Diagnostic yield and impact on patient management from [18F]FDG-PET/CT in FUO/IUO in the adult population.

Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions due to their diverse etiologies and non-specific presentations. Despite advances in diagnostic techniques, a significant proportion of cases remain unexplained, often leading to delays in treatment and increased healthcare burden. In recent years, [¹⁸F]FDG-PET/CT has emerged as a powerful diagnostic tool offering whole-body metabolic imaging, particularly valuable in the early stages of disease when structural changes may be absent. In this review a literature search was conducted in PubMed and Web of Science for original studies on the use of FDG-PET/CT in adults with FUO/IUO published between January 2005 and June 2025. The authors evaluated the diagnostic yield and clinical impact of [¹⁸F]FDG-PET/CT in adults with FUO/IUO based on 56 studies comprising over 7,400 patients. The [¹⁸F]FDG-PET/CT was helpful in up to 90% of cases when both true-positive and true-negative results were considered. Furthermore, [¹⁸F]FDG-PET/CT led to changes in patient management in a substantial proportion of cases, particularly when used early in the diagnostic algorithm. It demonstrates robust diagnostic performance, guiding therapeutic decisions, and guide subsequent interventions hereby avoiding futile examinations. Despite its growing recognition, standardization in study design and outcome reporting is needed to further consolidate its role in clinical guidelines.