OVERVIEW

Fever of unknown origin (FUO) describes prolonged undiagnosed fevers. In 1961, Petersdorf introduced a standard definition of FUO; his criteria included fevers of temperature >101°F that lasted ≥3 weeks that remained undiagnosed after 1 week of intensive, in-hospital diagnostic testing. This classical definition of FUO still applies today but with one modification. Because of advanced imaging techniques available on an outpatient basis, the intensive diagnostic workup may be conducted in the outpatient setting. The causes of FUO include a wide variety of infectious and noninfectious disorders capable of eliciting fever. By definition, acute febrile disorders are not included in the definition and, even if diagnosed, should not be termed FUOs. Prolonged, difficult-to-diagnose fevers may be due to infection, malignancy, rheumatic diseases, or a variety of other miscellaneous causes.

CAUSES OF FEVER OF UNKNOWN ORIGIN

The types of disorders that are associated with prolonged fevers have remained relatively constant over time, but the relative proportion of different disease categories has changed over the years. In Petersdorf's initial description, infectious diseases constituted the largest single category of disorders causing FUO. Decades later, in reevaluating the distribution of FUO causes, Petersdorf noted that malignancies had exceeded infectious diseases as the most important singular cause of FUO. Recently, in some series, the distribution has changed again, which reflects the demographics of the population being studied. For example, a recent study of FUOs indicates a majority of patients had unexplained fevers due to noninfectious, inflammatory conditions (ie, predominantly rheumatic disorders).