Further characterization of clinical and laboratory features in VEXAS syndrome: large‐scale analysis of a multicentre case series of 116 French patients*
Sophie Georgin‐Lavialle, Benjamin Terrier, Alexis F. Guédon, Maël Heiblig, T. Comont, Estibaliz Lazaro, Valentin Lacombe, Louis Terriou, Samuel Ardois, Jean‐David Bouaziz, Alexis Mathian, G. Le Guenno, Achille Aouba, R. Outh, A. Meyer, Marielle Roux‐Sauvat, Mikaël Ebbo, Lin‐Pierre Zhao, Adrien Bigot, Yvan Jamilloux, Vivien Guillotin, Edouard Flamarion, Pierrick Henneton, Guillaume Vial, Vincent Jachiet, Julien Rossignol, S. Vinzio, Thierry Weitten, J. Vinit, C. Deligny, S. Humbert, Maxime Samson, N. Magy‐Bertrand, T. Moulinet, R. Bourguiba, Thomas Hanslik, Claude Bachmeyer, Marie Sébert, Marie Kostine, Boris Bienvenu, P. Biscay, É. Liozon, L. Sailler, François Chasset, Alexandra Audemard‐Verger, Eugénie Duroyon, Guillaume Sarrabay, Felippe Borlot, C. Diéval, Thomas Cluzeau, Paola Marianetti, Hervé Lobbes, Guilaine Boursier, Mathieu Gerfaud‐Valentin, Juliette Jeannel, Amélie Servettaz, Sylvain Audia, M. Larue, Basile Henriot, B. Faucher, J. Graveleau, B. De Sainte Marie, Joris Galland, Laurence Bouillet, Catherine Arnaud, Lionel Adès, Fabrice Carrat, Pierre Hirsch, Pierre Fenaux, O. Fain, Pierre Sujobert, Olivier Kosmider, A. Mékinian, French VEXAS group, GFEV, GFM, CEREMAIA, MINHEMON
Abstract
BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.