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Pathophysiology
Clinical meaning
Fever is defined as a core body temperature >38.0C (100.4F), representing an upward shift in the hypothalamic set point mediated by prostaglandin E2 (PGE2). During infection, macrophages release endogenous pyrogens (IL-1, IL-6, TNF-alpha) that stimulate cyclooxygenase-2 (COX-2) in the hypothalamic organum vasculosum, producing PGE2. PGE2 raises the thermoregulatory set point, triggering heat conservation (vasoconstriction, shivering) until body temperature matches the new set point. Fever is a beneficial host defense mechanism that enhances immune function: neutrophil migration, lymphocyte proliferation, and antimicrobial protein production are all augmented at febrile temperatures. The risk of serious bacterial infection (SBI) is stratified by age: neonates <28 days have the highest risk (10-15%) due to immature immune systems, warranting aggressive evaluation. Infants 29-60 days have intermediate risk (5-10%), while children >60 days with no high-risk features have low risk (<1%). The Rochester, Philadelphia, and Boston criteria help stratify risk in febrile infants.
Diagnostics & workup:
- Neonates <28 days with fever: FULL sepsis workup (CBC, blood culture, UA with culture, CSF analysis, chest X-ray if respiratory symptoms)
- Infants 29-60 days: CBC, UA with culture, blood culture; CSF if ill-appearing or abnormal labs
- Infants 61-90 days: UA mandatory; CBC and blood culture based on clinical assessment
- Children 3-36 months: based on clinical appearance, vaccination status, and temperature
- Order procalcitonin (more specific for bacterial infection than CRP or WBC)
- UTI evaluation: catheterized specimen in non-toilet-trained children (bag specimens are unreliable)
Risk factors:
- Age <28 days (highest risk for SBI regardless of appearance)
- Age 29-60 days (intermediate risk)
- Temperature >39C (102.2F) in infants <3 months
- Prematurity or perinatal complications
- No prior vaccinations
- Ill-appearing infant (toxic appearance)
- Immunocompromised (sickle cell, HIV, asplenia, chemotherapy)
- No identifiable source of fever
- History of UTI (especially uncircumcised males <6 months)
Management
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Prescribing & monitoring
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Takeaways
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