Background: VEXAS syndrome is a monogenic somatic autoinflammatory syndrome associated with UBA1 mutations that was firstly described in 2020 by Beck et al. The clinical picture is heterogeneous and the disease seems to be not so rare among men >50 years old.

Objectives: To describe main presentation at diagnosis of a large multicentric cohort.

Methods: All patients with a genetically proven VEXAS syndrome with a pathogenic UBA1 mutation were collected in a redcap e-CRF in France between December 2020 and December 2024. Ethical agreements were obtained from Cochin ethic committee. Statistics were performed thru easymedstat® software.

Results: Among 318 patients, 308 (96,9%) were males with median age at diagnosis of 74.3 years old [min 51 -max 96,3]. The main clinical features were skin lesions (77%), mainly sweet syndrome and erythematous papules but also vasculitis lesions 21.2%, livedo 13% and urticaria 9%; followed by alteration of general status with weight loss (56,7%), fever (57,3%) lung involvement (49.6%), mostly pulmonary infiltrates; thrombosis (47%) was frequent, almost always veinous. Ocular inflammatory involvement was present in 46.2%, mainly conjonctivitis (n=18), orbital mass (n=16) uveitis (n=15) episcleritis (n=14) and scleritis (n=10). The other main features were respectively relapsing chondritis in 35,5%; arthralgia (36.8%), adenopathies in 23.9%; nervous system (23.6%) with mainly aseptic meningitidis (60%); gastrointestinal involvement (18.6%), splenomegaly in 14.6%, followed by hepatomegaly in 8.5%, kidney involvement in 8%, heart involvement in 5,3%. AA amyloidosis was present in only 2 cases. Median hemoglobin rate was 9,9 g/dL [6-10,5] and median globular volume (MGV) 101,2 [82-122]; median platelets were 189000 [5-196000]. Median CRP levels were at 60 [0,5-335] mg/l; median ferritin was 860 [1-977]. UBA1 sequencing was mostly performed by NGS panel (53.4%) and sanger (45,9%) and showed as most frequent mutations: p.M41T (40,7%), p.M41V (27,1%), p.M41L (20,3%), and other (11%). The mean VAF was 50.8%. Other myeloid somatic mutations were detected by panel in 70 cases (34,8%) mostly DNMTA3 and TET2 . Hematological disease was present myelodysplastic syndrome (MD; 40%), mostly MDS with single lineage dysplasia (14.2%) or multiple (13.3%); monoclonal gammapathy of unknown significance was detected in (n=43, 21.3%). Karyotype had been performed in 175 cases and normal in 64.6%. When researched (patients underwent bone marrow aspiration in 268 cases (95.4%), vacuoles were present in 70,5%.

Conclusion: To date this is the largest cohort of VEXAS syndrome patients showing the heterogeneity of clinical presentation with mainly biological inflammation and systemic features such as alteration of general status and predominance of various cutaneous features with elevated MGV. Vacuoles are not always present. Recurrent chondritis and myelodysplastic syndrome are not mandatory.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Sophie Georgin-Lavialle SOBI and novartis, Benjamin Terrier: None declared, Vincent Jachiet: None declared, Rim Bourguiba: None declared, Kosmider Olivier: None declared, Arsene Mekinian: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.