Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study

Abstract

ObjectiveFever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO.DesignA nationwide retrospective study.Setting17 hospitals affiliated with the Japanese Society of Hospital General Medicine.ParticipantsThis study included patients ≥18 years diagnosed with ‘classical fever of unknown origin’ (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011.ResultsA total of 121 patients with FUO were enrolled. The median age was 59 years (range 19–94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients.ConclusionsWith the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

Fever of unknown origin

“…[15][16][17][18] In several recent studies no cause could be found in a large proportion of patients (Table 1). 3,5,[19][20][21] Lower incidences of specifi c infections, such as tuberculosis and brucellosis, and differences in availability of modern imaging techniques, such as CT, MRI and FDG-PET/CT, may among others cause these differences.…”

“…Measurement of cryoglobulins and fundoscopic examination should be performed in an early stage, because of the frequent absence of typical symptoms in diseases that can be found by these investigations and their relatively low cost. 4 When these tests do not lead to the fi nal diagnosis, one should proceed to whole body imaging, 6 preferably with 18 FDG-PET/CT. 23 …”

A Cross-sectional Study of Undiagnosed Fever in a Rural Population at a Tertiary Care Hospital of West Bengal

“…Use of 18 FDG PET and PET CT has been documented in several studies to differentiate various etiologies without resorting to invasive techniques as employed by our centres when the first line investigations fail to give a diagnosis. [19,20] PET CT had contributed to 25%-69% of final diagnosis of FUO especially focal abdominal/ thoracic infections, osteomyelitis, large vessel vasculitis, sarcoidosis and malignancies. [20] Absence of PET CT, electron microscopy and viral marker probes can be considered a limitation of our study.…”

Polymyalgia rheumatica update, 2015

“…Paraneoplasiát, infekciót mindig ki kell zárni, előfordul, hogy belgyógyászati vagy neurológiai betegség jelenik meg hasonló formában. Ismeretlen eredetű láz (FUO) egy részében is PMR igazolható [34]. Sok esetben társul GCA, ilyenkor annak ischaemiás differenciáldiagnosztikáját is szem előtt kell tartani [4].…”