静脉注射免疫球蛋白无反应川崎病的危险因素分析

Risk factors of non-response to intravenous immunoglobin in Kawasaki disease

目的探讨静脉注射免疫球蛋白(intravenous immunoglobulin,IVIG)无反应川崎病(Kawasaki disease,KD)的危险因素。方法回顾性分析2018年6月至2019年8月首都医科大学附属北京儿童医院心脏内科确诊的391例KD患儿的临床资料,根据IVIG治疗效果分为IVIG敏感组与IVIG无反应组,比较两组发热时间、WBC、中性粒细胞绝对值、CRP、PLT、ESR、血清钠、血清钾、ALB、细胞因子;通过多因素logistic回归分析,评价IVIG无反应的独立危险因素。结果IVIG无反应患儿45例,占11.5%。KD急性期,IVIG敏感组中性粒细胞绝对值[8.36(5.88,11.08)×10^9/L比9.27(7.49,14.99)×10^9/L]、IFN-γ[1.17(0.40,2.12)pg/ml比1.86(0.67,4.34)pg/ml]、IL-10[5.20(3.24,8.97)pg/ml比8.02(5.19,14.03)pg/ml]、IL-6[19.38(11.12,41.60)pg/ml比87.41(52.99,172.33)pg/ml]低于IVIG无反应组,ALB高于IVIG无反应组[36.00(33.10,38.33)mg/L比33.90(30.35,36.35)mg/L],差异均有统计学意义(P<0.05)。多因素logistic回归分析显示,中性粒细胞绝对值的OR值(95%CI)为1.169(1.001~1.365),IFN-γ的OR值(95%CI)为1.248(1.065~1.464),IL-6的OR值(95%CI)为1.105(1.002~1.208),均是IVIG无反应的独立危险因素(P<0.05),数值越高,IVIG无反应风险越高;ALB的OR值(95%CI)为0.895(0.808~0.991),是IVIG无反应的保护性因素(P<0.05),ALB越高,IVIG无反应风险越低。结论中性粒细胞绝对值、IFN-γ、IL-6是IVIG无反应的独立危险因素(P<0.05),ALB是IVIG无反应的保护性因素(P<0.05)。对首次IVIG治疗无效的高危患儿,应尽早再次IVIG或应用二线治疗药物,以改善预后。

Objective To analyze the risk factors of non-response to intravenous immunoglobin(IVIG)in Kawasaki disease(KD).Methods The medical records of 391 children diagnosed with KD in Beijing Children’s Hospital,Capital Medical University,were reviewed.All the patients were divided into two groups according to their response to the first high dose IVIG,sensitive group and non-response group.The fever duration,WBC,neutrophil absolute value,CRP,PLT,ESR,serum sodium,serum potassium,ALB and cytokines were compared between the two groups.Logistic regression analysis was conducted to determine the independent risk factors of non-response to IVIG.Results There were 45 children who had non-response to IVIG.The incidence was 11.5%.In the acute stage,the data as follows in the sensitive group were significantly lower than those in the non-response group(all P<0.05),neutrophil absolute value[8.36(5.88,11.08)×10^9/L vs.9.27(7.49,14.99)×10^9/L],IFN-γ[1.17(0.40,2.12)pg/ml vs.1.86(0.67,4.34)pg/ml],IL-10[5.20(3.24,8.97)pg/ml vs.8.02(5.19,14.03)pg/ml],IL-6[19.38(11.12,41.60)pg/ml vs.87.41(52.99,172.33)pg/ml].ALB in the sensitive group was significantly higher[36.00(33.10,38.33)mg/L vs.33.90(30.35,36.35)mg/L]than that in the non-response group(P<0.05).Logistic regression analysis showed that the OR(95%CI)of factors were as follows:neutrophil absolute value was 1.169(1.001-1.365),IFN-γwas 1.248(1.065-1.464),IL-6 was 1.105(1.002-1.208),all of them were independent risk factors for IVIG non-response(P<0.05).The higher value,the higher risk of non-response to IVIG;ALB was 0.895(0.808-0.991),which was the protective factor of IVIG nonresponse(P<0.05).The higher ALB,the lower risk of non-respons to IVIG.Conclusions Neutrophil absolute value,IFN-γ,IL-6 are the independent risk factors for IVIG non-response(P<0.05).ALB is the protective factor of IVIG non-response(P<0.05).In order to improve the prognosis of KD patients who have non-response to IVIG,IVIG should be reused or second-line treatment should be used as soon as possible.