Kawasaki Disease in Children: A Comprehensive Review
1. Alam Khan
2. Mohammad Abdulrahman
(1. Student, Tashkent Medical Academy, Tashkent, Uzbekistan
2. Student, Tashkent Medical Academy, Tashkent, Uzbekistan.)
Abstract
Kawasaki Disease (KD) is an acute, self-limiting systemic vasculitis predominantly affecting children under five years of age. It represents one of the leading causes of acquired heart disease in children in developed and developing nations alike. First described by Dr. Tomisaku Kawasaki in 1967, the disease has since been recognized worldwide as a critical pediatric condition due to its potential to cause coronary artery aneurysms if untreated. This article presents a detailed review of the current understanding of Kawasaki Disease, including its epidemiology, immunopathogenesis, clinical presentation, diagnostic criteria, and treatment modalities. Emphasis is placed on the role of early recognition and timely administration of intravenous immunoglobulin (IVIG) and aspirin therapy to prevent cardiovascular complications. The discussion further highlights recent insights into the genetic, infectious, and immunological mechanisms underlying KD and reviews advances in therapeutic interventions aimed at improving long-term outcomes.
Keywords
Kawasaki Disease, Vasculitis, Coronary Artery Aneurysm, Children, Immunopathogenesis, Intravenous Immunoglobulin
Introduction
Kawasaki Disease (KD) is an acute febrile illness of unknown etiology characterized by systemic vasculitis affecting medium-sized arteries. It primarily occurs in children younger than five years and is most prevalent in East Asian populations, particularly in Japan, Korea, and Taiwan. Although the exact cause remains elusive, current evidence supports a multifactorial pathogenesis involving genetic susceptibility, infectious triggers, and immune-mediated endothelial injury. The disease is of major clinical importance due to its potential to cause coronary artery lesions, which can result in long-term cardiovascular morbidity and mortality if untreated. KD has surpassed rheumatic fever as the most common cause of acquired heart disease in children in many countries. Early diagnosis and prompt initiation of IVIG and aspirin therapy are crucial to prevent coronary complications. This review aims to synthesize current knowledge on Kawasaki Disease in children, highlighting recent developments in understanding its pathophysiology, diagnostic methods, and treatment approaches.
Review of Literature
Since its first description in 1967, extensive research has been conducted to elucidate the etiology, clinical spectrum, and management of KD. Epidemiological studies from Japan and other parts of Asia revealed a significantly higher incidence among children of Asian descent, suggesting a genetic predisposition. The disease was initially misinterpreted as an infectious exanthem until the discovery of its vascular complications, notably coronary artery aneurysms. Subsequent investigations demonstrated immune activation involving cytokines, endothelial injury, and T-cell activation. Despite decades of research, the precise infectious agent responsible for triggering KD remains unidentified. However, advances in molecular genetics, such as genome-wide association studies (GWAS), have identified several loci associated with susceptibility, including ITPKC, CASP3, and FCGR2A genes. These discoveries have contributed to a better understanding of the disease’s immunopathogenic mechanisms and opened new avenues for targeted therapy.
Epidemiology and Etiology
Kawasaki Disease affects children worldwide, with the highest incidence reported in Japan (approximately 264 per 100,000 children under five years). In contrast, incidence rates are significantly lower in Europe and North America. Boys are affected more frequently than girls, and seasonal variations are observed, with peaks during winter and spring. The etiology remains unclear, but hypotheses suggest a viral or bacterial agent triggering an abnormal immune response in genetically predisposed individuals. Environmental and immunological factors, such as exposure to superantigens and cytokine dysregulation, also play roles. Familial clustering and higher concordance rates in monozygotic twins further support the contribution of genetic susceptibility.
Pathophysiology and Immunopathogenesis
The central pathological feature of KD is necrotizing vasculitis involving small and medium-sized arteries, particularly the coronary arteries. Inflammation progresses through three distinct phases: the acute necrotizing phase, the subacute/chronic inflammatory phase, and the convalescent healing phase. Endothelial cells become activated by inflammatory cytokines such as IL-6, TNF-α, and IL-1β, leading to vascular damage. Macrophages and activated T cells infiltrate the vessel wall, resulting in intimal proliferation and aneurysm formation. Genetic studies suggest dysregulation of calcium signaling pathways, apoptosis, and immune cell activation as central mechanisms. The persistent immune activation even after fever resolution may explain the chronicity of vascular inflammation observed in some patients.
Clinical Manifestations
Kawasaki Disease typically presents with high-grade fever lasting more than five days, accompanied by at least four of the following five principal features: bilateral non-exudative conjunctivitis, polymorphous rash, changes in the lips and oral cavity (strawberry tongue, fissured lips), changes in the extremities (erythema, edema, desquamation), and cervical lymphadenopathy. The disease progresses through three stages — acute, subacute, and convalescent. During the acute stage, systemic inflammation and irritability are prominent. The subacute stage, occurring after fever resolution, is characterized by peeling of the skin, thrombocytosis, and an increased risk of coronary artery aneurysm development. The convalescent stage marks the gradual normalization of laboratory parameters. Incomplete or atypical KD may occur, particularly in infants under six months, posing diagnostic challenges.
Diagnostic Criteria and Investigations
Diagnosis of KD is primarily clinical, based on the presence of prolonged fever and the characteristic mucocutaneous findings. Laboratory findings are nonspecific but supportive, including elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocytosis, anemia, and thrombocytosis. Echocardiography is the cornerstone of diagnostic evaluation to detect coronary artery abnormalities such as dilation or aneurysms. Additional imaging modalities like cardiac MRI and CT angiography are used in complex cases. The American Heart Association has outlined criteria for both complete and incomplete KD, emphasizing the importance of early recognition to prevent coronary complications.
Management and Therapeutic Approaches
The mainstay of treatment for Kawasaki Disease relies primarily on the administration of high-dose intravenous immunoglobulin (IVIG). This crucial therapy is typically administered at a dosage of 2 grams per kilogram (g/kg) of body weight, delivered as a single infusion over a period of 10 to 12 hours. For optimal effectiveness and to significantly reduce the risk of coronary artery complications, this treatment should be initiated ideally within the first 10 days of the onset of illness
Complications and Prognosis
If left untreated, KD carries a significant risk of developing coronary artery aneurysms (CAA), affecting approximately 20% to 25% of diagnosed patients. This is a severe cardiovascular complication involving the dilation of the coronary arteries. However, the introduction of timely intravenous immunoglobulin (IVIG) therapy dramatically improves patient outcomes. Administering IVIG promptly reduces the probability of CAA formation to less than 5%, highlighting the therapeutic efficacy and necessity of this treatment. The overall prognosis is generally considered excellent for the vast majority of children who are able to receive early and appropriate treatment. Nevertheless, a subgroup of patients, specifically those who develop giant coronary aneurysms, face a continuing risk of long-term sequelae. These serious, persistent complications can include the formation of thrombosis (blood clots), the possibility of myocardial infarction (heart attack), and, tragically, an elevated risk of sudden death. Due to these persistent dangers, lifelong cardiology follow-up is strongly and specifically recommended for all patients who have developed giant coronary aneurysms.
Discussion
Kawasaki Disease remains a major diagnostic and therapeutic challenge in pediatric practice. Despite being recognized for over five decades, its etiology continues to elude researchers. Current research focuses on identifying the infectious triggers and immunogenetic factors contributing to disease susceptibility. Advances in imaging and laboratory diagnostics have enhanced early detection, while new biologic agents offer hope for refractory cases. There is growing interest in understanding the long-term vascular consequences of KD, as even children without apparent coronary involvement may exhibit endothelial dysfunction and increased cardiovascular risk in adulthood. Future directions include genetic screening, biomarker identification, and personalized immunomodulatory therapies.
Conclusion
Kawasaki Disease is a significant cause of acquired heart disease in children, with potential for serious coronary complications if not promptly recognized and treated. The disease’s multifactorial etiology and complex immune-mediated pathogenesis underscore the need for continued research and awareness among clinicians. Early diagnosis, timely administration of IVIG and aspirin, and long-term cardiac monitoring remain the cornerstones of management. Ongoing advancements in immunology and genetics hold promise for uncovering the underlying causes of KD and improving patient outcomes globally.
References
· American Heart Association. (2017). Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals. Circulation, 135(17), e927–e999.
· Kawasaki, T. (1967). Acute febrile mucocutaneous lymph node syndrome: clinical observation of 50 cases. Japanese Journal of Allergology, 16, 178–222.
McCrindle, B. W., Rowley, A. H., Newburger, J. W., et al. (2020).
· Kawasaki disease: a comprehensive review. The Lancet, 396(10263), 322–334.
Rowley, A. H., & Shulman, S. T. (2018). The epidemiology and pathogenesis of Kawasaki disease. Frontiers in Pediatrics, 6, 374.