Fever of Unknown Origin (FUO)

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Presentation :

• Defined as: Fever ≥38°C for ≥3 weeks undiagnosed after 2 office visits

Pathophysiology :

Diagnostic Testing:

• Fever of unknown origin is categorized as: classic, health care–associated, neutropenic, and HIV-associated.
• A careful history and physical examination should be performed, including past procedures or surgeries, presence of foreign bodies or implants, immunosuppression, travel, animal or other exposures, dietary habits, and medications.
• Initial testing for classic FUO should address any focal signs and symptoms and additionally includes:
  • Common panels: Complete blood count with differential, electrolyte levels, kidney and liver chemistries (hepatitis serology if results are abnormal), lactate dehydrogenase level
  • Autoimmune panels: Erythrocyte sedimentation rate, C-reactive protein, antinuclear antibodies, rheumatoid factor
  • Infectious workup: UA and urine culture, HIV testing, CMV PCR, blood cultures (three sets, each set obtained at least several hours apart), tuberculosis testing, and chest radiography (or chest CT).
    • Q-fever serology should be considered if risk factors exist.
• If initial tests do not suggest a cause:
  • Abdominal or pelvic CT may be considered to evaluate for intra-abdominal abscess or lymphoproliferative disorders.
    • Liver, lymph node, and temporal artery biopsies have a diagnostic yield of about 35%, particularly when performed when infection is unlikely.
    • Posterior cervical, supraclavicular, infraclavicular, epitrochlear, hilar, mediastinal, and mesenteric lymph node biopsies are more likely to provide a diagnosis than that of other lymph nodes.
    • Bone marrow biopsy can be helpful when leukopenia or thrombocytopenia is present.
    • The utility of nuclear imaging (PET scan, leukocyte scan) is limited.
• A definitive diagnosis is lacking in up to half of patients after extensive evaluation.
  • FUO lasting more than 1 year is unlikely to be caused by infection or malignancy.
  • Undiagnosed FUO is generally associated with a benign long-term course, particularly when fever is not associated with weight loss or other signs of underlying serious disease.

Treatment :

Prognosis:

References:

• MKSAP