Description

• Kawasaki syndrome (KS) is a self-limited acute, febrile, systemic vasculitis of small- and medium-sized arteries that predominantly affects patients aged 6 months to 5 years.
• The most prominent cause of acquired coronary artery disease in children in developed countries (1)
• Vasculitis of coronary arteries results in aneurysms/ectasia, myocardial infarction (MI)/ischemia, or sudden death.
• System(s) affected: cardiovascular, gastrointestinal, hematologic/lymphatic/immunologic, musculoskeletal, nervous, pulmonary, renal/urologic, skin/exocrine
• Synonym(s): mucocutaneous lymph node syndrome (MCLS), infantile polyarteritis, Kawasaki disease

Epidemiology

Incidence

• Worldwide: affects all races but most prevalent in Asia; Japan annual incidence rate of 265/100,000 in children <5 years old
• In the United States, annual incidence in children aged <5 years is 20/100,000. Compared to white people, African Americans have 1.5 times risk, and Asian Americans have 2.5 times risk. The highest state incidence is in Hawaii.
• Leading cause of acquired heart disease in children in developed countries
  • Predominant age: 1 to 5 years; median age of diagnosis is 1.5 years of age.
  • 85% of cases are children <5 years of age and 50% <2 years of age.
  • Male-to-female ratio = 1.5:1

Prevalence

• Highest to lowest prevalence: Asian > African American > Hispanic > white
• Seasonal variation: peaks in winter and early spring (January to March) in temperate places; peaks in summer in Asia
• Outbreaks at 2- to 3-year intervals

Etiology and Pathophysiology

• Infectious agent triggers abnormal inflammatory reaction in children with genetic predisposition.
• Acute KS causes a necrotizing arteritis in the smooth muscle layer of medium extraparenchymal arteries, destroying arterial walls into the adventitia, especially in coronary arteries.
• Inflammatory cells secrete cytokines (TNF-α), interleukins 1 and 6, and matrix metalloproteases that cause fragmentation of the internal elastic lamina
• As the acute process resolves, active neutrophilic inflammatory cells are succeeded by a subacute/chronic, lymphocytic vasculitis; fibroblasts and monocytes cause tissue repair/remodeling that may cause vascular fibrosis and stenosis.

Genetics

• Populations at higher risk and family link suggest a genetic predisposition.
• Siblings of patients in Japan have a 10- to 30-fold increased risk, and >50% develop KS within 10 days of first case; increased occurrence of KS in children whose parents also had illness in childhood
• Single-nucleotide polymorphisms in six different genes have been implicated in KS (Fcγ receptor 2A, CASP3, HLA class II, B-cell lymphoid kinase, IPTKC, CD40).
• Coronary aneurisms are associated with variants in TGF-β signaling pathways.

Risk Factors

• Male to female prevalence 1.5:1 in the United States
• African Americans at 1.5 times risk; Asian Americans at 2.5 times risk
• Sibling with Kawasaki

General Prevention

None