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
Sorbonne Université, AP-HP, Hôpital Tenon, Service de Médecine Interne, CeRéMAIA, Paris, France.
Department of Internal Medicine, University of Paris, AP-HP, Cochin Hospital, Paris, France.
Br J Dermatol. 2022 Mar;186(3):564-574. doi: 10.1111/bjd.20805. Epub 2021 Nov 28.
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').
To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.
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.
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.
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.
最近描述了一种与UBA1体细胞突变相关的新型自身炎症综合征，称为VEXAS综合征（“空泡、E1酶、X连锁、自身炎症、体细胞综合征”）。
描述VEXAS综合征的临床特征、实验室检查结果及预后。
2020年11月至2021年5月期间，116例VEXAS综合征患者被纳入法国多中心登记处。记录从诊断到随访结束时各项参数的频率和中位数以及生命状态。
发现VEXAS综合征的主要临床特征为皮肤病变（83%）、非感染性发热（64%）、体重减轻（62%）、肺部受累（50%）、眼部症状（39%）、复发性软骨炎（36%）、静脉血栓形成（35%）、淋巴结（34%）和关节痛（27%）。58例（50%）存在血液系统疾病：骨髓增生异常综合征（MDS；n = 58）和意义未明的单克隆丙种球蛋白病（n = 12；所有MGUS患者也患有MDS）。UBA1突变包括p.M41T（45%）、p.M41V（30%）、p.M41L（18%）和剪接突变（7%）。中位随访3年后，18例患者死亡（15.5%；9例死于感染，3例死于MDS进展）。无监督分析确定了三个聚类：聚类1（47%；轻至中度疾病）；聚类2（16%；基础MDS且死亡率较高）；聚类3（37%；体质性表现、较高的C反应蛋白水平且软骨炎较少见）。聚类1的5年生存率为84.2%，聚类2为50.5%，聚类3为89.6%。UBA1 p.Met41Leu突变与较好的预后相关。
VEXAS综合征有广泛的器官表现，呈现不同的临床和预后特征。它还凸显了已鉴定的UBA1突变的潜在影响。
