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

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.

Differences and similarities of multisystem inflammatory syndrome in children, Kawasaki disease and macrophage activating syndrome due to systemic juvenile idiopathic arthritis: a comparative study.

To compare the clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C), patients with Kawasaki disease (KD) and with macrophage activating syndrome due to systemic juvenile idiopathic arthritis (sJIA-MAS) on real-life data. Patients diagnosed with MIS-C, KD, and sJIA-MAS from 12 different centers in Turkey who were followed for at least 6 months were included in the study. Demographic, clinical, and laboratory findings of all patients were analyzed. A total of 154 MIS-C, 59 KD, and 31 sJIA-MAS patients were included. The median age of patients with MIS-C were higher than those with KD while lower than those with sJIA-MAS (8.2, 3, 12 years, respectively). Myalgia (39.6%), cardiac (50.6%), gastrointestinal (72.7%), and neurological (22.1%) involvements were more common in patients with MIS-C compared to others. MIS-C patients had lower levels of lymphocyte (950 vs 1700 cells/µl) and thrombocyte (173,000 vs 355,000 cells/µl) counts and higher pro-BNP (1108 vs 55 pg/ml) levels than KD. Ferritin levels were higher in patients with MIS-C compared to patients with KD while they were lower than patients with sJIA-MAS (440, 170, 10,442 ng/ml, respectively). Patients with MIS-C had a shorter duration of hospitalization than sJIA-MAS (p = 0.02) while they required intensive care unit admission more frequently (55 vs 8 patients, p < 0.001). The median MAS/sJIA score of MIS-C patients was - 1.64 (- 5.23 to 9.68) and the median MAS/sJIA score of sJIA-MAS patients was -2.81 ([- 3.79] to [- 1.27]). MIS-C patients displayed certain differences in clinical and laboratory features when compared to KD and sJIA-MAS. Definition of the differences and similarities between MIS-C and the other intense inflammatory syndromes of childhood such as KD and MAS will help the clinicians while making timely diagnosis.

Does immunosuppressive treatment entail an additional risk for children with rheumatic diseases? A survey-based study in the era of COVID-19.

The aim of the research was to further extend current knowledge of whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease 2019 (COVID-19) entails a risk for children with various rheumatic diseases under immunosuppressive treatment. Telephone survey was administered by conducting interviews with the parents from May 1, 2020 to May 20, 2020. A message containing a link to the actual questionnaire was sent to their phones simultaneously. The medical records of the patients were reviewed for gathering information about demographic data, clinical follow-up, and treatments. Patients who were followed-up under immunosuppressive treatment (n = 439) were attempted to be contacted. The diagnostic distribution of patients (n = 414) eligible for the study was as follows: juvenile idiopathic arthritis (JIA) (n = 243, 58.7%), autoinflammatory diseases (n = 109, 26.3%), connective tissue diseases (n = 51, 12.3%), and vasculitis (n = 11, 2.7%). In the entire cohort, the mean age was 12 ± 4.7 years, and 54.1% (n = 224) were female. Nine patients have attended the hospital for COVID-19 evaluation, 6 of whom were in close contact with confirmed cases. One patient with seronegative polyarticular JIA, previously prescribed methotrexate and receiving leflunomide during pandemic was identified to be diagnosed with COVID-19. None, including the confirmed case, had any severe symptoms. More than half of the patients with household exposure did not require hospitalization as they were asymptomatic. Although circumstances such as compliance in social distancing policy, transmission patterns, attitude following contact may have influenced the results, immunosuppressive treatment does not seem to pose an additional risk in terms of COVID-19.