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Kawasaki disease: insights into pathogenesis and approaches to treatment

Key Points

  • Epidemiologic data strongly suggest an infectious aetiology for Kawasaki disease, which is the leading cause of acquired heart disease among children in developed countries

  • Necrotizing arteritis, subacute chronic vasculitis, and luminal myofibroblastic proliferation are three linked processes underlying the arteriopathy associated with Kawasaki disease

  • Genetic susceptibility is indicated by the strikingly high rate of Kawasaki disease in children of Asian ethnicity and by its increased incidence in first-degree relatives of affected patients

  • Timely diagnosis and treatment of Kawasaki disease with intravenous immunoglobulin (IVIg) and aspirin substantially decreases the risk of developing coronary artery abnormalities

  • Adjunctive therapy with corticosteroids is of value in Japanese patients at particularly high risk of coronary complications, but identification of such high-risk patients is difficult in ethnically diverse populations

  • Management of patients who do not respond to standard therapy is challenging; options include pulsed steroids, additional IVIg, and infliximab or other immunomodulatory agents

Abstract

This Review summarizes recent advances in understanding of the pathologic processes and pathophysiologic mechanisms leading to coronary arteritis in Kawasaki disease, and describes current approaches to its treatment. Kawasaki disease is the most common cause of acquired heart disease among children in developed countries, in whom the resulting coronary artery abnormalities can cause myocardial ischaemia, infarction and even death. Epidemiologic data strongly suggest an infectious aetiology, although the causative agent has yet to be identified. Genetic factors also increase susceptibility to Kawasaki disease, as indicated by its strikingly high incidence rate in children of Asian ethnicity and by an increased incidence in first-degree family members. The treatment of Kawasaki disease is based on timely administration of intravenous immunoglobulin and aspirin. However, the management of patients who do not respond to this standard therapy remains challenging; although several options are available, comparative data on which to base treatment decisions are scarce. The added value of adjunctive therapy with corticosteroids in patients at particularly high risk of coronary complications has been demonstrated in Japanese populations, but identification of high-risk patients has proven to be difficult in ethnically diverse populations.

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Figure 1: Three linked processes of Kawasaki disease arteriopathy.

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Acknowledgements

The authors' research work is funded by NIH grants HL63771, HL109955 and AI106030 (to A.H.R.), the American Heart Association of Metropolitan Chicago (to A.H.R.), the Max Goldenberg Foundation (to A.H.R.), and the Centre for Kawasaki Disease at the Ann & Robert H. Lurie Children's Hospital of Chicago (to both authors).

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S.T.S. and A.H.R. contributed equally to researching data for the article, discussions of its content, writing the article, and review or editing of the manuscript before submission.

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Correspondence to Stanford T. Shulman.

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Shulman, S., Rowley, A. Kawasaki disease: insights into pathogenesis and approaches to treatment. Nat Rev Rheumatol 11, 475–482 (2015). https://doi.org/10.1038/nrrheum.2015.54

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