Kuo Ho-Chang, Lo Mao-Hung, Hsieh Kai-Sheng, Guo Mindy Ming-Huey, Huang Ying-Hsien
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, 83301.
Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, 83301.
PLoS One. 2015 Dec 10;10(12):e0144603. doi: 10.1371/journal.pone.0144603. eCollection 2015.
Kawasaki disease (KD) is also known as multiple mucocutaneous lymph node syndrome of systemic vasculitis and is a leading cause of coronary artery lesions (CAL) in childhood. Intravenous immunoglobulin (IVIG) has been proven to effectively reduce the incidence of CAL, but the role and effect dose of aspirin in KD is still unclear. Moreover, overt bleeding and anemia are associated with the use of aspirin, and anemia is common in patients with KD. Thus, the aim of this study was conducted to compare the treatment efficacy, degree of anemia and inflammation, and changes in serum hepcidin in children who received a combination of high-dose aspirin and IVIG in the acute stage of KD, and those who received IVIG alone.
KD patients from two medical centers were retrospectively analyzed from 1999-2009. All patients were initially treated with a single dose of IVIG (2 g/kg) as the standard care of treatment. In group 1, high-dose aspirin was prescribed (> 30 mg/kg/day) until the fever subsided, and then low-dose aspirin (3-5 mg/kg/day) was prescribed until all the inflammation signs had resolved. In group 2, low-dose aspirin was prescribed without high-dose aspirin. Laboratory data were collected for analysis in both groups.
A total of 851 KD patients (group 1, N = 305, group 2, N = 546) were enrolled in this study. There were no significant differences between group 1 and group 2 in terms of gender (p = 0.51), IVIG resistance rate (31/305 vs. 38/546, p = 0.07), CAL formation (52/305 vs. 84/546, p = 0.67), and duration of hospitalization (6.3 ± 0.2 vs. 6.7 ± 0.2 days, p = 0.13). There were also initially no significant differences in total white blood cell count, hemoglobin level, platelet count, and CRP before IVIG treatment between groups (all p>0.1). After IVIG treatment, group 1 had significantly lower levels of hemoglobin (p = 0.006) and higher CRP (p<0.001) as well as a smaller decrease in CRP level (p = 0.012). Furthermore, there was also a higher serum level of hepcidin and a delayed decrease in hepcidin level after receiving IVIG in group 1 (p = 0.04 and 0.02, respectively).
These results provide evidence demonstrating that high-dose aspirin in the acute phase of KD does not confer any benefit with regards to inflammation and it does not appear to improve treatment outcomes. Therefore, high-dose aspirin is unnecessary in acute phase KD.
川崎病(KD)又称系统性血管炎的多黏膜皮肤淋巴结综合征,是儿童冠状动脉病变(CAL)的主要病因。静脉注射免疫球蛋白(IVIG)已被证明可有效降低CAL的发生率,但阿司匹林在KD中的作用和有效剂量仍不清楚。此外,明显出血和贫血与阿司匹林的使用有关,且贫血在KD患者中很常见。因此,本研究旨在比较在KD急性期接受高剂量阿司匹林和IVIG联合治疗的儿童与仅接受IVIG治疗的儿童的治疗效果、贫血和炎症程度以及血清铁调素的变化。
回顾性分析了1999年至2009年来自两个医疗中心的KD患者。所有患者最初均接受单剂量IVIG(2 g/kg)作为标准治疗。在第1组中,给予高剂量阿司匹林(>30 mg/kg/天)直至发热消退,然后给予低剂量阿司匹林(3 - 5 mg/kg/天)直至所有炎症体征消失。在第2组中,仅给予低剂量阿司匹林,不使用高剂量阿司匹林。收集两组的实验室数据进行分析。
本研究共纳入851例KD患者(第1组,N = 305;第2组,N = 546)。第1组和第2组在性别(p = 0.51)、IVIG抵抗率(31/305 vs. 38/546,p = 0.07)、CAL形成(52/305 vs. 84/546,p = 0.67)和住院时间(6.3±0.2天 vs. 6.7±0.2天,p = 0.13)方面无显著差异。两组在IVIG治疗前的白细胞总数、血红蛋白水平、血小板计数和CRP水平最初也无显著差异(所有p>0.1)。IVIG治疗后,第1组的血红蛋白水平显著较低(p = 0.006),CRP水平较高(p<0.001),且CRP水平下降幅度较小(p = 0.012)。此外,第1组在接受IVIG后血清铁调素水平也较高,且铁调素水平下降延迟(分别为p = 0.04和0.02)。
这些结果提供了证据表明,KD急性期的高剂量阿司匹林在炎症方面没有任何益处,似乎也不能改善治疗结果。因此,KD急性期无需使用高剂量阿司匹林。