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To define the prevalence of subclinical synovitis on magnetic resonance imaging (MRI) in a large cohort of patients with juvenile idiopathic arthritis (JIA) in clinical remission and to evaluate its predictive value in terms of disease flare and joint deterioration.Ninety patients with clinically inactive JIA who underwent a contrast-enhanced (CE)-MRI of a previously affected joint were retrospectively included. Each joint was evaluated for synovitis, tenosynovitis, and bone marrow edema. Baseline and follow-up radiographs were assessed to evaluate structural damage progression.CE-MRI was acquired in 45 wrists, 30 hips, 13 ankles, and 2 knees. Subclinical synovitis was detected in 59 (65.5%) of 90 patients and bone marrow edema in 42 (46.7%) of 90 patients. Fifty-seven of 90 (63.3%) patients experienced a disease flare during follow-up. Forty-four of 59 (74.6%) patients with subclinical synovitis experienced a disease flare versus 13 (41.9%) of 31 patients with no residual synovitis on MRI (P = 0.002). The presence of subclinical synovitis was the best predictor of disease flare on multivariable regression analysis (hazard ratio [HR] 2.45, P = 0.003). Baseline and follow-up radiographs were available for 54 patients, and 17 (31.5%) of 54 patients experienced radiographic damage progression. The presence of bone marrow edema (HR 4.40, P = 0.045) and being17 years old (HR 3.51, P = 0.04) were strong predictors of joint damage progression in the multivariable analysis.MRI-detected subclinical inflammation was present in a large proportion of patients with JIA despite clinical remission. Subclinical synovitis and bone marrow edema have been shown to play a role in predicting the risk of disease relapse and joint deterioration, with potential implications for patients' management of the disease.

Background Functional variants of the cytotoxic T-lymphocyte antigen-4 (CTLA4) could contribute to the pathogenesis of disorders characterized by abnormal T-cell responses. Case presentation We report a case of a 13-year-old girl who first presented with polyarticular juvenile idiopathic arthritis poorly responsive to treatment. During the following years the patient developed cytopenias, chronic lymphoproliferation, high values of T-cell receptor αβ+ CD4- CD8- double-negative T cells and defective Fas-mediated T cells apoptosis. Autoimmune lymphoproliferative syndrome was diagnosed and therapy with mycophenolate mofetil was started, with good hematological control. Due to the persistence of active polyarthritis, mycophenolate mofetil was replaced with sirolimus. In the following months the patient developed hypogammaglobulinemia and started having severe diarrhea. Histologically, duodenitis and chronic gastritis were present. Using the next generation sequencing-based gene panel screening, a CTLA4 mutation was detected (p.Cys58Serfs*13). At the age of 21 the patient developed acute autoimmune hemolytic anemia; steroid treatment in combination with abatacept were started with clinical remission of all symptoms, even arthritis. Conclusions Targeted immunologic screening and appropriate genetic tests could help in the diagnosis of a specific genetically mediated immune dysregulation syndrome, allowing to select those patients who can take advantage of target therapy, as in the case of abatacept in CTLA4 deficiency.

Objective.To investigate the effect of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinically inactive disease (CID).Methods.We examined 652 visits in which patients fulfilled 2004 or 2011 Wallace criteria for CID. Parent-reported outcomes were compared among patients with no MS or with MS < or ≥ 15 min.Results.Among 652 visits with CID by 2004 criteria, no MS was reported in 554 visits (85%), MS < 15 min in 53 (8%), and MS ≥ 15 min in 45 (7%). The frequency of altered physical function, health-related quality of life and well-being, pain, and disease activity visual analog scales was proportionally greater in patients without MS than those with longer MS. The frequency of parent subjective rating of disease state as remission was 87.7%, 58%, and 26.7% among patients with no MS, MS < 15 min, and MS ≥ 15 min, respectively.Conclusion.Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered.

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. Morning stiffness is a major symptom of JIA, and is usually associated with active disease. The 2004 preliminary criteria for inactive disease (ID) in JIA did not include the assessment of morning stiffness, whereas the 2011 revision of the criteria has allowed the presence of morning stiffness (MS) lasting ≤ 15 minutes. MS was included in 2011 revision based on the consideration that MS of a short duration (i.e., ≤ 15 minutes) can represent residua of previously active disease without current active disease. However, it is unclear whether the disease status of children with ID who have or do not have morning stiffness is comparable. Objectives: To compare the disease status of children with JIA who met the 2004 and 2011 revised criteria for ID in relation to the presence or absence morning stiffness. Methods: A database of 1208 Italian children included in 2 multicenter studies (1,2) who underwent a total of 3380 visits was examined to identify all visits in which the patients fulfilled the 2004 or 2011 criteria for ID. In case a patient met the ID criteria in more than 1 visit, only the first visit was retained. For each visit with ID, the duration of morning stiffness was categorized as ≤ 15 min or > 15 min. Clinical assessments included demographic features and parent-reported outcomes Results: A total of 668 visits in which patients met the criteria for ID were identified. Absence of morning stiffness was reported in 564 (84.4%) visits, whereas in 104 visits (15.5%) there was morning stiffness. Among the visits with morning stiffness, in 55 (8.2%) duration was ≤15 min, and in 49 (7.3%) duration was > 15 min. The table shows the comparison of disease duration and parent-reported outcomes between patients with absence or presence of morning stiffness. MS: morning stiffness; IQR: interquartile range, *above the mean of healthy children (2) Conclusion: Among patients who met the 2011 criteria for ID, those with morning stiffness ≤15 min had worse parent-reported outcomes than those without morning stiffness. This finding suggests that parents may not perceive their child’s disease state as true remission when lower degrees of morning stiffness are present. Notably, a sizeable proportion (7,3%) of children meeting the 2004 ID criteria had morning stiffness lasting > 15 min. The removal of the criterion “Duration of morning stiffness of ≤ 15 minutes” to “Absence of morning stiffness” in the definition for ID should be considered. References [1] Filocamo, et al. A new approach to clinical care of juvenile idiopathic arthritis: the Juvenile Arthritis Multidimensional Assessment Report. J Reumatol 2011 [2] Verazza, et al. Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept. PROJ 2016 Disclosure of Interests: Maria Francesca Gicchino: None declared, Gabriella Giancane: None declared, Alessandra Alongi: None declared, Silvia Rosina: None declared, Jessica Tibaldi: None declared, Marta Mazzoni: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer

Background: remission is becoming a realistic target in JIA, but clinical remission (CR) may not accurately reflect real absence of synovitis. It would be desirable to have instruments to predict the risk of relapse in patients in CR in order to establish the most appropriate therapeutic strategy. Despite in RA the role of imaging to predict disease flare is established, this field has remained almost unexplored in JIA. Objectives: 1) to investigate the prevalence of musculoskeletal ultrasound (MSUS)-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare; 5) MSUS data will be integrated with serum levels of inflammatory biomarkers to develop a multidimensional measure of remission. Methods: it is a longitudinal prospective 4 years study started on November 2017. So far we have enrolled 99 consecutive JIA patients who met the Wallace criteria for CR. For each patient 46 joints were scanned for synovial hyperplasia/joint effusion and PD signal, all graded semiquantitatively on a 0–3 scale independently by 2 expert ultrasonographers. Subclinical synovitis was defined when total synovitis score for each joint was ≥2. MSUS was performed at baseline and at 6 month follow up visit. At inclusion serum assays have been stored to determine levels of inflammatory biomarkers (S100A8/9-A12, bFGF, IL-6, IL-10, CXCL9-10, VEGF, YKL40). A flare of synovitis was defined as a recurrence of clinically active arthritis. Results: 99 patients (79.8% F; median age 11.3 y; median disease duration 5.3 y; median CR duration 1.6 y) were included. Thirty-eight/99 (38.4%) patients had persistent oligoarthiritis; 34/99 (34.3%) extended oligoarthiritis; 22/99 (22.2%) polyarthiritis; 5/99 (5.1%) systemic arthritis. Fifty-nine/99 (59.6%) patients were in CR on medication. Subclinical synovitis was detected in 54/99 (54.5%; 95% CI: 45.2 – 65.5%) patients, PD in 18/99 (18.2%; 95% CI: 11.1 – 27.2%) patients; subclinical tenosynovitis in 7/99 (7.1%; 95% CI: 2.9 – 14%) patients. Subclinical synovitis was found more frequently in the ankle [31/54 (57.4%) patients] and wrist joints [17/54 (31.5%) patients]. No patients had subclinical synovitis in the hip. A 14-joint reduced count including bilateral knee, ankle (tibiotalar, subtalar and talonavicular joints), wrist (radiocarpal and intercarpal joints) and elbow joints, detected 92.6% of children with subclinical synovitis. Twenty-five/99 (25.2%) patients in persistent CR were reassessed with MSUS at a follow up visit (median follow up duration 7 months): 82.3% of patients showed persistent subclinical synovitis. Sixty-four/99 (64.6%) patients had a clinically follow up of at least 6 months and 9/64 (14%) patients experienced a disease flare (median time to flare 6.6 months). Six/9 (66.7%) patients who experienced a relapse had subclinical synovitis at baseline. Conclusion: our preliminary results confirm the discrepancy between clinical and imaging remission and that clinical evaluation may not sensitive to detect an inflammation-free state. Bilateral US assessment of the elbow, wrist, knee and ankle joints is reliable to detect subclinical synovitis. So far, patients who have relapsed are a small percentage, but to extend follow up is crucial to test predictive value of MSUS. Imaging findings will be combined with serum biomarkers leading to the construction of a predictive model. References: [1] De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018Oct;77(10):1426-1431. Disclosure of Interests: Marta Mazzoni: None declared, Silvia Merlo: None declared, Angela Pistorio: None declared, Stefania Viola: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Clara Malattia: None declared

Background:The accurate assessment of remission status in JIA patients is of utmost relevance to taper medications and prevent side effects from their long-term administration. In RA patients in clinical remission (CR), musculoskeletal ultrasound (MSUS) allows to detect persistent joint inflammation (subclinical synovitis), which predicts disease flare and structural damage progression. Although subclinical synovitis has been reported in a substantial proportion of JIA patients with inactive disease, its prognostic value is still being defined.Objectives:1) to investigate the prevalence of MSUS-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare and whether it should affect the therapeutic strategy.Methods:135 consecutive JIA patients who met the Wallace criteria for CR were included in this 3-years prospective study. All patients underwent MSUS assessment of 56 joints at study entry and at 6 months follow-up visit. Joints were scanned for synovial hyperplasia, joint effusion and Power Doppler (PD) signal by two independent ultrasonographers. Patients were followed clinically for 3 years. A flare of synovitis was defined as a recurrence of clinically active arthritis. The association between clinical and MSUS variables with flare, was evaluated by adjusted logistic regression models.Results:135 patients (78.5% F; median age 11.3 y; median disease duration 5.7 y; median CR duration 1.4 y) were included. Fifty-seven/135 (42.2%) patients had persistent oligoarthiritis; 41/135 (30.4%) extended oligoarthiritis; 32/135 (23.7%) polyarthiritis; 5/135 (3.7%) systemic arthritis. Seventy-eight/135 (57.7%) patients were in CR on medication. Subclinical synovitis was detected in 32/135 (23.7%) patients and in 53/7560 (0.7%) joints. Subclinical tenosynovitis was present in 20/135 (14.8%) patients. Subclinical synovitis was found more frequently in the ankle and wrist joints. 58.6% of patients showed persistent subclinical synovitis at 6 month follow up MSUS examination. During the 3-year follow up 45/135 (33.3%) patients experienced a disease flare (median survival time 2.2 y). PD positivity in tendons was the stronger independent risk factor of flare on multivariable regression analysis (HR: 4.8; P=0.04). Other predictors of flare were the JIA subtype (oligo-extended form: HR: 2.3; P=0.031) and the status of CR on medication (HR: 3.7; P=0.002).Conclusion:our results confirm that MSUS is more sensitive than clinical evaluation in the assessment of persistent synovial inflammation in JIA patients. Subclinical tenosynovitis was the best predictor of disease flare. To date, the role of tenosynovitis in the diagnosis and prognosis of JIA has been poorly investigated. Our results further support the role of MSUS, especially of the wrist and the ankle, in monitoring JIA patients in clinical remission and to predict disease flare.References:[1]De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018 Oct;77(10):1426-1431.[2]Filippou G, et al. The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study. Ann Rheum Dis 2018;77:1283-9.Disclosure of Interests:None declared

This paper aims to provide a summary of the recent therapeutic advances and the latest research on outcome measures for clinical trials in juvenile dermatomyositis (JDM). Recent randomized controlled trials (RCTs) have demonstrated the superiority of the combination of prednisone with methotrexate over other conventional therapies and the potential effectiveness of rituximab in refractory cases. A multinational project has led to develop new criteria for the definition of minimal, moderate, and major improvement in future JDM clinical trials. This effort has been paralleled by the establishment of criteria for clinically inactive disease. The validation of the first composite disease activity score for JDM is in progress. The new outcome measures will increase the reliability of assessment of clinical response in JDM clinical trials and foster future multinational RCTs aimed to investigate novel treatment strategies for refractory forms of JDM.

Methods patients with JIA and active wrist arthritis who started receiving a second line therapy (DMARDs or biological agent) at the study Unit between 2008 and 2010 were enrolled in the study. The clinically more affected wrist was studied with MRI (1.5 T), US and conventional radiography (CR), coupled with standard clinical assessment at the study enrollment and after 1 year. Patients were characterized according to the pACR response criteria, and to the current criteria for inactive disease.