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Diagnostic workup for fever of unknown origin: a multicenter collaborative retrospective study
  1. Toshio Naito1,
  2. Masafumi Mizooka2,
  3. Fujiko Mitsumoto3,
  4. Kenji Kanazawa4,
  5. Keito Torikai5,
  6. Shiro Ohno6,
  7. Hiroyuki Morita7,
  8. Akira Ukimura8,
  9. Nobuhiko Mishima9,
  10. Fumio Otsuka10,
  11. Yoshio Ohyama11,
  12. Noriko Nara12,
  13. Kazunari Murakami13,
  14. Kouichi Mashiba14,
  15. Kenichiro Akazawa15,
  16. Koji Yamamoto16,
  17. Shoichi Senda17,
  18. Masashi Yamanouchi1,
  19. Susumu Tazuma2,
  20. Jun Hayashi3
  1. 1Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
  2. 2Department of General Internal Medicine, Hiroshima University Hospital, Hiroshima, Japan
  3. 3Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
  4. 4Department of General Internal Medicine, Kobe University Hospital, Kobe, Japan
  5. 5Department of General Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan
  6. 6Department of General Medicine, Nara Medical University, Nara, Japan
  7. 7Department of General Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
  8. 8Department of General Medicine, Osaka Medical College, Osaka, Japan
  9. 9Department of General Internal Medicine, Kainan Hospital, Aichi Prefectural Welfare Federation of Agricultural Cooperatives, Aichi, Japan
  10. 10Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  11. 11Department of General Medicine, Gunma University Graduate School of Medicine, Gunma, Japan
  12. 12Department of General Medicine, Yokohama City University Medical Center, Yokohama, Japan
  13. 13Department of General Medicine, Faculty of Medicine, Oita University, Oita, Japan
  14. 14Department of General Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
  15. 15Department of Internal Medicine, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan
  16. 16Department of General Medicine, Sumitomo Hospital, Osaka, Japan
  17. 17Department of Integrated Medicine, Kagawa University School of Medicine, Kagawa, Japan
  1. Correspondence to Dr Toshio Naito; naito{at}


Objective Fever 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.

Design A nationwide retrospective study.

Setting 17 hospitals affiliated with the Japanese Society of Hospital General Medicine.

Participants This 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.

Results A 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.

Conclusions With 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.


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