背景:VEXAS(空泡,E1酶,X-linked,自身炎症,体细胞)综合征是一种新发现的自身炎症性疾病,其特征是UBA1基因的体细胞突变。该综合征导致多系统炎症,主要影响皮肤,肺和骨髓.
方法:我们对VEXAS综合征中观察到的多系统特征和基因型进行了系统评价。包括讨论VEXAS综合征的文章。Medline,检索Embase和Cochrane数据库。信息被提取:人口统计数据,临床表现的类型和患病率,基因突变和治疗。使用随机效应模型的Meta分析用于确定血清标志物的汇总估计。
结果:来自303篇文章,包括90个,包括394名VEXAS患者。99.2%为男性,发病时平均年龄为67.1岁(SD8.5)。在VEXAS之前最常见的诊断是:复发性多软骨炎(n=59);斯威特综合征(n=24);结节性多动脉炎(n=11);和骨髓增生异常综合征(n=10)。270例(68.5%)发热,79例(20.1%)体重减轻。大多数患者有血液病(n=342;86.8%),皮肤病学(n=321;81.5%),肺(n=297;75.4%)和肌肉骨骼(n=172;43.7%)受累,尽管也记录了其他不同患病率的器官表现。最常报道的突变是“c.122T>CpMET41Thr”(n=124),\"c.121A>GpMET41Val\"(n=62)和\"c.121A>CpMet41Leu\"(n=52)。大多数患者接受糖皮质激素(n=240;60.9%),然后是甲氨蝶呤(n=82;20.8%)和IL-6抑制剂(n=61,15.4%)。1例患者接受脾切除术;24例接受骨髓移植。
结论:VEXAS综合征是一种罕见的疾病,主要影响中年男子。这是第一个系统的审查,以捕获临床表现,遗传学和报告病例的治疗。需要进一步的研究来优化治疗并随后降低发病率和死亡率。
BACKGROUND: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow.
METHODS: We undertook a systematic
review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers.
RESULTS: From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet\'s syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were \"c.122T > C pMET41Thr\" (n = 124), \"c.121A > G pMET41Val\" (n = 62) and \"c.121A > C pMet41Leu\" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants.
CONCLUSIONS: VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic
review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.