Koster Matthew J, Kourelis Taxiarchis, Reichard Kaaren K, Kermani Tanaz A, Beck David B, Cardona Daniela Ospina, Samec Matthew J, Mangaonkar Abhishek A, Begna Kebede H, Hook C Christopher, Oliveira Jennifer L, Nasr Samih H, Tiong Benedict K, Patnaik Mrinal M, Burke Michelle M, Michet Clement J, Warrington Kenneth J
Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN.
Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN.
Mayo Clin Proc. 2021 Oct;96(10):2653-2659. doi: 10.1016/j.mayocp.2021.06.006. Epub 2021 Sep 3.
The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.
本研究的目的是描述新定义的空泡、E1酶、X连锁、自身炎症性、体细胞（VEXAS）综合征患者的临床特征和结局。鉴定出9名患有UBA1基因体细胞突变的男性；最常见的变异是p.Met41Thr（9例中的7例，78%）。VEXAS诊断时的中位年龄为74（67，76.5）岁，患者在诊断前症状的中位持续时间为4年。难治性全身症状（88%）、耳和鼻软骨炎（55%）以及炎症性关节炎（55%）是常见的临床特征。44%的患者出现血管炎。所有患者的炎症标志物均显著升高且存在大细胞性贫血。VEXAS诊断时66%的患者存在血小板减少。8名患者进行了骨髓活检。所有骨髓均细胞增多，红系（100%）或髓系前体细胞（75%）有空泡形成。糖皮质激素在泼尼松剂量≥20 mg/天时可减轻症状，但没有其他免疫抑制剂显示出对疾病的持续长期控制。1例合并浆细胞骨髓瘤的患者接受了针对浆细胞的治疗，炎症反应得到改善，这是一个新发现。总之，VEXAS综合征是一种由UBA1基因体细胞突变引起的临床异质性、治疗难治性炎症性疾病。患者常表现出重叠的风湿病表现和持续的血液学异常。因此，内科医生和包括病理学家在内的专科医生应了解这种疾病，以避免诊断延误，因为该综合征病因已明确。
