Defining criteria for disease activity states in juvenile dermatomyositis based on the Juvenile Dermatomyositis Activity Index.

OBJECTIVES: To develop and validate the cut-offs in the Juvenile DermatoMyositis Activity Index (JDMAI) to distinguish the states of inactive disease (ID), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) in children with juvenile dermatomyositis (JDM). METHODS: For cut-off definition, data from 139 patients included in a randomised clinical trial were used. Among the six versions of the JDMAI, JDMA1 (score range 0-40) and JDMAI2 (score range 0-39) were selected. Optimal cut-offs were determined against external criteria by calculating different percentiles of score distribution and through receiver operating characteristic curve analysis. External criteria included the modified Pediatric Rheumatology International Trials Organization (PRINTO) criteria for clinically ID in JDM (for ID) and PRINTO levels of improvement in the clinical trial (for LDA and HDA). MDA cut-offs were set at the score interval between LDA and HDA cut-offs. Cut-off validation was conducted by assessing construct and discriminative ability in two cohorts including a total of 488 JDM patients. RESULTS: The calculated JDMAI1 cut-offs were ≤2.4 for ID, ≤6.6 for LDA, 6.7-11 for MDA and >11 for HDA. The calculated JDMAI2 cut-offs were ≤5.2 for ID, ≤8.5 for LDA, 8.6-11.3 for MDA and >11.3 for HDA. The cut-offs discriminated strongly among disease activity states defined subjectively by caring physicians and parents, parents' satisfaction or non-satisfaction with illness outcome, levels of pain, fatigue, physical functional impairment and physical well-being. CONCLUSIONS: Both JDMAI1 and JDMAI2 cut-offs revealed good metrologic properties in validation analyses and are, therefore, suited for application in clinical practice and research.

Defining patient perception of overall well-being and disease activity in the OMERACT Juvenile Idiopathic Arthritis (JIA) core domain set: A report from the JIA working group.

OBJECTIVE: The OMERACT Juvenile Idiopathic Arthritis (JIA) Working Group (WG) aimed to reach agreement on a consensus-based definition and description of the core domain related to patient perception of overall well-being and disease activity. METHODS: A committee of patient research partners, clinicians, methodologists, and researchers drafted working definitions and descriptions. The WG conducted two iterative electronic stakeholder surveys to obtain consensus on domain description, definition, and the distinction between patient perception of overall well-being and disease activity. These definitions were then presented at the OMERACT 2023 Special Interest Group (SIG) session for agreement. RESULTS: Forty-five participants, from 7 countries and 4 continents, were comprised of six patients, 18 caregivers, and 21 healthcare providers. The consensus threshold (70%) was exceeded on all survey questions from both stakeholder groups (patients/caregivers, all others). Agreement was obtained on the new definition, description, and domain title, along with agreement on separate assessments of two target domains, patient perception of overall well-being as it relates to disease and patient perception of disease activity. CONCLUSION: Through an iterative consensus process and achieving agreement from the OMERACT SIG session attendees, the JIA WG has created a detailed definition and description for the two target domains in the patient perception of overall well-being related to disease core domain of the JIA mandatory core domain set. The next phase of this work will be instrument selection using the OMERACT filter 2.2.

Early anakinra treatment improves cardiac outcome of multisystem inflammatory syndrome in children, regardless of disease severity.

OBJECTIVE: The main aim of this study was to define the best treatment option for multisystem inflammatory syndrome in children (MIS-C) and to analyse the role of anakinra. METHODS: This is a multicentre retrospective cohort study. Patients were treated according to the attending physician's decision. The patients were divided into four groups on the basis of the first treatment at time of admittance: (i) IVIG, (ii) IVIG and methylprednisolone (≤2 mg/kg/day), (iii) IVIG with high-dose methylprednisolone (>2 mg/kg/day) and (iv) anakinra with or without IVIG and/or methylprednisolone. Primary outcomes were defined as the presence of at least one of the following features: death, the failure of initial treatment, meaning the need for additional treatment for clinical worsening and cardiac involvement at the end of follow-up. RESULTS: Two hundred thirty-nine patients were recruited. At univariate analysis, persistent heart involvement at discharge was more frequent in those not receiving anakinra as initial treatment (3/21 vs 66/189; P = 0.047). After comparisons between the four treatment regimens, adjusting for the propensity score, we observed that early treatment with anakinra was associated with a lower probability of developing persistent heart disease at the end of follow-up (odds ratio: 0.6; 95% CI: 0.4-1.0). CONCLUSION: We report that early treatment with anakinra is safe and very effective in patients with severe MIS-C. In addition, our study suggests that early treatment with anakinra is the most favourable option for patients with a higher risk of developing a severe disease outcome.

Clinical features, treatment and outcomes of Italian children with enthesitis-related arthritis and juvenile psoriatic arthritis: a cross-sectional cohort study.

OBJECTIVES: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA. METHODS: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and laboratory tests, and recording of ongoing therapies. RESULTS: Of the 9081 children with JIA enrolled in the EPOCA Study, 1300 were recruited at 18 paediatric rheumatology centres in Italy. 45 (3.5%) had ERA and 49 (3.8%) had JPsA. Several remarkable differences in demographic features and frequency of articular and extra-articular manifestations, disease damage, impairment in physical function and health-related quality of life, school-related problems, comorbidities, and ongoing treatments were observed between ERA and JPsA and the other JIA categories. CONCLUSIONS: We described the characteristics of Italian children with ERA and JPsA and highlighted their peculiarities and their differences from the other JIA subsets. These data provide useful insights for future revisions of JIA classification and a benchmarking against which the features from other cohorts may be compared.

Skin manifestations help identifying different phenotypes of paediatric SAPHO syndrome.

OBJECTIVES: to evaluate whether the heterogeneous skin manifestations might influence the disease presentation and outcome of a cohort of SAPHO children. METHODS: the clinical, serological, imaging and therapeutic data of 14 SAPHO patients, followed between 2001 and 2022 at the Unit for Autoinflammatory diseases at the Gaslini Hospital, were reviewed. According to their cutaneous manifestations, patients were divided into 2 groups: the acne-hidradenitis suppurativa (HS) and the Palmo-Plantar Pustulosis (PPP) group. Data were retrieved from the Eurofever database. RESULTS: all patients presented bone involvement characterized by Chronic Recurrent multifocal Osteomyelitis (CRMO): 8 patients presented acne-HS while 6 patients had PPP. In the PPP group, all patients were female, characterized by a prepuberal disease onset with osteoarticular manifestations, followed by the appearance of PPP in the following 6 months. This group responded well to the treatments. In the acne-HS group, 7/8 patients were male: the disease onset was characterized by skin manifestations in pubertal age, followed by osteoarticular manifestations in the following year. This group presented a severe refractory skin disease that required in most cases the addition of biological therapies. A literature review confirmed our data highlighting the association males-acne-puberal age and female-PPP-prepuberal age. CONCLUSION: paediatric SAPHO patients should be mainly stratified according to their skin involvement. In fact, our data suggest that two different skin phenotypes may be identified in SAPHO: the first is constituted by prepuberal females with PPP and a prevalent osteoarticular involvement, while the second by puberal males with a difficult-to-treat acne-HS.

Treat-to-Target in Pediatric Rheumatic Diseases.

PURPOSE OF REVIEW: To summarize the current evidence on the adoption of the treat-to-target (T2T) strategy in pediatric rheumatic diseases (PRD). RECENT FINDINGS: The recent advances in the management of PRD have markedly increased the ability to achieve disease remission. Complete disease quiescence is regarded as the ideal therapeutic goal because its attainment leads to lesser long-term damage and physical disability, and to optimization of quality of life. Studies in adult rheumatic diseases have shown that patient outcomes are improved if complete suppression of the inflammatory process is aimed for by frequent adjustments of therapy according to quantitative indices. This approach, which underlies the T2T concept, has been applied in strategic trials in rheumatoid arthritis (RA). Furthermore, recommendations for the T2T have been issued for RA and other adult rheumatic diseases. There is currently a growing interest for the introduction of T2T in PRD, and recommendations for treating juvenile idiopathic arthritis (JIA) to target were promulgated. A similar initiative has been undertaken for childhood-onset systemic lupus erythematosus. Preliminary therapeutic studies have explored the T2T design in JIA. The T2T strategy is a modern therapeutic approach that holds the promise of improving the outcomes in patients with PRD.

Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers.

Introduction: New early low-invasive biomarkers are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic pediatric rheumatic disease in Western countries and a leading cause of disability. A deeper understanding of the molecular basis of OJIA pathophysiology is essential for identifying new biomarkers for earlier disease diagnosis and patient stratification and to guide targeted therapeutic intervention. Proteomic profiling of extracellular vesicles (EVs) released in biological fluids has recently emerged as a minimally invasive approach to elucidate adult arthritis pathogenic mechanisms and identify new biomarkers. However, EV-prot expression and potential as biomarkers in OJIA have not been explored. This study represents the first detailed longitudinal characterization of the EV-proteome in OJIA patients. Methods: Fourty-five OJIA patients were recruited at disease onset and followed up for 24 months, and protein expression profiling was carried out by liquid chromatography-tandem mass spectrometry in EVs isolated from plasma (PL) and synovial fluid (SF) samples. Results: We first compared the EV-proteome of SF vs paired PL and identified a panel of EV-prots whose expression was significantly deregulated in SF. Interaction network and GO enrichment analyses performed on deregulated EV-prots through STRING database and ShinyGO webserver revealed enrichment in processes related to cartilage/bone metabolism and inflammation, suggesting their role in OJIA pathogenesis and potential value as early molecular indicators of OJIA development. Comparative analysis of the EV-proteome in PL and SF from OJIA patients vs PL from age/gender-matched control children was then carried out. We detected altered expression of a panel of EV-prots able to differentiate new-onset OJIA patients from control children, potentially representing a disease-associated signature measurable at both the systemic and local levels with diagnostic potential. Deregulated EV-prots were significantly associated with biological processes related to innate immunity, antigen processing and presentation, and cytoskeleton organization. Finally, we ran WGCNA on the SF- and PL-derived EV-prot datasets and identified a few EV-prot modules associated with different clinical parameters stratifying OJIA patients in distinct subgroups. Discussion: These data provide novel mechanistic insights into OJIA pathophysiology and an important contribution in the search of new candidate molecular biomarkers for the disease.

Paediatric rheumatologists do not score the physician's global assessment of juvenile idiopathic arthritis disease activity in the same way.

OBJECTIVES: To assess the heterogeneity in factors affecting physician's global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient's case scenarios. METHODS: An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation. RESULTS: The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72). CONCLUSIONS: In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients.

Use of Telemedicine Healthcare Systems in Pediatric Assistance at Territorial Level: Consensus Document of the Italian Society of Telemedicine (SIT), of the Italian Society of Preventive and Social Pediatrics (SIPPS), of the Italian Society of Pediatric Primary Care (SICuPP), of the Italian Federation of Pediatric Doctors (FIMP) and of the Syndicate of Family Pediatrician Doctors (SIMPeF).

Technological innovation can contribute to a reorganization of healthcare, particularly by supporting the shift in the focus of care from the hospital to the territory, through innovative citizen-centered models, and facilitating access to services in the territory. Health and social care delivery modalities, enabled by telemedicine, are crucial in this regard. The objective of this Consensus document, written by the main Italian Scientific Societies involved in the use of telemedicine in pediatrics, is to define a standard for its use at the territorial level in various declinations in the pediatric field; this paper also identifies priority areas for its application and the types of services that most require intervention and investment. The changes that are underway in digital transformation in all sectors are unstoppable, and for the digital transformation to take place in a productive sense, the contribution of not only all health professionals, but also of patients, is necessary. From this perspective, authors from different backgrounds were involved in the drafting of this Consensus and, in the future, other figures, primarily patients, are expected to be involved. In fact, this belongs to the vision of connected care, in which the citizen/patient actively participates in the treatment path so that they are assisted in a personalized, predictive and preventive way. The future scenario must be able to provide for the involvement of patients from the initial stages of planning any treatment path, even in the pediatric age, and increasing, where possible, the proximity of the health service to the families.

Use of Telemedicine Healthcare Systems in Children and Adolescents with Chronic Disease or in Transition Stages of Life: Consensus Document of the Italian Society of Telemedicine (SIT), of the Italian Society of Preventive and Social Pediatrics (SIPPS), of the Italian Society of Pediatric Primary Care (SICuPP), of the Italian Federation of Pediatric Doctors (FIMP) and of the Syndicate of Family Pediatrician Doctors (SIMPeF).

Telemedicine is considered an excellent tool to support the daily and traditional practice of the health profession, especially when referring to the care and management of chronic patients. In a panorama in which chronic pathologies with childhood onset are constantly increasing and the improvement of treatments has allowed survival for them into adulthood, telemedicine and remote assistance are today considered effective and convenient solutions both for the chronic patient, who thus receives personalized and timely assistance, and for the doctors, who reduce the need for direct intervention, hospitalizations and consequent management costs. This Consensus document, written by the main Italian Scientific Societies involved in the use of telemedicine in pediatrics, has the objectives to propose an organizational model based on the relationships between the actors who participate in the provision of a telemedicine service aimed at minors with chronic pathologies, identifying specific project links between the areas of telemedicine in the developmental age from the first 1000 days of life to the age adult. The future scenario will have to be able to integrate digital innovation in order to offer the best care to patients and citizens. It will have to be able to provide the involvement of patients from the very beginning of the design of any care pathway, increasing where possible the proximity of the health service to citizens.

Information and Training on the Use of Telemedicine in Pediatric Population: Consensus Document of the Italian Society of Telemedicine (SIT), of the Italian Society of Preventive and Social Pediatrics (SIPPS), of the Italian Society of Pediatric Primary Care (SICuPP), of the Italian Federation of Pediatric Doctors (FIMP), and of the Syndicate of Family Pediatrician Doctors (SIMPeF).

Telemedicine has entered the daily lives of doctors, although the digital skills of healthcare professionals still remain a goal to be achieved. For the purpose of a large-scale development of telemedicine, it is necessary to create trust in the services it can offer and to favor their acceptance by healthcare professionals and patients. In this context, information for the patient regarding the use of telemedicine, the benefits that can be derived from it, and the training of healthcare professionals and patients for the use of new technologies are fundamental aspects. This consensus document is a commentary that has the aim of defining the information on and training aspects of telemedicine for pediatric patients and their caregivers, as well as pediatricians and other health professionals who deal with minors. For the present and the future of digital healthcare, there is a need for a growth in the skills of professionals and a lifelong learning approach throughout the professional life. Therefore, information and training actions are important to guarantee the necessary professionalism and knowledge of the tools, as well as a good understanding of the interactive context in which they are used. Furthermore, medical skills can also be integrated with the skills of various professionals (engineers, physicists, statisticians, and mathematicians) to birth a new category of health professionals responsible for building new semiotics, identifying criteria for predictive models to be integrated into clinical practice, standardizing clinical and research databases, and defining the boundaries of social networks and new communication technologies within health services.

Juvenile Psoriatic Arthritis: Myth or Reality? An Unending Debate.

Juvenile psoriatic arthritis (JPsA) accounts for 1-7% of all cases of juvenile idiopathic arthritis (JIA) and its definition has been a matter of controversy among pediatric rheumatologists for many years. The traditional attribution of JPsA to the spondyloarthropathy group was challenged in the early 1990s, whereas the recent demonstrations of its heterogenous nature have led to questions about its identification as a distinct category in JIA classification. It has been shown that children with the phenotype of JPsA can be divided in two subgroups, one presenting with the features of early-onset ANA-positive JIA, and another that belongs to the spectrum of spondyloarthropathies. The few studies that have compared the clinical characteristics and genetic determinants of JPsA with those of the other JIA categories have obtained contrasting findings. The debate on the categorization of JPsA as a distinct entity within JIA classification is still ongoing and has prompted the revision of its current classification.

Validity and Reliability of Four Parent/Patient-Reported Outcome Measures for Juvenile Idiopathic Arthritis Remote Monitoring.

OBJECTIVE: The aim of this work was to provide evidence of validity and reliability for 4 parent/child-reported outcome measures included in the Outcome Measures in Rheumatology juvenile idiopathic arthritis core domain set: the evaluation of the child's pain and level of disease activity, the assessment of morning stiffness duration, and an active joint count for proxy/self-assessment. METHODS: Patients were included in the multinational study Epidemiology Treatment and Outcome of Childhood Arthritis. Criterion validity was assessed by examining the correlation of the 4 tested measures with physician measures and the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) in the whole sample and after grouping patients by International League of Associations for Rheumatology (ILAR) category, geographic area, and education level. Reliability was assessed comparing 2 visits 7-14 days apart with intraclass correlation coefficients (ICCs). RESULTS: A total of 8,643 parents and 6,060 patients had all the evaluations available. Correlations of tested measures were moderate (0.4-0.7) with physician-reported measures. The level of correlation with the cJADAS10 remained stable after grouping patients by ILAR category, geographic areas, and level of education of the parent filling the questionnaire. In 442 parents and 344 children, ICCs ranged between 0.79 and 0.87 for parents and 0.81 and 0.88 for children. CONCLUSION: The 4 tested parent/child-reported outcomes showed good criterion validity and excellent reliability. These tools can be considered for remote patient assessment, when in-person evaluation might not be possible.

Experience with the use of mycophenolate mofetil in juvenile idiopathic inflammatory myopathies.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of MMF in juvenile idiopathic inflammatory myopathies (JIIMs). METHODS: Patients diagnosed with JIIM and treated with MMF enrolled in the Juvenile Dermatomyositis Research Group (JDRG) in the UK or followed at the Giannina Gaslini Institute in Genoa, Italy, were included. The following information was collected retrospectively at MMF initiation, at 3, 6 and 12 months after treatment start, and at last follow-up visit: clinical manifestations, laboratory data, physicians' subjective assessment of disease activity, standardized outcome measures of muscle strength/endurance, cutaneous disease activity, physical function, global disease activity, cumulative damage, and ongoing treatment. RESULTS: Of the 29 patients included, 23 had juvenile DM and 6 had overlap myositis. During administration of MMF, improvement in measures of muscle strength, skin disease activity, and overall disease activity was seen, with an increase in the frequency of normal scores for Manual Muscle Test-8 from 50.0% to 83.3%, Childhood Myositis Activity Score from 53.5% to 88.9%, muscle component of DAS from 55.2% to 84.2%, skin component of DAS from 31.0% to 42.1%, visual analogue scale for skin disease activity from 25.0% to 47.4%, and visual analogue scale for overall disease activity from 7.1% to 42.1%. The number of patients with inactive disease increased from 10.3% at baseline to 68.5% at last follow-up. CS dose was significantly reduced, from 0.3 to 0.1 mg/kg/day. No relevant side effects were reported. CONCLUSION: Our experience suggests that MMF is a valuable therapeutic option for the management of JIIM.

Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study.

BACKGROUND: Etanercept (ETN) and adalimumab (ADA) are considered equally effective biologicals in the treatment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a differential effect on patient-reported well-being in non-systemic JIA using real-world data. METHODS: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3-12 months afterwards. Primary outcome at follow-up was the improvement in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed effects models. RESULTS: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched resulting in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (interquartile range (IQR): 0.0 - 4.0) and scores were significantly better (P = 0.01) for ETN starters (median 0.0, IQR: 0.0 - 1.0) compared to ADA starters (median 1.0, IQR: 0.0 - 3.5). The estimated mean difference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 - 1.78; P = 0.06). The estimated mean difference in active joint count decrease was -0.36 (95% CI: -1.02 - 0.30; P = 0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 -1.44; P = 0.19). One uveitis event was observed in the ETN group. CONCLUSIONS: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger effect for ETN, but larger studies are needed to confirm this given the lack of statistical significance.

Looking for the best strategy to treat children with new onset juvenile idiopathic arthritis: presentation of the "comparison of STep-up and step-down therapeutic strategies in childhood ARthritiS" (STARS) trial.

BACKGROUND: Although a satisfactory disease control is nowadays achievable in most patients with JIA, a substantial proportion of them still do not respond adequately or reach long-term drug-free remission. According to current recommendations, treatment should be escalated in subsequent steps. A different approach is based on the assumption that the initial start of an aggressive therapy may take advantage of the "window of opportunity" and could alter the biology of the disease, leading to an improvement of long-term outcomes, including the prevention of cumulative joint damage. OBJECTIVES: This randomised clinical trial aims to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation and driven by the treat-to-target approach, with that of an early aggressive intervention based on the initial start of a combination of conventional and biological DMARDs. METHODS: JIA patients with oligoarthritis or RF negative polyarthritis aged more than 2 years and with less than 4 months of disease course will be included in the study. Children will be randomised into two arms: patients in Step-up arm with less severe oligoarthritis will undergo an intra-articular corticosteroid injection (IACI) in all affected joints; patients with polyarthritis or severe oligoarthritis will receive IACI and methotrexate. Subsequent treatment will follow a standardised protocol based on the patients' level of disease activity measured with the JADAS, according to a treat-to-target strategy. Patients in Step-down arm will receive a 6-month early combined treatment (methotrexate plus IACI for less severe oligoarthritis, methotrexate plus etanercept for severe oligoarthritis and polyarthritis). The primary endpoint is the frequency of achievement of the status of clinical remission (i.e. persistence of inactive disease for at least 6 months) at the 12-month visit. Safety events, physician-centred measures and parent/patient-reported outcomes will be collected through the Paediatric Rheumatology International Trials Organisation on line database. EXPECTED RESULTS: The STARS trial aims to provide important evidence supporting the first-line treatment choices in the care of children with oligoarticular and polyarticular JIA. If the superiority of an early aggressive therapy will be demonstrated, this will demand further studies on the biological definition of the window of opportunity for JIA. TRIAL REGISTRATION: The Trial is registered on the ClinicalTrials.gov registry (NCT03728478) on the 31st October 2018 and EU Clinical Trials Register on the 14th May 2018 (EudraCT Number: 2018-001931-27).

Protection against MIS-C outweighs the risk of myocarditis after Covid-19 vaccination in children.

From March 2020 to July 2022, in Liguria region (North-West Italy) incidence of MIS-C among pediatric patients infected by SARS-CoV-2 was 38.7/100.000, which is higher than that of myocarditis after COVID-19 vaccination. In our opinion severity of MIS-C-related cardiac disease outweigh the risk of myocarditis after COVID-19 vaccine.

Cardiovascular Manifestations in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19 According to Age.

Cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus-19 disease is often observed with a high risk of heart failure. The aim is to describe cardiovascular involvement, management and early outcome in MIS-C by comparing cardiovascular manifestations in children younger and older than 6 years old. This retrospective observational study included 25 children with MIS-C, admitted to a single pediatric center between March 2020 and September 2021. The median age was 5 years (13 patients under 6 years and 12 over 6 years); coronary artery abnormalities were observed in 77% of preschoolers, with small and medium aneurysms in half of the cases and two cases of mild ventricular dysfunction. School-age children presented myopericardial involvement with mild to moderate ventricular dysfunction in 67% of cases, and two cases of transient coronary dilatation. There was a significant NT-pro-BNP and inflammatory markers increase in 25 of the patients, and mild elevation of troponin I in 9. All patients were treated with intravenous immunoglobulin and corticosteroids, and 8 with anakinra. None of the patients needed inotropes or intensive care unit admission. Our study shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to different age group: coronary artery anomalies were more frequent in the younger group, and myopericardial disease in the older one. A prompt multitarget, anti-inflammatory therapy could probably contribute to a favorable outcome.