What is the efficacy of corticosteroid therapy in Kawasaki disease?
First described in 1967 in Japan, Kawasaki disease (KD), or mucocutaneous lymph node syndrome, is an acute systemic vasculitis of unclear etiology which primarily affects infants and children. Of significant clinical concern, 30%-50% of untreated patients develop acute coronary artery dilatation, and about one fourth progress to serious coronary artery abnormalities (CAA) such as aneurysm and ectasia.1,2 These patients have a higher risk of long-term complications, such as coronary artery thrombus, myocardial infarction, and sudden death.3 KD is typically treated with a combination of intravenous immunoglobulin (IVIG) and aspirin, which reduces the risk of CAA.1 However, more than 20% of cases are resistant to this conventional therapy and have higher risk of CAA than nonresistant patients.4 Corticosteroids have been suggested as therapy in KD, as the anti-inflammatory effect is useful for many other vasculitides, but studies to date have had conflicting results. This study was performed to comprehensively evaluate the effect of corticosteroids in KD as initial or rescue therapy (after failure to respond to IVIG).
Systematic review and meta-analysis.
The population of interest was children diagnosed with KD. The intervention of interest was treatment with adjunctive corticosteroids either as initial or rescue therapy. Comparisons were made between the corticosteroids group and the conventional therapy (IVIG) group. Outcome measurements included the incidence of CAA (primary outcome), duration until defervescence, and adverse events. IVIG resistance was defined as persistent or recurrent fever lasting (or relapsed within) 24-48 hours after the initial IVIG treatment.
A total of 681 articles were initially retrieved, and after exclusions, 16 comparative studies were enrolled for meta-analysis. In these studies, a total of 2,746 cases were involved, with 861 in the corticosteroid group and 1,885 in the IVIG group. Ten studies used corticosteroids as initial treatment (comparing this plus IVIG versus IVIG therapy alone), and six used steroids as rescue treatment after initial IVIG failure (comparing corticosteroids with additional IVIG therapy). Four studies enrolled patients with KD who were predicted to have high risk of IVIG resistance, based on published scoring systems. All patients in the studies received oral aspirin.
Overall, this meta-analysis found that adding corticosteroid therapy was associated with a relative risk reduction of 58% in CAA (odds ratio, 0.424; 95% confidence interval, 0.270-0.665; P less than .001). Further analysis showed that the longer the duration of illness prior to corticosteroids, the less of a treatment effect was noticed. The studies using steroids as initial adjunctive therapy had duration of illness 4.7 days prior to treatment, and showed an advantage, compared with IVIG alone, while studies using steroids as rescue therapy had a longer duration of illness prior to steroid therapy (7.2 days), and did not show significant benefit, compared with additional IVIG. In analyzing patients predicted to be at high risk of IVIG resistance at baseline, addition of corticosteroids with IVIG as initial therapy showed a significantly lower risk of CAA development (relative risk reduction of 76%) versus IVIG alone (OR, 0.240; 95% CI, 0.123-0.467; P less than .001). As a secondary outcome, the use of adjunctive corticosteroid therapy was associated with a quicker resolution of fever, compared with IVIG alone (0.66 days vs. 2.18 days). There was no significant difference in adverse events between the two groups.
Although this is the most comprehensive study of corticosteroids in KD, there are some limitations. High-risk patients were found to receive the greatest benefit, but the predictive ability of published scoring systems have not been optimized or generalized to all populations. Most of the studies included in this review were conducted in Japan, so it is uncertain if the results are applicable to other regions. Also, the selection of corticosteroids and treatment regimens were not consistent between studies.
This study suggests that corticosteroids combined with IVIG as initial therapy for KD showed a more protective effect against CAA, compared with conventional IVIG therapy, and the efficacy was more pronounced in the high-risk patient group.
Chen S, Dong Y, Kiuchi MG, et al. Coronary Artery Complication in Kawasaki Disease and the Importance of Early Intervention: A Systematic Review and Meta-analysis. JAMA Pediatr. 2016;170(12):1156-1163.
1. Newburger JW, Takahashi M, Gerber MA, et al. Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease. Council on Cardiovascular Disease in the Young; American Heart Association; American Academy of Pediatrics: diagnosis, treatment, and long-term management of Kawasaki disease. Circulation. 2004;110:2747-71.
2. Daniels LB, Tjajadi MS, Walford HH, et al. Prevalence of Kawasaki disease in young adults with suspected myocardial ischemia. Circulation. 2012;125(20):2447-53.
3. Gordon JB, Kahn AM, Burns JC. When children with Kawasaki disease grow up: myocardial and vascular complications in adulthood. J Am Coll Cardiol. 2009;54(21):1911-20.
4. Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008;153(1):117-21.
Dr. Galloway is a pediatric hospitalist at Sanford Children’s Hospital in Sioux Falls, S.D., assistant professor of pediatrics at the University of South Dakota Sanford School of Medicine, and vice chief of the division of hospital pediatrics at USD SSOM and Sanford Children’s Hospital.