Salicylate for the treatment of Kawasaki disease in children

 

Abstract

Background

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. Salicylate (acetyl salicylate acid (ASA), aspirin) and intravenous immunoglobulin (IVIG) are widely used for this purpose. Salicylate is largely otherwise avoided in children because of concerns about serious side effects, particularly the risk of Reyes syndrome.

Objectives

The objective of this review was to evaluate the effectiveness of salicylate in treating and preventing cardiac consequences of Kawasaki disease in children.

Search methods

For this update the Cochrane Peripheral Vascular Diseases Group searched their trials register (last searched January 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2009). The authors searched MEDLINE (January 1966 to July 2006), EMBASE (January 1980 to July 2006), and CINAHL (1982 to July 2006), and reference list of articles. In addition, we contacted experts in the field.

Selection criteria

Randomised controlled trials (RCTs) of salicylate to treat Kawasaki disease in children were eligible for inclusion.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information.

Main results

We found one trial involving 102 children which was described as randomised, but it was not possible to confirm the method of treatment allocation. A second comparative study, possibly with a randomised treatment allocation, was also identified. The one randomised trial reported no association between the addition of ASA to IVIG treatment on the rate of coronary artery abnormalities at follow up, but with wide confidence limits. The second, possibly randomised trial did demonstrate a reduction in duration of fever with high dose ASA compared with low dose ASA, but was insufficiently powered to establish the effect on coronary artery abnormalities at follow up.

Authors' conclusions

Until good quality RCTs are carried out, there is insufficient evidence to indicate whether children with Kawasaki disease should continue to receive salicylate as part of their treatment regimen.

 

Plain language summary

Salicylate for treating Kawasaki disease in children and to prevent long-term cardiac abnormalities

Kawasaki disease is an inflammation of the blood vessels (vasculitis) which predominantly affects young children, under the age of five years. It was first recognised in children in Japan and is the most common cause of acquired heart disease in children in developed countries. Kawasaki disease can be difficult to diagnose because it has similar symptoms to many common childhood infections. The most important complication of Kawasaki disease is caused by inflammation of the heart (coronary) arteries supplying blood to the heart muscle. This may lead to immediate heart problems and damage to the coronary arteries can also have long-term effects. Salicylate (acetyl salicylate acid, aspirin) and intravenous immunoglobulin (IVIG) are widely used to treat Kawasaki disease, although salicylate is generally avoided in children because of concerns about serious side effects, particularly the risk of Reye's syndrome causing swelling of the brain and liver.

The review authors identified only one randomised controlled trial, from Japan, reported in 1991. A total of 102 children were randomised to receive IVIG with or without salicylate. There was no clear benefit of adding salicylate to immunoglobulin treatment on the rate of coronary artery abnormalities observed, up to 30 days. The spread of findings was wide and could include a beneficial effect of salicylate. There are theoretical grounds for using salicylate to prevent damage to the coronary arteries. However, there are concerns that aspirin use in children to treat fever can have adverse effects and children with Kawasaki disease who are treated with immunoglobulins have a very low rate of coronary artery abnormalities.

 

摘要

背景

使用水楊酸(salicylate)治療幼童川崎氏症(Kawasaki disease)

川崎氏症是開發中國家幼童最常見的一種後天性心臟疾病，供給心臟的冠狀動脈可能會因為川崎氏症受到破壞。即時診斷的好處是可以早期治療來預防這種併發症，水楊酸(acetyl salicylate acid (ASA), aspirin)和靜脈注射免疫球蛋白(IVIG)是廣泛使用於這個目的的藥物。但是水楊酸對於幼童可能會產生嚴重的副作用，特別是會有雷氏症候群(Reyes syndrome.)這個副作用的風險，所以一般會盡量避免使用水楊酸。

目標

本回顧的目的在於評估水楊酸對於治療和預防川崎氏症幼童心臟疾病的效果。

搜尋策略

Cochrane Peripheral Vascular Disease Group 搜尋其試驗登錄中心(最後一次搜尋為2006年7月)及 Cochrane Central Register of Controlled Trials (CENTRAL) (最後一次搜尋為 Issue 3, 2006年)。我們搜尋MEDLINE(1966年1月−2006年7月)、EMBASE(1980年1月∼2006年7月)，以及CINAHL (1982年7月∼2006年)，以及文章的參考文獻清單。此外我們還與該領域的專家聯繫。

選擇標準

使用水楊酸治療川崎氏症幼童的隨機性對照試驗都可被納入。

資料收集與分析

有2名作者分別獨立的評估試驗品質和萃取數據，連繫研究作者取得其他資訊。

主要結論

我們發現了1個包含有102名幼童的隨機性試驗，但是並無法確認治療方法的分配方式。第2個比較性研究，可能是使用隨機治療的分配。第1個隨機性試驗提到，使用水楊酸和 IVIG 在後續追蹤期間，對於冠狀動脈的異常發生率並沒有關連性，但是其信心區間較寬廣。第2個可能是隨機性試驗，顯示使用高劑量水楊酸，比起使用低劑量水楊酸，發燒之時間有減短。但是並沒有足夠的效力能證實在追蹤期間對於冠狀動脈異常化的影響。

作者結論

在具有良好品質的隨機性對照試驗出現前，並沒有足夠的證據可以指出川崎氏症的幼童是不是應該持續使用水楊酸作為其療程的一部分。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

使用水楊酸治療幼童的川崎氏症和預防長期的心臟異常。 川崎氏症是一種血管的發炎反應(血管炎，vasculitis)，主要是對幼童產生影響，特別是5歲以下的幼童。第一次發現這個疾病是在日本，是開發中國家幼童最常見的後天性心臟疾病。川崎氏症的診斷並不容易，因為其症狀與許多幼童常見的感染症狀十分相似。 川崎氏症最重要的併發症是造成供給心肌血液的心臟(冠狀的)動脈發炎，這可能會引發直接性心臟問題，且對於冠狀動脈的破壞也會造成長期性的影響。水楊酸(acetyl salicylate acid, aspirin)和靜脈注射免疫球蛋白(IVIG)已經廣泛的用於治療川崎氏症，但是幼童通常會避免使用水楊酸，因為水楊酸可能會產生嚴重的副作用，特別是造成腦部和肝臟水腫的雷氏症候群之風險。本回顧的作者確認了一個來自日本，並在1991年提出的隨機性對照試驗，其中共納入102名幼童，在使用IVIG時隨機分配使用或不使用水楊酸，使用水楊酸合併IVIG並沒有辦法在30天內使冠狀動脈異常的比例減少。這些發現的延伸是廣泛的，且包括水楊酸有功效。使用水楊酸來預防冠狀動脈的破壞有理論背景，但是對於使用水楊酸治療幼童發燒可能會有不良事件的疑慮。使用IVIG來治療川崎氏症可以產生相當低的機率的冠狀動脈異常之效果。