Further characterization of clinical and laboratory features in VEXAS syndrome: large‐scale analysis of a multicentre case series of 116 French patients. (1st March 2022)

• Record Type: Journal Article
• Authors: Georgin‐Lavialle, S.; Terrier, B.; Guedon, A.F.; Heiblig, M.; Comont, T.; Lazaro, E.; Lacombe, V.; Terriou, L.; Ardois, S.; Bouaziz, J.‐D.; Mathian, A.; Le Guenno, G.; Aouba, A.; Outh, R.; Meyer, A.; Roux‐Sauvat, M.; Ebbo, M.; Zhao, L.P.; Bigot, A.; Jamilloux, Y.; Guillotin, V.; Flamarion, E.; Henneton, P.; Vial, G.; Jachiet, V.; Rossignol, J.; Vinzio, S.; Weitten, T.; Vinit, J.; Deligny, C.; Humbert, S.; Samson, M.; Magy‐Bertrand, N.; Moulinet, T.; Bourguiba, R.; Hanslik, T.; Bachmeyer, C.; Sebert, M.; Kostine, M.; Bienvenu, B.; Biscay, P.; Liozon, E.; Sailler, L.; Chasset, F.; Audemard‐Verger, A.; Duroyon, E.; Sarrabay, G.; Borlot, F.; Dieval, C.; Cluzeau, T.; Marianetti, P.; Lobbes, H.; Boursier, G.; Gerfaud‐Valentin, M.; Jeannel, J.; Servettaz, A.; Audia, S.; Larue, M.; Henriot, B.; Faucher, B.; Graveleau, J.; de Sainte Marie, B.; Galland, J.; Bouillet, L.; Arnaud, C.; Ades, L.; Carrat, F.; Hirsch, P.; Fenaux, P.; Fain, O.; Sujobert, P.; Kosmider, O.; Mekinian, A.;
• Is Part Of: British journal of dermatology. Volume 186:Number 3(2022)
• Page Start: 564
• Page End: 574
• Publication Date: 2022-03-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.20805
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: 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.