VEXAS综合征的诊治现状和展望
收稿日期: 2025-11-03
修回日期: 2025-11-19
录用日期: 2025-11-19
网络出版日期: 2026-02-25
基金资助
国家自然科学基金(82370145);上海市科学技术委员会医学创新研究专项重大项目(21Y31920400)
Current status and prospects of diagnosis and treatment of VEXAS syndrome
Received date: 2025-11-03
Revised date: 2025-11-19
Accepted date: 2025-11-19
Online published: 2026-02-25
VEXAS（vacuoles， E1 enzyme， X-linked， autoinflammatory， somatic）综合征是一种新近被认识的、由体细胞泛素样修饰物激活酶1（ubiquitin-like modifier activating enzyme 1， UBA1）基因突变引起多系统受累的自身炎症性疾病。该病自2020年被首次报道以来，全球报道病例数迅速增加，在我国亦陆续有个案及系列病例报道。VEXAS综合征好发于中老年男性，其临床表现复杂多样，常累及多系统，表现包括发热、皮损、软骨炎、肺浸润、血管炎和大细胞性贫血等，易被误诊为其他风湿免疫病或血液系统疾病。VEXAS综合征的诊断高度依赖UBA1基因测序，对于具有上述特征性临床表现、骨髓活检见髓系及红系前体细胞空泡变性的患者，应进行该基因检测。VEXAS综合征的治疗极具挑战，目前尚无完整的规范化治疗指南。糖皮质激素是控制急性炎症的首用治疗药物，但多数患者呈激素依赖；传统的免疫抑制剂大多疗效不佳或难以持续，而Janus激酶（Janus kinase， JAK）抑制剂、白细胞介素（interleukin， IL）-6抑制剂及去甲基化药物在部分患者中显示出良好疗效。异基因造血干细胞移植是目前唯一可以根治VEXAS综合征的手段，但需严格评估患者的获益与风险，而针对UBA1突变克隆的靶向精准治疗则可能成为未来的研究方向。
关键词： VEXAS综合征; 泛素样修饰物激活酶1基因; 克隆性造血
钱昊洲 , 常春康 . VEXAS综合征的诊治现状和展望[J]. 诊断学理论与实践, 2026 , 25(01) : 21 -29 . DOI: 10.16150/j.1671-2870.2026.01.004
VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized autoinflammatory disease involving multiple systems, caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. Since the disease was first reported in 2020, the number of cases has increased rapidly worldwide, and single case and case series have also been reported in China. VEXAS syndrome predominantly occurs in middle-aged and elderly males, with complex and diverse clinical manifestations that often involve multiple systems, including fever, skin lesions, chondritis, pulmonary infiltrates, vasculitis, and macrocytic anemia, making it prone to misdiagnosis as other rheumatic or hematologic diseases. Diagnosis of VEXAS syndrome highly relies on UBA1 gene sequencing, which should be performed in patients with characteristic clinical presentations mentioned above and vacuolization of myeloid and erythroid precursor cells observed in bone marrow biopsy. The treatment of VEXAS syndrome is highly challenging, and there is currently no comprehensive standardized treatment guideline. Glucocorticoids are the first-line treatment for controlling acute inflammation, but most patients exhibit steroid dependence. Traditional immunosuppressants are mostly ineffective or difficult to sustain, while Janus kinase (JAK) inhibitors, interleukin-6 (IL-6) inhibitors, and hypomethylating agents have shown good efficacy in some patients. Allogeneic hematopoietic stem cell transplantation is currently the only method that can cure VEXAS syndrome, but the benefits and risks for patients must be strictly evaluated. Targeted precision therapy against UBA1-mutant clones may become a future research direction.
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