APPROACH TO

THE FEBRILE PATIENT

Dr. Awadh Al-Anazi, M.D
College of Medicine
KING SAUD UNINERSITY

1440-1441/2019-2020
 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:

Basal metabolic activity.

Muscle movement.

And is lost by:

Conduction.
Convection (which is increased by wind or fanning).
Evaporation which is increased by sweating. or sometimes by breathing
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.
as a mechanism of compensation in hot and cold environment the
thermoregulatory center in hypothalamus will play an extreme important
role.

if you was in a hot environment, sweating is the mechanism to decrease

body temperature by loss of heat, the opposite mechanism in the cold
weather, shivering and twitching of the muscles will rise the body
temperature.
 FEBRILE RESPONSE
The initiation of fever begins when exogenous or
endogenous stimuli are presented to specialized host cells,
principally monocytes and macrophages.

They will stimulates the synthesis and release of various

pyrogenic cytokines including:

interleukin-1, interleukin-6
TNF- , and
IFN- .
 EXOGENOUS
Stimuli from outside the host like:
microorganism, their products, or toxins which are called
Endotoxin (lipopolysaccharide).

Lipopolysaccharide (LPS): are found in the outer

membrane of all gram negative organisms.

Action :
Through stimulation of monocytes and macrophages.
Direct on endothelial cell of the brain to produce fever.
 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.

What pyrogens are there?

Cytokines: regulatory polypeptides that are produced by:

Monocytes / macrophages.
Lymphocytes.
Endothelial and epithelial cell and hepatocytes.
The most important ones are :
Interleukin 1 and 1 (the most pyrogenic). In Labs when they inject this
substance to animals the temperature will rise immediately
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 center.
 Diurnal variation:
6 am : 37.2 o C
4 pm : 37.7 o C

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 :
Brucellosis and malaria.
Sepsis with abscess.
Lymphoma. and autoimmune diseases

Excessive sweating:
Night sweats are characteristic of tuberculosis, but
sweating from any cause is usually worse at night.
When the patient wake up with all his clothing wet this is consider pathologic sweating
 PRESENTATION OF FEVER
Headache:
Fever from any cause may provoke headaches.
Severe headache and photophobia, may suggests
meningitis.or sinusitis

Delirium:
Mental confusion during fever is well described and
relatively more common in extreme of age.
Because with aging the blood vessels become sclerotic and the elasticity decrease, so when there is fever the oxygen demand of
the brain will increase and its need to be compensated by increase blood flow but with the sclerosis and reduced elasticity the
blood flow remains the same, this leads to decrease level of consciousness and confusion.

Muscle pain:
Myalgia is characteristic of viral infections(influenza),
and other infections( malaria and brucellosis etc.)
 HYPERTHERMIA
There is a difference between hyperthermia and fever which is secondary to stimuli

Is an elevation of core temperature without elevation of

the hypothalamic set point.

Cause: inadequate heat loss, such as:

Heat stroke. ‫تكثر في موسم الحج‬
Drug induced such as: tricyclic antidepressant.
Malignant hyperthermia associated with psychiatric
drugs. and anesthesia
 FEVER: BENEFICIAL/DANGEROUS?
Elevation of body temperature increases chance for
survival.

Temperatures appear to increase the phagocytic and

bactericidal activity of neurtrophils, and the cytotoxic
effects of lymphocytes. So it has some benefit but not enough to control the infection

Thus the growth and virulence of several bacterial species

are impaired at high temperature.
 FEVER PATTERNS
Fever patterns Important when we take history
Intermittent fever.
Remittent fever.
Hectic fever.
Sustained fever.
Relapsing fever.
Intermittent fever:
Exaggeration of the normal circadian rhythm and temperature.
falls daily to normal.
when the variation is large it is called hectic.

Causes:
Deep seated infection.
Malignancy.
Drug fever.

Quotidian fever: hectic fever that occur daily.

Remittent fever:
Temperature falls daily but not to normal.

Causes:
Tuberculosis.
Viral infection.
Many bacterial infections.
Relapsing fever:
Febrile episodes are separated by intervals of normal
temperature. Such as:

Malaria: fever every 3 days (tertian) caused by (plasm.

Falciparam). Or every 4 days (quartan) caused by
(plasm. Vivax).
Borrelia: Days of fever followed by days of no fever.
 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 :

Antipyretics.
Steroids.
Antibiotics.
factors determine the clinical improvement:
1- follow patient daily with T- max which is the maximum temperature per day.
2- duration between fever spikes.
 FEVER PATTERN

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

Causes:
Hodgkin lymphoma.
Tuberculosis.
Temperature-pulse dissociation (Relative bradycardia)
is seen in: The normal body reaction to fever is tachycardia .. 1 degree increase in temperature will
rise the heart rate by 10 to 15 beats

Typhoid fever.
Brucellosis.
Leptospirosis. It’s a wrong reading fever, for example if the nurse measures the temperature orally when the
Factitious fever. patient is drinking coffee or tea.
sometimes patient do rubbing to the thermometer to increase the temperature.

Acute rheumatic fever with cardiac conduction

abnormality.
Viral myocarditis.
Endocarditis with valve ring abscess affecting
conduction.
Beta blockers
 FEVER PATTERNS..DEGREE
Fever with extreme degree:

Gram-negative bacteremia.
Legionnaires disease.
Bacteremic pyelonephritis.

Noninfectious cause of extreme pyrexia:

Heat stroke.
Intracerebral hemorrhage. Called central fever
 APPROACH TO THE FEBRILE
PATIENT
What is the easiest and most cost effective way
of reaching a diagnosis and thus offering the
right treatment for a febrile patient?
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:

Chronology of symptoms:

Detailed complain of the patient with the

symptoms arranged chronologically.

Use of drugs:
Don’t jump to drug fever until you rule out serious causes like infection

Drug fever is uncommon and therefore easily missed. The

culprits include:
Penicillin.
Cephalosporin.
Sulphonamide.
anti tuberculous agents.
anticonvulsants particularly phenytoin.
Surgical or dental procedure:

Patient known to have rheumatic heart disease is at risk to

develop infective endocarditis if not given prophylaxis.

Occupational history:

Exposure to animals: brucellosis & Q fever.

Exposure to infected person tuberculosis or influenza.
Brucellosis and Q fever zoonotic diseases share the same risk factors:
Unpasteurized milk + eat raw liver + uncooked meat.
Symptoms of common respiratory infections:

Sore hroa , nasal discharge, snee ing ?URTI (VIRAL).

Sin s pain and headache. .? S gges ing sin si is.
Elicit symptoms of lower respiratory tract infection
cough, sputum, wheeze or breathlessness.
Frontal and maxillary Sinus pain increase with praying.
Genitourinary symptoms:

Ask specifically about:

frequency of micturition, dysuria, loin pain, and vaginal
or urethral discharge, suggesting:
Urinary tract infection.
Pelvic inflammatory disease.
Sexually transmitted infection (STI).
Abdominal symptoms:
Diarrhea + nausea + vomiting most likely food poising or viral/ bacterial infection.

Ask about diarrhea, with or without blood, weight loss and

abdominal pain, suggesting:
Gastroenteritis.
Intra-abdominal sepsis. Post op or trauma
Inflammatory bowel disease.
Malignancy.
Lymphoproliferative like lymphoma and leukemia.
Hepatoma
Renal cell carcinoma
 Joint symptoms:

Joint pain, swelling or limitation of movement . If present

ask about:
Distribution: mono, oligo or poly arthritis.
Appearance: fleeting or additive.

It suggests:
Infec i e ar hri is oligo.
Collagen asc lar disease ..Flee ing.
Reactive arthritis.
-Mono most likely septic arthritis.
-Brucellosis most commonly affects sacroiliac joint.
-infections that can cause poly arthritis:
Rheumatic fever, disseminated gonorrhea and reiter syndrome which is triggered by certain infection like
chlamydia and other genitourinary infections.
Family history of:

Tuberculosis.
Arthritis.
Other infectious diseases.
Any one with symptoms of Polyserositis or bone pain.

Ethnic origin of the patient:

Turks, Arabs, Armenians likely to have Familial

Mediterranean fever (FMF).
Geographic area of living:
Very important in history taking.

If the patient has been in an endemic area common diagnoses

include:
‫تكون في املناطق الساحلية املنخفضة مثل جازان … أبها والباحة تعتبر مناطق جبلية ماتعيش فيها الباعوضة‬
Malaria. ‫اللي تنقل املالريا لكن بعض السكان ينتقلون للمناطق املنخفضة خالل فصل الشتاء وممكن يصابون في املرض‬
Typhoid fever. ‫منتشر في جنوب آسيا < باكستان و بنقالدش‬
Viral hepatitis.

Dengue fever & other viral diseases:

‫حمى الضنك توجد في املناطق الغربية مثل جدة وايضا ً في جازان ونجران‬

Hemorrhagic fevers (eg: Rift valley)

Ebola ‫أفريقيا‬
CORONA(MERS-COV)
Zika virus ‫أمريكا الجنوبية‬
Nipah virus Fever + picture of hemolysis + low platelet + prolonged PTT + liver impairment + hx of traveling to
these area > I should put in mind hemorrhagic viruses which is endemic at these areas.

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.
 PHYSICAL EXAMINATION
Approach considerations:
Fever may sometimes be absent in some cases, such as:
Patient might be septic but because he is under one of these categories you will not find fever so in SIRS (systemic inflammatory
response syndrome) we are looking for high temperature or hypothermia both can be signs of infection.

Seriously ill newborns.

Elderly patients.
Uremic patient.
Malnourishment.
Corticosteroid use.
Continuous treatment with anti-inflammatory or
antipyretic agents.
Repeated meticulous examination on a regular basis
(better by different colleagues) until diagnosis is reached.

Temperature should be taken

Orally or,
Rectally. to measure the core temperature ... used in pediatrics and neonates
Axillary temperature is notoriously unreliable .

Cautions while taking oral temperature

Recent consumption of hot or cold drinks.
Smoking.
Hyperventilation.
Document the presence of fever.

A careful examination is vital and must be repeated

regularly.

Particular attention should be paid to:

The skin for rash.

Throat for pharyngitis.
Eyes for jaundice, scleritis.
Nail bed for clubbing, splinter hemorrhage.
lymph nodes for enlargement.
abdomen for ascites or sign of peritonitis.
heart for murmurs indicating endocarditis.
Head:
-tenderness around sinuses
-Increase headache when patient Ear:
moving his head left & right > CNS -cellulitis in external ear.
-oral thrush > candida
infections -malignant otitis externa > in DM patients
-tonsillitis
caused by pseudomonas
-peri-tonsillar abscess
-look for discharge and abscess

-pulging of the eye > cavernous sinus thrombosis

-jaundice > hepatitis, malaria -neck stiffness > meningitis
Puffiness, swelling > periorbital abscess

-Injection marks in drug abuse

-thrombophlebitis signs > tender,
redness and feels like a thread on
palpation

-clubbing > bronchiactasis and lung abscess

-pulse > reactive bradycardia

• Neck swelling > Internal jugular venous thrombosis (septic thrombophlebitis) in

lemierre syndrome which is secondary to certain types of bacteria
“fusobacterium” affect oral mucosa and teeth
 SKIN
Look for rash.
Erythematous rash (rash that blanch on
pressure):

Causes:
Measles: often accompanied by upper respiratory tract
symptoms and conjunctivitis.
Other viral infection like: rubella, scarlet fever.
-Swelling, redness, hotness > cellulitis ... caused by staph
if the margins well demarcated > impetigo … caused by staph and streptococcus
-Whitish spots in front of second molar teeth is pathognomonic feature of measles > called koplik spots, appears early
before rash
Purpuric or petechial rash (do not blanch on
pressure):

May suggest meningococcal septicemia.

Vesicular rash:

May be caused by chickenpox or shingles.

 MOUTH AND OROPHARYNX
Vesicular lesions, tonsillar exudate
suggest Infectious etiology:

Streptococcal pharyngitis.
Coxsackie infection.

Hairy leukoplakia or oropharyngeal

candidiasis suggest:

HIV /AIDS Black patches > kaposi sarcoma

-strawberry tounge > kawasaki disease and scarlet fever

 EYES
Conjunctival petechiae may suggest meningococcal
meningitis.

Jaundice may suggest acute hepatitis A.

 LYMPH NODES
Cervical lymph node enlargement and tonsillar
enlargement suggest:
Acute pharyngitis or tonsillitis.

Posterior lymphadenopathy suggest:

Infectious mononucleosis.
HIV infection.

Axillary lymph node enlargement may suggest:

Sepsis.
Leukemia.
Lymphoma.
 JOINTS

Any joint but commonly the knee and ankle.

Look for swelling, redness, hotness and effusion
suggesting active arthritis ..? infective/septic arthritis

If single joint affected its in favor

of infection always do:
-fluid analysis to see cell count,
presence of crystals.
-gram stain & culture
Neck: look for stiffness. may suggest meningitis

Chest and heart:

Sign of consolidation.
Pleural effusion. -chest expansion impaired.
-percussion > dull or stony dullness.

Pericardial rub.
-increase tactile fremitus.
-auscultation > crepitations & crackles, eagophony and bronchial breathing.

Cardiac murmur: Endocarditis or acute rheumatic fever.

Abdomen: Look for tenderness (especially in the RIF) acute

appendicitis and other types of acute abdomen.

Rectal examination: look for

Perianal abscess. Abdomen:
-organomegaly
-rebound tenderness
-murphy’s sign > cholecystitis

Acute prostatitis. -liver bruits > disseminated gonorrheal infection

-ascites
-liver shrinkage + ascites + fever > Spontaneous Bacterial Peritonitis, we should analyze the fluid to see:
1- serum albumin ascites gradient
2- turbid fluid
3- neutrophils > 250
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

Hip flexor spasm due to psoas abscess secondary to
staphylococcus septicemia with seeding into the muscle.
 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.
Normal ESR and CRP despite high fever.

Useful methods for the detection of factitious fever

include:
Supervised (observed) temperature measurement.
Measuring the temperature of freshly voided urine.
 LABORATORY TESTS
Laboratory investigations are indicated if the presentation
suggests more than a simple viral infection or acute
pharyngitis in children.

Lab test can be focused if the history is suggesting a certain

diagnosis.

-Leukopenia > viral infection

-high neutrophils > bacterial infection
-vey high leukocytosis > acute leukemia
-low platelet > septic shock, malaria, hemorrhagic viruses, HUSTTP ( hemolytic uremic syndrome thrombotic thrombocytopenic purpura )
which is fever + renal impairment + low platelet + normal PTT & aPTT + sometimes confusion
-low hemoglobin > malaria, chronic infection like TB & brucellosis.
CBC with differential:
Band forms(%of neutrophils), and toxic
granulation(periph.B.F) suggest bacterial infection.

Neutropenia may be seen with:

Infection: Typhoid, brucellosis ,viral infection.
Vasculitis: systemic lupus erythematosus.

Lymphocytosis may be seen in:

Tuberculosis, brucellosis and viral disease.

Monocytosis is seen with:

Tuberculosis, typhoid and brucellosis.
Lymphoma.
Eosinophilia is seen in:
Hypersensitivity drug syndrome.
Hodgkin disease.
Adrenal insufficiency.
Drug induce fever, dress syndrome

Blood films to exclude Malaria. Taken from periphery...best time during spike of fever

Urinalysis.
Sample any fluid and examine: pleural, peritoneal,
joint.
Bone marrow aspirate & biopsy for
microbiologic& histopathology.
Stool exam for occult blood, O, C & parasites.
Chemistry: electrolytes ,glucose, urea , and liver
function.

Microbiology:
Samples from sputum, urethra, joint aspirates, pleural
fluid, ascetic fluid and send for smears and culture.

Sputum evaluation:
Gram staining.
Z-N staining for acid fast bacilli.

Cultures for: blood, abnormal fluid collection and urine.

-Tissue culture if there is wound

CSF: if meningitis is suspected do gram stain and culture.

-histopathology and tissue biopsy to rule out malignancy & TB.
 HIV testing:
1- pre-employment
2- before donating blood
3- pre-marital
Special blood tests: 4- antenatal care
5- TB

HIV screening for patient who has risk 6- clinical picture “opportunistic infections”
7- high risk behavior

factor (high risk behaviors):

Recent travel with high risk behaviors.
Injection drug user.
Sex workers.
Blood transfusion recipient.

Radiology:
Chest x ray is indicated for any patient
with significant febrile illness.
CT PET scan > hot spot indicate malignancy or infection
OUTCOME OF DIAGNOSTIC EFFORTS
Patient recover spontaneously suggesting:
viral illness or some of the spontaneously recovering
bacterial infection (mainly intracellular organism like
typhoid or brucellosis).

If fever persist for more than 2-3 weeks with no diagnosis is

reached by repeated physical examination and laboratory
es s hen i s:

PYREXIA OF UNKNOWN ORIGIN(PUO,FUO)

 TREATMENT OF FEVER
-Central fever caused by stroke with large infarction or hemorrhage > no need for further work up or treatment.

Is it fever or hyperthermia?

Hyperthermia:
1. Heat stroke.
2. Drug-induced hyperthermia.
3. Malignant hyperthermia.
Heat stroke:
Thermoregulatory failure in association with a warm
environment.

Exertional: young person exercising at ambient

temperature and or humidity that is higher than normal.
Non Exertional: typically occur in the elderly.
Hyperpyrexia: more than 40 should be treated with
antipyretics and physical cooling.

While resetting the hypothalamic set point with antipyretic

will speed the process. Antipyretics also help treating
headaches, myalgia and chills.
Low grade or moderate fever is not harmful; so no
antipyretics use except for:
Pregnant women.
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:

UTI
Respiratory tract infection
CNS infection
Cellulitis
-Each patient before we give him antibiotics we need to categorize him as health care associated or community acquired infection
because Health care associated infection means patient has risk factor for multi-drug resistant organism and certain type organisms
including pseudomonas.

-Antibiogram is a summary of the cultures has been done during the year, for example 1000 culture of urine showed most
common organism E.coli and the most pattern of sensitivity is to a specific antibiotic > so I can start that antibiotic
empirically with patients present with UTI.
 ANTIBIOTICS USE IN UTI
Upper urinary tract infection

Symptoms: Fever, flank pain, dysuria

lab test: Pyuria, bacteria
Treatment: cotrimoxazole , cephalosporin or
aminoglycoside (duration: 7-10 days)
 ANTIBIOTICS USE IN-RESPIRATORY
TRACT INFECTION
Pneumonia:
Cough, fever, sputum or not.

Clinical manifestations: consolidation.

CXR: opacity with air bronchogram interstitial infiltrate.
Sputum: gram s s ain.
Treatment: 3rd generation cephalosporins and
macrolides.
ANTIBIOTIC USE IN-RESPIRATORY TRACT
INFECTION
Nosocomial fever:
Fever acquired after 48 hours of admission to the hospital.
Maybe:
Pneumonia.
Catheter related infection.
UTI.

Consider hospital pathogen while selecting antibiotics.

 ANTIBIOTICS USE IN-CNS
INFECTIONS
Bacterial meningitis:
Use aggressive antibiotics-due to prognosis and sequence.
cephalosporin Vancomycin.

Viral meningitis:
Observation, s/s Tx.
Herpes meningitis: acyclovir.

TB meningitis:
Anti-TB agents.
Prognosis: variation.

Fungal meningitis: antifungal agents.

 ANTIBIOTICS USE IN-CELLULITIS
Pathogens: common streptococcus, or staphylococcus.

Antibiotics: PCN G or oxacillin/synthetic penicillin's

 PITFALLS
Depend on laboratory data.
Incomplete history and examination.

Atypical presentation:
Immunocompromised patient.
Newborn.
Early sign.
Dehydration.
Thank you