MIS-C
Since the beginning of the COVID-19 pandemic, the majority of serious and life-threatening outcomes have occurred in adults. But in late April, clinicians in the U.K. reported a cluster of previously healthy children who presented with cardiovascular shock, fever and hyperinflammation. On May 14, the CDC issued a national health advisory to report cases meeting the criteria for multi-system inflammatory syndrome in children.
Dr. Mehta realized the recommendations for MIS-C would differ from general recommendations targeted to SARS-CoV-2-exposed children with rheumatic disease who did not exhibit inflammatory syndromes and that specific diagnostic pathways could provide better guidance for clinicians. He helped convene a second task force, which in less than a month has now prepared a clinical guidance document specific for MIS-C associated with SARS-CoV-2 and hyperinflammation in COVID-19.
Lauren Henderson, MD, MMSc, an attending physician at Boston Children’s Hospital and assistant professor of pediatrics, Harvard Medical School, Boston, was chosen to lead the MIS-C task force, because she has experience developing treatment guidelines for children with hyperinflammatory syndromes and had seen numerous children with MIS-C.
The multidisciplinary task force included nine pediatric rheumatologists, two adult rheumatologists, two pediatric cardiologists, two pediatric infectious disease specialists and one pediatric critical care physician. During an initial webinar on May 22, the participants divided into four work groups to address different topic areas, such as the diagnostic evaluation of MIS-C, cardiac management and the role for immunomodulatory treatment. Each work group took a week to gather data for its evidence reports and to develop preliminary statements or recommendations. Those statements were submitted to the group at large for voting.
Similar to the general pediatric task force, the MIS-C task force built consensus through a modified Delphi process involving two rounds of anonymous voting and two webinars for discussion of anonymous voting results. A 9-point scale was used to determine the appropriateness of guidance statements, with 1 = inappropriate and
9 = appropriate.
MIS-C Distinct from Kawasaki Disease
Dr. Mehta notes that MIS-C case definitions from the CDC and the World Health Organization were “very broad, because they were designed for reporting cases rather than diagnostic purposes.” So the MIS-C task force relied on many sources of evidence and clinical pathways from several institutions, including the CHOP MIS-C clinical pathway, to develop their guidance.
As many early cases of MIS-C appeared, reports noted the clinical features closely resembled those seen with Kawasaki disease. Overlapping features include fever; conjunctival injection; oropharyngeal symptoms, such as red or cracked lips and strawberry tongue; rash; and cervical lymphadenopathy. The clinical guidance document specifies the ways in which MIS-C cases associated with SARS-CoV-2 differ from Kawasaki disease. For example, MIS-C patients exhibit a broader age range, and Kawasaki disease patients tend to be younger. MIS-C patients are more likely to display cardiac dysfunction, to have prominent gastrointestinal and neurologic symptoms, and to present in shock.
Dr. Henderson also points out that Kawasaki disease is most common in those of East Asian descent, while cases of MIS-C are more common in patients of Afro-Caribbean and possibly Hispanic descent. “There may be biologic factors that explain this, or it may be due to socioeconomic factors and thus greater exposure to SARS-CoV-2,” she says. More research is needed to supply answers to these observed patterns.
