Approach To

The Febrile Patient

Dr. Awadh Al-Anazi

• FEVER
• Is an elevation of body temperature above the
normal circadian range as the result of a change
in the thermoregulatory center located in the
anterior hypothalamus and pre-optic area
Thermoregulation
Body heat is generated by:
a) basal metabolic activity
b) muscle movement

Lost by:
1) Conduction
2) Convection (which is increased by wind or
fanning)
3) Evaporation which is increased by sweating
• Body temperature is controlled in the
hypothalamus, which is directly sensitive to
changes in core temperature

• The normal 'set-point' of core temperature is

tightly regulated within 37 ± 0.5°C, as required
to preserve normal function of many enzymes
and other metabolic processes.
• In a hot environment,
• Sweating is the main mechanism for increasing
heat loss.
• This usually occurs when the ambient
temperature rises above 32.5°C or during
exercise
Febrile Response
• The initiation of fever begins
• when exogenous or endogenous stimuli are
presented to specialized host cells, principally
monocytes and macrophages ,they will stimulate
the synthesis and release of various pyrogenic
cytokines including:
1)interleukin-1, interleukin-6
2)TNF-α, and
3)IFN-γ.
• 1) Exogenous : stimuli from out side the host
Like : microorganism, their products, or toxins and
it is called Endotoxin
• Endotoxin : lipopolysaccharide ( LPS)
• LPS: is found in the outer membrane of all gram
negative organism
• Action :
• 1) through stimulation of monocytes and
macrophages
• 2) direct on endothelial cell of the brain to produce
fever
• 2) Endogenous pyrogens:
• Polypeptides that are produced by the body ( by
monocytes and macrophages ) in response to
stimuli that is usually triggered by infection or
inflammation stimuli
• Pyrogens:
Substances that cause fever are called pyrogens

• What are these pyrogens:

Cytokines:
• Definition:
• Cytokines are regulatory polypeptides that are
produced by
• 1) monocytes / macrophages
• 2) lymphocytes
• 3) endothelial and epithelial cell and hepatocytes
• The most important ones are :
• Interleukin 1 and 1 - :The most pyrogenic
• Tumor necrosis factor 
• Interferon
• Interleukin 6 ……………The least pyrogenic
• cytokines>fever develop within 1h of injection
Mechanism of Action
• Cytokine-receptor interactions in the pre-optic
region of the anterior hypothalamus
activate phospholipase A.
This enzyme liberates plasma membrane
arachidonic acid as substrate for the cyclo-
oxygenase pathway. The resulting mediator,
prostaglandin E2, then modifies the
responsiveness of thermosensitive neurons in
the thermoregulatory centre.
• Diurnal variation
• 6 am : 37.2 &4pm : 37.7
• Rectal temperature>0.6oC oral temperature
• Fever: Morning : AM >37.2o C
Evening : PM >37.7o C
Presentation of Fever

• Feeling hot
A feeling of heat does not necessarily imply fever
• Rigors.
profound chills accompanied by chattering of the teeth
and severe shivering and implies a rapid rise in body
temperature. Can be produced by :
1) brucellosis and malaria
2) sepsis with abscess
3) lymphoma
Excessive sweating.
Night sweats are characteristic of tuberculosis, but
sweating from any cause is usually worse at night.
Presentation of Fever

• Headache
Fever from any cause may provoke headache.
Severe headache and photophobia, may suggests
meningitis
• Delirium
Mental confusion during fever is well described and
relatively more common in extreme of age.
• Muscle pain
Myalgia is characteristic of
Viral infections such as influenza
Malaria and brucellosis
• Hyperthermia
• Is an elevation of core temperature without
elevation of the hypothalamic set point.
• Cause: inadequate heat loss
• Examples:
• 1) Heat stroke
• 2) Drug induced such as tricyclic antidepressant
• 3) Malignant hyperthermia. associated with
psychiatric drugs
 Fever: Beneficial/Dangerous?
• Elevation of body temperature increases chance
for survival
• Temperatures appear to increase
1) The phagocytic and Bactericidal activity of
neurtrophils, and
2) The cytotoxic effects of lymphocytes
3)Thus:the growth and virulence of several
bacterial species are impaired at high
temperature .
Fever Patterns
• Intermittent fever
• Remittent fever
• Hectic fever
• Sustained fever
• Relapsing
• Intermittent fever: exaggeration of the normal circadian
rhythm,& temp. falls daily to normal, when the variation
is large it is called hectic
Cause: a) Deep seated infection
b) Malignancy
c) Drug fever
Quotidian fever: hectic fever that occur daily.

• Remittent fever: Temperature falls daily but not to

normal.
Causes: a) tuberculosis
b) viral infection
c) many bacterial infections
• Relapsing fever: febrile episodes are separated
by intervals of normal temperature
a) Malaria fever every 3days (tertian).plasm.
falciparam.
or every 4 days (quartan) ..plasm .vivax
b) Borrelia ..Days of fever followed by days of
no fever.
Fever Pattern

• Pel-Ebstein fever : fever for 3 to 10 days followed by no

fever for 3 to 10 days
Causes : a) Hodgkin lymphoma
b) Tuberculosis
Fever Pattern
• Fever pattern cannot be considered diagnostic
for a particular infection or disease and the
typical pattern is not usually seen because of use
of :
1) Antipyretics
2) Steroids
3) Antibiotics
• Temperature – pulse dissociation ( Relative bradicardia )
• is seen in
A) Typhoid fever
B) Brucellosis
C) leptospirosis
D) factitious fever
E) acute rheumatic fever with cardiac conduction
abnormality
F) Viral myocarditis
G) Endocarditis with valve ring abscess affecting
conduction .
Fever Patterns..Degree
• Fever with extreme degree:
• gram-negative bacteremia,
• Legionnaires‘ disease, and
• bacteremic pyelonephritis
• Noninfectious cause of extreme pyrexia:
• heat stroke, intracerebral hemorrhage
Physical Examination
• Fever may sometimes be absent:
• Seriously ill newborns
• Elderly patients,
• Uremic patient,
• Significantly malnourished individuals,
• Receiving corticosteroids or
• Continuous treatment with anti-inflammatory or
antipyretic agents
Approach to the Febrile Patient
The most important step is

Meticulous detailed history

Approach to Fever
Rule out common infection
REMEMBER:
UNCOMMON MANIFESTATIONS OF COMMON
DISEASES ARE COMMONER THAN COMMON
MANIFESTATIONS OF UNCOMMON ONES

Careful history:
1) chronology of symptoms
Detailed complain of the patient with the
symotoms arranged chronologically
 2) Use of drugs

• Drug fever is uncommon and therefore easily

missed.
The culprits include:
penicillin and
cephalosporin
sulphonamide
anti tuberculous agents
anticonvulsants particularly phenytoin
 3) Surgical or dental procedure

Patient known to have rheumatic heart disease

is at risk to develop infective endocarditis if not
given prophylaxis

4) Nature of any prosthetic material or implanted

devices prosthesis implant for: the knee joint
prosthetic valve replacement
5) Occupational history including:
Exposure to animals: brocellosis & Q fever
exposure to infected person at home ..tuberculosis
or infleunza.
Geographic Area of Living
If the patient has been in an endemic area common
diagnoses include:
• Malaria
• Typhoid fever
• Viral hepatitis
Dengue fever & other haemrrhagic fevers:
• Ebola
• CORONA(MERS-COV)
• ZIKA VIRUS
Malaria must be excluded whatever the presenting
symptoms.
Further Points in History
• Household pets
• Ingestion of unpasteurized milk or cheeses
• Sexual practice
• Iv drug abuse
• Alcohol intake
• Prior transfusion or immunization
• Drug allergy
History-Taking in Febrile Patients
Symptoms of common respiratory infections.
1) Sore throat, nasal discharge, sneezing …?URTI
(VIRAL)
2) Sinus pain and headache.….? Suggesting A sinusitis
3) Elicit symptoms of lower respiratory tract infection
cough, sputum, wheeze or breathlessness
• Genitourinary symptoms.
• Ask specifically about:
frequency of micturition, dysuria, loin pain, and
vaginal or urethral discharge ….suggesting
a) Urinary tract infection,
b) Pelvic inflammatory disease and
c) Sexually transmitted infection (STI)
• Abdominal symptoms
Ask about diarrhea, with or without blood,
weight loss and abdominal pain ..suggesting:
a) Gastroenteritis,
b) Intra-abdominal sepsis,
c) Inflammatory bowel disease,
d) Malignancy
• Joint symptoms
joint pain, swelling or limitation of movement . If
present ask about
A) distribution: mono, oligo or poly arthritis
B) appearance: fleeting or additive
It suggests:
1) infective arthritis…oligo
2) collagen vascular disease…..fleeting
3) reactive arthritis
• Drug history
• Drug fever is uncommon and therefore easily missed.
The culprits include :
penicillin and
cephalosporin
sulphonamide
anti tuberculous agents
anticonvulsants particularly phenytoin
• Alcohol consumption
Alcoholic hepatitis,
hepatocellular carcinoma
are all recognized causes of fever.
• Family history of:
a) Tuberculosis
b) Arthritis
c) Other infectious diseases
d) Any one with symptoms of Polyserositis or
bone pain
• Ethnic origin of the patient
is important. Example:
Turks, Arabs, Armenians likely to have Familial
Mediterranean fever (FMF)
Physical examination/important points:
REPEATED METICULOUS EXAMINATUION
on a regular basis(better by diff.colleagues) until
diagnosis is reached.
Temperature should be taken
1) Orally ..or
2) Rectally ….
Axillary temperature is notoriously unreliable .
• Cautions while taking oral temperature
1) Recent consumption of hot or cold drinks
2) Smoking
3) Hyperventilation
Examination
Document the presence of fever
• A careful examination is vital and must be repeated
regularly
• Particular attention should be paid to :
The skin ………….for skin rash
Throat…………….for pharyngitis
Eyes………………for jaundice , scleritis.
Nail bed ………….for clubbing, splinter hemorrhage.
lymph nodes…….. for enlargmant
abdomen …………for ascitis or sign of peritonitis
heart ……………...for murmurs indicating endocarditis.
• 2) Look for RASH
• a) Erythmatous rash (rash that blanch on
pressure)
Causes:
1) Meseals: often accompanied by
upper respiratory tract symptoms
and conjunctivitis
2) other viral infection like : rubella , scarlet
fever
• B) a purpuric or petechial rash: (do not blanch
on pressure)
• May suggest meningococcal septecemia
• Vesicular rash: may be caused by
• chickenpox or shingles
• Mouth and oropharynx
• Vesicular lesions, tonsillar exudate: suggest
Infectious etiology:
1) streptococcal pharyngitis
2) coxsakie infection

• Hairy leukoplakia. OR oropharyngeal candidiasis

suggest:
HIV /AIDS

• Oropharyngeal candidiasis.. suggest

Immunodefficiency syndrome
• Eyes
• Conjunctival petechiae….
• …may suggest …..meningococcal meningitis
• Jaundice …………may suggest acute hepatitis A
• Cervical lymphnodes enlargment :
Tonsillar LN enlargmant ….suggest :
Acute pharyngitis or tonsillitis

Posterior lymphadenopathy…suggest :
1) Infectious mononucleosis
2) HIV infection
• Axillary lymph node enlargement ....may suggest:
1) Sepsis
2)leukemia
3) lymphoma
Joints (any joint but commonly the knee and ankle)
Look for swelling, redness, hotness and effusion
suggesting active arthritis ..? infective/septic
arthritis
• Neck ..look for stiffness ..may suggest meningitis
• Abdomen:
• Look for : Tenderness( especially in the RIF)…&
ac.append./other types of ac abdomen

Chest and heart

1) Sign of consolidation
2) Pleural effusion
3) Pericardial rub
4) Cardiac murmur………Endocarditis or acute
rheumatic fever
• Rectal examination: look for
• 1) perianal abscess
• 2)acute prostatitis
Drug-IV user
20 years male who is a heroin drug abuser for a long
time, came to ER c/o left thigh pain and fever.
Look at the picture and guess what is his problem
• The answer :

• Hip flexor spasm due to psoas abscess

• Secondary to staphylococcus septicemia with
seeding into the muscle
REMEMBER;
Factitious Fever
• This is defined as fever created by the patient By
manipulating the thermometer and/or
temperature chart apparently to obtain medical
care.
• uncommon and typically presents in young
women who work in paramedical professions.
• Examples include
The dipping of thermometers into hot drinks to
fake a fever,
• The factitious disorder is usually medical
but may relate to a psychiatric illness with
reports of depressive illness.
Clues to the Diagnosis of Factitious Fever

• A patient who looks well

• Absence of temperature-related changes in pulse rate
• Temperature > 41°C
• Absence of sweating during defervescence
• Normal ESR and CRP despite high fever

Useful methods for the detection of factitious fever include

1) Supervised (observed) temperature measurement
2) Measuring the temperature of freshly voided urine
Laboratory Tests
• Laboratory investigation is indicated if
• presentation suggests more than
Simple viral infection or
acute phartngitis in children

• Lab test can be focused if the history is

suggesting certain diagnosis
1) Investigations:
• complete blood count with differential,
** band forms and toxic granulation ..suggest bacterial
infection
** Neutropenia : may be seen with:
Infection : Typhoid,brucellosis ,viral infection
vasculitis : systemic lupus erythromatosis
** lymphocytosis : may be seen in:
a) Tuberculosis, brucellosis, Viral disease.
** Monocytosis: is seen with
a) Tuberculosis, typhoid and brucellosis
b) lymphoma
**Eosinophilia is seen in:
a) Hypersensitivity drug syndrome
b) Hodgkin disease
c) Adrenal insufficiency
• blood films to exclude Malaria
• Urinalnalysis
• Sample any fluid and examine: pleural,
peritoneal, joint.
• Bone marrow aspirate & biopsy for
microbiologic& histopathology.
• Stool exam for occult blood, O, C & parasites.
• 2) chemistry: electrolytes ,glucose, urea , and liver
function
• 3) microbiology
• Samples from: sputum, urethra and other sites like joint,
pleural fluid, ascetic fluid and send for smears and
culture
• Sputum evaluation : a) gram staining
b) Z-N staining for acid fast bacilli
Culture for: blood, abnormal fluid collection and urine
CSF: if meningitis is suspected ..gram stain and culture
• SPECIAL BLOOD TEST:
• HIV screening for patient who has risk factor (high risk
behaviors)
1) Recent travel with high risk behaviors
2) Injection drug user
3) Sex workers
4) Blood transfusion recipient
• Radiology
• Chest x ray is indicated for any patient with significant
febrile illness.
Outcome of Diagnostic Efforts
1) Patient recover spontaneously
suggesting: viral illness or some of the spontaneously
recovering bacterial infection: mainly intracellular
organism like typhoid or brucellosis
2) Diagnosis is reached
3) If fever persist for more than 2-3 weeks with no
diagnosis is reached by : a) repeated physical examination.
b) laboratory test ….then
It is pyrexia of unknown origin(PUO,FUO)
Treatment of Fever
• Is it fever or hyperthermia
• Hyperthermia
1. Heat stroke
Classic heat stroke
2. Drug-induced hyperthermia
3. Malignant hyperthermia
• Heat stroke
• Thermoregulatory failure in association with a
worm environment
• 1) Exertional: young person exercising at
ambient temperature and or humidities that are
higher than normal.
• 2)non Exertional: typically occur in elderly.
• Hyperpyrexia: more than 40 should be treated
by: anti pyretics and physical cooling
• While resetting the hypothalamic set point with
antipyretic will speed the process.
• Antipyretics also help for:
• Headache, myalgia, chills.
Low grade or moderate fever is not harmful; so no
antipyretics use except for
• 1) Pregnant women
• 2) Child with febrile seizures
Why No Antipyretics for Mild Fever
• Obscure the natural history of the patient
disease or syndrome
• Gives false feeling of well being ..may miss/mask
meningitis ... which may be Imminently life-
threatening
Antibiotics use in ER
• Pathogens
• Infection focus
• host factors (Immune factors)
• Common infection in ER
1. UTI
2. Respiratory tract infection
3. CNS infection
4. Cellulitis
Antibiotics use in-UTI
Upper urinary tract infection
• Symptoms: Fever, flank pain, dysuria
lab test: Pyuria, bacteria
• Treatment: cotrimoxasole , Cephalosporin or
aminoglycoside …….duration: 7-10 days
Antibiotics use In-Respiratory tract
infection
• Pneumonia
1. Cough, fever, sputum or not
clinical manifestations: consolidation
CXR: opacity with air bronchogram interstitial
infiltrate
sputum: gram’s stain
Treatment: 3rd generation cephalsporine and
macrolides
Antibiotic use in-respiratory tract
infection
• Nosocomial fever
• Fever acquired after 48 hours of admission to
the hospital
• 1) pneumonia
• 2) catheter related infection
• 3) UTI

• Consider hospital pathogen while selecting

antibiotics
Antibiotics use in-CNS infection
• Bacterial meningitis
1. Aggressive antibiotics-due to
prognosis and sequence
2. cephalosporin
Vancomycin
• Viral meningitis
1. Observation, s/s Tx
2. Herpes meningitis- acyclovir

continuing
Antibiotic use in- CNS infection
• TB meningitis
1. Anti-TB agents
2. Prognosis: variation
• Fungal meningitis: antifungal agents
Antibiotics use In-cellulitis
• Pathogens: common streptococcus, or
staphylococcus
• Cellulitis →
• Antibiotics: PCN G or oxacillin/synthetic
penicillins
Pitfalls
• Depend on laboratory data
• Incomplete Hx.&EX

• Atypical presentation
1. Immunocompromised patient
2. Newborn
3. Early sign
4. Dehydration
Thank you