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Purpose: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [F]FDG-PET/CT in FUO and IUO based on current evidence.
Methods: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with "patients with FUO/IUO" as population, "[F]FDG-PET/CT" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness.
Results: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations.
Conclusion: FUO and IUO remains a clinical challenge and [F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50-60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.
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http://dx.doi.org/10.1007/s00259-024-06732-8 | DOI Listing |
J Clin Med
August 2025
Section of Nuclear Medicine, Department of Radiological Sciences and Hematology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) remain complex diagnostic challenges due to their heterogeneous presentations and broad differential diagnoses. FUO was first described by Petersdorf and Beeson in 1961 and later redefined by Durack and Street, while IUO was introduced more recently by Vanderschueren et al. in 2009.
View Article and Find Full Text PDFEur J Intern Med
August 2025
First Department of Internal Medicine and Laboratory of Molecular Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address:
Fever and inflammation of unknown origin (FUO/IUO) remain challenging clinical syndromes today, in which the internists play a central role in orchestrating the diagnostic process and interpreting key findings. FUO and IUO share similar diagnostic evaluations and overlapping etiologies, although the relative frequencies of their causes may differ. The established five-category classification includes infectious diseases (INF), non-infectious inflammatory diseases (NIID), malignancies (MAL), miscellaneous (MISC) and undiagnosed illnesses (UI).
View Article and Find Full Text PDFDiagnosis (Berl)
August 2025
Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Shimotsuga, Tochigi, Japan.
Introduction: The differential diagnosis of fever of unknown origin (FUO) resembles that of inflammation of unknown origin (IUO), but the concept and differential diagnosis of FUO with no inflammatory laboratory evidence (FUO-NIL) are unknown. The aim was to propose the concept of FUO-NIL and explore its differential diagnosis.
Content: The present study is a scoping review of FUO-NIL, defined as FUO with normal serum C-reactive protein (CRP).
Open Access Rheumatol
February 2025
University of Health Sciences, Prof. Dr. Cemil Taşçıoğlu City Hospital, Department of Internal Medicine, Division of Endocrinology, İstanbul, Turkey.
Introduction: Patients with fever of unknown origin (FUO) and/or inflammation of unknown origin (IUO) challenge clinicians in daily rheumatology practice. Positron emission tomography-computed tomography (PET/CT) is being used in the diagnostic workup of patients with FUO and/or IUO. This study aims to evaluate the clinical utility and diagnostic performance of PET/CT in the rheumatology outpatient clinic among FUO and IUO patients.
View Article and Find Full Text PDFSci Rep
November 2024
Department of General Internal Medicine, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Despite advancements in medical technology, the challenges of diagnosing fever of unknown origin (FUO) and inflammation of unknown origin (IUO) persist. Positron emission tomography/computed tomography (PET/CT) has been used to assess these conditions; however, it is unclear which patients most benefit from this approach. This study aimed to assess the clinical value and optimal use of fluorine-18-labelled-fluorodeoxyglucose (F-FDG)-PET/CT in patients with FUO/IUO.
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