The Multifaceted Presentation of the Multisystem Inflammatory Syndrome in Children: Data from a Cluster Analysis

Abstract

Background: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course. Methods: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group. Results: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features (n = 100); cluster II, predominantly MAS-like features (n = 34); cluster III, predominantly LV dysfunction (n = 47); cluster IV, other presentations (n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil–lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts. Conclusion: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management.

The role of indices in predicting disease severity and outcomes of multisystem inflammatory syndrome in children

“…Since inflammatory cells such as neutrophils and lymphocytes play an important role in the pathogenesis of MIS‐C, it seems reasonable to focus on NLR. Sönmez et al found higher NLR in patients with a severe disease course in a multicenter study that included 293 MIS‐C patients 41 . Our study determined that NLR was effective in predicting disease severity, admission to hospital, need for intensive care, and anakinra treatment in MIS‐C patients.…”

“…Sönmez et al found higher NLR in patients with a severe disease course in a multicenter study that included 293 MIS-C patients. 41 Our study determined that NLR was effective in predicting disease severity, admission to hospital, need for intensive care, and anakinra treatment in MIS-C patients. The sensitivity of NLR in predicting disease severity and specificity was 83.6% and 81.4%, respectively.…”

Multisystem inflammatory syndrome in children: clinical presentation, management, and short- and long-term outcomes

“…Sixty-seven (54.5%) patients were followed up in the intensive care unit (ICU). According to studies from Turkey, the rate of intensive care hospitalization was 29.6-46.7%, the need for mechanical ventilation was 11.1-12.4%, and the need for vasoactive drug support was 17.7-35.7% [20][21][22][23][24]. In the review of [15].…”

Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C)

“…Over half of children with MIS-C present to the intensive care unit (ICU) 4-6 weeks after initial SARS-CoV-2 infection (Cui et al, 2021; Patel, 2022; Vogel et al, 2021). Hallmark symptoms of MIS-C include a prolonged high fever, rash, gastrointestinal symptoms, cardiovascular dysfunction, and signs of inflammation (Feldstein et al, 2020; Hoste et al, 2021; Sönmez et al, 2022; Whittaker et al, 2020). Early recognition and treatment of MIS-C are essential to prevent serious complication and death.…”