Watanabe Ryu, Kiji Manami, Hashimoto Motomu
Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Front Med (Lausanne). 2022 Aug 15;9:983939. doi: 10.3389/fmed.2022.983939. eCollection 2022.
Vasculitis is an inflammatory disorder of the blood vessels that causes damage to a wide variety of organs through tissue ischemia. Vasculitis is classified according to the size (large, medium, or small) of the blood vessels. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. Somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation, are attributed to this disorder. This new disease entity connects seemingly unrelated conditions: inflammatory syndromes (relapsing chondritis, Sweet's syndrome, or neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Notably, such patients sometimes develop vasculitis, such as giant cell arteritis and polyarteritis nodosa, and fulfill the corresponding classification criteria for vasculitis. Thus, vasculitis can be an initial manifestation of VEXAS syndrome. In this research topic exploring the link between autoinflammatory diseases and vasculitis, we first provide an overview of the disease mechanisms and clinical phenotypes of VEXAS syndrome. Then, a literature review using the PubMed database was performed to delineate the clinical characteristics of vasculitis associated with VEXAS syndrome. Finally, the therapeutic options and unmet needs of VEXAS syndrome are discussed.
血管炎是一种血管的炎症性疾病,通过组织缺血对多种器官造成损害。血管炎根据血管大小(大、中或小)进行分类。2020年,一种新型自身炎症综合征——VEXAS(空泡、E1酶、X连锁、自身炎症、体细胞)综合征被描述。引发泛素化的主要E1酶UBA1的第41位甲硫氨酸发生体细胞突变被认为是导致该疾病的原因。这个新的疾病实体将看似不相关的病症联系起来:炎症综合征(复发性软骨炎、Sweet综合征或嗜中性皮病)和血液系统疾病(骨髓增生异常综合征或多发性骨髓瘤)。值得注意的是,这类患者有时会发生血管炎,如巨细胞动脉炎和结节性多动脉炎,并符合血管炎的相应分类标准。因此,血管炎可能是VEXAS综合征的初始表现。在这个探索自身炎症性疾病与血管炎之间联系的研究主题中,我们首先概述了VEXAS综合征的疾病机制和临床表型。然后,利用PubMed数据库进行文献综述,以描述与VEXAS综合征相关的血管炎的临床特征。最后,讨论了VEXAS综合征的治疗选择和未满足的需求。