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Background: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up., Methods: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models., Results: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I 2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I 2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I 2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I 2 0 %)., Conclusion: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024. Published by Elsevier B.V.)

Background: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18 F-fluorodesoxyglucose positron emission tomography ( 18 F-FDG-PET)., Methods: Prospective study to test diagnostic utility of 18 F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18 F-FDG-PET/CT. Patients with FUO or IUO received 18 F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18 F-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 18 F-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 IgG 4 -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), 18 F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18 F-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: 18 F-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 18 F-FDG-PET/CT., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)