托珠单抗治疗重症IVIG无应答川崎病临床观察

Clinical observation of tocilizumab in the treatment of severe IVIG non-responsive kawasaki disease

目的观察托珠单抗(tocilizumab,TCZ)治疗静脉免疫球蛋白(intravenous immunoglobulin,IVIG)无应答川崎病(Kawasaki disease,KD)的临床效果。方法选择2021年1月-2022年12月于乌鲁木齐儿童医院住院的3例重症IVIG无应答川崎病患儿使用TCZ治疗后的临床资料及随访结果进行分析,并以“IVIG无应答川崎病治疗”“托珠单抗治疗IVIG无应答川崎病”(包括中英文)为关键词或主题词对PubMed和中国知网中截至2022年12月收录的论文进行检索,收集并分析检索到的病人的资料。结果3例KD患儿IVIG联合静脉甲泼尼龙(intravenous methylprednisolone,IVMP)效果不佳,使用TCZ治疗后,在体温、皮肤黏膜表现、HB、PLT、CRP、白介素-6(interleukin-6,IL-6)、NT-pro-BNP恢复上有明显效果,2例未发现冠脉扩张,1例出现巨大冠脉瘤,未发现使用TCZ后出现感染不良反应。检索文献共收集到1篇相关病例报道,4例患儿均为IVIG治疗无效,TCZ治疗后,所有患儿在48h时内体温恢复,其他临床症状同时得到改善,CRP和白细胞计数迅速下降,2例发展为巨大冠脉瘤,其中1例在6月后消退,另外1例在2年后因冠状动脉狭窄行经皮冠状动脉介入治疗。结论重症IVIG无应答KD治疗可选择,IVMP、IVIG、TCZ联合治疗,TCZ对重症IVIG无应答KD疗效显著,且用药安全,建议对IVIG无应答KD患者尽早使用,以期减少冠脉病变发生。

Objective To observe the clinical effect of tocilizumab(TCZ)in the treatment of intravenous immunoglobulin(IVIG)nonresponsive Kawasaki disease(KD).Methods The clinical data and follow-up results of 3 patients with severe IVIG non-responsive Kawasaki disease hospitalized in Urumqi Children’s Hospital from January 2021 to December 2022 were analyzed after treatment with TCZ.The papers included in PubMed and CNKI up to December 2022 were searched with the keywords or subject words of“IVIG non-responsive Kawasaki disease treatment”and“tocilizumab treatment of IVIG non-responsive Kawasaki disease”(including both Chinese and English),and the data of retrieved patients were collected and analyzed.Results The effect of IVIG combined with intravenous methylprednisolone(IVMP)in 3 children with KD was poor.After treatment with TCZ,there were significant effects on the recovery of body temperature,skin and mucous membrane manifestations,HB,PLT,CRP,interleukin-6(IL-6),NT-pro-BNP,2 patients did not find coronary artery dilation,1 patient had huge coronary artery tumor,and no adverse reaction of infection were found after treatment with TCZ.A total of 1 related case report was collected from the retrieved literature.All 4 children were ineffective in IVIG treatment.After TCZ treatment,the temperature of all children recovered within 48 hours,and other clinical symptoms were improved at the same time.CRP and white blood cell count decreased rapidly.Two patients developed into giant coronary artery tumors,one of which subsided after 6 months,and the other one underwent percutaneous coronary intervention for coronary artery stenosis 2 years later.Conclusion IVMP,IVIG and TCZ can be selected for the treatment of severe IVIG nonresponsive KD.TCZ is effective and safe for the treatment of severe IVIG nonresponsive KD.It is recommended to use it as soon as possible for patients with IVIG nonresponsive KD in order to reduce the occurrence of coronary artery disease.