Vu Khiem T, Wolfe Rachel M, Lambird Jonathan E, Maracaja Danielle L V
Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC, 27157, USA.
BMC Rheumatol. 2023 Jul 10;7(1):18. doi: 10.1186/s41927-023-00343-w.
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.
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.
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.
VEXAS是一种最近发现的由UBA1基因突变引起的炎症性疾病。症状多样，包括发热、软骨炎症、肺部炎症、血管炎、嗜中性皮病和大细胞性贫血。骨髓中髓系和红系祖细胞的胞质内含物是其标志性特征。在此，我们报告首例骨髓中出现非干酪样肉芽肿的VEXAS病例。
一名62岁的亚洲男性出现发热、结节性红斑、炎症性关节炎和眶周炎症。实验室检查显示炎症标志物持续升高和大细胞性贫血。多年来，他的症状和炎症标志物仅在使用糖皮质激素时有所改善，当泼尼松剂量降至每日15 - 20毫克以下时症状复发。他接受了骨髓活检，显示非干酪样肉芽肿，PET扫描显示肺门/纵隔淋巴结病。他最初被诊断为IgG4相关疾病（接受利妥昔单抗治疗），后来又被诊断为结节病（接受英夫利昔单抗治疗）。在这些药物治疗失败后，考虑了VEXAS的可能性，后来通过分子检测得以证实。
据我们所知，这是首次在VEXAS中观察到非干酪样肉芽肿，这警示了其非特异性，因为错误解读可能导致诊断延迟。对于对类固醇（但对B细胞耗竭或TNF抑制无反应）有阳性反应的慢性炎症症状患者，VEXAS应列入鉴别诊断，这与先前的文献一致。
