Fever of Unknown Origin

The original criteria for fever of unknown origin (FUO) as set forth in 1961 by Petersdorf and Beeson were fever higher than 38.3°C on several occasions of at least 3 weeks’ duration and uncertain diagnosis after 1 week of study in the hospital (1). This definition was later revised, and the criterion of 1 week of hospitalization has been replaced by 3 days of hospitalization or three outpatient visits (2,3). In addition to the previously described classic FUO, additional categories have been added: nosocomial, neutropenic, and HIV-associated FUO (3,4). Nosocomial FUO refers to the hospitalized patient with a temperature of ≥38.3°C (≥101°F) on several occasions, who is receiving acute care, and in whom infection was not manifest or incubating on admission. The diagnosis of nosocomial FUO is made after 3 days of illness under investigation, including at least 2 days’ incubation of cultures. Examples of diseases causing nosocomial FUO are septic thrombophlebitis, sinusitis, Clostridium difficile colitis, and drug fever. Neutropenic FUO includes patients with fever of ≥38.3°C (≥101°F) on several occasions, a neutrophil count either <500 cells/mL or expected to reach that level in 1 to 2 days, in whom initial cultures are negative and the diagnosis remains unknown after 3 days of investigation. Frequent causes of neutropenic FUO are perianal infection, aspergillosis, and candidemia. The HIV-associated FUO refers to HIV-positive patients with fever of ≥38.3°C (≥101°F) on several occasions for 4 weeks as an outpatient or 3 days of illness as an inpatient under investigation, including at least 2 days for cultures to incubate. Mycobacterium avium intracellulare (MAI) infection, tuberculosis, non-Hodgkin’s lymphoma, and drug fever are common causes of HIV-associated FUO.