Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison

Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly asymptomatic or have mild symptoms compared with the more severe coronavirus disease 2019 (COVID-19) described in adults. However, SARS-CoV-2 is also associated with a widely reported but poorly understood paediatric systemic vasculitis. This multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. Epidemiological, clinical and immunological differences classify MIS-C as being distinct from Kawasaki disease. Differences include the age range, and the geographical and ethnic distribution of patients. MIS-C is associated with prominent gastrointestinal and cardiovascular system involvement, admission to intensive care unit, neutrophilia, lymphopenia, high levels of IFNγ and low counts of naive CD4+ T cells, with a high proportion of activated memory T cells. Further investigation of MIS-C will continue to enhance our understanding of similar conditions associated with a cytokine storm.
In this timely Review, the authors compare and contrast two forms of childhood inflammatory vasculitis: Kawasaki disease and the coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children, highlighting epidemiological, clinical and immunological differences that suggest they should be classified as distinct syndromes.
Key points Multisystem inflammatory syndrome in children (MIS-C) is characterized by exaggerated innate and adaptive immune responses following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in predisposed children.Clinical presentation of MIS-C involves multiple organ systems, with prominent involvement of the gastrointestinal and cardiovascular systems.The factors that trigger the development of MIS-C in children exposed to or infected with SARS-CoV-2 are not yet known.Results from epidemiological, clinical and immunological investigations have revealed that although MIS-C has phenotypic similarities to Kawasaki disease, they are different syndromes.The approach to treatment of MIS-C aims to mute the augmented inflammatory response.