 38˚C (100.5˚F)
Cefotetan (Cefotan), Clindamycin (measured orally). She has moderate lower abdomi-
2 g IV q12h (Cleocin), 900 mg nal tenderness on palpation. No rebound tenderness
or IV q8h
Cefoxitin (Mefoxin), plus
is noted. She does have some involuntary guarding.
2 g IV q6h Gentamicin Pelvic examination shows bilateral adnexal tender-
plus (Garamycin), ness and cervical motion tenderness. Copious puru-
Doxycycline (Vibramycin), loading dose IV lent discharge is seen in the vaginal vault.
100 mg PO or IV q12h or IM (2 mg/kg
body weight), Laboratory Tests
followed by a
maintenance
Cultures performed earlier for N. gonorrhoeae and
dose of 1.5 mg/kg Chlamydia are negative. A CBC count showed WBCs
q8h at 17.0 (normal, 4.5 to 11) with 66% neutrophils,
27% lymphocytes, 4% monocytes, and 2%
Adapted from CDC. 2002 guidelines for treatment eosinophils. Hemoglobin is 13.5 (normal, 12.0 to 16.0
of sexually transmitted diseases. MMWR Morb g/dL), CRP is 12.0 (normal, 0 to 10.0 mg/L), and ESR
Mortal Wkly Rep 2002;51:48–52. is 18 (normal, 0 to 15 mm/hr). A hepatitis B screen
was negative. Results of a rapid plasma reagin test and
HIV test are also negative. The pelvic CT scan shows
free fluid in the pelvis and dilated fallopian tubes
bilaterally, which suggests PID (Figs. 82-1 to 82-3).
(Tables 82-1 and 82-2). Several recent studies have The radiologist recommends pelvic US to better
evaluated the use of azithromycin (Zithromax) in the assess for PID.
treatment of PID. However, the data are not suffi-
cient to recommend azithromycin in the treatment
of PID (CDC, 2002● C ). Results from the Pelvic
Assessment and Plan
Inflammatory Disease Evaluation and Clinical Health
(PEACH) trial showed no difference in outcomes Since Ms. W. has nausea and vomiting and is unable
between inpatient and outpatient treatment in to tolerate outpatient therapy, she is admitted to the
women with mild to moderate PID (Ness et al., hospital and started on cefoxitin (Mefoxin), 2 g intra-
2002● A). Fertility is better preserved when patients venously (IV) every 6 hours, and doxycycline
are treated within 48 hours of symptom onset (Beigi (Vibramycin), 100 mg IV every 12 hours. The pelvic
and Wisenfeld, 2003● B ; Hollie and Workowski, US shows inflammation of the fallopian tubes, nor-
2003● B ). mal ovaries, and purulent peritoneal free fluid (Figs.
82-4 and 82-5), but no evidence of a tubo-ovarian
Patient Education abscess. Since Ms. W.’s condition is not responding
The patient is counseled regarding safer sex prac- clinically to treatment, laparoscopy is performed and
tices, STDs, and the use of barrier contraceptives. shows a tubo-ovarian abscess and peritoneal free
Hepatitis B vaccination is offered, as well as syphilis fluid (Figs. 82-6 and 82-7). The abscess is drained
and HIV testing. No douching is also discussed surgically.
because douching may flush bacteria higher into
the genital tract and mask the discharge that may
Discussion
signal a problem. The importance of a 48-hour fol-
low-up visit to check the response to treatment is Close follow-up of outpatients within 24 to 48 hours
emphasized. after treatment is started is crucial. Patients who
fail to improve after initiation of therapy require
hospitalization, additional diagnostic testing to
FOLLOW-UP VISIT reconfirm the diagnosis, and possibly surgical inter-
vention (Beigi and Wisenfeld, 2003● B ; CDC, 2002● C ).

Subjective Additional criteria for hospitalization include preg-

nancy, nausea and vomiting, tubo-ovarian abscess,
Ms. W. returns for her follow-up visit in 2 days. She and inability to tolerate outpatient therapy (Box 82-
reports continuing lower abdominal pain, low-grade 3). Women older than 35 years who are hospitalized
fever, and nausea. She has tried to take the oral with PID are more likely to have a complicated
antibiotics but cannot keep them down. course (CDC, 2002● C ; Jamieson et al., 2000●
B ). Only

600
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

Uterus

Abundant free fluid

Figure 82-1 Pelvic CT scan showing abundant free fluid around the uterus.

Uterus

Ovarian cysts
or tubo-ovarian
abscesses

Cul-de-sac fluid

Figure 82-2 Pelvic CT scan shoping enlarged fallopian tubes and cul-de-sac fluid.

20% to 25% of PID patients treated in the United and Wisenfeld, 2003● B ). Tubo-ovarian abscesses are
States are hospitalized (Hollie and Workowski, also polymicrobial, with anaerobic organisms pre-
2003●B ). dominating. They may manifest with atypical
Tubo-ovarian abscess (TOA) is a serious acute abdominal pain, low-grade fevers, and weight loss.
complication of PID and is estimated to occur in Another acute complication of PID is perihep-
33% of women hospitalized with acute PID (Beigi atitis (Fitz-Hugh-Curtis syndrome). The presenting

601
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

Hydrosalpinx

Figure 82-3 Pelvic CT scan showing hydrosalpinx.

Uterus Fluid with

echogenic
debris

Figure 82-4 Longitudinal endovaginal pelvic ultrasound image showing the uterus and surrounding echogenic free
fluid.

complaint is right upper quadrant pain, which is due Wisenfeld, 2003● B). Characteristic stringlike adhe-
to perihepatic inflammation and adhesions between sions are seen on laparoscopy.
the liver and anterior abdominal wall. Liver function The long-term sequelae of PID include tubal
test results may also be elevated. This complication is factor infertility, ectopic pregnancy, pelvic adhe-
seen in 5% to 20% of all women with PID (Beigi and sions, and chronic pelvic pain. A study by Westrom

602
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

Increased doppler Hydrosalpinx Free fluid

flow from inflammation

Figure 82-5 Longitudinal endovaginal pelvic ultrasound image with increased Dopper flow from inflammation,
hydrosalpinx, and free fluid.

Figure 82-6 An enlarged fallopian tube corresponding

to tubo-ovarian abscess was seen on laparoscopy.

(1980) showed a 10 times greater risk of infertility

in women who had had PID compared with con-
trols. In addition, the risk of infertility is directly
related to the number of episodes of PID. With one
episode of PID, a woman’s risk of infertility is 11%.
After two episodes, the risk rises to 34%, and with
three or more episodes the risk rises to 54% (Hollie
and Workowski, 2003● B ). Scarring of the fallopian
tubes also increases the risk for ectopic pregnancy,
with a 7 to 10 times greater rate of ectopic preg-
nancy seen in women with a prior history of PID
(Beigi and Wisenfeld, 2003● B ). Rates of ectopic
pregnancy also increase with successive episodes of
PID. Increasing severity of infection also seems to
predict a higher chance of ectopic pregnancy (Beigi Figure 82-7 Abundant free fluid was also seen on
and Wisenfeld, 2003● B ). Scarring from PID can laparoscopy.

603
 Chapter 82 Lower Abdominal Pain (Pelvic Inflammatory Disease)

produce pelvic adhesions that may result in

Box 82-3 Criteria for Hospitalization for chronic pelvic pain. Approximately one third of
Pelvic Inflammatory Disease women with PID develop chronic pelvic pain and
associated depression, dyspareunia, postcoital
Surgical emergencies such as appendicitis can- pain, and vaginismus (Haggerty et al., 2003●
A).
not be excluded
Pregnancy
No response to oral antibiotics Material Available on Student Consult
Unable to follow or tolerate oral antibiotic reg-
imen Review Questions and Answers about Pelvic
Nausea, vomiting, high fever, and severe illness Inflammatory Disease
Tubo-ovarian abscess present
Adapted from CDC. 2002 guidelines for treatment of
sexually transmitted diseases. MMWR Morb Mortal
Wkly Rep 2002;51:48–52.

REFERENCES
Beigi RH, Wisenfeld HC. Pelvic inflammatory disease: New talized with pelvic inflammatory disease. Infect Dis
diagnostic criteria and treatment. Obstet Gynecol Clin Obstet Gynecol 2000;8:88–93.● B
North Am 2003;30:777–793.● B Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpa-
Boardman LA, Peipert JF, Brody JM, et al. Endovaginal tient and outpatient treatment strategies for women
sonography for the diagnosis of upper genital tract with pelvic inflammatory disease: Results from the
infection. Obstet Gynecol 1997;90:54–57.● B Pelvic Inflammatory Disease Evaluation and Clinical
Centers for Disease Control and Prevention, 1998 guidelines Health (PEACH) Randomized Trial. Am J Obstet
for treatment of sexually transmitted diseases. MMWR Gynecol 2002;186:929–937.● A
Morb Mortal Wkly Rep 1998;47:1–116.● C Peipert JF, Ness RB, Soper DE, Bass B. Association of lower
Centers for Disease Control and Prevention, 2002 guide- genital tract inflammation with objective evidence of
lines for treatment of sexually transmitted diseases. endometritis. Infect Dis Obstet Gynecol 2000;8:83–87.● A
MMWR Morb Mortal Wkly Rep 2002;51:48–52.● C Risser WL, Cromwell PF, Bortot AT, Risser JMH. Impact of
Eschenbach DA, Harnisch JP, Holnes KK. Pathogenesis of new diagnostic criteria on the prevalence and incidence
acute pelvic inflammatory disease: Role of contracep- of pelvic inflammatory disease. J Pediatr Adolesc
tion and other risk factors. Am J Obstet Gynecol Gynecol 2004;17:39–44.● B
1977;128:838–850.● B Scholes D, Daling JR, Stergachis A, et al. Vaginal douching
Haggerty CL, Schulz R, Ness RB. Lower quality of life as risk factor for acute pelvic inflammatory disease.
among women with chronic pelvic pain after pelvic Obstet Gynecol 1993;81:601–606.● B
inflammatory disease. Obstet Gynecol 2003;102 Westrom L. Incidence, prevalence, and trends of acute
(5 Pt 1):934–939.● A pelvic inflammatory disease and its consequences in
Hall MN, Leach L, Beck E. Which blood tests are most industrialized countries. Am J Obstet Gynecol 1980;
helpful in evaluating pelvic inflammatory disease? 138:880–892.
J Fam Pract 2004;53:326, 330–331.● A Yudin MH, Hillier SL, Wisenfeld, HD, et al. Vaginal poly-
Hollie LM, Workowski K. Treatment of sexually transmit- morphonuclear leukocytes and bacterial vaginosis as
ted diseases in women. Obstet Gynecol Clin North Am markers for histologic endometritis among women
2003;30:751–775.● B without symptoms of pelvic inflammatory disease. Am
Jamieson DJ, Duerr AM, Macasaet MA, et al. Risk factors J Obstet Gyencol 2003;188:318–323.● B
for a complicated clinical course among women hospi-

604
 C h a p t e r

83 Breast Cancer

Virginia D. Aguila

Medical History
KEY POINTS Mrs. P. had menarche at age 11, first pregnancy at age
20, and last pregnancy at age 26. She used oral con-
1. A new palpable mass in a patient with traceptives from ages 27 to 35 and had a tubal liga-
advanced age, a history of exposure to exoge- tion at age 35. She was menopausal at 53 and took
nous estrogen, a weak family history of breast Prempro for 5 years. At age 58, she underwent total
cancer despite several annual negative mammo- abdominal hysterectomy with bilateral salpingo-
grams and a clinical breast examination should oophorectomy with removal of large left benign
increase our index of suspicion for malignancy. ovarian mucinous cystadenoma. Subsequently, she
2. Mammography and clinical breast examinations was started on Premarin but discontinued use a year
remain the cornerstone for the screening of ago. She has yearly physical examinations and mam-
breast cancer. mograms and performs monthly self-breast exami-
3. Minimally invasive breast biopsy (MIBB), the nations. Last year’s mammogram was normal. Other
least surgical procedure, provided the patient medical conditions include hypertension, hypercho-
with a diagnosis and tumor marker status and lesterolemia, type 2 diabetes mellitus, and asthma.
aided in treatment planning.
4. Sentinel node mapping, now the standard of Medications
care for axillary nodal status in patients with Enalapril, 20 mg; Pravachol, 40 mg; albuterol
breast cancer, was positive; therefore, full axil- metered-dose inhaler as needed.
lary node dissection had to be done.
5. Accurate staging of cancer remains the most Family History
important factor in planning treatment and Her mother had lung cancer and uterine cancer.
prognostication; therefore, early diagnosis is A maternal aunt was diagnosed with breast cancer at age
essential in patients with breast cancer. 43. Her father died of a myocardial infarction at age 57.
6. The multidisciplinary approach done in this
patient greatly enhanced the overall quality of Review of Systems
care to the patient with breast cancer. Unremarkable.
7. Vigilant surveillance is a must in follow-up of all
patients with breast cancer. Objective
Physical Examination
Well-developed, well-nourished white female in no
acute distress. Vital signs: weight, 205 pounds; height,
64.5 inches; blood pressure, 130/80; temperature,
INITIAL VISIT 98.1˚F (36.7˚C); pulse, 92; and RR, 18. Head, eyes,
ears, nose, and throat: normal. Lungs: clear. Heart:
Subjective regular rate and rhythm without murmurs or gallop.
Breast examination: left breast reveals a 0.75-cm firm,
Patient Identification and Presenting Problem nonmovable mass in the upper outer quadrant
Mrs. Rossalyn P., a 62-year-old white woman G4, P3, without notable tenderness, erythema, skin changes,
Ab1, comes into the clinic for her annual physical nipple discharge, or induration; right breast normal.
examination. She denies any complaints. Abdominal examination: no palpable masses, no

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

605
 Chapter 83 Breast Cancer

hepatosplenomegaly. Pelvic examination: normal 7. Mammary abscess is typically painful and erythe-
external genital and vaginal vault, no pelvic masses or matous, often associated with Staphylococcus
tenderness. Rectal examination: no masses, hemoccult aureus. It can clinically mimic inflammatory
negative. Neurologic examination: intact. Lymph breast cancer.
nodes: axilla and supraclavicular nodes reveal no lym- 8. Granulomatous mastitis accounts for fewer than
phadenopathy. 1% of all breast masses. It can be associated with
sarcoidosis, Wegener’s granulomatosis, or infec-
Assessment tious agents like Mycobacteria or fungal organisms.
9. Hematomas can mimic carcinoma clinically and
Working Diagnosis mammographically. They are most common
A new breast mass in a 62-year-old menopausal post-traumatically.
woman, after total abdominal hysterectomy with 10. Miscellaneous nonbreast tissue benign tumors
bilateral salpingo-oophorectomy with a weak family include lipomas, leiomyomas, hemangiomas,
history of breast cancer on maternal side. and neurofibromas (Schnitt et al., 1991).
Malignancy cannot be ruled out.
Plan
Differential Diagnosis
1. Breast cancer is commonly seen with advanced age Diagnostic
and exogenous estrogen exposure. Most women Mrs. P. underwent mammography that showed a
with breast cancer do not have identifiable risk 1 × 1-cm irregular mass with indistinct margins in the
factors. Early findings include nontender, firm, ill- outer upper quadrant of the left breast. Ultrasound
defined masses, whereas late findings include skin imaging of the mass showed a 1.3 × 1.3-cm irregular,
changes and lymph node involvement. hypoechoic mass with posterior shadowing. The sus-
2. Fibrocystic disease is the most common disease of picious results of the mammogram and ultrasound
the breast, peaking before menopause and rarely were discussed with the patient, and she was referred
seen before adolescence or after menopause. for surgical consultation. The patient was seen in a
Fibrocystic disease includes several disease multidisciplinary breast clinic that included the
processes associated with risks for cancer develop- involvement of a surgical oncologist, diagnostic radi-
ment. These processes are divided into three broad ologist, medical oncologist, radiation oncologist, and
categories: (1) nonproliferative lesions, (2) prolif- social worker. An ultrasound-guided fine needle
erative lesions without atypia, (3) atypical hyper- aspiration was done. The biopsy showed poorly differ-
plasia. The first category shows no increased risk of entiated infiltrating ductal adenocarcinoma.
cancer development, whereas the second and third Simultaneously, vacuum-assisted core biopsy of the
show a relative risk of 1.6% and 4.4%, respectively. mass confirmed the same histopathologic findings.
3. Fibroadenoma, the most common benign tumor The tumor was estrogen receptor and progesterone
of the breast in younger women, peaks in the late receptor negative and negative for HER2/NEU.
20s and early 30s. The tumors are composed of
fibrous and glandular tissue and do not increase Staging and Therapeutic
the risk of breast cancer. The patient underwent a left breast lumpectomy with
4. Solitary intraductal papillomas, occurring be- sentinel node mapping. The sentinel node was identi-
tween the ages of 30 and 50, are papillary prolif- fied and was positive for malignancy. A full axillary
erations of epithelial cells in the main lactiferous node dissection was performed. With the exception of
duct. Patients often present with bloody nipple the sentinel node, 21 axillary lymph nodes were nega-
discharge and occasionally have a palpable mass tive for malignancy. The final staging of the tumor was
that is smaller than 1 cm but that can be as large T1C, N1, and M0. The patient underwent adjuvant
as 4 to 5 cm. These tumors rarely increase the chemotherapy with four cycles of epirubicin and
patient’s risk of developing breast cancer. Cytoxan, followed by radiation therapy for 6 weeks.
5. Fat necrosis, difficult to distinguish from cancer, Except for some nausea and vomiting with chemother-
both clinically and mammographically, is often apy, the patient did well with this treatment.
associated with trauma, surgical intervention, or
radiation therapy. Histologically, it consists of
walled-off, lipid-laden macrophages, and neu- DISCUSSION
trophils and can occur in the subareolar region.
6. Duct ectasia, commonly seen in the fifth and Breast cancer remains the most common nonskin
sixth decades of life, is a palpable mass character- cancer in women in the United States, with its
ized by dilation of subareolar ducts with debris incidence continuing to increase since the 1980s
accumulation and inflammation. It is often asso- (Fig. 83-1). The U.S. Breast Cancer Statistics 2004
ciated with thick, “cheesy” nipple secretion. showed 215,999 new cases of invasive cancer,

606
 Chapter 83 Breast Cancer

250

200

Rate per 100,000 150 Breast

100

Colon and rectum

50 Lung
Uterine corpus
Ovary
0
1980
1981
1982
1983
1984
1985
1979

1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
Figure 83-1 Cancer incidence rates for women in the United States, 1979–2000. Age-adjusted to the 2000 U.S. stan-
dard population. (From U.S. Surveillance Epidemology, 1970–2000.)

accounting for 32% of all cancer diagnoses in improved survival. Five-year survival rate for stage
women, and 59,390 new cases of in situ breast can- 0 is 99%, and for stage IV it is 14% (Table 83-2 and
C ). The
cers due to better screening (Jemal et al., 2004● Fig. 83-3). Those with certain risk factors have a
lifetime probability that a woman will develop inva- higher incidence (Box 83-1). A positive family
sive breast cancer is 13.36%, that is, the illness will history, regardless of paternal/maternal lineage, is
strike one in every seven women (Table 83-1). present in less than 10% of women with breast
Despite the increase in incidence, there has been a cancer but remains an important risk factor. The
decrease in mortality, with a mortality rate of 2.2% presence of genetic gene mutation in BRCA1 and
per year from 1990 to 2000, most likely due to earlier BRCA2 increases the risk immensely but accounts
detection and improvement in the various treatment for only 5% to 10% of all diagnosed breast cancer
modalities now available (Fig. 83-2). (National Institutes of Health Consensus
Breast cancer is a progressive, hormonally Development Panel, 2001● C ).
driven disease. It is extremely important that early Mammography is currently the most valuable
diagnosis be made because early arrest can lead to and important screening test for early detection. It is
widely available, has more than 90% sensitivity, is
inexpensive, and can detect two to six cancer cases
per 1000 mammograms done. Limitations include
Table 83-1 Lifetime Probability of very dense breasts, such as in young women, breast-
Developing Cancer, by Site, feeding women, and those on hormone replacement
U.S. Women, 1998–2000 therapy, for whom both sensitivity and specificity are
Site Risk reduced (Linver, 2005). Clinical breast examination
by a physician is the other cornerstone for early
All sites 1 in 3 detection. Many studies have shown that self-breast
Breast 1 in 7 examination is not an effective screening tool
Lung and bronchus 1 in 17 (Mincey and Perez, 2004● C ). Current guidelines for
Colon and rectum 1 in 18 screening are outlined in Box 83-2.
Uterine corpus 1 in 38
Non-Hodgkin’s lymphoma 1 in 57
Ultrasonography should be used as an adjunct to
Ovary 1 in 59 mammography, detecting whether a lesion is solid or
Pancreas 1 in 83 cystic, and can be used to further categorize the solid
Melanoma 1 in 82 lesion. Generally recommended for women with very
Urinary bladder 1 in 91 dense breasts, it has an overall lower sensitivity, espe-
Uterine cervix 1 in 128 cially in detecting calcifications and lower specificity
than mammography (Smith et al., 2003● C ).
From DevCan. Probability of Developing or Dying of
Cancer Software, Version 5.1. Statistical Research Magnetic resonance imaging of the breast, now
and Applications Branch. Available at available in many centers, is currently not recom-
http://srab.cancer.gov/devcan. mended as a screening test because of expense and

607
 Chapter 83 Breast Cancer

120 111.3
ACS early detection

(All ages and races, age adjusted)

guidelines
Per 100,000 women
90 82.5 Incidence
Mortality

30
26.9 25.2

0
1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995

Figure 83-2 Rising incidence, falling mortality. Invasive breast cancer in the United States, 1973–1995. (From SEER
Cancer Statistics Review, 1973–1995 [1998].)

100% specificity (Fuhrman et al., 1998● C ). Stereotactic

Table 83-2 Breast Cancer Survival Rates
biopsy is often used in calcifications, whereas ultra-
5-Year Relative sound-guided biopsies, fine-needle aspirations, and
Stage Survival Rate core biopsies are used in most masses detectable by
ultrasonography. With MIBBs, diagnosis and treat-
0 99%
ment planning can be done in advance of any surgical
I 92%
IIA 82% intervention, permitting all surgical treatment to be
IIB 65% completed in a single surgical procedure.
IIIA 47% Once the diagnosis of breast cancer is established,
IIIB 44% further treatment is discussed with the patient, family,
IV 14% and, ideally, a multidisciplinary team. Treatment will
depend on the stage of the disease, age and general
Data from National Cancer Institute SEER
(Surveillance, Epidemiology, and End Results)
health of the patient, menopausal status, estrogen-
Program, 2004. Available at http://seer.cancer.gov. receptor status, progesterone-receptor status, and
presence of HER2/NEU gene amplication. The pres-
ence of estrogen receptor and/or progesterone recep-
tor is a good prognostic indicator, but the presence of
lack of both availability and physician expertise as HER2/NEU is a negative prognostic factor (Lippman,
compared to mammography (Smith et al., 2003● C ). 2005). Of all the above prognostic factors, the stage of
More trials of this test are currently under way. Its the tumor, characterized by size, nodal involvement,
use is mainly in high-risk patients or when mammo- and presence of distant metastasis, is most important
grams with ultrasonographic results are inconclu- in planning treatment and prognostication.
sive. Magnetic resonance imaging does not replace
mammography as the preferred screening test for Staging
detecting breast cancer.
Currently, breast cancer staging uses the American
Joint Committee on Cancer TNM system. This system
Diagnosis
classifies cancers based on their tumor size, nodal
Once an abnormality (i.e., a palpable mass, abnormal status, and metastases (Table 83-3 and Box 83-3).
mammogram, abnormal ultrasound scan, abnormal This classification has been refined with the use of sen-
magnetic resonance imaging scan) is found, a breast tinel node mapping. Sentinel node mapping has now
biopsy is performed. Seventy to 80% of breast become the standard of care in axillary staging of
biopsies are benign (Hall et al., 1988). Traditionally, a breast cancer. This is based on the concept that lym-
breast biopsy is done with open excisional biopsy, and phatic spread to the axilla occurs in an orderly manner.
if malignancy is found, definitive surgery is recom- The sentinel node is defined as the first lymph node to
mended and performed. receive drainage from a breast cancer (Fig. 83-4). This
Excisional breast biopsies have been replaced with is identified using a radioisotope tracer and blue dye
MIBBs. MIBBs include stereotactic biopsy, ultra- using one of several protocols. The sentinel node is
sound-guided fine needle aspiration, and ultrasound- localized with an intraoperative gamma probe and
guided core biopsy. MIBB has 90% sensitivity and identified by its blue color. If the sentinel node is nega-

608
 Chapter 83 Breast Cancer

100

Percentage of cases
Stage
0
50 I
II
III
IV

0
1 2 3 4 5 6 7 8 9 10
Years of survival after diagnosis
Figure 83-3 Survival by stage at diagnosis.

Box 83-1 Risk Factors for Breast Cancer Box 83-2 Screening Guidelines for the
Development Early Detection of Breast
Cancer, American Cancer
Advanced age Society, 2003
Family history of breast cancer (paternal or
maternal risk) ■ Yearly mammograms are recommended start-
Presence of genetic mutations (BRCA1, BRCA2) ing at age 40 and continuing for as long as a
Early menarche woman is in good health.
Late menopause ■ A clinical breast examination should be part
Nulliparity of a periodic health examination, about every
Absence of history of breast-feeding 3 years for women in their 20s and 30s, and
Birth of first child after age 30 every year for women 40 and older.
Data from American Cancer Society, 2005. Available
■ Women should know how their breasts nor-
at www.cancer.org. mally feel and report any breast changes
promptly to their health care providers.
Breast self-examination is an option for
tive for malignancy, no further axillary dissection is women starting in their 20s.
needed. If the sentinel node is positive or not found, a ■ Women at increased risk (e.g., family history,
full axillary node dissection is performed. This genetic tendency, past breast cancer) should
approach has significantly reduced the number of full talk with their doctors about the benefits and
axillary node dissections and long-term postoperative limitations of starting mammography screen-
complications and morbidity, i.e., lymphedema and ing earlier, having additional tests (i.e., breast
C ).
pain of involved upper extremity (Green et al., 2002● ultrasound and Magnetic resonance imag-
ing), or having more frequent examinations.
Treatment From Smith AR, Saslow D, Sawyer KA, et al. American
Cancer Society guidelines for breast cancer screen-
Breast cancer is commonly treated by a combination ing: Update 2003. CA Cancer J Clin 2003;53:141–169
of surgery, systemic therapy in the form of either
chemotherapy and/or hormonal therapy, and radio-
therapy. to those of mastectomy. BCT offers the patient a cos-
metically acceptable result and the psychological
Surgical Treatment benefit that goes with it. Not all patients are candi-
Breast conservation therapy (BCT) is preferred over dates for BCT. Conditions that preclude BCT include
the more deforming mastectomy. Multiple studies multicentric breast tumors, patients requesting a
have shown that BCT provides survival rates similar mastectomy, tumors larger than 5 cm, and tumors
609
 Chapter 83 Breast Cancer

Table 83-3 Summary of Breast Cancer Stages

Stage Description

Stage 0: Tis, N0, M0 Ductal carcinoma in situ (DCIS) is the earliest form of breast cancer. In
DCIS, cancer cells are located within a duct and have not invaded
the surrounding fatty breast tissue, or lobular carcinoma in situ
(LCIS), which is sometimes classified as stage 0 breast cancer, but
most oncologists believe it is not a true breast cancer. In LCIS,
abnormal cells grow within the lobules or milk-producing glands,
but they do not penetrate through the wall of these lobules or is
Paget’s disease of the nipple. In all cases, the cancer has not spread
to lymph nodes or distant sites.
Stage I: T1, N0, M0 The tumor is ≤ 2 cm (~4/5 inch) in diameter and has not spread to
lymph nodes or distant sites.
Stage IIA: T0, N1, M0/T1, No tumor is found in the breast but it is in one to three axillary
N1, M0/T2, N0, M0 lymph nodes, or the tumor is <2 cm and has spread to one to three
axillary lymph nodes or found by sentinel node biopsy as
microscopic disease in internal mammary nodes but not on imaging
studies or by clinical examination, or the tumor is >2 cm in
diameter and <5 cm but has not spread to axillary nodes. The
cancer has not spread to distant sites.
Stage IIB: T2, N1, M0/T3, The tumor is >2 cm in diameter and <5 cm and has spread to one to
N0, M0 three axillary lymph nodes or found by sentinel node biopsy as
microscopic disease in internal mammary nodes, or the tumor is
>5 cm and does not grow into the chest wall and has not spread to
lymph nodes. The cancer has not spread to distant sites.
Stage IIIA: T0–2, N2, M0/T3, The tumor is <5 cm in diameter and has spread to four to nine
N1–2, M0 axillary lymph nodes, or found by imaging studes or clinical
examination to have spread to internal mammary nodes, or the
tumor is >5 cm and has spread to one to nine axillary nodes or to
internal mammary nodes. The cancer has not spread to distant sites.
Stage IIIB: T4, N0–2, M0 The tumor has grown into the chest wall or skin and may have spread to
no lymph nodes or as many as nine axillary nodes. It may or may
not have spread to internal mammary nodes. The cancer has not
spread to distant sites.
Stage IIIC: T0–4, N3, M0 The tumor is any size, has spread to ≥10 nodes in the axilla or to one
or more lymph nodes under the clavicle (infraclavicular) or above
the clavicle (supraclavicular) or to internal mammary lymph nodes,
which are enlarged because of the cancer. All these are on the
same side as the breast cancer. The cancer has not spread to distant
sites.
Inflammatory breast cancer Classified as stage III, unless it has spread to distant organs or lymph
nodes that are not near the breast, in which case it would be stage IV.
Stage IV: T0–4, N0–3, M1 The cancer, regardless of its size, has spread to distant organs such as
bone, liver, or lung, or to lymph nodes far from the breast.

Data from American Cancer Society, 2005. Available at www.cancer.org.

involving the nipple areola complex and persistent Hormonal Therapy For postmenopausal women,
positive margins. If a mastectomy is chosen, the most hormonal adjuvant therapy for invasive breast cancer
common type is the modified radical mastectomy that is estrogen and/or progesterone receptor positive
with or without breast reconstruction using implants is 5 years of therapy with tamoxifen, an estrogen
or autogenous tissue. Frequently, both procedures receptor antagonist. A new form of hormonal abla-
can be done at the same time. BCT is always followed tion is aromatase inhibitors. These work by inhibiting
by radiation therapy (Mincey and Perez, 2004● C; aromatase, the enzyme responsible for the conversion
Lippman, 2005). of androstenedione to estrone and testosterone to
estradiol in the adrenal gland. Hormonal ablation is
Adjuvant Systemic Therapy the most powerful adjuvant therapy available today.
This includes chemotherapy and/or hormonal ther-
apy. The treatment goal is prevention of recurrence Chemotherapy Combination chemotherapy is recom-
and increased survival. mended for invasive breast cancer in premenopausal

610
 Chapter 83 Breast Cancer

Box 83-3 The 2002 American Joint Committee on Cancer TNM System

The most common system used to describe the stages of cancers is the American Joint Committee on
Cancer TNM system. This staging system classifies cancers based on their T, N, and M stages:
■ T stands for tumor (its size and how far it has spread within the breast and to nearby organs).

■ N stands for spread to lymph nodes (bean-shaped collections of immune system cells that help

fight infections and cancers).

■ M is for metastasis (spread to distant organs).

The approach to staging used here is based on the findings after surgery, when the pathologist has
looked at the breast mass and lymph nodes (the pathologic stage).
Additional letters or numbers appear after T, N, and M to provide more details about the tumor,
lymph nodes, and metastasis:
■ The letter T followed by a number from 0 to 4 describes the tumor’s size and spread to the skin or

chest wall under the breast. Higher T numbers indicate a larger tumor and/or wider spread to tis-
sues near the breast.
■ The letter N followed by a number from 0 to 3 indicates whether the cancer has spread to lymph

nodes near the breast and, if so, how many lymph nodes are affected.
■ The letter M followed by a 0 or 1 indicates whether the cancer has spread to distant organs, for

example, the lungs or bones, or to lymph nodes that are not next to the breast, such as those
above the collarbone.
Once the T, N, and M categories have been determined, this information is combined in a process
called stage grouping to determine your disease stage. This is expressed as stage 0 and in Roman
numerals from stage I (the least advanced stage) to stage IV (the most advanced stage).
Data from Green FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Handbook. In American Joint Committee on
Cancer (eds): AJCC Staging Manual, 6th ed. New York, Springer-Verlag, 2002.

Nodal
basin

Nonsentinel
nodes
Primary
tumor
Sentinel
node

Figure 83-4 Drainage to one node before others. (From Kapteijn BA. Biopsy of the Sentinel Node in Melanoma Penile
Carcinoma and Breast Carcinoma, Enschede, The Netherlands, Print Parters Ipskamp, 1997.)

611
 Chapter 83 Breast Cancer

and selected postmenopausal patients. Anthracyclines Radiation Therapy

(doxorubicin or epirubicin), cyclophosphamide, Radiation therapy is currently delivered using exter-
methotrexate, and 5-fluorouracil are mainly used. nal beam radiation to the whole breast as part of the
Antimetabolites (capecitabine, gemcitabine) and anti- standard local treatment. It is also used in metastatic
tubulin agents like taxanes (paclitaxel, docetaxel, bone lesions for relief of symptoms. Radiation ther-
and vinorelbine) have also been used. The most apy is administered over a 5- to 6-week period. If rec-
common side effects of chemotherapy are nausea, ommended with chemotherapy, radiation is given
vomiting, myelosuppression, alopecia, and mucositis. after chemotherapy.
Chemotherapy treatment is individualized for each Neoadjuvant chemotherapy consists of chemo-
patient (Mincey et al., 2002● C ). For current guidelines therapy given before surgery to shrink and down-
of drugs used to treat breast cancer, see Table 83-4. stage tumors so that BCT can be performed.

Table 83-4 Drugs of Choice for Breast Cancer

Drugs of Choice Some Alternatives or Additional Drugs

Risk reduction: Tamoxifen

Adjuvant2 Adjuvant2
Doxorubicin + cyclophosphamide ± Cyclophosphamide + epirubicin3 + fluorouracil (CEF)
fluorouracil (AC or CAF) ±
followed by paclitaxel or docetaxel
Cyclophosphamide + methotrexate +
fluorouracil (CMF)
Tamoxifen for hormone receptor positive Anastrazole for postmenopausal hormone receptor
positive4
Metastatic Metastatic
Doxorubicin + cyclophosphamide ± Capecitabine; paclitaxel; docetaxel;
fluorouracil (AC or CAF) vinorelbine; mitoxantrone; epirubicin;
Cyclophosphamide + methotrexate + fluorouracil by continous infusion
fluorouracil (CMF)
For hormone receptor positive: For hormone receptor positive:
Letrozole,5,6 anastrozole,5,7 Megestrol acetate
exemestane,5,8 tamoxifen, Fluoxymestrone
toremifene, or fulvestrant9
For tumors overexpressing HER2 protein: For tumors overexpressing HER2 protein:
Trastuzumab10 + vinorelbine or + paclitaxel Trastuzumab10 + docetaxel
Pegylated lipsomal doxorubicin + trastuzumab10 or
gemcitabine

1
Available in the United States for investigational use only.
2
Adjuvant treatment with chemotherapy and/or hormone therapy is generally recommended node-positive
patients, and for node-negative patients with tumors >1 cm in size or other unfavorable prognostic features.
Use of hormone therapy is limited to patients with tumors that are hormone receptor positive or unknown
and should begin after completion of chemotherapy (KS Albain et al. Proc Am Soc Clin Oncol 2002; 21:37a,
abstract 143). If radiation therapy is used, it is probably best to have a similar delay. An anthracyline-
containing regimen is preferred in patients with node-positive disease.
3
Med Lett 2000;42:12.
4
For adjuvant therapy of postmenopausal women with tumors that are hormone receptor positive, initial data
suggest that anastrozole may be more effective than tamoxifen but longer follow-up is needed (ATAC
Trialists’ Group, Lancet 2002;359:2131). Anastrozole can be considered as an alternative to tamoxifen for
postmenopausal women.
5
For premenopausal hormone receptor-positive women, a luteinizing hormone releasing hormone agonist
(goserelin, leuprolide, or tritorelin) should be given in combination with an aromatase inhibitor (anastrozole,
letrozole, or exemestane).
6
Mouridsen H, et al. J Clin Oncol 2001;19:2596.
7
Bonneterre J, et al. J Clin Oncol 2000;18:3748; Nabholtz JM, et al. J Clin Oncol 2000;18:3758.
8
Med Lett 2000;42:35.
9
Med Lett 2002;44:65.
10
Slamon DJ et al. N Engl J Med 2001;344:783; liposomal doxurubicin is being studied because concurrent
trastuzumab increases the cardiac toxicity.
Data from Med Lett 2003;1(7):42.

612
 Chapter 83 Breast Cancer

Commonly Used Treatment Options improved survival. Currently, more aggressive

Stage 0 Carcinoma in situ is where the tumor cells approaches, such as high-dose chemotherapy plus
are confined to the ducts or the lobules. Ductal autologous stem cell transplantation, do not appear
carcinoma in situ is a preinvasive lesion. If left C ).
to improve survival (Green et al., 2002●
untreated, it can potentially progress to invasive
cancer. Current recommendations include BCT + Follow-up Surveillance
radiation therapy ± tamoxifen; total mastectomy
± tamoxifen. Lobular carcinoma in situ is also an Current recommendations from the American
indicator lesion for potential increased risk of Society of Clinical Oncology include history and
invasive cancer of 1% per year (Recht, 2003). Close routine physical examination every 2 to 6 months
observation of both breasts after diagnostic biopsy during the first 3 years after primary therapy, every
is recommended. Treatment with tamoxifen in 6 to 12 months for the next 2 years, then annually.
patients with lobular carcinoma in situ has shown Visits should focus on signs of local recurrence as
to decrease the incidence of subsequent breast well as evidence of metastasis, which occurs prima-
cancer. rily in the bone, liver, and lungs. A pelvic examina-
tion, including a Pap smear and endometrial
Early Invasive Breast Cancer Stage I (tumor < 2 cm, ultrasound scan, should be obtained annually, espe-
axillary nodes negative) and stage II (ipsilateral mov- cially for those patients using tamoxifen. Yearly
able axillary nodes positive, tumor > 2 cm, or a tumor mammography cannot be overemphasized, with
< 5 cm that is node negative) are considered early more frequent mammography if needed.
stage. BCT and radiation therapy or mastectomy ±
breast reconstruction and adjuvant systemic therapy Advances in Breast Cancer Screening
(chemotherapy ± hormonal therapy) are recom- and Treatment
mended (Mincey and Perez, 2004● C ; Lippman, 2005).
Advances in breast cancer screening in mammogra-
Locally Advanced Breast Cancer Stage III (exten- phy, including digital imaging and computer-aided
sive axillary node involvement, supraclavicular devices, have increased cancer detection. Trials are
node involvement, direct extension to chest wall or under way on the use of magnetic resonance imaging
skin, or inflammatory breast cancer): neoadjuvant with contrast to enhance the detection of breast can-
chemotherapy, surgery, and radiation are recom- cer. Newer techniques on evaluating partial breast
mended. irradiation (brachytherapy) are being studied; in
these radiation is administered to the tumor bed and
Inflammatory Breast Cancer This is an aggressive the area surrounding the margin, allowing tumorici-
form of locally advanced breast cancer. A multi- dal doses of radiation with a shortened course of
modality approach, combining induction chemo- treatment duration. Furthermore, advances in genet-
therapy, surgery, and radiation, is used. ics continue, and these will help physicians detect
high-risk patients and will lead to advances in pre-
Metastatic Breast Cancer Stage IV tumors are vention and treatment
unlikely to be cured. Multimodality approaches,
including local and systemic treatment, may pro-
vide those with oligometastatic disease (limited Material Available on Student Consult
metastasis) with improved survival rates. For posi-
Review Questions and Answers about Breast
tive HER2/NEU cases, use of trastazumab (mono- Cancer
clonal antibody) with other drugs has shown

REFERENCES
Fuhrman GM, Bolton JS, Cederbom GJ, et al. Image- biopsy based on suspicion of carcinoma at mammogra-
guided core-needle breast biopsy is an accurate tech- phy. Radiology 1988;167:353–358.
nique to evaluate patients with nonpalpable imaging Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004.
abnormalities. Ann Surg 1998;227:932–939.● C CA Cancer J Clin 2004;54:8–29.● C
Green FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Linver MN. The medical audit. In Bassett LW, Jackson VP,
Handbook. In American Joint Committee on Cancer Jahan R, Fu YS, Gold RH (eds): Diagnosis of Diseases
(eds): AJCC Staging Manual, 6th ed. New York, of the Breast, 2nd ed. Philadelphia, Saunders, 2005, pp
Springer-Verlag, 2002.●
C 141–143.
Hall FM, Storella JM, Silverstone DZ, Wyshak G. Lippman ME. Breast cancer. In Kasper DL, Fauci AS,
Nonpalpable breast lesions: Recommendations for Longo DL, Braunwald E, Hauser SL, Jameson JL

613
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

(eds): Harrison’s Principles of Internal Medicine, cancer, November 1–3, 2000. J Natl Cancer Inst 2001;
16th ed. New York, McGraw-Hill, 2005, pp 516–523. 93:979–989.● C
Mincey BA, Palmieri FM, Perez EA. Adjuvant therapy for Recht A. Integration of systemic therapy and radiation ther-
breast cancer: Recommendations for management apy for patients with early-stage breast cancer treated with
based on consensus review and recent clinical trials. conservative surgery. Clin Breast Cancer 2003;4:104–113.
Oncologist 2002;7:246–250.●C Schnitt SJ, Connolly JL, Sclafani L, Smith BL, Morrow M,
Mincey BA, Perez EA. Advances in screening, diagnosis, Eberlein TJ. Benign breast disorders. In Harris JR,
and treatment of breast cancer. Mayo Clin Proc 2004; Hellman S, Handerson IC, Kidney DW (eds): Breast
79:810–816.●C Diseases. Philadelphia, Lippincott, 1991, pp 15–50.
National Institutes of Health Consensus Development Smith RA, Saslow D, Andrews-Sawyer K, et al. American
Panel. National Institutes of Health Development cancer society guidelines for breast cancer screening:
Conference Statement: Adjuvant therapy for breast Update 2003. CA Cancer J Clin 2003;53:141–169.● C

C h a p t e r

84 Vaginal Bleeding
(Endometrial Cancer)
Giang T. Nguyen

INITIAL VISIT
KEY POINTS
Subjective
1. Endometrial cancer is a common malignancy in
women. Patient Identification and Presenting
2. Postmenopausal women with vaginal bleeding Problem
should be evaluated for endometrial cancer. Huong N. is a 66-year-old Vietnamese woman who
3. Prognosis is determined by histologic type, presents for a new patient visit with the complaint of
grade, and stage of the disease. vaginal bleeding.
4. Racial disparities exist in the prognosis of
endometrial cancer, with African-American and History of Present Illness
Asian-Pacific Islander patients having poorer Mrs. N. is accompanied today by her husband and her
outcomes than Caucasian patients. adult son. She speaks minimal English but refuses
5. Treatment of endometrial cancer consists of professional interpretation, choosing to use her son
hysterectomy and may also include radiation for translation instead. You explain to the son that he
therapy, hormonal therapy, and palliative will need to translate everything verbatim during the
chemotherapy. visit, and he agrees to do this. Mrs. N. complains of
6. Annual screening with endometrial biopsy starting vaginal bleeding that started 1 week ago and ended
at age 35 is recommended for women with or at 3 days before this visit. She describes it as thick clots
risk for hereditary nonpolyposis colon cancer. and heavy flow that was more than an average
menstrual period. She experienced menopause at

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

614
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

(eds): Harrison’s Principles of Internal Medicine, cancer, November 1–3, 2000. J Natl Cancer Inst 2001;
16th ed. New York, McGraw-Hill, 2005, pp 516–523. 93:979–989.● C
Mincey BA, Palmieri FM, Perez EA. Adjuvant therapy for Recht A. Integration of systemic therapy and radiation ther-
breast cancer: Recommendations for management apy for patients with early-stage breast cancer treated with
based on consensus review and recent clinical trials. conservative surgery. Clin Breast Cancer 2003;4:104–113.
Oncologist 2002;7:246–250.●C Schnitt SJ, Connolly JL, Sclafani L, Smith BL, Morrow M,
Mincey BA, Perez EA. Advances in screening, diagnosis, Eberlein TJ. Benign breast disorders. In Harris JR,
and treatment of breast cancer. Mayo Clin Proc 2004; Hellman S, Handerson IC, Kidney DW (eds): Breast
79:810–816.●C Diseases. Philadelphia, Lippincott, 1991, pp 15–50.
National Institutes of Health Consensus Development Smith RA, Saslow D, Andrews-Sawyer K, et al. American
Panel. National Institutes of Health Development cancer society guidelines for breast cancer screening:
Conference Statement: Adjuvant therapy for breast Update 2003. CA Cancer J Clin 2003;53:141–169.● C

C h a p t e r

84 Vaginal Bleeding
(Endometrial Cancer)
Giang T. Nguyen

INITIAL VISIT
KEY POINTS
Subjective
1. Endometrial cancer is a common malignancy in
women. Patient Identification and Presenting
2. Postmenopausal women with vaginal bleeding Problem
should be evaluated for endometrial cancer. Huong N. is a 66-year-old Vietnamese woman who
3. Prognosis is determined by histologic type, presents for a new patient visit with the complaint of
grade, and stage of the disease. vaginal bleeding.
4. Racial disparities exist in the prognosis of
endometrial cancer, with African-American and History of Present Illness
Asian-Pacific Islander patients having poorer Mrs. N. is accompanied today by her husband and her
outcomes than Caucasian patients. adult son. She speaks minimal English but refuses
5. Treatment of endometrial cancer consists of professional interpretation, choosing to use her son
hysterectomy and may also include radiation for translation instead. You explain to the son that he
therapy, hormonal therapy, and palliative will need to translate everything verbatim during the
chemotherapy. visit, and he agrees to do this. Mrs. N. complains of
6. Annual screening with endometrial biopsy starting vaginal bleeding that started 1 week ago and ended
at age 35 is recommended for women with or at 3 days before this visit. She describes it as thick clots
risk for hereditary nonpolyposis colon cancer. and heavy flow that was more than an average
menstrual period. She experienced menopause at

Evidence levels ● A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

614
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

age 50. She has not had any pain and denies bleeding laboratory for evaluation. After discussion of risks
or bruising anywhere else on her body. She admits and benefits of the procedure, the patient consents to
that she did have another similar bleeding episode having an endometrial biopsy as well, and this spec-
several months ago, but it was mild and self-limited, imen is also sent to the laboratory. A blood sample
and she did not tell anyone. The episode that for complete blood count is also sent.
prompted today’s visit, however, was much more
severe, which is why she decided to tell her family. She
Assessment
was reluctant to go today since the problem has
stopped already, but her family insisted that she see a Working Diagnosis
doctor. The working diagnosis is abnormal vaginal bleeding
Mrs. N. has never used birth control pills or in an obese postmenopausal Asian female.
hormonal therapy. She had a normal Pap smear and
normal mammogram about 10 years ago.
Differential Diagnosis
Medical History There are a number of conditions that can result in
No major medical problems, hospitalizations, sur- vaginal bleeding in a postmenopausal woman.
geries, cancer, tuberculosis, blood clotting disorders, 1. Atrophic vaginitis. This is more common in older
chronic conditions, or allergies. No other history of women. Atrophic vaginal tissue may be more at
gynecologic problems. Four uncomplicated full-term risk for irritation. Severely atrophic tissue can
vaginal deliveries between ages 20 and 28. No med- very rarely be associated with bleeding (Pandit
ications except for occasional acetaminophen for and Ouslander, 1997). Physical examination can
mild headaches. suggest this diagnosis.
2. Cervical lesions. This may be due to cervicitis, cer-
Family History vical polyps, or cervical cancer. When cervical
No family history of breast, colon, or gynecologic polyps cause bleeding, it is often in the setting of
cancer. Her parents died in their 80s of natural postcoital bleeding. Cervicitis can cause bleeding
causes. in rare instances. Other causes of bleeding include
submucosal myomas and condylomata acumi-
Social History nata (Beers and Berkow, 1999). During the exam-
The patient is married. She is a retired secretary. No ination, attention should be paid to the presence
alcohol, tobacco, or illicit drug use. She does have of any lesions on the cervix or cervical tenderness.
passive exposure to smoke from her husband and Routine Pap smears should be performed to
sons. No history of sexually transmitted infections screen for cervical cancer, which is a highly treat-
and no sexual intercourse for several years. able malignancy when diagnosed early.
3. Uterine polyp, fibroid, or adenomyosis. Benign uter-
Review of Systems ine tumors are a frequent cause of dysfunctional
She denies weight loss, fatigue, fever, night sweats, uterine bleeding. Endometrial polyps can account
chest pain, shortness of breath, bowel changes, for 25% of abnormal bleeding; they can be treated
melena, bloody stool, dysuria, myalgias, arthralgias, with curettage. Fibroids (leiomyomas) can cause
depression, and neuralgias. bleeding and pelvic pressure. In general, they do
not require surgery unless they cause persistent
Objective bleeding problems, pain, or deleterious mass
effects on neighboring structures. Adenomyosis is
Physical Examination a benign condition in which endometrial tissue is
Mrs. N. is an obese Asian woman in no acute distress. present within the myometrium and can result in
Vital signs: height, 62 inches; weight, 185 pounds; hypertrophy of the surrounding myometrium
temperature, 99.0˚F (37.2˚C); respiratory rate, 18; (Feldman and Stewart, 1999).
blood pressure, 100/63; heart rate, 90. Cardiac exam- 4. Endometrial hyperplasia. Like endometrial cancer,
ination is unremarkable. Lungs are clear bilaterally. endometrial hyperplasia most commonly presents
Abdomen is nontender with no hepatosplenomegaly with dysfunctional uterine bleeding. Although
or masses. Gynecologic examination shows no hyperplasia without atypia usually has a benign
inguinal lymphadenopathy and normal female geni- course, atypical hyperplasia has a high risk of
talia. There is a large blood clot in the vagina, but no developing into cancer (Montgomery et al., 2004).
active bleeding. No lesions, lacerations, or polyps are 5. Endometrial/uterine cancer. Uterine cancers
noted. Bimanual examination reveals no cervical develop as endometrial carcinomas and uterine
tenderness, no adnexal masses, and no uterine mass. sarcomas. Uterine sarcomas (including leiomyo-
Rectal examination shows normal tone, no masses, sarcomas, endometrial stromal sarcomas, and
and guaiac-negative stool. A Pap smear is sent to the mixed müllerian sarcomas) represent only 2% of

615
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

uterine malignancies. The overwhelming major- 2001). The median age at diagnosis is 61 years, with
ity of uterine cancers are endometrial carcinomas only 5% of cases being diagnosed at less than 40 years
(Feldman and Stewart, 1999). of age (Feldman and Stewart, 1999). Death rates from
endometrial cancer have dropped dramatically over
Plan the past century (American Cancer Society, 2004● C ).
Endometrial carcinoma generally has a survival rate of
Diagnostic 65% or better (Stenchever, 2001), with an 89% 5-year
Preliminary laboratory studies were ordered (Pap survival reported in cases that are limited to the
smear, endometrial biopsy, complete blood count). mucosa (Abeler and Kjorstad, 1991● B ). Some racial
disparities do exist. Cox proportional hazards models
Therapeutic derived from Surveillance, Epidemiology, and End
The patient is not currently bleeding and is clinically Results (SEER) data showed an unadjusted hazard
stable (vital signs and symptoms are not worrisome ratio of 2.57 for death from endometrial cancer for
at this time). Therefore, no acute management is African-American women as compared to white
necessary at this point. Further therapeutic women. African-American women were significantly
approaches will be determined based on test results less likely to undergo primary surgery and had shorter
and clinical course. survival than white women (Randall and Armstrong,
2003● B ). Among Asian Americans, some evidence sug-
Patient Education gests that women born in the United States have
Mrs. N. is instructed to follow up in 2 weeks to dis- higher rates of endometrial cancer than their Asian-
cuss the results of her tests and to see how she is born counterparts (Liao et al., 2003●B ). A multivariate
doing clinically. She is also instructed to call if any analysis of data from the Department of Defense
new or recurrent symptoms develop in the mean- tumor registry showed that the Asian-Pacific Islander
time. She is provided with counseling and education race also independently predicts poor outcome for
about the potential diagnoses, and the importance endometrial cancer (Kost et al., 2003● B ).
of good follow-up is emphasized. In addition, not- The majority of cases of endometrial cancer are
ing that she has had no consistent health care, you diagnosed as the result of an evaluation for abnormal
advise her that to maintain her health, she should vaginal bleeding (Canavan and Doshi, 1999). Vaginal
also consider other matters for her general health, bleeding in a postmenopausal woman (i.e., after
including cholesterol testing, vaccinations (includ- 1 year without menses) should prompt an evalua-
ing pneumonia, influenza, and tetanus), mammog- tion. The differential diagnosis of abnormal vaginal
raphy, and other screening. bleeding includes endometrial/uterine cancer,
endometrial hyperplasia, uterine polyp or fibroid,
cervical disease, and atrophic vaginitis.
FOLLOW-UP VISIT
Risk
Mrs. N. returns with her husband and son for the
2-week follow-up visit. She reports no recurrent Risk factors for endometrial cancer include a history
bleeding and no new symptoms. She is eager to learn of colon cancer (especially hereditary nonpolyposis
about her test results. Review of the laboratory tests colon cancer), unopposed estrogen therapy, late
show evidence of endometrial carcinoma in the menopause, tamoxifen therapy, nulliparity, infertility
biopsy specimen. The Pap smear is normal, as is the or failure to ovulate, obesity, diabetes, and hyperten-
complete blood count. sion (National Guideline Clearinghouse, 2001● C ).
Mrs. N. is counseled about the results of the A family history of endometrial cancer may also
tests. She and her family are frightened about the increase risk (Parslov et al., 2000● B ), but there is
diagnosis, but they are willing to proceed with what- insufficient evidence to suggest that a family history
ever the doctor recommends. Mrs. N. is referred to of breast cancer affects endometrial cancer risk
gynecologic oncology specialists for further workup (Kazerouni et al., 2002● B ).
and surgical evaluation. In addition to being linked to endometrial can-
cer, increased estrogen exposure is also associated
with endometrial hyperplasia with atypia, which is a
DISCUSSION premalignant disease (Feldman and Stewart, 1999).
Estrogen exposure can occur through increased
Endometrial cancer is the fourth most common endogenous production, particularly in patients with
malignancy in women in the United States and the obesity, estrogen-secreting tumors, and anovulatory
most common gynecologic malignancy (American cycles (Canavan and Doshi, 1999). Patients with
Cancer Society, 2004●
C ). One in every 50 women in the polycystic ovary syndrome are therefore at increased
United States will develop this disease (Stenchever, risk (Lobo and Carmina, 2000). Obesity increases

616
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

production as well as bioavailability of estrogen. Women classified as at high risk of endometrial

Women who are overweight by up to 22.7 kg have a cancer are those known to carry mutations associated
threefold increase in risk of endometrial cancer, and with hereditary nonpolyposis colorectal cancer, women
those more than 22.7 kg overweight have a ninefold who have a substantial likelihood of being a mutation
increase in risk (Feldman and Stewart, 1999). carrier for it (i.e., family history), and women from
Women with early menarche (before age 12), late families with an autosomal dominant predisposition to
menopause (after age 52), or nulliparity also have colon cancer in the absence of genetic testing results.
increased exposure to estrogen throughout their life- For these women, the American Cancer Society recom-
times and are at increased risk (Canavan and Doshi, mends annual endometrial biopsy starting at age 35. In
1999). Clinicians should therefore be particularly addition, those high-risk women who are no longer
aware of this in the case of patients who are lesbians considering child-bearing and who are undergoing sur-
or who practice lifelong celibacy. gery for colorectal cancer should be offered prophylac-
Unopposed estrogen can also come from exoge- tic hysterectomy (National Guideline Clearinghouse,
nous sources. A Danish case-control study of 237 2001●C ). This recommendation is supported by reports
endometrial cancer patients and 538 controls of occult endometrial cancer identified by prophylactic
demonstrated an odds ratio of 3.1 (95% confidence hysterectomy in patients with hereditary nonpolyposis
interval 1.4 to 7.0) for women younger than age 50 colorectal cancer (Chung et al., 2003).
who received estrogen-only hormone replacement
therapy for 1 to 5 years (Parslov et al., 2000● B ). The
Initial Evaluation
use of combined estrogen and progestin therapy,
however, produced endometrial cancer rates similar The majority of patients with endometrial cancer
to placebo; the hazard ratio for this regimen in the present initially with abnormal vaginal bleeding.
Women’s Health Initiative was 0.81 (95% confidence Occasionally, older patients may present with pelvic
interval 0.48 to 1.36). Although the combined ther- pain associated with retained blood in the uterus due
apy did not appear to increase endometrial cancer to stenosis of the cervical os. Asymptomatic patients
rates, it was associated with increased rates of may also present with abnormal Pap smears showing
endometrial biopsies to assess vaginal bleeding atypical endometrial cells. On physical examination,
(Anderson et al., 2003● A). Like HRT, tamoxifen (com- clinicians should carefully examine the external geni-
monly used for breast cancer chemoprevention) has tal structures and note the size, shape, position, and
estrogenic properties in the female genital tract mobility of the uterus as well as any abnormalities in
(Canavan and Doshi, 1999). When compared to the adnexal regions (to determine the presence of pos-
placebo, tamoxifen is associated with increases in sible estrogen-secreting ovarian tumors) (Canavan
endometrial cancer risk, particularly in women 50 and Doshi, 1999). Patients presenting with abnormal
years of age and older (Kinsinger et al., 2002● A ). vaginal bleeding should receive a Pap smear because
Some evidence suggests that the use of oral con- cervical bleeding is often difficult to differentiate from
traceptives for 1 to 5 years decreases the risk of uterine bleeding (Feldman and Stewart, 1999).
endometrial cancer (odds ratio 0.2; 95% confidence Evaluation of any suspected case of endometrial
interval 0.1 to 0.3) (Parslov et al., 2000●B ). Smoking cancer should include endometrial biopsy for histo-
also reduces the risk of endometrial cancer. The logic examination. Endometrial sampling can be
mechanism may be related to higher serum accomplished in the outpatient setting, and this is an
androstenedione levels and, among overweight appropriate skill for family physicians to have. It is a
women, lower estradiol levels (Austin et al., 1993● B ). blind procedure performed using sterile technique
However, this benefit is clearly surpassed by the with the patient in lithotomy position. Local anes-
other risks associated with smoking. thesia can be used in addition to oral nonsteroidal
Because women with endometrial cancer tend anti-inflammatory medications. A detailed descrip-
to present with symptoms at an early, favorable stage, tion of this procedure is provided in Zuber (2001).
the American Cancer Society does not recommend Some recent work has suggested that a negative
screening for endometrial cancer, even in women transvaginal ultrasound (showing endometrial
with “increased risk” (e.g., obesity, nulliparity, thickness ≤ 4 mm) with or without a normal Pap
tamoxifen therapy) (National Guideline Clearing- smear may negate the need for an endometrial
house, 2001● C ). The U.S. Preventive Services Task biopsy (Gull et al., 2000● B ; 2003● B ). The sensitivity
Force does not have any recommendations for rou- of transvaginal ultrasonography has been reported
tine endometrial cancer screening either. A consen- to be 90% for endometrial disease (Langer et al.,
sus conference in Europe also concluded that repeat 1997● B ) and 100% for endometrial cancer (Gull
endometrial biopsies in women on tamoxifen ther- et al., 2003●B ). However, because endometrial biop-
apy are of little value, and transvaginal ultrasonogra- sies are fairly simple and only minimally invasive,
phy is likely to yield many false-positive results it is still prudent to proceed with endometrial
(Neven and Vergote, 1998● C ). sampling in cases of suspected cancer. Table 84-1

617
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

Table 84-1 Response to Biopsy Results

Pathologic Finding on Biopsy Response

Endometrial carcinoma Referral for hysterectomy

Progestin therapy if surgery is contraindicated
Possible role for radiation or chemotherapy
Endometrial hyperplasia with atypia High risk of progression to cancer
Offer hysterectomy (especially if child-bearing
is complete) or treat with progestin and
closely monitor with endometrial biopsy
every 3 months
Endometrial hyperplasia without atypia Low risk of progression to cancer
Often regresses to normal tissue in 1 year
Treat with progestin and repeat biopsy in
3 months
Consider hysterectomy for persistent
hyperplasia despite hormone treatment
Atrophic endometrium Treat with progestin and reevaluate
Normal endometrium Treat abnormal bleeding with progestin
Additional workup if continued suspicion of
cancer (transvaginal ultrasound, fractional
dilation and curettage, hysteroscopy).
See Canavan and Doshi (1999), Zuber (2001), Triwitayakorn and Rojanasakul (1999), Weinberg et al. (1999).

lists recommended responses to pathologic findings program database demonstrated a standardized inci-
on biopsy. dence ratio for colorectal cancer of 3.39 (95% confi-
dence interval 2.73 to 4.17) among women
After Diagnosis diagnosed with endometrial cancer before the age of
B ).
50 (Tabata et al., 2001●
On detection of endometrial cancer, further evalua-
tion should include a complete history and examina-
tion, a complete blood count (to rule out anemia),
liver function tests (to screen for occult metastatic Table 84-2 Grade and Staging of
disease), and a chest radiograph (to rule out pul- Endometrial Cancer
monary metastases) (Feldman and Stewart, 1999). Grade Stage
Definitive treatment of endometrial cancer
requires surgery (total abdominal hysterectomy, 1 Well differen- I Corpus uterus
bilateral salpingo-oophorectomy, and surgical evalu- tiated only
2 Intermediate
ation for metastatic disease). Staging can be deter-
differentiation II Corpus uterus
mined at the time of surgery (Canavan and Doshi, and cervix
1999). For patients who cannot tolerate surgery, stag- only
ing can be attempted through use of transvaginal 3 Poorly differen- III Extending
ultrasonography or magnetic resonance imaging tiated beyond the
(Feldman and Stewart, 1999). Table 84-2 shows basic uterus but
grading and staging schemata. Patients beyond stage confined to
IB grade 2 should also be offered postoperative radi- the pelvis
ation therapy. Cytotoxic chemotherapy is reserved IV Extending
only for palliative therapy because tumor response is outside the
pelvis or
generally poor. Progestin therapy is another option,
into bladder
but it also is not highly effective against endometrial or rectal
cancer (Canavan and Doshi, 1999). mucosa
Patients diagnosed with endometrial cancer
should also be screened routinely for colorectal Histologic grade and stage affect the prognosis for
cancer. A retrospective cohort analysis of the endometrial cancer. Patients with higher grade
and stage have worse prognosis (Stenchever,
Surveillance, Epidemiology, End Results (SEER) 2001).

618
 Chapter 84 Vaginal Bleeding (Endometrial Cancer)

In summary, endometrial cancer is a com- physicians play an important role in the prompt
mon malignancy. While routine screening is not diagnosis of this disease.
recommended for most women, any occurrence
of abnormal vaginal bleeding, particularly in a Material Available on Student Consult
postmenopausal woman, should prompt an evalua-
Review Questions and Answers about Endometrial
tion for this diagnosis. Early stages of endometrial
Cancer
cancer have a very good prognosis, and primary care

REFERENCES
Abeler VM, Kjorstad KE. Endometrial adenocarcinoma in Kost ER, Hall KL, Hines JF, et al. Asian-Pacific Islander race
Norway. A study of a total population. Cancer independently predicts poor outcome in patients with
1991;67:3093–3103.● B endometrial cancer. Gynecol Oncol 2003;89:218–226.● B
American Cancer Society. Cancer Facts and Figures 2004. Langer RD, Pierce JJ, O’Hanlan KA, et al. Transvaginal
Atlanta: American Cancer Society, 2004.● C ultrasonography compared with endometrial biopsy
Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estro- for the detection of endometrial disease. Post-
gen plus progestin on gynecologic cancers and associated menopausal Estrogen/Progestin Interventions Trial. N
diagnostic procedures: The Women’s Health Initiative Engl J Med 1997;337:1792–1798.● B
randomized trial. JAMA 2003;290:1739–1748.● A Liao CK, Rosenblatt KA, Schwartz SM, Weiss NS.
Austin H, Drews C, Partridge EE. A case-control study of Endometrial cancer in Asian migrants to the United
endometrial cancer in relation to cigarette smoking, States and their descendants. Cancer Causes Control
serum estrogen levels, and alcohol use. Am J Obstet 2003;14:357–360.● B
Gynecol 1993;169:1086–1091.● B Lobo RA, Carmina E. The importance of diagnosing the
Beers MH, Berkow R. Menstrual abnormalities and abnor- polycystic ovary syndrome. Ann Intern Med 2000;132:
mal uterine bleeding. In Beers MH, Berkow R (eds): 989–993.
The Merck Manual of Diagnosis and Therapy, 17th ed. Montgomery BE, Daum GS, Dunton CJ. Endometrial
Rahway, NJ, Merck, 1999, Section 18, Chapter 235. hyperplasia: A review. Obstet Gynecol Surv 2004;59:
Canavan TP, Doshi NR. Endometrial cancer. Am Fam 368–378.
Physician 1999;59:3069–3076. National Guideline Clearinghouse. American Cancer
Chung L, Broaddus R, Crozier M, Luthraa R, Levenback Society guidelines on testing for early endometrial can-
C, Lu K. Unexpected endometrial cancer at prophy- cer detection—Update 2001. In American Cancer
lactic hysterectomy in a woman with hereditary non- Society Guidelines for the Early Detection of Cancer.
polyposis colon cancer. Obstet Gynecol 2003; Available at www.guideline.gov. Accessed 9/24/2004.● C
102:1152–1155. Neven P, Vergote I. Should tamoxifen users be screened for
Feldman S, Stewart EA. The uterine corpus. In Ryan KJ, endometrial lesions? Lancet 1998;351:155–157.● C
Kistner RW (eds): Kistner’s Gynecology and Women’s Pandit L, Ouslander JG. Postmenopausal vaginal atrophy
Health, 7th ed. St. Louis, Mosby, 1999. pp 121–142. and atrophic vaginitis. Am J Med Sci 1997;314:228–231.
Gull B, Carlsson S, Karlsson B, Ylostalo P, Milsom I, Parslov M, Lidegaard O, Klintorp S, et al. Risk factors
Granberg S. Transvaginal ultrasonography of among young women with endometrial cancer: A
the endometrium in women with postmenopausal Danish case-control study. Am J Obstet Gynecol
bleeding: Is it always necessary to perform an 2000;182:23–29.● B
endometrial biopsy? Am J Obstet Gynecol 2000;182: Randall TC, Armstrong K. Differences in treatment and out-
509–515.● B come between African-American and white women with
Gull B, Karlsson B, Milsom I, Granberg S. Can ultrasound endometrial cancer. J Clin Oncol 2003;21:4200–4206.● B
replace dilation and curettage? A longitudinal evalua- Stenchever MA. Neoplastic diseases of the uterus. In
tion of postmenopausal bleeding and transvaginal Stenchever MA (ed): Comprehensive Gynecology, 4th
sonographic measurement of the endometrium as pre- ed. St. Louis, Mosby, 2001, pp 919–954.
dictors of endometrial cancer. Am J Obstet Gynecol Tabata T, Yamawaki T, Yabana T, Ida M, Nishimura K, Nose
2003;188:401–408.● B Y. Natural history of endometrial hyperplasia: Study of
Kazerouni N, Schairer C, Friedman HB, Lacey JV, Jr, 77 patients. Arch Gynecol Obstet 2001;265:85–88.● B
Greene MH. Family history of breast cancer as a deter- Triwitayakorn A, Rojanasakul A. Management of endome-
minant of the risk of developing endometrial cancer: A trial hyperplasia: A retrospective analysis. J Med Assoc
nationwide cohort study. J Med Genet 2002;39: Thailand 1999;82:33–39.● B
826–832.● B Weinberg DS, Newschaffer CJ, Topham A. Risk for colorec-
Kinsinger LS, Harris R, Woolf SH, Sox HC, Lohr KN. tal cancer after gynecologic cancer. Ann Intern Med
Chemoprevention of breast cancer: A summary of the 1999;131:189–193.● B
evidence for the U.S. Preventive Services Task Force. Zuber TJ. Endometrial biopsy. Am Fam Physician 2001;
Ann Intern Med 2002;137:59–69, I62.● A 63:1131–1135, 1137–1141.

619
 C h a p t e r

85 Cervical Cancer Screening

Wendy Brooks Barr

no other history of sexually transmitted diseases

KEY POINTS (STDs).
Her obstetric history includes four previous
1. Papanicolaou (Pap) smears have played a major pregnancies resulting in two spontaneous vaginal
role in decreasing the incidence of cervical deliveries without complications, one miscarriage in
cancer. the first trimester, and one first-trimester induced
2. Both the traditional slide method and the liq- abortion. Her last delivery was 2 years ago with you
uid-based Pap smear method are appropriate as her provider. She underwent a tubal ligation
for routine cervical cancer screening. immediately post partum for future contraception.
3. The current role of testing for high-risk types of Tests for HIV were negative at the time of delivery of
human papillomavirus is to lengthen screening her last child.
intervals to every 3 years in low-risk women
older than 30 and to triage to colposcopy Social and Family History
women who have a Pap smear showing Ms. L. reports having one current male sexual partner
atypical squamous cells of undetermined whom she has been with for 9 months. She thinks he
significance. is monogamous with her. She states she does not use
4. Women who have undergone a total hysterec- tobacco, alcohol, or drugs. Her family history is sig-
tomy for benign disease do not need further nificant for diabetes in both her mother and father.
Pap smears if they have no recent history of an Her mother did not take diethylstilbestrol.
abnormal result.
Review of Systems
Ms. L. states she has not had any vaginal discharge or
discomfort, or any irregular bleeding. She has not
INITIAL VISIT noticed any changes or masses in her breasts or any
nipple discharge.
Subjective
Patient Identification and Presenting
Objective
Problem
Altagracia L., a 32-year-old Latina, comes to the On physical examination, the patient has normal
office for her annual gynecologic examination. She external female genitalia without any evidence of
has no complaints and reports good general health. external or perianal warts. The speculum examina-
tion discloses no abnormalities of the introitus,
Gynecologic and Obstetric History vagina, or cervix. The cervix is not friable. The exter-
Ms. L. entered menarche at age 13 and began having nal cervical os is slightly open, consistent with previ-
intercourse at age 16. She reports her periods as reg- ous vaginal deliveries. No abnormal discharge is
ular and occurring approximately every 28 days, with noted in the posterior fornix. A Pap smear is
the flow lasting 5 to 6 days. Her last period was 2 obtained, along with a swab for Neisseria gonorrhoeae
weeks ago. She has no previous history of abnormal and Chlamydia testing. On bimanual examination,
Papanicolaou (Pap) smears. Her last Pap smear was no abnormalities are noted on palpation of the
1 year ago. She has a distant history of Chlamydia vagina, and there is no cervical motion tenderness.
infection when she was 18 that was treated. She has The uterus is of normal size and anteverted. No

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

620
 Chapter 85 Cervical Cancer Screening

adenexal tenderness or masses are noted. Exami- The traditional slide method typically involves collect-
nation of the breasts reveals no dimpling or thicken- ing squamous cells from the cervix using a spatula and
ing of the skin on visual inspection, no masses on then collecting endocervical cells with a cytobrush
palpation of the breast or adenexal lymph nodes, and placed into the cervical os. The cells are then spread
no nipple discharge. onto a slide from both the spatula and cytobrush and
quickly sprayed with a cell fixative to prevent drying
Assessment artifact. With the liquid-based cytology method the
sample typically is collected using a cytologic broom
This is a normal female gynecologic examination. placed into the cervical os and turned to obtain both
the squamous and endocervical cells or by using an
Plan extended-tip plastic spatula. The collection instru-
ment is then placed into the fixative and agitated to
Provide anticipatory guidance by discussing the use release the cells into the liquid medium. Liquid-based
of condoms to prevent STDs, including HIV and cytology has a slightly higher sensitivity than the tra-
human papillomavirus (HPV) infection. Also discuss ditional slide sample technique but is more expensive
HIV testing for Ms. L. and her partner, and discuss and has not been shown to be cost-effective in
her risk for cervical dysplasia and HPV infection and improving patient-oriented outcomes (U.S. Preven-
whether she should have yearly versus every third tive Services Task Force [USPSTF], 2003● C ). For this
year cervical cancer screening. reason, current guidelines do not recommend for
or against the use of the liquid-based cytology tech-
nique over the conventional slide-based Pap smear
DISCUSSION
technique (American College of Obstetricians and
Gynecologists [ACOG], 2003 ● C ; USPSTF, 2003● C ). The
Cervical Cancer Screening: The Pap Smear
advantage of liquid-based cytology is that it is useful
The Pap smear is a screening test designed to detect for colposcopy triage. Reflex HPV testing can be done
precancerous lesions of the cervical epithelium that, with the Pap sample without the need for a second
if left untreated, could develop into invasive cervical collection at a later date.
cancer. These precancerous lesions are known as cer- The Bethesda system, a uniform system for read-
vical intraepithelial neoplasia (CIN). Most intraep- ing and reporting Pap smear results, was developed
ithelial lesions and cervical cancer lesions contain by a consortium of groups involved in cervical cancer
HPV. There are many types of HPV, which vary in screening. The most recent revision of the Bethesda
their ability to transform cervical epithelium into system occurred in 2001. The accepted Bethesda 2001
CIN and cancerous lesions. The high-risk types most terminology for cervical epithelial cell abnormalities
frequently associated with moderate to severe dys- is given in Table 85-1 (Solomon, 2002● C ). Table 85-2
plasia (CIN II or III) and carcinoma in situ are types presents the known epidemiology for abnormal
16, 18, 31, 33, and 35 (Cannistra and Niloff, 1996● C ). epithelial and glandular cell Bethesda categories for
The Pap smear does not diagnose CIN but rather CIN and cervical cancer (Wright et al., 2001● C ).
samples for abnormal-appearing cells from the cervi-
cal epithelium. It is ideal to sample from the epithelial HPV Testing
transformation zone (t-zone) where normal endocer-
vical columnal cells change into normal squamous A recent addition to Pap smear testing for cervical
cells of the exocervix. The t-zone is the area of the cancer screening has been molecular testing for high-
cervix where dysplasia is most likely to occur. The test risk types of HPV. This testing can be done directly
can be performed at any time during the menstrual from the liquid medium for liquid-based cytology
cycle except during menstruation itself, since the red smears, or the specimen can be collected separately
blood cells can obscure the epithelial cells on the along with a traditional slide-based Pap smear spec-
smear. Ideally, specimen collection for the Pap smear imen. The testing can be done at the same time as
should be done before bimanual examination or other Pap smear testing (routine testing) or it can be per-
manipulation of the cervix is performed to avoid formed after the processing of a Pap smear that is
lubricant artifact and disruption of cells on the surface read as atypical squamous cells of undetermined sig-
of the cervix. After the speculum has been placed and nificance (ASC-US) (reflex testing). The current pre-
the cervix is visualized, a dry swab can be used to ferred approach (of the three currently approved
remove any obscuring cervical mucus, and then the approaches) for managing ASC-US includes using
specimen should be obtained. Currently, Pap smear reflex HPV testing to determine who should proceed
specimens can be collected directly onto slides (tradi- to colposcopy versus retesting in 12 months (Wright
tional slide method) or the cells can be placed in a liq- et al., 2002●
C ). Table 85-3 gives the 2001 recommen-
uid medium and later placed on a slide by the dations of the American Society of Colposcopy and
pathologist (liquid-based cytology, e.g., ThinPrep). Cervical Pathology (ASCCP) for managing patients

621
 Chapter 85 Cervical Cancer Screening

Table 85-1 The 2001 Bethesda System (Abridged)

Specimen Adequacy
Satisfactory for evaluation (note presence/absence of endocervical/transformation zone component)
Unsatisfactory for evaluation (specify reason)
Specimen rejected/not processed (specify reason)
Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of
(specify reason)

General Categorization (Optional)

Negative for intraepithelial lesion or malignancy
Epithelial cell abnormality
Other

Interpretation/Result
Negative for Intraepithelial Lesion or Malignancy
Organisms
Trichomonas vaginalis
Fungal organisms morphologically consistent with Candida species
Shift in flora suggestive of bacterial vaginosis
Bacteria morphologically consistent with Actinomyces species
Cellular changes consistent with herpes simplex virus
Other non-neoplastic findings (optional to report)
Reactive cellular changes associated with:
Inflammation (includes typical repair)
Radiation
Intrauterine contraceptive device
Glandular cells status post hysterectomy
Atrophy

Epithelial Cell Abnormalities

Squamous cell
Atypical squamous cells (ASC)
Of undetermined significance (ASC-US)
Cannot exclude HSIL (ASC-H)
Low-grade squamous intraepithelial lesions (LSIL)
Encompassing: human papillomavirus, mild dysplasia, CIN I
High-grade squamous intraepithelial lesions (HSIL)
Encompassing: moderate and severe dysplasia, carcinoma in situ, CIN II, and CIN III
Squamous cell carcinoma
Glandular cell
Atypical glandular cells (AGC) (specify endocervical, endometrial, or not otherwise specified)
Atypical glandular cells, favor neoplasia (specify endocervical or not otherwise specified)
Endocervical adenocarcinoma in situ (AIS)
Adenocarcinoma

Automated Review and Ancillary Testing (Include as Appropriate)

Educational Notes and Suggestions (Optional)
CIN, cervical intraepithelial neoplasia; HSIL, high-grade squamous intraepithelial lesions.
From Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda system: Terminology for reporting results of
cervical cytology. JAMA 2002;286:2114–2119.

with abnormal screening cytology results (Wright, tions from this group for managing results based on
2002● C ). For women older than 30, the National simultaneous cytologic and HPV testing.
Cancer Institute, the ASCCP, and the American
Cancer Society have recommended combined testing
Cervical Cancer Screening Intervals
with cytology (Pap smear) and HPV testing, with the
advantage of prolonging the testing interval to every There is increasing controversy over the interval at
3 years if the results of both are negative (Wright which women should have Pap smears done as part of
et al., 2004●C ). Table 85-4 provides the recommenda- a routine gynecologic examination. Traditionally,

622
 Chapter 85 Cervical Cancer Screening

Table 85-2 Risk of Significant Cervical Dysplasia or Invasive Cancer

Based on Cervical Cytology Result
Bethesda Identified as CIN Identified as Invasive
Abbreviation Bethesda Description II or III (%) Cancer (%)

ASC-US Atypical squamous cells of

undetermined significance 10–20 0.1
ASC-H Atypical squamous cells––
cannot exclude HSIL 24–94 N/D
LSIL Low-grade squamous
intraepithelial lesion
(includes HPV, mild cervical
dysplasia, CIN I) 15–30 N/D
HSIL High-grade squamous in-
traepithelial lesion
(includes moderate and
severe dysplasia, carcinoma
in situ, CIN II, CIN III) 70–75 1–2
AGC Atypical glandular cells 9–54 <1–8
AGC––favor neoplasia Atypical glandular cells, favor 27–96 (includes AIS
neoplasia and invasive cancer) N/D
AIS Endocervical adenocarcinoma
in situ 48–69 (with AIS) 38

CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; N/D, no data reported.
Data from Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda system: Terminology for reporting results of
cervical cytology. JAMA 2002;286:2114–2119; Wright TC, Cox JT, Massad LS, et al. 2001 consensus guidelines for
the management of women with cervical cytological abnormalities. JAMA 2002;287:2120–2129.

Table 85-3 Management of Cervical Cytology Results: Bethesda/ASCCP 2001 Guidelines

Pap (Cytology) Result Follow-up Test Follow-up Timing

Negative Pap (cytology) 12 mo¶

ASC-US* (no reflex HPV† test) Pap (cytology) 4–6 mo
ASC-US (negative reflex HPV) Pap (cytology) 12 mo
ASC-US (positive reflex HPV) Colposcopy Immediately
ASC-H Colposcopy Immediately
AGC Colposcopy and endometrial
sampling Immediately
LSIL‡,§ Colposcopy Immediately
HSIL Colposcopy Immediately
*
ASC-US in postmenopausal women can be triaged using intravaginal estrogen therapy for 1 week and repeat
cytology. If the study is negative, the Pap smear can be repeated in 4 months; otherwise, colposcopy is
required.
†
HPV testing is molecular testing for high-risk types of HPV DNA.
‡
LSIL in postmenopausal women with evidence of atrophy can be managed similarly to ASC-US (see first note
above).
§
LSIL in adolescents can be managed as indicated or with repeat cytologic examination in 6 months or with HPV
testing in 12 months, with colposcopy after repeat testing if the result remains abnormal.
¶
See text for discussion of testing intervals for routine screening.
HPV, human papillomavirus.
Data from Wright TC, Cox JT, Massad LS, et al. 2001 consensus guidelines for the management of women with
cervical cytological abnormalities. JAMA 2002;287:2120–2129.

many patients and physicians have believed that the by 70% in the United States after the introduction of
annual Pap smear was an essential part of routine care mass screening programs (Cannistra and Niloff,
for women to prevent cervical cancer. Indeed, the Pap 1996●C ). Today, approximately 50% of women found to
smear has been a success story for cancer screening and have invasive cervical cancer never had a Pap smear
prevention. The incidence of cervical cancer decreased prior to diagnosis, and 10% did not have a Pap smear

623
 Chapter 85 Cervical Cancer Screening

Table 85-4 Management of Combined Cervical Cytology and HPV Testing

Pap (Cytology) Result HPV Result Follow-up Test Follow-up Timing

Negative Negative Pap/HPV 36 mo

Negative Positive Pap/HPV 6-12 mo*
ASC-US Negative Pap/HPV 12 mo
ASC-US Positive Colposcopy Immediately
ASC-US or worse Positive Colposcopy Immediately
ASC-US or worse Negative Colposcopy Immediately
AGC Positive or negative Colposcopy and
endometrial sampling Immediately
*
If follow-up testing is both cytology and HPV negative, the woman can return to routine screening every
3 years. If follow-up testing is ASC-US and HPV negative, the woman can undergo rescreening with both tests
in 12 months. Otherwise, any HPV positive findings or any cytology ASC-US or worse requires immediate
colposcopy.
HPV, human papillomavirus.
Data from Wright TC, Schiffman M, Solomon D, et al. Interim guidance for the use of human papillomavirus DNA
testing as an adjunct to cervical cytology for screening. Obstet Gynecol 2004;103:304–309.

Table 85-5 Summary of Cervical Cancer Screening Recommendations

ACOG ASCCP ACS USPSTF

Start screening Within 3 years of first 18 or the onset of Within 3 years of Within 3 years of
intercourse or sexual activity first intercourse or first inter-
age 21 (whichever age 21 (whichever course or age
comes first) comes first) 21 (whichever
comes first)
Screening Every year if <30 years. Same as ACOG Same as ACOG Screen at least
interval Every 3 years if >30 every 3 years
years and previous
three Pap smears were
normal or if combined
testing was negative
and patient has low
risk for disease
Stop screening No set age; instead, Same as ACOG Age 70 if 3 previous Age 65 if has
should base on Paps normal and previous
individual risk no abnormal Pap normal Paps
in 10 years and low risk
for disease
Screening patients Screening Same as ACOG Same as ACOG Same as ACOG
with total not needed
hysterectomy
for benign
disease

Data from American of Obstetricians and Gynecologists (ACOG). Cervical Cytology Screening. ACOG Practice
Bulletin no. 45. Obstet Gynecol 2003;102:417–425; Saslow D, Ranowicz CD, Solomon D, et al. American Cancer
Society guidelines for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002;52:342–362;
U.S. Preventative Services Task Force. Screening for cervical cancer: Recommendations and rationale. 2003.
Available at www.preventativeservices.ahrq.gov. Accessed 1/26/2006; Wright TC, Cox JT, Massad LS, et al. 2001
consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;
287:2120–2129.

in the previous 5 years. There is agreement that every should stop. The introduction of testing for high-risk
woman should have some type of regular Pap smear types of HPV has also complicated this picture and
screening for some portion of her life. The disagree- may affect recommendations for screening intervals
ments concern when screening should start, how often and cessation of screening. Interim guidelines state that
women should have Pap smears done, and when they for women older than 30, routine screening can occur

624
 Chapter 85 Cervical Cancer Screening

every 3 years if the patient has both negative cytology patient population. For example, longer screening
and negative high-risk HPV results (Wright et al., intervals with combined testing may be appropriate for
2004● C ). They do not recommend using combined test- a non-sexually active 25-year-old woman until she
ing routinely, but only if a patient is interested and it is becomes sexually active but may not be appropriate for
appropriate to increase the screening interval to every a 35-year-old woman with multiple sexual partners or
3 years. If there is any reason why the patient would a new sexual partner in a population with a high inci-
want to continue with yearly screening (such as a pre- dence of cervical dysplasia. Table 85-5 summarizes cur-
vious history of abnormal cytology), then only cytol- rent cervical cancer screening recommendations,
ogy with reflex HPV testing for ASC-US results should including when to start, how often to screen, and when
be performed. These guidelines specifically recom- to stop routine screening.
mend against using combined testing to lengthen
screening intervals to every 3 years in women in several
Discussion of Case
categories: (1) women less than 30 years old, because of
the high prevalence of transient HPV infection; (2) Our patient, Altagracia L., is at lower risk for cervical
women who are immunosuppressed, including HIV- dysplasia in that she has no known history of abnor-
positive women, because of their high risk for rapidly mal Pap smear results and is older than 30 years, but
progressive cervical dysplasia, which mandates fre- because she has recently changed sexual partners and
quent screening; and (3) women who have undergone is a Latina (a population at higher risk for cervical dys-
a total hysterectomy for benign disease, who, because plasia compared to non-Latin white women), she may
of their very low risk of disease, do not need screening. want to proceed with yearly screening instead of com-
The age cutoff of 30 years for combined testing is based bined screening at 3-year intervals. Even if Ms. L. opts
on the age strata prevalence of HPV, which decreases for combined testing, with a plan to repeat in 3 years
after age 30; the fact that very few cases of cervical can- if all testing is normal, she should be informed that she
cer occur before age 25; and the observation that most should still return yearly for annual gynecologic
clinical trials investigating the use of HPV testing have examinations, including an internal pelvic examina-
been conducted in women more than 30 years old. The tion and breast examination (ACOG, 2003● C ).
underlying assumption is that by age 30, most women
in the United States are engaging in lower-risk sexual
behaviors (i.e., they have fewer changes in partners or
fewer new partners, and there is a lower prevalence of Material Available on Student Consult
STDs in the sexual cohort). This may not be true for all
Review Questions and Answers about Cervical
patient populations, which means these guidelines may
Cancer Screening
need to be modified based on the particular patient or

REFERENCES
American College of Obstetricians and Gynecologists U.S. Preventive Services Task Force. Screening for cervical
(ACOG). Cervical Cytology Screening. ACOG Practice cancer: Recommendations and rationale. 2003. Avail-
Bulletin no. 45. Obstet Gynecol 2003;102:417–425.●
C able at www.preventiveservices.ahrq.gov. Accessed
Cannistra SA, Niloff JM. Cancer of the uterine cervix. 1/26/2006.● C
N Engl J Med 1996;334:1030–1038.● C Wright TC, Cox JT, Massad LS, et al. 2001 consensus guide-
Saslow D, Ranowicz CD, Solomon D, et al. American lines for the management of women with cervical cyto-
Cancer Society guidelines for the early detection of logical abnormalities. JAMA 2002;287:2120–2129.● C
cervical neoplasia and cancer. CA Cancer J Clin Wright TC, Schiffman M, Solomon D, et al. Interim guidance
2002;52:342–362. for the use of human papillomavirus DNA testing as an
Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda adjunct to cervical cytology for screening. Obstet Gynecol
system: Terminology for reporting results of cervical 2004;103: 304–309.● C
cytology. JAMA 2002;286:2114–2119.● C

625
 C h a p t e r

86 Cervical Dysplasia:
Diagnosis and Management
Jon C. Calvert

KEY POINTS

1. Routine Pap smear screening has markedly 8. Several groups have published guidelines recom-
reduced the incidence of cervical cancer. mending when and from whom to obtain Pap
2. Currently, half of those who develop cervical smears.
cancer either never had a Pap smear or have 9. HPV-DNA testing is playing an increasingly
not had a Pap smear within the past 5 years. important role in the diagnosis and manage-
3. Risk factors for cervical cancer include human ment of cervical dysplasia and cervical cancer.
papillomavirus (HPV), smoking, and human 10. The Bethesda system 2001 revision clarifies and
immunodeficiency virus (HIV). redefines Pap smear interpretation.
4. To optimize Pap smear test sensitivity and speci- 11. Approximately one third of high-grade squa-
ficity, adequate numbers of cells need to be col- mous intraepithelial lesions (HSILs) regress to
lected from the squamocolumnar junction and normal in 2 years, and most women infected
the transition zone. with HPV do not develop significant cervical
5. New liquid-based Pap smear preparation tech- abnormality.
niques overcome some of the causes of false 12. Management has changed for the Pap smear
negative results associated with the traditional with absent endocervical cells.
methods of cervical cell collection and processing. 13. Management of atypical squamous cells
6. Of the three conventional Pap smear methods, has changed. It is different for ASC-H
the endocervical brush/spatula method transfers and for ASC-US (with and without HPV-DNA
the most cells to the slide. testing).
7. The correct timing of a Pap smear collection 14. Colposcopy is a skill that can be mastered by
improves the quality of the Pap smear. the practicing family physician.

INITIAL VISIT she lives with her boyfriend and has been in a
monogamous relationship with him for the past
Subjective 2 years. She is aware that during these 2 years her
boyfriend has had other sexual encounters outside
Patient Identification and Presenting
their relationship. She has had previous Pap smears;
Problem the last one was 6 years ago at the time of her last
Aletha W. is a 24-year-old single woman who returns pregnancy. To her knowledge, all of her Pap smears
today to discuss the results of her abnormal Pap have been normal. She has been treated twice in the
smear. past at the health department, once for gonorrhea
(3 years ago) and then for Trichomonas vaginitis (last
Present Illness year). She did not keep her posttreatment test-of-cure
Aletha has been sexually active since age 14, with a appointments. She has been treated at the health
total of at least 11 different male partners. Currently department with cryoablation for genital warts. She

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

626
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

has been pregnant three times, has one child, and has of the acetowhite lesions is seen in its entirety. The
had two elective abortions, both prior to her third entire transition zone can be visualized. Biopsy spec-
pregnancy. She is currently using oral contraceptive imens are obtained from each of the three lesions.
pills as a method of birth control. Because the colposcopy is satisfactory, endocervical
Four months ago she had an abnormal Pap curettage is not done.
smear, ASC-H, and was scheduled for colposcopy
3 months ago but did not keep her appointment.
Assessment
After several missed appointments she presents
today for colposcopy. The Pap smear is ASC-H, with colposcopy findings
suggestive of cervical intraepithelial neoplasia (CIN)
Medical History and cervical condylomata acuminata.
Aletha has had no major medical illnesses. She had
an appendectomy at age 8. She has been admitted to
Plan
a hospital for the appendectomy and for the delivery
of her child. Aletha is asked to make a follow-up appointment to
review the results of the biopsies and discuss future
Family History management.
Aletha does not know the family medical history on
her father’s side because he left home when she was
Discussion
4 years old. Her mother has previously been diag-
nosed with cervical dysplasia and has been treated. According to the new Bethesda guidelines (Table 86-1),
Aletha does not know the type of treatment. There is the Pap smear finding of ASC-H (a new designation)
no family history of breast cancer, cervical cancer, requires that a colposcopy be performed. With col-
uterine cancer, colon cancer, hypertension, diabetes poscopy and biopsy, 5% to 15% of ASC-H Pap smears
mellitus, or heart disease. will be either CIN 2 or CIN 3.

Social History FOLLOW-UP VISIT

Aletha lives with her boyfriend and works as a wait-
ress at a local restaurant. She has smoked one to two Subjective
packs of cigarettes per day since age 14. She occa-
sionally drinks alcohol and has used marijuana in the Aletha returns to review her colposcopy findings. She
past, but not for the past 4 years. has been quite concerned and is apprehensive that
she may have cancer. She says she had some spotting
Review of Systems for 2 days following the procedure but is not cur-
The review of systems is unremarkable except as rently experiencing vaginal spotting or discharge.
described above.
Objective
Objective
You review with her the pathology findings: mild
Colposcopy is performed. Examination of the exter- dysplasia or CIN 1 (6 and 12 o’clock biopsies) and
nal genitalia and vagina does not reveal any evidence human papillomavirus (HPV) (10 o’clock biopsy).
of condylomata or dysplasia. The cervix is visualized
in its entirety. There is a small, 2- to 3-mm area of Assessment
leukoplakia at 10 o’clock, just proximal to the new
squamocolumnar junction in the transition zone The assessment is CIN 1 in a 24-year-old woman
(Color Plate 86-1). Three percent acetic acid is who is a smoker, has genital HPV, and is living with
applied. The area of leukoplakia becomes a denser a partner who has been and is sexually active with
white without mosaicism or punctation or abnormal multiple individuals.
blood vessels, with and without the use of a green
filter. Two areas of acetowhite are identified, at Plan
12 o’clock and at 6 o’clock, in the transition zone
between the new squamocolumnar junction and the There are two management options. The first is to
old squamocolumnar junction. Linear and geo- repeat the Pap smears every 4 to 6 months four times.
graphic in shape, each demonstrates fine punctation It is explained to Aletha that 60% to 70% of cases of
and mosaicism without evidence of abnormal blood CIN 1 resolve. Of those that do not regress, about half
vessels. The previously identified area of leukoplakia progress to a higher grade of dysplasia and half remain
becomes a deeper white after acetic acid is applied unchanged. If follow-up Pap smears indicate that the
but does not exhibit punctation or mosaicism. Each CIN 1 is staying the same or worsening, another

627
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-1 Comparison of the 1991 Bethesda System for Reporting Cervical/Vaginal
Cytologic Diagnoses and the Bethesda (2001) Revision
1991 Bethesda System 2001 Revision of Bethesda System
Specimen Adequacy Specimen Adequacy

Satisfactory for evaluation Satisfactory for evaluation (describe presence or

absence of endocervical T zone component and
any other quality indicators)
Satisfactory for evaluation but limited [category eliminated*]
[reason specified]
Unsatisfactory for evaluation [reason specified] Unsatisfactory for evaluation (specify reason)
Specimen may be processed and unsatisfactory or
unprocessed

General Categorization (Optional)

Within normal limits Negative for intraepithelial lesion or malignancy
(NIL)
Benign cellular changes; see descriptive diagnosis [category eliminated†]
Epithelial cell abnormality; see descriptive Epithelial cell abnormality; see interpretation/result
diagnoses (specify squamous or glandular)
Other (see interpretation/result)

Descriptive Diagnoses Interpretation/Result

Benign Cellular Changes Negative for Intraepithelial Lesion or Malignancy
Infection Organisms
Trichomonas vaginalis Trichomonas vaginalis
Fungal organisms morphologically consistent Fungal organisms morphologically consistent with
with Candida species Candida species
Predominance of coccobacilli consistent with Shift in vaginal flora suggestive of bacterial
shift in vaginal flora vaginosis
Bacteria morphologically consistent with Bacteria morphologically consistent with
Actinomyces species Actinomyces species
Cellular changes consistent with Herpes Cellular changes associated with Herpes simplex
simplex virus virus
Other Other non-neoplastic findings (optional to report;
list not inclusive)
Reactive and reparative changes Reactive cellular changes associated with
inflammation (includes typical repair), radiation,
intrauterine contraceptive device
Reactive cellular changes associated with Atrophy, benign-appearing glandular cells post
inflammation (includes typical repair), atrophy hysterectomy
with inflammation (atrophic vaginitis), radiation,
intrauterine contraceptive device, or other

Epithelial Cell Abnormalities Epithelial Cell Abnormalities

Squamous cells Squamous cells
Atypical squamous cells of undetermined Atypical squamous cells
significance Of undetermined significance
Cannot exclude HSIL‡
Low-grade squamous intraepithelial lesion Low-grade squamous intraepithelial lesion
encompassing human papillomavirus/mild encompassing human papillomavirus/mild
dysplasia/CIN 1 dysplasia/CIN 1
High-grade squamous intraepithelial lesion High-grade squamous intraepithelial lesion
encompassing moderate and severe dysplasia, encompassing moderate and severe dysplasia,
CIN 2, and CIN 3/CIS CIS/CIN 2, and CIN 3
With features suspicious for invasion (if invasion
is suspected)
Squamous cell carcinoma Squamous cell carcinoma

628
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-1 Comparison of the 1991 Bethesda System for Reporting Cervical/Vaginal
Cytologic Diagnoses and the Bethesda (2001) Revision (Continued)
1991 Bethesda System 2001 Revision of Bethesda System
Specimen Adequacy Specimen Adequacy

Glandular cells Glandular cells

Endometrial cells, cytologically benign in Category reported as NIL (above)
postmenopausal women
Atypical glandular cells of undetermined Atypical endocervical cells, endometrial cells,
significance glandular cells
Atypical glandular/endocervical cells, favor
neoplastic
Endocervical adenocarcinoma in situ
Adenocarcinoma
Endocervical adenocarcinoma Endocervical
Endometrial adenocarcinoma Endometrial
Extrauterine adenocarcinoma Extrauterine
Adenocarcinoma not otherwise specified Not otherwise specified

Other Malignant Neoplasms Other Malignant Neoplasms (specify)

Hormonal evaluation (applies to vaginal Educational Notes
smears only)
Hormonal pattern compatible with age
and history
Hormonal pattern incompatible with age and
history [reason specified]
Hormonal evaluation not possible owing to
[reason specified]
*
These smears are categorized as satisfactory and the limiting factors are described.
†These smears are categorized as either NIL if they are clearly negative or as ASC-US if an epithelial abnormality
is suspected.
‡New category.
CIN, cervical intraepithelial neoplasia; CIS, carcinoma in situ.
From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and Practice. Philadelphia, WB Saunders, 2002.

colposcopy will be recommended. If the results of the cancer (early detection) is associated with a 5-year
four follow-up Pap smears are all satisfactory and neg- survival rate of 92%, whereas with late detection,
ative, she can return to annual Pap smears. when distant disease is present at the time of diagno-
The second option is cryotherapy. This proce- sis, the 5-year survival rate is 13%.
dure entails freezing the skin of the cervix, causing it In the 1930s, cervical cancer was the leading cause
to slough off, taking with it the abnormal cells. The of cancer death in women. Today, worldwide, cervical
healing that follows replaces the abnormal skin with cancer is the third most common neoplastic disease
normal skin. After cryotherapy, Aletha would be (9.8%) in women, after breast cancer (21%) and col-
asked to have four follow-up Pap smears obtained orectal cancer (10.1%). In the United States, cervical
every 4 to 6 months. cancer is the eighth most common female malignancy.
George Papanicolaou first proposed evaluation
DISCUSSION of cervical/vaginal cells for purposes of diagnosing
cervical cancer in 1948. Refining and improving the
Pap Smears and Cervical Dysplasia in cell collection technique, J. Ernest Ayre introduced
the use of a wooden spatula to harvest cells directly
Perspective
from the cervical transition zone. In 1954
The impact of Pap smear technology on the reduc- Papanicolaou introduced the cytologic classification
tion of cervical cancer rates is impressive. If Pap system dividing Pap smear results into five classes
smear screening were implemented in a group of (I, II, III, IV, and V), a system still used by some
women never before tested, the rate of cancer would pathologists today. With the development of these
be reduced by 60% to 90% within 3 years and the cytologic criteria, the World Health Organization
mortality from cervical cancer would be reduced by embraced this classification system in the late 1950s.
20% to 60%. The early detection of cervical cancer Using histologic criteria based on the microscopic
significantly improves survival. Localized cervical assessment of the cervical biopsy specimen, Richart

629
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-2 Papanicolaou Smear Nomenclature

Papanicolaou Class
System (1954) Descriptive (1968) CIN (1978) Bethesda System (1988)

Class 1 Negative for malignant cells Negative Within normal limits

Class 2 Inflammatory atypia Reactive and reparative
changes
Squamous atypia Atypical squamous cells of
undetermined significance
Koilocytotic atypia Low-grade SIL; includes
condyloma
Class 3 Mild dysplasia CIN 1 Low-grade SIL; includes
condyloma
Moderate dysplasia CIN 2 High-grade SIL
Severe dysplasia CIN 3 High-grade SIL
Class 4 Carcinoma in situ CIN 3 High-grade SIL
Class 5 Invasive carcinoma Invasive carcinoma Invasive carcinoma
CIN, cervical intraepithelial neoplasia; SIL, squamous intraepithelial lesion.
Modified from Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and Practice. Philadelphia, WB
Saunders, 2002.

introduced the concept of cervical intraepithelial HPV virus types, type 16, has been shown to persist
neoplasia, with the CIN 1, 2, and 3 classification sys- in the same host for at least 5 years. HPV is incorpo-
tem in 1978 (Table 86-2). In an effort to develop a rated into the host DNA. Factors affecting this incor-
Pap smear classification system more broadly poration include age, nutritional status, immune
accepted by pathologists, an expert panel was function, smoking, and genetic polymorphism. HPV
convened in 1988. The result was the proposal and has been identified in 75% to 95% of high-grade
adoption of the Bethesda system. This system squamous intraepithelial lesions (HSILs) and in
remains in use today and has undergone two revi- 95% to 100% of squamous cell cervical cancers.
sions, the latest in 2001. There are currently more than 60 viral types of HPV
The introduction of the Pap smear as a screen- (Table 86-4). The four types that carry the highest
ing tool has had a major impact on the incidence of risk for cervical cancer are 16, 18, 31, and 45. With
cervical cancer in the United States. It is largely as a the advent of hybrid capture technology and clarifi-
result of Pap smear screening that the mortality from cation of the role of intermediate-risk HPV virus
cervical cancer has fallen by more than 70% over the types in the development of cervical cancer, some
past 50 years. In the United States in the year 2004 it groups combine the high- and intermediate-risk
was estimated that there were 11,520 new cases of groups into one group and call it “high risk.”
cervical cancer and 3,900 cervical cancer-related
deaths. In 1998 there were 8 new cases of cervical
cancer per 100,000 women, compared with 44 new
cases per 100,000 women in 1947. Table 86-3 Risk Factors for an Abnormal
Work remains to be done in the area of cervical Pap Smear Result
cancer detection. Currently, more than one-half of
all new cervical cancer cases identified each year fall History of human papillomavirus
into two subgroups. Fifty percent of the new cases Exposure to diethylstilbesterol
are in women who have never had a Pap smear History of an abnormal Pap smear result
Initiation of early sexual activity
(Nuovo et al., 2001● C ). Ten percent of new cases are
More than one sexual partner (ever)
in women who have not had a Pap smear test during Partner with history of human papillomavirus
the preceding 5 years. (HPV)
Illicit drug use
Risk Factors Smoking habit
Infection with HIV
There are several risk factors for cervical cancer Having never had a Pap smear
(Table 86-3). HPV infection is the most important of Having had no Pap smear for preceding 5 years
these risk factors. Among U.S. women, the mean age Modified from Apgar BS, Brotzman G, Spitzer M
for occurrence of HPV is in the mid-20s. Most HPV (eds). Colposcopy: Principles and Practice.
infections are transient, but one of the high-risk Philadelphia, WB Saunders, 2002.

630
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-4 Human Papillomavirus Types

High risk 16, 18, 31, 45
Intermediate risk 33, 35, 39, 51, 56, 58, 59,
W13B
Low cancer risk 6, 11, 53, 54, 66, PAP 155,
PAP 291

Modified from Apgar BS, Brotzman G, Spitzer M

(eds). Colposcopy: Principles and Practice.
Philadelphia, WB Saunders, 2002

In addition to HPV, other risk factors include

smoking and human immunodeficiency virus (HIV)
infection. There is a two- to fourfold increase in
abnormal Pap smears in woman who smoke. Women Figure 86-1 There are several providers of liquid thin
with HIV have a higher prevalence of dysplasia. prep Pap smear technology. A “paint brush” tip (lower
brush) can be used to obtain the specimen when the
Contrary to initial assumptions, recent findings sug- squamocolumnar junction is visible. The narrow tip
gest that the speed with which dysplasia progresses to (upper brush) can be used to obtain the specimen when
cervical cancer does not appear to be increased in the squamocolumnar junction has moved deeper in the
women with HIV. endocervical canal and cannot be visualized. Either the
collected materials are deposited in the liquid container
with a rapid movement or the tip is dislodged and
Cytologic Screening Method dropped into the container.

The goal of cytologic screening is to sample superfi-

cial cells (shed or mechanically dislodged) from the
surface of the transformation zone. To optimize the labeling stating that they are equivalent to or supe-
test sensitivity and specificity, cells need to be col- rior to the conventional Pap smear slide technology
lected at the point of physiologic cell transformation for the detection of cervical cancer precursor lesions
(squamous metaplasia) from endocervical columnar (Wright and Cox, 2004● C ). With improved sensitivity
cells to ectocervical squamous cells (Nuovo et al, (decreased false negative interpretations) there is
2001● C ). An optimal cytologic cell sample would con- decreased specificity (increased percentage of false
tain three cell types: endocervical cells, squamous positive interpretations). With liquid-based methods
cells, and squamous metaplastic cells (cells trans- there appears to be improved identification of
forming from endocervical to ectocervical cell glandular cells associated with atypical glandular
types). Recognizing the squamocolumnar junction cells of undetermined significance associated with
(the point at which endocervical cells meet squa- adenocarcinoma of the cervix. As of early 2004, there
mous cells) and collecting cells from this line of were no published prospective studies comparing the
transformation increases the sensitivity of the Pap new liquid-based technology with conventional Pap
smear test by reducing the number of false negative smear prep technology.
test results. The optimal conventional method for collecting
The sensitivity of the conventional Pap smear and transferring cervical cells has been studied. The
test is 57% (95% confidence interval [CI]: 37% to area from which cell samples should be obtained is
66%) with a specificity of 98% (95% CI: 97% to the transformation zone and the endocervical canal,
99%). The major causes of false negative results using a spatula and a brush (Fig. 86-2). The transfor-
include inadequate sampling (i.e., not obtaining ade- mation zone is that surface of the portion of the
quate numbers of cells from appropriate areas of the cervix that lies between the old squamocolumnar
cervix) and inappropriate sample transfer through junction and the new squamocolumnar junction.
traditional methods (e.g., drying artifact on slides, Whether a spatula is used, as in the conventional
inappropriate application of collected specimen to Pap smear collection method, or a brush, as in the
slide, inappropriate fixation of slide). It is apparent liquid-based technology, harvesting cells from the
that the transfer of cells to the slide is a random event. transition zone markedly improves the detection of
New liquid-based preparation techniques cervical cancer and precervicalcancer changes.
promise to overcome some of these deficiencies Of the three conventional Pap smear methods
(Fig. 86-1). Two current liquid-based techniques, studied—swab/spatula, endocervical brush/spatula,
ThinPrep and Autocyte Prep, have been approved by and the use of a broomlike device—the endocervical
the U.S. Food and Drug Administration (FDA) with brush/spatula method transferred more than twice

631
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Figure 86-2 Traditional Pap smear. Note that the spatula is positioned to collect cells from the squamocolumnar junc-
tion and transition zone (left). The brush (cytobrush) is used to collect cells from the squamocolumnar junction that is
not easily visualized within the external os of the endocervical canal (right). (From Apgar BS, Brotzman G, Sptizer
M (eds). Colposcopy: Principles and Practice. Philadelphia, WB Saunders, 2002.)

as many cells, 18%, versus 7% and 8% for the other When spraying on fixative, the preparer should hold
methods. When the spatula is used, cells collected the container far enough away from the slide that
from the transformation zone should be placed on the force of the spray does not disrupt the cells on
a properly labeled glass slide with a single stroke, the slide and cause them to pile up.
using moderate pressure to thin out the clumps of There are several other techniques to optimize
cells and mucus. To decrease the amount of blood collection of cells. Cells should be collected before
collected and to lessen the risk of cells air-drying the bimanual examination is performed. Recent
before they can be fixed, the cytobrush is used after studies suggest that a small amount of water-based
the spatula. The cytobrush is rotated 180 degrees in lubricant can be used on the speculum when
the endocervical canal, then removed, and the cells collecting a Pap smear specimen without adversely
are transferred from the brush to the slide by rolling affecting the interpretation (Amies et al., 2002 ● A;
the bristles across the slide by twisting the brush Harer et al., 2002●A). Cells for cytologic study should
handle (Fig. 86-3). Fixative should immediately be be collected before cervical specimens are obtained
applied before the cells have had a chance to air dry. for culture. The entire portion of the cervix should

Figure 86-3 Cells are obtained from the transformation (transition) zone and the squamocolumnar junction (Fig. 86-2)
with a wooden spatula and then a cytobrush. The collected cells are applied to the slide in a thin layer using the spat-
ula in a firm, steady stroke from one end of the slide to the other. The bristles of the brush are then gently rolled
across the same slide from one end of the slide to the other. Finally, fixative is applied.

632
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

be visualized and the transition zone identified 2. Have the first Pap smear done 3 years after
before a sample is obtained. Routine swabbing of becoming sexually active or at age 21, whichever
discharge from the cervix may result in a cytologic occurs first.
sample of scant cellularity. Normally, less than 20% 3. Once begun, continue conventional Pap smears
of the cells collected are transferred to the slide. Too annually or liquid-based Pap smears every other
few cells may result in a true false negative interpre- year until age 30.
tation. Air-drying artifact can be avoided by transfer- 4. If the woman is 30 years old or older and three
ring and fixing the specimen as quickly as possible. previous annual Pap smears have been negative,
Rapid transfer is important whether a liquid-based and in the absence of high risk behavior, then,
method or a conventional method is used. regardless of method (conventional or liquid),
The correct timing of the collection of a Pap screening can be performed every 2 to 3 years.
smear improves the quality of the Pap smear. Although 5. If the woman is HIV positive, screen twice the
some liquid-based technology is capable of separating first year and then annually.
out red blood cells, it is best not to collect a specimen 6. If there is a history of diethylstilbestrol exposure
during menses. The following should be avoided for 48 while in utero or an immunocompromised state,
hours prior to collection: vaginal medications, vaginal Pap smears should be done annually.
contraceptives, and douches. Intercourse should be 7. If there is a past history of CIN 2, CIN 3, or a
avoided the night prior to and the day of sample col- DNA test positive for HPV, annual Pap smears
lection. Allow for reparative changes to be complete by are indicated.
obtaining Pap smears no sooner than 6 to 8 weeks after 8. If the woman has had a hysterectomy for a
delivery. In postmenopausal woman, when a Pap benign condition, a Pap smear is no longer indi-
smear identifies atrophy and inflammation or when cated. If the hysterectomy was supracervical (the
endocervical cells are lacking, a 3-week course of vagi- cervix was not removed), manage as if uterus
nal estrogen should precede a repeat Pap smear. were still present.
9. If the woman has had a hysterectomy for CIN 2,
Pap Smears: When and for Whom CIN 3, or cervical cancer, or if the reason for the
hysterectomy cannot be documented, or the
More frequent Pap smears (e.g., yearly or every other absence of a history of CIN 2 or CIN 3 cannot be
year) have a more favorable impact on the reduction documented, continue annual Pap smears. If
of invasive cervical cancer than less frequent Pap then three consecutive annual Pap smears are
smears (e.g., every 3, 5, or 10 years). As noted previ- negative and no abnormal or positive test in past
ously certain risk factors or risk behaviors also affect 10 years can be documented, annual Pap smears
the incidence of abnormal pap smears. In 1987 the may be stopped.
American Cancer Society (ACS) and the American 10. If a Pap smear is normal but endocervical cells
College of Obstetricians and Gynecologists (ACOG) are absent and there is no history of an abnormal
presented a joint statement in an effort to quell con- Pap smear or high-risk behavior, repeat the Pap
troversy and establish an optimal interval for cervical smear in 1 year; otherwise repeat in 4 to 6
cytology. In summary, all sexually active women months.
(past or present) or women 18 years old or older 11. If the individual is pregnant and the Pap smear
should have annual Pap smears; after three or more is negative but there are no endocervical cells,
consecutive negative annual Pap smears, a Pap smear repeat the Pap smear postpartum.
may be performed less frequently, at the discretion of 12. If the Pap smear is negative, repeat in 6 months
the woman’s physician. if (a) there is a recent abnormal Pap smear
More recently, in an effort to incorporate cur- (ASC-US or worse), (b) the abnormal result is
rent research data, several groups have published incompletely evaluated, (c) the cervix was
their individual guidelines for obtaining Pap smears. incompletely visualized, (d) the individual is in
Some of these groups include the American an immunocompromised state, or (e) there is
Academy of Family Physicians, the U.S. Preventive a history of a poor prior screening.
Services Task Force (2003● C ; 2004● C ), ACS (Schroeder, 13. If the individual is 65 to 70 years old and has had
2003● C ), and ACOG (2003● C ). A combined summary three consecutive, annual normal Pap smear and
of these recommendations follows. As with any no positive test within the past 10 years, stop Pap
health care guidelines, they should be applied at the smears.
discretion of the physician and with patient under- 14. If the individual is 65 to 70 years old and
standing and agreement. involved in at-risk behavior (see Table 86-3),
continue annual Pap smears.
1. Obtain annual Pap smears as long as the indi- 15. Screening in woman 70 years or older is recom-
vidual is at risk or is involved in high-risk behav- mended if no previous screening has been per-
ior (see Table 86-3). formed or is unlikely to have been performed, or

633
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

if information about previous screening is not Interpretation Result is divided into three subcate-
available. gories: Negative for Intraepithelial Lesion or
16. Testing may be stopped in women who have Malignancy, Epithelial Cell Abnormalities (squa-
severe comorbid or life-threatening illness. mous cells and glandular cells), and Other
17. As with any set of guidelines, the physician Malignant Neoplasms (specified).
should assess the clinical situation and adjust the With regard to adequacy of the specimen, the
guideline accordingly. phrase “satisfactory but limited by . . .” is no longer
used. Slides are not to be reported “satisfactory” or
“unsatisfactory.” If the specimen is unsatisfactory for
When Is HPV Testing Appropriate?
evaluation, a specific reason is to be given.
The application of liquid film Pap smear technology The category Negative for Intraepithelial Lesion
and the development of HPV testing by Hybrid or Malignancy does not include slides with evidence
Capture II technology allow for specific HPV typing of neoplasm. It may include findings specific either
from the same cellular material that was obtained for for infection or for reactive cellular changes associ-
the Pap smear. The FDA has approved liquid-based ated with inflammation, radiation therapy, an
preparation technology for cervical cancer screening. intrauterine contraceptive device (IUD), or atrophy.
The FDA has also approved Hybrid Capture II tech- Endometrial cells found in women age 40 years or
nology for the screening of cells obtained from the older will be placed in this category. In women
cervix for HPV DNA. Using the cells present in the younger than 40, the presence of endometrial cells
liquid prep medium, the presence or absence of will not be reported.
high-risk or intermediate-risk HPV types is deter- In the subcategory Epithelial Cell Abnormalities
mined (see Table 86-4). (squamous cells and glandular cells), under the sub-
There currently are two situations in which HPV- heading squamous cells there is a significant change
DNA typing is called for (Wright and Cox, 2004● C ). in atypical cell terminology that impacts manage-
The first is in the presence of Pap smears read as ment decisions (Wright et al., 2002● C ). The term
atypical squamous cells of undetermined signifi- “atypical squamous cells of undetermined signifi-
cance (ASC-US). With the liquid film preparation cance, favor reactive” (ASCUS, favor reactive) has
and ASC-US there is an automatic “reflex testing” to been replaced with “atypical squamous cells of
Hybrid Capture II. Current guidelines recommend col- undetermined significance” (ASC-US). Depending
poscopy for ASC-H when identified by Pap smear only. on the presence or absence of risk factors, this find-
Colposcopy is also recommended if there is an ASC- ing may or may not require colposcopy. If there are
US Pap smear with a high-risk test positive for HPV. no risk factors, a Pap smear may be repeated in 12
This situation carries a 79% to 98% sensitivity for months. If there are risk factors, a Pap smear may be
identification of CIN II/III at colposcopy. repeated in 6 months. If HPV DNA testing is per-
A second application of HPV DNA testing is formed and high-risk HPV is also present, col-
when a Pap smear identifies ASC-US, ASC-H, or low- poscopy is indicated.
grade squamous intraepithelial lesions (LSIL) and The term “atypical squamous cells of undeter-
both the colposcopy and the colposcopically directed mined significance, favor dysplasia” (ASCUS, favor
biopsy are negative (Wright et al., 2002●C ). At the time dysplasia), is no longer used. It has been replaced
of the next Pap smear (in 6 or 12 months), HPV typ- with “atypical squamous cells, cannot exclude HSIL”
ing should be obtained. If the typing is positive for (ASC-H). Because 5% to 15% of women with ASC-U
high-risk HPV, even if the Pap smear is normal, col- Pap smears will have CIN 2/3 by colposcopic exami-
poscopy should be considered. nation/biopsy, women with ASC-H should be sched-
uled for colposcopy.
The Bethesda System of Pap Smear In the subcategory Epithelial Cell Abnormalities
(squamous cells and glandular cells), under glandu-
Reporting
lar cells the term “atypical glandular cell” has
First proposed in 1988 and revised in 1991 and 2001, replaced the term “atypical glandular cells of unde-
the Bethesda system is most widely used in the termined significance.” The finding atypical glandu-
United States (Apgar et al., 2003●
C ). A comparison of lar cell (AGC) is more likely to be associated with
the 1991 Bethesda system for reporting cervical/vagi- both glandular and squamous abnormalities than
nal cytologic diagnoses and the 2001 revision of the the term ASC-US. The three types of AGC reported
Bethesda system is given in Table 86-1. Several are endocervical, endometrial, and glandular cells
important changes occurred with the 2001 revision not otherwise specified. The addition of the term
(Solomon et al., 2002●C ). “favor neoplastic” AGC has been retained, but “favor
The Bethesda system 2001 revision is divided reactive” has been dropped. The third and fourth cat-
into two large categories: Specimen Adequacy egories listed under glandular cells are endocervical
and Interpretation/Result. In turn, the category adenocarcinoma in situ and adenocarcinoma.

634
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

The category of AGC is less clearly defined Management of the Pap Smear Result
(Levine et al., 2003●C ; Solomon et al., 2002●
C ). Unlike
in squamous disease, there are no intermediary The Pap smear test has been performed and the
categories between AGC and adenocarcinoma. report is back. Now, what to do? Various groups have
Therefore, there is an intermixing of benign causes of recommended guidelines (Levine et al., 2003● C;

AGC with premalignant and malignant causes. Wright et al., 2002● C ). If the Pap smear is satisfactory

Benign causes of AGC include polyps, IUD use, and negative, schedule the patient for the next
cervical endometriosis, previous cervical conization, appropriate Pap smear according to age and risk fac-
tubal metaplasia, inflammatory changes, microglan- tors (see subsequent discussion under Pap Smears:
dular hyperplasia, and pregnancy-associated changes. When and for Whom).
Unlike ASC-US cytology, AGC cytology carries with it If the Pap smear is ASC-US, repeat in 6 to 12
a very high rate of invasive and preinvasive cancer, months, depending on level of risk. If there are risk
although the incidence of AGC cytology is low, vary- factors (see Table 86-3), repeat in 6 months. If there
ing from 0.1% to 0.4% of all smears. are no risks, repeat in 1 year. If the Pap smear is ASC-
US and liquid cytology was performed with reflex to
HPV DNA typing and the HPV type is high risk,
Progression from Dysplasia to Cervical schedule the patient for colposcopy.
Cancer If the Pap smear is ASC-H or LSIL or HSIL,
The progression of HSIL to invasive cancer is 1.44%. schedule the patient for a colposcopy. If colposcopic
In 35% of cases, HSIL regresses to normal in 2 years. results identify CIN 1 and this finding matches the Pap
Even though HPV is necessary to foster the develop- smear findings, follow-up Pap smears can be per-
ment of cervical dysplasia, most women infected with formed every 4 to 6 months until three negative results
HPV do not develop significant cervical abnormality. are noted; after three negative results are found, return
HPV is transmitted during intercourse, and once to routine Pap smears according to the individual
infection with HPV takes hold, the viral load is patient’s particular level of risk. Cryotherapy also can
reduced to undetectable levels in 8 to 24 months. In be performed, followed by Pap smears every 4 to
the development of dysplasia, in addition to HPV two 6 months until three negative tests are noted, and then
other cofactors may include smoking and a compro- return to routine Pap smears according to the individ-
mised immune system. Though many consider there ual patient’s particular level of risk.
to be a continuum in the development of dysplasia If the colposcopic biopsy reveals CIN 2,
from CIN 1 to CIN 3, this is currently being debated. cryotherapy or cone biopsy can be performed,
depending on the practitioner’s level of confidence
in his or her ability to identify by colposcopy the area
Absence of Endocervical Cells
of most advanced dysplastic involvement. If the col-
Recent data have led to a reevaluation regarding the poscopic biopsy reveals CIN 3 or the endocervical
management of Pap smears reported unsatisfactory curettings reveal CIN 2 or CIN 3, a cone biopsy (loop
because of the absence of endocervical cells. The electrosurgical excision procedure [LEEP] or cold-
assumption has been that when endocervical cells knife-cone) is the next step.
are present, the cell population sampled represents the If the Pap smear is interpreted as invasive squa-
transition zone of the cervix. This is also assumed to mous cell cancer, refer the patient to a gynecologist
be true if metaplastic squamous cells are present or gynecologic oncologist. If the Pap smear is inter-
(squamous metaplasia occurs at the interface of the preted as AGC, a colposcopically directed evaluation
squamous cells with the columnar endocervical cells- and biopsy with endocervical curettage should be
new squamocolumnar junction). ACOG suggests the performed (Wright et al., 2002● C ). If the result is neg-
following guideline for the management of Pap smears ative, monitor with a Pap smear every 4 to 6 months
where endocervical cells are reported absent. until a minimum of three normal Pap smears have
If a recent Pap smear is negative and there are no been obtained. If the Pap smear identified glandular
findings of ASC-US or worse, repeat the Pap smear abnormality recurs, a cone biopsy should be per-
in 1 year. In the absence of endocervical cells, the Pap formed. If the patient with AGC is postmenopausal
smear should be repeated in 6 months if (1) a recent or perimenopausal and has irregular bleeding or is
Pap smear is not normal (finding of ASC-US or otherwise at risk for endometrial cancer, an endome-
worse), (2) there is an incompletely evaluated abnor- trial biopsy should be performed.
mal test result, (3) the cervix was incompletely visu- If the Pap smear is interpreted as AGC, favor neo-
alized, (4) the woman has an immunocompromised plasia, a colposcopy with endocervical curettage should
status, or (5) there is a history of poor prior screen- be performed. If this is positive for adenocarcinoma
ing. During pregnancy a Pap smear that does not in situ (AIS), referral to an appropriate specialist is the
contain endocervical cells should be repeated 6 to 10 next step. If the colposcopy and endocervical curettage
weeks postpartum. (ECC) are negative, a cervical conization is the next

635
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

step because there is a 50% false negative rate in this pre-owned scopes and even inexpensive new scopes.
situation. If the patient is postmenopausal, many rec- Good colposcopy can be done without a lot of bells
ommend an endometrial biopsy along with col- and whistles. For instance, the scope need not have
poscopy and endocervical curettage. more than two magnification settings (for example, 8×
and 13× are sufficient) (Fig. 86-9). An expensive zoom
lens is not needed. Most colposcopy is performed
COLPOSCOPY: GETTING STARTED around 8× magnification; only rarely is a higher mag-
nification needed. A green or blue filter should be
available to facilitate identification of abnormal blood
Colposcopy: The Equipment
vessel patterns. Gross focus is achieved by moving the
To perform colposcopy, certain forms or documents entire scope toward and away from the cervix. This can
are helpful, and proper equipment is necessary. A be achieved with the colposcope on rollers or on a sta-
patient colposcopy information sheet (Fig. 86-4), an tionary stand with an elbow where the support rod
informed consent form for biopsies of the cervix, attaches to the floor plate. Selection of one or the other
endocervix, vagina, introitus, perineum, or anus is usually a personal preference, so it is helpful to try
(Fig. 86-5), a comprehensive patient intake form to out different stands before making a purchase. The
be completed by the patient before the colposcopy is mechanism for fine focus takes various forms and is
performed (Fig. 86-6), and an example of a form found on the colposcope head (see Fig. 86-9).
that can be used to record colposcopic findings, A supply and equipment setup for colposcopy is
results, and management plans (Fig. 86-7). demonstrated in Figure 86-10. Because it is wider
The equipment and instruments necessary to than a Pederson speculum, a metal Graves speculum
perform colposcopy need not be expensive. Most of is most commonly used to optimize visualization of
them can be purchased used. The primary consider- the cervix. Sometimes it is necessary to use a
ation should be the colposcope (Fig. 86-8), and in Pederson speculum or even a large pediatric specu-
particular the optics. Good optics are available on lum when the vaginal opening does not allow com-

Colposcopy Information Sheet

What is colposcopy? It is a close-up examination What is the examination like? It is like a regular
of the cervix using a special microscope called a col- pelvic examination, except that instead of looking
poscope. at the cervix with the naked eye, the clinician will
be looking through the colposcope. The entire
Why do I need it? It will help identify the cause of examination takes approximately 20 to 30 minutes.
your abnormal Papanicolaou (Pap) smear. An abnor- If a biopsy is obtained, a slight pinching sensation
mal Pap smear may indicate cancerous and precancer- may be experienced. The final step is to do a scrap-
ous conditions, as well as some relatively harmless ing of the inside of the cervix. This is called an
conditions. The Pap smear alone, however, cannot endocervical curettage. This part of the examina-
give a definitive diagnosis. The cervix must be magni- tion lasts only about 15 seconds and is usually asso-
fied many times by the colposcope to look for the ciated with some cramping.
source of the abnormal cells. A small segment of each
of these areas is then obtained for study by a pathol- What happens after the examination? You will
ogist. This is called a biopsy. be given a sanitary napkin to wear. No time off from
work is needed. Intercourse should be avoided until
Is any preparation necessary? You should not all bleeding stops. No other limitation of activities is
douche, use any vaginal creams, or have intercourse needed. The biopsy results will be back within 2
2 days before the examination. It is ideal to per- weeks, at which time your clinician will contact you
form the colposcopy just after your period has to discuss treatment plans, if necessary, as well as
ended. Many women find it helpful to take three what follow-up is needed. Please contact your clini-
ibuprofen tablets 1 to 2 hours before their appoint- cian if she or he has not contacted you within 2
ment to reduce any cramping associated with a weeks of your appointment. If your phone number
biopsy (do not use ibuprofen if you are allergic to it or address changes, please inform_____ at _____ so
or to aspirin or if you are pregnant). that we can update your chart.

Figure 86-4 Colposcopy information sheet. (From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and
Practice. Philadelphia, WB Saunders, 2002.)

636
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Informed Consent for Colposcopy with Biopsy of Cervix, Endocervix,

Vagina, Introitis, Perineum, or Anus
_______________________ or his/her assistant has I have also been informed of the following bene-
explained to me the procedures and local anesthe- fits of the procedure:
sia necessary to diagnose my condition or my — Can be done in the office
dependent’s condition. I understand the nature of — Helps diagnose cause of abnormal Pap smear
the procedure summarized below and I request and — Helps plan future therapy
authorize the performance of biopsy of the cervix,
endocervix and possibly the vagina, vulva, per- I understand that the procedure to be performed
ineum or anus. will be done under the guidance of a colposcope (a
I have been informed and understand that the special microscope). I consent to the administration
following are possible risks associated with the pro- of such local anesthesia as is considered necessary. I
cedure: understand that video or photographic equipment
— Light bleeding that may require a sanitary nap- may be used during my procedure for later educa-
kin tional purposes.
— Heavy bleeding (rare) that may require a stitch The procedure of biopsy of the cervix, endo-
or hospitalization cervix, vagina, vulva, perineum, and anus has been
— Pain during the procedure (usually mild) explained to me. I have read and understand this
— Infection of biopsy site or uterine lining information, and I have had all questions answered
to my satisfaction. I consent to the procedures out-
lined in this form.

(Adult patient): _______________________________________

Signature: _________________________________________ Date: _________________________________________

Witness: ____________________________________ Time: ______________ Date: ____________________________

(Minor patient accompanied by parent or guardian): __________________________________

I, the parent or legal guardian of the above-named minor, an unemancipated minor, do hereby consent
to the procedures described above.

Signature (parent/guardian): _____________________________________ Date: ____________________________

Witness: ____________________________________ Time: ______________ Date: ____________________________

Telephone authorization for unaccompanied minors:

Parent/guardian name: ________________________________ Telephone:

__________________________________

Caller (clinician) signature: ________________________________________ Date:

____________________________

FIgure 86-5 Informed consent for colposcopy with biopsy of cervix, endocervix, vagina, introitus, perineum, or anus.
(From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and Practice. Philadelphia, WB Saunders, 2002.)

fortable passage of a larger speculum. In some When the new squamocolumnar junction is difficult
women the lateral side walls of the vagina collapse to visualize in the endocervical canal or when trying
inward and partially or completely obscure visual- to visualize the full extent of an acetowhite lesion
ization of the cervix. Two methods are available to into the endocervical canal, an endocervical specu-
improve visualization. One is the use of a lateral wall lum can be used (Fig. 86-12).
retractor. The second is using a condom, which is less Several types of punch biopsy forceps are avail-
expensive and usually just as satisfactory (Fig. 86-11). able. The handles vary in length and the biopsy teeth

637
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Patient Intake Form

Referred by: ________________________ Your name: _________________________________________
Your address: ________________________ City/State: _________________Zip code: _________________
Home telephone: _____________________ Work telephone: _______________________
Your age now: ________ Date of your last menstrual period: _______________________

Please answer the following questions. Your answers will remain strictly confidential.
Reason(s) for referral: _____ Abnormal Pap smear
_____ Vaginal discharge
_____ Vaginal bleeding
_____ DES exposure
_____ Warts For how long?_____________________
_____ Other ______________________________________
Any prior treatment for abnormal Pap smears? _____ Yes _____ No
If yes, please list date and type of treatment: _____________________
Martial status: ___________ Married ___________ Single ___________ Divorced
Age at first intercourse: _____ (0 = not applicable)
Total number of sexual partners in your lifetime: _____
Total # of pregnancies: _____ # of miscarriages or abortions: _____
Type of birth control currently used: _____ Birth control pill
_____ IUD
_____ Tubal ligation
_____ Norplant
_____ Vasectomy in partner
_____ Barrier method
_____ Other What? ____________________________________
Do you smoke cigarettes? _____ Yes _____ No
If yes, how many packs a day? _____ For how many years? _____
Have you ever been treated for any of the following:
_____ Herpes _____ Chlamydia _____ Trichomoniasis _____ Other ___________________
_____ Gonorrhea _____ Syphilis _____ Warts _____ No
Has your sexual partner ever been treated for the following:
_____ Herpes _____ Chlamydia _____ Trichomoniasis _____ Other ___________________
_____ Gonorrhea _____ Syphilis _____ Warts _____ No
Have you ever taken an AIDS test? _____ Yes_____ No
If yes, was the result _____ positive or _____ negative?
Do you use intravenous drugs presently? _____ Yes _____ No
In the past? _____ Yes _____ No
Do you have a history of a bleeding disorder? _____ Yes _____ No

Figure 86-6 Patient intake form. (From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and Practice.
Philadelphia, WB Saunders, 2002.)

638
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Colposcopy Form
Patient ID#:

Examiner name(s): Date: Primary care physician:

Reason(s) for colposcopy:

Colposcopic findings: LK — leukoplakia, WE — white epithelium, PN — punctation, MO — mosaic,

AV — atypical vessel, SCJ — squamocolumnar junction, X — biopsy sites
Pap smear done: Yes No

ECC Biospy of Cervix Vagina Vulva

HPV testing Wet prep Other

Colposcopy findings:

*Vulva, vagina, perineum, perianal area normal: Yes No

If no, describe:

*Entire SCJ seen: Yes No

*Limits of lesion seen: Yes No NA

*Invasive cancer seen: Yes No

Colposcopic diagnosis:

Cytology diagnosis:

Biopsy diagnosis:

Final impression:

Low-grade CIN

High-grade CIN

Invasive carcinoma

Condyloma acuminatum

Ectropion

Squamous metaplasia

Endocervical polyp Endometrial polyp

Other
Remarks:

• Results and plan discussed with patient: Yes No

by Phone Letter Other ( ) Date:

• Treatment options discussed, including:

LEEP LEEP cone Laser Cryo CKC TCA Observation Other

Management option selected:
• Follow-up date:

• Note sent to primary care physician: Yes Date:

Colposcopist signature

Figure 86-7 Colposcopy form. (From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and
Practice. Philadelphia, WB Saunders, 2002.) 639
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Figure 86-10 Basic supply and equipment setup for col-

poscopy. Top row from left to right: Monsel’s solution, 3%
acetic acid, Lugol’s solution, formalin specimen container,
Graves speculum. Bottom row from left to right: Small
and large cotton tip applicators, endocervical curette,
endocervical speculum, ring forceps, biopsy forceps.

Figure 86-8 Colposcope on a stand. A, Twisting this

handle moves the body of the colposcope toward or
away from the object being viewed, allowing for fine
focus. B, Twisting this handle moves the head of the
scope vertically to allow for best visualization of the
cervix. C, This box contains the light source, an on-off
switch, and a rheostat to adjust the brightness of the
light.

Figure 86-11 Although a lateral wall retractor can be

used, it is usually sufficient to use a condom placed on a
Grave’s speculum to retract collapsing vaginal side walls.

Figure 86-9 The colposcope head has bifocal lenses that

adjust for varying intraocular distance and have an indi-
vidual adjustment for focal length. A, This dial allows for
selection of various lens magnifications. B, This is the Figure 86-12 An endocervical speculum is helpful in
green filter. It is in place at this time; flipping the silver opening the external os of the cervix to evaluate the
handle horizontally will remove the green filter from full extent of the squamocolumnar junction or to deter-
the light source path. C, This handle moves the colpo- mine the distance an acetowhite lesion extends into the
scope to allow for fine focus. D, When this white cap is endocervical canal. Inset: The tip of the endocervical
removed, a camera can be attached to allow colposcopic speculum comes in two sizes to accommodate various
pictures to be taken. endocervical canal openings.

640
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Figure 86-13 Biopsy forceps come in different lengths

and with a variety of tips, varying in shape and size. This
is a Tischler punch biopsy forceps. Inset: The two tips
demonstrated here are the regular size Tischler and the
baby Tischler.

Figure 86-14 Endocervical curette. These come in vari-

ous lengths and with various curette tips, some with a Figure 86-15 Monsel’s solution is ferric subsulfate.
“basket” and some without. The inset shows a curette Straight out of the bottle it is a dark watery liquid.
tip without a basket. When allowed to sit in a container that is open to the air
for several days it will gradually thicken and change to a
yellow-brown color. If it becomes too thick, it can be
thinned by adding a small amount of ferric subsulfate
straight out of the bottle.
vary in size and shape (Fig. 86-13). Because the focal
length of most colposcopes is 30 cm, punch biopsy
instruments with long handles may be difficult to
maneuver. Again, personal preference comes into
play. The endocervical curette also comes in various
lengths and various tip configuration (with and
without a basket) (Fig. 86-14). Some prefer a basket
to help collect the curettings, others do not.
After a punch biopsy is performed, the biopsy site
will bleed. Ferric subsulfate (Monsel’s solution) is
commonly used to achieve hemostasis (Fig. 86-15). To
control bleeding, place Monsel’s solution (Fig. 86-16)
on a small, cotton-tipped swab and apply pressure to
hold the swab to the biopsy site defect. Though this is
almost always sufficient to stop bleeding, rarely it may
be necessary to place a suture to stop the bleeding. For
this purpose long instruments (needle driver, forceps,
scissors) with needle and suture should be sterilized
and available.

Colposcopy: The Examination Figure 86-16 Each colposcopist has his or her favorite
consistency of Monsel’s solution for “best” application
Vulua to the biopsy site to stop the bleeding. When it comes in
contact with blood, the solution changes to a dark
Because condylomata and dysplasia can occur any- brown or black color. It is wise to warn the patient that
where in the lower reproductive tract, colposcopy she will have a colored discharge for several days fol-
should include examination of the vulva, vagina, and lowing the application of Monsel’s solution.

641
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-5 Site-Specific Colposcopy: Vulva

The Kinds of Observations You Can Expect to Make at
This Step of the Examination

Steps in Colposcopic Assessment Normal Findings Abnormal Findings

1. Assess before the application of Hart’s line Benign epithelial

3%–5% acetic acid. Hair-bearing and non– abnormalities (lichen
hair-bearing selerosus, lichen planus,
squamous epithelium squamous cell hyperplasia)
Sebaceous hyperplasia Lentigo maligna
Bartholin’s cyst/abscess
Epithelial cysts
2. Assess with 3% acetic acid. Micropapillomatosis labialis Condyloma acuminatum
Nonspecific acetowhite Acetowhite epithelium
epithelium specific for preinvasive
disease or invasion VIN
1, 2, 3
Vulvar carcinoma
3. Perform colposcopic-directed biopsy*
(local anesthesia, punch, excision).
4. Perform hemostasis (direct pressure,
Monsel’s solution [small amount, wipe
away excess]).
5. Apply protective dressing.*
*
Not required.
VIN, vulvar intraepithelial neoplasia.

cervix. Before a speculum is placed in the vagina 86-14), and vulvar squamous cell carcinoma (Color
begin with examination and colposcopy of the vulva Plates 86-15 and 86-16).
(Table 86-5). Before applying acetic acid, begin the Suspicious areas should be biopsied using local
examination with the hair-bearing mons pubis and anesthesia (topical application followed by injection)
labia major lateral to Hart’s line. Move medially eval- and punch biopsy. Hemostasis is achieved using
uating the clitoral area outer aspect of labia minora direct pressure, a silver nitrate stick, and/or Monsel’s
and inner aspect. Continue to move the examination solution. Rarely, suture placement may be necessary
medially to and including the hymenal ring. Then to achieve hemostasis. A protective dressing may or
examine the skin of the fourchette and move may not be applied. A topical broad-spectrum
down to include the perineum and perianal area. antibiotic can be applied.
Sebaceous hyperplasia is a common normal finding.
Abnormal vulvar findings prior to application of Vagina
acetic acid may include: vulvar atrophy, psoriasis Colposcopy of the vagina is achieved in two steps
(Color Plate 86-2), lichen simplex chronicus (Color (Table 86-6). The lateral walls of the vagina are exam-
Plate 86-3), lichen sclerosis (Color Plates 86-4 and ined after the speculum has been placed and opened.
86-5), and lichen planus (Color Plate 86-6). The cervix is gently moved in all directions with the
To apply 3% to 5 % acetic acid, fold 4 × 4-inch open speculum to promote complete visualization of
gauze in fourths, soak with acetic acid, gently spread the anterior, posterior, and lateral fornices represent-
the labia minora, and place the gauze just distal to ing the cervical-vaginal junction. The anterior and
the hymenal ring between the labia minora. Leave in posterior walls of the vagina can be examined as the
place for 3 to 5 minutes (acetowhite changes take speculum is removed slowly, allowing visualization of
longer to manifest in the less moist vulvar epithelium the vaginal epithelium as it rolls over the ends of the
than in the more moist cervical epithelium). Normal speculum. These steps will need to be repeated while
findings include micropapillomatosis labialis (Color applying acetic acid and after application of Lugol’s
Plate 86-7), nonspecific acetowhite epithelium solution. Lugol’s iodine solution can be applied, with
(Color Plate 86-8) and lentigo simplex (Color Plate the normal glycogenated epithelium staining a dark
86-9). Abnormal findings include condylomata mahogany. In comparing the appearance before and
acuminata (Color Plate 86-10), vulvar intraepithelial after application of Lugol’s solution, the abnormal
neoplasia (VIN) 1, 2, and 3 (Color Plates 86-11 to epithelium will not stain (Color Plate 86-17).

642
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-6 Site-Specific Colposcopy: Vagina

The Kinds of Observations You Can Expect to Make at
This Step of the Examination

Steps in Colposcopic Assessment Normal Findings Abnormal Findings

1. Clean the vagina with saline* Squamous epithelium Adenosis

and assess. (no glands) Vaginal polyps
Vaginal cysts
DES morphology
2. Assess the vagina with a green filter Abnormal vascular patterns
before the application of 3%–5% (punctation)
acetic acid.* Atypical vessels
Patches of superficial
erosions (strawberry
spots caused by vaginitis)
3. Assess the vagina after the application Nonspecific acetowhite Acetowhite epithelium
of 3%–5% acetic acid. epithelium specific for preinvasive or
invasive disease
VAIN 1, 2, 3
Vaginal carcinoma
4. Assess the vagina after the application Dark, mahogany Nonstaining
of diluted Lugol’s iodine solution. staining (glycogenated (nonglycogenated
epithelium) epithelium)
Variegated
5. Perform colposcopic-directed biopsy*
(vaginal biopsy punch, local anesthesia,
excision).
6. Perform hemostasis (pressure, Monsel’s
solution, silver nitrate).
*
Not required.
DES, diethylstilbestrol; VAIN, vaginal intraepithelial neoplasia.
From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and Practice. Philadelphia, WB Saunders,
2002.

Before the application of acetic acid, abnormal Cervix

findings may include adenosis, vaginal polyps, With the exception of use of the terms “satisfactory” or
vaginal cysts, diethylstilbestrol (DES) morphology “unsatisfactory,” colposcopy of the cervix is similar in
such as adenosis (Color Plate 86-18), atrophy with many respects to colposcopy of the vulva and vagina
petechial hemorrhages (Color Plate 86-19), and (Table 86-7). The focus of the colposcopic examination
endometriosis. Examination using the green filter is the ectocervix (Color Plate 86-25). For the colpo-
will accentuate punctation and other atypical vas- scopic examination to be satisfactory all of the transi-
cular pattern such as the “strawberry” pattern tion zone must be visualized and the full extent of any
(Color Plate 86-20) associated with infection. cervical lesion must be visualized. For example if an
Application of 3% to 5% acetic acid will identify acetowhite lesion is present at the cervical os and it
acetowhite areas with or without abnormal vascular extends up into the endocervical canal such that the
patterns, which may represent squamous metapla- deep margin within the endocervical canal cannot be
sia, human papillomavirus (Color Plate 86-21), VIN visualized, the examination would be referred to as
1, 2, and 3 (Color Plates 86-22 and 86-23), or vagi- unsatisfactory. The transition zone is the area of the
nal squamous cell carcinoma (Color Plate 86-24). cervix located between the old squamocolumnar junc-
After application of local anesthetic, a cervical tion (Color Plate 86-26) and the new squamocolumnar
punch biopsy instrument can be used to obtain a tis- junction. The new squamocolumnar junction may be
sue sample. Hemostasis is achieved by applying near the endocervical canal os (Color Plate 86-27) or
direct pressure with Monsel’s solution. If bleeding is may be separated from the endocervical os by the pres-
light, a brief application of silver nitrate is sufficient. ence of ectropion (Color Plate 86-28).
Rarely, suture placement may be necessary to achieve The entire transition zone should be visualized,
hemostasis. since this is where dysplasia begins. A large “Texas

643
 Chapter 86 Cervical Dysplasia: Diagnosis and Management

Table 86-7 Site-Specific Colposcopy: Cervix

The Kinds of Observations You Can Expect to Make at
This Step of the Examination

Steps in Colposcopic Assessment Normal Findings Abnormal Findings

1. Clean the cervix with saline.* Mature squamous and Leukoplakia

columnar epithelia Polyps
Nabothian cysts
2. Assess the cervix with a green filter Abnormal vascular patterns
before the application of 3%–5% Atypical vessels
acetic acid.*
3. Assess the cervix after the application Gland openings Condyloma acuminatum
of 3%–5% acetic acid. Squamous metaplasia Acetowhite changes specific
Squamocolumnar junction for preinvasive and invasive
Nonspecific acetowhite disease
changes CIN 1, 2, 3
Cervical carcinoma
Abnormal vascular patterns
Atypical vessels
4. Assess the cervix after the application Dark, mahogany staining Nonstaining
of diluted Lugol’s iodine solution.* (glycogenated epithelium) Variegated (nonglycogenated
epithelium)
5. Perform endocervical sampling*
(ECC, cytobrush).
6. Perform colposcopic-directed biopsy*
(cervical biopsy punch).
7. Perform hemostasis (pressure,
Monsel’s solution, silver nitrate).*
*
Not required.
CIN, cervical intraepithelial neoplasia; ECC, endocervical curettage.
From Apgar BS, Brotzman G, Spitzer M (eds). Colposcopy: Principles and Practice. Philadelphia, WB Saunders,
2002.

swab” can be used to apply acetic acid and move the coxcomb anterior lip suggests prior exposure to DES
cervix, allowing complete visualization of the transi- and increases the risk for adenosis and related cancer.
tion zone (Color Plate 86-29). Before 3% to 5% acetic If the colposcopy is unsatisfactory, an endocer-
acid is applied, the colposcopic examination should vical sampling should be obtained using either an
be completed, first without using the green filter and endocervical curette or a cytobrush. The endocervi-
then with the green filter. Acetic acid is applied for cal curette is used to pull endocervical cells from a
1 to 2 minutes to allow the acetowhite areas to depth of 1 to 1.5 cm in a circumferential fashion to
become evident. Without continuous application of the external cervical os. The sample of cells is
acetic acid, the acetowhite lesions will fade. Not all deposited there and once the sampling is complete, a
colposcopists use Lugol’s solution. If it is used, it is ring forceps is used to gather the accumulated cell
applied after all other examinations are completed. sample and place it in formalin. Following endocer-
Prior to application of acetic acid, abnormal vical sampling the biopsy forceps are used to obtain
findings might include leukoplakia (Color Plate 86- as many biopsies as are indicated. In most situations
30), polyps, and nabothian cysts (Color Plate 86-31). anesthesia is not necessary prior to obtaining the
Abnormal vascular patterns include mosaicism and biopsy. A general rule of thumb is, if a lesion is sus-
punctation (Color Plates 86-32 and 86-33) and picious or you are not certain what it represents,
atypical blood vessels (Color Plate 86-34). After biopsy it. Hemostasis is achieved using direct pres-
application of 3% to 5% acetic acid, condylomata sure and Monsel’s solution. Rarely, suture placement
acuminata, CIN I, II, or III, cervical cancer, abnormal may be necessary to achieve hemostasis.
vascular patterns, and atypical vessels may be seen.
Acetowhite changes tend to occur in a geographic
maplike pattern that can extend across the entire Material Available on Student Consult
transition zone from the new squamocolumnar junc-
Review Questions and Answers about Cervical
tion to the old squamocolumnar junction (Color
Dysplasia
Plate 86-35). The presence of a cervical collar or a

644
 Chapter 87 Feeling Depressed (Drug Dependency)

REFERENCES
American College of Obstetricians and Gynecologists. Schroeder BM. ACS Updates: Guidelines for the early
ACOG Practice Bulletin: Clinical management guide- detection of cervical neoplasia and cancer, Am Fam
lines for obstetrician-gynecologists. No. August 2003. Physician 2003;67:2011–2016.● C
Cervical cytology screening. Obstet Gynecol 2003;102: Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda
417–427.● C System: Terminology for reporting results of cervical
Amies AE, Miller L, Lee SK, Koutsky L. The effect of vagi- cytology. JAMA 2002;287:2116–2119.● C
nal speculum lubrication on the rate of unsatisfactory U.S. Preventive Services Task Force. Screening for cervical
cervical cytology diagnoses. Obstet Gynecol 2002;100: cancer: Recommendations and rationale. Am Fam
889–892.● A Physician 2003;67:1759–1766.● C
Apgar BS, Zoschnick L, Wright, TC. The 2001 Bethesda U.S. Preventive Services Task Force. Screening for cervical
system terminology. Am Fam Physician 2003;68: cancer. Rockville, MD, Agency for Healthcare Research
1992–1998.● C and Quality, 2003. Available at www.ahrq.gov/clinic/
Harer WB, Valenzuela G, Lebo D. Lubrication of the vaginal uspstf/uspscerv2.htm. Accessed 11/6/2004.● C
introitus and speculum does not affect Papanicolaou Wright TC, Cox JT. Clinical Uses of Human Papillomavirus
smears. Obstet Gynecol 2002;100: 887–888.● A (HPV) DNA Testing. American Society for Colposcopy
Levine L, Lucci III JA, Dinh TV. Atypical glandular cells: and Cervical Pathology, 2004, pp 1–26.●C
New Bethesda terminology and management guide- Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ.
lines. Obstet Gynecol Surv 2003;58:399–406.● C 2001 Consensus guidelines for the management of
Nuovo J, Melnikow J, Howell LP. New tests for cervical cancer women with cervical cytologic abnormalities. JAMA
screening. Am Fam Physician 2001;64: 780–786.● C 2002;287:2120–2129.● C

C h a p t e r

87 Feeling Depressed
(Drug Dependency)
Timothy Scanlan

INITIAL VISIT
KEY POINTS
Subjective
1. Screen all adult patients for drug problems.
2. The CAGE questions are effective and easy to Patient Identification and Presenting
remember. Problem
3. It’s easy to miss a drug problem through focus- Lisa is a 35-year-old white woman complaining of
ing on the chief complaint. Be sure to ask feeling “terribly depressed” and wondering if an anti-
specifically about drug use. depressant “would help me feel better.” Lisa states
4. A brief intervention may help to reduce or elim- that she has been feeling really depressed for the last
inate drug use. couple of weeks and has lost interest in everything,
5. Adjunct medication can be helpful to some even things she previously enjoyed. She believes her
patients in stopping drug use. symptoms started about a year ago but have become
worse recently. She states that she has been “stressed

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

645
Color Plate 86-1 Colposcopic findings for patient,
Aletha. Acetic acid has been applied, demonstrating
acetowhite epithelium in a geographic pattern. (From
Apgar BS, Brotzman G, Spitzer M, eds. Colposcopy:
Principles and Practice. Philadelphia, WB Saunders,
2002.)

Color Plate 86-3 A, Lichen simplex chronicus. Note

Color Plate 86-2 Psoriasis. Note the red, thin plaque of marked lichenification, erythema, and swelling of labia
erythema in a horseshoe pattern around the labia majora with excoriations, erosions, and perianal crust-
majora and mons pubis. No scaling is visible. (From ing. B, Lichen simplex chronicus. Lichenification of
Apgar BS, Brotzman G, Spitzer M, eds. Colposcopy: medial aspects of the labia majora is evident. (From
Principles and Practice. Philadelphia, WB Saunders, Apgar BS, Brotzman G, Spitzer M, eds. Colposcopy:
2002.) Principles and Practice. Philadelphia, WB Saunders,
2002.)
 Color Plate 86-4 Lichen sclerosus. This is the classic “fig-
ure-eight” pattern with abnormal skin changes sur-
rounding the vaginal opening (upper part of the “8”)
and similar skin changes surrounding the anal opening
(lower part of the “8”). The skin is pale and thin, with a
shiny lichenified (cellophane-like) appearance.
Agglutination of the labia minora to labia majora and
clitoral folds to each other results in a loss of labia
minora and most of the clitoris. (Courtesy of Jon C.
Calvert, MD.)

Color Plate 86-5 Lichen sclerosus. A, Thinning of the vulvar epithelium is noted with a pale shiny appearance to the
skin. B, With retraction of labia the demarcation between the normal-appearing, pink labial skin and the thin, cello-
phane-like skin representing lichen sclerosus is evident. Agglutination between the right labia minor and the labia
majora is also noted. (Courtesy of Jon C. Calvert, MD.)
Color Plate 86-6 A, Lichen planus. Note diffuse, whitish pink involvement of the whole vulvar, perineal, perianal area,
with extension into the labiocrural area and small erosions secondary to scratching. There is scarring with loss of most
of the clitoris and right labium minus in a patient with severe pruritus and secondary candidiasis. B, Whitish, scarred
vulva with complete loss of the clitoris and labia minora and partial vaginal stenosis. C, Periclitoral erosions with sur-
rounding whitish, scarred areas with no loss of architecture. (From Apgar BS, Brotzman G, Spitzer M, eds. Colposcopy:
Principles and Practice. Philadelphia, WB Saunders, 2002.)
 Color Plate 86-8 Acetowhitening resulting from suba-
cute or chronicinflammation. (From Apgar BS, Brotzman
G, Spitzer M, eds. Colposcopy: Principles and Practice.
Philadelphia, WB Saunders, 2002.)

Color Plate 86-7 Squamous vestibular micropapillo-

matosis. (From Apgar BS, Brotzman G, Spitzer M, eds.
Colposcopy: Principles and Practice. Philadelphia, WB
Saunders, 2002.)

Color Plate 86-9 Lentigo simplex is a hyperpigmented macular lesion most commonly seen on the vulvar skin of older
women. Lesions are frequently multiple and flat, with irregular borders. They may vary in size from 1 to 2 mm to more
than 1 cm (arrows). Biopsy may be used to exclude atypical nevi and melanoma. (Courlesy of Jon C. Calvert, MD.)
Color Plate 86-10 Multiple condyloma of the introitus,
raised, “cauliflower-like,” varying in color from white
(leukoplakia) to pearly-pink-white. (Courtesy of V. Cecil
Wright, MD.)

Color Plate 86-12 This is a subtle finding. On the per-

ineum between the fourchette and the anal opening, in
the midline there is an area of thickening fine nodular-
ity with central leukoplakia. The skin surrounding the
raised lesion is slightly reddened. Palpation of this lesion
reveals it to be about 1–1.5 cm in diameter, firm, and
extending just beneath the epithelium. Biopsy revealed
VIN III (carcinoma in situ of the perineum). (Courtesy of
Jon C. Calvert, MD.)

Color Plate 86-11 The vulva is dotted with pigmented

raised lesions varying in diameter from 1 mm to 6 mm.
These lesions extend from the hair line of the mons
superiorly laterally and inferiorly to the perineum. There
are lesions on the clitoral hood, on the skin of the
fourchette, and on the perineal body down to just supe-
rior to the perineal body. Biopsy of these lesions
revealed VIN III (carcinoma in situ of the vulva).
(Courtesy of Jon C. Calvert, MD.)

Color Plate 86-13 Patient presented concerned a “skin

tag” near the opening of the vagina. Palpation of the
“skin tag” found it to be firm, with thickening of the
skin at the base of the tag extending out from the point
of attachment. Biopsy revealed VIN III (carcinoma in situ
of the vulva) with microscopic invasion at the margins of
the biopsy. (Courtesy of Jon C. Calvert, MD.)
Color Plate 86-14 Viral vulvar intraepithelial neoplasia
grade 3 involving the clitoral prepuce, labia minora, and
introitus. Human papillomavirus studies were positive.
(From Apgar BS, Brotzman G, Spitzer M, eds.
Colposcopy: Principles and Practice. Philadelphia, WB
Saunders, 2002.) Color Plate 86-15 Large eroding squamous cell carci-
noma of the vulva in a 23-year-old drug addict whose
presenting symptom was foul-smelling discharge. The
cancer had eroded into the perineum and capsule of the
anal sphincter. (Courtesy of Jon C. Calvert, MD.)

Color Plate 86-16 A, Exophitic squamous cell caracinoma of the vulva displaying the three skin color changes most
commonly associated with advanced vulvar dysplasia or cancer (red, black, and white). B, The pedunculated exophytic
cancer is attached to the left labia minora. Palpation reveals it to have an irregular surface and to be rubber hard in
consistency. The surface also has areas of erosion/infection, where the tumor has been “rubbed raw.” (Courtesy of Jon
C. Calvert, MD.)
Color Plate 86-17 A, In the center of the picture of the apex of this posthysterectomy vagina there is a small area of
thickened white skin (postapplication of 3% acetic acid), just above the red area of erosion at 6 o’clock. B, Following
the application of Lugol’s, the normal vaginal epithelium has taken up the dye. In the center of the picture there is a
linear area that has not taken up the dye. It is smooth and appears slightly raised with well-defined margins. Biopsy
revealed VAIN III (carcinoma in situ of the vagina). (Courtesy of Jon C. Calvert, MD.)

Color Plate 86-19 Vaginal atrophy: Loss of normal pink

color, loss of circular rugation and vaginal dryness are
characteristic of vaginal atrophy. If atrophy is marked,
petechial lesion of varying sizes can be noted and may
be exacerbated by trauma such as speculum placement.
(Courtesy of V. Cecil Wright, MD.)

Color Plate 86-18 Adenosis of the posterior cul-de-sac.

(From Apgar BS, Brotzman G, Spitzer M, eds.
Colposcopy: Principles and Practice. Philadelphia, WB
Saunders, 2002.)
Color Plate 86-20 Vagina, near vaginal cuff, demon-
strating “strawberry” pattern of ulceration of epithe- Color Plate 86-22 Deep white thickened vaginal epithe-
lium associated with vaginal infections such as lium after application of acetic acid. Biopsy revealed
trichomoniasis. (Courtesy of V. Cecil Wright, MD.) vaginal intraepithelial neoplasia grade 3, VAIN III.
(Courtesy of V. Cecil Wright, MD.)

Color Plate 86-21 Vaginal condyloma. After application

of acetic acid multiple white, flat condyloma are noted Color Plate 86-23 Two different, adjacent vaginal wall
to be present on the vaginal wall. (Courtesy of V. Cecil lesions. The first is acetowhite in appearance and the sec-
Wright, MD.) ond is raised and deep red. Biopsy of the first revealed
vaginal intraepithelial neoplasia grade 3, VAIN III, and
biopsy of the second revealed adenocarcinoma.
(Courtesy of V. Cecil Wright, MD.)
Color Plate 86-24 Vaginal cuff of a woman who had a
hysterectomy for carcinoma in situ of the cervix. The
majority of the lesion is acetowhite. Biopsy of the areas
that bled easily revealed squamous cell carcinoma of the
vagina. (Reproduced with the permission of V. Cecil Color Plate 86-25 Ectocervix (exocervix), the portion of
Wright, MD.) the cervix covered by stratified squamous epithelium.
(From Apgar BS, Brotzman G, Spitzer M, eds.
Colposcopy: Principles and Practice. Philadelphia, WB
Saunders, 2002.)

Color Plate 86-26 Transformation zone: the geographic Color Plate 86-27 This cervix, portio, and external os do
area of transformation or metaplasia between the origi- not demonstrate ectropion. Though the cervical opening
nal (old) squamocolumnar junction and the new squamo- is small, the demarcation between the squamous epithe-
columnar junction. Nabothian cysts, mature squamous lium of the portio and the columnar epithelium of the
epithelium, squamous metaplasia, mature columnar cervical canal can be identified. This demarcation is
epithelium, and gland crypts may be present. Practically termed the new squamocolumnar junction. (From Apgar
speaking, once the transformation is complete, no rem- BS, Brotzman G, Spitzer M [eds]. Colposcopy: Principles
nants of the metaplastic process remain (such as gland and Practice. Philadelphia, WB Saunders, 2002.)
openings and nabothian cysts), and the original squamo-
columnar junction may be unidentifiable. (From Apgar
BS, Brotzman G, Spitzer M, eds. Colposcopy: Principles
and Practice. Philadelphia, WB Saunders, 2002.)
 Color Plate 86-30 Leukoplakia: an elevated white
Color Plate 86-28 The “new” squamocolumnar junction. plaque seen before the application of 3% to 5% acetic
The current junction where the squamous and columnar acid. a nonspecific finding that may represent trauma,
cells meet on the surface of the cervix at the time the infection or human papillomavirus–related disease,
patient is being evaluated, it demarcates the junction of including invasive disease. It usually requires a biopsy for
the endocervical glandular epithelium and the squamous specific diagnosis. (From Apgar BS, Brotzman G, Spitzer
epithelium after squamous metaplasia is completed. M, eds. Colposcopy: Principles and Practice. Philadelphia,
(From Apgar BS, Brotzman G, Spitzer M, eds. Colposcopy: WB Saunders, 2002.)
Principles and Practice. Philadelphia, WB Saunders, 2002.)

Color Plate 86-31 Nabothian cysts: dilated, occluded

endocervical gland crypts indicating that squamous
metaplasia has occurred. Nabothian cysts may display
exaggerated vessels overlying the cyst, but there is usu-
ally normal branching, distinguishing them from atypical
vessels. They provide markers of the transformation
zone because they are in squamous areas but are rem-
nants of columnar epithelium. (From Apgar BS,
Color Plate 86-29 The cervix can be manipulated with a Brotzman G, Spitzer M, eds. Colposcopy: Principles and
large Q-tip placed in the lateral fornix to maximize Practice. Philadelphia, WB Saunders, 2002.)
visualization. This adequate examination showed mild
acetowhite epithelium anteriorly and a central, 12-o’clock,
denser acetowhite area with coarse punctation. A biopsy
of the area of punctation revealed cervical intraepithelial
neoplasia, grade 2. (From Apgar BS, Brotzman G, Spitzer
M, eds. Colposcopy: Principles and Practice. Philadelphia,
WB Saunders, 2002.)
 Color Plate 86-34 Atypical blood vessels represent
microinvasive squamous cell carcinoma of the cervix.
Vessels vary from irregular, coarse caliber to coiled and
Color Plate 86-32 This is an example of punctation with bizarre branching vessels. Intercapillary distance
a few areas of mosaicism. The caliber of the vessels vary between the vessels is greatly increased and irregular.
from a fine to a coarse pattern. A relatively moderate (Courtesy of V. Cecil Wright, MD.)
white epithelium is present after application of acetic
acid. Biopsy revealed CIN III severe dysplasia. (Courtesy of
V. Cecil Wright, MD.)

Color Plate 86-33 This is a high magnification view of

mosaicism with infrequent punctation. The mosaic pat-
tern varies only slightly in size, shape and configuration.
Biopsy revealed CIN II, moderate dysplasia. (Courtesy of
V. Cecil Wright, MD.) Color Plate 86-35 This lesion represents a geographic
map-like, low-grade dysplasia. The lesion itself is irregular
and extends to the posterior cervical portion. (From Apgar
BS, Brotzman G, Spitzer M, eds. Colposcopy: Principles and
Practice. Philadelphia, WB Saunders, 2002.)
 Chapter 87 Feeling Depressed (Drug Dependency)

REFERENCES
American College of Obstetricians and Gynecologists. Schroeder BM. ACS Updates: Guidelines for the early
ACOG Practice Bulletin: Clinical management guide- detection of cervical neoplasia and cancer, Am Fam
lines for obstetrician-gynecologists. No. August 2003. Physician 2003;67:2011–2016.● C
Cervical cytology screening. Obstet Gynecol 2003;102: Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda
417–427.● C System: Terminology for reporting results of cervical
Amies AE, Miller L, Lee SK, Koutsky L. The effect of vagi- cytology. JAMA 2002;287:2116–2119.● C
nal speculum lubrication on the rate of unsatisfactory U.S. Preventive Services Task Force. Screening for cervical
cervical cytology diagnoses. Obstet Gynecol 2002;100: cancer: Recommendations and rationale. Am Fam
889–892.● A Physician 2003;67:1759–1766.● C
Apgar BS, Zoschnick L, Wright, TC. The 2001 Bethesda U.S. Preventive Services Task Force. Screening for cervical
system terminology. Am Fam Physician 2003;68: cancer. Rockville, MD, Agency for Healthcare Research
1992–1998.● C and Quality, 2003. Available at www.ahrq.gov/clinic/
Harer WB, Valenzuela G, Lebo D. Lubrication of the vaginal uspstf/uspscerv2.htm. Accessed 11/6/2004.● C
introitus and speculum does not affect Papanicolaou Wright TC, Cox JT. Clinical Uses of Human Papillomavirus
smears. Obstet Gynecol 2002;100: 887–888.● A (HPV) DNA Testing. American Society for Colposcopy
Levine L, Lucci III JA, Dinh TV. Atypical glandular cells: and Cervical Pathology, 2004, pp 1–26.●C
New Bethesda terminology and management guide- Wright TC, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ.
lines. Obstet Gynecol Surv 2003;58:399–406.● C 2001 Consensus guidelines for the management of
Nuovo J, Melnikow J, Howell LP. New tests for cervical cancer women with cervical cytologic abnormalities. JAMA
screening. Am Fam Physician 2001;64: 780–786.● C 2002;287:2120–2129.● C

C h a p t e r

87 Feeling Depressed
(Drug Dependency)
Timothy Scanlan

INITIAL VISIT
KEY POINTS
Subjective
1. Screen all adult patients for drug problems.
2. The CAGE questions are effective and easy to Patient Identification and Presenting
remember. Problem
3. It’s easy to miss a drug problem through focus- Lisa is a 35-year-old white woman complaining of
ing on the chief complaint. Be sure to ask feeling “terribly depressed” and wondering if an anti-
specifically about drug use. depressant “would help me feel better.” Lisa states
4. A brief intervention may help to reduce or elim- that she has been feeling really depressed for the last
inate drug use. couple of weeks and has lost interest in everything,
5. Adjunct medication can be helpful to some even things she previously enjoyed. She believes her
patients in stopping drug use. symptoms started about a year ago but have become
worse recently. She states that she has been “stressed

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

645
 Chapter 87 Feeling Depressed (Drug Dependency)

out” since her divorce 3 years ago. Lisa complains of Objective

loss of energy, difficulty sleeping, poor concentration
at work, and pervasive sadness. She has experienced Physical Examination
decreased appetite and some weight loss, but she is On physical examination, blood pressure is 130/75,
pleased about that. She denies any thoughts of harm- pulse is 90, respirations are 20/min, and temperature
ing herself but really wants to feel better. She usually is 37.2˚C (99˚F). Weight is 110 pounds; height, 5 feet
sees you about every 2 years for her well-woman 4 inches.
examinations. The ear, nose, and throat examination is normal,
including an intact nasal septum. The chest is clear to
Medical History auscultation. The cardiac examination shows normal
Lisa has no history of medical problems and no prior sinus rhythm; no murmur is detected. The extremities
surgery. She takes oral contraceptives. She has had show no needle tracks. The abdomen is nontender on
only one pregnancy, when she was 18, but termi- palpation, and no organomegaly is detected.
nated it. She has no history of sexually transmitted In appearance, Lisa is thin but well nourished
diseases (STDs). and well hydrated. She exhibits sad affect and a
depressed mood, and is guarded in conversation. She
Family History expresses no suicidal ideation or thought disorder.
Lisa’s parents are divorced; both are alive and well.
There is no family history of depression. Her mother Assessment
is an alcoholic. She has two siblings, a brother and a
sister, with no known health problems. Lisa clearly is having problems with cocaine and
meets criteria for cocaine dependence. She might not
Social History have been so open about her cocaine use if she were
Lisa was married for 10 years but divorced 3 years not depressed and if you were not her family physi-
ago. She has no children. She denies being physically cian. Her openness is not an indication of under-
abused but states that her ex-husband used cocaine. standing, acceptance, or readiness to quit on her
She is not currently in a relationship. Lisa is part. In all likelihood her depression is due in part to
employed as a secretary. She reports no legal prob- her cocaine use and her susceptibility to drug prob-
lems but admits she is having financial difficulties. lems is in part due to genetic susceptibility. To diag-
nose major depression as an independent condition,
Health Habits she would need to have persistent symptoms after
Lisa states she has smoked half a pack of cigarettes being drug-free for 2 to 4 weeks. Lisa urgently needs
a day since age 15 and has never attempted to quit. treatment for cocaine dependence and symptoms of
She drinks alcohol when out socially with friends, depression.
usually only two to three drinks or beers once a Other concerns are her high-risk sexual behavior
week. After some hesitation in answering questions and her smoking while taking oral contraceptives. It is
regarding drug use, she admits to using cocaine. probable that her sexual behavior is directly linked to
She states she experimented a few times when she her drug use and will stop when her drug problem is
was married, with her husband’s encouragement, adequately treated. She likely is not ready to quit smok-
and then started using cocaine on her own to party ing right now, but this issue needs to be addressed with
after her divorce. She initially snorted but now her. Her weight loss is evident (current weight, 110
smokes crack cocaine. She uses cocaine at least 5 to pounds) and is probably due to her cocaine use.
7 days a week if she can afford it. She uses a lot on
weekends when out with her friends. She says she
Plan
likes the way it makes her feel, and it makes her
depression go away for a while. Recently, she has Diagnostic
been using every day. She doesn’t seem to think it’s A urine drug screen (UDS) can be helpful when it is
a big problem. Her main concern is getting into not clear whether someone is using a specific drug, and
legal trouble if caught. She says she can quit any- it can also be used to rule out use of other drugs. Urine
time she wants. She admits that cocaine makes her drug testing can detect the common drugs of abuse,
promiscuous, and she feels guilty about that some- such as cocaine, opiates, marijuana, amphetamines,
times. Her last use of cocaine was last night. Lisa and phencyclidine (PCP). Urine drug testing does not
denies using other substances and denies intra- routinely test for benzodiazepines or barbiturates.
venous (IV) drug use. Also, a routine UDS can have false positive results from
prescription and over-the-counter medications.
Review of Systems Obtaining a complete blood cell count, compre-
The review of systems is unremarkable for any addi- hensive metabolic profile, and thyroid-stimulating
tional symptoms. hormone level can help rule out other contributing

646
 Chapter 87 Feeling Depressed (Drug Dependency)

factors to her depression. Given Lisa’s history, an This is also an opportunity to discuss other
evaluation for STDs is appropriate. healthy lifestyle changes, such as smoking cessation
(especially since she is taking oral contraceptives)
Therapeutic and increasing exercise, while recognizing that she
Lisa needs referral to a drug treatment program for may not be ready to address these issues right now.
further evaluation and treatment. It is helpful and
reinforcing for the physician to assist with this refer-
ral appointment, even discussing your concerns with DISCUSSION
the treatment professional in the patient’s presence.
Starting antidepressant medication is also Patients should always be asked about drug use.
appropriate. Lisa’s depression is likely to improve While this is a fairly typical presentation for cocaine
with treatment of her drug dependence, but she use in a family practice setting, it would have been
would benefit more from that treatment if she expe- easy to overlook drug use given the other potential
rienced some relief of her depressive symptoms. factors that may have contributed to Lisa’s symp-
Tricyclic antidepressants (TCAs) and selective sero- toms, such as a prior abortion, divorce, and finan-
tonin reuptake inhibitors (SSRIs) seem to have equal cial problems. The clues that lead you to at least
efficacy in the treatment of depression. Some consid- suspect the possibility of drug use are her age, her
erations are the incidence of side effects and the ex-husband’s use, the pattern of symptoms (depres-
mechanism of action. Since depression from cocaine sion, weight loss, smoker), and a family history of
abuse is thought to be due to dopamine depletion, alcoholism. Drug use often masquerades as psycho-
TCAs might be the drug of choice, and in fact there logical problems. Depending on the drug, patients
is some evidence that desipramine works well for may present with depression, anxiety, psychosis, or
both the depression associated with cocaine use and delirium in the office or emergency department.
the relief of craving. SSRIs may also have some ben- Checking for drug use by asking is the best way to
efit in treating the depression, especially if TCAs are screen. A UDS can also be helpful. The CAGE ques-
not tolerated. tions are useful in the presence of drug use to
evaluate the extent of the problem (Box 87-2).
Patient Education Differentiating between drug abuse and drug
This patient needs support and encouragement and dependence is not as clear-cut as with alcohol use,
firm advice to follow through with treatment. You although the criteria are the same (Box 87-3). The
should be clear about your concern for her well- health risks of drug abuse increase significantly
being. The FRAMES format for a brief intervention as the amounts used and the frequency of use
(Box 87-1) provides a helpful guide to thinking increase, and also increase with the onset of IV
about what to discuss in these situations, even drug use.
though this case is not ideal for brief intervention Some patients are “unsafe” users of illicit drugs
because of the severity of the problem. You should but do not meet abuse or dependence criteria. The
discuss the relationship between her cocaine use and social use of illegal drugs is a nebulous area and
her symptoms of depression, her weight loss, and her not one easily addressed. Insofar as there is no
financial problems. Making the connections explicit known safe use of illicit drugs, brief intervention
will help her understand that treatment will help her involves discussing with the patient the health risks
return to full function and satisfaction with her life of drug use and recommending abstinence.
and help her resolve her current problems.

Box 87-2 CAGE Questions (for Drugs)

Box 87-1 FRAMES: Outline for a Brief 1. Have you ever felt you should cut down
Intervention on your drug use?
2. Do you ever feel annoyed when others
Feedback—regarding concerns, risks, problem criticize your drug use?
indicators 3. Have you ever felt bad or guilty about
Responsibility—emphasize choice and personal –
your drug use?
control to change 4. Have you ever used drugs the next day
Action—advice/recommendations about to relieve symptoms from the previous
appropriate steps day’s drug use (“eye-opener”)?
Menu—options or strategies
Empathy—warm, reflective understanding Adapted from Ewing JA. Detecting alcoholism: The
CAGE questionnaire. JAMA 1984;252:1905–1907.
Support—optimize self-empowerment Cited in

647
 Chapter 87 Feeling Depressed (Drug Dependency)

Box 87-3 DSM-IV Criteria for Diagnosing Substance Abuse and Substance Dependence
Substance Abuse
A maladaptive pattern of substance use leading to clinically significant impairment or distress, as
manifested by one (or more) of the following within a 12-month period:
1. Failure to fulfill major role obligations
2. Use that is physically hazardous
3. Recurrent legal problems
4. Continued use despite persistent adverse social or interpersonal problems/consequences

Substance Dependence
A maladaptive pattern of substance use leading to clinically significant impairment or distress, as
manifested by three (or more) of the following within a 12-month period:
1. Tolerance
2. Withdrawal
3. Using larger amounts or over a longer period than intended
4. A persistent desire or unsuccessful efforts to cut down or quit
5. Spending a great deal of time to obtain, use, and/or recover from the drug
6. Giving up social, occupational, or recreational activities because of substance use
7. Continued use despite persistent or recurrent physical or psychological problems
Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text
Revision (DSM-IV-TR). Bethesda, MD, American Psychiatric Association, 2000.

This patient clearly shows very disturbing pat- patients who do not have that discussion. Family
terns of her drug use. Her use is accelerating, and physicians should show care and concern, be open
she is depressed and losing weight. She is not likely about the issues, and give firm, sensible advice. It is
to respond to an antidepressant alone. Her sexual also important to recognize that patients who attempt
behavior is very risky. Her denial is currently being to stop drug use with a treatment program may still
supported by the positive reinforcement of the use drugs intermittently during or after treatment. An
euphoria that cocaine produces. Knowing she needs understanding approach that does not instill guilt will
to quit using drugs and being willing to do so are help patients through this period of early recovery.
vastly different things. It is important to consider a The evaluation of patients with possible alcohol
backup plan should she refuse to see a substance or drug problems should include an evaluation of
abuse counselor. Some alternatives include moni- medical and psychiatric stability, as well as the risks
toring her in your office with UDSs and insisting associated with withdrawal.
she at least attend Cocaine Anonymous (CA) meet-
ings. She could also still be treated with antidepres-
sants. She may not see the need for more formal Table 87-1 Common Drugs of Abuse
treatment until her problems become more severe.
Percent Who Reported
Cocaine is not the only drug of abuse seen in Use in Past Year/
family medicine. Marijuana and methamphetamines Drug Past Month
are also commonly used. It is important to note that
prescription drug abuse is becoming more common Marijuana 11.0 / 6.2
than illicit drug use in the United States. Table 87-1 Cocaine, metham-
shows the most recent statistics from the National phetamines 3.2 / 1.2
Household Survey on the prevalence of drug use in Heroin 0.2 / 0.1
Hallucinogens 2.0 / 0.5
American communities. Past month use as described
Inhalants 0.9 / 0.3
in this table is more descriptive of current use than is Psychotherapeutics
past year use. The prevalence of drug use by patients (prescription) 6.2 / 2.6
in our practices may be higher than is indicated in
the table because drug users tend to use primary Data from U.S. Department of Health and Human
health care services more than nonusers do. Services, Substance Abuse and Mental Health
Services Administration. 2002 National Survey on
Patients who are advised by their family physician Drug Use and Health. Bethesda, MD, U.S.
about their alcohol or drug use are more likely to Department of Health and Human Services
attend and complete a treatment program than Adminstration, 2002.

648
 Chapter 87 Feeling Depressed (Drug Dependency)

Treatment or dependence on scheduled drugs. Avoid these med-

ications whenever possible and use noncontrolled
The treatment of drug problems may include formal alternatives.
inpatient or outpatient treatment, depending on the The management of drug withdrawal is also an
severity of the problem. Attending meetings of self- important consideration. Although most drug with-
help groups such as CA or Narcotics Anonymous (NA) drawal syndromes, with the exception of alcohol and
is an important component of recovery. The emphasis benzodiazepine withdrawal, are not life-threatening,
of treatment is on abstinence from all mood-altering drug withdrawal is very uncomfortable and is typi-
substances; even modest alcohol use can lead back to cally associated with drug craving. Failure to manage
drug use. Some narcotic addicts with addiction unre- these symptoms often leads to resumption of drug
sponsive to other forms of therapy might benefit from use. Two excellent resources for help with with-
methadone or buprenorphine therapy. drawal management are noted in the list of suggested
Monitoring patients in recovery helps motivate readings.
them and ensure their adherence. Urine and hair
drug testing are accurate and useful. Patients who
have been IV drug users should also be tested for
hepatitis and HIV. Material Available on Student Consult
Great care should be taken when prescribing
Review Questions and Answers about Drug
medications for patients with a history of drug prob-
Dependency
lems because they are at risk for developing abuse of

SUGGESTED READINGS
Giannini A J. An approach to drug abuse, intoxication and Schuckit M. Drug and Alcohol Abuse: A Clinical Guide to
withdrawal. Am Fam Physician 2000;61:2763–2774. Diagnosis and Treatment, 5th ed. New York, Plenum, 2000.
A Guide to Substance Abuse Services for Primary Care Weaver M, Jarvis M. Overview of the recognition and man-
Physicians (Treatment Improvement Protocol Series agement of the drug abuser. UpToDate, Jan. 9, 2004.
No. 24, DHHS Publication No. 97-3139). Bethesda, Available at www.patients.uptodate.com/topic.asp?
MD, U.S. Department of Health and Human Services, file=genr_med/21475. Accessed 11/15/2004.● B
Substance Abuse and Mental Health Services Wilford B. Principles of Addiction Medicine, 3rd ed. Chevy
Administration, 1997. Available at www.ncbi.nlm.nih. Chase, MD, American Society of Addiction Medicine,
gov/books. Accessed 11/15/2004.●C 2003.

649
 C h a p t e r

88 Chest Pain and Fatigue

(Anxiety Disorder)
Katherine Margo

often wakes up early. She has no history of psychi-

KEY POINTS atric illness including panic attacks. She denies any
recent changes in her work, life, or marriage.
1. Consider generalized anxiety disorder (GAD) However, on careful questioning, she is able to recall
when an otherwise healthy patient is excessively feeling worried over the past 7 to 8 months, but it has
worried and the symptoms are interfering with become such a constant part of her daily experience
functioning. that she did not think to mention it.
2. Psychotherapeutic and pharmacologic treat-
ments are both effective and when used Medical History
together have the greatest efficacy. Susan is generally healthy with no hospitalizations
3. Benzodiazepines, buspirone, and anti- except for childbirth. She does not like taking medi-
depressants are effective first line pharmaco- cine but does take vitamins and some herbs from a
logic treatments for GAD, although local health food store. She denies alcohol, cigarettes,
benzodiazepines have a more rapid onset. or illicit drug use.
4. Look for concomitant illness or other anxiety
disorders including phobias and panic disorder. Family History
Her father is an alcoholic, and she does not see him
much. Her mother’s health is fair, but her mother has
no specific disease that Susan knows about.
INITIAL VISIT
Social History
Subjective Susan is married and has one child, age 3. She works
full time as an account executive in an advertising
Patient Identification and Presenting agency. She is a hard worker but reports that recently
Problem she is not as productive as she would like to be
Susan M. is a 32-year-old woman who presents for because she functions less efficiently when she feels
the first time with chest pain and fatigue. so stressed. When asked about this, she says that her
concentration is not what it used to be and she wor-
Present Illness ries that something is seriously wrong.
Susan started having chest pains in the past week,
which is why she finally decided to come in. She was Review of Systems
in the emergency department two nights ago where She has no history of diabetes, hypertension, or thyroid
they did several tests and told her it was not her disease. She denies problems with her eyes, ears, or
heart. She does not understand what it could be and mouth but does get headaches from time to time. She
is very worried. Her pain is sharp and on the left side has no trouble with her heart, although she does notice
of her chest. It comes and goes, and nothing really that her heart beats fast. She has no trouble breathing
helps it. Susan also says that she has been feeling and no cough or history of asthma. She does not have
more and more tired over the past few months. She urinary problems but does have loose stools. She has
does admit that she is having trouble sleeping and no joint problems. Her periods have been normal.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

650
 Chapter 88 Chest Pain and Fatigue (Anxiety Disorder)

Objective
Box 88-1 Diagnostic Criteria
Physical Examination for Generalized Anxiety
Susan is a healthy-appearing woman who looks Disorder (GAD)
anxious. Vital signs: height, 5 feet 7 inches tall;
weight, 140 pounds; temperature, 36.9˚C (98.5˚F); The following criteria describe GAD
respiratory rate, 18; pulse, 100; blood pressure,
1. Excessive anxiety and worry about several
110/70. Head, eyes, ears, nose, and throat are all
events or activities, occurring most of the
normal. Pupils are equal and reactive with normal
time for at least 6 months, and which seem
extraocular muscle function. Neck: thyroid is nor-
out of proportion.
mal and symmetrical. No bruit or lymphadenopa-
2. The worry is pervasive and difficult to con-
thy. Her lungs are clear and her heart has a regular
trol.
rate and rhythm with a grade 1/6 systolic flow mur-
3. The anxiety and worry are associated with
mur. Her chest wall is tender diffusely. Her breast
three (or more) of the following six symp-
examination is normal. Neurologic examination is
toms:
normal, including deep tendon reflexes throughout,
Restlessness or feeling on edge
sensation, and muscle strength. Abdominal exami-
Being easily fatigued
nation is nontender, with no masses or organo-
Trouble concentrating
megaly.
Irritability
Muscle pain or tightness
Assessment Sleep disturbance (difficulty falling or staying
asleep, or restless sleep)
Working Diagnosis
4. The anxiety, worry, or physical symptoms
Generalized anxiety disorder (GAD). This is one of a
cause effects on social, occupational, or
number of conditions collected under the heading of
other important areas of functioning.
anxiety disorders. The Diagnostic and Statistical
5. There is no other explanation, such as drug
Manual of Mental Disorders, 4th Edition, criteria for
use, prescribed or abused, or a medical con-
diagnosing GAD are listed in Box 88-1. Susan has
dition that explains the symptoms.
been feeling anxious for more than 6 months, even
though she has not used this term to describe her Adapted from American Psychiatric Association.
feelings. This differentiates it from panic attacks that Diagnostic and Statistical Manual for Mental
are brief, intense attacks of anxiety. The anxiety has Disorders, 4th Edition. Washington, DC, American
Psychiatric Association, 1994.
been sufficient to disrupt her work functioning and
she feels that something is seriously wrong. Her sleep
has been disturbed lately, leaving her tired and irrita-
ble during the day. The chest pain that brought her to
medical attention seems to be from muscle soreness 2. Drugs, prescribed (sympathomimetics) or not
of her chest wall. (caffeine, cocaine, amphetamines), can produce
anxiety, as can alcohol and sedative-hypnotic
withdrawal.
Differential Diagnosis
3. Metabolic and endocrine diseases associated with
Anxiety can be considered a symptom as well as an ill-
anxiety include hyperthyroidism, pheochromo-
ness. All conditions, both psychological and somatic,
cytoma, hypoadrenalism, hypoglycemia, and
that include anxiety as an associated symptom should
hypokalemia.
be considered in the differential diagnosis.
4. Heart disease. Anxiety is commonly seen in coro-
1. Psychiatric illnesses. Other anxiety disorders are nary artery disease, especially during myocardial
agoraphobia and other phobias, social phobia, infarction, when the anxiety is an expression of
panic disorder, obsessive-compulsive disorder, the fear that the patient has of dying. The com-
and post-traumatic stress disorder, in addition to mon cardiac illnesses that are often associated
the anxiety disorder associated with medical con- with anxiety include coronary artery disease,
ditions and substances noted earlier. However, heart failure of any cause, rhythm disturbances,
any psychiatric illness in which patients feel that and mitral valve prolapse.
something frightening is happening to them will 5. Respiratory illness associated with dyspnea can
have an anxiety component. Such a list includes have associated anxiety. This includes common
depression, schizophrenia and other psychoses, illnesses such as asthma and chronic obstructive
and even early dementia. These, especially pulmonary disease as well as uncommon con-
depression, should be specifically assessed for to ditions like pulmonary embolism and sclero-
determine whether they are also present. derma.

651
 Chapter 88 Chest Pain and Fatigue (Anxiety Disorder)

Plan philosophical. Unless the distinction is understood,

we may find ourselves overtreating our patients,
Susan’s history and physical examination show no medicating the ups and downs of life rather than lis-
evidence of other psychiatric or substance abuse tening to a story of real but limited distress.
conditions or any major medical illness including Treatments of GAD can be primarily psycholog-
cardiac or pulmonary disease. Her electrocardio- ical or pharmacologic. In practice, it is common for
gram is normal. Laboratory studies confirm normal patients, especially those with more severe symp-
electrolyte and glucose levels and normal thyroid sta- toms, to receive combined psychological and phar-
tus. Because there are no clinical findings pointing to macologic treatment.
other potential anxiety-associated nonpsychiatric Psychological treatments can be broadly divided
diseases, additional testing is not indicated. However, into those aimed primarily at symptom control
in the course of the slow and careful history taking, it through cognitive and behavioral methods and those
is evident that Susan is facing a number of emotion- aimed at exploring the psychological meaning of the
ally troubling issues. She is bothered that she has to symptom followed by working through and resolu-
leave her young daughter in day care for a long day. tion of underlying psychological issues. Examples of
She is particularly sensitive to perceived criticism at the first approach are supportive counseling and
work for not being more productive, and in a coun- cognitive-behavioral therapy. Supportive work
terproductive way, her anxiety leads to increasing includes psychoeducational efforts directed at reduc-
irritability at home, alienating her usually supportive ing symptoms by educating the patient about the
husband. Her alcoholic father is doing badly, and she disorder and the generally good outcome. Cognitive-
avoids him but feels guilty for doing so. behavioral therapy takes this further by identifying
unrealistic or distorted thinking patterns behind the
anxiety, and learning new ways to solve problems
DISCUSSION and cope with symptoms (Gliatto, 2000● B ).
Exploratory or psychodynamic therapies work
GAD is the most common anxiety disorder. The on the assumption that the anxiety arises as a signal
prevalence in primary care is approximately 5% of underlying psychological distress, such as that
(Roy-Byrne and Katon, 1997● A ). caused by conflicts, disrupted relationships, and so
It is more common in women than men: 60% to on. The anxiety is relieved by identifying the psycho-
40%. It tends to follow a chronic course and fluctu- logical causes of distress, looking at the issues in
ates in intensity over time. There is often a familial therapy, and finding new ways or meanings that
pattern to anxiety, but whether this is genetic or allow for a new psychological equilibrium (Gabbard,
learned is not clear (American Psychiatric 2000● B ). Psychodynamic psychotherapy receives little
Association, 1994● C ). attention in the family medicine literature, and the
Medical conditions can produce anxiety as part common perception is that the approach has no
of their symptom picture. More common examples sound evidence base. This is not correct, and a full
include hyperthyroidism and mitral valve prolapse discussion is beyond the scope of this case. However,
(Gliatto, 2000● B ). Medical conditions typically asso- an unusual study warrants a mention as a beginning
ciated with stress, such as irritable bowel syndrome of discussion of this topic. Consumers Union, the
and headache, can have concurrent GAD. As noted in publishers of Consumer Reports, studied a self-
the differential diagnosis section, there are multiple selected sample of 3079 of their readers who had
possibilities to consider. GAD is also often seen with sought help for anxiety, depression, or a combination
other anxiety disorders, depression, and substance of both. In general, patients who received psy-
abuse (Brawman-Mintzer et al., 1993 ● A ). Patients chotherapy for periods of 13 weeks or more did as
with GAD tend to be high utilizers of medical serv- well as or better than those receiving drugs alone.
ices and to have poorer health. The therapy is described as “talk therapy,” a phrase
A discussion of GAD is complicated by multiple used to describe an exploratory approach to treat-
connotations of the word anxiety. Anxiety, as it is ment (Consumer Reports, 2004● B ).
used in this case, refers to one of a group of psychi- Pharmacologic treatments follow from the idea
atric disorders. The word is also used in common that anxiety symptoms are the result of a disordered
language to refer to psychological distress of a wor- response of the neurotransmitters norepinephrine,
ried or fearful kind and as such is seen widely in all serotonin, and γ-aminobutyric acid to stress. The
illnesses and in any aspect of human life. In this mainstay of anxiety medication management has
sense, an anxiety disorder would not be diagnosed. been the benzodiazepines (Gliatto, 2000● B ). While
The formal designation of “anxiety disorder” is given these drugs do not cure anxiety, they effectively
when the experience of anxiety reaches a certain level reduce or eliminate the experience of anxiety. Short-
of severity, interferes with function, and lasts for a acting benzodiazepines are effective but must be
period of time. This distinction is more than just taken every 2 to 3 hours for continued symptom

652
 Chapter 88 Chest Pain and Fatigue (Anxiety Disorder)

control. In addition to this practical disadvantage, category (American Psychiatric Association, 1994● C ).
the shorter-acting benzodiazepines tend to be more Even though anxiety disorders have much in com-
addictive than the longer-acting forms. Some mon in terms of treatment, some key differences
patients like the rapid onset and “buzz” of alprazo- from the treatment of GAD are noted.
lam, but the problems of addiction and subsequent In phobias, there is a clearly recognizable precip-
struggles over withdrawal cause many practitioners itant for the anxiety. The most common phobia, ago-
to avoid it. Lorazepam (Ativan) has the advantage raphobia, arises from the fear of being exposed or
of quick onset, especially when used sublingually, trapped in a situation perceived as dangerous or
and longer duration of action (4 to 5 hours). embarrassing. In its severe form, such patients tend
Clonazepam (Klonopin) is a particularly advanta- to stay at home or in familiar places or may only ven-
geous benzodiazepine for ongoing use in that it ture out accompanied by a friend or relative. Other
requires only twice-daily dosing. Dosing starts at phobias such as fear of dogs and snakes are easily
0.25 to 0.5 mg twice daily with a maximum daily recognized. Cognitive-behavioral therapy is most
dose of 3 to 4 mg. The rule is to start low and titrate helpful for phobias, with the addition of an antide-
upward slowly to reach acceptable symptom control. pressant in agoraphobia.
Drowsiness is the most significant adverse effect. Social phobia is also known as social anxiety dis-
Withdrawal must be done slowly, cutting 10% of the order; this is probably a better name because “pho-
dose per week, and adding imipramine if necessary bia” usually refers to a specific precipitant, whereas in
to make the taper easier. Given this information, it is social anxiety disorder, a whole range of social expo-
reasonable to avoid these drugs in patients with anx- sure leads to crippling anxiety. Such patients avoid
iety associated with chronic illnesses, in addicts, and interactions with others to the extent that they may
in those with a severe personality disorder. be unable to eat in a social setting or work with col-
Buspirone (BuSpar) is also an effective antianx- leagues. They often end up in solitary jobs, often on
iety agent but with a slow onset of action over several the night shift. This disorder is particularly difficult
weeks. It is not addictive and can be withdrawn with- to treat. Selective serotonin reuptake inhibitors are
out difficulty. Doses range between 15 and 30 mg the mainstay of treatment, often combined with
twice daily (Davidson et al., 1999● A ). behavior therapy.
Many antidepressant drugs are effective for treat- Panic disorder is diagnosed when panic attacks
ment of GAD. Tricyclics, selective serotonin reuptake are recurrent and are followed by at least a month of
inhibitors, and venlafaxine (Effexor) have all been anxiety about another attack or about the effect of the
shown to be useful (Kapczinski et al., 2003 ● A). attacks. Panic attacks are a particular variant of anxi-
Tricyclics tend to be used less often nowadays because ety characterized by severe, discrete episodes of sym-
of their side effect profile and greater risk of overdose. pathetic discharge with symptoms such as sweating,
However, there is no difference in efficacy that would palpitations, shortness of breath, trembling, choking,
make one choose one antidepressant over another in chest pain, dizziness, paresthesias, nausea, as well as a
GAD other than considerations of side effects and fear of dying or of losing control. Tricyclics, selective
cost. It is important to remember two clinical pearls: serotonin reuptake inhibitors, and venlafaxine are
response to these drugs is variable among individuals, used in treatment.
so that an unsuccessful trial of 3 to 4 weeks of one Obsessive-compulsive disorder is a severe, com-
drug should be followed by a different drug, prefer- plex illness characterized by recurrent obsessive
ably of a different class; and, second, although the thinking and/or compulsive behavior. These patients
new antidepressants are promoted as being better tol- suffer from anxiety usually provoked by any factor
erated than the old tricyclics, there is no one drug that that may interfere with the expression of their com-
is uniformly well tolerated. pulsions or obsessions. It not possible to do justice to
GAD can be regarded as a diagnosis of exclusion the complexity and morbidity of obsessive-compul-
in that anxiety is the dominant symptom without sive disorder here. It is the least anxiety disorder-like
specific precipitants as found, for example, in pho- of the group and probably deserves a diagnostic cat-
bias, and without the severe dominant physical egory all its own. Both cognitive-behavioral therapy
symptoms such as seen in panic attacks. Likewise, and antidepressants (clomipramine and the selective
GAD is diagnosed when no obvious medical illness serotonin reuptake inhibitors) are primary treatment
or substance abuse or withdrawal is causing the anx- modalities.
iety symptoms. Although the focus here is on GAD, Post-traumatic stress disorder follows for some
it is important to be able to differentiate between the people after a real or potential life-threatening expe-
major anxiety disorders. Correct diagnosis is impor- rience. The symptoms can be considered in three
tant in tailoring treatment for the patient. The groups: anxiety-associated with recurrent, intrusive
following review of the diagnostic criteria for recollections of the event; nightmares of the trau-
the various anxiety disorders allows the practitioner matic event and waking re-experiencing the event;
to place an anxious patient into the appropriate avoiding situations that remind the patient of the

653
 Chapter 88 Chest Pain and Fatigue (Anxiety Disorder)

traumatic experience and a general numbing of office some months later, she is happy to report that
responsiveness; and symptoms of increased arousal the pieces in her life are falling into place. For exam-
such as hypervigilance, exaggerated startle, and irri- ple, she had not consciously realized how difficult it
tability. Acute stress disorder refers to the develop- was for her to leave her child for as long a day as she
ment of a stress disorder within a month of the was doing. She felt that she had to show that she was
experience, whereas post-traumatic stress disorder is tough and capable in the work world. As she looked
used for a disorder that persists longer than a month. at this, she realized that she could make some
Treatment is difficult and combinations of psy- changes that allowed for a better compromise
chotherapy of all types, antianxiety agents, and anti- between her wish to pursue her career and desire to
depressants are all used. be a loving mother. She also allowed herself to ask
for, and to accept, more help from her husband. He
was delighted, and their relationship found a new
FOLLOW-UP VISIT and better balance. She says that now for the first
time in years, she is ready to take another look at her
Susan and her physician discuss the material pre- relationship with her father, whose drinking had had
sented here. This psychoeducational approach helps a significantly adverse effect on her life. She thanks
her gain a perspective on what at first were puzzling her physician for discussing the full range of treat-
and frightening symptoms. She is psychologically ment options and for encouraging her to make her
minded but initially felt embarrassed to acknowledge own choices once she had the information.
that “my mind could play such tricks on me.” Once
she overcomes that hurdle, she is intrigued at the
range of treatment options. Because she prefers to
avoid taking medicine and because she is curious Material Available on Student Consult
about the idea of understanding where her anxiety is
Review Questions and Answers about Anxiety
coming from, she accepts a referral to a psychody- Disorder
namic psychotherapist. When she returns to the

REFERENCES
American Psychiatric Association. Diagnostic and Gabbard GO. Psychodynamic Psychiatry in Clinical
Statistical Manual of Mental Disorders, 4th ed. Practice, 3rd ed. Washington, DC, American Psychiatric
Washington, DC, American Psychiatric Association, Association, 2000, pp 233–266.● B
1994, pp 432–436.● C Gliatto MF. Generalized anxiety disorder. Am Fam
Brawman-Mintzer O, Lydiard RB, Emmanuel N, et al. Physician 2000;62:1591–1602.● B
Psychiatric comorbidity in patients with generalized anx- Kapczinski F, Lima MS, Souza JS, Schmitt R. Anti-
iety disorder. Am J Psychiatry 1993;150:1216–1218.● A depressants for generalized anxiety disorder. Cochrane
Consumer Reports. Drugs vs. talk therapy. Consumer Rep Database Syst Rev 2003:CD003592.● A
2004:69:22–29.● B Roy-Byrne PP, Katon W. Generalized anxiety disorder in
Davidson JR, DuPont RL, Hedges D, Haskins JT. Efficacy, primary care: The precursor/modifier pathway to
safety, and tolerability of venlafaxine extended release increased health care utilization. J Clin Psychiatry 1997;
and buspirone in outpatients with generalized anxiety 58(Suppl 3):34–38.● A
disorder. J Clin Psychiatry 1999;60:528–535.● A

654
 C h a p t e r

89 Multiple Somatic Complaints

(Generalized Anxiety Disorder)
Michael G. Kavan

turn has resulted in concentration difficulties at

KEY POINTS work and home. Although her symptoms have been
present over the past year, she says they have wors-
1. In a patient who presents with various long- ened considerably over the past 3 months.
standing physical complaints and excessive wor-
rying suggestive of generalized anxiety disorder, Present Illness
medical disorders and the physiologic effects of Katherine initially believed she was hyperthyroid
substances must be properly ruled out through based on a conversation with a nurse at her medical
the history, physical examination, and labora- clinic. However, when queried further, Katherine
tory testing. thinks her symptoms are more likely related to her
2. Psychosocial management includes REST— tendency to “worry about everything”—specifically,
reassurance, education, stress management, her health, her son’s academic problems, and
and possibly formal therapy with a psychologist finances.
or psychiatrist.
3. Pharmacologic management may include selec- Medical History
tive serotonin reuptake inhibitors, nonbenzodi- Katherine reports a history of migraine headaches
azepines such as buspirone, or benzodiazepines. that began at age 15 years. She has had excessive
4. Combined treatment is often most effective, absenteeism from work due to her migraine
especially for patients with more severe anxiety. headaches and physical symptoms. She denies any
5. Patient education resources are an essential other significant medical history.
adjunct to any intervention.
Family and Social History
Katherine is single and has a 15-year-old son who
lives with her. She has been living with her boyfriend,
INITIAL VISIT who is employed as a cabinet maker, for the past 8
years. Katherine describes her relationships with her
Subjective boyfriend and son as “fine” and supportive.

Patient Identification and Presenting Health Habits

Problem Katherine admits to smoking one-half pack of ciga-
Katherine M. is a 36-year-old single white woman rettes per day. She had quit for several months but
who works as a receptionist for a medical clinic. She recently reinitiated the habit to cope with her “nerv-
is referred by a medical staff member at her place of ousness.” She states she consumes a few alcoholic
employment because of her various somatic com- beverages per week but denies problems when
plaints, which have worsened over the past 3 months. queried with the CAGE questions (Box 89-1)
This is her first visit to this clinic. (Ewing, 1984). She says she drinks six or seven cans
Katherine reports that she has been experienc- of caffeinated cola per day. Katherine denies any
ing shakiness, shortness of breath, rapid heart rate, other substance use at this time but reports a history
chest pain, light-headedness, sleep difficulties, and of intermittent cocaine use when she was younger.
weight loss. She has also been worrying excessively She reports consuming a normal diet but says she
about several issues in her life, and this worrying in does not get any regular exercise.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

655
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

mild level of depression. Most of her points accrued

Box 89-1 Cage Questionnaire from symptoms associated with anxiety. During the
interview she mentions occasionally feeling sad but
C Have you ever felt you ought to CUT down states she is not depressed.
on your drinking?
A Have people ANNOYED you by criticizing
your drinking? Assessment
G Have you ever felt bad or GUILTY about Working Diagnosis
your drinking? The working diagnosis for Katherine’s presenting
E Have you ever had a drink first thing in the complaint is generalized anxiety disorder, since she
morning to steady your nerves or get rid of has been worrying excessively about many issues,
a hangover (EYE-opener)? including her health, her son, and finances. Her wor-
rying is longstanding and has affected her perform-
Answering yes to two or more items is ance at work.
indicative of an alcohol problem and should be
investigated further by the physician.
Plan
From Ewing JA. Detecting alcoholism: The CAGE
Questionnaire. JAMA 1984;252:1905-1907. The initial plan is to educate Katherine about anxiety
and stress and how to better cope with these through
psychological and behavioral strategies. The provider
gives her an educational handout on these topics.
Review of Systems Because of her score on the ZSRDS instrument,
Katherine reports a weight loss of 15 pounds over the Katherine is asked about suicidal ideation, which she
past 3 months. She states she does not currently suf- denies, referring to the impact it would have on her
fer from headaches, shortness of breath, or any aches son. The provider asks her to return in 1 week for
or pains but does experience nervousness. She has no assessment of her status and to further discuss treat-
known allergies. ment strategies.

Differential Diagnosis
Objective
Based on Katherine’s presenting complaints and his-
Physical Examination tory, the following diagnoses may be considered by
Katherine is well developed, slightly underweight, the physician.
cooperative, and friendly. She is 5 feet 6 inches tall
and weighs 118 pounds. Her blood pressure is 1. Generalized anxiety disorder. The most likely diag-
104/76, respiratory rate is 16, and oral temperature is nosis for Katherine is generalized anxiety disorder.
36.9˚C (98.4˚F). Her heart rate is 72 with a normal She admits to a tendency to “worry about every-
rhythm. Breast and abdominal examinations are thing,” including her health, her son, and finances.
normal. The patient exhibits no distress, other than She also reported excessive worrying on the SPDS
fidgeting, and shows normal affect. instrument. Her anxiety and worry appear to be
associated with numerous physical symptoms
Laboratory Tests (e.g., shakiness, shortness of breath, rapid heart
Laboratory testing includes thyroid function (serum rate, chest pain, light-headedness, weight loss) and
TSH, free T4, and serum T3), serum glucose, elec- difficulties with sleep. Katherine’s anxiety and
trolytes, and a complete blood cell count. All results physical concerns have resulted in work-related
are within normal limits. problems (absenteeism). Therefore, she meets the
Diagnostic and Statistical Manual of Mental
Psychological Screening Disorders (DSM-IV) criteria for generalized anxi-
Katherine is given the Sheehan Panic Disorder Scale ety disorder (Box 89-2) (American Psychiatric
(SPDS), formerly the Sheehan Patient Rated Anxiety Association [APA], 1994).
Scale (SPRAS) (Sheehan and Harnett-Sheehan, 1990) 2. Anxiety disorder due to a general medical condi-
(Table 89-1) and the Zung Self-Rating Depression tion. Anxiety may be directly related to the
Scale (ZSRDS) (Zung, 1965● B ) (Table 89-2) to com- physiologic effects of various medical conditions
plete. The SPDS is a 35-item self-report screening (APA, 1994). These conditions should be con-
measure for anxiety. Katherine’s score is 83, indicat- sidered in the differential diagnosis and ruled
ing a high degree of anxiety, with physical complaints out as appropriate. They include endocrine dis-
and excessive worrying being most prominent. The orders, cardiovascular problems, respiratory con-
ZSRDS is a 20-item self-report screening measure for ditions, metabolic conditions, and neurologic
depression. Katherine’s score is 54, which suggests a conditions (Table 89-3).

656
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Table 89-1 Sheehan Panic Disorder Scale (SPDS)*

Instructions: Below is a list of problems and complaints that people sometimes have. Indicate how you
have felt during THE PAST WEEK. Mark only one box for each problem and do not skip any items.

Moderately

Extremely
Markedly
Not at all

A little
During the past week, how much did you suffer from:

1. Difficulty in getting your breath, smothering, or

overbreathing

2. Choking sensation or lump in throat.

3. Skipping, racing, or pounding of your heart.

4. Chest pain, pressure, or discomfort.

5. Bouts of excessive sweating.

6. Faintness, lightheadedness, or dizzy spells.

7. Sensation of rubbery or “jelly” legs.

8. Feeling off balance or unsteady like you might fall.

9. Nausea or stomach problems.

10. Feeling that things around you are strange, unreal,

foggy, or detached from you.

11. Feeling outside or detached from part or all of your

body, or a floating feeling.

12. Tingling or numbness in parts of your body.

13. Hot flashes or cold chills.

14. Shaking or trembling.

15. Having a fear that you are dying or that something

terrible is about to happen.

16. Feeling you are losing control or going insane.

17. Situational Anxiety Attack: Sudden anxiety attacks

with 4 or more of the symptoms (listed previously)
that occur when you are in or about to go into a
situation that is likely, from your experience, to bring
on an attack.

18. Unexpected Anxiety Attack: Sudden unexpected

anxiety attacks with 4 or more symptoms (listed
previously) that occur with little or no provocation
(i.e., when you are not in a situation that is likely,
from your experience, to bring on an attack).

19. Unexpected Limited Symptom Attack: Sudden

unexpected spells with only one or two symptoms
(listed previously) that occur with little or no
provocation (i.e., when you are not in a situation that
is likely, from your experience, to bring on an attack).

Continued
657
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Table 89-1 Sheehan Panic Disorder Scale (Continued)

Moderately

Extremely
Markedly
Not at all

A little
During the past week, how much did you suffer from:

20. Anticipatory Anxiety Episode: Anxiety episodes that

build up as you anticipate doing something that is
likely, from your experience, to bring on anxiety that
is more intense than most people experience in
such situations.

21. Avoiding situations because they frighten you.

22. Being dependent on others.

23. Tension and inability to relax.

24. Anxiety, nervousness, restlessness.

25. Spells of increased sensitivity to sound, light, or touch.

26. Attacks of diarrhea.

27. Worrying about your health too much.

28. Feeling tired, weak, and exhausted easily.

29. Headaches or pains in neck or head.

30. Difficulty in falling asleep.

31. Waking in the middle of the night, or restless sleep.

32. Unexpected waves of depression occurring with little

or no provocation.

33. Emotions and moods going up and down a lot in

response to changes around you.

34. Recurrent and persistent ideas, thoughts, impulses, or

images that are intrusive, unwanted, senseless, or
repugnant.

35. Having to repeat the same action in a ritual, e.g.,

checking, washing, counting repeatedly, when it’s not
really necessary.

Not at all = 0
A little = 1
Moderately = 2
Markedly = 3
Extremely = 4

25–37 37–57 57–77 >77

Mild Moderate Severe Very severe

Although originally developed for use with panic disorder, the SPDS has extensive breadth of symptom
coverage. Scores may range from 0 to 140.

*Formerly Sheehan Patient Rated Anxiety Scale.

From Sheehan JV. The Sheehan Patient Rated Anxiety Scale. J Clin Psychiatry 1999;60(Suppl 18):63–64.

658
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Table 89-2 Zung Self-Rating Depression Scale

Name_________________________________________ None or
a little of Some of Good part Most or all
Age_____Sex_____Date______________ of the time the time the time of the time

1. I feel downhearted, blue and sad.

2. Morning is when I feel the best.

3. I have crying spells or feel like it.

4. I have trouble sleeping through the night.

5. I eat as much as I used to.

6. I enjoy looking at, talking to and

being with attractive women/men.

7. I notice that I am losing weight.

8. I have trouble with constipation.

9. My heart beats faster than usual.

10. I get tired for no reason.

11. My mind is as clear as it used to be.

12. I find it easy to do the things I used to.

13. I am restless and can’t keep still.

14. I feel hopeful about the future.

15. I am more irritable than usual.

16. I find it easy to make decisions.

17. I feel that I am useful and needed.

18. My life is pretty full.

19. I feel that others would be

better off if I were dead.

20. I still enjoy the things I used to do.

Key for Scoring the Self-Rating Depression Scale (SDS)

Responses

None or a
SDS item little of Some of Good part Most or all
number the time the time of the time of the time

1 1 2 3 4
2 4 3 2 1
3 1 2 3 4
4 1 2 3 4
5 4 3 2 1
6 4 3 2 1
7 1 2 3 4
8 1 2 3 4

Continued

659
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Table 89-2 Zung Self-Rating Depression Scale (Continued)

Responses

None or a
SDS item little of Some of Good part Most or all
number the time the time of the time of the time

9 1 2 3 4
10 1 2 3 4
11 4 3 2 1
12 4 3 2 1
13 1 2 3 4
14 4 3 2 1
15 1 2 3 4
16 4 3 2 1
17 4 3 2 1
18 4 3 2 1
19 1 2 3 4
20 4 3 2 1
Patients are requested to rate themselves (from “None or a little of the time” to “Most or all of the time”) on
various items related to depression. Scores range from 0 to 80, with scores of 50 or more indicating
depression.
From Zung, WW. A self-rating depression scale. Arch Gen Psychiatry 1965;12:63–70.

Box 89-2 DSM-IV Diagnostic Criteria for Generalized Anxiety Disorder

A. Excessive anxiety and worry (apprehensive, expectation), occurring more days than not for at least
6 months, about a number of events or activities (such as work or school performance).
B. The person finds it difficult to control the worry.
C. The anxiety and worry are associated with three (or more) of the following six symptoms (with at
least some symptoms present for more days than not for the past 6 months). Note: Only one item
is required in children.
1. Restlessness or feeling keyed up or on edge
2. Being easily fatigued
3. Difficulty concentrating or mind going blank
4. Irritability
5. Muscle tension
6. Sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)
D. The focus of the anxiety and worry is not confined to features of an Axis I disorder (e.g., the anxiety
or worry is not about having a panic attack [as in panic disorder], being embarrassed in public [as in
social phobia], being contaminated [as in obsessive-compulsive disorder], being away from home or
close relatives [as in separation anxiety disorder], gaining weight [as in anorexia nervosa], having mul-
tiple physical complaints [as in somatization disorder], or having a serious illness [as in hypochondri-
asis]), and the anxiety and worry do not occur exclusively during posttraumatic stress disorder.
E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
F. The disturbance is not due to the direct physiological effects of a substance or a general medical
condition and does not occur exclusively during a mood disorder, a psychotic disorder, or a perva-
sive developmental disorder.
From American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text
Revision (DSM-IV-TR). Bethesda, MD, American Psychiatric Association, 1994.

660
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Table 89-3 Potential Medical Diagnoses in Patients with Anxiety

Endocrine Intoxication
Hyperthyroidism (thyrotoxicosis) Caffeine
Hypothyroidism Alcohol
Hypoglycemia Amphetamines
Hyperadrenocorticism Cannabis
Graves’ disease Cocaine
Hallucinogens
Cardiovascular Inhalants
Angina pectoris Phencyclidine
Cardiomyopathy Sympathomimetics
Congestive heart failure
Pulmonary embolism Withdrawal
Arrhythmia Alcohol
Mitral valve prolapse Cocaine
Myocardial infarction Sedatives
Opiates
Respiratory Hypnotics
Chronic obstructive pulmonary disease Anxiolytics (e.g., benzodiazepines)
Pneumonia Nicotine
Hypoxia
Nutritional Deficiencies
Metabolic Conditions Vitamin B12
Acidosis Pyridoxine
Electrolyte abnormalities Folate
Pernicious anemia
Medications
Neurologic Corticosteroids
Neoplasms Herbal medicines (e.g., ginseng)
Vestibular dysfunction Over-the-counter sympathomimetics
Encephalitis SSRIs
Parkinson’s disease Digoxin
Thyroxine
Theophylline
SSRIs, selective serotonin reuptake inhibitors.

Katherine presented with symptoms similar losing control, dying, or going crazy; paresthesias;
to those indicative of hyperthyroidism, including and/or hot flushes or cold chills that peak within
weight loss, nervousness, a rapid heart rate, light- 10 minutes of their onset (APA, 1994). Katherine
headedness, and sleep problems. The results reports physical symptoms; however, her symp-
of laboratory tests suggested that Katherine’s thy- toms do not occur abruptly and do not peak
roid functioning, as measured by serum thyroid- within 10 minutes of their onset. She also denies
stimulating hormone, free T4, and serum T3, is persistent concern about such attacks. Therefore,
normal. These results, in combination with phys- this disorder may be ruled out.
ical findings, rule out medical disorders. 4. Major depressive disorder. Katherine describes vari-
3. Panic disorder. For a diagnosis of panic disorder to ous symptoms associated with depression, includ-
be made, a person must experience recurrent and ing weight loss, sleep problems, and difficulty
unexpected panic attacks, with at least one of these concentrating. In addition, her ZSRDS score sug-
attacks followed by persistent concern regarding a gests mild levels of depression. However, in order
future attack, worrying about the implications of to be diagnosed with major depressive disorder, a
such an attack, and significant behavioral change person must experience at least five of the follow-
due to the attacks. A panic attack is characterized ing nine symptoms nearly every day for at least
by a discrete period of intense fear or discomfort 2 weeks: (a) depressed mood, (b) markedly dimin-
that is accompanied by symptoms such as palpita- ished interest or pleasure in all or nearly all activi-
tions, sweating, shaking, shortness of breath, ties, (c) significant weight loss or gain, or a decrease
choking sensations, chest pain, nausea, and dizzi- or increase in appetite, (d) insomnia or hyper-
ness; derealization or depersonalization; fear of somnia, (e) psychomotor agitation or retardation,

661
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

(f) fatigue or loss of energy, (g) feelings of worth- FOLLOW-UP VISITS

lessness or excessive or inappropriate guilt,
(h) diminished ability to think or concentrate, or A week later Katherine returns to the clinic for her
indecisiveness, and/or (i) recurrent thoughts of first follow-up visit. She reports having difficulty
death, recurrent suicidal ideation without a specific focusing on the patient education material. She
plan, or a suicide attempt or a specific plan for notes that her mind continues to wander onto vari-
committing suicide (APA, 1994). Katherine does ous topics of worry. The provider then raises med-
not meet the full criteria since she experiences only ication as a management option, with the hope that
a limited number of these symptoms and does not it will allow her to focus more effectively on the cog-
experience those consistently (Box 89-3 gives the nitive and behavioral strategies provided to her.
SIG E CAPS + Mood mnemonic for major depres- Katherine is interested in giving it a try; therefore,
sive episode). she is prescribed the selective serotonin reuptake
5. Adjustment disorders (with anxiety or with mixed inhibitor (SSRI) escitalopram oxalate (Lexapro) for
anxiety and depressed mood). To be diagnosed her generalized anxiety. The starting dose is 10
with an adjustment disorder, a person must expe- mg/day. The provider asks Katherine to try again to
rience emotional or behavioral symptoms within read the patient education materials given to her
3 months of the onset of a particular stressor or previously and asks her to return to the clinic in 2
stressors. Either the person must experience weeks.
marked distress, in excess of what would be At her second follow-up visit, Katherine reports
expected, or the symptoms must result in sig- that her symptoms have lessened and her concentra-
nificant social or occupational (or academic) im- tion has improved enough that she could read and
pairment (APA, 1994). Although Katherine is understand the materials. She is continued on esci-
experiencing emotional symptoms that cause talopram oxalate.
occupational impairment, there does not appear Over the next several visits, Katherine is
to be a specific stressor or stressors responsible for instructed in relaxation techniques, cognitive strate-
her symptoms. In addition, her symptoms are gies such as thought stopping, and the importance
better accounted for by a diagnosis of generalized of initiating a regular exercise regimen. Smoking ces-
anxiety disorder. sation and caffeine reduction are also broached
6. Substance-induced anxiety disorder. This diagnosis with her.
is considered when there is evidence from the his-
tory, physical examination, or laboratory findings
that the patient’s anxiety developed during or
within 1 month of substance intoxication or with- DISCUSSION
drawal or when medication is etiologically related
to the anxiety (APA, 1994) (see Table 89-3). Prevalence of the Disorder
Although Katherine describes cocaine use in the Generalized anxiety disorder is a common problem
past, she denies current use of cocaine or other in the United States. According to results from the
substances and denies significant alcohol use. U.S. National Comorbidity Survey (Kessler et al.,
Therefore, this diagnosis is not likely. 1994), the 12-month prevalence rate for generalized
anxiety disorder is 3.1% and the lifetime prevalence
rate is 5.1%. The lowest rates occurred in the 15- to
24-year-old age group (2.0%) and the highest rates
occurred in the 45- to 55-year-old age group (6.9%).
Box 89-3 SIG E CAPS + Mood Mnemonic
Women are almost twice as likely as men to be diag-
S Sleep (insomnia or hypersomnia)
nosed with generalized anxiety disorder over their
I Interests (diminished interest or pleasure in
lifetime (6.6% vs. 3.6%) (Wittchen et al., 1994), and
activities)
whereas the prevalence of the disorder decreases
G Guilt (excessive or inappropriate guilt; feel-
with age in men, it increases in women (Halbreich,
ings of worthlessness)
2003).
E Energy (loss of energy or fatigue)
Wittchen (2002) reported that 5.3% of patients
C Concentration (diminished concentration or
seen in primary care settings have generalized anxi-
indecisiveness)
ety disorder. The highest incidence was found in
A Appetite (decrease or increase in appetite;
patients aged 35 to 60 years. It is the most frequently
weight loss or gain)
seen anxiety disorder in primary care, and only 28%
S Suicide (recurrent thoughts of death, suici-
of patients with generalized anxiety disorder are cor-
dal ideation, or suicide attempt)
rectly diagnosed. Of these, many are improperly
+ Mood (depressed mood or sadness)
managed with pharmacologic or nonpharmacologic
treatments.

662
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

There is also a high degree of comorbidity with Management of Generalized Anxiety

generalized anxiety disorder, with 66.3% of patients Disorder
having an additional concurrent psychiatric diagno-
sis and 90.4% having a lifetime history of another Medical conditions, psychosocial issues, and person-
psychiatric disorder. Studies suggest that major ality factors all must be considered before any treat-
depressive disorder, panic disorder, and alcohol ment plan for generalized anxiety disorder can be
abuse are the three most common diagnoses associ- developed (Katon and Geyman, 2002). Once this
ated with generalized anxiety disorder (Fricchione, occurs, the physician and patient should work collab-
2004; Wittchen, 2002). oratively to develop a treatment plan. Physician inter-
ventions may include psychosocial interventions,
pharmacologic interventions, or combined therapy.
Diagnostic Criteria and Clinical Presentation
The essential feature of generalized anxiety disorder is Psychosocial Management
excessive anxiety and worry (apprehensive, expecta- Several psychosocial interventions are available to
tion) that occurs persistently for at least 6 months and the physician when treating a patient with chronic
is directed toward a number of events or activities, anxiety. A useful way to organize one’s approach to
such as work or school performance (see Box 89-2). interventions is the REST mnemonic, which cues
In the clinical setting, patients with generalized anxi- the physician to address several important areas (Box
ety disorder typically do not present with anxiety as 89-4). The R stands for reassurance and support.
their primary complaint. More often, patients present Patients with chronic anxiety, especially those pre-
with rather general, vague, or nonspecific somatic senting with physiologic symptoms, are often wor-
complaints such as headaches, low back pain, gas- ried about health problems and related issues.
trointestinal distress, fatigue, and insomnia (Anxiety Therefore, assurances that an appropriate history,
Disorders Association of America, 2004). Patients physical examination, and laboratory testing will be
with generalized anxiety disorder use health care completed to rule out medical disease is necessary.
services to a greater extent for these symptoms. The E represents education of the patient and possi-
Whereas most visit primary care physicians, gas- bly family members about anxiety, factors that may
troenterologists are the most frequently seen special- cause it, and how the body responds. A discussion of
ists (Kennedy and Schwab, 1997● B ). the neuroendocrine response to stress (i.e., the fight-

Box 89-4 Psychosocial Management of Anxiety: REST Mnemonic

R Reassurance and support provided to patient in causing anxiety; teach the patient how to
regarding the physician’s ability to conduct monitor his or her thoughts and then to catch
an appropriate history, physical examina- the negative thinking that leads to stress,
tion, and laboratory testing in order to rule “stop” it, and replace it with more rational or
out medical disease. This should be done in positive thinking)
a supportive manner. • Exercise (encourage the patient to begin a
E Education provided to the patient and possi- reasonable exercise program such as walk-
bly family members on anxiety, its etiology, ing, riding a bicycle, or jogging)
the neuroendocrine response (fight-or-flight • Time management (help the patient under-
response), and how this may lead to psycho- stand how to break large tasks into smaller
logical, physiological, and behavioral prob- tasks, make lists, prioritize, learn to say no)
lems. • Social support (encourage the patient to
S Stress management techniques are introduced talk to and to participate in activities with
and taught to the patient. These include: others)
• Deep breathing (teach the patient how to • Habit reduction (assist the patient to reduce
belly breathe and to take slow breaths) nicotine, caffeine, and so on)
• Relaxation training (teach the patient T Therapy may be necessary for patients who
how to participate in progressive muscle continue to experience significant anxiety
relaxation, imagery, and so forth; provide despite the use of the above interventions.
a relaxation tape to the patient) For these patients, referral to a psychologist
• Thought-stopping strategies (talk to the or psychiatrist for formal therapy may be
patient about the role of negative thinking necessary.

663
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

or-flight response) and how this may lead to various self-talk, (4) time management, (5) social support,
physiologic symptoms is helpful. All information and (6) habit reduction strategies. Information
should be presented at the patient’s level of compre- should be supplemented with patient education
hension. The S stands for stress management inter- handouts, once again keeping in mind the compre-
ventions. These interventions include (1) deep hension level of the patient (Box 89-5). In addition,
breathing and relaxation, (2) exercise, (3) positive patients will likely benefit from other resources such

Box 89-5 A Patient’s Guide to Anxiety and Stress Management

Background stopping it immediately—you can either say

aloud “stop” or think it to yourself— and
Anxiety and stress are very common problems.
replacing the unproductive self-talk with more
Generalized anxiety involves excessive worrying
rational self-talk (“I have a lot to study, but if I
about a variety of issues or events. Worrying typ-
focus on one section at a time, I should be OK”).
ically results in various physical symptoms that
The key is to notch it down and keep the cata-
include restlessness, fatigue, difficulty concentrat-
strophizing to a minimum.
ing, muscle tension, and sleep problems. Some
Relaxation training begins by assuming a
persons may develop other physical problems
comfortable position (such as relaxing in a reclin-
such as headaches (typically in the back of the
ing chair) and taking slow, deep belly breaths.
neck area or a bandlike effect around the head),
Think of these as taking 7-second breaths
low back pain, indigestion, constipation, diar-
(breathe in to a mental count of one one-thou-
rhea, and bruxism (grinding one’s teeth). In addi-
sand, two one-thousand, three one-thousand,
tion to physical symptoms, persons may
then pause for a count of one one-thousand,
experience increased irritability, frustration, and
then exhale for a count of one one-thousand,
impatience. Eventually, these symptoms may
two one-thousand, three one-thousand), all the
result in excessive tardiness and absenteeism from
time making sure that as you breathe in your
school or work, withdrawal from social activities,
belly goes out and as you exhale your belly goes
and isolation from others.
back in. You can then accompany this breathing
with cue words such as “relax” or “let go,” along
Anxiety Management with muscle relaxation and imagery. Imagery
involves putting yourself in any place that is com-
There are several strategies available to assist in
fortable or peaceful for you (in your family room
the management of anxiety. The more effective
by a fireplace, on a quiet beach). Continue with
techniques for dealing constructively with anxi-
the breathing and imagery for 20 minutes and
ety include time management, cognitive strate-
end your relaxation session by saying something
gies, and relaxation techniques.
positive about yourself. Allow this relaxation and
Time management. Key here is to break large
accompanying affirmation to carry you through
tasks into smaller tasks. Don’t put off til tomor-
your day.
row what you can do now. Schedule important
events, prioritize, and say no if you are feeling
Watch Those Habits
overwhelmed.
Cognitive strategies attempt to change how There are a variety of substances that people
you think about events in your life, knowing take that can make their anxiety worse. These
that how you think determines how you feel. include the excessive use of caffeine, nicotine, or
Many people will look at an upcoming exami- any other stimulant. Decreasing or eliminating
nation or interview as a terrible event that they these substances from your daily routine will
are doomed to fail. They then catastrophize by have a positive impact on your psychological and
thinking about how this failure will lead to physical health. Also, avoid using substances
additional problems, and so forth, until a such as alcohol or marijuana to calm down, since
mountain is made from a molehill. Thought- their use can lead to abuse and dependency
stopping strategies can be used to stop or at problems. More productive coping involves
least minimize this process. The first step is rec- using the techniques described above. They may
ognizing your unproductive self-talk (“There is take more time to work, but in the end, they will
so much to study, I’m going to fail miserably”), be much more effective.

664
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Box 89-5 A Patient’s Guide to Anxiety and Stress Management (Continued)

Final Suggestions Organizations and Internet Site Resources

If you recognize early when anxiety and stress is A variety of resources are available to persons
impacting you negatively, you are wise to use interested in learning more about anxiety and
the strategies mentioned above and then to take stress. These include the following:
action. More appropriately, it is better to take a Anxiety Disorders Association of America
proactive approach by doing things that will (ADAA)—www.adaa.org
buffer you against the anxiety and stress that International Association of Anxiety Manage-
everyone encounters naturally as part of daily ment—www.anxman.org
life. These include a regimen of positive think- American Psychiatric Association—www. psych.
ing, socializing, relaxation, and exercise. If you org
find that you need more help, seek professional American Psychological Association—www.apa.
assistance. org

as books, Web sites, and self-help groups. If these SSRIs are available in the United States for the
strategies are not totally effective, the physician may treatment of generalized anxiety disorder (Table 89-4).
consider referring the patient for T, or formal therapy Escitalopram oxalate (Lexapro), which received FDA
with a psychologist or psychiatrist. approval for the treatment of generalized anxiety
In Katherine’s case, medical factors were ruled disorder in 2003, was prescribed for Katherine. It is a
out and it was determined that her physiologic pure S-enantiomer (single isomer) of the racemic
symptoms were due mainly to her tendency to worry bicyclic phthalane derivative citalopram. Its action
about various life issues. During her first visit she results from inhibiting serotonin (5-HT) reuptake
was provided with reassurance and support and was and neuronal firing rate.
then educated about anxiety and stress. At her first The initial starting dose of escitalopram oxalate
follow-up visit she continued to complain of con- is 10 mg once daily in either the morning or evening.
centration difficulties, so medication was prescribed. It may be increased to 20 mg after a minimum of
In subsequent sessions, Katherine was further 1 week. Major side effects include headache (24%),
instructed in deep breathing and relaxation strate- nausea (18%), ejaculation disorder (14%), somno-
gies. A relaxation training cassette tape was given to lence (13%), and insomnia (12%).
her and she was instructed to practice with the tape Some patients taking SSRIs may experience a
at least once daily. In addition, she was taught decrease in symptoms during the first 2 weeks; how-
thought-stopping strategies that entail catching neg- ever, most respond gradually with continued
ative thinking or “self-talk,” immediately stopping it, improvement for 8 to 12 weeks or for as long as 6
and then replacing those thoughts with more months. Therefore, optimal trials of SSRIs for gener-
rational thinking. Katherine was also instructed to alized anxiety disorder should be at least 8 weeks of
begin an exercise program of walking 3 days per adequate dosing before other options are considered
week for 20 minutes each time. When she returned to by the physician. Because of the potential for a
the clinic, Katherine noted that she did practice delayed response, it is not uncommon to use benzo-
relaxation several times each week and walked diazepines in combination with antidepressant med-
almost daily as part of her new exercise program. ication during the initial treatment of an anxiety
She continued to have difficulty with catching nega- disorder (Augustin, 2005).
tive thinking and worrying. She was commended for A major advantage of the SSRIs is that they seem
her progress with relaxation and exercise and was to be more effective than the benzodiazepines in
further assisted with thought-stopping strategies. ameliorating cognitive symptoms (i.e., excessive
Medication was also prescribed. worry) of generalized anxiety disorder. They also
have less potential for abuse and dependence.
Pharmacologic Management
Three major classes of pharmacologic agents are Nonbenzodiazepines Buspirone (Buspar) is consid-
available for the treatment of generalized anxiety dis- ered a first-line treatment for generalized anxiety
order: SSRIs, nonbenzodiazepines, and benzodi- disorder. It is the only nonbenzodiazepine available
azepines. and is thought to exert its influence by acting as an
agonist at presynaptic serotonin (5-HT1A) receptor
SSRIs SSRIs are now considered first-line agents for sites. Its onset of action is slower than that of the ben-
treating anxiety disorders (Augustin, 2005). Various zodiazepines and it may take several days to 2 weeks

665
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

Table 89-4 Pharmacologic Agents Used in the Management of

Generalized Anxiety Disorder
Usual Starting Total Dosage
Agent Dose (mg) Range (mg/day) Half-life (hr)

Selective Serotonin Reuptake Inhibitors

Citalopram (Celexa) 20 qd 20–60 35
Escitalopram oxalate (Lexapro) 10 qd 10–20 27–32
Fluoxetine (Prozac) 24–384†
Obsessive-compulsive disorder 20 qd 20–80
Panic disorder 10 qd 10–60
Paroxetine (Paxil)
Generalized anxiety disorder 20 qd 20–50 21
Obsessive-compulsive disorder 20 qd 20–60
Panic disorder 10 qd 10–60
Post-traumatic stress disorder 20 qd 20–50
Social anxiety 20 qd 20–60
Paroxetine (Paxil CR) 15–20
Panic disorder 12.5 qd 12.5–75
Social anxiety 12.5 qd 12.5–37.5
Sertraline (Zoloft)
Panic disorder, 25 qd 25–200 26
post-traumatic stress disorder,
social anxiety disorder

Nonbenzodiazepines
Buspirone (BuSpar) 7.5 bid 15–60 2–3

Benzodiazepines*
Alprazolam (Xanax) 0.25–0.5 tid 0.75–4 6–27
Chlordiazepoxide (Librium) 5 bid, tid, or qid 10–100 6–20
Clonazepam (Klonopin) 0.5 tid 1.5–20 18–50
Chlorazepate (Tranxene) 7.5–15 qd 7.5–60 48
Diazepam (Valium) 2 bid–qid 4–40 >20
Lorazepam (Ativan) 1–3 qd in divided 1–10 12–18
doses
Oxazepam (Serax) 10 tid 30–90 6–11

Serotonin/Norepinephrine Reuptake
Inhibitors
Venlafaxine (Effexor) 75 qd in 2–3 divided 75–225 3–13‡
doses
Venlafaxine (Effexor XR) 75 qd (some patients 37.5–225 3–13‡
may be started on
37.5 mg for 4–7
days)

Heterocyclic Antidepressants
Trazodone (Desyrel) 150 qd in divided 150–600 3–9
doses

Tricyclic Antidepressants
Clomipramine (Anafranil) 25 qd 25–250 19–77§
Desipramine (Norpramin) 25 bid to qid 50–300 21
Imipramine (Tofranil) 75 qd 75–200 30
Nortriptyline (Aventyl) 25 tid or qid 75–150 26

*
Rate of onset for benzodiazepines: alprazolam, diazepam, and chorazepate—fast; chordiazepoxide, lorazepam,
and clonazepam—intermediate; oxazepam—slow.
†
Includes both fluoxetine and norfluoxetine.
‡
Includes both venlafaxine and N-desmethylvenlafaxine.
§
Includes both clomipramine and desmethylclomipramine.

666
 Chapter 89 Multiple Somatic Complaints (Generalized Anxiety Disorder)

or longer to reach full therapeutic benefit. Buspirone rocyclic antidepressants, and tricyclic antidepres-
lacks general central nervous system depressant sants. Monoamine oxidase inhibitors, beta blockers,
effects and is relatively free from any significant abuse and antihistamines have also been used for symp-
or dependence potential. Therefore, buspirone is pre- toms related to anxiety.
ferred over benzodiazepines in persons with a sub-
stance abuse/dependency history and in persons who Summary
are elderly or medically ill. Reported side effects
include dizziness, drowsiness, nausea, and headaches. Generalized anxiety disorder is a common problem
characterized by chronic, excessive anxiety and
Benzodiazepines Benzodiazepines are still the most worry about a number of events or activities, diffi-
widely used anxiolytic for anxiety disorders. The ben- culty controlling the worry, associated physical
zodiazepines are believed to influence four types (α1, symptoms, and functional impairment. Generalized
anxiety disorder is frequently seen in primary care;
α2, α3, and α5) of GABAA, with anxiolytic effects occur-
however, it often goes undiagnosed or improperly
ring on the α2 GABAA receptors within the CNS.
managed. Once medical disease is ruled out, the
Overall, the benzodiazepines are safe and well-
physician may use psychosocial strategies and/or
tolerated medications, with sedation, fatigue, cognitive
pharmacologic interventions. SSRIs, nonbenzodi-
impairment, and psychomotor impairment being their
azepines, and benzodiazepines have proved effective
major side effects. Sedation and psychomotor impair-
in the management of generalized anxiety disorder.
ment typically resolve within a few weeks of ongoing
A combination of psychosocial and pharmacologic
treatment. Withdrawal symptoms are usually associ-
interventions is most effective in the long-term man-
ated with a quicker rate of cessation, larger doses,
agement of this disorder.
longer-term use, and higher-potency medications.
Although abuse of benzodiazepines is a concern, mis-
use and abuse are typically limited to persons with a
history of substance abuse.
Material Available on Student Consult
Other Medications Other medications used in the
Review Questions and Answers about Generalized
treatment of generalized anxiety disorder include Anxiety Disorder
serotonin/norepinephrine reuptake inhibitors, hete-

REFERENCES
American Psychiatric Association. Diagnostic and Kennedy BL, Schwab JJ. Utilization of medical specialists
Statistical Manual of Mental Disorders, 4th ed., Text by anxiety disorder patients. Psychosomatics 1997;38:
Revision (DSM-IV-TR). Bethesda, MD, American 109–112.● B
Psychiatric Association, 1994. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and
Anxiety Disorders Association of America. Improving the 12-month prevalence of DSM-III-R psychiatric disor-
Diagnosis and Treatment of Generalized Anxiety ders in the United States: Results from the National
Disorder: A Dialogue Between Mental Health Comorbidity Survey. Arch Gen Psychiatry 1994;51:
Professionals and Primary Care Physicians. Silver Spring, 8–19.
MD, Anxiety Disorders Association of America, 2004. Sheehan JV. The Sheehan Patient Rated Anxiety Scale.
Augustin SG. Anxiety disorders. In Koda-Kimble MA, Young J Clin Psychiatry 1999;60(Suppl 18):63–64.
LY, Kradjan WA, Guglielmo BJ (eds): Applied Thera- Sheehan DV, Harnett-Sheehan K. Psychometric assess-
peutics: The Clinical Use of Drugs, 8th ed. Philadelphia, ment of anxiety disorders. In Sarorius N, Andreoli V,
Lippincott Williams & Wilkins, 2005, pp 76-1–76-47. Cassano G, et al. (eds): Anxiety: Psychobiological and
Ewing JA. Detecting alcoholism: The CAGE Questionnaire. Clinical Perspectives. Washington, DC, Hemisphere,
JAMA 1984;252:1905–1907. 1990, pp 85–98.
Fricchione G. Generalized anxiety disorder. N Engl J Med Wittchen H-U. Generalized anxiety disorder: Prevalence,
2004;351:675–682. burden, and cost to society. Depression Anxiety
Halbreich U. Anxiety disorders in women: A develop- 2002;16:162–171.
mental and lifecycle perspective. Depression Aging Wittchen H-U, Zhao S, Kessler RC, Eaton WW. DSM-III-R
2003;17:107–110. generalized anxiety disorder in the National Comorbidity
Katon W, Geyman JP. Anxiety disorders. In Rakel RE (ed): Survey. Arch Gen Psychiatry 1994;51:355–364.
Textbook of Family Practice, 6th ed. Philadelphia, WB Zung WW. A self-rating depression scale. Arch Gen
Saunders, 2002, pp 1438–1453. Psychiatry 1965;12:63–70.● B

667
 C h a p t e r

90 Delirium (Hypomagnesemia)

Robert S. Freelove

KEY POINTS
1. Delirium causes significant morbidity and mor- 6. Disruptive behavior can be treated using the
tality and is often the first sign of problem in antipsychotic haloperidol when a patient is at
an elderly patient. risk for harming him- or herself or others.
2. The features of delirium include a disturbance 7. Failure to recognize delirium results in significant
of consciousness, a change in cognition, an morbidity and mortality. The Confusion
acute onset and fluctuating course, and an Assessment Method diagnostic algorithm can
underlying medical illness. aid in the diagnosis of delirium.
3. Delirium may manifest with hyperactivity or 8. Delirium should not be misidentified as demen-
hypoactivity. tia. Dementia has a much slower onset and pri-
4. Medications are a common cause of delirium, marily involves problems with memory.
especially in the hospitalized patient, and 9. Benzodiazepines should not be used in the
should be carefully reviewed, including management of the disruptive behavior of delir-
over-the-counter drugs and herbal ium as they will only worsen confusion.
products. 10. Failure to initially identify a cause should prompt
5. The treatment of delirium involves identify- further investigation, because the cause of
ing and treating the underlying medical delirium by definition is an underlying medical
cause. condition.

INITIAL VISIT him, and he pushed her down. She subsequently called
emergency medical services. Mrs. B. notes that Mr. B.
Subjective went to his bowling league earlier that evening and
came home acting normally. She had not smelled
Patient Identification and Presenting alcohol on his breath. Mr. B. pays no attention to ques-
Problem tions and provides no history.
George B. is a 66-year-old man who is brought to the
emergency department (ED) of a rural hospital by Medical History
ambulance for confusion and agitation. His wife Mrs. B. provides Mr. B.’s medical history. To her knowl-
accompanies him and states that everything started edge, he has no medical illnesses, is not taking any
3 hours earlier, when she found Mr. B. urinating in the medications, and is not allergic to any medications. His
kitchen sink. When she asked him what he was doing, only surgery was an inguinal herniorrhaphy at age 31.
he seemed confused and mumbled nonsensically. She
helped him back to bed and reawakened 21⁄2 hours later Family History
to find him pacing about the bedroom, shouting and Mr. B. was adopted and never indicated to Mrs. B.
talking to people who were not there. She tried to calm that he knew anything about his biological parents.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

668
 Chapter 90 Delirium (Hypomagnesemia)

Social History
Mr. B. is a retired city maintenance worker who now Box 90-1 Possible Causes of Delirium
runs a small family farm. He smokes two to four Acute metabolic disturbances (uremia, liver
cigars daily and has a history of alcoholism but has failure)
been sober for 18 years. There is no history of illegal Acute vascular disease (stroke, vasculitis,
drug use, to his wife’s knowledge. He is married and subarachnoid hemorrhage, sagittal vein
has three children and seven grandchildren. thrombosis)
Central nervous system (CNS) disease (tumor,
Review of Systems space-occupying lesions, seizure)
The review of systems cannot be performed because Dehydration
the patient does not respond to questions. He con- Electrolyte disturbances (hypo- or hyperna-
tinues to moan, mumble words that have no relation tremia, hypoglycemia, acidosis, hypercal-
to the questions asked, and call out names. His wife cemia, hypomagnesemia)
indicates that the names are those of deceased Endocrinopathy (hypo- or hyperthyroid, adrenal
friends and family members. He becomes agitated crisis)
when approached or touched. Environmental exposure (hypo- or hyper-
thermia, sleep deprivation, unfamiliar
Objective surroundings)
Heavy metals (lead, mercury)
Physical Examination Hypoxia
Mr. B. is sitting upright, awake, hypervigilant, and star- Infection (encephalitis, meningitis, syphilis,
tled when touched. His temperature is 37.4˚C (99.3˚F), CNS abscess, sepsis)
pulse is 106, blood pressure is 162/88, respiratory rate Intoxication (alcohol, amphetamines, cocaine)
is 22. Examination of the head reveals no evidence of Medication
trauma. He does not allow evaluation of the ears, nose, Nutritional deficiencies (vitamin B12, niacin,
or throat. His pupils are equally round and reactive to thiamine, malnourishment)
light, and there is no scleral icterus. He does not allow Pain (fractures, burns, surgery)
palpation of the neck. His lungs are clear to ausculta- Toxins (pesticides, carbon monoxide, cyanide,
tion. Cardiac auscultation reveals normal S1 and S2 solvents)
without a murmur, rub, or heave. The abdomen is soft, Trauma (intracranial hemorrhage, closed head
without guarding. He is unable to follow directions for injury)
a neurologic examination, but there are no obvious Withdrawal (alcohol, barbiturate, benzodi-
gross motor deficits. As the physical examination pro- azepene, opiate)
gresses, he becomes more agitated and eventually tries
to strike anyone who touches him. Note: Causes are listed in alphabetical order.
Data from Gleason OC. Delirium. Am Fam Physician
2003;67:1027–1034.
Assessment
Working Diagnosis
The working diagnosis is delirium, etiology rapidly identified and treated. Similarly, infection of
unknown. the urinary tract, respiratory tract, or skin and soft
tissues or sepsis from any source may also produce
Underlying Medical Conditions acute alterations in consciousness. Usually, the phys-
Delirium is a generally reversible syndrome of dis- ical examination and simple laboratory tests, includ-
turbed consciousness, attention, and cognition or ing a complete blood cell (CBC) count and urinalysis
perception that develops acutely, fluctuates during with culture, will identify a focus of infection.
the course of the day, and is attributable to a physical Routine lumbar puncture is not necessary; however,
disorder. The presence of delirium indicates an if headache or meningismus is present or if an infec-
underlying medical condition that should be aggres- tious focus is not readily identified, lumbar puncture
sively investigated and treated, because the mortality should be performed.
associated with any serious disease increases if delir- Withdrawal from substances with sedative prop-
ium ensues (Cole and Primeau, 1993● B ; McCusker erties often results in delirium. A history of alcohol,
et al., 2002●B ). There are many potential causes to barbiturate, benzodiazepine, opiate, or other sedative
consider (Box 90-1), and often more than one source hypnotic use should be elicited and quantified.
is discovered. Occasionally, previously unrecognized alcoholism is
Infection of the central nervous system (CNS)–– diagnosed when a patient admitted for another reason
for example, encephalitis, meningitis, syphilis, CNS subsequently goes through withdrawal. Signs and
abscess—may manifest with delirium and should be symptoms of withdrawal typically include restlessness,

669
 Chapter 90 Delirium (Hypomagnesemia)

tachycardia, tremor, nausea, sweats, tactile and visual

hallucinations, and occasionally seizures. Intoxication Box 90-2 Commonly Prescribed
with alcohol or street drugs, such as amphetamines or Medications That Can
cocaine, also induces delirium. Blood alcohol level Cause Delirium
determination and urine or serum drug screening cor-
roborate suspected intoxication. Antibiotics
Fluid and electrolyte disturbances and other acute Clarithromycin
metabolic disturbances may cause delirium, including Fluoroquinolones
dehydration, hypo- or hypernatremia, hypo- Anticholinergics
glycemia, acidosis, hypercalcemia, hypomagnesemia, Antiemetics
uremia, and liver failure. A complete metabolic pro- Antihistamines
file (CMP) and serum calcium and magnesium lev- Antiparkinsonian agents
els should be obtained in patients when a cause is not Antipsychotics
immediately evident. Special attention should be Antispasmodics
paid to fluid balance and hydration status during the Tricyclic antidepressants
physical examination. In addition to hydration sta- Anticonvulsants
tus, the nutritional status should be determined, Anti-inflammatories
because general malnutrition, as well as specific Corticosteroids
nutritional deficiencies (vitamin B12, niacin, thi- Nonsteroidal anti-inflammatory drugs
amine), may play a role. Salicylates
Intracranial hemorrhage or other closed head Benzodiazapines
injury from head trauma may be the underlying Cardiovascular drugs
cause. Patients with delirium and evidence of a head β-blockers
injury should undergo immediate computed tomog- Antidysrhythmics
raphy (CT). Pain from other forms of trauma, Antihypertensives
including fractures, burns, or surgery, can cause Digoxin
delirium. Postoperative pain is especially trouble- H2-receptor antagonists
some because it may be unclear whether the symp- Lithium
toms are due to the pain or to the opioid analgesic Narcotic analgesics
medication used to treat the pain. This uncertainty Note: Drugs are listed in alphabetical order.
may lead to inadequate pain management and wors- Data from Francis J. Drug-induced delirium:
ening delirium. Diagnosis and treatment. CNS Drugs 1996;5:103.
Delirium may accompany many CNS diseases.
Focal neurologic deficits suggest the presence of a
tumor or other space-occupying lesion. Focal deficits
should be assessed with CT. Other acute vascular dis- should be carefully reviewed and potential drug-
eases such as stroke, vasculitis, subarachnoid hemor- drug interactions considered, including over-the-
rhage, sagittal vein thrombosis, and hypertensive counter drugs and any other medications the patient
emergency must be ruled out if they are suggested by may have access to in the household. Drugs with lev-
the overall clinical picture. els that can be checked (digoxin, lithium, certain
Environmental exposure should be taken into anticonvulsants) should be checked because they
account, and hypo- or hyperthermia should be read- may cause symptoms even in the therapeutic range.
ily recognized and treated. A common iatrogenic Endocrinopathies (thyroid storm, myxedema
cause is the so-called ICU psychosis that can occur in coma, adrenal crisis) are uncommon but serious
critically ill patients on closed units who are not causes of delirium. Myxedema coma is a rare compli-
exposed to diurnal cues or are sleep deprived. Other cation of severe hypothyroidism, often induced by
environmental considerations, including exposure to an underlying infection, with severe hypothermia,
toxins such as pesticides, industrial poisons (carbon hypoventilation, hypoxia, hyponatremia, hypoten-
monoxide, cyanide, solvents), or heavy metals (lead, sion, and hypercapnia. Thyroid storm is a very rare
mercury), are generally elicited in the history. form of thyrotoxicosis manifested by delirium, tachy-
Hypoxia causes fluctuations in consciousness, cardia, vomiting, diarrhea, dehydration, and high
attention, and cognition characteristic of delirium. fever. A thyroid-stimulating hormone (TSH) level is
This occurs with acute hypoxia from respiratory fail- usually adequate to screen for thyroid dysfunction.
ure, worsening of chronic lung disease, or hypoten- Acute adrenal insufficiency, or adrenal crisis, most
sion and decreased cerebral perfusion. commonly occurs following stress or illness in a
Up to 30% of cases of delirium are attributable patient with latent insufficiency or treated insuf-
to medication toxicity (Francis, 1996). Many medica- ficiency if steroid replacement is not increased to
tions can cause delirium (Box 90-2). Medication lists account for increased stress. A cosyntropin stimula-

670
 Chapter 90 Delirium (Hypomagnesemia)

tion test establishes the diagnosis, and an elevated Plan

plasma adrenocorticotropic hormone (ACTH) level
distinguishes primary adrenal disease from secondary. Mr. B. is admitted to the hospital and given 2 g of
magnesium sulfate intravenously over 30 minutes;
followed by 6 g of magnesium sulfate in 1 liter of
Plan normal saline over 24 hours. He is placed on
Diagnostic haloperidol, 5 mg every 8 hours scheduled and 2 mg
Mr. B. is too combative to allow blood to be drawn or every 2 to 4 hours as needed for agitation, to prevent
other testing. So, before further testing is under- him from removing his IV line and monitors.
taken, he is given 2 mg of haloperidol intramuscu-
larly (IM). His agitation does not improve after 30
minutes, so he is given a repeat dose of 2 mg. He FOLLOW-UP
calms significantly, and blood is drawn for a CMP,
CBC, blood culture, and TSH and blood alcohol level The next morning, Mr. B.’s magnesium level is 1.5
determination. A fingerstick blood glucose level is mg/dL. The haloperidol is tapered to 2 mg every
normal at the bedside. Urine is collected for urinaly- 8 hours, and Mr. B. is back to normal mentation. He
sis and drugs of abuse screen. An electrocardiogram remembers nothing of the previous 2 days. Atenolol,
(ECG) and chest radiograph (using portable equip- 50 mg/day, replaces the hydrochlorothiazide. The IV
ment) are obtained while the patient is cooperative. magnesium is continued for another 24 hours and
oral magnesium replacement is started. The haloperi-
Therapeutic dol is tapered further and discontinued after 48 hours.
Intravenous (IV) access is obtained, and 100 mg of
thiamine is administered. Physical restraints are not
employed, as he is cooperative after the haloperidol. DISCUSSION
ED Course Delirium is a serious problem that is encountered
Mr. B. remains calm but does not respond appropri- in up to 30% of elderly hospitalized patients
ately to questions. He occasionally points and says (Francis, 1992) and 10% of elderly ED patients
the names of dead family and friends. Other than (Lewis et al., 1995● B). Elderly patients who develop
being calmer, there is no significant change in his delirium have longer hospital stays (Ely et al.,
physical examination. 2001● B ), a more rapid deterioration in function, and
an increased risk of institutionalization (Inouye
Laboratory/Special Studies et al., 1998● B ). Both 1-month and 6-month mortal-
The CBC, CMP, TSH, urinalysis, blood alcohol level, ity double for patients with delirium versus those
and urinary drug screen are normal. The ECG shows without (Cole and Primeau, 1993● B ). Mortality
sinus tachycardia but is otherwise unremarkable. remains increased for up to a year (McCusker et al.,
The chest radiograph shows poor inspiratory effort 2002● B). Risk factors include advanced age, preexist-
but no infiltrate or increased vascular markings. ing dementia or cognitive impairment, severe
chronic medical illness, multiple medical condi-
Further Testing tions, polypharmacy, sensory impairment, and
More blood is drawn for serum magnesium and B12 sleep deprivation (Gleason, 2003).
level determination. Arterial blood gas values are nor- Box 90-3 lists the diagnostic criteria for delir-
mal. Mr. B. allows a head CT to be performed, which ium (American Psychiatric Association, 2000). The
is normal. A lumbar puncture performed after seda- hallmark characteristic is an acute change in level of
tion with 1 mg of midazolam (Versed) reveals clear consciousness and in ability to focus, sustain, or
fluid with a normal cell count and normal protein shift attention. Initially these changes may be subtle
and glucose levels, and no organisms are seen on and tend to fluctuate, making early recognition a
Gram stain. The remaining test results show a normal challenge. Short-term memory deficits and disori-
B12 level but a low magnesium level at 0.8 mg/dL. entation to date, place, or situation are very com-
mon. Patients with delirium may be agitated or
apathetic and withdrawn, resulting in hyperactive,
Assessment
hypoactive, and mixed subtypes of delirium.
Mr. B. suffers from delirium secondary to hypomag- Perceptual disturbances commonly accompany
nesemia. Mrs. B. returns from the house with a bot- delirium. Auditory hallucinations are more typical
tle of hydrochlorothiazide prescribed for her than tactile or visual, but all three can occur. Most
husband 2 weeks earlier. Hypomagnesemia is an important, delirium is caused by an underlying
adverse reaction to hydrochlorothiazide, although it medical illness and will not improve if the underly-
usually does not occur in isolation. ing illness is not addressed.

671
 Chapter 90 Delirium (Hypomagnesemia)

Delirium often goes unrecognized (Lewis et al., 95% in medical and surgical settings (Inouye et al.,
1995● B). The Confusion Assessment Method (CAM) 1990● B).
(Box 90-4) can be used as a diagnostic tool. It has a Evaluation of a patient with delirium starts with
sensitivity of 94% to100% and a specificity of 90% to a thorough history and physical examination,
including a careful review of the medication list.
Special attention should be paid to signs and symp-
Box 90-3 DSM-IV Diagnostic Criteria toms implicating one of the underlying causes listed
for Delirium in Box 90-1. Often, the initial assessment identifies
the cause, and focused laboratory testing verifies the
A. Disturbance of consciousness (i.e., reduced diagnosis. When a cause is not readily apparent, a
clarity of awareness of the environment) CMP, a CBC, and a urinalysis are appropriate initial
with reduced ability to focus, sustain, or testing. Fingerstick blood glucose testing rapidly
shift attention. assesses glycemic status in diabetics. Chest radiogra-
B. A change in cognition (such as memory phy and lumbar puncture should be performed if
deficit, disorientation, language distur- infection is suspected and a source is not readily
bance) or the development of a perceptual found. Evidence of head trauma, focal neurologic
disturbance that is not better accounted for deficits, or severe impairment of consciousness war-
by a pre-existing, established, or evolving rants neuroimaging with CT. Further studies should
dementia. be performed as indicated by the history and physi-
C. The disturbance develops over a short cal examination findings.
period (usually hours to days) and tends to Treatment is aimed at correcting the underlying
fluctuate during the course of the day. medical condition causing the problem, including
D. Evidence from the history, physical examina- discontinuation of any medication known to cause
tion, or laboratory findings indicates that delirium. Supportive needs should be addressed,
the disturbance is caused by the direct phys- including hydration, nutrition, mobility, pain relief,
iologic consequences of a general medical and aspiration precautions. Thiamine is safe and
condition. inexpensive and should be administered to all
patients prior to glucose- or dextrose-containing
Adapted from American Psychiatric Association.
Diagnostic and Statistical Manual of Mental Dis- solutions to decrease the risk of precipitating
orders, 4th ed., Text Revision (DSM-IV-TR). Bethesda, Wernicke’s encephalopathy in those with unrecog-
MD, American Psychiatric Association, 2000. nized thiamine deficiency or chronic alcoholism.

Box 90-4 The Confusion Assessment Method (CAM) Diagnostic Algorithm

Feature 1—Acute onset and fluctuating course Feature 3—Disorganized thinking

This feature is usually obtained from a family This feature is shown by a positive response to
member or nurse and is shown by positive the following question: Was the patient’s
responses to the following questions: Is there thinking disorganized or incoherent such as
evidence of an acute change in mental status rambling or irrelevant conversation, unclear or
from the patient’s baseline? Did the (abnormal) illogical in flow of ideas, or unpredictable and
behavior fluctuate during the day, that is, tend switching from subject to subject?
to come and go, or increase and decrease in
severity? Feature 4—Altered level of consciousness
This feature is shown by any answer other
Feature 2—Inattention
than “alert” to the following question: Over-
This feature is shown by a positive response to all, how would you rate this patient’s level of
the following question: Did the patient have consciousness (alert [normal], vigilant [hyper-
difficulty focusing attention, for example, alert], lethargic [drowsy, easily aroused],
being easily distractible, or have difficulty stupor [difficult to arouse], or coma [unarou-
keeping track of what was being said? sable])?

Note: CAM positive for delirium if patient has both features 1 and 2 and either feature 3 or 4.
Adapted from Inouye SK, vanDyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: The
Confusion Assessment Method, a new method for detection of delirium. Ann Intern Med 1990;113:941–948.

672
 Chapter 90 Delirium (Hypomagnesemia)

Symptomatic treatment for agitation, hallucina- treatments, phlebotomy, and recording of vital signs
tions, or disruptive behaviors is accomplished with the to occur during waking hours. Physical restraints
antipsychotic haloperidol (Haldol). Most adults will should be used only in extreme cases after other
respond to 1 to 2 mg administered orally (PO) or IM methods have failed to manage disruptive behaviors
and repeated every 2 to 6 hours as needed. The dosage and patient safety is of concern.
can range from 0.5 to 10 mg PO or IM every 1 to 4 hours Delirium is a serious condition that significantly
as needed. Haloperidol can be given IV, but patients increases morbidity and mortality when present.
should be on a cardiac monitor, because IV administra- Recognizing delirium and rapidly assessing for the
tion can cause QTc prolongation. Benzodiazepines gen- underlying cause are crucial. Information gleaned
erally worsen confusion and sedation, and their use is from the history, physical examination, medication
limited to the treatment of delirium due to withdrawal review, and focused laboratory and imaging studies
from alcohol or sedative hypnotics or as an adjunct for usually reveals the cause. Treatment is primarily
sedation for diagnostic procedures. aimed at correcting the underlying medical problem.
Nonpharmacologic interventions can be helpful Both pharmaceutical and nonpharmaceutical
in managing patients with delirium (Meagher, 2001). treatments help manage symptoms to facilitate
Many of these interventions are common sense and evaluation or treatment of the underlying problem.
easily accomplished. Family members should remain Most patients will experience complete resolution if
with the patient and provide orientation. Family the correct cause of the delirium is identified and
members can also bring familiar objects from home treated appropriately; however, symptoms of delir-
to place in the room. It is important to ensure that ium can persist for several months.
eyeglasses and hearing aids are available and easy to
locate. A clock and a calendar with large, easy-to-
read numbers placed conspicuously in the room help
maintain orientation to time. The facility should Material Available on Student Consult
maintain consistency in nursing staff and avoid hav-
Review Questions and Answers about Hypomag-
ing the patient change rooms. Uninterrupted sleep nesemia
during the night can be maximized by arranging

REFERENCES
American Psychiatric Association. Diagnostic and A three-site epidemiologic study. J Gen Intern Med
Statistical Manual of Mental Disorders, 4th ed., Text 1998;13:234–242.●B
Revision (DSM-IV-TR). Bethesda, MD, American Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP,
Psychiatric Association, 2000. Horwitz RI. Clarifying confusion: The Confusion
Cole MG, Primeau FJ. Prognosis of delirium in elderly hos- Assessment Method, a new method for detection of
pital patients. CMAJ 1993;149:41–46.● B delirium. Ann Intern Med 1990;113:941–948.● B
Ely EW, Bautam S, Margolin R, et al. The impact of delir- Lewis LM, Miller DK, Morley JE, et al. Unrecognized delir-
ium in the intensive care unit on hospital length of stay. ium in ED geriatric patients. Am J Emerg Med
Intensive Care Med 2001;27:1892–1900.● B 1995;13:142–145.
Francis J. Delirium in older patients. J Am Geriatr Soc McCusker J, Cole M, Abrahamowicz M, Primeau F, Belzile
1992;40:829–838. E. Delirium predicts 12-month mortality. Arch Intern
Francis J. Drug-induced delirium: Diagnosis and treat- Med 2002;162:457–463.● B
ment. CNS Drugs 1996;5:103. Meagher DJ. Delirium: Optimizing management. BMJ
Gleason OC. Delirium. Am Fam Physician 2003;67: 2001;322:144–149.
1027–1034.
Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei
P. Does delirium contribute to poor hospital outcomes?

673
 C h a p t e r

91 Chest Pain and Shortness of Breath

(Panic Disorder)
Layne A. Prest

symptoms begin with and are exacerbated by activ-

KEY POINTS ity, he has stopped exercising and has stopped all
sexual activity. After the initial onset of these symp-
1. Panic disorder (PD) is a potentially debilitating toms, he experienced a diminished appetite and
yet treatable condition. weight loss of 15 pounds. He reports that in his
2. The symptoms of PD can masquerade as a capacity as an emergency department (ED) nurse,
“medical” problem. he had recently taken care of several men around
3. Comprehensive treatment (medical, behavioral, his age who “had a look of panic in their eyes before
psychological) is usually the most effective they died.” They had been complaining of symp-
approach. toms similar to his own. Because of these concerns,
over the past 2 months he has obtained through
colleagues at work several electrocardiograms, a
treadmill test, 24-hour Holter monitoring, and
INITIAL VISIT blood tests for cardiac enzymes. The results of all
these tests were negative.
Subjective
Patient Identification and Presenting Medical History
Problem Andy takes atorvastatin for hypercholesterolemia
Andy B. is a 41-year-old white man who comes to the and ibuprofen as needed for chronic back pain due
clinic with chest pain, shortness of breath, and a fear to an old injury. He also has a history of gastro-
that he was having a heart attack and dying. He also esophageal reflux, but this is not currently a regular
reports some mild nausea and feeling hot or flushed. problem and is not being treated. He has no known
Andy says he came to the clinic this morning because allergies. His immunizations are up to date.
he is afraid of what these symptoms might mean,
especially since this isn’t the first time he has experi- Family History
enced them. The symptoms come on relatively sud- Andy is the second of three children. His parents,
denly and usually unexpectedly, although he is more who divorced when he was 20, are still alive. His
likely to experience one or more of them when he is father has coronary artery disease, hypertension, and
exerting himself emotionally or physically, especially hyperlipidemia. The latter two conditions seem to be
at work. well controlled by medication at this point. Andy’s
mother is in fairly good health for her age. She has
Present Illness some minor osteoarthritic pain that is well con-
Andy reports that he has had increasing problems trolled with medication.
that he first noticed on Super Bowl weekend
3 weeks ago. In addition to the symptoms men- Social History
tioned above, Andy is concerned about dizziness Andy is married and has one daughter. He is an ED
with exercise, hyperventilation, numbness and tin- nurse. Although he finds his work challenging, he is
gling in his hands, chest pain that extends up into somewhat dissatisfied because he had hoped to
the side of his face, the perception of a rapid heart become a flight nurse. Andy’s wife is a data manager
rate, and subsequent anticipatory anxiety when he for an insurance company. The two of them are con-
detects the onset of similar symptoms. Because the sidering adopting her cousin’s 2-year-old son (the

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

674
 Chapter 91 Chest Pain and Shortness of Breath (Panic Disorder)

cousin has been imprisoned on theft and drug pink. The oropharynx is moist, with no erythema
charges; the identity of the biological father is or exudate noted. His dental hygiene is good.
unknown). Andy reports being ambivalent about
this adoption because of financial concerns and his Neck Examination of the neck discloses no
fear that they would be “taking on someone else’s lymphadenopathy, thyromegaly, venous distention,
problems.” Andy is an ex-smoker (he quit 10 years or cervical bruits.
ago). Although he has drunk socially since college,
Andy reports that he has recently noticed he has been Lungs Andy appears to be slightly tachypneic, but
drinking more than usual (12 to 15 beers per day), in respirations are quiet and the lungs are clear to aus-
part to cope with his worries about his health. But he cultation bilaterally.
has wondered if the alcohol intake might actually be
contributing to his cardiac symptoms. As a result, in Abdomen The abdomen is soft, nontender, and
the past 2 weeks he has made largely unsuccessful nondistended. No masses or organomegaly is pres-
attempts to cut down. Andy’s last attempt to quit ent. Bowel sounds are normal.
began 2 days ago. He reports not having had a drink
for 48 hours. He denies symptoms of withdrawal. He Extremities No tenderness, weakness, muscle atro-
denies illegal drug use. phy, deformity, edema, ischemic changes, or cyanosis
is present.
Review of Systems
Andy reports some general muscle aches and weak- Laboratory Tests
ness of a couple of months’ duration, as well as A complete blood cell count, comprehensive meta-
fatigue. He denies cough, orthopnea, or paroxysmal bolic panel, erythrocyte sedimentation rate, thyroid-
nocturnal dyspnea. He reports occasionally having stimulating hormone level, and creatinine kinase
some epigastric pain after eating meals, but he does level are within normal limits. Fasting lipids are at
not identify any specific food intolerance and says he goal levels. A review of the tests he previously had
does not vomit. He denies nocturia or any other gen- obtained through his colleagues confirms that all
itourinary symptoms. He says he has no vision or results were normal.
hearing disturbance, vertigo, tinnitus, or ataxia. He
does describe some low back pain when he engages
Assessment
in activity involving lifting, bending, or twisting. The
review of systems is otherwise negative. Working Diagnosis
The working diagnoses for Andy’s presenting com-
Objective plaint are (1) panic attacks and (2) alcohol with-
drawal–induced anxiety.
Physical Examination
General Andy is a well-developed, well-nourished Differential Diagnosis
man. He appears somewhat agitated, trembling, and The patient in this case presents with symptoms con-
in some emotional distress. His speech is goal- sistent with panic attacks. However, the presence of
directed and well organized, but somewhat pres- panic attacks does not necessarily indicate a diagno-
sured. He is well oriented. His height is 6 feet 2 inches sis of panic disorder, since they are a commonly asso-
and his weight is 210 pounds (with a body mass ciated feature of several other disorders. Therefore,
index of 27). the clinician must differentiate between panic disor-
der and other entities.
Vital Signs His temperature 36.9˚C (98.4˚F), pulse is Panic attacks can result from certain medical con-
75 and regular, and respiratory rate is 25. His blood ditions (e.g., hyperthyroidism, cardiac arrhythmias),
pressure is 156/109 initially and 135/85 on repeat test- the ingestion of various central nervous system (CNS)
ing. Blood pressure and pulse readings remain stimulants (cocaine, caffeine), or the withdrawal from
unchanged on orthostatic testing. Pulse oximetry CNS depressants (alcohol, barbiturates). If the attacks
yields a value of 99%. occur only during the medical illness or substance
use/withdrawal, panic disorder is not diagnosed.
Head, Eyes, Ears, Nose, and Throat Andy’s head is Consequently, after the onset of panic attacks, all
normocephalic and without signs of trauma. patients should be evaluated by a physician to rule out
Extraocular movements are intact. Pupils are the presence of medical factors. As a result of consid-
equal, round, and reactive to light and accommo- erable discussion about panic disorder in the popular
dation. Funduscopic examination is normal. The media, increasing numbers of patients are self-diag-
external ears, canals, and tympanic membranes nosing and presenting directly to mental health
are normal bilaterally. Conversational hearing is professionals. Although this is beneficial in that
normal. The nose is normal. The conjunctivae are appropriate treatment can occur more quickly, the

675
 Chapter 91 Chest Pain and Shortness of Breath (Panic Disorder)

therapist now has the added responsibility of ensuring Although most people with panic disorder expe-
that all patients have been medically evaluated. rience some symptoms of depression, dysthymia is
Once organic causes are ruled out, panic disor- more common than major depression. If the panic
der must be differentiated from other DSM-IV dis- disorder remains untreated, however, the comorbid
orders that include panic attacks. In order to arrive at depression worsens over a lifetime because of the
an accurate diagnosis, it is necessary to understand debilitating effects of this anxiety disorder. Patients
the context and pattern of the symptoms. Panic with panic disorder and a current or past history of
attacks that occur in the context of panic disorder are major depression have a chronic course, more severe
not associated with a situational stimulus but instead symptoms, more frequent panic attacks, and more
appear to occur “out of the blue” (unexpected or extensive phobic avoidance.
uncued panic attacks). Those that almost always
occur on exposure to, or in anticipation of, a specific
Plan
stimulus are referred to as situationally bound (cued)
panic attacks. Panic attacks that are likely to occur on The plan for helping Andy manage his symptoms
exposure to a specific stimulus but are not invariably includes four recommendations. First, recommen-
associated with that stimulus are referred to as situa- dations for medication are made. The provider sug-
tionally predisposed panic attacks. Both of these types gests that a short course of a medication (e.g., a
of panic attacks are associated with other anxiety dis- benzodiazepine) might help to alleviate the most
orders. Patients who experience panic attacks only problematic physical symptoms. A selective sero-
when in uncomfortable social settings (social pho- tonin reuptake inhibitor (SSRI) is suggested for
bia), in response to trauma-associated stimuli (post- long-term management. Second, Andy is encour-
traumatic stress syndrome), in response to specific aged to consider cognitive-behavioral therapy and
stimuli (specific phobia), or as the object of obsessions stress management training. Third, he is counseled
and compulsions (obsessive-compulsive disorder) to slowly work back into an exercise regimen. Last,
should not be given a diagnosis of panic disorder. he is counseled on behavior change regarding his
Although patients with panic disorder may experience alcohol use.
situationally bound and situationally predisposed Andy’s initial response to reassurance about not
attacks following the development of agoraphobia being in a life-threatening situation is a mixture of
(e.g., a patient with panic disorder always experiences relief and disbelief. He states that he has been reas-
a panic attack when getting into an elevator), for the sured before and is glad to know it is not his heart,
diagnosis of panic disorder to be warranted, the initial but he asks about the possibility of having more
attacks had to have been unexpected. extensive or repeat testing done to make sure. When
It is possible for a person to have more than one he is told that further tests are not necessary except
disorder (that is, comorbid conditions). The major- to reassure him, he acknowledges that he gets very
ity of people with panic disorder do have a comorbid anxious about these issues. The provider then begins
disorder, usually an additional anxiety disorder or to discuss anxiety and the flight-or-fight response,
depression. A diagnosis of panic disorder does not and makes the recommendations about medications,
preclude the diagnosis of other anxiety disorders as cognitive-behavioral therapy, stress management,
well. Approximately 25% have generalized anxiety and exercise. The provider also asks more about
disorder and specific phobia. Slightly fewer have Andy’s alcohol use. Andy is judged to be in the action
social phobia. On the other hand, obsessive-compul- stage of readiness for change but lacks a cogent plan
sive disorder and post-traumatic stress disorder are for doing so. The provider commends Andy for his
infrequently diagnosed. The diagnosis of panic dis- decision to quit and recommends that he consider
order usually takes priority, but the other conditions regular attendance at Alcoholics Anonymous (AA)
need to be treated as well. meetings, rely on stress management and social sup-
One of the more common conditions occurring port, and take the medication as prescribed to treat
along with panic attacks and panic disorder is agora- the anxiety that seems to fuel his alcohol intake.
phobia. Specific or social phobias can be distin- Andy agrees to try the breathing exercise and to take
guished from agoraphobia by taking a careful the medication. He will consider the other recom-
history. If the avoidance of certain situations (e.g., mendations and come back in 1 week.
driving, flying, public transportation, enclosed
places) preceded the onset of the panic attacks, then
specific or social phobia is likely a more appropriate FOLLOW-UP VISITS
diagnosis. However, if the patient began having panic
attacks unexpectedly and subsequently began avoid- At his first follow-up visit, Andy reports that he has
ing those situations for fear of having another panic had another attack but that it wasn’t as serious as pre-
attack (anticipatory anxiety), then he or she should vious episodes. He has taken the medication as
be diagnosed with panic disorder with agoraphobia. prescribed and reports that it seems to help. He

676
 Chapter 91 Chest Pain and Shortness of Breath (Panic Disorder)

has not tried exercising because his symptoms have Psychiatric Association [APA], 2000● C ). Twice as
been triggered in the past by physical exertion. He has many women as men, beginning as early as in ado-
tried the breathing exercise a few times, but he does lescence, experience the debilitating effects of this
not think it helps. He went to AA with a friend from disorder. Many of these individuals are likely to seek
work, but he didn’t like the atmosphere. He is not help from physicians in a variety of settings, most
sure he needs the meetings and would prefer a meet- notably the ED and outpatient primary care clinics.
ing where there was less religious talk. During this In fact, they are more likely than patients with
conversation he appears more receptive to the idea of depression to visit a physician for help (Kessler et al.,
cognitive-behavioral psychotherapy, so a referral is 1999● B ). Panic disorder is one of the more distressing
made. He is also given a handout on the management mental health problems experienced by patients vis-
of panic disorder, including the role of stress manage- iting primary care physicians. As many as 80% of pri-
ment and exercise. The provider recommends that mary care patients with this disorder present with
Andy consider starting a slow build-up to a regular alarming physical symptoms such as chest pain,
aerobic exercise program. An appointment is made dyspnea, and tachycardia (Roy-Byrne et al., 2002● B ).
for another follow-up visit in 2 weeks. Panic attacks can be so distressing that a significant
At the 2-week follow-up visit, Andy reports that number of people become suicidal.
he drank on two occasions. He states that he felt ini- According to the American Psychiatric
tially better but later felt worse. As a result, he went Association’s Diagnostic and Statistical Manual of
back to AA (a different meeting) and made an Mental Disorders—Fourth Edition, the defining
appointment with the counselor. His next meeting is characteristic of panic disorder is recurrent, unex-
in 2 days. A release for exchange of information is pected panic attacks. Panic attacks can occur several
signed by Andy so that the provider may discuss the times a day or only a few times during a year.
treatment plan with the cognitive-behavioral thera- A panic attack is defined as a discrete period of
pist. Andy and his wife both read the handout on intense fear or discomfort that develops abruptly
panic disorder management. He believes the diag- and reaches a peak within 10 minutes and is accom-
nosis fits him very well, so he is encouraged to con- panied by at least four of the following 13 somatic
tinue with this treatment plan. He reports not and cognitive symptoms: shortness of breath, dizzi-
having any more symptoms and is overall a bit ness, palpitations, trembling, sweating, feeling
calmer, which supports the likelihood of with- of choking, nausea/abdominal distress, depersonal-
drawal. He is reluctant to stop the short-term med- ization, paresthesias (numbness/tingling), flushes/
ication altogether, so it is agreed that he will cut the chills, chest pain, fear of dying, and fear of going
dose in half for the next 2 weeks. Further education crazy or fear of doing something uncontrolled. An
about the different roles of benzodiazepines and individual must experience at least two unexpected
SSRIs is provided. panic attacks followed by at least 1 month of con-
At a follow-up appointment 2 weeks later, Andy cern about having another panic attack in order to
reports that he has begun feeling better and did not be diagnosed with panic disorder (APA, 2000● C ).
use the benzodiazepine on several different days. He Panic disorder may or may not be accompanied by
has discontinued attending AA meetings but has agoraphobia, or the experience of anxiety in situa-
decided the counseling will work well for him, espe- tions in which escape might be difficult or where
cially since his wife agreed to the therapist’s request help may not be immediately available in the event
that she attend as well (in order to become educated of the occurrence of a panic attack (e.g., on air-
about the issues, provide support and accountability, planes, buses, trains, or elevators; being alone; being
and address marital and family issues that have been in a crowd of people) (Sanderson and Rego,
contributing to Andy’s stress). It is agreed that Andy 2002● B ).
can rely on the stress management, support, and Andy presents with the classic symptoms of panic
cognitive-behavioral therapy to handle day-to-day attacks. After obtaining a detailed history, it is clear
pressures at this point. The benzodiazepine is dis- that Andy is also experiencing comorbid problems as
continued. He agrees to take the SSRI regularly. He a result of alcohol abuse. Both need to be treated
has remained abstinent from alcohol. The provider aggressively, since the outcome for each is poor if
and Andy agree to follow up in 3 months, or sooner untreated; in addition, they exacerbate each other.
if needed.

DISCUSSION Material Available on Student Consult

Review Questions and Answers about Panic
Millions of people throughout the world experi- Disorder
ence panic disorder in their lifetime (American

677
 Chapter 92 Bizarre Behavior (Schizophrenia)

REFERENCES
American Psychiatric Association, Committee on Nomen- Roy-Byrne P, Russo J, Dugdale DC, Lessler D, Cowley D,
clature and Statistics. Diagnostic and Statistical Manual Katon W. Under-treatment of panic disorder in pri-
of Mental Disorders, 4th ed., Text Revision. Washington, mary care: Role of patient and physician characteristics.
DC, American Psychiatric Association, 2000.● C J Am Board Fam Pract 2002;15:443–450.● B
Kessler RC, Zhao S, Katz SJ, et al. Past-year use of outpa- Sanderson WC, Rego SA. Empirically supported psycho-
tient services for psychiatric problems in the National logical treatment of panic disorder and agoraphobia.
Comorbidity Survey. Am J Psychiatry 1999;156: Psychiatry MedPulse, 2002. Available at www.med-
115–123.● B scape.com/psychiatryhome. Accessed 3/1/2005.● B

C h a p t e r

92 Bizarre Behavior (Schizophrenia)

Leslie Brott

Present Illness
KEY POINTS Juan’s father reports that Juan has not been acting
normally for the last 6 to 8 months. Over the last
1. Schizophrenia is a psychotic disorder with an 4-week period, his bizarre behavior has intensified.
onset usually during adolescence or early adult- Juan has not been talking much unless he is asked a
hood. question. He sits much of the time, doing nothing.
2. Cognitive impairment is a key element in the Often he seems to smile or laugh for no particular rea-
course of schizophrenia. son. His parents have been concerned about his depres-
3. Diagnosis of schizophrenia involves ruling out a sion for months and have considered taking him to a
general medical condition or substance abuse counselor. His father has been taking Juan to work with
that could cause the symptoms. him, as he is concerned about leaving Juan home alone.
4. A psychiatrist’s assistance in the management Matters worsened acutely 3 weeks ago when Juan left
of schizophrenia is invaluable. home alone for several hours. On his return he was
5. Treatment of schizophrenia includes antipsy- behaving strangely, speaking incoherently, and acting
chotic medications, life-skills training, and fam- confused. His parents were concerned that he might
ily education and support. have hit his head. They noticed no seizure activity or
abnormal movements. Juan’s father does not believe
that alcohol or drugs are an issue, and Juan denies any
use of them. Juan initially denies auditory or visual hal-
INITIAL VISIT lucinations or feelings of depression or anxiety.

Subjective Medical History

The patient’s history is unremarkable except for
Patient Identification and Presenting episodes of gastroesophageal reflux disease.
Problem
Juan A. is a 19-year-old man first seen with his father, Family History
who is concerned about Juan’s abnormal behavior Juan’s parents and siblings are alive and well. No
and the possibility of a head injury. family history of mental illness is known.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

678
 Chapter 92 Bizarre Behavior (Schizophrenia)

REFERENCES
American Psychiatric Association, Committee on Nomen- Roy-Byrne P, Russo J, Dugdale DC, Lessler D, Cowley D,
clature and Statistics. Diagnostic and Statistical Manual Katon W. Under-treatment of panic disorder in pri-
of Mental Disorders, 4th ed., Text Revision. Washington, mary care: Role of patient and physician characteristics.
DC, American Psychiatric Association, 2000.● C J Am Board Fam Pract 2002;15:443–450.● B
Kessler RC, Zhao S, Katz SJ, et al. Past-year use of outpa- Sanderson WC, Rego SA. Empirically supported psycho-
tient services for psychiatric problems in the National logical treatment of panic disorder and agoraphobia.
Comorbidity Survey. Am J Psychiatry 1999;156: Psychiatry MedPulse, 2002. Available at www.med-
115–123.● B scape.com/psychiatryhome. Accessed 3/1/2005.● B

C h a p t e r

92 Bizarre Behavior (Schizophrenia)

Leslie Brott

Present Illness
KEY POINTS Juan’s father reports that Juan has not been acting
normally for the last 6 to 8 months. Over the last
1. Schizophrenia is a psychotic disorder with an 4-week period, his bizarre behavior has intensified.
onset usually during adolescence or early adult- Juan has not been talking much unless he is asked a
hood. question. He sits much of the time, doing nothing.
2. Cognitive impairment is a key element in the Often he seems to smile or laugh for no particular rea-
course of schizophrenia. son. His parents have been concerned about his depres-
3. Diagnosis of schizophrenia involves ruling out a sion for months and have considered taking him to a
general medical condition or substance abuse counselor. His father has been taking Juan to work with
that could cause the symptoms. him, as he is concerned about leaving Juan home alone.
4. A psychiatrist’s assistance in the management Matters worsened acutely 3 weeks ago when Juan left
of schizophrenia is invaluable. home alone for several hours. On his return he was
5. Treatment of schizophrenia includes antipsy- behaving strangely, speaking incoherently, and acting
chotic medications, life-skills training, and fam- confused. His parents were concerned that he might
ily education and support. have hit his head. They noticed no seizure activity or
abnormal movements. Juan’s father does not believe
that alcohol or drugs are an issue, and Juan denies any
use of them. Juan initially denies auditory or visual hal-
INITIAL VISIT lucinations or feelings of depression or anxiety.

Subjective Medical History

The patient’s history is unremarkable except for
Patient Identification and Presenting episodes of gastroesophageal reflux disease.
Problem
Juan A. is a 19-year-old man first seen with his father, Family History
who is concerned about Juan’s abnormal behavior Juan’s parents and siblings are alive and well. No
and the possibility of a head injury. family history of mental illness is known.

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

678
 Chapter 92 Bizarre Behavior (Schizophrenia)

Social History neously. Questions are answered with brief one-word

Juan lives with his parents, two younger brothers, and answers, if at all. He does not maintain any eye contact.
one younger sister. He dropped out of high school last He is oriented to the day, date, month, year, and place,
year, before graduation. He has never held a job. He but he declines to answer a question about why he is in
denies use of tobacco, alcohol, or illicit drugs. the clinic today. He is able to subtract serial 7s. He will
not answer questions regarding judgment (i.e., What
Review of Systems would you do if you found a sealed, stamped envelope on
Juan has had no recent fevers, chills, fatigue, or the sidewalk?) and abstraction (i.e., What does the
malaise. His weight has not significantly changed in phrase “People who live in glass houses should not thrown
the last 6 months. He experiences epigastric and stones” mean?). On persistent questioning, Juan admits
chest pain occasionally, and his symptoms are to hearing voices. Sometimes he thinks the voices are
relieved with antacids. He denies palpitations, coming from the television in his house, but at other
shortness of breath, and dyspnea on exertion. No times he senses the voices are inside his head. He can-
nausea, vomiting, diarrhea, or constipation has not associate the voices with anyone he knows and
occurred. often cannot understand what they are saying. He
denies visual hallucinations.
Objective
Assessment
Physical Examination
Vital Signs Working Diagnosis
Blood pressure, 128/88 Juan is diagnosed with a psychotic disorder, as evi-
Heart rate, 95 denced by his hallucinations and disorganized speech
Temperature, 36.4˚C (97.6˚F) and behavior. His symptoms are consistent with dis-
Respiratory rate, 18 orders in the schizophrenia spectrum, including
Weight, 177 pounds schizophrenia and schizophreniform disorder.
Schizophrenia is defined by positive and negative
General Patient is a well-developed, slightly symptoms as well as social and occupational dysfunc-
disheveled young man in no acute distress. tion. The positive symptoms include those that are
classified as psychotic: delusions and hallucinations.
Head, Eyes, Ears, Nose, and Throat Normocephalic, Delusions are defined as thoughts that are completely
no evidence of trauma. Pupils are equal, round, and disconnected from reality. In schizophrenia, the delu-
reactive to light. Extraocular muscles intact. No sions may be paranoid, grandiose, or persecutory. The
nystagmus. Fundoscopic examination is normal. hallucinations in schizophrenia are most commonly
Tympanic membranes and oropharynx are within auditory but occasionally can be visual or olfactory.
normal limits. Disorganized speech and grossly disorganized or cata-
tonic behavior are other positive symptoms identified
Neck Supple, no lymphadenopathy or thyromegaly. in schizophrenics. The untreated schizophrenic
patient has difficulty holding a normal conversation
Heart Regular rate and rhythm, no murmurs. and has trouble making sense of everyday input.
Negative symptoms are those of apathy, avoli-
Lungs Clear. tion, and social withdrawal. Schizophrenic patients
have a flat affect and have trouble expressing emo-
Abdomen Normal bowel sounds, no hepatos- tions. They lack the motivation to initiate and com-
plenomegaly. plete everyday tasks, including self-care duties. As a
result, they often demonstrate social withdrawal and
Extremities No clubbing, cyanosis, or edema. isolation.
For a diagnosis of schizophrenia, a patient must
Neurologic Cranial nerves II to XII intact. Brachial have positive or negative symptoms with evidence of
and patellar reflexes are brisk and symmetrical. functional decline for at least 6 months. In those
Upper and lower extremity strength is grossly sym- 6 months, the patient must exhibit two or more posi-
metrical. Gait is within normal limits. Romberg is tive symptoms for at least 1 month. Only one positive
negative. No pronator drift. symptom is needed for the diagnosis if the delusions
are bizarre or if the auditory hallucinations include
Psychiatric Juan appears his stated age. He is dressed in two or more voices or one voice making a running
faded jeans and a torn T-shirt. He sits quietly making commentary. The patient’s symptoms must not be
exaggerated facial expressions. He smiles and laughs due to a medical condition or to drug or alcohol use.
for no particular reason, and he appears to be attend- An associated mood disorder may be included in the
ing to internal stimuli. He does not speak sponta- diagnosis of schizophrenia.

679
 Chapter 92 Bizarre Behavior (Schizophrenia)

If an individual has symptoms as described for Obsessive-compulsive disorder. Classified as an anxi-

schizophrenia but has had them for less than ety disorder, obsessive-compulsive disorder
6 months, then a diagnosis of schizophreniform dis- (OCD) is characterized by delusions. Patients with
order is made. Individuals with schizophreniform OCD have persistent and recurrent thoughts that
disorder do not exhibit the marked social and occu- cause distress or dysfunction in their lives. They
pational dysfunction, likely because of the brief perform repetitive behaviors in response to their
period of symptoms. Schizophreniform patients obsessive thoughts. These patients have insight
have a complete remission of symptoms, without the into their disorder; however, they recognize that
benefit of medication, before 6 months. If the symp- their thoughts are irrational. Their behaviors,
toms persist beyond 6 months, a diagnosis of schizo- however, may mimic the disorganized behavior
phrenia may be made. found in schizophrenics. Interestingly, a large per-
Juan exhibits symptoms consistent with schizo- centage of patients with schizophrenia exhibit
phrenia. His social dysfunction has lasted more than obsessive-compulsive behaviors. A significant
6 months. His positive symptoms––hallucinations number of patients initially diagnosed with OCD
and disorganized behavior and speech—have lasted will later have a psychotic decompensation and
for at least 1 month. He has no underlying medical meet criteria for schizophrenia.
condition or substance abuse that would better Alcoholic hallucinosis. Patients with an addiction to
explain his symptoms. alcohol can develop psychotic symptoms, espe-
cially paranoid delusions, which mimic symptoms
Differential Diagnosis of schizophrenia. Schizophrenic patients likewise
Psychosis, a loss of contact with reality, occurs in sev- may have a dependence on alcohol. Distinguishing
eral mental conditions. The following are the most the two can be problematic unless the full history
common conditions, in addition to the schizophre- of a patient is known. Schizophrenic individuals
nia spectrum, considered in the workup of psychosis. will exhibit psychosis before, or early in, the devel-
Some argue that the various disorders lie on a con- opment of alcohol abuse. Differentiation also can
tinuum of mental disease and that diagnoses overlap. be made when abstinence occurs. If the delusions
Nevertheless, the differential diagnoses are listed as resolve after 6 months of abstinence, then alco-
outlined in the Diagnostic and Statistical Manual of holic hallucinosis is the diagnosis.
Mental Disorders, 4th edition (DSM-IV). Delusional disorder. Some patients have delusions
that are not bizarre. Their delusions are plausible
Schizoaffective disorder. Some patients meet the crite- but without any basis in reality. If such nonbizarre
ria for schizophrenia but also meet criteria for a delusions last for at least 1 month, the other crite-
mood disorder such as major depressive disorder ria for schizophrenia are not met, and the patient
or generalized anxiety disorder. In this case, a is able to function, a diagnosis of delusional disor-
diagnosis of schizoaffective disorder is assigned, der is made.
and patients are treated for both disorders.
Schizotypal personality disorder. This disorder is an
Plan
axis II diagnosis with characteristics similar to
those of schizophrenia but without hallucinations Diagnostic
or delusions. Schizotypal patients exhibit social To confirm that no medical condition or substance
detachment and isolation. They are often socially use better explains Juan’s symptoms, laboratory and
inept and prefer to be alone. Unlike schizophren- radiologic studies are performed. A complete meta-
ics, they do not exhibit chronic psychosis, and bolic panel and complete blood count, as well as thy-
their clinical course is stable over time. roid studies and a urine drug screen, are performed.
Bipolar disorder. Recurrent episodes of depression and A head computed tomography (CT) is performed as
mania with intervening periods of euthymia charac- well. The results of all studies are normal.
terize bipolar disorder. In the throes of a depressive
or manic period, patients may have hallucinations or Therapeutic
delusions. It can be differentiated from schizophre- Once the results of laboratory and radiologic studies
nia by the presence of psychosis which occurs only are obtained, Juan and his parents return to the
in the setting of depression or mania. Usually the clinic. Juan is started on an atypical antipsychotic at
depressive or manic symptoms will precede the a low dose: risperidone (Risperdal), 1 mg nightly. He
onset of psychotic behavior. Delusions, if present, are is referred to the county health department’s psychi-
mood congruent in bipolar disorder, whereas in atrist for further evaluation and treatment.
schizophrenia, the delusions tend to be unrelated to
mood. In any event, at the time of the manic or Patient Education
depressive exacerbation, it may be very difficult to The patient and his parents are informed that schiz-
distinguish bipolar disorder from schizophrenia. ophrenia is a chronic condition that requires lifelong

680
 Chapter 92 Bizarre Behavior (Schizophrenia)

care. Literature describing the disorder is given to the The acute phase is characterized by the onset of
family. The need for family education and support is psychotic symptoms. The positive symptoms of delu-
emphasized. sions, hallucinations, and bizarre, disorganized behav-
ior become evident. It is at this point that the
Disposition diagnosis of schizophrenia is established. This is fol-
An appointment is made with the psychiatrist, and lowed by the recovery phase in which the positive
chart notes and evaluation results are forwarded. symptoms begin to wane, but the disorganization and
Juan’s parents are informed of the signs of acute confusion continue. A residual phase ensues, in which
decompensation and are directed to take Juan to the the negative symptoms of schizophrenia predominate.
local emergency department should they occur. Schizophrenia can be divided into four sub-
types, with the prognosis affected by the subtype.
The subtypes are characterized as paranoid, cata-
DISCUSSION tonic, disorganized, or simple. Patients who do not
fit into any category are characterized as undifferen-
Demographics tiated. Paranoid and catatonic subtypes tend to
demonstrate a fluctuating course throughout their
Schizophrenia has a 1% lifetime prevalence. The lifetimes, whereas disorganized and simple subtypes
onset in male patients is earlier than that in female tend to be more chronic.
patients, but overall an even sex distribution is One marked feature of schizophrenia, regardless
found. Its onset is usually in adolescence or early of subtype, is cognitive impairment. Cognitive deficits
adulthood but can range from ages 13 to 40. persist throughout the phases of schizophrenia. They
are evident both during and after psychotic episodes
Etiology and are progressive throughout the schizophrenic’s
lifetime. The specific cognitive deficits include impair-
Clearly a genetic component to schizophrenia exists. ment in working memory (ability to remember infor-
Studies of monozygotic twins demonstrate a 50% mation for a short time and then use it to perform a
concordance rate. Those individuals with a first- task), executive function (ability to plan actions, prob-
degree family member with schizophrenia have a 5% lem solve), attention and information processing,
prevalence rate of schizophrenia versus the 1% for long-term memory, and ability to learn.
the general population. Although it is known that
schizophrenia has a strong genetic component, it has
Diagnosis and Treatment
not yet been linked to a specific gene.
In addition to the strong genetic component, No diagnostic test will confirm the diagnosis of
environmental factors play a role in the development schizophrenia. The workup essentially serves to rule
of schizophrenia. Schizophrenia is thought to be a out medical conditions or substance use as the
neurodevelopmental disorder characterized by defec- cause of symptoms. The history and physical exam-
tive neuronal migration. This is evidenced by the fact ination should guide the workup. Basic laboratory
that patients with schizophrenia have cortical atrophy studies should include complete blood count,
and dilated ventricles on brain CT and magnetic res- serum chemistries, thyroid function, urinalysis, and
onance imaging at the onset of the disease. The defec- drug and alcohol screens. Imaging studies and elec-
tive neuronal migration is postulated to have been troencephalograms should be ordered as needed
caused by either obstetrical/birth trauma or by an in based on the history and physical.
utero viral infection. Evidence for the latter lies in the A psychiatrist’s assistance with the diagnosis
preponderance of winter births among schizophren- and treatment of schizophrenia is extremely help-
ics. In any event, it is clear that both genetic and envi- ful. The treatment of schizophrenia includes anti-
ronmental forces are at work in the development of psychotic medications, psychotherapy, and social
schizophrenia. skills training. Patients may be initially hospital-
ized, especially if their psychosis creates a danger-
Natural History ous environment for themselves or others. Those
with severe delusions or hallucinations, those who
Although schizophrenia can have an insidious or cannot take care of themselves, and those who are
acute onset, four phases have been identified. A pro- suicidal warrant inpatient hospitalization. Some
dromal period usually precedes the development of patients may be repeatedly hospitalized throughout
active disease. During this period, patients demon- their lives, whereas others may be managed well at
strate unusual behaviors, social withdrawal, and a home or in group or foster home settings.
generalized decline in function. Individuals will Antipsychotic medications are a mainstay of
experience failure in academic and occupational schizophrenia treatment. Medication is started dur-
endeavors. ing the acute phase to curb the psychosis and then

681
 Chapter 92 Bizarre Behavior (Schizophrenia)

mitter systems, whereas the typical antipsychotics are

Table 92-1 Antipsychotic Medications purely dopamine antagonists (Table 92-2).
Typical Atypical Once the pharmacotherapy has been estab-
lished, therapy turns to cognitive-behavioral
Chlorpromazine Aripiprazole (Abilify) treatment for the patient and supportive therapy for
(Thorazine) the patient’s family. Schizophrenics benefit from
Fluphenzine (Prolixin) Clozapine (Clozaril)
Haloperidol (Haldol) Olanzapine (Zyprexa)
social-skills training, including self-care and inde-
Perphenazine (Trilafon) Quetiapine (Seroquel) pendent-living skills. Insight-based psychotherapy is
Thioridazine (Mellaril) Risperidone (Risperdal) contraindicated in these patients as it can exacerbate
Thiothixene (Navane) Ziprasidone (Geodon) their illness. Family therapy includes instruction in
Trifluoperazine the course of the disease, its treatment, and realistic
(Stelazine) expectations for the patient’s future. Family support
groups can provide much of this information. It has
been shown that family intervention results in
continued as maintenance therapy. The medications reduced relapse rates for the schizophrenic as well as
are divided into older “typical” antipsychotics and the improved well-being in the family.
newer “atypical” ones (Table 92-1). The older, typical
antipsychotics include haloperidol, chlorpromazine, Prognosis
and fluphenazine. These agents tend to be much less
expensive than the newer drugs. Haloperidol and Schizophrenia is a lifelong condition for the majority
fluphenazine are uniquely available in injectable, of patients. Complete remission does occur, but this
long-acting formulations. A high potential exists for is unusual. Although the positive and negative symp-
extrapyramidal side effects including dystonia, toms can be moderately controlled with medication,
akathisia, and parkinsonism with the older medica- it is the ongoing cognitive and functional impair-
tions, especially haloperidol. ment that debilitates the schizophrenic. Only 10%
The newer atypical antipsychotics tend to have are employed on a full-time basis, and only 20%
fewer extrapyramidal side effects than the older succeed with part-time employment. Meaningful
medications. They are as effective for positive symp- interpersonal relationships are rare.
toms and perhaps better for negative symptoms than
their older counterparts. The newer medications
include clozapine, risperidone, olanzapine, quetiap-
ine, ziprasidone, and aripiprazole. These agents Material Available on Student Consult
antagonize the dopamine and serotonin neurotrans- Review Questions and Answers about Schizo-
phrenia

Table 92-2 Common Side Effects of Antipsychotic Medications

Side Effect Characteristics Associated Medications

Extrapyramidal side effects Dystonia (muscle spasms), Predominantly typical

akathisia (restless, jittery), antipsychotics but can occur
parkinsonism (tremors, with any
bradykinesia)
Tardive dyskinesia Writhing movements of hands, Predominantly typical
mouth and tongue. Associated antipsychotics
with long-term use of medication
Anticholinergic symptoms Dry mouth, blurred vision, urinary Low-potency typical
retention, constipation, confusion antipsychotics
Neuroleptic malignant Hyperthermia, catatonic rigidity, All antipsychotics, predominantly
syndrome unstable blood pressure, dyspnea. typical antipsychotics
Mortality rate ≤ 20%
Galactorrhea Elevated prolactin Atypical antipsychotics
Agranulocytosis Severe leukocytopenia Clozapine
Diabetes mellitus Elevated fasting blood glucose Atypical antipsychotics
levels
Weight gain Associated with development of Atypical antipsychotics
diabetes and hyperlipidemia
Cardiac dysrhythmia Prolonged QT Atypical antipsychotics

682
 Chapter 93 Cold and Numb Hands and Feet (Frostbite)

SUGGESTED READINGS
Adler CM, Strakowski SM. Boundaries of schizophrenia. Lehman AF, Buchanan RW, Dickerson FB, et al. Evidence-
Psychiatr Clin North Am 2003;26:1–23. based treatment for schizophrenia. Psychiatr Clin
American Academy of Child and Adolescent Psychiatry. North Am 2003;26:939–954.
Practice parameter for the assessment and treatment of Moore DP, Jefferson JW. Schizophrenia: Handbook of
children and adolescents with schizophrenia. J Am Medical Psychiatry, 2nd ed. St. Louis, Mosby, 2004, pp
Acad Child Adolesc Psychiatry 2001;20:4S–23S.● C 115–124.
American Psychiatric Association. Diagnostic and Statistical Expert consensus treatment guidelines for schizophrenia:
Manual of Mental Disorders, 4th ed. Washington, DC, A guide for patients and families. J Clin Psychiatry
American Psychiatric Association, 1994.●
C 1996;57(Suppl 12B):51–58.
Flashman LA, Green MF. Review of cognition and brain
structure in schizophrenia: Profiles, longitudinal
course, and effects of treatment. Psychiatr Clin North
Am 2004;27:1–18.

C h a p t e r

93 Cold and Numb Hands and Feet

(Frostbite)
Stephen G. Cook

INITIAL VISIT
KEY POINTS
Subjective
1. Frostbite is the result of actual freezing of
tissue. Patient Identification and Presenting
2. Exposure to cold (such as through winter out- Problem
door activities or homelessness) and decreased Joe C. is a 19-year-old college student brought to the
awareness of cold and numbness (due to alco- emergency department with hands and feet that are
hol, drugs, or psychiatric illness) are the main cold, white, and numb.
factors contributing to frostbite.
3. Frostbitten tissue is extremely fragile and should Present Illness
never be rubbed in an attempt to thaw it. Joe was attending a late November college football
4. Careful tissue rewarming in warm water slightly game with his friends. Despite the weather forecast
above body temperature is the mainstay of ini- predicting snow, they wore body and face paint and
tial therapy. no shirts during the game. Joe’s friends say they kept
5. Recovery typically is quite prolonged. Surgery, warm by drinking vodka from a large wineskin; they
especially amputation, should be delayed until it had also had “a bunch” of beer before going to the
becomes absolutely necessary. game. As the sun dropped in the late afternoon, Joe
began to say that his hands felt funny. His friends

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

683
 Chapter 93 Cold and Numb Hands and Feet (Frostbite)

SUGGESTED READINGS
Adler CM, Strakowski SM. Boundaries of schizophrenia. Lehman AF, Buchanan RW, Dickerson FB, et al. Evidence-
Psychiatr Clin North Am 2003;26:1–23. based treatment for schizophrenia. Psychiatr Clin
American Academy of Child and Adolescent Psychiatry. North Am 2003;26:939–954.
Practice parameter for the assessment and treatment of Moore DP, Jefferson JW. Schizophrenia: Handbook of
children and adolescents with schizophrenia. J Am Medical Psychiatry, 2nd ed. St. Louis, Mosby, 2004, pp
Acad Child Adolesc Psychiatry 2001;20:4S–23S.● C 115–124.
American Psychiatric Association. Diagnostic and Statistical Expert consensus treatment guidelines for schizophrenia:
Manual of Mental Disorders, 4th ed. Washington, DC, A guide for patients and families. J Clin Psychiatry
American Psychiatric Association, 1994.●
C 1996;57(Suppl 12B):51–58.
Flashman LA, Green MF. Review of cognition and brain
structure in schizophrenia: Profiles, longitudinal
course, and effects of treatment. Psychiatr Clin North
Am 2004;27:1–18.

C h a p t e r

93 Cold and Numb Hands and Feet

(Frostbite)
Stephen G. Cook

INITIAL VISIT
KEY POINTS
Subjective
1. Frostbite is the result of actual freezing of
tissue. Patient Identification and Presenting
2. Exposure to cold (such as through winter out- Problem
door activities or homelessness) and decreased Joe C. is a 19-year-old college student brought to the
awareness of cold and numbness (due to alco- emergency department with hands and feet that are
hol, drugs, or psychiatric illness) are the main cold, white, and numb.
factors contributing to frostbite.
3. Frostbitten tissue is extremely fragile and should Present Illness
never be rubbed in an attempt to thaw it. Joe was attending a late November college football
4. Careful tissue rewarming in warm water slightly game with his friends. Despite the weather forecast
above body temperature is the mainstay of ini- predicting snow, they wore body and face paint and
tial therapy. no shirts during the game. Joe’s friends say they kept
5. Recovery typically is quite prolonged. Surgery, warm by drinking vodka from a large wineskin; they
especially amputation, should be delayed until it had also had “a bunch” of beer before going to the
becomes absolutely necessary. game. As the sun dropped in the late afternoon, Joe
began to say that his hands felt funny. His friends

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

683
 Chapter 93 Cold and Numb Hands and Feet (Frostbite)

noticed that he became clumsier and was unable to are very cold to the touch. Tympanic membranes are
open a bag of peanuts or get money out of his unremarkable. Oral mucous membranes are dry.
pocket. His friends thought his clumsiness was due
to Joe’s being drunk, and they all stayed at the game Neck No masses or adenopathy is noted.
until the end. After they returned home, Joe’s friends
noted that his hands remained very white and cold. Lungs The lungs are clear to auscultation bilaterally.
When he complained that he still could not feel any-
thing in his hands or his feet, they brought him to the Heart The heart exhibits a bradycardic regular
school’s health center. rhythm without a murmur.

Medical History Abdomen Bowel tones are absent. No tenderness or

Joe was treated 1 year ago for a broken wrist sus- masses are noted.
tained when he fell from a fraternity porch during a
party; his blood alcohol level at the time was 0.29. He Neurologic There is decreased sensation to pin-
has no history of chronic illness and is taking no prick, light touch, and vibration below the ankles
medications. His immunizations are all up to date, and in the hands. Patellar and ankle jerk reflexes are
according to college health service records. He has no absent. Romberg’s sign cannot be tested for, as Joe is
history of prior cold exposure injury. unable to stand without assistance.

Family History Assessment

Joe’s father is 48 and is a recovering alcoholic; he has
hypertension and hypercholesterolemia. Joe’s mother Working Diagnosis
is in excellent health at age 45. He has two younger Frostbite is injury due to the actual freezing of tis-
siblings who have no health problems. sues. The condition was historically seen mainly in
soldiers but has become more common in recent
Social History years as winter sports and outdoor activities have
Joe is a C student in his sophomore year at the col- become more popular and as an increasing number
lege. His friends report that he “parties hard” at least of people become homeless (Murphy et al., 2000● B ).

3 days per week. He smokes tobacco, one-half pack Generally, frostbite occurs at temperatures from –4˚C
per day, and occasionally uses marijuana, but denies to –10˚C (25˚F to 14˚F) or lower. Wind, decreased
other illicit drug use. mobility, venous stasis, malnutrition, and occlusive
arterial disease all increase the risk for frostbite
(Tierney et al., 2004● B ). Lack of awareness of cold
Review of Systems
exposure contributes significantly to cold injury.
There are no recent acute illnesses. He reports no
Psychiatric illness is quite common among frostbite
pain in his hands and feet, only numbness.
victims, with prevalences estimated as high as 61%
to 65%. Alcohol use is also highly correlated with
Objective frostbite (Murphy et al., 2000● B). Alcohol decreases a
person’s awareness of cold and numbness, thus lead-
Physical Examination ing to prolonged exposure. Alcohol also inhibits
General Joe appears very drowsy on the gurney heat generation through shivering and can acceler-
and smells strongly of alcohol, but he opens his eyes ate heat loss due to its vasodilatory effects (Biem
in response to voice command and gives simple et al., 2003●B). Nicotine use exacerbates peripheral
answers to questions. vasoconstriction and may worsen tissue injury. It
may also be associated with preexisting peripheral
Vital Signs His temperature (measured rectally) is vascular disease. Patients with peripheral neuro-
32˚C (89.6˚F), blood pressure is 92/50, pulse is 48, pathy from diabetes or other causes are at increased
and respiratory rate is 10. Weight and height are risk for frostbite injury owing to their decreased
reported at 195 pounds and 71 inches, respectively, ability to sense cold, particularly in the extremities,
but Joe is unable to stand on the scale. where frostbite is most likely to occur (Murphy
et al., 2000● B ). Hypothyroidism, adrenal insuffi-
Skin Green paint is noted on Joe’s face, chest, and ciency, hypoglycemia, and central nervous system
upper arms, but his forearms and hands are white, abnormalities also may predispose to frostbite
cold, and pulseless. When his wet shoes are removed, (Biem et al., 2003● B ).
his feet are also white, cold, and pulseless. Frostbite occurs when skin is exposed to sub-
freezing temperatures for time sufficient to allow ice
Head, Eyes, Ears, Nose, and Throat The tip of the crystals to form within tissue. Extracellular ice crys-
nose and both earlobes appear waxy and white and tals form initially, damaging the cell membrane,

684
 Chapter 93 Cold and Numb Hands and Feet (Frostbite)

changing its permeability, and leading to intracellu- ing, liquid. Temperatures from 0˚C to 10˚C (32˚F to
lar dehydration and dramatic changes in cell elec- 50˚F) are typically enough to cause immersion syn-
trolyte concentrations. With longer exposure and drome; damp exposure as mild as 12.8˚C (55˚F) for
further cooling, intracellular ice forms; as these ice 10 hours has been sufficient to cause this disorder.
crystals expand, they cause mechanical destruction Typical stages in immersion syndrome can include:
of cells (Murphy et al., 2000● B ). Rewarming and
thawing of ice crystals leads to further damage due to 1. A prehyperemic stage, characterized by cold and
cellular and tissue edema, red cell and platelet aggre- numbness without pain
gation, thrombosis, and skin bleb formation. Tissue 2. A hyperemic stage with intense burning and
death is caused by ischemia and thrombosis of shooting pains
smaller vessels, as well as by actual freezing of tissue 3. A posthyperemic stage with pallor or cyanosis
at the cellular level. Tissue injury is worst when cool- and decreased pulsations
ing is slow, cold exposure is lengthy, rewarming is
prolonged, and especially when tissue is thawed and Immersion syndrome can present with a wide
then refreezes (Mechem, 2005● B ). variety of visible changes, including blistering,
The severity of frostbite injury generally corre- swelling, redness, heat, ecchymosis, hemorrhage,
lates more with the duration of cold exposure than necrosis, and gangrene (Tierney et al., 2004● B).
with the temperature to which skin is exposed. Though some of these skin changes may be apparent
Although skin freezes more quickly at lower tempera- at presentation, as with frostbite, the degree of tissue
tures, once frozen, it is the length of time the tissue necrosis may take weeks or months to fully assess.
remains frozen that determines the degree of irre- Peripheral vascular disease can lead to absent
versible damage. Hands and feet account for 90% of pulses and a cool or cold extremity, but it is unlikely
all injuries. Other commonly involved sites include the to be of rapid onset with a symmetric distribution.
ears, nose, cheeks, and penis (Murphy et al., 2000● B ). Other systemic illnesses, including diabetes and
Like burns, frostbite can be classified by degree. other causes of neuropathy, may exacerbate the
First-degree injury may manifest with hard white problems caused by frostbite but would be unlikely
plaques on waxy-looking skin, along with some early to present with the acute changes seen in this case.
sensory deficits. Progressively deeper levels of freez-
ing lead to worsening symptoms, including paresthe- Plan
sia and stiffness; the skin becomes increasingly white
or yellowish, inelastic, and immobile. In second- Diagnostic
degree frostbite, clear blisters form that are typically Although the full extent of freezing injury is often
high in thromboxane; many experts advocate difficult to assess clinically, imaging modalities such
debridement of these blisters to avoid thromboxane- as triple-phase bone scanning and magnetic reso-
mediated tissue injury. Third-degree injury blisters nance angiography have been used to assess the
usually are filled with blood; owing to the risk of severity of injury and to discriminate viable from
infection, these blisters should generally be left nonviable tissue (Tierney et al., 2004● B ). However,
intact. Fourth-degree injury denotes full-thickness controlled trials establishing the effectiveness of
freezing, including freezing of the muscles, tendons, these techniques are lacking (Biem et al., 2003● B ).
and bones (Mechem, 2005● B ). Laboratory studies are rarely helpful in the diagnosis,
though they may show hemoconcentration and
Differential Diagnosis decreased liver function (Mechem, 2005● B ).
Frostnip is the mildest form of cold exposure, involv-
ing only the subcutaneous tissue. It may manifest Therapeutic
with numbness, prickling, and itching, and there may Rapid thawing of tissue at temperatures slightly above
be visible whitening of the skin, commonly at the tips body heat can help decrease or limit tissue necrosis.
of the fingers, ears, and nose. It is rapidly reversible However, if there is any possibility of refreezing, thaw-
with removal from the cold exposure and does not ing should be delayed until long-term warmth can be
cause long-term damage (Tierney et al., 2004● B ). assured, as refreezing leads to a marked increase in tis-
Chilblain, or erythema pernio, occurs when pro- sue death (Tierney et al., 2004● B). Frostbitten skin is
longed cold exposure does not cause actual freezing extremely fragile, and rubbing the affected areas can
of the tissues. It is a mild form of cold injury and markedly worsen tissue damage (Biem et al., 2003).
most often manifests with red, itchy plaques. There Rewarming is best done by immersion in a moving
may be some degree of blistering or edema, but no water bath at 40˚C to 42˚C (104˚F to 108˚F); dry heat
necrosis of tissue occurs (Tierney et al., 2004●B ). is much more difficult to regulate, and excessive heat
Immersion syndrome, or trench foot, represents a can further damage tissue. Once the distal part of the
more serious exposure. It is caused by prolonged con- frozen area flushes, thawing can be considered com-
tact of the extremity with cold or cool, but not freez- plete. At that point, external heat should be removed

685
 Chapter 93 Cold and Numb Hands and Feet (Frostbite)

and the affected body parts should be elevated and left ciotomy is called for in the case of compartment syn-
uncovered. During the recovery period, contact with drome (Mechem, 2005● B ). Frostbitten tissue may
blistered skin should be minimal (Mechem, 2005● B ). appear dead but can still prove viable even 6 to
As skin and deeper tissues thaw, pain can be 8 weeks after cold injury. Even with obvious overly-
quite severe. Morphine or similar analgesics should ing necrosis and black eschar formation, underlying
be employed liberally in the early stages of treatment. tissue can still heal over a period of months.
Ibuprofen, 200 to 400 mg taken four times per day, Therefore, amputation should be put off until
and aloe vera applied to blistered skin, have been absolutely indicated (Tierney et al., 2004● B ).
used to prevent dermal ischemia. Due to the exten-
sive tissue disruption, tetanus immunization boost- Patient Education
ers are recommended in cases of frostbite. Patients After a frostbite injury, the affected part is often very
who have not previously been fully immunized cold sensitive and usually remains increasingly suscep-
should also receive tetanus immune globulin. Some tible to recurrent cold injury (Tierney et al., 2004● B ).
experts advocate prophylactic antibiotics, but this is Neuropathic changes may include pain, numbness,
not universally recommended (Mechem, 2005● B ). tingling, anhydrosis or hyperhydrosis, cold sensitivity,
Local infection can be treated with soaks in soapy and nerve conduction abnormalities, and may persist
water or application of povidine-iodine. Whirlpool for years after the cold injury (Mechem, 2005● B ).
therapy can help with cleaning and debridement of
sloughing tissue (Tierney et al., 2004● B ). In all cases,
rubbing or scrubbing must be avoided.
Surgical management to debride or amputate
tissue may be needed eventually but should be Material Available on Student Consult
delayed as long as possible. The one exception in Review Questions and Answers about Frostbite
which early surgery would be needed is when fas-

REFERENCES
Biem J, Koehncke N, Classen D, Dosman J. Out of the cold: Tierney LM, Jr, McPhee SJ, Papadakis MA. 2004 Current
Management of hypothermia and frostbite. Can Med Medical Diagnosis and Treatment, 43rd ed. New York,
Assoc J 2003;168:305–311.●B McGraw-Hill, 2004, pp 1530–1531.●B
Mechem CC. Frostbite. Available at www.emedicine.com.
Accessed 3/21/2006.●B
Murphy JV, Banwell PE, Roberts AHN, McGrouther DA.
Frostbite: Pathogenesis and treatment. J Trauma
2000;48:171–178.●B

686
 C h a p t e r

94 Disorientation (Heat Stroke)

Scott Kinkade

It is now about 1 PM, and Mr. K. is able to tell you

KEY POINTS that he feels fine, except he is a little tired and has
some muscle soreness. He was in his usual state of
1. Heat stroke is a medical emergency defined as health this morning when he started working on his
a core temperature greater than 40˚C (104˚F) tractor. He had a half-gallon water jug that he says he
with significant central nervous system dysfunc- drank from frequently because of the hot, humid
tion and usually multiorgan dysfunction as well. conditions. He remembers feeling dizzy and nause-
2. Treatment involves cooling, modest fluid resus- ated and thinking he should head back to the house
citation, and correction or supportive care of to rest. The next thing he can recall is that he was
the complications. lying on his couch with his shirt off and his wife
3. Heat stroke is preventable, and mortality is low standing over him. He urinated once this morning,
if it is recognized early and treated rapidly. before going to the fields, and has not had an urge to
urinate since. He cannot recall ever having any sig-
nificant problems because of the heat. He does note
that during prolonged work in the summer, when he
INITIAL VISIT is sweating quite a bit, he occasionally gets some
cramps in his legs and arms. They resolve if he rests
Subjective and drinks some Gatorade.

Patient Identification and Presenting Medical History

Problem Hypertension well controlled with hydrochloroth-
Mr. K. is a 52-year-old white man whom you have iazide, 25 mg daily, and lisinopril, 10 mg daily. Diet-
been seeing for many years. He is brought to the controlled diabetes.
clinic by his wife, who noticed he was disoriented
this morning. Family History
He has a brother who is alive and well and a sister who
Present Illness had breast cancer several years ago. His father died of
Piecing the history together from Mr. K. and his wife, cardiac disease, and his mother died of complications
it seems he came in from baling hay because he felt of Parkinson’s disease and Alzheimer’s dementia.
dizzy, fatigued, and nauseated. He had been baling
hay on his open-air tractor from 7 AM to 10 AM. Mr. K. Social History
does not remember parking his tractor and coming Mr. K. lives in the country with his wife, owns a small
inside. His wife says she noticed him standing in the business, and raises cattle. He uses smokeless tobacco
kitchen having trouble remembering where the and drinks an average of one or two beers every day.
drinking glasses were kept. She also noticed that he He denies any illicit drug use.
was very hot and was sweating, so she helped him
take off his shirt, had him lie on the couch, and got Review of Systems
him a glass of water. Although he kept telling her,“I’m The patient denies headache, blurred vision, nasal
fine,” he could not recall whether he had finished bal- congestion, or sore throat. He denies chest pain, pal-
ing his hay and what else he was going to do today. pitations, or shortness of breath. He has not had any
She estimates that his mental status seemed to return emesis, diarrhea, or abdominal pain. His last bowel
to normal after about 45 minutes. movement was last night. He has not noticed any

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

687
 Chapter 94 Disorientation (Heat Stroke)

blood in his stool or dark stool. He denies any overwhelmed, and therefore these patients do not
dysuria or change in his urine. He has not noticed cool spontaneously. Whether his core temperature
any weakness or dysequilibrium before this morning. was greater than 40˚C when he came inside and his
wife began modest cooling measures is unknown.
Objective
Differential Diagnosis
Physical Examination Other heat-related illnesses, such as heat syncope or
Mr. K. is a well-developed white man in no apparent heat exhaustion, are possible. Heat syncope is loss of
distress. consciousness with prolonged standing or on standing
in hot environments. This is unlikely, given that no loss
Vital Signs of consciousness was reported. It is due to mild-volume
Height, 5 feet 10 inches dehydration, peripheral vasodilation, lack of acclimati-
Weight, 205 pounds zation, and orthostasis. It is fairly common with pro-
Temperature, 99.3˚F longed standing in outdoor warm events (marching
Respirations, 16 band rehearsals, military formations, concerts, and
Blood pressure, 138/84 spectator sports). Recovery is spontaneous once the
Pulse, 92 individual is in the horizontal position, and treatment
involves hydration and modest cooling measures.
No significant orthostatic change occurs in One of the distinctions between heat exhaustion
pulse or blood pressure. and heat stroke is that no significant neurologic
impairment is found with heat exhaustion. The 45 or
Head and Neck Eyes are clear, nares without dis- more minutes of disorientation Mr. K. exhibited are
charge, oropharynx appears slightly dry, but no not typical of heat exhaustion. Patients with heat
lesions or drainage. The neck is supple without lym- exhaustion may have mild neurologic symptoms such
phadenopathy. The thyroid is not palpable. as irritability, confusion, impaired judgment, dizzi-
ness, and headache. Sweating, thirst, fatigue, weakness,
Heart and Lungs Normal cardiac rate and rhythm muscle cramps, and myalgias are common, often with
without any murmurs. The lung fields are clear. nausea and sometimes vomiting. Temperature can be
elevated, but is still less than 40˚C. If the thermoregu-
Abdomen Normal bowel sounds, nontender and latory mechanisms are not overwhelmed, sponta-
nondistended. neous cooling can occur, but if untreated, heat
exhaustion can progress to heat stroke.
Extremities Pulses are strong in all extremities, with Hyperthermia with mental status changes is
no edema. concerning for infectious diseases such as sepsis and
meningitis. Given the lack of preceding or residual
Neurologic Alert and oriented; no deficiencies on symptoms and the resolution of the hyperthermia
mental-status testing. Motor strength, 5/5 in all without antipyretics, infectious diseases are unlikely.
extremities. Cerebellar function intact. Sensation is However, even milder infections (sinusitis, strep
intact to light touch and vibration. Cranial nerves are pharyngitis, pneumonia, etc.), although not cau-
intact. Deep tendon reflexes in the upper and lower sative of the heat illness, may be predisposing factors
extremities are normal. and make an individual more susceptible.
Hyper- or hypoglycemia is possible. Hyper-
Assessment glycemia usually does not resolve on its own or with
one glass of water. Hypoglycemia, besides being
Working Diagnosis uncommon in someone not taking any hypoglycemic
Mr. K. probably has a heat-related illness, most likely medicines, usually does not resolve until treated.
heat stroke. Heat stroke is characterized by a core A cerebrovascular accident, such as a transient
temperature greater than 40˚C (104˚F), acute men- ischemic attack, is a possibility. Given the lack of
tal-status changes, and other organ dysfunction focal weakness at the time and the current normal
(renal, cardiac, hepatic, hematologic). In severe heat examination, it is hard to confirm. At this time, it
stroke, the central nervous system symptoms can would be part of the differential, but most likely a
include coma and seizures. Heat stroke is a medical diagnosis of exclusion.
emergency. However, the spectrum ranges from mild Mr. K. may have had cardiac ischemia or
heat exhaustion to severe heat stroke, and some cases arrhythmia. Although these are possible, without
can be difficult to differentiate, particularly when symptoms of palpitations or chest discomfort, they
mental-status changes are resolving and cooling has are unlikely.
been instituted. Heat stroke usually implies that the Drug ingestion either (illicit or too much of a
body’s normal thermoregulatory mechanisms are usual medicine) or toxins can cause mental-status

688
 Chapter 94 Disorientation (Heat Stroke)

changes and hyperthermia. Farmers would be sus- with ongoing mental-status changes or other neuro-
ceptible to organophosphate poisoning. Addi- logic deficits should undergo computed tomography
tionally, drug or toxin ingestion may not be the scanning of the head. Patients with respiratory dis-
direct etiology but may make an individual more tress or pulmonary edema should have an echocar-
susceptible to heat injury. diogram to assess ventricular function.

Plan Laboratory Data

Na: 131
Diagnostic K: 3.3
One important aspect of diagnosing heat stroke is Cl, bicarb, Ca, Mg are normal
measuring core temperature. Ideally this should be Glucose, 135
done early in the course of treatment. In this case, BUN, 42
Mr. K. is now afebrile and has cooled on his own. Cr, 1.5
Because heat stroke can cause multiorgan failure, Complete blood count is normal
testing directed at finding organ dysfunction is war- Urine: tea colored, specific gravity, >1030; trace RBC,
ranted. Ruling out predisposing infectious diseases trace protein. The remainder of the urinalysis
may be necessary. Finally, heat illnesses usually including microscopy is negative. Urine myoglobin is
involve electrolyte imbalances and some degree of positive.
dehydration. Diagnostic testing will be directed by AST: 142
the severity of the symptoms and initial laboratory ALT: 185
findings. Because the laboratory values cannot be Lactate dehydrogenase, Alk phos, and bilirubin: nor-
obtained in the office, Mr. K. is admitted to the hos- mal
pital across the street. CPK, 3500
A basic starting point would include blood urea ECG and chest radiograph are normal.
nitrogen and creatinine to look for renal dysfunction
and degree of dehydration. Urinalysis typically Therapeutic
shows elevated specific gravity and sometimes casts Beyond the lifesaving ABCs (airway, breathing, and
and red blood cells (RBCs). The urine also can be circulation), cooling is the most important immedi-
checked for the presence of myoglobin, which would ate intervention. This patient is no longer hyperther-
indicate rhabdomyolysis and would increase the risk mic and therefore does not need aggressive cooling.
of acute renal failure. In instances in which a urine Heat-stroke patients typically do not need large
myoglobin is not readily available, the presence of amounts of IV fluids. Mr. K. is given 1 L of normal
myoglobin can be assessed with a routine urine dip- saline via IV. Because his nausea has resolved, he is
stick and microscopic urine sediment examination. able to continue rehydration with oral fluid intake.
With true hematuria, the microscopic analysis of the His urine output is monitored to confirm adequate
urine will show RBCs or fragmented RBCs in addi- hydration and within 6 hours is averaging more than
tion to changing the color of the urine dipstick. With 50 mL urine per hour. Laboratory tests are repeated
rhabdomyolysis and myoglobinuria, no RBCs will the next morning and have normalized. His urine is
appear in the microscopic examination, but because clear, and no myoglobin is detected. His examination
the dipstick cannot distinguish between hemoglobin is unchanged and still within normal limits.
and myoglobin, it will still register as positive. It is
important to check electrolytes, with particular Patient Education
attention to sodium and potassium in addition to Mr. K. is discharged home the next morning. He is
calcium and phosphate, which are often low. The advised to avoid strenuous activity for 72 hours and
complete blood count typically shows hemoconcen- to avoid prolonged exposure to the heat for 1 week.
tration and often a leukocytosis related to the inflam- Unfortunately, an area in which research is severely
matory response. Persistently elevated white blood lacking is in the prognosis of heat-stroke patients
cell counts should prompt an investigation for infec- and their potential for recurrence. Some heat-stroke
tion. Low platelet levels would be concerning for patients seem more susceptible to recurrent heat
disseminated intravascular coagulation (DIC). injuries than others who have not had any heat-
Measurement of the prothombin time, and activated related illnesses. How to discern who is more suscep-
partial thromboplastin time, D-dimer, and fibrin tible or how long they are more susceptible has not
split products also may be necessary to rule out DIC. been well studied.
Liver transaminases are almost always elevated. Mr. K. is counseled about fluid and electrolyte
A chest radiograph may be obtained to rule out intake, early warning signs of heat illness, and avoidance
pneumonia, acute respiratory distress syndrome, and measures such as mandatory rest breaks and cooling
pulmonary edema, which is sometimes a complica- techniques. He is instructed to consider any future heat-
tion of vigorous intravenous rehydration. A patient exhaustion or heat-stroke symptoms as an emergency.

689
 Chapter 94 Disorientation (Heat Stroke)

DISCUSSION
Box 94-1 Risk Factors for Heat Stroke
Heat-related illness ranges from the mild to severe, Drugs: cocaine, phenothiazines, diuretics, stim-
although only heat stroke requires emergency treat- ulants (including ephedra, ma huang, pseu-
ment. Heat-related illnesses include the following, in doephedrine), anticholinergics, antihistamines
order of severity. Improper work/rest cycles
Heat edema is benign and self-limited swelling of the Dehydration
hands and feet. It is due to vasodilation. Treatment Lack of fitness or acclimatization
is with elevation of the affected extremities or com- High environmental temperature and high
pression stockings or both. Diuretics should be humidity
avoided because they can cause volume depletion. Heavy equipment or too much clothing (over-
Heat cramps are painful spasms of skeletal muscles. bundled babies, firemen’s protective gear,
They are usually due to a combination of physical football gear).
activity, salt loss, and dehydration. They can be Alcohol
prevented with adequate fluid and salt intake. Obesity
Most people obtain enough salt in foods or from History of heat illness
sports drinks and do not need to use salt pills, Illness, particularly febrile illnesses, gastroen-
which are available over the counter. teritis, or hyperthyroidism
Heat syncope and heat exhaustion were described pre-
viously.
Heat stroke is defined as a core temperature greater stroke patient, and the temperature should be meas-
than 40˚C with signs of organ dysfunction and ured rectally. This can help with the diagnosis and be
mental-status changes. Commonly, tachycardia, used to monitor cooling. Start immediate cooling
hyperventilation, and anhidrosis (lack of sweat- measures, preferably by using cool mist and fans.
ing) are noted, although many heat-stroke Other methods include ice baths, ice packs in the
patients will still be found to be sweating. groin and axilla, ice-water gastric or peritoneal
Although a distinction is made between classic lavage, and cooling blankets. Ice baths can be techni-
heat stroke and exertional heat stroke, the ultimate cally difficult because it is difficult to record rectal
treatment measures are the same. The classifications temperatures and perform procedures including
have different epidemiologic characteristics, and possible cardiac defibrillation. Because many of these
possibly different pathophysiology. Classic heat methods can cause peripheral vasoconstriction, vig-
stroke is due to exposure to high environmental tem- orous massage of the skin is usually required to help
peratures and occurs more commonly in the very promote heat loss. Cooling measures can be stopped
young or elderly, the poor or socially isolated, those when the core temperature is less than 38˚C
with chronic medical conditions (cardiovascular dis- (100.4˚F). Antipyretics and dantrolene are ineffec-
ease, psychiatric disorders, obesity), and those with- tive. Frequent monitoring is required to avoid
out access to air conditioning. Exertional heat stroke hypothermia. Shivering (or seizures), which can
is due to strenuous activity that may or may not be in generate additional body heat, can be treated with
a hot environment, although hot humid conditions benzodiazepines.
confer higher risk. It generally occurs in young, oth- Heat-stoke patients should be resuscitated with
erwise healthy individuals (Box 94-1). normal saline, but typically do not require more than
The mortality for heat stroke ranges from 5% to 1 or 2 L of IV fluids unless they are hypotensive.
more than 50% (Bouchama, 2002, Rav-Acha, 2004), Initial laboratory studies include electrolytes, glu-
depending on how rapidly and effectively it is cose, calcium, complete blood count, prothrombin
treated. When heat stroke is anticipated and medical time and activated partial thromboplastin time,
personnel are prepared, such as in military training blood urea nitrogen, creatinine, liver panel, arterial
or sporting events, the mortality should be less than blood gases, urinalysis and urine myoglobin, and
10%. For patients in whom the diagnosis is not rec- creatine phosphokinase. Observe the patient for evi-
ognized promptly (such as heat waves leading to dence of rhabdomyolysis; renal, cardiac, or hepatic
classic heat stroke) or if medical care is not readily failure; disseminated pulmonary edema, or adult res-
available (i.e., religious pilgrimages to Mecca), the piratory distress syndrome, and treat accordingly.
mortality may exceed 50%. For survivors of heat
stroke, usually complete recovery ensues, with no
long-term neurologic sequelae.
Treatment of heat stroke begins with prompt Material Available on Student Consult
recognition and attention to the ABCs of resuscita- Review Questions and Answers about Heat Stroke
tion. All clothing should be removed from a heat-

690
 Chapter 95 Spider Bites

REFERENCES
Bouchama A, Knochel JP. Heat stroke. N Engl J Med Rav-Acha M, Hadad E, Epstein Y, et al. Fatal exertional heat
2002;346:1978–1988. stroke: A case series. Am J Med Sci 2004;328:84–87.

SUGGESTED READINGS

Coris EE, Ramirez AM, Van Durme DJ. Heat illness in ath- Lugo Amador NM, Rothenhaus T, Moyer P. Heat-related
letes: The dangerous combination of heat, humidity, illness. Emerg Med Clin North Am 2004;22:315–327.
and exercise. Sports Med 2004;34:9–16. Wexler RK. Evaluation and treatment of heat-related ill-
Hadad E, Rav-Acha M, Heled Y, Epstein Y, Moran DS. Heat nesses. Am Fam Physician 2002;65:2307–2314.
stroke: A review of cooling methods. Sports Med Yeo TP. Heat stroke: A comprehensive review. AACN Clin
2004;34:501–511.● C Issues 2004;15:280–293.●C

C h a p t e r

95 Spider Bites

Jeffery Alan May

KEY POINTS

1. The staple of spider bite management is sup- 2. In severe circumstances (e.g., in patients with dis-
portive, primum non nocere, with RICE—rest, seminated intravascular coagulation) steroids are
ice, compression, and elevation. Prudent use of useful; antibiotics or even inhibitors of polymor-
tetanus + diphtheria immunization, antihista- phonuclear leukocyte migration, such as dap-
mines, and antibiotics (if the bite is deemed sone, may be considered.
infected) is the best recognized plan and holds 3. Without an obvious perpetrator (a spider or rem-
the least potential for worsening the patient’s nants thereof), the clinician should think of other
condition. causes of the lesion.

INITIAL VISIT
A 20-year-old woman comes to the office com-
Subjective plaining that something bit her on the right lower
back 3 days earlier. The lesion is approximately 1.5
Patient Identification and Presenting cm, erythematous, macular, pruritic, and slightly
Problem papular. It blanches on pressure, indicating a nonvas-
On a typical spring day in our large rural practice, on culitic lesion. She is given a tetanus + diphtheria (Td)
average three people present with “spider bites.” booster and diphenhydramine, and released.
These patients have lesions consistent with an insect Our patient later returns to the office com-
bite, which is ubiquitous in the human experience. plaining of headaches, myalgias, and chills. By this
The typical signs of inflammation—rubor, dolor, time a 1-cm necrotic lesion on her right lower back
calor, and tumor—as well as pruritus are likely to be has formed. Two other individuals seen on the
associated in all cases. same day also have lesions, which they attribute to

691
 Chapter 95 Spider Bites

REFERENCES
Bouchama A, Knochel JP. Heat stroke. N Engl J Med Rav-Acha M, Hadad E, Epstein Y, et al. Fatal exertional heat
2002;346:1978–1988. stroke: A case series. Am J Med Sci 2004;328:84–87.

SUGGESTED READINGS

Coris EE, Ramirez AM, Van Durme DJ. Heat illness in ath- Lugo Amador NM, Rothenhaus T, Moyer P. Heat-related
letes: The dangerous combination of heat, humidity, illness. Emerg Med Clin North Am 2004;22:315–327.
and exercise. Sports Med 2004;34:9–16. Wexler RK. Evaluation and treatment of heat-related ill-
Hadad E, Rav-Acha M, Heled Y, Epstein Y, Moran DS. Heat nesses. Am Fam Physician 2002;65:2307–2314.
stroke: A review of cooling methods. Sports Med Yeo TP. Heat stroke: A comprehensive review. AACN Clin
2004;34:501–511.● C Issues 2004;15:280–293.●C

C h a p t e r

95 Spider Bites

Jeffery Alan May

KEY POINTS

1. The staple of spider bite management is sup- 2. In severe circumstances (e.g., in patients with dis-
portive, primum non nocere, with RICE—rest, seminated intravascular coagulation) steroids are
ice, compression, and elevation. Prudent use of useful; antibiotics or even inhibitors of polymor-
tetanus + diphtheria immunization, antihista- phonuclear leukocyte migration, such as dap-
mines, and antibiotics (if the bite is deemed sone, may be considered.
infected) is the best recognized plan and holds 3. Without an obvious perpetrator (a spider or rem-
the least potential for worsening the patient’s nants thereof), the clinician should think of other
condition. causes of the lesion.

INITIAL VISIT
A 20-year-old woman comes to the office com-
Subjective plaining that something bit her on the right lower
back 3 days earlier. The lesion is approximately 1.5
Patient Identification and Presenting cm, erythematous, macular, pruritic, and slightly
Problem papular. It blanches on pressure, indicating a nonvas-
On a typical spring day in our large rural practice, on culitic lesion. She is given a tetanus + diphtheria (Td)
average three people present with “spider bites.” booster and diphenhydramine, and released.
These patients have lesions consistent with an insect Our patient later returns to the office com-
bite, which is ubiquitous in the human experience. plaining of headaches, myalgias, and chills. By this
The typical signs of inflammation—rubor, dolor, time a 1-cm necrotic lesion on her right lower back
calor, and tumor—as well as pruritus are likely to be has formed. Two other individuals seen on the
associated in all cases. same day also have lesions, which they attribute to

691
 Chapter 95 Spider Bites

spiders, but only one actually saw and killed a spi- end of 5 weeks the wound has healed, with no need
der, which was in a pair of pants he was putting on. of revision or grafting.
He was bitten on the thigh. These pants had lain on
the floor overnight. This young man also has a
lesion similar to the young woman’s, but other DISCUSSION
than ensuing local necrosis, requiring 4 weeks’
healing time, he suffered no further sequelae. The Two of our patients probably sustained envenoma-
other patient’s wounds did not progress, nor were tion by the brown recluse spider (Loxosceles reclusa).
there other problems. It is the primary culprit in significant cases of
necrotic arachnidism in the United States. Of lesser
Assessment significance are the black widow (Latrodectus mac-
tans), the hobo spider (Tegenaria agrestis), and the
On her return visit to our office, the young woman is tarantula. To place the problem of spider bites in
now moderately ill. The wound has grown to an ulcer perspective, it should be recognized that of the
3 by 5 cm in circumference and 1 cm deep near the 60,000 members of the phyllum Arthropoda, class
original lesion. She also reports darkening of her urine Arachnida, 30,000 are spiders. We are seldom
for 3 to 4 days. A complete blood cell count shows a more than a few feet from a member of these groups
hemoglobin value of 7 g/dL and a hematocrit of 20%, whether we are indoors or outside, and so, luckily,
with a white blood cell count of 13,000/mm3. There is our topic narrows to only a few significant exem-
a neutrophilic predominance with five to seven band plars. They are discussed here in order of priority to
cells (a left shift). Her reticulocyte count is 16% with a their bite, prevalence, severity, and U.S. geographic
positive indirect Coomb’s test. The INR, or interna- locale.
tional normalization ratio, of her prothrombin time is
1.2; her activated partial thromboplastin time is 31 Brown Recluse Bites
(i.e., both of these coagulation parameters are ele-
vated, revealing a mild coagulopathy); and her ery- Brown recluse envenomation may result in local
throcytic sedimentation rate is 132. necrosis and sometimes a more generalized systemic
response, which may range from local necrosis to
intravascular hemolysis and even disseminated
Treatment
intravascular coagulation. Although other Loxosceles
She is hospitalized and treated with corticosteroids species exist in the United States, L. reclusa is of
and intravenous fluids, with prompt relief of symp- greatest significance. The spiders’ habitat range cen-
toms. She is treated with a high dose of prednisone ters on the mid-South, the Southeast, and parts of
(60 mg) every day for 3 weeks and seen in the office the Southwest, including more than 16 states extend-
once a week. She has no further complications. At the ing to the Midwest (Fig. 95-1).

Figure 95-1 Range of recluse

(Loxosceles) spiders. (Courtesy of
Rick Vetter, www.spiders.ucr.edu.)

692
 Chapter 95 Spider Bites

The arachnid prefers temperatures above 40˚F,

enjoys the dry environment of woodpiles and out-
buildings, and particularly likes attics, basements,
closets, and storage areas. It is a nocturnal hunter
and can be aggressive, although its general behavior
befits its name.
The leg spread of the adult is commonly 3 to
4 cm, with a body length of about 5 mm. It is dark
to medium brown with a characteristic violin shape
(the neck of which points caudad) on the dorsal
cephalothorax. This marking is more prominent in
some species than in others, but L. reclusa in its
mature form usually has the marking (Fig. 95-2).
The clinical presentation of a brown recluse bite is
called loxoscelism or necrotic arachnidism (Fig. 95-3). Figure 95-3 Clinical appearance of a brown recluse
Although all spiders possess some venom designed to bite. (From Sams H. Cortland Forum, July 2000, p 35.)
immobilize and begin digestion of their prey, few
species have the mouthparts and fangs to penetrate
and envenomate human skin (Table 95-1). Most
encounters with humans are caused by spiders nesting at the site, followed by a bluish bleb, usually occur-
or foraging in clothes that are put on by the unsus- ring within 12 to 24 hours. This necrotic bleb is often
pecting victim. Bites of the brown recluse are probably surrounded by a white ischemic halo, which may
more numerous than once suspected because the vast then have an erythematous margin. The classic der-
majority probably result only in minimal inflamma- monecrotic lesion is red, white, and blue and may be
tory responses and thus are unreported. To some extremely pruritic. The bleb usually drains within
extent, people who have been bitten several times may a day, leaving an ulcer. In more severe cases, the
develop neutralizing antibodies. erythematous ulceration may progress. Areas with
Brown recluse venom is both cytotoxic and abundant adipose deposits, such as the thigh,
hemotoxic and contains a complex mixture of abdomen, and buttocks, may be more severely
enzymes, the most well-known constituent of which affected. By the third or fourth day, if no spreading
is sphingomyelinase-D. The clinical presentation has occurred, the envenomation will probably not be
varies dramatically from a small, local phenomenon
to coagulopathy and, rarely, death. In the worst of
lesions there is an aching, painful lesion with redness
Table 95-1 Differential Diagnosis
of Possible Necrotizing
Arachnidism Lesions
Vascular ulcers (arterial or venous insufficiency)
Diabetic ulcer
Infection
Bacterial (e.g., Streptococcus, Staphylococcus,
anthrax)
Mycobacterial (e.g., Mycobacterium ulcerans)
Fungal
Viral (?)
Foreign body
Focal vasculitis
Injection of toxin (accidental or deliberate)
Drug reaction
Physical/mechanical trauma (may be deliberate)
Burns (especially chemical burns)
Pyoderma gangrenosum
Neoplasm
Immunosuppression
α-Antitrypsin deficiency
Figure 95-2 Brown recluse spider. (From Crown LA, Fat herniation with infarction
Loftin B, Magill E. Successful treatment of hemolytic
anemia secondary to brown recluse bite. Family Practice From Hawdon GM, Winkel KD. Venomous marine
Recertification 1998;20:22–29.) creatures. Aust Fam Phys 1997;26:1369.

693
 Chapter 95 Spider Bites

significant. Ulcers have progressed to as much as only three are black. Latrodectus mactans is shiny
30 cm in diameter and have taken months to heal. black and has the classic red hourglass figure on the
Systemic responses may also occur, including fever, ventral abdomen (Fig. 95-4).
chills, nausea, vomiting, headache, malaise, myalgias, Most victims are bitten on the hand while reach-
arthralgias, and maculopapular rashes. Severe reac- ing into the spider’s web lair. The bite usually causes
tions are rare and usually affect very young, very old, a pinprick sensation but may go totally unrecog-
or immunocompromised individuals. Treatment of nized. The venom consists primarily of neurotoxins,
these very ill patients includes systemic steroids and and therefore necrotic local tissue damage is unlikely.
supportive measures aimed at ameliorating the Latrodectism is the syndrome produced by the black
symptoms. widow venom. These neurotoxins exert, via acetyl-
Management of the noncritically ill or milder choline release, extremes of either pallor or hyper-
cases of loxoscelism is problematic. There are no cur- emia at the site. This may then spread locally and, in
rent practical tests for envenomation and there is no larger envenomations, systemically. Presynaptic
antivenom available. Local wound care, tetanus pro- acetylcholine release is increased and uptake is inhib-
phylaxis, and, rarely, antibiotics (if the wound is truly ited postsynapatically, resulting in myriad symptoms
infected) may be considered. Antibiotics are not rou- that are proportional to the quantity of envenoma-
tinely of use; however, the antileprosy drug dapsone tion but may also to some extent be idiosyncratic,
has been advocated by some. As mentioned earlier, based on size, age, and immunocompetence of the
sphingomyelinase-D is a relatively large and well- victim. Symptoms may manifest as severe cramping
studied constituent of brown recluse venom. It is a usually occurring within 30 to 90 minutes and pro-
potent chemotactic agent for polymorphonuclear ceeding in a migratory fashion from the inoculation
leukocytes, whose proteolytic enzymes are then site. Cramping may involve the entire body, although
responsible for probably most of the inflammation children particularly exhibit abdominal musculature
and tissue destruction. Inhibition of this migration contractions. Confusion and mixed autonomic dys-
might be useful in diminishing the extent of the function follow: nausea, vomiting, diaphoresis, dizzi-
necrosis; thus is the theoretical utility of the drug ness, headache, extreme restlessness or agitation and
dapsone derived. The downside is that at doses high even motor paralysis may occur. Seizures and hyper-
enough to gain this utility (the suggested dose is 50 tensive crises with tachycardia and tachypnea are
to 200 mg/day), many patients will suffer some indicators of severe envenomation. Except in the spe-
degree of hemolysis (especially those with glucose- cial populations of the very old, young, immuno-
6-phosphate dehydrogenase deficiency) or methe- compromised, or pregnant women, complications
moglobinemia (if they have NADH reductase are rare. Recovery is the rule. Peak symptoms usually
deficiency). Testing for both prior to initiating treat- occur during the few hours after the bite and subside
ment complicates use of the drug. Furthermore,
there are no studies that validate its use.
Methods of dealing with these necrotic lesions
have included local excision, oxygen, electric shock,
antihistamines, isotretinoin, nicotine patches, phen-
tolamine, dextran, low molecular weight heparin,
and meat tenderizer, among others. Ice and diphenhy-
dramine, as well as problem-focused wound care, are
the only modalities that do not risk worsening or
confounding the condition. Laboratory work is also
focused on any specific systemic symptoms the
patient develops.

Black Widow Bites

Black widow spiders (Latrodectus) are endemic to
nearly all of the United States except the extreme
ecological niches of deserts, glaciers, and areas above
the mountain tree lines. The female body length is up
to 1.5 cm with a leg span of 4 to 5 cm. The male is
approximately one-third that size. The male cannot
envenomate humans and suffers a grim fate after
mating with the female black widow. Only the female
has fangs that are capable of penetrating human epi-
dermis. Several species exist in the United States, but Figure 95-4 Black widow spider.

694
 Chapter 95 Spider Bites

Table 95-2 Systemic Signs and

Symptoms of Black Widow
Spider Bite
Common Occasional

Abdominal rigidity Arrhythmia

Agitation Bradycardia
Cutaneous Convulsion
hyperesthesia Hypertension
Headache Mild fever
Muscle cramps Priapism
and spasms Psychosis
Nausea Shock Figure 95-5 Wolf spider.
Pain Tachycardia
Perspiration Tachypnea and
Restlessness dyspnea of the 20th century to Washington, Idaho, and
Vomiting
Oregon, may contribute to cases of necrotic arachni-
From Koh WL. When to worry about spider bites: dism similar to Loxosceles reclusa. Because experience
Inaccurate diagnosis can have serious, even fatal, is minimal and cases are few, it is to date managed
consequences. Postgrad Med 1998;103:235. similarly.
The wolf spider’s moniker Lycosidae developed
because the Greeks thought these spiders hunted in
packs (Fig. 95-5). Its most famous member, Lycosa
within a day or so. Some residual subjective com- tarantula, was credited with causing stuporous
plaints such as paresthesias, weakness, and malaise, intoxication and wild dancing. However, a different
as well as headaches, joint pain, and insomnia, may European spider, Latrodectus tredecimguttatus, was
persist for weeks (Table 95-2). Management of severe found to be the real culprit of this syndrome. In real-
envenomation from the black widow consists prima- ity, Lycosa tarantulas are not true tarantulas and do
rily of supportive care with attention to airway, little more than cause trivial stinging pain.
breathing, circulation, appropriate laboratory tests, The last spiders of clinical importance in North
and interventions to counteract symptoms. The pri- America are the 40 species of large, slow, and long-
mary goal is to relieve the spasms and associated lived tarantulas (Fig. 95-6). These somewhat fear-
pain. Intravenous calcium gluconate has been used some-appearing spiders are not aggressive, although
for some time but may be of limited use. If used, 10 they possess potent tissue-toxic venom. The geome-
mL of a 10% solution is given over 20 minutes and try of their jaws is more vertical than that of the other
may be repeated every 2 to 4 hours. Dantroline (a spiders discussed here, and this puts them in a differ-
skeletal muscle relaxant) given intravenously may ent suborder, Orthognatha, and requires that they
prove to be useful for severe envenomations. must strike their victims after assuming a raised
Analgesics and narcotics, either parenteral or oral, position anteriorly. To date, treatment is purely sup-
are appropriate. Antivenom use is problematic; portive. No human demise from envenomation of
although it is very effective, up to 9% of patients will these arachnids in the United States is known.
develop a serum sickness from the equine-based
product, and hypersensitivity reactions are also a
risk. Authorities recommend that the use of antiven-
oms be restricted to situations involving life-threat-
ening manifestations such as cardiovascular collapse,
severe hypertension, or in pregnant woman with
severe symptoms. If available, antivenom is given at a
dose of 1 to 2 vials over 20 to 60 minutes. Skin test-
ing should be performed before administration.

Other Spiders
Less frequent, and hence less important clinically, are
the hobo spider (Tegenaria agrestis), wolf spider
(Lycosidae species), and the tarantula. Tegenaria
agrestis, the hobo spider, also known as the
Northwestern brown spider, a European immigrant Figure 95-6 Tucson blonde tarantula.

695
 Chapter 95 Spider Bites

Summary The primary job for practitioners when patients

present with an assumed bite is to attempt to ascer-
The much maligned spiders usually are problematic tain whether the lesion was caused by the accused. As
for humans only during mutually unexpected clinicians, we should never immediately accept a
encounters. The brown recluse is the most significant diagnosis purely on a hunch. The differential diag-
member with the most frequently seen bites. It and nosis of a necrotic lesion is extensive and depends on
others mentioned here, with the exception of the setting, circumstances, presence of an eight-
Latrodectus, use mostly cytotoxic and hemotoxic poi- legged perpetrator, and progress of the lesion (see
sons, and their bites are ultimately best treated with Table 95-1).
supportive care only. This care may include cool com-
presses, limb immobilization, tetanus prophylaxis,
and diphenhydramine, as deemed appropriate. The
black widow and its Latrodectans ilk use neurotoxins
and may cause broader and more serious symptoms, Material Available on Student Consult
but they are much less frequently encountered.
Review Questions and Answers about Spider
Although antivenom exists, its use is problematic and
Bites
necessary only in the most severe circumstances.

SUGGESTED READINGS
Auerbach PS (ed). Wilderness Medicine: Management of Hardman J (ed). Goodman and Gilman’s The Pharma-
Wilderness and Environmental Emergencies, 3rd ed. St. cological Basis of Therapeutics, 10th ed. New York,
Louis, Mosby, 1995, pp 769–782. McGraw-Hill, 2001, pp 1288–1289.
Crown LA, Loftin B, Magill E. Successful treatment of Treatment varies for severe Loxosceles spider bite. Family
hemolytic anemia secondary to brown recluse bite. Practice News, May 1, 2004, p 15.
Family Practice Recertification 1998;20:22–29.
Family Practice News, Clinical Rounds, April 10, 2004, p 15.

696
 C h a p t e r

96 Upper Extremity Numbness and Pain

(Double Crush Syndrome)
James M. Daniels

KEY POINTS
1. The key to identifying patients with numbness entrapment can be traced back to our embry-
in the upper extremity is a careful history and ologic development.
physical examination. 7. A number of populations are at increased risk of
2. Physical examination and history should focus thoracic outlet syndrome and include patients
first on elementary central nervous system involved in strenuous upper extremity work,
lesions and then progress peripherally to female patients, patients with diabetes, patients
peripheral nerve entrapments to rule out sys- involved in long work in a slumped over posi-
temic processes that are associated with periph- tion such as office computer work.
eral neuropathy. 8. The hallmark of carpal tunnel syndrome is noc-
3. A differential diagnosis of the upper extremity turnal pain and paresthesias.
may include stroke, focal seizures, multiple scle- 9. The clinical course of patients with carpal
rosis, or some type of spinal cord tumor. It may tunnel syndrome can be separated into three
include entrapment of the cervical spine, tho- distinct groups: those with neurapraxia who
racic outlet syndrome, or peripheral nerve have mild symptoms; those with axonotmesis
entrapment. who often have burning pain in their hands
4. Patients with confusing physical examination as a major complaint; and those with
findings may be considered for the diagnosis of neurotmesis, which causes pronounced
“double crush” syndrome or thoracic outlet thenar wasting.
syndrome. 10. Double crush syndrome involves a nerve entrap-
5. Nerve root entrapment of the cervical spine ment at multiple sites. Patients may present
may cause bilateral upper extremity symptoms. with symptomatic nerve compression and have
The sixth cervical nerve root can cause the same negative electromyographic nerve conduction
sensory changes that are associated with carpal studies. One single site may not be sufficient to
tunnel syndrome. Cervical spondylosis is com- cause the patient to have symptoms, but when
mon, and the diagnosis should be considered in a second site is compressed, the patient may
evaluating patients for carpal tunnel syndrome. become symptomatic. Once identified, patients
6. The thoracic outlet can be divided into four can be treated conservatively and symptoms can
specific anatomic areas and nerve root greatly improve in 3 to 4 months.

INITIAL VISIT History of Present Illness

Approximately 2 years ago, Tish S. underwent endo-
Subjective scopic surgery on her left hand for carpal tunnel syn-
drome. Her symptoms abated slowly over 1 month.
Patient Identification and Presenting Problem For the past 3 months, she has been waking at
Tish S. is a 45-year-old white right-hand dominant approximately 2 AM complaining of a “pins and nee-
computer analyst who presents to your clinic com- dles” feeling in both hands. Her symptoms are
plaining of right hand numbness. relieved if she lets her arms hang over the edge of the

Evidence levels ●A Randomized, controlled trials (RCTs), meta-analyses, well-designed systematic reviews of RCTs.
●B Case-control or cohort studies, nonrandomized clinical trials, systematic reviews of studies other than RCTs, cross-
sectional studies, retrospective studies, certain uncontrolled studies. ●
C Consensus statements, expert guidelines,
usual practice, opinion.

697
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

bed. In the morning, both of her hands feel numb at night. During a recent vacation to the Caribbean
and clumsy. She has trouble putting on her makeup; with her husband, her symptoms greatly improved.
after this she is okay for the rest of the day. She Her job involves the use of a computer at work and a
recently started an aerobics fitness program and her laptop at home. She spends approximately 6 hours
symptoms have worsened. She is now having diffi- per day on a computer. When she was in the
culty completing her exercise program because of Caribbean, she was without any type of computer.
these symptoms. Over the past week her symptoms
have started affecting her work.
Objective
Medical History Physical Examination
Allergies: none. Medications: venlafaxine (Effexor XR), The patient is a 5 feet 4 inch, 164-pound white woman
75 mg at bedtime for depression; ramipril (Altace), 10 sitting on the examination table. She is tearful with her
mg every morning for blood pressure; glyburide and head down and sits in a “slumped over” position. Her
metformin (Glucovance), 1.25 mg/250 mg every blood pressure is 120/80. Her pupils are equal, round,
morning for diabetes; 81 mg coated aspirin every and reactive to light and accommodation. She has
morning for stroke/myocardial infarction prevention; complete range of motion of her neck. Spurling’s
calcium and vitamin D (Citracal: 315 mg of calcium + maneuver does not reproduce any of her symptoms.
200 IU of vitamin D), two in the morning and two at Figure 96-1 illustrates this test. There is symmetry of
night, for osteoporosis prevention. her shoulders except for a large bone callus over the
middle of her right clavicle. She has indentations on
Social History her shoulders where her brassiere is resting.
She has been treated for depression for approximately Her lungs are clear to auscultation and heart
3 years. She is married with three children. Tish drinks sounds are within normal limits. There are no bruits
about three glasses of wine per week; she smokes noted.
socially, approximately eight cigarettes per week. A modified Roos maneuver reproduces the
patient’s symptoms in approximately 8 seconds. Figure
Surgeries 96-2 illustrates this maneuver. The Valsalva maneuver
Her last child was born by cesarean section. She has does not reproduce any of the symptoms in her
had a laparoscopic cholecystectomy. She had the extremities. There is no evidence of any increased spas-
endoscopic carpal tunnel surgery on her left wrist ticity in her extremities or clonus and her deep tendon
performed by a board-certified hand surgeon at the reflexes are +2 and symmetrical. She can extend and
nearby regional medical center a few years ago. flex her elbow without any difficulty and reports no
symptoms with resisted pronation of the forearm. She
Review of Systems has a negative Tinel’s sign of the proximal forearm and
The patient has been in good health her whole life negative Phalen’s test in the proximal forearm. Median
except for her diabetes, which was diagnosed 3 to 4 nerve compression tests at the wrist are done bilaterally
years ago. Tish was a gymnast in college, and she had for 1 minute. Figure 96-3 illustrates this tests. The
a vaulting accident in which she fractured her right patient complains that her hands feel swollen, but her
clavicle. Two months ago, she saw the surgeon who physical examination is normal. Her hands are warm
previously operated on her. The surgeon ordered elec- to touch, and there is no increase in perspiration or evi-
tromyographic nerve conduction studies of her upper dence of any type of weakness in the upper extremities.
extremities, and they were normal. He prescribed neu- The patient has a well-healed surgical scar on her left
tral wrist night splints and placed her on pyridoxine wrist from her previous surgery. There is no redness or
(vitamin B6), 200 mg daily. He diagnosed her with a inflammation of any of her joints.
very mild case of carpal tunnel syndrome but felt that She has a negative Tinel’s sign at the cubital tun-
she was not a candidate for surgery at that time. She nel, and flexion of both elbows for 60 seconds does
recently started perimenopausal symptoms, including not reproduce any symptoms. Flexion of both wrists
hot flashes and worsening of her depression. for 60 seconds does not reproduce any of the
The numbness in her hand is located in the patient’s symptoms.
thumb and index finger, but she occasionally feels
that her whole hand will fall asleep. A year ago she
Assessment
was involved in a motor vehicle accident and under-
went chiropractic manipulative therapy for approxi- Differential Diagnosis
mately 3 months. The patient plays the violin in the 1. Central nervous system lesions can produce numb-
local municipal symphony. She has difficulty with ness in the upper extremities. A stroke or some
her violin technique and feels she no longer has the type of focal seizure could cause these symptoms.
control of her hands that she once had. The only The patient has diabetes and does smoke. Her
thing that seems to help her is sleeping in a recliner blood pressure has been under good control. She

698
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

Figure 96-1 Spurling’s maneuver. A, Axial load being applied to the top of the patient’s head with the neck in a neu-
tral position. B, The patient rotating her neck to approximately 45 degrees while slightly extending her neck. The
physician then places an axial load to the patient’s head, which causes compression of the ipsilateral nerve root. A pos-
itive test results in the patient complaining of reproduction of the symptoms in the affected extremity. Pain or dis-
comfort in the neck is not considered a positive test. C, The patient rotated to the opposite direction at a 45-degree
angle with her chin in extension. An axial load should not reproduce symptoms.

699
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

sixth cervical nerve root exits the central nervous

system between the C5 and C6 vertebrae. Sixth
cervical nerve root entrapment causes weakness
of biceps and wrist extension. The patient has nei-
ther of these findings. The sixth cervical nerve
also innervates the brachioradialis reflex and is
partially responsible for the biceps reflex. Sixth
cervical nerve entrapment can also cause sensory
changes in the forearm and thumb similar to that
of carpal tunnel syndrome. Cervical spondylolysis
commonly occurs in middle-aged or elderly
patients and can have almost identical symptoms
to those of a median nerve pathology. The patient
did not have symptoms with the Valsalva maneu-
ver, and she had a negative Spurling’s test.
Figure 96-2 Roos maneuver. The patient abducts her
arms to 90 degrees. It is considered a positive test if
Cervical spine films and magnetic resonance
there is reproduction of the patient’s symptoms in the imaging of the neck can be ordered to help iden-
affected extremity within 1 minute. tify cervical spine lesions.
4. Thoracic outlet syndrome. Pancoast’s tumor can
cause myosis, ptosis, and anhydrosis of the ipsilat-
eral side of the face. This diagnosis should always
be considered in a smoker. A chest radiograph or,
if necessary, computed tomography of the chest
can rule out this condition. The thoracic outlet
consists of a triangle of muscle and bone in the
shoulder and neck region in which the cervical
spine nerve roots and brachial plexus transition
into the upper extremity. The thoracic outlet can
be divided into four sections. The first is the ster-
nocostovertebral space, which can be occupied by
Pancoast’s tumor. The second is the scalene trian-
gle bordered by the scalene muscles. These mus-
cles can become taut or traumatized such as in a
whiplash injury. They can then scar and exert
pressure on the plexus. The third division of the
thoracic outlet is the costoclavicular space. This is
Figure 96-3 Median nerve compression test. This test is the space between the clavicle and the first rib.
shown to be more reproducible than Phalen’s test. It This space can be compromised if there is a his-
requires the examiner to place pressure on the volar tory of trauma to the mid-clavicle and there is a
aspect of the wrist on the affected extremity. The thumb large bone callus formation.
is placed just proximal to the distal radial crease in the
central part of the wrist. If the patient has palmaris
The fourth space is the coracopectoral space,
longus tendon, intersection of these structures may act which can be compromised if there is tightness in
as a landmark for the examiner to place his or her the anterior shoulder. This often happens in mid-
thumb. A positive test results in the patient’s symptoms dle-aged people or people who have a job that
being reproduced within 60 seconds of compression. requires them to be in a bent or stooped-over posi-
tion for long periods of time. The anterior muscu-
lature of the chest hypertrophies while the
does have some risk factors for cardiovascular posterior musculature of the upper back stretches.
disease, but her physical examination is not con- The long dynamic tunnel of the thoracic outlet is
sistent with this problem. greatly affected by posture. Rare anatomic abnor-
2. Syringomyelia, multiple sclerosis, or some type of malities can cause symptoms in this area.
spinal cord tumor may also produce these symp- Approximately 1% of the population has a con-
toms. The patient’s symptoms have been inter- genital abnormality of the cervical spine that can
mittent and not constant. She also lacks any long be seen on a radiograph. An unusually long trans-
track signs that would go along with any cord verse process of the seventh cervical vertebra is
lesion. associated with a fibrotic band. This band origi-
3. Nerve root entrapment of the cervical spine can nates at the transverse process of C7 and inserts on
cause bilateral upper extremity symptoms. The the body of T2. A cervical rib on the C7 vertebrae

700
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

may be associated with one of these bands but can more common, and tests performed to detect
impinge on the brachial plexus itself. change in the patient’s pulse such as Addison’s and
Thoracic outlet syndrome can be traced back to Wright’s maneuver are not particularly helpful.
our embryologic development. During develop- This condition usually responds to conservative
ment of the forelimb, buds must rotate 270 therapy in the form of specialized stretching and
degrees to produce the position of the upper strengthening exercises of the neck and shoulder
extremity at our side as opposed to the forward coupled with diaphragmatic breathing exercises.
flexed position of quadrupeds. This rotation of Over time, this often leads to complete resolution,
the brachioplexus causes it to be circumducted if not great improvement of the patient’s symp-
between the clavicle and the first rib. As we age, toms. The process, however, usually takes 3 to 4
the clavicle has a tendency to “sag” and cause months to complete.
more imbalance between the anterior and poste- 5. Pronator teres syndrome. The proximal median
rior thorax. This patient participates in a number nerve courses through the anterior part of the fore-
of activities that can predispose her to thoracic arm. As it does so, it passes through a number of
outlet syndrome. Playing the violin causes the structures in the elbow in which it can become
patient to work with her arm in an abduction trapped (Fig. 96-4). This syndrome can be differ-
position, which causes increased tension of the entiated from carpal tunnel syndrome by a number
scalene muscle and the superior trapezius. These of aspects. There is usually more pain in the fore-
muscles become activated and will sometimes fire arm than in the hand. Symptoms can be brought
inappropriately during breathing. Usually these on by wrist movement. There may be a positive
muscles have only a secondary function when one Tinel’s sign of the forearm. Resisted pronation and
is breathing. In some individuals, an abnormal passive supination bring on symptoms.
pattern can develop and these muscles become 6. Anterior interosseous syndrome. The anterior
primarily responsible for breathing instead of the interosseous nerve arises from the median nerve
usual diaphragmatic pattern. In a relaxed position approximately 5 to 8 cm distal to the lateral epi-
with arms at the side, the diaphragm accounts for condyle. It is a pure motor nerve. This nerve
most of the effort in breathing by approximately a innervates the flexor pollicis longus, the flexor
3:1 magnitude. In females, the medial third of the
clavicle is lower than in males, thus shrinking the
costoclavicular space. In addition to this, in women,
the second dorsal vertebra is more caudad to the
top of the sternum compared with men. This par- Abductor
ticular patient has what is referred to as “droopy pollicis
brevis m.
shoulder syndrome.” Patients hold their head in a
slightly flexed position and the shoulders are
flexed forward. This causes scapular ptosis, espe-
cially in females with larger breasts. The breasts
attach to the pectoralis major muscles and exert a
downward pull on the medial aspect of the clavi-
cle. The problem is accelerated when brassiere
straps are located more laterally further increas-
ing forward flexion of the shoulders.
The patient also has some endocrine issues that
can affect neural physiology. She has diabetes and
recently has experienced perimenopausal symp-
toms. The patient received relief when she went
on vacation, decreasing the amount of physical
work that she did with her violin as well as the
computer keyboard. Many patients with thoracic
outlet syndrome will notice that if they do any
type of strenuous work during the day, that
evening they will “pay the price.” The patients may Figure 96-4 Manual abductor pollicis brevis testing for
eventually realize that after a few days of a “lazy median nerve injury. Weakness manifests as a decreased
holiday,” their symptoms improve. ability to abduct the thumb, making it difficult to grasp
Controversy exists about thoracic outlet syn- a large object. Eventually an adduction deformity of the
thumb may result (ape hand). (From Saidoff DC,
drome, and in the past only patients with vascular McDonough AL. Critical Pathways in Therapeutic Inter-
compromise were considered to have this entity. vention: Upper Extremity. St. Louis, Mosby Yearbook,
Neurogenic thoracic outlet syndrome is much 1997, p 28.)

701
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

digitorum profundus, and the pronator quadra- patients can discriminate two points at 5 mm or
tus muscle. These patients may have specific greater at their fingertips). Group 3 patients (those
problems with pincer grip. The pronator quadra- with neurotmesis) are characterized by pro-
tus muscle can be tested with the elbow in flexion nounced thenar wasting. The thenar eminence can
and the forearm in pronation, while one stretches be easily evaluated by having the patient put his or
the pronator quadratus into extreme supination. her hands together in a “praying position.” There
7. Diabetic neuropathy. This usually manifests itself could be noted loss of thenar mass when compared
by symmetrical “stocking glove” distribution and with the opposite hand. These patients have poor
is caused by a decreased blood supply to the nerve prognosis regardless of treatment.
or the nerve trunks. It usually happens in the 9. Double crush syndrome. Double crush syndrome
lower extremities and would be rare to present was first described by Nakomis, who proposed
only in the upper extremities. that patients could become symptomatic with
8. Carpal tunnel syndrome. The most commonly nerve compression if the nerve was compressed at
entrapped nerve in the upper extremity is the multiple levels. One single site may not be suffi-
median nerve at the carpal tunnel. The nerve cient to cause the patient to have symptoms, but
enters the osteofibrous tunnel, which is dorsally when a second site is compressed, the patient may
and laterally bounded by the bony carpus and become symptomatic. This syndrome can explain
superiorly bounded by a thick transverse carpal why some patients continue to have symptoms or
ligament. The median nerve shares this tunnel will have recurrent symptoms after nerve decom-
with nine other flexor tendons covered by two lay- pression surgery. Although each site in isolation
ers of synovium. This syndrome often affects may not be sufficient to completely relieve symp-
patients between the ages of 40 and 60. toms or electrical diagnostic abnormalities, multi-
There can be a number of causes for this syn- ple compression sites may together produce these
drome: (1) increased volume of the tunnel content symptoms. Patients may be mislabeled with the
secondary to nonspecific tenosynovitis of the flexor diagnosis of somatization or malingering when in
tendon; (2) thickening or fibrosis of the transverse reality they have double crush syndrome. Figure
carpal ligament; (3) alteration of the margins of the 96-5 shows potential sites of “double crush” of the
carpus caused by fractures, dislocations, or arthritic median nerve. Figure 96-6 shows the most com-
changes; (4) tumors; or (5) systemic disease. This mon areas of nerve injury to the upper extremity.
patient has no history of any type of injury to her It is only through a thorough history and physical
wrist or any evidence that would make us think that examination that this entity can be diagnosed.
she has any type of tumor in her wrist.
The hallmark of this clinical syndrome is noc-
Clinical Course
turnal pain and paresthesia. The patients are often
awakened with a burning pain or tingling in their A radiograph of the patient’s cervical spine shows a
hand. It is relieved with shaking or wringing of rudimentary C7 cervical rib (Fig. 96-7). In addition
their hands. In some cases, the patient’s symptoms to this finding, the seventh spinous process is twice
can be relieved by running their hands under hot the length of the other spinous processes. At this time
or cold water. The median nerve has both sensori- the patient is diagnosed with double crush syndrome
motor branches, and usually the sensory abnor- because of her congenital abnormalities of her cervi-
malities are noted first. Later they progress into cal spine and her posture.
motor involvement, and clinical findings are pro- The patient is referred for physical and occupa-
portional to the degree of nerve damage. tional therapy. The occupational therapist reviews her
The clinical course of this disorder can be pre- workspace and helps her make some adjustments,
dicted by placing the patient into one of three such as repositioning her computer at her desk and
groups: those with neurapraxia, those with chair. The physical therapist recommends postural
axonotmesis, and those with neurotmesis. Group 1 re-education, selective muscle strengthening, and
patients (those with neurapraxia) would have mild selective soft-tissue stretching. The treatment plan
symptoms including weakness or clumsiness consists of a 90-day program aimed at controlling her
brought on by manual labor or by computer work. symptoms, restoration of shortened tissue, restora-
Symptoms are sporadic but increase over time, and tion of muscle balance, improvement of posture, and
there are usually no abnormal findings on clinical development of stress management techniques.
examination. Group 2 patients (those patients with The insurance company denies the physical
axonotmesis) often have burning pain in their therapist’s treatment plan and recommends that Tish
hands, and this is usually the major complaint. be evaluated by a neurologist. The neurologist
There may also be some thenar weakness and atro- repeats her electromyographic nerve conduction
phy, sensory loss, and loss of dexterity. These studies, which remain normal, and obtains a mag-
patients will lose two-point discrimination (most netic resonance imaging scan of the cervical spine.

702
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

NERVE GLIDING PROGRAM

For Median Nerve Decomposition at the Wrist

Exercises to be done__________times each,_________times a day.

Hold position to a count of_____________.

Starting position 1 Position 2 Position 3

Wrist in neutral, fingers Wrist in neutral, fingers and Thumb in neutral, wrist and
and thumb in flexion thumb extended fingers extended

Wrist, fingers, and thumb Same as position 4, with fore- Same as position 5, other hand
extended arm in supination (palm up) gently stretching
thumb

Position 4 Position 5 Position 6

Figure 96-5 Nerve-gliding exercises permit mobilization of the median nerve. (From Hunter JM, Schneider LH, Mackin
EJ, Callahan AD (eds): Rehabilitation of the Hand: Surgery and Therapy, 3rd ed. St. Louis, Mosby, 1990.)

The scan shows degenerative changes in the cervical toward the end of the work week. The patient is
spine but no evidence of any type of nerve root referred to a counselor with background in biofeed-
impingement or cord tumor. The neurologist agrees back techniques and is instructed on diaphragmatic
with the assessment of the physical therapist. The breathing exercises (Fig. 96-10). At the end of her
patient is instructed on the “rest position” for scapu- prescribed program, the patient continues to have
lar abduction and elevation (Fig. 96-8). The patient some intermittent symptoms but is very pleased with
is also instructed on cervical retraction exercises the result of the program. She describes her symp-
(Fig. 96-9) and a brachioplexus gliding program. The toms now as “manageable.”
occupational therapist advises the patient to switch
to a sports-type brassiere, which gives the patient Material Available on Student Consult
support without depressing her distal clavicle.
Review Questions and Answers about Double
In approximately 1 month, the patient’s symp- Crush Syndrome
toms improve, but she continues to have symptoms
703
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

The most frequently encountered

causes of damage at the
various sites are indicated
C5 and C6 Roots
Most frequently involved roots
C7 Root in cervical spondylosis.
By far the most frequent “acute cervical C7 involved occasionally.
disc lesion” occurs at this level. C6 Others very rarely
and C5 less often. Other levels very rarely
Axillary nerve
Fracture of humeral neck
Dislocation of the humerus
Intramauscular injections
Lower trunk of the brachial plexus
Cervical rib syndrome. Altered anatomy
(outlet syndrome). Pancoast tumor of
Radial nerve in spiral groove lung apex
Direct blow laterally. During
anesthesia medially. While drunk Radial nerve in the axilla
medially (“Saturday night palsy”). Incorrect use of a crutch
Fractures of the humerus-
immediate or delayed
Ulnar nerve
Radial nerve Damage from repeated minor trauma
(Posterior interosseus nerve) Prolonged bed rest
Nerve enters forearm through Delayed after fractures
supinator muscle. Occupational
overuse of muscle may damage
nerve. Also occurs idiopathically.
Median nerve
Extensors of thumb and index
At elbow. Rarely damaged by
finger mainly affected
direct trauma or fracture
(Anterior interosseus nerve)
Rarely damaged nerve lies very deep
Flexors of thumb and index finger are
affected by damage to nerve

Median nerve
(Carpal tunnel syndrome)
Nerve damaged by swelling of infiltration
of tunnel it transverses. Transiently seen
in pregnancy. Idiopathically in females.
Complicates rheumatoid arthritis.
Rarely seen in other systemic diseases

Ulnar nerve
(deep branch)
Trauma to heel of the hand. Idiopathically
(often a ganglion found on exploration)
No sensory loss in typical cases

Figure 96-6 Common sites of nerve injury in the upper extremity. (From Patten J. Neurologic Differential Diagnosis.
London, Springer-Verlag, 1996.)

704
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

Figure 96-7 Radiographs of the patient’s cervical spine show rudimentary C7 cervical rib.

Figure 96-8 Sitting rest position using a pillow to sup-

port the arm. (From Saidoff DC, McDonough AL. Critical
Pathways in Therapeutic Intervention: Upper Extremity.
St. Louis, Mosby Yearbook, 1997, p 226.)

705
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

A B C

Figure 96-9 Cervical retraction exercises. A, Poor technique: elevated chin. B, Poor technique: depressed chin. C, Good
technique. (From Saidoff DC, McDonough AL. Critical Pathways in Therapeutic Intervention: Upper Extremity. St. Louis,
Mosby Yearbook, 1997, p 227.)

16 inches

Figure 96-10 Rest position in supine. Pillows or use of a triangle foam wedge should be used to support the thoracic
spine, scapula, and arm. (From Saidoff DC, McDonough AL. Critical Pathways in Therapeutic Intervention: Upper
Extremity. St. Louis, Mosby Yearbook, 1997, p 230.)

706
 Chapter 96 Upper Extremity Numbness and Pain (Double Crush Syndrome)

SUGGESTED READINGS
Cherniack M, Warren N. Ambiguities in office-related Magee DJ. Orthopedic Physical Assessment, 2nd ed.
injury: The poverty of present approaches. Occup Med Philadelphia, WB Saunders, 1992.
1999;14:1–18● B Saidoff DC, McDonough AL. Critical Pathways in
Derebery VJ. Determining the cause of upper extremity Therapeutic Intervention: Upper Extremity. St. Louis,
complaints in the workpace. Occup Med Mosby Yearbook, 1997.● C
1998;13:569–582.●B
Kasdan ML. Occupational Hand and Upper Extremity
Injuries and Diseases, 2nd ed. Philadelphia, Hanley &
Belfus, 1998.●
A

707
 Index

Note: Page numbers followed by f indicate figures; those followed by t indicate tables; those followed by b indicate
boxed material.

A Acetaminophen with Codeine (Tylenol 3, Acyclovir, for varicella, 274, 276

AA (Alcoholics Anonymous), 676, 677 Tylenol 4), 211, 213t Adapalene (Differin), for acne, 454
AAFP (American Academy of Family Acetaminophen with hydrocodone Addiction, to opioids, 210, 216
Physicians), 33 (Lorcet, Lortab, Vicodin, Adenoma(s)
AAS (Abuse Assessment Screen), 83t Norco), 211, 215t parathyroid, 188–189
ABCDE rule, of melanoma, 483, 484, 484t, for chronic pain, 209, 213t toxic, hyperthyroidism due to, 416
485 for migraines, 501 Adenoma Prevention with Celecoxib
Abdomen Acetaminophen with oxycodone (APC) trial, 120
cost of imaging of, 173t (Percocet), 209, 211, 214t Adenomyosis
CT of, 174f, 175t Acetaminophen with tramadol (Ultracet), dysmenorrhea due to, 583
ultrasound of, 178t 211 vaginal bleeding due to, 615
Abdominal aortic aneurysm, 185 Acetowhite lesions Adenosine stress testing, for angina
Abdominal obesity, in metabolic on cervix, 627, 644, CP86–1, CP86–29 pectoris, 308
syndrome, 393f, 394–395, 395f, on vagina, 643, CP86–23, CP86–24 Adenosis, of posterior cul-de-sac of
399t on vulva, 642, CP86–8 vagina, CP86–18
case study on, 397–399 Acetylsalicylic acid (ASA). See Aspirin AD/HD. See Attention-
disease risk for, 394–395, 395t (acetylsalicylic acid, ASA). deficit/hyperactivity disorder
and free fatty acids, 392 Achilles tendon strain, 532 (AD/HD).
Abdominal pain ACIP (Advisory Committee on Adherence, 89
due to appendicitis, 361–363 Immunization Practices), 200 Adiposity, visceral, in metabolic
due to cholelithiasis, 359–365 Aciphex (rabeprazole), for GERD, 374 syndrome, 392, 393f, 394–395,
due to endometriosis, 577–580 Acne cosmetica, 452 395f, 399t
due to hypercholesterolemia, 324–340 Acne vulgaris, 451–454 case study on, 397–399
due to irritable bowel syndrome, case study on, 451–452 disease risk for, 394–395, 395t
366–370 differential diagnosis of, 452 and free fatty acids, 392
due to pancreatitis, 376–380 pathogenesis of, 453 Adjustment disorders, with anxiety, 662
Abductor pollicis brevis testing, 701f patient education on, 452 Adjuvant analgesics, 210, 216
ABFM (American Board of Family severity of, 453–454, 453t Adolescent patients
Medicine), 5 treatment of, 452, 453–454, 453t confidentiality with, 72
ABI (ankle/brachial index), 343, 344–345, Acoustic neuroma, 260 informed consent of, 73–74
344f Acral-lentiginous melanoma, 486t, 487, ADR(s). See Adverse drug reaction(s)
Abscess CP63–33––CP63–36 (ADRs).
mammary, 606 Actigall (ursodiol acid), for cholestasis, Adrenal crisis, 670–671
tubo-ovarian, 600, 601, 603f 256t Adrenal hyperplasia, congenital, short
Absolute risk, 67 Actigraphy, 248 stature due to, 559
Abuse, intimate partner. See Intimate Actinic keratoses, 117 Adrenal insufficiency, nail pigmentation
partner violence (IPV). Action tremor, 507 due to, 462
Abuse Assessment Screen (AAS), 83t Actiq (fentanyl), 209, 211, 213t, 215, 215t Adult Treatment Panel III (ATP III), 104
Academic health centers, role of family Acute myocardial infarction, vs. congestive Advance directives, 518, 521
medicine in, 25 heart failure, 316 Adverse drug reaction(s) (ADRs),
Acanthosis nigricans, 398, 398f Acute otitis media (AOM), 226–231 445–450
of nail, 462 case study on, 226–228 case study on, 445–448, 446f
Acarbose (Precose), for diabetes mellitus, defined, 228t classification of, 448–449, 449t
388 diagnosis of, 227, 228 to commonly used drugs, 448t
Accessibility, of family physician, 13 differential, 226–227, 226t defined, 448
Accutane (isotretinoin), for acne, 453t, natural history of, 230–231, 231t diagnosis of, 447, 449–450
454 patient education on, 227 differential, 447
ACE (angiotensin-converting enzyme) risk factors for, 229–230, 230t drugs that rarely cause, 449b
inhibitors treatment of, 227–229, 229t epidemiology of, 448
for congestive heart failure, 317, 318 Acute renal failure (ARF), 429–434 risk factors for, 449, 450b
for hypertension, 322, 323 case study on, 429–431 treatment of, 447–448, 450
for prevention of coronary heart defined, 431 Advicor (lovastatin-niacin), for
disease, 334t diagnosis of, 430, 431, 432 hypercholesterolemia, 336t, 337t
Acetaminophen, aspirin, and caffeine differential, 430, 431b Advil. See Ibuprofen (Motrin, Advil).
(Excedrin), for migraines, 501 epidemiology of, 432 Advisory Committee on Immunization
Acetaminophen (Tylenol), 211, 212t etiology of, 431b, 432–433, 433f, 434t Practices (ACIP), 200
adverse reactions to, 448t hyperkalemia in, 434 Afrin (oxymetazoline)
for osteoporosis, 587 treatment of, 430–431, 433–434, 434b for allergic rhinitis, 225
for otitis media, 228 Acute tubular necrosis (ATN), 432 rhinitis medicamentosa due to, 223

709
 Index

AGC (atypical glandular cells), 634–635 Alprazolam (Xanax), for anxiety Anemia (Continued)
Agoraphobia, 653, 676 disorders, 653, 666t causes of, 356t, 357–358
Agranulocytosis, due to antipsychotic ALT (alanine aminotransferase), 161, 162t of chronic disorders, 357
medications, 682t Alternative medicine. See Integrative classification of, 356
AIT (allergic immunotherapy), 225 medicine. due to decreased RBC production,
Akathisia, vs. restless legs syndrome, 492 Altoprev (lovastatin), for 357–358
Alanine aminotransferase (ALT), 161, 162t hypercholesterolemia, 336t, 337t defined, 356
Albendazole (Albenza), for giardiasis, 272 AMA (American Medical Association), 29, diagnosis of, 355
Albumin, serum, 159, 160t 30, 33, 71, 77 differential, 355
Albuterol Amantadine (Symmetrel) due to increased plasma volume, 358
for acute bronchitis, 290 for influenza, 280, 280t due to increased RBC destruction, 358
for acute exacerbation of COPD, 295 for Parkinson’s disease, 508 initial evaluation of, 358
Alcohol intoxication, delirium due to, Ambien (zolpidem), for insomnia, iron deficiency, 158
670 248–249 pruritus due to, 253t
Alcohol use Ambulatory visits, mean time for, 39 screening for, 128
benefits of, 109 American Academy of Family Physicians pernicious, 354–356
and cancer, 113 (AAFP), 33 in pregnancy, 548
and frostbite, 684 American Academy of General Practice, sideroblastic, 357
and injuries, 126 33 signs and symptoms of, 357–358
during pregnancy, 549 American Board of Family Medicine treatment of, 355
Alcohol withdrawal, delirium due to, (ABFM), 5 vitamin B12 deficiency, 354–356, 357
669–670 American Board of Family Practice, 5, 32, Aneurysm, aortic
Alcoholic hallucinosis, 680 33 abdominal, 185
Alcoholic pancreatitis, 378, 380 American Heart Association, 103, dissecting
Alcoholics Anonymous (AA), 676, 677 332t–335t chest pain due to, 307
Alcoholism, 108–110 American Medical Association (AMA), 29, imaging of, 185
vs. anemia, 355 30, 33, 71, 77 vs. pancreatitis, 378
epidemiology of, 108–109, 109f American Society of Colposcopy and Angina pectoris, 305–309
and health, 129 Cervical Pathology (ASCCP), case study on, 305–308
impact on family unit of, 110 621–622, 623t clinical manifestations of, 306–307
management of, 676, 677 Aminotransferases, 161, 162t defined, 307
prevention of, 109–111 Amitriptyline (Elavil) diagnosis of, 306–307, 308–309
screening for, 109–110 for fibromyalgia, 524 differential, 306–307, 306t
terminology for, 111f for pain, 216 vs. hypercholesterolemia, 327
Aldara (imiquimod 5% cream), for for prevention of migraines, 499 imaging of, 182–183, 183t, 308–309,
condyloma acuminata, 457, Amoxicillin 309t
457t, 459 for acute exacerbation of COPD, 295, pathogenesis of, 306
Alendronate, for osteoporosis, 589 296 treatment of, 307, 309
Alinia (nitazoxanide), for giardiasis, 272 for otitis media, 228, 229, 230t Angiography, 173f, 173t
Alkaline phosphatase (ALP), 160–161, for sinusitis, 283, 285, 285t cerebral, 173t
161t for streptococcal pharyngitis, 220t for transient ischemic attack, 179, 179f
Allegra (fexofenadine), for allergic Amoxicillin-clavulanate (Augmentin) coronary, 173t, 183
rhinitis, 225 for otitis media, 229, 230t magnetic resonance, 175t, 177
Allergic contact dermatitis, 450 for sinusitis, 285, 285t, 286 pulmonary, 173t, 185
pruritus due to, 251, 252t for streptococcal pharyngitis, 220t Angiokeratomas, CP63–24
Allergic disorders, 224 for UTI, 421 Angiomas, 486, CP63–23, CP63–24
Allergic immunotherapy (AIT), 225 Ampicillin Angioplasty, for peripheral arterial
Allergic interstitial nephritis, 433 for streptococcal pharyngitis, 220t disease, 343, 346
Allergic rhinitis (AR), 200, 222–225, 243, for UTI, 422t Angiotensin receptor blockers
283 Amputation for hypertension, 323
and asthma, 435–437 for frostbite, 686 for prevention of coronary heart
Allergic rhinosinusitis, and asthma, for peripheral arterial disease, 343, 346 disease, 334t
435–437 Amylase, serum, 164, 164t, 379 Angiotensin-converting enzyme (ACE)
Allergic shiners, 224 Amylin, synthetic, for diabetes mellitus, inhibitors
Allergy(ies) 388 for congestive heart failure, 317, 318
drug, 448–449 Amyloid A, serum, and coronary heart for hypertension, 322, 323
food, 135 disease, 330 for prevention of coronary heart
and immunization, 201 Anafranil (clomipramine), for generalized disease, 334t
Allergy shots, 225 anxiety disorder, 666t Animal dander, allergy to, 223, 224, 437
ALLHAT (Antihypertensive and Lipid Analgesic(s), 211–216, 212t–215t Anion gap, 154
Lowering Treatment to Prevent adjuvant, 210, 216 Ankle
Heart Attack Trial), 322 opioid, 210, 211–216, 213t–215t cost of imaging of, 173t
Allodynia, in fibromyalgia, 524–525 step 1, 211, 212t–213t radiographs of, 536–538, 538b
All-or-none therapies, 54 step 2, 211, 213t–214t Ankle fracture, 532, 536–538, 538b
Alosetron, for irritable bowel syndrome, step 3, 211–216, 213t–215t Ankle joint, septic, 532
370 Analgesic ladder, 210, 211f Ankle ligaments, 533, 534f
ALP (alkaline phosphatase), 160–161, 161t Anaphylaxis, due to contrast agent, 172, Ankle sprain, 531–538
Alper, Brian, 58 174 case study on, 531–533
Alpha Tocopherol Beta-Carotene (ATBC) Anastrozole, for breast cancer, 612t diagnosis of, 532, 533–536, 535f–537f
trial, 114 Anemia, 354–358 differential, 532
α-fetoprotein test, 550 case study on, 354–356 epidemiology of, 533

710
 Index

Ankle sprain (Continued) Anxiety disorder(s) (Continued) ASD (autistic spectrum disorder), 562,
grading of, 536, 537t diagnosis of, 651, 652, 653, 663 563, 563t, 564
mechanism of, 533, 535f criteria for, 651, 651b, 656, 660b ASP (application service provider) system,
patient education on, 533 differential, 651, 652, 656–662, 661t, 145
treatment for, 532–533, 538 662b Aspartate aminotransferase (AST), 161,
Ankle syndesmosis injury, 532, 533–535, psychological screening in, 656, 162t
536f, 537f 657t–660t Asperger’s syndrome, 563t
Ankle/brachial index (ABI), 343, 344–345, due to general medical condition, Aspiration, of foreign body, 244
344f 656–661, 661t Aspirin (acetylsalicylic acid, ASA), 211,
Anonymity, collusion of, 9–10 management of, 652–653, 663–667 212t
Anorectal gonorrhea, 593 pharmacologic, 652–653, 662, adverse reactions to, 448t
Ansaid (flurbiprofen), 212t 665–667, 666t for migraines, 501
Antacids, for GERD, 374 psychosocial, 652, 663–665, for peripheral arterial disease, 343, 345,
Anterior cruciate ligament tear, 191, 192f 663b–665b 345t
Anterior drawer test, 533, 535f prevalence of, 662 for polycythemia vera, 256t
Anterior inferior tibiofibular ligament, 534f resources on, 665b for prevention of colorectal cancer, 120
Anterior interosseous nerve injury, 704f social, 653 for prevention of coronary heart
Anterior interosseous syndrome, 701–702 substance-induced, 662 disease, 334t
Anterior talofibular ligament (ATFL), 533, types of, 651, 653–654 for prevention of myocardial infarction,
534f, 535f AOM. See Acute otitis media (AOM). 104
Anthracyclines, for breast cancer, 612 Aorta, angiogram of, 173f for prevention of stroke, 335t
Antianxiety medications, 652–653 Aortic aneurysm Assisted suicide, 77–78
Antibody testing, in pregnancy, 548–549, abdominal, 185 AST (aspartate aminotransferase), 161,
551 dissecting. See Aortic dissection. 162t
Anticholinergic bronchodilators, for acute Aortic dissection Asthma, 435–444
exacerbation of COPD, 295, 296 chest pain due to, 307 allergic rhinitis and, 435–437
Anticholinergic drugs, for Parkinson’s imaging of, 185 case study on, 435–437
disease, 508 vs. pancreatitis, 378 vs. COPD, 294, 294t
Anticholinergic symptoms, of APC (Adenoma Prevention with cough due to, 242–245
antipsychotic medications, 682t Celecoxib) trial, 120 cough-variant, 243
Anticipatory anxiety, 676 Apolipoprotein A, and coronary heart defined, 437
Anticonvulsants, for restless legs disease, 329 diagnosis of, 436, 437, 438, 444f
syndrome, 495t, 496 Apolipoprotein B, and coronary heart pathogenesis of, 437–438
Antidepressants disease, 329 treatment of, 437, 438–444
for anxiety disorders, 653, 662, 665, Appendicitis in adults and older children, 438,
666t vs. cholelithiasis, 361–362 440t–441t
for bedwetting, 427 imaging of, 186–187 medications in, 442t, 443t
for depression, 647 Appendicolith, 186–187 in young children, 438, 439t–440t
for pain, 216 Application service provider (ASP) Astrocytomas, 515
for prevention of migraines, 499, 502t system, 145 Atarax (hydroxyzine HCl)
Antigenic drift, 278–279 Appointment reminders, and compliance, for allergic rhinitis, 225
Antihistamines 95, 96 for drug reaction, 447
for acute bronchitis, 290 Apprentice model, 52 ATBC (Alpha Tocopherol Beta-Carotene)
for allergic rhinitis, 225 AR (allergic rhinitis), 200, 222–225, 243, trial, 114
for drug reaction, 450 283 Atenolol, for atrial fibrillation, 313
Antihypertensive and Lipid Lowering and asthma, 435–437 ATFL (anterior talofibular ligament), 533,
Treatment to Prevent Heart ARF. See Acute renal failure (ARF). 534f, 535f
Attack Trial (ALLHAT), 322 Aripiprazole, for schizophrenia, 682 Athletic physical examinations, 71
Antihypertensive medications, for Aristocort (triamcinolone acetonide) Ativan (lorazepam), for anxiety disorders,
prevention of migraines, 502t for asthma, 443t 653, 666t
Anti-inflammatory diet, 135, 136b for drug reaction, 447–448 ATN (acute tubular necrosis), 432
Antimetabolites, for breast cancer, 612 Arm laceration, repair of, 539–545, Atomoxetine, for AD/HD, 570
Antioxidant supplements, and 541f–544f Atopic dermatitis
cardiovascular disease Arrhythmia vs. drug reaction, 447
prevention, 335t due to antipsychotic medications, 682t pruritus due to, 250, 251, 252t, 256
Antipsychotic medications, 680, 681–682 vs. heat stroke, 688 Atopic disorders, 224
side effects of, 682, 682t Artane (trihexyphenidyl), for Parkinson’s Atopic eczema, 250, 251
Antireflux surgery, 375 disease, 508 Atorvastatin (Lipitor), for
Antiseizure medications, for prevention of Arthritis hypercholesterolemia, 330–331,
migraines, 502t of elbow, 529 336t, 337t
Antitubulin agents, for breast cancer, 612 osteo-, vs. intermittent claudication, 342 ATP III (Adult Treatment Panel III), 104
Antitussives, 289, 290 ASA (acetylsalicylic acid). See Aspirin Atrial fibrillation, 310–313
Anxiety (acetylsalicylic acid, ASA). cardiac conditions seen with, 311
adjustment disorders with, 662 ASCCP (American Society of Colposcopy case study on, 310–312
anticipatory, 676 and Cervical Pathology), diagnosis of, 311–312
vs. cholelithiasis, 362 621–622, 623t differential, 311, 311b
in palliative care, 520t ASC-H (atypical squamous cells, cannot epidemiology of, 312
Anxiety disorder(s), 650–654, 655–667 exclude HSIL), 634, 635 in hyperthyroidism, 415–416
case studies on, 650–652, 654, 655–662 ASC-US (atypical squamous cells of noncardiac associations for, 311
clinical presentation of, 663 undetermined significance), paroxysmal, 311
comorbidity with, 663 621, 623t, 624t, 634, 635 permanent, 311

711
 Index

Atrial fibrillation (Continued) Ayre, J. Ernest, 629 Benign paroxysmal positional vertigo, 259,
persistent, 311 Ayurveda, 140b 261–262
and risk of stroke, 311–312, 312t, Azelaic acid (Azelex), for acne, 453t, 454 Benzathine penicillin, for streptococcal
334t–335t Azithromycin (Zithromax) pharyngitis, 220t
treatment of, 312–313 for Chlamydia, 593, 593b Benzocaine (Auralgan), for otitis media,
Atrial Fibrillation Follow-up Investigation for otitis media, 229t 228
of Rhythm Management trial, for pelvic inflammatory disease, Benzodiazepines
313 599–600 for anxiety disorders, 652–653, 666t,
Atrial flutter for sinusitis, 285t 667
in hyperthyroidism, 415–416 for streptococcal pharyngitis, 220t for insomnia, 248
with variable block, 311 Azotemia, prerenal, 432 for panic disorder, 676, 677
Atrial tachycardia, multifocal, 311 for restless legs syndrome, 495t, 496
Atrophic vaginitis, 615 B Benzoin, for laceration repair, 544
Atrovent (ipratropium bromide) Babesiosis, 469t Benzonatate (Tessalon), for acute
for acute exacerbation of COPD, 295 Back pain bronchitis, 290
for vasomotor rhinitis, 223 differential diagnosis of, 587 Benzoyl peroxide, for acne, 452, 453t, 454
Attendance, monitoring of, 92, 95 imaging for, 179–180, 180f, 181f Benztropine (Cogentin), for Parkinson’s
Attention-deficit/hyperactivity disorder due to metastatic cancer, 209 disease, 508
(AD/HD), 566–572 due to osteoporosis, 586–589 Bereavement support, 518, 519, 521
case study on, 567–568, 570–572 Bacterial endocarditis, 465, 467t Berry, Henry, 57
comorbid conditions with, 568, 568b Bacterial infection, serious, in children Best evidence sources, 50, 57
diagnosis of, 568–570, 568b fever due to, 237, 239, 240–241 Beta-agonists, for acute bronchitis, 290
epidemiology of, 568 vaccines and, 240–241 Beta2-agonists
vs. learning disabilities, 569, 569b Bacterial pharyngitis, 218–219, 219t for acute exacerbation of COPD, 295,
pathogenesis of, 568 Bacterial vaginosis, 591, 592, 592b 296
rating scales for, 568–569, 568b, 570 Bacteriuria, occult, during pregnancy, 550 for asthma, 439t–442t
resources for parents on, 569, 569b Bactrim. See ß-blockers
treatment of, 569, 570, 571–572 Trimethoprim/sulfamethoxazole adverse reactions to, 448t
Attributable risk, 67–68, 67t, 68t (Bactrim). for congestive heart failure, 316–317, 318
Atypical glandular cells (AGC), 634–635 Baker’s cyst, vs. deep venous thrombosis, for hypertension, 323
Atypical moles, 485, 485t, 350t for prevention of coronary heart
CP63–12––CP63–17 Balanitis, 381–383 disease, 334t
Atypical nevi, 485, 485t, Balint, Michael, 9 Betadine (povidone-iodine), for laceration
CP63–12––CP63–17 Bandolier, 63t repair, 541
Atypical squamous cells, cannot exclude Barium enema, 173t ß-lactam antibiotics, adverse reactions to,
HSIL (ASC-H), 634, 635 Barium esophagogram, 187, 187f 448t
Atypical squamous cells of undetermined Barium swallow, 187, 187f Bethesda system, 621, 622t, 623t, 627,
significance (ASC-US), 621, Barrett’s esophagus, 375 628t–630t, 630, 634–635
623t, 624t, 634, 635 Basal cell carcinoma, 472–476 Bedwetting, 423–427
Auditory hallucinations, in schizophrenia, case study on, 473–475 case history on, 423–426
679 cryosurgery for, 474–476, 472f complex or complicated, 424
Augmentin. See Amoxicillin-clavulanate complications and side effects of, diagnosis of, 424, 425
(Augmentin). 474–475, 475t differential, 425, 425b
Auralgan (benzocaine), for otitis media, contraindications to, 475t epidemiology of, 424, 424t
228 efficacy of, 473, 473t patient education on, 425, 427
Authority, deferral to, 52 skin care after, 474b primary, 424
Autism, 561–565 tumor selection for, 476 secondary, 424
behaviors associated with, 563, 563b diagnosis of, 472–474, 472f treatment of, 425–426, 426f, 427
case study on, 561–563 Basal ganglia disease, tremor with, 507 Bias(es), 69
defined, 563, 563t BATHE model, 42 healthy user, 66
developmental “red flags” for, 564b BCT (breast conservation therapy), selection, 56
diagnosis of, 562–563, 564, 564b 609–610 Biaxin (clarithromycin), for otitis media,
differential, 562 Beclomethasone 229t
epidemiology of, 563–564 for asthma, 443t Bifurcate ligament, 534f
and epilepsy, 565 for chronic cough, 244 Biggs, Walter D., 31
genetics and neuroanatomy of, 564 Behavior change, for metabolic syndrome, Biguanides, for diabetes mellitus, 385, 386,
online resources on, 566 400, 401t 387t
patient education on, 563 Behavior change strategies, to improve Biliary colic, 364
treatment of, 563, 565 compliance, 90, 91t vs. pancreatitis, 377
Autistic disorder, 563t Behavior change visit, 41t, 42–43, 42t, 44t, Biliary tract disease, vs. GERD, 372–373
Autistic spectrum disorder (ASD), 562, 45t Biliary tract obstruction, imaging of, 186
563, 563t, 564 Behavior problem, due to autism, 561–563 Bilirubin, 161–162, 163t
AutoCyte Prep, 631 Behavioral modification conjugated (direct), 162
Aventyl (nortriptyline) for AD/HD, 570, 571 unconjugated (indirect), 162
for generalized anxiety disorder, 666t for autism, 563, 565 Biopsy
for pain, 216 Benadryl (diphenhydramine) breast, 606, 608
for smoking cessation, 290 for allergic rhinitis, 222, 225 cervical, 635, 644
Avita (tretinoin), for acne, 452, 454 with contrast agents, 174 endometrial, 617–618, 618t
Axillary nerve injury, 704f for varicella, 274 for pelvic inflammatory disease, 599
Axillary node dissection, for breast cancer, Benign juvenile melanoma, 486, of melanoma, 487
608–609 CP63–19 of thyroid nodule, 188

712
 Index

Biopsy forceps, for colposcopy, 637–641, Breast cancer, 605–613 CAGE questionnaire, 110
641f case study on, 605–606 for alcohol, 655, 656b
Biostatistics, 53–54 diagnosis of, 605–606, 608 for drugs, 647, 647b
Biphasic-pattern kinesia, with levodopa, differential, 606 Calcaneofibular ligament (CFL), 533,
509 early invasive, 613 534f, 535f
Bipolar disorder, 680 epidemiology of, 118, 193, 606–607, Calcitonin, for osteoporosis, 587, 589
Bisphosphonates, for osteoporosis, 587, 607f, 607t, 608f Calcium, for osteoporosis, 587, 589
589 follow-up surveillance for, 613 Calcium channel blockers, for
Bizarre behavior, due to schizophrenia, in situ, 613 hypertension, 323
678–681 inflammatory, 613 Calcium intake, and osteoporosis, 122
Black widow spider bites, 694–695, 694f, locally advanced, 613 Calcium levels, 155–156, 156t
695t metastatic, 613 Calf muscle pull or tear, vs. deep venous
Blackhead, 453 prevention of, 118–119, 193–194, 193f, thrombosis, 350t
Black-pigment gallstones, 364, 364f 194f Callus, 478
Bladder cancer, 121 risk factors for, 113, 118, 607, 609b CAM (Confusion Assessment Method),
vs. UTI, 419, 420 screening for, 118, 193–194, 193f, 194f, 672, 672b
Bladder capacity, 425 607–608, 609b, 613 CAM (complementary and alternative
Bladder-retention training, 425 staging of, 606, 608–609, 610t, 611b, 611f medicine). See Integrative
Blastomycosis, North American, 467t survival rate with, 607, 608t, 609f medicine.
Bleeding, vaginal treatment of, 606, 609–613, 612t Canadian Task Force on Preventive Care,
postmenopausal, 614–616 Breast conservation therapy (BCT), 63t
during third trimester, 573–576 609–610 Cancer, 110–121
Blood cell tests, 148–152, 149t–151t Breast examination, clinical, 607, 609b bladder, 121
Blood pressure Breast imaging, 193–194, 193f, 194f vs. UTI, 419, 420
classification of, 321–322 Breast tenderness, due to pregnancy, breast. See Breast cancer.
high. See Hypertension. 546–547 cervical. See Cervical cancer.
and hypercholesterolemia, 333t Breslow’s depth of invasion number, for childhood, 121
measurement of, 321 melanoma, 487 colorectal, 119–120
normal, 322 Bromocriptine, for Parkinson’s disease, hereditary nonpolyposis, 617
Blood pressure screening, 104 508 defined, 113
Blood typing, in pregnancy, 548, 551 Bronchiectasis, vs. COPD, 294–295, 294t endometrial. See Endometrial cancer.
Blood urea nitrogen (BUN), 166 Bronchiolitis, obliterative, vs. COPD, 294t, epidemiology of, 110, 111f, 112f
Bloodletting, 28, 29 295 lung, 113–115, 114f, 115f
“Bloody show,” 574 Bronchitis, acute, 287–291 hiccups due to, 232–235
BNP (brain natriuretic peptide), in case study on, 287–289 oral, 121
congestive heart failure, 316, 318 cigarette smoking and, 287, 288, ovarian, 119
Body mass index (BMI), 395t 289–290 pancreatic, 120–121
Bodywork, therapeutic, 137–138 diagnosis of, 288–289 prevention of, 113
Boerhaave, Hermann, 28, 35 differential, 288 prostate, 117
Bone age, and short stature, 556, 557t etiology of, 289 risk factors for, 113
Bone marrow disorders, anemia due to, treatment of, 289–290 skin, 116–117. See also Basal cell
355, 358 Bronchodilators, for acute exacerbation of carcinoma; Melanoma.
Bone mineral density, 122 COPD, 295, 296 testicular, 120
in osteoporosis, 588 Bronchoprovocation, 243 thyroid, 121
Bone scan, 189 Bronchoscopy, fiberoptic, 185 weight loss due to, 414
cost of, 178t Brown recluse spider bites, 692–694, 692f, Cancer pain, 209–216, 211f, 212t–215t
Bony articular injuries, of elbow, 528 693f, 693t Candida albicans, vaginal discharge due
Bowel movements, loose, due to Brown-pigment gallstones, 364 to, 591
hypercholesterolemia, 324–340 Bryson, J. Gordon, 31 Candida albicans antigen, for plantar
Boyd, William, 139 Budesonide, for asthma, 443t warts, 479, 480–481, 481f
Brachioradial pruritus, 253t Buerger’s disease, vs. intermittent Candida glabrata, vaginal discharge due
Brachytherapy, for breast cancer, 613 claudication, 343 to, 591
Brain Bullous pemphigoid, pruritus due to, 252t Candida tropicalis, vaginal discharge due
fetal, imaging of, 182, 182f BUN (blood urea nitrogen), 166 to, 591
MRI of, 176f Bupropion (Zyban), for smoking Candidiasis
Brain natriuretic peptide (BNP), in cessation, 290 due to diabetes mellitus, 381–383
congestive heart failure, 316, Burnham, Clara, 30 disseminated, 466t
318 Buspirone (BuSpar), for anxiety disorders, vulvovaginal
Brain tumor(s), 511–516 653, 665–667, 666t case study on, 590–591
case study on, 511–513 Butorphanol (Stadol), 215 complicated, 592
diagnosis of, 511, 513–515, 514f, 515b Byetta (exenatide), for diabetes mellitus, diagnosis of, 591–592
differential, 512 388 differential, 591–596
metastatic, 513 Bypass, for peripheral arterial disease, 343, treatment for, 592
imaging of, 181, 181f, 182f 346 Capecitabine, for breast cancer, 612, 612t
primary, 513 Capsaicin cream (Zostrix), for pruritus
prognosis for, 516 C due to notalgia paresthetica, 256t
treatment for, 511–512, 514f, 515–516, C-125 tumor marker, 119 due to uremia, 256t
515b Cable, George Washington, 30 Captopril renal study, 192
BRCA1, 118, 119, 607 CAD (coronary artery disease) Carafate (sucralfate), for GERD, 374
BRCA2, 118, 119, 607 vs. congestive heart failure, 316 Carbamazepine, for restless legs
Breast biopsy, 606, 608 imaging of, 182–183, 183t syndrome, 496

713
 Index

Carbidopa/levodopa (Sinemet) Celiac disease, vs. irritable bowel Cervical nerve root injuries, 704f
for Parkinson’s disease, 509 syndrome, 367 Cervical polyps
for restless legs syndrome, 495, 495t Cellulitis, vs. deep venous thrombosis, dysmenorrhea due to, 583
Carbohydrate counting, for diabetes 350t vaginal bleeding due to, 615
mellitus, 384, 386t Central nervous system (CNS) diseases, Cervical retraction exercises, for double
Carbon dioxide (CO2) content, 154–155, delirium due to, 670 crush syndrome, 703, 706f
155t Central nervous system (CNS) infection, Cervical rib syndrome, 704f
Carcinoid, malignant, pruritus due to, delirium due to, 669 Cervical spine, nerve root entrapment of,
253t Central nervous system (CNS) lesions, vs. vs. double crush syndrome, 700
Cardiac arrhythmia double crush syndrome, Cervical spondylolysis, vs. double crush
due to antipsychotic medications, 698–700 syndrome, 700
682t Cephalexin (Keflex) Cervical stenosis, dysmenorrhea due to,
vs. heat stroke, 688 for drug reaction, 448 583
Cardiac catheterization, for angina for streptococcal pharyngitis, 220t Cervicitis, vaginal bleeding due to, 615
pectoris, 307, 309 Cephalosporin, for UTI, 421 Cervix
Cardiac disease. See Cardiovascular Cerebellar tremor, 507 colposcopy of, 643–644, 644t, CP86–1,
disease (CVD). Cerebral angiography, 173t CP86–25––CP86–35
Cardiac dysrhythmia Cerebral artery, middle, angiogram of, leukoplakia of, 627, CP86–30
due to antipsychotic medications, 682t 179f mosaicism of, 644, CP86–32, CP86–33
vs. heat stroke, 688 Cerebral infarction. See Stroke. Nabothian cysts of, 644, CP86–31
Cardiac ischemia, vs. heat stroke, 688 Cerebral metastases, 513 punctation of, 644, CP86–32
Cardiac rehabilitation, for imaging of, 181, 181f, 182f squamocolumnar junction of, 643,
hypercholesterolemia, 332t–333t Cerebral tumors, imaging of, 181, 181f, CP86–28
Cardiac stress testing, 182, 183t 182f squamous epithelium of, CP86–27
Cardiovascular disease (CVD) Cerebrovascular accident. See Stroke. transformation zone of, 621, 631, 632f,
anxiety due to, 651 Certification, maintenance of, 5 643–644, CP86–26
in hyperthyroidism, 416 Cervical biopsy, 635, 644 Cesarean delivery, for placenta previa, 575,
metabolic syndrome and, 395–396, 399 Cervical cancer 576
and stroke, 106 colposcopy of, CP86–34 Cetirizine (Zyrtec), for allergic rhinitis,
Cardiovascular imaging, 182–185, 183t, condyloma acuminata and, 458, 459 225
185f epidemiology of, 115 CFL (calcaneofibular ligament), 533, 534f,
Cardioversion, for atrial fibrillation, 312, impact on family of, 116 535f
313 prevention of, 115–116 CGD. See Constitutional growth delay
ß-Carotene and retinol efficacy trial progression from dysplasia to, 635 (CGD).
(CARET), 114 risk factors for, 115–116, 630–631, 630t Chadwick’s sign, 547
Carotid bruits, and stroke, 107, 108 screening for, 116, 620–625 Charisma, of family physician, 13
Carpal tunnel syndrome, 702, 704f case study on, 620–621, 625 CHD. See Coronary heart disease (CHD).
Case-control studies, 65 HPV testing in, 621–622, 623t, 634 Checklist for Autism in Toddlers,
CAST study, 55–56 intervals for, 622–625, 624t, 633–634 562–563, 564
Cat dander, allergy to, 223, 224 Pap smear in, 621, 622t, 623t, Checkup visit, 41t, 42, 42t, 44t, 45t
Cataflam (diclofenac), 212t 629–630 Chemical dependency. See Drug
Catapres (clonidine), for smoking vaginal bleeding due to, 615 dependency.
cessation, 290 Cervical collar, 644 Chemotherapy, for breast cancer, 606,
CBD (common bile duct) stones, 361, Cervical dysplasia, 626–644 610–612, 612t
365 Bethesda guidelines for, 627, 628t–629t, neoadjuvant, 612
CCR (Continuity of Care Record), 634–635 Cherry angiomas, 486, CP63–23
144–145, 144b case study on, 626–629, CP86–1 Chest CT, 175t
Cefdinir (Omnicef) and cervical cancer, 635 Chest pain
for otitis media, 229t colposcopy of, 627, 636–644, 644t, due to angina pectoris, 305–309
for sinusitis, 286 CP86–1, CP86–35 due to anxiety disorder, 650–652
Cefixime (Suprax), for gonorrhea, 594b case study on, 627 differential diagnosis of, 306–307,
Cefotaxime (Claforan), for gonorrhea, equipment for, 636–641, 640f, 641f 306t
594b forms for, 636b–639b Chest radiography
Cefotetan (Cefotan), for pelvic procedure for, 641–644, 642t–644t cost of, 173t
inflammatory disease, 595t, 600t cryotherapy for, 629 in infants and children, 239
Cefoxitin (Mefoxin), for pelvic cytologic screening method for, CHF. See Congestive heart failure (CHF).
inflammatory disease, 595t, 600, 631–633, 631f, 632f Chicken pox. See Varicella.
600t human papillomavirus and, 630–631, Chilblain, 685
Cefpodoxime (Vantin) 631t Child(ren)
for otitis media, 229t Pap smears and, 629–630, 630t, cancer in, 121
for sinusitis, 285, 286 633–634 exposed to intimate partner violence
Ceftriaxone (Rocephin) management of results of, 627–629, health effects on, 81, 82, 82t
for gonorrhea, 594b 635–636 management of, 86
for otitis media, 229, 229t, 230t unsatisfactory, 635 genital warts in, 459–460, 460f
for pelvic inflammatory disease, 595t risk factors for, 630–631, 630t, 631t hypercholesterolemia in, 339
Cefuroxime (Ceftin), for otitis media, 229t Cervical intraepithelial neoplasia (CIN), serious bacterial infection in
Ceiling effects, of analgesics, 211 115, 621, 627–629, 630, 630t, fever due to, 237, 239, 240–241
Celecoxib (Celebrex), 212t 635, CP86–29 vaccines and, 240–241
in prevention of colorectal cancer, 120 Cervical ligament, 534f Child abuse/neglect
Celexa (citalopram), for generalized Cervical nerve root entrapment, vs. mandatory reporting of, 86–87
anxiety disorder, 666t double crush syndrome, 700 prevalence of, 83

714
 Index

Childhood disintegrative disorder, 563t Chronic fatigue syndrome, 525 Clonazepam (Klonopin)
Childhood nocturnal enuresis. See Chronic illness, 10 for generalized anxiety disorder, 653,
Bedwetting. Chronic illness visit, 41t, 42, 42t, 44t, 45t 666t
Chinese medicine, 140b Chronic obstructive pulmonary disease for restless legs syndrome, 495t, 496
Chiropractic, 137, 138b (COPD) Clonidine (Catapres), for smoking
Chlamydia acute exacerbation of, 293–296 cessation, 290
diagnosis of, 593 case study of, 293–295 Clopidogrel
epidemiology of, 123, 592 diagnosis of, 294–296 for peripheral arterial disease, 345t
screening for, 123, 124, 593 differential, 294–295, 294t for prevention of coronary heart
treatment of, 593, 593b treatment of, 295, 296, 297f disease, 334t
vaginal discharge due to, 591, 592–593, vs. congestive heart failure, 316 Clorazepate (Tranxene), for generalized
593b long-term management of, 296, 298t anxiety disorder, 666t
Chlamydia testing, during pregnancy, 549 Chronic pelvic pain, 578, 578t Clozapine, for schizophrenia, 682
Chlamydia trachomatis, 592, 593 due to pelvic inflammatory disease, 604 Clue cells, 592
pelvic inflammatory disease due to, 598 Chronic systemic illness, short stature due Clumsiness, due to brain tumor, 511–513
Chlordiazepoxide (Librium), for to, 559 Cluster headache, 502–503
generalized anxiety disorder, CI (confidence interval), 67 CNS (central nervous system) diseases,
666t Cigarette smoking delirium due to, 670
Chlorhexidine gluconate (Hibiclens), for and acute bronchitis, 287, 288, CNS (central nervous system) infection,
laceration repair, 541 289–290 delirium due to, 669
Chloride levels, 154, 154t and cancer, 113 CNS (central nervous system) lesions, vs.
Chlorpromazine, for schizophrenia, 682 cervical, 631 double crush syndrome,
Choice in Dying, 77 lung, 113, 114, 114f, 115f 698–700
Cholangiography, 185 and coronary heart disease, 104 CO2 (carbon dioxide) content, 154–155,
percutaneous transhepatic, 186 epidemiology of, 114, 114f, 115f 155t
Cholangiopancreatography and frostbite, 684 Coagulopathy
endoscopic retrograde, 183t, 185, 186 and health, 129 in Cushing’s syndrome, 406
for cholelithiasis, 363 impact on family unit of, 114–115 in metabolic syndrome, 400
magnetic resonance, 185, 186 during pregnancy, 549 “Co-alcoholic,” 110
for cholelithiasis, 363 and stroke, 107, 108 Cocaine use, 645–647, 648
Cholecystectomy, laparoscopic, for Cilostazol (Pletal), for peripheral arterial Coccidioidomycosis, 467t
cholelithiasis, 363, 365 disease, 343, 345, 345t Cochrane, Archie, 54
Cholecystitis CIN (cervical intraepithelial neoplasia), Cochrane Collaboration, 54
acalculous, 363 115, 621, 627–629, 630, 630t, Cochrane Database, 63t
imaging of, 186 635, CP86–29 Cochrane Library, 50
vs. pancreatitis, 377 Ciprofloxacin (Cipro) Cochrane Reviews, 54, 62
Cholecystogram, 185 for gonorrhea, 594b Code of medical ethics, 29
Choledocholithiasis, 361, 365 for UTI, 422t Codeine, 211, 213t, 215t
Cholelithiasis, 359–365 Citalopram (Celexa), for generalized Coenzyme Q10, for Parkinson’s disease,
black-pigment, 364, 364f anxiety disorder, 666t 508
brown-pigment, 364 Claforan (cefotaxime), for gonorrhea, Cogentin (benztropine), for Parkinson’s
cholesterol, 364, 364f, 365f 594b disease, 508
complications of, 364 Clarithromycin (Biaxin), for otitis media, Cognitive deficits
diagnosis of, 360–363, 364–365 229t in Cushing’s syndrome, 406
differential, 361–363, 361b, 364–365 Claritin (loratadine) in schizophrenia, 681
epidemiology of, 363–364 for allergic rhinitis, 225 Cognitive strategies, for stress reduction,
imaging of, 185 for varicella, 274 664b
vs. irritable bowel syndrome, 367 Clark levels, for melanoma, 487 Cognitive-behavioral therapy
natural history of, 364 Claudication, intermittent, 341–346 for generalized anxiety disorder, 652
pathogenesis of, 364 case study on, 341–343 for panic disorder, 676, 677
risk factors for, 362b clinical presentation of, 343, 344 for schizophrenia, 682
treatment of, 363, 365 defined, 342 “Cogwheel rigidity,” 508
Cholestasis, pruritus due to, 251–252, diagnosis of, 342–343, 344–345, 344f Cohen, Matthew, 569
253t, 256t differential, 342–343, 342t Cohort studies, 65–66
in pregnancy, 254–255 pathogenesis of, 343 Cold, common, 283
Cholesterol risk factors for, 343–344, 343t, 345t Cold hands and feet, due to frostbite,
optimal levels of, 333t treatment of, 343, 345–346, 345t, 683–686
screening for, 102–103 346f “Cold” nodule, 188
testing for, 327, 328 Clindamycin (Cleocin) Colestipol, for hypercholesterolemia, 331
Cholesterol control, 103, 104 for acne, 453t, 454 Colic, biliary, 364
Cholesterol gallstones, 364, 364f, 365f for bacterial vaginosis, 592, 592b vs. pancreatitis, 377
Cholestyramine (Questran) for otitis media, 229, 229t, 230t Colitis
for cholestasis, 256t Clinical breast examination, 607, 609b ischemic, irritable bowel syndrome and,
for hypercholesterolemia, 331 Clinical epidemiology, 54–55 370
Choline magnesium trisalicylate Clinical Evidence, 50 ulcerative, vs. irritable bowel syndrome,
(Trilisate), 212t Clinical Inquiries, 51, 58, 62, 64t 367
Chromosomal disorders, short stature due Clinical significance, 67–68, 68t, 69 Collateral ligament injury, medial, 528
to, 560 Clinoril (sulindac), 213t Collusion of anonymity, 9–10
Chronic disease adverse reaction to, 445–448, 446f Colon cancer, vs. irritable bowel
anemia of, 357 Clomipramine (Anafranil), for generalized syndrome, 367
weight loss due to, 415 anxiety disorder, 666t Colonography, CT, 120, 174–175

715
 Index

Colonoscopy, for prevention of colorectal Computerized appointment systems, 96 Coordination of care, for terminal illness,
cancer, 120 Concealed allocation, 49 518, 519
Color flow Doppler ultrasound, 177 Concordance, 89 Coordinator, family physician as, 14–15
Colorectal cancer Condyloma acuminata, 455–460 COPD. See Chronic obstructive
epidemiology of, 119 case study on, 456–459 pulmonary disease (COPD).
hereditary nonpolyposis, 617 and cervical cancer, 458, 459 “Core Content of Family Medicine, The,”
prevention of, 119–120 in children, 459–460, 459f 33
screening for, 120 diagnosis of, 456–457, 456f Corn, 478
Colposcope, 636, 640f differential, 456–457, 457f Coronary angiography, 173t, 183
Colposcopy, 636–644 epidemiology of, 459 Coronary arteriography, for angina
case study on, 627, CP86–1 of introitus, CP86–10 pectoris, 309
of cervix, 643–644, 644t, CP86–1, pathogenesis of, 459 Coronary artery catheterization, for
CP86–25––CP86–35 patient education on, 458–459 angina pectoris, 307, 309
equipment for, 636–641, 640f, 641f treatment of, 457–458, 457t, 458f, 459 Coronary artery disease (CAD)
examination form for, 636, 639b of vagina, CP86–21 vs. congestive heart failure, 316
informed consent for for, 636, 637b Condyloma lata, 456 imaging of, 182–183, 183t
patient information sheet on, 636, Condylox (podofilox 0.5% solution or Coronary atherosclerosis, chest pain due
636b gel), for condyloma acuminata, to. See Angina pectoris.
patient intake form for, 636, 638b 457, 457t, 459 Coronary heart disease (CHD), 101–105
procedure for, 641–644, 642t–644t Cone biopsy, of cervical intraepithelial diabetes mellitus and, 388–389
of vagina, 642–643, 643t, neoplasia, 635 epidemiology of, 101–102, 102f, 103f
CP86–17––CP86–24 Confidence interval (CI), 67 familial heterozygous
of vulva, 641–642, 642t, Confidentiality, 71–72 hypercholesterolemia and, 329,
CP86–2––CP86–16 Confusion 338
Coma, myxedema, 670 due to hypomagnesemia, 668–669, 670, hormone replacement therapy and,
Comedolytics, 452 671 64–68, 68t
Comedone, 453 due to pulmonary embolism, 299–302 impact on family unit of, 105
Common bile duct (CBD) stones, 361, Confusion Assessment Method (CAM), LDL cholesterol and, 103, 104, 328–329,
365 672, 672b 328f, 329t, 330, 338
Common cold, 283 Congenital adrenal hyperplasia, short metabolic syndrome and, 395–396
Common warts, 479–480, 479f, 480f stature due to, 559 prevention of, 102, 103–105, 334t
Communication, in palliative care, 518, Congenital nevi, 485, CP63–9––CP63–11 risk factors for, 105, 105f, 328–330,
519, 520–521 Congestive heart failure (CHF), 314–319 329t, 339
Communication approach, to compliance, case study on, 314–317 screening for, 102–103, 104
90 vs. COPD, 294, 294t Coronary vasospasm, vs.
Compartment syndrome, vs. intermittent defined, 317 hypercholesterolemia, 327
claudication, 342–343 diagnosis of, 315–316, 316t, 317–318 Corticosteroids
Compassion, 7, 8, 13 differential, 315–316 for acne, 453t
Compazine (prochlorperazine), for imaging of, 183–184 for allergic rhinitis, 225
migraines, 501 prevention of, 318–319 for asthma, 439t–443t
Complementary and alternative medicine risk factors for, 317, 317t for COPD, 295, 296, 297t
(CAM). See Integrative signs and symptoms of, 317–318 for drug reaction, 447–448, 450
medicine. treatment of, 316–317, 318 and immunization, 201, 206t
Complex regional pain syndrome, 532 Conjunctivitis, gonococcal, 593 for lateral epicondylitis, 529
Compliance, 88–97 Connective tissue disorder, vs. for pruritus, 255–256
behavior-change strategies for fibromyalgia, 523 for spider bites, 692
improving, 91t Connors scale, 568 Cortisol, in Cushing’s syndrome
defined, 89 Consensus, 52–53 salivary, 404
ethical issues with, 96 Consent, informed, 72–74, 73t urinary, 403–404
future trends with, 96 for colposcopy, 636, 637b Cost-effective care, 11, 11f, 23
inducements of, 95 Constipation Cough
poor vs. irritable bowel syndrome, 367 due to asthma, 242–245
defined, 89 in palliative care, 520t chronic, in children, 242–245
detection of, 92–94, 93t Constitutional growth delay (CGD), habit (psychogenic), 243
factors in, 74, 74t, 89–92 554–560 due to influenza, 277–278
intentional vs. unintentional, 89 case study on, 554–558 productive, due to acute bronchitis,
misconceptions about, 94 diagnosis of, 555–557 287–291
prevalence of, 88–89 differential, 555, 556b, 557t, 558–560 Cough medicine, 289, 290
prevention and treatment of, 94–96, growth guidelines and, 555f, 558, 558t Cough receptor sensitivity, increased, 243
95t growth hormone treatment for, 560 Cough-variant asthma, 243
Compound nevus, 485, CP63–2 patient education on, 557 Coumadin. See Warfarin (Coumadin).
Comprehensive care, 12–13 Contact dermatitis Country Doctor, A, 30
Computed tomography (CT), 174–175, allergic, 450 COX-2 (cyclo-oxygenase-2) inhibitors,
174f, 175t pruritus due to, 251, 252t 211, 212t
multidetector, 174 vs. drug reaction, 447 in prevention of colorectal cancer, 120
of pelvic inflammatory disease, 600, Continuing education, 5, 24 Coxe, John Redman, 28, 29, 35
601f, 602f Continuity of Care Record (CCR), Cramps, due to irritable bowel syndrome,
single-photon emission, 177–178 144–145, 144b 366–370
spiral, 174 Contrast agents, 171–174, 173f Cranial trauma
Computer hardware, for electronic with CT, 174 delirium due to, 670
medical record, 145, 145b with MRI, 175–177 imaging of, 178–179

716
 Index

C-reactive protein, and coronary heart Cyst(s) Delusional disorder, 680

disease, 329 due to foreign body, 478 Demerol (meperidine), 213t, 215, 215t
Creatinine (Cr), 165, 166t horn, 486 for migraines, 501
serum, 165–166 Nabothian, 644, CP86–31 Depression
in acute renal failure, 431 ovarian, dysmenorrhea due to, 583 vs. cholelithiasis, 362
Creatinine (Cr) clearance, 165 popliteal (Baker’s), 350t in Cushing’s syndrome, 406
in acute renal failure, 431 Cystitis, 420 due to drug dependency, 645–647, 648
Crestor (rosuvastatin), for chemical, 420 vs. fibromyalgia, 524
hypercholesterolemia, 331, 336t, interstitial, 419, 420 in palliative care, 520t
337t radiation, 420 with panic disorder, 676
Critical appraisal, 50 recurrent, 419 Depressive disorder, major, 661–662,
Critical Appraisal Worksheets, 59 relapsing, 419 662b
Crohn’s disease, 270 viral, 420 Dermal nevi, 485, CP63–3––CP63–8
vs. irritable bowel syndrome, 367 Cystourethrograms, voiding, for UTI, 421, Dermatitis
Cromolyn, for asthma, 439t, 442t 421b atopic
Crown-rump length, 548 Cytobrush, 632, 632f vs. drug reaction, 447
Cruciate ligament tears, 191, 192f Cytologic screening method, with Pap pruritus due to, 250, 251, 252t, 256
Cryosurgery, 474–476, 474f smear, 631–633, 631f, 632f contact
complications and side effects of, Cytoxan (cyclophosphamide), for breast allergic, 450
474–475, 475t cancer, 606, 612, 612t pruritus due to, 251, 252t
contraindications to, 475t vs. drug reaction, 447
efficacy of, 473, 473t D herpetiformis, pruritus due to, 252t
skin care after, 474b Danazol, for endometriosis, 580 Dermatofibromas, 486,
tumor selection for, 476 Dantrolene, for spider bites, 695 CP63–25––CP63–29
Cryotherapy Dapsone, for spider bites, 694 Dermatomyositis, vs. fibromyalgia, 523
for cervical intraepithelial neoplasia, Darvocet (propoxyphene), 215 Desipramine (Norpramin)
629, 635 Data entry, structured, 143 for generalized anxiety disorder, 666t
for common warts, 480 DDAVP (desmopressin acetate), for for pain, 216
for condyloma acuminata, 457–458, bedwetting, 427 Desmopressin acetate (DDAVP), for
458f, 459 D-dimer testing bedwetting, 427
Cryptococcosis, 467t for deep venous thrombosis, 351 Desyrel (trazodone), for generalized
CT. See Computed tomography (CT). for pulmonary embolism, 303 anxiety disorder, 666t
CT colonography, 120, 174–175 Death with Dignity Act, 78 DEXA (dual x-ray absorptiometry), 173t,
Cullen, William, 28, 35 Debridement, for laceration repair, 541, 191
Cullen’s sign, 379 541f Dexamethasone suppression test (DST),
Cupp, Charles Daniel, 31 Decision tree, 43 for Cushing’s syndrome, 404
Current best evidence, 50, 57 Declaration of Independence, 28, 34 Dextroamphetamine, for AD/HD, 569
Current Contents, 50 Decongestants Dextromethorphan, for acute bronchitis,
Cushing’s syndrome, 402–406 for allergic rhinitis, 225 289, 290
case study on, 402–405 rhinitis medicamentosa due to, 223 Diabetes, gestational, 550–551
coagulopathy in, 406 Deep breathing, for anxiety, 663b Diabetes mellitus
diagnosis of, 403–404, 405f Deep venous thrombosis (DVT), 347–353 due to antipsychotic medications, 682t
differential, 403, 403b, 403t, 404 case study on, 348–351 in Cushing’s syndrome, 405
features of, 403, 403t clinical presentation of, 351 metabolic syndrome and, 393–394,
glucose intolerance and, 405 diagnosis of, 349–350, 350t, 351, 352f 394f
gonadal axis in, 405–406 differential, 349–350, 350t and peripheral arterial disease, 345,
hyperlipidemia and, 405 epidemiology of, 351 345t
hyperpigmentation in, 406 etiology of, 351–352 screening for, 127
hypertension and, 405 vs. intermittent claudication, 342 and stroke, 107
mortality rate for, 405 and pulmonary embolism, 300, 302, type 2, 381–389
and nephrolithiasis, 406 303 candidiasis due to, 381–383
obesity and, 405 risk factors for, 351 complications and comorbid
and osteoporosis, 406 treatment of, 350, 353 conditions of, 388–389
and polycystic ovary disease, Deep-brain stimulation, for Parkinson’s diagnosis of, 382
405–406 disease, 510 differential, 382
psychological and cognitive Deferral to authority, 52 patient education on, 383–384, 384b
disturbances in, 406 Delirium, 668–673 prevention of, 389
short stature due to, 559 case study on, 668–671 screening for, 383
somatotropic axis in, 406 defined, 669 symptoms of, 383
thyroid axis in, 406 diagnosis of, 671–672, 682b taking care of patients with, 385t
treatment of, 404–405 epidemiology of, 671 treatment of, 383–388
Cutaneous T-cell lymphoma, pruritus due etiology of, 669–671, 669b, 670b diet in, 382–383, 384, 386t, 387t
to, 252t in palliative care, 520t goals of, 383, 384t
CVD. See Cardiovascular disease (CVD). risk factors for, 671 medical, 384–388, 387t
CVD (cardiovascular disease), metabolic treatment of, 671, 672–673 physical activity for, 383, 384
syndrome and, 395–396, 399 Deltoid ligament, 534f weight loss due to, 415
Cyclo-oxygenase (COX)-2 inhibitors, 211, deep portion of, 534f Diabetic neuropathy, vs. double crush
212t superficial, 534f syndrome, 702
in prevention of colorectal cancer, 120 Delusion(s) Diagnoses, seen in family medicine, 16,
Cyclophosphamide (Cytoxan), for breast of parasitosis, 253t, 256t 17t, 39–40
cancer, 606, 612, 612t in schizophrenia, 679 Diagnostic skills, 13–14

717
 Index

Diarrhea Disorientation, due to heat stroke, Drug abuse, 108–110

due to giardiasis, 269–272 687–690 common drugs in, 648, 648t
infectious, 269–270, 271 Dissecting aortic aneurysm diagnosis of, 647, 647b, 648t
Diastolic failure, 183, 317 chest pain due to, 307 epidemiology of, 108–109, 109f
Diazepam (Valium) imaging of, 185 prevention of, 109–111
for generalized anxiety disorder, 666t vs. pancreatitis, 378 screening for, 109–110
for vertigo, 261 Disseminated candidiasis, 466t Drug allergy, 448–449
DIC (disseminated intravascular Disseminated gonococcemia, 465, 468 Drug dependency, 108–110, 645–649
coagulation), with heat stroke, Disseminated intravascular coagulation CAGE questions on, 647, 647b
689 (DIC), with heat stroke, 689 case study on, 645–647, 648
Diclofenac (Cataflam, Voltaren), 212t Distal humerus fracture, 529 defined, 647, 648t
Dicyclomine, for irritable bowel Diuretics diagnosis of, 646–647, 648t
syndrome, 368 for acute renal failure, 434 epidemiology of, 108–109, 109f
Diet adverse reactions to, 448t FRAMES outline for brief intervention
anti-inflammatory, 135, 136b for hypertension, 322 for, 647, 647b
for cholelithiasis, 363 Diverticulum, urethral, 420 patient education on, 647, 647b
and colorectal cancer, 119–120 Dix-Hallpike maneuver, 258, 259f, 261 prevention of, 109–110
for diabetes mellitus, 382–383, 384, Dizziness, 257–262 screening for, 109–110
386t, 387t assessment of, 258–259, 259f, 261 treatment for, 647, 649
elimination, 135, 136b case study on, 257–259 Drug eruption
for GERD, 374 classification of, 260–261, 260t case study on, 445–448, 446f
for health, 129 etiology of, 260–261, 260t diagnosis of, 447, 449–450
for hypercholesterolemia, 327, 330, prevalence of, 259–260 differential, 447
332t, 338 treatment of, 259, 261–262, 262f drugs that rarely cause, 449b
for hypertension, 322 Dobutamine, for congestive heart failure, with secondary bacterial infection, 447
in integrative medicine, 135–136, 318 Drug hypersensitivity reactions, 448, 449,
136b Docetaxel, for breast cancer, 612, 612t 449t
for irritable bowel syndrome, 368, Docosahexaenoic acid, for Drug ingestion, vs. heat stroke, 688–689
369 hypercholesterolemia, 330 Drug intoxication, delirium due to, 670
for metabolic syndrome, 400 Does Using Parachutes Eliminate Death Drug levels, and compliance, 94
during pregnancy, 549 (DUPED) study, 54 Drug reaction(s), 445–450
for prevention of coronary heart Dolobid (diflunisal), 212t case study on, 445–448, 446f
disease, 103, 104–105 Dolophine (methadone), 211, 214t, 215t classification of, 448–449, 449t
for prevention of lung cancer, 114 Domestic violence (DV). See Intimate to commonly used drugs, 448t
for prevention of migraines, 501b partner violence (IPV). defined, 448
Dietary Approaches to Stop Hypertension Dopamine, for congestive heart failure, diagnosis of, 447, 449–450
eating plan, 322 318 differential, 447
Dietary indiscretion, vs. irritable bowel Dopamine agonists drugs that rarely cause, 449b
syndrome, 367–368 for Parkinson’s disease, 508 epidemiology of, 448
Differin (adapalene), for acne, 454 for restless legs syndrome, 495–496, risk factors for, 449, 450b
Diflucan (fluconazole), for vulvovaginal 495t treatment of, 447–448, 450
candidiasis, 591, 592 Dopaminergic agents, for restless legs Drug screen, 646
Diflunisal (Dolobid), 212t syndrome, 495, 495t Drug withdrawal, 649
Digoxin Doppler ultrasound, 177 delirium due to, 669–670
adverse reactions to, 448t Dose frequency, and noncompliance, headache due to, 498
for atrial fibrillation, 313 91–92, 94–95 Drug-induced acanthosis nigricans, 398
for congestive heart failure, 318 Double crush syndrome, 697–706 Drug-induced anemia, 355
Dilaudid (hydromorphone), 211, 213t, clinical course of, 702–703, 705f, 706f Drug-induced anxiety, 651
215t common sites of, 702, 703f, 704f Drug-induced edema, vs. deep venous
Diltiazem, for atrial fibrillation, 313 diagnosis of, 698, 699f, 700f, 702, 705f thrombosis, 350t
Dimenhydrinate, for vertigo, 261 differential, 698–702, 701f Drug-induced gastrointestinal symptoms,
Dimple sign, 486 management of, 702–703, 703f, 705f, 367
Diphenhydramine (Benadryl) 706f Drug-induced tremor, 506–507
for allergic rhinitis, 222, 225 physical examination for, 698, 699f, Dry powder inhaler (DPI), for asthma,
with contrast agents, 174 700f 442t
for varicella, 274 Douching, and pelvic inflammatory Dry-bed training, 426
Diphtheria and tetanus toxoids (DT, Td), disease, 598 DST (dexamethasone suppression test),
125f, 126f, 204f, 208t Doxorubicin, for breast cancer, 612, 612t for Cushing’s syndrome, 404
Diphtheria and tetanus toxoids and Doxycycline (Vibramycin) DT (diphtheria and tetanus toxoids), 125f,
acellular pertussis (DTaP) for acne, 454 126f, 204f, 208t
vaccine, 125f, 202f, 203t, 206t, for Chlamydia, 593, 593b DTaP (diphtheria and tetanus toxoids and
207t for pelvic inflammatory disease, 595t, acellular pertussis) vaccine,
Dipyridamole (Persantine) stress testing, 600, 600t 125f, 202f, 203t, 206t, 207t
for angina pectoris, 308 for Rocky Mountain spotted fever, 470 Dual x-ray absorptiometry (DEXA), 173t,
Disalcid (salsalate), 213t for sinusitis, 285, 285t 191
Disease factors, in noncompliance, 90–91 DPA (dual-photon absorptiometry), 191 Dual-photon absorptiometry (DPA), 191
Disease-oriented evidence, patient- DPI (dry powder inhaler), for asthma, Duct ectasia, 606
oriented vs., 55–56 442t Duct tape, for common warts, 480
Disease-oriented outcomes, 55–56, 68 Dr. Latimer: A Story of Casco Bay, 30 Due date, 547–548
Disequilibrium, 260t, 261, 262 Dr. Sevier, 30 DUPED (Does Using Parachutes
Disk herniation, 179–180, 180f, 181f Dressings, for laceration repair, 544 Eliminate Death) study, 54

718
 Index

Durable power of attorney, 518, 521 Ecthyma gangrenosum, 466t Emesis

Duragesic (fentanyl), 209, 211, 213t, 215, Ectocervix, CP86–25 due to acute renal failure, 429–431
215t Ectopic pregnancy dehydration due to, 430
Dust mite allergy, 225, 437 pelvic inflammatory disease and, 603 in palliative care, 520t
DV (domestic violence). See Intimate ruptured, vs. pancreatitis, 378 Emotions, 76–77
partner violence (IPV). Eczema Empiricism, 53
DVT. See Deep venous thrombosis (DVT). atopic, 250, 251 EMR. See Electronic medical record
Dwarfism, 560 xerotic, 252t (EMR).
Dying, assistance in, 77–78 Effexor (venlafaxine) “Enabler,” 110
Dying patient, 517–521 for anxiety disorders, 653 Endarterectomy, for peripheral arterial
case study on, 517–519 for generalized anxiety disorder, disease, 346
communication and goal planning for, 666t Endocarditis, bacterial, 465, 467t
518, 519, 520–521 EHR (electronic health record). See Endocervical curette, 641, 641f, 644
coordination of care for, 518, 519 Electronic medical record (EM). Endocervical speculum, for colposcopy,
pain and symptom management for, Ehrlichiosis, 469t 637, 640f
518, 519–520, 520t Eicosapentaenoic acid, for Endocrine diseases
psychosocial, spiritual, and bereavement hypercholesterolemia, 330 anxiety due to, 651
support for, 518, 519, 521 Elavil (amitriptyline) delirium due to, 670–671
DynaMed, 50–51, 55, 57, 58 for fibromyalgia, 524 weight loss due to, 415
Dysfunctional elimination syndrome, 424 for pain, 216 Endocrine system, imaging of, 188–189,
Dysfunctional voiding, 424 for prevention of migraines, 499 189f
Dyskinesias, with levodopa, 509 Elbow, radiographs of, 172f Endocrinologic causes, of short stature,
Dyslipidemia Elbow pain, 527–530 559
with diabetes mellitus, 388 Eldepryl (selegiline), for Parkinson’s End-of-dose failure, with
in metabolic syndrome, 394 disease, 505–506, 508 carbidopa/levodopa, 509
Dysmenorrhea Elderly patients, confidentiality with, 72 End-of-dose kinesia, with levodopa, 509
primary, 582–585 Electrocardiogram (ECG), for angina Endoluminal probes, 177
case study on, 582–584 pectoris, 307 Endometrial biopsy, 617–618, 618t
clinical presentation of, 582–583 Electrocardiographic (ECG) stress testing, for pelvic inflammatory disease, 599
diagnosis of, 582–583, 584, 584t for angina pectoris, 308 Endometrial cancer, 614–619
differential, 583 Electrolyte(s), 152–156, 152t–156t case study on, 614–616
epidemiology of, 584 Electrolyte disturbances diagnosis of, 615–616, 617–618, 618t
prostaglandins in, 583 delirium due to, 670 differential, 615–616
treatment of, 584–585 with heat stroke, 689 epidemiology of, 117, 616
secondary, 583, 584t Electron beam tomography (EBT), 183 grading and staging of, 618, 618t
Dyspepsia Electronic health record (EHR). See prevention of, 117–118
vs. cholelithiasis, 361 Electronic medical record risk factors for, 117–118, 616–617
vs. GERD, 372 (EMR). screening for, 118, 617
medication-induced, 373 Electronic Health Record Readiness treatment of, 616, 618
warning symptoms with, 372, 372b Assessment tool, 146 vaginal bleeding due to, 614–616
Dysplastic nevi, 485, 485t, Electronic medical record (EMR), Endometrial hyperplasia, vaginal bleeding
CP63–12––CP63–17 142–146 due to, 615
Dyspnea advantages of, 142 Endometrial polyps, dysmenorrhea due
due to congestive heart failure, 314–317 applications and functionalities of, to, 583
in palliative care, 520t 142–143, 143b Endometriosis, 577–580
due to pulmonary embolism, 299–302 challenges of, 145–146 case study on, 577–579
Dysrhythmia computer hardware for, 145, 145b diagnosis of, 578–579
due to antipsychotic medications, 682t Continuity of Care Record in, 144–145, differential, 578–579, 578t
vs. heat stroke, 688 144b dysmenorrhea due to, 583
Dysuria, due to urinary tract infection, Internet resources on, 146b epidemiology of, 579
418–420 of laboratory test results, 143 etiology of, 579
for medication reconciliation, pain of, 578, 579
E 142–143 treatment of, 579–580
Ear(s), ringing in. See Tinnitus. and New Model of practice, 23, 24, 26 Endoscopic retrograde
Ear infection, middle. See Otitis media. of office visits, 143 cholangiopancreatography
Ear pain, differential diagnosis of, and office workflow, 144 (ERCP), 183t, 185, 186
227–228, 227t and paperless office, 146 for cholelithiasis, 363
Ebell, Mark, 57 and practice management, 143 Endoscopy, for acute gastrointestinal
EBM. See Evidence-based medicine of prescriptions, 142 bleeding, 188
(EBM). quality systems embedded in, 145 Energy medicine, 138, 138b
EBT (electron beam tomography), 183 standards for, 144–145 Enoxaparin, for pulmonary embolism, 303
ECG (electrocardiogram), for angina structured data entry, 143 Enteritis, regional, 270
pectoris, 307 Elimination diets, 135, 136b Enteroclysis, cost of, 173t
ECG (electrocardiographic) stress testing, ELISA (enzyme-linked immunosorbent Enterprise system, 145
for angina pectoris, 308 assays), for deep venous Enuresis, nocturnal. See Bedwetting.
Echocardiography (ECHO), 177, 178t thrombosis, 351 Enuresis alarms, 426, 426f, 427
of congestive heart failure, 183–184 Embolism, pulmonary. See Pulmonary Environmental exposure, delirium due to,
stress, 178t, 183 embolism (PE). 670
for angina pectoris, 309, 309t Emergency exception, to informed Enzyme-linked immunosorbent assays
transesophageal, 177, 183–184 consent, 72–73 (ELISA), for deep venous
for atrial fibrillation, 311–312, 313 Emerson, Ralph Waldo, 35 thrombosis, 351

719
 Index

Eosinophilic nonallergic rhinitis, 223 Evidence sources, examples of, 63t–64t Exploratory therapy, for generalized
Ephelides, 486 Evidence-based clinical practice, 55 anxiety disorder, 652
Epicondylitis Evidence-based databases, 62, 62t Extensor retinaculum, inferior, 534f
lateral, 527–530 Evidence-based health care, 55 External ear pain, 227t
case study on, 527–528 Evidence-based literature surveillance, 55 External rotation test, 533–535, 537f
diagnosis of, 529, 530 Evidence-based medicine (EBM), 47–60 Extrapyramidal side effects, of
differential, 528–529, 528b anecdotes of, 55–57 antipsychotic medications, 682t
etiology of, 530 barriers to use of, 61 Ezell, Uberto Desaix, 31
prevention of, 530 benefits of, 47–48 Ezetimibe (Zetia), for
treatment of, 529–530 building clinical evidence from hypercholesterolemia, 331, 336t
medial, 528 published research in, 65–66,
Epidemic typhus, 469t 65f F
Epidemiology, 53 challenges of, 48 Familial atypical mole/nevi syndrome,
clinical, 54–55 classic steps in, 49b 483, 485
Epigastric pain, due to acute pancreatitis, coining of term, 54 Familial heterozygous
376–380 defined, 47 hypercholesterolemia, 326,
Epilepsy, autism and, 565 derivations and mutations of, 55, 55b 328–329, 335–338
Epinephrine, for laceration repair, 540 distinguishing characteristics of, 48–51, Familial short stature (FSS), 559
Epirubicin, for breast cancer, 606, 612, 49b, 49t, 51b Family dynamics, 80–87
612t example of, 47 Family history, 80
Episiotomy, 56 family medicine approach to, 57–59 Family medicine, 3–18
Epley maneuver, 262, 262f goal of, 47 in academic health centers, 25
ERCP (endoscopic retrograde interpreting study results in, 67–69, chronic illness in, 10
cholangiopancreatography), 68t comprehensive care in, 12–13
183t, 185, 186 lag time in, 50–51 continuing education in, 5, 24
for cholelithiasis, 363 limitations of, 59–60 core values of, 21
Ergot products, for migraines, 501 literature evaluation in, 61–69 cost-effective care in, 11, 11f, 23
Errors, 76 methods of producing best evidence defined, 5
Erythema multiforme, 450 for, 49b diagnoses seen in, 16, 17t, 39–40
Erythema pernio, 685 origins and evolution of, 47, 53–55, 55t electronic health records in, 23, 24, 26
Erythromycin, for acne, 453t, 454 vs. other approaches, 51–53, 52t enhancing science of, 24–25
Erythromycin base, for Chlamydia, 593b source of clinical information in, 62, future of, 19–26
Erythromycin ethylsuccinate 62t history of, 4–5, 20, 28–38
for Chlamydia, 593b understanding statistical significance of integrated care in, 26
for streptococcal pharyngitis, 220t, study results in, 66–67, 67t integrative medicine as, 132–134
221 using evidence at point of care in, key challenges facing, 21–23, 22t, 23t
Erythromycin/sulfisoxazole (Pediazole), 62–65, 62t–64t leadership and advocacy in, 25
for otitis media, 229t Evidence-Based Medicine Working Group, new model of, 22–26, 22t, 23t, 24
Escitalopram oxalate (Lexapro), for 54–55 physician and patient satisfaction in,
generalized anxiety disorder, Evidence-based practice, 55 4, 4t
662, 665, 666t Evidence-based summaries, 62, 62t research in, 24–25
Esomeprazole, for GERD, 375 Excedrin (acetaminophen, aspirin, and rewards of, 3–4
Esophageal dysfunction, imaging for, 187, caffeine), for migraines, 501 services provided by, 23t
187f Excoriations, neurotic, 253t, 256t for uninsured, 11–12
Esophagogram, barium, 187, 187f Exemestane, for breast cancer, 612t Family physician, 3–18
Esophagus, Barrett’s, 375 Exenatide (Byetta), for diabetes mellitus, accessibility of, 13
Essential tremor, 507 388 attributes of, 4, 4t, 8, 21
Estrogen, and endometrial cancer, Exercise vs. collusion of anonymity, 9–10
616–617 for ankle sprain, 533 continuing responsibility of, 9
Ethics, 70–79 for anxiety, 663b as coordinator, 14–15
code of medical, 29 for diabetes mellitus, 383, 384 defined, 5–6
of confidentiality, 71–72 for fibromyalgia, 525–526 diagnostic skills of, 13–14
of euthanasia and assisted suicide, for health, 129 house calls by, 17–18
77–78 for hypercholesterolemia, 327, 328, 332t as human being, 76–77
of financial gatekeeping, 75–76 for lateral epicondylitis, 529–530 interpersonal skills of, 13
of informed consent, 72–74, 73t for metabolic syndrome, 396, 400 personalized care by, 7–8, 7f
of noncompliance, 74, 74t, 96 for osteoporosis, 122, 588 in practice, 15–18, 16f
of physician as human being, 76–77 for panic disorder, 676, 677 practice content of, 16–17, 17t
of physician-patient relationship, for peripheral arterial disease, 345, 345t in prevention, 100
70–71 during pregnancy, 549 quality of care by, 10–11, 25
of referrals, 75 for prevention of coronary heart recruiting of, 25
of work- and school-related disease, 105 training of, 15–16, 16f, 24, 25
evaluations, 71 for prevention of stroke, 107 Family Physicians Inquiries Network
Ethopropazine (Parsidol), for Parkinson’s for restless legs syndrome, 495 (FPIN), 57, 58–59
disease, 508 Exercise stress testing, 182, 308 Family Practice Inquiries Network, 69
Etodolac (Lodine), 212t cost of, 183t Family therapy, for schizophrenia, 682
Euthanasia, 77–78 Exercise therapies, 136–137, 137b FAS (fetal alcohol syndrome), 108, 549
Evidence Exocervix, CP86–25 Fasting hypoglycemia, 157
building strength of, 65–66, 65f Expectations, of patient, 40–41, 41t Fasting lipoprotein analysis, 327
patient-oriented vs. disease-oriented, Experience, opinion based on, 52 Fat necrosis, vs. breast cancer, 606
55–56 Explanatory model, of patient, 40 Fat reduction, for diabetes mellitus, 384

720
 Index

Fatigue Financial gatekeeping, 75–76 Freckles, 486

due to anxiety disorder, 650–652 Fine-needle aspiration biopsy (FNAB), of Free fatty acids (FFAs), in metabolic
due to Cushing’s syndrome, 402–405 thyroid nodule, 188 syndrome, 392, 393b, 394
differential diagnosis of, 408, 408t Fish oil, for hypercholesterolemia, 330 Frostbite, 683–686
in fibromyalgia, 525 Fisher, Ronald, 54 classification of, 685
due to hypothyroidism, 407–410 Fitz-Hugh-Curtis syndrome, due to pelvic defined, 684
due to pregnancy, 546–547 inflammatory disease, 601–602 diagnosis of, 684–685
Fe. See Iron (Fe). 5 Minute Medical Consult (5MMC), 58 differential, 685
Fecal occult blood testing, 120 Flagyl. See Metronidazole (Flagyl). factors contributing to, 684
Feelings, 76–77 Flat warts, 480 pathogenesis of, 684–685
Feinstein, Alvin, 54 Flavonoids, for hypercholesterolemia, patient education on, 686
Feldene (piroxicam), 212t 330 treatment of, 685–686
Female reproductive system, imaging of, Flexible sigmoidoscopy, for prevention of Frostnip, 685
194–195, 194f, 195f colorectal cancer, 120 FSS (familial short stature), 559
Femoropopliteal bypass, for peripheral Floxin. See Ofloxacin (Floxin). Fulvestrant, for breast cancer, 612t
arterial disease, 343 Flu. See Influenza. Fundal height, 550, 551f
Fentanyl (Duragesic, Actiq, Sublimaze), Fluconazole (Diflucan), for vulvovaginal Furadantin (nitrofurantoin), for UTI, 420,
209, 211, 213t, 215, 215t candidiasis, 591, 592 421, 422t
Fenugreek, for hypercholesterolemia, 330 Fluid and electrolyte disturbances, Furazolidone (Furoxone), for giardiasis,
Ferric subsulfate, for colposcopy, 641, 641f delirium due to, 670 272
Ferritin, 158, 159t Fluid management, for bedwetting, 425 Furosemide (Lasix)
Fetal alcohol syndrome (FAS), 108, 549 Flumadine (rimantadine), for influenza, for acute renal failure, 434
Fetal brain, imaging of, 182, 182f 278, 280, 280t for congestive heart failure, 316, 318
Fetal heart tones, 547 Flunisolide, for asthma, 443t Future of Family Medicine (FFM) Project,
Fetal ultrasound, 177, 178t, 194–195, Fluoroquinolones, for UTI, 421, 422t 20–25
194f Fluoroscopy, 171
FEV1 (forced expiratory volume in 1 5-Fluorouracil, for breast cancer, 612, G
second), 243 612t Gabapentin (Neurontin)
Fever Fluoxetine (Prozac), for generalized for chronic pain, 209
defined, 237 anxiety disorder, 666t for hiccups, 235
due to influenza, 277–278 Fluoxymesterone, for breast cancer, 612t for pain, 216
life-threatening conditions associated Fluphenazine, for schizophrenia, 682 for restless legs syndrome, 492, 495t,
with, 464–471, 466t–470t Flurbiprofen (Ansaid), 212t 496
Rocky Mountain spotted, 464–471 Fluticasone, for asthma, 443t GABHS (group A ß-hemolytic
without source, in infants and children, Fluticasone/salmeterol, for asthma, 442t streptococcus), pharyngitis due
236–241, 238f, 239t, 240f Fluvastatin (Lescol), for to, 217–221, 220t
of unknown origin, 239–240 hypercholesterolemia, 336t, 337t GAD. See Generalized anxiety disorder
Fexofenadine (Allegra), for allergic FMS (fibromyalgia syndrome), 524–526 (GAD).
rhinitis, 225 FNAB (fine-needle aspiration biopsy), of Gadolinium dimeglumine, 175–177
FFAs (free fatty acids), in metabolic thyroid nodule, 188 Galactorrhea, due to antipsychotic
syndrome, 392, 393b, 394 Folic acid medications, 682t
FFM (Future of Family Medicine) Project, for hypercholesterolemia, 332t Galen, 28, 29, 34, 35, 53
20–25 during pregnancy, 549 Gallbladder hydrops, 364f
Fiber Folic acid deficiency, 355, 357 Gallstone(s), 359–365
for hypercholesterolemia, 330 Folliculitis black-pigment, 364, 364f
for irritable bowel syndrome, 368, 369 vs. acne, 452 brown-pigment, 364
Fiberoptic bronchoscopy, 185 pruritus due to, 252t cholesterol, 364, 364f, 365f
Fibrate therapy, for hypercholesterolemia, Folsum Report, 33 complications of, 364
333t, 334t Food allergies, 135 diagnosis of, 360–363, 364–365
Fibroadenoma, 606 Food intolerances, 135 differential, 361–363, 361b, 364–365
Fibrocystic disease, 606 Forced expiratory volume in 1 second epidemiology of, 363–364
Fibroids (FEV1), 243 vs. GERD, 372–373
dysmenorrhea due to, 583 Foreign body imaging of, 185, 186
vaginal bleeding due to, 615 aspiration of, 244 natural history of, 364
Fibromyalgia, 522–526 granuloma or cyst due to, 478 pathogenesis of, 364
allodynia in, 524–525 Foreign body reaction, to retained thorn, risk factors for, 362b
case study on, 522–524 478 treatment of, 363, 365
conditions coexisting with, 525, 525b Foreskin, swollen, 381–383 Gallstone ileus, 362
defined, 523 Formoterol, for asthma, 442t Gallstone pancreatitis, 378, 380
diagnosis of, 523–525, 524f Fosfomycin, for UTI, 421 Gamma rays, 177
differential, 523–524 FPIN (Family Physicians Inquiries γ-glutamyl transferase (GGT), 161
epidemiology of, 525 Network), 57, 58–59 Gardnerella vaginalis, 592
fatigue in, 525 Fracture(s) Garlic, for hypercholesterolemia, 330
hyperalgesia in, 524–525 ankle, 532, 536–538, 538b Gastroesophageal reflux disease (GERD),
pathophysiology of, 525 imaging of, 189, 190f, 191f 371–375
sleep disturbance in, 525 osteoporotic, 586–588 case study on, 371–374
tender points in, 523, 524, 524f of pubic ramus, 173f complications of, 375
treatment of, 524, 525–526 skull, 178–179 cough due to, 243, 244
Fibromyalgia syndrome (FMS), 524–526 spinal, 181 diagnosis of, 372–373, 374
Fieldes, Luke, 7, 7f stress, 189 differential, 372–373, 372b
Filariasis, pruritus due to, 253t FRAMES format, 647, 647b

721
 Index

Gastroesophageal reflux disease Giardiasis (Continued) Grey Turner’s sign, 379

(GERD) (Continued) pathogenesis of, 270–271 Group A ß-hemolytic streptococcus
epidemiology of, 374 during pregnancy, 272 (GABHS), pharyngitis due to,
Helicobacter pylori in, 375 symptoms of, 271 217–221, 220t
pathophysiology of, 374 treatment of, 270, 271–272 Group A streptococcus, scarlet fever due
patient education on, 373, 373b Gibran, Kahlil, 3 to, 467t
refractory, 375 Glaucoma, 127–128 Group B streptococcal infection, during
treatment of, 373–375, 373b, 375b Gliadel wafers, 516 pregnancy, 551, 551b
warning symptoms with, 372, 372b Glial cells, 515 Growth curves, 555f, 556
Gastrointestinal (GI) bleeding, imaging Gliomas, 515 Growth delay, constitutional. See
for, 188 Glipizide, for diabetes mellitus, 386 Constitutional growth delay
Gastrointestinal (GI) conditions, chest Glitazars, for diabetes mellitus, 388 (CGD).
pain due to, 307 Glomerular filtration rate (GFR), in acute Growth guidelines, for children, 558, 558t
Gastrointestinal (GI) disorders, weight renal failure, 431 Growth hormone (GH) deficiency, short
loss due to, 414 Glomerulonephritis, 432–433 stature due to, 559–560
Gastrointestinal (GI) side effects, of Glucose intolerance, during pregnancy, Growth hormone (GH) treatment, for
NSAIDs, 430 550–551 constitutional growth delay, 560
Gastrointestinal (GI) system, imaging of, Glucose levels, 156–157 Growth retardation, in Cushing’s
185–188, 187f Glucose tolerance, impaired, in Cushing’s syndrome, 406
Gatifloxacin (Tequin), for UTI, 422t syndrome, 405 Gugulipids, for hypercholesterolemia, 330
Gell and Coombs classification, of drug Glucose-lowering agents, oral, 385–386, Guyatt, Gordon, 54
hypersensitivity reactions, 449, 387t Gynecology, imaging in, 194–195, 194f,
449t a-Glucosidase inhibitors, for diabetes 195f
Gemcitabine, for breast cancer, 612, mellitus, 387t, 388
612t Glutamate pyruvate transaminase, serum, H
General practice, 5 161 Habit cough, 243
General practitioner, 5 Glutamic-oxaloacetic transaminase, Habit reduction, for anxiety, 663b, 664b
Generalist physician, 5, 6 serum, 161 Habituation, in tinnitus retraining
Generalized anxiety disorder (GAD), Gluten-sensitive enteropathy, vs. irritable therapy, 267–268, 267f
650–654, 655–667 bowel syndrome, 367 Haemophilus influenzae type b (Hib)
case studies on, 650–652, 654, 655–662 Glyburide, for diabetes mellitus, 386 vaccine, 125f, 202f, 204t, 207t,
comorbidity with, 663 Glycemic index, 135, 136b 240
diagnosis of, 651, 652, 653, 663 Glycemic load, 135 Hallucinations, in schizophrenia, 679
criteria for, 651, 651b, 656, 660b, Glycosylated hemoglobin (HbA1c), 157, Hallucinosis, alcoholic, 680
663 157t Halo nevus, 485–486, CP63–18
differential, 651, 652, 656–662, 661t, Glyset (miglitol), for diabetes mellitus, Haloperidol (Haldol)
662b 388 for delirium, 671, 673
psychological screening in, 656, GnRH (gonadotropin-releasing hormone) for schizophrenia, 682
657t–660t agonists, for endometriosis, 580 Hand, imaging of, 173t, 190f
epidemiology of, 652 Goal(s), of patient, 40 Hart’s line, 642, 642t
vs. hypercholesterolemia, 326 Goal planning, in palliative care, 518, 519, Harvey, William, 28, 35, 53
management of, 652–653, 663–667 520–521 “Hay fever,” 224
pharmacologic, 652–653, 662, Goal-oriented tremor, 507 Hb. See Hemoglobin (Hgb, Hb).
665–667, 666t Goiter, multinodular, 188 HbA1c (glycosylated hemoglobin), 157, 157t
psychosocial, 652, 663–665, toxic, hyperthyroidism due to, 416 hCG (human chorionic gonadotropin), in
663b–665b Golfer’s elbow, 528 urine pregnancy test, 547
prevalence of, 662 Gonadal axis, in Cushing’s syndrome, hCG (human chorionic gonadotropin)
resources on, 665b 405–406 tests, 157–158, 158t, 194
Genital herpes, 123 Gonadotropin-releasing hormone ß-hCG (ß-human chorionic
Genital warts. See Condyloma acuminata. (GnRH) agonists, for gonadotropin), 194
Gentamicin, for UTI, 422t endometriosis, 580 Hct (hematocrit), 148–149
GERD. See Gastroesophageal reflux Gonococcal conjunctivitis, 593 in pregnancy, 548
disease (GERD). Gonococcal infection. See Gonorrhea. HDL cholesterol. See High-density
Gestational diabetes, 550–551 Gonococcemia, disseminated, 465, 468t lipoprotein (HDL) cholesterol.
GFR (glomerular filtration rate), in acute Gonorrhea, 593–594 Head
renal failure, 431 diagnosis of, 594 CT of, 175t
GGT γ-glutamyl transferase), 161 disseminated, 593–594, 594b MRA of, 175t
GH (growth hormone) deficiency, short epidemiology of, 123 MRI of, 175t
stature due to, 559–560 screening for, 123 Head trauma
GH (growth hormone) treatment, for sites of, 593 delirium due to, 670
constitutional growth delay, treatment of, 594, 594b imaging of, 178–179
560 vaginal discharge due to, 591 Headache(s), 497–503
GI. See Gastrointestinal (GI). Gonorrhea testing, during pregnancy, 549 case study on, 497–499
Giardia duodenalis, 270 Granuloma, due to foreign body, 478 cluster, 502–503
Giardia intestinalis, 270 Granulomatous mastitis, 606 diagnosis of, 499
Giardia lamblia, 270 Graves’ disease, 188 differential, 500f
Giardiasis, 269–272 hyperthyroidism due to, 416, 417 “red flags” in, 499, 501b
assessment of, 270, 271 Graves speculum, for colposcopy, 636, 640f epidemiology of, 499
case study on, 269–270 GREPCO (Rome Group for the imaging for, 180
differential diagnosis of, 270, 271 Epidemiology and Prevention of migraine, 497–502, 501b, 502t
epidemiology of, 270 Cholelithiasis), 364 primary, 499t

722
 Index

Headache(s) (Continued) Hereditary nonpolyposis colorectal H&P (history and physical examination), 39
secondary, 499t cancer, 617 HPV. See Human papillomavirus (HPV).
substance-withdrawal, 498 Herniated disk, 179–180, 180f, 181f H2RA (histamine H2-receptor
tension-type, 502, 502t Herpes, genital, 123 antagonist), for GERD, 373,
transformed, 501 Herpes gestationis, pruritus due to, 374–375, 375b
types of, 499t 253–254 HRT. See Hormone replacement therapy
Healing, steps in facilitating, 132–133, Herpes zoster, 275, 469t (HRT).
133t pruritus due to, 253t HSIL (high-grade squamous
“Healing power of Nature,” 29, 35 Herzog, Sofie, 32 intraepithelial lesion), 630, 635
Health habits, 80 Heterocyclic antidepressants, for Human chorionic gonadotropin (hCG),
Health-belief model, of compliance, 90 generalized anxiety disorder, in urine pregnancy test, 547
Healthy Heart Diet, 327, 332t 666t Human chorionic gonadotropin (hCG)
Healthy user bias, 66 Heterophil antibody test, for infectious tests, 157–158, 158t, 194
Heart disease mononucleosis, 219 ß-Human chorionic gonadotropin
anxiety due to, 651 Hgb. See Hemoglobin (Hgb, Hb). (ß-hCG), 194
in hyperthyroidism, 416 Hib (Haemophilus influenzae type b) Human immunodeficiency virus
metabolic syndrome and, 395–396, 399 vaccine, 125f, 202f, 204t, 207t, (HIV)
and stroke, 107 240 and cervical cancer, 631
Heart failure, congestive. See Congestive Hibiclens (chlorhexidine gluconate), for epidemiology of, 123
heart failure (CHF). laceration repair, 541 fever and rash due to, 467t
Heartburn, due to gastroesophageal reflux Hiccups, 232–235, 234b and immunization, 201
disease, 371–375 HIDA (99mTc-hepatobiliary iminodiacetic during pregnancy, 549
Heat cramps, 690 acid) scan, 178t, 186 pruritus due to, 252, 253t
Heat edema, 690 High blood pressure. See Hypertension. Human papillomavirus (HPV)
Heat exhaustion, 688 High-density lipoprotein (HDL) and cervical cancer, 116, 621–622, 623t,
Heat stroke, 687–690 cholesterol 630
classic vs. exertional, 690 and coronary heart disease, 103, 104, condyloma acuminata due to, 456, 457,
defined, 688, 690 328–329, 330, 339 459
diagnosis of, 688–689 with diabetes mellitus, 388 epidemiology of, 123
differential, 688–689, 690 normal values for, 328–329, 333t plantar warts due to, 478, 479
mortality for, 690 testing for, 327, 328 screening for, 123
patient education on, 689 High-grade squamous intraepithelial testing for, 621–622, 623t, 634
recurrence of, 689 lesion (HSIL), 630, 635 types of, 630, 631t
risk factors for, 690, 690b Hill, Austin Bradford, 54 Humatin (paromomycin), for giardiasis,
treatment for, 689, 690 Hip fracture, osteoporotic, 587, 588 272
Heat syncope, 688 Hippocrates, 28, 29, 34, 35, 88 Hutchinson’s sign, 461, 462f, 487,
Heavy metals, delirium due to, 670 Hippocratic Oath, 71 CP633–35
Height measurement, 556 Hirsch, Lawrence, 33 Hydrochlorothiazide, hypomagnesemia
Helical CT, 174 Histamine H2-receptor antagonist due to, 671
Helicobacter pylori, in GERD, 375 (H2RA), for GERD, 373, Hydrocodone with acetaminophen
Hematocrit (Hct), 148–149 374–375, 375b (Lorcet, Lortab, Vicodin,
in pregnancy, 548 Histoplasmosis, 467t Norco), 211, 215t
Hematomas, of breast, 606 History for chronic pain, 209, 213t
Hematuria, painless, 420 family, 80 for migraines, 501
Hemlock Society, 77 medical, 80 Hydrocodone with ibuprofen
Hemodialysis, for acute renal failure, 434, social, 80 (Vicoprofen), 211, 213t
434b History and physical examination Hydrogen peroxide, for laceration repair,
Hemoglobin (Hgb, Hb), 148–149, 149t (H&P), 39 541
glycosylated, 157, 157t HITS, 83t Hydromorphone (Dilaudid), 211, 213t,
normal values for, 356t HIV. See Human immunodeficiency virus 215t
in pregnancy, 548 (HIV). Hydrosalpinx, 602f
Hemoglobin A1C, in diabetes mellitus, Hobo spider bites, 695 3-Hydroxy-3-methylglutaryl coenzyme A
383, 384, 384t, 386, 387t Hodgkin’s lymphoma, pruritus due to, 253t reductase inhibitors, for
Hemostasis, for laceration repair, 542 Homeopathy, 140b hypercholesterolemia, 328,
Heparin Homocysteine, and coronary heart 330–331, 333t–334t, 336t, 337t
for atrial fibrillation, 312 disease, 329 Hydroxyzine HCl (Atarax)
for deep venous thrombosis, 350–351 Hormonal rhinitis, 223 for allergic rhinitis, 225
for pulmonary embolism, 300, 303–304 Hormonal therapy, for breast cancer, for drug reaction, 447
Hepatic metastases, 188 610 Hyoscyamine, for irritable bowel
Hepatitis, sexual transmission of, 123 Hormone replacement therapy (HRT) syndrome, 368
Hepatitis A vaccine, 125f, 126f, and cardiovascular disease prevention, Hyperacusis, 264
202f, 205t 335t Hyperalgesia, in fibromyalgia, 525
Hepatitis B (HepB) vaccine, 125f, 126f, and endometrial cancer, 617 Hyperalphalipoproteinemia, vs.
202f, 204t, 206t–208t evidence-based medicine on, 47, 50, 51, hypercholesterolemia, 327
99m
Tc-Hepatobiliary iminodiacetic acid 61–68 Hyperbilirubinemia, 162, 163t
(HIDA) scan, 178t, 186 for osteoporosis, 589 Hypercalcemia, 155t, 156
Hepatomegaly, 188 Horn cysts, 486 Hypercholesterolemia, 324–340
Hepatosplenomegaly, 188 Hospice medicine, 78 in children, 339
HER2/NEU gene amplification, in breast “Hospital standardization” movement, 33 and coronary heart disease, 103, 104
cancer, 608, 612t “Hot” nodule, 188 prevention of, 331
Herbal medicine, 136, 136b House calls, 17–18 risk of, 328–329, 329t

723
 Index

Hypercholesterolemia (Continued) Hypothyroidism, 407–411 Infection(s) (Continued)

diagnosis of, 326–327, 329–330 vs. anemia, 355 upper respiratory tract, in toddler,
differential, 326–327 case study on, 407–410 199–200
familial heterozygous, 326, 328–329, causes of, 409–410, 409t urinary tract. See Urinary tract
335–338 congenital, 559 infection (UTI).
patient education on, 327–328, 331 in Cushing’s syndrome, 406 vaccine-preventable, 124, 125f, 126f
resources on, 340 diagnosis of, 408–410 vaginal, CP86–20
treatment of, 327, 330–331, 331t–337t, differential, 408, 408t weight loss due to, 415
338–339 epidemiology of, 410 Infectious bowel disease, vs. irritable
Hypercortisolism. See Cushing’s vs. fibromyalgia, 523 bowel syndrome, 367
syndrome. vs. hypercholesterolemia, 326 Infectious mononucleosis (Mono), 218,
Hyperglycemia, 156 patient education on, 410 219, 220
vs. heat stroke, 688 primary, 409, 409t Infectious rhinitis, 223
Hyperkalemia, 153t, 154 screening for, 411, 411t Infective endocarditis, 465, 467t
in acute renal failure, 434 secondary, 409–410 Inferior extensor retinaculum, 534f
Hyperlipidemia short stature due to, 559 Infertility, pelvic inflammatory disease
in Cushing’s syndrome, 405 signs and symptoms of, 409, 409t and, 603
and peripheral arterial disease, 345, subclinical, 411 Inflammatory bowel diseases, 270
345t treatment of, 410 vs. irritable bowel syndrome, 367
Hypernatremia, 152t, 153 Hypoxia, delirium due to, 670 Inflammatory myopathy, vs. fibromyalgia,
Hyperpigmentation, in Cushing’s Hysterosalpingogram, 195, 195f 523
syndrome, 406 Hysterosonography, 177 Influenza, 277–281
Hyperprolactinemia, in Cushing’s case study on, 277–278
syndrome, 406 I diagnosis of, 278, 279–280
Hypersensitivity, drug, 448, 449, 449t IBM (information-motivation-behavior differential, 278
Hypertension, 320–323 skills model), of compliance, 90 epidemiology of, 278
case study on, 320–321 IBS. See Irritable bowel syndrome (IBS). increased risk of complications of, 279t
causes of, 322 Ibuprofen (Motrin, Advil), 212t pathogenesis of, 278–279
control of, 104 for endometriosis, 579 patient education on, 278
in Cushing’s syndrome, 405 for frostbite, 686 prevention of, 279
with diabetes mellitus, 388 gastrointestinal side effects of, 430 symptoms of, 279
diagnosis of, 321 for menstrual cramps, 582 treatment of, 278, 280–281, 280t
in metabolic syndrome, 394, 396, 399t for migraines, 501 Influenza vaccine, 125f, 126f, 202f, 204t, 279
and peripheral arterial disease, 345, for otitis media, 228 during pregnancy, 550
345t IC. See Intermittent claudication (IC). InfoPOEMs, 62
pre-, 322 ICS (inhaled corticosteroid) therapy, for InfoRetriever, 50–51, 55, 57–58, 62, 63t,
risk factors for, 322 asthma, 438, 439t–443t 64–65
and stroke, 107, 107f, 108f ICU (intensive care unit) psychosis, 670 Information, acquiring and synthesizing,
treatment of, 322–323, 322t Idiopathic rhinitis, 223, 283 41, 42t
workup for, 322 Ileus, gallstone, 362 Information mastery, 62
Hyperthermia, vs. heat stroke, 688 Imipramine (Tofranil), for generalized Information needs, recognized and
Hyperthyroidism, 412–417 anxiety disorder, 666t unrecognized, 57
case study on, 412–415 Imiquimod 5% cream (Aldara), for Information-motivation-behavior skills
causes of, 416b condyloma acuminata, 457, model (IBM), of compliance, 90
diagnosis of, 414–415, 415b, 416 457t, 459 Informed consent, 72–74, 73t
differential, 414–415, 414b Imitrex (sumatriptan), for migraine, 499 for colposcopy, 636, 637b
epidemiology of, 415 Immersion syndrome, 685 Inhaled corticosteroid (ICS) therapy, for
pruritus due to, 253t Immobilization asthma, 438, 439t–443t
signs and symptoms of, 415–416 for ankle sprain, 533 Initial visit, 80–81
treatment of, 416–417 and pulmonary embolism, 303 Injury(ies)
Hypertriglyceridemia Immunization, 200–201. See also cranial (skull, head), 178–179
and heart disease, 339 Vaccine(s). delirium due to, 670
vs. hypercholesterolemia, 326 contraindications to, 201, 203t–205t epidemiology of, 124–126
Hypnosis, 139 schedule of, 125f, 126f, 201, 202f impact on family unit of, 127
Hypnotic medications, for insomnia, accelerated, 201, 207f, 208f knee
248–249 Immunocompromised individuals, vs. deep venous thrombosis, 350t
Hypocalcemia, 155, 155t immunization of, 201 imaging of, 191, 192f
Hypochondriasis, vs. Impaired competency, informed consent prevention of, 126–127
hypercholesterolemia, 326–327 with, 73 Injury risk factors, screening for, 127
Hypoglycemia, 156–157 Inactivated poliovirus (IPV) vaccine, 125f, INR (international normalized ratio), 162,
vs. heat stroke, 688 202f, 204t, 207t, 208t 163t
rebound, 135 Incidence rate, 66–67, 67t, 68t Insomnia, 246–249
Hypogonadotropic hypogonadism, in Incretin mimetic, for diabetes mellitus, 388 differential diagnosis of, 247
Cushing’s syndrome, 406 Indomethacin (Indocin), 212t evaluation of, 247–248
Hypokalemia, 153t, 154 Infection(s) treatment of, 248–249
Hypomagnesemia, delirium due to, delirium due to, 669 Instrument tie, 543
668–669, 670, 671 intracranial, 180–181 Insulin
Hyponatremia, 152–153, 152t middle ear. See Otitis media. for diabetes mellitus, 387t, 388
pseudo-, 153 serious bacterial, in children inhaled, 388
Hypopituitarism, congenital, short stature fever due to, 237, 239, 240–241 side effects of, 388
due to, 559–560 vaccines and, 240–241 types of, 388

724
 Index

Insulin deficiency, 384 Intimate partner violence (IPV) (Continued) K

Insulin resistance, 384, 391, 392–393, 392t, safety assessment and plan for, 83, 85t Kadian Tabs (morphine), 209, 210, 211,
393b screening for, 82–83, 83t 214, 214t, 215, 215t
acanthosis nigricans with, 398 victims of, 81, 82t Kawasaki disease, 470t
Insulin resistance syndrome. See management of, 83–85, 84t, 85t Kayexalate (sodium polystyrene
Metabolic syndrome (MES). Intoxication, delirium due to, 670 sulfonate), for acute renal
Insulin sensitizers, for diabetes mellitus, Intracranial infections, 180–181 failure, 434
385 Intraductal papillomas, solitary, 606 Keflex (cephalexin)
Integrated care, 26 Intrahepatic cholestasis of pregnancy, for drug reaction, 448
Integrative medicine, 132–140 pruritus due to, 254–255 for streptococcal pharyngitis, 220t
case study of, 134–135 Intrarenal causes, of acute renal failure, Kelsey, Mavis, Sr., 33
defined, 133b 431b, 432–433, 433f, 434t Kemadrin (procyclidine), for Parkinson’s
eight perspectives on, 135–140 Intrauterine devices, dysmenorrhea due disease, 508
energy medicine in, 138, 138b to, 583 Keratoses
exercise and movement therapies in, Intravenous pyelogram (IVP), 173t, 191 actinic, 117
136–137, 137b Intrinsic factor antibody assay, 357 seborrheic, 473, 486,
as family medicine, 132–134 Introitus, condyloma of, CP86–10 CP63–20––CP63–22
herbal medicine in, 136, 136b Intron A (interferon alfa-2b), for Ketoprofen (Orudis), 212t
manipulative therapies in, 137–138, melanoma, 488 Ketorolac (Toradol), 212t
138b Inversion stress test, 533, 536f Kidney, ureter, and bladder (KUB) film,
mind-body influence in, 138–139, 139b Inverted knot, 542, 543f 191
nutrition in, 135–136, 136b Iodine 131, for hyperthyroidism, 417 Kinetic tremor, 507
other medical systems in, 139, 140b Ipratropium bromide (Atrovent) Klonopin (clonazepam)
spiritual connection in, 139–140 for acute exacerbation of COPD, 295 for generalized anxiety disorder, 653,
steps in facilitating healing in, 132–133, for vasomotor rhinitis, 223 666t
133f IPV. See Intimate partner violence (IPV). for restless legs syndrome, 495t, 496
Integrative methods, 49b IPV (inactivated poliovirus) vaccine, 125f, Knee
Intensive care unit (ICU) psychosis, 670 202f, 204t, 207t, 208t MRI of, 175t
Intention tremor, 507 IRLSSG (International Restless Legs radiography of, 190f, 191, 191f, 192f
Interferon alfa, for polycythemia vera, 256t Syndrome Study Group), 492, Knee injury
Interferon alfa-2b (Intron A), for 493, 494b vs. deep venous thrombosis, 350t
melanoma, 488 Iron (Fe), serum, 158, 159t imaging of, 191, 192f
Interleukin-6, and coronary heart disease, Iron deficiency, 158, 159 Koebner phenomenon, 447
330 and restless legs syndrome, 493, 495 KUB (kidney, ureter, and bladder) film,
Intermediate outcomes, 68 Iron deficiency anemia, 158 191
Intermittent claudication (IC), 341–346 pruritus due to, 253t
case study on, 341–343 screening for, 128 L
clinical presentation of, 343, 344 Iron overload, 159 Labial melanotic macules, 486
defined, 342 Iron studies, 158–159, 159t Laboratory tests, 147–168
diagnosis of, 342–343, 344–345, 344f Iron-binding capacity, total, 158, 159t of blood cells, 148–152, 149t–151t
differential, 342–343, 342t Irritable bowel syndrome (IBS), 366–370 of electrolytes, 152–156, 152t–156t
pathogenesis of, 343 alarm features with, 368 electronic medical record of, 143
risk factors for, 343–344, 343t, 345t case study on, 366–368 of glucose, 156–157
treatment of, 343, 345–346, 345t, 346f diagnosis of, 367–368, 369t, 370t of glycosylated hemoglobin, 157, 157t
International normalized ratio (INR), 162, differential, 367–368 of human chorionic gonadotropin,
163t epidemiology of, 368 157–158, 158t
International Restless Legs Syndrome vs. giardiasis, 270 interpretation of, 147–148
Study Group (IRLSSG), 492, and ischemic colitis, 370 of iron, 158–159, 159t
493, 494b symptoms of, 368, 369t for liver function, 159–164, 160t–163t
Interosseous talocalcaneal ligament, 534f treatment of, 368–370 with multiple concurrent illnesses, 148
Interpersonal skills, of family physician, Ischemic colitis, irritable bowel syndrome of pancreatic enzymes, 164–165, 164t,
13 and, 370 165t
Interstitial cystitis, 419, 420 Ischemic heart disease, vs. GERD, 373 predictive value of, 148
Intestinal obstruction Isometric tremors, 507 reference ranges for, 147–148
vs. cholelithiasis, 362 Isotretinoin (Accutane), for acne, 453t, 454 of renal function, 165–166, 166t
vs. pancreatitis, 377 Itch. See Pruritus. of thyroid function, 166–167, 167t, 168t
Intimate partner violence (IPV), 81–86 IVP (intravenous pyelogram), 173t, 191 and treatment assumptions, 148
child exposed to, 81, 82, 82t Labyrinthitis, 258
management of, 86 J Laceration repair, 539–545, 541f–544f
defined, 81 Jaundice, 162 Lactose intolerance, vs. irritable bowel
health care costs of, 81 imaging for, 188 syndrome, 367
health effects of, 81 Jenner, Edward, 53 Laparoscopic cholecystectomy, for
management of abusive couple in, 86, Jewett, Sarah Orne, 30 cholelithiasis, 362, 365
86t Jod-Basedow disease, hyperthyroidism Laparoscopy
mandatory reporting of, 86 due to, 416 of endometriosis, 579
perpetrators of, 81–82 Joint Commission on the Accreditation of of pelvic inflammatory disease, 599,
identification and management of, 85 Healthcare Organizations, 33 600, 603f
treatment options for, 85–86 Joint Commission on the Accreditation of Lasix (furosemide)
during pregnancy, 549 Hospitals, 33 for acute renal failure, 434
prevalence of, 81 Journals, as reference materials, 62t for congestive heart failure, 316, 318
resources on, 87 Junctional nevus, 485, CP63–1 Last menstrual period (LMP), 547

725
 Index

Lateral epicondylitis, 527–530 Lexapro (escitalopram oxalate), for LMP (last menstrual period), 547
case study on, 527–528 generalized anxiety disorder, Lodine (etodolac), 212t
diagnosis of, 529, 530 662, 665, 666t Longitudinal melanonychia, 462
differential, 528–529, 528b Librium (chlordiazepoxide), for Long-term disability, 71
etiology of, 530 generalized anxiety disorder, Loop diuretics, adverse reactions to, 448t
prevention of, 530 666t Loose bowel movements, due to
treatment of, 529–530 Lice infestation, pruritus due to, 252t hypercholesterolemia, 324–340
Lateral talocalcaneal ligament, 534f Lichen planus Loperamide, for irritable bowel syndrome,
Latrodectism, 694 pruritus due to, 252t 370
Latrodectus mactans, 694–695, 694f, of vulva, CP86–6 Loratadine (Claritin)
695t Lichen sclerosus, of vulva, CP86–4, for allergic rhinitis, 225
LDL cholesterol. See Low-density CP86–5 for varicella, 274
lipoprotein (LDL) cholesterol. Lichen simplex chronicus, of vulva, Lorazepam (Ativan), for anxiety disorders,
Lead levels, screening for, 128 CP86–3 653, 666t
Lead poisoning, anemia due to, 357 Lidocaine, epinephrine, and tetracaine Lorcet (hydrocodone with
Learning, from patient encounters, 44–45, (LET), for laceration repair, acetaminophen), 211, 215t
46t 541 for chronic pain, 209, 213t
Learning disabilities, 569, 569b Lidocaine HCl (Xylocaine) for migraines, 501
Left shift, in white blood cells, 149 for laceration repair, 540 Lortab (hydrocodone with
Leg cramps, nocturnal, 492 for lateral epicondylitis, 529 acetaminophen), 211, 215t
Leg pain Lifelong learning, 5, 24 for chronic pain, 209, 213t
due to deep venous thrombosis, Lifestyle(s), for health, 129 for migraines, 501
347–353 Lifestyle interventions Loudness matching, 265
due to peripheral arterial disease, for diabetes mellitus, 382–383, 384, Louis, Pierre-Charles-Alexandre, 35
341–346 386t, 387t Lovastatin (Altoprev), for
Leg swelling, due to deep venous for GERD, 373, 373b, 374 hypercholesterolemia, 336t,
thrombosis, 347–353 for hypercholesterolemia, 332t–333t, 337t
Leiomyomata 338 Lovastatin-niacin (Advicor), for
dysmenorrhea due to, 583 for hypertension, 322 hypercholesterolemia, 336t, 337t
vaginal bleeding due to, 615 for metabolic syndrome, 396 Low-density lipoprotein (LDL) cholesterol
Lentigo(igines), 486, CP63–29 for restless legs syndrome, 495 and coronary heart disease, 103, 104,
of nail, 461–463, 462f Lightheadedness, nonspecific, 260t, 261, 328–329, 328f, 329t, 330, 338
Lentigo maligna melanoma, 486t, 487, 262 with diabetes mellitus, 388
CP63–32 Lind, James, 53, 54 diet and, 330
Lentigo simplex, of vulva, CP86–9 Linolenic acid, for hypercholesterolemia, lipid-lowering drugs for, 327, 330–331,
Leopold’s maneuvers, 551, 551t, 552f 330 333t–334t, 336t, 337t
Leptin resistance, 393b Lipase optimal levels of, 333t
Leptospirosis, 468t pancreatic, 164–165, 165t testing for, 327, 328
Leriche syndrome, 344 serum, 379 treatment goals for, 330, 331t
Lescol (fluvastatin), for Lipid(s), optimal levels of, 333t Lower esophageal sphincter relaxation,
hypercholesterolemia, 336t, 337t Lipid disorders, screening for, 102–103 transient, 374
Leslie, John, 30 Lipid profile, 327 Lower segment, of height, 556
LET (lidocaine, epinephrine, and Lipid-lowering drugs, for Low-grade squamous intraepithelial
tetracaine), for laceration repair, hypercholesterolemia, 327, lesions (LSIL), 634, 635
541 330–331, 333t–334t, 336t, 337t, Loxosceles reclusa, 692–694, 692f, 693f,
Lethargy, due to acute renal failure, 338–339 693t
429–431 Lipitor (atorvastatin), for Loxoscelism, 693
Letrozole, for breast cancer, 612t hypercholesterolemia, 330–331, Lp(a) lipoprotein, and coronary heart
Leukopenia, 149 336t, 337t disease, 329
Leukoplakia, cervical, 627, CP86–30 Lipoprotein(s), optimal levels of, 333t Lugol’s solution, for colposcopy, 642,
Leukotriene modifiers, for asthma, 442t Lipoprotein analysis, fasting, 327 644
Levaquin. See Levofloxacin (Levaquin). Lipoprotein-associated phospholipase A2, Lumbar spine, cost of imaging of, 173t
Levodopa, for Parkinson’s disease, and coronary heart disease, 330 Lumbosacral disk herniation, 179–180,
508–509 Lister, Joseph, 31, 36 180f, 181f
Levodopa/benserazide, for restless legs Literature evaluation, 61–69 Lumbosacral radiculopathy, 342
syndrome, 495 building clinical evidence from Lumbosacral spine, MRI of, 175t
Levodopa/carbidopa (Sinemet) published research in, 65–66, Lumpectomy, 606
for Parkinson’s disease, 509 65f Lung cancer
for restless legs syndrome, 495, 495t interpreting study results in, 67–69, 68t epidemiology of, 113
Levo-Dromoran (levorphanol), 213t, reference materials for, 62, 62t hiccups due to, 232–235
215t understanding statistical significance of prevention of, 113–115, 114f, 115f
Levofloxacin (Levaquin) study results in, 66–67, 67t screening for, 113
for Chlamydia, 593b using evidence at point of care in, Lupus, vs. fibromyalgia, 523
for gonorrhea, 594b 62–65, 62t–64t Lycosidae, 695, 695f
for pelvic inflammatory disease, 595t, Literature surveillance, evidence-based, 55 Lyme disease, 465, 468t
599t Literature surveillance systems, 57 Lymphedema, vs. deep venous
for sinusitis, 285, 285t, 286 Liver disease thrombosis, 350t
for UTI, 422t vs. anemia, 355 Lymphoma
Levorphanol (Levo-Dromoran), 213t, 215t pruritus due to, 251–252 cutaneous T-cell, pruritus due to, 252t
Levothyroxine (Synthroid), for Liver spot, 486, CP63–29 Hodgkin’s, pruritus due to, 253t
hypothyroidism, 410 Liver tests, 159–164, 160t–163t Lymphopenia, 149

726
 Index

M Melanoma, 482–490 Metabolic syndrome (MES) (Continued)

Macroglia, 515 ABCDE rule of, 483, 484, 484t, 485 patient education on, 391
Magnesium sulfate, for hypomagnesemia, acral-lentiginous, 486t, 487, proinflammatory/prothrombotic state
671 CP63–33––CP63–36 in, 400
Magnetic resonance angiography (MRA), benign juvenile, 486, CP63–19 treatment of, 391, 396, 400–401
175t, 177 biopsy of, 487 visceral adiposity in, 393f, 394–395,
Magnetic resonance case study on, 483–484 395f, 399t
cholangiopancreatography classification of, 486–487, 486t case study on, 397–399
(MRCP), 185, 186 clinical presentation of, 485 disease risk for, 394–395, 395t
for cholelithiasis, 363 diagnosis of, 483, 488 and free fatty acids, 392
Magnetic resonance imaging (MRI), differential, 485–486, 485t, Metastases
175–177, 175t, 176f CP63–1––CP63–29 breast cancer, 613
of breast, 607–608 epidemiology of, 116, 484 cerebral, 513
Major depressive disorder, 661–662, 662b excision of, 487, 487t imaging of, 181, 181f, 182f
Malabsorption syndromes, 270 follow-up guidelines for, 488, 490t hepatic, 188
Male reproductive system, imaging of, in situ, 488 of melanoma, 483, 483t, 487–488, 488t,
192–193, 192f, 193f lentigo maligna, 486t, 487, CP63–32 489t
Malignant acanthosis nigricans, 398 medical treatment of, 488 spinal, 209
Malignant melanoma. See Melanoma. metastatic, 483, 483t, 487–488, 488t, Metered-dose inhaler (MDI), for asthma,
Malnutrition, short stature due to, 559 489t 439t, 442t
Mammary abscess, 606 of nail, 461–462, 462f, 463, 463b, Metformin
Mammography CP63–36 and contrast agents, 174
cost of, 173t nodular, 486t, 487, CP63–31 for diabetes mellitus, 383, 385, 386
diagnostic, 606 pathogenesis of, 484–485 Methadone (Dolophine), 211, 214t, 215t
screening, 118, 193–194, 193f, 607, 609b prevention of, 116–117, 490 Methotrexate, for breast cancer, 612, 612t
Managed care, 8 prognostic factors for, 487 Methylphenidate, for AD/HD, 569, 572
Management plan, negotiation of, 43–44, risk factors for, 116–117, 484, 484t Methylprednisolone
45t screening for, 116–117, 483–484, for acute exacerbation of COPD, 295,
Manipulative therapies, 137–138, 138b 484t 296
Manual abductor pollicis brevis testing, sites of, 484 for asthma, 442t
701f staging of, 487–488, 488t, 489t for lateral epicondylitis, 529
Massage, 138 superficial spreading, 483, 486–487, for vertigo, 261
Mastitis, granulomatous, 606 486t, CP63–30 Methylxanthines, for asthma, 442t
Maxillary sinuses, transillumination of, Melanonychia, longitudinal, 462 Metoclopramide (Reglan), for migraines,
283, 284 Melanotic freckle of Hutchinson, 487 501
McBurney’s point, 361 Meniere’s disease, 259, 261, 262, 264 Metoprolol, for atrial fibrillation, 312, 313
MDCT (multidetector CT), 174 Meningitis, 180–181 Metronidazole (Flagyl)
MDI (metered-dose inhaler), for asthma, Meningococcal vaccine, 125f for bacterial vaginosis, 592, 592b
439t, 442t Meningococcemia, 465, 466t for giardiasis, 270, 271, 272
Mean corpuscular volume (MCV), 148, Meniscal tear, imaging of, 191, 192f for pelvic inflammatory disease, 595t,
150–152, 151t Menstrual cramps, severe, 582–585 599t
Measles, mumps, rubella (MMR) vaccine, Menstruation, irregular, due to Cushing’s for trichomoniasis, 595–596
125f, 126f, 202f, 204t, 206t–208t syndrome, 402–405 MIBB (minimally invasive breast biopsy),
and autism, 563–564 Meperidine (Demerol), 213t, 215, 215t 608
Mechanical acne, 452 for migraines, 501 Microcomedone, 453
Meclizine, for vertigo, 259, 261 Meropenem (Merrem IV), for UTI, 422t Microglia, 515
Medial collateral ligament injury, 528 MES. See Metabolic syndrome (MES). Micropapillomatosis labialis, CP86–7
Medial epicondylitis, 528 Mesenteric infarction, vs. pancreatitis, 377 Middle cerebral artery, angiogram of, 179f
Median nerve compression test, 698,700f Mesenteric ischemia, vs. pancreatitis, Middle ear effusion (MEE), 227, 228,
Median nerve entrapment, 529 377 230–231, 231t
Median nerve injury, 704f Meta-analysis, 66, 69 Middle ear pain, 227t
manual abductor pollicis brevis testing Metabolic disorders Miglitol (Glyset), for diabetes mellitus,
for, 701f anxiety due to, 651 388
Medicaid, 33 delirium due to, 670 Migraine(s), 499–502
Medical history, 80 Metabolic syndrome (MES), 390–401 case study on, 497–499
Medical nutrition therapy, for diabetes and cardiovascular disease, 395–396, clinical presentation of, 499–500
mellitus, 382–383, 384, 386t, 387t 399 diagnosis of, 498, 500f
Medicare, 33 case studies on, 390–391, 397–399 patient education on, 501–502
Medication reconciliation, electronic chest pain due to, 307 precipitating factors in, 501b
medical record of, 142–143 vs. Cushing’s syndrome, 403, 403t prevention of, 499, 501, 501b, 502t
Medication toxicity, delirium due to, 670, defined, 399–400, 399t vs. tension-type headache, 502t
670b and diabetes mellitus, 393–394, 394f treatment of, 499, 501
Medroxyprogesterone, for endometriosis, diagnosis of, 391, 392t, 398–399, 399t Millis Commission Report, 5, 7, 9, 14–15,
580 dyslipidemia in, 394 33
MEE (middle ear effusion), 227, 228, epidemiology of, 391–392, 400 Mind-body influences, 138–139, 139b
230–231, 231t free fatty acids in, 392, 393b, 394 Minerals, in integrative medicine,
Mefoxin (cefoxitin), for pelvic vs. hypercholesterolemia, 326 135–136, 136b
inflammatory disease, 595t, 600, hypertension in, 394 Minimal masking level, 265
600t insulin resistance in, 391, 392–393, Minimally invasive breast biopsy (MIBB),
Megestrol acetate, for breast cancer, 612t 392t, 393b 608
Meglitinide, for diabetes mellitus, 385, 386 pathogenesis of, 391, 391f Minocycline (Minocin), for acne, 454

727
 Index

Mirapex (pramipexole) Nabothian cysts, 644, CP86–31 Neuropathy

for Parkinson’s disease, 508 Nabumetone (Relafen), 212t diabetic, vs. double crush syndrome,
for restless legs syndrome, 495–496, NAEPP (National Asthma Education and 702
495t Prevention Program), 438–444 peripheral
Mirizzi syndrome, 362 Naftidrofuryl, for peripheral arterial pruritus due to, 253t
Misophonia, 264 disease, 345, 345t vs. restless legs syndrome, 492
Mistakes, 76 Nail, melanoma of, 461–462, 462f, 463, tremor with, 507
Mitoxantrone, for breast cancer, 612t 463b, CP63–36 ulnar, 528
5MMC (5 Minute Medical Consult), 58 Nail lentigo, 461–463, 462f Neurophysiologic model, of tinnitus,
MMR (measles, mumps, rubella) vaccine, Nalbuphine (Nubain), 215 266–267, 266f
125f, 126f, 202f, 204t, 206t–208t for opioid-induced pruritus, 256t Neurotic excoriations, pruritus due to,
and autism, 563–564 Nalmefene (Revex), for cholestasis, 256t 253t, 256t
Moles, atypical, 485 Naproxen (Naprosyn), 212t Nevus(i), 485–486
Molluscum contagiosum, 456–457 for chronic pain, 209 acquired (benign), 485
Mononucleosis (Mono), infectious, 218, for primary dysmenorrhea, 584 atypical (dysplastic), 485, 485t,
219, 220 Nasal congestion, 199–200, 222–225 CP63–12––CP63–17
Monospot test, 219 Nateglinide, for diabetes mellitus, 386 familial, 483, 485
Monounsaturated fat, 384 National Ambulatory Medical Care changing, due to melanoma, 482–484
Monsel’s solution, for colposcopy, 641, Survey, 16 common, 485t
641f National Asthma Education and compound, 485, CP63–2
Montelukast, for asthma, 442t Prevention Program (NAEPP), congenital, 485, CP63–9––CP63–11
Morphine (Kadian Tabs; Ora-Morph-SR, 438–444 dermal, 485, CP63–3––CP63–8
MS Contin), 209, 210, 211, 214, National Cholesterol Education Program halo, 485–486, CP63–18
214t, 215, 215t (NCEP), 103, 327, 329t junctional, 485, CP63–1
Mosaicism, of cervix, 644, CP86–32, National Guideline Clearinghouse, 62, of nail bed, 462
CP86–33 63t Spitz, 486, CP63–19
Motivational therapy, for bedwetting, 425 Nature, healing power of, 29, 35 New problem visit, 41–42, 41t, 42t, 44t,
Motrin. See Ibuprofen (Motrin, Advil). Nausea 45t
Movement therapies, 136–137, 137b due to acute renal failure, 429–431 Niacin, for hypercholesterolemia, 331,
MRA (magnetic resonance angiography), in palliative care, 520t 333t, 334t, 336t, 337t
175t, 177 due to pregnancy, 546–547 Nitazoxanide (Alinia), for giardiasis, 272
MRCP (magnetic resonance NCEP (National Cholesterol Education Nitrofurantoin (Furadantin), for UTI,
cholangiopancreatography), Program), 103, 327, 329t 420, 421, 422t
185, 186 Neck, radiographs of, 171f Nitroglycerin, for congestive heart failure,
for cholelithiasis, 363 Necrotic arachnidism, 693, 693t 318
MRI (magnetic resonance imaging), Nedocromil, for asthma, 442t Nixon, Pat, 32, 37
175–177, 175t, 176f Neisseria gonorrhoeae, 593, 594 Nociceptive pain, 210
of breast, 607–608 pelvic inflammatory disease due to, Nocturnal enuresis. See Betwetting.
MS Contin (morphine), 209, 210, 211, 598 Nocturnal leg cramps, 492
214, 214t, 215, 215t Nephritis, allergic interstitial, 433 Nodular melanoma, 486t, 487, CP63–31
Mucolytics, for acute bronchitis, 290 Nephrolithiasis Nonbenzodiazepines, for generalized
Multidetector CT (MDCT), 174 in Cushing’s syndrome, 406 anxiety disorder, 665–667, 666t
Multigated acquisition (MUGA) study, imaging of, 191–192 Noncompliance
178t, 183 Nephropathy, radiocontrast, 172–174 defined, 89
Multiple myeloma, pruritus due to, 253t Nerve root compression, imaging of, detection of, 92–94, 93t
Multiple sclerosis, vs. double crush 179–180, 180f, 181f ethical issues with, 74, 74t, 96
syndrome, 700 Nerve root entrapment, cervical, vs. factors in, 74, 74t, 89–92
Multiple sleep latency testing, 248 double crush syndrome, 700 future trends with, 96
Muraglitazar, for diabetes mellitus, 388 Nerve-gliding exercises, for median nerve intentional vs. unintentional, 89
Murine typhus, 469t decomposition, 703f misconceptions about, 94
Murphy’s sign, 186 Nesiritide, for congestive heart failure, prevalence of, 88–89
Muscular strain, vs. fibromyalgia, 523 318 prevention and treatment of, 94–96,
Musculocutaneous nerve entrapment, Neural plasticity, and tinnitus, 266, 267 95t
529 Neural tube defects, 549, 550 Noninvasive positive-pressure ventilation
Mycoplasma pneumoniae infection, 468t Neuritis, vestibular, 257–259, 261 (NPPV), for acute exacerbation
Mycosis fungoides, pruritus due to, 252t Neurodermatitis, pruritus due to, 253t of COPD, 296
Myelography, 180 Neurogenic itch, 251, 255 Nonsteroidal anti-inflammatory drugs
Myeloma, multiple, pruritus due to, 253t Neuroleptic malignant syndrome, 682t (NSAIDs), 211, 212t–213t
Myocardial imaging studies, 183 Neurologic system, imaging of, 178–182, adverse reactions to, 448t
Myocardial infarction 179f–182f for ankle sprain, 533
aspirin for prevention of, 104 Neuroma, acoustic, 260 for endometriosis, 579, 580
vs. congestive heart failure, 316 Neuromuscular conditions, chest pain due gastrointestinal side effects of, 430
vs. pancreatitis, 377 to, 307 for migraines, 501
Myocardial perfusion scan, 178t Neurontin (gabapentin) in prevention of colorectal cancer, 120
Myositis, vs. intermittent claudication, 342 for chronic pain, 209 for primary dysmenorrhea, 584–585
Myxedema coma, 670 for hiccups, 235 for tension-type headaches, 502
for pain, 216 Nonstimulants, for AD/HD, 570
N for restless legs syndrome, 492, 495t, Norco (hydrocodone with
NAATs (nucleic acid amplification tests) 496 acetaminophen), 211, 215t
for Chlamydia, 593 Neuropathic itch, 251, 255 for chronic pain, 209, 213t
for Neisseria gonorrhoeae, 594 Neuropathic pain, 210 for migraines, 501

728
 Index

Norpramin (desipramine) Omega-3 fatty acids, for Ovarian cancer, 119

for generalized anxiety disorder, 666t hypercholesterolemia, 330, 332t Ovarian cysts, dysmenorrhea due to, 583
for pain, 216 Omnicef (cefdinir) Overweight, defined, 395t
North American blastomycosis, 467t for otitis media, 229t Oxazepam (Serax), for generalized anxiety
North American Menopause Society, 62 for sinusitis, 286 disorder, 666t
Northwestern brown spider, 695 OMT (osteopathic manipulative Oxycodone (OxyContin), 209, 211–214,
Nortriptyline (Aventyl, Pamelor) treatment), 137 214t, 215, 215t
for generalized anxiety disorder, 666t Onchocerciasis, pruritus due to, 253t for restless legs syndrome, 496
for pain, 216 Ondansetron (Zofran) Oxycodone with acetaminophen
for smoking cessation, 290 for cholestasis, 256t (Percocet), 209, 211, 214t
Notalgia paresthetica, pruritus due to, for opioid-induced pruritus, 256t Oxycodone with ASA (Percodan), 214t
253t, 256t Open-access scheduling, 13 Oxygen, for cluster headache, 503
NPPV (noninvasive positive-pressure Opinion based on experience, 52 Oxygen therapy, for COPD, 295, 296,
ventilation), for acute Opioid analgesics, 211–216, 213t–215t 297t
exacerbation of COPD, 296 addiction to, 210, 216 Oxymetazoline (Afrin)
NSAIDs. See Nonsteroidal anti- for chronic pain, 210, 211–215 for allergic rhinitis, 225
inflammatory drugs (NSAIDs). for migraines, 501 rhinitis medicamentosa due to, 223
Nubain (nalbuphine), 215 in palliative care, 519, 520t
for opioid-induced pruritus, 256t pruritus due to, 252, 256t P
Nuclear imaging, 177–178, 178t for restless legs syndrome, 495t, 496 P value, 67
Nucleic acid amplification tests (NAATs) side effects of, 215–216 Paclitaxel, for breast cancer, 612, 612t
for Chlamydia, 593 withdrawal from, 216 PAD. See Peripheral arterial disease
for Neisseria gonorrhoeae, 594 Oppositional-defiant disorder (ODD), (PAD).
Numb hands and feet, due to frostbite, 568, 569, 572 Pain
683–686 Oral cancer, 121 abdominal
Number needed to harm, 68, 68t Oral contraceptives due to appendicitis, 361–362
Number needed to treat, 67t, 68 for acne, 453t, 454 due to cholelithiasis, 359–365
Nutrition. See Diet. and endometrial cancer, 617 due to endometriosis, 577–580
Nutritional deficiencies, delirium due to, for endometriosis, 580 due to hypercholesterolemia,
670 for primary dysmenorrhea, 584, 585 324–340
Nystagmus, spontaneous, 261 Oral glucose-lowering agents, 385–386, due to irritable bowel syndrome,
387t 366–370
O Ora-Morph-SR (morphine), 209, 210, due to pancreatitis, 376–380
Obesity 211, 214, 214t, 215, 215t back
abdominal, in metabolic syndrome, Orap (pimozide), for delusions of differential diagnosis of, 587
393f, 394–395, 395f, 399t parasitosis, 256t due to osteoporosis, 586–589
case study on, 397–399 Orudis (ketoprofen), 212t chest
disease risk for, 394–395, 395t Oseltamivir (Tamiflu), for influenza, 280, due to angina pectoris, 305–309
and free fatty acids, 392 280t due to anxiety disorder, 650–652
in Cushing’s syndrome, 405 Osler, William, 7, 31–32, 33, 36 differential diagnosis of, 306–307,
defined, 395t Osteoarthritis, vs. intermittent 306t
prevalence of, 128, 129f claudication, 342 chronic, 209–216
screening for, 128 Osteochondritis dissecans, 532 assessment of, 210, 210f
Obliterative bronchiolitis, vs. COPD, 294t, Osteochondrodysplasias, short stature due classification of, 210
295 to, 560 epidemiology of, 209
Obsessive-compulsive disorder (OCD), Osteopathic manipulative treatment etiology of, 209–210
653, 680 (OMT), 137 management of, 210–216, 211f,
Obstetric risk assessment, 128 Osteopathic medicine, 137 212t–215t
Obstetrical ultrasound, 177, 178t Osteoporosis, 121–123, 586–589 pelvic, 578, 578t
Obstructive uropathy, 191–192 case study on, 586–587 due to pelvic inflammatory
Obturator sign, 361 in Cushing’s syndrome, 406 disease, 604
Occult bacteriuria, during pregnancy, 550 defined, 588 delirium due to, 670
Occupational therapy, for double crush epidemiology of, 121–122, 121f, 588 ear, 227–228, 227t
syndrome, 702 imaging of, 191 elbow, 527–530
OCD (obsessive-compulsive disorder), impact on family unit of, 122–123 due to fibromyalgia, 522–526
653, 680 prevention and treatment of, 122–123, leg
ODD (oppositional-defiant disorder), 588–589 due to deep venous thrombosis,
568, 569, 572 risk factors for, 122, 588 347–353
Office visits, electronic medical record of, screening for, 122, 588 due to peripheral arterial disease,
143 treatment for, 122 341–346
Office workflow, electronic medical record vertebral fractures due to, 586–588 neuropathic, 210
and, 144 Otitis media, 226–231 nociceptive, 210
Ofloxacin (Floxin) case study on, 226–228 somatic, 210
for Chlamydia, 593b defined, 228t upper extremity, due to double crush
for gonorrhea, 594b diagnosis of, 227, 228 syndrome, 697–706
for pelvic inflammatory disease, 595t, differential, 226–227, 226t visceral, 210
599t natural history of, 230–231, 231t Pain management
for UTI, 422t patient education on, 227 analgesics for, 211–216, 212t–215t
Olanzapine, for schizophrenia, 682 risk factors for, 229–230, 230t nonpharmacologic modalities for, 216
Oligodendrogliomas, 515 treatment of, 227–229, 229t in palliative care, 518, 519–520, 520t
Omalizumab, for asthma, 444 Ottawa ankle rules, 536–538, 538b Pain scales, 210, 210f

729
 Index

Palliative care, 517–521 Papillomas, solitary intraductal, 606 Pelvic inflammatory disease (PID)
case study on, 517–519 Papillomavirus. See Human (Continued)
communication and goal planning for, papillomavirus (HPV). laparoscopy in, 599, 600, 603f
518, 519, 520–521 Parasitic infections, pruritus due to, 253t pelvic CT in, 600, 601f, 602f
coordination of, 518, 519 Parasitosis, delusions of, 253t, 256t pelvic ultrasound in, 600, 602f, 603f
pain and symptom management in, Parathyroid adenomas, 188–189 dysmenorrhea due to, 583
518, 519–520, 520t Parkinson’s disease (PD), 504–510 and ectopic pregnancy, 603
psychosocial, spiritual, and case study on, 504–506 epidemiology of, 597
bereavement support for, 518, clinical presentation of, 507–508 hospitalization for, 600–601, 604t
519, 521 diagnosis of, 505, 507–508 and infertility, 603
Palmer, D.D., 137 differential, 505, 506–507 long-term sequelae of, 602–604
Palpitations, due to atrial fibrillation, epidemiology of, 507 lower abdominal pain due to, 597–600
310–312 treatment of, 505–506, 508–510 pathogenesis of, 598
Pamelor (nortriptyline) Paromomycin (Humatin), for giardiasis, patient education for, 600
for generalized anxiety disorder, 666t 272 perihepatitis due to, 601–602
for pain, 216 Paroxetine (Paxil) prevention of, 598
for smoking cessation, 290 for generalized anxiety disorder, 666t risk factors for, 597–598, 598b
Panbronchiolitis, diffuse, 294t, 295 for polycythemia vera, 256t symptoms of, 594, 597, 598
Pancoast’s tumor, vs. double crush Parsidol (ethopropazine), for Parkinson’s treatment of, 594, 595t, 599–601, 599t,
syndrome, 700 disease, 508 600t
Pancreatic cancer, 120–121 Partner abuse. See Intimate partner with tubo-ovarian abscess, 600, 601,
Pancreatic enzymes, 164–165, 164t, 165t violence (IPV). 603f
Pancreatic lesions, imaging of, 188 Partner Violence Screen (PVS), 83t vaginal discharge due to, 591
Pancreatitis Parvovirus B19 infection, pruritus due to, Pelvic pain, chronic, 578, 578t
acute, 376–380 253t due to pelvic inflammatory disease, 604
case study on, 376–378 Pasteur, Louis, 31 Pelvis
causes of, 378, 380 Pathophysiologic reasoning, 52, 56–57 cost of imaging of, 173t
clinical presentation of, 378–379 Patient encounters, learning from, 44–45, radiograph of, 173f
complications of, 380 46t Pemphigoid, bullous, pruritus due to, 252t
diagnosis of, 377–378, 379 Patient factors, in noncompliance, 90, 91t Penicillin, for streptococcal pharyngitis,
differential, 377–378 Patient identification, 80 218, 220–221, 220t
vs. hypercholesterolemia, 327 Patient information, acquiring and Penicillin V, for streptococcal pharyngitis,
mild vs. severe, 378 synthesizing, 41, 42t 218, 220t
prognosis for, 379–380, 379b Patient-controlled analgesia (PCA), 209 Pentazocine (Talwin), 215
treatment of, 378, 380 Patient-oriented evidence, disease- Pentoxifylline (Trental), for peripheral
alcoholic, 378, 380 oriented vs., 55–56 arterial disease, 345, 345t
vs. cholelithiasis, 362 Patient-oriented evidence that matters PEPID (Portable Electronic Physicians
gallstone, 378, 380 (POEM), 54, 55, 57–58, 62 Information Database), 58–59
Panic attacks Patient-oriented outcomes, 55–56, 68 Peptic ulcer
defined, 677 Paxil (paroxetine) vs. cholelithiasis, 361
due to medical conditions, 675–676 for generalized anxiety disorder, 666t vs. GERD, 372
with other anxiety disorders, 676 for polycythemia vera, 256t vs. pancreatitis, 377
in panic disorder, 653, 661, 675 PCA (patient-controlled analgesia), 209 Percocet (oxycodone with
situationally bound (cued), 676 PCP (Primary Care Plus), 58–59 acetaminophen), 209, 211, 214t
situationally predisposed, 676 PCV (pneumococcal polysaccharide Percodan (oxycodone with ASA), 214t
unexpected or uncued, 676 vaccine), 125f, 126f, 202f, 205t, Percutaneous transhepatic
Panic disorder, 674–677 207t, 240–241 cholangiography (PTC), 186
comorbid conditions with, 676 PD. See Parkinson’s disease (PD). Performance measures, 145
diagnosis of, 653, 661, 675–676, 677 PE. See Pulmonary embolism (PE). Pergolide (Permax)
differential, 675–676 PE (pressure equalization) tubes, 230–231 for Parkinson’s disease, 508
epidemiology of, 677 Peabody, Francis, 4, 14 for restless legs syndrome, 495, 495t
vs. hypercholesterolemia, 326 Peak bone mass, and osteoporosis, 588 Pergolide European Australian RLS study
treatment of, 676–677 Peak expiratory flow rate, 243–244 (PEARLS Study), 495
Pap smear, 116 Peak-dose kinesia, with levodopa, 509 Pericarditis, chest pain due to, 307
Bethesda system for, 621, 622t, 623t, PEARLS Study (Pergolide European Perihepatitis, due to pelvic inflammatory
627, 628t–630t, 630, 634–635 Australian RLS study), 495 disease, 601–602
and cervical dysplasia, 629–630, 630t, Pearly penile papules, 457, 457f Periodic limb movements of sleep
633–634 Pederson speculum, for colposcopy, (PLMSs), 493
cytologic screening method with, 636–637 Peripheral arterial disease (PAD), 341–346
631–633, 631f, 632f Pediazole (erythromycin/sulfisoxazole), case study on, 341–343
intervals for, 622–625, 624t, 633–634 for otitis media, 229t clinical presentation of, 343, 344
management of results of, 627–629, Pediculosis, pruritus due to, 252t diagnosis of, 342–343, 344–345, 344f
635–636 Pelvic inflammatory disease (PID), 594, differential, 342–343, 342t
nomenclature for, 629–630, 630t 596–604 pathogenesis of, 343
for prevention of cervical cancer, 116 case study on, 597–600 risk factors for, 343–344, 343t, 345t
screening, 620–625, 622t–624t chronic pelvic pain due to, 604 treatment of, 343, 345–346, 345t,
sensitivity and specificity of, 631 complications of, 601–604 346f
timing of, 633 defined, 594 Peripheral neuropathy
unsatisfactory, 634, 635 diagnosis of, 597–599, 600 pruritus due to, 253t
Papanicolaou, George, 629 criteria for, 594, 595b vs. restless legs syndrome, 492
Paperless office, 146 differential, 597, 597b tremor with, 507

730
 Index

Peripheral vascular disease Placenta previa, 573–576 Postinfectious tremor, 506

vs. frostbite, 685 clinical presentation of, 575–576 Postrenal causes, of acute renal failure,
vs. restless legs syndrome, 492 complete vs. marginal, 575, 576 430, 431b, 432, 433f
Permax (pergolide) diagnosis of, 574–575 Postrenal obstruction, 430, 431b
for Parkinson’s disease, 508 differential, 574, 576 Post-traumatic stress disorder, 653–654
for restless legs syndrome, 495, 495t epidemiology of, 575 vs. cholelithiasis, 362
Pernicious anemia, 354–356 management of, 575, 576 Post-traumatic tremor, 507
Peroneal tendon subluxation, 532 risk factors for, 575 Postural tremor, 507
Perpetrators, of intimate partner violence Placental abruption, 574, 576, 576b Potassium levels, 153–154, 153t
characteristics of, 81–82 Plantar warts, 477–481 Potter, Claudia, 32
identification and management of, 85 case study of, 477–479 Povidone-iodine (Betadine), for laceration
treatment options for, 85–86 diagnosis of, 478, 480, 481f repair, 541
Persantine (dipyridamole) stress testing, differential, 478 Power, 69
for angina pectoris, 308 epidemiology of, 479 PPI (proton-pump inhibitor), for GERD,
Personal medical home, 24 pathogenesis of, 479 373–374, 375, 375b
Personalized care, 7–8, 7f treatment of, 478–479, 480–481, 481f PPV (pneumococcal polysaccharide
Pervasive developmental disorder, 563t Plasma volume, increased, anemia due to, vaccine), 125f, 126f, 202f, 205t,
PET (positron emission tomography), 358 207t, 240–241
178 Platelet aggregation, and peripheral Practice management system, 143
of brain tumor, 515 arterial disease, 345, 345t Pramipexole (Mirapex)
PFTs (pulmonary function tests), 243 Platelet count, 150, 151t for Parkinson’s disease, 508
for asthma, 438 Pletal (cilostazol), for peripheral arterial for restless legs syndrome, 495–496,
Phalen’s test, 698 disease, 343, 345, 345t 495t
Pharmacologic stress testing, for angina PLMSs (periodic limb movements of Pramlintide (Symlin), for diabetes
pectoris, 308 sleep), 493 mellitus, 388
Pharmacy refill records, and compliance, Pneumococcal polysaccharide vaccine Pravastatin (Pravachol), for
93–94 (PCV, PPV), 125f, 126f, 202f, hypercholesterolemia, 336t
Pharyngeal gonorrhea, 593 205t, 207t, 240–241 Precose (acarbose), for diabetes mellitus,
Pharyngitis, acute, 217–221 Pneumonia, in infants and children, 239 388
bacterial, 218–219, 219t Pneumothorax, chest pain due to, 307 Predictive value, of test, 148
case study of, 217–218 Podofilox 0.5% solution or gel Prednisone
diagnostic workup for, 219–220, 220t (Condylox), for condyloma adverse reactions to, 448t
differential diagnosis of, 218–219, acuminata, 457, 457t, 459 for allergic rhinitis, 225
219t Podophyllin resin 10% to 25% (Podofin), for asthma, 442t
streptococcal, 217–221, 220t for condyloma acuminata, 458 with contrast agents, 174
therapy for, 220–221, 220t POEM (patient-oriented evidence that for spider bites, 692
viral, 218, 219t matters), 54, 55, 57–58, 62 Pregnancy, 546–553
d-Phenylalanine derivative, for diabetes Poisons bacterial vaginosis in, 592
mellitus, 385 delirium due to, 670 due date for, 547–548
Phobias, 653 vs. heat stroke, 688–689 diagnosis of, 547
Phospholipase-associated complex tremor due to, 506 ectopic
(PLAC) test, 330 Poliovirus vaccine, 125f, 202f, 204t, 207t, pelvic inflammatory disease and, 603
Physical activity. See Exercise. 208t ruptured, 378
Physical therapy, for double crush Polycythemia rubra vera, pruritus due to, first follow-up visit for, 550
syndrome, 702 253t, 256t fundal height during, 550, 551f
Physician, as human being, 76–77 Polymyalgia rheumatica, 523 gestational diabetes during, 550–551
Physician factors, in noncompliance, Polyps giardiasis during, 272
91–92 cervical group B streptococcal infection during,
Physician-assisted suicide, 77–78 dysmenorrhea due to, 583 551–552, 551b
Physician-patient relationship, 70–71 vaginal bleeding due to, 615 initial visit for, 546–550
Physiologic outcomes, 55–56, 68 endometrial, dysmenorrhea due to, Leopold’s maneuvers during, 551, 551t,
Physiologic tremors, 507 583 552f
Pick-lists, 143 uterine, vaginal bleeding due to, 615 occult bacteriuria during, 550
PID. See Pelvic inflammatory disease Polysomnography, 248 prenatal screening tests during,
(PID). Polyunsaturated fat, 384 548–549, 548b, 553t
Pigmented thumbnail, 461–463 Pomade acne, 452 prevention of unwanted, 128
Pill counting, and compliance, 93 Popliteal artery entrapment, vs. promotion of healthy, 549
Pimecrolimus, for pruritus, 256 intermittent claudication, 343 pruritus in, 252–255
Pimozide (Orap), for delusions of Popliteal cyst, vs. deep venous thrombosis, “quickening” during, 550
parasitosis, 256t 350t subsequent follow-up visits for,
Pioglitazone, for diabetes mellitus, 386 Portable Electronic Physicians 550–552
PIOPED (Prospective Investigation of Information Database (PEPID), ultrasound during, 177, 178t, 194–195,
Pulmonary Embolism 58–59 194f, 195f
Diagnosis) study, 302–303 Positron emission tomography (PET), 178 U.S. Preventive Services Task Force
Piperacillin and tazobactam (Zosyn), for of brain tumor, 515 recommendations for, 553t
UTI, 422t Posterior inferior tibiofibular ligament, vaginal bleeding during third trimester
Piroxicam (Feldene), 212t 534f of, 573–576
Pitch masking, 265 Posterior interosseous nerve entrapment, varicella during, 275
Pituitary thyrotropin, 166–167, 167t 529 weight gain during, 550
PLAC (phospholipase-associated Posterior talofibular ligament, 534f Pregnancy test, 547
complex) test, 330 Posterior tibiotalar ligament, 534f Prehypertension, 322

731
 Index

PreMEDLINE, 50 Primary care, 6 PSA (prostate-specific antigen), 117

Prenatal screening, 548–549, 548b, 553t Primary care physician, 6–7, 9 Pseudoacanthosis nigricans, 398
Preplacement examinations, 71 Primary Care Plus (PCP), 58–59 Pseudoephedrine (Sudafed), for allergic
Prerenal azotemia, 432 Primary physician, 9 rhinitis, 225
Prerenal causes, of acute renal failure, Principles of Medical Ethics, 71 Pseudohyponatremia, 153
431b, 432, 433f, 434t Probiotics, 136b Pseudomonas septicemia, 466t
Prescription(s), electronic medical record Problem solving, 39–46 Psoas sign, 361
of, 142 acquiring and synthesizing patient Psoriasis
Prescription costs, and noncompliance, information in, 41–43, 42t vs. drug reaction, 447
74, 91 ambulatory encounter checklist in, 45–46 pruritus due to, 251, 252t
Prescription refill records, and assessing patient’s expectations in, 40–41, of vulva, CP86–2
compliance, 93–94 41t Psychiatric disorders
Presenting illness, 80 developing therapeutic relationship in, anxiety component in, 651
Pressure equalization (PE) tubes, 230–231 43, 44t weight loss due to, 414
Presyncope, 260–261, 260t learning from encounter in, 44–45, 46t Psychodynamic psychotherapy, for
Prevention, 100–130 negotiating management plan in, generalized anxiety disorder,
of cancer, 110–121, 111f, 112f 43–44, 45t 652
bladder, 121 Prochlorperazine (Compazine), for Psychogenic cough, 243
breast, 118–119, 193–194, 193f migraines, 501 Psychogenic itch, 251
cervical, 115–116 Procyclidine (Kemadrin), for Parkinson’s Psychological disturbances, in Cushing’s
childhood, 121 disease, 508 syndrome, 406
colorectal, 119–120 Professional practice standard, 73 Psychological screening, for generalized
endometrial, 117–118 Progesterone, for endometriosis, 580 anxiety disorder, 656, 657t–660t
lung, 113–115, 114f, 115f Proinflammatory state, in metabolic Psycho-neuro-endo immunology,
oral, 121 syndrome, 400 138–139
ovarian, 119 Pronator syndrome, vs. epicondylitis, 529 Psychosis, ICU, 670
pancreatic, 120–121 Pronator teres syndrome, vs. double crush Psychosocial deprivation, short stature
prostate, 117 syndrome, 701, 701f due to, 559
skin, 116–117 Propionibacterium acnes, 453 Psychosocial management, of generalized
testicular, 120 Propoxyphene (Darvocet), 215 anxiety disorder, 652, 663–665,
thyroid, 121 Prospective Investigation of Pulmonary 663b–665b
of congestive heart failure, 318–319 Embolism Diagnosis (PIOPED) Psychosocial support, for terminal illness,
of coronary heart disease, 101–105, study, 302–303 518, 519, 521
102f, 103f, 105f Prospective reimbursement systems, 76 Psychosocial visit, 41t, 42, 42t, 44t, 45t
of diabetes mellitus, 127 Prostaglandins, in primary dysmenorrhea, Psychotherapy, for generalized anxiety
diet in, 129 583 disorder, 652
evaluating activities for, 100–101, Prostate cancer Psyllium, for irritable bowel syndrome,
101t epidemiology of, 117 368
exercise in, 129 imaging of, 193 PT (prothrombin time), 162–164, 163t
flowsheet for, 130 prevention of, 117 PTC (percutaneous transhepatic
of glaucoma, 127–128 screening for, 117 cholangiography), 186
of infections via vaccines, 124, 125f, 126f Prostate-specific antigen (PSA), 117 Pubic ramus, fracture of, 173f
of influenza, 279 Protein, total, 159–160, 160t PubMed, 62, 63t, 64
of injuries, 124–127 Prothrombin time (PT), 162–164, 163t Pulmonary angiography, 173t, 185
of iron deficiency anemia, 128 Prothrombotic state, in metabolic Pulmonary embolism (PE), 299–304
of lateral epicondylitis, 530 syndrome, 400 case study on, 299–302
of lead poisoning, 128 Proton-pump inhibitor (PPI), for GERD, chest pain due to, 307
of melanoma, 490 373–374, 375, 375b vs. congestive heart failure, 315–316
of migraines, 499, 501, 501b, 502t Prototypic experiences, of patient, 40 diagnosis of, 300, 300t, 301f, 302–303
of noncompliance, 94–95.95t Prozac (fluoxetine), for generalized differential, 300
of obesity, 128, 129f anxiety disorder, 666t imaging of, 184–185, 184f, 302–303
of obstetric risk, 128 Prurioceptive itch, 251, 255 prevention of, 303–304, 304t
of osteoporosis, 121–123, 121f, 588–589 Pruritic rash, due to drug reaction, risk factors for, 302, 302b
other activities in, 128 445–448, 446f treatment of, 300, 303, 303t
of pelvic inflammatory disease, 598 Pruritic urticarial papules and plaques of Wells rule for, 300, 300t, 302
primary, 100 pregnancy, 253 Pulmonary function tests (PFTs), 243
of pulmonary embolism, 303–304, Pruritus, 250–256 for asthma, 438
304t brachioradial, 253t Pulmonary tuberculosis, vs. COPD, 294t,
role of family physician in, 100 case study of, 250, 256 295
secondary, 100 categories of, 251 Punctation, of cervix, 644, CP86–32
of sexually transmitted diseases, defined, 250 Pure tone testing, 265
123–124 dermatologic causes of, 251, 252t Purging, 28, 29
of stroke, 105–108, 106f–108f evaluation of, 254f, 255 Purpura fulminans, 466t
of substance abuse, alcoholism, and neurogenic, 251, 255 Purulent rhinitis, 223
other drug dependency, neuropathic, 251, 255 PVS (Partner Violence Screen), 83t
108–110, 109f, 111f physiologic basis for, 250–251 Pyelogram, intravenous, 173t, 191
tertiary, 100 pregnancy-related, 252–255 Pyelonephritis, 419, 420–421
of thyroid disease, 128 prurioceptive, 251, 255
of unwanted pregnancies, 128 psychogenic, 251 Q
of urinary tract infections, 422, 422t systemic causes of, 251–252, 253t Quality improvement, 145
Prevention visit, 41t, 42, 42t, 44t, 45t treatment of, 255–256, 255t, 256t Quality of care, 10–11, 25

732
 Index

Questran (cholestyramine) Radiographic imaging (Continued) Reference materials, 62, 62t

for cholestasis, 256t of pancreatic lesions, 188 Reference ranges, 147–148
for hypercholesterolemia, 331 of parathyroid adenomas, 188–189 Referrals, 75
Quetiapine, for schizophrenia, 682 of pregnancy, 194–195, 194f Referred pain
“Quickening,” 550 ectopic, 194–195 to ear, 227t
Quinacrine, for giardiasis, 272 of prostate carcinoma, 192–193, 192f vs. epicondylitis, 529
of pulmonary embolism, 184–185, 184f, Reflex sympathetic dystrophy, 532
R 302–303 Regimen, and noncompliance, 91, 94–95
Rabeprazole (Aciphex), for GERD, 374 of renal failure, 192 Regional enteritis, 270
Radial neck fracture, 529 of renal mass, 192 Registry, 145
Radial nerve injury, 704f of renal stones, 191–192 Reglan (metoclopramide), for migraines,
Radial tunnel syndrome, 528–529 of respiratory system, 184–185, 184f, 501
Radiation cystitis, 420 185f, 186f Relafen (nabumetone), 212t
Radiation therapy, for breast cancer, 612 of scrotal lesions, 192–193, 192f Relative risk (RR), 66–67, 67t, 68t
Radiculopathy, lumbosacral, 342 of sinusitis, 185, 186f Relaxation training, for anxiety, 663b,
Radioactive iodine (RAIU), for of skeletal system, 189–191, 190f–192f 664b
hyperthyroidism, 417 of small bowel obstruction, 187, 187f Relenza (zanamivir), for influenza, 280,
Radioactive iodine (RAIU) scan, for of spinal injuries, 181 280t
hyperthyroidism, 416 with standard x-rays, 171, 171f–173f, Renal failure
Radioallergosorbent test (RAST), 225 173t acute, 429–434
Radiocontrast nephropathy, 172–174 of stroke, 179 case study on, 429–431
Radiographic imaging, 169–195 of testicular torsion, 192–193, 192f defined, 431
of abdominal aortic aneurysm, 185 of thyroid gland enlargement, 188, 189f diagnosis of, 430, 431, 432
for acute gastrointestinal bleeding, 188 of thyroid nodule, 188, 189f differential, 430, 431b
of adnexal masses, 195, 195f of transient ischemic attack, 179, 179f epidemiology of, 432
advances in, 170 with ultrasound, 177, 178t etiology of, 431b, 432–433, 433f,
for angina pectoris, 182–183, 183t of ureteral stones, 191–192 434t
of aortic dissection, 185 of urinary system, 191–192 hyperkalemia in, 434
of appendicitis, 186–187 uses of, 170–171 treatment of, 430–431, 433–434, 434b
for back pain, 179–180, 180f, 181f RAIU (radioactive iodine), for chronic, pruritus due to, 253t
of biliary tract obstruction, 186 hyperthyroidism, 417 due to contrast agent, 172–174
of breast, 193–194, 193f, 194f RAIU (radioactive iodine) scan, for drug-induced, 430–431
of cardiovascular system, 182–185, hyperthyroidism, 416 imaging for, 192
183t, 185f Rakel, Robert, 33 Renal mass, imaging of, 192
of cerebral tumors or metastases, 181, Raloxifene, for prevention of breast Renal stones
181f, 182f cancer, 118 in Cushing’s syndrome, 406
of cholecystitis, 186 Randomized controlled trials (RCTs), imaging of, 191–192
of cholelithiasis, 185 49–50, 54, 66 Renal tests, 165–166, 166t
with computed tomography, 174–175, Ranitidine (Zantac), for GERD, 373 Reproductive system, imaging of
174f, 175t Rapid streptococcal antigen test, 219–220 female, 194–195, 194f, 195f
of congestive heart failure, 183–184 Rash male, 192–193, 192f, 193f
contrast material for, 171–174, 173f due to drug reaction, 445–448, 446f Requests, by patient, 40
of coronary artery disease, 182–183, life-threatening conditions associated Requip (ropinirole)
183t with, 464–471, 466t–470t for Parkinson’s disease, 508
of cranial trauma, 178–179 due to Rocky Mountain spotted fever, for restless legs syndrome, 495, 495t, 496
of endocrine system, 188–189, 189f 464–471 Residual inhibition, 265
of esophageal dysfunction, 187, 187f vesicular, due to varicella, 273–276 Resistin, 393b
of female reproductive system, RAST (radioallergosorbent test), 225 Respiratory illness, anxiety due to, 651
194–195, 194f, 195f Rat-bite fever, 468t Respiratory system, imaging of, 184–185,
of fetal brain, 182, 182f Rate Control versus Electrical 184f, 185f, 186f
of fractures, 189, 190f Cardioversion for Persistent Response to treatment, and compliance,
of gastrointestinal system, 185–188, Atrial Fibrillation study, 313 92
187f Rating scales, for AD/HD, 568–569, 568b, REST mnemonic, 663–665, 663b
for headache, 180 570 Rest positions, for double crush
of hepatomegaly or RBCs (red blood cells), 148 syndrome, 703, 705f, 706f
hepatosplenomegaly, 188 decreased production of, anemia due Resting tremor, 506–507
of knee injury with meniscal tear, 191, to, 357–358 Restless legs syndrome (RLS), 491–496
192f increased destruction of, anemia due to, case study on, 491–492
of lumbosacral disk herniation with 358 clinical presentation of, 493, 493b
nerve root compression, RCTs (randomized controlled trials), diagnosis of, 492, 493, 493b
179–180, 180f, 181f 49–50, 54, 66 differential, 492
with magnetic resonance imaging, Readiness to change, assessing, 400b epidemiology of, 492–493
175–177, 175t, 176f Reasonable person standard, 73, 73t pathophysiology of, 493
of male reproductive system, 192–193, Recertification, 5 secondary, 493, 494–495
192f, 193f Red blood cells (RBCs), 148 severity of, 492, 493–494, 494b
of meningitis, 180–181 decreased production of, anemia due treatment of, 492, 494–496, 495t
of neurologic system, 178–182, to, 357–358 Restoril (temazepam), for restless legs
179f–182f increased destruction of, anemia due to, syndrome, 495t
nuclear, 177–178, 178t 358 Retin-A (tretinoin), for acne, 452, 454
of obstructive uropathy, 191–192 Red yeast rice, for hypercholesterolemia, Retin-A Micro (tretinoin), for acne, 452,
of osteoporosis, 191 330 454

733
 Index

Retinoids, topical, for acne, 453t, 454 Safety assessment and plan, with intimate Screening (Continued)
Retraction sign, 486, CP63–28 partner abuse, 83, 85t for prostate cancer, 117
Rett’s syndrome, 563t Salicylic acid for sexually transmitted diseases, 123
Revascularization, for peripheral arterial for acne, 453t, 454 for skin cancer, 116–117
disease, 346 for common warts, 480 for stroke, 107
Revex (nalmefene), for cholestasis, 256t for plantar wart, 478 for thyroid disease, 128
Review of systems, 80 Salmeterol, for asthma, 442t Scrotal lesions, imaging of, 192–193, 192f
Rh incompatibility, 548, 551 Salmonella typhi, 468t Seasonal allergies, 224
Rheumatic fever, acute, 469t Salsalate (Disalcid), 213t Seborrheic keratoses, 473, 486,
Rhinitis Sarcomas, uterine, 615–616 CP63–20––CP63–22
allergic, 198, 222–225, 243, 283 Saturated fat, 384 Secondary smoke exposure, 114–115
and asthma, 435–437 Saurette, Jenny, 38 Secondary sources, 62
eosinophilic nonallergic, 223 SBI (serious bacterial infection), in Secretagogues, for diabetes mellitus, 385,
hormonal, 223 children 386
idiopathic, 223, 283 fever due to, 237, 239, 240–241 Secretin, for autism, 565
infectious, 223 vaccines and, 240–241 Segmental pressure measurements, in
medicamentosa, 223, 283 SBO (small bowel obstruction), 187, peripheral arterial disease, 343,
purulent, 223 187f 345
vasomotor, 223, 283 Scabies, pruritus due to, 251, 252t Seizures
Rhinosinusitis Scar(s), 545 autism and, 565
acute, 223 Scarlet fever, 467t vs. double crush syndrome, 698
allergic, and asthma, 435–437 Schistosomiasis, pruritus due to, 253t Selection bias, 56
Rickettsia rickettsii, 464, 465 Schizoaffective disorder, 680 Selective serotonin reuptake inhibitors
Rifampin (Rifadin), for cholestasis, 256t Schizophrenia, 678–682 (SSRIs)
Right lower quadrant (RLQ) abdominal cognitive deficits in, 681 for anxiety disorders, 653, 662, 665, 666t
pain, due to appendicitis, defined, 679 for depression, 647
361–362 demographics of, 681 for panic disorder, 676, 677
Right upper quadrant (RUQ) abdominal diagnosis of, 679–680, 681 Selegiline (Eldepryl), for Parkinson’s
pain, due to cholelithiasis, differential, 680 disease, 505–506, 508
359–365 etiology of, 681 Sentinel node mapping, for breast cancer,
Rimantadine (Flumadine), for influenza, natural history of, 681 606, 608–609, 611f
278, 280, 280t patient education on, 680–681 Septic joint, 532
Ringing in ears. See Tinnitus. phases of, 681 Serax (oxazepam), for generalized anxiety
Risperidone (Risperdal), for positive and negative symptoms of, disorder, 666t
schizophrenia, 680, 682 679 Serious bacterial infection (SBI), in
RLQ (right lower quadrant) abdominal prognosis for, 682 children
pain, due to appendicitis, subtypes of, 681 fever due to, 237, 239, 240–241
361–362 treatment of, 680, 681–682, 682t vaccines and, 240–241
RLS. See Restless legs syndrome (RLS). Schizophreniform disorder, 680 Serotonin/norepinephrine reuptake
Rocephin (ceftriaxone) Schizotypal personality disorder, 680 inhibitors, for generalized
for gonorrhea, 594b School absence excuses, 71 anxiety disorder, 666t
for otitis media, 229, 229t, 230t School release evaluations, 71 Sertraline (Zoloft), for generalized anxiety
for pelvic inflammatory disease, 595t School-related evaluations, 71 disorder, 666t
Rochester criteria, 237–238, 239t Scientific medicine, 54 Serum amyloid A (SAA), and coronary
Rocky Mountain spotted fever, 464–471, Scleroderma, pruritus due to, 253t heart disease, 330
467t Screening Serum glutamate pyruvate transaminase
Rofecoxib (Vioxx), 211 for alcohol and substance abuse, (SGPT), 161
Rome Group for the Epidemiology and 109–110 Serum glutamic-oxaloacetic transaminase
Prevention of Cholelithiasis for breast cancer, 118, 193–194, 193f, (SGOT), 161
(GREPCO), 364 194f, 607–608, 609b, 613 Sexual activity, during pregnancy, 549
Roos maneuver, 698, 700f for cervical cancer, 116, 620–625, Sexual dysfunction, in hyperthyroidism,
Ropinirole (Requip) 622t–624t, 629–630 416
for Parkinson’s disease, 508 for Chlamydia, 123, 124, 593 Sexually transmitted diseases (STDs),
for restless legs syndrome, 495, 495t, for colorectal cancer, 120 123–124
496 for coronary heart disease, 102–103, Shaughnessy, Allen, 57
Rosacea, vs. acne, 452 104 Sheehan Panic Disorder Scale (SPDS),
Rosiglitazone, for diabetes mellitus, 386 for diabetes mellitus, 127, 383 656, 657t–658t
Rosuvastatin (Crestor), for for endometrial cancer, 118, 617 Sheehan Patient Rated Anxiety Scale
hypercholesterolemia, 331, 336t, for glaucoma, 128 (SPRAS), 656
337t for hypothyroidism, 411, 411t Shingles, 275, 469t
Rovsing’s sign, 361 for injury risk factors, 127 pruritus due to, 253t
RR (relative risk), 66–67, 67t, 68t for intimate partner violence, 82–83, Short child
RUQ (right upper quadrant) abdominal 82t, 83t case study on, 554–558
pain, due to cholelithiasis, for iron deficiency anemia, 128 differential diagnosis of, 555, 556b,
359–365 for lead levels, 128 557t, 558–560
Rush, Benjamin, 28, 33, 34, 35 for lung cancer, 113 Short stature, familial, 559
for malignant melanoma, 484 Sideroblastic anemia, 357
S for obesity, 128 SIL (squamous intraepithelial lesion), 630t
SAA (serum amyloid A), and coronary for osteoporosis, 122, 588 high-grade, 630, 635
heart disease, 330 for ovarian cancer, 119 low-grade, 634, 635
Sackett, David, 54 prenatal, 548–549, 548b, 553t Simple suture, 543, 544f

734
 Index

Simvastatin (Zocor), for Social-skills training, for schizophrenia, Spurling’s maneuver, 698, 699f
hypercholesterolemia, 336t, 337t 682 Squamocolumnar junction, of cervix, 643,
Simvastatin-ezetimibe (Vytorin), for Society for the Right to Die, 77 CP86–28
hypercholesterolemia, 336t Sodium levels, 152–153, 152t Squamous cell carcinoma
Sinemet (carbidopa/levodopa) Sodium polystyrene sulfonate vs. basal cell carcinoma, 473
for Parkinson’s disease, 509 (Kayexalate), for acute renal of cervix, CP86–34
for restless legs syndrome, 495, 495t failure, 434 vs. plantar wart, 478
Single-photon emission CT (SPECT), Soluble intracellular adhesion molecule, of vagina, CP86–24
177–178 and coronary heart disease, 330 of vulva, CP86–15, CP86–16
Singultus, 232–235, 234b Soluble vascular cell adhesion molecule, Squamous epithelium, of cervix, CP86–27
Sinus congestion, 282–286, 285f and coronary heart disease, 330 Squamous intraepithelial lesion (SIL),
Sinus infection, 223 Somatic complaints, multiple, due to 630t
Sinus tachycardia, in hyperthyroidism, generalized anxiety disorder, high-grade, 630, 635
415 655–662 low-grade, 634, 635
Sinusitis, 282–286, 285f Somatic pain, 210 Squeeze test, 533, 536f
case study on, 282–283 Somatization disorder SSRIs (selective serotonin reuptake
chronic, 243 vs. hypercholesterolemia, 326 inhibitors)
diagnosis of, 283–284, 285t vs. irritable bowel syndrome, 367 for anxiety disorders, 653, 662, 665,
differential, 283 Somatoform disorder, vs. fibromyalgia, 666t
epidemiology of, 284 523 for depression, 647
imaging of, 185, 186f Somatotropic axis, in Cushing’s for panic disorder, 676, 677
risk factors for, 284 syndrome, 406 Stadol (butorphanol), 215
treatment of, 283, 284, 285, 285t Sonata (zaleplon), for insomnia, 248–249 Stages-of-change model
duration of, 285 Sore throat, 217–221 of compliance, 90, 91t
SJS (Stevens-Johnson syndrome), 450, case study of, 217–218 of problem solving, 42–43
466t diagnostic workup for, 219–220, 220t Stages-of-change questions, 399, 400b
Skeletal dysplasias, short stature due to, differential diagnosis of, 218–219, Standard radiographic x-rays, 171,
560 219t 171f–173f, 173t
Skeletal system, imaging of, 189–191, therapy for, 220–221, 220t Staphylococcal toxic shock syndrome, 465,
190f–192f SORT (Strength of Recommendation 466t
Skin cancer, 116–117. See also Basal cell Taxonomy), 59 Staples, for laceration repair, 541
carcinoma; Melanoma; SPDS (Sheehan Panic Disorder Scale), Starr, Paul, 32, 36–37
Squamous cell carcinoma. 656, 657t–658t STaT, 83t
Skin lesion, due to basal cell carcinoma, SPECT (single-photon emission CT), Statin drugs
472–476, 472f 177–178 for hypercholesterolemia, 328, 330–331,
Skin testing, 225 Spectinomycin (Trobicin), for gonorrhea, 333t–334t, 336t, 337t, 338–339
Skull fracture, 178–179 594b interactions with, 338, 339t
Skull trauma Speech discrimination scores, 265 for prevention of stroke, 108
delirium due to, 670 Speech reception thresholds, 265 side effects of, 331, 338
imaging of, 178–179 SPF (sun protection factor), 117 Statistical significance, 66–68, 67t, 68t
Slawson, David, 57 Spider bites, 691–696 Statistics, 53–54
Sleep disturbance, in fibromyalgia, 525 by black widow spiders, 694–695, 694f, STDs (sexually transmitted diseases),
Sleep hygiene, 248 695t 123–124
Sleep log, 248 by brown recluse spiders, 692–694, Step 1 Diet, 327
Sleep state misrepresentation, 247, 249 692f, 693f, 693t Step 2 Diet, 327
Slo-Niacin (sustained-release niacin), for case study on, 691–692 Steri-Strips, for laceration repair, 544
hypercholesterolemia, 331, 336t, by hobo spiders, 695 Steroid(s). See Corticosteroids.
337t by tarantulas, 695, 695f Steroid acne, 452
Small bowel obstruction (SBO), 187, 187f by wolf spiders, 695, 695f Stevens-Johnson syndrome (SJS), 450,
Smith, Ashbel, 35 Spinal compression fractures, due to 466t
Smoking. See Cigarette smoking. osteoporosis, 586–588 Still, Andrew Taylor, 137
Smoking cessation Spinal cord tumor, vs. double crush Stimulants, for AD/HD, 569–570, 571
for acute bronchitis, 287, 288, 289–290 syndrome, 700 Strength of association, 67
for COPD, 295, 296, 297t Spinal fractures, imaging of, 181 Strength of Recommendation Taxonomy
for hypercholesterolemia, 332t Spinal injuries, imaging of, 181 (SORT), 59
for hypertension, 323 Spinal metastases, 209 Streptobacillus moniliformis, rat-bite fever
for peripheral arterial disease, 345, Spiral CT, 174 due to, 468t
345t Spirillum minus, rat-bite fever due to, Streptococcal pharyngitis, 217–221,
for prevention of coronary heart 468t 220t
disease, 104 Spiritual connection, 139–140 Streptococcal toxic shock syndrome, 466t
for prevention of lung cancer, 114 Spiritual support, for terminal illness, 518, Streptococcus pyogenes, scarlet fever due to,
Snow, John, 53 519, 521 467t
Social anxiety disorder, 653 Spirometry, 243 Stress echocardiography, 178t, 183
“Social contracts,” 33 Spironolactone, for congestive heart for angina pectoris, 309, 309t
Social history, 80 failure, 318 Stress fractures, 189
Social phobia, 653 Spitz nevus, 486, CP63–19 Stress management techniques, 663b,
Social support Spouse abuse. See Intimate partner 664–665, 664b–665b
for anxiety, 663b violence (IPV). Stress myocardial perfusion imaging, for
for terminal illness, 518, 519, 521 SPRAS (Sheehan Patient Rated Anxiety angina pectoris, 309, 309t
Social Transformation of American Scale), 656 Stress reduction program, 139b
Medicine, The, 32 Spring ligament, 534f Stress testing, 182, 183t

735
 Index

Stroke, 105–108 Symmetrel (amantadine) Td (tetanus, diphtheria) vaccine, 125f,

atrial fibrillation and, 311–312, 312t, for influenza, 280, 280t 126f, 204f, 208t
334t–335t for Parkinson’s disease, 508 TEACCH (Treatment and Education of
vs. brain tumor, 512 Symptom management, in palliative care, Autistic and Related
vs. double crush syndrome, 698 518, 519–520, 520t Communication Handicapped
epidemiology of, 105–106, 106f, 107f Syndesmotic sprain, 532, 533–535, 536f, Children), 565
vs. heat stroke, 688 537f TEE (transesophageal echocardiography),
imaging of, 179 Syndrome X. See Metabolic syndrome 177, 183–184
prevention of, 106–108, 107f, 108f (MES). for atrial fibrillation, 311–312, 313
screening for, 107 Synovitis, of elbow, 529 Tegaserod, for irritable bowel syndrome,
Structured data entry, 143 Synthroid (levothyroxine), for 369
Structured reviews, 66 hypothyroidism, 410 Tegenaria agrestis, 695
Struma ovarii, hyperthyroidism due to, 416 Syphilis Temazepam (Restoril), for restless legs
Study designs, 49b condyloma lata in, 456 syndrome, 495t
Sublimaze (fentanyl), 209, 211, 213t, 215, epidemiology of, 123 TEN (toxic epidermal necrolysis), 450,
215t secondary, 469t 466t
Substance abuse, 108–110 Syphilis screening, during pregnancy, Tender points, in fibromyalgia, 523, 524,
common drugs in, 648, 648t 549 524f
diagnosis of, 647, 647b, 648t Syringomyelia, vs. double crush Tennis elbow, 527–530
epidemiology of, 108–109, 109f syndrome, 700 Tennis elbow bands, 529
prevention of, 109–111 Systematic reviews, 54, 69 Tension-type headache, 502, 502t
screening for, 109–110 Systolic dysfunction, 317 Tequin (gatifloxacin), for UTI, 422t
Substance dependency. See Drug Systolic failure, 183 Terconazole (Terazol), for vulvovaginal
dependency. candidiasis, 592
Substance withdrawal, 649 T Terminal illness, 517–521
delirium due to, 669–670 T1-weighted images, 175, 176f case study on, 517–519
headache due to, 498 T2-weighted images, 175, 176f communication and goal planning for,
Substance-induced anxiety disorder, T3 (triiodothyronine), 167 518, 519, 520–521
662 free, in hyperthyroidism, 416 coordination of care for, 518, 519
Sucralfate (Carafate), for GERD, 374 T3 (triiodothyronine)-resin uptake, pain and symptom management for,
Sudafed (pseudoephedrine), for allergic 167–168, 167t, 168t 518, 519–520, 520t
rhinitis, 225 T4. See Thyroxine (T4). psychosocial, spiritual, and
Suffering, 76–77 T-ACE questions, 110 bereavement support for, 518,
Suicide, assisted, 77–78 Tacrolimus, for pruritus, 256 519, 521
Sulfamethoxazole/trimethoprim. See Talar tilt test, 533, 536f Tessalon (benzonatate), for acute
Trimethoprim/sulfamethoxazole Talipexole, for Parkinson’s disease, 508 bronchitis, 290
(Bactrim). “Talk therapy,” for generalized anxiety Testicular cancer, 120
Sulfonamides, adverse reactions to, 448t disorder, 652 Testicular torsion, 192–193, 192f
Sulfonylureas, for diabetes mellitus, 385, Talocalcaneal ligament Tetanus, diphtheria (Td) vaccine, 125f,
386, 387t interosseous, 534f 126f, 204f, 208t
Sulindac (Clinoril), 213t lateral, 534f Tetanus immune globulin (TIG), for
adverse reaction to, 445–448, 446f Talofibular ligament laceration, 540
Sumatriptan (Imitrex), for migraine, anterior, 533, 534f, 535f Tetanus toxoid
499 posterior, 534f for frostbite, 686
Sun exposure, and malignant melanoma, Talwin (pentazocine), 215 for laceration, 540
483–484 Tamiflu (oseltamivir), for influenza, 280, Tetracycline(s)
Sun protection factor (SPF), 117 280t for acne, 452, 454
Sunburn, pruritus due to, 252t Tamoxifen for acute exacerbation of COPD, 296
Sunscreen for breast cancer, 610, 612t for Rocky Mountain spotted fever, 470
and malignant melanoma, 483–484 prevention of, 118 “Texas swab,” 643–644
for prevention of skin cancer, 117 and endometrial cancer, 118, 617 Textbooks, as reference materials, 62t
Superficial deltoid ligament, 534f Tarantula bites, 695, 695f Thalassemia, 357
Superficial spreading melanoma, 483, Tardive dyskinesia, due to antipsychotic Thallium stress test, 183
486–487, 486t, CP63–30 medications, 682t THBI (thyroid hormone binding index),
Superficial thrombophlebitis, vs. deep Task-oriented processes in care model, 168, 168t
venous thrombosis, 350t 41–43 THBR (thyroid hormone binding ratio),
Superficial tibiotalar ligament, 534f Task-specific tremors, 507 168, 168t
Supportive counseling, for generalized Taxanes, for breast cancer, 612 Theophylline, for asthma, 442t
anxiety disorder, 652 Taylor, Robert, 33 Therapeutic bodywork, 137–138
Suprax (cefixime), for gonorrhea, TBG (thyroxine-binding globulin), Therapeutic Lifestyle Changes dietary
594b 167–168 guidelines, 327, 330
Sustained-release niacin (Slo-Niacin), for TBPA (thyroxine-binding prealbuimin), Therapeutic privilege, 73
hypercholesterolemia, 331, 336t, 167–168 Therapeutic relationship, development of,
337t TCA(s). See Tricyclic antidepressants 43, 44t
Sutures (TCAs). Thiazide-type medications, for
for laceration repair, 541, 542–544, TCA (trichloroacetic acid), for condyloma hypertension, 322
543f, 544f acuminata, 458, 458f Thiazolidinediones, for diabetes mellitus,
removal of, 545 T-cell lymphoma, cutaneous, pruritus due 385, 386–388, 387t
Sydenham, Thomas, 28, 35 to, 252t ThinPrep, 631
Symlin (pramlintide), for diabetes Td (diphtheria and tetanus toxoids), 125f, Thoracic outlet syndrome, vs. double
mellitus, 388 126f, 204f, 208t crush syndrome, 700–701

736
 Index

Thorn, foreign body reaction to, 478 Ticlopidine, for peripheral arterial disease, Tramadol (Ultram), 211, 214t
Thought-stopping strategies, for anxiety, 345 Trans fat, 384
663b, 664b TICS (Two-Item Conjoint Screen), 110 Transesophageal echocardiography (TEE),
Three-dimensional ultrasound, 177 TIG (tetanus immune globulin), for 177, 183–184
“Thrifty genotype” hypothesis, 393b laceration, 540 for atrial fibrillation, 311–312, 313
Throat, sore, 217–221 Time management, for anxiety, 663b, Transferrin, 158, 159t
case study of, 217–218 664b Transformation zone (t-zone), 621, 631,
diagnostic workup for, 219–220, 220t Timentin (ticarcillin and clavulanate), for 632f, 643–644, CP86–26
differential diagnosis of, 218–219, 219t UTI, 422t Transformed headache, 501
therapy for, 220–221, 220t Tincture of benzoin, for laceration repair, Transient ischemic attack (TIA)
Throat culture, 220 544 vs. brain tumor, 512
Thromboangiitis obliterans, vs. Tinel’s sign, 528, 698 vs. heat stroke, 688
intermittent claudication, 343 Tinidazole (Tindamax), for giardiasis, 272 imaging for, 179, 179f
Thromboembolism, atrial fibrillation and, Tinnitus, 263–268 and stroke, 107, 108
311–312, 312t assessment of, 264–265 Transient lower esophageal sphincter
Thrombophilia case study on, 263–264 relaxation (TLESR), 374
and deep venous thrombosis, 351, 352 conditions associated with, 264t Transillumination, of maxillary sinuses,
inherited, 302b, 303, 304t epidemiology of, 266 283, 284
Thrombophlebitis, superficial, vs. deep medicines and substances that may Transluminal ultrasound, 177
venous thrombosis, 350t cause, 265t Transrectal ultrasound probe, 177
Thumbnail, pigmented, 461–463 nonpulsatile, 264 Transtheoretical stages-of-change model
Thyroid cancer, 121 nonvascular, 264 of compliance, 90, 91t
Thyroid disease objective (vibratory, extrinsic), 264 for metabolic syndrome, 400, 401t
vs. congestive heart failure, 316 pathogenesis of, 266–267, 266f Transthyretin, 167
vs. irritable bowel syndrome, 367 patient information resources on, 268 Transvaginal ultrasound, 177
screening for, 128 pulsatile, 264 of endometrial cancer, 617
Thyroid function, in Cushing’s syndrome, subjective (idiopathic), 264 Tranxene (clorazepate), for generalized
406 treatment of, 265–266, 265t, 267–268, anxiety disorder, 666t
Thyroid gland enlargement, imaging of, 267f Trastuzumab, for breast cancer, 612t
188 vascular, 264 Trauma, cranial (skull, head), 178–179
Thyroid hormone binding index (THBI), Tinnitus Handicap Inventory, 264–265 delirium due to, 670
168, 168t Tinnitus Questionnaire, 265 Trazodone (Desyrel), for generalized
Thyroid hormone binding ratio (THBR), Tinnitus retraining therapy (TRT), anxiety disorder, 666t
168, 168t 265–266, 267–268, 267f Treatment and Education of Autistic and
Thyroid nodule, 188, 189f Tinzaparin, for pulmonary embolism, 303 Related Communication
Thyroid scan, 188, 189f Tiredness, due to anemia, 354–358 Handicapped Children
for hyperthyroidism, 416 TLESR (transient lower esophageal (TEACCH), 565
Thyroid storm, 670 sphincter relaxation), 374 Treatment regimen, and noncompliance,
Thyroid tests, 166–167, 167t, 168t TM (tympanic membrane), bulging of, 91, 94–95
Thyroiditis, hyperthyroidism due to, 416, 227, 228 Tremor(s)
417 TNF (tumor necrosis factor), and insulin action, 507
Thyroid-stimulating hormone (TSH), resistance, 393b with basal ganglia disease, 507
166–167, 167t TNM (tumor-node-metastasis) staging cerebellar, 507
in hyperthyroidism, 416 system differential diagnosis of, 505, 506–507
in hypothyroidism, 410, 411 for breast cancer, 608, 610t, 611b drug-induced, 506–507
pituitary, 166–167, 167t for melanoma, 487–488, 488t essential, 507
Thyrotoxicosis. See Hyperthyroidism. TOA (tubo-ovarian abscess), 600, 601, goal-oriented, 507
Thyrotropin. See Thyroid-stimulating 603f intention, 507
hormone (TSH). Tocolysis, for placenta previa, 576 isometric, 507
Thyroxine (T4), 167, 167t, 168t Tofranil (imipramine), for generalized kinetic, 507
free, 167, 168t anxiety disorder, 666t due to Parkinson’s disease, 504–506
in hyperthyroidism, 416 Tomography with peripheral neuropathy, 507
total, 167, 168t computed. See Computed tomography physiologic, 507
Thyroxine-binding globulin (TBG), 167 (CT). postinfectious, 506
Thyroxine-binding prealbuimin (TBPA), electron beam, 183 post-traumatic, 507
167 Topiramate, and contrast agents, 174 postural, 507
TIA. See Transient ischemic attack (TIA). Toradol (ketorolac), 212t resting, 506–507
TIBC (total iron-binding capacity), 158, Toremifene, for breast cancer, 612t task-specific, 507
159t Total iron-binding capacity (TIBC), 158, toxin-induced, 506
Tibiocalcaneal ligament, 534f 159t vocal, 507
Tibiofibular ligament Toxic adenoma, hyperthyroidism due to, in Wilson’s disease, 507
anterior inferior, 534f 416 writing, 507
posterior inferior, 534f Toxic epidermal necrolysis (TEN), 450, Trench foot, 685
Tibionavicular ligament, 534f 466t Trental (pentoxifylline), for peripheral
Tibiotalar ligament Toxic multinodular goiter, arterial disease, 345, 345t
posterior, 534f hyperthyroidism due to, 416 Tretinoin (Retin-A, Retin-A Micro, Avita),
superficial, 534f Toxic shock syndrome, 465, 466t for acne, 452, 454
Ticarcillin and clavulanate (Timentin), for Toxin(s) Triamcinolone acetonide (Aristocort)
UTI, 422t delirium due to, 670 for asthma, 443t
Tickborne infections, 464–471 vs. heat stroke, 688–689 for drug reaction, 447–448
Ticked Off, 471 Toxin-induced tremor, 506 Trichinosis, pruritus due to, 253t

737
 Index

Trichloroacetic acid (TCA, Tri-chlor), for UGI/SBFT (upper gastrointestinal series Urine culture
condyloma acuminata, 458, 458f with small bowel follow- in infants and children, 239
Trichomonas vaginalis, 594 through), 187, 187f for UTI, 421
Trichomoniasis, 591, 594–596, CP86–20 Ulcer, peptic Urine drug screen (UDS), 646
Tricyclic antidepressants (TCAs) vs. cholelithiasis, 361 Urine pregnancy test, 547
for anxiety disorders, 653, 666t vs. GERD, 372 Urine sample, from infant or child,
for bedwetting, 427 vs. pancreatitis, 377 239
for depression, 647 Ulcerative colitis, vs. irritable bowel Uropathy, obstructive, 191–192
for pain, 216 syndrome, 367 Ursodiol acid (Actigall), for cholestasis,
Triglycerides Ulnar nerve injury, 704f 256t
optimal levels of, 333t Ulnar neuropathy, 528 Urticaria, 449–450
testing for, 327, 328 Ultracet (acetaminophen with tramadol), pruritus due to, 253t
Trihexyphenidyl (Artane), for Parkinson’s 211 US. See Ultrasound (US).
disease, 508 Ultram (tramadol), 211, 214t U.S. Preventive Services Task Force
Triiodothyronine (T3), 167–168 Ultrasound (US), 177, 178t (USPSTF)
free, in hyperthyroidism, 416 of breast, 607 on disease prevention, 100, 101t
Triiodothyronine (T3)-resin uptake, of pelvic inflammatory disease, 600, on hormone replacement therapy, 51
167–168, 168t 602f, 603f recommendations for low-risk
Trilisate (choline magnesium trisalicylate), during pregnancy, 547–548 pregnancies by, 553t
212t three-dimensional, 177 U.S. Public Service Task Force Guide to
Trimethoprim/sulfamethoxazole transluminal, 177 Clinical Preventive Services of,
(Bactrim) transrectal, probe for, 177 63t
for acne, 454 transvaginal, 177 Uterine fibroids
for acute exacerbation of COPD, 296 of endometrial cancer, 617 dysmenorrhea due to, 583
for otitis media, 229t Ultraviolet (UV) radiation vaginal bleeding due to, 615
for sinusitis, 285, 285t and malignant melanoma, 484 Uterine polyp, vaginal bleeding due to,
for UTI, 421, 422t and skin cancer, 116, 117 615
TRIP (Turning Research into Practice), Underinsured, 11–12 Uterine sarcomas, 615–616
64t Undermining, for laceration repair, UTI. See Urinary tract infection (UTI).
Triptans, for migraines, 501 541–542, 542f UV (ultraviolet) radiation
Trobicin (spectinomycin), for gonorrhea, Undifferentiated problems, 13–14 and malignant melanoma, 484
594b Uninsured, 11–12 and skin cancer, 116, 117
Trophoblastic tumors, hyperthyroidism Universal health insurance, 12
due to, 416 Upper extremity nerve injury, common V
TRT (tinnitus retraining therapy), sites of, 704f Vaccination, 200–201
265–266, 267–268, 267f Upper extremity numbness and pain, due contraindications to, 201, 203t–206t
TSH. See Thyroid-stimulating hormone to double crush syndrome, schedule of, 125f, 126f, 200, 202f
(TSH). 697–706 accelerated, 201, 207f, 208f
Tuberculin skin test, measles vaccination Upper gastrointestinal series with small Vaccine(s)
and, 206t bowel follow-through diphtheria and tetanus toxoids and
Tuberculosis, vs. COPD, 294t, 295 (UGI/SBFT), 187, 187f acellular pertussis (DTaP), 125f,
Tubo-ovarian abscess (TOA), 600, 601, Upper respiratory tract infection, in 202f, 203t, 206t, 207t
603f toddler, 197–198 Haemophilus influenzae type b (Hib),
Tucson Children’s Respiratory Study, Upper segment, of height, 556 125f, 202f, 204t, 207t, 240
438 Upper-to-lower segment ratio, 556 hepatitis A, 125f, 126f, 202f, 205t
Tumor necrosis factor (TNF), and insulin UpToDate, 50, 59 hepatitis B (HepB), 125f, 126f, 202f,
resistance, 393b Urea, 165 204t, 206t–208t
Tumor-node-metastasis (TNM) staging Uremia, pruritus due to, 252, 256t influenza, 125f, 126f, 202f, 204t, 279
system Ureteral stones, imaging of, 191–192 measles, mumps, rubella (MMR), 125f,
for breast cancer, 608, 610t, 611b Urethral diverticulum, 420 126f, 202f, 204t, 206t–208t
for melanoma, 487–488, 488t Urethritis, vs. UTI, 420 and autism, 563–564
Turner’s syndrome, short stature due to, Urinalysis meningococcal, 125f
560 for heat stroke, 689 pneumococcal polysaccharide (PCV,
Turning Research into Practice (TRIP), in infants and children, 239 PPV), 125f, 126f, 202f, 205t,
64t for UTI, 420, 421 207t, 240–241
Two-Item Conjoint Screen (TICS), 110 Urinary free cortisol (UFC), in Cushing’s poliovirus, 125f, 202f, 205t, 207t, 208t
Tylenol. See Acetaminophen (Tylenol). syndrome, 403–404 and serious bacterial infection, 240–241
Tympanic membrane (TM), bulging of, Urinary frequency, due to UTI, tetanus, diphtheria (Td), 125f, 126f,
227, 228 418–420 204f, 208t
Tympanometry, 265 Urinary system, imaging of, 191–192 varicella, 275–276
Typhoid fever, 468t Urinary tract infection (UTI), 418–422 contraindications to, 204t, 275–276
Typhus bacterial prevalence in, 419t efficacy of, 275
epidemic, 469t complicated, 419, 419t, 422 recommended schedule for
murine, 469t diagnosis of, 419–421, 419t, accelerated, 207t, 208t
T-zone (transformation zone), 621, 631, 421b for adults, 125f, 126f, 275
632f, 643–644, CP86–26 differential, 419, 420–421 for children and adolescents, 125f,
in infant or child, 239 202f, 275
U patient education for, 420 and MMR vaccine, 206t
UDS (urine drug screen), 646 prophylaxis for, 422, 422t side effects of, 276
UFC (urinary free cortisol), in Cushing’s treatment of, 420, 421–422, 422t Vaccine Adverse Events Reporting System
syndrome, 403–404 uncomplicated, 419, 419t (VAERS), 200, 202f

738
 Index

Vaccine Injury Compensation Program Venlafaxine (Effexor) V/Q (ventilation/perfusion) scan, 178t,
(VICP), 200 for anxiety disorders, 653 184
Vaccine-preventable infections, 124, 125f, for generalized anxiety disorder, 666t Vulva
126f Venous valvular insufficiency, vs. deep acetowhitening of, CP86–8
Vagina venous thrombosis, 350t colposcopy of, 641–642, 642t,
adenosis of, CP86–18 Ventilation/perfusion (V/Q) scan, 178t, CP86–2–CP86–16
colposcopy of, 642–643, 643t, 184 condyloma of, CP86–10
CP86–17––CP86–24 Verapamil, for atrial fibrillation, 313 lentigo simplex of, CP86–9
condyloma of, CP86–21 Verruca plana, 480 lichen planus of, CP86–6
Vaginal atrophy, CP86–19 Verruca plantaris, 477–481 lichen sclerosus of, CP86–4, CP86–5
Vaginal bleeding case study of, 477–479 lichen simplex chronicus of, CP86–3
postmenopausal, 614–616 diagnosis of, 478, 480, 481f psoriasis of, CP86–2
third-trimester, 573–576 differential, 478 squamous vestibular
Vaginal carcinoma, CP86–17, epidemiology of, 479 micropapillomatosis of, CP86–7
CP86–22––CP86–24 pathogenesis of, 479 Vulvar carcinoma, CP86–11––CP86–13,
Vaginal discharge treatment of, 478–479, 480–481, 481f CP86–15, CP86–16
due to bacterial vaginosis, 591, 592, Verruca vulgaris, 479–480, 479f, 480f Vulvar intraepithelial neoplasia (VIN),
592b Vertebral compression fractures, due to CP86–11––CP86–14
due to Chlamydia infection, 591, osteoporosis, 586–588 Vulvovaginal candidiasis
592–593, 593b Vertical mattress suture, 543, 543f case study on, 590–591
due to gonorrhea infection, 591, Vertigo, 258, 260, 260t, 261 complicated, 592
593–594, 594b benign paroxysmal positional, 259, diagnosis of, 591–592
due to pelvic inflammatory disease, 261–262 differential, 591–596
591, 594, 595b, 595t Vesalius, Andreas, 28, 34–35, 53 treatment for, 592
due to trichomoniasis, 591, 594–596 Vesicular rash, due to varicella, 273–276 Vytorin (simvastatin-ezetimibe), for
due to vulvovaginal candidiasis, Vestibular neuritis, 257–259, 261 hypercholesterolemia, 336t
590–592 Vibramycin. See Doxycycline VZIG (varicella-zoster immune globulin),
Vaginal infections, CP86–20 (Vibramycin). 276
Vaginal intraepithelial neoplasia (VAIN), Vibrio vulnificus infection, 466t
CP86–17, CP86–22, CP86–23 Vicodin (hydrocodone with W
Vaginitis acetaminophen), 211, 215t Waist circumference, in metabolic
atrophic, 615 for chronic pain, 209, 213t syndrome, 393f, 394–395, 395f,
vs. UTI, 419, 420 for migraines, 501 399t
Vaginosis, bacterial, 591, 592, 592b VICP (Vaccine Injury Compensation case study on, 397–399
Valium (diazepam) Program), 200 disease risk for, 394–395, 395t
for generalized anxiety disorder, 666t Victims, of intimate partner violence and free fatty acids, 392
for vertigo, 261 health effects on, 81, 82t Walking, difficulty in, due to brain tumor,
Valproic acid, for restless legs syndrome, identification of, 82–83, 82t, 83t 511–513
496 management of, 83–85, 84t, 85t Warfarin (Coumadin)
Vantin (cefpodoxime) safety assessment and plan for, 83, 85t adverse reactions to, 448t
for otitis media, 229t screening for, 82–83, 83t for atrial fibrillation, 312, 313,
for sinusitis, 285, 286 Vicuprofen (hydrocodone with 334t–335t
Varicella, 273–276 ibuprofen), 211, 213t for deep venous thrombosis, 350
in adults, 275 VIN (vulvar intraepithelial neoplasia), for pulmonary embolism, 300, 303,
case study on, 273–275 CP86–11––CP86–14 303t
complications of, 275 Vinorelbine, for breast cancer, 612, 612t Warner, John Harley, 29
diagnosis of, 274 Violence, intimate partner. See Intimate Warts
differential, 274 partner violence (IPV). common, 479–480, 479f, 480f
pathogenesis of, 275 Vioxx (rofecoxib), 211 flat, 480
patient education on, 274–275 Viral pharyngitis, 218, 219t genital. See Condyloma acuminata.
during pregnancy, 275 Visceral adiposity, in metabolic syndrome, plantar, 477–481
treatment of, 274 393f, 394–395, 395f, 399t case study of, 477–479
postexposure, 276 case study on, 397–399 diagnosis of, 478, 480, 481f
Varicella vaccine, 275–276 disease risk for, 394–395, 395t differential, 478
contraindications to, 204t, 275–276 and free fatty acids, 392 epidemiology of, 479
efficacy of, 275 Visceral pain, 210 pathogenesis of, 479
recommended schedule for Vitamin(s), in integrative medicine, treatment of, 478–479, 480–481, 481f
accelerated, 207t, 208t 135–136, 136b WAST (Woman Abuse Screening Tool),
for adults, 125f, 126f, 275 Vitamin B12 deficiency anemia, 354–356, 83t
for children and adolescents, 125f, 357 Waters’ view, 185
202f, 275 Vitamin D, for osteoporosis, 587, 589 WBC (white blood cell) count, 149–150,
and MMR vaccine, 206t Vitamin E, for Parkinson’s disease, 508 150t
side effects of, 276 Vocal tremor, 507 Wearing-off effect, with
Varicella-zoster immune globulin (VZIG), Voiding, dysfunctional, 424 carbidopa/levodopa, 509
276 Voiding cystourethrograms (VCUGs), for Weight gain
Varicella-zoster virus, 275 UTI, 421, 421b due to antipsychotic medications, 682t
Vasa previa, ruptured, 574 Voltaren (diclofenac), 212t during pregnancy, 550
Vascular diseases, delirium due to, 670 Vomiting Weight loss
Vasomotor rhinitis, 223, 283 due to acute renal failure, 429–431 for diabetes mellitus, 384
VCUGs (voiding cystourethrograms), for dehydration due to, 430 differential diagnosis of, 414–415, 414b
UTI, 421, 421b in palliative care, 520t for hypercholesterolemia, 332t

739
 Index

Weight loss (Continued) Workflow, electronic medical record and, Zaleplon (Sonata), for insomnia, 248–249
due to hyperthyroidism, 412–415 144 Zanamivir (Relenza), for influenza, 280,
pruritus due to, 253t Work-related evaluations, 71 280t
Weight measurement, 556 World Health Organization, analgesic Zantac (ranitidine), for GERD, 373
Wells rule, for pulmonary embolism, 300, ladder of, 210, 211f Zetia (ezetimibe), for
300t, 302 Wound debridement, for laceration repair, hypercholesterolemia, 331, 336t
Wentz, Henry, 32–33 541, 541f Zileuton, for asthma, 442t
Wheezing, 245, 438, 444f Wound revision, for laceration repair, 541, Ziprasidone, for schizophrenia, 682
WHI (Women’s Health Initiative), 47, 541f, 542f Zithromax. See Azithromycin
49–51, 65, 66, 67 Wrist splinting, for lateral epicondylitis, 529 (Zithromax).
“Whiff ” test, 592 Writing tremor, 507 Zocor (simvastatin), for
White blood cell (WBC) count, 149–150, hypercholesterolemia, 336t, 337t
150t X Zofran (ondansetron)
Whitehead, 453 Xanax (alprazolam), for anxiety disorders, for cholestasis, 256t
Willard Committee Report, 5, 33 653, 666t for opioid-induced pruritus, 256t
Williamson, Harold, 56 Xerosis, 251 Zoloft (sertraline), for generalized anxiety
Wilson’s disease, tremor in, 507 Xerotic eczema, 252t disorder, 666t
Withdrawal, 649 X-ray absorptiometry, 191 Zolpidem (Ambien), for insomnia, 248–249
delirium due to, 669–670 X-rays, 171, 171f–173f, 173t Zostrix (capsaicin cream), for pruritus
headache due to, 498 Xylocaine (lidocaine HCl) due to notalgia paresthetica, 256t
Wolf spider bites, 695, 695f for laceration repair, 540 due to uremia, 256t
Woman Abuse Screening Tool (WAST), for lateral epicondylitis, 529 Zosyn (piperacillin and tazobactam), for
83t UTI, 422t
Women’s Health Initiative (WHI), 47, Y Zung Self-Rating Depression Scale
49–51, 65, 66, 67 Young, J.W., Sr., 31 (ZSRDS), 656, 659t–660t
Wong-Baker Faces Scale, 210, 210f Zyban (bupropion), for smoking
Work release evaluations, 71 Z cessation, 290
Worker’s compensation, 71 Zafirlukast, for asthma, 442t Zyrtec (cetirizine), for allergic rhinitis, 225

740