IM4.{9,14,18} | Fever of Unknown Origin — Summary & Reflection

KEY TAKEAWAYS

FUO definition (Petersdorf-Beeson): temperature >38.3°C for ≥3 weeks, undiagnosed after appropriate investigation. Four categories: classic (immunocompetent), nosocomial (hospital-acquired, think devices/CDAD/drugs), neutropenic (immediate empiric antibiotics, fungi after day 7), HIV-associated (tier by CD4 count).

Indian FUO aetiology: infections 35–40% (extrapulmonary TB, endocarditis, kala-azar, brucellosis, typhoid); inflammatory 20–25% (AOSD: ferritin >5000, quotidian fever, salmon rash; SLE: ANA screen; GCA: ESR >80, temporal biopsy); malignancy 15–20% (lymphoma, RCC); miscellaneous 10–15% (drug fever, sarcoidosis).

Key tests: blood cultures ×3 (5–14 day hold), HIV (universal, never omit), ESR/CRP/ferritin/LDH, procalcitonin (specific for bacterial), bone marrow (kala-azar/miliary TB/HLH/lymphoma), ANA/ANCA panel, rK39 (Bihar/Jharkhand/West Bengal), IGRA (more specific than Mantoux in BCG-vaccinated).

Diagnostic plan (IM4.18): Step 1 urgent exclusions → Step 2 clinical clue review → Step 3 ranked differential (probability + danger + treatability) → Step 4 tiered investigations → Step 5 AVOID empiric antibiotics or steroids until diagnosis established (exception: clinical deterioration demanding immediate action).

Cardinal rule: never start empiric corticosteroids for suspected autoimmune FUO without excluding TB and kala-azar — steroids cause catastrophic deterioration in both.

REFLECT

Revisit the patient in the opening vignette — five weeks of fever, three antibiotic courses, no diagnosis. Now that you have the FUO framework, what is your ranked differential? What clinical clues would you specifically look for on re-examination? Which tier-1 investigations would you order first, and which single investigation is non-negotiable regardless of her clinical story? Think about the principle that in FUO, the investigation itself is the primary intervention — not the antibiotic. How does this reframe the way you should counsel the patient about the diagnostic process, including the possibility of invasive biopsy?