Fever of unknown origin: a systematic review of the literature for 1995-2004

Background Fever of unknown origin (FUO) identifies a pattern of fever with temperature higher than 38.38C on several occasions over more than 3 weeks, in which the diagnosis remains uncertain after an initial diagnostic work-up. The identification of the cause of FUO is a challenge in clinical practice despite recent advances in diagnostic techniques. There are more than 200 reported causes of FUO and they can be classified in four diagnostic categories: infections, neoplasms, non-infectious inflammatory diseases and miscellaneous. Methods We performed a systematic research of the literature on classical FUO to retrieve the review articles and case series published from 1995 to 2004, including articles from developing countries. The case series were reviewed to identify the tests commonly used both to qualify a fever as FUO and to determine the cause of the FUO, and to design an updated flow chart for the diagnosis of classical FUO. Results and Conclusions No standardized diagnostic strategy could be determined. The diagnostic process should be guided by the potential diagnostic clues (PDCs) emerging from the history, physical examination and baseline tests. A standardized flow chart can be applied only in absence of PDCs or when the PDCs are contradictory. Nuclear medicine techniques are a valuable aid in the search for the origin of FUO due to bacterial infections or in the absence of PDCs.