January 16, 2024
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Key takeaways:
- Almost one in five patients with MIS-C based on an initial definition no longer fit the definition.
- Children may suffer permanent microvascular damage from MIS-C.
Nearly one in five patients diagnosed with multisystem inflammatory syndrome in children based on a 2020 definition would not be diagnosed with the illness using an updated definition, researchers reported in Pediatrics.
According to the most recent CDC definition, multisystem inflammatory syndrome in children (MIS-C) “is a rare condition associated with SARS-CoV-2 [that] usually occurs 2 to 6 weeks after a child is infected … may be very mild or have no symptoms at all and may go unrecognized.”
Data derived from Day-Lewis M, et al. Pediatrics. 2023;doi:10.1542/peds.2023-063259.
The syndrome “causes different body parts to become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal tract,” the CDC says. “MIS-C can be serious, even deadly, but most children who are diagnosed with this condition get better with medical care.”
The CDC published an updated version of the MIS-C definition in late 2022, which took effect on Jan. 1, 2023. It replaced a definition from 2020 that required “the presence of fever, systemic inflammation using a number of biomarkers, and involvement of at least two of seven organ systems,” the authors of the new study wrote. The new case definition no longer required a duration of subjective or measured fever but did require C-reactive protein (CRP) of 3 mg/dL or more to indicate systemic inflammation, among other changes.
“The CDC’s intentionally broad definition allowed for inclusion of the full spectrum of a novel illness. However, the overlap with other infectious and inflammatory conditions posed a challenge for clinicians across care settings,” the authors of the new study wrote.
They specifically noted that Kawasaki disease — primarily characterized by fever, inflammation and cardiovascular findings — was among the most frequent conditions to overlap with MIS-C. Under the 2020 definition, patients who met criteria for both diseases were considered to have MIS-C, whereas the 2023 definition lists Kawasaki disease as an “alternative diagnosis.”
17% no longer fit definition
The researchers assessed the cases of 119 patients hospitalized between March 2020 and November 2022 at a single hospital with a diagnosis of MIS-C per the 2020 definition.
Of the 112 patients with SARS-CoV-2 antibody testing, 97% were positive. Of the 109 patients in whom SARS-CoV-2 PCR or point-of-care testing was performed, 25% were positive. Four patients had negative tests, or no test, but a documented exposure to an individual with known COVID-19 within the appropriate time frame.
Using the 2023 definition, 17% of the patients would not have been diagnosed with MIS-C, the researchers found. Among the differences, 11 of the 17 patients no longer had involvement with two organ systems and seven had CRP below 3 mg/dL, they reported.
Although the 2023 case definition seems better able to discern MIS-C from Kawasaki disease, there continues to be overlap in diagnose, they said.
“In comparing the 2020 and 2023 MIS-C case definitions and the risk of misclassification of [Kawasaki disease] in our cohort, we identified likely improvements in accuracy of MIS-C cases identified for surveillance and in the ability to differentiate between [Kawasaki disease] and MIS-C,” they wrote. “Nonetheless, MIS-C cases with severe features such as shock or cardiac involvement were excluded in our cohort by the updated MIS-C 2023 case definition. As such, clinicians are encouraged to consider MIS-C in patients with a MIS-C phenotype and such features.”
‘Significant, persistent microvascular damage’
A second study conducted in Finland and published in JAMA Pediatrics examined the long-term clinical impact of MIS-C on vascular changes in children.
Between April 8 and Dec. 16, 2022, the researchers assessed 18 children diagnosed with MIS-C according to WHO criteria and without significant comorbidities, matching them for age and sex to 17 healthy control participants.
During the acute phase, patients with MIS-C compared with controls exhibited significantly damaged microcirculation, including lower median microvascular flow index (2.36 [interquartile range (IQR), 2.23-2.72] vs. 2.8 [IQR, 2.69-2.86]; P = .01), quantified total vessel density (16.14 [IQR, 14.61-17.85] mm/mm2 vs. 19.61 [IQR, 19.22-20.66] mm/mm2; P = .004), and proportion of perfused vessels (12.31% [IQR, 11.46%-15.59%] vs. 18.10% [IQR, 17.67%-19.7%] P = .004).
“Impaired microcirculatory parameters persisted during follow-up, even without ongoing inflammation,” they wrote. “These findings remained significant when adjusting for known confounders as age, body mass index, and sex.”
The authors also found that arterial stiffness was significantly increased in MIS-C but only during follow-up (median, 7.05 [IQR, 15.72 to 0.54] vs. 18.01 [IQR, 30.46 to 10.03]; P = .009).
“This study found significant, persistent microvascular damage with redistribution of the vessel architecture (ie, loss of capillaries with relative increase in larger vessels), in patients with MIS-C and suggests a long-term association with arterial stiffness,” the authors wrote. “Our findings suggest that MIS-C’s pathogenesis may go beyond the acute hyperinflammatory reaction, possibly involving independent effects of SARS-CoV-2 on the endothelium and vascular system.”
References:
Boever J, et al. JAMA Pediatrics. 2023;doi:10.1001/jamapediatrics.2023.6022.
Day-Lewis M, et al. Pediatrics. 2023;doi:10.1542/peds.2023-063259.
Melgar M, et al. MMWR Recomm Rep. 2022;doi:10.15585/mmwr.mm7147a1.
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