Work

Fever of unknown origin in adults: diagnostic spectrum, the contribution of FDG-PET/CT and targeted sequencing, and spontaneous resolution

Year: 2026

Type: article

Abstract: The diagnostic paradigm for fever of unknown origin (FUO) has shifted with the advent of functional imaging and genomic technologies. This study evaluated the clinical impact of targeted next-generation sequencing (NGS) and 18-FDG-PET/CT in a single-center FUO cohort, while examining clinical features associated with spontaneous resolution. Among 116 patients analyzed, definitive diagnoses were established in 75.9%. In a selected subgroup with strong clinical suspicion of autoinflammatory disease, targeted NGS identified candidate variants in 88.9%, supporting clinico-genomic diagnostic confirmation in integration with clinical criteria. In a descriptive series of 15 cases evaluated by FDG-PET/CT at attending physicians’ discretion, imaging contributed to direct diagnosis in 33.3%. Notably, 25 of 28 undiagnosed patients experienced spontaneous resolution. Higher hemoglobin, higher albumin, absence of renal dysfunction, and a preserved appetite were identified as exploratory clinical markers associated with spontaneous remission; however, the association for appetite was attenuated in multivariable models adjusted for baseline status. While advanced technologies are valuable diagnostic tools in selected high-pre-test probability settings, a substantial proportion of undiagnosed FUO cases resolve spontaneously. A preserved appetite, alongside systemic baseline stability, may serve as an exploratory clinical surrogate supporting a cautious “watchful waiting” strategy in selected patients.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1899032