Recent Advances in the Understanding and Management of Kawasaki Disease
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Kawasaki disease (KD) is an acute systemic inflammatory illness of childhood that can result in coronary artery aneurysms, myocardial infarction, and sudden death. Clinical and epidemiologic data point to an unknown infectious agent as the cause. We discovered that an oligoclonal IgA immune response is present in arterial tissue in acute KD. Synthetic versions of prevalent IgA antibodies in the KD arterial wall identify cytoplasmic inclusion bodies in acute KD ciliated bronchial epithelium and other inflamed KD tissues. Light and electron microscopic studies show that the inclusion bodies are consistent with aggregates of viral protein and RNA, and are likely formed by the KD etiologic agent. KD susceptibility is likely to be polygenic. Treatment of gammaglobulin nonresponders usually consists of additional intravenous immunoglobulin, methylprednisolone, and/or infliximab. Additional data regarding KD pathogenesis are urgently needed to provide other targets for therapy for those patients at highest risk of developing coronary artery abnormalities.
KeywordsIgA Inclusion bodies Intravenous immunoglobulin Coronary artery aneurysm
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- 1.Newburger JW, Takahashi M, Gerber MA, et al.: Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics 2004, 114:1708–1733.CrossRefPubMedGoogle Scholar
- 19.•• Rowley AH, Baker SC, Orenstein JM, Shulman ST: Searching for the cause of Kawasaki disease—cytoplasmic inclusion bodies provide new insight. Nat Rev Microbiol 2008, 6:394–401. This article reviews etiologic, pathologic, and immunologic studies in KD, including the discovery that viral-like cytoplasmic inclusion bodies are present in KD tissues, and proposes a model of KD pathogenesis.Google Scholar
- 25.• Rowley AH, Baker SC, Shulman ST, et al.: RNA-containing cytoplasmic inclusion bodies in ciliated bronchial epithelium months to years after acute Kawasaki disease. PLoS ONE 2008, 3:e1582. This article describes a study demonstrating the presence of RNA-containing cytoplasmic inclusion bodies in 85% of acute and late-stage KD fatalities, and in 25% of adult controls, consistent with the hypothesis that KD is the result of infection with a previously unidentified, ubiquitous, persistent RNA virus.Google Scholar
- 29.• Onouchi Y, Gunji T, Burns JC, et al.: ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 2008, 40:35–42. This study shows an association between a polymorphism of ITPKC that results in inefficient downregulation of T-lymphocyte activation and susceptibility both to KD and to the development of coronary artery abnormalities.Google Scholar
- 30.•• Onouchi Y: Molecular genetics of Kawasaki disease. Pediatr Res 2009, 65(5 Pt 2):46R–54R. This article is an outstanding review of the history of genetics studies in KD, and a discussion of future research in this area.Google Scholar
- 33.•• Newburger JW, Sleeper LA, McCrindle BW, et al.: Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med 2007, 356:663–675. This study demonstrated a lack of efficacy of intravenous methylprednisolone with IVIG and aspirin as compared with IVIG and aspirin alone as primary therapy of KD.Google Scholar
- 34.Asai T: Evaluation method for the degree of seriousness in Kawasaki disease. Acta Paediatr Jpn 1983, 25:170–175.Google Scholar