Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3°C on several occasions during at least 3 weeks with uncertain diagnosis after a number of obligatory tests. FUO remains a clinical challenge as no diagnosis is reached in up to 50% of cases. In general, infection accounts for one-fourth of cases of FUO, followed by neoplasm and noninfectious inflammatory diseases. FDG-PET is a sensitive diagnostic technique for the evaluation of FUO. Especially integrated imaging combining PET and CT facilitates anatomical localization of focally increased FDG uptake, thereby guiding further diagnostic tests to achieve a final diagnosis. FDG-PET/CT appears to be a more sensitive diagnostic tool in FUO than stand-alone FDG-PET, because of the precise anatomical localization of small lesions and better differentiation between physiological and pathologic metabolic foci. With FDG-PET/CT becoming widely available, FDG-PET/CT should be a routine procedure in the workup of FUO.
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