激素与静脉丙种球蛋白及其联合应用治疗静脉丙种球蛋白无反应川崎病的回顾性对照研究

Retrospective controlled study of steroid and IVIG treatment for IVIG unresponsive Kawasaki disease

目的探讨激素对静脉丙种球蛋白(IVIG)无反应川崎病(KD)患儿的治疗价值。方法回顾性收集重庆医科大学附属儿童医院IVIG无反应KD住院患儿,根据再治疗情况分为IVIG组、激素组和IVIG+激素组;将应用激素者根据激素应用途径分为静脉滴注序贯口服激素组和口服激素组。统计各组患儿的总热程、平均热退时间、治疗前后实验室检查结果并计算治疗前后的差值与治疗前值的比值(即差值比△)、急性期及出院后6、12、24个月冠状动脉病变和随访中的血栓形成情况。结果 IVIG无反应KD患儿143例进入本文分析。IVIG组107例,激素组12例,IVIG+激素组24例,3组性别、年龄、体重差异无统计学意义。IVIG+激素组治疗后WBC高于IVIG组,△WBC、△PLT均低于IVIG组,△CRP高于IVIG组,总热程长于IVIG组;急性期冠状动脉瘤发生率及随访至6个月时冠状动脉扩张发生率高于IVIG组,差异均有统计学意义;激素组△WBC低于IVIG组,总热程长于IVIG组,差异均有统计学意义。静脉滴注序贯口服激素组和口服激素组各18例,2组性别、年龄、体重差异无统计学意义,口服激素组再次治疗前和再次治疗后CRP均低于静脉滴注序贯口服激素组,口服激素组△PLT高于静脉滴注序贯口服激素组,2组随访时点冠状动脉扩张和冠状动脉瘤发生率差异均无统计学意义。随访病例中,静脉滴注序贯口服激素组有2例出现血栓,经积极抗凝治疗后血栓消失。结论 IVIG无反应KD患儿再治疗时应用激素或再次IVIG无反应后应用激素,与单纯IVIG相比急性期治疗效果相近,且均不增加远期冠状动脉损伤的发生率;选择普通剂量口服或者静脉滴注序贯口服疗法临床效果相近,但静脉滴注序贯口服激素较口服激素有更高的血栓形成风险。

Objective To investigate the treatment effect of steroid for intravenous immunoglobulin（ IVIG ） unresponsive Kawasaki disease（ KD ）. Methods Data of children with initial IVIG unresponsive KD in Children′s Hospital of Chongqing Medical University were retrospectively collected. Total cases were divided into 3 groups：IVIG only,steroid only and IVIG plus steroid according to re-treatment methods. Those who used steroid including steroid group and IVIG plus steroid group were divided into intravenous sequentially oral steroid group（ intravenous-oral steroid group ） and oral steroid group. The whole fever time, duration of fever after re-treatment,laboratory examination results before and after re-treatment were focused and the difference ratio△（ the ratio of the difference value before and after re-treatment to the value before re-treatment）was calculated. Coronary artery lesions（ CALs）outcomes were observed in acute stage and CALs and thrombus 6,12 and 24 months after hospital discharge were followed-up. Results A total of 143 children with initial IVIG unresponsive KD were analyzed. There were 107 cases in IVIG group,12 cases in steroid group and 24 cases in IVIG plus steroid group. There was no significant difference in gender,age and weight among three groups. Compared with IVIG group,WBC and PLT after re-treatment and △CRP were higher in IVIG plus steroid group,and the whole fever time of this group was longer. However the△WBC and△PLT were lower in IVIG plus steroid group. The incidence of coronary artery aneurysm in acute stage and coronary artery dilatation 6 months after hospital discharge was higher in IVIG plus steroid group than that of IVIG group. Compared with IVIG group,△WBC was lower and the whole fever time was longer in steroid group. There were 18 cases in intravenous-oral steroid group and oral steroid group respectively. No statistically significant difference in gender,age and weight was found between those two groups. In oral steroid group,△CRP was lower and △PLT was higher than those of intravenous-oral steroid group. There was no significant difference in long-term progression of coronary artery between the two groups. In the follow-up cases,2 cases with thrombosis were found in the intravenous-oral steroid group,but the thrombus disappeared after anti-coagulation therapy. Conclusion This study suggested that direct application of steroid treatment is effective and relatively safe in acute stage for initial IVIG unresponsive KD patients,and the incidence of CALs does not increase in long-term follow-up. Taking ordinary dose steroid orally or intravenous-oral way showed no significant difference on the effect of the treatment in acute period and long-term prognosis for initial IVIG unresponsive KD patients. But intravenous-oral way has an increased thrombotic risk.