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Intravenous immunoglobulin (IVIG) and aspirin is the standard initial therapy in the treatment of Kawasaki disease. Some patients have persistent or recrudescent fever despite this therapy. Although there is no conclusive body of evidence defining the best second and third-line therapies for Kawasaki patients, there have been several recent studies published describing the results of these therapies.This review summarizes the current recommendations for the initial therapy and describes the second and third-line therapies studied in Japan and the United States. A recent study in a Japanese population of Kawasaki disease patients at high risk for IVIG resistance found that the group receiving steroids, in addition to IVIG and aspirin, had fewer coronary artery abnormalities than the group receiving IVIG and aspirin alone. Small studies of etanercept and infliximab have showed these TNF-alpha blockers to be well tolerated and effective in the resolution of fever.Although most practitioners in the USA use IVIG as a second-line therapy for those Kawasaki disease patients who have persistent or recrudescent fever, promising new therapies are under study. Infliximab and steroids are currently the two agents that have been most studied. However, larger studies and studies in genetically diverse populations are needed.