Al-Hakim Adam, Savic Sinisa
Department of Clinical Immunology and Allergy, Leeds Teaching Hospitals, NHS Trust, Leeds, UK.
Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), School of Medicine, University of Leeds, Leeds, UK.
Expert Rev Clin Immunol. 2023 Feb;19(2):203-215. doi: 10.1080/1744666X.2023.2157262. Epub 2022 Dec 26.
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described, late-onset, acquired autoinflammatory disorder caused by mutations in the gene. The various clinical manifestations of VEXAS broadly divided into inflammatory or haematological. VEXAS defines a new disease category - the hematoinflammatory disorders triggered by somatic mutations restricted to blood but causing systemic inflammation with multi-organ involvement and associated with aberrant bone marrow status. VEXAS causes significant morbidity and reduced life expectancy, but the optimum standard of care remains undefined.
This review describes the discovery of VEXAS, relevant genetic causes and immunopathology of the disease. A detailed account of its various clinical manifestations and disease mimics is provided. Current treatment and management options are discussed.
New rare variants in and VEXAS-like negative cases are reported. Consensus diagnostic criteria might be required to define VEXAS and its related disorders. Investigation of sporadic, VEXAS-like cases will require the application of deep sequencing using DNA obtained from various cellular or tissue locations. Prospective studies are needed to define the optimal supportive and treatment options for patients with varying disease severity and prognosis. VEXAS-specific hematopoietic stem cell transplant selection criteria also require development.
VEXAS（空泡、E1酶、X连锁、自身炎症性、体细胞）综合征是一种最近被描述的迟发性获得性自身炎症性疾病，由该基因的突变引起。VEXAS的各种临床表现大致分为炎症性或血液学表现。VEXAS定义了一种新的疾病类别——由局限于血液的体细胞突变引发的血液炎症性疾病，但会导致全身炎症并累及多个器官，并与异常的骨髓状态相关。VEXAS会导致严重的发病率和预期寿命缩短，但最佳的治疗标准仍不明确。
本综述描述了VEXAS的发现、相关的遗传病因和疾病的免疫病理学。详细介绍了其各种临床表现和类似疾病。讨论了当前的治疗和管理选择。
报告了该基因的新的罕见变异和VEXAS样阴性病例。可能需要共识诊断标准来定义VEXAS及其相关疾病。对散发性VEXAS样病例的调查将需要应用从各种细胞或组织部位获得的DNA进行深度测序。需要进行前瞻性研究，以确定针对不同疾病严重程度和预后的患者的最佳支持和治疗选择。还需要制定VEXAS特异性造血干细胞移植选择标准。
