Inflammation of unknown origin versus fever of unknown origin: two of a kind

Eur J Intern Med. 2009 Jul;20(4):415-8. doi: 10.1016/j.ejim.2009.01.002. Epub 2009 Feb 1.


Objectives: A vast literature exists on fever of unknown origin (FUO), characterized by prolonged and perplexing fevers >38.3 degrees C. In contrast, no studies are available to guide the approach to inflammation of unknown origin (IUO), defined as prolonged and perplexing inflammation with temperatures <38.3 degrees C. We aimed to determine the diagnostic yield, the case-mix, and the outcome of patients with IUO, relative to patients with FUO.

Methods: We matched 57 patients with IUO to 57 patients with FUO of the same gender (54% male) and a similar age (median: 67 years).

Results: A diagnosis was established in 35 patients with IUO (61%) and in 33 patients with FUO (58%) (p=.70). The case-mix did not differ significantly (p=.43). Non-infectious inflammatory disorders were the dominant diagnostic category in the IUO group (16 patients), while in the FUO group, similar numbers of malignancies [10], infections [9], and non-infectious inflammatory diseases [9] were diagnosed. (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan contributed comparably to the diagnosis in both groups (in 18 of 50, 36%, patients with IUO and in 13 of 40, 33%, patients with FUO) (p=.83). In both groups, 7 patients (12%) died during an average follow-up of 1 year.

Conclusion: Diagnostic yield, case-mix, contribution of FDG-PET scan and vital outcome were similar in patients with IUO and FUO. These data suggest that the 38.3 degrees C boundary may be arbitrary and that the diagnostic approaches used in FUO can be applied to IUO.

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Databases, Factual
  • Diagnosis-Related Groups / classification*
  • Female
  • Fever of Unknown Origin / diagnostic imaging*
  • Fever of Unknown Origin / etiology
  • Fever of Unknown Origin / mortality
  • Fluorodeoxyglucose F18
  • Follow-Up Studies
  • Humans
  • Infections / complications
  • Infections / diagnostic imaging*
  • Inflammation / diagnostic imaging*
  • Inflammation / etiology
  • Inflammation / mortality
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / diagnostic imaging*
  • Positron-Emission Tomography*
  • Rheumatic Diseases / complications
  • Rheumatic Diseases / diagnostic imaging


  • Fluorodeoxyglucose F18
  • C-Reactive Protein