Approach to Fever of Unknown Origin

  • Overview:
    • The syndrome of fever of unknown origin (FUO) was defined in 1961 by Petersdorf and Beeson as the following: (1) a temperature greater than 38.3°C (101°F) on several occasions, (2) more than 3 weeks’ duration of illness, and (3) failure to reach a diagnosis despite one week of inpatient investigation.
  • Etiology:
    • Majority of cases fall into the following 3 large buckets:
      • Infectious: HIV, fungal, atypical organisms, syphillis, mycobacterial, parasite, tick-borne, osteomyelitis, endocarditis, dental, sinusitis, abscesses ( e.g., liver)  etc.
      • Malignancy: hematological (e.g., leukemia, lymphoma) vs. solid (e.g., testicular, RCC, HCC) vs paraneoplastic
      • Inflammatory: giant cell arteritis, Sarcoid, Behcets, Stills, other vasculitis
      • Other: VTE, drug/meds, hematoma, central dysregulation – pheochromocytoma, thyroid disease, familial (FMF, PFAPA, cyclic neutropenia)
  • Evaluation:
    • Start with complete history and physical exam.
    • Minimum diagnostic evaluation should include: NP swab, blood cultures x3, erythrocyte sedimentation rate or C-reactive protein, serum lactate dehydrogenase, HIV test, Hepatitis serology, ANA, rheumatoid factor, monospot, CK, RPR, serum protein electrophoresis, and computed tomography scan of abdomen and chest. 

Below is a helpful summary of some investigations you might want to consider ordering after your initial set of investigations, dep.

Further reading:

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