Identifying children with Kawasaki disease at high risk for coronary aneurysms

Abstract

Kawasaki disease, a childhood vasculitis manifested by symptoms of high fever, mucocutaneous inflammation, and unilateral cervical adenopathy, can cause lasting damage to the coronary arteries, and more rarely, other medium-sized muscular arteries. Most children respond well to prompt treatment with high-dose intravenous immunoglobulin (IVIG). However, coronary artery aneurysms, defined by internal lumen diameter at least 2.5 SDs above the population mean for body surface area (Z≥2.5), occur in ∼25% of affected children and are the principal cause of long-term morbidity and mortality in Kawasaki disease. Several risk scores have attempted to predict which children are likely to develop coronary aneurysms. In previous studies in North America, baseline risk factors for coronary artery aneurysms on echocardiography performed 2-8 weeks after Kawasaki disease onset have included higher coronary artery dimensions on baseline echocardiography, IVIG resistance (the persistence or recrudescence of fever after a single dose of IVIG), young age (<12 months or <6 months depending upon the risk score), Asian race, and late diagnosis and treatment with IVIG. Japanese risk scores based upon clinical and laboratory variables have been highly accurate in predicting IVIG resistance, one of the strongest risk factors for coronary artery aneurysms. In Japanese children predicted to have high risk of IVIG resistance, primary adjunctive therapy with corticosteroids or cyclosporine has been shown in randomized clinical trials to reduce the incidence of coronary artery aneurysms. However, Japanese children predicted to be at low risk for aneurysms on the basis of laboratory measures may still develop coronary abnormalities. Understanding the risk factors for aneurysm development thus requires further refinement. In this volume of The Journal, Iio et al analyze independent risk factors for development of coronary artery aneurysms in 1632 Japanese children with Kawasaki disease who were predicted to be at low risk for resistance to primary IVIG treatment. In this low-risk group, 5.5% of patients developed any coronary artery aneurysms and 1%, medium or large coronary aneurysms. In multivariable analysis, baseline coronary artery Z score >2.5, age <12 months at fever onset, and IVIG resistance were independent risk factors for diagnosis of coronary artery aneurysms on echocardiography one month after disease onset. Among these risk factors, coronary artery Z score ≥2.5 was most strongly associated with aneurysm development. Taken together with previous literature, these data suggest that enlarged coronary Z scores measured on baseline echocardiography can be used to select children at high risk for subsequent coronary artery aneurysms and thus who may benefit from adjunctive therapy. The study of Iio et al adds weight to the concept that a high-risk cohort for randomized clinical trials of primary adjunctive therapy in Kawasaki disease may be most simply selected through findings on baseline echocardiography. The ability to select such a high-risk cohort is critical to the design of trials to answer remaining questions in Kawasaki disease therapy: In children of all races and ethnicities, who should receive treatment with adjunctive therapies? How do antiinflammatory therapies compare with each other, and what is the cost/benefit ratio for these therapies? Article page 158 Risk Factors of Coronary Artery Aneurysms in Kawasaki Disease with a Low Risk of Intravenous Immunoglobulin Resistance: An Analysis of Post RAISEThe Journal of PediatricsVol. 240PreviewTo detect risk factors of coronary artery aneurysm (CAA) development in patients with Kawasaki disease determined to have a low risk for resistance to primary intravenous immunoglobulin (IVIG) treatment based on the Kobayashi score. Full-Text PDF