Mucocutaneous Lymph Node Syndrome; new strategies

Kawasaki Disease (KD) is a self-limited vasculitis of unknown etiology that predominantly affects children younger than 5 years. It is now the most common cause of acquired heart disease in children in Asia. KD was first reported in 1967 by professorTomisaku Kawasaki. He described the clinical signs and symptoms of 50 Japanese children with acute mucocutaneous lymph node syndrome.One year later, Yamamoto T, published the electrocardiogram abnormalities of KD patients. Finally, Japanese physicians established the relationship between KD and coronary vasculitis in 1972.Back to the Future: 1871–1984 and Other Riddles of KD:More than 100 years of pathologic records from the first description of fatal KD, by Samuel Gee in 1871, (Gee, St Barth Hosp Rep 7:148, 1871) infantile periarteritisnodosa .The Era of Enhanced Discovery and International Collaboration: 1984–2015:The most recent period, from the mid-1980s to the present, marks the period of international cooperation, heightened interest, and scientific progress in the understanding of this still enigmatic disease. Histopathological observation of Kawasaki disease has focused on the coronary artery because coronary arterial lesions are directly associated with mortality and long-term outcomes. However, noncardiac lesions must also be considered when describing KD pathology and etiology.ITPKC and CASP3 are common susceptibility genes for Kawasaki disease. The recent identification of the FCGR2A, BLK, CD40, and HLA class II gene regions in genome-wide association studies has shed new light on the pathogenesis of Kawasaki disease.Although the cause of KD remains unknown, understanding of its pathogenesis has increased.An overt immune reaction triggered by unknown infectious agents may cause systemic vasculitis. The mediators of this reaction are mainly inflammatory cytokines such as TNF-α, IL-1β, and IFN-γ.The agent of KD remains unknown after more than 40 years of intensive research, but new information from analyses of KD time series from locations worldwide suggests that KD activity is modulated by weather and climate processes.Heavy metals such as zinc and mercury can be transported on aerosolized particles and act as haptens that render antigenic the proteins towhich they bind.The standard therapy for acute Kawasakidisease is high-dose IVIG, 2 g/kg, over 8–12 h, together with aspirin, for its anti-inflammatory and then anti-platelet effects.Despite such treatment, however, up to 5% of children will develop coronary artery aneurysms.Adjunctive therapies have included additional IVIG therapy, corticosteroids, tumor necrosis factor (TNF)-α blockers (e.g., infliximab, etanercept), calcineurin inhibitors (e.g., cyclosporine), interleukin-1 receptor antagonist (IL1RA) agents (e.g., anakinra), MTX, and cyclophosphamide.Among these adjunctive therapies, only corticosteroids have been proven to be effective in reducing the incidence of coronary artery aneurysms, in a phase IIIrandomized trial in a high-risk Japanese population.