背景:液泡,E1酶,X-linked,自身炎症,体细胞(VEXAS)是由UBA1基因的体细胞突变引起的风湿病和血液学特征重叠的自身炎症性疾病。表现出高度可变症状的患者及其诊断路径通常很复杂,并以广泛的检查为特征。是的,因此,关键是临床医生熟悉VEXAS的临床表现,以促进对该疾病患者的识别。
目的:我们的目的是(1)在三级风湿病转诊中心诊断为VEXAS的患者的特征,(2)确定可能将VEXAS与其他风湿性疾病区分开的常见风湿性生物标志物,以及(3)建议哪些临床发现应促进VEXAS的基因检测。
方法:在风湿病科确定和诊断患者,奥胡斯大学医院(AUH),丹麦。在临床免疫学部门通过Sanger测序检查血液样本中与VEXAS相关的UBA1变体,AUH.从医院电子病历表中检索临床和生化数据。
结果:11名临床怀疑VEXAS的男性患者接受了测序。这些中的五个携带已知的VEXAS相关变体。诊断时的中位年龄为84(75-87)岁。所有患者的炎症标志物均显着升高,其中C反应蛋白(CRP)的中位数为297(196-386)mg/L,并且患有大细胞性贫血。没有患者出现自身免疫的常见生物标志物。
结论:患有VEXAS综合征的丹麦患者是患有持续性炎症的男性,全身症状和异质性临床表现。这项研究中所有患者的共同特征是高度升高的炎症标志物,大细胞性贫血和自身免疫标志物阴性。
BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is an autoinflammatory condition with overlapping features of rheumatology and haematology caused by somatic mutations in the UBA1 gene. Patients present with highly variable symptoms and their path towards diagnosis are often complicated and characterised by extensive examinations. It is, therefore, pivotal that clinicians become familiar with the clinical presentation of VEXAS to advance identification of patients with the disease.
OBJECTIVE: We aimed to (1) characterise patients diagnosed with VEXAS in a tertiary rheumatology referral centre, (2) identify common rheumatological biomarkers that may distinguish VEXAS from other rheumatic diseases and (3) suggest which clinical findings should motivate genetic testing for VEXAS.
METHODS: Patients were identified and diagnosed at the department of Rheumatology, Aarhus University Hospital (AUH), Denmark. Blood samples were examined for VEXAS-associated UBA1 variants by Sanger sequencing at the department of Clinical Immunology, AUH. Clinical and biochemical data were retrieved from the hospital electronic patient chart.
RESULTS: Eleven male patients with clinical suspicion of VEXAS underwent sequencing. Five of these carried known VEXAS-associated variants. Median age at diagnosis was 84 (75-87) years. All patients had significantly elevated inflammatory markers with a median C-reactive protein (CRP) of 297 (196-386) mg/L and macrocytic anaemia. None of the patients presented common biomarkers for autoimmunity.
CONCLUSIONS: Danish patients with VEXAS syndrome are men with persistent inflammation, constitutional symptoms and heterogeneous clinical presentations. Shared features for all patients in this study were highly elevated inflammatory markers, macrocytic anaemia and negative autoimmune biomarkers.