ABSTRACT
Introduction: Multisystem inflammatory syndrome in children (MISC), also known as paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS), is a condition characterised by persistent fever, elevation of inflammatory indexes and evidence of organs involvement or shock. Objectives: To describe clinical characteristics, diagnostic findings and therapeutic interventions of monocentric cohort of MIS-C. Methods: Diagnosis of MIS-C was done following CDC criteria. Patients were hospitalised at Santobono-Pausilipon Children's Hospital in Naples, Italy, from November 2020 to March 2021. Results: MIS-C was diagnosed in 29 patients, 14 males (48.3%). Mean age at diagnosis was 7,2 years old (range 4 months-12,9 years). Contact with SARS-CoV-2-positive patient emerged in 18/29 patients (62%) while 5/29 patients (17,2%) reported symptomatic COVID-19 in the weeks before. SARS-CoV-2 serologic assayrevealed IgG +/IgM- in 100% of the patients. No one presented concurrent conditions but obesity in 6/29 (20,7%). Mucocutaneous involvement was evidenced in 21/29 patients (72%), gastrointestinal symptoms 22/29 (75.9%), cardiac involvement in 27/29 (93,1%). The most frequent symptoms were fever (100%), conjunctivitis (65.5%), abdominal pain (62%), diarrhoea (48,2%), rash (44,9%), vomiting (31%) and cheilitis (31%). Laboratory findings are summarised in table 1. Troponin resulted elevated in 16/29 (55,1%), associated elevation of BNP was evidenced in 12/29 (62%). Electrocardiography showed alterations in 25/29 (86,2%) while echocardiography in 21/29 (72%). Concerning therapy, 27/29 (93%) patients underwent parenteral antibiotics at the admission. Intravenous immunoglobulin (IVIG) was performed in 25/29 (86,2%) of patients. Due to cardiac involvement 13/29 patients (44,8%) received bolus of steroids. 4/29 patients (13,8%) presented worsening of clinical and laboratoristic parameters during treatment with steroids, requiring Anakinra. One patient died due to cardiogenic shock at the admission. Conclusion: Mucocutaneous, gastrointestinal and cardiac involvement are the most common manifestations in our cohort, as also reported in literature. Biologic treatment was necessary in minority of patients. MIS-C is a new emerging condition and represent a challenge to paediatricians due to the severity of presentation. More data are needed to better define incidence and prognosis of that condition.
ABSTRACT
Introduction: Multisystem inflammatory syndrome in children (MISC) is a severe and recently described disease affecting pediatric patients, triggered by SARS-CoV2. Current treatment is based upon IVIG and steroids but some patients are resistant to first line therapy. In these patients some authors have used IL1 receptor antagonist (Anakinra) with benefit, but data regarding efficacy, dose and route of administration are lacking. Objectives: To analyze the outcomes of MIS-C patients treated with anakinra (ANK) in Italy since 1/4/20. Methods: We performed an anonymous retrospective multicenter study of patients diagnosed with MIS-C, according to the preliminary WHO case definition, treated with ANK from 1/4/20 to 28/2/21. SARSCoV2 infection was demonstrated either by serology or by positive molecular swab (RT-PCR) in the six weeks prior to admission. After the start of ANK we measured the following outcomes: rate of patients needing further therapeutic step-up, rate of patients achieving clinical (fever defervescence in 24 hours) and laboratory response (CRP halving in 48 hours), rate of Coronary Artery Anomalies (CAA) development during follow-up. Results: In the study period 35 MIS-C patients were treated with ANK: 13 patients (37.1%) in Intensive Care Unit (ICU, Group A) and 22 (62.9%) in non-ICU settings (Group B). Epidemiological, clinical, and laboratoristic features at ANK prescription are described below: In Group A the most common indication for ANK was cardiac function worsening (46.1%), while in Group B ANK was started mostly for persistent elevation in inflammatory markers (ferritin, CRP) unresponsive to IVIG and/or steroids (31.8%). Endovenous (ev) ANK was used in all Group A patients (mean dose 8mg/Kg), while most patients in Group B (72.7%) received subcutaneous (sc) ANK (mean dose 4mg/Kg). Overall only 2 patients (5.7%) needed a step-up treatment after ANK start (1 required IVIG, 1 methylprednisolone dose increase), most of the patients achieved clinical (85.7%) and laboratory response (74.3%). 2 patients had CAA before ANK, none developed CAA after starting ANK. Overall NT-proBNP halved in 2.5 days in Group A and 2 days in Group B, while Ejection Fraction (EF) normalized respectively in 2 and 3 days. None of the patients in Group B needed ICU admission or inotropic support after ANK. The most frequently observed side effect was ALT increase (30.8% in Group A and 9.1% in Group B), only 1 patient had injection site reaction. Conclusion: MIS-C is a severe emerging disease with a high ICU admission rate. Our retrospective data suggest that both ev and sc ANK is effective in controlling inflammation, fever and cardiac dysfunction. Side effects are transient and usually mild. Overall the reported incidence of CAA in MIS-C cohorts is 10%, interestingly in our cohort no patient has developed CAA after beginning ANK, possibly suggesting a protective role of IL1 inhibition in aneurysm formation. Further studies in bigger cohorts are needed to define the most effective timing and dose of ANK in MIS-C.