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Fever of Unknown Origin

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FUO Fundamentals - Defining the Mystery

  • Original (Petersdorf & Beeson): Fever >38.3°C, >3 wks; diagnosis unclear post 1 wk inpatient.
  • Modified Types (Durack & Street):
    • Classical FUO:

      ⭐ Classical FUO: Fever >38.3°C (101°F) on several occasions, duration >3 weeks, and failure to reach a diagnosis despite 1 week of inpatient investigation or 3 outpatient visits.

    • Nosocomial: Hospital-acquired fever >38.3°C; unclear post 3 days.
    • Neutropenic: Neutrophils <500/µL, fever >38.3°C; unclear post 3 days.
    • HIV-associated: HIV+; fever >38.3°C for >4 wks (outpt) / >3 days (inpt); unclear post 3 days.

FUO Culprits - The Usual Suspects

Common causes of Fever of Unknown Origin (FUO) can be broadly categorized:

CategoryCommon Examples (India)Key Differentiator/Test
InfectionsTB (EPTB, Miliary), Brucellosis, Enteric fever, Abscesses, EndocarditisAFB, Cultures, Serology, Imaging, Echo
MalignanciesLymphoma, Leukemia, RCC, HCCBiopsy, BM exam, CT/PET
Collagen Vasc./Inflamm.Adult Still's, SLE, Vasculitis (PAN, GCA)Ferritin, ANA, ANCA, ESR/CRP, Biopsy
MiscellaneousDrug fever, Factitious feverDrug withdrawal, Observation

FUO Detective Work - Cracking the Case

FDG-PET/CT is highly valuable for localizing occult inflammatory or neoplastic foci in FUO when initial investigations are unrevealing, guiding further targeted biopsies.

FUO Hotspots - Alarms & Alerts

  • Elderly: Giant Cell Arteritis (GCA), malignancy.
  • Immunocompromised: Opportunistic infections (PJP, CMV, fungal).
  • Travel History: Malaria, typhoid, dengue, rickettsial diseases.
  • Drug-Induced: Beta-lactams, phenytoin.
  • Factitious Fever: Discrepancy oral/rectal temp, no ↑HR.
  • Naproxen Test: Lysis suggests neoplastic fever. Temporal artery biopsy in Giant Cell Arteritis

⭐ In elderly patients (>65 years) with FUO, headache, and elevated ESR (>50 mm/hr), strongly consider Giant Cell Arteritis (Temporal Arteritis); temporal artery biopsy is the gold standard for diagnosis.

High‑Yield Points - ⚡ Biggest Takeaways

  • FUO: Fever > 38.3°C for ≥ 3 weeks, undiagnosed after 1 week inpatient or 3 outpatient visits.
  • Main Causes: Infections (TB, endocarditis), malignancies (lymphoma), autoimmune (Still's, temporal arteritis).
  • Elderly: ↑ Temporal arteritis, malignancies.
  • HIV-FUO: Opportunistic infections (TB, MAC), lymphoma.
  • Investigations: Cultures, ESR/CRP, CT abdomen/pelvis.
  • Naproxen test: Suggests neoplastic fever; not diagnostic.
  • Empirical therapy: Generally avoid unless critically ill/neutropenic_._

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