What is the role of lab studies in the workup of fever of unknown origin (FUO)?

Updated: May 17, 2021
  • Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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While a workup of FUO should emphasize clinical clues, the following, if not already performed, are essential laboratory and imaging tests that are of value in eliciting further diagnostic direction:

  • Complete blood cell (CBC) count with white blood cell (WBC) differential
  • Peripheral blood smear
  • Complete metabolic panel (CMP; provides data on electrolytes, glucose, acid-base, renal, liver, protein status)
  • C-reactive protein (CRP)
  • Erythrocyte sedimentation rate (ESR)
  • Urinalysis (used to detect glomerulonephritis, occult hematuria; pyuria is insensitive for detecting urinary tract infection in absence of suggestive symptoms, as asymptomatic bacteriuria is common) [19]
  • Blood cultures, preferably 3 blood draws from separate sites, performed at different times
  • HIV serology
  • Hepatitis A and B serology, and if epidemiologically applicable, Hepatitis E serology
  • Tuberculosis screening tests – Purified protein derivative (PPD, or Mantoux test); interferon gamma release assays (IGRA)
  • Posteroanterior and lateral chest radiography

Beyond the above essentials in early screening, some would add antinuclear antibody titers, rheumatoid factor, and thyroid stimulating hormone (TSH) and thyroxine level in diagnosing certain conditions (lupus, RA, thyroiditis, hyperthyroidism). Their diagnostic accuracy is limited in other autoimmune and collagen vascular diseases.

Further examinations should be guided by historical and physical diagnostic clues, as well as clues from the initial results of the above.

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