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The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study
  1. Verena Schönau1,
  2. Kristin Vogel1,
  3. Matthias Englbrecht1,
  4. Jochen Wacker1,
  5. Daniela Schmidt2,
  6. Bernhard Manger1,
  7. Torsten Kuwert2,
  8. Georg Schett1
  1. 1 Department of Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum, Erlangen, Germany
  2. 2 Clinic of Nuclear Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum, Erlangen, Germany
  1. Correspondence to Professor Georg Schett, Department of Internal Medicine 3, Rheumatology and Immunology, University Clinic of Erlangen-Nuremberg, Erlangen; Ulmenweg 18, Erlangen 91054, Germany; georg.schett{at}


Background Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET).

Methods Prospective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT.

Results 240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still’s disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001).

Conclusion 18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.

  • fever of unknown origin
  • inflammation of unknown origin
  • positron emission tomography
  • computed tomography

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  • Handling editor Tore K Kvien

  • Contributors VS, KV, JW and BM collected the data. DS and TK read the scans. VS, KV, BM and GS analysed the data. ME performed statistical analyses. VS and GS wrote the manuscript.

  • Competing interests None declared.

  • Ethics approval University of Erlangen-Nuremberg.

  • Provenance and peer review Not commissioned; externally peer reviewed.