Spectrum and significance of 18F-FDG-PET/CT abnormalities in VEXAS syndrome

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently identified adult-onset autoinflammatory disorder caused by somatic mutations in UBA1. It is characterized by heterogeneous inflammatory and haematological manifestations, making diagnosis challenging. 18F-FDG-PET/CT imaging, which identifies metabolic activity associated with inflammation and malignancy, is often performed during the diagnostic work-up. However, its utility in VEXAS syndrome remains unclear.

We conducted a multicentre retrospective observational study of patients with genetically-confirmed VEXAS syndrome who underwent 18F-FDG-PET/CT imaging. Clinical, laboratory and imaging data were collected, and 18F-FDG-PET/CT findings were analysed according to disease activity, myelodysplastic syndrome status and mortality. Qualitative 18F-FDG-PET/CT interpretations were based on local nuclear medicine reports.

A total of 125 18F-FDG-PET/CT scans were analysed in 66 patients. Bone marrow (83%) and lymph nodes (53%) were the most frequent sites of abnormal FDG uptake, with combinations of bone marrow, lungs, lymph nodes and spleen being the most common patterns. Pulmonary (38%) and vascular involvement (11%) were also observed. The number of organs with abnormal FDG uptake was significantly higher in patients with active disease compared with remission (median 2 vs 1 abnormal sites, P < 0.001). However, 90% of scans performed during presumed clinical remission showed persistent abnormalities, especially in the bone marrow (57%).

18F-FDG-PET/CT imaging reveals frequent but non-specific abnormalities in VEXAS syndrome, with persistent bone marrow hypermetabolism suggesting subclinical disease activity. While 18F-FDG-PET/CT may have limited diagnostic utility, it holds potential for disease monitoring.