不同剂量静脉免疫球蛋白治疗川崎病的临床及免疫学效应比较

A comparative analysis of clinical and immunologic effectiveness of intravenous immunoglobulin at different doses in treatment of kawasaki disease

目的评价应用静脉注射免疫球蛋白(IVIG)的不同治疗方案治疗川崎病(KD)的临床疗效及免疫学效应。方法 232例KD患儿随机分为3组:IVIG 1g/kg×1次组,IVIG 1g/kg×2次组,IVIG 2g/kg×1次组。对三种治疗方法的疗效进行前瞻性对比研究,观察患儿总热程、退热时间、黏膜充血、手足肿胀和颈部淋巴结肿大消退时间,监测外周血白细胞计数(WBC)、C反应蛋白(CRP)、血沉(ESR)、血浆纤维蛋白原(FIB)、冠状动脉病变(CAL)恢复情况,以及血清免疫球蛋白(Ig)、T、B淋巴细胞、自然杀伤(NK)细胞变化情况,并对治疗前后组内结果、治疗后组间结果进行比较。结果三组患儿治疗后的WBC、FIB、CRP、CD3、CD4、CD19细胞百分比、CD4/CD8较治疗前显著降低(P均<0.05),IgG、CD8、NK细胞百分比较治疗前显著升高(P均<0.05),ESR、IgA、IgM与治疗前比较,差异无统计学意义(P均>0.05);三组患儿治疗前的CAL发生率、WBC、FIB、CRP水平、CD3、CD4、CD19、CD8、NK细胞百分比、IgG水平、CD4/CD8差异无统计学意义(P均>0.05);治疗后三组患儿的临床症状恢复时间、CAL发生率、WBC、FIB、CRP水平、CD3、CD4、CD19、CD8、NK细胞百分比、CD4/CD8差异亦无统计学意义(P均>0.05);治疗后的IgG水平三组间差异有统计学意义,其中IVIG 1g/kg×2次组及IVIG 2g/kg×1次组均高于IVIG 1g/kg×1次组(P<0.05),IVIG 1g/kg×2次组与IVIG 2g/kg×1次组的差异无统计学意义(P>0.05)。结论 IVIG 1g/kg×1次治疗KD与IVIG 1g/kg×2次及IVIG 2g/kg×1次治疗的临床疗效及免疫学效应相当,其对冠状动脉的近期及远期保护效应相当,按照效益/价值比原则,IVIG 1g/kg×1次的治疗方法值得推荐。

Objective To evaluate the clinical and immunologic effectiveness of intravenous immunoglobulin （IVIG） at different doses in treatment of kawasaki disease （KD）. Methods A total of 232 children with KD were enrolled in the study, and randomly divided into three groups, IVIG 1 g/kg×1, IVIG 1 g/kg×2, and IVIG 2 g/kg× 1. Prospective comparative analysis was made of the clinical and immunologic effectiveness of the three treatments. The occurrence and restoration of coronary artery lesion （CAL） as well as the clinical and laboratory indexes including total duration of fever, fever clearance time, mucous mem- brane hyperemia, extremity swell, cervical lymphadenopathy, white blood cells count （WBC）, C reactive protein （CRP）, erythro- cyte sedimentation rate （ESR）, fibrinogen （FIB）, immunoglobulin （Ig）, T lymphocyte subsets, natural killer cells （NK cells） and B cells were observed. The levels of T lymphocyte subsets, NK cells and B cells were analyzed by flow cytometry. Results In the three groups, the levels of WBC, FIB, CRP, CD3, CD4, and CD19 significantly decreased after treatment as compared with those before treatment （P〈0.05）, while the levels of IgG, CD8, and NK were higher after treatment than those before treatment （P〈0.05）. The ESR, IgA and IgM values were not different between after and before treatment （P〉0.05）. There were no differences in the occurrence rate of CAL, the levels of WBC, FIB, CRP, CD3, CD4, CD19, CD8, NK, IgG and the ratio of CD4/CD8 before treat- ment between the three groups （P〉0.05）. After treatment, the duration of clinical symptoms, the occurrence rate of CAL, the levels of WBC, FIB, CRP, CD3, CD4, CD19, CDS, NK and the ratio of CD4/CD8 were not different among three groups （P〉0.05）,while the level of IgG was different （P〈0.05）. The level oflgG was higher in the IVIG 1 g/kg×2 group than that in IVIG 1 g/kg×1 group （P〈0.05）, and IgG level in IVIG 2 g/kg× 1 group was higher than that in group IVIG 1 g/kg× 1 （P〈0.05）, but the difference between IVIG 1 g/kg×2 group and IVIG 2 g/kg× 1 group was not different （P〉0.05）. Conclusions The clinical and immunologic effectiveness of these three therapeutic methods were not significantly different, and they have similar protective effects on CAL in short-term and long-term. Thus, according to the cost effectiveness principle, the therapeutic method of IVIG 1 g/kg× 1 can be recommended as the first choice.