Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan.
Department of Clinical Genomics, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan.
Mod Rheumatol Case Rep. 2023 Dec 29;8(1):199-204. doi: 10.1093/mrcr/rxad041.
We herein describe the case of a 52-year-old male patient who presented with fever, arthritis, and neutrophilic dermatosis in 2013 and subsequently experienced macrophage activation syndrome treated with high-dose glucocorticoid therapy. Due to the persistent symptoms refractory to several immunomodulatory and immunosuppressive (IS) drug therapies with dapsone, methotrexate, tacrolimus, infliximab (IFX), and tocilizumab (TCZ), he received prednisolone (PSL) ≥20 mg/day to suppress disease activity. In 2017, Epstein-Barr virus (EBV)-associated haemophagocytic lymphohistiocytosis (HLH) was diagnosed and initially treated with immunochemotherapy consisting of dexamethasone, cyclosporine (CyA), and etoposide (ET). Because of the suboptimal response to the initial therapy, cytoreduction therapy consisting of CHOP (combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and PSL) was administered. This regimen improved the EBV-associated HLH. Later, the patient's condition stabilised with methylprednisolone 1 mg/day and CyA 100 mg/day. In 2022, ubiquitylation-initiating E1 enzyme (UBA1) variant analysis using Sanger sequencing of peripheral blood leukocytes detected a previously reported somatic variant (NM_003334.3: c.118-1G>C), confirming the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The clinical course in the present case suggested the possibility that CHOP could be a potential treatment option for VEXAS syndrome, in the pathophysiology of which the expansion of clones with UBA1 variant seems to play a pivotal role.
我们在此描述了一位 52 岁男性患者的病例，他于 2013 年出现发热、关节炎和中性粒细胞皮肤病，并随后因巨噬细胞活化综合征接受了大剂量糖皮质激素治疗。由于对几种免疫调节和免疫抑制（IS）药物治疗（包括氨苯砜、甲氨蝶呤、他克莫司、英夫利昔单抗和托珠单抗）的持续症状反应不佳，他接受了泼尼松龙（PSL）≥20mg/天以抑制疾病活动。2017 年，诊断为 EBV 相关噬血细胞性淋巴组织细胞增多症（HLH），并最初接受了包括地塞米松、环孢素（CyA）和依托泊苷（ET）在内的免疫化学疗法治疗。由于对初始治疗反应不佳，给予了包括 CHOP（环磷酰胺、多柔比星、长春新碱和 PSL 组成的联合化疗）在内的细胞减少治疗。该方案改善了 EBV 相关 HLH。后来，患者的病情稳定在每天 1mg 甲基泼尼松龙和每天 100mg CyA。2022 年，通过对外周血白细胞进行 Sanger 测序对泛素起始 E1 酶（UBA1）变异进行分析，检测到先前报道的种系变异（NM_003334.3：c.118-1G>C），从而确诊 VEXAS 综合征。本病例的临床过程提示 CHOP 可能是 VEXAS 综合征的一种潜在治疗选择，在其病理生理学中，具有 UBA1 变异的克隆扩增似乎起着关键作用。
