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  • Title: Kawasaki disease: a comprehensive review of treatment options.
    Author: Patel RM, Shulman ST.
    Journal: J Clin Pharm Ther; 2015 Dec; 40(6):620-5. PubMed ID: 26547265.
    Abstract:
    WHAT IS KNOWN AND OBJECTIVE: Kawasaki disease (KD) is an acute self-limiting systemic vasculitis with specific predilection for the coronary arteries that affects previously healthy young infants and children. It is the leading cause of childhood-acquired heart disease in the developed world. Although the stimulus for the cascade of inflammation in KD is unknown, prompt treatment within 10 days of symptom onset has been shown to improve clinical outcomes and reduce the risk of coronary artery complications. Standard initial therapy is intravenous immunoglobulin (IVIG) and aspirin. Non-responders to initial therapy remain a challenge. This present review summarizes the treatment options for initial and refractory KD, including the role of steroids and other immunosuppressive therapies. METHODS: Literature search using PubMed database to identify pharmacologic studies in KD using the terms Kawasaki disease, intravenous immunoglobulin, refractory, corticosteroids, infliximab, cyclosporine, methotrexate, high risk from January 1988-May 2015 was performed. Bibliographies of selected references were also evaluated for relevant articles. Results were limited to those published in English. All articles identified from the PubMed searches were evaluated. RESULTS AND DISCUSSION: Initial IVIG therapy results in rapid resolution of clinical symptoms in 80-90% of patients and has been shown to reduce the risk of coronary disease. Although concomitant aspirin remains the standard of care for the initial management of KD, the evidence to support its efficacy in improving coronary artery outcomes are lacking. Initial therapy with corticosteroids in addition to intravenous immunoglobulin and aspirin improves outcomes in patients in Japan. However, identifying patients at high risk who may benefit from additional corticosteroids in heterogeneous populations has been challenging. Therapeutic options for non-responders to initial therapy are also challenging given the paucity of data. Patients who fail to respond to the first dose of IVIG will most often receive a second dose. Patients who fail to respond to two doses of IVIG present a unique challenge as the appropriate treatment remains uncertain. Although their effectiveness remains unproven, treatment with infliximab, cyclosporine or methotrexate may be considered in those patients who fail multiple doses of IVIG and steroids. WHAT IS NEW AND CONCLUSION: The role of steroids in high-risk non-Japanese patients is unclear, with the biggest challenge being early identification of patients at high risk of developing adverse coronary artery outcomes. Limited data evaluating other immunosuppressive agents are available and should be reserved for patients failing two doses of IVIG. Although recent advances in research have broadened our understanding of the epidemiology, genetic susceptibility and pathogenesis of KD, the aetiology of KD remains unclear. Ongoing research will help determine more precise pathogenesis and may assist in developing a diagnostic test as well as identifying new targets for more precise treatment interventions.
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