Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Center, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Policlinico "Le Scotte", Viale Bracci 1, 53100, Siena, Italy.
Hematology, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.
Intern Emerg Med. 2023 Apr;18(3):711-722. doi: 10.1007/s11739-023-03193-z. Epub 2023 Jan 20.
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described pathological entity. It is an acquired monogenic autoinflammatory disease caused by somatic mutations of the UBA1 gene in blood cells precursors; the gene encodes one of the two E1 enzyme isoforms that initiates ubiquitylation in cell's cytoplasm. VEXAS syndrome leads to systemic inflammation, with all organs and tissues potentially involved. The clinical picture may be extremely heterogenous, mimicking different other systemic rheumatologic entities coexisting with haematological disorders, especially myelodysplastic syndrome. This new disease represents a very intriguing clinical condition in several respects: it accounts for the paradigm of adult-onset monogenic autoinflammatory diseases determined by a genetic mosaicism resulting in the development of a challenging multiorgan inflammatory condition. Moreover, VEXAS syndrome is perhaps not an exceptionally rare condition and represents an example of a systemic genetic autoinflammatory disease drawing its origin in bone marrow disorders. VEXAS syndrome should be strongly considered in each adult patient with an unexplained systemic inflammatory condition, especially when recurrent fevers, neutrophilic dermatosis, relapsing polychondritis, ocular inflammation and other systemic inflammatory symptoms accompanying myelodysplastic syndrome or other haematological disorders. The syndrome deserves a multidisciplinary approach to reach the diagnosis and ensure the best management of a potentially very challenging condition. To quickly describe the clinical course, long-term outcomes, and the optimal management of this new syndrome it is essential to join forces internationally. To this end, the international AutoInflammatory Disease Alliance (AIDA) registry dedicated to VEXAS syndrome has been developed and is already active.
VEXAS（空泡、E1 酶、X 连锁、自身炎症、体细胞）综合征是一种新近描述的病理实体。它是一种获得性单基因自身炎症性疾病，由血细胞前体细胞中 UBA1 基因的体细胞突变引起；该基因编码两种 E1 酶同工型之一，该同工型在细胞质中启动泛素化。VEXAS 综合征导致全身炎症，所有器官和组织都可能受到影响。临床表现可能极其异质，模仿其他不同的全身性风湿性实体，同时存在血液系统疾病，特别是骨髓增生异常综合征。这种新疾病在几个方面代表了一种非常有趣的临床情况：它代表了由遗传镶嵌导致的成年发病的单基因自身炎症性疾病的范例，从而导致具有挑战性的多器官炎症性疾病的发展。此外，VEXAS 综合征可能不是一种异常罕见的疾病，而是骨髓疾病起源的系统性遗传自身炎症性疾病的一个例子。对于每个原因不明的全身性炎症性疾病的成年患者，尤其是当伴有骨髓增生异常综合征或其他血液系统疾病的复发性发热、中性粒细胞皮肤病、复发性多软骨炎、眼部炎症和其他全身性炎症症状时，应强烈考虑 VEXAS 综合征。该综合征需要多学科方法来达到诊断，并确保对潜在的非常具有挑战性的疾病进行最佳管理。为了快速描述该新综合征的临床过程、长期结果和最佳管理，必须在国际范围内联合力量。为此，专门用于 VEXAS 综合征的国际自身炎症性疾病联盟（AIDA）登记处已经开发并已经启用。
