Effective treatment of TNFα inhibitors in Chinese patients with Blau syndrome
Effective treatment of TNFα inhibitors in Chinese patients with Blau syndrome
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DOI：
10.1186/s13075-019-2017-5
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发表时间：
2019-11-12
影响因子：
4.9
通讯作者：
Shen, Min
中科院分区：
文献类型：
--
作者：
Chen, Jing;Luo, Yi;Shen, Min
Blau综合征（BS）是一种罕见的显性遗传性自身炎症性疾病，与NOD 2基因突变有关。BS的生物治疗产生了不同的结果。我们旨在评估中国BS患者接受肿瘤坏死因子（TNF）α抑制剂治疗的临床特征和结局。方法2015年至2018年，北京协和医院共收治4例BS患者，均接受英夫利西单抗（IFX）治疗，并随访18个月。对所有患者的治疗结果进行系统研究，包括临床表现和炎症标志物。我们还进行了一个全面的文献综述TNF α抑制剂治疗BS。结果四BS患者都是中国汉族，三个是女性。平均发病年龄为43.5岁，平均诊断延迟时间为19 ± 11年。所有患者均接受IFX联合甲氨蝶呤治疗，在6个月的首次随访中，所有患者的皮肤病变和多关节炎均迅速临床缓解，红细胞沉降率和C反应蛋白恢复正常，炎性细胞因子、患者视觉模拟评分、医生总体评估和简明健康量表（SF）-36改善。两名患者在延长IFX间隔和停用甲氨蝶呤后复发。根据38篇英文出版物，报告了62例接受TNF α抑制剂治疗的BS患者，包括31例使用IFX，24例使用阿达木单抗，7例使用依那西普。27例患者对IFX耐受良好，2例仍有葡萄膜炎，2例出现药物不良反应。结论早期识别BS，有效治疗，可避免不可逆的器官损害。TNF α抑制剂，如IFX可能是一个有前途的方法，BS患者有不满意的反应，糖皮质激素和传统的疾病缓解抗风湿药物。
ObjectivesBlau syndrome (BS) is a rare dominantly inherited autoinflammatory disorder associated with mutations in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Biologic therapy of BS yielded diverse results. We aimed to evaluate clinical features and outcomes of Chinese patients with BS who were treated with tumor necrosis factor (TNF)alpha inhibitors.MethodsA total of four patients with BS were diagnosed and treated with infliximab (IFX) at the Peking Union Medical College Hospital during 2015 to 2018 and were followed up for 18months. All patients were systematically studied for treatment outcomes including the clinical manifestations and inflammatory markers. We also conducted a comprehensive literature review about TNF alpha inhibitor therapy in BS.ResultsFour BS patients were all Chinese Han, and three were women. The mean age of disease onset was 4 3.5years, and the mean time of diagnosis delay was 19 +/- 11years. All patients received IFX plus methotrexate, and all achieved clinical remission of skin lesions and polyarthritis rapidly, as well as normalization of erythrocyte sedimentation rate and C-reactive protein and improvements in inflammatory cytokines, patient visual analogue scale, physician global assessment, and Short Form (SF)-36, at the first follow-up of 6months. The disease relapsed in two patients after they lengthened the interval of IFX and discontinued methotrexate. According to the 38 English-language publications, 62 patients with BS were reported who underwent TNF alpha inhibitor therapy, including IFX used in 31, adalimumab in 24, and etanercept in 7. IFX was well tolerated in 27 patients, while 2 still had uveitis, and the other 2 experienced an adverse drug reaction.Conclusions Early recognition and effective treatment of BS are very important to avoid irreversible organ damage. TNF alpha inhibitors such as IFX may be a promising approach for BS patients who have unsatisfactory response to corticosteroids and traditional disease-modifying antirheumatic drugs.