Pediatric Treatment Guidelines

New Guidelines

2007 Edition

Karen Scruggs, MD

Michael T. Johnson, MD

Copyright © 2007 by Current Clinical Strategies Publishing.

All rights reserved. This book, or any parts thereof, may not
be reproduced or stored in a retrieval network without the
written permission of the publisher. The reader is advised
to consult the drug package insert and other references
before using any therapeutic agent. No warranty exists,
expressed or implied, for errors and omissions in this text.

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Neonatology
Normal Newborn Care
I. Prenatal pediatric visit
A. The prenatal pediatric visit usually takes place
during the third trimester of the pregnancy. Maternal
nutrition, the hazards of alcohol, cigarette smoking
and other drugs, and the dangers of passive smok-
ing should be discussed. Maternal illnesses and
medications should be reviewed.

Prenatal Pediatric Visit Discussion Issues

Maternal History
General health and nutrition
Past and present obstetric history
Maternal smoking, alcohol, or drug use
Maternal medications
Infectious diseases: Hepatitis, herpes, syphilis,
Chlamydia rubella
Maternal blood type and Rh blood groups
Family History
Newborn Issues
Assessment of basic parenting skills
Feeding plan: Breast feeding vs formula
Car seats
Circumcision of male infant

II. Delivery
A. Neonatal resuscitation
1. All equipment must be set up and checked before
delivery. The infant who fails to breath spontane-
ously at birth should be placed under a radiant
warmer, dried, and positioned to open the airway.
The mouth and nares should be suctioned, and
gentle stimulation provided.
2. The mouth should be suctioned first to prevent
aspiration. Prolonged or overly vigorous
suctioning may lead to bradycardia and should be
avoided unless moderate-to-thick meconium is
present in the airway.
3. The infant born with primary apnea is most likely
to respond to the stimulation of drying and gentle
tapping of the soles of the feet. The infant who
fails to respond rapidly to these measures is
experiencing secondary apnea and requires
positive pressure bag ventilation with oxygen.
4. Adequate ventilation is assessed by looking for
chest wall excursions and listening for air ex-
change. The heart rate should be assessed while
positive pressure ventilation is being applied. If
the heart rate does not increase rapidly after
 ventilation, chest compressions must be started
by an assistant. If the infant fails to respond to
these measures, intubation and medications are
necessary. Epinephrine can be administered via
the endotracheal tube. Apgar scores are used to
assess the status of the infant at 1 and 5 min
following delivery.

Apgar Scoring System

Sign 0 1 2

Heart rate Absent Slow (<100 100

beats/min) beats/min
or more

Respira- Absent Weak cry; Strong cry

tions hypoventi-
lation

Muscle Limp Some Active mo-

tone flexion tion

Reflex irri- No re- Grimace Cough or

tability sponse sneeze

Color Blue or Body pink; Completely

pale extremities pink
blue

III. Early routine care of the newborn

A. Vitamin K is given to the infant by intramuscular
injection to prevent hemorrhagic disease of the
newborn.
B. Ocular prophylaxis against gonorrheal and
chlamydial infection is administered after birth with
erythromycin ophthalmic ointment.
C. Umbilical cord blood syphilis serology is com-
pleted if there is no documented record of a nega-
tive third-trimester maternal test. Umbilical cord care
consists of local application of triple dye or
bacitracin ointment.
D. Hepatitis B prophylaxis. If the mother is hepatitis
B surface antigen-positive, or if she has active
hepatitis B, the infant should be given an IM injec-
tion of hepatitis B immune globulin and a course of
three injections of hepatitis B vaccine (before hospi-
tal discharge, and at 1 and 6 months of age).
IV. Physical examination of the newborn
A. General gestalt. The examiner should assess
whether the infant appears to be sick or well. An
unusual cry may indicate sepsis, hypothyroidism, a
congenital anomaly of the larynx, or a chromosomal
abnormality.
B. Vital signs. The normal temperature of the newborn
is 36.5 to 37.0 degrees C. The normal respiratory
rate ranges from 40 to 60 breaths per minute, and
the normal heart rate can range from 94 to 175
beats per minute.
C. Assessment of the adequacy of fetal growth
1. Gestational age assessment. The gestational
age of the newborn infant is assessed with the
Ballard score of neuromuscular and physical
maturity.
2. Premature infants
a. A preterm infant is defined as an infant of less
than 37 weeks' gestation, and a postterm
infant is defined as being of greater than 42
weeks' gestation.
b. Preterm infants may develop respiratory dis-
tress syndrome, apnea, bradycardia, and
retinopathy of prematurity. Respiratory distress
syndrome is recognized by tachypnea, grunt-
ing, retractions, an elevated oxygen require-
ment, and a roentgenographic picture of poor
inflation and a fine homogeneous
ground-glass appearance.
D. Premature infants of less than 34-1/2 to 35 weeks'
gestation are at increased risk for apnea and
bradycardia. Apnea is defined as a respiratory
pause of 20 sec or longer and frequently is accom-
panied by a drop in heart rate.
E. Measurements and growth charts
1. Height, weight, and head circumference should
be measured. A low-birth-weight infant is defined
as any neonate with a birthweight <2,500 g.
 Height, weight, and head circumference should
be plotted as a function of gestational age on an
intrauterine growth chart.
2. Factors that may result in an infant who is small
for gestational age include chromosomal and
other dysmorphic syndromes, congenital infec-
tions, maternal hypertension, smoking, uterine
anomalies, and multiple gestations.
3. The small-for-gestational age infant is at greater
risk for cold stress, hypoglycemia, hypocalcemia,
and polycythemia.
4. The differential diagnosis for the
large-for-gestational age infant includes maternal
diabetes and maternal obesity. The
large-for-gestational age infant is at risk for
shoulder dystocia, birth trauma, and
hypoglycemia.
F. Examination of organ systems and regions
1. Head, face, and neck
a. The head circumference is measured and
plotted, and the scalp, fontanelles, and sutures
are examined. Bruising and hematomas of the
scalp should be noted. Cephalohematomas
are subperiosteal and do not cross suture
lines, whereas caputs are subcutaneous and
do cross suture lines.
b. Facial features that suggest a chromosomal
anomaly include midfacial hypoplasia, small
eyes, or low-set ears. Fetal alcohol syndrome
is suggested by a small upper lip and a
smooth philtrum.
c. The eyes should be examined with an oph-
thalmoscope to document a red reflex. The
absence of a clear red reflex is indicative of a
retinoblastoma, cataract, or glaucoma.
d. The lips, mouth, and palate are inspected
and palpated for clefts. Nares patency can be
documented by closing the mouth and occlud-
ing one nostril at a time while observing air
flow through the opposite nostril.
2. Thorax and cardiovascular systems
a. Chest wall excursions should be observed
and the respiratory rate determined. The
normal neonatal respiratory rate is 40 to 60
breaths per minute.
b. Auscultation of breath and heart sounds.
The normal heart rate during the first week of
life may range from 94 to 175 beats per min-
ute.
3. Abdomen and gastrointestinal system
a. Visual inspection of the abdomen should
assess symmetry and distension.
b. Abdominal palpation for masses,
hepatosplenomegaly, or renal masses is
completed, and the anus should be visually
inspected.
4. Genitourinary system. The genitalia are exam-
ined for ambiguous genitalia, which requires
immediate endocrinologic and urologic consulta-
tion.
5. Musculoskeletal system
a. Hip examination may detect developmental
dysplasia. Risk factors for hip dysplasia in-
clude a family history, foot deformities, con-
genital torticollis, Down syndrome, and breech
presentation. The female to male ratio is 7:1.
Ultrasonography is used to evaluate sus-
pected hip dysplasia.
b. Fracture of the clavicle occurs in 0.2-3.5% of
vaginal deliveries. Physical findings include
local swelling and crepitations and an asym-
metric Moro reflex. Treatment consists of
making a sling by pinning the shirt sleeve of
the involved side to the opposite side of the
shirt.
6. Neurologic system
a. The degree of alertness, activity, and muscle
tone should be noted. The head circumference
is plotted on the growth chart.
b. The posterior midline area should be exam-
ined for evidence of neural tube defects.
Pilonidal dimples with tufts of hair are evalu-
ated with ultrasonography.
V. Common neonatal problems
A. Hypoglycemia
1. Hypoglycemia is common in premature infants,
infants who are small for gestational age, infants
 of diabetic mothers, and infants who have experi-
enced perinatal asphyxia.
2. Hypoglycemia is defined as a blood glucose of
<40-45 mg/dL. Hypoglycemic infants require early
feedings or IV glucose.
B. Anemia during the newborn period may be caused
by hemolytic and congenital anemias, fe-
tal-to-maternal hemorrhage, placental abruption,
and occult hemorrhage.
C. Bilirubin metabolism
1. Hyperbilirubinemia occurs frequently in the nor-
mal newborn because of increased production
and decreased elimination of this breakdown
product of heme.
2. Initial workup for neonatal hyperbilirubinemia
includes measurements of total and direct biliru-
bin levels, hematocrit, Coombs test, and testing
of urine for reducing substances to exclude
galactosemia. High levels of bilirubin can cause
an acute encephalopathy (ie, kernicterus).
D. Gastrointestinal problems
1. Ninety-six percent of full-term newborns pass a
meconium stool before 24 hours of age. A de-
layed or absent passage of meconium may be
caused by meconium plug syndrome,
Hirschsprung disease, meconium ileus (cystic
fibrosis), or imperforate anus.
2. Bilious vomiting in the newborn is always abnor-
mal and usually is caused by an intestinal ob-
struction. Vomiting in the newborn also may be
caused by inborn errors of metabolism and
congenital adrenal hyperplasia.
E. Urinary problems. Ninety-nine percent of normal
full-term infants will urinate by 24 hours. If urination
has not occurred within 24 hours, renal ultra-
sonography should be done and an intravenous
fluid challenge may be given.
References, see page 182.

Neonatal Jaundice
Jaundice is defined by a serum bilirubin concentration
greater than 5 mg/dL. Clinical jaundice develops in 50% of
newborns, and breast-fed infants have an increased
incidence of jaundice. Differentiation between physiologic
jaundice, which is seen in many infants during the first
week of life, and pathologic jaundice is essential because
pathologic jaundice is a sign of a more serious condition.

I. Pathophysiology
A. Physiologic versus pathologic jaundice
1. Physiologic jaundice is characterized by
unconjugated hyperbilirubinemia that peaks by
the third or fourth day of life in full-term newborns
and then steadily declines by 1 week of age.
Asian newborns tend to have higher peak biliru-
bin concentrations and more prolonged jaundice.
Premature infants are more likely to develop
jaundice than full-term babies.
2. Causes of physiologic jaundice
a. Increased bilirubin load due to the high red
blood cell volume in newborns and shortened
blood cell survival.
b. Deficient hepatic uptake and deficient conju-
gation of bilirubin.
c. Increased enterohepatic bilirubin reabsorp-
tion.
d. Deficient excretion of bilirubin.
3. Pathologic jaundice usually appears within the
first 24 hours after birth and is characterized by a
rapidly rising serum bilirubin concentration (>5
mg/dL per day), prolonged jaundice (>7 to 10
days in a full-term infant), or an elevated direct
bilirubin concentration (>2 mg/dL). Conjugated
hyperbilirubinemia never has a physiologic cause
and must always be investigated.
II. Clinical evaluation of jaundice in newborns
A. History may reveal abdominal distention, delayed
passage of meconium, lethargy, light colored stools,
dark urine, low Apgar scores, poor feeding, weight
loss, or vomiting.
B. Physical examination should seek bruising,
cephalhematoma, congenital anomalies,
hepatosplenomegaly, pallor, petechiae, or small or
large size for gestational age.
 C. Maternal history should assess history of
chorioamnionitis, forceps delivery, vacuum extrac-
tion, diabetes, dystocia, or exposure to drugs.
Failure to receive immune globulin in a previous
pregnancy or abortion that involved risk of
isoimmunization should be sought. Family history of
jaundice, anemia, liver disease, splenectomy, Greek
or Asian race, preeclampsia, or unexplained illness
during pregnancy should be assessed.
III. Laboratory evaluation
A. Diagnostic tests include blood group typing of both
mother and infant, a direct Coombs’ test, and
measurement of serum bilirubin concentration.
B. Ill or premature infants, or those with significant
jaundice (serum bilirubin >15 mg/dL) require a
complete blood cell count or hemoglobin,
reticulocyte count, blood smear, and direct bilirubin
level. In infants of Asian or Greek descent, glucose-
6-phosphate dehydrogenase (G6PD) should be
measured.
IV. Differential diagnosis of unconjugated
hyperbilirubinemia
A. Increased bilirubin production
1. Fetal-maternal blood group incompatibility is
one cause of increased bilirubin production. Rh
sensitization occurs when an Rh-negative mother
is exposed to Rh-positive blood cells. Subse-
quent Rh-positive fetuses may develop
hemolysis. Other minor blood group incompatibili-
ties also can cause hemolysis and jaundice.
2. ABO incompatibility is the most common type of
isoimmune hemolytic disease. It can occur when
the mother’s blood group is O and the baby’s is A
or B. This type of hemolysis is relatively mild.
3. G6PD deficiency, a sex-linked disease, is an
important cause of hyperbilirubinemia and ane-
mia in infants of Greek and Asian descent.
4. Abnormalities of the red blood cell membrane,
such as spherocytosis and elliptocytosis, may
cause hyperbilirubinemia. Alpha thalassemia may
occur in the neonatal period.
5. Hematoma, occult hemorrhage, or
polycythemia (fetomaternal or twin-to-twin
transfusion, delayed cord clamping, intrauterine
growth retardation, or maternal diabetes) may
lead to hyperbilirubinemia.
B. Decreased bilirubin excretion
1. Delay in intestinal transit time, because bowel
obstruction, increases the enterohepatic circula-
tion. Relief of the obstruction results in a decline
in bilirubin concentration.
2. Crigler-Najjar syndrome is a rare, inherited,
lifelong deficiency of bilirubin excretion. Type I is
autosomal recessive. Patients present with
extreme jaundice (bilirubin concentration >25
mg/dL) and have a very high risk of bilirubin
encephalopathy. Type II is autosomal dominant,
and it can effectively be treated with phenobarbi-
tal.
3. Neonatal hypothyroidism is another cause of
prolonged indirect hyperbilirubinemia.
C. Increased bilirubin production and decreased
excretion. Sepsis often causes increased break-
down of red blood cells and decreased hepatic
excretion of bilirubin. Certain drugs given to the
newborn may also induce hemolysis or decrease
bilirubin excretion.
D. Breast feeding is associated with neonatal
hyperbilirubinemia. In healthy newborns, the danger
of an elevated bilirubin concentration is minimal, and
switching to formula feeding is unnecessary.
V. Consequences of unconjugated hyperbilirubinemia.
Bilirubin encephalopathy (kernicterus) is defined as
the acute and often fatal syndrome characterized by
opisthotonos, hypotonia, a high-pitched cry, and late
neurologic sequelae of choreoathetosis, spasticity,
upward-gaze paresis, and central hearing loss.
VI. Treatment
A. Low-risk infants with minimal jaundice are ob-
served for an increase in the jaundice intensity or a
spread to the baby’s feet (jaundice advances from
head-to-foot).
 Management of Hyperbilirubinemia in the Healthy
Term Newborn

Total serum bilirubin level, mg/dL

Age (H) Consider Photothe Ex- Ex-

photothe rapy change change
rapy transfu- transfu-
sion if sion and
photo- photo-
therapy therapy
fails

<24 ... ... ... ...

25-48 >12 >15 >20 >25

49-72 >15 >18 >25 >30

>72 >17 >20 >25 >30

B. Phototherapy with blue light causes

photoconversion of bilirubin to a water-soluble
product that is excreted in urine and stool. Bilirubin
concentrations are measured once or twice a day
during phototherapy, and treatment is discontinued
when the bilirubin concentration drops below 12
mg/dL.
C. Exchange transfusion therapy. Exchange transfu-
sion is used for emergent treatment of markedly
elevated bilirubin and for correction of anemia
caused by isoimmune hemolytic disease.
References, see page 182.

Respiratory Disorders of the New-

born
Respiratory distress is a common problem during the first
few days of life. Respiratory distress may present with
tachypnea, nasal flaring, sternal and intercostal retrac-
tions, cyanosis, and apnea.

I. Transient tachypnea of the newborn

A. Transient tachypnea of the newborn (TTN) usually
presents as early respiratory distress in term or
preterm infants. It is caused by delayed reabsorption
of fetal lung fluid.
B. TTN is a very common, and it is often seen following
cesarean section because babies born by cesarean
section have delayed reabsorption of fetal lung fluid.
C. Symptoms of TTN include tachypnea, retractions,
nasal flaring, grunting, and cyanosis.
D. Arterial blood gas reveals respiratory acidosis and
mild-to-moderate hypoxemia.
E. Chest x-ray often reveals fluid in the interlobar
fissures and perihilar streaking. Hyperaeration of the
lungs and mild cardiomegaly may be seen; alveolar
edema may appear as coarse, fluffy densities.
F. Transient tachypnea of the newborn usually resolves
within12-24 hours. The chest radiograph appears
normal in 2-3 days. The symptoms rarely last more
than 72 hours.
G. Treatment of TTN consists of oxygen therapy.
Infants will usually recover fully, without long-term
pulmonary sequelae.
II. Respiratory distress syndrome
A. RDS is a lung disease caused by pulmonary
surfactant deficiency. It occurs almost always in
preterm infants who are born before the lungs are
able to produce adequate amounts of surfactant.
B. Respiratory distress usually begins at, or soon after,
delivery and tends to worsen over time. Infants will
have tachypnea, nasal flaring, intercostal and sternal
retractions, and expiratory grunting.
C. Chest radiography shows diffuse atelectasis, which
appears as reduced lung volume, with homogeneous
haziness or the “ground glass” appearance of lung
fields, and air bronchograms.
D. RDS is diagnosed when a premature infant has
respiratory distress and a characteristic chest radio-
graph. The differential diagnosis includes pneumonia
caused by group B streptococci.
 E. Ventilatory management
1. Continuous positive airway pressure (CPAP)
improves oxygenation and survival (5-7 cm H2O
pressure).
2. For infants exhibiting respiratory acidosis,
hypoxemia or apnea, intermittent positive pres-
sure ventilation will be required in addition to
positive end-expiratory pressure (PEEP).
3. An umbilical or radial arterial line is used to
monitor blood gas levels and blood pressure.
F. Surfactant replacement therapy
1. Surfactant therapy reduces mortality by 30-50%
and pneumothorax by 50%.
2. Surfactant replacement therapy should be initi-
ated as soon as respiratory distress has been
clinically diagnosed. As long as the infant requires
significant ventilatory support, Survanta (every 6
hours for 4 doses) or Exosurf (every 12 hours for
2 doses) should be given.
G. General supportive care. Sepsis and pneumonia
are part of the differential diagnosis of RDS. Pre-
sumptive treatment with ampicillin plus gentamicin or
cefotaxime usually is given until blood and CSF
cultures are negative.
III. Bronchopulmonary dysplasia (BPD, chronic lung
disease)
A. BPD is characterized by hypoxia, hypercarbia, and
oxygen dependence that persists beyond 1 month of
age. The chest radiograph shows hyperexpansion
and focal hyperlucency, alternating with strands of
opacification.
B. BPD is extremely common among infants who have
severe RDS treated with mechanical ventilation. The
incidence of BPD is inversely proportional to
birthweight. Virtually all babies who develop BPD
have had mechanical ventilation, suggesting an
important role for barotrauma and oxygen toxicity.
C. Respiratory distress syndrome is the most common
pulmonary disease causing BPD. Other neonatal
diseases requiring oxygen and mechanical ventila-
tion may also cause BPD, including immature lungs,
meconium aspiration syndrome, congenital heart
disease, neonatal pneumonia, and aspiration pneu-
monia.
D. Signs of BPD include tachypnea and retractions,
after extubation. Blood gas measurements show
respiratory acidosis with elevated PaVCO2; in-
creased HCO3 indicates metabolic compensation.
Higher inspired oxygen concentration is required to
maintain normal oxygenation.
E. Management of bronchopulmonary dysplasia
1. Bronchopulmonary dysplasia (BPD), also
known as neonatal chronic lung disease
(CLD), is an important cause of respiratory
illness in preterm newborns. Most patients
with BPD gradually improve as healing occurs
and lung growth continues.
2. Respiratory support
a. Mechanical ventilation. Infants who re-
main ventilator-dependent for several
weeks should be weaned gradually. Small
tidal volumes are preferable to avoid addi-
tional mechanical injury. Maintaining a
positive end-expiratory pressure of 6 or 7
cm H2O may minimize atelectasis. A
slightly prolonged inspiratory duration of
0.5-0.6 sec sometimes is needed to pro-
mote uniform lung inflation. To facilitate
weaning, the arterial carbon dioxide tension
should be allowed to rise to 55-60 mm Hg,
as long as pH is in the normal range. In-
fants who can maintain this PCO2 level with
spontaneous breathing can be weaned to
continuous positive airway pressure and
then to supplemental oxygen alone.
b. Oxygen. Supplemental oxygen should be
provided to maintain arterial PO2 above 50-
55 mm Hg. Hypoxemia also may increase
airway resistance in infants who have been
weaned from assisted ventilation, supple-
mental oxygen can be provided by hood or
nasal cannula.
c. Monitoring. Oxygenation should be moni-
tored with pulse oximetry. Oxygen satura-
tion should be maintained at 92-95 percent.
The oxygen concentration (or flow rate by
nasal cannula) may need to be increased
 during feedings and sleep to maintain
adequate oxygenation.
d. In ventilator-dependent infants, capillary
blood gas (CBG) samples should be moni-
tored to check PCO2 and pH.
3. Nutrition. Appropriate nutrition must be pro-
vided to ensure recovery and growth. Human
milk or premature formula must be supple-
mented to meet these needs.
4. Fluid restriction
a. Fluid intake should be restricted in infants
with BPD to avoid pulmonary edema. How-
ever, adequate nutrition must be provided
in the reduced volume of feeding. Most
infants can be managed with modest re-
striction of 140-150 mL/kg per day. A pre-
mature formula or human milk with added
fortifier is used in preterm infants. When
infants reach term postmenstrual age,
supplemented human milk or a transitional
formula is used. Additional calories and/or
protein may be added.
b. Growth should be monitored. Protein and
mineral intakes should be calculated each
week to ensure that they are optimal. Se-
rum concentrations of calcium, phospho-
rus, and alkaline phosphatase are mea-
sured weekly or every other week.
5. Diuretics. Pharmacologic therapy may in-
clude diuretics.
a. Thiazide diuretics. Acute and chronic
administration of diuretics (thiazide and/or
spironolactone) improve lung mechanics in
preterm infants with BPD. Diuretics in
infants with evolving or established BPD to
achieve acute improvements in pulmonary
function are useful.
b. In infants who have pulmonary exacerba-
tions attributed to pulmonary edema, or to
minimize the circulatory effect of a packed
red blood cell transfusion, furosemide
should be given (1 mg/kg per day IV or 2
mg/kg per day PO). In infants with severe
BPD who appear to have short-term benefit
from diuretic treatment, a longer course of
furosemide (4 mg/kg in two divided doses
PO on alternate days) may be given.
c. In infants three to four weeks old who
remain ventilator-dependent with evolving
BPD, chlorothiazide (10 to 20 mg/kg in two
divided doses, PO) may be used as an
alternative to furosemide.
d. Serum electrolytes should be measured
one to two days after initiating diuretic
therapy, with an increase in dose, and at
least weekly with chronic use. Electrolyte
supplements should be administered to
compensate for increased urinary loss.
Initial supplementation is 2 to 4 meq/kg per
day of sodium chloride and 2 meq/kg per
day of potassium chloride, and adjust as
needed.
6. Bronchodilators. Infants with BPD have
increased airway resistance and may have
episodes of bronchoconstriction. Inhaled or
subcutaneous administration of beta-2
agonists (eg, salbutamol, albuterol,
terbutaline) acutely decreases resistance and
increases compliance. The metered dose
inhaler (MDI) often is used in infants with BPD.
a. Albuterol
(1) In some ventilator-dependent preterm
infants with evolving BPD who are two
to three weeks of age, the beta-
adrenergic agonist albuterol may im-
prove pulmonary function. Albuterol is
administered as one MDI actuation per
dose (approximately 0.1 mg) every four
to six hours.
(2) If the infant appears to improve with
albuterol use of a long-acting beta-
adrenergic agonist such as salmeterol
may be preferred to avoid adverse
effects that have been associated with
chronic use of albuterol. These ad-
verse effects include tachycardia,
arrhythmias, hypokalemia, and irritabil-
 ity.
b. Salmeterol is given as one MDI actuation
twice daily. If possible, treatment should be
discontinued gradually as lung function
stabilizes and before hospital discharge.
c. Ipratropium bromide
(1) Administration of the anticholinergic
bronchodilator ipratropium bromide
(inhaled doses of 25 micrograms/kg) to
ventilator-dependent preterm infants
improves respiratory system resistance
and compliance.
(2) Ipratropium can be used for its syner-
gistic effect with albuterol in the treat-
ment of acute episodes of reactive
airway disease. A combination of in-
haled ipratropium bromide and
albuterol (Combivent) may be adminis-
tered as one to two MDI actuations
every four hours, in ventilator-depend-
ent infants with BPD.
7. Corticosteroids. Corticosteroids may reduce
inflammation and improve lung function in
infants with BPD. Both systemic and inhaled
administration have been used. However,
systemic corticosteroid administration is asso-
ciated with serious adverse effects and should
be avoided if possible.
a. Systemic corticosteroids. Systemic
corticosteroids improve lung mechanics
and reduce the need for assisted ventila-
tion in infants with established BPD. Sys-
temic dexamethasone should be reserved
for the exceptional infant with severe BPD
who cannot be weaned from maximal
ventilatory and oxygen support.
b. Inhaled corticosteroids. Infants with
severe BPD who are dependent upon
substantial support with mechanical ventila-
tion and high concentrations of supplemen-
tal oxygen, may sometimes be treated with
inhaled beclomethasone or fluticasone.
Beclomethasone (42 µg per puff) or
fluticasone (50µg per puff) may be used by
MDI connected to the endotracheal tube,
and give one to two puffs every 12 hours.
8. Acute exacerbations
a. Infants with severe BPD may have acute
episodes of bronchospasm leading to
respiratory decompensation. These may be
associated with viral infections, although
bacterial pneumonia is uncommon.
b. A chest radiograph should be obtained to
detect pulmonary parenchymal changes.
Culture and Gram stain should be obtained
of tracheal secretions that are purulent or
have changed in volume or quality. If bac-
terial infection is suspected, antibiotic
treatment should be initiated while awaiting
culture results.
c. Management
(1) Treatment should be initiated with
albuterol, which is administered by MDI
and spacer (two to four puffs) or by
nebulization (0.15 mg/kg in 2 mL sa-
line) every 20 minutes for three doses.
Either regimen is followed by adminis-
tration every one to four hours; the
frequency is decreased as airflow im-
proves, or with tachycardia of >200
bpm. Another approach is continuous
nebulization of albuterol (0.5 mg/kg per
hour may be given for one to two
hours). Ipratropium should be added if
the response to albuterol is poor.
(2) If acute bronchospasm occurs in an
infant receiving inhaled corticosteroids,
the dose is doubled for 7 to 14 days. If
treatment with a beta-adrenergic agent
and inhaled corticosteroids fails to
reestablish stable pulmonary function,
a short (five to seven days) tapering
course of systemic dexamethasone
(initial dose 0.25 mg/kg), may be con-
sidered. Alternatively, a short course of
prednisone (initial dose 1 mg/kg per
day, tapered over five days) may be
 tried.
9. Monitoring
a. Growth. Patients should be weighed every
one to three days while in the hospital, and
length and head circumference should be
measured weekly. Nutritional monitoring
includes initial weekly measurement of
blood urea nitrogen, albumin, calcium,
phosphorus, and alkaline phosphatase
concentrations. Serum electrolyte concen-
trations should be measured every week in
infants on diuretic therapy.
b. Oxygenation
(1) Oxygen saturation is monitored contin-
uously with pulse oximetry during hos-
pitalization. After discharge, oxygen
saturation should be measured for at
least six to eight hours every one to
two weeks, including periods while
awake, sleeping, and feeding.
(2) A target oxygen saturation of 92 to 94
percent is adequate to avoid
hypoxemia and minimize the risk of
additional lung injury caused by expo-
sure to excessive oxygen concentra-
tions. The target saturation should be
higher (94 to 96 percent) in infants with
pulmonary hypertension.
References, see page 182.

Neonatal Resuscitation
Neonatal resuscitation skills are important because of the
potential for serious disability or death in high-risk infants
and in a few unpredicted full-term, low-risk deliveries.

I. Preparation
A. Advanced preparation requires acquisition and
maintenance of proper equipment and supplies.
B. Immediate preparation
1. Suction, oxygen, proper-sized face mask and the
resuscitation bag should be checked.
2. Appropriately sized ET tubes, cut to 13 cm,
should be laid out.
3. Medications should be prepared and an umbili-
cal catheter and tray should be prepared.

Neonatal Resuscitation Equipment and Supplies

Suction Equipment

Bulb syringe Mechanical Suction

Suction catheters, 5 (or 6), 8 Fr feeding tube and 20 cc
8, 10 Fr syringe
Meconium aspirator

Bag-and-Mask Equipment

Oral airways, newborn and Oxygen with flow meter and

premature sizes tubing
Infant resuscitation bag with Cushion rim face masks in
a pressure-release newborn and premature sizes
valve/pressure gauge to give
90-100% O2

Intubation Equipment

Laryngoscope with straight Stylet

blades, No. 0 (preterm) and Scissors
No.1(term newborn). Gloves
Extra bulbs and batteries for
laryngoscope
Endotracheal tubes, size
2.5, 3.0, 3.5, 4.0 mm

Medications

Epinephrine 1:10,000, 3 cc Volume expanders-one or

or 10 cc ampules more of these:
Naloxone 0.4 mg/mL,1 mL Albumin 5% solution
ampules Normal Saline
Dextrose 10% in water, 250 Ringer’s Lactate solution
cc
Sterile water, 30 cc
 Miscellaneous

Radiant warmer and towels Alcohol sponges

or blankets 3-way stopcocks
Stethoscope 3 Fr feeding tube
Adhesive tape, ½ or 3/4 inch Umbilical tape
width Needles, 25, 21, 18 gauge
Syringes, 1 cc, 3 cc, 5 cc, 10 Umbilical catheters, 3 ½ and
cc, 20 cc, 50 cc 5 Fr
Umbilical artery
catheterization tray
Cardiotachometer and ECG
oscilloscope

II. Neonatal resuscitation procedures

A. During delivery, infant evaluation includes assess-
ment of muscle tone, color, and respiratory effort.
B. After delivery, the infant should be placed on a
preheated radiant warmer. The infant should be
quickly dried with warm towels. The infant should be
placed supine with its neck in a neutral position. A
towel neck roll under the shoulders may help pre-
vent neck flexion and airway occlusion.
C. The upper airway is cleared by suctioning; the
mouth first, and then the nose, using a bulb syringe.
Suctioning should be limited to 5 seconds at a time.
D. If breathing is effective and pulse is >100 beats/min,
positive pressure ventilation (PPV) is not needed. If
cyanosis is present, oxygen should be adminis-
tered.
E. Free-flowing oxygen may be given at a rate of 5
L/min by holding the tubing 1/2 inch in front of the
infant’s nose, or an oxygen mask may be used.
When the infant’s color is pink, the oxygen is gradu-
ally discontinued.
F. Positive pressure ventilation should be initiated if
the infant is not breathing effectively after the initial
steps. Tactile stimulation should be administered by
gently slapping the soles of the feet or rubbing the
back. If the infant is apneic or gasping, begin PPV
with 100% O2. If the heart rate is <100 beats/min,
give PPV immediately by bag-mask.
1. Bag-mask ventilation. Ventilations should be
given at a rate of 40-60/min. Visible chest wall
movement indicates adequate ventilation.
2. Endotracheal intubation is initiated if the infant
is nonresponsive to bag-mask PPV.

Endotracheal Tube Size and Depth of Insertion

From Upper Lip
Weight Gestational Size Depth
Age
<1000 g <28 weeks 2.5 mm 7 cm
1000-2000 28-34 weeks 3.0 mm 8 cm
g
2000-3000 34-38 weeks 3.5 mm 9 cm
g
3000 g or 39->40 weeks 4.0 mm 10 cm
more

G. Evaluation of heart rate

1. If the heart rate is >100 beats/min, PPV can be
gradually discontinued after the infant is breath-
ing effectively.
2. Chest compressions should be started if the
heart rate is <80 beats/min after 15-30 seconds
of adequate ventilation.
a. Chest compressions are alternated with
ventilations at a ratio of 3:1. The combined
rate should be 120/min (ie, 80 compressions
and 30 ventilations).
b. After 30 seconds, evaluate the response. If
the pulse is >80 beats/min, chest compres-
sions can be stopped and PPV continued
until the heart rate is 100 beats/min and
effective breathing is maintained.
3. Epinephrine should be given if the heart rate
remains below 80/minute after 30 seconds of
PPV and chest compressions.
 Neonatal Resuscitation Medications

Medica- Concentr Prepar Dosage Rate/Prec

tion ation ation autions

Epinep 1:10,000 1 mL 0.1-0.3 Give rap-

hrine mL/kg IV idly. May
or ET. dilute 1:1
May re- with nor-
peat in 3- mal saline
5 min if if given via
HR is ET
<80/min

Volume Whole 40 mL 10 mL/kg Give over

expand- blood IV 5-10 min
ers Albumin by syringe
5% or IV drip
Normal
saline
Ringer
lactate

Naloxon 0.4 mg/mL 1 mL 0.1 mg/kg Give rap-

e (0.25 idly
mL/kg)
IV, ET,
IM, SQ

Naloxon 1.0 mg/mL 1 mL 1 mg/kg IV, ET

e (0.1 preferred.
mL/kg) IV, IM, SQ
ET, IM, accept-
SQ able

Sodium 0.5 20 mL 2 mEq/kg Give

bicarbo mEq/mL or two IV slowly,
nate (4.2% so- 10-mL over at
lution) di- prefilled least 2
luted with syringes min.
sterile wa-
ter to
make 0.5
mEq/mL

4. Other medications
a. Volume expanders. Volume expansion is
indicated for patients who have known or
suspected blood loss and poor response to
other resuscitative measures. Albumin 5%,
normal saline, or Ringer’s lactate can be
given in boluses of 10 mL/kg over 5 to 10
minutes.
b. Sodium bicarbonate is recommended
during prolonged resuscitation for infants
refractory to other measures.
c. Naloxone hydrochloride is given to in-
fants with prolonged respiratory depression
following narcotic anesthesia given to the
mother within 4 hrs before delivery.
Naloxone is contraindicated in infants of
mothers who are addicted to narcotics.
5. Umbilical vessel catheterization is recom-
mended when vascular access is required.
The large, centrally located, thin-walled and
flat vein is used, and a 3.5 or 5.0 Fr
radiopaque catheter is inserted into the vein
until a free flow of blood can be aspirated.
References, see page 182.
General Pediatrics
Diabetes Mellitus
Diabetes mellitus consists of hyperglycemia caused by
insulin deficiency, impairment of insulin action, or both.
Five percent of the population is affected by diabetes, 10%
of whom have type 1 diabetes.

I. Classification of diabetes mellitus

A. Diabetes mellitus is classified into two types: type 1
and type 2.
B. Type 1 diabetes
1. Type 1 diabetes is caused by absolute insulin
deficiency. Most cases among children and ado-
lescents (95%) result from autoimmune destruc-
tion of the beta cells of the pancreas.
2. The peak age at diagnosis is 12 years, and 75-
80% of individuals develop type 1 diabetes before
age 30.
C. Type 2 diabetes is caused by insulin resistance and
relative insulin deficiency. Most type 2 diabetics do
not require insulin injections and are obese.

Criteria for Diagnosis of Diabetes

Fasting plasma glucose 126 mg/dL or higher

or
Random plasma glucose 200 mg/dL or higher with symptoms
of diabetes (fatigue, weight loss, polyuria, polyphagia,
polydipsia)
or
Abnormal two-hour 75-g oral glucose tolerance test result,
with glucose 200 mg/dL or higher at two hours
Any abnormal test result must be repeated on a subsequent
occasion to establish the diagnosis

II. Management of diabetic ketoacidosis

A. DKA can be seen at the time of diagnosis of type 1
diabetes or in the patient who has established
disease if diabetes management is inadequate. DKA
is caused by insulin deficiency, which leads to
hyperglycemia and ketogenesis.
B. Symptoms include polyuria, polydipsia, hyperpnea
with shortness of breath, vomiting, and abdominal
pain. Hyperosmolar dehydration and acid/base and
electrolyte disturbances occur.
C. Rehydration
1. Immediate evaluation should assess the degree
of dehydration by determining capillary refill, skin
temperature, and postural heart rate and blood
pressure.
2. Initial fluid resuscitation consists of a 10-mL/kg
bolus of 0.9% saline over 30-60 minutes, re-
peated if hypovolemic shock persists. Patients
then should begin to receive maintenance fluid
requirements added to the calculated fluid deficit
(>2 y: 30 mL/kg for mild deficit, 60 mL/kg for
moderate deficit, 90 mL/kg for severe deficit; <2
y: 50 mL/kg for mild deficit, 100 mL/kg for moder-
ate deficit, 150 mL/kg for severe deficit). The
sodium concentration of the fluid should provide
50% of the sodium deficit in the first 12 hours and
the remainder in the next 36 hours (75 to 125
mEq/L sodium chloride).

Laboratory Monitoring During DKA

Blood glu- At presentation, then hourly by

cose: fingerstick with glucose meter

Serum so- At presentation, then at 4- to 6-h inter-

dium and vals
potassium:

Acid/base At presentation, then at 2- to 4-h inter-

status: vals. Venous pH and serum carbon
dioxide

Serum urea nitrogen, complete blood count, acetone

and cultures can be obtained at presentation.

D. Potassium replacement. DKA is associated with

total body potassium depletion. This deficit should
be replaced by infusing potassium chloride at a rate
 of 3 mEq/kg per 24 hours after completion of the
normal saline fluid resuscitation. If the patient
requires more than 4 mEq/kg of a potassium
infusion, 50% can be administered as potassium
phosphate to help prevent hyperchloremic acidosis
and hypophosphatemia.
E. Lowering the glucose level
1. Regular insulin should be initiated as an intrave-
nous infusion of 0.1 U/kg per hour. The goal of
therapy is to lower the glucose level by 50 to 100
mg/dL per hour.
2. Once the glucose level is in the range of 250 to
350 mg/dL, 5% glucose should be initiated;
when the glucose level is between 180 to 240
mg/dL, the infusate can be changed to 10%
glucose.
F. Correcting acidosis. Alkali therapy is usually not
necessary to correct the acidosis associated with
DKA. If acidosis is severe, with a pH less than 7.1,
sodium bicarbonate can be infused slowly at a rate
of 1 to 3 mEq/kg per 12 hours and discontinued
when the pH exceeds 7.2.
III. Long-term diabetes management
A. Intensive management of diabetes results in a
significant reduction in the development of diabetic
complications: a 76% reduction in retinopathy, a
39% reduction in microalbuminuria, and a 60%
reduction in neuropathy.

Target Blood Glucose Range (Preprandial)

Age Glucose Levels (mg/dL)

Infants, tod- 120-220

dlers

Preschool 100-200
children

School-age 70-150
children

B. Insulin regimens
1. Starting dose of insulin. Most newly diagnosed
patients with type 1 diabetes can be started on
0.2 to 0.4 units of insulin per kg. Adolescents
often need more. The dose can be adjusted
upward every few days based upon symptoms
and blood glucose measurements.
2. Dosing regimens. Insulin should be provided in
two ways – as a basal supplement with an
intermediate- to long-acting preparation and as
pre-meal bolus doses of short-acting insulin (to
cover the extra requirements after food is ab-
sorbed).
3. Monomeric insulins
a. Insulin lispro (Humalog) has an onset of
action within 5 to 15 minutes, peak action at
30 to 90 minutes, and a duration of action of
2 to 4 hours. Insulin lispro is the preferred
insulin preparation for pre-meal bolus doses.
b. Insulin aspart (Novolog) is another
monomeric insulin. It is a rapid-acting insulin
analog with an onset of action within 10 to 20
minutes. Aspart reaches peak concentrations
in 40-50 minutes and has a duration of action
of 3-5 hours. Insulin aspart, like insulin lispro,
can be injected immediately before meals,
and has a shorter duration of action than
regular insulin. Insulin aspart has a slightly
slower onset and longer duration of action
than insulin lispro.
Pharmacokinetics of Insulin Preparations

Type of Onset Peak Dura- Common pitfalls

insulin of of tion
action action of
ac-
tion

Insulin 5 to 15 45 to 2 to 4 Hypoglycemia oc-

lispro min- 75 hours curs if the lag time
(Humalog utes min- is too long; with
) utes high-fat meals, the
dose should be
Insulin 10 to 40 to 3 to 5 adjusted down-
aspart 20 50 hours ward.
(Novolog) min- min-
utes utes

Regular 30 2 to 4 5 to 8 The insulin should

insulin min- hours hours be given 20 to 30
(Humulin utes minutes before the
R) patient eats.

Insulin 1 to 3 5 to 7 13 to Has a constant

glargine hours hours 18 glucose-lowering
(Lantus) hours profile without
peaks and valleys,
allowing it to be
administered once
every 24 hours.

NPH in- 1 to 3 6 to 12 18 to In many patients,

sulin hours hours 28 breakfast injection
(Humulin hours does not last until
N) the evening meal;
administration with
the evening meal
does not meet in-
sulin needs on
awakening.

Lente 1 to 3 4 to 8 13 to Loses its effect if it

insulin hours hours 20 is left in the sy-
(Humulin hours ringe for more than
L) a few minutes.

Total Daily Insulin Dosage

<5 Years 5-11 Years 12-18 Years

(U/kg) (U/kg) (U/kg)

0.6-0.8 0.75-0.9 0.8-1.5

Newly diagnosed patients and those who are in the

remission phase may require less insulin.

4. Twice-daily regimens. If the goal is relief from

hyperglycemic symptoms with a regimen that is
simple, then twice-daily NPH insulin will be
effective in many patients. Injection of regular
plus NPH insulin before breakfast and before
dinner results in four peaks of insulin action,
covering the morning, afternoon, evening, and
overnight, but the peaks tend to merge.
5. Insulin glargine (Lantus). While NPH insulin is
the insulin most commonly given at bedtime,
insulin glargine may be equally effective for
reducing HbA1c values and cause less
hypoglycemia.
C. Insulin regimens for intensive therapy of diabe-
tes mellitus
1. Multiple daily injections. The most commonly
used multiple-dose regimen consists of twice-
daily injections of regular and intermediate-
acting insulin (NPH).
2. Although a twice-daily regimen improves
glycemic control in most patients, the morning
dose of intermediate-acting insulin may not be
sufficient to prevent a post-lunchtime rise in
blood glucose concentrations. The intermediate-
acting insulin administered before the evening
meal may not be sufficient to induce
normoglycemia the next morning unless a larger
dose is given, which increases the risk of
hypoglycemia during the night. If necessary, the
twice-daily regimen can be converted into a
three- or four-injection program.
3. In contrast to NPH insulin, the time-action profile
for insulin glargine has virtually no peak, which
may make it the ideal basal insulin for intensive
insulin therapy in type 1 diabetes.
 4. Monomeric insulins, insulin lispro and insulin
aspart, may be most useful in patients in whom
high postprandial blood glucose concentrations
and unexpected high blood-glucose values at
other times are problems.
5. Inhaled insulin may become an alternative to
monomeric insulins in the future. It causes a very
rapid rise in serum insulin concentrations (similar
to that achieved with subcutaneous insulin
lispro). Typical premeal doses consists of 1.5
units per kg taken five minutes before a meal.
D. Blood glucose monitoring. Children and adoles-
cents should test their blood glucose levels at least
four times a day, before meals and at bedtime.
Quarterly measurement of hemoglobin A1c (HbA1c)
assesses glycemic control and reflects the average
blood glucose over the last 120 days.

Assessment of HbA1c Values

HbA1c Values Level of Glycemic Control

HbA1c >10% Poor or minimal

HbA1c 8.0-10.0% Average

<8.0% Excellent or intensive

References, see page 182.

Menstrual Disorders
The median age of menarche is 12.8 years, and the
normal menstrual cycle is 21 to 35 days in length. Bleed-
ing normally lasts for 3 to 7 days and consists of 30 to 40
mL of blood. Cycles are abnormal if they are longer than
8 to 10 days or if more than 80 mL of blood loss occurs.
Soaking more than 25 pads or 30 tampons during a
menstrual period is abnormal.

I. Pathophysiology
A. Regular ovulatory menstrual cycles often do not
develop until 1 to 1.5 years after menarche, and 55-
82% of cycles are anovulatory for the first 2 years
after menarche. Anovulatory cycles typically cause
heavier and longer bleeding.
B. Adolescents frequently experience irregular men-
strual bleeding patterns, which can include several
consecutive months of amenorrhea.
II. Amenorrhea
A. Primary amenorrhea is defined as the absence of
menarche by age 16. Puberty is considered delayed
and warrants evaluation if breast development (the
initial sign of puberty in girls) does not begin by the
age of 13. The mean time between the onset of
breast development and menarche is 2 years.
Absence of menses within 2 to 2.5 years of the
onset of puberty should be evaluated.
B. Secondary amenorrhea is defined as the absence
of 3 consecutive menstrual cycles or 6 months of
amenorrhea in patients who have already estab-
lished regular menstrual periods.
Differential Diagnosis of Amenorrhea

Pregnancy Outflow Tract-related Dis-

Hormonal Contraception orders
Hypothalamic-related Dis- Imperforate hymen
orders Transverse vaginal sep-
Chronic or systemic ill- tum
ness Agenesis of the vagina,
Stress cervix, uterus
Athletics Uterine synechiae
Eating disorders Androgen Excess
Obesity Polycystic ovarian syn-
Drugs drome
Tumor Adrenal tumor
Pituitary-related Disorders Adrenal hyperplasia
Hypopituitarism (classic and
Tumor nonclassic)
Infiltration Ovarian tumor
Infarction Other Endocrine Disorders
Ovarian-related Disorders Thyroid disease
Dysgenesis Cushing syndrome
Agenesis
Ovarian failure
Resistant ovary

C. Amenorrhea with pubertal delay

1. Hypergonadotropic hypogonadism is caused
by ovarian failure associated with elevated
gonadotropin levels. An elevated FSH will estab-
lish this diagnosis.
a. Turner syndrome (XO) may cause ovarian
failure and a lack of pubertal development.
Females with Turner syndrome have streak
gonads, absence of one of the X chromo-
somes, and inadequate levels of estradiol.
They do not initiate puberty or uterine devel-
opment. This syndrome is characterized by
short stature, webbed neck, widely spaced
nipples, shield chest, high arched palate,
congenital heart disease, renal anomalies,
and autoimmune disorders (thyroiditis, Addi-
son disease). It may not be diagnosed until
adolescence, when pubertal delay and
amenorrhea occur together.
b. Ovarian failure resulting from autoimmune
disorders or exposure to radiation or chemo-
therapy may also cause amenorrhea with
p u b e r t a l d e l a y a s s o c i a t e d wi t h
hypergonadotropic hypogonadism.
2. Hypogonadotropic hypogonadism is caused
by hypothalamic dysfunction or pituitary failure.
Low or normal levels of LH and FSH will be
present, and decreased estradiol levels may be
present.
a. Abnormalities of the pituitary and hypo-
thalamus, and other endocrinopathies (thy-
roid disease and Cushing syndrome) may
present with pubertal delay and low gonado-
tropin levels.
(1) Amenorrhea may be caused by problems
at the level of the pituitary gland, such as
congenital hypopituitarism, tumor (pitu-
itary adenoma), or infiltration
(hemochromatosis).
(2) Prolactin-secreting pituitary adenoma
(prolactinoma) is the most common
pituitary tumor. Prolactinomas present
with galactorrhea, headache, visual fields
cuts, and amenorrhea. Elevated prolactin
levels are characteristic.
(3) Craniopharyngioma is another tumor of
the sella turcica that affects hypothalamic-
pituitary function, presenting with pubertal
delay and amenorrhea.
(4) Other disorders associated with
galactorrhea and amenorrhea include
hypothyroidism, breast stimulation, stress
associated with trauma or surgery,
phenothiazines, and opiates.
b. Hypothalamic suppression is most com-
monly caused by stress, competitive athletics,
and dieting (anorexia nervosa).
c. Hypothalamic abnormalities associated
with pubertal delay include Laurence-Moon-
Biedl, Prader-Willi, and Kallmann syndromes.
Laurence-Moon-Biedl and Prader-Willi pres-
ent with obesity. Kallmann syndrome is asso-
ciated with anosmia.
D. Amenorrhea with normal pubertal development
1. Pregnancy should be excluded when
amenorrhea occurs in a pubertally mature
female.
2. Contraceptive-related amenorrhea occurs with
depot medroxyprogesterone (Depo-Provera); it
does not require intervention; however, a preg-
nancy test should be completed.
3. Uterine synechiae (Asherman syndrome)
should be suspected in amenorrheic females
with a history of abortion, dilation and curettage,
or endometritis.
4. Sheehan syndrome (pituitary infarction) is
suggested by a history of intrapartum bleeding
and hypotension.
5. Other disorders associated with amenorrhea
and normal pubertal development. Ovarian
failure, acquired abnormalities of the pituitary
gland (prolactinoma), thyroid disease, and
stress, athletics, and eating disorders may
cause amenorrhea after normal pubertal devel-
opment. Polycystic ovarian disease, which is
usually associated with irregular bleeding, can
also present with amenorrhea.
E. Genital tract abnormalities
1. Imperforate hymen will appear as a membrane
covering the vaginal opening. A history of cyclic
abdominal pain is common, and a midline ab-
dominal mass may be palpable.
2. Transverse vaginal septum may cause ob-
struction. It is diagnosed by speculum examina-
tion.
3. Agenesis of the vagina appears as a blind-
ended pouch. Normal pubertal development of
breast and pubic hair occurs, but menarche
does not occur.
4. Androgen insensitivity (testicular
feminization syndrome) is another common
cause of vaginal agenesis.
a. Breast development and a growth spurt
occur, but little if any pubic or axillary hair is
present. These women have an XY chromo-
somal pattern with intra-abdominal or inguinal
testes that produce testosterone, but an X-
linked inherited defect of the androgen recep-
tor prevents response to testosterone.
b. Female-appearing external genitalia are
present, but the uterus and vagina are ab-
sent. During puberty, breast development
occurs because of conversion of androgens
to estrogens.
c. The testes are at increased risk for develop-
ing tumors and must be removed. Hormone
replacement therapy is provided to initiate
puberty.
F. Polycystic ovary syndrome
1. PCO is the most common cause of persistent
irregular menses. Only 70% of patients have
polycystic ovaries on ultrasound. The most
common symptom is irregular periods beginning
with menarche; however, intervals of
amenorrhea may also occur. Signs include
hirsutism, acne, clitoromegaly, and obesity
(50%). Insulin resistance, glucose intolerance,
and lipid abnormalities are common.
2. Increased facial hair and midline hair over the
sternum and lower abdomen are often present.
If hirsutism is severe, an ovarian and adrenal
tumor or adrenal enzyme deficiency should be
excluded.
3. PCO is probably an autosomal recessive disor-
der that affects ovarian steroidogenesis. Ovula-
tion occasionally can occur spontaneously;
therefore, amenorrhea secondary to pregnancy
always must be considered.
G. Clinical evaluation of amenorrhea
1. Chronic or systemic illness, eating disorders,
and drug use, including hormonal contraception,
should be excluded. Tanner staging, pelvic
examination, and possibly pelvic
ultrasonography should be completed.
2. Absence of the uterus, vagina, or both re-
quires a chromosomal analysis, which can
determine if the karyotype is XX or XY, and it
can help differentiate between müllerian
agenesis and androgen insensitivity.
3. If the anatomy is normal, LH, FSH, and estradiol
 are indicated in order to distinguish ovarian
failure from hypothalamic dysfunction. High FSH
and LH levels and a low estradiol level are
indicators of gonadal dysgenesis (Turner syn-
drome) or autoimmune oophoritis. Normal or low
LH, FSH, and estradiol levels indicate hypotha-
lamic suppression, central nervous system
tumor, or an endocrinopathy (eg,
hypothyroidism).
4. Pregnancy must always be excluded if the
individual is mature pubertally.
5. Free-T4, TSH, and prolactin levels are checked
to exclude hypothyroidism and
hyperprolactinemia. If the prolactin level is
elevated, an MRI is necessary to exclude
prolactinoma.
6. Hirsutism and acne are indicative of androgen
excess and PCO. Total testosterone and
dehydroepiandrosterone sulfate (DHEAS) levels
are necessary to exclude ovarian and adrenal
tumors. A testosterone level >200 ng/dL and
DHEAS >700 μg/dL require further investigation
to exclude a tumor.
7. A morning 17-hydroxyprogesterone level will
screen for nonclassic adrenal hyperplasia. A 17-
hydroxyprogesterone >2 ng/mL is followed by an
ACTH stimulation test to diagnose 21-hydroxy-
lase deficiency.
8. An elevated LH-to-FSH ratio is common with
PCO; an ultrasonographic examination may
detect polycystic ovaries.
H. Treatment of amenorrhea
1. Anovulation and the resulting lack of progester-
one increases the risk of endometrial hyperpla-
sia and endometrial cancer. Or a l
medroxyprogesterone or an oral contraceptive
(OCs) should be prescribed to eliminate this
risk. Oral progestins can be given cyclically for
12 days every month or every third month.
2. PCO is treated with OCs to regulate menses
and to decrease androgen levels. Electrolysis
and spironolactone (50 mg tid) can decrease
hirsutism.
3. Hypoestrogenic and anovulatory patients
with hypothalamic suppression caused by an-
orexia, stress, or strenuous athletics should
modify their behavior and be prescribed calcium
and hormonal replacement therapy (OCs) to
reduce the risks of osteoporosis.
4. Turner syndrome or ovarian failure requires
estrogen and progesterone at a dosage suffi-
cient to induce pubertal development, after
which time they can be switched to an OC.
III. Abnormal vaginal bleeding
A. Abnormal vaginal bleeding is characterized by
excessive uterine bleeding or a prolonged number
of days of bleeding. The most common cause of
abnormal vaginal bleeding in adolescence is
anovulation. Abnormal bleeding is common during
the first 1 to 2 years after menarche because
anovulatory cycles are frequent.
B. Differential diagnosis of abnormal vaginal
bleeding
1. Pregnancy, pregnancy-related complications,
sexually transmitted diseases, pelvic inflamma-
tory disease, and retained tampons should be
excluded.
2. Vaginal tumors, uterine or cervical carcinoma,
and uterine myomas are rare in adolescents.
3. Blood dyscrasias or coagulation defects may
occasionally be the initial presentation of abnor-
mal vaginal bleeding.
4. Hormonal contraceptives are a common
cause of breakthrough bleeding.
C. Clinical evaluation of irregular vaginal bleeding
1. Age of menarche, menstrual pattern, amount of
bleeding, symptoms of hypovolemia, history of
sexual activity, genital trauma, and symptoms of
endocrine abnormalities or systemic illness
should be evaluated.
2. Postural vital signs may suggest hypovolemia. A
pelvic examination should assess pelvic anat-
omy and exclude trauma, infection, foreign body,
or a pregnancy-related complication. Pelvic
ultrasonography can be used to further assess
pelvic anatomy.
 Differential Diagnosis of Abnormal Vaginal Bleed-
ing

Pregnancy related. Ectopic pregnancy, abortion

Hormonal contraception. Oral contraceptives, depo-
medroxyprogesterone
Hypothalamic-related. Chronic or systemic illness, stress,
athletics, eating disorder, obesity, drugs
Pituitary related. Prolactinoma, craniopharyngioma
Outflow tract-related. Trauma, foreign body, vaginal tumor,
cervical carcinoma, polyp, uterine myoma, uterine carci-
noma, intrauterine device
Androgen excess. Polycystic ovarian syndrome, adrenal
tumor, ovarian tumor, adrenal hyperplasia
Other endocrine causes. Thyroid disease, adrenal disease
Hematologic causes. Thrombocytopenia, clotting abnormali-
ties, abnormalities of platelet function, anticoagulant
medications
Infectious causes. Pelvic inflammatory disease, cervicitis

3. Laboratory evaluation
a. A pregnancy test and complete blood
count should be completed.
b. A history of a very heavy period with
menarche or repeated prolonged or heavy
menses warrants a prothrombin time and
partial thromboplastin time to screen for
bleeding abnormalities; a bleeding time and
von Willebrand screening panel will identify
more specific coagulation disorders.
c. Signs of androgen excess indicate a need
to exclude PCO.
d. Chronic irregular vaginal bleeding man-
dates that prolactinoma and endocrine
abnormalities (thyroid disease) be excluded.
D. Treatment of irregular vaginal bleeding
1. Mild bleeding or shortened cycles associated
with a normal physical examination and normal
vital signs requires only reassurance.
2. Mild anemia associated with stable vital signs
is treated with a 35 to 50 mcg monophasic
combination OC as follows: One pill QID x 4
days. One pill TID x 3 days. One pill BID x 7
days. One pill QD x 7-14 days. Stop all pills for
7 days and then begin cycling on a low dose
OCP QD.
3. The patient should be continued on low-dose
OCs for 3 to 4 months before allowing resump-
tion of normal cycles. Iron therapy should be
included.
4. If the hematocrit is <7-8 mg/dL or if vital
signs are unstable, hospitalization is recom-
mended. Intravenous conjugated estrogens
(Premarin), 25 mg IV every 4-6 hours for 24
hours, will stop the bleeding quickly. Conjugated
estrogen therapy is followed immediately by
OCs and iron therapy. Blood transfusion is
warranted only if the patient is severely symp-
tomatic. Dilatation and curettage is used as a
last resort; however, it is rarely necessary.
5. Antiprostaglandin medications (NSAIDs)
decrease menstrual blood loss significantly by
promoting platelet aggregation and
vasoconstriction. They do not have the hor-
monal side effects of OCs, and they can be
used alone in mild cases of abnormal vaginal
bleeding.
IV. Dysmenorrhea
A. Fifty percent of adolescents experience
dysmenorrhea
B. Primary dysmenorrhea consists of crampy lower
abdominal and pelvic pain during menses that is
not associated with pelvic pathology. It is the most
common form of dysmenorrhea, usually beginning
6 months to 1 year after menarche.
C. Secondary dysmenorrhea is defined as painful
menses associated with pelvic pathology
(bicornate uterus, endometriosis, PID, uterine
fibroids and polyps, cervical stenosis, ovarian
neoplasms). If dysmenorrhea is severe, obstructing
lesions of the genital tract should be excluded.
Endometriosis is the most common cause (50%) of
chronic pelvic pain in adolescents.
D. Evaluation of dysmenorrhea
1. Gynecologic history should determine the
relationship of the pain to the menstrual cycle,
severity, and sexual activity.
2. If the pain is mild, easily relieved by NSAIDs,
 and the physical examination (including the
hymen) are normal, a speculum examination is
not necessary.
3. Severe pain requires a pelvic examination to
exclude genital tract obstruction, adnexal and/or
uterosacral pain (endometriosis), PID, or a
mass. Ultrasonography is useful for evaluating
pelvic abnormalities or obstruction.
E. Treatment of dysmenorrhea
1. Initial treatment consists of a prostaglandin
synthesis inhibitor, initiated with the onset of
bleeding and continued for as long as pain
lasts. Gastric irritation can be reduced by taking
the drug with food.
a. Mefenamic acid (Ponstel) 500 mg loading
dose, then 250 mg q6h.
b. Ibuprofen (Advil) 400-600 mg q4-6h.
c. Naproxen sodium (Aleve) 550 mg load,
then 275 mg q6h.
d. Naproxen (Naprosyn) 500 mg load, then
250 mg q6-8h.
2. Oral contraceptives are also very effective and
can be added if the antiprostaglandin is not fully
effective.
References, see page 182.

Nocturnal Enuresis
Nocturnal enuresis affects approximately 5 to 7 million
children in the United States. Parents may become
concerned about nocturnal enuresis when their child
reaches 5 to 6 years of age. There is a slight male pre-
dominance of 60% for nocturnal enuresis. Etiologic factors
include genetics, sleep arousal dysfunction, urodynamics,
nocturnal polyuria, psychological components, and
maturational delay.

I. Clinical evaluation
A. History
1. A detailed toilet training history and a family
history of enuresis should be sought. Other
pertinent details include the onset and pattern of
wetting, voiding behavior, sleep pattern,
parasomnias, medical conditions, daytime urinary
symptoms, bowel habits, and psychosocial fac-
tors.
2. Urgency or a history of small, frequent voids
suggests bladder instability or small bladder
capacity. Dysuria suggest a urinary tract infection.
Polyuria and polydipsia suggest diabetes
insipidus or mellitus. Encopresis suggests consti-
pation. Nighttime snoring suggests adenoidal
hypertrophy.
B. Physical examination
1. Most children who have nocturnal enuresis will
have normal findings on physical examination.
Height, weight, and blood pressure should be
recorded.
2. A palpable bladder, palpable stool, ectopic ureter,
signs of sexual abuse, or abnormal gait should be
sought. Cremasteric, anal, abdominal, and deep
tendon reflexes that reflect spinal cord function all
should be tested.
3. The skin of the lower back should be inspected
for a sacral dimple, hair patches, or vascular
birthmarks, which indicate spinal dysraphism.
Mouth breathing may suggest sleep apnea with
associated enuresis due to adenoidal hypertro-
phy.
4. Direct observation of the urinary stream is impor-
tant if findings suggest an abnormality. Bladder
capacity can be measured in the office by having
the child drink 12 oz of fluid on arrival, then
voiding into a calibrated cup.
C. Laboratory/imaging studies. All children should
have urinalysis of a clean-catch midstream urine
specimen. The ability to concentrate urine to 1.015
or greater rules out diabetes insipidus and the
absence of glucose rules out diabetes mellitus. A
urine culture should be obtained if the child has
dysuria or an abnormal urinalysis.
II. Treatment
A. Nonpharmacologic therapy
1. Motivational therapy. The child should be taken
out of diapers or training pants and encouraged to
 empty the bladder completely prior to going to
bed. The child should participate in morning
cleanup. Fluids should be restricted for 2 hours
prior to bedtime.
2. Behavioral therapy
a. Hypnotherapy involves having the child prac-
tice imagery of awakening to urinate in the
toilet or staying dry all night.
b. Dry-bed training involves waking the child
over several nights, and having the child walk
to the toilet when voiding is needed. The
eventual goal is to have the child self-awaken
to void.
c. Enuresis alarms have the highest overall cure
rate. Alarm systems can be used in combina-
t i o n wi t h b e h a v i o r a l t h e r a p y o r
pharmacotherapy. The cure rate may be as
high as 70% long-term.
B. Pharmacotherapy. Medication for nocturnal
enuresis seldom should be considered before 8
years of age.
1. Imipramine (Tofranil)
a. Imipramine increases bladder capacity and
also may decrease detrusor muscle contrac-
tions. The starting dose is 25 mg taken 1 hour
before bedtime for children ages 6 to 8 years
and 50 to 75 mg for older children and adoles-
cents. The dose may be increased in 25-mg
increments weekly up to 75 mg. Therapy may
continue from 3 to 9 months, with a slow taper-
ing over 3 to 4 weeks. Imipramine is inexpen-
sive. The success rate is 15 to 50%.
b. Mild side effects include irritability, dry mouth,
decreased appetite, headaches, and sleep
disturbances. Overdose can be lethal.
2. DDAVP (Stimate)
a. DDAVP is a synthetic analog of arginine
vasopressin (ADH). It decreases urine volume.
The bioavailability is only 1% for the tablet and
10% for the nasal spray. The initial dose of
DDAVP is 20 mcg PO or one 10-mcg puff in
each nostril within 2 hours of bedtime. The
dose may be increased in increments of 10
mcg every 1 or 2 weeks up to a maximum
dose of 40 mcg. Patients may remain on
medication for 3 to 6 months, then should
begin a slow decrease of the dose by 10
mcg/mo. If oral medication is preferred, the
starting dose is 0.2 mg (one tablet) 1 hour
before bedtime. If there is no response within
1 week, the dose can be titrated by 0.2 mg up
to a maximum of 0.6 mg nightly.
b. Side effects of DDAVP are rare and include
abdominal discomfort, nausea, headache, and
epistaxis. Symptomatic hyponatremia with
seizures is very rare. Contraindications include
habit polydipsia, hypertension, and heart
disease. About 22% become dry with DDAVP.
c. The high initial response rate of DDAVP is
attractive for episodic use for summer camp
and sleepovers.
C. Age-related treatments
1. Younger than age 8 years. Motivational and
behavioral methods that assist the child in waking
to void and that praise successful dryness are
recommended.
2. Ages 8 through 11 years. The enuresis alarm
gives the best results in terms of response rate
and low relapse rate. Intermittent use of medica-
tion such as DDAVP can be useful for special
events.
3. Ages 12 years and older. If use of an enuresis
alarm does not stop wetting episodes, continuous
use of medication is justified.
References, see page 182.

Poisoning
Poisoning is defined as exposure to an agent that can
cause organ dysfunction, leading to injury or death.
Children less than 6 years of age account for 60.8% of
poisonings.

I. Clinical evaluation of poisoning

A. The type of toxin involved should be determined.
 The time of the exposure and how much time has
elapsed should be assessed.
B. The dose of the toxin should be assumed to be the
maximum amount consistent with the circumstances
of the poisoning.
C. Munchausen syndrome by proxy
1. Chemical child abuse should be suspected when
childhood poisonings are associated with an
insidious and/or inexplicable presentation (eg,
recurrent acidosis, polymicrobial sepsis, recurrent
malabsorption syndrome, factitious hypoglycemia,
failure to thrive).
2. The syndrome is referred to as “Munchausen
syndrome by proxy” when the abuse is perpe-
trated by a caretaker. Agents may include aspirin,
codeine, ethylene glycol, fecal material, insulin,
ipecac, laxatives, phenothiazines, table salt, and
vitamin A.
II. Physical examination
A. The first priority in a severely poisoned child is to
maintain an airway, ventilation, and circulation.
B. The vital signs, breath odors, skin, gastrointestinal,
cardiovascular, respiratory, and neurologic systems
should be assessed.

Physical Findings Associated with Specific Drugs

and Chemicals

Symptom Agents
or Sign

Fever Amphetamines, anticholinergics, antihista-

mines, aspirin, cocaine, iron, phencyclidine,
phenothiazines, thyroid, tricyclic antidepres-
sants

Hypother- Barbiturates, carbamazepine, ethanol,

mia isopropanol, narcotics, phenothiazines

Breath
odors: Naphthalene, paradichlorobenzene
Moth- Isopropanol, acetone, nail polish remover
balls Arsenic, organophosphates
Fruity Cyanide
Garlic N-3-pyridylmethyl-N-4-nitrophenylurea
Bitter (VACOR rat poison)
almond
Peanuts

Hyperten- Amphetamines, cocaine, ephedrine, ergotism,

sion norepinephrine, phenylpropanolamine, tricyclic
antidepressants (early)

Hypotensio Antihypertensives, arsenic, barbiturates,

n benzodiazepines, beta blockers, calcium chan-
nel blockers, carbon monoxide, cyanide,
disulfiram, iron, nitrites, opiates,
phenothiazines, tricyclic antidepressants (late)

Tachypnea Amphetamine, cocaine, carbon monoxide,

cyanide, iron, nicotine, phencyclidine, salicy-
lates

Hypoventila Alcohols, anesthetics, barbiturates,

tion benzodiazepines, botulism, chlorinated hydro-
carbons, cholinesterase-inhibiting pesticides,
cyclic antidepressants, narcotics, nicotine, par-
alytic shellfish poisoning, solvents, strychnine

Coma Alcohols, anticonvulsants, barbiturates,

benzodiazepines, carbon monoxide, chloral
hydrate, cyanide, cyclic antidepressants, hy-
drocarbons, hypoglycemics, insulin, lithium,
narcotics, phenothiazines, salicylates,
sedative-hypnotics, solvents

Seizures Amphetamines, camphor, carbon monoxide,

cocaine, gyromitra mushrooms, isoniazid, lead,
lindane, nicotine, pesticides, phencyclidine,
salicylates, strychnine, theophylline, tricyclic
antidepressants

Miosis Narcotics, organophosphates, phenothiazines,

phencyclidine

Mydriasis Amphetamine, anticholinergics, antihistamines,

atropine, cocaine, phenylpropanolamine,
tricyclic antidepressants

Nystagmus Phencyclidine, phenytoin

Peripheral Acrylamide, carbon disulfide, heavy metals

neuropathy
 C. Skin examination
1. Cyanosis suggests hypoxia secondary to aspira-
tion (eg, hydrocarbon) or asphyxia (eg, apnea
due to central nervous system depressants).
2. The adolescent substance abuser may have
needle tracks along veins or scars from subcuta-
neous injections. Urticaria suggests an allergic
reaction. Jaundice may signify hemolysis from
naphthalene mothballs.
D. Cardiovascular effects
1. Sympathetic stimulation can cause hypertension
with tachycardia.
2. Hypotension is caused by beta adrenergic block-
ade, calcium channel blockade, sympatholytic
agents, cellular toxins, psychopharmaceutical
agents, disulfiram-ethanol, and shock associated
with iron or arsenic.
E. Respiratory effects
1. Tachypnea and hyperpnea may result from
salicylate poisoning. Nervous system stimulants
may be associated with tachypnea. Cellular
poisons will increase the respiratory rate.
2. Central nervous system depressants may
depress the respiratory drive.
3. Apnea may be associated with toxins causing
weakness of respiratory muscles. The respiratory
examination may reveal poisoning-associated
wheezing (eg, beta-blocker overdose or inhal-
ants) or crackles (aspiration pneumonia, pulmo-
nary edema).
F. Neurologic examination
1. Depressed consciousness, confusion, delirium,
or coma may result from toxins, such as ethanol.
Central nervous system stimulants or neurotrans-
mitter antagonists produce seizures.
2. Pupils. Dilated pupils can be caused by sympa-
thetic stimulation (eg, amphetamine, cocaine).
Constricted pupils are caused by parasympa-
thetic stimulation (eg, organophosphate pesti-
cides) or sympathetic blockade (eg,
phenothiazines).
3. Sensorimotor examination may reveal periph-
eral anesthesia caused solvents, pesticides, or
acrylamide.
4. Neurologic signs of substance abuse
a. Ethanol, isopropyl alcohol, ethylene glycol,
or methanol can cause an alcoholic state of
intoxication. Amphetamine or cocaine often
cause agitation, euphoria, or paranoia. Lyser-
gic acid diethylamide (LSD), mescaline or
amphetamines can cause visual or auditory
hallucinations.
b. Benzodiazepines and narcotics (oxycodone)
can cause drowsiness, slurred speech, confu-
sion, or coma. Phencyclidine (PCP) causes
agitation, dissociative delusional thinking,
rhabdomyolysis, and rotatory nystagmus. Glue
or gasoline sniffing can result in exhilaration,
grandiose delusions, irrational behavior, and
sudden death from cardiac dysrhythmias.
III. Laboratory assessment
A. Toxic screens
1. The history and physical examination will usually
provide enough information to make a diagnosis
and begin therapy. Occasionally, toxin screening
of blood and/or urine can confirm the diagnosis.
2. A toxic screen of the blood and urine may include
assays for acetone, acetaminophen, amphet-
amines, anticonvulsants, antidepressants, anti-
histamines, benzodiazepines, ethanol,
isopropanol, methanol, narcotics, neuroleptics, or
phencyclidine.
B. Serum osmolarity
1. The osmolar gap is derived from the measured
serum osmolality minus the calculated serum
osmolality (2 x Na + BUN/2.8 + glucose/18).
When exogenous osmoles are present (eg,
ethanol, isopropyl alcohol, methanol, acetone, or
ethylene glycol), the osmolar gap will be ele-
vated.
2. Anion gap acidosis
a. Lactic acid (eg, in ethanol, isoniazid, iron
poisonings), ketoacids (eg, diabetes, ethanol),
or exogenous organic acids may cause a
metabolic acidosis.
b. Metabolic acidoses are classified as either
 increased anion gap ([Na+ K] - [Cl + HCO3])
above 15 mEq/L (ethylene glycol, iron,
isoniazid, methanol, or salicylate), or de-
pressed anion gap (lithium), or normal anion
gap (laxatives, colchicine).
C. Other frequently ordered tests
1. Hepatic and renal function should be monitored
because most toxins are detoxified in the liver
and/or excreted in the urine. Many poisonings
are accompanied by rhabdomyolysis (elevated
creatinine phosphokinase levels) from seizures,
hyperthermia, or muscle spasms.
2. Urine that fluoresces under Wood lamp exam-
ination is diagnostic of antifreeze poisoning.
3. Chest and abdominal radiographs may show
radiopacities from calcium tablets, chloral hy-
drate, foreign bodies, iodine tablets, phenothi-
azine and antidepressant tablets, and en-
teric-coated capsules.
4. Serial electrocardiograms are essential with
antiarrhythmic drugs, beta- blockers, calcium
channel blockers, lithium, phenothiazines,
theophylline, or tricyclic antidepressants.
IV. Diagnostic trials
A. For a few poisons, a “diagnostic trial” of an antidote
can implicate an agent as the cause of a poison-
ing.

Diagnostic Trials

Toxin Diagnostic Rou Positive Re-

Trial te sponse

Benzo- Flumazenil IV Consciousness im-

diazepine 0.02 mg/kg proves

Digitalis Specific Fab IV Dysrhythmia resolves,

antibodies hyperkalemia im-
proves,
consciousness im-
proves

Insulin Glucose 1 IV Consciousness im-

g/kg proves

Iron Deferoxamine IM Pink “vin rose” urine

40 mg/kg

Isoniazid Pyridoxine 5 g IV Seizures abate

Opiate Naloxone 0.1 IV Consciousness im-

mg/kg proves

Phenothi- Diphenhydra IV Dystonia and

azine mine 1 mg/kg torticollis resolve

V. Management
A. Poison centers can help with the diagnosis and
management of poisonings, and assist in locating
exotic antidotes.
B. Initial management of poisoning involves main-
taining an airway, providing ventilatory support,
securing vascular access, and initiating resuscita-
tion.
C. Decontamination
1. Skin, mucous membrane, or eye exposures
should be washed with a stream of lukewarm
water for 15 to 20 minutes. Soap is used to
decontaminate skin exposures.
2. Gastric lavage
a. Decontamination by lavage is preferred over
emesis in the emergency department be-
cause it is controllable. Contraindications
include nontoxic ingestions, ingestions in
which the substance is already past the stom-
ach or absorbed, and caustic or hydrocarbon
ingestions. It is most successful when per-
formed within 90 minutes of the ingestion. For
toxins associated with delayed gastric empty-
ing (eg, aspirin, iron, antidepressants,
antipsychotics) or for those that can form
concretions (eg, iron, salicylates), lavage may
be beneficial hours later.
b. A large-bore (24-32F) orogastric tube is
used, and 100- to 200-cc aliquots of warm,
normal saline are infused/withdrawn until no
more pill fragments are detectable in the
lavage fluid or until about 2 liters have been
exchanged.
c. Activated charcoal is effective for absorbing
 most drugs, but it is ineffective for alcohols,
caustics, cyanide, heavy metals, lithium, and
some pesticides.
d. Overdoses of carbamazepine, tricyclic antide-
pressants, and procainamide are managed
with multiple doses of charcoal. Contraindica-
tions to charcoal include a poisoning where
esophageal endoscopy is contemplated, one
in which the toxin is not adsorbed by charcoal,
or a poisoning in which the patient has an
ileus, gastrointestinal hemorrhage, or re-
peated retching.
3. Enhanced elimination
a. Multiple doses of charcoal also can enhance
elimination by “gastrointestinal dialysis.”
Repetitive doses of charcoal are recom-
mended for phenobarbital, salicylate, and
theophylline poisoning.
b. A cathartic, such as magnesium citrate, is
recommended when charcoal is used be-
cause charcoal is constipating. Hemodialysis
or hemoperfusion can be life-saving for se-
vere intoxications.
VI. Specific toxins
A. Acetaminophen (APAP)
1. Single overdoses of greater than 150 mg/kg can
cause liver failure. Nausea and abdominal pain
are common. The patient may vomit repeatedly,
be mildly lethargic, or remain asymptomatic. At
24 to 36 hours after the ingestion, abdominal
tenderness and rising serum transaminase
levels signify onset of hepatitis that peaks in
severity by 96 hours.
2. The Rumack nomogram predicts the likelihood
of hepatitis. The peak concentration is measured
4 hours after the ingestion; levels greater than
200 mcg/mL at 4 hours are associated with liver
toxicity.
3. When acetaminophen has been taken in high
dose, or when acetaminophen levels are in the
range likely to cause hepatotoxicity,
N-acetylcysteine (NAC) is given at a loading
dose of 140 mg/kg, followed by 17 doses of 70
mg/kg separated by 4-hour intervals.
4. Once NAC has been started because of one
toxic level, the full course should be given; there
is no need to get repeated APAP concentrations.
B. Alcohols
1. Alcohols include ethanol, ethylene glycol, metha-
nol, and isopropyl alcohol. Antifreeze contains
ethylene glycol, Sterno and windshield wiper
fluid contain methanol, jewelry cleaners and
rubbing alcohol contain isopropanol.
2. All of the alcohols cause inebriation, loss of
motor control and coma. Ethylene glycol may
cause acidosis, renal failure, and seizures.
Methanol may cause metabolic acidosis, sei-
zures, and blindness. Isopropyl alcohol can
produce gastritis, ketosis, and hypotension.
3. Concentrations of ethylene glycol or methanol
>20 mg/dL require the use of ethanol therapy to
block alcohol dehydrogenase conversion to the
toxic metabolites; hemodialysis is indicated for
concentrations >50 mg/dL. Isopropanol or etha-
nol intoxications usually require only close
monitoring with frequent measurements of
serum glucose. Respiratory depression, sei-
zures, and coma from ethanol poisoning and
levels >300-400 mg/dL require hemodialysis.
C. Caustics
1. Drain cleaners contain sodium hydroxide or
sulfuric acid; toilet cleaners may contain hydro-
chloric or sulfuric acids.
2. Laundry or dishwasher detergents may con-
tain sodium metasilicate or sodium triphosphate.
3. Signs of caustic ingestion include lip or tongue
swelling; burning pain; dysphagia; drooling; and
whitish or red plaques on the tongue, buccal or
palatal mucosa, or in the perioral area. Caustics
can cause severe burns to the esophagus or
stomach even in the absence of symptoms.
4. Inhalations are managed with humidified oxy-
gen. Skin exposures are washed carefully with
soap and water and then treated like any other
burn.
5. Strongly alkaline agents damage the upper
esophagus. Hydrochloric, sulfuric (muriatic),
 and other acids damage the lower esophagus
and stomach.
6. Treatment of caustic ingestions. The child
should be given nothing by mouth, and endo-
scopic evaluation should be performed 12 to 24
hours after the ingestion. Emesis, lavage and
charcoal are contraindicated.
D. Foreign body ingestion
1. Aspirated objects will cause symptoms of
choking, gasping, coughing, cyanosis, wheezing,
fever, and poor air entry. While chest radiogra-
phy can confirm the diagnosis, a negative film
does not rule out aspiration. A foreign body
requires immediate removal by bronchoscopy.
2. Ingestion of disc batteries requires removal
when lodged in the esophagus; those in the
stomach or beyond should be followed with
repeated abdominal films every 2 to 3 days to
ensure passage. Disc batteries that have re-
mained in one position for more than 7 days may
require surgical removal. Coins or other foreign
bodies past the esophagus can be managed
with serial radiographs and parental vigilance for
their passage.
E. Hydrocarbons
1. Aliphatic hydrocarbons include kerosene,
mineral oil, gasoline, and petrolatum. Kerosene
and gasoline are capable of causing an aspira-
tion pneumonia and CNS depression. Petrola-
tum, mineral oil and motor oil do not carry signifi-
cant risk of injury. Aliphatic hydrocarbons in
small doses are not harmful if left in the stom-
ach. Emesis is contraindicated because of the
risk of aspiration; decontamination should be
attempted only if a very large dose was taken.
2. Aromatic hydrocarbons, such as xylene or
toluene, are toxic. Aromatic hydrocarbon inges-
tions necessitate lavage.
3. Aspiration pneumonia is suggested by gasp-
ing, choking, coughing, chest pain, dyspnea,
cyanosis, leukocytosis, and fever. A chest radio-
graph may not be diagnostic until hours after
ingestion.
F. Iron
1. Iron is present in many children’s multivitamins,
although the worst cases of iron poisoning
usually involve prenatal vitamins, which contain
60 mg of elemental iron per tablet. Iron is a
metabolic poison and is corrosive to gastric
mucosa, resulting in shock.
2. Ferrous sulfate is 20% elemental iron, ferrous
fumarate 33%, and ferrous gluconate 11%. Little
toxicity is seen at a dose of elemental iron less
than 20 mg/kg. Mild symptoms of poisoning are
seen at doses of 20-60 mg/kg; moderate-to-
severe symptoms at doses of 60 to 100 mg/kg;
life-threatening symptoms at doses greater than
100 mg/kg; and a lethal dose is 180 to 300
mg/kg.
3. Early symptoms include nausea, vomiting,
fever, hemorrhagic diarrhea, tachycardia,
hypotension, hyperglycemia, and acidosis.
Intermediate symptoms (8 to 48 hours after
ingestion) may include obtundation, coma,
fulminant hepatitis, hypoglycemia, clotting abnor-
malities, pulmonary edema, and renal tubular
dysfunction.
4. Laboratory findings include a metabolic acido-
sis with a high anion gap, an abdominal radio-
graph showing radiopaque pills in the stomach,
an elevated white blood cell count greater than
15,000/mm3, and an elevated blood glucose
>150 mg/dL. A serum iron concentration, ob-
tained 4 hours after the ingestion, of less than
300 mcg/dL is not toxic; 300 to 500 mcg/dL is
mildly toxic; 500 to 1000 mcg/dL is moderately to
severely toxic; greater than 1000 mcg/dL is life-
threatening.
5. Treatment. Decontamination by lavage should
be initiated; charcoal is not effective. Volume
expansion with intravenous fluids, correction of
electrolyte/acid-base disturbances, and intrave-
nous deferoxamine are recommended.
G. Salicylates
1. Aspirin overdoses greater than 150 mg/kg are
toxic. Salicylates are locally corrosive, and
tablets can form bezoars near the gastric outlet.
 Salicylates stimulate the central respiratory
center, so that the metabolic acidosis is compen-
sated by a respiratory alkalosis.
2. Early symptoms of toxicity include gastrointesti-
nal pain, nausea, vomiting, tinnitus, confusion,
lethargy, and fever. Respirations often are rapid
and deep. Severe poisonings can be associated
with seizures, coma, and respiratory and cardio-
vascular failure.
3. Laboratory findings include hypocalcemia,
hypomagnesemia, h yp okalemia, and
hyperglycemia (early) or hypoglycemia (late).
4. Serum aspirin concentration obtained 2 and 6
hours after the ingestion higher than 30 mg/dL
are considered toxic, those greater than 70
mg/dL are associated with severe symptoms,
and those greater than 100 mg/dL are life-threat-
ening.
5. Management includes lavage, which may be
effective as long as 4 to 6 hours after the inges-
tion. Multiple-dose activated charcoal is effec-
tive. Correction of acidemia, hypokalemia, and
hypocalcemia are important. Hemodialysis is
indicated for serum concentrations greater than
100 mg/dL.
References, see page 182.
Developmental Pediatrics

Infant Growth and Development

Infancy consists of the period from birth to about two years
of age. Advances occur in physical growth, motor develop-
ment, cognitive development, and psychosocial develop-
ment.

I. Physical growth milestones

A. Birth weight is regained by 2 weeks of age and
doubles by 5 months. During the first few months of
life, this rapid growth continues, after which the
growth rate decelerates.

Average Physical Growth Parameters

Age Head cir- Height Weight Dentition

cumference

Birth 35.0 cm 50.8 cm 3.0 to 3.5 Central

(13.8 in) (20.0 kg incisor
+2 cm/mo (0 in) (6.6 to s--6
to 3 mo) 7.7 lb) mo
+1 cm/mo (3 Regains Lateral
to 6 mo) birthw incisor
+0.5 cm/mo eight s--8
(6 to 12 by 2 mo
mo) wk
Mean = 1 Doubles
cm/mo birthw
eight
by 5
mo

1 year 47.0 cm 76.2 cm 10.0 kg First

(18.5 in) (30.0 (22 lb) molar
in) Triples s--14
birth- mo
weight Canines--
19 mo

2 49.0 cm 88.9 cm 12.0 to Second

years (19.3 in) (35.0 12.5 molar
in) kg s--24
(26.4 mo
to 27.5
lb)
Quadru-
ples
birthwe
ight

B. Occipitofrontal circumference
1. Microcephaly is associated with an increased
incidence of mental retardation, but there is no
direct relationship between small head size and
decreased intelligence. Microcephaly associated
with genetic or acquired disorders usually has
cognitive implications.
2. Macrocephaly may be caused by hydrocepha-
lus, which is associated with learning disabilities.
Macrocephaly without hydrocephalus is associ-
ated with cognitive deficits caused by metabolic
or anatomic abnormalities. Fifty percent of cases
of macrocephaly are familial and have no effect
on intellect. When evaluating the infant with
macrocephaly, the finding of a large head size in
one or both parents is reassuring.
C. Height and weight
1. Although the majority of individuals who are of
below- or above-average size are otherwise
normal, there is an increased prevalence of
developmental disabilities in these two groups.
2. Many genetic syndromes are associated with
short stature; large stature syndromes are less
common. When considering deviation from the
norm, short stature in the family is reassuring.
D. Dysmorphism. Most isolated minor dysmorphic
features are inconsequential; however, the pres-
ence of three or more indicative of developmental
dysfunction. Seventy-five percent of minor superfi-
cial dysmorphisms can be found by examining the
face, skin, and hands.
II. Motor development milestones
A. Motor milestones are ascertained from the develop-
mental history and observation. Gross motor devel-
opment begins with holding head up, rolling and
 progresses to sitting, and then standing, and ambu-
lating.
B. Fine motor development
1. In the first year of life, the pincer grasp develops.
During the second year of life, the infant learns to
use objects as tools during play.
2. Reaching becomes more accurate, and objects
are initially brought to the mouth for oral explora-
tion. As the pincer grasp and macular vision
improve, precise manual exploration replaces
oral exploration.
C. Red flags in motor development
1. Persistent listing to one side at 3 months of age
often is the earliest indication of neuromotor
dysfunction.
2. Spontaneous frog-legs posturing suggests
hypotonia/weakness, and scissoring suggests
spastic hypertonus. Early rolling (1 to 2 months),
pulling directly to a stand at 4 months (instead of
to a sit), W-sitting, bunny hopping, and persistent
toe walking may indicate spasticity.
3. Hand dominance prior to 18 months of age
should prompt the clinician to examine the
contralateral upper extremity for weakness
associated with a hemiparesis.
III. Cognitive development milestones
A. Language is the single best indicator of intellectual
potential; problem-solving skills are the next best
measure. Gross motor skills correlate least with
cognitive potential; most infants with mental retarda-
tion walk on time.
B. Problem-solving skills
1. The 1-year-old child recognizes objects and
associates them with their functions. Thus, he
begins to use them functionally as “tools” instead
of mouthing, banging, and throwing them.
2. Midway through the second year, the child begins
to label objects and actions and categorize them,
allowing the child to match objects that are the
same and later to match an object to its picture.
3. Object permanence
a. Prior to the infant’s mastery of object perma-
nence, a person or object that is “out of sight”
is “out of mind,” and its disappearance does
not evoke a reaction.
b. The child will progress to finding an object that
has been hidden under a cloth.
c. The next skill in this sequence is the ability to
locate an object under double layers (eg, a
cube is placed under a cup and then the cup
is covered with a cloth).
4. Causality. Initially, the infant accidentally discov-
ers that his actions produce a certain effect. The
infant then learns that actions cause consistent
effects.
C. Language development
1. Receptive language skills reflect the ability to
understand language. Expressive language skills
reflect the ability to make thoughts, ideas, and
desires known to others.
2. Prespeech period (0 to 10 months). Receptive
language is characterized by an increasing ability
to localize sounds, such as a bell. Expressive
language consists of cooing. At 3 months, the
infant will begin vocalizing after hearing an adult
speak. At 6 months of age, the infant adds con-
sonants to the vowel sounds in a repetitive
fashion (babbling). When a random vocalization
(eg, “dada”) is interpreted by the parents as a
real word, the parent will show pleasure and joy.
In so doing, parents reinforce the repeated use of
these sounds.
3. Naming period (10 to 18 months). The infant’s
realizes that people have names and objects
have labels. The infant begins to use the words
“dada” and “mama” appropriately. Infants next
recognize and understand their own names and
the meaning of “no.” By 12 months of age, some
infants understand as many as 100 words. They
can follow a simple command as long as the
speaker uses a gesture. Early in the second year,
a gesture no longer is needed.
4. The infant will say at least one “real” word (ie,
other than mama, dada) before his first birthday.
At this time, the infant also will begin to verbalize
with sentence-like intonation and rhythm (imma-
ture jargoning). As expressive vocabulary in-
 creases, real words are added (mature
jargoning). By 18 months, the infant will use
about 25 words.
5. Word combination period (18 to 24 months).
Children begin to combine words 6 to 8 months
after they say their first word. Early word combi-
nations are “telegraphic” (eg, “Go out”). A
stranger should be able to understand at least
50% of the infant’s speech.
D. Red flags in cognitive development
1. Language development provides an estimate of
verbal intelligence; problem-solving provides an
estimate of nonverbal intelligence. If deficiencies
are global (ie, skills are delayed in both do-
mains), there is a possibility of mental retarda-
tion.
2. When a discrepancy exists between problem-
solving and language abilities, with only language
being deficient, the possibility of a hearing impair-
ment or a communication disorder should be
excluded. If either language or problem-solving
skills is deficient, the child is at high risk for a
learning disability later.
3. All children who have delayed language develop-
ment should receive audiologic testing to rule out
hearing loss. Deaf infants will begin to babble on
time at 6 months, but these vocalizations will
gradually decline thereafter.
IV. Psychosocial development
A. Emotional development. Emotions are present in
infancy and motivate expression (pain elicits crying).
B. Social development
1. Social milestones begin with bonding, which
reflects the feeling of the caregiver for the child.
Attachment represents the feeling of the infant for
the caregiver, and it develops within a few
months.
2. When recognition of and attachment to a care-
giver develops, the simple sight of this person will
elicit a smile. The infant becomes more discrimi-
nating in producing a smile as he begins to
differentiate between familiar and unfamiliar
faces. The infant learns to use smiling to manipu-
late the environment and satisfy personal needs.
3. Temperament represents the style of a child’s
emotional and behavioral response to situations.
C. Adaptive skill development. Adaptive skills consist
of the skills required for independence in feeding,
dressing, toileting, and other activities of daily living.
Development of adaptive skill is influenced by the
infant’s social environment, and by motor and cog-
nitive skill attainment.
D. Red flags in psychosocial development
1. Colic may be an early indication of a “difficult”
temperament.
2. Delay in the appearance of a smile suggests
an attachment problem, which may be associ-
ated with maternal depression. In severe cases,
child neglect or abuse may be suspected.
3. Failure to develop social relationships sug-
gests autism when it is accompanied by delayed
or deviant language development and stereotypic
behaviors.
4. Delays in adaptive skills may indicate overpro-
tective parents or an excessive emphasis on
orderliness.
References, see page 182.

Toddler Development
Toddlerhood consists of the years from about 1 to 3 years
of age. Affective development is highlighted by the tod-
dler’s striving for autonomy and independence, attachment
to family, and the development of impulse control. Cogni-
tive development is characterized by the transition from
sensorimotor to preoperational thought.

I. Growth rate and physical appearance

A. After the rapid growth of infancy, the rate of growth
slows in the toddler years. After age 2, toddlers gain
about 5 lb in weight and 2.5 inches in height each
year. Growth often occurs in spurts. Between the
ages of 2 and 2.5 years, the child will have reached
50% of his adult height.
B. Growth of the lower extremities often is accompa-
 nied by tibial torsion and physiologic bowing of the
legs, which usually corrects by age 3 years. The
percentage of body fat steadily decreases from 22%
at age 1 year to about 15% at age 5 years.
II. Gross motor skills
A. Most children walk without assistance by 18 months.
At 2 years, the stiff, wide-leg gait of early
toddlerhood becomes a flexible, steady walking
pattern, with heel-toe progression.

Gross Motor Abilities

18 Months

• Walking fast, seldom falling

• Running stiffly
• Walking up stairs with one hand held
• Seating self in a small chair
• Climbing into an adult chair
• Hurling a ball

24 Months

• Running well without falling

• Walking up and down stairs alone
• Kicking a large ball

36 Months

• Walking up stairs by alternating feet

• Walking well on toes
• Pedaling a tricycle
• Jumping from a step
• Hopping two or three times

III. Fine motor skills

A. The 18-month-old can make a tower of four
blocks. One year later, he can stack eight blocks.
Most 18-month-olds will hold the crayon in a fist
and scribble spontaneously on paper.

Fine Motor Abilities

18 Months

• Making a tower of four cubes

• Releasing 10 cubes into a cup
• Scribbling spontaneously
• Imitating a vertically drawn line

24 Months

• Building a seven cube tower

• Aligning two or more cubes to form a train
• Imitating a horizontally drawn line
• Beginning circular strokes
• Inserting a square block into a square hole

36 Months

• Copying a circle
• Copying bridges with cubes
• Building a tower of 9 to 10 blocks
• Drawing a person’s head

IV. Affective development

A. Autonomy and independence. Because of im-
proved motor skills, the transition from infancy to
toddlerhood is marked increased autonomy and
independence. The toddler may refuse to eat
unless allowed to feed himself, and the child may
no longer may be willing to try new foods.
B. Impulse control. Toddlers begin to develop im-
pulse control. The 18-month-old may have minimal
impulse control and display several temper tan-
trums each day. Most 3-year-olds have some
degree of self-control.
C. Successful toileting usually occurs toward the end
of the third year when the child becomes able to
control his sphincter, undress, get onto the potty,
and has the willingness to participate. Success with
consistent daytime dryness usually is not achieved
until about 2.5 to 3 years of age.
 Social/Emotional Skills

18 Months

• Removing a garment
• Feeding self and spilling food
• Hugging a doll
• Pulling a toy

24 Months

• Using a spoon; spilling little food

• Verbalizing toileting needs
• Pulling on a simple garment
• Verbalizing immediate experiences
• Referring to self by name

36 Months

• Showing concern about the actions of others

• Playing cooperatively in small groups
• Developing the beginnings of true friendships
• Playing with imaginary friends

D. Attachment refers to the bond that forms between

the infant and the caregiver. Disorders of attach-
ment may result from inconsistent caregiving and
are more common in the presence of poverty, drug
use, or emotional illness.
E. Temperament determines how a child approaches
a given situation. Ten percent of children are less
adaptable and tend to be emotionally negative and
are considered “difficult.”
V. Cognitive development
A. Toddlerhood is characterized by a transition from
sensorimotor to preoperational thinking.
Preoperational thought is marked by the develop-
ment of symbolic thinking, as the child becomes
capable of forming mental images and begins to
solve problems. Progression from sensorimotor to
symbolic thought occurs typically between 18 and 24
months of age.
B. Complete object permanence has developed, and
the child can find an object under a blanket, despite
not seeing it hidden.
C. By 3 years, he can draw primitive figures that repre-
sent people, and he develops elaborate play and
imagination.

Intellectual Abilities

18 Months

• Pointing to named body parts

• Understanding of object permanence
• Beginning to understand cause and effect

24 Months

• Forming mental images of objects

• Solving problems by trial and error
• Understanding simple time concepts

36 Months

• Asking “why” questions

• Understanding daily routine
• Appreciating special events, such as birthdays
• Remembering and reciting nursery rhymes
• Repeating three digits

VI. Language
A. Beginning around age 2 years, toddlers use lan-
guage to convey their thoughts and needs (eg,
hunger). The 18-month-old has a vocabulary of at
least 20 words, consisting primarily of the names of
caregivers, favorite foods, and activities.
B. After 18 months, the toddler begins to put together
phrases. Early two and three word sentences are
referred to as “telegraphic speech,” and about 50%
of what the child says should be intelligible to
strangers.
C. By the age of 3 years, the vocabulary increases to
about 500 words, and 75% of speech is understand-
able to strangers. He begins to make complete
sentences, and frequently asks “why” questions.

Language Skills
 18 Months

• Looking selectively at a book

• Using 10 to 20 words
• Naming and pointing to one picture card
• Naming an object (eg, ball)
• Following two-directional commands

24 Months

• Using two to three word sentences

• Using “I,” “me,” “you”
• Naming three picture cards
• Naming two objects
• Knowing four-directional commands

36 Months

• Using four to five word sentences

• Telling stories
• Using plurals
• Recognizing and naming most common objects

References, see page 182.

Preschooler Development
I. Family relationships
A. Separation. The average 3-year-old child can
separate easily from parents. Some children cope by
adopting a transitional object, usually a soft object,
which serves as a symbolic reminder of the parent.
B. Fears and fantasies. Early fantasy, may be indistin-
guishable from reality, resulting in a tendency for
fears. By the age of 4, children frequently have
frightening dreams that they can state are “not real.”
C. Temper tantrums are characteristic of 2-year-olds,
but they should be infrequent by age 5, although
there is another peak at 6 years in response to the
stresses of schooling.
D. Oppositionality. Preschool children comply with
adult requests about 50% of the time. Parents who
are authoritative and firm but also warm, encourag-
ing, and rational are more likely to have children who
are self-reliant and self-controlled. A system of
discipline should include positive reinforcement for
desired behaviors; consequences for undesired
behaviors; and interactions that promote the parent-
child relationship.
E. Sibling interactions
1. Factors associated with greater sibling rivalry,
include opposite gender, difficult temperament,
insecure pattern of attachment, family discord,
and corporal punishment. Preschool children
often “regress” when a new baby is born, exhibit-
ing increased naughtiness, thumb sucking, and
altered toileting.
2. Sibling classes, avoidance of forced interactions,
a strong relationship between the older child and
the father, good support for the mother, individual
time with each parent, and talking about the new
baby are helpful.
II. Peer relationships
A. Play
1. At the age of 2 years, most play is parallel. By the
age of 3, children should have mastered aggres-
sion and should be able to initiate play with a
peer, have joint goals in their play together, and
take turns. Fantasy or pretend play gains promi-
nence at about age 3.
2. Pretend friends are very common in children up to
the age of 4. Mastery of aggressive impulses
should improve after 2 1/2 years of age.
Peer Relationships

2-year 3-year 4-year 5-year

visit visit visit visit

Amount Parallel Takes on Interac- Group of

of inter- play with a role, tive friends
action peers, prefers games,
copies some best
others, friends friend <2
self-talk, over oth- y differ-
solitary ers, plays ence,
play, of- associa- may visit
fers toy, tively with neighbor
plays others by self,
games plays
coopera-
tively with
others

Duration Briefly 20 min Prefers

of inter- alone with peer play
action from peers to solitary
adult,
sudden
shifts in
intensity
of activity

Level of Symbolic Simple Elaborate Make-

fantasy doll, ac- fantasy fantasy believe
tion fig- play; un- play, dis- and dress
ures; familiar tinguishe up
mimics may be s fantasy
domestic monsters from real-
activities ity, tells
fanciful
tales

Imaginary May have Common If pres-

friends one ent, pri-
vate

Favorite Things Listens to Sings a

toys/activi that stories, song,
ties move, dresses dances,
turn, or fit and acts, lis-
together; undress- tens to
water; es dolls stories
books;
music;
listens to
stories

Rule use Able to Shares Shares Follows

take some sponta- rules of
turns, neously, the
beginning follows game,
property rules in follows
rights, simple commu-
“mine,” games, nity rules
“right facility
places” with
rules,
alter-
nately
demand-
ing/coope
rative

Aggres- Aggres- Negoti- Wants to

sion sive to ates con- please
get things flicts friends

Development of Independence

2-year 3-year 4-year 5-year

visit visit visit visit

Eating Uses Spills Helps set Helps

utensils little, table cook
pours
some

Dressing Un- Dresses Dresses

dresses, with su- all but
pulls on pervision, tying
simple unbut-
garment tons
some

Toileting Clean Clean Inde-

and dry, and dry pendent
but with by self-
adult ef- motivated
fort and approach
motiva-
tion
 Motor and Cognitive Play Skills

2-year 3-year 4-year visit 5-year visit

visit visit

Pencil Point Awk- Standard

grip down ward,
high

Drawings
Identi- Vertical, Shapes Longer line Directions
fies scribble Hori-
Imi- zontal,
tates cross Cross be- Square
Circle fore square before tri-
Copies before 6 parts angle
cross 10, includ-
2 parts ing head,
Perso body, arms,
n-body legs
parts

Scissors One Across Cuts out

hand paper square

Block 6-9 Tower

tower of 10

Block Aligns 4 3 block 5 block Steps

figure for train bridge gate

Other Turns Ties knot in

pages 1 string,
at a prints let-
time ters

III. Communication
A. The 2-year-old has a vocabulary of approximately
150 to 500 words. The child should be speaking in
two-word utterances (eg, “My Mommy” or “More
Milk”). They often mimic what others say (echolalia)
up to age 2.5 years. Criterion for referral at 2 years
of age is a less than a 50-word vocabulary or not
putting two words together.
B. The 3-year-old speaks in simple sentences of three
or four words. Sentence length increases by one or
two words annually throughout the preschool
period, with at least the same number of words that
the child is old. The typical 3-year-old can count
three items, and a 4-year-old can count four items.
A 4-year-old who cannot converse with familiar
people with sentences averaging three words
should be evaluated.
C. A 5-year-old should use complete sentences
containing five words. The 5-year-old can count ten
objects or more and should understand “before,”
“after,” and “until”; “if, then.” They can discuss
emotions and tell jokes. Preschool children who
have expressive language disorders tend to speak
less often and convey less information than their
peers.
D. Strangers should be able to understand 25% to
50% of what the 2-year-old child says. By 3 years
of age, strangers should be able to understand the
child 75% of the time. By the age of 4, strangers
can understand the child 100% of the time, al-
though errors in “r,” “s,” “l,” “sh,” and “th” sounds
are not uncommon until age 7.
E. Dysfluency (aberration of speech rate and rhythm)
occurs transiently between about 2.5 and 4 years
of age. Persistent and worsening stuttering beyond
the age of 4 should be evaluated.

Communication Skills in Preschoolers

2-year 3-year 4-year 5-year

visit visit visit visit

Vocabu- No jargon; Defini-

lary 150 to tions
500 words

Sentence 2 words 3 to 4 4 to 5
length words words

Intelligi- 25% 75% 100%

bility to
stranger
 2-year 3-year 4-year 5-year
visit visit visit visit

Grammat Verbs, Plurals, Past Future

ic forms some ad- pro- tense tense
jectives nouns
and ad-
verbs

Typical Talks Tells Describes Counts to

examples about cur- own recent 10 or
rent ac- age and experi- more,
tion, no sex, ences, recog-
jargon, counts can sing nizes
names to 3 songs, letters of
pictures gives first the al-
and last phabet,
names, knows
counts to tele-
4, identi- phone
fies gen- number
der and ad-
dress

Fluency Dysfluenc Dysflue Some Dysfluen

y common ncy dysfluenc cies not
com- y expected
mon

Comprehension

2-year 3-year 4-year 5-year

visit visit visit visit

Number 100% for 2 3

step com- 1 without
mand gesture

Number Names 1,
of body identifies
parts 7

Number 2 4 named
of colors named

Gender Self Self and

others

Own Refers to First

names self by and last
name

Numbers Says “2" Counts 10,

counted (not to 3 knows
counted) number

Relation- Which Which is

ships is big- longer, 2
ger, opposites
under

Motor development

2-year 3-year 4-year 5-year

visit visit visit visit

Walks Slightly Swings Tandem

forward bent arms walks

Walks 10 ft Tandem
backward

Runs Changing Alter-

direction nating
arms

Climbs Out of crib High

(2.5 y) equip-
ment

Jumps Both feet 26 to 30 32 in, one Over 10

off floor in from foot leads in
both
feet

Jumps Step with 16 in, 18 in,

down both feet lands lands on
on one both feet
foot first

Stairs-up One step Without

at a time rail, al-
ternatin
g
 2-year 3-year 4-year 5-year
visit visit visit visit

Stairs- One step Alter- Alternat-

down at a time nating, ing
no rail

Stands Tries 1 sec 5 to 6 sec 10 sec

on one on 1 on each
foot foot foot

Kicks kicks ball

6 ft

Hops 3 hops 5 forward 20 ft for-

in place ward 10
times

Throws Throws 5 Bounce 10 ft, 1 or

ft , over- 2 arms
hand

Catches Straight Bent arm Bounce

arms pass

Skips Skips

Pedals 10 ft,
tricycle

References, see page 182.

School-Age Child Development

Middle childhood consists of years six through twelve. This
period is characterized by the ability to consider several
factors, evaluate oneself and perceive the opinions of
others. Self-esteem is essential to the development of the
school-aged child. Healthy development requires increas-
ing separation from parents and the ability to find accep-
tance in the peer group and to meet challenges outside
the home.

I. Physical development
A. Growth during the period averages 3-3.5 kg (7 lb)
and 6 cm (2.5 in) per year. Growth occurs in irregu-
lar spurts lasting on average 8 wk, three to six times
per year. The head grows only 2-3 cm in circumfer-
ence.
B. Loss of deciduous (baby) teeth begins at about age
6 years of age.
C. Muscular strength, coordination, and stamina in-
crease progressively, as does the ability to perform
complex movements such as dancing, shooting
basketballs, or playing the piano.
D. The sexual organs remain physically immature, but
interest in gender differences and sexual behavior
remains of interest to many children. Masturbation is
common.
II. Cognitive and language development
A. School-aged children increasingly apply rules,
consider multiple points of view, and interpret their
perceptions in view of realistic principles.
B. By third grade, children need to be able to sustain
attention through a 45-min period. The first 2 years
of elementary school are devoted to acquiring the
fundamentals of reading, writing, and basic mathe-
matics. By third or fourth grade, children use those
fundamentals to learn increasingly complex materi-
als.
C. Factors that determine classroom performance
include eagerness to please adults, cooperative-
ness, competitiveness, willingness to work for a
delayed reward, self-confidence, and ability to risk
trying.
D. Beginning in third or fourth grade, children increas-
ingly enjoy strategy games and word play (puns and
insults) that exercise growing cognitive and linguistic
mastery.
 Perceptual, Cognitive, and Language Processes
Required for Elementary School Success

Process Description Associated Problems

Perceptual

Visual analy- Ability to break a Persistent letter confusion

sis complex figure (eg, between b, d, and g);
into components difficulty with basic reading
and understand and writing
their spatial rela-
tionships

Proprioceptio Ability to sense Poor handwriting, requiring

n and motor body position by excessive effort
control feel and uncon-
sciously program
complex move-
ments

Phonologic Ability to perceive Delayed receptive lan-

processing differences be- guage skills; attention and
tween similar behavior problems caused
sounding words by not understanding direc-
and to break tion
down words into
sounds

Cognitive

Long-term Ability to acquire Delayed mastery of the

memory "automatic" skills alphabet (reading and writ-
ing letters); slow handwrit-
ing; inability to progress
beyond basic mathematics

Selective Ability to listen Difficulty following multistep

attention and ignore dis- instructions, completing
tractions assignments, and behaving
well

Sequencing Ability to remem- Difficulty organizing assign-

ber things in or- ments, planning, spelling,
der; ability to un- and telling time
derstand time

Language

Receptive Ability to compre- Difficulty following direc-

language hend complex tions; wandering attention;
constructions, problems with reading
function words comprehension; problems
(eg, if, when, with peer relationships
only, except),
nuances of
speech, and long
blocks of lan-
guage (eg, para-
graphs)

Expressive Ability to recall Difficulty expressing feel-

language required words ings and using words for
effortlessly (word self-defense, with resulting
finding), to con- frustration and physical
trol meanings by acting out; struggling dur-
varying position ing "circle time" and with
and word end- language skills.
ings, to construct
meaningful para-
graphs and sto-
ries

III. Social and emotional development

A. School-aged children identify with same-sex par-
ents, adopting them as role models. The parents’
moral judgments are internalized as the superego.
School-aged children display decreased emotional
lability toward parents and an increasing involve-
ment in relationships outside of the home.
B. Social and emotional development proceeds in
three contexts: the home, the school, and the
neighborhood. The home is the most influential.
Milestones of a school child’s increasing independ-
ence include the first sleepover at a friend’s house
and the first time at overnight camp.
C. Parents should make demands for effort in school
and extracurricular activities, celebrate successes,
and offer unconditional acceptance when failures
occur. Regular chores provide an opportunity for
children to contribute to the family, supporting self-
esteem. Siblings have critical roles as competitors,
loyal supporters, and role models. Sibling relation-
ships influence self-image, approach to conflict
resolution and interests.
D. The beginning of school coincides with a child’s
 further separation from the family and the increas-
ing importance of teacher and peer relationships. In
addition to friendships that may persist for months
or years, experience with a large number of superfi-
cial friendships and antagonisms contributes to a
child’s growing social competence. Popularity, an
important part of self-esteem, may be won through
possessions (having the right toys) as well as
through personal attractiveness, accomplishments,
and social skills.
E. Conformity is rewarded in school-aged children.
Some children conform readily and enjoy easy
social success; those who adopt individualistic
styles or have visible differences may be stigma-
tized.
F. Dangers such as busy streets, bullies, and strang-
ers tax school-aged children’s common sense and
resourcefulness. Interactions with peers call on
increasing conflict resolution or pugilistic skills.
Children may feel powerlessness in the world, and
compensatory fantasies of being powerful may lead
to a fascination with superheroes.
References, see page 182.

Attention-Deficit/Hyperactivity Dis-
order
Attention-deficit/hyperactivity disorder (AD/HD) is a
condition that appears in early childhood with symptoms of
inattention, hyperactivity, and impulsivity. The symptoms
affect cognitive, academic, behavioral, emotional, and
social functioning, and persist into adulthood in 70% of
cases. The prevalence of AD/HD between 8 and 10% in
school-aged children. AD/HD occurs two to four times
more commonly among boys than girls.

I. Clinical features. AD/HD is comprised of three catego-

ries of symptoms: hyperactivity, impulsivity, and inatten-
tion.
A. Core symptoms
1. Hyperactivity
a. Hyperactive behavior is identified through
excessive fidgetiness or talking, difficulty
remaining seated, difficulty playing quietly, and
frequent restlessness or seeming to be always
“on the go.”
b. The hyperactive symptoms typically are ob-
served by the time the child reaches four
years of age and increase during the next
three to four years. They peak in severity
when the child is seven to eight years of age,
after which they begin to steadily decline. By
the adolescent years, the hyperactive symp-
toms are barely discernible.
2. Impulsivity
a. Impulsive behavior, which almost always
occurs in conjunction with hyperactivity in
younger children, is manifested by difficulty
waiting turns, blurting out answers, disruptive
classroom behavior, intruding or interrupting
other’s activities, and unintentional injury.
b. The impulsive symptoms typically are ob-
served by the time the child is four years of
age and increase during the next three to four
years to peak in severity when the child is
seven to eight years of age. In contrast to
hyperactive symptoms, impulsive symptoms
usually remain a problem throughout the life of
the individual.
3. Inattention
a. Inattention may include forgetfulness, being
easily distracted, losing or misplacing things,
disorganization, academic underachievement,
poor follow-through with assignments or tasks,
poor concentration, and poor attention to
detail.
b. Inattention typically is not apparent until the
child is eight to nine years of age. Similar to
the pattern of impulsivity, symptoms of inatten-
tion usually are a lifelong problem.
 B. Diagnostic criteria

DSM-IV Diagnostic Criteria for Attention-Defi-

cit/Hyperactivity Disorder

At least six of the following symptoms of inattention or

hyperactivity-impulsivity must be evident:

Inattention
Lack of attention to details or careless mistakes in school-
work or other activities
Difficulty sustaining attention in tasks or play activities
Impression of not listening when spoken to directly
Failure to follow through on instructions or finish school-
work or duties
Difficulty organizing tasks and activities
Avoidance or dislike of tasks that require sustained mental
effort (eg, school
work or homework)
Tendency to lose things necessary for tasks or activities
(eg, toys, school
assignments, pencils, books)
Distractions by extraneous stimuli
Forgetfulness in daily activities

Hyperactivity
Fidgeting with hands or feet or squirming in seat
Not remaining seated when expected
Running about or climbing excessively
Difficulty engaging in leisure activities quietly
Often “on the go” or “driven by a motor”
Excessive talking

And/Or

Impulsivity
Tendency to blurt out answers before questions have
been completed
Difficulty awaiting turn
Tendency to interrupt or intrude on others (eg, butting into
conversations or
games)

Exclusionary Criteria
A. Some hyperactive-impulsive or inattentive symptoms that
caused impairment must have been present before age 7.
B. Some impairment from the symptoms must be present in
two or more settings (eg, at school and at home).
C. There must be clear evidence of clinically significant im-
pairment in social, academic or occupational functioning.
D. The symptoms do not occur exclusively during the course
of a pervasive developmental disorder, schizophrenia, or
other psychotic disorder, and are not better accounted for
by another mental disorder.

1. The symptoms must be present in more than one

setting (eg, school and home).
2. The symptoms must persist for at least six
months.
3. The symptoms must be present before the age of
seven years.
C. Classification. Three subtypes of AD/HD have
been identified:
1. The predominantly inattentive type.
2. The predominantly hyperactive-impulsive type.
3. The combined type.
4. Predominantly inattentive. Children with the
predominantly inattentive type of AD/HD (AD/HD-
I) usually are diagnosed at 9 to 10 years of age,
the age at which symptoms of inattention become
noticeable.
5. Predominantly hyperactive-impulsive. Children
with the predominantly hyperactive-impulsive type
of AD/HD (AD/HD-HI) usually are diagnosed at
six to seven years of age, as symptoms of hyper-
activity and impulsivity peak.
6. Combined type of AD/HD (AD/HD-C) usually is
diagnosed at six to seven years of age, as symp-
toms of hyperactivity and impulsivity peak.
II. Differential diagnosis
A. The symptoms of AD/HD overlap with those of
learning disabilities and behavioral and emotional
problems, such as depression, anxiety, or post
traumatic stress disorder. These disorders fre-
quently coexist with AD/HD.
B. Other conditions to consider in children with symp-
toms of inattention, hyperactivity, and impulsivity
include mental retardation, fragile X syndrome,
stressful home environment, inappropriate educa-
tional setting, hearing or visual impairment, diabe-
tes mellitus, asthma, fetal alcohol syndrome, sleep
disorder, and seizure disorder.
III. Clinical evaluation
A. The medical history should include prenatal expo-
sures (eg, drugs, alcohol), perinatal complications
or infections, central nervous system infection,
head trauma, recurrent otitis media, and medica-
tions. Family history of similar behaviors is impor-
tant because the heritability of AD/HD is 80%.
B. Developmental history should include the onset and
course of AD/HD symptoms and psychological,
medical, and developmental events. Developmental
milestones, particularly language milestones,
school absences, and psychosocial stressors,
should be obtained. Parent-child interactions
should be observed.
C. The examination should include height, weight,
head circumference, and vital signs. Dysmorphic
and neurocutaneous findings should be noted. A
neurologic examination should be performed. The
child’s behavior in the office setting should be
observed, although symptoms of AD/HD may not
be apparent in the clinic setting.
D. Family assessment should determine the age of
onset of the symptoms, the duration of symptoms,
the settings in which the symptoms occur, and the
degree of functional impairment.
E. School assessment should document the core
symptoms, with an AD/HD-specific behavior check-
list and a narrative summary of classroom behavior
and interventions, learning patterns, and functional
impairment. Copies of report cards and samples of
school work should be obtained.
F. Rating scales should be completed by parents and
teachers for diagnosis, during medication titration,
and at regular medication follow-up visits.
G. Comorbid disorders. One-third of children with
AD/HD have one or more comorbid conditions,
including oppositional defiant disorder, conduct
disorder, depression, anxiety disorder, and learning
disabilities.
H. Oppositional defiant disorder (ODD) coexists
with AD/HD in 35% of cases.
I. Conduct disorder coexists with AD/HD in 26% of
cases. DSM-IV criteria for conduct disorder include
a repetitive and persistent pattern of behavior in
which the basic rights of others or major age-
appropriate societal norms or rules are violated.
J. Anxiety disorder coexists with AD/HD in 26% of
cases and is more common occurrence in children
with the inattentive type of AD/HD.
K. Depression coexists with AD/HD in 18% of cases
and occurs more commonly in the inattentive and
combined types.
L. Learning disability coexists with AD/HD range
from 20 to 60%.
M. Psychometric testing is not necessary for the
routine diagnosis of AD/HD and does not distin-
guish children with and without AD/HD. Nonethe-
less, psychometric testing is valuable in narrowing
the differential diagnosis because the core symp-
toms of AD/HD can be related to delayed process-
ing skills, language disorders, and learning disabili-
ties.
IV. Treatment of attention-deficit/hyperactivity disor-
der in children
A. Stimulant medications. Methylphenidate and
dextroamphetamine are the stimulants most
commonly used to treat AD/HD in children. These
drugs have similar efficacy and have mild, usually
reversible adverse effects.
1. Stimulant drugs affect the dopaminergic and
noradrenergic systems, causing the release
of catecholamines in the central nervous
system synapses.
2. The response rate for stimulant medication
(ie, reduction in hyperactivity or increase in
attention is 70 percent. As many as 90 per-
cent of children will respond to at least one
stimulant.
3. Methylphenidate (Ritalin). Significant reduc-
tion in symptoms occurs at doses between
0.3 and 0.6 mg/kg. Methylphenidate is avail-
able in immediate and sustained release
preparations.
4. Dextroamphetamine (Dexedrine). Similar to
methylphenidate, both formulations are avail-
able in immediate and sustained release
preparations. The immediate release prepara-
 tion of dextroamphetamine-amphetamine has
a duration of as long as six hours.
5. Adverse effects. Many of the side effects
associated with methylphenidate and
dextroamphetamine are mild, of short dura-
tion, and reversible with adjustments of dos-
ing. Common side effects include anorexia or
appetite disturbance (80 percent), sleep
disturbances (3 to 85 percent), and weight
loss (10 to 15 percent); less common side
effects include increased heart rate and blood
pressure, headache, social withdrawal, ner-
vousness, and irritability. Deceleration of
linear growth may occur, but adult height is
not affected.
6. Approximately 15 to 30 percent of children
who are treated with stimulant medications
develop motor tics, most of which are tran-
sient.

Immediate-Release Stimulant Preparations for

Children with Attention-Deficit/Hyperactivity
Disorder

Medication Initial dos- Dose ad- Maxi-

ing vancement mum
dose

Methylpheni 5 mg/day x Weekly in- <25 kg

date* 1 day crements of 35 mg
Methylpheni 5 mg 2 5 mg per <25 kg
date times/day x dose 60 mg
Ritalin 1 day
Methylin (5, 5 mg 3
10, 20 mg times/day
tablets)

Focalin• 2.5 mg 2 Weekly in- 10 mg 2

(2.5, 5, 10 times per crements of times/day
mg tablets) day 2.5 to 5 mg

Dextroamph 3 to 5 Weekly in- 20 mg

etamine years crements of
Dexedrine 2.5 2.5 mg/dose
(5 mg tab- mg/day
lets) x 1 day. 40 mg
2.5 mg 2 Weekly in-
Dextrostat times/da crements of
(5, 10, mg y 5 mg/dose
tablets) >6 years
5 mg x 1
day
5 mg 2
times/da
y

Amphetami 3 to 5 Weekly in- 40 mg

ne- years crements of
Dextroamph 2.5 2.5 mg/dose
etamine mg/day
Adderall (5, x 1 day
7, 10, 12.5, 2.5 mg 2
15, 20, 30 times/da Weekly in-
mg tablets) y crements of
>6 years 5 mg/dose
5 mg x 1
day
5 mg 2
times/da
y

*Duration of action: 1 to 4 hours; half-life: 2 to 3 hours

•
For children >6 years of age

Sustained-release Stimulant Preparations for

Children with Attention-Deficit/Hyperactivity
Disorder

Medication How sup- Duration Maxi-

plied of action mum
dose

Methylpheni 20 mg tab- 8 hours 60 mg

date lets
Methylpheni
date SR
one-pulse
system

Ritalin-SR 20 mg tab- 8 hours 60 mg

one-pulse lets
system
Ritalin-SR 20, 30, 40 8 hours 60 mg
two-pulse mg capsules
system

Methylin ER 10, 20 mg 8 hours 60 mg

one pulse tablets
system

Metadate 20 mg cap- 8 hours 60 mg

CD two- sules
pulse sys-
tem

Metadate 10, 20 mg 8 hours 60 mg

ER one- tablets
pulse sys-
tem

Concerta 18, 36, 54 12 hours 72 mg

three-pulse mg tablets
system

Dextroamph 5, 10, 15 mg 5 to 6 45 mg
etamine capsules hours
Dexedrine
spansule
one-pulse
system

Amphetamin 5, 10, 15, 8 hours 40 mg

e- 20, 25, 30
Dextroamph mg capsules
etamine
Adderall XR

B. Other medications. Nonstimulant medications

usually are used when children respond poorly to a
trial of stimulants, have unacceptable side effects, or
have significant comorbid conditions.
1. Atomoxetine (Strattera), a selective
norepinephrine reuptake inhibitor, is approved for
the treatment of children with AD/HD who are
older than six years of age, adolescents, and
adults. Atomoxetine has been demonstrated to be
more effective compared to placebo. It has not
been compared directly to methylphenidate or
dextroamphetamine. Thus, methylphenidate and
dextroamphetamine continue to be the treatments
most widely recommended.
a. Atomoxetine is an oral capsule (5, 10, 18, 25,
40, and 60 mg) and can be taken once or
twice per day. Children weighing less than 70
kg should be started at a dose of 0.5 mg/kg for
a minimum of three days and then titrated up
to a daily dose of 1.2 mg/kg in either one or
two daily doses; the maximum daily dose
should not exceed 1.4 mg/kg or 100 mg.
Patients who weigh more than 70 kg should
be started at a dose of 40 mg for a minimum
of three days, followed by an increase to 80
mg; after two to four weeks, the dose may be
increased to a maximum of 100 mg.
b. Adverse effects include weight loss, abdomi-
nal pain, decreased appetite, vomiting, nau-
sea, dyspepsia, and sleep disturbance.
Atomoxetine is the only AD/HD medication
that is not a controlled substance.
2. Antidepressants
a. Tricyclic antidepressants (TCAs [eg,
imipramine, desipramine, nortriptyline]) and
dopamine reuptake inhibitors (eg, bupropion)
have been reported to be beneficial in AD/HD,
particularly if the patient has comorbid anxiety,
depression, or tic disorder. Tricyclic antide-
pressants are second-line therapy for AD/HD.
improvement in attention has not been docu-
mented objectively and the effects of these
agents may be short-lived.
b. Electrocardiogram should be obtained at
baseline and when the dose has been opti-
mized because these agents can cause ar-
rhythmia. Side effects include anticholinergic
effects (eg, dry mouth, constipation) and
lowering of the seizure threshold.
c. Bupropion (Wellbutrin), an antidepressant
that blocks the reuptake of norepinephrine
and dopamine, has more stimulant properties
than do the TCAs. It is of modest efficacy in
decreasing hyperactivity and aggressive
behavior. Adverse effects include motor tics
 and a decreased seizure threshold.
3. Clonidine (Catapres), an alpha-2-adrenergic
agonist, has been found to be effective in reduc-
ing symptoms in AD/HD, but not as effective as
stimulants. Clonidine may be useful in
overaroused, easily frustrated, highly active, or
aggressive individuals. It has been used in chil-
dren with AD/HD and comorbid tics or Tourette
syndrome. Side effects of clonidine include
sedation, depression, headache, and
hypotension.
4. Guanfacine (Tenex), a long-acting alpha-2-
noradrenergic agonist, has a longer half-life and
fewer side effects than does clonidine. It has
been used to treat AD/HD with Tourette syn-
drome when tics worsened with stimulants or
when clonidine was poorly tolerated.
C. Titration. During the titration stage, the optimal
dosage and frequency of medication are determined.
Short-acting forms of medication usually are used to
determine the optimal dose. Once the optimal dose
is determined, the comparable dose of the long-
acting agent can be tried.
1. The medication should be started on a weekend
day so that parents can watch for adverse effects
with the first doses. A child with predominantly
inattentive type of AD/HD may need medication
only on school days, whereas a child with the
combined type of AD/HD who has difficulty with
peer relationships may need medication every
day.
2. During the titration stage, the child’s behavior
rating scales should be assessed weekly and the
medication adjusted as indicated. The child
should be seen at least every two to four weeks
during this phase.
D. Behavioral and psychological interventions have
not been demonstrated to significantly reduce the
core symptoms of AD/HD. However, they can im-
prove the behavior problems often seen in children
with AD/HD.
References, see page 182.

Failure to Thrive
Failure to thrive (FTT) is usually first considered when a
child is found to weigh less than the third percentile for
age and gender. Although FTT occurs in all socioeco-
nomic strata, it is more frequent in families living in
poverty. FTT describes a sign; it is not a diagnosis. The
underlying etiology must be determined. Ten percent of
children seen in the primary care setting show signs of
growth failure. Children with FTT attain lower verbal
intelligence, poorer language development, less devel-
oped reading skills, lower social maturity, and have a
higher incidence of behavioral disturbances.

I. Pathophysiology
A. Diagnostic criteria for failure to thrive
1. A child younger than 2 years of age whose weight
is below the 3rd or 5th percentile for age on more
than one occasion.
2. A child younger than 2 years of age whose weight
is less than 80% of the ideal weight for age.
3. A child younger than 2 years of age whose weight
crosses two major percentiles downward on a
standardized growth grid.
B. Exceptions to the previously noted criteria include
the following:
1. Children of genetically short stature.
2. Small-for-gestational age infants.
3. Preterm infants.
4. “Overweight” infants whose rate of height gain
increases while the rate of weight gain decreases.
5. Infants who are normally lean.
C. Many patients with FTT have either an organic or
nonorganic cause; however, a sizable number of
patients have both psychosocial and organic causes
for their condition. FTT is a syndrome of malnutrition
brought on by a combination of organic, behavioral,
and environmental factors.
II. Clinical evaluation of poor weight gain or weight
loss
A. Feeding history should assess details of breast or
formula feeding, timing and introduction of solids,
 who feeds the infant, position and placement of the
infant for feeding, and stooling or vomiting patterns.
B. Developmental history should cover gestational
and perinatal history, developmental milestones,
infant temperament, and the infant’s daily routine.
C. Psychosocial history should include family compo-
sition, employment status, financial status, stress,
isolation, child-rearing beliefs, maternal depression,
and the caretaker’s own history of possible child-
hood abuse or neglect.
D. Family history should include heights, weights,
illnesses, and constitutional short stature, inherited
diseases, or developmental delay.

Causes of Inadequate Caloric Intake

Lack of Appetite
! Anemia (eg, iron deficiency)
! Psychosocial problems (eg, apathy)
! Central nervous system (CNS) pathology (eg, hydro-
cephalus, tumor)
! Chronic infection (eg, urinary tract infection, acquired
immunodeficiency syndrome)
! Gastrointestinal disorder (eg, pain from reflux
esophagitis)

Difficulty with Ingestion

! Psychosocial problems (eg, apathy, rumination)
! Cerebral palsy/CNS disorder (eg, hypertonia, hypotonia)
! Craniofacial anomalies (eg, choanal atresia, cleft lip and
palate micrognathia, glossoptosis)
! Dyspnea (congenital heart disease, pulmonary disease)
! Feeding disorder
! Generalized muscle weakness/pathology (eg,
myopathies)
! Tracheoesophageal fistula
! Genetic syndrome (eg, Smith-Lemli-Opitz-syndrome)
! Congenital syndrome (eg, fetal alcohol syndrome)

Unavailability of Food
! Inappropriate feeding technique
! Inadequate volume of food
! Inappropriate food for age
! Withholding of food (abuse, neglect, psychosocial)

Vomiting
! CNS pathology (increased intracranial pressure)
! Intestinal tract obstruction (eg, pyloric stenosis,
malrotation)
! Gastroesophageal reflux
! Drugs (eg, syrup of ipecac)

III. Physical examination

A. Height, weight, and head circumference should
be plotted on a growth curve. Three measurements
that are below the 3rd percentile indicate an under-
lying organic disease. If all three measurements are
consistently below the third percentile but show the
same rate of increase over a period of time, the
infant probably had intrauterine growth retardation.
If the child’s median age for weight is less than the
median age for height, the child may be under-
nourished.
B. Dysmorphic features and physical signs of
central nervous system, pulmonary, cardiac, or
gastrointestinal disorders, or signs of neglect or
abuse (poor hygiene, unexplained bruises or scars,
or inappropriate behavior) should be sought.
C. Observation of the infant and caretaker. While
feeding and playing, the infant may avoid eye
contact or withdraw from physical attention and may
show a poor suck or swallow, or aversion to oral
stimulation. Ineffective feeding technique or inap-
propriate response to the infant’s physiologic or
social cues may be displayed by the caretaker.
D. Diagnostic testing
1. Laboratory testing. Tests that will usually
exclude an organic pathology include a complete
blood count, urinalysis, urine culture, blood urea
nitrogen, creatinine, serum electrolyte levels,
and a tuberculin test.
2. Radiologic determination of bone age. If the
bone age is normal, it is unlikely that the infant
has a systemic chronic disease or a hormonal
abnormality as the cause of poor weight gain.
3. Severe malnutrition requires measurement of
albumin, alkaline phosphatase, calcium, and
phosphorous to assess protein status and to
look for biochemical rickets.
4. Human immunodeficiency virus screening or a
sweat test may be considered.
 E. A feeding evaluation by a nutritionist or an occupa-
tional therapist may detect a subtle feeding disor-
der.

Causes of Inadequate Calorie Absorption

Malabsorption
• Biliary atresia or cirrhosis
• Celiac disease
• Cystic fibrosis
• Enzymatic deficiencies
• Food (protein) sensitivity or intolerance
• Immunologic deficiency
• Inflammatory bowel disease

Diarrhea
• Bacterial gastroenteritis
• Parasitic infection

Hepatitis

Hirschsprung Disease

Refeeding diarrhea

Causes of Increased Calorie Requirements

Increased Metabolism/Increased Use of Calories

• Chronic/recurrent infection (eg, urinary tract infection, tuber-
culosis)
• Chronic respiratory insufficiency (eg, chronic lung disease)
• Congenital heart disease/acquired heart disease
• Malignancy
• Chronic anemia
• Toxins (lead)
• Drugs (eg, excess levothyroxine)
• Endocrine disorders (eg, hyperthyroidism,
hyperaldosteronism)

Defective Use of Calories

• Metabolic disorders (eg, aminoacidopathies, inborn errors
of carbohydrate metabolism)
• Renal tubular acidosis
• Chronic hypoxemia (eg, cyanotic heart disease)

IV. Treatment of failure to thrive

A. The normal, healthy infant requires an average of
100 kcal/kg of body weight per day. Nutritional
requirements in children with FTT usually are 150
kcal/kg per day.
B. Treatment of infants
1. The number of calories per ounce of formula
can be increased by adding less water (13 oz
infant formula concentrate mixed with 10 oz
water provides 24 kcal/oz high-calorie formula)
or by adding more carbohydrate in the form of
glucose polymers corn starch or fat in the form
of medium-chain triglycerides or corn oil.
2. Once nutritional recovery begins, the infant often
demands and eats enough food to gain weight.
At this point, ad libitum oral feedings are appro-
priate.
C. Treatment of older children. Foods can be forti-
fied with such items as milk products, margarine,
oil, and peanut butter.
References, see page 182.

Speech and Language Development

Language is defined as a symbolic system for the storage
and exchange of information. Language consists of
auditory expressive ability (speech), receptive ability
(listening comprehension), and visual communication
(gestures).

I. Normal speech and language development

A. Auditory expressive language development
1. In the first 4 to 6 weeks, the earliest sounds
consist of cooing.
2. In the first few months, bilabial sounds begin,
consisting of blowing bubbles or the “raspberry.”
3. By 5 months, laughing and monosyllables ap-
pear, such as “da,” “ba,” or “ga.”
4. Between 6 and 8 months, infants begin polysyl-
labic babbling, consisting of the same syllable
repeated, such as “mamama,” “dadadada.”
5. By 9 months, infants sporadically say “mama” or
“dada” without knowing the meaning of these
 sounds.
6. By 10 months of age, infants use “mama” and
“dada” consistently to label the appropriate
parent.
7. By 12 months, infants acquire one or two words
other than “mama,” or “dada.”
8. During the second year of life, vocabulary
growth velocity accelerates, starting at one new
word per week at 12 months of age and increas-
ing to one or more new words per day by 24
months of age.
9. By 18 to 20 months, a toddler should be using a
minimum of 20 words; the 24-month-old should
have a vocabulary of at least 50 words.
10. Early during the second year of life toddlers
produce jargon, consisting of strings of differ-
ent sounds, with rising and falling, speech-like
inflection. These speech inflection patterns of
are referred to as prosody.
11. By 24 months of age, toddlers are producing
two-word phrases, such as “want milk!”
12. In the second year of life, pronouns appear
(“me” and “you”).
13. Third year. Vocabulary growth velocity
reaches a rate of several new words per day.
A 30-month-old’s vocabulary should be too
large for the parent to count (>150 words).
14. By 24 to 30 months, children develop “tele-
graphic” speech, which consists of three- to
five-word sentences.
15. By 2 years, the child’s speech should be
one-half intelligible; by 3 years, it should be
three-fourths intelligible, and it should be
completely intelligible by age 4 years.
B. Auditory receptive language development
1. Newborn infants respond to vocal stimuli by eye
widening or changes in sucking rate.
2. The 2- or 3-month-old infant watches and
listens intently to adults and may vocalize back.
3. By 4 months of age the normal infant will turn
his head to locate the source of a voice; turning
to inanimate stimuli, such as a bell, occurs 1
month later.
4. By 7 to 9 months of age, an infant will attend
selectively to his own name.
5. By 9 months of age, infants comprehend the
word “no.”
6. By 1 year of age, infants respond to one-step
commands such as “Give it to me.”
7. By 2 years of age, toddlers can follow novel
two-step commands. (eg, “Put away your shoes,
then go sit down”).
8. By 2 years, children will point to objects on
command and name simple objects on com-
mand.
9. By 36 months, a child’s receptive vocabulary
includes 800 words, expanding to 1500-2000
words by age 5.
10. By 5 years, children are able to follow three-
and four-step commands.
C. Visual language development
1. During the first few weeks, the infant will dis-
play alert visual fixation.
2. By 4 to 6 weeks, a social smile appears.
3. By age 4 to 5 months, the infant will turn to-
wards a voice.
4. By 6 to 7 months, infants play gesture games,
such as patty cake and peek-a-boo.
5. Between 8 and 9 months, infants reciprocate
and eventually initiate gesture games.
6. By 9 months, infants appropriately wave bye-bye
on command.
7. Between 9 and 12 months, infants express their
desire for an object by reaching and crying.
8. By 12 months, infants indicate desired objects
by pointing with the index finger.
II. Classification of speech and language disorders
A. Hearing loss
1. One infant per thousand is born with bilateral,
severe-to-profound hearing loss. Two children
per thousand are deafened during the first 3
years of life.
2. One-third of congenital deafness is genetic in
origin, one-third is nongenetic, and one-third is of
unknown etiology. The most common nongenetic
cause of deafness is fetal CMV infection.
 B. Mental retardation
1. Three percent of children are mentally retarded,
and all children who are mentally retarded are
language-delayed. Mental retardation (MR) is
defined as significantly subaverage general
intellectual function plus delayed adaptive skills in
the first 5 years of life.
2. Intelligence that is “significantly subaverage” is
defined as more than 2 standard deviations (SD)
below the mean. “Mild” MR is defined as -2 to -3
SD. Intelligence tests are standardized to a mean
score of 100, and mild MR is equivalent to an
intelligence quotient (IQ) of 69 to 55. Moderate
MR = -3 to -4 SD (IQ 54 to 40), severe MR = -4 to
-5 SD (IQ 39 to 25), and below -5 SD is profound
MR (IQ <25).
C. Developmental language disorders (DLD)
1. DLD are disorders characterized by selective
impairment of speech and/or language develop-
ment. General intelligence is normal. DLD affects
5-10% of preschool children, and affected boys
outnumber affected girls by 3:1.
2. In the majority of cases, the etiology of DLD
remains unknown; however, DLD can be caused
by sex chromosome aneuploidy, fragile X syn-
drome, neonatal intracranial hemorrhage, fetal
alcohol effects, head trauma, or human immuno-
deficiency virus encephalopathy.
3. Autism manifests as delayed and deviant lan-
guage development, impaired affective develop-
ment, monotonously repetitious behaviors with an
insistence on routines, and an onset before 30
months of age. The prevalence is 0.2%. Autism
can be caused by most of the same etiologies
that cause MR.
4. Stuttering
a. Physiologic dysfluency is characterized by a
transient loss of normal rate and rhythm of
speech, and it is normal in children between 2
and 4 years of age. Physiologic disfluency
involves repetition of whole words (“I want . . .
I want . . . I want to go home”).
b. Stuttering involves repetition of shorter
speech segments (“I wu . . . wu . . . wwwwant
to go home”) or a complete inability to initiate
a word, referred to as “blockage.” The preva-
lence peaks at 4% between 2 and 4 years of
age and declines to 1% among older children
and adults.
5. Dysarthria is caused by a physical impairment of
the muscles of speech production. Dysarthria in
children usually is caused by cerebral palsy.
III. Clinical evaluation of speech and language
disorders
A. Infants with hearing-impairment. Deaf infants coo
and babble normally until 6 months of age. Thereaf-
ter, vocal output gradually diminishes.
B. Mentally retarded children manifest delay in all
language areas. Cooing and babbling may be
reduced and delayed.
C. Developmental language delay presents with
expressive and receptive impairment, such as
impaired intelligibility and delayed emergence of
sentence structure. Speech may be effortful and
reduced in amount.
D. Autistic children manifest delayed and deviant
language, impaired affective development, and
repetitious behaviors with an insistence on routines.
Autistic type language disorder is marked by im-
paired pragmatics--failure to use language as a
medium of social interaction.
IV. Diagnostic evaluation of speech and language
disorders
A. Developmental testing by a speech/language
pathologist should be undertaken once speech or
language delay has been detected.
B. Audiologic testing is indicated for all children with
a sign of a speech or language disorder.
C. Karyotype and DNA probe studies for fragile X
are indicated in children who have mental retarda-
tion, autism, or developmental language disorder.
D. Human immunodeficiency virus (HIV) serology is
recommended in higher risk speech-delayed chil-
dren to exclude HIV encephalopathy.
E. Creatine kinase measurement to exclude Du-
chenne muscular dystrophy is indicated for boys
who have speech delay plus gross motor delay but
 who do not have increased deep tendon reflexes.
F. Cranial MRI is indicated in the presence of focal
neurologic abnormalities or dysmorphic features
suggestive of a structural brain abnormality (eg,
hypertelorism, midfacial hypoplasia, aberrant hair
patterning).
V. Management of speech and language disorders.
The child who has DLD should be referred for speech
therapy. Stuttering requires referral to a speech pathol-
ogist. Hearing loss is treated with amplification. Therapy
for autism is directed at enhancing communication and
social skills.
References, see page 182.
Cardiac Disorders

Heart Murmurs
Ninety percent of children will have an audible heart
murmur at some point in time. Normal murmurs include
vibratory and pulmonary flow murmurs, venous hums,
carotid bruits, and the murmur of physiologic branch
pulmonary artery stenosis. Less than 5% of heart murmurs
in children are caused by cardiac pathology.

I. Clinical evaluation of heart murmurs

A. Cyanosis, exercise intolerance, feeding difficulties,
dyspnea, or syncope signify potential cardiac dys-
function. Failure to thrive, diffuse diaphoresis,
unexplained persistent irritability or lethargy, and
atypical chest pain also suggest the possibility of
organic heart disease.
B. The majority of children who have heart murmurs
are asymptomatic. In early infancy, however, cardiac
malformations may manifest as persistent peaceful
tachypnea (a respiratory rate greater than 60
breaths/min).
C.Family history of a congenital cardiovascular
malformation increases the risk of a cardiac defect,
such as with DiGeorge syndrome (type B interrupted
aortic arch, truncus arteriosus).
D. Gestational course should be reviewed for expo-
sure to teratogens or maternal illnesses. Fetal
exposure to lithium may cause Ebstein anomaly of
the tricuspid valve. Ventricular and atrial septal
defects occur with fetal alcohol syndrome. Transient
hypertrophic cardiomyopathy and tetralogy of Fallot
are associated with maternal diabetes. Maternal
collagen vascular disease may lead to fetal com-
plete heart block.
II. Physical examination
A. Noncardiac malformations. Twenty-five percent of
children who have heart disease have extracardiac
anomalies. Diaphragmatic hernia, tracheoesoph-
ageal fistula and esophageal atresia, omphalocele,
or imperforate anus are associated with congenital
cardiac defects in 15-25% of infants.
B. Cyanotic infants or children, abnormal rate or
pattern of breathing, a persistently hyperdynamic
precordium, precordial bulging, or asymmetric
pulses should be referred to a cardiologist. Signs of
congestive heart failure (inappropriate tachycardia,
tachypnea, hepatomegaly, abnormal pulse volume)
also should prompt referral to a cardiologist.
C. Auscultatory criteria signifying cardiac disease
1. Loud, pansystolic, late systolic, diastolic, or
continuous murmurs; an abnormally loud or
single second heart sound
2. Fourth heart sound or S4 gallop
3. Ejection or midsystolic clicks
D. Ventricular septal defect (VSD) is a harsh
pansystolic murmur of even amplitude that is
audible at the lower left sternal border.
E. Patent ductus arteriosus (PDA) causes a murmur
that is continuous, louder in systole, and located at
the upper left sternal border.
F. Ejection (crescendo-decrescendo) murmurs are
caused by ventricular outflow obstruction. Ejection
murmurs begin after the first heart sound.

Characteristics of Organic Murmurs

Lesion Shape Timing Loca- Other

tion Findings

Ventricular Plateau Holosysto LLSB Apical mid-

septal de- lic diastolic
fect murmur

Mitral re- Plateau Holosysto Apex Higher

gurgitation lic pitched
than VSD
murmur

Atrial Ejection Systolic ULSB Persistent

septal de- S2 split
fect
 Lesion Shape Timing Loca- Other
tion Findings

Patent Dia- Continu- ULSB Bounding

ductus mond ous pulses
arteriosus

Aortic valve Ejection Systolic URSB Ejection

stenosis click

Subvalvula Ejection Systolic ML- No ejection

r aortic ste- URSB click
nosis

Hypertro- Ejection Systolic LLSB- Laterally

phic apex displaced
cardiomyo- PMI
pathy

Coarctation Ejection Systolic ULSB- Pulse dis-

Left parity
back

Pulmonary Ejection Systolic ULSB Ejection

valve ste- click; wide
nosis S2 split

Tetralogy Ejection Systolic MLSB Cyanosis

of Fallot

LLSB = lower left sternal border, ULSB = upper left sternal border, URSB =
upper right sternal border, MLSB = mid-left sternal border, S2 = second
heart sound, PMI = point of maximal impulse.

III. Differentiation of normal from pathologic murmurs

A. Criteria for diagnosis of a normal heart murmur
1. Asymptomatic patient.
2. No evidence of associated cardiac abnormali-
ties, extracardiac congenital malformations, or
syndromes.
3. Auscultatory features are characteristic of an
innocent murmur.

Normal Murmurs

Type Shape Timing Pitch Loca- Other

tion Find-
ings

Vibra- Ejec- Midsyst Low LLSB- Inten-

tory tion olic apex sity
<grade
II

Venous Dia- Contin- Me- Subcla Disap-

hum mond uous dium vicular pears
in su-
pine
position

Pulmo- Flow Sys- Me- ULSB Normal

nary tolic dium S2 split
flow

Physio- Ejec- Sys- Me- Entire Disap-

logic tion tolic dium chest pears
branch by 4 to
pulmo- 6
nary months
artery of age
steno-
sis

LLSB = lower left sternal border, ULSB = upper left sternal

border, S2 = second heart sound.

IV. Heart murmurs in the newborn infant

A. Sixty percent of healthy term newborn infants have
normal heart murmurs. One-third of neonates who
have serious heart malformations may not have a
detectable heart murmur during the first 2 weeks of
life. Thirty percent of newborn infants subsequently
determined to have heart disease are discharged
from the newborn nursery as ostensibly healthy.
B. Persistent peaceful tachypnea should not be
dismissed; 90% of infants who have serious car-
diac disease have persistent tachypnea after birth.
C. A persistently hyperdynamic precordium sug-
gests organic heart disease.
D. Auscultation of the second heart sound. In
healthy neonates, the second heart sound is split
audibly by 12 hours of age. A single second heart
sound in a quiet neonate indicates: 1) the absence
 of one outflow tract valve (aortic or pulmonary
atresia); 2) an abnormal position of the great
vessels (transposition of the great arteries or
tetralogy of Fallot); or 3) pulmonary hypertension
(ventricular defect, persistent pulmonary hyperten-
sion).
References, see page 182.

Chest Pain in Children

Chest pain is the presenting complaint in 6 per 1,000
children who present to pediatric clinics. Young children
are more likely to have a cardiorespiratory cause of their
pain, such as cough, asthma, pneumonia, or heart dis-
ease; adolescents are more likely to have pain associated
with a psychogenic disturbance.

I. Differential diagnosis of chest pain in children

A. Cardiac disease
1. Cardiac disease is a rare cause of chest pain in
children. However, myocardial infarction can
rarely result from anomalous coronary arteries.
Some children will have a pansystolic, continuous
or mitral regurgitation murmur or gallop rhythm
that suggests myocardial dysfunction.
2. Arrhythmias may cause palpitations or abnormali-
ties on cardiac examination. Supraventricular
tachycardia is the most common arrhythmia, but
premature ventricular beats or tachycardia also
can cause episodes of brief sharp chest pain.
3. Hypertrophic obstructive cardiomyopathy is
an autosomal dominant structural disorder;
therefore, there often is a family history of the
condition. Children may have a murmur that may
be audible when standing or when performing a
Valsalva maneuver.
4. Mitral valve prolapse may cause chest pain
secondary to papillary muscle or endocardial
ischemia. A midsystolic click and a late systolic
murmur may be detected.
5. Cardiac infections are uncommon causes of
pediatric chest pain.
a. Pericarditis presents with sharp, stabbing
pain that improves when the patient sits up
and leans forward. The child usually is febrile;
is in respiratory distress; and has a friction rub,
distant heart sounds, neck vein distention, and
pulsus paradoxus.
b. Myocarditis presents as mild pain that has
been present for several days. After a few
days of fever, vomiting and lightheadedness,
the patient may develop pain or shortness of
breath on exertion. Examination may reveal
muffled heart sounds, fever, a gallop rhythm,
or tachycardia.
c. Chest radiography will show cardiomegaly in
both of these infections, and the electrocardio-
gram will be abnormal. An echocardiogram will
confirm the diagnosis.
B. Musculoskeletal pain
1. Musculoskeletal pain is one of the most common
diagnoses in children who have chest discom-
fort. Children frequently strain chest wall muscles
while exercising.
2. Trauma to the chest may result in a mild contu-
sion or a rib fracture. The physical examination
will reveal chest tenderness.
3. Costochondritis is common in children, and it is
characterized by tenderness over the
costochondral junctions. The pain is sharp and
exaggerated by physical activity or breathing.
C. Respiratory conditions
1. Severe cough, asthma, or pneumonia may
cause chest pain because of overuse of chest
wall muscles. Crackles, wheezes, tachypnea, or
decreased breath sounds are present.
2. Exercise-induced asthma may cause chest
pain, which can be confirmed with a treadmill
test.
3. S p o n t a n e o u s pneumothorax or
pneumomediastinum may occasionally cause
chest pain with respiratory distress. Children with
asthma, cystic fibrosis or Marfan syndrome are
at high risk. Signs include respiratory distress,
decreased breath sounds on the affected side,
 and palpable subcutaneous air.
4. Pulmonary embolism is extremely rare in
pediatric patients, but it should be considered in
the adolescent girl who has dyspnea, fever,
pleuritic pain, cough, and hemoptysis. Oral
contraceptives or recent abortion increase the
risk. Young males who have had recent leg
trauma also are at risk.
D. Psychogenic chest pain may present with hyper-
ventilation or an anxious appearance. A recent
stressful event (separation from friends, parental
divorce, school failure) may often be related tempo-
rally to the onset of the chest pain.
E. Gastrointestinal disorders
1. Reflux esophagitis often causes chest pain,
which is described as burning, substernal, and
worsened by reclining or eating spicy foods. This
condition is confirmed with a therapeutic trial of
antacids.
2. Foreign body ingestion may cause chest pain
when the object lodges in the esophagus. A
radiograph confirms the diagnosis.
F. Miscellaneous causes of pediatric chest pain
1. Sickle cell disease may cause an acute chest
syndrome.
2. Marfan syndrome may cause chest pain and
fatal abdominal aortic aneurysm dissection.
3. Collagen vascular disorders may cause chest
pain and pleural effusions.
4. Shingles may cause chest pain that precedes or
occurs simultaneously with the rash.
5. Coxsackievirus infection may lead to
pleurodynia with paroxysms of sharp chest pain.
6. Breast tenderness during puberty or early
breast changes of pregnancy may present as
chest pain.
7. Idiopathic chest pain. No diagnosis can be
determined in 20-45% of cases of pediatric chest
pain.
II. Clinical evaluation of chest pain
A. A history and physical examination will reveal the
etiology of chest pain in most cases. The history
may reveal asthma, previous heart disease, or
Kawasaki disease. Family history may reveal
familial hypertrophic obstructive cardiomyopathy.
B. The frequency and severity of the pain and
whether the pain interrupts the child’s daily activity
should be determined. Pain that wakes the child
from sleep is more likely to be related to an organic
etiology.
C. Burning pain in the sternal area suggests
esophagitis. Sharp stabbing pain that is relieved by
sitting up and leaning forward suggests pericarditis
in a febrile child.
D. Mode of onset of pain. Acute onset of pain is more
likely to represent an organic etiology. Chronic pain
is much more likely to have a idiopathic or psycho-
genic origin.
E. Precipitating factors
1. Trauma, muscle strain or choking on a for-
eign body should be sought.
2. Exercise-induced chest pain may be caused
by cardiac disease or exercise-induced asthma.
3. Syncope, fever or palpitations associated with
chest pain are signs of an organic etiology.
4. Joint pain, rash or fever may be suggested by
the presence of collagen vascular disease.
5. Stressful conditions at home or school should
be sought.
6. Substance abuse (cocaine) or oral contracep-
tives should be sought in adolescents.
F. Physical examination
1. Severe distress warrants immediate treatment
for life-threatening conditions, such as
pneumothorax.
2. Hyperventilation may be distinguished from
respiratory distress by the absence of cyanosis
or nasal flaring.
3. Pallor or poor growth may suggest a malig-
nancy or collagen vascular disease.
4. Abdominal tenderness may suggest abdominal
pain that is referred to the chest.
5. Rales, wheezes, decreased breath sounds,
murmurs, rubs, muffled heart sounds or
arrhythmias suggest a cardiopulmonary pathol-
ogy.
 6. The chest wall should be evaluated for bruises
(trauma), tenderness (musculoskeletal pain), or
subcutaneous air (pneumothorax or
pneumomediastinum).
III. Laboratory evaluation
A. A chest radiograph is warranted if the patient has
fever, respiratory distress, or abnormal breath
sounds. Fever and cardiomegaly suggests
pericarditis or myocarditis.
B. Electrocardiography is recommended if the pain
was acute in onset (began in the last 2-3 days) or if
there is an abnormal cardiac examination (unex-
plained tachycardia, arrhythmia, murmur, rub, or
click).
C. Exercise stress testing or pulmonary function
testing is appropriate for evaluation of cardiac
disease or asthma.
D. Holter monitoring is warranted for syncope or
palpitations.
E. Children with chronic pain, a normal physical
examination, and no history suggestive of cardiac
or pulmonary disease do not require laboratory
studies.
F. Blood counts and sedimentation rates are of
value if collagen vascular disease, infection, or
malignancy is suspected.
G. Drug screening may be indicated in the older child
who has acute pain associated with anxiety,
tachycardia, hypertension, or shortness of breath.
IV. Management of pediatric chest pain
A. Emergency department referral is necessary if
the child is in severe distress or has a history of
significant trauma.
B. Referral to a cardiologist is recommended for
children with known or suspected heart disease,
syncope, palpitations, or pain on exertion.
C. Musculoskeletal, psychogenic or idiopathic pain
usually will respond to reassurance, analgesics,
rest, and application of a heating pad. If esophagitis
is suspected, a trial of antacids may be beneficial.
References, see page 182.
Allergic and Dermatologic
Disorders
Asthma
Asthma is a chronic inflammatory disorder of the airways,
causing recurrent episodes of wheezing, breathlessness,
chest tightness, and cough.

I. History
A. The classic triad of symptoms associated with
asthma consists of cough, shortness of breath, and
wheezing. Postnasal drip syndrome can also lead to
symptoms that include cough, wheezing, dyspnea,
and/or expectoration of phlegm.
B. There is a parental history of asthma in 50 percent
of children with asthma.

Diagnosis of Asthma

PEF (% per-
sonal best)
or FEV2 (%
Asthma di- Days with Nights with predicted
agnosis symptoms* symptoms best)

Step 4: se- Continual Frequent <60

vere persis-
tent

Step 3: mod- Daily >5 times per >60 to <80

erate persis- month
tent

Step 2: mild >2 times per 3 to 4 times >80

persistent week per month

Step 1: mild >2 times per <2 per >80

intermittent week month

II. Physical examination

A. Widespread, high-pitched, musical wheezes are
characteristic of asthma, although they are not
specific. The presence or absence of wheezing on
physical examination is a poor predictor of the
severity of airflow obstruction in asthma. Wheezing
may be heard in patients with mild, moderate, or
severe airway narrowing; significant airway narrow-
ing also may be present without wheezing.
B. Physical findings that suggest severe airflow ob-
struction in asthma, including use of the accessory
(eg, sternocleidomastoid) muscles of breathing and
a pulsus paradoxus.
III. Laboratory testing
A. Spirometry, which includes measurement of forced
expiratory volume in one second (FEV1) and forced
vital capacity (FVC), is a useful pulmonary function
test.
1. The FEV1 is the most important spirometric
variable for assessment of airflow obstruction.
The FEV1 reflects the average flow rate during
the first second of forced vital capacity (FVC). It
declines in direct and linear proportion with
clinical worsening of airways obstruction, and it
increases with successful treatment of airways
obstruction. The FEV1 can be used for determin-
ing the degree of obstruction (mild, moderate, or
severe).
2. Administration of a bronchodilator (eg, Albuterol)
by metered-dose inhaler (MDI) is indicated
during an initial work-up if baseline spirometry.
B. Chest radiograph is almost always normal in
patients with asthma. Its potential value is to detect
rare complications and to exclude alternative diag-
noses.
C. Tests for allergy
1. Allergy skin testing involves prick skin tests.
Drops of antigen-containing solution are placed
in parallel rows on each forearm using a panel of
up to 30 different allergens.
2. RAST involves blood measurement of the min-
ute quantities of IgE antibody directed at particu-
lar antigens. Various panels of antibodies can be
ordered.
IV. Differential diagnosis
A. In children, considerations include foreign body
aspiration, cystic fibrosis, and viral bronchiolitis.
 B. In young and middle-aged adults considerations
include bronchiectasis, pulmonary embolism,
gastroesophageal reflux disease (GERD), and
sarcoidosis.
C. In older patients, especially cigarette smokers,
considerations include COPD and heart failure.
D. When persistent cough is the presenting complaint
and the chest radiograph and lung function are
normal, the differential includes post-nasal drip,
GERD, post-viral tussive syndrome, and cough
induced by angiotensin converting enzyme inhibi-
tors. With the exception of aspiration, diffuse musi-
cal expiratory wheezing is not found in any of these
other causes of persistent cough.
E. Some illnesses are common comorbidities with
asthma, including seasonal allergic rhinitis and
conjunctivitis (“hay fever”), perennial rhinitis, recur-
rent or chronic sinusitis, and post-nasal drip associ-
ated with rhinitis or sinusitis.
V. Management of asthma
A. Monitoring. Regular monitoring of the peak
expiratory flow rate (PEFR) should be encouraged
in patients with moderate-to-severe asthma. PEFR
measurement can be used to follow the impact of
any relevant change in therapy upon lung function
and to assess the severity of acute asthmatic
exacerbations.
B. Controlling trigger factors. Identifying and
avoiding asthma "triggers" are essential in pre-
venting asthma flare-ups. Common asthma trig-
gers generally fall into the following six categories:
allergens; respiratory infections; irritants; chemi-
cals; physical activity; and emotional stress. An-
nual influenza vaccination is recommended for
patients with asthma.
C. Pharmacologic treatment of intermittent
asthma. Patients with mild intermittent asthma are
defined as those who have:
1. Symptoms of asthma occurring two or fewer
times per week.
2. Two or fewer nocturnal awakenings per month.
3. Peak-flow measurements when asymptomatic
that are within the normal range (ie, PEFR >80
percent of predicted normal).
4. Short-acting inhaled beta-agonists. Patients
with mild intermittent asthma are best treated
with an intermittent inhaled beta-2-selective
adrenergic-agonist. Patients for whom trigger-
ing of asthmatic symptoms can be predicted
(eg, exercise-induced bronchoconstriction) are
encouraged to use their inhaled beta-agonist 10
minutes prior to exposure. Inhaled beta-
agonists with rapid onset of action, intermediate
duration of effect (four to six hours), and beta-2
selectivity are recommended.
5. Mast cell stabilizing agents. Mast cell stabiliz-
ing agents such as cromolyn (Intal) and
nedocromil (Tilade) are alternative medications
for prevention of exercise-induced
bronchoconstriction. These medications provide
additive protection when used in combination
with a beta-agonist. Cromolyn and nedocromil
are effective when taken prior to an exposure
but have no ability to relieve asthmatic symp-
toms once they have developed.
Stepwise Approach for Managing Asthma

Asth Quick relief Long-term Medication

ma control

Step Short-acting Daily Oral

4: bronchodilat anti-inflam- corticosteroids
se- or as needed: matory medi- :
vere, cations: Methylpredniso
persis • Inhaled • High-dose ne (Medrol),
tent short-acting inhaled 2-mg tablet
beta2 agonist corticosteroi Prednisolone
or d (Prelone syrup),
• Oral beta2 and 5 mg per 5 mL
agonist • If needed, (Pediapred liq-
add sys- uid), 5 mg per 5
temic mL. Prednisone
corticoster- 5-mg tablet
oids (0.25 (Deltasone),
to 2 mg per 5-mg tab
kg per day) (Intensol), 5
and reduce mg/mL liquid
to lowest
dosage.

Step Short-acting Daily Short-acting

3: bronchodilat anti-inflam- beta2 agonist
mod- or as needed: matory medi- Albuterol (Airet
erate, • Inhaled cations, ei- nebulizer), 2.5
per- short-acting ther: mg in 3 mL q4-
sisten beta2 agonist • High-dose 6h PRN
t by nebulizer inhaled (Proventil-HFA
or spacer corticosteroi MDI) 2 puffs q4-
and face d 6h PRN
mask or, once (Ventolin
or control is Rotacaps DPI),
• Oral beta2 established 1-2 caps q4-6h
agonist • Low- to PRN
medium- Long-acting
dose in- beta2 agonist
haled corti- Salmeterol
costeroid (Serevent MDI,
and Serevent
long-acting Diskus DPI) 2
bronch- puffs q12h; 1
odilator (eg, inhalation q12h
long-acting Albuterol SR
inhaled (Volmax tablet,
beta2 ago- Proventil Repe-
nist or tabs) 4-8 mg bid
theophylline Salmeterol/Fluti
SR) casone (Advair
Diskus)
100 μg/50 μg
250 μg/50 μg
500 μg/50 μg
1 puff q12h
Stepwise Approach for Managing Asthma

Asth Quick relief Long-term Medication

ma control

Step Short-acting Daily Inhaled

2: bronch- anti-inflam- corticosteroids
mild, odilator as matory medi- • Beclomethaso
persis needed: cations ne
tent • Inhaled (Beclovent
short-acting MDI) 4-8 puffs
beta2 agonist bid (Vanceril
or DS MDI) 2-4
• Oral beta2 puffs bid
agonist • Budesonide
(Pulmicort
Turbuhaler
DPI)1-2 inha-
lations bid.
Pulmicort
Respules,
0.25 mg, 0.5
mg. 1-2 bid.
• Flunisolide
(AeroBid MDI)
2-4 puffs bid
• Fluticasone
(Flovent), 2-4
puffs bid
(Flovent
Rotadisk) 1
bid.
• Triamcinolone
(Azmacort
MDI) 4 puffs
bid.
Theophylline
200 mg, 300
mg (SR), 450
mg (TR). 100-
300 mg bid
Antileukotriene
s
• Zafirlukast
(Accolate),
10-mg tablet,
20 mg bid
• Montelukast
(Singulair), 4-
or 5-mg
chewable tab,
10 mg qhs
• Zileuton (Zyflo
Flimtab),
600-mg tab,
600 mg qid
• Cromolyn (In-
tal) inhaler, 2-
4 puffs tid-qid
• Nedocromil
(Tilade) in-
haler, 2-4
puffs bid-qid

Step Short-acting No daily medi- Short-acting

1: bronchodilat cation beta2 agonist
mild, or as needed Albuterol (Airet
interm <2 times per nebulizer), 2.5
ittent week: mg in 3 mL q4-
• Inhaled, 6h PRN
short-acting (Proventil-HFA
beta2 agonist MDI) 2 puffs q4-
or 6h PRN
• Oral beta2 (Ventolin
agonist Rotacaps DPI),
1-2 caps q4-6h
PRN

Drugs for Asthma

Drug Formulation Dosage

Inhaled beta2-adrenergic agonists, short-acting

Albuterol
Proventil metered-dose 2 puffs q4-6h
Proventil-HFA inhaler (90 PRN
Ventolin μg/puff)
Ventolin
Rotacaps dry-powder in- 1-2 capsules q4-
haler (200 6h PRN
μg/inhalation)

Albuterol nebulized 2.5 mg q4-6h

Proventil PRN
multi-dose vials
Ventolin Nebules
Ventolin
Drug Formulation Dosage

Levalbuterol - nebulized 0.63-1.25 mg q6-

Xopenex 8h PRN

Inhaled beta2-adrenergic agonist, long-acting

Formoterol - dry-powder in- 1 puff bid.

Foradil haler (12 μg/puff)

Salmeterol metered-dose 2 puffs q12h

Serevent inhaler (21
Serevent Diskus μg/puff) 1 inhalation q12h
dry-powder in-
haler (50
μg/inhalation)

Fluticasone/Sal dry-powder in- 1 puff q12h

meterol Advair haler (100, 250 or
Diskus 500 μg/puff)

Inhaled Corticosteroids

Beclomethasone
dipropionate
Beclovent metered-dose 4-8 puffs bid
Vanceril inhaler (42
Vanceril Double- μg/puff) (84 2-4 puffs bid
Strength μg/puff)

Budesonide dry-powder in- 1-2 inhalations

Pulmicort haler (200 bid
Turbuhaler μg/inhalation)

Flunisolide - metered-dose 2-4 puffs bid

AeroBid in-
hale
r
(250 μg/puff)

Fluticasone metered-dose 2-4 puffs bid

Flovent inhaler (44 μg/puff)
(44, 110 or 220 1 inhalation bid
Flovent Rotadisk μg/puff) (100
dry-powder in- μg/inhalation)
haler (50, 100 or
250 μg/inhalation)

Triamcinolone metered-dose 2 puffs tid-qid or

acetonide inhaler (100 4 puffs bid
Azmacort μg/puff)

Leukotriene Modifiers

Montelukast - tablets 10 mg qhs

Singulair

Zafirlukast - tablets 20 mg bid

Accolate

Zileuton - Zyflo tablets 600 mg qid

Mast Cell Stabilizers

Cromolyn metered-dose 2-4 puffs tid-qid

Intal inhaler (800
μg/puff)

Nedocromil metered-dose 2-4 puffs bid-qid

Tilade inhaler (1.75
mg/puff)

Phosphodiesterase Inhibitor

Theophylline
Slo-Bid extended-release 100-300 mg bid
Gyrocaps, Theo- capsules or tab-
Dur, Unidur lets

D. Treatment of mild persistent asthma

1. It is appropriate to begin regular treatment with
anti-inflammatory medications when a patient has
one of the following:
a. Asthmatic symptoms requiring relief with an
inhaled bronchodilator more than once per
week.
b. Nocturnal awakenings as often as once every
two weeks.
c. Observed fluctuations in PEFR of more than 20
percent.
2. Inhaled corticosteroids. For adults, the most
frequently recommended choice of anti-inflamma-
tory therapy is an inhaled corticosteroid. Inhaled
corticosteroids are administered twice daily.
a. Use of a spacer device (eg, Aerochamber,
Optichamber, Ellipse, or InspirEase) with the
inhaled corticosteroids is recommended. The
triamcinolone acetonide MDI is manufactured
 with an attached spacer. The budesonide
Turbuhaler is not appropriate for use with a
spacer.
b. Oral candidiasis (thrush) is the most common
side effect from the use of inhaled
corticosteroids. This complication is infrequent
when inhaled corticosteroids are administered
with spacers and when patients rinse their
mouths with water immediately after use. Hoarse
voice and sore throat are less common side
effects.
c. Long-term use of inhaled corticosteroids in the
doses recommended for mild asthma is gener-
ally well tolerated. Adverse effects related to the
eye and to skeletal metabolism are some of the
more serious potential consequences of inhaled
corticosteroid use. Suppression of the
hypothalamic-pituitary-adrenal axis can also
occur.
d. Patients receiving regular anti-inflammatory
therapy should continue to use their inhaled
bronchodilator as needed for relief of symptoms
and prior to exposure to known triggers of their
symptoms.
3. Leukotriene-modifying agents. Leukotrienes
(leukotriene C4, D4 and E4) are potent chemical
mediators of the allergic response in asthma. 5-
lipoxygenase enzyme inhibitors block production
of leukotrienes. The leukotriene-receptor antago-
nists inhibit the action of leukotrienes at their
receptor.
a. Zafirlukast (Accolate) is orally administered; its
relatively long half-life permits twice-daily dosing.
Absorption is optimized by ingestion on an
empty stomach. The only significant drug inter-
action is with warfarin, resulting in an increase in
the prothrombin time. A second member of this
drug category, montelukast (Singulair) is suitable
for once-daily dosing.
b. Zileuton (Zyflo) inhibits production of
leukotrienes by interfering with metabolism of
arachidonic acid by 5-lipoxygenase. It is admin-
istered orally on a QID schedule. A small inci-
dence (2 to 4 percent) of hepatic inflammation is
associated with zileuton, leading to the recom-
mendation that liver function tests be checked
before initiating therapy, monthly for the first
three months of therapy, and at three- to six-
month intervals thereafter. Drug interactions
include warfarin (increased prothrombin time)
and theophylline (increased serum concentra-
tion).
4. Mast cell stabilizing agents
a. The mast cell stabilizing agents, cromolyn and
nedocromil, are alternative choices when initiat-
ing regular preventive therapy in mild asthma.
These drugs are particularly well suited to use in
patients who refuse to use of any steroid prepa-
ration.
b. Cromolyn and nedocromil appear to be some-
what less effective than inhaled corticosteroids in
controlling asthma. Treatment with cromolyn and
nedocromil requires compliance with a QID
dosing schedule. Patients whose asthma is well
controlled with nedocromil taken four times daily
can gradually reduce the dosing schedule to
twice daily.
E. Long-acting inhaled beta-agonists. Salmeterol
(Serevent) and formoterol (Foradil) are inhaled beta-
adrenergic agonists with a duration of action of at
least 12 hours. Twice-daily dosing provides 24-hour
bronchodilation. Long-acting beta-agonists are not
recommended as monotherapy for mild asthma. A
short-acting beta-agonist should be used as needed.
F. Treatment of moderate persistent asthma. The
presence of any of the following is considered an
indication of moderate disease:
Daily symptoms of asthma.
Daily need for bronchodilator medications.
The development of asthmatic attacks that interfere
with activity.
Nocturnal awakenings more than once per week.
PEFR 60 to 80 percent of normal.
1. High-dose inhaled steroid. Fluticasone (Flonase)
110 or 220 µg/puff or budesonide (Rhinocort) 200
µg/inhalation provides potent topical corticosteroid
therapy for moderate asthma with the convenience
 of 2 to 4 puffs twice daily.
a. High doses of inhaled corticosteroids (greater
than 1000 to 1500 µg/day) may cause several
adverse systemic effects after long-term use:
(1) Increased intraocular pressure.
(2) Cataracts.
(3) Growth retardation.
(4) Possibly increased bone loss.
(5) Hypothalamic-pituitary-adrenal axis suppres-
sion.
2. Long-acting inhaled beta-agonists. In patients
requiring dual therapy, combined dry powder
formulations allow simultaneous delivery of both a
corticosteroid and a long-acting beta-agonist (eg,
Advair Diskus, Seretide, Symbicort). The steroid
dose is variable (100, 250, or 500 mcg per inhala-
tion).
3. Leukotriene-modifying agents. Addition of a
lipoxygenase inhibitor or leukotriene-receptor
antagonist may improve asthma control (and
permit reduction of the dose of inhaled
corticosteroids) in moderate or severe asthma.
4. Long-acting oral bronchodilators. Theophylline
and sustained-release albuterol tablets are effec-
tive disease controllers when used in combination
with regular anti-inflammatory therapy.
a. The major disadvantages of these drugs include
the frequency of side effects, a narrow therapeu-
tic window, and relative lack of bronchodilator
potency
b. Theophylline is a reasonable alternative for
patients who are intolerant of long-acting beta-
agonists or who are unable to use a metered
dose inhaler properly. Attention to theophylline
pharmacokinetics is essential in order to avoid
toxicity.
G. Treatment of severe asthma. The patient with
severe chronic asthma has frequent asthma exacer-
bations as a result of viral illnesses, allergens,
exercise, or air pollutants; is usually awakened from
sleep four to seven nights per week; has an FEV1
below 60 percent of predicted; and is unable to
achieve normal lung function despite chronic treat-
ment with multiple medications, including inhaled
steroids at moderate-to-high dose or continuous,
every-other-day or multiple-short courses of oral
steroids. These individuals usually require multiple-
controller medications and bronchodilator medica-
tions used on a regular basis.
References, see page 182.

Atopic Dermatitis and Eczema

Atopic dermatitis is a chronic inflammation of the skin that
occurs in persons of all ages but is more common in
children. Atopic dermatitis affects 10 percent of children.
The symptoms of atopic dermatitis resolve by adolescence
in 50 percent of affected children.

I. Diagnosis
A. Exposure to aeroallergens, irritating chemicals,
foods and emotional stress may worsen the rash.
B. Acute lesions are papules and vesicles on a back-
ground of erythema. Subacute lesions may develop
scales and lichenification. Chronically involved areas
become thick and fibrotic. Lesions can develop
secondary infections with crusting and weeping.
Xerosis (dry skin) is characteristic.
 Diagnostic Features of Atopic Dermatitis

Major features
Pruritus
Chronic or relapsing dermatitis
Personal or family history of atopic disease
Typical distribution and morphology of atopic dermatitis rash:
Facial and extensor surfaces in infants and young children
Flexure lichenification in older children and adults

Minor features
Eyes Nipple eczema
Cataracts (anterior Positive type I hypersensitiv-
subcapsular) ity skin tests
Keratoconus Propensity for cutaneous
Infraorbital folds affected infections
Facial pallor Elevated serum IgE level
Palmar hyperlinearity Food intolerance
Xerosis Impaired cell-mediated im-
Pityriasis alba munity
White dermatographism Erythroderma
Ichthyosis Early age of onset
Keratosis pilaris
Nonspecific dermatitis of the
hands and feet

C. In infants and young children, pruritus commonly is

present on the scalp, face (cheeks and chin) and
extensor surfaces of the extremities. Older children
and adults typically have involvement of the flexor
surfaces (antecubital and popliteal fossa), neck,
wrists and ankles.
D. Exposure to pollens, molds, mites and animal
dander may be important in some patients.
II.Treatment
A. Bathing and moisturizers. Bathing should occur
once daily with warm water for five to 10 minutes.
Soap should not be used unless it is needed for the
removal of dirt. A mild cleanser (eg, Dove, Basis,
Kiss My Face or Cetaphil) may be used. After
bathing, patients should apply a moisturizer liberally
(eg, Vaseline, Aquaphor, Eucerin, Moisturel, mineral
oil or baby oil). Ointments are superior to creams.
Lotions are least effective because of their alcohol
content. To avoid injury to the skin from scratching,
fingernails should be cut short, and cotton gloves
can be worn at night.
B. Pruritus that is refractory to moisturizers and conser-
vative measures can be treated with sedating agents
such as hydroxyzine (Atarax) and diphenhydramine
(Benadryl). Tricyclic antidepressants such as
doxepin (Sinequan) and amitriptyline (Elavil) also
induce sleep and reduce pruritus.
C. Systemic corticosteroids should be reserved for use
in patients with severe treatment-resistant atopic
dermatitis.
D. It is reasonable to use a mild topical steroid initially
in infants and for intertriginous areas in patients of
any age. If the dermatitis is severe, a more potent
steroid is needed.

Commonly Used Topical Corticosteroids

Preparation Size

Low-Potency Agents

Hydrocortisone ointment, cream, 1, 2.5% (Hytone) 30 g

Mild-Potency Agents

Alclometasone dipropionate cream, ointment, 0.05% 60 g

(Aclovate)

Triamcinolone acetonide cream, 0.1% (Aristocort) 60 g

Fluocinolone acetonide cream, 0.01% (Synalar) 60 g

Medium-Potency Agents

Triamcinolone acetonide ointment (Aristocort A), 60 g

0.1%

Betamethasone dipropionate cream (Diprosone), 45 g

0.05%

Mometasone cream 0.1% (Elocon) 45 g

Fluocinolone acetonide ointment, 0.025% (Synalar) 60 g

Betamethasone valerate cream, 0.1% (Valisone) 45 g

Hydrocortisone valerate cream, ointment, 0.2% 60 g

(Westcort)
 E. Immunosuppressants and antineoplastics
1. Pimecrolimus (Elidel) is a non-steroid cream for
the treatment of mild to moderate eczema.
Pimecrolimus has anti-inflammatory activity. It
does not cause skin atrophy. Topical application
is comparable to that of a potent topical steroid.
1% pimecrolimus cream is applied twice daily. It
may be used in children >2 years old. The FDA
has issued warnings about a possible link be-
tween the topical calcineurin inhibitors and can-
cer.
2. Tacrolimus (Protopic) is more potent than
pimecrolimus in the treatment of severe or refrac-
tory atopic dermatitis, with few adverse effects.
Tacrolimus is available in 0.1% and 0.03%. The
lower strength may be used in children >2 years
old. The FDA has issued warnings about a
possible link between the topical calcineurin
inhibitors and cancer.
3. Cyclosporine (Sandimmune) has been effective
in patients with refractory atopic dermatitis. The
condition returns after the cessation of therapy,
although not always at the original level of sever-
ity.
References, see page 182.

Contact Dermatitis
Contact dermatitis is an extremely common in the pediatric
age group. There are two major forms of contact dermati-
tis: irritant and allergic. Common causes of irritant contact
dermatitis include overbathing, drooling, prolonged contact
with moisture and feces in the diaper, and bubble baths.

I. Clinical evaluation
A. Contact dermatitis usually first appears in infants 2-6
months of age. Infants and children have rashes on
the shoulders, chest, abdomen, and back. Infants
usually also have a rash on the face, scalp and
around the ears. Children older than 18 months old
tend to have rashes on the neck and antecubital and
popliteal fossae. Contact dermatitis usually resolves
by puberty, but it sometimes recurs at times of
stress.
B. Acute lesions are itchy, red, edematous papules and
small vesicles, which may progress to weeping and
crusting lesions. Chronic rubbing and scratching may
cause lichenification and hyperpigmentation.
C. Patch testing is useful for evaluation of persistent,
localized reactions. It also may be useful in patients
who have atopic dermatitis and experience a flare or
persistence of disease despite appropriate therapy.
II. Treatment of contact dermatitis
A. Moisture. Avoidance of excessive bathing, hand
washing, and lip licking is recommended. Showers or
baths should be limited to no more than 5 minutes.
After bathing, patients should apply a moisturizer
(Aquaphor, Eucerin, Vaseline) to noninflamed skin.
B. Contact with irritants
1. Overuse of soap should be discouraged. Use of
nonirritating soaps (eg, Dove, Ivory, Neutrogena)
should be limited to the axilla, groin, hands, and
feet.
2. Infants often have bright red exudative contact
dermatitis (slobber dermatitis) on the cheeks,
resulting from drooling. A corticosteroid will usu-
ally bring improvement.
C. Topical corticosteroids
1. Corticosteroid ointments maintain skin hydration
and maximize penetration. Corticosteroid creams
may sting when applied to acute lesions.
2. Mid- and low-potency topical corticosteroids are
used twice daily for chronic, atopic dermatitis.
High-potency steroids may be used for flare-ups,
but the potency should be tapered after the
dermatitis is controlled.
3. Use of high-potency agents on the face, genitalia
and skinfolds may cause epidermal atrophy
(“stretch marks”), rebound erythema, and suscep-
tibility to bruising.

Commonly Used Topical Corticosteroids

 Preparation Size

Low-Potency Agents

Hydrocortisone ointment, cream, 1, 2.5% (Hytone) 30 g

Mild-Potency Agents

Alclometasone dipropionate cream, ointment, 0.05% 60 g

(Aclovate)

Triamcinolone acetonide cream, 0.1% (Aristocort) 60 g

Fluocinolone acetonide cream, 0.01% (Synalar) 60 g

Medium-Potency Agents

Triamcinolone acetonide ointment (Aristocort A), 60 g

0.1%

Betamethasone dipropionate cream (Diprosone), 45 g

0.05%

Mometasone cream 0.1% (Elocon) 45 g

Fluocinolone acetonide ointment, 0.025% (Synalar) 60 g

Hydrocortisone butyrate 0.1% cream, ointment 45 g

(Locoid)

Betamethasone valerate cream, 0.1% (Valisone) 45 g

Hydrocortisone valerate cream, ointment, 0.2% 60 g

(Westcort)

High-Potency Agents

Amcinonide ointment, 0.1% (Cyclocort) 60 g

Betamethasone dipropionate ointment (Diprosone) 45 g

0.05%

Fluocinonide cream, ointment, 0.05% (Lidex) 60 g

4. Allergic reactions to topical corticosteroids

may occur. Mometasone (Elocon) is the least
likely to cause an allergic reaction.
D. Antihistamines, such as diphenhydramine or
hydroxyzine (Atarax), are somewhat useful for
pruritus and are sedating. Nonsedating antihista-
mines, such as cetirizine (Zyrtec), loratadine
(Claritin) and fexofenadine (Allegra), are helpful.
E. Systemic corticosteroids are reserved for severe,
widespread reactions to poison ivy, or for severe
involvement of the hands, face, or genitals. Predni-
sone, 1-2 mg/kg, is given PO and tapered over 10-18
days.
References, see page 182.

Diaper Dermatitis
Diaper rash occurs in 50% of infants, with 5% having
severe rash. The peak incidence is between 9 and 12
months of age.

III. Pathophysiology. Breast fed infants have fewer

diaper rashes than formula-fed infants. The frequency
and severity of diaper dermatitis are significantly
lower when the number of diaper changes per day is
eight or more. Superabsorbent disposable diapers
significantly reduce the severity of diaper rash when
compared to cloth diapers.
IV. Classification of diaper dermatitis
A. Dermatoses related to diaper wearing
1. Irritant diaper dermatitis is the most common
form of diaper dermatitis. It is accentuated on the
convex areas, including the buttocks, lower
abdomen, genitalia, and upper thigh, sparing the
creases. It varies in severity from mild erythema
(with or without scales) to papules and macerated
lesions.
a. Management
(1) Irritant diaper dermatitis can best be pre-
vented by keeping the skin in the diaper area
protected from urine and feces by increasing
the frequency of diaper changes and by using
superabsorbent disposable diapers.
(2) A low-potency corticosteroid ointment (hydro-
cortisone 1%) should be applied four times
daily with diaper changes. Anticandidal
agents such as nystatin (Mycostatin),
clotrimazole (Lotrimin), or ketoconazole
 (Nizoral) should also be added.
(3) Thickly applied barrier creams, such as A&D
ointment, zinc oxide pastes or Vaseline, may
be helpful.
2. Candidal diaper dermatitis
a. Candidal diaper dermatitis is characterized by
beefy red plaques with white scales and satel-
lite papules and pustules, which almost always
involve the inguinal creases. It often develops
after an episode of diarrhea. KOH scrapings
may demonstrate pseudohyphae.
b. Candidiasis is treated with topical nystatin
(Mycostatin), clotrimazole (Lotrimin),
miconazole (Monistat), or ketoconazole
(Nizoral) applied 3-4 times daily. Hydrocortisone
1% ointment may help decrease erythema and
inflammation and can be applied at the same
time. Oral nystatin (Mycostatin) suspension,
four times a day, should be used if repeated
episodes of candidal dermatitis occur. The
mother should be evaluated for candidal infec-
tion of the nipples or genital tract. In severe
cases, oral fluconazole (Diflucan) 3 mg/kg per
day as a pulse dose weekly x 2 or for a short
course of 5 to 7 days may be of benefit.
References, see page 182.

Dermatophyte Infections
Dermatophytes constitute a group of about 40 fungal
species that cause superficial infections called
dermatophytoses, ringworm, or tinea.

I. Tinea capitis
A. Tinea capitis presents as inflammation with hair
breakage and loss. Inflammatory changes can
range from minimal scaling and redness that resem-
bles mild seborrhea to tenderness, redness, edema,
purulence, and hair loss (kerion).
B. A hypersensitivity reaction to fungal antigen can
develop, called a dermatophytid or “id” reaction. Id
reactions can present with either a dermatitis that
includes redness, superficial edema involving the
epidermis, and scaling or with a “pityriasis rosea-
like” reaction that involves red, scaly papules and
ovoid plaques on the face, neck, trunk, and proximal
extremities.
C. Topical antifungals are not effective for hair infec-
tion. Griseofulvin is preferred for initial treatment at
a starting dose of about 20 mg/kg per day.
D. Selenium sulfide shampoo (Selsun Blue) is used in
conjunction with oral antifungals to reduce conta-
gion. Tinea capitis is contagious until after 2 weeks
of systemic treatment. Dermatophytid reactions can
be treated with topical corticosteroids.
II. Tinea corporis (ring worm) and tinea cruris
A. Dermatophyte infection of the body surface is
termed tinea corporis. Tinea cruris describes infec-
tion of the upper thigh and inguinal area. Examina-
tion reveals red, scaly papules and small plaques.
These progressively enlarge to form expanding
rings, arcs, or annular patterns.
B. Clearing in previously affected areas produces the
typical “ringworm” appearance. Topical therapy is
the initial treatment approach.
III. Tinea pedis and tinea manuum
A. Tinea pedis infection is often interdigital and is
induced by the warmth and moisture of wearing
shoes. The web spaces become red and scaly.
Fungal infection frequently spreads to involve the
soles of the feet or the palms, with dry scale and
minimal redness. Scaling extends to the side of the
foot or hand. Vesicle and blister formation and
itching are common.
B. Dermatophyte infection often leads to secondary
bacterial infection. A dermatophytid reaction may
occur, as described for tinea capitis.
C. Dermatophyte hand infection presents as dry scale
on the palm. Infection of just one hand in conjunc-
tion with infection of both feet is the most common
pattern.
D. Topical therapy and keeping the involved areas as
dry as possible is recommended for hand or foot
tinea. Oral therapy may be necessary for recalcitrant
disease.
IV. Onychomycosis (tinea unguium)
A. Dermatophyte infection of the nail plate is referred to
as onychomycosis, characterized by dystrophy of
the nail, discoloration, ridging, thickening, fragility,
breakage, accumulation of debris beneath the distal
aspect of the nail and little or no inflammation.
B. Oral treatment is required to clear infection, but
recurrence is very common.
V. Diagnosis
A. Potassium hydroxide (KOH) examination of
scale, hair, or nail is the most rapid diagnostic
method. A sample of scale, hair, or nail from a
possibly infected area is placed on a glass slide,
covered with a few drops of 30% KOH, and gently
heated. The specimen is examined for spores
and/or fungal hyphae.
B. Fungal culture of scale and affected hair or nail can
be accomplished by incubation at room temperature
for 2 to 3 weeks.
VI. Treatment
A. Oral griseofulvin is effective and safe for treatment
of tinea capitis in children. However, its erratic oral
absorption necessitates doses of about 20 mg/kg
per day of the liquid preparation, always adminis-
tered with a fatty meal or beverage (such as milk).
Ultramicrosize griseofulvin can be administered at
the lower dose of 8 to 10 mg/kg per day.
B. Treatment should be continued for 8 to 12 weeks.
Liver function testing is not required when
griseofulvin is used for 6 months or less. Adverse
effects associated with griseofulvin include head-
aches and gastrointestinal upset.

Systemic Antifungal Agents

Griseofulvin 20 mg/kg per day of microsize liquid or 7 to 10

mg/kg per day of ultramicrosize tablets. Microsize: Cap: 250
mg, susp: 125 mg/5 mL, tab: 250, 500 mg
Ultramicrosize: Tab: 125, 165, 250, 330 mg

Itraconazole (Sporanox) 4 to 6 mg/kg per day. Cap: 100 mg,

soln: 10 mg/mL

Terbinafine (Lamisil) 3 to 5 mg/kg per day. Tab: 250 mg

Topical Treatments for Tinea Pedis, Tinea Cruris

and Tinea Corporis

Antifungal Pres Cre Sol Lot Pow Freque

agent crip- am utio ion der ncy of
tion n or appli-
spra cation
y

Imidazoles

Clotrimazol X X X Twice
e 1 percent daily
(Lotrimin,
Mycelex)

Miconazole X X X X Twice
2 percent daily
(Micatin,
Monistat-
Derm)

Econazole X X Once
1 percent daily
(Spectazol
e)

Ketoconaz X X X Once
ole 2 per- daily
cent
(Nizoral)

Oxiconazol X X X Once
e 1 percent daily or
(Oxistat) twice
daily

Allylamines

Naftifine 1 X X Once
percent daily or
(Naftin) twice
daily
 Topical Treatments for Tinea Pedis, Tinea Cruris
and Tinea Corporis

Antifungal Pres Cre Sol Lot Pow Freque

agent crip- am utio ion der ncy of
tion n or appli-
spra cation
y

Terbinafine X X X Once
1 percent daily or
(Lamisil) twice
daily

Butenafine X Once
1 percent daily or
(Mentax) twice
daily

C. Itraconazole (Sporanox) is effective and can be

given orally at 3 to 5 mg/kg per day for 4 to 6 weeks
or until clearing, followed by a 4-week period off of
therapy. A liquid formulation is available. Cap: 100
mg, soln: 10 mg/mL
D. Terbinafine (Lamisil) orally at 3 to 6 mg/kg per day
for 4 to 6 weeks is effective. Tab: 250 mg
E. Topical antifungals can be used once to twice daily
to clear infections other than tinea capitis and
onychomycosis. Newer, more potent topical agents
with once-daily dosing can improve compliance.
F. Hydrocortisone 1% or 2.5% can be added to
antifungal therapy to reduce inflammation. Affected
areas should be kept as cool and as dry as possible.
References, see page 182.

Herpes Simplex Virus Infections

HSV is a member of the herpes-virus family, which
includes varicella zoster virus, Epstein-Barr virus, and
cytomegalovirus. Like all herpes viruses, HSV tends to
establish latent infection and eventually it reactivates and
becomes infectious. Most HSV-infected patients have
asymptomatic infections or the symptoms are only mildly
uncomfortable. However, a substantial number of patients
experience frequent painful recurrences or severe or life-
threatening illnesses.

I. Virology and pathogenesis

A. Two types of HSV exist: HSV-1 and HSV-2. Both
types can infect any anatomic site.
B. HSV-1 may cause asymptomatic infection, oral
lesions, nonoral or non-genital skin lesions, enceph-
alitis, neonatal disease, and genital lesions
C. HSV-2 may cause asymptomatic infection, genital
lesions, neonatal disease, nonoral, nongenital skin
lesions, meningitis, and oral lesions
II. Transmission
A. HSV-1 and HSV-2 are transmitted from person to
person through contact with infected skin lesions,
mucous membranes, and secretions. The incubation
period is 1 to 26 days, and both types may be
transmitted in utero or perinatally.
B. Asymptomatic virus shedding may transmit the
disease. Women who have had previous genital
HSV-2 infection shed virus on 2% of days.
C. Oral/facial HSV infections
1. HSV-1 infection is extremely common in infants
and children. The most common clinical
manifestation of primary HSV-1 infection is
gingivostomatitis, characterized by fever, mal-
aise, myalgia, pharyngitis, irritability, and cer-
vical adenopathy. The illness is self-limited and
usually of short duration.
2. Recurrent HSV-1 infections are most frequently
characterized by oral and lip lesions. Many
individuals who have oral HSV lesions have no
known history of prior gingivostomatitis.
3. HSV-2 also may cause oral lesions and pharyn-
gitis, particularly in sexually active individuals.
D. Genital HSV infections
1. Many HSV infections are asymptomatic, but they
can also cause papular, vesicular, or ulcerative
lesions with pain, itching, urethral or vaginal dis-
charge, and dysuria.
2. Primary infections cause more severe symptoms
and signs, including extensive skin lesions, ten-
 der inguinal adenopathy, and extragenital le-
sions. Primary infections are often associated
with fever, headache, malaise, abdominal pain,
and aseptic meningitis.
3. Eighty percent of persons who have a first
episode of HSV-2 genital infection will experi-
ence a recurrence in the first year. Most patients
who have genital HSV infection have few symp-
tomatic recurrences.
E. HSV encephalitis
1. HSV encephalitis is the most common viral
infection of the CNS. The incidence peaks at 5
to 30 years and at more than 50 years. Ninety-
five percent of cases are caused by HSV-1. HSV
encephalitis is characterized by acute fever,
altered mental status, and focal neurologic
symptoms and signs.
2. Routine CSF findings are not diagnostic. Poly-
merase chain reaction (PCR) can detect HSV
DNA in CSF. HSV is rarely isolated by culture of
the CSF.
3. Electroencephalographic (EEG) findings can be
diagnostic, with spike and slow wave activity
localized to the temporal region.
4. CT scan and MRI may reveal localized edema
and hemorrhage suggestive of HSV infection.
5. The prognosis for HSV encephalitis without
treatment is poor, and even with antiviral ther-
apy, substantial morbidity and mortality occurs.
Prompt institution of empiric therapy is essential
when the clinical diagnosis is suspected.
F. Neonatal HSV infections
1. Infection in neonates results from vertical trans-
mission during the peripartum period in 85%; in
utero or postpartum transmission rarely occurs.
Seventy percent of untreated infants will prog-
ress to disseminated or CNS disease. Most
neonatal infections are caused by HSV-2, al-
though 30% of cases are caused by HSV-1.
Seventy to 80% of infected infants are born to
mothers who are unaware that they have genital
HSV infection.
2. Skin, eye, mouth (SEM) disease accounts for
45% of peripartum infections. SEM disease most
commonly presents in the first or second weeks
of life with vesicular skin lesions which may
occur anywhere on the body. Skin lesions have
an erythematous base with clear or cloudy fluid.
If the infection does not progress to involve the
CNS or viscera, SEM disease has a low mortal-
ity.
3. Central nervous system disease is manifest
as encephalitis, and it accounts for 35% of
peripartum infections.
a. Neonatal HSV CNS disease most commonly
presents in the second to third week of life.
Only 60% will develop skin lesions during the
illness. HSV CNS disease has a 50% mortal-
ity if not treated; with treatment, mortality is
18%. The diagnosis must be considered in
any infant who presents with encephalitis,
seizures, apnea, bradycardia, or cranial
nerve abnormalities.
b. Cerebrospinal fluid findings are nonspecific
and include pleocytosis and increased pro-
tein. Early initiation of therapy is critical when
the diagnosis is suspected.
4. Disseminated disease is characterized by
hepatitis, pneumonitis, and disseminated
intravascular coagulation, and it accounts for
20% of peripartum infections.
a. HSV disseminated disease presents in the
first week of life. Bilateral patchy infiltrates
are indicative of pneumonitis. Skin lesions
may not be present initially.
b. Disseminated HSV disease should be con-
sidered in any infant presenting with sepsis
that is unresponsive to antibiotic therapy, or
who has both pneumonitis and hepatitis.
5. Eye infections
a. HSV is the most common cause of corneal
blindness. HSV keratitis is characterized by
conjunctivitis and dendritic lesions of the
cornea.
b. Topical steroids are contraindicated because
they may facilitate spread of infection to the
deep structures of the eyes.
III. Management of perinatal HSV infection
A. The most reliable predictor of the risk of perinatal
transmission is whether a woman has active genital
lesions at the time of delivery.
B. A thorough physical examination, including vaginal
speculum exam, at the onset of labor should
exclude the presence of active genital lesions. If
HSV lesions are found during labor, prompt cesar-
ean section is recommended.
C. Management of infants exposed to HSV at
delivery
1. Virus cultures of the infant’s conjunctivae, phar-
ynx, skin folds, CSF, and rectum at 24-48 hours
can indicate whether HSV has been transmitted.
Infants who are culture positive for HSV from
any site after 24 hours of life are given acyclovir.
2. During the time when HSV-exposed infants are
in the hospital, they should be placed in contact
isolation. Circumcision is deferred.
IV. Diagnosis of HSV infection
A. HSV-1 and HSV-2 can be isolated by virus culture
from active skin, eye, and genital lesions. In cases
of recurrent disease, virus shedding may be too
brief to be detected by virus culture. Herpes sim-
plex is rarely is recovered from CSF by culture.
B. Although less sensitive and specific than culture,
staining for virus antigens with fluorescent antibod-
ies detects HSV more rapidly.
C. PCR is a useful diagnostic procedure for HSV
encephalitis, with a sensitivity of 75% and a speci-
ficity of 100%.
V. Therapy for HSV infections
A. Parenteral acyclovir is indicated for severe or
potentially severe infections, such as neonatal HSV
infection, HSV encephalitis, and non-localized
infections in immunocompromised patients. Oral
acyclovir decreases new lesion formation and
improves symptoms in first episode genital HSV.
Oral acyclovir has limited effect on the resolution of
recurrent HSV disease.
B. Topical acyclovir is not effective for skin or oral
lesions. The ophthalmic solution is useful for HSV
keratitis, in combination with IV acyclovir.
C. Acyclovir (Zovirax)
1. For serious infections, such as neonatal disease
and encephalitis, 5-10 mg/kg IV is given q8h for
10 to 21 days. Doses up to 20 mg/kg IV q8h are
used for infants who have CNS or disseminated
infection.
2. Oral acyclovir dosage is 20 mg/kg every 8 hours
or 200 mg five times a day for 7-10 days. The
adult regimen is 400 mg three times a day.
3. S u p p r e s s i o n is indicated for
immunocompromised patients or patients who
have more than 6 genital recurrences a year; 5
mg/kg q8h or 400 mg bid. Suppressive therapy
is also used for infants who have HSV SEM
disease.
D. Valacyclovir (Valtrex) is an ester of acyclovir that
has better oral absorption; 1 gm orally twice a day
for 5 days. It has a more convenient dosage sched-
ule than acyclovir and is approved for adolescents.
E. Famciclovir (Famvir) has a more convenient
dosage schedule than acyclovir and is approved for
adolescents. Dosage for first episodes of genital
HSV infection is 250 mg q8h for 5 days, and for
recurrent episodes it is 125 mg twice a day for 5
days.
F. Sexually active individuals known to have genital
HSV infection should be advised to use latex
condoms even during asymptomatic periods.
References, see page 182.

U rticaria, Angi o e d e m a and

Anaphylaxis
Urticaria, angioedema, and anaphylaxis are manifesta-
tions of the immediate hypersensitivity reaction. Immediate
hypersensitivity is an antibody mediated reaction that
occurs within minutes to hours of exposure to a particular
antigen by an immune individual. Twenty percent of the
population will have one of these manifestations, espe-
cially urticaria, at some time during life.

I. Pathophysiology
 A. Urticaria (or hives) is an intensely itchy rash that
consists of raised, irregularly shaped wheals. The
wheals have a blanched center, surrounded by a red
flare. Antigens, chemicals and physical agents
(detergents or ultraviolet light) can cause urticaria.
B. Angioedema is an area of circumscribed swelling of
any part of the body. It may be caused by the same
mechanisms that cause hives except that the immu-
nologic events occur deeper in the cutis or in the
submucosal tissue of the respiratory or gastrointesti-
nal tract.
C. Anaphylaxis is the acute reaction that occurs when
an antigen is introduced systemically into an individ-
ual who has preexisting IgE antibodies.
1. The patient has difficulty breathing from constric-
tion of the major airways and shock due to
hypotension caused by histamine release.
2. Anaphylactoid reactions are not immunologically
mediated. Mannitol, radiocontrast material, and
drugs (opiates, vancomycin) may degranulate
mast cells and cause a reaction that resembles
anaphylaxis.
II. Anaphylaxis
A. Causes of anaphylaxis include penicillins, insect
venoms, airborne allergens, foods (peanuts, eggs,
milk, seafoods, and food dyes and flavors), antitox-
ins to tetanus, and products of animal origin.
B. Symptoms of anaphylaxis include pruritus, injec-
tion of the mucous membranes, bronchospasm, and
hypotension.
C. Prevention of anaphylaxis. Anaphylaxis is best
prevented by avoidance of the cause. However,
anaphylaxis frequently is unanticipated. Individuals
with a history of anaphylaxis should be provided with
injectable epinephrine. Short-term desensitization
may be needed in a patient requiring antibiotic
treatment.
D. Treatment of acute anaphylaxis
1. Epinephrine in a 1:1000 dilution (1.0 mg/mL)
should be injected at 10-20 min intervals at 0.01
mL/kg SQ per dose, with a maximum dose of 0.3
mL per dose SQ.
2. Oxygen should be administered (100%, 4 L/min)
and the airway should be secured.
3. Albuterol, 0.1-0.2 mL/kg in a 5 mg/mL solution,
should be given via nebulizer every 4-6 hours.
4. Administration of diphenhydramine or
chlorpheniramine and corticosteroids should be
considered when a complete response to epi-
nephrine does not occur.
III. Urticaria
A. Hives most commonly results from ingestion of
foods, food additives, or drugs. These usually cause
hive formation for only a few hours to two days.
B. Cold urticaria may be induced by exposure to cold,
which may result in hypotension after immersion in
cold water.
C. Cholinergic urticaria is characterized by the ap-
pearance of small punctate wheals, surrounded by
a prominent erythematous flare. These small papular
urtications are pruritic and appear predominantly on
the neck and upper thorax. The lesions often de-
velop after exercise, sweating, exposure to heat, or
anxiety.
D. Solar urticaria may be caused by various wave-
lengths of light (280-500 nm). It is uncommon, and
it is treated with sun screens.
E. Chronic urticaria is caused by ingestion of food
substances that contain natural salicylates. Sensitiv-
ity to the food additive tartrazine yellow No. 5 fre-
quently is found in patients with salicylate sensitivity.
F. Exercise urticaria is characterized by hives and
bronchospasm after exercise.
G. Genetic deficiencies of complement factor H or
factor I may cause urticaria. Patients who have these
defects frequently develop severe hives, particularly
after exposure to cold or hot water or alcohol inges-
tion.
H. Treatment of urticaria. Urticaria generally is a self-
limiting disorder and usually requires only antihista-
mines. Hydroxyzine 0.5 mg/kg is the most effective
treatment. Diphenhydramine 1.25 mg/kg every 6 hrs
is also effective.
IV. Angioedema
A. Angioedema is similar to hives, but the reaction
occurs deeper in the dermis. It causes diffuse
circumscribed swelling. Angioedema is often ac-
 quired, or it may be observed in an inherited disease
known as hereditary angioneurotic edema (HANE).
B. Hereditary Angioneurotic Edema (HANE)
1. HANE is characterized by episodes of localized
subcutaneous edema of any part of the body.
Attacks of severe abdominal cramps and vomiting
may be caused by edema of the bowel wall.
Severe attacks of colic may occur during infancy.
2. Laryngeal edema may sometimes progress to
total upper airway obstruction, pulmonary edema,
and death. Attacks of palatal and laryngeal
edema may follow dental trauma or occur during
upper respiratory infections.
3. HANE is inherited as an autosomal dominant
disease. However, about 10% of cases are
caused by new spontaneous mutations, which are
passed to offspring.
4. Prophylaxis against attacks of angioedema can
be achieved with impeded androgens (ie, andro-
gens that are only minimally virilizing). Stanozolol,
at a dose of 2 mg/day; or danazol, 50-300
mg/day, can prevent attacks of angioedema.
C. Acute angioedema does not generally respond to
epinephrine, antihistamines, or steroids. Treatment
consists of supportive therapy with IV fluids, analge-
sics, and airway management. Fresh frozen plasma
is generally effective.
References, see page 182.
Infectious Diseases
Fever Without a Source in Children
3 to 36 Months of Age
Most children have a febrile illness before their third
birthday. The majority of children have either a self-limited
viral infection or a source of bacterial infection. When the
history and physical examination cannot identify a specific
source of fever in an acutely ill, nontoxic-appearing child
less than three years of age, the illness is called fever
without a source.

I. Assessment of fever is based upon core temperature,

measured rectally. The threshold of fever that indicates
the need for evaluation in a well-appearing child 3 to 36
months of age is 39ºC (102.2ºF).
II. Causes of fever. The vast majority of young children
with fever have an infectious cause. Acute fever is
defined as <7 days in duration. The source of infection
may be a bacterial or viral illness.
A. In children 3 to 36 months of age presenting with a
febrile illness, an infectious syndrome, usually a
virus, such as croup, bronchiolitis, varicella, or
roseola, is identified in 4 percent. A readily identifi-
able presumed bacterial illness is diagnosed in 56
percent of children. Over 86 percent of these are
otitis media.
B. Serious bacterial infectious syndromes in children 3
to 36 months of age include meningitis, pneumonia,
and cellulitis. Less than one percent have meningi-
tis, 30 percent have pneumonia, and 10 percent
have focal soft tissue infections.
C. Pneumonia. Most children with fever and pneumo-
nia have an abnormality on physical exam, usually
tachypnea, suggesting respiratory tract disease.
Highly febrile young children (<5 years) may have
occult pneumonia with fever and leukocytosis,
without clinical evidence of pneumonia. Twenty-six
percent of 146 patients with fever >39ºC and WBC
>20,000/microL, have pneumonia diagnosed on
chest radiograph.
D. Urinary tract infection (UTI) may be the source of
occult infection in infants and young children with
fever.
E. Bacteremia sometimes occurs in a seriously ill
patient with meningitis, septic arthritis, or cellulitis.
Sepsis is suggested by a child who is ill-appearing,
febrile and without a source of infection.
F. Risk factors or bacteremia
1. Age 3 to 36 months.
2. >39ºC.
3. >15,000/microL.
III. Evaluation
A. History must include information about oral intake,
irritability or lethargy, cough, vomiting, or change in
activity. Children with pneumonia may have cough
or tachypnea, and vomiting without diarrhea can
occur in urinary tract infections. A child with a deep
soft tissue or bone infection may be protecting the
affected area. Underlying medical conditions that
increases the child’s risk for serious infection include
sickle cell disease and urinary tract reflux.
B. The child who has not received three doses of the
Hib and pneumococcal vaccines is at greater risk for
occult bacteremia than the one who is fully immu-
nized.
Clinical and Laboratory Findings in Toxic and
Non-toxic Infants and Children

Febrile Infants at Low Risk Toxic Infant or Child

History Slow, irregular or decreasing

No previous hospitaliza- respiratory rate
tions or chronic illness Head bobbing
Term delivery without Stridor
complications Paradoxic or abdominal
No previous antibiotic breathing
therapy Chest retractions
Physical Examination Central cyanosis
Nontoxic clinical appear- Altered level of conscious-
ance ness
No focal bacterial infection Fever with petechiae
(except otitis media) Tachypnea
Activity, hydration and per- Grunting
fusion normal Prolonged expiration
Social Situation Nasal flaring
Parents/caregiver mature Poor muscle tone
and reliable Poor or delayed capillary refill
Thermometer and tele- Tachycardia
phone at child’s home
Laboratory Criteria
White blood cell count of
5,000-15,000/mm3
Band cell count
<1,500/mm3
Normal urinalysis (<5
white blood cells/high-
power field)
When diarrhea is present,
less than 5 white blood
cells/high-power field in
stool

C. Physical examination. Febrile children who are

acutely ill with lethargy, poor perfusion, hypoventila-
tion or hyperventilation, and cyanosis have the
appearance of being toxic or septic. They are
considered to have a significant bacterial infection
until proven otherwise. Cultures of blood, urine, and
CSF should be obtained, fluid and antibiotic therapy
initiated, and admission to the hospital arranged.
1. Signs of infection
a. Abnormal vital signs such as tachycardia,
tachypnea, or pulse oximetry <95 percent.
b. Lesions in the oropharynx may identify herpes
gingivostomatitis (anterior ulcers) or
coxsackie virus (pharyngeal vesicles).
c. Increased work of breathing is indicated by
nasal flaring, retractions or use of accessory
muscle, rales or decreased breath sounds.
d. Abdominal tenderness.
e. Pain with bone palpation or passive joint
range of motion.
f. Skin findings, such as petechiae, cellulitis, or
viral exanthem.
D. Laboratory testing
1. WBC and ANC counts. Occult bacteremia is
suggested by WBC >15,000/microL and abso-
lute neutrophil count (ANC) >10,000/microL.
However, 20 percent of patients with occult
bacteremia may have a WBC <15,000/microL.
2. Cultures. The definitive diagnosis of a serious
bacterial infection is often made with cultures,
although the inherent delay between the initial
evaluation of the patient and the availability of
culture results complicates management deci-
sions.
3. Blood. Continuously monitored blood culture
systems have decreased the length of time for a
blood culture to turn positive.
4. Urine. A clean catch is the preferred method of
urine collection for culture in the child who is
toilet-trained. For the diapered child, urine
should be collected by catheterization or
suprapubic aspiration. Bag specimens should
not be sent for culture because they are fre-
quently contaminated.
5. CSF. Children who are being evaluated for fever
without a source should be well-appearing and,
therefore, not require lumbar puncture. CSF
should be obtained from any patient with sus-
pected meningitis.
6. Chest radiograph may be appropriate in pa-
tients with tachypnea, respiratory distress, oxy-
gen saturation <97 percent, or WBC >20,000-
25,000/microL.
IV. Management
A. Pre-conjugate vaccine strategies
1. Treatment is required for children with WBC
>15,000/microL or an abnormal urinalysis with
parenteral ceftriaxone, pending blood and/or
urine culture results. The prevalence of occult
bacteremia and the possibility of missing a case
of meningitis were high enough to justify testing
many children and using broad spectrum antibi-
otics.
2. For those children <6 months or those who are
incompletely immunized, urinalysis, urine cul-
ture, CBC, blood culture, and chest radiograph
if WBC >20,000-25,000/microL are recom-
mended. Patients with WBC >15,000/microL
should receive antibiotic therapy.
V. Recommendations. Children who are ill-appearing or
have unstable vital signs should receive cultures of
blood, urine and, when meningitis is suspected, CSF.
Presumptive antibiotic therapy should be initiated. For
children 3 to 36 months of age, with fever >39ºC, who
are well-appearing, have no underlying medical condi-
tion that would alter susceptibility to infection, and no
identifiable focus of infection should be evaluated as
follows:
A. For children <6 months, and for any child <36
months who has not been completely immunized,
the following testing and treatment strategies are
recommended: CBC, urinalysis, blood and urine
cultures, CXR when WBC >20,000/microL, and
antibiotic therapy with parenteral ceftriaxone when
WBC >15,000/microL.
B. Alternatives for children who cannot receive
ceftriaxone include clindamycin or a macrolide. For
girls between 6 and 24 months of age and
uncircumcised boys between 6 and 12 months who
have received three doses each of Hib vaccine and
PCV7, urinalysis and urine culture should be
obtained.
References, see page 182.

Bacterial Meningitis
Therapy should be initiated immediately after the results
of lumbar puncture (LP) are received or immediately after
LP alone if the clinical suspicion is very high. Should this
procedure be delayed by the need for cranial imaging,
blood cultures should be obtained and antibiotics should
be administered empirically before the imaging study,
followed as soon as possible by the LP.

I. Pretreatment evaluation
A. History. Bacterial meningitis often presents with
fever, vomiting, and nuchal rigidity. Symptoms
consistent with a viral infection of the upper respira-
tory tract commonly precede the development of
meningitis.
B. Older children may complain of headache,
photophobia, or neck or back pain. Younger children
are commonly irritable or lethargic. 20 to 30 percent
of children have a seizure prior to diagnosis.
C. Children have a stiff neck, and Kernig and
Brudzinski signs may be present. A bulging or tense
fontanelle in an infant or a sixth cranial nerve palsy
suggests increased intracranial pressure (ICP).
Advanced illness is characterized by lethargy,
dehydration, or signs of septic shock.
D. Seizure activity should be assessed, and the follow-
ing historical information should be obtained before
antibiotic treatment of presumed bacterial meningitis
is instituted:
1. Serious drug allergies.
2. Vaccines received.
3. Recent travel.
4. Recent exposure to someone with meningitis.
5. Recent infections (especially respiratory and otic
infections).
6. Recent head trauma or craniotomy.
7. Recent use of antibiotics.
8. The presence of a progressive petechial or
ecchymotic rash.
E. Blood tests. Initial blood tests should include a
complete blood count with differential and platelet
count, and two sets of blood cultures. Serum electro-
lytes, blood urea nitrogen and serum creatinine
 concentrations are helpful in planning fluid adminis-
tration.
F. CSF examination should be obtained for cell count
and differential, glucose and protein concentration,
Gram stain, and culture. Cytocentrifugation of CSF
enhances the likelihood of detection of bacteria on
Gram-stained specimens. The CSF Gram stain is
positive in 90 percent with pneumococcal meningitis
and in 80 percent with meningococcal meningitis.
G. Characteristic findings include an increased white
blood cell (WBC) count, usually composed primarily
of neutrophils; an elevated protein concentration;
and a low glucose concentration, which may be less
than 10 mg/dL. Bacterial antigen tests should be
reserved for cases in which the initial CSF Gram
stain is negative and culture is negative at 48 hours.
Polymerase chain reaction (PCR) of CSF and blood
is most helpful for documenting meningococcal
disease in the patient with negative cultures.
H. Children with focal neurologic findings or coma
should receive a computer tomographic scan before
LP.

Cerebrospinal Fluid Findings in Normal and In-

fected Hosts

Disorder Colo WBC Gluc- Pro- Gram’

r Count ose tein s Stain
(/mm3) (mg/d (mg/d and
L) L) culture

Normal clear <10 >40 90 negat-

infant ive

Normal clear 0 >40 <40 negat-

child or ive
adult

Bacterial cloud 200- <40 100- usually

mening- y 10000 500 positive
itis

Viral clear 25-1000 >40 50-100 negat-

mening- (<50% ive
itis PMN)

Common Etiologic Agents of Meningitis by Age

Group

Organism 0-3 3-36 3-21 Immun

Mont Month Years o-
hs s comp-
romise
d

Group B X
Streptococcus

Escherichia X
coli

Listeria X
monocytogen
es

Streptococcus X X X
pneumoniae

Neisseria X X X
meningitidis

Fungus X

Cryptococcus X

Tuberculosis X

Virus X X X X

Note: Haemophilus influenzae no longer is a com-

mon pathogen in countries where the conjugate
vaccines are used routinely.

I. Neurologic sequelae and steroids. Permanent

neurologic sequelae occur in 16 to 36 percent of
children who survive an episode of bacterial menin-
gitis. A common complication of bacterial meningitis
is hearing loss of varying severity.
 1. Corticosteroid therapy should be administered
for H. influenzae type b meningitis. Dexametha-
sone for pneumococcal meningitis is recom-
mended for infants and children 6 weeks of age
and older.
J. Repeat CSF analysis. Selected infants and chil-
dren with bacterial meningitis have a repeat analy-
sis of CSF between 24 and 36 hours after initiating
therapy. Reexamination of CSF is recommended in
the following situations:
1. To assure sterilization of the CSF in patients with
resistant organisms, such as pneumococci
resistant to cefotaxime or ceftriaxone.
2. When dexamethasone is administered for
pneumococcal meningitis, which might interfere
with the ability of the physician to assess clinical
response such as resolution of fever.
3. When the clinical response to therapy for
pneumococcal meningitis is poor despite treat-
ment with appropriate agents.
4. Two to three days after the initiation of therapy
for meningitis caused by a Gram negative rod.
5. Repeat CSF cultures should be sterile.
II. Empiric therapy
A. From age 1 to 24 months of age, S. pneumoniae
followed by N. meningitidis are the two most com-
mon causes of bacterial meningitis.
B. From age 2 through 18 years, N. meningitidis was
the most common cause, accounting for more than
one-half of cases, followed by S. pneumoniae.
C. Infants and children with no known immune
problem. Meningococcus and pneumococcus are
the most likely organisms in immunocompetent
infants and children who have been immunized with
the conjugate H. influenzae vaccine. High doses of
third-generation cephalosporins, such as
cefotaxime (225 to 300 mg/kg per day in three or
four divided doses; maximum dose 12 g per day) or
ceftriaxone (100 mg/kg per day in one or two
divided doses; maximum dose 4 g per day) plus
vancomycin (60 mg/kg per day in four divided
doses) should be started.

Dosages of Antibiotics Administered Intrave-

nously to Newborn Infants and Children

Antibiotic Age (Days) Dosage Desired Se-

rum Con-
centrations
(Mcg/mL)

Ampicillin 0-7 50 Not critical to

7-30 mg/kg/dose measure
q8h
>30 50-75
mg/kg/dose
q6h
50-75 q6h

Cefotaxime 0-7 50 Not critical to

(Claforan) 7-30 mg/kg/dose measure
q8h
>30 50-75
mg/kg/dose
q6h
75 q6h

Ceftriaxone All 80-100 Not critical to

(Rocephin) mg/kg/dose. measure
At diagnosis,
12 h, 24 h,
and every 24
h thereafter

Gentamicin 0-7 2.5 Peak, 6-10

7-30 mg/kg/dose Trough,<2
q12h
>30 2.5
mg/kg/dose
q8h
2.5
mg/kg/dose
q8h
 Antibiotic Age (Days) Dosage Desired Se-
rum Con-
centrations
(Mcg/mL)

Vancomycin 0-7 15 Peak, 30-40

7-30 mg/kg/dose Trough, 5-10
>30 q12h
15
mg/kg/dose
q8h
15
mg/kg/dose
q6h

D. Children with known immune deficiency

1. S. pneumoniae and S. aureus were the two most
common isolates causing meningitis among
children with cancer and neutropenia.
Cefotaxime or ceftriaxone plus vancomycin given
are empiric coverage. If a Gram negative rod is
observed on Gram stain of the CSF, the addition
of an aminoglycoside is recommended.
2. S. pneumoniae and L. monocytogenes are the
most likely causes of bacterial meningitis with
defective cell-mediated immunity. In patients
who are at risk for developing listerial infection,
high doses of ampicillin (300 to 400 mg/kg per
day in four or six divided doses) should be given
along with cefotaxime or ceftriaxone plus
vancomycin until results of cultures return.
E. Patients with recent neurosurgery. In addition to
the usual nosocomial pathogens, coagulase-nega-
tive staphylococci (S. epidermidis) and S. aureus
are important causes of meningitis after neurosur-
gery. Empiric therapy in this setting consists of a
combination of vancomycin and a third-generation
cephalosporin. An aminoglycoside should be added
if Gram-negative bacilli are noted on CSF Gram
stain.
III. Therapy for specific pathogens
A. Haemophilus influenzae. Third-generation
cephalosporins such as cefotaxime (200 mg/kg per
day in three or four divided doses) and ceftriaxone
(loading dose of 75 mg/kg followed by 100 mg/kg
per day in one or two divided doses) are effective.
Rifampin prophylaxis is indicated for the patient and
selected close contacts.
B. Neisseria meningitidis. Meningococcal meningitis
is suggested by disease occurring in children and
young adults, often accompanied by a diffuse,
petechial rash. This infection is best treated with
penicillin. A third-generation cephalosporin is an
effective alternative to penicillin. The index patient
may need to take rifampin or ceftriaxone to eradi-
cate the organism from the nasopharynx, unless
the meningitis was treated with ceftriaxone or
cefotaxime.
C. Streptococcus pneumoniae is the most common
cause of meningitis in infants and children from 1 to
23 months of age. Treatment consists of penicillin
for 10 to 14 days at a dose of 300,000 units/kg per
day intravenously every four to six hours. Good
results are also obtained with cefotaxime.
Vancomycin would be administered until the
pneumococcal isolate is determined to be suscepti-
ble to penicillin or cefotaxime.
D. Listeria monocytogenes, a Gram positive rod, is
an important cause of bacteremia and meningitis,
particularly in patients with impaired cell-mediated
immunity. Listeria is treated with ampicillin and
gentamicin.
References, see page 182.

Acute Otitis Media

Otitis media is the most frequent diagnosis in sick children
visiting physicians’ offices. The disease is most prevalent
in infancy. Fluid may persist for weeks to months after the
onset of signs of acute otitis media despite treatment.

I. Epidemiology
A. The highest incidence of acute otitis media occurs
between six and 24 months of age. The incidence
then declines with age except for a limited reversal
of the downward trend between five and six years of
 age, the time of school entry. Acute otitis media is
infrequent in school age children, adolescent, and
adults.
B. Risk factors
1. Age. The peak age-specific attack rate occurs
between six and 18 months of age. Children who
have had little or no experience with otitis media
by the age of three years are unlikely to have
subsequent severe or recurrent disease.
2. Sex. Males have a higher incidence of acute otitis
media than females.
II. Microbiology
A. Bacteria. Most of the bacterial isolates from middle
ear fluid are streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella catarrhalis.
The conjugate Haemophilus influenzae type b (Hib)
vaccine has had little impact on Haemophilus acute
otitis media because more than 90 percent of cases
of Haemophilus acute otitis media are due to
nontypable strains.
B. Streptococcus pneumoniae is the most important
bacterial cause of otitis media, associated with 25 to
40% of cases.
C. Haemophilus influenzae. Nontypable strains of H.
influenzae are second in importance in causing
acute otitis media, responsible for 10 to 30% of
cases. One-third to one-half of strains of H.
influenzae recovered from middle ear fluids produce
beta-lactamase.
D. Moraxella catarrhalis has increased in frequency in
middle ear aspirates of children with acute otitis
media, responsible for 10%. More than 90% of
strains produced beta-lactamase.
E. Other bacteria. Group A streptococcus is only an
occasional pathogen. Small numbers are identified
for Staphylococcus aureus and anaerobic bacteria.
Gram-negative bacilli are responsible for 20% of
cases of acute otitis media in the first months of life,
but these organisms are rarely present in the
middle-ear effusions of older infants and children
with acute otitis media. Pseudomonas aeruginosa is
associated with chronic suppurative otitis media.
F. Viruses. Viral infection is frequently associated with
acute otitis media. Sixteen percent of middle-ear
fluids of children with acute otitis media are associ-
ated with viruses, most frequently are respiratory
syncytial virus, rhinoviruses, influenza viruses and
adenoviruses.
III. Clinical manifestations. Symptoms of acute otitis
media include otalgia or ear pain, hearing loss, and
vertigo. Otalgia is more common in adolescents and
adults than in young children.
A. Otorrhea or ear discharge or swelling about the ear
(which may indicate disease of the mastoid) are
specific physical findings, if present. Nonspecific
symptoms and signs include fever, irritability, head-
ache, apathy, anorexia, vomiting and diarrhea.
IV. Diagnosis. The diagnosis of acute otitis media re-
quires evidence of an acute history, signs and symp-
toms of middle ear inflammation, and the presence of
middle ear effusion.
A. The hallmark of establishing the diagnosis is the
demonstration of fluid by pneumatic otoscopy; the
finding of a red tympanic membrane alone is not
sufficient to make a diagnosis.
B. Otoscopic examination identifies a tympanic
membrane that is often erythematous due to
inflammation, bulges because of the expansion of
fluid in the middle ear and is immobile because the
middle ear is fluid rather than air filled. Cloudiness
is also common.
C. Aspiration of the middle ear fluid is warranted if the
patient with acute otitis media is toxic, has immune
deficits, or has failed prior courses of antibiotics.
V. Treatment and Prevention of Acute Otitis Media
A. Symptomatic therapy
1. Ibuprofen and acetaminophen may improve
pain. The topical agent, Auralgan (combination
of antipyrine, benzocaine, and glycerin) im-
proves ear pain scores at 30 minutes after
treatment.
2. First-line antimicrobial therapy. Amoxicillin is
the drug of choice for otitis media because it is
effective, safe, is relatively inexpensive, and
has a narrow microbiologic spectrum. Doubling
the dose to 80 to 90 mg/kg per day divided into
two doses increases the concentration of
amoxicillin in the middle ear. The increased
concentrations provide activity against most
intermediate strains of S. pneumoniae and
many of the resistant strains. Only S.
pneumoniae that are highly resistant to penicil-
lin will not respond to this regimen.
3. Penicillin-allergic patients. In patients who
report penicillin allergy but who did not experi-
ence a Type 1 hypersensitivity reaction (urti-
caria or anaphylaxis), cefdinir (14 mg/kg per
day in 1 or 2 doses), cefpodoxime (10 mg/kg
per day, once daily), or cefuroxime (30 mg/kg
per day in 2 divided doses) can be used.
4. A macrolide (erythromycin plus sulfisoxazole,
azithromycin, or clarithromycin) is preferred for
children who have had a Type 1 reaction to
amoxicillin or other beta-lactam antimicrobial
agents. Erythromycin plus sulfisoxazole
([Pediazole] 50 to 150 mg/kg per day divided
into 4 doses) may be the most effective, but is
has an unpleasant taste. Five days of
azithromycin (Zithromax) 10 mg/kg per day as
a single dose on day 1 and 5 mg/kg per day for
days 2 through 5) or clarithromycin ([Biaxin] 15
mg/kg per day divided into 2 doses) can be
used. Trimethoprim-sulfamethoxazole (Bactrim)
may still be useful in regions where
pneumococcal resistance to this combination is
not a concern.
5. Duration of therapy
a. A 10-day course of an oral antimicrobial is
recommended for the treatment of acute
otitis media. However, a shorter course may
be adequate, and a single dose of
azithromycin has been approved.
b. Ten-day therapy is more effective in patients
under age 6. A five- to seven-day course of
antibiotics is appropriate for children ages 6
and older who have mild to moderate dis-
ease.
6. Treatment failures. With antimicrobial therapy,
the signs of systemic and local illness usually
resolve in 24 to 72 hours. Lack of improvement
by 48 to 72 hours suggests either another
disease is present or the initial therapy was not
adequate.
a. High-dose amoxicillin-clavulanate (90 mg/kg
per day amoxicillin, with 6.4 mg/kg per day of
clavulanate in two divided doses) is recom-
mended. Alternatives include the drugs cited
above for penicillin allergic patients, includ-
ing cefdinir, cefpodoxime, and cefuroxime.
b. Ceftriaxone (50 mg/kg IM) is effective for the
treatment of acute otitis media in children
who fail amoxicillin. Three consecutive doses
is superior to a single dose. Children should
be given the first dose and then observed
carefully for 48 hours, a second or even third
dose should be given if clinical symptoms
and signs do not respond to the first injec-
tion. Patients who fail amoxicillin-clavulanate
should be treated with a three day course of
parenteral ceftriaxone.
 Second-Line Antibiotic Therapy for Acute Otitis
Media

Drug Dosage Comments

Amoxicillin- 40 mg/kg of Diarrhea com-

clavulanic acid amoxicillin compo- mon
(Augmentin) nent in 3 divided
doses

Cefuroxime axetil 500 mg in 2 divided

(Ceftin) doses

Ceftriaxone 50 mg/kg IM
(Rocephin)

7. Persistent middle-ear effusion is common after

the resolution of acute symptoms and is not an
indication of treatment failure. Middle-ear effusion
may persist after the onset of acute otitis media in
70 to 10% at three months.
8. Chemoprophylaxis should be considered for
patients with three or more episodes of otitis
media in six months and four or more episodes in
12 months. Amoxicillin or sulfisoxazole is used at
one-half the therapeutic dose administered once
a day during the fall, winter and early spring.
9. Vaccines
a. Conjugate pneumococcal vaccine is recom-
mended for universal immunization of infants to
age two years and selective immunization of
children two to five years of age. Children with
severe and recurrent episodes of otitis media in
the two- to five-year-old age groups are candi-
dates for the conjugate vaccine.
b. Influenza vaccine is now recommended for all
infants 6 to 24 months of age and should be
given in the fall to older children who have had
recurrent episodes of acute otitis media in the
preceding winter.
10. Surgery
a. Tympanostomy tubes have been accepted as
a treatment for chronic otitis media or otitis
media with effusion, their role in the prevention
of recurrent acute otitis media is more contro-
versial.
b. Adenoidectomy with or without tonsillec-
tomy has been documented to be of value in
reducing the number of acute episodes for
children who have recurrences after an initial
placement of tympanostomy tubes. These
surgical procedures do not appear to be an
effective primary preventive measure for chil-
dren with recurrent acute otitis media.
References, see page 182.

Pneumonia
A lower respiratory tract infection (LRI) develops in one in
three children in the first year of life. Twenty-nine percent
of these children develop pneumonia, 15% develop croup,
34% tracheobronchitis, and 29% bronchiolitis.

I. Clinical evaluation of pneumonia

A. Cough. Pneumonia usually causes cough that
persists day and night. Patients who cough sponta-
neously throughout the office visit are likely to have
lower respiratory tract disease.
B. Grunting occurs in 20% of infants who have
bronchiolitis or pneumonia. Grunting prevents
collapse of narrowed airways and improves oxygen-
ation.
C. Chest pain. Pneumonia causes chest pain when
the infection develops near the pleura. Pneumonia
that involves the diaphragmatic pleura may present
as abdominal pain. Older children may complain of
diffuse chest or abdominal pain, which is caused by
persistent cough and repeated muscle contraction.
D. Tachypnea. Increased respiratory rate is one of the
earliest and most consistent signs of lower respira-
tory tract disease.
 Abnormal Respiratory Rates by Age

Age Abnormal

<2 months >60 bpm

2-12 months old >50 bpm

>1 year old >40 bpm

E. Retractions of the intercostal spaces may occur

with pneumonia because of decreased compliance
or increased airway resistance.
F. Auscultation
1. Signs of consolidation include dullness to
percussion and increased transmission of the
voice on auscultation.
2. Crackles are the fine popping sounds that occur
when previously closed airways open suddenly.
They indicate pulmonary parenchymal disease.
3. Wheezing is generated by narrowed airways. It
can be caused by bronchiolitis, asthma, early
pulmonary edema, subglottic stenosis, or tra-
cheal compression.
G. Cyanosis occurs at an oxygen saturation of 67%;
however, cyanosis will not manifest in the presence
of anemia. It is not a sensitive predictor of pneumo-
nia because significant hypoxemia may be present
before cyanosis is visible.
II. Diagnostic evaluation of lower respiratory infec-
tions
A. Chest radiograph. A chest radiograph should be
obtained when the child with pneumonia appears
acutely ill.
B. Laboratory tests
1. WBC count should be obtained for children who
have significant fever (>38EC in infants, >39EC
in children), who appear ill, or who are hos-
pitalized.
2. Blood cultures are rarely positive in children
with pneumonia. They should be obtained in
infants and children with high fever, ill appear-
ance, or upon hospitalization.
3. Bacterial antigen assays of urine by latex
agglutination, or antibody tests of blood are
indicated when unusual infections are suspected
or when pneumonia is unresponsive to therapy.
4. Nasopharyngeal cultures for viruses and
immunofluorescence studies for viral antigens
are obtained when therapy with antiviral agents
is being considered.
Empiric Antibiotic Treatment of Pediatric Pneu-
monia

Age group Empiric regimen

Neonate Ampicillin (for those

Bacterial (not <2000 g and 0 to
chlamydia) 7 days old: 100
mg/kg per day in two
divided doses; <2000
g and 8 to 28 days
old: 150 mg/kg per
day in 3 divided
doses; >2000 g and
0 to 7 days old: 150o
mg/kg per day in 3
divided doses; >2000
g and 8 to 28 days
old: 200 mg/kg per
day in four divided
doses; PLUS
Gentamicin (gestational
age plus weeks
of life - for those <26
weeks: 2.5 mg/kg per
dose every 24 hours;
27-34 weeks: 2.5r/kg
per dose every 18
hours; 35-42 weeks:
2.5 mg/kg per dose
every 12 hours; >43
weeks: 2.5 mg/kg per
dose every 8 hours)

Viral (herpes simplex) Acyclovir (60 mg/kg per

day IV in three divided
doses

One to four months Cefuroxime (150 mg/kg

Bacterial (not per day IV in three di-
chlamydial) vided doses [MAX 4
g/day]); OR
Ceftriaxone (75 to 100
mg/kg once daily OR
cefotaxime (100 to 200
mg/kg per day IV in 4
divided doses [MAX 10
to 12 g/day]) PLUS
clindamycin (30 to 40
mg/kg per day IV in 3 or
4 divided doses [MAX 1
to 2 g/day]) if compli-
cated by parapneumonic
effusion

Chlamydial Erythromycin (4o to 50

mg/kg per day in four
divided doses); OR
Azithromycin (10 mg/kg
on day 1 followed by 5
mg/kg daily for 4 more
days [MAX 500 mg on
day 1 and 250 mg there-
after]);
OR Clarithromycin (15
mg/kg per day in two di-
vided doses [MAX 1
g/day])

Four months to five Oral regimens

years Amoxicillin (80 to 100
Bacterial (not mg/kg per day PO in 3
Mycoplasmal or divided doses [MAX 600
Chlamydia) mg/day])
Parenteral regimens
Ampicillin (150 to 200
mg/kg per day IV in 4
divided doses [MAX
10 to 12 g/day])
OR
Cefuroxime (dosing
as above)
 Age group Empiric regimen

Older than five years Eryth r o m ycin ,

Mycoplasmal/chlamydial a z i t h r o m yc i n ,
Bacterial clarithromycin (dosed as
above); OR doxycycline.
Ampicillin (dosed as for 4
months to 5 years); OR
cefuroxime (dosed as
above) + coverage for
Mycoplasma or
Chlamydia

III. Treatment of Community-Acquired Pneumonia in

Children
A. Neonates
1. Pneumonia is treated with empiric intravenous
ampicillin (150 mg/kg per day divided every 12
hours if meningitis is also suspected and 50 to
100 mg/kg every 12 hours if not) and gentamicin
(dose based upon gestational age and renal
function). This regimen will cover the most likely
pathogens, group B streptococcus, Listeria
monocytogenes, and Enterobacteriaceae spp.,
especially Escherichia coli K1.
2. During the first two weeks of life, herpes simplex
virus (HSV) is a possible cause of pneumonia.
Intravenous acyclovir (60 mg/kg in three divided
doses for 21 days) should be considered for
suspected patients.
B. Infants and older children
1. Bacterial pneumonia. When bacterial disease
is suspected, the second-generation
cephalosporin, cefuroxime (150 mg/kg per day
in three divided doses up to a maximum of 4 to
6 g/d), provides good coverage against the
usual pathogens.
2. Other possible regimens include: a third-genera-
tion cephalosporin, ceftriaxone (75 to 100 mg/kg
once daily up to a maximum dose of 4 g/d) or
cefotaxime (100 to 200 mg/kg per day in four
divided doses up to a maximum of 10 to 12 g/d),
for patients three weeks to three months old or
ampicillin (150 to 200 mg/kg per day in four
divided doses) for those four months to four
years old since disease caused by beta-
lactamase-producing organisms (eg, Staphylo-
coccus aureus and Haemophilus influenzae) is
not likely in this older age group.
3. With the concern for increasing beta-lactam
resistance among Streptococcus pneumoniae
isolates and the increasing prevalence of
community-acquired methicillin-resistant S.
aureus (MRSA) infections, empiric treatment
with Clindamycin (30 to 40 mg/kg per day in
three to four divided doses up to a maximum of
1 to 2 g/d) is reasonable for complicated cases
of community-acquired pneumonia.
4. Since there are reports of antibiotic failures due
to treatment of non-susceptible S. pneumoniae
with beta-lactams and concern for MRSA, se-
verely ill patients requiring admission to the
intensive care unit should be treated with
vancomycin (40 mg/kg per day IV in four divided
doses up to a maximum of 2 to 4 g/d) in addition
to a third-generation cephalosporin and
azithromycin.
5. Amoxicillin is generally considered the drug of
choice for the outpatient treatment of patients
younger than five years of age with community-
acquired pneumonia. Because of the increasing
prevalence of pneumococcal penicillin-resis-
tance, higher doses (80 to 100 mg/kg per day
PO in three divided doses up to a maximum of 2
to 3 g/d) are recommended.
a. The macrolides are generally recommended
for the outpatient treatment of the older child
and adolescent because of the greater likeli-
hood of infection due to Mycoplasma
pneumoniae and Chlamydia pneumoniae.
Doxycycline (4 mg/kg PO per day in two
divided doses up to a maximum of 200 mg/d)
is an alternative, especially if a macrolide
hypersensitivity exists. Approximately 50
percent of S. pneumoniae isolates are now
 resistant to the macrolides, so a failure to
respond may indicate the need to change
therapy to high-dose amoxicillin or a
cephalosporin for better pneumococcal
coverage. For the older child admitted to the
hospital, addition of a macrolide to the previ-
ously suggested antibacterial regimen may
be necessary if M. pneumoniae, C.
pneumoniae or legionellosis is suspected.
6. Duration of therapy. Seven to 10 days should be
adequate for routine pathogens causing uncom-
plicated infection. Switch to oral therapy in
patients who have received parenteral antibiot-
ics when the patient has become afebrile for 24
to 48 hours and is able to keep down food.
C. Hospitalization. Children who are toxic,
hypoxemic, dyspneic, apneic, significantly
tachycardic for age, unable to feed, dehydrated, or
have an underlying condition that may be worsened
by the pneumonia require hospitalization. Hospital-
ization should be considered for most children less
than four months of age, unless a viral etiology is
suspected and they are relatively asymptomatic.
IV. Neonates
A. Bacterial pneumonia in the first day of life may be
impossible to distinguish from hyaline membrane
disease or transient tachypnea of the newborn.
Therefore, respiratory distress in newborns should
be treated as bacterial pneumonia until proven
otherwise. When associated with chorioamnionitis,
it is caused most commonly by Escherichia coli or
by group B streptococci (GBS). However,
Haemophilus influenzae, Streptococcus
pneumoniae (pneumococcus), group D strepto-
cocci, Listeria, and anaerobes also may be present
in this setting.
B. Infants also may develop bacterial pneumonia
transnatally, secondary to GBS. The onset of
symptoms tends to occur 12 to 24 hours after birth.
C. Chest radiographs of infants who have bacterial
pneumonia may exhibit a diffuse reticular nodular
appearance; but, in contrast to hyaline membrane
disease, they tend to show normal or increased lung
volumes with possible focal or coarse densities.
D. In the newborn who has bacterial pneumonia, blood
cultures obtained before the initiation of antibiotics
commonly grow the offending organism. Cultures of
urine and cerebrospinal fluid should be obtained at
the time of the blood culture.
E. Empiric treatment should be initiated with
ampicillin 100 mg/kg per day divided every 12 hours
(infants <1.2 kg) or every 8 hours (infants >1.2 kg)
and cefotaxime 100 mg/kg per day divided every 12
hours or 150 mg/kg per day divided every 8 hours
(infants >1.2 kg and >7 days old). Gentamicin is an
alternative. Treatment should be continued for at
least 10 days.
References, see page 182.

Bronchiolitis
Bronchiolitis is an acute wheezing-associated illness,
which occurs in early life, preceded by signs and symp-
toms of an upper respiratory infection. Infants may have a
single episode or may have multiple occurrences in the
first year of life.

I. Epidemiology
A. Bronchiolitis occurs most frequently from early
November and continues through April.
B. Bronchiolitis is most serious in infants who are less
than one year old, especially those 1-3 months old.
Infants at risk include those who are raised in
crowded living conditions, who are passively ex-
posed to tobacco smoke, and who are not breast-
fed.
II. Pathophysiology
A. Respiratory syncytial virus (RSV) is the leading
cause of bronchiolitis in infants and young children,
accounting for 50% of cases of bronchiolitis requir-
ing hospitalization.
B. Infants born prematurely, or with chronic lung dis-
ease (CLD), immunodeficiency or congenital heart
disease are at especially high risk for severe RSV
illness.
 C. RSV is transmitted by contact with nasal secretions.
Shedding of virus occurs 1 to 2 days before symp-
toms occur, and for 1 to 2 weeks afterwards. Symp-
toms usually last an average of 5 days.
D. Parainfluenza viruses are the second-most-frequent
cause of bronchiolitis. They cause illness during
autumn and spring, before and after outbreaks of
RSV. Influenza A virus, adenovirus, rhinovirus and
Mycoplasma pneumonia can all cause bronchiolitis.
Rhinovirus and mycoplasma pneumonia cause
wheezing-associated respiratory illness in older
children, while parainfluenza virus and RSV can
cause wheezing at any age.
III. Clinical evaluation of bronchiolitis
A. Symptoms of RSV may range from those of a mild
cold to severe bronchiolitis or pneumonia. RSV
infection frequently begins with nasal discharge,
pharyngitis, and cough. Hoarseness or laryngitis is
not common. Fever occurs in most young children,
with temperatures ranging from 38E°C to 40E°C
(100.4E°F to 104E°F).
B. Hyperresonance of the chest wall may be present,
and wheezing can be heard in most infants without
auscultation. The wheezing sound is harsh and low
in pitch, although severely affected infants may not
have detectable wheezing. Fine “crackles” are
usually heard on inspiration. Substernal and inter-
costal retractions are often noted.
C. Cyanosis of the oral mucosa and nail beds may
occur in severely ill infants. Restlessness and
hyperinflation of the chest wall are signs of impend-
ing respiratory failure.
IV. Diagnosis
A. Infants with bronchiolitis present symptoms of an
upper respiratory illness for several days and wheez-
ing during the peak RSV season.
B. Chest radiography typically shows hyperexpansion
and diffuse interstitial pneumonitis. Consolidation is
noted in about 25% of children, most commonly in
the right upper or middle lobe.
C. Oxygen saturation values of <95% suggest the
need for hospitalization.
D. Arterial blood gases should be obtained to assess
the severity of respiratory compromise. Carbon
dioxide levels are commonly in the 30-35 mm Hg
range. Respiratory failure is suggested by CO2
values of 45-55 mm Hg. Oxygen tension below 66
mm Hg indicates severe disease.
E. White blood cell count may be normal or elevated
slightly, and the differential count may show
neutrophilia.
F. Enzyme-linked immunosorbent assays (ELISA) of
nasal washings for RSV are highly sensitive and
specific.
V. Management
A. Outpatient management of bronchiolitis is appropri-
ate for infants with mild disease.
B. Criteria for hospitalization
1. History of prematurity (especially less than 34
weeks).
2. Congenital heart disease.
3. Other underlying lung disease
4. Low initial oxygen saturation suggestive of respi-
ratory failure (O2 saturation <95%, with a toxic,
distressed appearance).
5. Age <3 months.
6. Dehydrated infant who is not feeding well.
7. Unreliable parents.
C. Before hospitalization, infants should receive an
aerosolized beta-adrenergic agent. A few infants will
respond to this therapy and avoid hospitalization. If
the response is good, the infant can be sent home,
and oral albuterol continued.
D. Hospitalized infants should receive hydration and
ambient oxygen to maintain an oxygen saturation
>92-93% by pulse oximetry.
E. Treatment of bronchiolitis in the hospital
1. Racemic epinephrine by inhalation may be
administered as a therapeutic trial. It should be
continued if an improvement in the respiratory
status is noted. Racemic epinephrine is adminis-
tered as 0.5 mL of a 2.25% solution, diluted with
3.5 mL of saline (1:8) by nebulization. It is given
every 20-30 minutes for severe croup, and it is
given every 4-6 hours for moderate croup.
2. Ribavirin, an antiviral agent, produces modest
 improvement in clinical illness and oxygenation.
Ribavirin is helpful in severely ill or high-risk
patients. The dosage is 2 gm (diluted to 60
mg/mL) aerosolized over 2 hours tid for 3-5 days
using an oxygen hood. Treatment with ribavirin
combined with RSV immune globulin adminis-
tered either parenterally or by aerosol is more
effective than therapy with either agent alone.
Corticosteroid use in the treatment of bronchiolitis
is not recommended.

Indications for Ribavirin Use in Bronchiolitis

Congenital heart disease, Immunodeficiency due to

especially cyanotic chemotherapy
Chronic lung disease Cystic fibrosis
Renal transplantation, recent Severe combined immunode-
Age <6 weeks ficiency
Neurologic diseases Multiple congenital anoma-
Heart failure of any cause lies
RSV bronchiolitis and arterial Certain premature infants
O2 <65 mmHg Metabolic diseases
RSV bronchiolitis and a rising
pCO2

VI. Prevention of RSV Infections

A. Palivizumab (Synagis) is a humanized mouse
monoclonal antibody that is given intramuscularly.
Palivizumab is administered intramuscularly in a dose
of 15 mg/kg once a month during the RSV season.

Recommendations by the American Academy of

Pediatrics for the use of palivizumab (Synagis)
and RSV-IGIV:

C Palivizumab (Synagis) or RSV-IGIV prophylaxis should be

considered for infants and children younger than 2 years of
age with chronic lung disease (CLD) who have required
medical therapy for CLD within 6 months before the antici-
pated RSV season. Palivizumab is preferred for most high-
risk children because of its ease of administration, safety,
and effectiveness. Patients with more severe CLD may
benefit from prophylaxis for 2 RSV seasons, especially
those who require medical therapy.
C Infants born at 32 weeks of gestation or earlier without
CLD or who do not meet the aforementioned criteria also
may benefit from RSV prophylaxis. Infants born at 28
weeks of gestation or earlier may benefit from prophylaxis
up to 12 months of age. Infants born at 29 to 32 weeks of
gestation may benefit most from prophylaxis up to 6
months of age. Decisions about duration of prophylaxis
should be individualized according to the duration of the
RSV season.
C For patients born between 32 and 35 weeks of gestation,
the use of palivizumab and RSV IGIV should be reserved
for infants with additional risk factors.
C Prophylaxis for RSV should be initiated at the onset of the
RSV season and terminated at the end of the RSV season.
In most areas of the United States, the usual time for the
beginning of RSV outbreaks is October to December, and
termination is March to May, but regional differences occur.
C Palivizumab does not interfere with the response to vac-
cines.
References, see page 182.
Pharyngitis
Approximately 30 to 65 percent of pharyngitis cases are
idiopathic, and 30 to 60 percent have a viral etiology
(rhinovirus, adenovirus). Only 5 to 10 percent of sore
throats are caused by bacteria, with group A beta-
hemolytic streptococci being the most common. Other
bacteria that occasionally cause pharyngitis include
groups C and G streptococci, Neisseria gonorrhoeae,
Mycoplasma pneumoniae, Chlamydia pneumoniae, and
Arcanobacterium haemolyticus.

I. Clinical presentation
A. Pharyngitis caused by group A beta-hemolytic
streptococci has an incubation period of two to five
days and is most common in children five to 12 years
of age. The illness is diagnosed most often in the
winter and spring.
B. Group A beta-hemolytic streptococcal pharyngitis
usually is an acute illness with sore throat and a
temperature higher than 38.5EC (101.3EF). Constitu-
tional symptoms include fever and chills, myalgias,
headaches and nausea. Physical findings may
include petechiae of the palate, pharyngeal and
tonsillar erythema and exudates, and anterior cervi-
cal adenopathy.
C. Patients with cough or coryza, are less likely to have
streptococcal pharyngitis. A sandpaperlike rash on
the trunk, which is sometimes linear on the groin and
axilla (Pastia’s lines), is consistent with scarlet fever.

Features of Streptococcal Tonsillopharyngitis

Sudden onset Marked inflammation of

Sore throat (pain on swallow- throat and tonsils
ing) Patchy discrete exudate
Fever Tender, enlarged anterior
Headache cervical nodes
Nausea, vomiting, abdominal Scarlet fever
pain (especially in children)

Features rarely associated with streptococcal

tonsillopharyngitis–suggestive of other etiologies

Conjunctivitis Diarrhea
Cough Nasal discharge (except in
Laryngitis (stridor, croup) young children)
Muscle aches/malaise

II. Diagnostic Testing

A. Throat culture is the gold standard for the diagnosis
of streptococcal pharyngitis. The sensitivity of throat
culture for group A beta-hemolytic streptococci is 90
percent. The specificity of throat culture is 99 per-
cent.
B. A rapid antigen detection test (rapid strep test) can
be completed in five to 10 minutes. This test has a
specificity of greater than 95 percent but a sensitivity
of only 76 to 87 percent.
C. A positive rapid antigen detection test may be
considered definitive evidence for treatment of
streptococcal pharyngitis. A confirmatory throat
culture should follow a negative rapid antigen detec-
tion test when the diagnosis of group A beta-
hemolytic streptococcal infection is strongly sus-
pected.

Complications of Group A Beta-Hemolytic Strep-

tococcal Pharyngitis

Nonsuppurative complications

Rheumatic fever
Poststreptococcal glomerulonephritis

Suppurative complications

Cervical lymphadenitis Otitis media

Peritonsillar or Meningitis
retropharyngeal abscess Bacteremia
Sinusitis Endocarditis
Mastoiditis Pneumonia

D. The annual incidence of acute rheumatic fever is

one case per 1 million population. Suppurative
complications of streptococcal pharyngitis occur as
infection spreads from pharyngeal mucosa to
 deeper tissues.
III. Antibiotic Therapy

Selected Antibiotic Regimens for Group A Beta-

Hemolytic Streptococcal Pharyngitis

Dosing fre-
Antibiotic Dose/dosage quency Duration

Penicillin V Child: 250 mg Two or 10 days

(Veetids) three times
daily

Adult: 500 mg Two or 10 days

three times
daily

Penicillin G Child: 600,000 Single injec- --

benzathine units tion
(Bicillin L-A)
Adult: 1,200,000 Single injec- --
units tion

Amoxicillin Child: 40 mg per Three di- 10 days

(Amoxil) kg per day vided doses

Adult: 500 mg Three times 10 days

daily

Erythromycin Child: 40 mg per Two to four 10 days

ethylsuccinat kg per day divided
e (E.E.S. doses
400)
Adult: 400 mg Four times 10 days
daily

Erythromycin Child: 20 to 40 Two to four 10 days

estolate mg per kg per divided
day doses

Adult: not rec- -- --

ommended

Azithromycin Child: 10 mg per Once daily 5 days

(Zithromax) kg on day 1; 5
mg per kg on
days 2 through
5

Adult: 500 mg Once daily 5 days

on day 1; 250
mg on days 2
through 5

Amoxicillin- Child: 40 mg per Two or 10 days

clavulanate kg per day three di-
potassium vided doses
(Augmentin)
Adult: 500 to Two times 10 days
875 mg daily

Cefadroxil Child: 30 mg per Two divided 10 days

(Duricef) kg per day doses

Adult: 1 g Once daily 10 days

Cephalexin Child: 25 to 50 Two to four 10 days

(Keflex) mg per kg per divided
day doses

Adult: 500 mg Two times 10 days

daily

A. Penicillin is the drug of choice for streptococcal

pharyngitis. This antibiotic has efficacy and safety,
a narrow spectrum of activity and low cost. About 10
percent of patients are allergic to penicillin. Cure
rates are similar for 250 mg of penicillin V given
two, three or four times daily. The use of intramus-
cularly administered penicillin may overcome
compliance problems.
B. Alternatives to penicillin
1. Amoxicillin
a. In children, the cure rates for amoxicillin given
once daily for 10 days are similar to those for
penicillin V. The absorption of amoxicillin is
unaffected by the ingestion of food.
b. Amoxicillin is less expensive and has a nar-
rower spectrum of antimicrobial activity than
the once-daily antibiotics. Suspensions of this
drug taste better than penicillin V suspen-
sions, and chewable tablets are available.
However, gastrointestinal side effects and skin
rash may be more common with amoxicillin.
 2. Macrolides
a. Erythromycin is recommended in patients with
penicillin allergy. Because erythromycin
estolate is hepatotoxic in adults, erythromycin
ethylsuccinate may be used. Erythromycin is
absorbed better when it is given with food.
About 15 to 20 percent of patients cannot
tolerate the gastrointestinal side effects of
erythromycin.
b. Azithromycin (Zithromax) allows once-daily
dosing and a shorter treatment course of five
days. Azithromycin is associated with a low
incidence of gastrointestinal side effects.
3. Cephalosporins
a. A 10-day course of a cephalosporin has been
shown to be superior to penicillin. The overall
bacteriologic cure rate for cephalosporins is
92 percent, compared with 84 percent for
penicillin.
b. Cephalosporins have a broader spectrum of
activity than penicillin V. Unlike penicillin,
cephalosporins are resistant to degradation
from beta-lactamase. First-generation agents
such as Cefadroxil (Duricef) and cephalexin
(Keflex, Keftab) are preferable to second- or
third-generation agents.
c. Cephalosporins are reserved for patients with
relapse or recurrence of streptococcal pharyn-
gitis.
4. Amoxicillin-clavulanate (Augmentin) is resis-
tant to degradation from beta-lactamase pro-
duced by copathogens. Amoxicillin-clavulanate is
often used to treat recurrent streptococcal phar-
yngitis. Its major adverse effect is diarrhea.
IV. Management Issues
A. Treatment Failure and Reinfection. Patients who
do not comply with a 10-day course of penicillin
should be offered intramuscular penicillin or a once-
daily oral macrolide or cephalosporin. Patients with
clinical failure should be treated with amoxicillin-
clavulanate, a cephalosporin, or a macrolide.
B. Contagion. Patients with streptococcal pharyngitis
are considered contagious until they have been
taking an antibiotic for 24 hours. Children should
not go back to day care or school until their temper-
ature returns to normal and they have had at least
24 hours of antibiotic therapy.
References, see page 182.

Acute Conjunctivitis
Conjunctivitis is defined as inflammation of the conjunc-
tiva; it is usually caused by infection or allergy. It is often
referred to as “pink eye.”

I. Etiology
A. Neonatal conjunctivitis occurs in 1.6-12% of new-
borns. The most common cause is chemical irritation
from antimicrobial prophylaxis against bacterial
infection, followed by Chlamydia trachomatis infec-
tion. Haemophilus influenzae and Streptococcus
pneumoniae may also cause infection in newborns.
B. Rarely, gram-negative organisms, such as Esche-
richia coli, Klebsiella, or Pseudomonas sp can cause
neonatal conjunctivitis. Neisseria gonorrhoeae is an
unusual cause of neonatal conjunctivitis because of
the use of ocular prophylaxis.
C. Herpes simplex can cause neonatal
keratoconjunctivitis; however, it is almost always
associated with infection of the skin and mucous
membranes, or with disseminated disease.
D. In older infants and children, H influenzae is by far
the most common identifiable cause of conjunctivitis,
causing 40-50% of episodes. S pneumoniae ac-
counts for 10% of cases, and Moraxella catarrhalis
is the third most common cause.
E. Adenovirus is the most important viral cause of
acute conjunctivitis. This organism often causes
epidemics of acute conjunctivitis. It causes 20% of
childhood conjunctivitis (most occurring in the fall
and winter months).
II. Clinical presentation
A. In the first day of life, conjunctivitis is usually
caused by chemical conjunctivitis secondary to
ocular prophylaxis.
 B. Three to 5 days after birth, gonococcal conjunctivi-
tis is the most common cause of conjunctivitis.
C. After the first week of life and throughout the
first month, chlamydia is the most frequent cause of
conjunctivitis. Severe cases are associated with a
thick mucopurulent discharge and pseudomembrane
formation.
D. Gonococcal conjunctivitis can present as typical
bacterial conjunctivitis, or as a hyperacute conjuncti-
vitis with profuse purulent discharge. There often is
severe edema of both lids.
E. In the older infant and child, both viral and bacterial
conjunctivitis may present with an acutely inflamed
eye. Typically, there is conjunctival erythema, with
occasional lid edema. Exudate often accumulates
during the night.
F. Many patients who have both adenoviral conjunctivi-
tis and pharyngitis also are febrile. The triad of
pharyngitis, conjunctivitis, and fever has been
termed pharyngoconjunctival fever.
III. Diagnosis
A. Neonates
1. In cases of neonatal conjunctivitis, a Gram stain
and culture should be obtained to exclude N
gonorrhoeae conjunctivitis.
2. Chlamydia trachomatis antigen detection assays
have a sensitivity and specificity of 90%.
B. Infants and older children. Outside the neonatal
period, a Gram stain is usually not needed unless
the conjunctivitis lasts longer than 7 days. The
presence of vesicles or superficial corneal ulcer-
ations suggests herpetic keratoconjunctivitis.
IV. Differential diagnosis of conjunctivitis
A. Systemic diseases. Most cases of red eye in
children are caused by acute conjunctivitis, allergy,
or trauma; however, Kawasaki disease, Lyme
disease, leptospirosis, juvenile rheumatoid arthritis,
and Stevens-Johnson syndrome may cause con-
junctivitis. Glaucoma is a significant cause of a red
eye in adults; however, it is rare in children.
B. Allergic conjunctivitis
1. Allergic eye disease is characterized by pro-
nounced ocular itching, redness, tearing, and
photophobia. This recurrent disease has seasonal
exacerbations in the spring, summer, and fall.
Children who have allergic conjunctivitis often
have other atopic diseases (rhinitis, eczema,
asthma) and a positive family history.
2. Treatment
a. Topical decongestants: Naphazoline 0.1%
(Naphcon), phenylephrine (Neo-Synephrine),
and oxymetazoline (OcuClear, Visine LR) may
be used qid, alone or in combination with
ophthalmic antihistamines, such as antazoline
(Vasocon-A) or pheniramine maleate (Naph-
Con-A).
b. Topical lodoxamide (Alomide) 0.1% ophthalmic
solution, 1-2 drops qid, is helpful in more
severe cases.
c. Topical corticosteroids are helpful, but
long-term use is not recommended; dexameth-
asone (Decadron) 1-2 drops tid-qid.
V. Treatment of acute infectious conjunctivitis
A. Gonococcal ophthalmia neonatorum is treated with
ceftriaxone (50 mg/kg/day IV/IM q24h) or cefotaxime
(100 mg/kg/day IV/IM q12h) for 7 days.
B. Neonatal conjunctivitis caused by C trachomatis is
treated with erythromycin, 50 mg/kg/day PO divided
in 4 doses for 14 days.
C. Bacterial conjunctivitis among older infants and
children is treated with polymyxin-bacitracin
(Polysporin) ointment, applied to affected eye tid.
References, see page 182.

Cat and Dog Bites

Bite wounds account for approximately 1% of all emer-
gency department visits: 10% of victims require suturing
and 1-2% require hospitalization.

I. Pathophysiology
A. Dog bites account for 80-90% of animal bites.
Infection develops in15-20% of dog bite wounds.
B. Cat bites account for 15% of animal bites. Cat bites
usually present as puncture wounds, of which 30-
 40% become infected.
II. Clinical evaluation of bite wounds
A. The circumstances of the injury should be docu-
mented, and the animal’s immunization status
should be determined. Determine whether the
animal was provoked and to record the time of the
injury.
B. The patient’s tetanus immunization status, current
medications and allergies, history of chronic illness,
or immunocompromising conditions should be
assessed.The wound is measured and classified as
a laceration, puncture, crush injury or avulsion.
Wounds are evaluated for injuries to tendons, joint
spaces, blood vessels, nerves, or bone. A
neurovascular examination and an assessment of
wound depth should be completed.
C. Photographs of the wound should be obtained if
disfigurement has occurred or if litigation is antici-
pated.
III. Laboratory and radiologic evaluation
A. Radiographs should be taken if there is consider-
able edema and tenderness around the wound or if
bony penetration or foreign bodies are suspected.
B. Wounds seen within 8 to 24 hours after injury,
that have no signs of infection, do not require cul-
ture. If infection is present, aerobic and anaerobic
cultures should be obtained.
IV. Microbiology
A. Bite wounds usually have a polymicrobial contami-
nation.
B. Pasteurella Multocida is a gram-negative aerobe
present in the oropharynx of dogs and cats. It is
found in 20-30% of dog bite wounds and more than
50% of cat bite wounds.

Microorganisms Isolated from Infected Dog and

Cat Bite Wounds

Aerobes. Afipia felis, Anaerobes. Actinomyces,

Capnocytophaga canimorsus, Bacteroides species,
Eikenella corrodens, Eubacterium species,
Enterobacter species, Fusobacterium species,
Flavobacterium species, Leptotrichia buccalis,
Haemophilus aphrophilus, Veillonella parvula
Moraxella species, Neisseria
species, Pasteurella multocida,
Unusual Pathogens.
Pseudomonas species, Staphy-
Blastomyces dermatitidis,
lococcus aureus, Staphylococ-
Francisella tularensis
cus epidermidis, Staphylococ-
cus intermedius, Streptococci:
alpha-hemolytic, beta-
hemolytic, gamma-hemolytic

V. Management of dog and cat bites

A. Wound care
1. The wound should be cleansed with 1%
povidone iodine solution (Betadine), and irri-
gated with normal saline with a 20- to 50-mL
syringe with an Angiocath. Devitalized, crushed
tissue should be sharply débrided.
2. Deep puncture wounds, wounds examined more
than 24 hours after injury, clinically infected
wounds, and bites of the hand should not be
closed primarily.
3. Low-risk wounds seen within 24 hours after
injury may be sutured; uninfected high-risk
wounds seen 72 hours after initial injury may
undergo delayed primary closure. Bites to the
face and head have a good outcome and may
be closed primarily.
B. Antimicrobial therapy
1. Prophylactic antibiotics are recommended for
wounds that have a high risk of infection.
Prophylactic antibiotic treatment is given for 3-
7 days.
2. High-risk bite wounds requiring prophylac-
tic antibiotics
a. Full-thickness puncture wounds, severe
crush injury and/or edema, wounds requir-
ing debridement.
b. Cat bite wounds.
c. Bite wounds to the hand, foot or face;
bone, joint, tendon or ligament, or wound
adjacent to a prosthetic joint.
d. Underlying diabetes, liver or pulmonary
disease, history of splenectomy, malig-
nancy, acquired-immunodeficiency syn-
drome, or other immuno-
 compromising condition.

Prophylactic Antibiotics for Dog and Cat Bites

Outpatient Antibiotics

Cephalexin Adults: 500 mg qid

(Keflex) Children: 40 mg/kg/d PO qid

Doxycycline Adults: 100 mg bid

(Vibramycin) Children: 2-4 mg/kg/day, in divided
doses bid

Amoxicillin/clavul Adults: 500 mg tid

anate Children: 40 mg amoxicillin/kg/day, in
(Augmentin) divided doses tid

Ceftriaxone Adults: 1 g every 24 hours IM or IV

(Rocephin) Children: 50 mg/kg/d qd

Penicillin V Adults: 500 mg qid

Children: 50 mg/kg/day, in divided doses
q6-8h

Amoxicillin Adults: 500 mg tid

Children: 40 mg/kg/d, in divided doses
tid

Intravenous Antibiotic of Choice

Cefoxitin Adults: 1-2 g q4-8h

(Mefoxin) Children: 25-50 mg/kg/day, in divided
doses q6h

Alternative Intravenous Antibiotics

Ampicillin/sulbact Adults: 1.5-3.0 g q6h

am (Unasyn)

Ticarcillin- Adults: 3.1 g q6h

clavulanate
(Timentin)

Ceftriaxone Adults: 1-2 g q24h

(Rocephin) Children: 50-100 mg/kg/day, in divided
doses q24h

C. Treatment of infected wounds. Infected bite

wounds are treated with amoxicillin/
clavulanate (Augmentin). Cellulitis is treated for 10-
14 days.
D. Rabies immunoprophylaxis
1. The incidence of rabies in persons who have
been bitten by a dog is very low because most
dogs have been vaccinated. An untreated person
has a less than 20% chance of contracting rabies
from the bite of a rabid animal. However, if rabies
is contracted, the mortality rate is 100%.
2. Wild animals (raccoons, skunks, bats) are the
most common source of rabies. Rabies is trans-
mitted when the saliva of an infected animal
comes into contact with the broken skin or mu-
cosa of another mammal. The incubation period
ranges from 10 days to one year.
3. If rabies infection is suspected, rabies prophy-
laxis is administered as follows:
a. Rabies immune globulin (RIG), 20 IU/kg, IM
(separate from human diploid cell vaccine
below).
b. Human diploid cell vaccine (HDCV), 1 cc IM
(not gluteal) given on days 1, 3, 7, 14, and 28.
E. Tetanus Immunization. Animal bites should be
regarded as tetanus prone, although tetanus infec-
tion resulting from cat and dog bites is rare.
References, see page 182.

Peripheral Lymphadenopathy in
Children
Palpable lymph nodes are often found in children because
their immune systems are being activated by environmen-
tal antigens and the common organisms.
Lymphadenopathy is caused by reactive hyperplasia of
undetermined etiology in 50%. Nearly one-third of children
have granulomatous diseases, including cat scratch
disease, mycobacterial infections, fungal infections, or
Langerhans cell histiocytosis (histiocytosis X). Thirteen
percent have neoplastic diseases, such as Hodgkin
disease. Chronic dermatopathic or bacterial infections
comprised the remaining 3 percent of patients. Only 20
percent of biopsies will demonstrate a treatable disease.

I. Anatomy and definitions Normal lymph nodes usually

are less than 1 cm in diameter. Lymph nodes often are
palpable in the inguinal region in healthy individuals,
perhaps because chronic trauma and infection are
common in the lower extremities. Nodes also may be
palpable in the neck (particularly submandibular)
because of previous head and neck infections.
A. Lymphadenopathy should be classified as localized
(in only one region such as the neck or axilla) or
generalized (more than one region).
II. Differential diagnosis. Lymphadenopathy can be
caused by a vast array of diseases and drugs.
A. Localized
1. Cervical. The anterior cervical lymph nodes often
are enlarged because of a variety of infections of
the head and neck, or because of a systemic
infection, such as toxoplasmosis and infectious
mononucleosis caused by Epstein-Barr virus or
cytomegalovirus. Only one-quarter of patients with
enlarged cervical nodes have another serious
disease, which most often is mycobacterial. Upper
posterior cervical lymphadenopathy rarely is
associated with significant diseases in children.
a. Inflamed cervical nodes that develop over a few
days and progress to fluctuation, especially in
children, typically are caused by staphylococcal
and streptococcal infection. Treatment begins
first with a course of antibiotics, often dicloxacillin,
but incision and drainage may be indicated.
Fluctuant cervical nodes that develop over weeks
to months without significant inflammation or
tenderness suggest infection with Mycobacterium
tuberculosis, atypical mycobacteria, or Bartonella
henselae, the agent of cat scratch disease.
b. Hard nodes, often associated with cancer in
adults, are found infrequently in children. The
nodes involved with Hodgkin disease are rub-
bery.

Infectious Etiologies of Cervical Adenitis

Bacterial Viral Fungal/prot Other
ozoal

Localized Acute

Staphylococcus Rubella Toxoplasmos Kawasaki

aureus Adenovi- is syn-
Streptococcus ruses Histoplasmos drome
pyogenes Herpes is Rickett-
Group B strepto- simplex sial pox
coccus virus
Anaerobes Mumps
Francisella Human
tularensis herpesvirus
6

Subacute or Chronic

Tuberculosis Syphilis Brucellosi

Atypical myco- Actinomyc s
bacteria osis
Cat-scratch dis- Nocardiosi
ease s

Generalized

Syphilis HIV Histoplasmos Rickett-

Tuberculosis Epstein- is sial
Scarlet fever Barr Toxoplasmos Scrub
Typhoid fever Cytomegal is typhus
Leptospirosis ovirus
Brucellosis virus Measles
Rubella
Varicella
Adenovirus

Organism Associated with Infectious Cervical

Lymphadenitis

Neonates

Staphylococcus aureus
Group B streptococcal “cellulitis-adenitis” syndrome

Infancy

As above
Kawasaki syndrome
1 to 4 Years

Staphylococcus aureus
Streptococcus pyogenes
Atypical mycobacteria

5 to 15 years

Anaerobic bacteria
Toxoplasmosis
Cat-scratch disease
Tuberculosis

Causes of Peripheral Lymphadenopathy

Cause Examples

Infections

Bacterial

Localized Streptococcal pharyngitis; skin

infections; tularemia;
plague; cat scratch fever dis-
ease; diphtheria; chancroid;
rat bite fever

Generalized Brucellosis; leptospirosis;

lymphogranuloma
venereum; typhoid fever

Viral Human immunodeficiency virus;

Epstein-Barr virus;
herpes simplex virus;
cytomegalovirus; mumps;
measles; rubella; hepatitis B;
dengue fever

Mycobacterial Mycobacterium tuberculosis;

atypical mycobacteria

Fungal H i s t o p l a s m o s i s ;
coccidiodomycosis; crypto-
coccus

Protozoal Toxoplasmosis

Spirochetal Secondary syphilis; Lyme dis-

ease

Cancer Metastatic; lymphoma; leukemia

Lymphoproliferat Angioimmunoblastic
ive lymphadenopathy with
dysproteinemia
Autoimmune lymphoroliferative
disease
Rosai-Dorfmans’s disease
H e m o p h a g o c y t i c
lymphohistiocytosis

Immunologic Serum sickness; drug reactions

(phenyutoin)

Endocrine Hypothyroidism; Addison’s dis-

ease

Miscellaneous Sarcoidosis; lipid storage dis-

eases; amyloidosis;
h i s t i o c yt o s i s ; chronic
granulomatous diseases;
Castlemans’ disease;
Kikuchi’s disease; Kawasaki
disease; inflammatory
pseudotumor; systemic lupus
erythematosus; rheumatoid
arthritis; Still’s disease;
dermatomysositis; Churg-
Strauss syndrome
 Drugs That Cause Lymphadenopathy

Allopurinol Penicillin
Atenolol Phenytoin
Captopril Primidone
Carbamazepine Pyrimethamine
Quinidine
Cephalosporins Sulfonamides
Gold Sulindac
Hydralazine

Causes of Generalized Lymphadenopathy

Mononucleosis syn- Systemic lupus

dromes erythematosus
HIV infection Rheumatoid arthritis
Secondary Syphilis Still’s disease
Hepatitis B Kawasaki disease
Tuberculosis Dermatomyositis
Lyme Disease Amyloidosis
Measles Serum sickness
Rubella Leukemia
Brucellosis Lymphoma
Typhoid fever

2. Supraclavicular (or lower cervical)

lymphadenopathy is associated with a high risk of
malignancy (up to 75 percent). Right
supraclavicular adenopathy is associated with
cancer of the mediastinal lymph nodes. Left
supraclavicular adenopathy (“Virchow’s node”)
suggests abdominal malignancy, also most often
a lymphoma.
3. Axillary. The axillary nodes receive drainage from
the arm, thoracic wall, and breast. Infections,
including cat scratch disease, are common causes
of axillary lymphadenopathy, although hyperplastic
nodes are found in over one-third.
4. Inguinal lymphadenopathy in children usually is
associated with no specific etiology unless the
nodes are very large (>3 cm).
5. Epitrochlear. Palpable epitrochlear nodes are not
always pathologic in children, and many biopsied
nodes show only hyperplasia. Other causes in-
clude infections of the forearm or hand, leukemia,
lymphoma, and atypical mycobacterial infections.
B. Generalized lymphadenopathy
1. HIV. Nontender adenopathy primarily involving the
axillary, cervical, and occipital nodes develops in
the majority of individuals during the second week
of acute symptomatic HIV infection. The nodes
decrease in size after the acute presentation, but
a modest degree of adenopathy tends to persist.
2. Mycobacterial infection can present with
lymphadenopathy alone, especially in the neck
(scrofula). Mycobacterium avium complex and M.
scrofulaceum, account for most cases in children.
Nodes typically are nontender, enlarge over weeks
to months and can progress to matting and fluctua-
tion. Miliary tuberculosis may cause generalized
lymphadenopathy.
3. Mononucleosis is characterized by the triad of
moderate to high fever, pharyngitis, and
lymphadenopathy. Lymph node involvement is
symmetric and involves the posterior cervical more
than the anterior chain. Lymphadenopathy also
may be present in the axillary and inguinal areas,
which helps to distinguish infectious mononucleo-
sis from other causes of pharyngitis. Nodes are
kidney-shaped.
4. Systemic lupus erythematosus. Enlargement of
lymph nodes occurs in 50 percent of patients with
systemic lupus erythematosus (SLE). The nodes
typically are soft, nontender, discrete, varying in
size from 0.5 to several centimeters, and usually
detected in the cervical, axillary, and inguinal
areas.
5. Medications may cause serum sickness that is
characterized by fever, arthralgias, rash, and
generalized lymphadenopathy. Phenytoin can
cause generalized lymphadenopathy.
III. Diagnostic approach
A. History
1. Localizing signs or symptoms suggestive of infec-
tion or malignancy.
2. Exposures (eg, cat [cat scratch disease], under-
 cooked meat [toxoplasmosis], tick bite [Lyme
disease]), travel, high-risk behavior (eg, sexual
behavior, injection drug use).
3. Constitutional symptoms such as fever, night
sweats, or weight loss suggestive of tuberculosis,
lymphoma, or other malignancy; fever typically
accompanies lymphadenopathy for the majority of
the infectious etiologies.
4. Use of medications that can cause
lymphadenopathy.
B. Physical examination
1. Location. Palpation of inguinal, cervical, and
axillary nodes, in addition to the liver and spleen,
can determine whether it is truly local
lymphadenopathy.
2. Size. Abnormal nodes generally are greater than
1 cm in diameter. Malignancy is more likely to be
found in nodes larger than 2 cm.
3. Consistency. Hard nodes are found in cancers
that induce fibrosis (scirrhous changes) and when
previous inflammation has left fibrosis. Firm,
rubbery nodes are found in lymphomas and
chronic leukemia; nodes in acute leukemia tend to
be softer.
4. Fixation. Normal lymph nodes are freely movable
in the subcutaneous space. Abnormal nodes can
become fixed to adjacent tissues (eg, deep fascia)
by invading cancers or inflammation. They also
can become fixed to each other (“matted”).
5. Tenderness suggests recent, rapid enlargement
that has put pain receptors in the capsule under
tension. This situation typically occurs with inflam-
matory processes, but it also can occur because of
hemorrhage into a node, immunologic stimulation,
and malignancy.
C. Diagnostic tests
1. Patients with generalized lymphadenopathy should
have a CBC and chest radiograph. If these tests
are normal, other considerations include an eryth-
rocyte sedimentation rate, serologic test for acute
EBV and CMV infections, PPD, HIV antibody
determination, RPR, ANA, and heterophile test.
2. Patients with localized (especially cervical)
lymphadenopathy can be observed for three to
four weeks and treated empirically with antibiotics
(first- or second-generation cephalosporin or
dicloxacillin) if nothing else in the history and
physical examination suggests malignancy. Biopsy
is appropriate if an abnormal node has not re-
solved after four weeks, or immediately in patients
with other findings suggestive of malignancy.
3. Incision and drainage. Fluctuant nodes may be
necessary to relieve pain and treat obvious infec-
tion.

Treatment of Acute Pyogenic Bacterial

Lymphadenitis

Symptomatic Therapy

1. Apply warm, moist dressings

2. Prescribe analgesics
3. Incise and drain nodes that have suppuration
 Antimicrobial Therapy

Suspected staphylococcal/group A and B streptococcal

disease
Cellulitis or marked enlargement, moderate-to-severe
systemic symptoms, or in infants 1 mo of age:
IV Nafcillin (Nafcil) 150 mg/kg day OR
IV Cefazolin (Ancef) 150 mg/kg/day after aspiration of
node
Suppuration:
IV antibiotics as above and incision and drainage
No prominent systemic symptoms, cellulitis, or sup-
puration:
Dicloxacillin (Dynapen) 25 mg/kg/day OR
Cephalexin (Keflex) 50 mg/kg/day OR
Clindamycin (Cleocin) 30 mg/kg/day
Suspected anaerobic infection with dental or periodontal
disease, include:
Penicillin V 50 mg/kg/day or
Clindamycin (Cleocin) 30 mg/kg/day OR
Group A streptococcal infection
Aqueous penicillin G 50 000 IU/kg/day IV OR
Penicillin V 50 mg/kg/day PO OR
Cephalexin 50 mg/kg/day PO OR
Erythromycin ethylsuccinate 40 mg/kg/day PO
Group B streptococcal disease in infants
Aqueous penicillin G 200 000 IU/kg/day IV, if sensitive.
References, see page 182.

Intestinal Helminths
Intestinal helminth infestations most commonly affect
travelers, migrant laborers, refugees, children of foreign
adoptions, and the homeless. These parasitic infections
are associated with day-care centers and overseas travel.

I. Clinical evaluation
A. Intestinal helminth infections are usually asymp-
tomatic, but serious infections may cause symptoms
ranging from abdominal discomfort to severe pain.
Anorexia, nausea, diarrhea, pruritus, rectal prolapse,
bowel obstruction, and death may occur. Hives and
eosinophilia may develop, and the worms may
sometimes spontaneously exit the body through the
anus.
B. Stool examination. Examination of the stool for ova
and parasites is the most important test for
helminthic infection. Stools are collected using
plastic wrap under the toilet seat. Fresh stool may
also be obtained by rectal examination.
II. Enterobiasis
A. The pinworm (Enterobius vermicularis) is the
most common helminth. Pinworms present as anal
pruritus in irritable children. The disorder tends to
occur in temperate climates. Many patients are
asymptomatic. Heavier infections may cause insom-
nia, restlessness, vulvovaginitis, loss of appetite,
and intractable anal itching.
B. Pinworms are about 10 mm in length. The female
worm has a pin-shaped tail. At night, worms migrate
through the anus, then deposit their eggs and die on
the perianal skin. Microscopic eggs infest clothing,
bedding, and other surfaces, often spreading to the
entire family.
C. Pinworms are diagnosed by examining the perianal
skin. The stool is usually negative for ova and
worms. To obtain the eggs, a tongue blade covered
with clear tape is placed sticky-side down over the
perianal skin in the morning. Specimens are collect-
ed on three separate mornings, then taped to glass
slides and taken to a laboratory for examination.
D. The elongate, colorless eggs measure 50 to 60 µm
and are flattened on one side. Worms may also be
visualized if the anus is examined late at night or
early in the morning.
E. Treatment
1. Mebendazole (Vermox), one 100-mg tablet
orally, is safe and effective. A second dose is
given 10 days later. The entire family is treated.
2. Infested clothing and bedding are washed and
fingernails should be kept trimmed, and the
perianal area kept clean. Dogs and cats do not
spread this infection. Relapses are common.
III. Ascariasis
A. Roundworms (Ascaris lumbricoides) measure up
to 18 inches in length. The infection is fairly common
in the rural southeastern United States and is fre-
quent among immigrants. A. lumbricoides only
 infests humans.
B. Ascaris eggs reach the soil in feces, and they may
persist in the soil for more than a decade until they
are accidentally consumed. In the gut, worms may
cause intestinal obstruction. However, most patients
experience only vague abdominal discomfort or
nausea.
C. Treatment
1. Mebendazole (Vermox), 100 mg bid for three
days.
2. A follow-up examination of stool for ova and
parasites should be performed in two months.
Family screening is recommended.
IV. Trichuriasis
A. Whipworm (Trichuris trichiura) infestation is less
common than Ascaris infestation, occurring in the
southeastern states and in foreign immigrants.
B. Whipworm eggs incubate in the soil. When swal-
lowed, they travel to the colon.
C. Adult whipworms are 30-50 µm in length, with a
thread-like anterior portion. They can live in the
intestine and produce eggs for several years, caus-
ing mild blood loss and symptoms similar to proctitis
and inflammatory bowel disease. Rectal prolapse,
diarrhea, loss of appetite, and hives may occur.
D. Treatment of trichuriasis is the same as for
ascariasis.
V. Less common parasites
A. Hookworms
1. Hookworms develop in the soil from eggs in
feces. The larvae are capable of penetrating the
bare feet and causing a pruritic rash. The larvae
eventually reach the small intestine.
2. Adult hookworms are about 10 µm in length, with
a hooked anterior end, which they use to con-
sume 0.03-0.15 mL of blood per day for 10 to 15
years. Manifestations include iron deficiency
anemia, chronic fatigue, geophagia, failure to
thrive, and depression.
3. Treatment consists of mebendazole as described
above and iron supplementation.
B. Strongyloidiasis
1. Filariform larvae are capable of penetrating intact
skin, persisting for 40 years or more in the small
intestine. It can also be spread in feces or as a
sexually transmitted disease. Persistent unex-
plained eosinophilia in a patient from a region
where Strongyloides infection is endemic should
prompt serologic testing because stool specimens
are often negative.
2. Symptoms are usually absent but may include
pruritus, pneumonia, abdominal cramping, and
colitis. Treatment consists of thiabendazole
(Mintezol).
C. Tapeworms
1. Beef tapeworm is transmitted by inadequately
cooked beef, reaching up to 10 to 15 feet in
length in the gut. Diagnosis is made by passage
of ribbon-like tapeworm segments or by finding
the eggs in a stool.
2. Pork tapeworm is far more dangerous than T.
saginata since its eggs can cause cysticercosis,
the invasion of human tissue by larval forms. In
severe cases, the larvae may invade the central
nervous system, causing neurocysticercosis.
a. Pork tapeworm is found in immigrants from
Central and South America. Patients with
neurocysticercosis frequently present with
seizures.
b. This diagnosis should be considered in the
evaluation of a patient from Central or South
America with a new-onset seizure disorder.
3. Dwarf tapeworm is the most common tapeworm
in the U.S. This tapeworm is 1 inch in length.
Ingestion of food contaminated with mouse drop-
pings may spread the infection. H. nana infection
may cycle in immigrant children for years.
4. Fish tapeworm is occasionally transmitted by
undercooked fish, especially from the Great
Lakes region. It can occasionally causes
megaloblastic anemia.
5. Treatment of all tapeworms consists of
praziquantel (Biltricide) or niclosamide
(Niclocide).
References, see page 182.
Orbital and Periorbital Cellulitis
Periorbital cellulitis is a bacterial infection of the skin and
structures superficial to the orbit; orbital cellulitis is a
bacterial infection of the orbit.

I. Pathogenesis of periorbital cellulitis

A. The most common causes of eyelid redness and
swelling are allergy, trauma, and insect stings or
bites. Periorbital cellulitis usually occurs after the
skin near the eye has been broken by trauma, an
insect bite, or infection with herpes simplex or
varicella zoster viruses. The organisms that most
frequently cause periorbital cellulitis following
trauma are Staphylococcus aureus and Streptococ-
cus pyogenes (group A beta-hemolytic strepto-
cocci).
B. A bacterial pathogen is identified in only 30% of
cases of periorbital cellulitis, and the pathogen is
isolated from the blood in about two thirds of these
cases.
C. Since the introduction of H influenzae type b conju-
gate vaccines (HbCV), Hib disease accounts for
fewer than 15% of periorbital cellulitis. A child who
has received a second dose of HbCV more than 1
week before the onset of eyelid swelling is very
unlikely to have HIB disease.
II. Pathogenesis of orbital cellulitis
A. Orbital cellulitis may progress to subperiosteal
abscess, orbital abscess, and cavernous sinus
thrombosis.
B. About one-fourth of isolates are S aureus; one-fifth,
S pyogenes; one-fifth, HiB; one-tenth, S
pneumoniae; one-tenth, anaerobic bacteria; and the
remaining 15%, other bacteria.
III. Clinical evaluation
A. Periorbital cellulitis usually occurs in children youn-
ger than 2 years of age. Clinical findings include a
temperature of 39°C or more and a peripheral white
blood cell count of greater than 15,000/mm³.
B. Periorbital and orbital cellulitis cause eyelid swelling,
with the swelling being unilateral in 95-98% of
cases. Virtually all involved eyelids will be
erythematous or violaceous.
C. Signs of trauma or local infection are observed in
one-third of patients. When conjunctival inflamma-
tion, a purulent discharge, and bilateral lid involve-
ment are present, the cause is much more likely to
be conjunctivitis, rather than periorbital or orbital
cellulitis.
D. Globe displacement (proptosis), abnormal
movement (ophthalmoplegia), or pain on move-
ment should be sought, and visual acuity should be
tested.
E. Laboratory evaluation
1. White blood cell count greater than 15,000/mm³
suggests bacteremic disease.
2. Lumbar puncture should be performed on all
children younger than 1 year of age who have not
had at least two doses of H influenzae B vaccine.
3. Blood culture for bacterial pathogens should
be obtained.
IV. Treatment
A. Orbital cellulitis. Children who have signs of orbital
cellulitis should be hospitalized, and antimicrobial
therapy should consist of a third-generation
cephalosporin, such as ceftriaxone (50 mg/kg qd IM
or IV) or cefotaxime (50 mg/kg/dose q6h IV), plus
clindamycin (10 mg/kg/dose q8h IV).
B. Periorbital cellulitis
1. Periorbital cellulitis can be managed on an outpa-
tient basis if there is no orbital involvement and
the child does not appear toxic.
2. Ceftriaxone (50 mg/kg, not to exceed 1 g) is
given IM or IV. If the blood culture remains nega-
tive, the child may be started on a
broad-spectrum oral agent such as
ampicillin/clavulanate (Augmentin) or Trimeth-
oprim/sulfamethoxazole (Bactrim) to complete a
7- to 10-day course of therapy.
References, see page 182.
Tuberculosis
The number of cases of tuberculosis in children younger
than five years of age in cities has increased 94.3% in the
last four years.

I. Natural history of tuberculosis

A. Tuberculosis infection is initiated by the inhalation of
organisms into the lung. During an incubation
period, that lasts 2 to 10 weeks, the organisms
spread to the hilar lymph nodes. This condition is
considered primary tuberculosis. During the incuba-
tion period, the purified protein derivative (PPD) test
usually becomes positive.
B. Primary tuberculosis is often completely asymp-
tomatic, and the chest radiograph may be only mini-
mally abnormal, with hilar adenopathy, and/or small
parenchymal infiltrates. Healed primary tuberculosis
may leave calcified deposits in the lung parenchyma
and/or hilum.
C. Extrapulmonary disease is more common in
children than in adults. In children, 25% of tuberculo-
sis disease is extrapulmonary. Children and young
adolescents are more likely than adults to have
tuberculous meningitis, miliary tuberculosis, adenitis,
and bone and joint infections.
D. Reactivation. Children who do not have clinical dis-
ease, but who harbor a reservoir of quiescent
organisms may develop tuberculous disease later in
life. Reactivation is most likely to occur during
adolescence, during an episode of
immunosuppression, in the presence of chronic
disease, or in the elderly.
II. Diagnosis of tuberculosis in children
A. Children exposed to tuberculosis
1. All household contacts of adults with active
disease should be tested by PPD. Thirty to 50%
of all household contacts of infectious adults will
have a positive PPD.
2. Children who are known contacts and who are
PPD negative, should receive prophylactic ther-
apy, usually isoniazid (Laniazid), 10 mg/kg/day.
The PPD is repeated in 3 months to check for
conversion to a positive PPD test, which would
indicate infection. If the repeat PPD test remains
negative, the child is assumed not to be infected,
and prophylactic therapy can be discontinued. If
the repeat PPD test is positive, the child should
be treated for 9 months.
3. Any child with a positive PPD test should be
evaluated for active pulmonary and
extrapulmonary tuberculosis with a history and
physical examination and posteroanterior and
lateral chest radiographs. The source of the
child’s infection should be determined. The sus-
ceptibility of the source case’s M. tuberculosis
strain is considered in selecting a prophylactic or
treatment regimen. Contact with the person with
contagious tuberculosis who infected the child
must be prevented until the source case is no
longer infectious.
B. Children at risk for infection
1. A PPD test is recommended for children in high-
risk groups. A screening PPD test of 5 tuberculin
units can be placed before a dose of measles-
mumps-rubella (MMR) vaccine, simultaneously
with the MMR vaccine dose, or 6 weeks after the
MMR vaccine dose. A false-negative PPD test
may occur within 6 weeks of an MMR vaccination,
because of transient immunosuppression from
the live MMR vaccine.
2. The size of the PPD reaction determined to be
positive varies with the risk of tuberculous infec-
tion. The diameter of the induration is measured
48 to 72 hours after PPD placement. A positive
PPD test requires an evaluation for tuberculous
disease.
 Criteria for a Positive PPD Test in Children

Reaction of 5 mm or more
Children suspected of having tuberculosis (chest x-ray
consistent with active or previously active tuberculo-
sis; clinical signs of tuberculosis)
Children in close contact with persons who have known
or suspected infectious tuberculosis
Children with immunosuppressive conditions (HIV infec-
tion, corticosteroid therapy)

Reaction of 10 mm or more
Children younger than 4 years of age
Children born in, or whose parents were born in, regions
where tuberculosis is highly prevalent
Children frequently exposed to adults who are HIV in-
fected, homeless persons, IV and other street drug
users, poor and medically indigent city dwellers, resi-
dents of nursing homes, incarcerated or institutional-
ized persons, and migrant farm workers
Children with other medical risk factors (Hodgkin’s dis-
ease, lymphoma, diabetes mellitus, chronic renal
failure)

Reaction of 15 mm or more
Children older than 4 years without any risk factors

3. Previous vaccination with bacille Calmette-

Guerin (BCG) vaccine does not change the
interpretation of the PPD test.
4. High tuberculous infection rates occur in South-
east Asia, Africa, Eastern Mediterranean coun-
tries, Western Pacific countries, Mexico, the
Caribbean, and South and Central America.
C. Clinical evidence suggestive of tuberculosis.
Tuberculosis must be considered when a child
presents with pneumonia that is unresponsive to
antibiotic treatment, “aseptic” meningitis, joint or
bone infection, hilar or cervical adenopathy, or
pleural effusion.
III. Evaluation of tuberculosis in children
A. The work-up for a child with a positive PPD test or
suspected tuberculosis includes the following:
1. History. Risk factors for exposure to tuberculo-
sis; symptoms of tuberculosis; adult source
case.
2. Physical examination. Adenopathy, positive
respiratory system findings, bone or joint dis-
ease, meningitis.
3. Diagnostic tests
a. Chest x-ray (posteroanterior and lateral).
b. Gastric aspirates in children who are too
young to produce a deep sputum sample
c. Sputum collection or induction in children
who are able to produce a deep sputum
sample.
d. Cultures and smears of appropriate body
fluids in children with suspected
extrapulmonary tuberculosis.
IV. Treatment of active tuberculosis
A. Treatments should be directly observed to ensure
compliance. If possible, the susceptibility results of
the adult source case should guide the medication
choice. If the organism may be resistant to one of
the standard medications, ethambutol (Myambutol
[or streptomycin in children too young for visual
acuity testing]) should be included.
B. Drug-resistant tuberculosis should be suspected in
children who are exposed to immigrants from Asia,
Africa and Latin America, children who live in large
cities, or who are from areas in which isoniazid
resistance occurs in more than 4% of cases,
children who are homeless, children who have
previously been treated for tuberculosis, and
children who are exposed to adults at high risk for
tuberculosis.
 Treatment Regimens for Active Tuberculosis

Type of Disease Primary Regimen Comments

Pulmonary dis- Two months of Medications

ease isoniazid, 10-15 can be given 2
mg/kg/day, max 300 o r 3
mg/day; rifampin times/week
(Rifadin), 10-20 under direct
mg/kg/day, max 600 observation in
m g/ d a y; a n d the initial
pyrazinamide, 20-40 phase
mg/kg/day, max 2.0
g/day, followed by 4
months of daily or
twice-weekly isoniazid
and rifampin

Extrapulmonary Same as for pulmonary

disease, except disease
meningitis, miliary
disease and
bone/joint disease

Meningitis, miliary Two months of daily

disease, and isoniazid, rifampin,
bone/joint disease pyrazinamide and strep-
tomycin, followed by 10
months of daily or
twice-weekly isoniazid
and rifampin

V. Treatment of latent tuberculosis infection

A. Children with a positive PPD test, but no signs of
active disease, should receive isoniazid for 9
months if they are younger than 18 years and for at
least 6 months if they are 18 years of age or older.
Exposure to drug-resistant tuberculosis requires
more specific therapy.
B. The child with tuberculous infection or disease may
return to school or child care after drug therapy has
been initiated and clinical symptoms have resolved.
HIV testing should be completed for any older child
or adult with tuberculosis.
References, see page 182.

Urinary Tract Infections in Children

Urinary tract infections (UTI) are a common problem in
childhood, which may lead to renal scarring, hypertension,
and end stage renal dysfunction. UTI includes both cystitis
and pyelonephritis.

I. Clinical features
A. Infants and young children with UTI can present
only with fever. The presence of another potential
source for fever (upper respiratory tract infection,
acute otitis media, acute gastroenteritis) does not
rule out the possibility of UTI. Other less common
symptoms of UTI in infants include conjugated
hyperbilirubinemia and failure to thrive.
B. Older children with UTI may have fever, urinary
symptoms (dysuria, urgency, frequency, inconti-
nence, macroscopic hematuria), and abdominal
pain. Occasionally, older children may present with
failure to thrive, nephropathy, or hypertension
secondary to prior unrecognized UTIs. Suprapubic
tenderness and costovertebral angle tenderness
may be present.

Signs and Symptoms of UTI In Children

Newborns Infants and Pre- School-Age Chil-

schoolers dren

Jaundice Diarrhea Vomiting

Hypothermia Failure to thrive Fever
Sepsis Vomiting Strong-smelling
Failure to thrive Fever urine
Vomiting Strong-smelling Abdominal pain
Fever urine Frequency
Dysuria
Urgency
Enuresis

C. History. The height and duration of fever, urinary

symptoms, vomiting, recent illnesses, antibiotics
administered, and use of barrier contraceptive
method should be assessed. The following past
 history should be obtained:
1. Chronic constipation.
2. Chronic urinary symptoms. Incontinence, lack of
proper stream, frequency, urgency, withholding
maneuvers.
3. Previous UTIs.
4. Vesicoureteral reflux (VUR).
5. Previous undiagnosed febrile illnesses.
6. Family history of frequent UTIs, VUR and other
genitourinary abnormalities.
D. Physical examination. Blood pressure, tempera-
ture, suprapubic and costovertebral tenderness, and
other sources of fever should be evaluated. External
genitalia should be examined for vulvovaginitis,
vaginal foreign body, sexually transmitted diseases
(STDs), and anatomic abnormalities.
E. Differential diagnosis of a well-appearing infant
with fever without a definite source includes UTI and
occult bacteremia.
1. In children vaccinated against Haemophilus
influenzae and Streptococcus pneumoniae, the
odds of UTI are much higher than the odds of
occult bacteremia.
2. The differential diagnosis of an older child pre-
senting with urinary symptoms and bacteriuria
includes nonspecific vulvovaginitis, urinary cal-
culi, urethritis secondary to an STD (particularly
Chlamydia), and a vaginal foreign body. Patients
with group A streptococcal infection, appendicitis,
and Kawasaki disease may present with fever,
abdominal pain, and pyuria.
II. Diagnosis
A. Decision to obtain urine
1. The presence of two or more of the following five
variables predicts UTI accurately:
a. Age under one year.
b. White race.
c. Temperature >39ºC.
d. Fever for more than two days.
e. Absence of another source of fever on history
or examination (ie, absence of upper respira-
tory infection, acute otitis media,
gastroenteritis).
2. All older girls with urinary symptoms suggestive of
UTI should have a urine specimen obtained for
urinalysis and culture.
B. Clean catch specimen is the preferred method of
urine collection in a toilet-trained child. A
catheterized specimen is preferred in the diapered
child. Suprapubic aspiration also may be used to
collect a specimen in young children. A suprapubic
aspirate is recommended when:
1. Catheterization is not feasible (eg, penile and
labial adhesions).
2. Results from catheterized specimen are inconclu-
sive (eg, repeated contaminated specimen or
repeated low colony counts).
C. Dipstick tests are convenient but may miss some
children with UTI (sensitivity 88%). Therefore, a
urine culture should still be obtained in children with
suspected UTI who have a negative dipstick test. A
child with a positive nitrite test is very likely to have
a UTI.
D. Microscopic examination
1. The accuracy of microscopic analysis is improved
by using:
a. An uncentrifuged specimen.
b. A Gram stained specimen.
c. A hemocytometer (results reported as
WBC/mm3).
2. Examination of urine using these three tech-
niques has been termed an “enhanced urinaly-
sis.” In young children, the enhanced urinalysis
offers the best combination of sensitivity and
specificity for predicting a UTI in children. Urine
culture should be performed in most patients.
III. Definition of a UTI
 Culture Criteria for Significant Bacteruria

Method Colony Count

Suprapubic aspiration Any bacteria

Urethral catheterization >10,000 cfu/mL

Best catch >50,000 cfu/mL

A. A blood culture is not necessary in children over two

months with UTI. Children less than one month of
age with high fever and a positive urinalysis should
have a lumbar puncture performed, since approxi-
mately 1 percent with UTI may also have bacterial
meningitis
IV. Imaging.
A. Routine imaging is recommended for:
1. Children under five years of age with a febrile
UTI.
2. Girls under three years of age with a first UTI.
3. Males of any age with a first UTI.
4. Children with recurrent UTI
5. Children with UTI who do not respond promptly to
therapy.
B. Renal ultrasonography can demonstrate the size
and shape of the kidneys, the presence of duplica-
tion and dilatation of the ureters, and the existence
of gross anatomic abnormalities.
C. Voiding cystourethrogram is an excellent test to
establish the presence and degree of VUR.
Radionuclide VCUG involves catheterization to fill
the bladder with a radioactive liquid and recording of
VUR during voiding. The radionuclide VCUG is
more sensitive than contrast VCUG has a sensitivity
of 78 to 91%). The contrast VCUG provides a better
anatomic resolution, which makes it more suited for
grading VUR.
D. Recommendations for imaging
1. Routine VCUG for children is recommended
under the age of five years with a febrile UTI,
males of any age with a first UTI, girls under the
age of three years with a first UTI, and children
with recurrent UTI.
2. Routine performance of renal ultrasonography is
not recommended following diagnosis of a first
UTI in children in whom prenatal ultrasonography
has been performed in a reputable center at >30
to 32 weeks of pregnancy. An ultrasound in
children with a UTI who do not respond promptly
to therapy is recommended.
I. Management, prognosis, and prevention of urinary
tract infections in children
A. Hospitalization. Children who are not responding
to outpatient therapy, who are vomiting and there-
fore cannot tolerate oral medication, or who are not
able to be adequately followed should be managed
as inpatients.
B. Choice of antibiotics. Gram staining of the urine
can aid in the choice of initial antimicrobial therapy.
1. E. coli is the most common pathogen causing
UTI, and 50 percent of E. coli are resistant to
amoxicillin or ampicillin. First-generation
cephalosporins, amoxicillin-
clavulanate or ampicillin-sulbactam, and
trimethoprim-sulfamethoxazole (TMP-SMX)
should be used with caution because increasing
resistance to these antibiotics.
2. Alternatives include second- and third-generation
cephalosporins and gentamicin although these
drugs are not effective in treating enterococcal
infections. Cefixime has been shown to be effec-
tive in the treatment of outpatients with UTI.
Quinolones are effective and resistance is rare,
but safety in children is still unknown.
C. Duration of therapy
1. A three-day course of antibiotics is recommended
in older children with their first episode of cystitis
(low risk of recurrence or complications). A 10- to
14-day course of an antimicrobial is recom-
mended for young children and for those with
recurrent or febrile UTIs.
Antibiotic Therapy for Urinary Tract Infections
with Severe Symptoms

Agent Dosage (mg/kg/day)

Neonate

Ampicillin and 7.5 mg/kg/day IV/IM q8h

Gentamicin 100 mg/kg/day IV/IM q6h

Older Child

Ceftriaxone 50 mg /kg/day (IM, IV) q24h

(Rocephin)

Cefotaxime 100 mg /kg/day (IV) q6-8h

(Claforan)

Ampicillin/sulbactam 100-200 mg of ampicillin/kg/day q6h

(Unasyn)

Gentamicin 3-7.5 mg /kg/day(IV, IM) q8h

Antibiotic Therapy for Urinary Tract Infections with Mild

Symptoms

Agent Dosage

Cefpodoxime 10 mg/kg/day PO q12h [susp: 50 mg/5

(Vantin) mL, 100 mg/5 mL; tabs: 100 mg, 200
mg]

Cefprozil (Cefzil) 30 mg/kg/day PO q12h [susp: 125

mg/5 mL, 250 mg/5 mL; tabs: 250,
500 mg]

Cefixime (Suprax) 8 mg/kg/d PO qd-bid [susp: 100 mg/5

mL, tab: 200,400 mg]

Cefuroxime (Ceftin) 125-500 mg PO q12h [125, 250, 500

mg]

Amoxicillin/clavulan 40 mg of amoxicillin kg/day PO q8h

ate (Augmentin) [susp: amoxicillin 125
mg/clavulanate/5 mL; tab: amoxicillin
250 mg/clavulanate; amoxicillin 500
mg/clavulanate]

Trimethoprim/sulfa 6-12 mg/kg/day (trimethoprim) q12h

methoxazole [susp: trimethoprim 40
(Bactrim) mg/sulfamethoxazole 200 mg/5 mL]

D. Long-term management and follow-up

1. Children with recurrent UTI symptoms. Eight
to 30 percent of children with UTI experience
reinfections. Breakthrough UTIs are most com-
mon in girls.
2. Prompt diagnosis and treatment of UTI reduces
renal scarring.
3. Low-dose long-term antimicrobial therapy, such
as six to 12 months of TMP-SMX or nitrofuran-
toin, should be prescribed for recurrent febrile
UTIs and scarring.
4. Children with VUR. The goal of treating
vesicoureteral reflux (VUR) is to prevent progres-
sive renal damage. The majority of young chil-
dren with VUR have low-grade (grade I to III)
VUR, which will resolve spontaneously. Children
with grades IV and V VUR and older children are
less likely to experience spontaneous resolution.
Mild-to-moderate VUR is treated with low-dose
long-term antimicrobials until resolution of VUR.
Prophylaxis should be discontinued after age five
to seven years, even if low-grade VUR persists.
Prophylaxis consists of TMP-SMX or nitrofuran-
toin in half the usual therapeutic doses given at
bedtime. One out of every five patients on pro-
phylactic nitrofurantoin doses, however, may
experience GI adverse events. Amoxicillin and
cephalosporins are not recommended for prophy-
laxis since infection with resistant strains is likely
to emerge.
5. Older children with persistent severe VUR
(grades IV and V), and those with lesser degrees
of VUR but with progressive scarring while on
prophylaxis, should undergo ureteral
reimplantation.
6. Children with dysfunctional elimination.
Treatment of dysfunctional elimination decreases
UTI recurrence and is associated with faster
resolution of VUR. Treatment of dysfunctional
 elimination includes the use of laxatives and
timed voiding (scheduled voids every two to three
hours).
References, see page 182.

Viral Laryngotracheitis (Croup)

Acute laryngotracheitis (viral croup) is the most common
infectious cause of acute upper airway obstruction in
pediatrics, causing 90% of cases. The disease is usually
self-limited. Children in the 1- to 2-year-old age group are
most commonly affected. Viral croup affects 3-5% of all
children each year. Croup is most common from the late
fall to early spring, although cases may occur throughout
the year.

I. Clinical evaluation of upper airway obstruction and

stridor
A. Stridor is the most common presenting feature of all
causes of acute upper airway obstruction. It is a
harsh sound that results from air movement through
a partially obstructed upper airway.
1. Supraglottic disorders, such as epiglottitis,
cause quiet, wet stridor, a muffled voice,
dysphagia and a preference for sitting upright.
2. Subglottic lesions, such as croup, cause loud
stridor accompanied by a hoarse voice and barky
cough.
B. Patient age
1. Upper airway obstruction in school age and older
children tends to be caused by severe tonsillitis
or peritonsillar abscesses.
2. From infancy to 2 years of age, viral croup and
retropharyngeal abscess are the most common
causes of upper airway obstruction.
C. Mode of onset
1. Gradual onset of symptoms, usually preceded by
upper respiratory infection symptoms, suggests
viral croup, severe tonsillitis or retropharyngeal
abscess.
2. Very acute onset of symptoms suggests
epiglottitis.
3. A history of a choking episode or intermittent res-
piratory distress suggests a foreign body inhala-
tion.
4. Facial edema and urticaria suggests
angioedema.
D. Emergency management of upper airway ob-
struction
1. Maintaining an adequate airway takes prece-
dence over other diagnostic interventions. If a
supraglottic disorder is suspected, a person
skilled at intubation must accompany the child at
all times.
2. Patients with suspected epiglottitis, severe respi-
ratory distress from an obstruction, or suspected
foreign body inhalation should be taken to the
operating room for direct laryngoscopic visualiza-
tion and possible intubation.

Causes of Upper Airway Obstruction in Children

Supraglottic Infectious Disorders
Epiglottitis
Peritonsillar abscess
Retropharyngeal abscess
Severe tonsillitis
Subglottic Infectious Disorders
Croup (viral laryngotracheitis)
Spasmodic croup
Bacterial tracheitis
Non-Infectious Causes
Angioedema
Foreign body aspiration
Congenital obstruction
Neoplasms
External trauma to neck
Characteristics of selected causes of Upper Air-
way Obstruction

Epiglott Laryngotr Bacte- Foreign

itis acheo- rial Body Aspi-
bronchi- Tracheit ration
tis is
(Croup)

History

Inci- 8% 88% 2% 2%
dence
in chil-
dren
pre-
senting
with
stridor

Onset Rapid, 4- Prodrome Prodrom Acute or

12 hours , 1-7 days e, 3 chronic
days,
then 10
hours

Age 1-6 years 3 mo-3 3 mo-2 Any

years years

Season None October- None None

May

Etiol- Haemop Parainflue Staphylo Many

ogy hilus in- nza vi- coccus
fluenza ruses

Pathol- Inflam- Edema Trachea Localized

ogy matory and l-bron- tracheitis
edema of inflamma- chial
epiglottis tion of edema,
and trachea necrotic
supra- and bron- debris
glottitis chial tree

Signs and Symptoms

Dysph Yes No No Rare

agia

Diffi- Yes No Rare No

culty
swallo
wing

Drool- Yes No Rare No

ing

Stridor Inspirator Inspiratory Inspirato Variable

y and expi- ry
ratory

Voice Muffled Hoarse Normal Variable

Cough No Barking Variable Yes

Temper Markedly Minimally Moder- Normal

ature elevated elevated ate

Heart In- Increased Propor- Normal

rate creased late tional to
early fever

Posi- Erect, No effect No effect No effect

tion anxious, on airway
“air hun- obstruc-
gry,” su- tion
pine po-
sition
exacer-
bates

Respi- In- Increased Normal Increased if

ratory creased late bronchial
rate early obstruction
present
 Differentiation of Epiglottitis from Viral
Laryngotracheitis
Clinical Feature Epiglottitis Viral Croup
Retractions present present
Wheezing absent occasionally present
Cyanosis present present in severe
cases
“Toxicity” present absent
Preference for yes no
sitting

II. Epidemiology and etiology of viral laryngotracheitis

(Croup)
A. Parainfluenza virus type 1 causes 40% of all
cases of laryngotracheitis. Parainfluenza type 3,
respiratory syncytial virus (RSV), parainfluenza type
2, and rhinovirus may also cause croup.
B. RSV commonly affects infants younger than 12
months of age, causing wheezing and stridor.
Influenza viruses A and B and mycoplasma have
been implicated in patients older than 5 years.
III. Clinical manifestations
A. Viral croup begins gradually with a 1-2 day
prodrome, resembling an upper respiratory infec-
tion. Subglottic edema and inflammation of the
larynx, trachea, and bronchi eventually develop.
B. Low-grade fever and nocturnal exacerbation of
cough are common. As airway obstruction increases
retractions, develop, restlessness, anxiety, tachycar-
dia, and tachypnea may occur.
C. Cyanosis is a late sign. Severe obstruction leads to
respiratory muscle exhaustion, hypoxemia, carbon
dioxide accumulation, and respiratory acidosis.
Stridor becomes less apparent as muscle fatigue
worsens.
D. Ten percent of croup patients have severe respi-
ratory compromise requiring hospital admission, and
3% of those children need airway support.
IV. Laboratory evaluation. The diagnosis of viral croup
is based primarily on the history and clinical find-
ings. When the diagnosis is uncertain or the patient
requires hospitalization, x-rays can be helpful. The
posteroanterior neck radiograph of a patient with
viral croup shows symmetrical narrowing of the
subglottic space (“steeple sign”).
V. Inpatient treatment of laryngotracheitis
A. The majority of patients who have croup do not
require hospitalization.
B. Indications for hospitalization
1. Dusky or cyanotic skin color.
2. Decreased air entry on auscultation.
3. Severe stridor.
4. Significant retractions.
5. Agitation, restlessness, or obtundation.
C. Signs that indicate the need for an artificial airway
include decreased respiratory effort and decreased
level of consciousness. Pulse oximetry may aid in
assessing the severity of respiratory compromise.
D. All patients suspected of having viral croup should
be given humidified air. Hypoxic or cyanotic patients
require oxygen via mask and may require intubation.
Oral hydration is essential to help loosen secretions;
however, intravenous hydration may become neces-
sary in the very ill child.
E. Racemic epinephrine has alpha-adrenergic prop-
erties, which decrease subglottic inflammation and
edema. Racemic epinephrine is administered as 0.5
mL of a 2.25% solution, diluted with 3.5 mL of saline
(1:8) by nebulization. It is given every 20-30 minutes
for severe croup, and it is given every 4-6 hours for
moderate croup.
F. Corticosteroids reduce subglottic edema and
inflammation. Dexamethasone (0.6 mg/kg IM)
given one time early in the course of croup results in
a shorter hospital stay and reduces cough and
dyspnea. Patients who do not require hospitalization
should not receive steroids.
G. Acetaminophen decreases fever and oxygen
consumption in the febrile patient with croup.
H. Patients with mild viral croup usually are not admit-
ted to the hospital and can be treated safely at
home. Vaporizers, oral fluids, and antipyretics are
the mainstays of home therapy. The prognosis for
croup is good; however, a subset of children who
 have croup will later be identified as having asthma.
References, see page 182.

Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is an acute infection of
the upper genital tract in women, involving any or all of the
uterus, oviducts, and ovaries. PID is a community-ac-
quired infection initiated by a sexually transmitted agent.
Pelvic inflammatory disease accounts for approximately
2.5 million outpatient visits and 200,000 hospitalizations
annually.

I. Clinical evaluation
A. Lower abdominal pain is the cardinal presenting
symptom in women with PID, although the charac-
ter of the pain may be quite subtle. The onset of
pain during or shortly after menses is particularly
suggestive. The abdominal pain is usually bilateral
and rarely of more than two weeks’ duration.
B. Abnormal uterine bleeding occurs in one-third or
more of patients with PID. New vaginal discharge,
urethritis, proctitis, fever, and chills can be associ-
ated signs.
C. Risk factors for PID:
1. Age less than 35 years.
2. Nonbarrier contraception.
3. New, multiple, or symptomatic sexual partners.
4. Previous episode of PID.
5. Oral contraception.
6. African-American ethnicity.
II. Physical examination
A. Only one-half of patients with PID have fever.
Abdominal examination reveals diffuse tenderness
greatest in the lower quadrants, which may or may
not be symmetrical. Rebound tenderness and
decreased bowel sounds are common. Tenderness
in the right upper quadrant does not exclude PID,
because approximately 10 percent of these patients
have perihepatitis (Fitz-Hugh Curtis syndrome).
B. Purulent endocervical discharge and/or acute
cervical motion and adnexal tenderness by
bimanual examination is strongly suggestive of PID.
Rectovaginal examination should reveal the uterine
adnexal tenderness.
III. Diagnosis
A. Diagnostic criteria and guidelines. The index of
suspicion for the clinical diagnosis of PID should be
high, especially in adolescent women.
B. The CDC has recommended minimum criteria
required for empiric treatment of PID. These major
determinants include lower abdominal tenderness,
adnexal tenderness, and cervical motion tender-
ness. Minor determinants (ie, signs that may in-
crease the suspicion of PID) include:
1. Fever (oral temperature >101EF; >38.3EC).
2. Vaginal discharge.
3. Documented STD.
4. Erythrocyte sedimentation rate (ESR).
5. C-reactive protein.
6. Systemic signs.
7. Dyspareunia.
C. Empiric treatment for pelvic inflammatory dis-
ease is recommended when:
1. The examination suggests PID.
2. Demographics (risk factors) are consistent with
PID.
3. Pregnancy test is negative.

Laboratory Evaluation for Pelvic Inflammatory

Disease

• Pregnancy test
• Microscopic exam of vaginal discharge in saline
• Complete blood counts
• Tests for chlamydia and gonococcus
• Urinalysis
• Fecal occult blood test
• C-reactive protein(optional)
IV. Diagnostic testing
A. Laboratory testing for patients suspected of
having PID always begins with a pregnancy test to
rule out ectopic pregnancy and complications of an
intrauterine pregnancy. A urinalysis and a stool for
occult blood should be obtained because abnor-
malities in either reduce the probability of PID.
Blood counts have limited value. Fewer than one-
half of PID patients exhibit leukocytosis.
B. Gram stain and microscopic examination of vaginal
discharge may provide useful information. If a
cervical Gram stain is positive for Gram-negative
intracellular diplococci, the probability of PID
greatly increases; if negative, it is of little use.
C. Increased white blood cells (WBC) in vaginal fluid
may be the most sensitive single laboratory test for
PID (78 percent for >3 WBC per high power field.
However, the specificity is only 39 percent.
D. Recommended laboratory tests:
1. Pregnancy test.
2. Microscopic exam of vaginal discharge in saline.
3. Complete blood counts.
4. Tests for chlamydia and gonococcus.
5. Urinalysis.
6. Fecal occult blood test.
7. C-reactive protein(optional).
E. Ultrasound imaging is reserved for acutely ill
patients with PID in whom a pelvic abscess is a
consideration.
V. Recommendations
A. Health-care providers should maintain a low thresh-
old for the diagnosis of PID, and sexually active
young women with lower abdominal, adnexal, and
cervical motion tenderness should receive empiric
treatment. The specificity of these clinical criteria
can be enhanced by the presence of fever, abnor-
mal cervical/vaginal discharge, elevated ESR
and/or serum C-reactive protein, and the demon-
stration of cervical gonorrhea or chlamydia infec-
tion.
B. If clinical findings (epidemiologic, symptomatic, and
physical examination) suggest PID empiric treat-
ment should be initiated.

Differential Diagnosis of Pelvic Inflammatory

Disease

Appendicitis Irritable bowel syndrome

Ectopic pregnancy Somatization
Hemorrhagic ovarian cyst Gastroenteritis
Ovarian torsion Cholecystitis
Endometriosis Nephrolithiasis
Urinary tract Infection

VI. Treatment of pelvic inflammatory disease

A. The two most important initiators of PID, Neisseria
gonorrhoeae and Chlamydia trachomatis, must be
treated, but coverage should also be provided for
groups A and B streptococci, Gram negative
enteric bacilli (Escherichia coli, Klebsiella spp., and
Proteus spp.), and anaerobes.
B. Outpatient therapy
1. For outpatient therapy, the CDC recommends
either oral ofloxacin (Floxin, 400 mg twice daily)
or levofloxacin (Levaquin, 500 mg once daily)
with or without metronidazole (Flagyl, 500 mg
twice daily) for 14 days. An alternative is an
initial single dose of ceftriaxone (Rocephin, 250
mg IM), cefoxitin (Mefoxin, 2 g IM plus
probenecid 1 g orally), or another parenteral
third-generation cephalosporin, followed by
doxycycline (100 mg orally twice daily) with or
without metronidazole for 14 days. Quinolones
are not recommended to treat gonorrhea ac-
quired in California or Hawaii. If the patient may
have acquired the disease in Asia, Hawaii, or
California, cefixime or ceftriaxone should be
used.
2. Another alternative is azithromycin (Zithromax,
1 g PO for Chlamydia coverage) and
Amoxicillin-clavulanate (Amoxicillin, 875 mg PO)
once by directly observed therapy, followed by
amoxicillin-clavulanate (Amoxicillin, 875 mg PO
BID) for 7 to 10 days.
C. Inpatient therapy
1. For inpatient treatment, the CDC suggests either
 of the following regimens:
a. Cefotetan (Cefotan), 2 g IV Q12h, or
cefoxitin (Mefoxin, 2 g IV Q6h) plus
doxycycline (100 mg IV or PO Q12h)
b. Clindamycin (Cleocin), 900 mg IV Q8h, plus
gentamicin (1-1.5 mg/kg IV q8h)
2. Alternative regimens:
a. Ofloxacin (Floxin), 400 mg IV Q12h or
levofloxacin (Levaquin, 500 mg IV QD) with
or without metronidazole (Flagyl, 500 mg IV
Q8h). Quinolones are not recommended to
treat gonorrhea acquired in California or
Hawaii. If the patient may have acquired the
disease in Asia, Hawaii, or California,
cefixime or ceftriaxone should be used.
b. Ampicillin-sulbactam (Unasyn), 3 g IV Q6h
plus doxycycline (100 mg IV or PO Q12h)
3. Parenteral administration of antibiotics should
be continued for 24 hours after clinical re-
sponse, followed by doxycycline (100 mg PO
BID) or clindamycin (Cleocin, 450 mg PO QID)
for a total of 14 days.
4. The following regimen may also be used:
Levofloxacin (Levaquin), 500 mg IV Q24h,
plus metronidazole (Flagyl, 500 mg IV Q8h).
With this regimen, azithromycin (Zithromax, 1 g
PO once) should be given as soon as the pa-
tient is tolerating oral intake. Parenteral therapy
is continued until the pelvic tenderness on
bimanual examination is mild or absent.
D. Annual screening is recommended for all sexually
active women under age 25 and for women over 25
if they have new or multiple sexual partners. A
retest for chlamydia should be completed in 3 to 4
months after chlamydia treatment because of high
rates of reinfection.
E. Additional evaluation:
1. Serology for the human immunodeficiency virus
(HIV).
2. Papanicolaou smear.
3. Hepatitis B surface antigen determination and
initiation of the vaccine series for patients who
are antigen negative and unvaccinated.
4. Hepatitis C virus serology.
5. Serologic tests for syphilis.
References, see page 182.

Gastrointestinal Disorders
Acute Abdominal Pain
The evaluation of abdominal pain in children is problem-
atic because the pain is often difficult to localize, and the
history in children is often nonspecific.

I. Localization of abdominal pain

A. Generalized pain in the epigastrium usually comes
from the stomach, duodenum, or the pancreas.
B. Periumbilical pain usually originates in small bowel
and colon or spleen.
C. Parietal pain, caused by inflammation, is usually
well localized.
D. Referred abdominal pain occurs when poorly
localized visceral pain is felt at a distant location.
1. Pancreatitis, cholecystitis, liver abscess, or a
splenic hemorrhage cause diaphragmatic irrita-
tion, which is referred to the ipsilateral neck and
shoulders.
2. Intraabdominal fluid may cause shoulder pain
on reclining.
3. Gallbladder pain may be felt in the lower back or
infrascapular area.
4. Pancreatic pain often is referred to the posterior
flank.
5. Ureterolithiasis often presents as pain radiating
toward the ipsilateral groin.
6. Rectal or gynecological pain often is perceived
as sacral pain.
7. Right lower lobe pneumonia may be perceived
as right upper quadrant abdominal pain.
II. Clinical evaluation
A. History should include the quality, timing, and type
of abdominal pain.
1. Pain of sudden onset often denotes colic,
 perforation or acute ischemia caused by torsion
or volvulus.
2. Slower onset of pain suggests inflammatory
conditions, such as appendicitis, pancreatitis, or
cholecystitis.
B. Colic results from spasms of a hollow viscus organ
secondary to an obstruction. It is characterized by
severe, intermittent cramping, followed by intervals
when the pain is less intense. Colic pain usually
originates from the biliary tree, pancreatic duct,
gastrointestinal tract, urinary system, or uterus and
tubes.
C. Inflammatory pain is caused by peritoneal irritation,
and the patient presents quietly without much
motion and appears ill. The pain is initially less
severe and is exacerbated by movement.
D. Vomiting. Usually abdominal pain will precede
vomiting. The interval between abdominal pain and
vomiting is shorter when associated with colic.
Delayed vomiting for many hours is often associated
with distal bowel obstruction or ileus secondary to
peritonitis.
E. Diarrhea. Mild diarrhea with the onset of abdominal
pain suggests acute gastroenteritis or early appendi-
citis. Delayed onset of diarrhea may indicate a
perforated appendicitis, with the inflamed mass
causing irritation of the sigmoid colon.
F. Physical examination
1. The abdomen should be observed, auscultated,
and palpated for distention, localized tenderness,
masses, and peritonitis. The groin must be exam-
ined to exclude an incarcerated hernia or ovary,
or torsion of an ovary or testicle.
2. Rectal examination
a. Gross blood in the stool suggests ectopic
gastric mucosa, Meckel’s diverticula, or pol-
yps.
b. Blood and mucus (currant jelly stool) sug-
gests inflammatory bowel disease or
intussusception.
c. Melena suggests upper gastrointestinal bleed-
ing, necessitating gastric aspiration for blood.
d. Tests for occult blood in the stool should be
performed.
3. Pelvic examinations are mandatory for
postmenarchal and/or sexually active female
patients. The rectal examination may also be
used to evaluate the cervix, uterus, adnexa, and
pelvic masses.
4. Fever
a. Thoracic disease (eg, pneumonia) may be the
cause of abdominal pain associated with fever.
b. Costovertebral angle tenderness with fever
suggests pyelonephritis or a high retrocecal
appendicitis.
III. Appendicitis
A. Fever, vomiting, irritability, lethargy with right
lower quadrant (RLQ) tenderness and guarding
are diagnostic of appendicitis in the very young
patient until proven otherwise. A mass may be felt
on rectal exam in 2-7% of younger patients with
appendicitis.
B. A WBC >15,000 supports the diagnosis. An ultra-
sound of the appendix may be useful.
C. Children older than 2 years old present with a
perforated appendix about 30-60% of the time. This
incidence declines as the age of the child increases.
IV. Intussusception
A. Intussusception is the most common cause of bowel
obstruction between 2 months and 5 years of age.
The most vulnerable age group is 4-10 months old,
but children up to 7 years old may be at risk.
B. Intussusception is characterized by vomiting, colicky
abdominal pain (85%) with drawing up of the legs,
and currant jelly stools (60%). Fever is common.
C. The abdomen may be soft and nontender between
episodes of colicky pain, but eventually it becomes
distended. A sausage-shaped mass in the right
upper quadrant (RUQ) may be palpable.
D. Abdominal x-ray. The leading edge of the
intussusception is usually outlined with air, which will
establish the diagnosis. Often there are radiographic
signs of bowel obstruction. When the plain abdomi-
nal x-ray is normal, intussusception cannot be
excluded without a barium enema.
E. Treatment consists of radiologic reduction, which is
 effective in 80-90%. Radiographic reduction is
contraindicated if there is peritoneal irritation or
toxicity.
V. Midgut volvulus
A. Midgut volvulus results from the improper rotation
and fixation of the duodenum and colon
(malrotation). Obstruction of the superior mesenteric
artery may cause ischemic necrosis of the gut,
which may be fatal.
B. Infants in the first month constitute the majority of
the cases. Symptoms usually begin about 5 days
before diagnosis. The first sign of volvulus is bilious
vomiting, followed by abdominal distention and GI
bleeding. Peritonitis, hypovolemia, and shock may
follow.
C. Abdominal x-ray reveals a classic double bubble
caused by duodenal obstruction. Pneumatosis
intestinalis or distal bowel obstruction may also be
apparent.
D. Infants with rapid deterioration and obstructed loops
of bowel require immediate surgery. If the infant is
not critically ill, an UGI series with water-soluble,
non-ionic, isoosmolar contrast will confirm midgut
volvulus. If malrotation or volvulus (beak, spiral or
corkscrew sign) is found, an immediate laparotomy
is necessary.
VI. Gallbladder disease
A. Cholecystitis in children occurs most commonly in
the adolescent female, but it may affect infants who
are only a few weeks of age. Cholecystitis is sug-
gested by RUQ pain, back pain, or epigastric pain,
radiating to the right subscapular area, bilious
vomiting, fever, RUQ tenderness, and a RUQ mass.
Jaundice is present in 25-55%, usually in associa-
tion with hemolytic disease.
B. Ultrasonography delineates gallstones and is the
study of choice to screen for gallbladder disease.
C. Radioisotopic scanning evaluates biliary and
gallbladder function.
VII. Ectopic pregnancy
A. Ectopic pregnancy must be considered in any
postmenarchal, sexually active adolescent with
abdominal pain. It is uncommon and usually seen in
late adolescence. Ectopic pregnancy occurs in 0.5-
3% of all pregnancies.
B. Signs of ectopic pregnancy include abdominal pain
in any location, vaginal bleeding, and/or
amenorrhea. Nausea and vomiting, other symptoms
of pregnancy, and lightheadedness may also be
present.
C. Abdominal, adnexal, and/or cervical tenderness are
often found on pelvic examination, but occasionally
abdominal tenderness is absent. The cervix may be
soft (Godell’s sign) and bluish in color (Chadwick’s
sign). The examination may reveal adnexal fullness
and uterine enlargement.
D. Evaluation includes a pregnancy test and ultra-
sound. Treatment consists of removal of the ectopic
pregnancy by laparoscopy or exploratory
laparotomy.
VIII. Gonadal pain in males
A. In males with lower abdominal pain, the scrotum and
its contents must be examined. Testicular torsion is
a surgical emergency and must be treated within 6
hours of the onset of the pain to save the testicle.
B. Testicular torsion may present as lower abdominal
pain, which may be associated with recent trauma or
cold. The gonad is tender and elevated in the
scrotum, with a transverse orientation. Although
testicular torsion may occur at any age, it usually
occurs in adolescent males at puberty or shortly
afterwards.
IX. Gonadal pain in females
A. The leading causes of gonadal pain in females are
ovarian cysts and torsion of uterine adnexal struc-
tures.
B. Ovarian cysts are responsible for 25% of childhood
ovarian tumors, most commonly in adolescents.
Bleeding into the cyst or cystic rupture causes pain,
which usually subsides within 12-24 hours. Ultra-
sound may show pelvic fluid and the cyst.
C. Torsion of uterine adnexal structures
1. Torsion is associated with unilateral, sudden,
severe pain with nausea and vomiting. The
patient may also have subacute or chronic symp-
toms, with intermittent pain for days. The pain is
usually diffuse and periumbilical in younger
 patients, but in older children and adolescents,
the pain may radiate initially to the anterior thigh
or ipsilateral groin.
2. Fever and leucocytosis are usually present.
Physical exam may reveal muscle rigidity and
fixation of the mass on pelvic examination.
3. Ultrasound will identify the mass accurately.
Surgical exploration may sometimes salvage the
ovary. Malignant neoplasms may cause torsion in
35% of cases.
X. Meckel diverticulum
A. Meckel diverticulum are present in 2% of the popula-
tion. It presents as a tender left lower quadrant
mass, associated with blood in the stool.
B. Vague abdominal pain with hemoccult positive
stools suggests a Meckel diverticulum. Bleeding is
seen in 35-40% of childhood cases. A technetium
nuclear scan may confirm the diagnosis.
References, see page 182.

Recurrent Abdominal Pain

Recurrent abdominal pain (RAP) includes any child or
adolescent who has recurrent abdominal pain for which
the family seeks medical attention and explanation. More
than 90% of the time a “disease” will not be defined and
the family will be left with a “functional” explanation.

I. Epidemiology
A. RAP occurs in 10-15% of children between the ages
of 4 and 16 years. About 13-17% of adolescents
experience weekly pain. The overall incidence
appears to peak at 10 to 12 years. RAP is rare
among children younger than 5 years of age.

Differential Diagnosis of Recurrent Abdominal

Pain

• Functional abdominal pain • Dysmenorrhea

• Fecal impaction - Endometriosis
• Parasitic infection - Ectopic pregnancy
• Partial small bowel ob- - Adhesions from pelvic
struction inflammatory disease
- Crohn disease • Cystic teratoma of ovary
- Malrotation with or with- • Musculoskeletal disorders
out volvulus - Muscle pain
- Intussusception - Linea alba hernia
- Postsurgical adhesions - Discitis
- Small bowel lymphoma • Vascular disorders
- Infection (tuberculosis, - Mesenteric thrombosis
Yersinia) - Polyarteritis nodosa
- Eosinophilic • Abdominal migraine
gastroenteritis • Acute intermittent
- Angioneurotic edema porphyria
• Ureteropelvic junction ob- • Psychiatric disorders
struction
• Appendiceal colic

Diagnostic Criteria for Functional Abdominal Pain

• Chronicity
• Compatible age range, age of onset
• Characteristic features of abdominal pain
• Evidence of physical or psychological stressful stimuli
• Environmental reinforcement of pain behavior
• Normal physical examination (including rectal examination
and stool guaiac)
• Normal laboratory evaluation (CBC, sedimentation rate,
urinalysis, urine culture, stool ova and parasites)

II. Clinical Aspects

A. Functional abdominal pain. The majority of chil-
dren who have RAP are considered to have a
functional etiology, and an organic etiology cannot
be found. The pain occurs in episodes that are
periumbilical, self-limited, unrelated to meals or
activities, and rarely if ever sufficient to awaken the
child from sleep. The growth pattern and findings on
the physical examination are normal. The degree of
interference with normal activities and school atten-
dance are out of proportion to the frequency and
severity of the episodes.
B. Irritable bowel syndrome. Some children who
have RAP manifest characteristics of irritable bowel
syndrome (IBS). The criteria for making this diagno-
sis are: 1) abdominal pain relieved by defecation, 2)
 more frequent stools at the onset of the pain, 3)
altered stool form (hard or loose or watery), 4)
passage of mucus, and 5) associated bloating or
abdominal distension.
C. Constipation. The most common causes of consti-
pation in children are inadequate intake of fruits,
vegetables and higher-fiber foods, and an unwilling-
ness to evacuate the bowels. The child goes days
between bowel movements and the stool is bulky
and hard. Findings on abdominal and rectal exami-
nations may confirm the diagnosis; a plain abdomi-
nal radiograph may be needed.
D. Inflammatory bowel disease. Ulcerative colitis
may present with abdominal pain, hematochezia
and tenesmus. Crohn disease may cause abdomi-
nal pain, diarrhea, lethargy, growth and pubertal
delay, and oral, joint, and perirectal involvement.
Endoscopy will confirm the diagnosis.
E. Lactose intolerance. Asian, Jewish, Mediterra-
nean, and African-American persons are predis-
posed to lactase deficiency. Lactose ingestion will
cause bloating, loose stools, and cramping abdomi-
nal pain. The diagnosis is made by breath hydrogen
testing or a therapeutic trial of restriction of milk
products.
F. Helicobacter pylori-associated peptic ulcer
disease should be suspected when abdominal pain
is primarily epigastric; when it awakens the child
from sleep; and when it is associated with anorexia,
nausea, recurrent vomiting, anemia, or gastrointesti-
nal bleeding. Peptic ulcer disease is very uncom-
mon is children; therefore, testing for H pylori should
not be part of the preliminary evaluation of a child
who has RAP.
G. Nonulcer dyspepsia is a symptom complex of
epigastric pain, bloating, and discomfort accompa-
nied by negative endoscopic and biopsy findings.
H. Abdominal migraine usually is recognized when
episodes of paroxysmal abdominal pain occur in
association with nausea and vomiting, sometimes
with associated headache. A strong family history of
migraine is usually present.
I. Infestation/infection. Infection with Yersinia
enterocolitica and giardia can cause diarrhea
associated with abdominal cramps and pain, but
diarrhea usually is the predominant complaint.
J. Gynecologic conditions. Early menarche,
endometriosis, pelvic inflammatory disease, and
ovarian cyst may cause RAP. These causes can be
diagnosed by ultrasonographic examination.
K. Physical and sexual abuse may cause RAP, and
sensitive history taking is required to elucidate its
possible role.
III. Clinical assessment
A. The history should assess the location, nature,
frequency of the pain, and associated symptoms.
The relationship of the pain to school and so-
cial/family stressors is important. Review of systems
should cover the child’s diet, bowel habits, sleep
patterns, and context in which the pain occurs.
B. The degree to which the pain interferes with the
child’s activities should be defined. Family function,
school performance, anxiety, depression, or social
maladjustment should be assessed. Medication use
should be assessed.

“Red Flags” on History of Recurrent Abdominal

Pain

• Localization of the pain away from the umbilicus

• Pain associated with change in bowel habits, particularly
diarrhea, constipation, or
nocturnal bowel movements
• Pain associated with night wakening
• Repetitive emesis, especially if bilious
• Constitutional symptoms, such as recurrent fever, loss of
appetite or energy
• RAP occurring in a child younger than 4 years of age

C. Physical Examination. Height and weight should

be recorded and compared to previous growth data.
The abdomen should be examined gently and
thoroughly while observing the child’s response to
palpation. The perianal area should be examined for
fissures, skin tags, or signs of sexual abuse. A rectal
examination is not routinely performed.
 “Red Flags” on Physical Examination for Recur-
rent Abdominal Pain

• Loss of weight or decline in height velocity

• Organomegaly
• Localized abdominal tenderness, particularly removed from
the umbilicus
• Perirectal abnormalities (eg, fissures, ulceration, or skin
tags)
• Joint swelling, redness, or heat
• Ventral hernias of the abdominal wall

IV. Investigations
A. Laboratory investigations should usually be limited
to a complete blood count, urinalysis, and examina-
tion of a stool specimen for occult blood. In the
presence of diarrhea, a stool for enteric culture and
ova and parasite examination is indicated.
B. Radiography. A single view of the abdomen can be
useful to confirm constipation.
C. Abdominal ultrasonography can be valuable when
obstructive uropathy hydronephrosis, ovarian cysts,
or gall bladder disorders are suspected. Enteric
duplication also may be revealed by ultrasonography.
Ultrasound is appropriate when the pain is
lateralized, when there are abnormalities on urinaly-
sis, or when the pain localizes to the lower quadrants
in a female.
D. Erythrocyte sedimentation rate, serum protein and
albumin levels, and stool for occult blood should be
obtained. If IBD is a possible diagnosis. Endoscopy
and biopsy will confirm the diagnosis. Upper gastroin-
testinal endoscopy with biopsies will confirm the
diagnosis when the pattern of pain strongly suggests
peptic ulcer disease.
V. Management
A. Functional recurrent abdominal pain will be the
diagnosis in the majority of cases. The parents
should maintain a sympathetic attitude that acknowl-
edges the pain but encourages continued activities
and school attendance. Parents should refrain from
questioning the child about the pain if the child is not
complaining. A trial of increasing fiber by dietary
modification may be useful.
B. Psychogenic pain may respond to the intervention
of a psychologist or psychiatrist.
C. Constipation requires treatment with regular stool
softeners, preceded by an enema.
D. Lactose malabsorption. A lactose-free diet for
several weeks with lactase-treated milk should be
tried. Ice cream and cheese should be avoided.
E. Enteric infections or infestations require treatment
with appropriate medications. Abdominal migraine
may warrant a trial of migraine prophylaxis. Prophy-
lactic pizotifen, cyproheptadine, propranolol, or ami-
triptyline could be considered.
References, see page 182.

Chronic Nonspecific Diarrhea

Diarrhea is considered chronic when it persists for longer
than 3 weeks. Chronic nonspecific diarrhea (CNSD)
presents in toddlers between 18 months and 3 years of
age, with frequent, large, watery stools in the absence of
physical or laboratory signs of malabsorption or infection
and without effect on growth or development. Children
have 3 to 6 large, watery bowel movements daily. The
diarrhea spontaneously resolves in 90% of children by 40
months of age.

I. Pathogenesis
A. Factors causing CNSD
1. Excess fluid intake
2. Carbohydrate malabsorption from excessive juice
ingestion
3. Disordered intestinal motility
4. Excessive fecal bile acids
5. Low fat intake
B. CNSD occurs when fluid intake exceeds the absorp-
tive capacity of the intestinal tract. Malabsorption of
carbohydrates (sucrose, fructose, sorbitol) in fruit
juices contributes to CNSD.
C. CNSD presents between 18 months and 3 years,
with 3-6 large, loose, watery stools per day for more
than 3 weeks.
 D. Stooling is most frequent in the morning and does
not occur during sleep. There is an absence of
nausea, vomiting, abdominal pain, flatulence, blood,
fever, anorexia, weight loss, or poor growth.
II. Clinical evaluation of chronic nonspecific diarrhea
A. The current number and type of stools should be
determined. A diet history should determine the total
calories, fat, milk and juice consumed daily, and it
should assess prior trials of food elimination.
B. The timing of introduction of foods into the diet
relative to the onset of diarrhea, and a 3-day diet
history should be assessed. Usage of antibiotics,
vitamins, iron, and medications should be sought.
C. A family history of irritable bowel syndrome, celiac
disease, inflammatory bowel disease, infectious
diarrhea, or food allergies should be sought.
D. Physical examination
1. Growth chart plotting of weight, height, and head
circumference are essential. Children who have
CNSD should continue to grow normally; devia-
tion from the growth chart or a downward trend
suggests inadequate caloric intake or a disease
other than CNSD.
2. Signs of malnutrition or malabsorption include
lack of subcutaneous fat, eczematoid rash (from
essential fatty acid deficiency), glossitis, easy
bruising, or hyporeflexia.
E. Laboratory tests
1. A fresh stool specimen is tested for neutral fat,
pH and reducing substances, occult blood, and
Giardia antigen. Neutral fat suggest pancreatic
insufficiency.
2. Fecal pH and reducing substances will reveal
carbohydrate malabsorption if the pH is less than
5.5 or if reducing substances are greater than 1+.
3. Occult fecal blood is inconsistent with CNSD
unless there is a perianal rash.
4. Giardia and Cryptosporidium are common and
should be excluded with 3 stool samples for ova
and parasites.

Stool Evaluation

Test Result Disease

pH <5.5 Carbohydrate
malabsorption
Reducing sub- >1+
stances

Neutral fat >40 globules/high Pancreatic insuffi-

power field ciency

Occult blood Positive Enteritis or colitis

Giardia antigen Positive Giardiasis

Ova and parasites Positive Giardiasis, crypto-

sporidiosis

III. Differential diagnosis

A. The differential diagnosis of chronic diarrhea in the
6- to 36-month-old child includes disaccharidase
deficiency, protein intolerance, enteric infection, and
malabsorption.
B. Lactase deficiency
1. Lactase deficiency may cause diarrhea associ-
ated with milk ingestion.
2. Congenital lactase deficiency is extremely rare
and symptoms are present from birth if an infant
is fed human milk or a lactose-containing for-
mula.
3. Genetically acquired lactase deficiency is
common, but it usually is not symptomatic before
5 years of age.
C. Congenital sucrase-isomaltase deficiency is
rare, producing symptoms when sucrose-containing
formula or foods are introduced.
D. Disaccharidase deficiency can be confirmed by
eliminating the specific carbohydrate or by breath
hydrogen analysis.
E. Milk-induced colitis occurs in infants younger than
1 year of age who typically appear healthy but lose
blood in their stool after ingesting milk protein.
Infants who have milk-induced enterocolitis are
younger, less than 3 months of age. These infants
may be severely ill with bloody diarrhea,
 hypoproteinemia, and growth failure. Children who
have protein allergies tend to come from families
that have allergic histories, and affected children
may have eczema, allergic rhinitis, asthma.
F. Giardia or Cryptosporidium enteric infections
are commonly transmitted by asymptomatic carriers
at child care centers. Foul-smelling diarrhea usually
is associated with abdominal distension and flatus.
Diagnosis is confirmed by Giardia antigen in stool or
three stools for ova and parasites.
G. Malabsorption presents with chronic diarrhea,
weight loss, poor appetite, weakness and de-
creased activity, bloating and flatulence, abdominal
pain, and chronic vomiting. The most common
causes are cystic fibrosis and celiac disease.
Chronic diarrhea and failure to thrive warrants a
sweat test. Screening for celiac disease consists of
a D-xylose absorption test and a serum celiac
disease panel (antigliadin, antiendomysial, and
antireticulin antibodies). Celiac disease must be
confirmed by intestinal biopsy.
IV. Management of CNSD
A. Fluid intake should be reduced to less than 100
mL/kg/day. Water is substituted for juice to reduce
the child’s interest in drinking. Switching from the
bottle to the cup also decreases fluid intake.
B. Fat intake is increased to 4 g/kg/day by adding
whole milk to the diet. If lactose intolerance is
present, low-lactose milk can be used or lactase
drops can be added to milk. Butter, margarine, or
vegetable oil are liberally added to foods for children
less than 2 years of age.
C. Dietary fiber can be increased by consumption of
fresh fruits and vegetables or by the addition of
bran.
References, see page 182.

Constipation
Constipation is common in infants and children. The
problem usually resolves after modification of the child’s
fluid and dietary regimen.

I. Pathophysiology
A. Persistent difficulty with the passage of stool may
lead to impaction, stool withholding, and fecal
soiling.

Conditions Associated With Constipation

Condition Common Causes

Lack of Fecal Bulk High-carbohydrate or high-pro-

tein diet
Undernutrition

Abnormally Hard Stools Excessive cow milk intake

Abnormally Dry Stools Dehydration

Infantile renal acidosis
Diabetes insipidus
Idiopathic hypercalcemia

Nervous System Lesion Spinal cord lesions

Mechanical Obstruction Anorectal stenotic lesions

Intrinsic and extrinsic masses
Strictures
Aganglionosis (Hirschsprung
disease)

Diseases That Complicate Amyotonia congenita

Defecation Cerebral palsy
Hypertonia
Hypothyroidism

II. Neonates and infants younger than 1 year of age

A. Evaluation of constipation in neonates and
infants
1. Inadequate fluid intake, undernutrition, and
excessive cow milk intake should be excluded
during the history.
2. Anal inspection at the time of birth reveals
anorectal anomalies in one in every 2,500 live
births. Anal stenosis accounts for 20% of these
abnormalities. The anus appears very small with
a central black dot of meconium, and the infant
 must make an intense effort to pass a ribbon-like
stool. The abdomen may be distended and stool
can often be palpated on abdominal examination.
3. Hirschsprung disease
a. Hirschsprung disease accounts for 20-25% of
cases of neonatal obstruction, and it is more
common in males. Symptoms develop during
the first month of life in 80%. The majority of
infants are unable to pass stool normally
during the first week.
b. Infants with Hirschsprung disease usually fail
to pass meconium during the first 48 hours of
life. The abdomen is usually distended and
tympanitic. Abdominal peristaltic activity may
be visible, and fecal masses may be palpable.
The anal canal and rectum are empty of feces.

c. Plain abdominal radiographs reveal gas and

stool in the colon above the rectum. A
rectosigmoid index (the diameter of the rectum
divided by the diameter of the sigmoid) of less
than one is consistent with Hirschsprung
disease.
d. When findings from the history, physical, and
plain abdominal radiographs suggest
Hirschsprung disease, contrast examination of
the unprepared colon should be obtained. The
diagnosis is confirmed by endoscopic biopsy.
B. Management of simple constipation in infants
1. Dietary corrective measures are the initial therapy
for infants with simple constipation. Increasing
fluid intake and adding carbohydrate sugar to the
formula often corrects the problem.
2. Infants that do not respond to dietary measures
are treated with a mineral oil preparation. Routine
suppository administration, enemas, and stimu-
lant laxatives should be avoided.
III. Older infants and children
A. Evaluation
1. Fluid and dietary fiber intake should be assessed.
Older children with chronic constipation and stool
withholding usually also have fecal incontinence.
2. Moveable fecal masses are often appreciated in
the left colon and sigmoid.
3. The lower back should be examined for a deep
pilonidal dimple with hair tuft and/or sacral
agenesis, suggestive of myelodysplasia. Anal
inspection may reveal primary anal disease.
Normal anal tone found on rectal examination
indicates normal anal innervation. The rectal
vault may be filled with inspissated stool.
4. Anteroposterior and lateral x-rays of the abdo-
men usually reveal a large rectal/rectosigmoid
impaction with variable amounts of stool through-
out the remainder of the colon.
B. Management of chronic constipation
1. Distal impaction should be removed with
hypertonic phosphate enemas (Fleet enema).
Usually three enemas are administered during a
36- to 48-hour period.
2. Mineral oil should be prescribed. The initial dose
of mineral oil is 30-75 mL twice daily. Mineral oil
is tasteless, and it can be taken with fruit juice,
Kool-Aid, or a soft drink. After one month, the oil
is tapered by 15 mL (0.5 oz) per dose. Haley’s
MO is a mineral oil solution of 1.4 gm/5 mL.
3. The child should sit on the toilet, with proper foot
support, for five minutes after the evening meal to
take advantage of the gastrocolic reflex. A
bulk-type stool softener (eg, Metamucil) should
be initiated when the mineral oil dosage has been
tapered to 15 mL twice daily.
References, see page 182.

Gastroenteritis
Acute gastroenteritis consists of diarrheal disease of rapid
onset, often with nausea, vomiting, fever, or abdominal
pain. It occurs an average of 1.3-2.3 times per year
between the ages of 0 and 5 years. Most episodes of
acute gastroenteritis will resolve within 3 to 7 days.

I. Pathophysiology. Gastroenteritis in children is caused

by viral, bacterial, and parasitic organisms, although
the vast majority of cases are viral or bacterial in origin.
II. Viral gastroenteritis
A. All of the viruses produce watery diarrhea often
accompanied by vomiting and fever, but usually not
associated with blood or leukocytes in the stool or
with prominent cramping.
B. Rotavirus is the predominant viral cause of dehy-
drating diarrhea. Rotaviral infections tend to pro-
duce severe diarrhea, causing up to 70% of epi-
sodes in children under 2 years of age who require
hospitalization. Rotavirus infection tends to occur in
the fall in the southwest of the US, then sweeping
progressively eastward, reaching the northeast by
late winter and spring.
C. Norwalk viruses are the major cause of large
epidemics of acute nonbacterial gastroenteritis,
occurring in schools, camps, nursing homes, cruise
ships, and restaurants.
D. Enteric adenovirus is the third most common
organism isolated in infantile diarrhea.
III. Bacterial gastroenteritis
A. The bacterial diarrheas are caused by elaboration
of toxin (enterotoxigenic pathogens) or by invasion
and inflammation of the mucosa (invasive patho-
gens).
B. Secretory diarrheas are modulated through an
enterotoxin, and the patient does not have fever or
myalgias or tenesmus, or white or red blood cells in
the stool. The diarrhea is watery, often is large in
volume, and often associated with nausea and
vomiting.
C. Invasive diarrhea is caused by bacterial
enteropathogens, and is accompanied by systemic
signs, such as fever, myalgias, arthralgias, irritabil-
ity, and loss of appetite. Cramps and abdominal
pain are prominent. The diarrhea consists of fre-
quent passing of small amounts of stool within the
mucus. Stool examination reveals leukocytes, red
blood cells, and often gross blood.

Acute Diarrhea Patterns and Associated Patho-

gens

Secretory/enterotoxigenic Inflammatory

Characterized by watery diar- Characterized by dysentery

rhea and absence of fecal (ie, fever and bloody stools),
leukocytes fecal leukocytes, and erythro-
cytes

Food poisoning (toxigenic)

Staphylococcus aureus Shigella

Bacillus cereus Invasive E coli
Clostridium perfringens Salmonella
Campylobacter

Enterotoxigenic

Escherichia coli C difficile

Vibrio cholera Entameba histolytica
Giardia lamblia
Cryptosporidium
Rotavirus
Norwalk-like virus

IV. General approach to the patient with

gastroenteritis
A. Determining and managing the fluid losses,
dehydration and electrolyte abnormalities is
more important than ascertaining the specific
microbiologic cause.
B. History should assess recent antibiotic use, under-
lying diseases, other illnesses in the family, travel,
untreated water, raw shellfish, attendance at a child
care center, and foods eaten recently.

Clinical Evaluation and Treatment of Acute Diarrhea

Step One--Assess child for degree of dehydration

No dehydration Continue oral hydration and feed-
ing

Mild/severe dehydration- Initiate rehydration by oral route

--------> (intravenous for severely dehy-
drated patients)
Step Two--Assess Clinical History for Etiologic Clues
Etiologic Clue Etiology Suggested

Fever, crampy abdomi- Inflammatory colitis or ileitis

nal pain, tenesmus

History of bloody stool Shigella, enteroinvasive E coli,

amebiasis, other bacterial causes

Fever and abdominal Yersinia enterocolitis

pain

Current or previous Antibiotic-associated enteritis or

antibiotic use pseudomembranous colitis

Multiple cases and Incubation <6 hours: Staphylococ-

common food source cus aureus, Bacillus cereus
Incubation >6 hours: Clostridium
perfringens

Ingestion of inade- Vibrio parahaemolyticus

quately cooked seafood

Recent measles, se- Bacterial (Salmonella), viral (rota-

vere malnutrition, AIDS, virus), or parasitic (isosporiasis,
other causes of Cryptosporidium)
immunosuppression

Step Three--Examine Stool:

Indicated Finding: Etiology Sug-
for: gested:

Visual ex- All patients Gross blood Dysentery,

amination colitis, invasive
organism

Micro- Patients who Red cells Shigella,

scopic have had and leuko- enterohemorrh
examina- diarrhea >3 cytes agic EC,
tion for days, fever, enteroinvasive
white/red blood in Red cells EC,
blood cells stool, weight without leu- Campylobacter
loss kocytes , Clostridium,
E histolytica

Parasitic Diarrhea >10 Positive Giardia,

examina- days Amoeba,
tion (wet Cryptosporidiu
mount, m, Isospora,
acid-fast Strongyloides
staining, or
concen-
tration)

Clostridium Patients tak- Positive C difficile coli-

difficile tox- ing antibiotics tis
in

Assessment of Diarrheal Dehydration

Mild Moderate Severe
Clinical (10-40 (50-90 mL/kg) (100-130
Finding mL/ mL/ kg)
kg)
Affect/se Normal Irrita Leth- Stupor
nsorium bility argy
Eyes Normal Sunk Deeply
en sunken
Mucous Normal Dry Very dry
mem-
brane
Tears Yes No No
when cry-
ing
Thirst Normal + ++ +++ ++++ or
unrespon-
sive
Skin Normal Re- Very re-
turgor duce duced (2-3
(capillary d (<1 sec)
refill) sec)
Fonta- Normal Depr Severely
nelle es- depressed
sed
Pulse Full Full Weak Feeble or
absent
Pulse rate Normal Eleva Very rapid
ted
Blood Normal Nor- Low or
pressure mal absent

C. Fluid therapy
1. Mild-to-moderate dehydration
a. Mildly or moderately dehydrated children.
Oral rehydration solution (ORS) is the pre-
ferred method of rehydrating a child with
 dehydration. In most western countries,
rotavirus is the most common cause of child-
hood diarrhea. In such patients, Pedialyte,
Infalyte, Ceralyte, Naturalyte or Pediatric
Electrolyte is appropriate. ORS should be
given at 50 mL/kg (mild dehydration) or 100
mL/kg (moderate dehydration) over a 4-hour
period. Replacement of stool losses (at 10
mL/kg for each stool) and of emesis (esti-
mated volume) will require adding appropri-
ate amounts of solution to the total.
2. Prevention of dehydration
a. Children who have diarrhea, but not dehy-
drated, may be given glucose-electrolyte
solution in addition to their regular diets to
replace stool losses. The well-hydrated child
should continue to consume an age-appropri-
ate diet and drink more than the usual
amounts of the normal fluids.
b. The diet should emphasize complex carbohy-
drates, such as starches, cereal, and fresh
fruits and vegetables, with no sugary or fatty
foods. Apple juice and soft drinks, such as
cola, should be avoided, whereas sports
drinks, such as Gatorade, are generally well
tolerated. If the child is breast fed, breast-
feeding should be continued.
3. Severely dehydrated children who are in a
state of shock must receive immediate and
aggressive intravenous (IV) therapy. When the
patient is stable, hydration may be continued
orally.
4. Intravenous rehydration
a. When intravenous rehydration is required, it
should begin with an isotonic solution (normal
saline, lactated Ringer). Severe dehydration
clinically is associated with a loss of 10-12%
of body weight in fluids and electrolytes (100
to 120 mL/kg); therefore, this amount plus
additional losses should be infused.
b. Infusion rates of up to 100 mL/min are appro-
priate in older children. Infusion rates of 40
mL/kg are given over the first 30 minutes,
with the remainder of the deficit (70 mL/kg)
over the next 2.5 hours, until the calculated
fluid loss has been replenished.
c. For infants, correction should be slower, with
infusion rates no more than 30 mL/kg over
the first hour and the remaining 70 mL/kg
over 5 hours.
d. Subsequent maintenance fluids should be
given orally. Oral fluids should be initiated as
soon as the patient can drink. They should be
given simultaneously with intravenous fluids
until the total fluids administered have replen-
ished the calculated deficit.
D. Antibiotic therapy. The effectiveness of
antimicrobial therapy is well established in
shigellosis. Shigella is the cause of bacterial dysen-
tery and is the second most commonly identified
bacterial pathogen in diarrhea between the ages of
6 months and 10 years. It causes watery diarrhea
with mucus and gross blood. Treatment consists of
ceftriaxone or cefixime.
E. Refeeding
1. Children who have diarrhea and are not dehy-
drated should continue to be fed age-appropriate
diets. Fatty foods and foods high in simple
sugars, such as juices and soft drinks should be
avoided. Well-tolerated foods include complex
carbohydrates (rice, wheat, potatoes, bread,
cereals), lean meats, yogurt, fruits, and vegeta-
bles. The BRAT diet (bananas, rice, applesauce,
toast) does not supply optimal nutrition.
2. Introducing the child’s regular form of milk early
in the course of therapy is recommended.
F. Antidiarrheal compounds (eg, loperamide,
diphenoxylate, bismuth compounds, Kaopectate)
should not be used to treat acute diarrhea.
V. Laboratory examinations
A. The presence of blood in the stool, fever, or persis-
tence of the diarrhea for more than 3 days may
trigger a laboratory pursuit of an etiologic agent.
B. Microscopic stool examination. If erythrocytes
and white blood cells are present, particularly in the
setting of fever, a bacterial pathogen
(Campylobacter, Yersinia, Salmonella, Shigella)
 should be suspected. Many red blood cells in the
absence of white blood cells suggests the presence
of Entamoeba.
C. Stool culture should be reserved for individuals
whose diarrhea has not responded to fluid and
feeding and for those who have fever and the
presence of leukocytes or red blood cells in the
stool.
D. Rotavirus should be suspected in a one-year-old
presenting in the winter months with a three-day
history of vomiting and watery diarrhea with mild
dehydration. Laboratory evaluation in this setting is
generally not indicated. If the diagnosis is unclear,
stool for viral particles or rotavirus antigen
(Rotazyme [R]) may be helpful.
References, see page 182.

Gastroesophageal Reflux
Gastroesophageal reflux (GER) is a common condition
involving regurgitation. GER implies a functional or
physiologic process in a healthy infant with no underlying
systemic abnormalities. The prevalence of GER peaks
between one to four months of age, and usually resolves
by six to 12 months of age. Regurgitation occurs in 40 to
65 percent of healthy infants.
Gastroesophageal reflux disease (GERD) is a patho-
logic process in infants manifested by poor weight gain,
signs of esophagitis, persistent respiratory symptoms, and
changes in neurobehavior. GERD occurs in approximately
one in 300 infants.

I. Clinical manifestations
A. Infants with GER regurgitate without inadequate
growth, esophagitis, or respiratory disease. Infants
with GER are thriving and represent the majority of
infants who present with this condition.
B. Patients with GERD may manifest persistent regurgi-
tation with secondary poor weight gain and failure to
thrive. Other infants may manifest signs of
esophagitis, including persistent irritability, pain,
feeding problems, and iron deficiency anemia.
II. Diagnostic evaluation. In most cases of GER, no
diagnostic study is required. Although scintigraphy may
best quantify gastric emptying or aspiration, it is not as
commonly used as the upper GI examination (barium
fluoroscopy).
III. Management
A. Conservative treatment of GER involves thickened
feedings and positional changes in infants, and
dietary modification in children. Healthy infants who
regurgitate may be managed by thickening feedings
with up to one tablespoon of dry rice cereal per 1 oz
of formula.
B. Smaller, more frequent feedings are recommended
in older infants and children. Completely upright and
prone positioning is beneficial in infants with GERD.
Soft bedding materials should be avoided in this
setting. Prone positioning is not routinely recom-
mended as first-line management of simple regurgi-
tation without evidence of GERD.
C. Pharmacologic management
1. H2-receptor antagonists
a. Cimetidine (Tagamet). The recommended
starting dosage is 10 mg per kg per dose four
times daily before meals and at bedtime for
eight weeks. Potential side effects include
headaches, dizziness, diarrhea, and
gynecomastia.
b. Ranitidine (Zantac) 1-2 mg per kg per dose
two to three times daily (2-6 mg per kg per
day) is the starting dosage. Potential side
effects include headaches and malaise, but
ranitidine has fewer central nervous system
and anti-androgenic side effects.
 Dosages and Side Effects of H2-Receptor
Agonists and Prokinetic Agents

Agents Dosage Side effects

Cimetidine 10 mg per kg per Headaches, dizzi-

(Tagamet) dose, four times ness, diarrhea,
daily gynecomastia

Ranitidine 1 to 2 mg per kg Headaches and

(Zantac) per dose, two to malaise
three times daily

Cisapride 0.2 mg per kg per Cardiac arrhyth-

(Propulsid)* dose, three to four mia,
times daily diarrhea

*Because of the small potential risk of serious arrhythmias,

this drug is only available via a limited access program.

2. Prokinetic agent: Cisapride (Propulsid) is the

prokinetic of choice for GERD. It increases lower
esophageal sphincter pressure and esophageal
contractile amplitude. Reports of fatal
arrhythmias have emerged. Cisapride is available
through a limited access program if other thera-
pies are not effective.
References, see page 182.

Inflammatory Bowel Disease

I. Initial evaluation of chronic diarrhea
A. The initial diagnostic evaluation of chronic diarrhea
includes stool cultures for enteric pathogens, tests
for ova and parasites, Clostridium difficile toxin, and
fecal leukocytes. Specific cultures for Yersinia
enterocolitica, isolation of toxigenic strains of
Escherichia coli, and serologic titers for Entamoeba
histolytica may also be necessary.
B. Laboratory studies include levels of C-reactive
protein, which correlates with severity of disease,
and levels of serum proteins (eg, albumin,
transferrin, prealbumin, retinol-binding protein),
which assess nutritional status. The degree of
anemia indicates the severity of mucosal injury and
duration of illness.
C. Colonoscopy or flexible sigmoidoscopy with
biopsy is valuable in characterizing mucosal injury.
D. Abdominal plain films with the patient in upright
and supine positions should be obtained in patients
with severe disease to detect perforation, toxic
megacolon, or thumbprinting.
II. Ulcerative colitis
A. Ulcerative colitis (UC) is the most common cause of
chronic colitis. Inflammation is localized primarily in
the mucosa. The most common symptoms are
abdominal pain, rectal bleeding, diarrhea, fever,
and malaise.
B. The incidence ranges from 4 to 15 cases per
100,000. Disease may present at any time but does
so most often during adolescence and young
adulthood, with a higher risk of the disease in
young females than males. Among family mem-
bers, the risk is tenfold higher. Ashkenazi Jews are
afflicted more often than non-Jewish populations.
C. Thirty percent of UC patients present with disease
limited to the rectum, 40% have more extensive
disease but not extending beyond the hepatic
flexure, and 30% have total colonic involvement.
D. Diagnostic evaluation
1. Inflammation characteristically begins in the
rectum. The mucosa is erythematous, friable,
and edematous, with superficial erosions and
ulcerations. Histologic features of ulcerative
colitis include diffuse shallow ulceration of the
mucosa, crypt abscesses, thickening of the
muscularis mucosa, and pronounced inflamma-
tory cell infiltration.
2. Extraintestinal manifestations
a. Musculoskeletal. Arthritis is the most com-
mon extraintestinal manifestation of ulcerative
colitis. It is migratory, often involving the hip,
ankle, wrist, or elbow. It is usually
monoarticular and asymmetric, and its course
parallels that of the colitis. Ankylosing
spondylitis and sacroiliitis, or axial arthritis,
typically present as low back pain with morn-
 ing stiffness.
b. Ocular. Episcleritis, uveitis, and iritis may
occur.
c. Dermatologic. Abnormalities may include
erythema nodosum, pyoderma gangrenosum,
lichen planus, and aphthous ulcers.
d. Hepatobiliary. Manifestations may include
hepatic steatosis, primary sclerosing
cholangitis (4%), cholelithiasis, and
pericholangitis.
e. Miscellaneous. Other complications include
nephrolithiasis and a hypercoagulable state.
III. Crohn disease
A. Crohn disease (CD) is a chronic inflammatory
process, which may involve any portion of the
gastrointestinal tract from the mouth to the anus.
Inflammation is characterized by transmural exten-
sion and irregular involvement of the intestinal tract,
with intervening normal tissue (“skip areas”). Most
often, the distal ileum and proximal colon are
involved; in about 25% of cases, only the colon is
affected.
B. Crohn disease often has its onset during adoles-
cence and young adulthood. It is more common in
females. The overall risk is two to four times higher
in first-degree relatives.
C. Fever, abdominal pain, diarrhea, weight loss, and
fatigue are common. Rectal bleeding is not as
prominent a feature in Crohn disease as it is in
ulcerative colitis. About 20% of patients have
evidence of perianal disease, such as perirectal
fistulas, anal skin tags, anal ulcerations or fissures,
or perirectal abscesses. Crohn disease causes
extra-intestinal manifestations like those of ulcer-
ative colitis.
D. Diagnostic evaluation
1. Anemia, caused by chronic blood loss and a
mildly elevated white blood cell count are com-
mon.
2. Endoscopic findings include focal ulcerations
and inflammation is interrupted by skip areas.
Other features of Crohn disease include rectal
sparing, cobblestone appearance, strictures, and
ileal involvement.
IV. Management of ulcerative colitis
A. Mild-to-moderate cases of ulcerative colitis
1. Mesalamine (Asacol) is an oral 5-ASA com-
pound used for active ulcerative colitis, and
olsalazine sodium (Dipentum) is used for main-
tenance therapy. The target dosage for the tablet
Asacol (in divided doses) is 2.4 g/day, the cap-
sule (Pentasa) 4 g/day, and capsule olsalazine
(Dipentum) 1 g/day.
2. Limited left-sided colonic disease or
rectosigmoid disease may respond to local
therapy (enemas, suppositories) with
corticosteroids and mesalamine.
3. Rectal preparations of mesalamine (Rowasa
enema and suppository) can deliver higher
concentrations to the distal colon for proctitis.
Rowasa (4 g) is the only enema preparation of 5-
ASA.
4. Balsalazide (Colazal). Balsalazide, a prodrug of
mesalamine (5-aminosalicylic acid) for oral
treatment of mildly to moderately active ulcer-
ative colitis. Patients treated with balsalazide are
more likely to achieve a symptomatic remission
(88% vs 57%) or a complete remission (62% vs
37%), and became asymptomatic in 10 days
compared to 25 days with delayed-release
mesalamine.
B. Moderately severe cases of ulcerative colitis
1. These patients may require rehydration or blood
transfusion. Corticosteroids, a low-residue diet,
and local therapy should be initiated.
2. Prednisone usually is started at a dose of 1 to 2
mg/kg per day for 1 to 2 weeks. Once the patient
has stabilized, the patient is weaned off the
steroids to alternate-day therapy over 4 to 8
weeks; mesalamine (Asacol) is usually started.
Hydrocortisone retention enema (Cortenema), is
effective for distal ulcerative colitis.
C. Fulminant ulcerative colitis requires immediate
hospitalization.
1. Fluid and electrolyte status must be stabilized
and blood transfusions given as needed. Intrave-
nous corticosteroids (methylprednisolone),
 broad-spectrum antibiotics (metronidazole, an
aminoglycoside, and ampicillin), parenteral
nutrition, and bowel rest are initiated.
2. If the patient deteriorates clinically or develops
complications (hemorrhage, toxic megacolon),
emergency surgery is performed. If the patient
has not improved for 2 to 4 weeks after maximal
medical therapy, a colectomy should be consid-
ered. Surgery is curative for UC.

Treatment of Inflammatory Bowel Disease

Dose/da Rout Side Effects

y e

5-Aminosalicylic Acid

Mesalamine 30-50 PO Nephrotoxicity

(Asacol) mg/kg
Mesalamine Chills, diarrhea
(Rowasa) 2-4 g qd
Enema PR
Supposi- 500 mg PR
tory bid PO Local irritation
Mesalamine
(Pentasa) 50-60 PO Nephrotoxicity
Olsalazine mg/kg
(Dipentum) PO Watery diarrhea
Basalazine 20-30
(Colazal) mg/kg

2.25 g tid

Steroids

Prednisone 1-2 PO Osteoporosis, hyper-

mg/kg tension, poor growth,
obesity, hirsutism,
cataracts, adrenal
suppression

Methylprednis 0.8-1.6 PO Same as for predni-

olone mg/kg sone

Hydrocorti-
sone 100 mg PR Local irritation
Enema QD-BID
80 mg PR Same as enema
Foam QD-BID

Immunosuppressants

6- 1-1.5 PO Pancreatitis, bone

mercaptopurin mg/kg marrow suppression
e

Azathioprine 1.5-2 PO Same as for 6-

mg/kg mercaptopurine

Cyclosporine 2-4 IV Nephrotoxicity

mg/kg PO Hirsutism, hyperten-
4-6 sion
mg/kg

Antibiotics

Metronidazole 10-20 PO/I Peripheral neuropa-

mg/kg V thy, metallic taste

Miscellaneous

Folic acid 1 mg PO

V. Management of Crohn disease. Treatment is similar

to that of ulcerative colitis. Corticosteroids and
mesalamine (Asacol) are the mainstays of therapy.
Patients with severe colitis, massive weight loss, and
significant systemic symptoms may need to be
hospitalized. Prednisone can induce a remission in
70% of patients who have small bowel disease.
A. Antibiotics (metronidazole and ciprofloxacin) are
useful in mild-to-moderate CD and perianal disease.
B. Immunosuppressive agents. Mercaptopurine and
azathioprine are reserved for patients with continu-
ous disease activity despite corticosteroid therapy.
Cyclosporine may be beneficial in refractory pa-
tients.
C. Surgery for Crohn disease is not curative. Indica-
tions include obstruction or intractable symptoms.
Disease almost always recurs after surgery.
References, see page 182.
Persistent Vomiting
Vomiting is defined as the forceful expulsion of gastric
contents through the mouth. Vomiting can be caused by a
benign, self-limited process or it may be indicative of a
serious underlying disorder.

I. Pathophysiology of vomiting
A. Vomiting is usually preceded by nausea, increased
salivation, and retching. It is distinct from regurgita-
tion, which is characterized by passive movement of
gastric contents into the esophagus.
B. Projectile vomiting results from intense gastric
peristaltic waves, usually secondary to gastric outlet
obstruction caused by hypertrophic pyloric stenosis
or pylorospasm.
C. Retching often precedes vomiting and is character-
ized by spasmodic contraction of the expiratory
muscles with simultaneous abdominal contraction.
II. Clinical evaluation of vomiting

Etiology of Vomiting by Age

Newborn Infant Older Child

Obstruction Malrotation Pyloric ste- Intussuscepti

of bowel nosis on
Volvulus Foreign bod- Foreign bod-
Intestinal ies ies
atresia Malrotation Malrotation
Intestinal (volvulus) (volvulus)
stenosis Duplication Meckel
Meconium of alimentary diverticulum
ileus tract Hirschsprun
Meconium Intussuscept g disease
plug ion Incarcerated
Hirschsprun Meckel hernia
g disease diverticulum Adhesions
Imperforate Hirschsprun
anus g disease
Incarcerated Incarcerated
hernia hernia

Gastroin- Necrotizing Gastroenterit Gastroenterit

testinal dis- enterocolitis is is
orders Gastroesoph Gastroesoph Peptic ulcer
(infecti- ageal reflux ageal reflux disease
ous/inflam- Paralytic Pancreatitis
matory) ileus Appendicitis
Peritonitis Celiac dis-
Milk allergy ease
Paralytic
ileus
Peritonitis

Infectious Sepsis Sepsis Meningitis

disorders Meningitis Meningitis Otitis media
(nongastro- Otitis media Pharyngitis
intestinal) Pneumonia Pneumonia
Pertussis Hepatitis
Hepatitis Urinary tract
Urinary tract infection
infection

Neurologic Hydrocepha- Hydrocepha- Subdural

disorders lus lus hematoma
Kernicterus Subdural Intracranial
Subdural hematoma hemorrhage
hematoma Intracranial Brain tumor
Cerebral hemorrhage Other mass-
edema Mass lesion occupying
(abscess, lesion
tumor) Migraine
Motion sick-
ness
Hypertensive
encephalopa
thy

Metabolic Inborn errors Inborn errors Adrenal

and endo- of metabo- of metabo- insufficiency
crine disor- lism: Urea lism Diabetic
ders cycle de- Fructose ketoacidosis
fects, galac- intolerance
tosemia, dis- Adrenal
orders of insufficiency
organic acid Metabolic
metabolism acidosis
Congenital
adrenal hy-
perplasia
Neonatal
tetany

Renal disor- Obstructive Obstructive Obstructive

ders uropathy uropathy uropathy
Renal insuf- Renal insuf- Renal insuffi-
ficiency ficiency ciency
 Newborn Infant Older Child

Toxins Digoxin Digoxin

Iron Iron
Lead
Food poison-
ing

Other Pregnancy
Anorexia
nervosa
Bulimia
Psychogenic
etiology

A. Clinical evaluation of vomiting in the neonate

1. Bilious vomiting, at any age, suggests intestinal
obstruction or systemic infection. Anatomic abnor-
malities of the gastrointestinal tract that may
present in the first week of life with bilious vomit-
ing and abdominal distention include malrotation,
volvulus, duplications of the bowel, bowel atresia,
meconium plug, meconium ileus, incarcerated
hernia, and aganglionosis (Hirschsprung dis-
ease).
2. Necrotizing enterocolitis
a. NEC is the most common inflammatory condi-
tion of the intestinal tract in the neonate.
Symptoms of NEC include abdominal disten-
tion, bilious vomiting, and blood in the stool.
b. The infant who has NEC also may present with
nonspecific signs of systemic infection, such
as lethargy, apnea, temperature instability, and
shock. NEC occurs mainly in preterm infants,
although 10% of affected newborns present at
term.
3. Metabolic disorders
a. Inborn errors of metabolism should be
considered in any acute neonatal illness,
including persistent vomiting. Factors that
suggest a metabolic disorder include early or
unexplained death of a sibling, multiple spon-
taneous maternal abortions, or history of
consanguinity.
b. Associated features may include lethargy,
hypotonia, and convulsions.
4. Neurologic disorders. Central nervous system
abnormalities, such as intracranial hemorrhage,
hydrocephalus and cerebral edema, should be
suspected in the neonate who has neurologic
deficits, a rapid increase in head circumference,
or an unexplained fall in hematocrit.
B. Clinical evaluation of vomiting in infancy
1. Pyloric stenosis
a. Pyloric stenosis is a major consideration in
infants. Hypertrophy of the pylorus causes
gastric outlet obstruction at the pyloric canal.
Five percent of infants whose parents had
pyloric stenosis develop this disorder. Males
are affected more often than females.
b. Symptoms of pyloric stenosis usually begin at
age 2 to 3 weeks, but may occur at birth or
present as late as 5 months. An olive-size
mass may be palpable in the right upper quad-
rant.
2. Gastroesophageal reflux
a. Gastroesophageal reflux (GER) is defined as
retrograde movement of gastric contents into
the esophagus. GER occurs in 65% of infants
and is caused by inappropriate relaxation of
the lower esophageal sphincter.
b. GER is considered “pathologic” if symptoms
persist beyond 18 to 24 months and/or if
significant complications develop, such as
failure to thrive, recurrent episodes of
bronchospasm and pneumonia, apnea, or
reflux esophagitis.
3. Gastrointestinal allergy. Cow milk allergy is rare
in infancy and early childhood and generally
resolves by 2 to 3 years of age. Vomiting, diar-
rhea, colic and gastrointestinal loss of blood may
occur.
III. Clinical evaluation of vomiting in childhood
A. Peptic ulcer in early childhood is often associated
with vomiting. Peptic ulcer disease should be sus-
pected if there is a family history of ulcer disease, or
if there is hematemesis or unexplained iron defi-
ciency anemia. Abdominal pain typically wakes the
patient from sleep.
 B. Pancreatitis
1. Pancreatitis is a relatively rare cause of vomiting,
but should be considered in the child who has
sustained abdominal trauma. Patients usually
complain of epigastric pain, which may radiate to
the mid-back.
2. Other factors predisposing to pancreatitis include
viral illnesses (mumps), drugs (steroids,
azathioprine), congenital anomalies of the biliary
or pancreatic ducts, cholelithiasis,
hypertriglyceridemia, and a family history of
pancreatitis.
C. Central nervous system disorders. Persistent
vomiting without other gastrointestinal or systemic
complaints suggests an intracranial tumor or in-
creased intracranial pressure. Subtle neurologic
findings (eg, ataxia, head tilt) should be assessed
and a detailed neurologic examination should be
performed.
IV. Physical examination of the child with persistent
vomiting
A. Volume depletion often results from vomiting,
manifesting as sunken fontanelles, decreased skin
turgor, dry mouth, absence of tears, and decreased
urine output.
B. Peritoneal irritation should be suspected when the
child keeps his knees drawn up or bends over.
Abdominal distension, visible peristalsis, and in-
creased bowel sounds suggests intestinal obstruc-
tion.
C. Abnormal masses, enlarged organs, guarding or
tenderness should be sought. A hypertrophic
pylorus may manifest as a palpable “olive” in the
right upper quadrant.
D. Intussusception is often associated with a tender,
sausage-shaped mass in the right upper quadrant
and an empty right lower quadrant (Dance sign).
E. Digital rectal exam. Decreased anal sphincter tone
and large amounts of hard fecal material in the
ampulla suggests fecal impaction. Constipation,
increased rectal sphincter tone, and an empty rectal
ampulla suggests Hirschsprung disease.
V. Laboratory evaluation
A. Serum electrolytes should be obtained when
dehydration is suspected.
B. Urinalysis may detect a urinary tract infection or
suggest the presence of a metabolic disorder.
C. Plasma amino acids and urine organic acids
should be measured if metabolic disease is sus-
pected because of recurrent, unexplained episodes
of metabolic acidosis.
D. Serum ammonia should be obtained in cases of
cyclic vomiting to exclude a urea cycle defect.
E. Liver chemistries and serum ammonia and
glucose levels should be obtained if liver disease is
suspected.
F. Serum amylase is frequently elevated in patients
who have acute pancreatitis. Serum lipase levels
may be more helpful because it remains elevated for
a number of days following an acute episode.
VI. Imaging studies
A. Ultrasonography of the abdomen is the initial
imaging test for suspected pyloric stenosis; however,
two-thirds of vomiting infants will have a negative
sonogram and will subsequently require an upper
gastrointestinal series.
B. Plain radiographs of the abdomen
1. Supine and upright or left lateral decubitus
radiographic views are necessary for detecting
congenital anatomic malformations or obstructive
lesions.
2. Air-fluid levels suggest obstruction, although this
finding is nonspecific and may be seen with
gastroenteritis.
3. Free air in the abdominal cavity indicates a
perforated viscus. Upright plain films may demon-
strate free air under the diaphragm.
C. Upper gastrointestinal series with nonionic,
iso-osmolar, water-soluble contrast is indicated
when anatomic abnormalities and/or conditions that
cause gastric outlet obstruction are suspected.
D. Barium enema should be performed to detect lower
intestinal obstruction, and it may also be therapeutic
in intussusception.
VII. Treatment
A. Initial therapy should correct hypovolemia and
 electrolyte abnormalities. In acute diarrheal illnesses
with vomiting, oral rehydration therapy is usually
adequate for treatment of dehydration.
B. Bilious vomiting and suspected intestinal ob-
struction is managing by giving nothing by mouth,
and by placing a nasogastric tube connected to
intermittent suction. Bilious vomiting requires surgi-
cal consultation.
C. Pharmacologic therapy
1. Antiemetic agents usually are not required
because most instances of acute vomiting are
caused by self-limited, infectious gastrointestinal
illnesses. Antiemetic drugs may be indicated for
postoperative emesis, motion sickness, cytotoxic
drug-evoked emesis, and gastroesophageal
reflux disease.
2. Diphenhydramine and dimenhydrinate are
useful in treating the symptoms of motion sick-
ness or vestibulitis.
3. Prochlorperazine and chlorpromazine have
anticholinergic and antihistaminic properties and
are used to treat vomiting caused by drugs,
radiation, and gastroenteritis.
References, see page 182.
Neurologic and Rheumatic
Disorders
Febrile Seizures
Febrile seizures are the most common convulsive disorder
of childhood. A febrile seizure is defined as a seizure
associated with fever in infancy or early childhood (usually
between 3 months and 5 years of age) without evidence of
intracranial infection or other cause.
The problem almost always resolves without sequelae.
Only a small minority will develop non-febrile seizures
later. There is no risk of brain damage.

I. Epidemiology. Febrile seizures occur in 2-4% of young

children. The most common age of onset is in the sec-
ond year of life. Higher temperature and a history of
febrile seizures in a close relative are risk factors for the
development of a febrile seizure.
A. Recurrence
1. After the first febrile seizure, 33% of children will
experience one or more febrile seizures, and 9%
of children who have febrile seizures will have 3
or more. The younger the child’s age when the
first febrile seizure occurs, the greater the likeli-
hood of recurrence.
2. Family history of febrile seizures is a risk factor for
recurrence. Short duration of fever before the
initial seizure and relatively lower fever at the time
of the initial seizure are risk factors.
B. Epilepsy. Fewer than 5% of children who have
febrile seizures develop epilepsy. Risk factors for the
development of epilepsy following febrile seizures
include suspicious or abnormal development before
the first seizure, family history of afebrile seizures,
and complex first febrile seizure.
II. Pathophysiology. Most febrile illnesses associated
with febrile seizures are caused by common infections
(tonsillitis, upper respiratory infections, otitis media).
Children of preschool age are subject to frequent
infections and high fevers.
III. Clinical evaluation
A. Febrile seizures usually occur early in the course of
a febrile illness, often as the first sign. The seizure
may be of any type, but the most common is tonic-
clonic. Initially there may be a cry, followed by loss
of consciousness and muscular rigidity. During this
tonic phase, apnea and incontinence may occur.
The tonic phase is followed by the clonic phase of
repetitive, rhythmic jerking movements, which is
then followed by postictal lethargy or sleep.
B. Other seizure types may be characterized by staring
with stiffness or limpness or only focal stiffness or
jerking. Most seizures last less than 6 minutes; 8%
last longer than 15 minutes.
C. An underlying illness that may require treatment
should be sought. Symptoms of infection, med-
ication exposure, or trauma should be assessed.
Family history of febrile or afebrile seizures should
be evaluated. A complete description of the seizure
should be obtained from a witness.
D. Physical examination
1. The level of consciousness, presence of
meningismus, a tense or bulging fontanelle,
Kernig or Brudzinski sign, and any focal abnor-
malities in muscle strength or tone should be
sought.
2. Encephalitis or meningitis must be excluded.
E. Laboratory studies should evaluate the source of
fever. A lumbar puncture (LP) is indicated if there is
any suspicion of meningitis. CT or MRI are seldom
helpful and are not performed routinely. The electro-
encephalogram (EEG) is not helpful in the evalua-
tion of febrile seizures because it is not predictive of
recurrence risk of later epilepsy.
IV. Management of febrile seizures
A. The child should be kept in the emergency depart-
ment or physician’s office for at least several hours
and re-evaluated. Most children will have improved
and be alert, and the child may be sent home if the
cause of the fever has been diagnosed and treated.
Hospital admission is necessary if the child is
unstable or if meningitis remains a possibility.
B. Parental counseling
 1. Parents are advised that febrile seizures do not
cause brain damage, and the likelihood of devel-
oping epilepsy or recurrent non-febrile seizures is
very small. There is a risk of further febrile sei-
zures during the current or subsequent febrile
illnesses.
2. If another seizure occurs, the parent should place
the child on his side or abdomen with the face
downward. Nothing should be forced between the
teeth. If the seizure does not stop after 10 min-
utes, the child should be brought to the hospital.
C. Control of fever with antipyretics (acetaminophen)
and sponging is recommended, but this practice has
not been proven to lower the risk of recurrent febrile
seizures.
D. Childhood immunizations. Febrile seizures occur
most commonly following a DPT immunization
because pertussis provokes fever. The advantages
of vaccines must be weighed against the risk of
pertussis if immunization is postponed.
V. Long-term management
A. Prophylaxis with diazepam or phenobarbital is not
routinely necessary, but is reserved for very young
children who have sustained multiple seizures
associated with focal postictal paralysis.
B. Diazepam may be administered orally and rectally
during febrile illnesses to prevent recurrences of
seizures. Oral diazepam is given in three divided
doses to a total of 1 mg/kg per day when the child is
ill or feverish.
References, see page 182.

Seizures
The majority of children with epilepsy have an idiopathic
disorder; the neurological examination and neuroimaging
studies are normal.

I. Clinical evaluation of seizures

A. The first seizure. A child’s first seizure may be
caused by an acute illness, such as a metabolic or
infectious disorder, may be idiopathic and non-
recurrent, or may represent the beginning of epi-
lepsy.
B. Prognosis after a first seizure. The child who is
neurologically normal, has no history of a prior
neurological illness, and has an unprovoked seizure
with no evident cause (idiopathic seizure) has a 24
percent risk of having another seizure in the next
year. The recurrence risk increases to 37 percent in
children in whom the seizure is related to a prior
neurological insult (remote symptomatic), such as
cerebral palsy, and increases to 70 percent in the
next year in patients who have had two seizures
(excluding sequential seizures in 24 hours).
C. Setting in which episodes occur. Most seizures
are random events; however, many nonepileptic
syndromes have characteristic precipitating circum-
stances or occur in specific locations. Thus, deter-
mining the time of day and the activity in which the
child was engaged prior to the seizure is important.
Did the seizures occur only with illness and fever?
D. Behavior immediately prior to the event. On rare
occasions, seizures may be precipitated by environ-
mental stimuli, such as sound or an unexpected
touch. More commonly, no obvious precipitating
circumstances are present. Thus, obtaining a history
of the events leading up to the seizure is important
because they may be more suggestive of a non-
seizure diagnosis.
E. What activity was the patient engaged in immedi-
ately prior to the seizure? Does the patient mention
any sensory or autonomic symptoms (numbness,
visual distortions, auditory or visual hallucinations or
illusions, nausea or unusual feelings in the abdomen
or chest, an unusual smell or taste, etc) or manifest
an alteration in behavior or mood?
F. Are the seizures precipitated by a particular stimu-
lus? Seizures rarely are precipitated by mild trauma.
G. Was focal motor activity, such as facial or extremity
twitching, present? These symptoms are considered
an "aura," which is actually the first clinical manifes-
tation of the seizure; this information is valuable for
localizing.
H. Physical description. The physician should obtain
 a description of the patient’s color. If a child has a
color change during a seizure, particularly a general-
ized motor seizure, he/she usually will become
cyanotic. A cardiac cause for the event should be
considered if the child is described as pale.

International Classification of Epileptic Seizures

Partial Seizures
–Simple partial (consciousness retained)
–Complex partial (consciousness impaired)
–Partial seizure with secondary generalization

Generalized Seizures
–Absence seizures
–Myoclonic seizures
–Clonic seizures
–Tonic seizures
–Tonic-clonic seizures
–Atonic seizures

Unclassified Seizures

I. Behavior during the event

1. Are limb movements unilateral, bilateral, synchro-
nous, true clonic (rhythmic flexion movements or
rhythmically interrupted tonus), or more irregular
and thrashing? Bilateral motor seizures, particu-
larly those involving all the extremities and the
trunk with generalized, relatively symmetric, tonic
or clonic movements, usually are associated with
an alteration of consciousness. A nonepileptic
seizure should be suspected if the patient has
minimal to no movement during the seizure and
is unresponsive for more than two minutes.
Stimulus-provoked clonic/tonic activity during a
generalized motor seizure is more consistent with
a pseudoseizure.
2. Are the eyes and mouth closed? A pseudoseizure
should be considered if the patient keeps the
eyes tightly closed during the seizure and, partic-
ularly, if passive opening is actively resisted.
Patients with true generalized motor seizures
tend to keep their mouths open during the tonic
phase of the seizure.
3. What was the patient’s response to verbal com-
mands, pinching, or more painful stimulation?
Generalized motor seizures cannot be interrupted
by vocal or tactile/painful stimulation. In contrast,
a patient with a pseudoseizure may suddenly
return to normal after a painful stimulus or shout-
ing of his or her name.
4. What was the duration of the event? Most sei-
zures are short-lived; an episode of confusion or
loss of contact with the environment that lasts
more than five minutes should raise the suspicion
of a nonepileptic event.
J. Behavior after the event
1. What was the patient’s behavior post-event? Did
the child recover immediately, or was there
postictal confusion or somnolence? Was the child
able to communicate verbally immediately after
the event?
2. Was postictal weakness present? Was it global or
focal, involving a limb or the face only?
K. Psychosocial assessment. Seizures often are
accompanied by cognitive and developmental delay.
The child may be having increasing difficulty at
school because of peer ridicule, a low academic
performance as a result of limited cognitive function,
and low self-esteem because of depression.
L. Other elements of the history
1. A developmental history should be obtained, with
particular attention given to any plateau or loss of
developmental milestones.
2. The examiner should search for a history of
previous illnesses that often are followed by
seizures (eg, meningitis, hypoxic-ischemic
encephalopathy).
3. Family history should assess the possibility of
consanguinity, which suggests an inherited
disorder, particularly a recessively metabolic
disorder. A family history of seizures is suggestive
of a dominantly inherited epileptic disorder.
II. Physical examination
A. Congenital ocular defects, the retinal changes of a
neurocutaneous disorder, or signs of an earlier
infection should be sought.
 B. The abdominal examination may reveal
organomegaly, suggesting a storage disease.
C. Cardiac examination, including an ECG, is neces-
sary if concern exists about a cardiogenic cause.
Episodes of disturbed neurological function caused
by decreased cardiac output (eg, prolonged QT
syndrome or pulmonary hypertension) may closely
mimic complex partial seizures.
D. Dysmorphic features should be sought and other
congenital anomalies, body asymmetries, and
unusual skull shapes noted.
E. The cutaneous features of tuberous sclerosis, the
facial angioma of Sturge-Weber syndrome, the café-
au-lait spots of neurofibromatosis, the nevi of the
linear nevus syndrome, and the swirling
hypopigmentation of Ito syndrome all are character-
istic physical findings.
III. Electroencephalogram (EEG). Virtually every child
with recurrent seizures should have an EEG awake
and while sleeping. Obtaining an awake and a sleep
EEG and optimizing the timing of the EEGs should
maximize the chances of finding epileptiform activity.
A. Sleep. An awake and asleep EEG should be ob-
tained. Epileptiform activity may appear in only one
state (usually sleep). In the benign partial epilepsies,
focal or multifocal spike and slow wave discharges
typically appear during drowsiness and light sleep.
Benign focal epilepsy syndromes may manifest
generalized EEG discharges as well as a
photoparoxysmal response (epileptiform activity
provoked by repetitive light flashes), which more
typically are seen in the idiopathic generalized
epilepsies. The most striking and diagnostic pattern,
however, is the sleep-activated focal spikes.
IV. Laboratory testing and neuroimaging
A. Neuroimaging. Most children with recurrent sei-
zures should have an MRI scan, usually without the
use of contrast.
B. Laboratory screening in undiagnosed epilepsy.
Routine assessment consists of a serum (and often
CSF) amino acid analysis, urine for quantitative
organic acids, serum calcium, glucose, carnitine,
ammonia, lactate and pyruvate, routine chromo-
somal karyotype (virtually all chromosomal syn-
dromes can manifest seizures), and DNA analysis
for fragile X syndrome, particularly in boys and
occasionally in girls with maternal family histories of
mental retardation. More sophisticated genetic
analyses, such as FISH studies, may be needed to
diagnose those syndromes missed on routine
karyotype analysis.
V. Treatment of Seizures and Epileptic Syndromes
in Children
A. Predictors of recurrence. In children with an idio-
pathic seizure, the EEG is the most valuable predic-
tor of recurrence. An idiopathic first seizure, the
recurrence risk was 41 percent in the first 12 months
after the initial seizure if the EEG was abnormal
compared with 15 percent in children with a normal
EEG.
B. Treating a child with an idiopathic first seizure is
usually not recommended. In children with seizures
that result from a past injury or insult, the risk of
seizure recurrence is higher.
C. Many parents elect to avoid therapy if the seizures
are infrequent and/or mild. Many patients with
benign partial epilepsy are not treated if seizures are
relatively infrequent. Children with absence seizures,
drop attacks, and infantile spasms are virtually
always treated.
Epileptic Syndromes and Recommended
Antiepileptic

Syndrome Antiepileptic drug

Localization-related 1 - CBZ. PB, VPA, TPM,

(partial, focal) PHT, LTG, OXC
2 - GBP, PRM, CRZ,
LEV

Generalized epilepsies 1 - ESM, VPA, LTG

Absence seizures 2 - CNZ

Generalized tonic-clonic 1 - CBZ, VPA, PHT, PB

TPM
2 - LTG

Juvenile myoclonic epi- 1 - VPA, LMG

lepsy 2 - PRM, CNZ, TPM

Myoclonic absence 1 - VPA, ESM

2 - LTG, CNZ, TPM

Infantile spasms 1 - ACTH, prednisone

2 - VPA (?), CNZ (?),
TPM (?)

Lennox-Gastaut syn-
drome 2 - ESM (drop attacks),
FBM

1: First-line drugs
2: Second-line drugs

CBZ: carbamazepine; CRZ: clorazepate; CNZ:

clonazepam; ESM: ethosuximide; FBM: felbamate;
GBP: gabapentin; LEV: levetiracetam; LTG:
lamotrigine; OXC: oxcarebazepine; PHT: pheytoin;
PB: phenobarbital; PRM: primidone; TPM: topiramate;
TGB: tiagabine; VPA: valproic acid (divalproex so-
dium)

D. Antiepileptic drug therapy

1. Drug dose
a. Most AEDs should be started at about 10 to 25
percent of the planned maintenance dose.
AEDs with a long half-life can be started at
close to the maintenance dose. If seizures are
frequent, the dose should be increased at
intervals not exceeding five half-lives to allow
the serum level to plateau between each
dosage increment.
b. The AED dose should be increased until
seizures stop (regardless of the serum level),
unremitting side effects occur, or levels reach
a high or supratherapeutic range without a
significant impact upon seizure frequency.
2. Serum levels should be used only as guides to
therapy. The therapeutic range is different for
each patient; many achieve seizure control at
levels below the recommended range, whereas
others require levels above the range.
3. Laboratory monitoring is done in all children
receiving AEDs, usually at every return visit.

Common Anticonvulsant Drugs

Drug Seizure Oral Dose Se- Side Ef-

Type rum fects and
Level Toxicities
mcg/
mL

Carbama Partial Begin 10 102 Dizziness,

zepine epilepsy mg/kg/d. drowsiness,
(Tegretol) Tonic- Increase by diplopia,
, carba- clonic 5 mg/kg/d liver, dys-
mazepine every wk to function,
XR 20-30 anemia,
(Tegretol mg/kg/d in 2 leucopoe-
XR) or 3 divided nia
doses
Drug Seizure Oral Dose Se- Side Ef-
Type rum fects and
Level Toxicities
mcg/
mL

Clonazep Myoclon Begin 0.05 6.3- Drowsi-

am ic mg/kg/d. 56.8 ness, irrita-
(Klonopin Absence Increase by bility, drool-
) 0.05 mg/kg ing, behav-
per wk. ioral abnor-
Maximum, malities,
0.2 mg/kg/d depression
in 2 or 3 di-
vided doses

Ethosuxi Absence Begin 10 to 40- Drowsi-

mide Myoclon 20 mg/kg/d 160 ness, nau-
(Zarontin) ic in 2 divided sea, rarely
doses; may blood
be in- dyscrasias
creased to
50 mg/kg/d

Felbamat Partial 600 to 1,200 Headache,

e epilepsy mg/ 2,400 to insomnia,
(Felbatol) Tonic- 3,600 mg aplastic
clonic two to three anemia,
times daily hepatitis

Gabapen Partial Begin 300 <2 Somno-

tin epilepsy mg/d. In- lence, dizzi-
(Neuronti Tonic- crease by ness.
n) clonic 300 mg/d ataxia,
every 3 to 5 headache,
days. Maxi- tremor,
mum 900 to vomiting,
1200 mg/d nystagmus,
in 3 equally fatigue,
divided weight gain
doses

Lamotrigi Partial Begin 2 3543 Severe

ne epilepsy mg/kg/d in 2 3 rashes,
(Lamictal) Tonic- equal doses. drowsiness,
clonic Increase to headache,
Lennox- mainte- blurred vi-
Gastaut nance dose sion
of 5 to 15
mg/kg/d.

Topirama Partial Begin 25 to Nephrolithia

te epilepsy 50 mg sis,
(Topama Tonic- Increase to paresthesia
x) clonic 200 to 400 s, weight
mg/day in 2 loss
doses

Tiagabin Partial Begin 4 mg Narrow

e epilepsy Increase to spectrum of
(Gabitril) 32 to 64 mg activity
in 2-4 doses

Oxcarbaz Partial Begin 300 to Hyponatre

epine epilepsy 600 mg mia
(Trileptal) Increase to
600 to 2,400
mg in 2
doses

Levetirac Focal Begin 1,000

etam epilepsy mg
(Keppra) Increase to
1,000 to
3,000 mg in
2 doses

Zonisami Focal Begin 100 to Nephrolithia

de epilepsy 200 mg sis, weight
(Zonegra Increase to loss
n) 400 to 600
mg every
day in 2
doses

Pheno- Tonic- 3 to 5 15-40 Hyperactiv-

barbital clonic mg/kg/d in 1 ity, irritabil-
Partial or 2 divided ity, short
epilepsy doses attention
span, tem-
per tan-
trums, al-
tered sleep
pattern,
Stevens-
Johnson
syndrome,
depression
of cognitive
function
Drug Seizure Oral Dose Se- Side Ef-
Type rum fects and
Level Toxicities
mcg/
mL

Phenytoi Partial 5m6 293 Hirsutism,

n epilepsy mg/kg/d in 2 gum hyper-
(Dilantin) Tonic- divided trophy, ata-
clonic doses xia, skin
rash,
Stevens
Johnson
syndrome

Primidon Tonic- Begin 50 132 Aggressive

e clonic mg/d in two behavior
(Mysoline Partial divided and per-
) epilepsy doses. sonality
Myoclon Gradually changes
ic increase to similar to
150 to 500 those for
mg/d divided phenobar-
into 3 equal bital
doses.

Sodium Tonic- Begin 10 50- Weight

valproate clonic mg/kg/d. 100 gain, alope-
(Depakot Absence Increase by cia, tremor,
e) Myoclon 5 to 10 hepato-
ic mg/kg per toxicity
Partial wk. Usual
epilepsy dose, 20 to
Unclas- 60 mg/kg/d
sified in 2 or 3 di-
vided doses.

Vigabatri Partial Begin 30 to 1.4- Agitation,

n (Sabril) epilepsy 40 mg/kg/d. 14 drowsiness,
Increase by weight gain,
10 mg/kg dizziness,
per wk. headache,
Maximum, ataxia
80 to 100
mg/kg/d in 2
equal doses

4. Valproic acid (divalproex) is associated with a

high incidence of minor elevations of liver en-
zymes and serum ammonia.
a. The serum gamma glutamyl transpeptidase
(GGT) elevated in 75 percent and alanine
aminotransferase (ALT) in 25 percent.
b. Hepatic enzyme elevations greater than
three times normal should be repeated in
several weeks and the medications stopped if
levels are increasing rapidly or the child is
symptomatic.
5. Carbamazepine. Leukopenia is not uncommon
with carbamazepine, often appearing in the first
two to three months of therapy. Severe aplastic
anemia or agranulocytosis is rare, occurring in
two per 575,000. Obtain a CBC after the first
month of carbamazepine therapy; if the white
blood count (WBC) or absolute neutrophil count
(ANC) is significantly decreased, a repeat study
is done in three to four weeks and may be re-
peated again until the counts stabilize. If the ANC
falls below 800 to 1000, the medication should be
stopped.
E. Topiramate causes a mild to moderate chronic
metabolic acidosis in two-thirds of children and can
cause nephrolithiasis. Complications of chronic
metabolic acidosis include impaired growth and
rickets or osteomalacia.
1. The serum bicarbonate should be measured at
baseline and monitored periodically thereafter.
Dose reduction or drug discontinuation should be
considered in patients with persistent or severe
metabolic acidosis.
F. Ketogenic diet consists of three to four parts fat to
one part protein and carbohydrate. The high-fat
content and relative absence of carbohydrate pro-
duces a persistent ketosis, which appears to have
an anticonvulsant effect. The level of ketosis can be
monitored daily in the urine and, intermittently, in the
serum. The diet suppresses seizure frequency by at
least 50 percent in 40 percent of patients.
G. Epilepsy surgery. Most children achieve reasonably
good seizure control with anticonvulsant medication.
Some are refractory despite numerous medications
and are not candidates for or fail the ketogenic diet.
 Surgical interventions should be considered in
children who have persistent, frequent seizures.
Surgical approaches can be divided into relatively
noninvasive (vagal nerve stimulator) and invasive
(local resection, lobar or multilobar resection, corpus
callosotomy, hemispherectomy, and multiple subpial
transection) procedures.
H. Vagal nerve stimulation. Many children who fail
AED therapy and the ketogenic diet are not candi-
dates for standard epilepsy surgery. Others may
undergo resective surgery and still have excessive
numbers of seizures. These patients may be candi-
dates for vagal nerve stimulation. Approximately 30
percent of adults treated in a randomized (high-
current stimulation) have a 50 percent or better
seizure reduction.
References, see page 182.

Headache
Chronic or recurrent headaches occur 75% of children by
15 years. Migraine is the most common headache syn-
drome in children. It is characterized by periodic episodes
of paroxysmal headache accompanied by nausea, vomit-
ing, abdominal pain, and relief with sleep.

I. Clinical evaluation
A. Headaches are characterized as isolated acute,
recurrent acute, chronic nonprogressive, or chronic
progressive. A social and educational history may
identify significant stresses. Analgesic use should be
determined.
B. Physical examination should include measurement
of growth parameters, head circumference, and
blood pressure. The teeth should be examined and
sinusitis should be sought. An arteriovenous malfor-
mation may cause an asymmetric, machinery-like
cranial bruit.
C. Papilledema. The presence of retinal venous
pulsation on funduscopy provides evidence of
normal intracranial pressure. Visual acuity should be
measured, and a detailed neurologic examination is
essential.
D. Investigations. If increased intracranial pressure or
an intracranial lesion is suspected, a computed
tomographic (CT) head scan should be performed.
Magnetic resonance imaging (MRI) may be required
to diagnose subtle vascular abnormalities or
hypothalamo-
pituitary lesions.
E. Lumbar puncture may be helpful if pseudotumor
cerebri is suspected. However, lumbar puncture may
result in herniation of the brain in patients who have
obstructive hydrocephalus, an intracranial mass
lesion, or cerebral edema. Neuroimaging should be
performed prior to the lumbar puncture.

Physical and Neurological Examination of the

Child with Headaches

Feature Significance

Growth parameters Chronic illness may affect linear

growth
Hypothalamopituitary dysfunction
may disturb growth

Head circumference Increased intracranial pressure

prior to fusion of the sutures may
accelerate head growth

Skin Evidence of trauma or a

neurocutaneous disorder

Blood pressure Hypertension

Neurologic examination Signs of increased intracranial

pressure
Neurologic abnormality

Cranial bruits May reflect an intracranial

arteriovenous malformation
 F. Migraine
1. Migraines may be associated with a preceding
aura, which usually involves visual phenomena.
The headache is usually unilateral or bilateral,
recurrent, throbbing, and associated with nausea
or vomiting. Photophobia or phonophobia is
common.
2. A family history of migraine is obtained in up to
80% of children who have migraine. A family
history of motion sickness is common. Migraine
episodes may be triggered by stress, lack of
sleep, excitement, menstruation, or certain foods.
II. Management of migraine headache in children
A. Abortive treatment
1. NSAIDs and acetaminophen. Early administra-
tion of acetaminophen or ibuprofen is helpful.
Ibuprofen may provide faster relief than
acetaminophen.
a. Acetaminophen is administered in an initial
dose of 10 to 20 mg/kg (one or two 325 mg
tablets), with a maximum dose of 1000 mg. A
second dose of 10 to 20 mg/kg may be given
in two to four hours if symptoms persist.
Additional doses may be given at four- to six-
hour intervals, but should not exceed three
doses in 24 hours.
b. Ibuprofen is given in a dose of 5 to 10 mg/kg
at 4 to 8-hour intervals (maximum 50 mg/kg in
24 hours). This dose may be repeated in two
to four hours; no more than three doses
should be given in 24 hours. Ibuprofen should
not be given to patients with abdominal pain,
dizziness, or tinnitus.
c. Naproxen (250 mg tablet) can be given to
children older than 12 years of age. The dose
can be repeated up to three times per day at
8- to 12-hour intervals. Naproxen should not
be given to patients with epigastric pain or
nausea.
d. Ketorolac can be administered intravenously
or orally. Intravenous ketorolac successfully
treats migraine in 55 percent. Doses are 0.5
mg/kg IV, followed by 1 mg/kg every six hours
or 0.25 mg/kg PO every six hours, up to a
maximum of 1 mg/kg per day.
2. Other analgesics. A combination analgesic can
be tried if single analgesics fail to relieve pain in
children older than eight years of age. Midrin
consists of isometheptene mucate (a
sympathomimetic agent), dichloralphenazonel (a
mild sedative), and acetaminophen. The dose for
adolescents is two capsules at the onset of the
headache, a third dose one hour later, and a
fourth capsule 90 minutes later, if needed.
3. Antiemetics. If nausea and vomiting are promi-
nent, early use of an antiemetic may relieve
symptoms and facilitate sleep. Rectal administra-
tion may be preferable.
a. Phenothiazines may have additional
antimigraine properties, and have a low inci-
dence of acute extrapyramidal reactions. The
dose is 0.25 to 0.5 mg/kg per dose orally,
intramuscularly, or rectally; it should not be
given intravenously.
b. Dimenhydrinate also is an effective
antiemetic. The dose is 1.25 mg/kg orally or
intramuscularly every four to six hours.
c. Metoclopramide administered intravenously
appears to reduce nausea and vomiting
associated with migraine. Its use is reserved
for the emergency department prior to the
administration of dihydroergotamine (DHE).
Acute dystonic reactions may occur.
4. Triptans are serotonin agonists with an affinity
for the 5-HT 1b/1d receptor.
a. Triptans are widely used in children, although
their use is not approved. Parenteral, oral,
and nasal preparations are available.
b. The triptans are highly effective. Sumatriptan
given by the subcutaneous or intranasal route
reduces headache severity in 70 percent; oral
administration is effective in 50 percent.
Triptans are contraindicated in basilar artery
and hemiplegic migraine because of
vasospasm.
c. Nasal sumatriptan spray is effective and
should be considered for the acute treatment
of migraine in adolescents 12 to 17 years old.
Nasal sumatriptan is given to younger chil-
dren in an initial dose of 5 mg. If this dose is
ineffective, 10 mg can be tried. In adoles-
cents, a dose of up to 20 mg can be given.
d. Subcutaneous sumatriptan is an effective
therapy for migraine. After a 6 mg dose,
headache is relieved within one or two hours
 in 46%.
e. Oral sumatriptan is effective and useful in
children. The initial dose in adolescents is 25
mg. This may be repeated in 20 minutes if the
symptoms persist. If no improvement occurs,
doses up to 50 mg can be used.
B. Prophylactic treatment is used when headaches
occur more than four times per month.
1. Cyproheptadine (Periactin) is a histamine and
serotonin antagonist, which is used for migraine
prophylaxis. Appetite stimulation with weight gain
limits use. Somnolence occurs. Cyproheptadine
(4 to 12 mg at bedtime) is used for prophylaxis in
the younger child.
2. Propranolol is the prophylactic treatment most
commonly used in children. Chronic therapy with
propranolol reduces the frequency of migraine in
60 to 80 percent.
a. Propranolol is initiated in a dose of 1 mg/kg in
three divided doses, with a maximum dose of
4 mg/kg per day. Heart rate and orthostatic
blood pressure should be monitored every
three months. The heart rate should be >60
bpm after one minute of exercise.
b. Beta-blockers are contraindicated in children
with asthma. They should be used with cau-
tion in depression, diabetes, or orthostatic
hypotension.
3. Valproate decreases headache frequency by 50
percent. Side effects include appetite stimulation
with weight gain, gastrointestinal upset, somno-
lence, dizziness, and tremor. Additional reported
adverse events include transient hair loss and
polycystic ovary syndrome. Valproate should be
used cautiously in children younger than age five
years of age because of potential hepatotoxicity.
a. Valproate has teratogenic effects. In adoles-
cent females at risk for pregnancy, folic acid
also should be given. Valproate is started in a
dose of 10 to 15 mg/kg in two divided doses.
The dose can be increased in increments of
15 mg/kg to a maximum dose of 60 mg/kg per
day.
b. Liver function tests and complete blood count
should be monitored every two to three
months. Thrombocytopenia may occur at
higher doses.
c. Serum anticonvulsant concentration should
be monitored every three to six months. A
reasonable therapeutic range is 50 to 100
mg/dL.
4. Amitriptyline is used commonly for migraine
prophylaxis in children. A single daily 5 mg oral
dose of amitriptyline, given at night, often is
effective. If frequent headaches persist, the dose
is advanced slowly by 5 mg increments, with at
least two weeks between changes. The dose
rarely should exceed 60 mg. Nonspecific
electrocardiographic changes and changes in
atrioventricular conduction may occur. Thus, an
electrocardiogram should be obtained.
5. Flunarizine is a calcium channel blocker, which
is unavailable in the United States. Treatment
with flunarizine 5 mg/day is associated with a
significant reduction in headache frequency.
C. Recommendations
1. Abortive treatment begins with either
acetaminophen or ibuprofen. Ibuprofen is given
in an initial dose of 10 mg/kg (maximum dose 50
mg/kg). This dose may be repeated in two to four
hours if needed; no more than three doses
should be given in 24 hours.
a. Children with nausea and vomiting should
receive promethazine (Phenergan) 0.25 to 0.5
mg/kg rectally and repeat as needed at inter-
vals of four to six hours.
b. In children at least five years of age, if analge-
sics do not provide relief a trial of sumatriptan
nasal spray should be initiated. Begin with 5
mg; it may be repeated once in four to six
hours if the headache returns. If there is no
benefit, two 5 mg units of nasal spray may be
given together. Similar doses of nasal spray
are used in older children, with a maximum of
20 mg.
c. In children older than 10 years without vomit-
ing, oral sumatriptan is an option. The initial
dose is 25 mg, with a maximum of 50 mg.
Other triptans may be tried in patients older
than 10 years of age who do not respond to
sumatriptan: rizatriptan ([Maxalt] 5 mg wafer)
or zolmitriptan ([Zomig] 2.5 or 5 mg).
2. Prophylactic treatment is used when head-
aches are frequent (more than four times per
month) or if severe and prolonged headache
 results in frequent school absences or prevents
important daily activities.
a. In children younger than six years of age,
cyproheptadine (Periactin) is used in a dose
of 4 to 12 mg per day, given orally once at
bedtime.
b. In older children, propranolol is the first choice
in a starting dose of 1 mg/kg in three divided
doses, with a maximum dose of 4 mg/kg per
day.
c. If propranolol is not well tolerated, valproate
(Depakote) should be used for prophylaxis.
Valproate is given primarily to boys older than
five years of age. This drug should bed
avoided in adolescent females because of
weight gain and polycystic ovary syndrome.
Valproate is started in a dose of 10 to 15
mg/kg in two to three divided doses orally.
The dose can be increased in increments of
15 mg/kg to a maximum dose of 60 mg/kg per
day.

Treatment of Acute Migraine Episodes

Simple analgesics

Acetaminophen Initial dose of 20 mg/kg PO, followed

by 10 to 15 mg/kg q 4 h up to a maxi-
mum dose of 65 mg/kg per day (maxi-
mum, 3,000 mg/day)

Ibuprofen (Advil) 1 to 12 years: 10 mg/kg PO q 4 to 6 h

More than 12 years: 200 to 400 mg
PO q 4 h; maximum dose 1,200
mg/day

Naproxen (Aleve) 5 mg/kg PO q 12 h; maximum dose

750 mg/day

Antiemetics

Promethazine Initial dose of 1 mg/kg PO (maximum,

(Phenergan) 25 mg); can be repeated at doses of
0.25 to 1 mg/kg q 4 to 6 h

Chlorpromazine 1 mg/kg IM for severe attacks

(Compazine)

Other Drugs

Sumatriptan 6 mg SC; may repeat in 1-2 hours;

(Imitrex) max 12 mg/day
Oral: 25-50 mg PO once; may repeat
in 2 hours
Intranasal: 5, 10, or 20 mg in one nos-
tril; may repeat after 2 hours

Dihydroergotamine 0.5 to 1 mg IV over 3 min in children

(DHE) >10 y. Can be repeated q8h. Used
with metoclopramide.

Prophylactic Agents for Migraine

Amitriptyline 5-10 mg qhs

(Elavil)

Propranolol 1 to 4 mg/kg per day; start at low dose and

(Inderal) increase slowly

Valproate 10 to 15 mg/kg in two divided doses; in-

(Depakote) creased by 15 mg/kg to a max 60 mg/kg
per day

References, see page 182.

Kawasaki Disease
Kawasaki disease (KD) is one of the most common
vasculitides of childhood. The annual incidence is highest
among Asians and Pacific Islanders (32.5/100,000
children <5 years of age), intermediate among African
Americans (16.9/100,000 children <5 years) and Hispan-
ics (11.1/100,000 children <5 years), and lowest among
Caucasians (9.1/100,000 children <5 years of age). KD
should be considered in any infant with prolonged, unex-
plained fever. It is typically a self-limited disorder; however,
complications such as coronary artery aneurysm, de-
pressed myocardial contractility and heart failure, myocar-
dial infarction, arrhythmias, and peripheral arterial occlu-
sion may develop.

I. Diagnosis
A. Diagnosis requires the presence of fever lasting
five days or more without any other explanation,
combined with at least four of the five following
physical findings:
1. Bilateral conjunctival injection.
 2. Oral mucous membrane changes, including
injected or fissured lips, injected pharynx, or
strawberry tongue.
3. Peripheral extremity changes, including ery-
thema of palms or soles or edema of hands or
feet (acute phase), and periungual desquama-
tion (convalescent phase).
4. Polymorphous rash.
5. Cervical lymphadenopathy (at least one lymph
node >1.5 cm in diameter).
B. Children who do not meet the criteria may have an
incomplete or atypical form of KD. In addition, some
patients who manifest five or six signs may have
other conditions.

Kawasaki Syndrome: Diagnostic Criteria

I. Fever for >5 days (usually >102EF)

II. At least four of five features
A. Bilateral conjunctival injection
B. Cervical adenitis (unilateral >1.5 cm diameter,
non-fluctuant)
C. Rash (truncal, perineal accentuation, polymor-
phous but non-
vesicular)
D. Inflamed oral mucosae (fissured lips, straw-
berry tongue)
E. Hand and feet inflammation (periungual peel-
ing around 14-21 days)
III. No alternate diagnosis
IV. Fever plus 3/5 criteria are diagnostic when coro-
nary abnormalities are present

II. Laboratory studies

A. Systemic inflammation is manifest by elevation of
acute phase reactants (eg, C-reactive protein
[CRP], erythrocyte sedimentation rate, and alpha-1
antitrypsin), leukocytosis, and a left-shift in the
white blood cell count. By the second week of
illness, platelet counts generally rise and may
reach 1,000,000/mm3 (reactive thrombocytosis).
B. KD often presents with a normocytic,
normochromic anemia.
C. The urinalysis commonly reveals white blood cells
on microscopic examination. Renal involvement
may occur in KD but is uncommon.
D. Elevated transaminase levels or mild
hyperbilirubinemia often occur. In addition, a
minority of children develop obstructive jaundice
from hydrops of the gallbladder.
III. Atypical Kawasaki disease. Children suspected of
having KD who do not fulfill diagnostic criteria (ie, have
fewer than four signs of mucocutaneous inflammation)
may have incomplete or atypical KD. Outcomes
appear to be comparable to children with complete
disease.
A. The cardinal manifestation most likely to be absent
in all cases of atypical KD is cervical
lymphadenopathy. Adenopathy is missing in up to
90 percent of children with atypical disease.
B. Rash may not be manifest in 7 to 10 percent of
children with KD.
C. Mucous membrane changes are most characteris-
tic of KD and are generally present in more than
90 percent of children with any form of the disease.
D. Children with incomplete KD fail to demonstrate
peripheral extremity changes in 40 percent of
cases. In comparison, at least 85 percent of those
with typical KD develop palmar erythema, dorsal
edema, or periungual desquamation.
IV. Differential diagnosis. KD is most commonly con-
fused with other infectious exanthems of childhood.
A. Measles, echovirus, and adenovirus cause
mucocutaneous inflammation but typically have
less evidence of systemic inflammation and lack
the extremity changes seen in KD.
B. Toxin-mediated illnesses, especially beta-
hemolytic streptococcal infection and toxic shock
syndrome, lack the ocular and articular involve-
ment typical of KD.
C. Drug reactions, such as Stevens-Johnson syn-
drome or serum sickness, may mimic KD but with
subtle differences in the ocular and mucosal
manifestations.
V. Initial management. Patients who fulfill the criteria for
Kawasaki disease are hospitalized and treated with
intravenous immune globulin (IVIG) and aspirin. Those
patients suspected of having atypical disease may
require further testing such as slit lamp examination
and echocardiography to confirm the diagnosis.
A. Intravenous immunoglobulin should be adminis-
tered at a dose of IVIG 2g/kg, as a single dose
over 8 to 12 hours. IVIG should be administered as
 soon as a diagnosis of KD is established.
B. Aspirin is given as 30 mg/kg/day to >100
mg/kg/day in four divided doses during the acute
phase of illness. Subsequently, aspirin is adminis-
tered in low doses (3 to 5 mg/kg/day) for its
antiplatelet action. Alternative anti-inflammatory
agents, such as ibuprofen, may be used for pro-
longed episodes of arthritis.
1. The risks of aspirin include transaminitis, chem-
ical hepatitis, transient hearing loss, and rarely
Reye syndrome.
2. Aspirin is continued until laboratory studies (eg,
platelet count and sedimentation rate) return to
normal, unless coronary artery abnormalities
are detected by echocardiography; this phase
of therapy typically is complete within two
months of the onset of disease.
C. Follow-up. An echocardiogram should be ob-
tained early in the acute phase of illness and six to
eight weeks after onset to confirm the efficacy of
treatment. Repeated examinations should be
performed during the first two months to detect
arrhythmias, heart failure, valvular insufficiency, or
myocarditis. Children with coronary artery abnor-
malities receive long-term antithrombotic therapy
with aspirin, and regular cardiac evaluation.
D. Vaccinations. The administration of live virus
vaccines, including measles and varicella, should
be postponed in children who have been treated
with IVIG. Passively acquired antibodies persist for
up to 11 months following IVIG administration, and
they may interfere with vaccine immunogenicity.
Patients older than six months of age who require
long-term aspirin therapy should receive yearly
influenza immunization because of the possible
increased risk of Reye syndrome. They should
receive the inactivated vaccine.
References, see page 182.

Juvenile Rheumatoid Arthritis

Pauciarticular onset juvenile idiopathic arthritis (JIA) is
defined as involvement of fewer than five joints. It is the
most common subgroup of JIA, constituting about 50
percent of cases of JIA.

I. Clinical presentation
A. Pauciarticular JIA affects females more often than
males. The peak incidence of pauciarticular JIA is in
the second and third years. It is less common over
five years of age and rarely begins after age 10. A
child with large joint involvement beginning in the
early teenage years most commonly has a
spondyloarthropathy.
B. The typical child with pauciarticular JIA is a girl who
is noticed to be limping without complaint. Often the
family notices that the child “walks funny” in the
morning, but after a little while seems fine. The knee
is often swollen.
C. Pauciarticular JIA affects the large joints (knees,
ankles, wrists, elbows), but virtually never begins in
the hips. Systemic manifestations (other than
uveitis) are characteristically absent. Thus, fever,
rash, or other constitutional symptoms suggest a
different diagnosis.
D. The involved joints are typically swollen and tender
to compression. They may be warm, but they should
not be erythematous. Limitation of motion may not
be present. Long-term complications of
pauciarticular JIA, include uveitis and leg length
discrepancy.

American College of Rheumatology Criteria for

Diagnosis of JRA

Diagnostic Requirements For JRA

• Documented arthritis of one or more joints for 6 weeks
or longer
• Exclusion of other conditions associated with childhood
arthritis
- Other rheumatic diseases
- Infectious diseases
- Childhood malignancies
- Nonrheumatic conditions of bones and joints
- Miscellaneous conditions

II. Diagnosis.
A. The diagnosis of pauciarticular onset JIA is based
upon the presence of arthritis in four or fewer joints
during the first six months of disease. If a single
joint is involved, arthritis must be present for at
least three months and multiple alternative causes
of arthritis must be excluded. If two or more joints
are involved, arthritis must be present for at least
 six weeks, with the elimination of exclusions.

Objective Signs of Arthritis

Joint Swelling Loss of Joint Motion

- Synovial hypertrophy - Stiffness of joints
- Increased amounts of Joint Warmth
synovial fluid Joint Erythema
- Swelling of periarticular
tissues
Joint Pain
- On motion
- On palpation (tender-
ness)
- At rest

B. Laboratory findings
1. Antinuclear antibodies (ANAs) are frequently
present in pauciarticular JIA and are associated
with an increased risk of iridocyclitis. ANAs are
typically present in low or moderate titers in a
homogeneous pattern. Antibodies to dsDNA, Ro,
La, Sm, and RNP, and rheumatoid factor should
be absent.
2. The erythrocyte sedimentation rate is close to
normal, there is a normal white blood cell count
without a left shift, and a normal platelet count.
C. Differential diagnosis
1. Dactylitis (a swollen finger or toe) may be
pauciarticular, but is more typical of psoriaform
arthritis.
2. Children over the age of 9 years with arthritis
involving the hips or knees and enthesiopathic
symptoms also do not have pauciarticular JIA;
these are manifestations of a
spondyloarthropathy.
3. Children with plant thorn synovitis, septic arthritis,
osteomyelitis, or even Lyme disease are mistak-
enly diagnosed with pauciarticular JIA. These
conditions are usually associated with elevated
acute phase reactants. These conditions are
often acutely painful with sudden and dramatic
onset, the opposite of pauciarticular JIA.
III. Course and prognosis. Most cases of pauciarticular
JIA are benign, resolving within six months. Fifty-four
percent remit completely. The major morbidity is
typically related to the development of uveitis. Recur-
rences occur in 20 percent of children. A few children
with typical pauciarticular disease evolve into chronic
destructive arthritis. There should not be any systemic
complications of pauciarticular JIA other than uveitis.
A. Uveitis
1. The most serious complication of pauciarticular
JIA, occurring in approximately 20 percent of
children, is the development of uveitis or
iridocyclitis (inflammation of the anterior uveal
tract and the adjacent ciliary body). The subgroup
of children with pauciarticular JIA who have
detectable ANAs are at greatest risk of develop-
ing iridocyclitis.
2. Uveitis is often initially silent; by the time the child
complains of pain in the eye or difficulty seeing, it
is likely that permanent and irreversible damage
has already occurred. Thus, routine screening is
necessary. Screening must be performed by an
ophthalmologist and includes a complete slit lamp
examination.
B. Leg length discrepancy. There may be significant
asymmetric overgrowth when a single knee joint is
involved, resulting in a leg length discrepancy over
time. Joint injection with glucocorticoids early in the
course of pauciarticular JIA may prevent leg length
discrepancies. Leg length discrepancies of less
than 1 cm are probably not important. When they
become greater, however, proper gait should be
maintained by placing an appropriate lift in the
opposite shoe.
IV. Treatment of juvenile rheumatoid arthritis
A. Medical therapy. Pauciarticular onset JIA is usually
responsive to nonsteroidal antiinflammatory drugs
(NSAIDs) or selective COX-2 inhibitors.
Methotrexate and other immunosuppressive drugs
are rarely, if ever, required. However, some chil-
dren will have disease activity in one or two joints
for a prolonged period that does not respond to
NSAIDs.
 NSAID Treatment of Juvenile Rheumatoid Arthri-
tis

Ibuprofen 1 to 12 years: 10 mg/kg PO q 4 to 6 h

(Motrin) More than 12 years: 200 to 400 mg PO q 4
h; maximum dose 1,200 mg/day

Naproxen 5 mg/kg PO q 12 h; maximum dose 750

(Aleve) mg/day

B. Intraarticular injection of glucocorticoids may be

helpful if only a single joint is involved and there
has been an inadequate response to NSAIDs after
three or more months of therapy.
C. Etanercept (Enbrel) is a soluble tumor necrosis
factor alpha (TNFa) receptor fusion protein that
binds TNFa, thereby reducing its activity.
Etanercept is best reserved for children with a
significant elevation of the erythrocyte sedimenta-
tion rate.
References, see page 182.

Renal and Urologic Disor-

ders
Hematuria
Hematuria occurs in about 0.5% and 1% of all children. It
is defined as more than 5 to 10 RBCs per high-power
microscopic field from a centrifuged midstream voided
urine sample. The urine may be yellow, pink, red, brown,
or smoky. Hemoglobin and myoglobin will produce the
same color changes on the dipstick as intact RBCs. Each
urine sample that tests positive for blood by dipstick must
be examined microscopically to confirm the presence of
intact RBCs.

I. Clinical evaluation
A. If microscopic hematuria has been present for 1
month or more, further investigation for the cause is
indicated. Vigorous exercise such as jogging or bike
riding may cause hematuria. Abdominal, back or
flank pain, especially when associated with bruising,
suggests child abuse. Dysuria, urinary frequency,
and suprapubic pain or tenderness suggests a
urinary tract infection or hypercalciuria.
B. Abdominal pain may be associated with an abdomi-
nal mass, nephrolithiasis, or Henoch-Schönlein
purpura. Aspirin, non-steroidal anti-inflammatory
agents, antibiotics, methyldopa, and other drugs can
cause hematuria.
C. A history of edema, hypertension, skin rash, pallor,
joint swelling or tenderness, abdominal pain, or
bloody diarrhea suggests postinfectious
glomerulonephritis, Henoch-Schönlein purpura,
lupus nephritis, hemolytic uremic syndrome, or
immunoglobulin (Ig) A nephropathy.
D. If sore throat or pyoderma precedes the hematuria
by 7 to 30 days, poststreptococcal acute
glomerulonephritis must be ruled out. Hematuria with
a concurrent upper respiratory infection strongly
suggests IgA nephropathy. Each of these forms of
glomerulonephritis usually is associated with
proteinuria and RBC casts.

Evaluation of Hematuria

Patient history, family history, physical examination

Examination of urine for red blood cell casts and crystals
Screening for proteinuria with a dipstick
Examination of urine of first-degree relatives for hematuria
Urine culture
Urinary calcium/urinary creatinine; 24-hour urinary calcium
excretion
Serum creatinine, C3, streptozyme titer
Renal ultrasonography
Plain abdominal film if nephrolithiasis is suspected
Differential Diagnosis of Persistent Hematuria

Without Proteinuria With Proteinuria

Urinary tract infection Urinary tract infection

Hypercalciuria Poststreptococcal acute

glomerulonephritis

Thin basement membrane IgA nephropathy

disease

Sickle cell disease or trait Henoch-Schönlein purpura

Renal cystic disease Membranoproliferative

glomerulonephritis

Nephrolithiasis Lupus nephritis

Renal anatomic abnormali- Alport syndrome

ties Hemolytic-uremic syndrome
Other forms of
glomerulonephritis

E. A family history of hematuria without renal failure

may be seen with thin basement membrane disease.
A family history of hematuria, chronic renal failure,
dialysis or renal transplantation with bilateral deaf-
ness and ocular abnormalities suggests Alport
syndrome. An audiogram is indicated for children
suspected of having Alport syndrome.
F. A family history of nephrolithiasis raises the diagnos-
tic possibility of nephrolithiasis or hypercalciuria. A
family history of autosomal dominant polycystic
kidney disease requires that this disease be ruled
out by ultrasound. Sickle cell disease or sickle cell
trait in the patient’s family may suggest this diagno-
sis.
G. Urinalysis. RBCs from areas of the urinary tract
other than glomeruli will be normal in size with
smooth edges (eumorphic). Nonglomerular bleeding
usually is associated with normal urinary protein
excretion and an absence of RBC casts.

Familial Causes of Hematuria

Polycystic kidney disease

Thin basement membrane disease
Sickle cell disease or trait
Alport syndrome (hereditary nephritis with deafness)
Hypercalciuria with family history of nephrolithiasis

H. Preliminary tests should include a urine culture,

blood sickle cell preparation in African-American
children, urinary calcium; urinary creatinine ratio,
serum creatinine; C3, and streptozyme titer.
Ultrasonography of the kidneys and urinary bladder
is recommended to rule out polycystic kidney
disease, tumor, ureteropelvic junction obstruction,
and stones.
I. The presence of proteinuria (>1+ on dipstick)
strongly suggests glomerulonephritis. The diagnosis
of glomerulonephritis demands microscopic inspec-
tion of the urinary sediment for RBC casts. RBCs
that have bizarre shapes, blebs, or burrs
(dysmorphic RBCs) correlate with a glomerular
origin of the RBC.
J. Proteinuria
1. If proteinuria is present on urinalysis, urinary
protein excretion should be measured by a timed
12- or 24-hour urine collection or a urine
protein:urine creatinine ratio on a single voided
sample.
2. A complete blood count, C3, C4, antistreptolysin-
O titer, streptozyme titer, serum electrolytes,
blood urea nitrogen, serum creatinine, serum
albumin, test for lupus erythematosus, hepatitis
B screen, and antinuclear cytoplasmic antibody
titer are indicated to clarify the type of
glomerulonephritis. A screening urinalysis on
first-degree family members is also important.
When confirmatory serologic tests are
nondiagnostic, a renal biopsy usually is indi-
cated.

Renal Structural Abnormalities Associated with

Hematuria

Polycystic kidney disease

Ureteropelvic junction obstruction
Vesicoureteral reflux
Renal or bladder stones, diverticula or tumors
Renal arteriovenous fistula
Foreign bodies
References, see page 182.

Fluids and Electrolytes

Disorders affecting the body fluids and electrolytes are
treated by supplying maintenance requirements, correct-
ing volume and electrolyte deficits, and by replacing
ongoing abnormal losses.

I. Dehydration
A. Maintenance fluid and electrolytes
1. Sensible losses, primarily urinary, account for
50% of daily fluid requirements. Caloric require-
ments for growth can be estimated as equivalent
on a kcal-for-mL basis to water requirements.
2. Factors that increase the requirements for calo-
ries and water are fever (10% for each degree),
physical activity, ongoing gastrointestinal losses,
hyperventilation, and hypermetabolic states.

Maintenance Requirements for Fluid and Electro-

lytes

Body 0 to 10 10 to 20 >20 kg
Weight kg kg
Water Vol- 100 mL/kg 1000 mL + 1500 mL + 20
ume 50 mL/kg for mL/kg for each
each kg >10 kg >20 kg
kg

Sodium 3 mEq/kg 3 mEq/kg 3 mEq/kg

Potassium 2 mEq/kg 2 mEq/kg 2 mEq/kg

Chloride 5 mEq/kg 5 mEq/kg 5 mEq/kg

3. Abnormal losses, such as those arising from

nasogastric aspiration, prolonged diarrhea or
burns, should be measured, and replaced on a
volume for volume basis.
B. Estimation of deficit
1. Estimation of volume depletion should assess
fever, vomiting, diarrhea, and urine output.
Recent feeding, including type and volume of
food and drink, and weight change should be
determined.

Estimation of Dehydration
Degree of Dehy- Mild Moderate Severe
dration

Weight Loss-- 5% 10% 15%

Infants

Weight Loss-- 3-4% 6-8% 10%

Children

Pulse Normal Slightly in- Very in-

creased creased

Blood Pressure Normal Normal to Orthostatic

orthostatic, to shock
>10 mm Hg
change

Behavior Normal Irritable Hyperirrit-

able to
lethargic

Thirst Slight Moderate Intense

Mucous Mem- Normal Dry Parched

branes

Tears Present Decreased Absent

tears,
sunken
eyes

Anterior Fonta- Normal Normal to Sunken

nelle sunken

External Jugular Visible when Not visible Not visible

Vein supine except with even with
supraclavicul supraclavi
ar pressure cular pres-
sure

Skin Capillary Delayed Very de-

refill <2 sec capillary re- layed cap-
fill, 2-4 sec illary refill
(decreased (>4 sec),
turgor) tenting;
cool, acro-
cyanotic or
mottled
skin

Urine Specific >1.020 >1.020; Oliguria or

Gravity (SG) oliguria anuria
 2. The percent dehydration is used to calculate
the milliliters of body water deficit per kilogram
of body weight.
C. Isonatremic dehydration
1. The most common cause of dehydration in
infants is diarrhea. Children who have a brief
illness and anorexia usually present with iso-
tonic dehydration.
2. Oral rehydration
a. Moderate volume depletion should be
treated with oral fluids. The majority of pa-
tients who have gastroenteritis can be
treated with oral rehydration therapy.
b. Small aliquots of oral hydration solution
(Ricelyte, Pedialyte, Resol, Rehydralyte) are
given as tolerated to provide 50 mL/kg over
4 hours in mild dehydration, and up to 100
mL/kg over 6 hours in moderate dehydra-
tion. Once rehydration is accomplished,
maintenance fluid is given at 100 mL/kg per
day.
3. Parenteral rehydration
a. Parenteral fluids should be given for severe
volume depletion, altered states of con-
sciousness, intractable vomiting, and ab-
dominal distention or ileus.
b. The first phase of treatment rapidly expands
the vascular volume. Intravenous normal
saline or Ringers lactate (10-20 mL/kg)
should be given over 1 hour.
c. The next phase of treatment is aimed at
correcting the deficit, providing mainte-
nance, and replacing ongoing abnormal
losses. In severe depletion, half of the
calculated deficit is given over the first 8
hours and the second half over the next 16
hours; maintenance needs are provided.
Five percent glucose should be used as the
stock solution and NaCl is added according
to the estimated need.
d. Children who have isonatremic dehydration
require 8 to 10 mEq of Na+ per kg of body
weight for repletion of deficit and 3 mEq/kg
per day for maintenance. This Na+ is given in
a volume consisting of the calculated main-
tenance for water and the estimated water
deficit. Once urine flow occurs, KCl is added
at a concentration of 20 mEq/L.
D. Hyponatremia and hyponatremic dehydration
1. The signs and symptoms of hyponatremia
correlate with the rapidity and extent of the fall
in serum Na+ concentration. Symptoms include
apathy, nausea, vomiting, cramps, weakness,
headache, seizures, and coma.
2. If the correction of fluid and electrolyte losses is
excessively rapid, the brain may sustain injury.
In severe hyponatremia, plasma Na+ concentra-
tion should be corrected at no more than 10-12
mEq/L/day.
3. Differential diagnosis of hyponatremia
a. Hypovolemia
(1) The most frequent cause of hypovolemic
hyponatremia is viral gastroenteritis with
vomiting and diarrhea. Other causes of
hypovolemic hyponatremia include
percutaneous losses or third space
sequestration of fluid (ascites, burns,
peritonitis).
(2) Renal sodium loss (urinary Na+ >20
mEq/L) may be caused by diuretics, salt-
wasting nephropathy, proximal renal
tubular acidosis, and lack of or resis-
tance to mineralocorticoid.
b. Euvolemia. The most common cause of
euvolemic hyponatremia is the syndrome of
inappropriate antidiuretic hormone secre-
tion, which is caused by water retention
(urinary Na+ is usually >20 mEq/L). Causes
include tumors, pulmonary disorders, CNS
infection, and certain drugs. Euvolemic
hyponatremia may also occur in infants fed
excessively diluted infant formula.
c. Hypervolemia. Hypervolemic hyponatremia,
associated with edema, may result from
water retention and excess Na+, as in
nephrosis, congestive heart failure, cirrho-
sis, or renal failure.
4. Management of hyponatremia
a. Hypovolemic patients who have
hyponatremia first require volume repletion
with normal saline, then a solution contain-
ing salt is given to correct the Na+ deficit (10
to 12 mEq/kg of body weight or 15 mEq/kg
in severe hyponatremia) and to provide the
Na+ maintenance needs (3 mEq/kg per day)
 in a 5% dextrose solution.
b. For a serum Na+ concentration of 120 to 130
mEq/L, this amount should be given over a
24-hour period. For a serum Na+ concentra-
tion <120 mEq/L, the rehydration should be
spread out over several days at a rate of 10
mEq/day.
c. Symptomatic hyponatremia (headache,
lethargy, disorientation) requires urgent
therapy to prevent seizures or coma.
(1) Hypertonic saline (3% saline solution)
should be used to raise the serum Na+
by 1 to 2 mEq/L per hour or halfway
toward normal during the first 8 hours.
(2) A correction using 3% saline over 4
hours can be calculated according to the
following formula:

Sodium deficit in mEq = (125 - observed

[Na+]) x body weight in kg x 0.6

E. Hypernatremia and hypernatremic dehydration

1. The hypernatremic patient is usually also
dehydrated. Total body Na+ most commonly is
decreased. Affected patients frequently exhibit
lethargy or confusion, muscle twitching,
hyperreflexia, or convulsions. Fever is com-
mon, and the skin may feel thickened or
doughy.
2. Differential diagnosis
a. Diarrhea, which usually results in
isonatremic or hyponatremic dehydration,
may cause hypernatremia in the presence of
persistent fever, anorexia, vomiting, and
decreased fluid intake.
b. Other causes of hypernatremia include
water and Na+ deficit from skin losses or
renal losses, and water losses from central
or nephrogenic diabetes insipidus (DI) or
drugs (lithium, cyclophosphamide).
3. Management
a. Initial therapy requires administration of nor-
mal saline or Ringers lactate to restore
circulating plasma volume. Hypovolemic
patients who have hypernatremia require a
hypotonic solution containing salt to restore
the Na+ deficit (2-5 mEq/kg of body weight)
and to provide the Na+ maintenance (3
mEq/kg of Na+) in a solution containing 20-
40 mmol/L of KCl and 5% glucose.
b. For a serum Na+ concentration of 150-160
mEq/L, this volume should be given over 24-
hours. An elevated serum Na+ concentration
should be corrected by no more than 10
mEq/L per day.
c. For a serum Na+ concentration >160 mEq/L,
the rehydration should be spread out over
several days to lower the Na+ concentration
to 150 mEq/L by 10 mEq/day.
II. Potassium disorders
A. Hypokalemia
1. Hypokalemia (serum K+ concentration <3
mEq/L) is most frequently caused by gastroin-
testinal K+ losses or renal losses (nasogastric
suction, protracted vomiting, diuretics, renal
tubular disease). Manifestations of
h yp o k a l e m i a i n c l u d e a r r h y t h m i a s ,
neuromuscular excitability (hyporeflexia or
paralysis, decreased peristalsis, ileus), and
rhabdomyolysis.
2. Intracellular K+ concentration can be estimated
from the electrocardiogram, which may reveal
flattened T waves, shortened P-R interval and
QRS complex, and eventually U waves.
3. Management
a. In the presence of cardiac arrhythmias,
extreme muscle weakness, or respiratory
distress, patients should receive KCl intrave-
nously with cardiac monitoring. Once the
serum K+ is stabilized, oral administration is
preferable.
b. If the patient is likely to be
hypophosphatemic, a phosphate salt should
be used. In metabolic alkalosis, KCl should
be used; in renal tubular acidosis, a citrate
salt should be used.
B. Hyperkalemia
1. The most common cause of hyperkalemia (K+
>5.5 mEq/L) is “pseudohyperkalemia” from
hemolysis of the blood sample. This cause
should be excluded by repeating the measure-
ment on a free-flowing venous sample. Chil-
dren may display hyperkalemia in metabolic
acidosis, tissue catabolism, renal failure, vol-
ume depletion, or hypoaldosteronism.
 2. In salt-losing congenital adrenal hyperplasia,
due to complete deficiency of the enzyme 21-
hydroxylase, the symptoms in affected male
infants appear in the first weeks of life and
include dehydration and failure to thrive to-
gether with low serum Na+ and high K+ con-
centrations. Affected female infants usually are
diagnosed at birth because of ambiguous
genitalia.
3. Manifestations of hyperkalemia include cardiac
arrhythmias, paresthesias, muscle weakness,
and paralysis.
4. The electrocardiogram demonstrates narrow,
peaked T waves and shortened QT intervals at
K+ concentrations >6 mEq/L and depressed ST
segment and widened QRS complex at K+
concentrations >8 mEq/L.
5. Management
a. Emergent therapy to reverse potentially life-
threatening hyperkalemia consists of intra-
venous calcium. The onset of action is rapid;
however, the duration is less than 30 min-
utes.
b. Emergent administration of glucose will
cause K+ to redistribute to the intracellular
space. Glucose, 0.5 gm/kg, can be given
over 30-60 minutes when EKG changes are
present.
c. Sodium polystyrene sulfonate (Kayexalate)
(1 gm/kg) can be given by high-rectal en-
ema or orally. Severe hyperkalemia is
treated with hemodialysis.
III. Acid-base disorders
A. The pH of the body fluids normally is between 7.35
and 7.45.
B. Metabolic acidosis
1. Acidosis results from the addition of acid or the
removal of alkali from body fluids, and it causes
a compensatory increase in ventilation (respira-
tory alkalosis) and a fall in pCO2. Manifestations
of acidosis include depressed myocardial con-
tractility, arrhythmias, hypotension, and pulmo-
nary edema.
2. Diagnosis
a. Addition of a fixed acid to the extracellular
fluid causes the formation of unmeasured
anions. These unmeasured anions are re-
ferred to as the anion gap, which can be
estimated as:

Anion gap = Na+ - (Cl +HCO3-) = 10-12 mEq/L

3. Differential diagnosis
a. Normal anion gap (hyperchloremic) aci-
dosis
(1) This disorder occurs when HCO3- is lost
from the body, either through the gastro-
intestinal tract or the kidneys. Diarrheal
fluid is high in HCO3-, high in K+, and low
in Cl - . Thus, diarrhea causes
hypokalemia and hyperchloremic acido-
sis.
(2) Failure to excrete acid occurs in mild
chronic renal insufficiency and RTA.
b. Increased anion gap acidosis may be
caused by diabetic ketoacidosis, lactic acido-
sis, ingestion of toxins (aspirin, ethylene
glycol), and renal failure.
4. Treatment of acidosis
a. Bicarbonate should be given when plasma
HCO3- is <5 mmol/L. Bicarbonate should be
added to a hypotonic solution and given as
a continuous infusion over 1 hour. The
amount to infuse is calculated with the fol-
lowing formula:

Amount to infuse in mEq = weight in kg (15

-observed [HCO3-]) x 0.5

b. With severe watery diarrhea, resulting in

moderate-to-severe metabolic acidosis,
volume replacement is the primary mode of
therapy.
C. Metabolic alkalosis
1. Alkalosis results from a gain of base or a loss of
acid. The common clinical manifestations are
lethargy, confusion, neuromuscular irritability,
arrhythmias, and seizures.
2. Differential diagnosis
a. Causes of metabolic alkalosis include alkali
administration, vomiting, and nasogastric
aspiration. In patients with GI loss of acid
from vomiting, urinary Cl- concentration is
usually below 20 mEq/L.
b. Cushing syndrome, Bartter syndrome or
 primary aldosteronism may cause metabolic
alkalosis.
3. Treatment
a. Therapy consists of identifying and treating
the underlying pathology.
b. In mild-to-moderate alkalosis, provision of Cl-
will allow the kidney to excrete the excess
base.
D. Respiratory acidosis
1. Respiratory acidosis is induced by an increase
in pCO2, which lowers plasma pH. Causes of
respiratory acidosis include airway obstruction,
and pulmonary disorders.
2. Treatment consists of mechanical ventilation
and correction of the underlying disorder.
E. Respiratory alkalosis
1. Respiratory alkalosis is caused by a decrease in
pCO2, secondary to hyperventilation, resulting in
dizziness, confusion, and seizures.
2. Causes of respiratory alkalosis include hyper-
ventilation caused by CNS disorders and panic
disorder. Treatment involves correcting the
underlying disorder. Rebreathing into a bag may
decrease the severity of symptoms.
References, see page 182.

Vesicoureteral Reflux
Vesicoureteral reflux (VUR) is defined as the retrograde
passage of urine from the bladder into the upper urinary
tract. Vesicoureteral reflux occurs in 1 percent of new-
borns and 30 to 45% in young children with urinary tract
infection.
VUR predisposes to acute pyelonephritis by allowing
bacteria to migrate from the bladder to the kidney.
Pyelonephritis may lead to renal scarring, renal injury with
subsequent hypertension, decreased renal function,
proteinuria, renal failure, and sometimes end stage renal
disease (ESRD).

I. Grading of VUR based on findings from a contrast

voiding cystourethogram (VCUG).
Grade I - Reflux only fills the ureter without dilation.
Grade II - Reflux fills the ureter and the collecting
system without dilation.
Grade III - Reflux fills and mildly dilates the ureter
and the collecting system with mild blunting of the calyces.
Grade IV - Reflux fills and grossly dilates the ureter
and the collecting system. One-half of the calyces
are blunted.
Grade V - Massive reflux grossly dilates the collect-
ing system. All the calyces are blunted with a loss of
papillary impression and intrarenal reflux may be
present. There is significant ureteral dilation and
tortuosity.
A. Grades I and II are classified as mild reflux, grade III
as moderate, and grades IV and V as severe.
II. Epidemiology. VUR is present in one percent of
newborns. The risk of VUR is increased in young
children with urinary tract infection, with an incidence
that ranges from 30 to 45%.
A. Caucasian children were three times more likely to
have VUR than African-American children. The
maximal grade of reflux Is significantly lower in
African-American children.
B. Gender. Girls were twice as likely to have reflux
than boys.
C. Age. Young children and infants (0 to less than 2
years of age) are more likely to have VUR than older
children.
III. Presentation, diagnosis, and course
A. Prenatal presentation. The presence of VUR is
suggested prenatally by the finding of
hydronephrosis via ultrasonography. VUR is present
in 10 to 40% of all fetuses with prenatally diagnosed
hydronephrosis.
B. Postnatal presentation. Postnatal diagnosis of
VUR is usually made after a UTI. Girls are twice as
likely to have VUR after an initial febrile UTI. Routine
VCUG should be therefore performed among the
following groups:
1. Any male child with a first UTI.
2. Girls under the age of three years with a first UTI.
3. Any child under five years of age with a febrile
UTI.
4. Children with recurrent UTI.
5. Children who have a positive RNC on screening.
6. Children with other prenatal renal anomaly.
7. Children with three urinary tract infections with
unusual organisms.
C. Screening of siblings and parents of children
with VUR. Screening of is recommended because
of the increased familial incidence of VUR.
 1. In siblings below two years of age without a
history of unexplained febrile illnesses or urinary
tract infections, a renal ultrasound is recom-
mended at three months of age, and a
radionuclide cystogram (RNC) is recommended
at six months or at the time of diagnosis of the
index patient.
2. In siblings between two and four years of age
without a history of unexplained illnesses or
urinary tract infections, a RNC is recommended.
3. In siblings above six years of age or parents
without a history of unexplained febrile illnesses
or urinary tract tract infections, a renal ultrasound
is recommended.
4. Siblings with a history of febrile illnesses or
recurrent urinary tract infections, abnormal ultra-
sound, or RNC, a VCUG is recommended.
IV. Clinical course
A. Grades I and II. By five years of age, spontaneous
resolution occurrs in 80% of patients.
B. Grade III. The oldest group of children 5 to 10 years
of age with bilateral reflux have less than 20%
resolution over five years. Children (one to two
years) with unilateral disease have a 70% resolution
rate.
C. Grade IV. There is a 60% resolution rate for unilat-
eral disease and less than 10% resolution rate for
bilateral reflux over five years regardless of age at
presentation.
D. Grade V. Spontaneous resolution is rare.
E. Renal scarring has been associated with VUR with
30 to 60% of patients having evidence of renal
scarring at initial diagnosis of VUR.
V. Management of vesicoureteral reflux

Treatment of Children with Vesicoureteral Reflux

Clinical presenta-
tion

Age of Grade Treatment Comments

patient, of reflux
years

Less All Antibiotic

than 1 grades prophylaxis

1 to 5 I and II Antibiotic
prophylaxis

1 to 5 III and IV Antibiotic If renal

prophylaxis scarring or
bilateral
reflux,
surgery
is op-
tional

1 to 5 V Antibiotic If renal
prophylaxis scarring or
bilateral
reflux,
surgery
is op-
tional

6 or I and II Antibiotic If renal

greater prophylaxis scarring or

bilateral
reflux,
surgery
is op-
tional

6 or III and IV Antibiotic If renal

greater prophylaxis scarring
or bilat-
eral
reflux,
surgery
is op-
tional

6 or V Surgical
greater repair

A. Children below one year of age, regardless of

grade of reflux, should be treated medically be-
cause they have a high likelihood of spontaneous
resolution. Surgery is a reasonable option if they
have grade V reflux and renal scarring.
B. All patients with grade I or II reflux, either with
 unilateral or bilateral disease, should be treated
medically as they have high likelihood of sponta-
neous resolution.
C. Children between one and five years of age with
grade III or IV reflux, either unilateral or bilateral
disease, should be treated medically. Surgery is a
reasonable option if there is bilateral reflux and
renal scarring.
D. Children between one and five years of age with
grade V without renal scarring can be treated
medically. If there is renal scarring, surgery is
recommended.
E. Children six years or older with unilateral grade III-
IV reflux without renal scarring can be treated
medically. If the reflux is bilateral and/or there is
renal scarring, surgical treatment is recom-
mended.
F. Children six years or older with grade V reflux
should be treated surgically.
G. Surgery should also be considered if medical
therapy fails either due to poor compliance, break-
through infections due to antibiotic resistance, or
significant antibiotic side effects.
VI. Follow-up
A. Urine cultures are required whenever there are
urinary symptoms suggestive of UTI or unex-
plained fever. Surveillance cultures are obtained
every three to four months.
B. Monitoring of reflux is done by either VCUG or
RNC. RNC is the preferred modality as there is
less radiation. Yearly evaluation is currently rec-
ommended. Patients who have undergone surgical
correction require a post-operative VCUG or RNC
to document whether the surgery was successful.
C. DMSA scans are recommended in patients with
reflux who have an abnormal ultrasound and in
infants who have a febrile urinary infection, dem-
onstrated reflux, and a normal ultrasound. Renal
ultrasound is not as sensitive in detecting renal
scars as DMSA scan and has not been as useful
in follow-up.
D. Postnatal. This group of patients are predomi-
nantly female and present after an initial febrile
illness. The rate of spontaneous resolution is
dependent upon age, grade of reflux, and whether
the reflux is unilateral or bilateral. Medical treat-
ment consists of prophylactic antibiotic therapy
with trimethoprim-sulfamethoxazole, trimethoprim
alone, or nitrofurantoin. One daily dose is adminis-
tered at bedtime at one-half the usual dose for
treating an acute infect
E. Patients who are treated medically need to be
monitored in the following manner:
1. Mandatory urine cultures are required when-
ever there are urinary symptoms suggestive of
UTI or unexplained fever.
2. Surveillance cultures are obtained every three
to four months.
3. Screening for VUR on a yearly basis with RNC.