Questions remain about mechanisms behind multisystem inflammatory syndrome in children
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PHOENIX — Although the CDC has presented a case definition of multisystem inflammatory syndrome in children, the COVID-19 complication continues to demand attention from researchers and providers alike.
Multisystem inflammatory syndrome in children (MIS-C) primarily impacts those aged 8 to 13 years who previously had COVID-19, with a possible disproportionate effect on minorities and a slight gender preference for boys, Sarah Henrickson, MD, PhD, attending physician in the division of allergy and immunology at Children’s Hospital of Philadelphia, told Healio.
Henrickson characterized these patients as previously healthy.
“It’s such a narrow group on some level, and they’re healthy. Why is it not hitting the unhealthy children?” said Henrickson, who led a session on MIS-C with Eveline Wu, MD, MSCR, attending physician in the division of pediatric allergy and immunology and division chief of pediatric rheumatology at the University of North Carolina at Chapel Hill, during the American Academy of Allergy, Asthma & Immunology Annual Meeting.
“That’s why a lot of people are studying the disease. I don’t think we have a clear picture of why it’s so selective, but we’re all seeing such a consistent, selective nature to the disease that indicates there’s something there to understand better,” she said.
Case definition of MIS-C
The case CDC definition for patients aged younger than 21 years includes fever of 38°C or higher for 24 hours or longer, or a report of a subjective fever lasting 24 hours or longer, as well as multisystem organ involvement, such as with cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological systems.
Further, there must be laboratory evidence of inflammation, including (but not limited to) reduced lymphocytes, low albumin or elevated C-reactive protein, erythrocyte sedimentation rate, fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase, IL-6 levels or neutrophils.
These patients additionally have tested positive for current or recent SARS-CoV-2 infection or have been exposed to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms, the case definition continues. Finally, MIS-C is diagnosed when there are no alternative plausible diagnoses.
“These kids can get sick pretty quickly,” Wu told Healio. “If there are any concerns that a child has MIS-C, send them to the nearest medical center. We believe that most if not all of these children require hospitalization.”
When MIS-C first emerged, many researchers and clinicians noted its similarities to Kawasaki disease. The discussion about the relationship between MIS-C and Kawasaki disease continues.
“There are some who feel very strongly about how we should keep MIS-C separate from Kawasaki disease and that they’re completely different. And then there are some who say we might be able to draw some comparisons between Kawasaki disease and MIS-C,” Wu said.
“Compared to what we know about Kawasaki disease, children with MIS-C tend to be a little bit older and have more shock,” Wu continued. “MIS-C children also tend to have lower platelet counts, more elevated C-reactive protein levels and lower troponin levels and lower albumin, so there are some clinical differences that may be underneath the surface.”
Treatment guidelines
Treatment currently targets the underlying inflammatory process with supportive care including fluid resuscitation and ionotropic and respiratory support. Rare cases also require extracorporeal membranous oxygenation.
“We used IVIG as frontline therapy early on, not always in conjunction with steroids,” Wu said. “But by looking at the more than 500 cases in the CDC surveillance registry, the use of IVIG and steroids up front did have better outcomes, including cardiovascular, with less need for escalating therapy.”
The CDC recommends follow-up for patients with MIS-C after they have been discharged from the hospital, including pediatric cardiology beginning 2 to 3 weeks later, although those guidelines may evolve as well.
“Do they follow up with their rheumatologist? Do they follow up with immunology? Unless they have some issues, do they need an echo every year, and for how long?” Henrickson said.
Ongoing research
The NIH is now funding multiple projects researching the diagnosis and mechanism of MIS-C, in addition to best practices for follow-up, Henrickson said.
“A lot of money is being spent to characterize these patients. Can we find them earlier? What are the early biomarkers?” she said.
“With presentation in the emergency room — because that’s usually where these cases are being found — what are the underlying differences in these patients? We haven’t found a lot of them, but it seems there ought to be something making people predisposed to this particular reaction,” she said.
As research continues into susceptibility to MIS-C, with an eye on the impact of SARS-CoV-2 variants on the disease, Wu noted that there also is a need for longitudinal surveillance studies.
“If these patients get COVID-19 again, are they at higher risk for MIS-C?” she asked. “We think the cardiac outcomes resolve, but in the long term, do they need follow-up with echocardiograms and similar treatment?”
Although the mechanism behind MIS-C remains a mystery, Henrickson and Wu emphasized that resources are available through the CDC to assist providers and that trusted medical practices remain effective.
“Everything you already know about medicine is still true,” Henrickson said.
References:
- Henrickson S and Wu E. Diagnosis and treatment of multisystem inflammatory syndrome (MIS-C) in children. Presented at: AAAAI Annual Meeting; Feb. 25-28, 2022; Phoenix (hybrid meeting).
- Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). https://www.cdc.gov/mis/mis-c/hcp/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fmis%2Fhcp%2Findex.html. Updated May 20, 2021. Accessed March 8, 2022.