背景:VEXAS是最近描述的由UBA1基因突变引起的炎症性疾病。症状多种多样,包括发烧,软骨炎症,肺部炎症,血管炎,嗜中性皮肤病,和大细胞性贫血.骨髓中的骨髓和红系祖细胞中的细胞质内含物是标志特征。在这里,我们报告了第一例VEXAS骨髓中的非干酪性肉芽肿。
方法:一名62岁的亚裔男性发烧,结节性红斑,炎性关节炎,和眶周炎症.实验室对于持续升高的炎症标志物和大细胞性贫血具有重要意义。多年来,他的症状和炎症标志物仅在使用糖皮质激素后得到改善,当泼尼松剂量降低至每日15-20mg以下时复发。他接受了骨髓活检显示非干酪样肉芽肿和PET扫描显示肺门/纵隔淋巴结肿大。他最初被诊断为IgG4相关疾病(用利妥昔单抗治疗),后来被诊断为结节病(用英夫利昔单抗治疗)。在这些特工失败后,我们考虑了VEXAS的可能性,后来通过分子检测证实了这一点.
结论:据我们所知,这是首次在VEXAS中观察到非干酪样肉芽肿,提醒人们注意其非特异性,因为误解可能导致诊断延迟.VEXAS应该在慢性炎症症状对类固醇反应积极的患者中存在差异(但不是B细胞耗竭或TNF抑制),这与以前的文献一致。
BACKGROUND: VEXAS is a recently described inflammatory disease caused by mutations in the UBA1 gene. Symptoms are diverse and include fevers, cartilaginous inflammation, lung inflammation, vasculitis, neutrophilic dermatoses, and macrocytic anemia. Cytoplasmic inclusions in myeloid and erythroid progenitors in the bone marrow are a hallmark feature. Here we report the first
case of VEXAS with non-caseating
granulomas in the bone marrow.
METHODS: A 62-year-old Asian male presented with fevers, erythema nodosum, inflammatory arthritis, and periorbital inflammation. Labs were significant for persistently elevated inflammatory markers and macrocytic anemia. Over the years his symptoms and inflammatory markers only improved with glucocorticoids and recurred when prednisone dose was lowered below 15-20 mg daily. He underwent bone marrow biopsy showing non-caseating
granulomas and PET scan showing hilar/mediastinal lymphadenopathy. He was initially diagnosed with IgG4-related disease (treated with rituximab) and later sarcoidosis (treated with infliximab). After failing these agents, the possibility of VEXAS was considered and later confirmed by molecular testing.
CONCLUSIONS: To the best of our knowledge, this is the first observation of non-caseating
granulomas in VEXAS, a cautionary reminder of its non-specificity since misinterpretation can lead to diagnostic delay. VEXAS should be in the differential in patients with symptoms of chronic inflammation responding positively to steroids (but not to B-cell depletion or TNF inhibition), which is in line with previous literature.