PDF(Pubmed)
Abstract：
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome has recently been described as an autoinflammatory disease associated with severe adult-onset inflammatory manifestations. The various clinical manifestations include recurrent high-grade fever, neutrophilic dermatoses, cutaneous vasculitis, chondritis of the ear and nose, pulmonary infiltrates, cytopenia, uveitis, gastrointestinal pain or inflammation, aortitis, hepatosplenomegaly, and hematological disorders. VEXAS syndrome is caused by somatic mutations of the ubiquitin-like modifier activating enzyme 1 (UBA1) gene in myeloid-lineage cells. It is characterized by vacuolated myeloid and erythroid progenitor cells seen by bone marrow biopsy. We report the case of a 64-year-old Japanese man with VEXAS syndrome. At age 63, he was referred to us with a recurrent erythema on the hands associated with a general fever of 38-40°C that had persisted for 4 or 5 days and had recurred about once a month for a year. The skin rash appeared 2 or 3 days after the onset of each fever episode. Computed tomography (CT) of the chest revealed bilateral hilar lymphadenopathy (BHL), and the mediastinal lymph nodes were swollen. Sarcoidosis was suspected but was ruled out by several tests. Laboratory examinations showed elevated inflammatory markers. Bone marrow examination showed the vacuolization of myeloid precursor cells. A skin biopsy revealed dense dermal, predominantly perivascular, infiltrates. These consisted of mature neutrophils admixed with myeloperoxidase-positive CD163-positive myeloid cells, lymphoid cells and eosinophils. Sequencing analysis identified the somatic UBA1 variant c.122T > C, which results in p.Met41Thr. Treatment with oral prednisone (15 mg/day) and monthly intravenous tocilizumab injections (400 mg) completely resolved the symptoms. Neutrophils are a major source of reactive oxygen species, and the present case demonstrated numerous neutrophilic infiltrates. We hypothesize that the patient might have had elevated derivatives of reactive oxygen metabolites (d-ROMs). d-ROM quantification is a simple method for detecting hydroperoxide levels, and clinical trials have proven it useful for evaluating oxidative stress. In this study, we measured serum d-ROM before and after oral prednisone and tocilizumab treatment. The levels decreased significantly during treatment.
摘要：
VEXAS（空泡，E1酶，X-linked,自身炎症,躯体）综合征最近被描述为与严重的成人发作性炎症表现相关的自身炎症性疾病。各种临床表现包括反复高烧,嗜中性皮肤病，皮肤血管炎,耳鼻软骨炎,肺浸润,血细胞减少,葡萄膜炎,胃肠道疼痛或炎症，主动脉炎,肝脾肿大,和血液病.VEXAS综合征由髓系细胞中泛素样修饰物激活酶1（UBA1）基因的体细胞突变引起。它的特征是骨髓活检可见的空泡状髓样和红系祖细胞。我们报告了一名64岁的日本男子患有VEXAS综合征的病例。在63岁时，他被转诊给我们，手上有复发性红斑，伴有38-40°C的一般发烧，持续了4或5天，并且每年每月复发一次。每次发烧发作后2或3天出现皮疹。胸部计算机断层扫描（CT）显示双侧肺门淋巴结肿大（BHL），纵隔淋巴结肿大。怀疑结节病，但被一些测试排除在外。实验室检查显示炎症标志物升高。骨髓检查显示髓样前体细胞空泡化。皮肤活检显示真皮致密，主要是血管周围，渗透。这些由成熟的中性粒细胞与髓过氧化物酶阳性CD163阳性骨髓细胞混合组成，淋巴细胞和嗜酸性粒细胞。测序分析确定了体细胞UBA1变体c.122T>C，这导致p.Met41Thr.口服泼尼松（15mg/天）和每月静脉注射托珠单抗（400mg）治疗完全解决了症状。中性粒细胞是活性氧的主要来源，和目前的情况下显示许多嗜中性粒细胞浸润。我们假设患者可能具有升高的活性氧代谢物衍生物(d-ROM)。d-ROM定量是检测氢过氧化物水平的简单方法，临床试验证明它对评估氧化应激有用。在这项研究中,我们测量了口服泼尼松和托珠单抗治疗前后的血清d-ROM.该水平在治疗期间显著降低。
