Oates-Whitehead R M, Baumer J H, Haines L, Love S, Maconochie I K, Gupta A, Roman K, Dua J S, Flynn I
Research Division, Royal College of Paediatrics, 50 Hallam Street, London, UK, W1W 6DE.
Cochrane Database Syst Rev. 2003;2003(4):CD004000. doi: 10.1002/14651858.CD004000.
Kawasaki disease is the most common cause of acquired heart disease in children in developed countries. The coronary arteries supplying the heart can be damaged in Kawasaki disease. The principal advantage of timely diagnosis is the potential to prevent this complication with early treatment. Intravenous immunoglobulin (IVIG) is widely used for this purpose.
The objective of this review was to evaluate the effectiveness of IVIG in treating, and preventing cardiac consequences, of Kawasaki disease in children.
Electronic searches of the Cochrane Peripheral Vascular Disease Group Specialised Register, CENTRAL, MEDLINE, EMBASE, and CINAHL were performed (last searched April 2003). We also searched references from relevant articles and contacted authors where necessary. In addition we contacted experts in the field for unpublished works.
Randomised controlled trials of intravenous immunoglobulin to treat Kawasaki disease were eligible for inclusion.
Fifty-nine trials were identified in the initial search. On careful inspection only sixteen of these met all the inclusion criteria. Trials were data extracted and assessed for quality by at least two reviewers. Data were combined for meta-analysis using relative risk ratios for dichotomous data or weighted mean difference for continuous data. A random effects statistical model was used.
The meta-analysis of IVIG versus placebo, including all children, showed a significant decrease in new coronary artery abnormalities (CAAs) in favour of IVIG, at thirty days RR (95% CI) = 0.74 (0.61 to 0.90). No statistically significant difference was found thereafter. A subgroup analysis excluding children with CAAs at enrollment also found a significant reduction of new CAAs in children receiving IVIG RR (95%) = 0.67 (0.46 to 1.00). There was a trend towards benefit from IVIG at sixty days (p=0.06). Results of dose comparisons showed a decrease in the number of new CAAs with increased dose. The meta-analysis of 400 mg/kg/day for five days versus 2 gm/kg in a single dose showed statistically significant reduction in CAAs at thirty days RR (95%) = 4.47 (1.55 to 12.86). This comparison also showed a significant reduction in duration of fever with the higher dose. There was no statistically significant difference noted between different preparations of IVIG. There was no statistically significant difference of adverse effects in any group.
REVIEWER'S CONCLUSIONS: Children fulfilling the diagnostic criteria for Kawasaki disease should be treated with IVIG (2 gm/kg single dose) within 10 days of onset of symptoms.
川崎病是发达国家儿童后天性心脏病最常见的病因。川崎病可损害供应心脏的冠状动脉。及时诊断的主要好处是有可能通过早期治疗预防这种并发症。静脉注射免疫球蛋白（IVIG）广泛用于此目的。
本综述的目的是评估IVIG治疗儿童川崎病及预防心脏后果的有效性。
对Cochrane外周血管疾病组专业注册库、Cochrane系统评价数据库、医学索引数据库、荷兰医学文摘数据库和护理学与健康领域数据库进行了电子检索（最后检索时间为2003年4月）。我们还检索了相关文章的参考文献，并在必要时联系了作者。此外，我们联系了该领域的专家以获取未发表的研究成果。
静脉注射免疫球蛋白治疗川崎病的随机对照试验符合纳入条件。
在初步检索中识别出59项试验。经仔细检查，其中只有16项符合所有纳入标准。试验数据由至少两名评价者提取并评估质量。对于二分数据，使用相对危险度比进行合并以进行Meta分析；对于连续数据，使用加权均数差进行合并以进行Meta分析。采用随机效应统计模型。
对IVIG与安慰剂进行的Meta分析，纳入所有儿童，结果显示新的冠状动脉异常（CAA）显著减少，支持IVIG，在30天时RR（95%CI）=0.74（0.61至0.90）。此后未发现统计学上的显著差异。排除入组时患有CAA的儿童的亚组分析也发现，接受IVIG治疗的儿童中新发CAA显著减少，RR（95%）=0.67（0.46至1.00）。在60天时，IVIG有获益趋势（p=0.06）。剂量比较结果显示，随着剂量增加，新发CAA数量减少。对5天内每日400mg/kg与单次剂量2g/kg进行的Meta分析显示，在30天时CAA有统计学上的显著减少，RR（95%）=4.47（1.55至12.86）。该比较还显示，较高剂量组发热持续时间显著缩短。不同制剂的IVIG之间未发现统计学上的显著差异。任何组中不良反应均无统计学上的显著差异。
符合川崎病诊断标准的儿童应在症状出现后10天内接受IVIG（单次剂量2g/kg）治疗。
