Etiology And Genetic Susceptibility
Exact etiology remains completely unknown. Epidemiological features strongly suggest infectious origin occurring in genetically susceptible individuals.
Environmental And Infectious Triggers
- Peaks in winter and spring months.
- Wavelike geographic spread indicates infectious triggers.
- Infrequent occurrence in infants under three months suggests protective maternal antibodies.
- Proposed agents include adenovirus, parvovirus B19, Epstein-Barr virus, and coronaviruses.
Genetic Factors
- Higher risk observed in Asian children, regardless of country of residence.
- Identical twin concordance rate approaches 13%.
- Genome-wide association studies identify significant associations with specific genes.
- Implicated genes include ITPKC (T-cell regulator), CASP3, BLK, and FCGR2A.
- Specific human leukocyte antigen regions influence disease risk.
Immunopathogenesis
Complex interaction between immune activation and vascular tissue destruction drives disease process.
Superantigen Hypothesis
- Striking clinical similarity exists between Kawasaki disease and superantigen toxin-mediated staphylococcal/streptococcal toxic shock syndromes.
- Selective expansion of Vβ2 and Vβ8.1 T cells indicates superantigen-mediated process.
- Conventional antigen response also remains plausible etiology.
Cytokine Cascade And Endothelial Injury
- Acute vascular inflammation characterizes disease hallmark.
- Immune activation of endothelium causes increased expression of adhesion molecules.
- Adhesion molecules entrap platelets and inflammatory cells.
- Inflammatory cells secrete extreme levels of proinflammatory cytokines.
- Tissue destructive enzymes increase significantly, including elastases, matrix metalloproteinases, and collagenolytic cysteine proteases.
- Macrophages act as main source of elastolytic proteases causing vascular damage.
- Cystatin C, possessing protective role in vascular remodeling, gets severely depressed.
- Enzymatic imbalance causes breakdown of internal elastic lamina.
Triphasic Arteriopathy Progression
Basic lesion constitutes necrotizing vasculitis of medium-sized muscular arteries, predominantly affecting coronary arteries. Vascular injury progresses through three distinct pathologic phases.
| Disease Phase | Timing | Pathological Features |
|---|---|---|
| Phase 1 | First 2 weeks | Neutrophilic necrotizing arteritis. Begins in endothelium. Moves through coronary wall. Results in saccular aneurysm formation. |
| Phase 2 | Weeks to months | Subacute/chronic vasculitis. Driven by lymphocytes, plasma cells, and eosinophils. Results in fusiform aneurysms. |
| Phase 3 | Months to years | Luminal myofibroblastic proliferation. Medial smooth muscle cells proliferate. Progressive stenosis occurs. Thrombi may form and obstruct blood flow. |
Structural Vascular Consequences
- Vascular endothelial hyperplasia features mononuclear and plasma cell infiltration.
- Continuing proliferation of medial smooth muscle cells after early degeneration causes late coronary artery stenosis.
- Intimal proliferation and scarring lead to narrowed vascular lumen.
- Disorganized blood flow within aneurysms promotes thrombosis and potential myocardial infarction.