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Objective: To develop and externally validate a prediction model for new-onset chronic uveitis in children with juvenile idiopathic arthritis (JIA) for clinical application. Methods: Data from the international Pharmachild registry were used to develop a multivariable Cox proportional hazards model. Predictors were selected by backward selection, and missing values were handled by multiple imputation. The model was subsequently validated and recalibrated in 2 inception cohorts: the UK Childhood Arthritis Prospective Study (CAPS) study and the German Inception Cohort of Newly diagnosed patients with juvenile idiopathic arthritis (ICON) study. Model performance was evaluated by calibration plots and C statistics for the 2-, 4-, and 7-year risk of uveitis. A diagram and digital risk calculator were created for use in clinical practice. Results: A total of 5, 393 patients were included for model development, and predictor variables were age at JIA onset (hazard ratio [HR] 0.83 [95% confidence interval (95% CI) 0.77-0.89]), ANA positivity (HR 1.59 [95% CI 1.06-2.38]), and International League of Associations for Rheumatology category of JIA (HR for oligoarthritis, psoriatic arthritis, and undifferentiated arthritis versus rheumatoid factor-negative polyarthritis 1.40 [95% CI 0.91- 2.16]). Performance of the recalibrated prediction model in the validation cohorts was acceptable ; calibration plots indicated good calibration and C statistics for the 7-year risk of uveitis (0.75 [95% CI 0.72-0.79] for the ICON cohort and 0.70 [95% CI 0.64-0.76] for the CAPS cohort). Conclusion: We present for the first time a validated prognostic tool for easily predicting chronic uveitis risk for individual JIA patients using common clinical parameters. This model could be used by clinicians to inform patients/parents and provide guidance in choice of uveitis screening frequency and arthritis drug therapy.

Multisystem inflammatory syndrome in children (MIS-C) is a pathologic condition that has emerged during the coronavirus disease 2019 (COVID-19) pandemic. Although the epidemiological evidence of association between MIS-C and SARS-CoV-2 infection has been demonstrated, its pathogenic mechanism is still undefined. We describe the case of a 17-year old female, previously vaccinated against SARS-CoV-2, presenting with a history of asthenia, fever, cough, anorexia, abdominal pain, and vomiting. During the hospitalization, the patient developed bilateral conjunctivitis, hand vasculitis, cutaneous rash, and multiple pulmonary nodules, following by hepatitis and pancreatitis. As she reported a high-risk contact with a SARS-CoV-2 positive patient 10 days before admission, the epidemiological link and the clinical picture characterized by multi-system organ disfunction and inflammatory biomarkers increase led us to the diagnosis of MIS-C. Therefore, the patient was treated with intravenous immunoglobulin and corticosteroids, resulting in a rapid resolution of fever, cutaneous, and pulmonary involvement, while the recovery of hepatitis and pancreatitis was observed in the following weeks. This case leads to the discussion on whether SARS-CoV-2 immunized children and adolescents should be considered at risk of developing MIS-C and on their possible presentation with non-classic clinical features. Additionally, due to the increasing number of vaccinated children and adolescents, the issues resulting either from the diagnostic suspect of MIS-C or from the consequent need of an early therapeutic approach are discussed.

Background: Dominantly gain-of-function mutations in the NLRP3 gene lead to Cryopyrin associated periodic syndromes (CAPS) characterized by constitutive activation of the inflammasome, increased secretion of interleukin (IL)-1beta and IL-18, and systemic inflammation. IL-1beta and active caspase-1 subunits are released in the serum together with the oligomeric particles of the adaptor ASC (apoptosis-associated Speck-like protein with a caspase-recruitment domain) after activation of the inflammosome complex and, as a consequence, patients with CAPS show an increased serum concentration of ASC+ particles. Objectives: Patients suffering from CAPS are characterized by clinical manifestation similar to other autoinflammatory diseases. This phenomenon together with the lack of specific laboratory tests makes difficult the diagnosis of CAPS. In this context the development of a test for the evaluation of serum ASC levels could provide novel biomarkers facilitating early disease diagnosis and able to monitor treatment responses. Methods: We analysed, with a novel ELISA assay, the levels of ASC particles in serum and plasma of normal subjects, CAPS patients and patients with autoimmune disorders (Multiple Sclerosis (MS), Type 1 Diabetes (T1D) and juvenile idiopathic arthritis), to confirm that ASC presence in the serum is not due to other chronic inflammatory processes characterizing autoimmunity. To evaluate the specificity of this biomarker in CAPS patients and not in individuals suffering from others inflammatory disorders, we also analysed sera from TNF receptor–associated periodic syndrome (TRAPS) patients. Results: ASC particles were higher in untreated CAPS patients with respect to healthy controls and patients suffering from MS and T1D. This tendency was also evident in patients with arthritis and TRAPS even if the difference was not statistically significant due to the small number of samples. In addition after pharmacological treatment there is a tendency to be confirmed through a reduction of ASC levels in CAPS patients. Conclusion: These data suggest that ELISA quantitation of ASC protein could represent a novel and additional strategy for the diagnosis and monitoring of CAPS.

Background: Acute pericarditis is an inflammatory condition causing the occurrence of pericardial effusion. In a third of patients, the disease is recurrent. Most of the cases are idiopathic or occur after a pericardial procedure. First line treatment of idiopathic pericarditis consists in NSAIDs and colchicine; glucocorticoids represent the second line treatment in resistant or intolerant cases. The use of different biologics and immunosoppressant has been reported, with variable responses. A recent clinical trial has enlightened the effectiveness of anakinra in patients with colchicine-resistant recurrent pericarditis. Objectives: To describe the clinical characteristics and response to treatment in a cohort of paediatric patients with recurrent pericarditis treated with IL inhibitors. Methods: Pediatric patients with recurrent pericarditis followed at 19 Italian centers of paediatric rheumatology or cardiology and treated with IL1 inhibitors were included in the study. Demographic, clinical and response to treatment data were retrospectively collected. Results: 55 patients were included in the study. The mean age at onset of the first episode of pericarditis was 12.53 years. The mean number of relapses of pericarditis before the beginning of treatment with IL1 inhibitors was of 3.4. 53 out of 55 patients had previously received treatment with NSAIDS and 44 colchicine. 44 patients received steroidal treatment: 2 of them displayed a steroidal-resistance and 39 steroidal-dependence with reoccurrence of the symptoms following any attempt to reduce or withdraw this treatment. Anakinra (mean dosage of 1.67 mg/kg/day) was used as first Il-1 inhibitor in 54 of the 55 patients, Canakinumab (150 mg every 4 weeks) in one. 53 out of 54 patients treated with anakinra displayed a complete clinical response to treatment within a mean of 2 days: NSAIDs, glucocorticoids and colchicine were withdraw in 25 out of 26, 31 out of 35 and 15 out of 32 patients respectively. 50 of 54 patients displayed a complete response; among these, three were switched to Canakinumab, 17 patients continued treatment at the same dosage while in 30 patients a reduction of treatment was attempted. 12 patients presented, during anakinra tapering, a disease flare, promptly resolved after an increasing of the dosage. The remaining 18 patients did not present any flare despite the reduction of the drug. Anakinra was withdrawn in 16 patients, with recurrence of the symptoms in 11 (9 restarted anakinra, 2 were treated with glucocorticoids and colchicine, with good response). 5 patients were treated with Canakinumab: 1 as first anti-IL1 drug, 4 were switched from anakinra (two for poor compliance, one for side effects and one for incomplete control of the disease). 2 out of five patients had a complete control of the diseases, 2 patients discontinued the treatment because of inefficacy and 1 patient required low dose of glucocorticoids to control the disease. At last follow-up 34 patients were on anakinra, 7 on anakinra and colchicine, 2 on canakinumab, 1 on canakinumab plus colchicine and NSAIDs. In 9 patients all treatments were withdrawn for complete control of the disease. Conclusion: This study confirm the effectiveness of IL-1 blockade in paediatric patients with recurrent pericarditis. However, most of the patients require prolonged treatment to maintain clinical remission. Moreover, in our cohort of patients the rate of response was higher for anakinra then for canakinumab, suggesting a possible role of IL1a in the pathogenesis of this condition.

Giorgio Costagliola, Susanna Cappelli, Rita Consolini Laboratory of Immunology, Department of Clinical and Experimental Medicine, Division of Pediatrics, University of Pisa, Pisa, ItalyCorrespondence: Giorgio Costagliola Email giorgio.costagliola@hotmail.comAbstract: Behçet’s Disease (BD) is an inflammatory disease of unknown etiology with multisystemic involvement, being the main clinical manifestations represented by recurrent oral and genital ulcerations and uveitis. The disease has typically a chronic-relapsing course and may cause significant morbidity and mortality due to eye, vascular and neurological involvement. Although BD is more frequently diagnosed in adulthood, the disease onset can also be in pediatric age. Pediatric-onset BD is commonly featured by an incomplete clinical picture, and therefore the diagnosis represents a considerable clinical challenge for the physicians. The first classification criteria for pediatric BD, based on a scoring system, have been proposed few years ago. This work focuses on the main difficulties concerning both the diagnostic approach and the treatment of BD in pediatric age. The recommendation for the treatment of pediatric BD has been recently updated and allowed a considerable improvement of the therapeutic strategies. In particular, the use of anti-TNFα drugs as a second-line option for refractory BD, and as a first-line treatment in severe ocular and neurological involvement, has demonstrated to be effective in improving the outcome of BD patients. The knowledge about the molecular pathogenesis is progressively increasing, showing that BD shares common features with autoimmune and autoinflammatory disorders, and thus leading to the use of new biologic agents targeting the main mediators involved in the determination of BD. Anti-IL-17, anti-IL-23, anti-IL-1 and anti-IL-6 agents have shown promising results for the treatment of refractory BD in clinical trials and will represent an important alternative for the therapeutic approach to the disease.Keywords: Behçet’s disease, aphtosis, differential diagnosis, autoinflammatory diseases, autoimmunity, biologic drugs