What Is a Fever of Unknown Cause?
Fever is part of the human body’s sickness response, mediated by inflammatory cytokines and other pyrogens. It is part of the innate immune system. When it continues unabated without a treatable cause, however, it is no longer a warning signal but an actual disease in itself.
Fever of Unknown Origin (FUO)
Fever of unknown origin (FUO) refers to a prolonged febrile illness whose cause is unknown even after an extensive workup of evaluation and testing. The key to this designation is that it be prolonged, for most fevers spontaneously resolve quickly before any cause is identified.
The criteria for FUO was derived in 1961 and remains the standard criteria list:
- Fever > than 38.3ºC (100.9ºF) at numerous times.
- Duration of fever ≥ 3 weeks.
- Uncertain diagnosis even after 1 week of hospitalized diagnostics.
The majority of FUO cases fall into one of 3 categories:
- Infection: Most commonly tuberculosis, occult abscesses, osteomyelitis, and bacterial endocarditis.
- Malignancy: Most commonly lymphoma, leukemia, and kidney or liver carcinoma.
- Non-infectious inflammatory/autoimmune diseases: E.g., rheumatoid arthritis and other rheumatic diseases, vasculitis, etc.
Age and FUO
- Children, in 1/3 of cases, have an undefined self-limited viral infection
- Older patients have multisystem diseases, such as the rheumatic illnesses, infections, or malignancies
Gender and FUO
- Men can have FUO from prostatitis.
- Women can have FUO from an occult abscess in the reproductive tract, i.e., ovary/fallopian tube.
Initial pursuit of a cause is based on an in-depth history and thorough physical exam with a focus on the most common causes. The list of uncommon causes is extensive, making them expensive and labor intensive to pursue along with the most common causes. Once the commonest etiologies are dismissed, however, the exploration of the less common or exotic causes is justified.