Multisystem inflammatory syndrome in children (MIS-C), which is also known as paediatric inflammatory multisystemic syndrome, has emerged as a rare but serious manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. In the face of the ongoing coronavirus disease 2019 (COVID-19) pandemic, the ACR has rapidly produced guidance to help clinicians provide the best possible care for children with COVID-19-related conditions, including MIS-C.
“Much like adults with COVID-19 pneumonia, children with complex medical problems can develop hyperinflammation in the setting of the acute, infectious phase of SARS-CoV-2 infections,” explains Lauren Henderson, corresponding author on the new ACR guidance. “In addition, previously healthy children can develop MIS-C, a condition characterized by fever, inflammation and multiorgan dysfunction that occurs late in the course of SARS-CoV-2 infections.”
The new guidance was compiled by a group of clinicians from a variety of subspecialties and covers several aspects of the diagnosis and treatment of MIS-C, including the importance of a broad differential diagnosis. “Children without life-threatening manifestations of MIS-C should undergo a diagnostic evaluation for other causes of the presentation (infectious and non-infectious), which may be more common than MIS-C,” suggests Henderson.
According to two studies just published in The Journal of Clinical Investigation, despite having a broad clinical phenotype, MIS-C is distinct from both Kawasaki disease and macrophage activation syndrome (which share overlapping symptoms with MIS-C), and from COVID-19 itself. In both studies, specific patterns of cytokine expression were present in patients with MIS-C that differed from patterns in patients with the other conditions; results that are supported by preliminary data from in depth studies of the immunological landscape of MIS-C.
“Most children with MIS-C will need care from a multidisciplinary team that includes infectious disease specialists, rheumatologists, cardiologists and haematologists, among others. In particular, cardiology follow up is needed to ensure that cardiac function is normal and there is no coronary involvement,” says Henderson.
The ACR guidance also covers the treatment of hyperinflammation associated with COVID-19 in children and recommends the use of immunomodulatory agents such as glucocorticoids, the IL-1 inhibitor anakinra or the IL-6 inhibitor tocilizumab. Glucocorticoids are also recommended as a first-line therapy for MIS-C in patients who are hospitalized, along with intravenous immunoglobulin.
“This guidance was developed over an expedited timeframe to help clinicians treating children during the current surge of COVID-19 cases in North America,” states Henderson. “We view the guidance as a ‘living document’ and expect to update the content as further information becomes available about children with COVID-19.”
Henderson, L. A. et al. American College of Rheumatology clinical guidance for pediatric patients with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 and hyperinflammation in COVID-19. Version 1. Arthritis Rheumatol. https://doi.org/10.1002/art.41454 (2020)
Diorio, C. et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J. Clin. Invest. https://doi.org/10.1172/JCI140970 (2020)
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Clarke, J. MIS-C clinical guidance released amid race to define the condition. Nat Rev Rheumatol 16, 538 (2020). https://doi.org/10.1038/s41584-020-0489-y