Albrecht Betrains1, Vincent Jachiet2, Yannick Dieudonne3, Jérémie Dion4, Estibaliz Lazaro5, Claire De Moreuil6, Samuel Ardois7, Sylvie Grosleron8, Jean-benoit Arlet9, Cécile-Audrey Durel10, Laure Delaval11, Sylvain Audia12, Cécile Golden13, Barbara Nicolas13, Vincent Langlois14, Antoinette Perlat7, Frédéric Vandergheynst15, Thomas Moulinet16, Maxime Samson17, Daniel Blockmans1, Olivier Kosmider18, Sophie Georgin-Lavialle19, Arsène Mekinian20 and Benjamin Terrier21, 1Department of General Internal Medicine, University Hospitals Leuven, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium, 2Service de médecine interne et Inflammation-Immunopathology-Biotherapy Department (DMU i3), Sorbonne Université, AP-HP, Hôpital Saint Antoine, Paris, France, 3Department of Clinical Immunology and Internal Medicine, National Reference Centre for Systemic Autoimmune Diseases (CNR RESO), Strasbourg University Hospital, Strasbourg, France, 4Internal Medicine Department, Toulouse University Hospital, Toulouse, France, 5Bordeaux Hospital University, Pessac, France, 6CHU de Brest, Brest, France, 7CHU Rennes, Rennes, France, 8CH Agen-Nérac, Agen, France, 9Hôpital Georges-Pompidou APHP, Paris, France, 10CHU Lyon, Lyon, France, 11Hôpital Bichat APHP, Paris, France, 12Department of Internal Medicine and Clinical Immunology, Dijon-Bourgogne University Hospital, Dijon, France, 13CHU Dijon, Dijon, France, 14Service de Médecine Interne, Hôpital Jacques Monod, Le Havre, France, 15Université Libre de Bruxelles, Bruxelles, Belgium, 16Department of Internal Medicine, Centre hospitalier universitaire de Nancy, Nancy, France, 17Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France, 18Hôpital Cochin APHP, Paris, France, 19AP-HP, Tenon hospital, Paris, France, 20Department of Internal Medicine, Hôpital Saint-Antoine, AP-HP, Paris, France, 21Department of Internal Medicine, Hôpital Cochin, AP-HP, Paris, France
Background/Purpose: VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is anautoinflammatory syndrome caused by somatic mosaicism in the UBA1 gene. [18F]-FDG-PET/CT is often performed during the diagnostic workup of patients with VEXAS syndrome, but the abnormalities that may be detected with this imaging examination are not well described.
Methods: We performed a retrospective multicenter study in France and Belgium. Patients with confirmed VEXAS syndrome, defined by the presence of an autoinflammatory syndrome and detection of a pathogenic UBA1mutation, who underwent at least one [18F]-FDG-PET/CT were considered eligible. Data on the clinical presentation, laboratory results, genetic analyses, and [18F]-FDG-PET/CT imaging results were collected using a standardized form. In an exploratory analysis, the observed abnormalities were compared according to the clinical disease activity status and the VEXAS syndrome clusters as previously defined by Georgin-Lavialle et al. (Br J Dermatol 2022;186:564–74).
Results: A total of 106 [18F]-FDG-PET/CT scans were performed in 57 VEXAS patients. All patients were male and had a median age of 71 (IQR, 66-76) years at symptom onset and 75 (IQR 69-79) years at diagnosis. The most frequent clinical manifestations included cutaneous lesions (86%), fever (79%), arthralgia or arthritis (68%), pulmonary manifestations (46%), ear or nose chondritis (37%), and venous thrombo-embolism (33%). Only 29% of scans were performed before treatment for VEXAS, as the majority of patients received corticosteroids (66%) and/or other immunosuppressive treatments (40%) at the time of imaging. Patients most commonly had increased FDG uptake in the bone marrow (82%), lymph nodes (54%), lungs (37%), and spleen (30%). Less frequently, patients had hypermetabolism in the pleura (18%), nose or ear cartilage (9%), joints (5%), and pericardium (2%). Increased arterial FDG uptake was identified in 12% of patients, including aortic involvement (5%) and asymmetric artery involvement (9%). Significantly more abnormalities were detected by [18F]-FDG-PET/CT in VEXAS patients with active disease (median 3 [IQR 2-4]) compared to those in clinical remission (median 1 [IQR 1-2]) (P < 0.001). However, abnormal FDG uptake often remained present in patients who were considered to be in clinical remission, particularly in the bone marrow (70%), lymph nodes (35%), lungs (20%), and arteries (10%). When comparing those with active disease according to the VEXAS syndrome clusters, we observed a trend towards more abnormalities in the inflammatory cluster (n=17; median 3 [IQR 2-5]) and the hematological/myelodysplasia cluster (n=24; median 3 [IQR 2-4]), compared to the mild-to-moderate cluster (n=7; median 1 [IQR 1-4]) (P=0.09).
Conclusion: We report on [18F]-FDG-PET/CT imaging results among patients with VEXAS syndrome. Although zones of abnormal FDG uptake occurred frequently in VEXAS syndrome, the abnormalities were mostly non-specific. More abnormalities were detected among those with active disease, but bone marrow hypermetabolism in particular often persisted in those considered to be in remission, suggesting subclinical disease activity.
A. Betrains: None; V. Jachiet: None; Y. Dieudonne: None; J. Dion: None; E. Lazaro: None; C. De Moreuil: None; S. Ardois: None; S. Grosleron: None; J. Arlet: None; C. Durel: None; L. Delaval: None; S. Audia: None; C. Golden: None; B. Nicolas: None; V. Langlois: None; A. Perlat: None; F. Vandergheynst: None; T. Moulinet: None; M. Samson: ARGENX, 2, Boehringer-Ingelheim, 2, CHUGAI, 2, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2, NOVARTIS, 2, 5; D. Blockmans: None; O. Kosmider: None; S. Georgin-Lavialle: None; A. Mekinian: None; B. Terrier: AstraZeneca, 5, CSL Vifor, 2, GlaxoSmithKlein(GSK), 2.
