Fever and Fever of Unknown Origin: Review, Recent Advances, and Lingering Dogma

Fever has preoccupied physicians since the earliest days of clinical medicine. It has been the subject of scrutiny in recent decades. Historical convention has mostly determined that 37.0°C (98.6°F) should be regarded as normal body temperature, and more modern evidence suggests that fever is a complex physiological response involving the innate immune system and should not be characterized merely as a temperature above this threshold. Fever of unknown origin (FUO) was first defined in 1961 by Petersdorf and Beeson and continues to be a clinical challenge for physicians. Although clinicians may have some understanding of the history of clinical thermometry, how average body temperatures were established, thermoregulation, and pathophysiology of fever, new concepts are emerging. While FUO subgroups and etiologic classifications have remained unchanged since 1991 revisions, the spectrum of diseases, clinical approach to diagnosis, and management are changing. This review considers how newer data should influence both definitions and lingering dogmatic principles. Despite recent advances and newer imaging techniques such as 18-fluorodeoxyglucose–positron emission tomography, clinical judgment remains an essential component of care.