A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol.

We conducted a prospective study to update our knowledge of fever of unknown origin (FUO) and to explore the utility of a structured diagnostic protocol. From December 2003 to July 2005, 73 patients with FUO were recruited from 1 university hospital (n = 40) and 5 community hospitals (n = 33) in the same region in The Netherlands. FUO was defined as a febrile illness of >3 weeks' duration, a temperature of >38.3 degrees C on several occasions, without a diagnosis after standardized history-taking, physical examination, and certain obligatory investigations. Immunocompromised patients were excluded. A structured diagnostic protocol was used. Patients from the university hospital were characterized by more secondary referrals and a higher percentage of periodic fever than those referred to community hospitals. Infection was the cause in 16%, a neoplasm in 7%, noninfectious inflammatory diseases in 22%, miscellaneous causes in 4%, and in 51%, the cause of fever was not found (no differences between university and community hospitals). There were no differences regarding the number and type of investigations between university and community hospitals. Significant predictors for reaching a diagnosis included continuous fever; fever present for <180 days; elevated erythrocyte sedimentation rate, C-reactive protein, or lactate dehydrogenase; leukopenia; thrombocytosis; abnormal chest computed tomography (CT); and abnormal F-fluorodeoxyglucose positron emission tomography (FDG-PET). For future FUO studies, inclusion of outpatients and the use of a set of obligated investigations instead of a time-related criterion are recommended. Except for tests from the obligatory part of our protocol and cryoglobulins in an early stage, followed by FDG-PET, and in a later stage by abdominal and chest CT, temporal artery biopsy in patients aged 55 years or older, and possibly bone marrow biopsy, other tests should not be used as screening investigations.

Clinical value of FDG PET in patients with fever of unknown origin and patients suspected of focal infection or inflammation.

Fever of unknown origin (FUO) and suspected focal infection or inflammation are challenging medical problems. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with FUO and patients with suspected focal infection or inflammation. All FDG PET scans ordered because of FUO or suspected focal infection or inflammation in the last 4 years were reviewed. These results were compared with the final diagnosis. Thirty-five FDG PET scans were performed in 35 patients with FUO. A final diagnosis was established in 19 patients (54%). Of the total number of scans, 37% were clinically helpful. The positive predictive value of FDG PET in these patients was 87% and the negative predictive value was 95%. Fifty-five FDG PET scans were performed in 48 patients with suspected focal infection or inflammation. A final diagnosis was established in 38 patients (82%). Of the total number of scans, 65% were clinically helpful. The positive predictive value of FDG PET in these 55 episodes of suspected infection or inflammation was 95% and the negative predictive value was 100%. It is concluded that FDG PET appears to be a valuable imaging technique in the evaluation of FUO and suspected focal infection or inflammation. Furthermore, FDG PET could become a useful tool for evaluating the effect of treatment of infectious and inflammatory processes that cannot reliably be visualised by conventional techniques. However, to assess the additional diagnostic value of this technique, prospective studies of FDG PET as part of a structured diagnostic protocol are warranted.