Interindividual Variability in IVIG Response in Kawasaki Disease: Pharmacokinetics, Immunology, and Clinical Outcomes

Abstract

Kawasaki disease (KD) is an acute, self-limited vasculitis of childhood and the leading cause of acquired heart disease in children in developed countries. Timely administration of high-dose intravenous immunoglobulin (IVIG) substantially reduces the incidence of coronary artery aneurysms, transforming the natural history of the disease. Nevertheless, approximately 10–20% of patients exhibit resistance to initial therapy, characterized by persistent or recrudescent fever and ongoing systemic inflammation. This subgroup is at markedly increased risk for coronary artery abnormalities, myocardial ischemia, and long-term cardiovascular morbidity. Interindividual variability in IVIG response arises from complex interactions among pharmacokinetic factors, immune activation pathways, genetic susceptibility, endothelial biology, and disease severity at presentation. Increasing evidence suggests that KD represents a heterogeneous spectrum of inflammatory phenotypes rather than a single uniform disorder, challenging traditional treatment paradigms based on standardized dosing. This comprehensive narrative review synthesizes current understanding of determinants of IVIG responsiveness, integrating insights from immunology, pharmacology, genetics, and clinical cardiology. Particular emphasis is placed on mechanisms of coronary artery injury, biomarkers of resistance, predictive models, and emerging targeted therapies. A deeper understanding of variability in treatment response is essential for developing personalized therapeutic approaches aimed at preventing irreversible cardiovascular damage and improving long-term outcomes.