FEVER
Endogenous pyrogens/pyrogenic cytokines
• An elevation of body temperature
that exceeds the normal daily
variation and occurs in conjunction
with an increase in the
hypothalamic set point
i.e. 37°C (normothermic)  39°C (febrile)
Pyrogenic cytokines (IL-1, IL-6, TNF, IFN)
and microbial toxins
Hypothalamus: increased PGE2 and cAMP
(+) Neurons in vasomotor center
Peripheral vasoconstriction and increased
metabolic activity
Decreased heat loss peripherally (person
feels cold)
“Shivering” heat production
FEVER
• Decreased pyrogens/ antipyretic
use  reset hypothalamic set point
 vasodilation & sweating (heat
loss)
Hyperpyrexia: fever of >41.5C (106.7F)
resulting from severe infection or CNS
hemorrhage
Hypothalamic fever: elevated temperature
caused by abnormal hypothalamic fxn
Exogenous pyrogens
• Microbial products
• Microbial toxins
o lipopolysaccahride
endotoxin of G-negative
bacteria
o Staph aureus enterotoxin
o GAS and GBS
• Whole microorganisms
• IL-1, IL-6, TNF, ciliary neurotropic
factor (CNTF), IFN-α
• Produced by monocytes,
neutrophils, and lymphocytes
• Production can be induced by
infection, trauma, inflammation,
and tissue necrosis
Approach to patient with fever
• Detailed history
o Chronology of symptoms
o Recently taken meds
(prescribed or not)
o Prosthetic or implanted
devices
o Occupational hazards
o Recent travel
o Unusual hobbies
o Dietary preferences
o Sexual practices
o Exposure to animals
o Drug use
o Exposure to people with
infection
• Physical examination
o Vital signs
o Axillary temperatures are
notoriously unreliable
o Skin, eyes, lymph nodes,
nail beds, cardiovascular
system, chest, abdomen,
musculoskeletal system,
and nervous system
o In women: do pelvic exam
(possible PID)
• Laboratory tests
o Clinical Pathology
 CBC with differential
(eosinophils, bands,
toxic granulations,
Dohle bodies)
 Neutropenia: parvovirus
B19, typhoid,
brucellosis, TB,
histoplasmosis
 Lymphocytosis:
typhoid, brucellosis,
TB, viral disease
 Atypical lymphocytes:
EBV. CMV, HIV, dengue,
 rubella, measles, • Either remittent or intermittent
varicella, viral hepatitis pattern
 Monocytosis: typhoid, • Temperature excursion >1.4 C (2.5
TB, brucellosis F)
 Eosinophilia: parasitic • Examples: Intermittent bacteremia
infection
(dental abscess, UTI), Epstein-Barr
 Smear: malarial and Virus , Familial Mediterranean
babesial pathogens Fever , Crohn's Disease, Still's
 ESR Disease (Juvenile Rheumatoid
 Urinalysis with Arthritis)
examination of 5. Sustained or Continuous Fever
sediment • Daily elevated temperature (>38 C
o Chemistry or 100.4 F)
 Electrolytes • Fluctuation of elevated
 Glucose temperature < 0.3 C (0.5 F)
 BUN • Associated conditions: Drug Fever,
 Creatinine Salmonella
o Microbiology
 Gram stain Mechanisms of antipyretic agents
 Culture and sensitivity • Inhibition of COX
o Radiology • Acetaminophen: centrally-acting
 CXR • Other antipyretics: ibuprofen,
aspirin, indomethacin,
Patterns of Fever
glucocorticoids, phenothiazine
(http://www.fpnotebook.com/ID44.htm)
1. Remittent Fever:
gεnεЅϊЅ ϋ
• Daily elevated temperature (>38 C
or 100.4 F)
• Returns to baseline but not to
normal
2. Intermittent Fever (Periodic Fever)
• Intermittently elevated
temperature (>38 C, 100.4 F)
• Return to baseline and to normal
• Examples: PFAPA Syndrome: Fever
every 3-4 weeks
• Most common cause in children age
<5 years
3. Relapsing Fever (Borrelia species):
Every 2-3 weeks
• Malaria: Fever every other or every
third day
• Rat Bite Fever: Fever every 3 to 5
days
• Hodgkin's Disease: Pel-Ebstein
Fever
• Cyclic Neutropenia: Fever every 3
weeks
4. Hectic Fever
• Daily elevated temperature (>38 C
or 100.4 F)