Fever of Unknown Cause: Diagnosis & Tests Menu

What Are Diagnosis Tests?

The list of all of the causes of fever of unknown origin (FUO) is exhaustive. True FUOs that meet the criteria of 1) repeated episodes of fever > 38.3ºC (100.9ºF) and 2) a duration of fever ≥ 3 weeks usually call for hospitalization, which after one week meets the third criterium of 3) no firm diagnosis even after 1 week of hospitalized diagnostics.

The crucial first step involves a through history and physical exam to garner clues from subtle findings such as a dental history to elicit any tooth or gum sensitivities that may point to a dental abscess; changes in cognition that suggest meningitis; sexual history to consider sexually transmitted infections (STIs); travel history to identify illness endemic elsewhere but rare in the U.S., e.g., malaria; immunosuppression and drug history; animal exposure or occupational toxin exposure; urinary habits, especially at night, that suggest prostatitis or urinary tract infections.

Diagnostic Tests

  • Blood test for the acute phase reactants, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), to identify and quantify inflammation.
  • Normal levels speaks against inflammatory processes.
  • Serum lactate dehydrogenase (LDH) that identifies tissue and cellular damage.
  • Creatine phosphokinase (CPK) as a biomarker to identify muscle damage, heart tissue necrosis, and neuromuscular disease.
  • TB skin test.
  • Blood tests for HIV, rheumatoid factor (RF), and antinuclear antibodies (ANA) to identify illness associated with vasculitis, immunosuppression, or autoimmunity.
  • Heterophile antibody test for children and young adults to identify Epstein-Barr infection/mononucleosis.
  • Serum protein electrophoresis to separate subsets of proteins that predict inflammation, malignancy, tissue injuries, or cell death. 
  • CT of the chest and abdomen. 
  • Blood cultures.
  • Serologic tests for syphilis, cytomegalovirus (CMV) and Lyme disease.
  • Lumbar puncture (LP, or “spinal tap”) for CNS etiologies.

Most of the patients in whom no definitive diagnosis is ever made do well. Rarely, FUO can persist for months or even years without a diagnosis, treated empirically with steroids or other anti-inflammatories.



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This information is provided by Vascular Health Clinics and is not intended to replace the medical advice of your doctor or healthcare provider. Please consult your healthcare provider for advice about a specific medical condition.

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