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Kawasaki disease (KD), a vasculitis affecting small- and medium- sized blood vessels, is the second most common childhood vasculitis, and the most common cause of pediatric acquired heart disease in the developed world.1 It was first described in 1967 and initially called mucocutaneous lymph node disease because of the predominant clinical features. Affected children present acutely with fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, cervical lymphadenopathy, rash, and extremity changes. These findings are usually self-limited, but 15% to 25% of untreated children develop coronary artery abnormalities, putting them at risk for developing ischemic heart disease or sudden death later in life.2 Therapy with intravenous immunoglobulin in the acute phase is aimed at reducing inflammation, thereby minimizing the risk of coronary artery aneurysms and other late sequelae.
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Children under 5 years of age are affected in 90% of cases; the median age is 2 years. There is a slight male preponderance. Children of all ethnicities may be affected, although the incidence is higher in the Asian population. The annual incidence of KD in children under 5 years of age in the United States and the United Kingdom is 20 and 8 per 100,000 children, respectively. The rates in Japan and Taiwan are approximately 5 times higher.3 Adults also may develop KD but far less often; fewer than 100 cases have been reported worldwide to date.
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The pathogenesis of KD remains unknown, though most hypotheses center on an infectious trigger. Several epidemiologic features of the disease support this theory. For example, the incidence of KD peaks in winter and springtime, corresponding to peak seasons for infectious diseases. Furthermore, KD exhibits “epidemics,” as demonstrated by years with up to a tenfold spike in disease incidence in Japan in the 1980s and 1990s. Nonetheless, extensive testing using culture, serologic, and sequencing techniques has not implicated a specific transmissible agent as the cause. Additionally, anti-inflammatory medications such as intravenous immunoglobulins (IVIG) and TNF-inhibitors are clinically beneficial, while antibiotics are not. Taken together, these facts suggest that KD represents an exaggerated inflammatory response to one or more infectious agents in genetically susceptible individuals. Alternative hypotheses include immune activation by a superantigen, analogous to staphylococcal or streptococcal toxin-mediated illnesses,4 or a heretofore unrecognized organism as the causative agent. Ultrastructural, immunofluorescence, and RNA evidence support the hypothesis of a “new” virus associated with Kawasaki disease.
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More recently, several genome-wide association studies have identified a variety of candidate genes and polymorphisms involved in inflammation and cardiovascular pathology showing preferential expression in children with KD.5-7 Studies to determine the significance of these findings are ongoing.
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CLINICAL PRESENTATION
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The diagnosis of KD is a clinical one, with epidemiologic criteria as defined by Dr. Tomisaku Kawasaki in 1967 as follows:
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