Causes of FUO

Q: Which of the following is the most common cause of Fever of Unknown Origin (FUO)? (select one)

A) Occult infections

B) Underlying connective tissue diseases

C) Occult malignancies

Answer: A

FUO has baffled clinicians for over many years. In modern medical literature, the first mention is as far as back to 1930.

Infections, most commonly tuberculosis (TB) is found to be the single most common infection in studies of most FUO series. This is followed by occult abscesses such as pyogenic liver abscesses, osteomyelitis and bacterial endocarditis.

Connective tissue diseases are second to infections. It includes adult-onset Still’s disease, and giant cell arteritis (GCA).

The most common malignancies for FUO lymphoma, especially non-Hodgkin's, leukemia, renal cell carcinoma and hepatocellular carcinoma or tumors metastatic to the liver.

Other causes of FUO are factitious fever, alcoholic hepatitis, thromboembolism, hematoma, hyperthyroidism, hereditary periodic fever syndromes and drugs.

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References:

1. Alt HL, Barker MH. Fever of unknown origin. JAMA 1930; 94:1457.

2. PETERSDORF RG, BEESON PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore) 1961; 40:1.

3. Popovska-Jovicić B, Canović P, Gajović O, Raković I, Mijailović Z. Fever of unknown origin: Most frequent causes in adults patients. Vojnosanit Pregl. 2016 Jan;73(1):21-5. doi: 10.2298/vsp140820128p. PMID: 26964380.