Abstract
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. Despite thorough investigations, a significant proportion of patients remain without a clear diagnosis, often resulting in prolonged hospital stays and increased healthcare costs. In recent years, [(18)F]FDG PET/CT has emerged as a valuable tool in the diagnostic workup of FUO and IUO, offering both metabolic and anatomical insights in a single scan. This review evaluates the diagnostic utility of [(18)F]FDG PET/CT, based on an analysis of 55 studies encompassing 6681 patients. The scan was found to be clinically helpful in 59% of cases, with diagnostic contributions from both true-positive and true-negative findings. Negative scans were frequently associated with spontaneous symptom resolution and fewer unnecessary interventions. However, differences in study design and definitions of diagnostic value make it difficult to compare results across studies. Overall, [(18)F]FDG PET/CT has proven to be a useful tool in the evaluation of FUO and IUO, and future research should focus on standardizing how its clinical benefit is measured and directly comparing its effectiveness with conventional imaging in well-designed prospective studies.