Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation
Clinical characteristics and treatment of 50 cases of Blau syndrome in Japan confirmed by genetic analysis of the NOD2 mutation
复制标题
DOI：
10.1136/annrheumdis-2020-217320
复制
发表时间：
2020-11-01
影响因子：
27.4
通讯作者：
Nishikomori, Ryuta
中科院分区：
文献类型：
--
作者：
Matsuda, Tomoko;Kambe, Naotomo;Nishikomori, Ryuta
目的收集Blau综合征患者的临床资料和NOD 2基因突变资料，并对其预后进行评估。通过报告基因测定在HEK 293细胞中评价每个NOD 2突变体的活性。临床资料收集从病历通过主治医师。结果研究人群包括26名男性和24名女性，年龄0-61岁。32例为散发性，18例为家族性，来自9个无关家系。在NOD 2中鉴定了15种不同的突变，包括2种新突变（p.W490 S和D512 V）;所有突变均显示自发的核因子κ B激活，最常见的突变是p.R334 W。26例患者在病程中相对较早的时间点出现发热。47例患者中有43例出现皮疹。9例患者在接种卡介苗后发现发病。49例患者中有45例有关节病变。50例患者中38例有眼部症状，其中7例导致失明。诊断为Blau综合征后，26例患者接受了生物制剂治疗;所有患者均为抗肿瘤坏死因子药物。仅3例患者单独接受生物制剂治疗;其他患者接受生物制剂联合甲氨蝶呤和/或泼尼松龙治疗。没有一个失明的患者接受了生物治疗。结论在Blau综合征患者中，如果诊断和适当的治疗延误，可能会发生严重的关节挛缩和失明。早期应用生物制剂治疗可改善预后。
Objectives To collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis.Methods Fifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.Results The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.Conclusions In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.