背景:液泡,E1酶,X-linked,自身炎症,体细胞(VEXAS)综合征是最近公认的由UBA1基因的体细胞突变引起的多系统疾病。
方法:对2020年6月至2022年5月在我们机构评估的所有VEXAS综合征患者进行了回顾性队列研究。回顾了病历和胸部影像学研究。
结果:我们确定了45名中位年龄为68岁的受试者(范围,57-89),所有的男人。在VEXAS诊断之前,大多数患者被诊断患有各种血液病,风湿病,和皮肤病。大多数患者(84%)表现出典型的UBA1蛋氨酸-41(p。Met41)造血细胞中的体细胞突变。发烧(82%),皮肤病变(91%),和呼吸道症状(93%)是常见的表现特征。91%的患者胸部CT表现出异常,包括25例(74%)的实质混浊,最常见的是毛玻璃混浊(47%),纵隔淋巴结肿大(29%),气道异常(29%),和胸腔积液(24%)。18例(40%)患者的肺功能检查结果显示轻度限制性损害或正常结果。在少数患者中进行的支气管肺泡灌洗和肺活检表现为中性粒细胞性肺泡炎和实质性炎症,分别。所有患者均接受糖皮质激素治疗,至少部分缓解,但复发是常见的,大多数患者使用其他免疫抑制剂。接受托珠单抗和JAK抑制剂的患者肺部受累似乎有所改善。
结论:VEXAS的肺部表现相对非特异性和非严重,发生在全身性炎症的背景下,对糖皮质激素剂量的增加有反应。
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently recognized multisystem disorder caused by somatic mutations in the UBA1 gene.
A retrospective cohort study was conducted on all patients with VEXAS syndrome evaluated at our institution from June 2020 through May 2022. Medical records and chest imaging studies were reviewed.
We identified 45 subjects with median age of 68 years (range, 57-89), all men. Prior to VEXAS diagnosis, most patients had been diagnosed with various hematologic, rheumatologic, and dermatologic disorders. Most patients (84%) demonstrated canonical UBA1 methionine-41 (p.Met41) somatic mutations in hematopoietic cells. Fever (82%), skin lesions (91%), and respiratory symptoms (93%) were common presenting features. Chest CT manifested abnormalities in 91% of patients including parenchymal opacities in 25 (74%), most commonly ground-glass opacities (47%), along with mediastinal lymphadenopathy (29%), airway abnormalities (29%), and pleural effusion (24%). Pulmonary function test results available in 18 (40%) patients demonstrated mild restrictive impairment or normal results. Bronchoalveolar lavage and lung biopsy performed in a minority of patients demonstrated neutrophilic alveolitis and parenchymal inflammation, respectively. All patients received glucocorticoid therapy with at least partial response, but relapses were common and other immunosuppressive agents were employed in most patients. Pulmonary involvement appeared to improve in patients who received tocilizumab and JAK inhibitors.
The pulmonary manifestations in VEXAS are relatively nonspecific and nonsevere, occur in the context of systemic inflammation and are responsive to escalation in glucocorticoid dosing.