Kawasaki Disease (KD) is an acute, self-limited vasculitis that primarily affects medium-sized arteries, with a predilection for coronary involvement.

Predominantly observed in children under five, it is now recognized as a leading cause of acquired heart disease in developed nations.

Despite decades of research, the etiology remains elusive, and diagnostic delays continue to increase the risk of coronary artery aneurysms (CAA).

Epidemiology and Emerging Global Trends

Recent surveillance from the American Heart Association (AHA, 2023) reported an uptick in KD incidence in East Asia and urban areas of North America. Japan continues to report the highest incidence, with over 300 per 100,000 children under 5 annually. In contrast, KD in sub-Saharan Africa remains underdiagnosed, possibly due to overlapping febrile illnesses and lack of awareness.

Multi-system Inflammatory Syndrome in Children (MIS-C), associated with SARS-CoV-2, has also raised questions about the immunologic overlap with atypical Kawasaki presentations. Dr. Jane C. Burns, a leading pediatric cardiologist at UC San Diego, recently stated, "The clinical resemblance of MIS-C to Kawasaki Disease underscores the complexity of the host immune response to viral triggers."

Pathogenesis: An Immune Firestorm in the Vascular Wall

Although the exact trigger remains unidentified, the prevailing hypothesis suggests an infectious agent precipitating an exaggerated immune response in genetically susceptible children. Genome-wide association studies have implicated polymorphisms in ITPKC, FCGR2A, and BLK genes, all involved in immune signaling. The cascade begins with endothelial activation, followed by infiltration of monocytes, neutrophils, and CD8+ T cells. These immune cells release cytokines such as IL-6, IL-1β, and TNF-α, leading to vascular damage. The most critical target: the coronary arteries.

Diagnostic Criteria and Atypical Variants

The diagnosis is clinical, based on persistent fever (≥5 days) plus four out of five principal features:

- Bilateral non-exudative conjunctivitis

- Polymorphous rash

- Cervical lymphadenopathy

- Changes in extremities (e.g., erythema, edema, desquamation)

- Mucosal changes (e.g., strawberry tongue, cracked lips)

Cardiac Complications: The Silent Progression

The primary threat of KD lies in its cardiovascular complications. Approximately 25% of untreated children develop coronary artery abnormalities, including aneurysms, stenoses, and thromboses. Early echocardiography is essential and should be repeated at 2 and 6 weeks after diagnosis.

Cardiac MRI is increasingly used for long-term surveillance, especially in adolescents, due to its ability to assess myocardial fibrosis and perfusion. Intravascular ultrasound (IVUS) and CT angiography are reserved for complex or evolving lesions.

First-Line Treatment: The Role of IVIG and Aspirin

High-dose intravenous immunoglobulin (IVIG), ideally within the first 10 days of illness, remains the cornerstone of treatment. A single dose of 2 g/kg over 10–12 hours has been shown to reduce coronary complications from 25% to <5%. Adjunctive aspirin therapy is initiated at anti-inflammatory doses (30–50 mg/kg/day) during the febrile phase, transitioning to anti-platelet dosing (3–5 mg/kg/day) once defervescence occurs. Aspirin is typically continued for 6–8 weeks in uncomplicated cases.

Long-Term Cardiac Monitoring and Adult Sequelae

Children with giant aneurysms (≥8 mm) require lifelong cardiology follow-up due to risks of myocardial infarction and sudden cardiac death. Recent studies in Circulation (2024) suggest that even those with normalized coronary dimensions post-KD may exhibit endothelial dysfunction in adolescence.

Functional stress testing, calcium scoring, and lipid profile monitoring are recommended throughout adolescence and early adulthood. Anticoagulation with warfarin or LMWH may be indicated in severe cases with aneurysmal dilation.

Kawasaki Disease exemplifies the critical importance of early recognition and timely intervention in pediatric vasculitis. It mimics benign childhood illnesses but harbors the potential for lifelong cardiac damage. Clinicians must remain alert to evolving presentations, especially in incomplete or MIS-C–overlapping cases, to prevent preventable coronary catastrophes.