肿瘤坏死因子-α抑制剂致药源性狼疮病例汇总分析

Literature analysis of drug-induced lupus erythematosus following treatment with tumor necrosis factor-α inhibitors

目的:从临床实例出发,探讨肿瘤坏死因子-α抑制剂(tumor necrosis factor-alpha inhibitor,TNFi)导致药源性狼疮的特点和关联性,为临床安全用药提供参考。方法:采用文献学计量方法,对国内外公开报道的TNFi致药源性狼疮病例进行总结性分析。结果:纳入TNFi致药源性狼疮文献44篇,共计52人发生54例不良反应,女性39例(75%),男性13例(25%)。致狼疮药物共5种,分别为英夫利昔单抗(23例,42.59%)、阿达木单抗(13例,24.07%)、依那西普(13例,24.07%)、戈利木单抗(3例,5.56%)、赛妥珠单抗(1例,1.85%)以及同时使用英夫利昔单抗与阿达木单抗(1例,1.85%)。37例不良反应发生在用药1年内;平均潜伏期12.07个月。54例不良反应的临床表现主要有:抗核抗体阳性(47例,88.68%)、抗双链DNA抗体阳性(30例,55.56%)、关节炎(28例,51.85%)、皮肤损害(21例,38.89%)、血液系统异常(21例,38.89%)、肺脏受累(14例,25.93%)、心脏受累(9例,16.67%)、肾脏受累(8例,14.81%)。49例患者停药后好转,1例死亡,1例维持透析治疗,1例失访。9例患者换用另一种TNFi治疗原患疾病,其中7例患者未见复发。结论:TNFi致药源性狼疮的临床表现具有多样性,关节受累最常见,其次为皮肤与血液系统,可累及重要脏器。在开始TNFi治疗前,临床工作者应重视评估临床和免疫学检查,治疗期间密切关注患者的临床表现和免疫抗体水平,重视可能累及的脏器和系统,确保药物治疗的安全。

Objective： To review clinical characteristics and relevance of lupus syndrome induced by tumor necrosis factor-α inhibitors,and provide references for safety of the drug therapy. Methods： By means of literature metrology method,cases of lupus induced by tumor necrosis factor-α inhibitors domestically and internationally reported were analyzed. Results： Totally 52 patients and 54 cases were included in 44 relevant literatures. Among these,39（75%） were female,13（25%） were men. A total of 5 tumor necrosis factor-α inhibitors induced lupus,23 patients（42. 59%） were treated with infliximab,and 13（24. 07%） with adalimub,13（24. 07%）with etanercept,3（5. 56%） with golimumab,1（1. 85%） with certolizumab pegol,and 1（1. 85%） with infliximab ＋ adalimub. Average latency of drug-induced lupus-like syndrome was 12. 07 months. Features of lupus included presence of antinuclear antibodies（47 patients,88. 68%）,anti-double-stranded DNA antibodies（30 patients,55. 56%）,arthriris（28 patients,51. 85%）,cutaneous disorders（21 patients,38. 89%）,hematologicabnormalities（21 patients,38. 89%）,lung disorders（14 patients,25. 93%）,heart disorder（9 patients,16. 67%）,and renal disorder（8 patients,14. 81%）. A total of 49 patients were improved after stopping tumor necrosis factor-α inhibitors therapy. One patient was IV lupus nephritis induced by etanercept with a fatal evolution,1 patient had been undergoing maintenance dialysis treatment because of end-stage renal disease,and one was lost to follow-up. Seven of 9 patients tolerated an alternative tumor necrosis factor-α inhibitor without recurrence of lupus syndrome. Conclusion： Clinical manifestations of tumor necrosis factor-α inhibitors-induced lupus syndrome are diverse,joint damage is the most common presenting symptom,cutaneous findings and hematologic disorder are less frequent,and major organ systems could be affected. Clinicians should consider the importance of a careful clinic and immunologic evaluation before starting the therapy,and be particularly vigilant to possibly involved organs and systems of lupus,in order to ensure the safety of therapeutic drugs.