Cause of Kawasaki Disease
The cause of Kawasaki disease remains unknown, though clinical and epidemiological features strongly suggest an infectious trigger in genetically predisposed children, particularly those of Asian descent. 1
Current Understanding of Etiology
The Infectious Hypothesis
The leading theory proposes that an unidentified infectious agent triggers an immune-mediated inflammatory cascade in genetically susceptible individuals. 1 The evidence supporting an infectious etiology includes:
- Clinical presentation consistent with infectious disease: self-limited illness with fever, rash, enanthem, conjunctival injection, and cervical adenopathy 1
- Epidemiological patterns suggestive of transmissible disease: winter-spring seasonality, community outbreaks with wave-like geographic spread, and apparent epidemic cycles 1
- Age distribution suggesting acquired immunity: rarity in the first few months of life (suggesting passive maternal antibody protection) and in adults (suggesting acquired immunity) 1
However, all attempts to identify a specific infectious agent through conventional bacterial and viral cultures, serological methods, and animal inoculation have failed. 1
Genetic Predisposition
Strong evidence supports genetic susceptibility as a critical factor: 1
- Marked ethnic variation in incidence rates: Japanese children have the highest rates (112-150 per 100,000 children <5 years old) 1
- U.S. race-specific rates demonstrate clear genetic patterns: Asian/Pacific Islander descent (32.5/100,000), African Americans (16.9/100,000), Hispanics (11.1/100,000), and whites (9.1/100,000) 1
- The specific genetic basis of susceptibility remains unknown 1
The Current Working Model
The most plausible hypothesis is that Kawasaki disease results from a ubiquitous infectious agent that produces clinically apparent disease only in genetically predisposed individuals. 1 This model assumes:
- Most infected children experience asymptomatic infection 1
- Only a small fraction develop overt clinical features of Kawasaki disease 1
- Little person-to-person transmission occurs 1
Pathophysiological Mechanisms
Once triggered, the disease involves: 1
- Marked immune perturbations including cytokine cascade stimulation 1
- Endothelial cell activation as a key step leading to coronary arteritis 1
- Cellular infiltration involving CD68 monocyte/macrophages, CD8 cytotoxic lymphocytes, and oligoclonal IgA plasma cells 1
Environmental Associations (Unconfirmed)
Several environmental factors have been reported but not consistently confirmed: 1
- Antecedent respiratory illness 1
- Exposure to carpet-cleaning fluids 1
- Preexisting eczema 1
- Humidifier use 1
- Living near standing bodies of water 1
Clinical Implications
Understanding that the cause remains unknown is critical for clinical practice because: 1
- No specific diagnostic test exists—diagnosis relies entirely on clinical criteria 1
- Early recognition is paramount—treatment with IVIG within 10 days reduces coronary artery abnormality risk from 25% to approximately 5% 1
- High suspicion is required in children with prolonged fever, especially those of Asian descent or infants <6 months who have the highest risk of coronary complications 1