Case report: Exploring under the tip of the iceberg: A case series of “self-limiting” multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a serious condition triggered by SARS-COV-2 infection, characterized by persistent fever, multiorgan dysfunction, and increased inflammatory markers. It requires hospitalization and prompt treatment, with nearly 60% of the cases needing intensive care and 2% fatality rate. A wide spectrum of clinical characteristics and therapeutic approaches has been reported in MIS-C. We describe a series of four patients with MIS-C, defined according to the current case definitions, with a self-limiting course and no need for immunomodulatory treatment (“self-limiting MIS-C”). Few data about self-limiting MIS-C are available to date and no information on medium- and long-term outcome of this subset of patients has been reported. Although limited in size, our experience provides new insights into the MIS-C syndrome, highlighting an underestimated aspect of the disease that may have significant therapeutic implications

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Juvenile diabetes and systemic sclerosis: just a coincidence?

Background Limited joint mobility (LJM), previously known as cheiroarthropathy, refers to the presence of reduced extension at the finger joints in people with diabetes and may be associated with scleroderma-like syndromes such as diabetic sclerodactyly. While scleroderma-like syndromes and LJM have been observed in patients with long-term diabetes and associated complications, the coexistence of diabetes with Juvenile systemic sclerosis (jSSc) is rarely described. Case presentation We describe the case of a 14-year-old boy with long-lasting type 1 diabetes (T1D) and suspected LJM associated with Raynaud phenomenon, sclerodactyly and tapering of the fingertips. A comprehensive work-up showed positive autoantibodies (ANA, anti-Ro-52, anti-Mi-2b), abnormal nailfold capillaroscopy with a scleroderma pattern, interstitial lung disease and cardiac involvement. The overall clinical picture was consistent with the diagnosis of jSSc. Conclusions LJM can be the initial sign of underlying systemic sclerosis. Nailfold capillaroscopy may help differentiate jSSc from classical LJM in pediatric patients with T1D and finger contractures or skin induration of no clear origin. This case report provides a starting point for a novel hypothesis regarding the pathogenesis of jSSc. The association between T1D and jSSc may be more than a coincidence and could suggest a relationship between glucose metabolism, fibrosis and microangiopathy

Strategic use of levofolinic acid for methotrexate-induced side effects in juvenile idiopathic arthritis: a prospective observational study

ObjectiveTo evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy.MethodsA prospective observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3-4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time.ResultsTwenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21.ConclusionsLVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug's efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX

Early detection of ventricular dysfunction in juvenile systemic sclerosis by speckle tracking echocardiography

OBJECTIVE: Cardiac involvement is the most important cause of mortality in juvenile systemic sclerosis (JSSc). Recent reports in adult patients underline that traditional techniques of imaging are inadequate to assess the subclinical cardiac involvement, while speckle tracking echocardiography (STE) is able to identify ventricular dysfunctions in the early stages. The aim of our study was to assess the role of STE in JSSc.METHODS: Demographic, clinical and laboratory data were collected from patients with JSSc. Cardiac investigations performed at baseline (T0) and 18 (T18) and 36months (T36) follow-up included electrocardiography, conventional echocardiography with measurement of the ejection fraction (EF) and STE with assessment of left and right ventricular global longitudinal strain (LV-GLS and RV-GLS). Cardiac parameters have been compared with demographic characteristics and disease severity, assessed by the Juvenile Systemic Sclerosis Severity Score (J4S).RESULTS: A total of 18 patients, 12 (67%) females, entered the study. At T0, electrocardiography was abnormal in three patients, EF was reduced in one, LV-GLS was abnormal in three (16.7%) and RV-GLS was abnormal in five (27.8%). At T18, EF remained stable while at T36 the result decreased in seven of nine patients. At the same time, LV-GLS also worsened (from -21.6% to -18.2%, P=0.01). LV-GLS and RV-GLS at baseline showed a significant correlation with J4S (P=0.012 and P=0.02, respectively).CONCLUSION: STE is more sensitive than standard echocardiography to identify cardiac involvement in JSSc. Over time, we observed a gradual worsening of LV-GLS, a sign of left ventricular dysfunction, that anticipated by several months the decrease of EF

Methotrexate in Linear Scleroderma: long-term efficacy in 50 children from a single Pediatric Rheumatology Centre

OBJECTIVE: to study disease course and long-term outcome of children with Linear Scleroderma (LiS) treated with methotrexate (MTX) since diagnosis.METHODS: Retrospective and cross-sectional study including consecutive children with LiS treated with MTX for >1 year and with at least 2 years follow-up. Disease course was analyzed by number of relapses and treatment changes. Relapse-free survival (RFS) was examined by Kaplan-Meier analysis comparing patients with LiS and other JLS subtypes. Disease activity and damage were assessed by Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography.RESULTS: Fifty patients with mean follow-up 7.8 years and MTX treatment duration 3.1 years were included. Sixteen percent did not respond to first course of MTX and 16% had at least one flare. Complete remission was observed in 18.2% patients with 2-5 years follow-up, 80.0% by 10 years and 87.5% by >10 years. No significant difference in RFS between patients with LiS and 17 with other JLS subtypes was observed. Tissue damage was mild in 42% patients, moderate in 32% and severe in 26%. No significant correlation between severity of tissue damage and LiS subtype, disease duration, relapses and remission emerged. Treatment duration was significantly related to disease relapses (p<0.05) and severity of tissue damage (p<0.005).CONCLUSION: Most patients with LiS treated with MTX achieve complete and long-lasting remission. Overall aesthetic and functional sequelae are moderate, probably because tissue damage establishes early and treatment likely stabilizes it. Early diagnosis and MTX treatment as well as long-term monitoring are crucial to improve outcome and promptly identify flares

Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma

OBJECTIVES: To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma.METHODS: Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis.RESULTS: MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P=0.008 and P=0.029, respectively), and linear scleroderma of the face in the MTX-group (P=0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P=0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy.CONCLUSION: The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment