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Key Clinical Questions

  • image What are the major categories of fever of unknown origin (FUO)?

  • image What basic tests should be done in evaluating patients with FUO?

  • image When is more specific laboratory testing or diagnostic imaging indicated?

  • image Which patients should receive empiric therapy?

  • image What is the prognosis of FUO?

The classic definition of fever of unknown origin (FUO) by ­Petersdorf and Beeson in 1961 was a fever greater than 38.3°C (101°F) on several occasions, persisting without diagnosis for at least 3 weeks, despite 1 week of investigation in the hospital. In the 50 years since, medical practice has changed substantially, and much of the diagnostic evaluation for FUO can be accomplished on an outpatient basis. One proposed revision of the definition of classic FUO is a febrile illness that has not been diagnosed after at least three outpatient visits or 3 days of hospitalization (Table 206-1). In practice, while an exact definition is difficult, FUO can be thought of as a persistent febrile illness that has eluded diagnosis despite a thorough history, physical examination, and routine diagnostic testing. Additionally, several specific categories of FUO have been proposed, including nosocomial FUO, HIV-related FUO, and FUO in the returning traveler. Over 200 different causes of FUO have been reported, but all etiologies fall into four broad groups: infectious, neoplastic, rheumatologic, and miscellaneous. The incidence of each etiology will vary with different patient populations and geographic locations.

TABLE 206-1Contemporary Definitions of Fever of Unknown Origin (FUO)

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