川崎病初始剂量丙种球蛋白治疗敏感或无反应的相关因素分析

Related factors for sensitivity or nonresponse to initial dose of gamma globulin in children with Kawasaki disease

目的探讨影响川崎病(KD)患儿应用初始剂量丙种球蛋白(IVIG)治疗敏感或者无反应的相关因素。方法选取2016年1月至2017年1月在重庆医科大学附属永川医院就诊的KD患儿120例进行回顾性分析,根据研究对象的临床治疗情况及其反应分为无反应组和敏感组。将无反应组与敏感组患儿的临床表现、实验室检查的各项指标和心脏超声影像学特征进行比较,应用Logistic回归分析两组间存在明显差异的指标,确定独立相关因素,并做受试者工作特征(ROC)曲线,对初始剂量IVIG治疗无反应的参考指标进行观察。结果敏感组95例(79.17%),无反应组25例(20.83%)。无反应组超高热比例较敏感组明显增高,差异具有统计学意义(χ~2=27.131,P<0.05);与敏感组比较,无反应组发生冠状动脉病变的概率明显升高,差异具有统计学意义(χ~2=24.262,P<0.05);初始剂量IVIG 2g^(-1)·kg^(-1)·d^(-1)单次给药患儿IVIG无反应的发生率明显高于每次1g^(-1)·kg^(-1)·d^(-1)分2次给药者,差异有统计学意义(χ~2=5.502,P<0.05),但冠状动脉病变的发生率比较差异无统计学意义(χ~2=0.674,P>0.05)。与敏感组比较,无反应组的C反应蛋白(CRP)、血小板(PLT)水平、中性粒细胞(N)比例和白细胞(WBC)计数均明显升高,而血清清蛋白(ALB)水平则无反应组较敏感组明显降低,差异均有统计学意义(t值分别为6.259、2.244、2.330、2.085、3.701,均P<0.05);多因素Logistic回归分析表明ALB水平降低、CRP水平及N比例升高是初始剂量IVIG治疗无反应的独立危险因素(OR值分别为0.781、1.111、1.175,均P<0.05);经ROC曲线下面积计算得出ALB、CRP和N比例可作为初始剂量IVIG治疗无反应有价值的预测指标,临界值分别为33.11g/L、78.5mg/L和0.72。结论当KD患儿出现ALB≤33.11g/L或CRP≥78.5mg/L、N比例≥0.72中任意一种情况时提示发生初始剂量IVIG治疗无反应的可能性升高。

Objective To explore the related factors for sensitivity or nonresponse to initial dose of intravenous immune globulin（IVIG）in children with Kawasaki disease（KD）.Methods Retrospective analysis was performed on clinical data of 120 children with KD who visited Yongchuan Hospital Affiliated to Chongqing Medical University from January 2016 to January 2017.Patients were divided into sensitive group and unresponsive group according to clinical treatment and their responses.The clinical manifestations,various indexes of laboratory examination and cardiac ultrasonographic image of children in sensitive group and unresponsive group were compared.Indexes with obvious difference in two groups were analyzed by Logistic regression analysis to determine independent related factors.In order to observe reference indexes indicating unresponsive to IVIG,a receiver operating characteristic（ROC）curve was made.Results There were 95 cases（79.17%）in sensitive group and 25 cases（20.83%）in unresponsive group.Hyperthermia rate in unresponsive group was greatly higher than that in sensitive group,and difference was statistically significant（χ~2=27.131,P〈0.05）.Probability of coronary artery disease in unresponsive group was higher than that in sensitive group with significant difference（χ~2=24.262,P〈0.05）.Non response rate in patients treated with single administration of IVIG 2 g/（kg·d）was higher than that in patients treated with two times of administration of IVIG 1 g/（kg·d）,and difference had statistical significance（χ~2=5.502,P〈0.05）,but incidence of coronary artery disease was not significant（χ~2=0.674,P〈0.05）.Levels of C-reactive protein（CRP）,platelet（PLT）,neutrophil（N）ratio and white blood cell（WBC）count in unresponsive group were significantly higher than those in sensitive group,while serum albumin（ALB）level was significantly lower with significant differences（t value was 6.259,2.244,2.330,2.085 and 3.701,respectively,all P〈0.05）.Multivariate Logistic regression analysis showed that decrease of ALB level,increase of CRP level and N ratio were independent risk factors for non response to initial dose IVIG treatment（OR value was 0.781,1.111 and 1.175,respectively,all P〈0.05）.According to calculated area under ROC curve,percentages of ALB,CRP and N could be effective predictors to non response to initial dose IVIG treatment,and critical values were 33.11 g/L,78.5 mg/L and 0.72,respectively.Conclusion Appearance of any of three situations including ALB≤33.11 g/L,CRP≥78.5 mg/L or N≥0.72 indicates high probability of non response to initial dose IVIG.