key: cord-0931447-qmoa9z28
authors: nan
title: Proceedings of the 27th European Paediatric Rheumatology Congress (PReS 2021): Virtual. 19-21 September 2021
date: 2021-11-08
journal: Pediatr Rheumatol Online J
DOI: 10.1186/s12969-021-00632-z
sha: 988a620c127a55cc88aec2f575a69a35ebfd8a94
doc_id: 931447
cord_uid: qmoa9z28

nan

Introduction: Mevalonate Kinase Deficiency (MKD) is a a rare monogenic autoinflammatory disease characterized by fever and generalized inflammation. Evidence-based therapy has become available since canakinumab proved effective to control disease activity and prevent flares.

Objectives: In this study we evaluated the long-term efficacy and safety of canakinumab in patients with MKD during the open label extension period (Epoch 4, weeks 41 to 113) of the randomized controlled CLUSTER trial. Methods: Patients received open label canakinumab 150 or 300mg every 4 or 8 (q4 or q8) weeks during the study period of 72 weeks. A stepwise dose increase was maintained if patients experienced a flare. Down-titration was not allowed in Epoch 4. The disease activity was evaluated every 8 weeks using physician global assessment (PGA) and counting the number of flares. Measurement of C reactive protein (CRP) and serum amyloid A (SAA) protein concentrations were performed. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analyzed separately in three subgroups of patients receiving a cumulative dose of less than <2700 mg, >=2700-5400mg or >5400 mg Results: Of the 74 MKD patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. Overall, 18 patients received a cumulative dose <2700 mg and 34 patients received 2700-5400 mg, while 14 patients received a cumulative dose of >5400 mg. At the start of Epoch 4, 19 patients (29%) were receiving the lowest dose regimen (150mg q8) and in 12 (18%) this dose was sufficient to control the disease throughout epoch 4. Another 20 patients (30%) received intermediate doses (150mg q4 and 300mg q8) at the end of the study. However, the highest dose (300mg q4) was required in 32 patients (49%) at the end of Epoch 4, while this regimen was only used to treat 18 patients (27%) at the start. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. At baseline, all patients had mild to severe disease activity according to PGA score. Low PGA scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/L. These CRP levels seemed slightly lower in patients receiving the highest cumulative dose (>5400mg). Median SAA concentrations remained only slightly above the normal range of 10mg/L. The exposure-adjusted rate of adverse events was 2.72 per 100 day. Infection was the most frequently reported class. Twenty-seven serious adverse events were reported in fourteen patients. Some of these serious adverse events were considered to be caused by MKD Results: Our data show that Δ4, Δ5, Δ7 and Δ9 NLRP3 splice variants lose the competence for inflammasome activation in both physiological and CAPS in vitro models. However, endogenous NLRP3-driven cleavage of IL-1β, GSDMD and Caspase-1 is not affected in unfunctional variants (Δ4, Δ5, Δ7, Δ9), indicating the absence of a dominant negative role of the variants. Moreover, the absence of significant ASC speck formation in unfunctional variants, suggest a functional role of the LRR domain upstream of ASC oligomerization.

Conclusion: At this point, our research shows a functional implication of the LRR alternative splicing in NLRP3 inflammasome activation, with some of the LRR exon skipping variants being completely inactive, suggesting a potential regulatory role. However, the exact function of the LRR domain in the cascade of inflammasome activation and how some of its splice variants impairs this process, remain to be elucidated. Introduction: Musculoskeletal (MSK) problems are common, often benign and self-limiting and present to healthcare professionals (HCPs) in the community who may not be MSK specialists; it can therefore be challenging to identify those with serious disease. pGALS (paediatric Gait, Arms, Legs and Spine) is a simple, quick MSK clinical assessment and has been shown to detect joint and functional problems in various MSK conditions including inflammatory arthritis. We aimed to develop an extended pGALS assessment, called pGALSplus, to facilitate identification of children with MSK disease who require onward referral to specialist services. Objectives: To pilot the pGALSplus assessment in CYP with Juvenile Idiopathic Arthritis (JIA), Mucopolysaccharidoses (MPS), Muscular Dystrophy (MD) or Developmental Coordination Disorder (DCD) as exemplar MSK conditions and compare feasibility and acceptability with healthy controls (HC). Methods: A 3-phase mixed methods approach; Phase 1 included a scoping review of the literature and qualitative interviews with expert HCPs within paediatric practice to identify key clinical assessments that inform diagnosis and progress. These results informed the initial 'pGALSplus' assessment which underwent iterative development in Phase 2 with an expert working group (including paediatric rheumatologists, expert MSK paediatric physiotherapists and neuromuscular specialists). Phase 3 focused on testing pGALSplus in the exemplar disease groups with feedback from HCPs, patients and carers. Patients; n=37 (JIA;n=10, DCD;n=10, MD;n=9, HC;n=8), age range 2-10 years).

Results: Phase 1 data identified key components of pGALSplus to include:

The pGALS assessment ('top to toe' approach), a questionnaire to identify further indicators of DCD, components of the North Star Ambulatory Assessment (NSAA) to identify early stages of neuromuscular disease (MD), and an assessment of static balance (found to be significantly worse in children with DCD). In Phase 2 pGALSplus was further expanded to include clinical assessment aiming to identify pain or restriction of range of movement (JIA or MPS), underlying weakness (MD) or issues with motor planning and co-ordination (DCD). The additional tests included; testing reflexes (to assess underlying neurology); leg lengths (which may indicate lower limb joint pathology); activity-based skills including standing from the floor and squatting (MD), hopping, jumping and catching a ball (DCD). Expert consensus derived a colour-coded approach to pGALSplus sequencing to facilitate identification of exemplar MSK conditions. Phase 3 demonstrated pGALSplus to be quick to complete (mean 12.6 minutes (9 -20) , with high satisfaction from patients and carers (100% 'about right' time taken). The assessment was deemed 'very easy or easy' for HCPs (35/37, 95%) and patients (32/37, 86%). Parents and children reported high acceptability (32/37, 86% reported it to be 'very comfortable or with minimal discomfort'). Conclusion: pGALSplus is an evidence and consensus-based tool to discriminate between MSK conditions with high acceptability and feasibility. pGALSplus includes resources to aid HCPs to undertake the assessment. Our aim is that pGALSplus is implemented amongst HCPs in the community who are likely to encounter children early in the clinical pathway and are integral to diagnosis and specialist referral. Introduction: Monogenic autoinflammatory diseases (AIDs) are a group of diseases characterized by dysregulation of innate immune responses. Here we describe a peculiar overlap phenotype of autoinflammation and immunodeficiency in a patient with a gain of function (GOF) mutation of oligoadenylate synthetase1 (OAS1). OAS1 is a type I interferon-induced, intracellular dsRNA sensor involved in antiviral defence. Recently OAS1 mutations have been linked with hereditary pulmonary alveolar proteinosis (PAP) and hypogammaglobulinemia but association with autoinflammation has never been reported.

Objectives: To describe the clinical phenotype of a patient affected by a novel AID due to monoallelic OAS1 GOF. Methods: The patient, a 13-months old boy, was admitted, 3 weeks after MMR vaccine, for severe cutaneous vasculitis involving cheeks, lips, and nose, acute encephalopathy, and nephrotic syndrome. He had severe hypogammaglobulinemia (IgG 50mg/dl) with absent IgA and IgM. Blood exams ruled out X-linked agammaglobulinemia and severe combined immunodeficiency. He was treated with a IVIG (2g/ kg, single dose) plus steroid (dexamethasone 0,6mg/kg/d than shifted to prednisone 2mg/kg); encephalopathy, vasculitis, and nephrotic syndrome slowly regressed. Three months later, he had a severe acute respiratory insufficiency during Influenza A infection. CT scan showed an ARDS picture with interstitial disease, and areas of consolidation of both lungs. The patient was treated with high dose pulse methylprednisolone (15mg/kg daily for 3 days), followed by oral prednisone with good response. Interferon (IFN) type 1 signature was constantly elevated but NGS panel for interferonopathies failed to show a known mutation. In the following months, IVIG substitution therapy was started due to progressive IgG reduction. Clinical exome revealed a previously published de novo monoallelic mutation (c.326G>A, C109Y) in OAS1. The patient recently received a matched unrelated donor hematopoietic stem cell transplantation (HSCT) and during the pre-HSCT evaluation a bronchoalveolar lavage was performed and was suggestive for PAP. Introduction: Antibiotic-refractory Lyme arthritis (ARLA) is defined by persistent arthritis after sufficient antibiotic treatment of acute Lyme arthritis and is seen in approximately 10 % of patients with Lyme arthritis. Although some clinical and genetic risk markers for ARLA have been elucidated, the disease pathogenesis is still inadequately understood. In detail, whether chronic inflammation is sustained by persistent borrelial antigens or triggered by autoantigens is not elucidated yet.

Objectives: Identifying the cellular correlate of ongoing immune responses in the inflamed joints of children with ARLA to elucidate antigen targets and disease specific pathomechanisms. Methods: Flow cytometric analysis of T and B cell populations in synovial fluid (SF) samples of children with ARLA and juvenile idiopathic arthritis (JIA). High-throughput sequencing of the T cell receptor β (TCR Vβ) repertoire of SF T cells and single cell immunoglobulin expression cloning of SF B cells in children with ARLA and JIA.

Results: Multidimensional flow-cytometric analysis revealed a striking expansion of an IL-21 and IFN-γ co-expressing PD-1 hi CXCR5 -HLA-DR + CD4 + T cell population resembling peripheral T helper (T PH ) cells in the joints of pediatric ARLA patients compared to JIA patients. Indeed, ARLA patients display the highest frequencies of T PH cells, which could separate this group of patients from JIA. Accumulating T PH cells exhibited signs of clonal expansion with restricted TCR clonotypes. Those clonotypes showed an overlap between different ARLA patients but not to JIA patients. Furthermore, distinct molecular patterns within the TCR Vβ repertoires diverged in ARLA and JIA patients. Paralleling the observations made in the T cell compartment, accumulating SF B cells showed oligoclonal expansion and almost exclusively displayed the phenotype of CD21 lo/-CD11c + doublenegative (DN) B cells.

Conclusion: The inflamed joints of children with ARLA are characterized by a striking expansion of oligoclonal T PH cells and DN B cells. The distinct features of the TCR Vβ repertoire of T PH from ARLA patients suggest that disease specific immune response may sustain chronic inflammation in ARLA. Having defined the cellular subsets of an ongoing immune response in the joints of children with ARLA, current experiments are ongoing to dissect whether this maladaptive immune response targets persisting Borrelial antigens or rather autoantigens.

Introduction: Clinical remission (CR) is regarded as the ideal therapeutic target in JIA because its achievement helps to prevent physical disability. Recently the question has been raised whether current measures used to define CR truly reflect the absence of synovial inflammation. In fact, musculoskeletal ultrasound (MSUS) studies have demonstrated subclinical synovitis in a sizeable proportion of JIA patients despite "clinical inactive disease". In addition, serum biomarkers such as S100A12 and MRP8/14 may identify patients with unstable remission and increased risk of relapse.

Objectives: 1) to investigate the prevalence of MSUS-detected subclinical synovitis in JIA patients in CR; 2) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis predicts disease flare and whether it should affect the therapeutic strategy; 5) to integrate MSUS data with serum biomarkers to develop a multidimensional measure of remission status. 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. At inclusion serum levels of the following cytokines were determined with cytofluorometry: ILR-1, G-CSF, GM-CSF, IL-6, IL-10, IL-12, CXCL9, CXCL10, MIP-1α, TNFRI, TNFRII, RANTES, VEGF. Patients were followed clinically for 3 years. A flare of synovitis was defined as a recurrence of clinically active arthritis that required a major therapeutic intervention. 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. Seventyeight/135 (57.7%) patients were in CR on medication. Subclinical synovitis was detected in 82/135 (60.7%) patients. Subclinical tenosynovitis was present in 20/135 (14.8%) patients. 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 strongest 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). Serum levels of G-CSF, TNFRII and CXCL10 significant differed between patients and healthy controls (P=0.010; P=0.025; P<0.0001, respectively). However serum cytokine levels were not associated with disease relapse. Conclusion: our results confirm that MSUS is more sensitive than clinical evaluation in the assessment of persistent synovial inflammation in JIA patients in CR. Subclinical tenosynovitis was the best predictor of disease flare, with important therapeutic implications.

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 in monitoring JIA patients in CR and to identify patients with higher risk of disease flare.

Introduction: Physician global assessment (PGA) is an essential outcome measure in Juvenile Idiopathic Arthritis (JIA), used alone or as part of composite scores and criteria for inactive disease (ID) to summarize providers' appraisal of disease activity. Some evidence suggests a lack of standardization of PGA, demonstrated by a tendency among physicians to assign values above zero despite no apparent signs of active disease, and little attention to the impact of factors contributing to PGA scoring. Objectives: To identify the determinants of the PGA in patients with JIA without active joints, and to evaluate the relative importance of their contributions to PGA. Methods: 7265 complete visit records from two multinational (the EtICA study, n = 422, and the EPOCA study, n = 9081) and one national (the Gaslini dataset, n = 669) cross-sectional cohorts were examined. Rheumatologic assessment data included active (AJC), painful (PJC), limited (LJC) and swollen joint counts. Patients with AJC = 0 were selected for the analysis. PGA was measured with a 21numbered circle VAS (0 = best; 10 = worse) and dichotomized as equal to or above zero. Presence of pain in axial (TMJ, sacroiliac and spinal joints), large (shoulders and hips), medium (elbows, wrists, knees, foot-ankles) and small (distal interphalangeal, proximal interphalangeal, metacarpophalangeal and metatarsophalangeal) joints was coded as a dummy variable for each pattern. Multivariate logistic regression models were fitted to explain the probability of a PGA > 0 in patients without active joints, based on erythrocyte sedimentation rate (ESR) values, systemic features, active uveitis, morning stiffness, axial, large, medium, and small painful joints, VAS-measured overall pain, total PJC, LJC and ILAR category. We used dominance analysis to compare the relative importance of predictors.

Results: Among 7265 patients, 4108 (56.5%) had negative AJC; within this subgroup, PGA was marked above zero in 32.4% (median 0, IQR 0.0 -0.5). In 14 CI 0.58 -0.97, p 0.028). The model's explanatory power was substantial (R M 2 = 0.27). As shown in the table, dominance analysis revealed pain in the large joints as the most important variable to explain PGA variability (average R M 2 0.073), followed by PJC (0.051) and axial joints pain (0.050). Conclusion: A substantial proportion of patients received a PGA above zero despite the absence of active joints. Large and axial joint pain, uveitis, systemic features and PJC were the main determinants of PGA. Painful joint patterns and PJC accounted for most of the variability in PGA scoring. Further research is needed to investigate factors driving PGA and their impact on classification and response assessment in JIA.

None declared Introduction: There is growing interest in the role of the microbiome in human health and increasing evidence of associations between components of the human gut microbiome and juvenile idiopathic arthritis (JIA). However, few findings have been replicated across studies, and robust evidence of a causal association is lacking. Most microbiomic studies are of cross-sectional or case-control design and are thus subject to confounding, reverse causation, and other biases. An alternative approach to examine the association between the human gut microbiome and JIA is using Mendelian Randomisation (MR), a method of causal inference which has recently been applied in the context of microbiome research. The reliance of MR on human genetic variation, assigned at the point of conception, makes it less susceptible to reverse causation and confounding, provided key assumptions are met. Objectives: To use MR to examine the evidence for a causal association between the human gut microbiome, as measured by faecal samples, and JIA risk. Methods: Genetic variants strongly associated with human faecal microbial taxa have recently been reported in a genome wide association study (GWAS) meta-analysis of three European cohorts (sample size 3,890), using a presence/absence and/or an abundance model. We combined this data with summary data from the most recent JIA GWAS (sample size 12,501) to examine the causal effect of 13 microbial taxa on JIA risk. We also examined this association in reverse (i.e. whether JIA has a causal effect on microbial taxa) using genetic variants associated with JIA from an Immunochip study (sample size 15, 872) and summary data from the Flemish Gut Flora Project (sample size 2,223). We undertook these analyses using the MR-Base platform. Additional sensitivity analyses were performed to assess the robustness of the MR estimates and identify potential violations of the core MR assumptions. Results: Of the 13 microbial taxa examined, we found strong evidence for a causal effect of a higher abundance of bacteria within the Firmicutes phylum on JIA risk (OR 1.75, 95% CI 1.12-2.72 per standard deviation (SD) higher abundance). This finding is supported by weaker evidence of a causal effect of two further taxa on JIA risk; the presence of bacteria within the Firmicutes phylum (OR 1.15, 95% CI 0.99-1.34 per doubling in genetic liability to bacteria within the Firmicutes phylum) and a higher abundance of bacteria within the Butyricicoccus genus (OR 1.50, 95% CI 0.94-2.38 per SD higher abundance). We found no evidence of a causal association in reverse; increased genetic liability to JIA was not causally associated with alterations in these microbial taxa. There was no strong evidence that there were violations of the core MR assumptions. Conclusion: Whilst our findings are inconsistent with much of the observational human literature (which suggests an inverse association between JIA and Firmicutes bacteria), these cross-sectional and casecontrol studies may reflect a post-disease or treatment-related association. Accordingly, current murine data suggests that arthritis is preceded by an increase in Firmicutes bacteria during the pre-clinical disease phase, as is found in our study. Further work to explore these putative causal relationships and to understand the dynamics of the microbiomic composition in disease is warranted.

Disclosure of Interest None declared O16 Twenty years experience with etanercept in treatment of juvenile idiopathic arthritis A. Klein 1,2 , D. Windschall 3 , A. Hospach 4 , K. Minden 5 , F. Weller-Heinemann 6 , F. Dressler 7 , G. Horneff 8 , on behalf of BIKER determined using the JADAS10. Safety assessments were based on adverse events reports (AE) processed according to MedDRA Results: Altogether, 2885 JIA patients covering 6560.3 patient years (PY) of exposure to ETA for up to eight years of continuous treatment, and 1517 biologic-naïve patients accumulating 3893.6 PY of exposure to MTX were enrolled. A higher percentage of patients in the ETA cohort had a polyarticular course (extended oligoarthritis [20.9%] , RF-negative-[33.2%] and positive [8.1%] polyarthritis) than the MTX cohort (13.5%, 27.3%, and 3.4%). Mean age at treatment start and disease duration was higher in the ETA cohort (12.1 +/-4.4 years; 4.1 +/-3.7 years) compared to the MTX cohort (9.8 +/-4.8 years; 2.1 +/-2.8 years). In all, 2531 AEs were reported during ETA exposure or up to 90 days of follow-up (38.5/100 PY [95% CI 37. 1-40.1] ). In the MTX cohort, 1354 AEs were reported (34 /100 PY [95% CI 32.9-36.6]). More SAEs (RR=2.88, 95% CI 2.12-3.9) and serious infections (RR=4.8, 95% CI 2.2-10.6) were observed in the ETA cohort. Also, more patients experienced herpes zoster reactivation (RR=3.7, 95% CI 1.3-10.6; 0.8% versus 0.3%, p= 0.027) and inflammatory bowel disease (RR=13.6, 95% CI 1.8-10.1; 0.8% versus 0.07%; p=0.0008). There was no statistical difference in the rates of malignancies in patients ever exposed to ETA or MTX. During treatment, a marked clinical response was documented with JIA-ACR 30/50/70/90 scores in 68%/61%/48%/34%. JADAS minimal disease activity/JADAS remission was achieved in 60%/38% at last follow-up on ETA. Reasons for discontinuation of ETA were remission in 40% of patients, inadequate efficacy in 35% and intolerance in 12% of all discontinuations Conclusion: This registry cohort represents the largest cohort of ETAtreated JIA patients studied. A rapid improvement upon ETA treatment was observed and could be maintained up to eight years of continuous drug use. More AEs, SAE and serious infections were observed in the ETA cohort. In all, paediatric patients demonstrated a safety profile consistent with observations in adults. he benefit-risk profile of ETA remains unchanged for the approved paediatric Tindication JIA.

Disclosure of Interest None declared Introduction: New biomarkers for early prediction of disease progression are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic pediatric rheumatic arthritis in Western countries. Since cells causing inflammation and tissue-destructive effects release extracellular vesicles (EV) both in plasma and synovial fluid of the inflamed joints, the characterization of EV content at disease onset may be valuable for the identification of early predictive biomarkers. Objectives: This study was aimed at identifying new candidate biomarkers able to predict disease progression and response to treatment. We developed an integrated strategy that combines classical approaches for the study of inflammatory cells in liquid biopsies and system biology-driven omics methods (miRNomic, proteomic) for the analysis of EV released by these cells Methods: 30 OJIA patients were enrolled in the study at disease onset and followed up for 12 months after diagnosis and initiation of therapy. EV miRNA (EV-miR) and EV-protein (EV-Prot) expression profiling were carried out in PL and SF samples using TaqMan Array RT-PCR and mass spectrometry. PL from 25 age-matched healthy children was used as control. Macrophages and T cells from 10 patients of the same cohort were isolated from SF aspirates and characterized by cytofluorimetry using Kaluza software Results: Principal Component Analysis showed a separation among different biological groups on the basis of Exo-miR expression profiles. Differential expression analysis identified 16 and 34 EV-miRs significantly up-and down-regulated, respectively, in SF vs both paired and control PL. Pathway analysis of these EV-miRs identified significantly enriched processes related to inflammatory responses, cartilage/bone homeostasis, and hypoxia, including TNF, NF-kappa B, mTOR, JAK-STAT, cytokine, chemokine, TGFb, HIF-1, and VEGF signaling pathways. Macrophage and T cell derivation of these EV-miR was suggested by in vitro experiments with mononuclear cells cultured for 48h. Five candidate miRNAs with differential expression were validated by qRT-PCR and selected as disease-specific, suggesting their implication in inflammatory condition at both local and systemic level. Unsupervised K-means Clustering analysis identified a few of these EV-miRs as able to discriminate subgroups of patients within the OJIA cohort, suggesting their potential predictive value. EV-Prot analysis demonstrated mean expression of about 1000 protein in both SF and PL samples, with a specific representativeness of the tissue of origin. Proteins with potential to modulate inflammatory and immunological processes were identified. The potential correlation between EV-miR and EV-Prot expression levels and patient clinical data is under study. The analysis of SF cells revealed different ratio of M1/M2 macrophages expressing the immunostimolatory hypoxic receptor TREM1 and activated CD4/CD8 T cells among outcome groups Introduction: Systemic Lupus Erythematosus (SLE) is a complex autoimmune/inflammatory disease. Juvenile-onset (j)SLE affects 15-20% of lupus patients and is characterized by increased organ involvement and damage, and higher need for immune suppressive treatment. Clinical heterogeneity between ethnicities, age groups and individual patients suggest variable pathophysiology.

Objectives: This study aimed at the definition of patient sub-cohorts with "genetic" vs. "classical" SLE to allow individualized care. Methods: Applying target enrichment and new generation sequencing, jSLE patients (N=348) from the UK JSLE Cohort Study were screened for disease-causing mutations. Findings were integrated with demographic information and clinical datasets, including SLEDAI, pBILAG organ domain and SLICC damage scores. Results: Approximately 5.5% of jSLE patients carried diseasecausing mutations, primarily affecting nucleic acid sensing and metabolism (68%), immune complex clearance (11%), their combination (11%), immune cell signalling (5%) and NFκB signalling (5%). Patients with "genetic SLE" were younger, and exhibited less organ involvement and damage at diagnosis (neuropsychiatric, haematological, gastrointestinal), while neuropsychiatric involvement developed over time. When compared to the remaining cohort, "genetic SLE" associated with anti-dsDNA antibody positivity at diagnosis, and reduced ANA, anti-LA and anti-Sm antibody positivity at last visit which may explain reduced renal and haematological involvement.

Conclusion: Genetic disease accounts for ≥5.5% of jSLE cases. It associates with peri-pubertal onset, and distinct immunological and clinical pictures. As less commonly present after treatment induction, in "genetic SLE", autoantibodies may be the result of tissue damage. Routine sequencing will allow for patient stratification, risk assessment, and target-directed treatment with reduced toxicity and increased efficacy. Introduction: Class IV lupus nephritis (LN) is one of the most severe involvements in systemic lupus erythematosus and is particularly frequent in case of pediatric onset. The gold standard induction treatment consists of intravenous (IV) pulses of Cyclophosphamide (CYC) in association with corticosteroids. It has considerably improved the renal prognosis but has potential short and long-term toxic effects. Recent studies in adults have shown similar efficacy of oral Mycophenolate Mofetil (MMF) as induction therapy with a lower toxicity. However, the pediatric literature is scarce and current treatment guidelines are extrapolated from the adult population. Objectives: The aim of the study was to compare the efficacy and tolerance of CYC and MMF as induction treatment of a first episode of class IV LN in children. Methods: We conducted a monocentric retrospective study including all consecutive children (<18 years) with at least 4 American college of rhumatology criteria for lupus, and biopsy-proven class IV LN according to the IRS/RPS classification, and who had not received any prior immunosuppressive treatment. Results: Among the 33 patients, 17 had been treated with oral MMF (51%) and 16 with IV CYC. The basic characteristics were similar in both groups except for more neurological involvement in the CYC group (6/17 vs. 0/16). There was a non-significant trend for more severity in the CYC group with higher grade proteinuria, lower albuminuria, and more frequent acute kidney injury. At one year, 53% of the patients from the MMF group and 77% from the CYC group had achieved remission (p=0.25). 59% of the patients from the MMF group had relapsed, versus 50% of patients from the CYC group (p=0.87), respectively at 3.4 years and 4.7 years after beginning of treatment (p=0.41). The severe and mild complication rates were not significantly different between the two groups. Conclusion: In conclusion, we found no difference in the kidney outcome and side effects in children receiving either MMF or CYC as induction therapy of class IV LN. However, in this retrospective study, no patient from the MMF group had neurological involvement, and there was a trend for more severity in the CYC group. Further studies are needed to confirm these results with stratification of children by disease severity.

Introduction: Paediatric systemic lupus erythematosus (pSLE) is an autoimmune disorder of childhood characterized by the production of autoantibodies against nuclear antigens. In the last decade, several studies showed an up-regulation of genes induced by type I interferons (IFNα) in peripheral blood and tissues of pSLE patients 2 . More recently, also the type II interferon (IFNγ) has been implicated in pSLE; however, its precise role has not been clarified yet 3 . Objectives: To investigate the role of IFNγ in the pathogenesis of pSLE evaluating: 1) the expression levels of IFNγ-related genes in the peripheral blood of pSLE patients followed longitudinally; 2) the expression of T-bet in B cells of pSLE patients; the induction of T-bet in B cells by IFNγ. Methods: Expression levels of IFNα-induced genes (IFI27, IFI44L, IFIT1, RSAD2, ISG15, SIGLEC1), IFNγ and IFNγ-induced genes (CXCL9, CXCL10, IDO1) were analysed by qPCR in whole blood of pSLE patients and healthy donors(HD). We developed a type II IFN score similarly to the type I IFN score described by Crow 4 . Expression of T-bet in B cells was evaluated by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from 5 HD were stimulated in vitro with recombinant human IFNγ and IFNα. Serum levels of CXCL9 were evaluated by ELISA. For each patient, SLEDAI was calculated. Results: Expression levels of both IFNα and IFNγ-induced genes was upregulated in patients with pSLE (n=39). The type II IFN score weakly correlated with the SLEDAI (r=0.33, P=0.03). As previously reported, the type I IFN score significantly correlated with SLEDAI (r= 0.50, P<0.01). We found increased serum levels of CXCL9 in pSLE patients compared to HD (mean±SD: HD 333±117pg/mL, SLE 2125± 4885pg/mL, P=0.0003). Eight patients were enrolled at disease onset before any treatment was administered: type I score decreased with initiation of immunosuppressive treatment; on the other hand, type II score and levels of CXCL9 were not significantly affected by treatment. Interestingly, type II score (mean±SD: No LN 3.3±3, LN 6.7±11, P=0.045) and CXCL9 (mean±SD: No LN 816±1225pg/mL, LN 2427± 5436pg/mL, P=0.031) were significantly higher in patients with lupus nephritis(LN). Thus, patients with pSLE have increased activity of IFNγ, and this particularly evident in patients with LN. B cells play a crucial role in the pathogenesis of SLE. In murine models of SLE, IFNγ was shown to activate B cells to make autoantibodies 4 . We evaluated the expression of T-bet (a transcrip-tion factor induced specifically by IFNγ) in B cells: we observed a population of B cells expressing T-bet in the naïve compartment in patients with pSLE. The frequency of T-bet + naïve B cells correlated with SLEDAI. To confirm the induction of T-bet in B cells by IFNγ, we stimulated PBMCs of HD with either IFNγ or IFNα: both chemokines induced the expression of T-bet in naïve B cells. Since it is known that IFNα can induce the expression of IFNγ, we stimulated cells with IFNα and an antibody blocking IFNγ: in this setting IFNα did not upregulate the expression of T-bet in B cells. Conclusion: Our data suggest a potential role of IFNγ in the pathogenesis of pSLE. IFNγ-induced genes in whole blood and CXCL9 in serum were increased in patients with pSLE, especially in patients with LN. We observed an expansion of T-bet+ naïve B cells in patients with pSLE. IFNγ specifically induced the expression of T-bet in naïve B cells. Thus, IFNγ is hyperactiaved in SLE, inducing the aberrant expression of T-bet in naïve B cells. Further research is needed to dissect the role of IFNγ-activated B cells in pSLE.

Introduction: sHLH is a life-threatening condition associated with several disorders, such as infections, malignancies and rheumatologic/inflammatory diseases. In a significant number of cases an apparent underlying disease cannot be found. Data on mortality rate and on clinical response to treatments (CRT) are lacking or limited to small series. Objectives: To evaluate mortality rate and CRT in a cohort of sHLH patients. Methods: A retrospective chart review of sHLH patients followed at Ospedale Pediatrico Bambino Gesù from April 2006 through September 2020 was performed. Patients with sHLH in the context of sJIA and secondary to malignancy were excluded. Clinical, laboratory features and treatment data were collected at onset, at 1, 3 and 6 months in order to assess CRT. The last follow-up was used to evaluate mortality. To evaluate CRT we divided the cohort in responders and non-responders. Responders were those who achieved the criteria for CRT in the emapalumab trial for pHLH [1] after conventional therapy. Conventional therapy was defined as glucocorticoids, cyclosporine-A, intravenous Ig and/or anakinra at the dose of ≤ 5mg/ kg/day. Non-responders were those who died, those who did not achieve CRT and those who required additional or prolonged (more than 1 month) treatment. Results: 82 sHLH patients, 49 males, with a median age at disease onset of 5.9 years, were included. 21 patients had HLH secondary to rheumatic/ inflammatory diseases (other than sJIA), 4 secondary to SLE, 2 to JDM, 1 to systemic vasculitis, 1 to Crohn's disease, 1 to Sjögren syndrome, 1 to antiphospholipid antibody syndrome and 11 to other rheumatic/ inflammatory diseases. 39 were secondary to infections, 8 to other conditions, such as metabolic disorders or immunodeficiencies and 14 had no evidence of underlining disease (unknown). The mortality rate of the entire cohort was 27% (Table 1) . To analyse CRT, 9 patients, who did not receive immunosuppressive therapy, as they responded rapidly to the treatment of the HLH trigger, were excluded from this analysis. There were 32 (44%) responders: of those 7 had HLH secondary to rheumatic/ inflammatory diseases, 22 to infections, 3 of unknown origin and none secondary to other conditions. 24/32 patients achieved CRT at 3 months. 41 (56%) were non-responders, included those who died (n=22), 14 of whom had HLH secondary to rheumatic/inflammatory diseases (3 to SLE), 11 to infections, 7 to other conditions and 9 of unknown. In the entire cohort only 7 patients received anakinra, 4 of them subcutaneously at the dose of 3 to 5 mg/kg/day and 3 received intravenous anakinra up to 10 mg/kg/day to treat the sHLH episode. Of the 3 patients treated with highdose anakinra, 2 died. Conclusion: The mortality rate of this cohort is high (27%) similar to those reported in smaller series. The percent of patients achieving complete response at 3 months is less than 50%, underlying the severity of the disease and the poor response to unspecific immunosuppression. Even though the use of anakinra is reported to be effective in some cases of sHLH, particularly in sHLH with an underlying rheumatic disease, in our cohort only few patients with a very severe disease were treated with anakinra. Introduction: T cell activation profiling has been recently demonstrated to be able to distinguish patients with primary and infection-associated hemophagocytic lymphohistiocytosis (HLH) from patients with sepsis (1) .

Objectives: In this study, we aimed to evaluate whether activated CD8 + T cell profile also characterizes patients with macrophage activation syndrome (MAS) in the context of systemic juvenile idiopathic arthritis (sJIA) and whether it is able to distinguish patients with MAS from those with active sJIA. Methods: Flow cytometric analyses were performed on peripheral blood mononuclear cells isolated from children with inactive sJIA (n= 17), active sJIA (n=27), MAS (n=14) and with HLH secondary to infection (n=7).

Results: To assess the activation status of CD8+ T lymphocytes, we evaluated the expression of the activation markers HLA-DR and CD38. In patients with MAS, the frequency of CD38 high /HLA-DR + , gated on CD8 + CD3 + cells, was significantly higher compared to those observed in patients with active and inactive sJIA (mean ± SD: 38.4 ± 21.1 % vs 6.9 ± 7.6 % and 2.6 ± 4.2 %, respectively). Receiver operating characteristic (ROC) curve analysis demonstrated that frequency of CD38 high /HLA-DR + CD8 + T cells was able to reliably discriminate patients with MAS from those with active sJIA [area under the curve (AUC) of 0.96 (95%CI 0.90-1.00, p<0.001)]. No statistically significant differences in the frequency of CD38 high /HLA-DR + CD8 + T cells between MAS and HLH secondary to infection were observed. In addition, CD38 high expressing cells represented the major source of IFNγ among CD8 + T cells. The percentage of CD38 high /HLA-DR + CD8 + T cells detected in MAS patients correlated with laboratory parameters of disease severity, including haemoglobin, lactate dehydrogenase and ferritin. Conclusion: We found that CD8 + T cell activation status also characterizes patients with MAS in the context of sJIA, demonstrating that T cell activation status in HLH does not vary depending on the underlying condition/trigger. Moreover, assessment of percentage of CD38 high /HLA-DR + CD8 + T cells represents a valid tool for an accurate identification of patients with MAS. The correlation, in MAS patients, between the increased number of IFNγ-producing CD38 high /HLA-DR + CD8 + T cells and the laboratory parameters of the disease, further confirms the pathogenic role of IFNγ in HLH. (table 1) . There is overlap in these disease states, with a strong association between MAS and sJIA-LD, and active sJIA is a risk factor for developing MAS. Currently, we are performing a systematic literature review in preparation for consensus processes including an international Delphi survey followed by a consensus meeting of experts to develop broadly acceptable definitions of refractory sJIA.

Conclusion: There is an unmet need for a better understanding and definition of refractory disease in sJIA. A consensus based definition is being developed together with patients and caregivers (incl. the Systemic JIA Foundation). Accepted definitions will then enable collaborative research aimed at understanding the disease mechanisms in sJIA patients fitting these definitions. This knowledge can then be translated into targeted therapeutic strategies, which are urgently needed to improve the outcomes and daily life of these patients.

Introduction: In terms of pathogenesis, systemic juvenile idiopathic arthritis (sJIA) is a unique JIA entity in that it is thought to feature characteristics of both autoinflammatory and autoimmune diseases.

A bi-phasic model of disease progression has been proposed, where initial systemic inflammation may develop to chronic destructive arthritis 1 .

Objectives: Our previous work indicated low interferon gamma (IFNg) expression by CD4 pos T helper (Th) cells in sJIA 2 , which echoed earlier findings on low IFNg immune cell exposure in disease 3 but is in sharp contrast to sJIA-associated macrophage activation syndrome (MAS) with IFNg as a central driver of cytokine storm and anemia 4 . Thus, appart from MAS we hypothesized that due to the likely lack of cognate sJIA-associated T cell antigens in an in vivo environment of proinflammatory mediators with the power to drive T cell polarization in different directions, CD4 pos T cells in sJIA may suffer from aberrant or incomplete polarization, which may translate into insufficient IFNg expression.

Methods: Naïve Th cells were isolated from pediatric healthy controls (HC, n = 12) and active (excluding MAS) and inactive sJIA patients (n = 21) and were cultured under various Th1, Th17 and Tfh polarizing conditions. Following super-stimulation with PMA/ionomycin, cell surface marker, transcription factor and cytokine expression was analyzed by flow cytometry, cyto-/chemokine release was quantified by multiplexed bead array assay or ELISA. For ex vivo studies, PBMCs were stimulated with PMA/ionomycin and analyzed by flow cytometry.

Results: Among naive peripheral CD4 pos T cells obtained from sJIA patients, we found an impaired IFNg expression and Th1 differentiation compared to healthy controls, when exposed to respective polarizing cytokines. Low IFNg production was linked to suboptimal Eomes expression. Surprisingly, we found a substantially increased release of IL-21, which was particularly pronounced under Th1 differentiation conditions and correlated to low IFNg and Eomes expression levels. Therefore, we tested a skewing of naive sJIA T cell differentiation towards T follicular helper (Tfh) cells (PD-1 pos ICOSpos CXCR5 pos ) as a major source of IL-21 in the Th cell compartment.

Under Th1 and Tfh differentiating conditions, we observed a strong up-regulation of the Tfh markers PD-1 and ICOS as well as the hallmark cyto-/chemokines IL-21 and CXCL13. PD-1 and ICOS expression levels were tightly correlated to high IL-21 expression and particularly evident in inactive disease patients' cells. Throughout, we only observed marginal expression of CXCR5. Ex vivo, we observed an expanded Tfh cell compartment and IL-21 expression among inactive disease sJIA patients, whereas active disease patients CD4 pos cells rather revealed signs of exhaustion (PD-1 hi ICOS neg ). Conclusion: In sJIA, naïve T helper cell differentiation appears skewed towards a peripheral T helper phenotype (PD-1 hi ICOS pos CXCR5 neg ), which has been described to occur in context of chronic inflammation 5, 6 . In sJIA pathogenesis this may represent an echo of autoimmunity, which could shed light on the mechanisms driving the progression towards chronic destructive arthritis. Introduction: Systemic juvenile idiopathic arthritis (SJIA) is a clinically heterogenous disease and can be complicated by macrophage activation syndrome (MAS) and lung disease (LD) thought to be driven by interferon signaling, though the contributing cell populations and distinctions between IFNγ and IFNα/β are undefined.

Objectives: To identify novel prognostic transcripts and potential patient subtypes, we aimed to characterize single-cell heterogeneity and patient-specific transcriptomics responses from the peripheral blood of children with SJIA, MAS and LD. Methods: 10x Genomics single-cell RNA Sequencing (scRNA-Seq) was performed on PBMCs from 7 active SJIA and 5 inactive SJIA patients, 2 SJIA-MAS and 6 SJIA-LD patients and 5 healthy controls. Integration analyses were performed with the software Seurat 3 to identify discrete cell populations while correcting for donor and disease-level differences. To identify subsets of patients with cell-type specific signatures, we developed a new hybrid supervised/unsupervised computational pipeline in the software AltAnalyze, called cellHarmony 2.0, designed specifically for large cohort single-cell genomic studies.

Results: scRNA-Seq analysis was performed on a total of 234,128 individual cells (ranging from 6,662-12,647 cells/patient), with a mean number of 21,637 genes detected per sample. To assess cell-population level differences, we identified and annotated based on marker genes 34 discrete cell populations across all submitted samples. This indicated a consistent increase in Natural Killer (NK) cells and decrease in naïve and regulatory T cells in SJIA-LD, with the distribution of cells from inactive SJIA patients similar to that of controls. To exploit anticipated heterogeneity within this cohort, we applied our new cell-type aware patient subtype discovery algorithm cellHarmony 2.0. We computed an aggregate cell signature for all cell populations or pseudo-bulks (n=34) for each patient and their associated fold differences relative to matched control cell clusters, and performed unsupervised clustering of the pseudo-bulks to identify patient subtypes associated within one or more cell types. This analysis uncovered 11 pseudo-clusters of cell type gene expression differences, both shared and unique across the patients. Specifically, pseudo-cluster 4 was defined by IL-2 mediated signaling genes, composed of mostly NK cells from all SJIA subtypes except MAS. SJIA-MAS PBMCs were almost exclusively represented in three separate pseudo-clusters that contained genes mediating T-cell receptor activation, immune response and interferon signaling. Finally, pseudocluster 8 was composed of mainly monocytes/macrophages with specific upregulation of IFNα/β induced genes IFITM3, IFI6 and ISG15, only in active SJIA, SJIA-MAS and SJIA-LD. Conclusion: Unsupervised single-cell cohort analysis provides new opportunities to uncover novel disease molecular programs and pathways in clinically heterogenous patient groups. Here, we found active SJIA, SJIA-MAS and SJIA-LD PBMCs have distinct monocytic responses characterized by upregulation of interferon-induced genes, highlighting the role for both IFNγ and IFNα/β in driving disease pathogenesis. Introduction: Juvenile Dermatomyositis (JDM) is a rare autoimmune disease causing skin and muscle inflammation with an average onset of 7 years old. At present, JDM aetiology is poorly understood and current treatment options are not evidence based. This highlights the need for research investigating underlying disease pathogenesis. A skewed T helper (Th)17 phenotype in CD4+ T cells resulting in a Th1/17 imbalance has been observed in both child and adult-onset immune-mediated diseases including rheumatoid arthritis, and multiple sclerosis.

Objectives: The aim of this project is to investigate whether a Th1/17 imbalance can be observed in patients with JDM compared to age/ sex-matched child healthy controls (CHC). Methods: Expression of IL-17 and IFNγ in CD4+ T cells within peripheral blood mononuclear cells (PBMC) from JDM pre-treatment (JDM Pre, n=7), JDM on-treatment (JDM On, n=28) and CHC (n=22) was assessed by flow cytometry after stimulation with PMA/Ionomycin/ Brefeldin A (P/I/B) for 4 hours. For secreted cytokine production, isolated CD4+ T cells were isolated by magnetic separation and stimulated with anti-CD3 or anti-CD3/anti-CD28 for 36 hours in the presence of IL-2. Supernatants were analysed for secreted IL-17 and IFNγ and measured by cytokine bead array. In parallel, extracellular Th1 (CD3+CD4+CXCR3+CCR6-), Th17 (CD3+CD4+CXCR3-CCR6+) and Treg (CD3+CD4+CD127-CD25hi) subsetting was carried out using flow cytometry and proliferative capacity of T cells was assessed following stimulation using Ki67.

Results: Both intracellular cytokine staining and stimulation experiments to assess secreted cytokine revealed a decreased trend of IFN-γ production in JDM compared to CHC within CD4+ T cells, regardless of treatment status. Ratio analysis of CD4+IFNγ+ to CD4+IL-17+ cells within peripheral blood after PMA/Ionomycin stimulation demonstrated that the JDM CD4+ T-cell phenotype is significantly skewed towards Th17 cells (p=<0.001) compared to CHC. A Th17 skew was also seen when analysing surface markers for Th1 and Th17 on JDM pre CD4+ T cells compared to controls (p=<0.0001 were cultured with IFN-α or oxmtDNA (+ LL37) with or without TLR-9 antagonist or the anti-oxidant n-acetyl cysteine (NAC). Post-culture, IFN1 gene expression was measured by qPCR.

Results: RNA-seq confirmed a strong IFN1 signature pre-treatment, and demonstrated that genes involved in mitochondrial function were abnormally expressed in both pre-and on-treatment CD14+ cells compared to controls, suggesting that mitochondrial dysfunction is not corrected by current treatment strategies. Validation of RNAseq using flow cytometry and western dot-blot showed that there was an increase in mitochondrial superoxide and oxmtDNA in CD14+ monocytes, JDM pre-treatment vs. CHC (p=0.034) and JDM Vs. CHC (p=0.061). This was complimented by increased plasma cellfree mtDNA was increased in JDM pre-treatment compared to controls (p=0.0076). In vitro, oxmtDNA and IFN-α induced a comparative up-regulation IFN1 genes compared to unstimulated control (MX1 (p<0.0001, p<0.0001); RSAD2 (p=0.1508, p=0.001)). Both TLR-9 antagonist and NAC were able to down-regulate IFN1 genes after 24hr of oxmtDNA stimulation, suggesting that both could translate to therapeutic targets (TLR-9 (MX1, p=0.0001; RSAD2, p=0.0374); NAC (MX1, p<0.0001; RSAD2, p=0.00014)).

Conclusion: This study establishes that in JDM, monocytes have an increased production of mitochondrial superoxide and oxmtDNA. There is also an increased amount of plasma cell free mtDNA. We have established a mechanism of oxmtDNA induction of IFN1 signature and the potential to block this pathway with TLR-9 antagonist and NAC, identifying these pathways as novel treatment targets. Further work will investigate the mechanistic relationship between IFN1 driven inflammation and altered mitochondrial metabolism in monocytes.

Introduction: Juvenile localized scleroderma (jLS) is a rare chronic inflammatory and fibrosing disease associated with a high risk for morbidity in children. Methotrexate (MTX) has been identified as effective treatment, but data is limited as to the optimal duration, and need for corticosteroid (CS) treatment. The LS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed standardized regimens (consensus treatment plans, CTPs) for comparative effectiveness studies. The results of a 1-year follow-up of a pilot multi-center study of the MTX-based CTPs were previously reported. Of the 50 patients enrolled, 44 (88%) completed 1 year of follow-up, with 33 (66%) of the patients rated as responders and 11 (22%) as non-responders. We now report on long-term follow-up of these patients.

Objectives: To determine the long-term response of jLS patients treated with MTX-based CTPs.

Methods: Patients enrolled in the pilot CTP study were eligible to enroll in the long-term extension, with study visits completed at 24 and 36 months. Each patient was evaluated by the same investigator for all 3 years of the study. Treatments and adverse events that occurred since the last study visit were collected. Descriptive analysis was performed, with p values calculated by Zscore or Mann Whitney U test. Inactive disease was defined as physician global assessment of activity (PGA-A) = 0, remission off medicine as PGA-A = 0 with the patient off treatment.

Results: Most patients were female (70%), had linear scleroderma (28/44), with a median age of onset 9.4 years. Thirty-seven (74%) of patients completed 3 years of follow-up (Table) . PGA-A and skin activity scores (mLoSSI, LSCAM) declined by 12 months and were then stable. Over time, more patients achieved inactive disease, with 20% able to achieve remission off methotrexate. Disease flares were most common in years 1 and 2 when~20% of patients flared. In addition to 11 non-responders in year 1, 5 additional patients were nonresponders in years 2 and 3. Non-responders most commonly received CS and mycophenolate mofetil. The frequency of adverse events decreased 3-fold by year 3. Conclusion: JLS patients treated with MTX-based standardized regimens were found to achieve further improvement in years 2 and 3 with continued treatment, with 20% able to achieve remission off medicine in year 3. Disease flares occurred in each year and overall, 16 (32%) patients were non-responders, requiring additional treatment for disease control. More work is needed to identify the at-risk patients and determine their optimal therapy.

None declared PGA-A (IQR) 5 (4-6) 1 (0-2) 0 (0-1. Objectives: The purpose of this study was to identify genetic variants associated with age of SLE diagnosis. Methods: Our cohort included patients who met ACR and/or SLICC classification criteria for SLE, followed at tertiary care centres. We censored patients with missing data on age at diagnosis. Patients were genotyped on the Illumina Multiethnic Array (MEGA) and Illumina Global Screen Array (GSA). Ungenotyped SNPs were imputed using the TopMed reference. We restricted to SNPs with a minor allele frequency (MAF) ≥ 0.01 and imputation quality R 2 ≥ 0.3. Ancestry was genetically inferred from principal components (PCs) and ADMIXTURE in reference to 1000 Genome Project. We completed genome-wide linear regression of log-transformed age at SLE diagnosis with GENESIS (genome-wide significance P<5x10 -8 ).

Multivariate models were adjusted for sex and 5 PCs. We also conducted a GWAS of childhood-onset SLE (cSLE) patients, defined as diagnosis <18 years of age, vs. adult-onset SLE (aSLE), using logistic regression, and adjusted for the same covariates. We conducted sensitivity analyses where we stratified GWAS by cSLE and aSLE, then meta-analyzed results using inverse variance weighting, as well as ancestry-stratified analyses (Europeans, East Asians, Africans, Amerindians and Admixed). Results: Our cohort included 1489 patients, 761 (51%) with cSLE, 1306 (88%) female. The median age at diagnosis was 17.7 years (IQR 14, 31) in the total cohort, 14.1 years (IQR 11.8, 15.8) in the cSLE, and 31.2 years (IQR 24.7, 42) in the aSLE groups. In the total cohort, 576 (39%) were of European ancestry, 278 (19%) East Asian, and 253 (17%) Admixed. We included 11.7M SNPs in GWAS. In the age of SLE diagnosis GWAS, 2 loci on chr16 were genome-wide significant associated to a younger age at diagnosis (top SNP rs11641349, Beta -0.03y, SE 0.15y, P=4.33x10 -8 , MAF 0.2). Both SNPs were intronic to CCDC113, a component of centriolar satellites. These loci were also the most significant in the GWAS of cSLE (top SNP rs16959933, OR 1.75 [95% CI: 1.43, 2.14, P=5.45 x10 -8 ]). Sensitivity analyses showed similar results, yet they did not reach genome-wide significance with top SNPs rs11641349 (P=3.84x10 -7 ) and rs16959933 (P=4.50x10 -7 ) in the age group model, and rs11641349 (P=3.52x10 -7 ) and rs16959933 (P=4.22x10 -7 ) in the ancestry model. Conclusion: In our multiethnic cSLE and aSLE cohort, we identified genome-wide significant loci associated with age at diagnosis and cSLE risk, both intronic to CCDC113 (chr16). Our study requires independent validation. Immunology; 2 Paediatric Rheumatology, University Medical Center Rotterdam, Rotterdam; 3 Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam University Medical Centre, Amsterdam; 4 Paediatric Rheumatology, st. Maartenskliniek; 5 12 , neutrophil (NPh)-and plasma cell (PLC) modules, followed by a principle component analysis was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood onset SLE cohorts (n=101 and n=34, respectively) and associated with clinical features. Disease activity was measured using SELENA-SLEDAI. Cluster analysis subdivided patients into three fingerprint groups termed 1) all-signatures-low, 2) only IFN high (M1.2 and/or M5.12) and 3) high NPh and/or PLC. Results: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC signature showed the highest association with disease activity. Also, in longitudinally collected samples, the PLC signature was associated with disease activity and showed a decrease over time. When patients were divided into the three fingerprints, the highest disease activity was observed in fingerprint-3, the high NPh and/or PLC group. The lowest disease activity was observed in fingerprint-1, the all-signatures-low group. The same distribution could be reproduced in samples from an independent SLE cohort. Conclusion: Gene signatures are associated with disease activity and can be suitable tools to sub-classify patients into groups with similar pathogenically activated immunological pathways. Introduction: Eye involvement in craniofacial juvenile scleroderma (CFJS) reported to present with sclerotic skin changes of eyelids and eyelashes, keratoconjunctivitis sicca and uveitis (anterior segment inflammation), the latter could result in reducing of the visual acuity Objectives: To analyze the frequency of uveitis in CFJS, specifity of its clinical presentation, and prognosis.

Methods: Retrospective analysis of clinical and instrumental observation, including brain magnetic resonance imaging (MRI), electroencephalography (EEG), ophthalmologic examination in particular with slit-lamp was done Results: We observed 105 children with CFJS, aged from 3 to 17 years, the mean age was 10,2 years (M ±2,52), 62 girls and 43 (girls\ boys boys = 1.4: 1). The majority patients (pts) -95 have linear skin lesions only on face and head ( linear scleroderma "en coupe de sabre"type -LSCD group), 10 pts have unilateral skin damage of trunk, extremities -(UlSl) affecting face and head. Uveitis was detected in 12 pts (11,4% ), among them 11 girls and 1 boy. Anterior uveitis was unilateral on the side of skin lesions in 10 pts, bilateral in 2. In 2 pts uveitis was accompanied by episcleritis, in one-by chorioretinitis. In group UlSl -there were 3 uveitis, detected after 3-5 year of disease duration, while in Lubricant eye drops group -uveitis appeared during this first year of disease outburst, in most cases simultaneously with appearance of skin lesions. In 4 girls uveitis was accompanied by focal seizures, with EEG epileptic pattern and brain foci on MRI on the side of skin damage.90% of uveitis pts were ANF positive. Pts with uveitis have no specific complains or overt symptoms of eye involvement. It was detected only by ophthalmologic examination screening with slit-lamp we use as a matter of routine in all scleroderma children .Mean follow up period for uveitis children was 5,5 (M ±0.3) years. All of 12 patients achieved remission of uveitis. Significant decrease of activity was seen in 1 month (mo) of therapy, remission in 6 mo. In 2 children uveitis relapsed, after systemic disease modifying antirheumatic therapy (BMART) was stopped by parents. In both cases it was uveitis in LSCD, in 18 and 36 mo after initiation of BMART and in 4-6 weeks (wk) of its discontinuation,the relapses of uveitis were diagnosed after exacerbation of skin lesions. BMART in all uveitis pts includes corticosteroids(CS) orally 1mg\kilo-12 wk, followed by taping and withdrawal, methotrexate(MTX) 12-15 mg.sw. parenterally 30-36 mo; in some cases of severe LSCD MTX in combination with mycophenolate mofetil (600 mg.sq. twice a day)-Local treatment -CS and non steroid anti-inflammatory drops, and lubricant eye drops for cornea protection Conclusion: Frequency of uveitis in our cohort of CFJS pts was 11,4%. In all the cases children did not have ocular complains -so called "white uveitis", but more than 30% uveitis pts had concomitant central nervous system involvement-seizures, brain foci on MRI on the side of skin damage. The prognosis of uveitis in our pts was benign. Pts with CFJS must be regularly ( every 3 mo) checked by ophthalmologist, with obligatory slit-lamp evaluation, compulsorily at the disease debut and before discontinuation of BMART in remission.

None declared e-Poster viewing: JIA (oligo, poly, psoriatic) P1 A Problem-oriented approach to assessment hand-related problems in patients with juvenile idiopathic arthritis: ICF perspective N. Arman 1 , E. Tarakci 1 , O. Kasapcopur 2

Introduction: A problem-oriented approach (POA) is suggested that the best way to assess and management in patients with chronic disease. POA provides to set a meaningful and purposeful goal for treatment. Creating a problem-oriented assessment algorithm specific to disease provides practical and efficient results in the clinic. There is no defined algorithm for POA in patients with JIA in the literature. So, our team has firstly defined an algorithm of POA in patients with JIA and use it in the clinic. Assessment and management of the hands and wrist that are the most included joints in JIA are also complex. There is little information about the prevalence of handand wrist-related symptoms (i.e. pain or stiffness) and impairments (i.e. problems in body function or structure, such as limitation of the range of motion (ROM)), and their resulting activity limitations (i.e. difficulties in dressing) and participation restrictions (i.e. problems with involvement in life situations, such as attending school) in JIA.

Objectives: The aim of this study was to use the POA for assessing hand-related problems in patients with JIA. Methods: 216 patients were evaluated for eligibility, 44 patients with JIA who have bilaterally affected wrist joints were included in the study. The POA with three steps was used to evaluate the patients.

In the first step in which the problems are determined, hand-related problems of the patients were questioned in 5 categories: pain, limitation of ROM, fatigue, weakness and functional incompetence. The patients were asked to rank these five problems as follows: the most important problem and the least important problem for them. In the second stage of POA, in which body structure and functions are assessed, pain and fatigue were evaluated with the Numeric Rating Scale (NRS). ROM of hand was assessed with a universal goniometer. Muscular strength was estimated at maximal isometric force for the wrist muscles by using a portable handheld dynamometer. Grip and pinch strengths were evaluated by a dynamometer. In the third stage of POA, in which activity and limitations were evaluated, activity performance was evaluated with the Jebsen Taylor Hand Function Test (JTHFT), activity limitation was performed with the Childhood Health Assessment Questionnaire (CHAQ) and Duruoz Hand Index (DHI). Results: 45.5% of the patients reported that their primary problem was functional incompetence, 34.1% of weakness, 13.6% of limitation, 4.5% of fatigue and 2.3% of pain. The score of NRS-pain was five and above in 54.5 % of the patients. Also, the score of NRSfatigue was five and above in 75 % of the patients. The ROMs of wrist flexion and extension were decreased in 72% of the patients. Also, all scores of the wrist muscle strengths and grip and pinch strengths of all patients were low according to the strength norms of healthy children. In the various grade of scores (1-3 points) according to CHAQ, 79.5% of the patients reported difficulty in dressing activities, 93.2% gripping, 70.5% arising and 51.1% eating. Significant relationships were found in the scores of JTHFT and all grip and pinch strengths, the strength of wrist extension, DHI and CHAQ-total (p< 0.05). Pinch strength was also a significant predictor of fatigue severity (p<0.05). Conclusion: We believe that POA is a useful method for a comprehensive evaluation in patients with JIA who hand involvement. We found that functional problems were the most critical problems reported by patients. Factors affecting functional abilities can be evaluated systematically through the POA by choosing the eligible assessment scale. Also, setting a short and long-term functional ability-oriented goal with POA will be provided with practical and systematic strategies for JIA treatment.

Introduction: Patients diagnosed with an autoimmune disease have a substantially increased risk for another autoimmune disease, e.g, psoriasis patients can develop multiple sclerosis [1] . Objectives: We present a patient with several rare autoimmune diseases.

Methods: Case presentation.

Results: A 15 y/o girl referred to a pediatric rheumatologist regarding pain of the left knee, increasingly prominent limping and clumsiness. The left wrist movements were painful and limited, and the left knee was slightly swollen, painful during flexion. There were a severe skin psoriasis seen in the head, that was bothering patient already a few years. Also granuloma annulare signs were seen in the armpits and on the ankle area. Ultrasound examination (UG) of the joints showed an effusion in the left knee and signs of a ganglionspecific cyst in the left wrist joint with synovitis signs. Psoriatic juvenile idiopathic arthritis (psJIA) was suspected. Medical anamnesis revealed that the patient was diagnosed with multiple sclerosis (MS) a year ago and received treatment with methylprednisolone pulse therapy. At that time additional studies for infectious and autoimmune disease were done. There were signs of previous citomegalovirus (CMV), Epstein -Barr virus (EBV) and Herpes Simplex virus (HSV) infections (positive IgG for CMV, HSV and EBV). Immunological tests (anti-dsDNA, ANCA, ANA) were in normal range. However, because of the relapsing-remitting course of the neurological disease immunomodulatory treatment with interferon β-1α subcutaneously was initiated. Unfortunately, treatment had to be changed regarding adverse reactions. As MS progressed with new symptoms, new foci in brain MRI and poor prognosis criteria were met, the patient was prescribed second-line treatment with Fingolimoda. During treatment with Fingolimoda, the patient's neurological status remains stable for 2 years. Although there is constant slight leukopenia and lymphopenia (LY: 0,9 x 10^9/l, norm: 1,2 -3,34 x 10^9/l) seen in complete blood count (CBC). Also episodic exacerbations of psoriasis, subsequent pain of joints and signs of inflammation in the left wrist are observed every 2-3 months. Episodic treatment with NSAIDs for 2-3 weeks for psJIA improves the patient's condition. Additionally, for the left wrist severe inflammation Kenalog injection was done according to the oligoarticular course of psJIA. For now treatment with disease modifying antirheumatic drugs (DMARDs) like methotrexate or others was resisted regarding lymphopenia constantly seen in the CBC. Conclusion: We present a complex patient with several rare autoimmune diseases from different organ systems (skin, joints and neurology) and remind specialists that in the presence of one autoimmune disease, other autoimmune diseases are also possible. In children psoriasis may be associated with multiple sclerosis and progress to psJIA. There are data that the development of different autoimmune diseases can be caused by certain viral infections, which in our case could be the EBV and CMV [2] . Treatment of these patients can be challenging as there is no experience with drug-drug interactions between Fingolimoda and DMARDs. Objectives: Aim of the study is to assess on a global scale the heterogeneity in PGA scoring and to clarify the factors having an impact on the PGA through a web-based survey. Methods: A questionnaire regarding factors affecting PGA was sent electronically to all 2640 PRINTO members. The responders were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PGA scoring. The factors were chosen based on consensus of the study panel. The questionnaire also included 17 detailed patient cases selected to represent a diverse spectrum of clinical situations. The responders were asked to indicate the PGA for each patient on a 0 to 100 scale. Results were compared also after grouping for the level of experience of the assessor in the field of pediatric rheumatology (<5 years, 5-10 years, or >10 years). The heterogeneity in the PGA scoring in the 17 cases was measured through the coefficient of variation (CV). The difference between groups was analysed by Kruskal-Wallis one-way analysis of variance. Results: Of the 708 health care providers who responded to the survey, 431 delivered a complete answer regarding the factors affecting PGA and 376 indicated the PGA for all the patients. There was a large individual variation in the impact of different factors on PGA (Table) . The smallest variation was seen in the number of swollen joints and tender joints. PGA was scored heterogeneously in most patient cases. The median PGA of the cases did not differ between physicians divided in groups based on experience in pediatric rheumatology. The CV of PGA was >50 in 12 and >100 in 3 out of 17 patient cases. To the question, "If a patient with oligoarticular non-systemic JIA and a polyarticular patient with nonsystemic JIA had the same clinical picture would your VAS be different?" 209 physicians replied "no" and 219 "yes". Conclusion: The PGA is scored heterogeneously throughout the world. Shared guidelines for scoring the PGA are needed to obtain consistent patient assessment in clinical trials and routine practice. In particular the weight of the patient clinical history (e.g. oligoarthritis versus polyarthritis), the presence of extra-articular manifestations and patient reported outcome measures should be discussed.

Disclosure of Interest None declared Introduction: The Juvenile Arthritis Damage Index (JADI) is used to assess articular and extraarticular damage caused by long-term inflammation in patients with Juvenile Idiopathic Arthritis (JIA) 1 . Virtually no research has been conducted about the quality of the JADI and the knowledge the index provides to us. Objectives: The aim of this study is to gain insight into the characteristics of JIA patients who scored positively on the articular part of the JADI (JADI-A) and to examine whether the JADI-A is a representative index for damage.

Methods: This is a retrospective cohort study in which data were analyzed from patients with JIA in the Wilhelmina Children's Hospital in Utrecht, the Netherlands. The JADI-A score is expected to increase or remain the same but not to decrease over time.

To evaluate this expectation, it was examined if ever-positive JADI-A scores have flipped into a zero on their last reported cumulative JADI-A score.

To evaluate if the JADI-A identified all joints with damage, the results of the JADI-A in the included patients were compared to the limited joint count in the last joint assessment and to radiographic damage. On the other hand, the number of inactive limited joints during the last joint assessment of patients with a never-positive JADI-A was determined to examine if there are patients with inactive limited joints and a negative JADI-A score, whereas they could be expected to have a positive JADI-A score. Finally, the results of the JADI-A of a selection of patients known to have radiographic damage were evaluated to examine the assumption that the JADI-A reflects (radiographic) damage when present. Results: 375 of the 914 patients (41.0%) in the database had an evercompleted JADI-A. Of these 375 patients 53 (14.1%) had an everpositive JADI-A with a total amount of 158 ever-positive joints. 14 of these 53 patients (26.4%) had a negative JADI-A at the last time the JADI-A was assessed.

Only 29.7% of the ever-positive joints was also limited in the last joint assessment and 69.2% of all ever-positive joints did show radiographic damage on the last X-ray. 14.6% of the 322 patients with a never-positive JADI-A did have inactive limited joint(s) in their last joint assessment. Only 50.0% of the 18 selected patients known to have radiographic damage and with an ever-completed JADI-A had an ever-positive JADI-A. Conclusion: A considerable discrepancy was seen between the results of the JADI-A on the one hand and the inactive limited joint count in the last joint assessment as well as radiographic damage on the other hand. Furthermore several positive JADI-A scores flipped to negative, suggesting either that rheumatologists did not complete the index correctly and/or that the JADI-A is not successful in detecting (lasting) damage in patients with JIA. Further research on this remarkable discrepancy is needed, because in the end we want to identify all children with damage as expeditiously as possible and to not unnecessarily burden children without joint damage with repeated radiographs.

Introduction: Live attenuated vaccines are not usually recommended in children with rheumatic diseases (RD) treated with immunosuppressive (IS) therapy (1) . However, a retrospective study which included 234 children with RD who received live attenuated booster measles-mumps-rubella (MMR) vaccine during treatment with IS therapy showed that the booster dose was safe (2) . Objectives: To evaluate safety and long-term immunogenicity of the MMR booster vaccine in children with RD treated with IS therapy in a prospective study.

Methods: This is an ongoing multinational, multicentre prospective study. Patients with immune-mediated diseases treated with DMAR Ds and/or biologic therapy with stable disease were included if they were scheduled, according to their national vaccination program, to receive 2 nd (booster or "catch-up") dose of MMR vaccine. Safety was monitored by tracking infection with vaccine or wild-type viruses after vaccination, possible adverse events of the MMR vaccine and by monitoring disease activity before and after vaccination. Immunogenicity was monitored by measuring protective antibodies before vaccination and then at predetermined time points after vaccination.

Results: By the end of May 2021, 22 patients from 4 centres were included (Greece, Slovakia, Slovenia and Turkey). One patient had localized scleroderma and all others had juvenile idiopathic arthritis (JIA) (12 oligoarticular JIA, 4 polyarticular JIA, 2 systemic JIA, 2 enthesitis-related arthritis, 1 psoriatic JIA) Median age at diagnosis was 3.8 years (range 1.4-10.5 years), median age at 1 st dose of MMR vaccine was 1.27 years (range 0.58-4.36 years) and median age at 2 nd dose of MMR vaccine was 8.05 years (range 2.8-14.3 years). At the time of 2 nd vaccination, 13 patients were treated with TNF-α inhibitors, 9 of them received methotrexate (MTX) concomitantly, 1 patient was on IL-1 inhibitor and corticosteroids (CS), 1 patient on IL-6 inhibitor and CS and 7 patients were on MTX. Regarding safety, there were no increase in disease activity, vaccine strain infection or serious adverse events after vaccination. Six patients reported mild local or systemic reactions (fever, fatigue, arthralgia, headache, cough) in the 6 weeks following vaccination. Protective antibodies against measles and mumps were measured in 9 patients, they were positive in 7/8 patients 2-3 months after 2 nd dose. Conclusion: These preliminary results of prospective study corroborate the findings of recently published retrospective study (2) . However, the number of included children is currently too small to draw any firm conclusions and long-term immunogenicity remains to be determined in the future. This is an ongoing project and we expect that other countries and centres will join this effort soon. Introduction: Distinction on clinical grounds between acute lymphoblastic leukemia presenting with arthropathy (ALL arthropathy ) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukemia may be vague. As the only study of lectin pathway in children with ALL indicate low serum M-ficolin levels and M-ficolin has proven to be a marker of disease activity in JIA, we hypothesized that it would be possible to differentiate ALL from JIA by M-ficolin. Objectives: The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALL arthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with hematology counts, ESR, CRP, blasts, relapse, and death.

Methods: In this observational study, we measured M-ficolin, CL-K1 and MASP-3 in children with ALL (n = 151) and JIA (n = 238) by time-resolved immunofluorometric assays in serum. Logistic regression was used for the predictions, considering risk of ALL as the outcome. We performed internal validation using repeated "10-fold cross-validation" with 100 repetitions computing the optimized corrected Area Under the ROC curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.

Results: The level of M-ficolin was more than 4-fold higher in JIA than in ALL total and the ALL arthropathy subgroup : 0.65 μg/mL (IQR 0.32-1.21) versus 3.01 μg/mL (IQR 2.43-3.85)μg/mL, p <0.001. The M-ficolin level normalized after remission of ALL to 1.57 μg/mL ( IQR 0.83-2.24), p <0.001. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and hemoglobin. In a dichotomy predictive model with optimal cut-offs for M-ficolin, platelets and hemoglobin AUC was 99% and PPV 98% in detecting ALL from JIA. Conclusion: M-ficolin is a valuable marker to differentiate the child with ALL from JIA. Results: 207 patients included in the study (69% female). Patients were evaluated by primary care physicians (62%), ER physicians (13%), and orthopedists (11%) prior to diagnosis. The median time until diagnosis was 56 days (1-2451 days). Patients diagnosed with ERA/SPA and psoriatic arthritis had the longest period until diagnosis (351 and 213 days respectively). A younger age was correlated with a later diagnosis (r=0.3, P<0.0001). Females were diagnosed earlier compared to males (median 48 vs 84 days respectively). The distance to the rheumatology center with regards to time until diagnosis was not significant (P=0. 19 ). Fever at presentation, significantly shortened the time to diagnosis (P< 0.0001), whereas involvement of the small joints/sacroiliac joints significantly lengthened the time (P<0.05).

Conclusion: This is the first nationwide multicenter study that analyzes the obstacles in the diagnosis of JIA in Israel. Raising awareness of JIA, especially of patients with SPA, is crucial in order to avoid delays in diagnosis and treatment. Introduction: Juvenile idiopathic arthritis is one of the most common chronic pediatric diseases. However, it remains little known by 1st line doctors to evoke the diagnosis. This results in a diagnostic delay, sometimes several months, potentially responsible for disabilities. The associated anterior uveitis is also unknown. This is probably related to a lack of teaching, but studies on this subject are scares.

Objectives: The main objective is to establish an inventory of the knowledge of medical professionals of Lower Normandy, but also to sensitize them to this pathology, to make better known its network of care, and its management. Methods: We carried out a cross-sectional descriptive study whose data were collected using a questionnaire addressed to the various medical professionals concerned by the AJI in the three departments of the former Basse-Normandie region: pediatricians, rheumatologists, pediatric orthopaedic surgeons, ophthalmologists, general practitioners and internal physicians of these different specialties. Three hundred and eleven questionnaires were collected out of the 178 sent out. Results: The response rate was 17.4%. Juvenile idiopathic arthritis is known to 89% of professionals. Dedicated rare disease reference and skills centers are known by 31% and 32% of them; the national diagnostic and care protocol (PNDS) by 20.5%. Amalgamation with inflammatory pathologies of the digestive tract (10%) and autoimmune pathologies (9%) is common. The anti-nuclear factors are performed by 19% of professionals. Systemic corticosteroids are prescribed in 23% of cases in 1st intention. Anterior uveitis is recognized in 76% of cases as a complication (ophthalmology). Quarterly eye monitoring is carried out by 35% of professionals, 45% of whom are ophthalmologists. Conclusion: Our results show that, although the majority of health professionals who responded to this questionnaire are aware of the AJI, there is a lack of education during initial training of physicians.

Specific training seems necessary in order to improve the management of this chronic pathology and thus avoid sequelae. These data must be confirmed by other studies of national scope in order to determine whether the lack of knowledge about this pathology is related to a lack of communication and local or national education. Introduction: Evidence for the role of vitamin D in juvenile idiopathic arthritis (JIA) risk is mixed across epidemiological studies, however such studies are challenging to undertake and are susceptible to considerable bias. Low vitamin D levels are common within the general population and easily corrected, therefore there is considerable potential public health benefit if a causal association between vitamin insufficiency and JIA is established. Mendelian randomisation (MR) is a method of causal inference which relies on the use of genetic variation, assigned at conception, as a proxy of the exposure of interest and thus limits bias due to confounding and reverse causation, subject to core assumptions being met.

Objectives: To use MR to test whether vitamin D levels are causally associated with JIA risk. Methods: Since 25-hydroxy-vitamin D (25OHD) is the major circulating form of vitamin D we used summary level data from the largest and most recent genome wide association study of 25OHD levels (sample size 443,734), alongside summary data from two JIA genome wide association studies (sample sizes 15,872 and 12,501), all from European populations. To test and account for potential bias due to violations of the core MR assumptions we employed multiple different MR methods and sensitivity analyses. Results: Using a genetic instrument for 25OHD, comprising 69 25OHD-associated single nucleotide polymorphisms, we show there is no evidence of a causal association between genetically predicted 25OHD levels and JIA risk (OR 1.00, 95% CI 0.76-1.33 per standard deviation increase in standardised natural-log transformed 25OHD levels). This estimate was consistent across all methods tested. There was also no evidence of reverse causation when assessing the causal effect of genetically predicted JIA on 25OHD levels (0.004 standard deviation decrease in standardised natural-log transformed 25OHD levels per doubling odds in genetically predicted JIA, 95% CI -0.009-0.002).

Conclusion: In this study we found no evidence that genetically increased 25OHD levels confers protection from JIA and that population level vitamin D supplementation is unlikely to contribute to a reduction in JIA incidence.

Disclosure of Interest None declared Introduction: Tofacitinib is an oral JAK inhibitor that is being investigated for several forms of JIA. The efficacy and safety of tofacitinib in patients (pts) with polyarticular course (pc)JIA were demonstrated in a Phase 3 trial.

Objectives: To evaluate the frequency of controlled disease, measured by achievement of low disease activity (LDA) status per the Juvenile Arthritis Disease Activity Score (JADAS), and normal physical function, measured by the Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), in tofacitinib-treated pts with pcJIA.

Methods: Data were analysed post hoc from pts with pcJIA aged 2 −<18 years in a Phase 3, randomised, double-blind, placebo (PBO)controlled withdrawal trial, where all pts received open-label tofacitinib 5 mg BID or body weight-based lower equivalent dose until Week (W)18 (end of Part 1). Pts with ≥JIA/ACR30 response at W18 were randomised 1:1 to continue tofacitinib or switch to PBO in the double-blind phase (Part 2, W18−44). Pts with JIA flare were discontinued from the trial. pcJIA disease control was assessed using: clinical JADAS in 10 joints (cJADAS10; no CRP/ESR laboratory measure), JADAS10-CRP and CHAQ-DI. LDA for cJADAS10 was defined as a score of ≤2.5 and for JADAS10-CRP as a score of ≤3.8. Normal function was defined as a CHAQ-DI score of 0.

Results: 184 pts with pcJIA entered Part 1 and 142 were randomised in Part 2 to continue tofacitinib (N=72) or switch to PBO (N=70). At Part 1 baseline, pcJIA control was absent, per mean (SD) values of: cJADAS10, 18.9 (4.7); JADAS10-CRP, 20.3 (5.5); and CHAQ-DI, 1.0 (0.7). At W18, disease control was improved, per mean (SD) values of: cJADAS10, 5.4 (4.8); JADAS10-CRP, 6.2 (4.9); and CHAQ-DI, 0.5 (0.6). cJADAS10 LDA and JADAS10-CRP LDA were achieved at the end of Part 1 by 42.9% and 44.2% of pts (N= 154), respectively, while 24.0% achieved cJADAS10 LDA + normal function and 24.0% achieved JADAS10-CRP LDA + normal function. In Part 2, LDA ± normal function frequency remained stable in pts who continued tofacitinib, while in pts who switched to PBO, LDA ± normal function frequency decreased over time (Table) . At the end of Part 2 (W44), in pts who continued tofacitinib vs pts who switched to PBO, cJADAS10 LDA was achieved in 47.2% vs 31.4% and JADAS10-CRP LDA in 47.2% vs 32.9%, respectively. Pts who discontinued treatment for any reason, except while in clinical remission, were counted as non-responders as of their discontinuation visit through W44 Conclusion: Tofacitinib reduced disease activity in a rapid and sustained fashion and improved function in pts with pcJIA. A large proportion of pts achieved LDA, a current pcJIA treatment target, at W18 and thereafter. LDA prevalence estimates were comparable using cJADAS10 vs JADAS10-CRP, suggesting that cJADAS10 may suffice to assess treatment targets in pts with pcJIA. Trial registration identifying number: ClinicalTrials.gov (NCT02592434)

Disclosure of Interest 

Usefulness of synovial biopsy in the differential diagnosis and as predictor of clinical course in juvenile idiopathic arthritis: a monocentric study on 100 patients S. Costi 1 , F. Pregnolato 1 , A. Parafioriti 2 , E. Armiraglio 2 , T. Giani 3 , R. Cimaz 4, 5 Introduction: While synovial biopsy is an invasive procedure and is not required for the diagnosis of juvenile idiopathic arthritis (JIA), it may be useful in doubtful cases. Histopathologic characterization with regard to future course of disease has not been well studied.

Objectives: Aims of this study were i. to investigate the usefulness of synovial biopsy for diagnostic purposes, and ii. to review histological specimens in order to evaluate possible associations between pathology features and JIA clinical outcome. Methods: We reviewed data from medical records of patients under the age of 18 years who underwent a synovial biopsy requested by our Pediatric Rheumatology Unit over the last 15 years. We collected information on clinical (remission criteria, number of disease flares, number of cDMARDs/bDMARDS used) and histological characteristic (number of layers of synovial lining, inflammatory infiltrate, elementary lesions of the subsynovia). Differences in numerical variable between groups were assessed by Mann-Whitney test while associations between categorical predictors and outcomes by Chisquare or Fisher's exact test. A logistic multivariable model with outcome as dependent variable was applied in order to measure the strength of and adjust for potential confounders. Results: We identified 100 patients who underwent a synovial biopsy during the study period. Of those, 99 (65% female) had complete data. Median age at onset of 8.5 years (range 1-17), median follow-up time was 161 months (range . We recognized two groups: patients with known/suspected JIA (44/99) and patients with unknown diagnosis (55/99). In the first group, 10 patients underwent synovial biopsy as a result as diagnostic doubt, while 34 had an orthopedic procedure. In all these 34 patients the biopsy results were consistent with JIA. Among the second group, 31/55 results were consistent with a chronic synovitis (final JIA diagnosis), while in others the histologic results led to a final diagnosis of other conditions (e.g. Giant cell tumor of the synovium and tendon sheat n=6, foreign body n=2, osteomyelitis n=1, sarcoidosis n=1). Between the two groups we identified 75 patients with JIA diagnosis. At the last follow-up visit 47 of them of patients were in clinical remission or had low disease activity, while 23 patients had a severe course of disease. In 43 cases the correlation between status at clinical outcome and histological score could be assessed. Subjects who had more than 4 flares during follow-up showed a significantly higher number of layers of synovial lining ( Introduction: Lubricin (coded for by the gene PRG4) is a mucinous glycoprotein, which provides mechanical lubrication and may also function as an inflammation modulator [1] . Lubricin protein is highly expressed in synovial fluid, blood and many other organs [1, 2] . In a rare, autosomal recessive condition, lubricin is absent or non-functioning causing disabling manifestations associated with the disease: camptodactyly, arthropathy, coxa-vara and pericarditis (CACP) [3] . There are limited treatment options for CACP patients as understanding the role of lubricin in normal and diseased states is still being defined [3] . To date, synovial fluid of adult Rheumatoid Arthritis and Osteoarthritis patients have shown reduced lubricin concentrations compared to healthy adult controls [4] . Concentrations in paediatric cohorts have never been described.

Objectives: To define the concentration of lubricin protein in blood and synovial fluid of juvenile idiopathic arthritis (JIA) patients, CACP patients, and blood serum of healthy child controls.

Methods: The mean age was 7 years (range 1-13 years). Lubricin concentrations in venous blood serum (VBS) and synovial fluid (SFS) were measured by sandwich ELISA (Mybiosource). Samples were from the following patient groups: rheumatoid factor negative polyarticular and oligoarticular JIA patients' blood (n=15) and synovial fluid (n=13), CACP blood (n=1) and synovial fluid (n=2) and child healthy control blood (n=10). Lubricin concentrations in JIA paired VBS and SFS samples (n=11) were analysed on SPSS by Spearman's Rank Order Coefficient. Lubricin concentrations in VBS from JIA and CACP patients were compared to data from child healthy controls by Kruskal Wallis ANOVA analysis.

Results: The median concentrations of lubricin were 3280ng/ml (IQR: 2640-3491ng/ml) in JIA synovial fluid, 3240ng/ml (IQR: 3085-3394ng/ml) in CACP synovial fluid, 341ng/ml (IQR: 182-645ng/ml) in JIA blood serum, 105ng/ml in CACP blood serum, and 115ng/ml (IQR: 106-195ng/ml) in healthy child control blood serum. The blood serum concentrations variation was significantly different between JIA, CACP and healthy child controls, p=0.008. The relationship of lubricin concentration between JIA paired blood and synovial fluid serum had a correlation coefficient 0.545 (p=0.083).

Conclusion: This study is the first to show measure of lubricin in both blood and synovial fluid of paediatric patients. The data suggest that lubricin concentration in JIA blood was significantly higher compared to CACP and healthy child controls, but there was no correlation between levels in VBS compared to SFS. Lubricin measured from the synovial space of CACP patients could be nonfunctioning lubricin, given the positive phenotype and confirmed PRG4 mutations in these patients. Further work will investigate the functionality of lubricin in patients.

Introduction: Body-worn accelerometers can accurately quantify joint movements, and could potentially assist with the diagnosis of juvenile idiopathic arthritis (JIA) as joint movement restriction is a feature of the condition.

Objectives: This proof-of-concept study aimed to evaluate the use of accelerometry to objectively quantify knee joint movements in children with clinically active JIA. Restriction in joint movement can be observed in JIA, so an accurate, cost effective, and portable tool that objectively measures restriction could aid diagnosis. Methods: Seven participants (age: 11.7 (2.7) years) with suspected active arthritis of a single knee joint were recruited. Participants had established diagnoses of oligoarticular (n = 2) and polyarticular JIA (n = 5) and were recruited just prior to planned appointments for steroid joint injections. paediatric Gait, Arms, Legs and Spine (pGALS) examination 1 was performed by an experienced practitioner on the day of data collection, to confirm the suspicion of active arthritis. The contralateral knee joint acted as reference. An accelerometer is a miniature sensor for measuring movements in three perpendicular dimensions. Four tri-axial accelerometers were integrated individually in soft elastic bands. The data from the accelerometers were collected using a microprocessor and stored on a computer. Accelerometers were placed above and below each knee and participants were asked to perform ten consecutive flexion and extension movements of each knee joint while lying, followed by walking ten meters. Accelerometry data were processed using a data analysis package called Matlab © to quantify knee movement according to range of movement, maximum velocity, maximum acceleration, angular displacement, and period of movement. A participant questionnaire was used to establish procedural acceptability.

Results: The accelerometry results were concordant with pGALS examinations in 86% (n = 6) of cases. In all variables measured, the extent of movement was reduced in the knee joint with active JIA, this was most pronounced during flexion and extension movements compared to walking. Joint range of movement had a greater standard deviation (16.6 degrees) and interquartile range (29.1 degrees) in the knees with active JIA compared to the healthy knees during flexion and extension movements, demonstrating inconsistency of movement in the joints with active JIA. There were statistically significant differences between the range of movement (p = 0.032) and angular displacement (p = 0.030) of the knees with active JIA and the healthy contralateral knee joints during flexion and extension. No statistically significant differences were identified between knee joints with active JIA and the healthy knee joints during walking. The questionnaire indicated one participant suggested future improvement in the accelerometer's band design due to discomfort, and the remaining participants found the procedure acceptable.

The study demonstrated proof-of-concept for the use of accelerometry to quantify knee joint movement in JIA. It examined accelerometry variables that suitably represented joint movement. It was found that accelerometry has potential for differentiating between joints with active arthritis and unaffected joints, particularly through assessment of flexion and extension movements. Further research is required to confirm these findings and refine the use of this novel technology in children with JIA. 

Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a rare autosomal recessive genetic disorder caused by a mutation in the PRG4 gene. It is characterized by congenital or early-onset camptodactyly and symmetric polyarticular non-inflammatory arthropathy of large joints with synovial hyperplasia, coxa vara, non-inflammatory pericarditis / pleurisy, and the absence of inflammatory markers. Symptoms appear from birth and do not differ by sex or race. This condition more common among children of blood related couples. Currently, there is no pathogenetic therapy. NSAIDs are used for symptomatic treatment and hip arthroplasty is used as surgical treatment of coxa vara. Therapy used for juvenile idiopathic arthritis (JIA) is ineffective.

To report a case of CACP in 2 siblings (sister and brother) in rheumatological practice.

The patients were examined in the rheumatology department. Both patients were diagnosed with the CACP using genetic analysis -Sanger sequencing. Two PRG4 mutations were identified on chromosome 1q25-q31 (pathogenic p.K918fs * 10 and probably pathogenic p.T1161Hfs * 2).

Case report: Girl and boy born in 2014 and 2017, respectively. Parents are not blood related. Objectives: To evaluate the efficacy and safety of vaccination against measles, rubella, mumps, and diphtheria in patients with JIA who continued to be vaccinated after the onset of JIA. Methods: In a cross-sectional study, from a database containing information on 170 patients with JIA aged 2 to 17 years, who were identified with antibodies against measles, rubella, mumps and diphtheria, patients were selected who continued to be vaccinated against measles, rubella and mumps (n=19) and diphtheria (n=25) or refused to be vaccinated against MMR (n=39) and diphtheria (n=51), due to the development of JIA. The decision on vaccination was entirely voluntary, made by the legal representatives of the patient together with the district pediatrician or the rheumatologist together with the immunologist of the child health center. All legal representatives signed an informed consent for revaccination. The study selected patients whose age corresponded to the terms of revaccination, according to the National Schedule of Vaccinations of the Russian Federation. The diagnosis of JIA was established based on the ILAR criteria. In all patients, the levels of antibodies (IgG) against vaccines were determined using ELISA. The data is presented with a median and 25%>75%.

Results: Children with the oligoarticular variant of JIA were more often subjected to revaccination against measles, rubella, and mumps. There were no significant differences in antibody levels and the proportion of patients who did not have protective antibodies against measles, rubella and mumps between the compared groups, as well as differences in the characteristics of the course of JIA and the therapy. Patients with less severe JIA, less frequently treated with methotrexate, and less likely to need both primary administration of biologics and switching between biologics were more likely to be revaccinated against diphtheria. Vaccination against diphtheria was effective, as evidenced by an almost twofold prevalence of patients with a protective antibody titer compared to those who refused revaccination. Methotrexate (OR = 9. Introduction: According to anecdotal reports, renal involvement due to uncontrolled inflammation or long exposure to anti-rheumatic drugs, may rarely occur during juvenile idiopathic arthritis (JIA). Most of these cases refer to systemic JIA, associated with inflammation and, eventually, renal amyloidosis. Little is known about oligoarticular JIA. Biological agents, such as adalimumab, can induce IgA nephropathy but this usually resolves following cessation of therapy. Objectives: To highlight potential aetiology of renal involvement in oligoarticular JIA. Methods: We herein report a case of a 13 years old boy affected by JIA and uveitis, who developed proteinuria and haematuria during adalimumab treatment. Results: The patient was diagnosed by ANA positive oligoarticular JIA at the age of 3. He was initially treated with intra-articular steroid injections and methotrexate, with subsequent switch to etanercept due to frequent articular relapses. Despite complete remission, he later presented relapsing uveitis for which adalimumab was started in Oct 2017. Complete remission was successfully obtained and maintained with ongoing treatment. However, on Nov 2020, unforeseen proteinuria and haematuria occurred regardless persistent JIA remission. Drug-induced renal damage was considered and adalimumab promptly discontinued. Infectious triggers were ruled out. Autoimmune profiling was unremarkable (i.e. negative ENA, dsDNA, p-ANCA, c-ANCA, p anti-phospholipase A2 receptor and glomerular basal membrane antibodies antibodies, anti-thyroid antibodies) except for known ANA positivity (1:160). Complement fractions were in normal range whereas IgA levels were slightly elevated (330 mg/dl, normal values 61-301). Intriguingly, laboratory tests unveiled the presence of HLA-DQ2/DQ8 positivity and IgA-class tissue transglutaminase antibodies (tTGA), which were persistently negative at previous yearly screening. Coeliac disease may actually elicit IgA nephropathy with consequent beneficial effect of gluten-free diet. However, tTGA levels remained in borderline ranges at following assessments, not allowing a definitive serological diagnosis. Meanwhile, given worsening course of proteinuria and haematuria, renal biopsy was performed, and unveiled findings consistent with mesangial IgA nephropathy. Unfortunately, discontinuation of biological therapy resulted in both ocular and articular disease relapse. In order to rapidly target either kidney and JIA disease manifestations, systemic corticosteroids regimen according to "Pozzi protocol" was started with prompt improvement of both proteinuria and haematuria, and resolution of articular and ocular relapse. Conclusion: The case herein presented addresses the multifactorial putative causes underlying onset of an IgA nephropathy in oligoarticular JIA. In particular, this report rises several considerations: 1) the patient developed IgA nephropathy during adalimumab therapy, with worsening proteinuria and haematuria despite drug discontinuation, weaking the drug-induced hypothesis; 3) several evidence indicate a role for gut-renal connection in IgA nephropathy onset and celiac disease is part of the autoimmune clinical spectrum including JIA. In conclusion, due to rarity of reports demonstrating safety of other anti-TNFα agents, once renal remission will be achieved by the ongoing steroid regimen, JIA maintaining therapy with different biologic drug (i.e. abatacept) will be considered. In addition, the ongoing suspicious celiac disease onset will need to be confirmed or excluded by small bowel biopsy as soon as the high dose steroid regimen will be concluded in other to avoid potential relapse of IgA Introduction: Biologic agents have revolutionized the treatment of Juvenile idiopathic arthritis (JIA). However, difficult to treat patients need several biological swaps. In this context, it is important to improve the effectiveness of available drugs and to spare our weapons with a lifespan perspective. The resetting of peripheral B cells promoted by rituximab (RTX), a chimeric monoclonal antibody against B-cell antigen CD20, represents a quite interesting option in autoimmune diseases such as JIA not only for the immediate advantage but also for the possible future use of subsequent therapies that might be necessary to achieve disease control.

Objectives: To evaluate whether TNF-α inhibition, which had already been used could be repurposed after RTX therapy.

Methods: This is a retrospective pilot study involving JIA patients who took a TNF-α inhibitior before and after having been treated with RTX. Clinical and laboratory data were collected and statistically analyzed. Clinical status, number of flares, and retention on treatment were then evaluated at different time points. Confidence intervals (CI) lower than 95% were used to estimate a probabilistic range of pre and post-RTX variations and trend was considered relevant when at least one of CI excluded the reference value of "no change". As the sample size was limited, a bootstrapping procedure (i.e. a statistical procedure that resamples a single dataset to create many simulated samples) was used to estimate disease activity parameters and related CI. Clinical remission was achieved in 7 patients on SB pre-RTX and in 8 patients on SB post-RTX; furthermore, the median time to achieve clinical remission was shorter (2 months vs 3 months) before and after RTX. Both the remission duration and the retention time of the TNF-α inhibitor were longer (3.9 years vs 2.2 years) on the SB post-RTX. After adjustment for the exposition time, the median number of flares was 1.03 (0.29 to 3.02) during the treatment with TNF-α inhibitor pre-RTX and decreases post-RTX to 0.64 (0.0 to 2.09). The bootstrapped differences of remission time, TNF-α inhibitor retention rate and flare rate ratio of post-versus pre-RTX are shown in Table 1 . As the reference value of no change (0 or 1 according to the effect measure used) does not fall within the 95% and 90% CI, our findings highlight a trend towards a substantial variation.

Conclusion: This pilot study documented a possible amelioration of disease response to TNF-α inhibition after treatment with RTX. A larger cohort is advisable in order to verify this opportunity in the context of a chronic disease starting in early childhood.

None declared Introduction: Juvenile idiopathic arthritis (JIA) is currently considered a heterogeneous group of inflammatory arthritis of unknown etiology (ACR, 2019). The formation of its pathological mechanisms is due to dysregulation of both adaptive and innate immunity, the key ligands of which are toll-like receptors (TLR). TLR4 play an important role in the recognition of inflammation caused by bacterial lipopolysaccharides (LPS), activation of the nuclear factor-κB (NF-κB) and other intracellular signaling pathways with subsequent expression of pro-inflammatory cytokine genes. An increased expression of endogenous TLR4 ligands (heat shock proteins, fibronectin, fibrinogen, HSP, EDA, etc.) has been found in the tissue synoviocytes and peripheral blood monocytes, which are recruited to the site of inflammation and participate in the pathogenesis of synovial inflammation, which is believed to be an important mechanism in the pathogenesis of rheumatoid arthritis. Conclusion: Uveitis was more frequent in opJIA and oeJIA patients and was related to ANA positivity, which is consistent with the literature. The need of ocular surgeries and prevalence of glaucoma seems to correlate with oeJIA.

Introduction: Physical activity (PA) is essential throughout growth and maturation to ensure optimal physical function and fitness, especially for those suffering from chronic conditions such as JIA [1] .

Objectives: This study aimed i) to estimate the proportion of JIA patients meeting the recommended minimum level of PA compared with general population controls and ii) to identify clinical parameters associated with physical (in)activity. Methods: Patients' (≥12 years) or parents' (≤11 years) self-reported data on PA were considered from the German Paediatric Rheumatologic Database. In accordance with the methodology used in the general population survey [2] , achievement of WHO recommendations on PA of at least 60 minutes per day was determined among 3-17-year-olds. For comparability reasons with the general population, 2017 served as the year for which sex-and age-matched pairs were formed. Multinomial logistic regression was used to analyze the association between physical (in)activity and clinical as well as selfreported outcomes. Introduction: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease in which immune-related mechanisms involved in the pathogenesis still remains unclear. Similarly, immunological markers of disease activity require explanation.

Objectives: The aim of the study was to assess the expression of programmed-death cell receptor 1 (PD-1) on lymphocytes in patients diagnosed with JIA and determine whether those results correlates with the type of the disease, chosen laboratory parameters, as well as disease activity. Methods: The study included 34 children, 18 patients with newly diagnosed JIA prior to any therapy and 16 healthy volunteers (HV) with a similar age distribution. 9 patients were diagnosed with the enthesitis-related (ERA) JIA type, 7 the oligo-and 2 poly-arthritis. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 71 (JADAS 71) calculated on the following parameters: parent global assessment of well-being, physician's global assessment of disease activity, number of active joints and erythrocyte sedimentation rate (ESR). After obtaining the appropriate consents, blood samples were taken from the patients and HV's. Samples after preparation according to the protocol were stained using anti-human antibodies (BD Biosciences, USA) and analyzed using FACSCaliburTM flow cytometer (BD Biosciences) and CellQuest Pro Software. Results were statistically analyzed using Statistica 12. Kruskal-Wallis test and Spearman rank correlation were used to determine statistical significance.

Results: Data analysis showed no significant differences in the percentages of PD-1 + CD4 + , PD-1 + CD8 + and PD-1 + CD19 + cells between the JIA patients and the control group. A higher level of PD-1 + lymphocytes was observed in patients with polyarthritis form, but this relationship was not statistically significant. Preliminary results indicated that there was no correlation between the percentage of PD-1 receptor and other laboratory and clinical parameters. However, there was a strong statistically significant correlation (p=0.0057) between the percentage of CD8 + PD-1 + lymphocytes and the disease activity measured by the JADAS 71 (Tab.1.) Conclusion: Our research showed a correlation between the percentage of PD-1+CD8+ T lymphocytes and the disease activity. The search for a molecular markers of the disease activity is extremely important in the process of choosing proper treatment strategies and preventing the disability of children diagnosed with JIA. Flow cytometry is a cheap, quick and clinically available method. The role of the PD-1+CD8+ cells in chronic inflammation is also interesting. More research is needed to assess whether the PD-1+CD8+ lymphocytes may be used as a marker of disease activity or the potential target of therapy. Bioethics Committee approval number KE-0254/93/2021.

None declared Introduction: Mild painful knee swelling with functional limitation is one of the most common clinical picture at onset of monoarticular juvenile idiopathic arthritis (JIA).

Objectives: To present an unusual condition featured by overlapping clinical signs typical of monoarticular JIA, which may need to be reminded during differential diagnosis. Methods: Diagnostic work up including routine and immunological blood test combined to imaging assessments (i.e. knee ultrasound and magnetic resonance imaging, MRI) and synovial biopsy was carried out. Literature revision of similar case reports was performed to confirm significance of the findings. Results: A 12 year-old female presented with left knee swelling, mild pain and functional limitation, persisting for 8 weeks without history of recent trauma nor infections. Morning stiffness was not referred. Physical examination was unremarkable except for local mild painful swelling in the absence of calor, rubor nor significant joint effusion, and associated to functional limitation at squatting. General condition were good except for obesity, in the absence of constitutional symptoms. By investigating her personal and medical history, a similar episode, occurring on the same joint 18 months earlier and resolved following evacuative arthrocentesis, was described. The procedure had been performed in emergency room with no further measures due to referred serosal synovial fluid and unremarkable routine blood tests with negative knee X-ray. Persistent well-being was referred until the ongoing relapse. Given the disease history and the presence of autoimmunity in the family (i.e. psoriasis and autoimmune thyroiditis in father and sibling, respectively), onset of JIA was suspected. Routine tests were normal with negative ERS, CRP and anti-streptococcal titer antibodies. Autoimmune profiling was unremarkable (i.e. negative ENA, dsDNA, rheumatoid factor, anticitrullinated antibodies, and eye examination ruled out signs of uveitis. Knee ultrasound reported a prominent diffuse synovial thickening with mamillated aspects, associated with mild corpuscolated joint effusion, without certain signs of hypervascularization. Pigmented villonodular hyperplasia was thus considered, and bilateral knee MRI performed. Surprisingly, MRI findings were consistent with lipoma arborescens, a benign intra-articular tumor featured by villous synovial hypertrophy and lipomatous infiltration of the subsynovial tissue. Namely, the MRI reported bilateral villous proliferation of the synovia with lipomatous features. Synovial biopsy eventually confirmed the diagnosis of lipoma arborescens and the patient was referred to orthopedics for therapeutical synovectomy. Patient lost at follow up. Conclusion: Lipoma arborescens usually affects the knee (mostly but not exclusively in monoarticular pattern) although every joint can be involved. Although rare in children, we revised the available literature in order to assess the significance of this finding. Actually, to date only 15 cases have been described in pediatric age, affecting one knee (N=9), bilateral knees (N=4), one ankle (N=1) and one knee and one elbow (N=1). Due to the rarity of this condition, delayed diagnosis (in terms of months-years) usually occurred. Interestingly, in at least 3 cases patients had been previously diagnosed with JIA and treated accordingly, mostly for years. In one case the patient also obtained diagnosis and treatment for rheumatic fever, before receiving JIA misdiagnosis. In conclusion, although rare, lipoma arborescens should be considered in differential diagnosis of oligoarticular JIA at onset, in order to avoid misdiagnosis and overtreatment. (Table) . Its increase was not determined in overweight children. The oligoarticular variant of JIA was more favorable with respect to both the initial and the repeated level of vitamin D. Children with achieved remission of the disease and a low degree of JIA activity did not show a significant increase in the level of vitamin D. There was no positive dynamics of vitamin D status in children who received MTX monotherapy for more than six months at a MTX dose of less than 10 mg / m 2 . Conclusion: Children with JIA have an impaired vitamin D status, its decrease. The effectiveness of additional supplementation with cholecalciferol is higher in children with low and normal body weight, with oligoarticular JIA. In order to achieve an optimal response to additional intake of vitamin D, its early prescription is necessary, especially against the background of high JIA activity. Rational prescription of basic therapy and its intensification after 6 months of use is one of the links in the prevention of vitamin D deficiency in children with JIA.

None declared Introduction: In Juvenile Idiopathic Arthritis (JIA), a treat-to-target (T2T) strategy is recommended to improve clinical outcomes and was proven effective in suppression of disease activity in the BeSt for Kids study. Does this approach also help to reduce pain in children with JIA?.. Objectives: To compare pain in three T2T strategies in JIA patients participating in the BeSt for Kids study and to identify baseline characteristics predicting high pain levels during follow up. Methods: DMARD naïve children who participated in the BeSt for kids study with oligoarticular JIA, RF-negative polyarticular JIA and juvenile psoriatic arthritis were treated with a T2T strategy aiming at (drug free) inactive disease in 1 of 3 initial treatment groups;

1) Initial sequential DMARD monotherapy (Methotrexate (MTX) or Sulphasalazine) 2) Initial MTX with 6 weeks of prednisolone bridging 3) Initial MTX with etanercept.

Pain intensity was measured using a 100 mm Visual Analogue Scale during 24 months of follow-up with 3-monthly intervals. Potential differences in VAS pain scores over time between treatment arms were compared using linear mixed models. A similar multivariable mixed model was used to assess the ability of several baseline characteristics to predict high pain levels during follow-up and to determine the effect of inactive disease on pain. Results: 92 patients were randomized. Overall, pain scores over time reduced from mean 55.3 (SD 21.7) mm at baseline to 19.5 (SD 25.3) mm after 24 months. When comparing pain over time per arm, pain scores decreased significantly β -1.37 (95% CI -1.73; -1.02). No significant difference was found in pain over time between initial treatment groups. Correction for sex and symptom duration as possible confounders yielded similar results. Inactive disease contributed to pain reduction by -11.36 mm (95% CI -13.80; -8.93). However, 7 children still experienced pain during inactive disease. Several baseline characteristics demonstrated a significant predictive value for pain over time when tested in a multivariable model. A higher baseline VAS pain and number of active joints at baseline were predictive of higher pain over time. VAS of the patient/parent, symptom duration and NSAID use were not predictive for pain over time.

Conclusion: In children with JIA participating in the BeSt for Kids study treatment to target (drug free) remission is effective in reducing pain irrespective of initial treatment. However, some children still experience pain despite reaching inactive disease. This emphasizes the necessity of patient related outcomes for targeted treatment. High VAS pain and many active joints at baseline can help to identify non-systemic JIA patients with a high risk of pain over time despite applying a treat-to-target strategy. Trial registration identifying number: Trial NL1504 (NTR1574) Disclosure of Interest None declared All of them had been receiving TNFi for more than 24 months and discontinued TNFi due to a long-term remission on treatment. Inactive disease was defined according to the criteria of Wallace et al. [1] .

The clinical subtypes of JIA were persistent oligoarthritis -39 (46%), RF-negative polyarthritis-34 (40%), extended oligoarthritis-9 (10,5%), enthesitis-related arthritis-3 (3,5%). 22 (26%) patients have been diagnosed with JIA-associated uveitis. TNFi were discontinued after 46 (range 10-114) months after initiation of therapy. Duration of remission prior to discontinuing TNFi was 41 (range 6 -121) months. In 60 (71%) patients TNFi had been withdrawn after long-term remission was achieved, in 17 (20%) patients as a result of side effects, in 4 (4,5%) patients had been discontinued because of organization problem, and in 4 (4,5%) patients had been stopped biologic therapy by parents. All of them had remission prior to discontinuing TNFi more than 24 months. The mean duration of remission after TNFi discontinuation was 29 (range 1-92) months. 14 (16%) of patients had flares after less than 6 months after discontinuing of TNFi, 33 (39%) had flares after 6 -24 months, 38 (45%) had not flares and had remission due to 24 months after discontinuation TNFi.

In 47/85 (55%) patients flares had been appeared, 37/47 (79%) of patients flared with active arthritis, while 10/47 (21%) flared with uveitis. Disease was successfully controlled in 7/47 (15%) patients with nonbiological DMARDs, 40/47 (89%) patients restarted TNFi after flares, due to lack of improvement after non-biological DMARDs.

The mean duration of TNFi therapy was 46 months, duration of remission prior to discontinuing TNFi was 41 months. The mean time of remission after discontinuation of TNFi was 29 months, although it should be noted that in as many as 38 children (45 %), flares occurred in more than 24 months. Data from our experience with TNFi in the treatment of JIA suggest that 45% of patients can be successfully withdrawn from TNFi for at least 24 months. Methods: Biologic therapy naïve non-systemic JIA patients without a history of uveitis were selected from the international observational Pharmachild registry. Patients who started ETN were matched 1:1 to patients who started ADA based on propensity score, i.e. the probability of receiving one of the two drugs. Outcomes were collected around therapy initiation and 3-12 months afterwards. Primary outcome at follow-up was the change in VAS well-being score from the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Secondary outcomes were the change in active joint count, number of adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed model analyses.

Results: 46 ADA and ETN starters were matched ( respectively. Minimum age of presentation was 13 months, a male child diagnosed with sJIA. Knee joint was the most common joint involved with bilateral involvement in polyarthritis and unilateral in rest of JIA. Hip joint, 6(37.5%) and axial skeleton, 1(6.25%) involvement was found exclusively in ERA while small joints of hands, were involved in all the patients of RF positive polyarthritis 6(100%). None of the patients had temporomandibular joint and cervical spine involvement. Five (62.5%) out of 8 patients of sJIA developed macrophage activation syndrome (MAS) with 50% mortality, may be due to late presentation to our institute. Antinuclear antibodies (ANA) was found positive in 65% cases of polyarthritis and 56% cases of oJIA while 94% (15 out of 16) cases of ERA had HLA B-27 positive. Only 2(3.3%) patients of oJIA had uveitis, both were ANA positive. After enrolment, 75% children were given nonsteroidal anti-inflammatory drugs (NSAIDs). Forty percent of sJIA patients required methylprednisolone pulse therapy and intravenous immunoglobulin (IVIg) for the management of MAS. Intra-articular corticosteroid injections (IACI) were used in 5(20%) patients of oligoarthritis and 4(25%) patients of ERA to alleviate inflammatory symptoms. Oral corticosteroids was given in 4(50%), 5(20%) and 4(25%) patients of sJIA, oJIA and ERA to relieve extra-articular manifestations in sJIA and to bridge the effect of disease modifying anti rheumatic drugs (DMARDs) in oJIA and ERA. Methotrexate (MTX) was the most commonly used DMARD, mainly in polyarthritis RF positive (83%) children. Sulfasalazine was used in 9(56%) children with ERA. Biological agents were not used in any of our patients.

The clinical and epidemiological profile of children in our study with JIA was different from the Western countries with almost equal frequency of JIA in boys and girls and high prevalence of ERA. Uveitis was uncommon. Majority of Patients are doing well on follow-up and thus use of biological agents has not been considered in some whereas cost is the limiting factor in others. Introduction: Tumor necrosis factor antagonists (anti-TNFa) have been paramount in the management of several autoimmune diseases. Despite their clinical effectiveness, there are reports documenting their potential role in the induction or aggravation of demyelination of the central nervous system (CNS) [1, 2] . Or it may be only a coincidence due to the underlying genetic susceptibility of these patients to disturbed autoimmune reactivity [3] . Objectives: We report two new cases of demyelinating events of the CNS, following treatment with anti-TNFa for two and nine years respectively, in two girls with polyarticular type of Juvenile idiopathic arthritis background, firstly diagnosed at the age of seven and twelve years old respectively. Methods: We investigated these cases of demyelination with laboratory examinations (screening for auto-antibodies, viral infection), lumbar puncture and magnetic resonance imaging (MRI) of the brain and spinal cord.

Conclusion: Inflammatory demyelination of the CNS may be associated with the use of anti-TNFa. Thus, all patients should, before and throughout the treatment, be monitored for any neurological complication, indicative of demyelination and evaluate appropriate treatment interventions [1] . However, we should not forget the cooccurrence of MS with other autoimmune disorders because of immunologic predisposition [4] . Methods: To evaluate clinical importance, we examined patient with Down syndrome who was presenting signs of arthralgia for a time frame more than 6 weeks and who was admitted to pediatric rheumatologist with suspicion of arthritis onset. Results: Patient D., 9 yr. came to the center 6 months ago. Patient became sick approximately 8 months ago, but due to difficulties associated with mental and behavior development, mother didn't concern about joint pain. Acute episode of the disease started with limping gait, child wasn't able to move at the morning, that was associated with pain syndrome in both knees. Before this episode of the disease child was healthy. The baby was delivered from the 1st pregnancy, in term, didn't have any complicated family or epidemiological anamnesis. Mom went to the family doctor; symptomatic treatment was started together with systemic antibacterial drugs. Within 14-day condition wasn't significantly improved, child still presented pain, less intense than at the onset of the disease, and as well limping gait. General practitioner diagnosed reactive arthritis and continued NSAIDs. The child was followed with complete blood count that showed mild inflammation, X-ray of the joints didn't show any pathological changes. General duration of the disease was longer than 6 weeks, but general practitioner ensured mom, that they don't require consultation of any other specialist. When the child was sick for 2 months mother by herself admitted him to the pediatric rheumatologist. During first investigation child showed signs of the arthritis of both knee joints, with typical swelling, mild to moderate pain, movements limitation, morning stiffness up to 1 hour. Other joints were not involved to the process, laboratory results showed mild increased ESR (21 mm/h), negative CRP, signs of the synovitis of both knee joints. Aspiration of the synovial fluid was presented with following intraarticular injection of the steroid. During detailed investigation child performed ANA 1:320, aCCP -34 IU/ml (Nup to 8 IU/ml). After the intraarticular injection situation much more improved, resolved pain syndrome, movement limitation. In 2-month, child returned back with the same complains on pain and movement limitation in both knee joints, but with minimal synovitis. Laboratory activity was mild, but taking into account previous disease anamnesis, results of additional investigations, diagnose of JIA was estimated and started treatment with methotrexate. By this time child was taking methotrexate for 3,5 months, JADAS-27 -5 was achieved (compare with initial JADAS-27 -9). Conclusion: By this time a lot of discussions are opened in arthritis associated with Down syndrome. Classical presentation has small joints involvement without autoimmune markers. Our patient showed other clinical signs so diagnose of the JIA is more adequate in this particular case. Introduction: Approximately 1 child in 1,000 is affected by chronic juvenile idiopathic arthritis (JIA). Persistent, undiagnosed JIA with high disease activity interferes with daily life and carries a risk of irreversible physical and psychosocial damage. Due to its relative rarity, primary physicians often do not recognize it; thus, diagnosis and referral to pediatric rheumatologists are delayed. Objectives: To evaluate the knowledge of Israeli pediatricians and pediatric-orthopedic surgeons regarding epidemiology, clinical manifestations, laboratory parameters and treatment of JIA. Methods: An 11-item online questionnaire regarding JIA sent to the lists of Israeli Society of Pediatrics and Pediatric Orthopedics, was completed by 274 pediatricians and 27 pediatric-orthopedic surgeons. Results: Average score was 67.8% overall participants. Several groups were associated with better overall scores: hospital physicians compared to community physicians; pediatric residents (especially after board exams) compared to seniors; exposure to rheumatology during residency; and more JIA patients during the last 5 years. No significant difference was found between pediatricians and pediatricorthopedic surgeons. 40% of participants underestimated the true incidence of JIA; 30-45% were not familiar with its clinical presentation (age of onset, pain characteristics, chronic uveitis symptoms), and up to 65% were not familiar with up-to-date treatments. Conclusion: Israeli pediatricians and pediatric-orthopedic surgeons have misconceptions regarding JIA. This could result in delayed referral and treatment, which might affect outcomes. The results of this study highlight the need for better education and exposure to a rheumatologist, leading to the goals of better health and quality of life for JIA patients by improving knowledge. Methods: Patients with diagnosis of sJIA with LD, including pulmonary alveolar proteinosis (PAP), interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), followed in European paediatric rheumatology centres were identified through a survey sent to the members of the MAS/SJIA Working Party. Results: Data from 26 sJIA-LD patients, diagnosed in 10 European paediatric rheumatology centres between 2006 and 2020, were collected. 25 patients were Caucasian and 1 African-American, 16 were female, the median age at sJIA onset was 6.4 years and LD onset occurred after a median time of 2.7 years. 15 patients had a chronic persistent sJIA disease course, 10 had a polycyclic course and only 1 patient had a monocyclic course; 24 (92%) had active sJIA at time of LD diagnosis. During the disease course, 21 (81%) patients developed MAS, 9 (34%) of whom had MAS at sJIA onset and 15 (57%) had fullblown MAS at time of LD diagnosis; 21 (80%) patients had >1 MAS episode. 19 (73%) patients were treated with at least one IL-1 or IL-6 inhibitor before LD diagnosis: 12 with canakinumab, 17 with anakinra and 10 with tocilizumab. 10 (38%) patients experienced drug adverse reaction to a cytokine inhibitor: 8 to tocilizumab and 2 to anakinra. 20 (77%) patients developed ILD, 4 (15%) PAP and 3 (11%) PAH. 13 (50%) patients presented acute digital clubbing; 10 (38%) patients developed hypoxia and 6 (23%) developed pulmonary hypertension. A chest CT scan was performed in all patients with evidence of septal thickening and peri-bronchovascular thickening in the majority of patients (22 and 14 respectively). In 12 patients a bronchoalveolar lavage was performed and 9 underwent a lung biopsy. The histopathological pattern was alveolar proteinosis in 4 patients, endogenous lipoid pneumonia in 3, vasculitis in 1 and fibrosis in 1. Twelve (46%) patients required ICU admission and 3 (11%) died. All patients were treated with glucocorticoids (GCs) at time of diagnosis, and 22 received IL-1 or IL-6 inhibitor after the diagnosis (12 canakinumab, 15 anakinra, 13 tocilizumab). Conclusion: Lung involvement is an emerging life-threatening complication of sJIA in Europe, especially in patients with a history of MAS, and a prompt recognition is crucial. New strategies are needed to reduce the risk and improve outcome of this complication. Introduction: Systemic juvenile idiopathic arthritis (sJIA), a prototype of systemic rheumatic diseases in children is one of the common conditions presenting as fever of unknown origin (FUO) in the pediatric age group. Children with sJIA often prsent initially with FUO with systemic features preceding the onset of arthritis by weeks, months or even years. Diagnosing sJIA in these cases is challenging and highlights the need for a diagnostic biomarker to facilitate an early diagnosis and treatment. Dysregulation of innate immune response with overproduction of macrophage derived cytokines IL-1, IL-6, IL-18, S100 calcium-binding proteins S100A8 and S100A9 (calprotectin) is implicated in the pathogenesis of sJIA. A few studies have assessed potential biomarkers for sJIA in the recent years, however no such study has been conducted in the Indian population. Objectives: To evaluate serum IL-1, IL-6, IL-18, S100A8 and S100A9 as potential diagnostic markers to distinguish sJIA from other conditions presenting as FUO in children.

Methods: A prospective cross-sectional study was conducted at a 1500-bedded tertiary care centre in Kerala, southern India between May 2019 and October 2020. Children under 16 years of age who presented with FUO defined as "fever > 38.0°C (100.4°F) lasting for at least 8 days without a clear source" were enrolled on the study. Patients who had already received glucocorticoids and/or immunosuppressive therapy were excluded. Serum concentrations of IL-1, IL-6, IL-18, S100A9 and S100A8 were determined using enzyme-linked immunosorbent assay (ELISA) kits. Receiver operating curve (ROC) analysis was used to determine the cut-off values for IL-1, IL-6, IL-18, S100A8 and S100A9 for differentiating sJIA from other causes of fever. Results: Forty-seven children (females-27) who presented with FUO were enrolled. Nineteen of them were eventually diagnosed with sJIA according to the International League of Associations for Rheumatology (ILAR) classification. In the other 28 children, fever was attributed to conditions other than sJIA (non-sJIA). The non-sJIA group comprised of children with acute lymphoblastic leukemia (n=6), hemophagocytic histiocytosis (n=5), systemic lupus erythematosus (n=4), systemic infections (n=4), Kawasaki disease(n=2), Kikuchi disease (n= 2) and inflammatory bowel disease (n=2). This group also included one child each diagnosed with Sweet syndrome with polyarthritis, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome and post-infection multisystem inflammatory disease. Serum levels of IL-18, S100A8 and S100A9 were significantly higher in patients with sJIA compared to the non-sJIA group (p<0.05) ( Table-1 ). ROC analysis showed that the area under the curve (AUC) was significant for IL-18 (77.9%), S100A8 (74.9%) and S100A9 (71.2%). A serum IL-18 cut-off level of > 2030.45 pg/ml was useful for differentiating between sJIA and other diseases with a sensitivity of 66.67% and specificity 75.86% for the diagnosis of sJIA. Conclusion: Serum IL-18, S100A8 and S100A9 can be useful in differentiating sJIA from other causes of FUO in children.

Disclosure of Interest None declared (1) . Monocytes are essential cellular components of the innate immune system and in systemic idiopathic arthritis (sJIA) monocytes play a central role (2) . In a glucose deprived milieu monocytes shift to increased FA metabolism so cytokine secretion, migration, and phagocytosis remain intact (3) . This is also the case in a low oxygen environment such at the synovium(4). Therefore FA uptake and metabolism might play a role in monocyte inflammation in sJIA. We hypothesize that investigating the effects of FA uptake inhibition on monocyte metabolism and inflammation can contribute to a better understanding of sJIA pathogenesis, the identification of cellular pathways contributing to disease and possibly to new therapeutic targets.

Objectives: To investigate the effects of fatty acid uptake inhibition on monocyte metabolism and phenotype, assessed by changes in cytokine production. Methods: We used the monomac 6 cell line, as well as primary monocytes from healthy control and SJIA patients in active disease. We measured the uptake of FA analog C 1 -BODIPY-C 12 using flow cytometry and studied the effects of inhibition of FA uptake by preincubation with FA uptake inhibitors, lipofermata and grassofermata.

In addition, we studied the effects of FA uptake inhibition on monocyte cytokine and prostaglandin production and metabolism using FACS and qPCR. Results: Monomac 6, a cell line for human monocytes, show increased uptake of FA after LPS stimulation compared to unstimulated cells. The uptake of the FA can be inhibited with lipofermata and grassofermata in a dose depend way. FA uptake inhibition decreases IL 8 and TNFα production in these cells upon LPS stimulation. Preliminary results from experiments using primary cells show an increased uptake of FA in monocytes from active SJIA synovium compared to monocytes derived from healthy donor blood and a decreased inhibition of FA uptake with lipofermata.

Conclusion: The analysis of FA uptake and metabolism offers new insights in immune regulation. Our preliminary results in a monocyte cell line and sJIA patient monocytes suggest that this might play a role as well in monocytes in the inflammatory cascade in active sJIA. Targeting FA immunometabolism could potentially be exploited for the treatment of autoimmune diseases in the future. Introduction: Thalidomide made a comeback at the turn of century for use in Erythema nodosum leprosum (anti TNF) and multiple myeloma (anti angiogenic). It has also been used in various pediatric autoinflammatory conditions notably sJIA. We report the largest experience with this drug in sJIA, adding to our earlier reported series.

Objectives: Share our experience with thalidomide in 30 patients of sJIA refractory to cDMARDs with /without biologicals. Methods: Thalidomide was commenced in 30 patients beyond 4 years of age (children who could vocalize pain and paraesthesia) who failed to achieve disease control with NSAIDs,steroids,cDMARDs like methotrexate (n=3) or combination of methotrexate and leflunomide (n=24). 23/30 refused step up treatment to biologics due to cost constraints. 7 had also received biologicals in combination with methotrexate (etanercept-4, tocilizumab-3) but were shifted to thalidomide due to poor response (6) and cost constraints (1). Before initiating thalidomide,families were educated in their preferred language about thalidomide,its adverse effects and limited evidence in medical literature for use in children and sJIA. After consent, thalidomide available as capsules of 50 /100 mg was commenced as a single night dose (2-3mg/kg/day) along with high fibre diet. Thalidomide was started along with at least one cDMARD. Results: Monitoring of lung changes during development of sJIA using microcomputer tomography revealed a moderate enlargement of lungs, a decrease in aerated and increase in non-aerated lung density. When lung function and airway reactivity to methacholine was assessed, gender differences were seen. While male mice showed an increased tissue hysteresivity, female animals were characterized by an increased airway hyperactivity, mirroring ongoing inflammation. Histologically, lungs of sJIA-like mice showed subpleural and parenchymal cellular infiltrates and formation of small granulomas. Flow cytometric analysis identified immature and mature neutrophils, and activated macrophages as major cell infiltrates. Lung inflammation in sJIA-like mice was accompanied by augmented expression of IL-1β and IL-6, two target cytokines in the treatment of sJIA. The increased expression of granulocyte colony stimulating factor, a potent inducer of granulopoiesis, in lungs of mice was striking considering the observed neutrophilia in patients.

We conclude that development of sJIA in a mouse model is associated with lung inflammation which is distinct to the lung manifestations seen in sJIA patients. Our observations however underscore the importance of monitoring lung disease during systemic inflammation and the model provides a tool to explore the underlying mechanism of lung pathology in an autoinflammatory disease context. Objectives: The objective of the study was to determine the efficacy, tolerability and safety of lenalidomide in patients with refractory SJIA and in whom biologics were not a plausible option either due to lack of affordability or non-availability. Methods: 9 SJIA patients who were refractory to steroids and methotrexate were started on lenalidomide after informed consent and followed up for a period of 6 months at least. Patients were monitored for clinical improvement in the form of subsidence of fever, joint symptoms and laboratory markers in the form of hemoglobin (Hb), WBC count, ESR and platelet count. All the subjects were also closely monitored for any adverse effects of the drug. The statistical analysis was performed by STATA 11.2 (College Station TX USA).

Results: At the end of 6 months of therapy all patients were free from systemic features and most of the patients experienced clinical improvement in articular symptoms. There was a statistically significant improvement in the Hb(p=0.045) and ESR(p=0.008) in the patients. Steroid dosage could be reduced in all the patients and marked improvement was noted in all the laboratory markers. The drug was tolerated well by all the patients and there were no major adverse events observed. The most common side effect observed was generalized hyperpigmentation of skin. Introduction: Juvenile idiopathic arthritis (JIA) is the most prevalent chronic rheumatic disease in children and young people, is a major cause of musculoskeletal disability. Low-income countries face a unique set of challenges, which limit the ability to deliver highquality care to patients with JIA. These challenges include a lack of trained pediatric rheumatologists or pediatricians, inadequate healthcare funding, delay in diagnosis and restricted access to medications.

Objectives: The objective of this study is to present the case of a pediatric patient with severe sequelae of systemic JIA, who failed in the diagnosis, treatment and timely referral, to raise awareness of the importance of early diagnosis and timely referral to the pediatric rheumatologist for effective treatment and prevention of disease progression and sequelae. Methods: We presented the case of a pediatric patient with Systemic JIA severe sequelae, that failed in diagnosis, treatment and timely referral to pediatric rheumatologists. Results: A 9-year-old patient who lives on a low socioeconomic and cultural level, came to the emergency room for fever of unknown origin. He has a history of hospitalization for fever in a second level care center 2 years ago. He received diagnosis of community-acquired pneumonia, and was treated intravenous antibiotics, with no response. Due to the persistence of fever, an approach is initiated, infectious causes are ruled out (negative blood and urine cultures, negative serologies for Brucellosis, Ricketssiosis and Lyme disease), and oncological causes too (negative bone marrow aspirate). A computed tomography of the thorax and abdomen reported lymphadenopathy and splenomegaly. Splenectomy is performed in that center, in the abstract of reference to our hospital, they do not explain the surgical indication, however, after the procedure apparently there was fever resolution as equal to the other symptoms, so they perform the hospital egress, but the family did not follow up with the pediatrician, so the patient lost tracing for more than 1 year. Two months before his admission to our center, presented high fever (100-104°F), arthralgia, arthritis, weight loss 8 pounds, and constitutional symptoms. Clinically patient presented cachexia, malnutrition, paleness, retrognathia, generalized adenopathy, hepatomegaly 4-4-5 cm, arthritis in more than 15 joints, including the temporomandibular joint, shoulders, elbows, wrists, knees and ankles, as well as an axial skeleton that include cervical and lumbar vertebrae with a 2cm Schober test. Presented severe functional limitation with decreased arches of mobility because of the ankylosis. Patient has microcytic anemia (8.4mg/dl), leukocytosis (14,000 cel/ml), thrombocytosis (900,000 cel/ml) and elevated acute phase reactants ESR 23 mm/seg and PCR 11mg/dl. On the radiography images can observe periarticular bone loss, juxtaarticular bone erosions and ankylosis. In two years of evolution, any paediatric rheumatologist had evaluated the patient, at the time of our evaluation, the patient had not received DMARDs or other JIA treatment. Conclusion: The early recognition of signs and symptoms suggestive of rheumatic disease is imperative to make a timely diagnosis and provide effective treatment, in order to avoid progression and sequelae. In low-income countries, we must seek strategies to solve the challenges they present, such as a lack of trained pediatricians or pediatric rheumatologists, inadequate funding, and restricted access to medications with the objective of implement a hard and early hit strategy to improve in the evolution and prognosis of the disease. Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a rare and serious autoinflammatory disease characterized by systemic inflammation (fever, typical rash, serositis, hepatosplenomegaly, lymphadenopathy, acute phase reaction) and is variously accompanied by chronic arthritis, but at the onset of the nonspecific symptoms may be similar to other diseases with a pronounced acute phase inflammatory reaction. Objectives: According to the data of a retrospective study, to analyze in which part of patients (pts) with sJIA the diagnosis is revised, in what time frame, what distinguishes this group at onset. Methods: A total of 104 pts (57 females) with an initial diagnosis of sJIA who underwent inpatient treatment at our center from 2012 to 2020yy were included. The diagnosis of sJIA was verified in accordance with the ILAR criteria (2001), after excluding infectious, neoplastic or autoimmune diseases in regional hospitals. The median age at the onset was 4.5 years [interquartile range (IQR) 2.0; 8.0]. Molecular genetic testing for mutations in the NLRP3, MVK and TNFR SF1A genes was carried out in 101 pts. Results: The diagnosis was changed in 27 pts (25.9%). The median duration of the disease at the time of the revision of the diagnosis was 3.5 [1.5; 6.25] years. Monogenic autoinflammatory diseases (mAIDs) were diagnosed in 22 pts (CAPS -13, TRAPS -7, HIDS -1, FMF -1). Diagnoses of mAIDs were confirmed by the detection of pathogenic mutations of causal genes. Also polymorphisms NLRP3 was revealed in 74.7% pts in the group who retained the diagnosis of sJIA, but they were clinical insignificant. In 2 pts verified inflammatory bowel disease, 1 -Behcet's disease, 1 -PFAPA, 1neuroblastoma. The median age at the onset and gender were not statistically different between the groups (sJIA and non sJIA). Erythematous rash, typical for sJIA, and arthritis were significantly less common in pts in whom the diagnosis was changed (p=0.048 and p=0.0043, respectively) without difference between groups by other criteria sJIA at onset (p>0.05). Conclusion: According to our data, about a quarter of pts with an inflammatory phenotype similar to the manifestations of sJIA suffer from mAIDS. Typical erythematous rash and arthritis are more likely to indicate the onset of sJIA, but the diagnosis of sJIA should be established with great caution, these pts need a thorough and critical assessment of all symptoms, anamnesis data and mandatory molecular genetic testing for the most common mAIDs. Identification of polymorphisms NLRP3 in pts with sJIA requires a dynamic assessment for a more correct interpretation of its clinical significance.

supporting the effectiveness of biologic drugs in the treatment of SIA, the clinical response to these treatment options has not been largely investigated in Turkey. Objectives: TURSIS, the 24-month, multicenter, retrospective, noninterventional study aimed to assess the clinical response to biological treatments for SJIA in Turkey and provide real life data that might help improve the disease outcomes. Methods: This was a retrospective and multicenter study in patients with SJIA for whom a biological treatment had been initiated during the index period. The data collection from medical records of patients evaluated at the 8 Pediatric Rheumatology Clinics in Turkey from July 2019 till December 2020. Patients' characteristics, clinical inactivity, and safety related variables and ACR70 response were assessed. Results: The study population of 147 patients consisted of 76 females (51.7%). The mean age (SD) at diagnosis and baseline were 4.25 (2.91) and 8.00 (4.99) years, respectively. The percentage of patients without corticosteroids were 27.9% at baseline and gradually increased up to Month 24 (p<0.001 for all visits). The proportion of patients with no articular involvement gradually increased from baseline to Month 6. The median (minmax; IQR) VAS was 0 (0-90;20) at Month 3. The overall functional ability of patients was good. The median (min-max) global assessment score was 7.00 (0.00-10.00). The scores differed significantly across biologics (p=0.026). The only significant difference between the drug pairs was observed between anakinra and etanercept (mean [SD]: 6.70 [2.69] vs 5.04 [2.87]; p= 0.007). During the 2-year study period, 51.0% of patients (n=75) remained on the same biologic. Sixty-two patients (42.2%) had experienced 1 switch in biologic treatment, and 10 patients (6.8%) switched twice. In patients who required switching, canakinumab was the first alternative for patients treated with anakinra (44.9%) followed by tocilizumab (14.5%). A total of 22 adverse events were observed in 12 patients (8.2%) and included one death. Thirty-two patients (22.4%) had experienced a MAS attack between the diagnosis of SJIA and baseline. Nine patients experienced MAS after baseline. At Month 3, 73.5% of patients were clinically inactive. The proportion of clinically inactive patients was highest at Month 18 (84.69%), and 45.5% of patients were reported to have ACR70 response at Month 3. ACR30, 50 and 70 responses could be achieved in 95.5%, 50% and 45.5% of patients, respectively. Conclusion: This study described the patient characteristics and the impact of biologics on disease activity in a real-life study of patients with SJIA in Turkey. Overall biological therapies resulted in improvement in clinical activity early after initiation. There was a decrease in the frequency of MAS after a biological drug initiation compared to the period to the start of biological therapy. Biologics were well tolerated. Further studies with larger study size can reveal the differences between the biologics on disease outcomes and guide treatment decisions, thereby improving patient management. Introduction: Enthesitis related arthritis (ERA) and ankylosing spondylitis (AS) can present with similar clinical symptoms but have a distinct age of onset. Peripheral arthritis is more common in ERA, whereas axial arthritis is more common in AS. Although validated in ERA, it is not fully understood how patient reported outcome measures (PROMs) for AS such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) perform in patients with ERA. Objectives: To compare the differences in commonly used PROMs including BASDAI and BASFI in patients with a diagnosis of ERA and AS. Methods: Adult patients with a diagnosis of AS or ERA under the care of the rheumatology department at University College London Hospital were included in this study. Data was collected over a 3 month period. Patients were asked to complete questionnaires of different PROMs as part of their routine clinical care. These included BASDAI, BASFI and also Global and Spinal Visual Analogue Scale (VAS), Jenkins Sleep Score (JSS), AS quality of life score (ASQOL) and the Mood & Feelings Questionnaire (MFQ). Baseline patient demographics were extracted manually from our electronic healthcare database. Data analysis was completed using IBM SPSS v26 and tested for significance using a Mann Whitney U test. Results: A total of 44 patients with ERA (n=29) and AS (n=15) were included. 23% of patients were female (n=10, AS=5/15 (33.3%), ERA=5/ 29 (17.2%)). Those with a diagnosis of ERA were significantly younger (p<0.0001) with a median age of 21 (range 18-30) compared to 40 (range 23-65) in the AS group. A similar proportion of patients in each group were on biologic treatment (ERA 15/29 (51.7%), AS 7/15 (46.7%)), although a higher proportion of patients with ERA were treated with conventional DMARDs (ERA 23/29 (79.3%), AS 2/15 (13.3%)). There was no significant difference between total mean BASDAI in the AS group compared to the ERA group (4.4 vs 3.18, p= 0.13). Interestingly, a significant difference was found for question 2 of the BASDAI which focuses on neck, back and hip pain and patients with AS recorded higher median scores (5 vs 3, p=0.01). The mean BASFI was significantly higher in patients with AS compared to patients with ERA Conclusion: Our results show that patients with a diagnosis of AS reported significantly worse PROMs in a wide range of domains compared to patients with ERA. Total BASDAI was the only PROM where no significant difference was found, although the higher score for question 2 in patients with AS may reflect the prominence of axial disease compared to ERA. Questions in the BASFI are also weighted towards spinal disease and may underestimate enthesitis and peripheral arthritis, resulting in lower scores in patients with ERA. However, poor levels of sleep, quality of life and low mood in patients with AS compared to those with ERA are not explained by this and need further investigation. Possible explanations include differences in disease duration and age of onset, patient age, HLA-B27 status, disease activity, early treatment with biologic medication and pattern of joint involvement. Although this study is limited to a single centre and a small cohort of patients, it identifies important differences between ERA and AS and may indicate PROMs for AS are not as sensitive in patients with ERA.

Introduction: Gastrointestinal (GI) symptoms are frequent in patients (pts) with chronic disease such as juvenile idiopathic arthritis (JIA). Disease-related drugs, psychological issues due to the chronic condition should be considered as possible causes. However, gut inflammation has been described in some forms of JIA and inflammatory bowel disease (IBD) occur in 7-10 % of pts with sponidloarthropaty (SpA). Accurate assessment of GI symptoms in JIA pts with is necessary to identify those requiring a further invasive diagnostic work-up with endoscopy. Objectives: To describe the presence and type of GI involvement in a population of children and adolescents with different subtypes of JIA. The secondary aim was to assess the accuracy of non-invasive tests, such as fecal calprotectin (FC) and bowel ultrasonography (BWUS), in identifying pts requiring a further diagnostic work-up with endoscopy. Methods: Consecutive JIA pts complaining of GI symptoms for at least 12 weeks were prospectively enrolled during a twelve-month period. All underwent a complete clinical assessment, including evaluation by a pediatric gastroenterologist, blood inflammatory markers, FC (Calprest®, Eurospital), and BWUS with Colour-Doppler examination (Esaote equipment, 3.5 MHz convex and 12 MHz linear transducers). US assessed parameters were: Bowel Wall Thickness (BWT) > 3 mm, presence of BW vascularity, presence of enlarged mesenteric nodes and mesenteric fat hypertrophy (MFH). In pts with high clinical suspicion of IBD upper and lower endoscopy with multiple biopsies was performed. Pts who received NSAID in the 14 days before enrolment were excluded to avoid any possible effect on symptoms and FC levels. Sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV) of laboratory and US parameters were analysed according to the final diagnosis of gut inflammation. Results: 32 pts (16 female) aged 5-16 years (median 11) were enrolled: 11 with oligoarthritis, 6 polyarthritis, 2 systemic, 10 SpA, 3 undefined. Eight pts were receiving methotrexate, 7 sulfasalazine, 10 anti-TNFα therapy, 1 canakinumab, 1 tocilizumab. All pts presented abdominal pain, 12 complained of diarrhoea, 7 also with blood in the stools, 2 failure-to-thrive and 2 recurrent oral aphthosis. 14 pts (43%) showed a first-degree relative with Rheumatoid Arthritis (8) or IBD (6) . The mean time between the diagnosis of JIA and clinical evaluation (months) was 20.5 ± 19.4. BWUS revealed increased BWT of the terminal ileum in 17 pts, increased BW vascularity in 13, enlarged mesenteric nodes and MFH in 8. Sixteen pts underwent endoscopy: 14 showed gut inflammation, 5 had a final diagnosis of IBD, 9 showed chronic aspecific inflammation at histology requiring a further GI follow-up. One pt had celiac disease, 15 were finally diagnosed as irritable bowel syndrome based on Rome IV criteria. Pts with gut inflammation at histology had higher FC levels (200 ± 190 ug/g vs 48 ± 25, p<0.001) and higher BWT at US (4 ± 0.5 vs 3.2 ± 0.7, p< 0.05 ) and a more frequent family history (10 vs 4, p=0.4). SE, SP, PPV, NPV of BWT and FC > 50 ug/g vs the final diagnosis of gut inflammation were (%): 92.8, 85.7, 81.2, 94.3, and 86.7, 81.2, 76.5, 90, respectively Conclusion: Pts with JIA and GI symptoms should be managed together by the pediatric rheumatologist and the pediatric gastroenterologist. FC and BWUS may be useful non-invasive tests to identify pts requiring a additional diagnostic workup with endoscopy. Further studies with larger number of pts are needed to assess the usefulness of non-invasive test in detecting sub-clinical gut inflammation also in asymptomatic pts with JIA. Methods: Consecutive patients with JSpA (defined as ERA, or UA according to ILAR) followed in our center with complete records were included. Randomly selected patients with oligoarthritis, systemic arthritis and polyarthritis RF negative served as controls. Variables recorded were: arthritis, enthesitis, tarsitis, inflammatory back pain, sacroiliac joint tenderness, presence of HLA-B27 antigen, acute anterior uveitis, history of SpA in a first-degree relative. Imaging on sacroiliac joints. Summary statistics included overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive Likelihood ratio (+LR Arthritis was observed more frequently in the control group at diagnosis and follow-up (p<0.001 for both), while enthesitis, sacroiliac joint tenderness, and inflammatory back pain were more common in the ERA group both at diagnosis and follow-up (p<0.001 for all). The presence of human leukocyte antigen (HLA)-B27 and elevated Creactive protein levels were also more frequent in the ERA group. In sacroiliac imaging, 70.1% of ERA patients had positive findings suggestive of sacroiliitis at diagnosis and 78% at follow-up. There was a low response rate to non-steroidal anti-inflammatory drugs in the ERA group compared to the control group. The sensitivities of ILAR and ASAS criteria for axial SpA, and peripheral SpA at diagnosis were 73.1%, 21.3%, and 83.3%, respectively which increased to 83.3%, 35.1%, and 92.5%, respectively at follow-up. The specificity of all three classification criteria was >90% at diagnosis and follow-up (Table 1) . Conclusion: The ASAS criteria for peripheral SpA was the most sensitive while ASAS classification criteria for axial SpA was the most specific criteria in ERA patients. The sensitivities of all three classification criteria has increased during follow-up, which is probably due to the additive nature of the disease.

None declared to define how rare autoinflammatory diseases are discussed and align the community voice.

Objectives: The aim of the manifesto is to explore the unmet needs of people living with rare autoinflammatory diseases and identify a call to action for key aspects of the patient journey, in order to improve patient care. Methods: Extensive research was conducted to gain a deeper understanding of rare autoinflammatory diseases and the patient journey, including disease burdens and unmet needs. Primary research included two virtual advisory board meetings in May and July 2020 with members of the Rare Autoinflammatory Disease Council and a physician specialising in periodic fevers to discuss their experiences. A literature review was performed to supplement the primary research.

Results: The manifesto clarifies key scientific aspects of rare autoinflammatory diseases including disease definition, categorisation and genetic background. It reports significant physical, emotional, social and financial burdens on people living with these conditions. Notably, the rarity and low awareness of disease results in substantial delays to appropriate patient care, and a lack of understanding and support from their social environment. We found that paediatric patients are especially impacted as symptoms disrupt physical, educational and social development. The transition to adult care is considered one of the most challenging times. The lifelong nature of these conditions places a substantial economic burden on healthcare systems. Early diagnosis, increasing therapy options, optimising disease management and facilitating patient engagement and empowerment were identified as key strategies to overcome the barriers to effective care. Based on these goals, the manifesto outlines actions targeted towards HCPs, policymakers, PAGs and other stakeholders to help improve care and health outcomes. Conclusion: The Rare Autoinflammatory Disease Manifesto is an important educational resource that was published on the Periodic Fevers website (www.periodicfevers.com/about-periodicfevers/manifesto) in March 2021 and has since been translated in six languages. A multi-channel campaign is underway to promote the manifesto internationally. Our efforts are focused on continued collaboration with PAGs to disseminate and evolve the manifesto as we uncover further insights from the rare autoinflammatory community. Introduction: Familial Mediterranean Fever (FMF) is the most common inherited autoinflammatory disease, which is characterized by recurrent fever attacks, inflammation of serosal membranes and arthritis mostly occurring in childhood. Although the clinical findings during attacks may vary, the most common attack type is a combination of fever, abdominal pain, and joint findings. Children and adolescents with FMF may also have symptoms not related to attacks, such as prolonged myalgia, exertional leg pain, post-exercise erythema, and sacroiliitis. Objectives: The aim of the study was to assess physical fitness and physical activity in children and adolescents with FMF. Methods: Eleven patients with FMF were included in the study. Health-related components of physical fitness were evaluated using the FitnessGram® Test Battery. These tests included curl-ups, pushups, a 20-m shuttle run test (20mSRT), trunk lift test, the modified back-saver-sit-and-reach test (mBSRT) and body composition measurements. The curl-up and push-up tests were used to evaluate muscular strength and endurance. The 20mSRT was used to evaluate cardiorespiratory fitness. The trunk lift test was used to evaluate trunk extensor strength. mBSRT was used to evaluate flexibility. The percent of body fat with Bioelectrical Impedance Analysis and Body Mass Index (BMI) were used to evaluate body composition. All tests were conducted according to the FitnessGram® measurement procedures. Participants were then classified according to the age and sexspecific cut-off points of FitnessGram as Needs Improvement (NI)health risk, NI and healthy fitness zone (HFZ). The Physical Activity Questionnaire (PAQ) was used to evaluate the physical activity levels of patients. Results: Four of the participants were male and 7 of them were female. The mean age was 13.54±3.69 and the mean disease duration was 6±3.90 years. When the FitnessGram standards were applied, %63.6 of them were categorized in the NI and %36.4 of them in the HFZ for curl-up test, %72.7 of them in the NI and %27.3 in the HFZ for the push-up test, %90.9 of them in the NI-health risk, %9.1 of them in the NI for the 20mSRT, %72.7 of them in the NI and %27.3 of them in the HFZ for the trunk lift test, %81.8 of them in the NI and %18.2 of them in the HFZ for the mBSRT. Besides, according to FitnessGram body composition classification criteria, %27.3 of them were categorized in the NI, %27.3 of them in the very lean and %45.5 of them in the HFZ for percent body fat, %9.1 of them in the NI-health risk, %18.2 of them in the NI, %9.1 of them in the very lean and %63.6 of them in the HFZ for BMI. The physical activity level of the patients was categorized "low-active" in %81.8 of them and "sufficiently active" in %18.2 of them, according to the PAQ. Conclusion: The results of this pilot study reveal that the physical fitness and physical activity levels in children and adolescents with FMF were considerably poor at a risk level for health. However, further research on physical fitness and physical activity in childhood FMF with larger sample sizes is required. We consider that physical activity and exercise programs should focus on improving physical fitness and increasing physical activity levels to minimize health risks in childhood FMF. Table 1 . Co-existing diseases were as follows: familial Mediterranean fever (n:4), psoriasis and severe acne (n: 2), Crohn's disease (n:1), and juvenile idiopathic arthritis (n: 1). A family history of autoinflammatory diseases was present in 4 patients (16.7%). All patients had multifocal bone lesions at diagnosis. The most affected bones were the pelvis (58.3%), femur (50%), and vertebra (50%). Long bone lesions were metaphyseal in 92.9% of the cases. Increased CRP levels were present in 70.8% and antinuclear antibody positivity in 16.7% of the patients. Patients with sacroiliitis were screened for the presence of HLA-B27 and one patient was found positive. More than 50% of the patients with a follow-up of more than 6 months had a persistent course who experienced remission after anti-TNF agents. All patients with two mutations in the MEFV gene (n: 4) benefitted from concurrent use of colchicine and anti-TNFs. Conclusion: Chronic nonbacterial osteomyelitis presents with a variety of clinical findings and has a variable disease course. NSAIDs are effective in treatment; however, persistent or recurrent disease activity may need biologics and other therapies.

Disclosure of Interest None declared Introduction: Periodic fever, aphthosis, pharyngitis, and adenitis (PFAP A) syndrome is an autoinflammatory recurrent fever syndrome which mainly affects children. Cimetidine, colchicine, and anti-IL-1 agents could be used to prevent attacks. Probiotics were previously reported to be beneficial in a few PFAPA patients for prevention of attacks. Objectives: We aimed to evaluate the response to probiotics in PFAPA patients. Methods: Patients with PFAPA syndrome who received probiotics were included in this retrospective study. Demographic and clinical features, and response to probiotics were assessed.

Results: Twenty patients with PFAPA syndrome (F/M:1) were included. All had pharyngitis during attacks while oral aphthosis (65%), lymphadenitis (50%), and fatigue (80%) were also common attack-associated features. 9 (45%) patients also had abdominal pain during attacks. Periodicity was present in 15 (75%) patients. Throat culture was performed during an attack in 16 (80%) patients and revealed normal flora in all. MEFV variant analysis (n=17) revealed heterozygosity for M680I in 3, M694V in 2, and E148Q in 3 patients. The median (min-max) ages at symptoms onset and diagnosis were 24 (3-72) and 51.5 (11-120) months, respectively. All patients received probiotics during the disease course. The probiotic they used included a combination of two lactobacilli as Lactobacillus plantarum HEAL9 (Lp HEAL9) and Lactobacillus paracasei 8700:2 (Lpa 8700:2). The median age at probiotic onset was 60 (33-192) months while duration of probiotic use was 4.5 (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) months. All patients except one experienced decrease in attack frequency with probiotic use. The attack frequency decreased significantly with probiotics (median number of attacks per 3 months: 3 vs. 1, respectively; p<0.001). 8 (40%) patients had no attacks during the 3-months period after probiotic initiation. And, 5 (42%) of 12 patients who had ≥1 attacks on probiotics mentioned that the attack severity (duration and the degree of fever) decreased significantly during probiotic use. Colchicine was also administered to 4 (20%) patients for a duration of 30 (6-55) months before the onset of probiotics. Two of them did not respond to colchicine and colchicine was discontinued. Other two patients experienced decrease in attack frequency with colchicine treatment; however, they were still having >1 attack/month. Probiotic was beneficial in all four of these patients. Conclusion: Intake of the probiotic strains Lp HEAL9 and Lpa 8700:2 were previously shown to decrease the incidence and severity of common cold in randomized controlled trials. A significant reduction in pharyngeal symptoms was also noted in these studies. We may speculate that these lactobacilli might be beneficial in PFAPA syndrome by down-regulating the inflammatory response in tonsils through changes in the microbiota. Introduction: There are currently two IL-1 inhibitors approved for clinical use in Europe. However, long term follow-up data of five or more years regarding security and efficacy of anti IL-1 treatment in autoinflammatory diseases (AID) in children are scarce. Objectives: A retrospective study of patients with AID diagnosed in a tertiary referral pediatric rheumatology department receiving anti IL-1 therapy for 5 years or longer was conducted. Demographic data, symptoms, treatments and adverse events (AE) were collected from clinical chart, not only from hospital but also from primary attention in order to improve information quality. Methods: A retrospective study of patients with AID diagnosed in a tertiary referral pediatric rheumatology department receiving anti IL-1 therapy for 5 years or longer was conducted. Demographic data, symptoms, treatments and adverse events (AE) were collected. We identified a total of 9 patients, 8 who received anakinra and one canakinumab. 5 diagnosed with systemic juvenile idiopathic arthritis, 2 recurrent pericarditis, one familial Mediterranean fever with renal and skin vasculitis and one with cryopyrin-associated periodic syndromes. 7/9 were males. Patients are currently 11 to 23 years old; mean disease duration being 6.2 years (range 4-12 y) and a mean therapy duration of 9.7 years (range 5-15 y). No laboratory abnormalities were detected. No malignancy or macrophage activation syndrome was observed, no fatalities occurred. Although infections were uncommon, 4 infectious episodes required admission, importantly no opportunistic infections were diagnosed. Other side effects were a vertebral fracture, cataract and an intracranial hypertension, probably related to steroid therapy. 4 patients are currently receiving antiIL-1 therapy as mono therapy only, all 4 being in full clinical remission not needing of steroid therapy. To date only 3 patients stopped treatment due to inactive disease without occurrence of flares. Conclusion: In our experience long-term use anti IL-1 therapy appears to be safe and effective in pediatric AID. Early treatment initiation can avoid prolonged corticoids treatment thereby reducing secondary adverse events. Introduction: Recurrent Fevers syndromes are autoinflammatory diseases characterized by febrile episodes associated with systemic symptoms and elevation of acute phase reactants; many of these diseases can present long-term complications, which can be avoided by an appropriate therapeutic approach. In light of this, monitoring of disease activity over time is mandatory. Currently, the available tools to assess disease activity in recurrent fever syndrome take into account the clinical manifestations of the diseases and not the laboratory parameters, that nowadays are clearly important in the definition of disease activity. Objectives: The purpose of the study is the creation of a composite score for the disease activity of autoinflammatory syndrome characterized by recurrent fever: FMF, TRAPS, MKD, PFAPA and systemic undefined recurrent fever (SURF). Methods: the project is divided into two main phases: the first dedicated to the selection of variables of the score, the second intended for the validation of the latter. In the first phase, a literature review was carried out to search for the parameters defining the disease activity. At the same time, through the Delphi method, a questionnaire was proposed to the main experts of Recurrent Fever, in which they were asked to list the variables used in the daily clinical practice to assess the disease activity of their patients. Finally, the same question was asked to the families of patients suffering from these conditions. In the second round of the Delphi Survey expert of the diseases and family representatives were ask to select and rank the 10 variables the think to be most effective for the purpose. Results: by the review of the literature, 3005 articles were taken into consideration, of those 90 presented parameters defining the disease activity. 54 patients/families responded to the questionnaire. 114 experts were contacted, of those 95 reply to the first Delphi survey. From the three parallel searches, a list of different variables (clinical, laboratory, instrumental and other) was obtained; repetitions and redundancies were deleted and a final list of 147 parameters was obtained. The second round of the Delphi survey is actually ongoing. Conclusion: the work lays the foundations for the creation of a composite score for the assessment of disease activity in patients with recurrent fever. We hope that this tool will be of help not only in the daily clinical practice, but also in future trials and experimental studies. Introduction: Because of their rarity, limited awareness among nonspecialists, and significant overlaps in their clinical presentation, autoimmune/inflammatory conditions represent a diagnostic and therapeutic challenge in paediatrics. Juvenile idiopathic arthritis (JIA), with its 7 sub-forms, is the most common paediatric "rheumatic" disease. Juvenile-onset systemic lupus erythematosus (jSLE) is a severe autoimmune/inflammatory disease that can affect any organ system and shares clinical features with JIA.

Objectives: To overcome challenges around diagnostic approaches in the context of clinical overlap, we aimed to define disease subtypes through specific cytokine and chemokine profiles. Methods: Serum samples from patients with JIA (n=77) and jSLE (n= 48), as well as healthy controls (n=30), were collected. Samples were analysed using the Meso Scale Discovery (MSD) U-PLEX Biomarker Group 1 (hu) panel. The antibody-set contains biotinylated capture antibodies and corresponding detection antibodies for 71 cytokines and chemokines involved in multiple biological processes. Results: Differential serum protein levels were investigated across disease groups and healthy controls. Significant differences were seen in several proteins, many of which have previously been implicated in the pathogenesis of JIA and/or jSLE. Partial least squares discriminant analysis (PLSDA) models of two components were trained to discriminate between samples from healthy controls, JIA or jSLE patients. This bioinformatic model allowed discrimination between the three groups with~90% accuracy. Variable importance in projection (VIP) scores of the model detailing the contribution of each feature (i.e. protein) towards each of the components in the PLSDA model were used to predict potential biomarkers. The top VIP proteins included IL-23, MIP-1β, MCP-1 and M-CSF as most promising candidates.

To estimate the minimum number of proteins necessary to quantify in order to accurately discriminate between groups, PLSDA models with various different feature counts and selection features were produced. Reduction of proteins to approximately 27 could be done without significant impact on the accuracy of the model. Furthermore, serum IL-18, MIF, MIP-5 and YKL-40 vary between systemic JIA and other JIA subtypes, while serum IL-33 levels were elevated in jSLE patients with "very high" (SLEDAI ≥ 10) when compared to patients with "high" (SLEDAI 5-9) or "moderate" (SLEDAI ≤ 4) disease activity. Conclusion: Distinct cytokine/chemokine signatures, including a minimum of 27 serum proteins, associate with paediatric autoimmune/inflammatory diseases, and discern between JIA and jSLE. Some of these proteins may correlate with disease activity in jSLE (IL-33) or associate with sub-forms of JIA (IL-18, MIF, MIP-5, YKL-40). Individual proteins or their combination may therefore be used for future diagnostic approaches, assessment of disease activity or to inform treatment decisions. Introduction: Many patients have a recurrent aphtosis 2 to 4 times a year (single aphtosis); others may have recurrent lesions after the recovery of the previous (complex aphtosis). We also distinguish minor and major aphtosis: the latter are often in patients affected by diseases such as systemic lupus erythematosus (SLE), and Behçet disease. Recurrent aphtosis is in several diseases such as celiac disease, chronic inflammatory intestinal diseases, autoimmune disorders (Behçet disease), SLE, in recurrent fever as PFAPA and in monogenic autoinflammatory syndromes. A20 haploinsufficiency, due to the mutation of the TNFAIP3 gene, shows a clinical picture similar to Behçet disease's. The PFAPA and Behçet disease are both associated with the mutation of IL12A gene. Therefore, recurrent aphtosis, PFAPA and Behçet disease are three clinical aspects of a single defect. Objectives: The main objectives of our retrospective study are:

to correlate the recurrent aphtosis with the most common rheumathological conditions and with defects in both innate and adaptive immunity in a paediatric population related to our Paediatric O.U. to detect genetic mutations related to defects of innate immunity associated with recurrent aphtosis.

We enlist 44 patients with recurrent aphtosis associated with fever or not, followed in our Pediatric Reumatology ward of Children Hospital "G. Di Cristina", ARNAS Palermo, in the past two years. The presence or absence of fever, complement alterations, serum amyloid increase, association with HLA, autoimmunity, ocular involvement, dermatological lesions and genetics for monogenic autoinflammatory diseases have been evaluated. Results: Out of 44 patients enlisted, we have seen recurrent aphtosis in 28 females and 16 males, with an average age of 12 years, M:F ratio 1:1.75. The prevalent symptom associated with aphtosis was fever (in 39/44 patients). Skin lesions were in 15/44 patients: 1 erythema nodosum, 2 vasculitis, 3 evanescent rash, 5 urticaria/maculopapular exantema and 1 chronic urticaria. Ocular disorders (in 6/44 patients): 2 anterior uveitis (with or without synechiae) and 4 conjunctivitis. Laboratory abnormalities: serum amyloid increased in 16/44 patients (very high in 5 patients and moderately high in 11). These patients had positive genetic diagnosis for FMF, cryopyrinopathy, TRAPS and A20 haploinsufficiency. The diagnosis were: 18 FMF, 5 TRAPS, 6 CAPS, 5 SLE, 1 Behçet disease, 4 PFAPA, 1 A20 haploinsufficiency, 1 RAP, aphtosis and cyclic vomiting, 1 Behçet with isolated uveitis, 1 autoimmune thyroiditis and 1 acrocyanosis. C3 changes were observed in three patients with SLE. We found HLA B51 in 1 patient, HLAB57 in 1 patient and HLAB27 in 1 patient. There were no serum amyloid increase far away from fever attacks or genetic for periodic fever syndromes in patients with PFAPA. The genetic alterations in our patients with aphtosis were:

--among patients with FMF, 5 heterozigosis mutation P369S and R408Q, and in 1 also the A744S and 1 R202Q mutations; 2 patients had heterozigosis E148Q. Another patient had heterozigosis mutations for R202Q, E148Q. --all patients with TRAPS had the R92Q mutation.

--among patients with CAPS, 2 had a NLRP3 (VAL200MET) mutation and 1 a NLRP12mutation . --One patient had heterozigosis mutations for the TNFAIP3 gene with A20 haploinsufficiency. --among patients with PFAPA 1 had TLR9 mutation.

Conclusion: Behçet disease in Paediatric population appears incomplete. From literature evidence bringing PFAPA to Behçet disease, it could be assumed that PFAPA could be an incomplete start of Behçet; so the genetic analysis should be extended to the IL12A gene sequencing. It is clear from our study that the recurring aphtosis is mostly associated with monogenic diseases. Introduction: Baricitinib has been used to treat pediatric patients with rare type I interferonopathies (1) . Safety profile including BK viral (BKV) reactivation in urine and pharmacokinetic model have been reported (1, 2) . Objectives: Given the association of BK nephropathy and BK viremia (3), we determined the prevalence of BKV reactivation [BKV load in urine/blood] in baricitinib-treated patients with rare type I interferonopathies and assessed the impact of BK viremia on renal function longitudinally. Methods: Between October 2011 and August 2018, 25 patients [10 CANDLE (Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 7 SAVI (Stimulator of IFN genesassociated [STING-associated] vasculopathy with onset in infancy), 8 other interferonopathies] were enrolled in an institutional review board approved protocol and their parents gave informed consent. Safety was longitudinally assessed during study period (cut off October 2020). After detection in an index patient in June 2015, BKV load and renal function were monitored longitudinally with baseline assessments in 7 additionally enrolled patients. Summary statistics and linear mixed model were used to characterize the association of BKV load and renal function. Results: The mean age at enrollment was 10.9 years [range 1.2-24.2]. On baricitinib, BKV loads (log 10 copy/mL) in blood and urine were monitored for a mean of 3.6±2.1 years [83.9 patient years] and 3.2±1.8 years [74.9 patient years] respectively. Of 23 patients monitored, 20 had BK viruria (3/20 pre-baricitinib) and 14 BK viremia (2/14 pre-baricitinib). All except one patient with BKV load in urine >7 log 10 copy/ml had BK viremia. Three patients with no BK viruria before treatment became positive at a mean age of 4.3 ± 1.5 years after 10.1 ± 13.2 months of baricitinib treatment. The time from achieving therapeutic doses of baricitinib to detection of BK viremia [n=12, 18.8±13.9 months] was twice as long as the time to detection of BK viruria. Of 14 patients with BK viremia, 4 had transient elevation >4 log 10 copy/ ml. Index patient developed significant BK viremia (6 log 10 copy/ ml) with azotemia and baricitinib was discontinued. One was on combination of baricitinib and a biologic agent at the time of transient elevation. Two were on baricitinib and BKV load in blood was associated with baricitinib dose and inversely associated with renal function. The baricitinib dose was adjusted to keep BK viremia <4 log 10 copy/ml and all except index patient had stable renal function over 83.9 patient years. No difference in BKV load between gender and disease groups was observed. Dermatomal herpes zoster reactivation was seen in 2 patients and resolved on antiviral treatment without holding baricitinib. Conclusion: Overall, baricitinib was well tolerated. Prevalence of BK viruria in patients on therapeutic doses of baricitinib was 87% (20/ 23), and 60% (14/23) for BK viremia. Our data suggest that BKV load should be monitored in blood and urine. The presence of prebaricitinib BK viremia/viruria suggests evaluation of BKV load in patients on other chronic immunosuppressive regimens. Dose adjustments to keep BK viremia <4 log 10 copy/ml preserved normal renal function over 83.9 patient years.

Much more than the fcas phenotype; NLRP12 related periodic syndrome, data from the uper-aid registry Introduction: NLRP12 associated periodic syndrome (NAPS12) is a rarely seen autoinflammatory disease also known as familial cold autoinflammatory syndrome 2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. Common clinical features of recurrent NAPS12 attacks have been described as fever, fatigue and musculoskeletal symptoms that are typically activated by cold exposure. Skin manifestations can be seen during attacks in about half of the patients. Objectives: We aimed to present our single-center NAPS12 patient experience and results. Methods: The data of 320 patients from next generation sequencing genetic database of autoinflammatory diseases, Umraniye Training and Resarch Hospital, Department of Pediatric Rheumatology (UPER-AID registry), were included in the study. Patients with VUS-likely pathogenic or pathogenic mutations in the NLRP12 gene were collected from these patients. In at least three months of follow-up, patients with autoinflammatory disease compatible recurrent episodes (with high acute phase response) were defined as NAPS12, in which other etiological reasons (infectious, autoimmune, malignant diseases) were excluded. Demographic, clinical and laboratory data, treatments and responses of patients with a diagnosis of NAPS12 were presented. Results: Eight patients were diagnosed with NAPS12. The F/M ratio was found as 5/3. The mean age of onset of the symptoms was 56.6 months (min-max: 7-120), and the mean age at diagnosis was 109 months (min-max: 10-122). The mean follow-up time was found 17.5 months (min-max: 3-42). The duration of the attack varied between 1-14 days. The attack findings frequency was found as follow respectively; fever (n: 7), urticarial rash (n: 6), myalgia (n: 4), arthralgia (n: 3), abdominal pain (n: 2), conjunctivitis (n: 2), diarrhea (n: 1) ranked as headache (n: 1) and pericarditis (n: 1). CRP and serum amyloid A levels were found to be elevated in all patients during the attack period. In the NGS gene panel, three patients had pathogenic, one had likely pathogenic, three had VUS, and one had novel variants. Partial response was obtained with colchicine in 3 patients and complete response in 2 patients. The other three patients that unresponsive to colchicine, were achieved to inactive disease with anti-IL 1 treatments. Conclusion: While the clinical findings were compatible with FCAS in four patients, attacks accompained with varied clinical findings and lasting longer than 3 days were observed in the other four. It was observed that the attack duration of patients who were not compatible with the FCAS, could extend up to 14 days. NAPS12 should be considered in the differential diagnosis in patients with a clinical manifestations of autoinflammatory diseases who do not show typical findings for any monogenic SAID. Trial registration identifying number: ( Introduction: Behçet's Disease (BD) is a systemic vasculitis affecting many organ systems with the involvement of all sized arteries and veins. Although recurrent oral aphthous and cutaneous lesions are the predominant features during the course of the disease, five different forms of disease have been defined previously: 1) mucocutaneous-only cluster, 2) papulopustular lesion-arthritisenthesopathy cluster, 3) ocular cluster, 4) gastrointestinal cluster, 5) vascular cluster. Objectives: To determine the main characteristics of pediatric BD patients and also analyze the clustering phenotype of pediatric BD in a large multicentric cohort. Methods: Eight pediatric rheumatology centers from Turkey have participated in this study. Demographic data, clinical manifestations, laboratory features, radiological findings, treatment schedules, and disease outcomes were achieved from patient charts retrospectively. A cluster analysis was performed according to five independent clinical forms. Results: A total of 241 patients with BD were enrolled in the study. Among them, 120 (49.7%) were male and 121 (50.3%) were female. Eighty-three (34.4%) patients had a family history of BD. The median age of diagnosis was 144 (36-216) months. The median time between onset of symptoms and diagnosis was 1 (0-196) months. Oral aphthous (83.8%) was both the most common initial symptom and the most frequent symptom (97.9%) during the disease course followed by genital ulcers (66.8%) and pseudofollicutis (33.2%). Uveitis was observed in 34 (14.1%) patients. Thirty-three (13.7%) patients had neurological involvement. Pathergy test was positive in 64 (26.6%) patients and HLA-B51 was positive in 108 (44.8%) patients. According to cluster analysis; 133 (55.1%) patients belonged to the mucocutaneous-only cluster while 37 (15.4%) patients fitted to papulopustular lesion-arthritisenthesopathy cluster, 33 (13.7%) were in ocular cluster, 19 (7.9%) were in gastrointestinal cluster and 19 (7.9%) belonged to the vascular cluster. Ocular and vascular clusters were more common in boys (p<0.001) while girls usually presented with mucocutaneous-only cluster. The age of diagnosis were similar among the clusters. The activity scores of disease at the diagnosis and at the last control were higher in ocular and gastrointestinal clusters (p=0.001). Conclusion: To our best of knowledge, this is the first cluster analysis in pediatric BD patients. Our analysis showed that mucocutaneous-only cluster was the common form while phenotype of the disease differed according to gender. Furthermore, ocular and gastrointestinal involvements affected disease activity not only at the diagnosis but also during the course of the disease. Trial registration identifying number: . Introduction: Behçet's disease is a multisystem vasculitis that can affect all sizes of arteries and veins. Diagnosis can be made mostly in adult ages. Evaluation of childhood findings is important for early diagnosis. Serious complications can be seen years after diagnosis in the disease, which has periods of exacerbation and recovery. Although the mortality of Behçet's disease is low, intestinal perforation and central nervous system involvement are risky in terms of morbidity and mortality. Long-term effects are related to organ involvement. Young age, male gender, early onset disease are poor prognostic factors (1, 2) . Objectives: We aimed to evaluate the demographic, clinical and laboratory data of patients who were followed up with a diagnosis of Behçet's disease in our clinic. Methods: In our study, data were collected by retrospectively examining the files of patients who were followed up with the diagnosis of Behçet's disease between 01.01.2010 and 01.01.2021 in Erciyes University Children's Hospital Pediatric Rheumatology Department. While making the diagnosis, the diagnostic criteria of the International Behçet's Disease Working Group and the Consensus Classification of pediatric Behçet's Disease-2016 were used. Patients with 2 other criteria (genital ulcers, skin lesions, uveitis, pathergy) in addition to recurrent oral ulcers according to the diagnostic criteria of the International Behçet's Disease Study Group were included in the study (3) . According to the Consensus Classification of Pediatric Behçet's Disease-2016 diagnostic criteria, three of six items are required (recurrent oral aphthae, genital ulcer, skin involvement, eye involvement, neurological involvement, vascular involvement) (4) Results: We had a total of 42 cases in the study group. 22 (52.4%) of the patients were female and 20 (47.6%) were male. The average age at the time of first application was 12.56 ± 3.34. There was first degree consanguinity among the parents of 9.5% (n = 4) of the patients. 35.7% of the patients (n = 15) had a family history of BD. Recurrent oral aphthae were present in 85.7% (n = 36) of the patients. Genital aphthae in 28.6% (n = 12) of patients, uveitis in 26.1% (n = 11), skin lesions in 21.4% (n = 9), 14.2% (n = 6) vascular involvement, 4.8% (n = 2) central nervous system vascular involvement, 7.14% (n = 3) had GIS findings, and one patient (2.4%) had epididymoorchitis. 45.4% (n = 5) of uveitis cases had anterior uveitis, 36.3% (n = 4) posterior uveitis, 9% (n = 4) middle uveitis and 9% (n = 1) ) panuveitti. Of the cases with skin lesions, 11.1% (n = 1) erythema nodosum, 22.2% (n = 2) pseudofolliculitis, 33.3% (n = 3) acneiform lesions and 33.3% ( n = 3) livedo reticularis was present. Pathergy test was positive in 11.9% of the patients (n = 5). One patient had GIS bleeding (rectal bleeding), one patient had chronic active inflammation in the colon, and one patient had an ulcer in the terminal ileum. HLA B51 was found to be positive in 57.14% (n = 24) of the patients. Systemic steroid in 28.6% (n = 12) of patients, colchicine in 95.2% (n = 40), azathioprine in 19% (n = 8), and methotrexate in 33.3% (n = 14), 11.9% (n = 5) sulfasalacin, 4.8% (n = 2) infliximab, 4.8% (n = 2) adalimumab were given. 26.1% (n = 11) of the patients had additional disease. Two patients had familial Mediterranean fever, 1 patient had phenylketonuria, 2 patients had atrial septal defect, 1 patient had epilepsy, 1 patient had essential tremor, 1 patient had ulcerative colitis, 1 patient had Sydenham's Chorea. Introduction: Mevalonate kinase deficiency (MKD) is an extremely rare autoinflammatory disorder with an autosomal recessive inheritance mechanism. According to the EUROFEVER register, the age of onset of MKD is on average 6 months, and the delay in establishing the diagnosis is 6.8 years. Patients are often treated as cases with infectious diseases, primary immunodeficiency conditions, or other autoinflammatory disorders In the clinical picture, the most important is the periodicity of fevers and associated rashes, cervical lymphadenopathy, hepatosplenomegaly and increased markers of inflammation (CRP, ESR). Early manifestation is usually associated with a severe course and poor prognosis Objectives: Show the efficiency of therapy with the IL-1 blocker canakinumab at the example of two cases of early onset of mevalonate kinase deficiency syndrome. Methods: Observation and description of clinical picture. Therapy with the IL-1 blocker canakinumab. Results: In the center, we observed 2 patients with genetically confirmed mevalonate kinase deficiency syndrome. Both babies (girl and boy) were born prematurely: 36 and 35 weeks. The girl matched the gestational age in terms of weight and height parameters, and the boy had signs of intrauterine growth retardation (P 10). The condition of the children at birth was assessed as severe. The leading symptoms were: thrombocytopenia (31*10)^9 and (98*10)^9, anemia (hemoglobin 68 g / l and 83 g / l), significant hepatosplenomegaly, stable over the entire observation period. Both babies were treated as patients with intrauterine infection and received repeated courses of combined antibiotic therapy, IVIG, transfusion of thrombus suspension and erythrocyte mass. Both babies had no fevers until age of 4 months. Equivalent to fevers there were periodic increases in CRP and ESR. A typical clinical picture appeared only by the age of 4 months. Genetic analysis revealed in the girl the pathogenic variant c.118C> T (p.R40W) and Introduction: Although familial Mediterranean fever (FMF) progresses with attacks, its subclinical inflammation may continue in attack-free periods. To date, increased inflammatory cytokines have been reported in many psychiatric diseases.

Objectives: In this study, we aimed to evaluate the psychological symptoms, especially inattention/hyperactivity, in children and adolescents with FMF. Methods: The study included 272 children and adolescents with FMF and 250 healthy peers as a control group. The Strengths and Difficulties Questionnaire-Parent Form was used to assess emotion, behavior and peer related problems, as well as inattention/hyperactivity and prosocial behavior in participants.

Results: The mean age of the patients was 12.35, ± 2.65 years, and the mean age of the control group was 12.08, ± 2.67. In total, 51% (n = 139) of patients with FMF and 56% (n = 140) of the control group were females. The age and gender of the children were similar across groups (p=0.265 for age; p=0.262 for gender). The emotional and behavioral problem subscale scores of patients with FMF were significantly higher than those of healthy controls. The inattention/ hyperactivity scores of patients with FMF were also significantly higher than those of the control group (3.99 ± 2.34 vs 2.93± 2.26, p <0.001). The psychological scale comparisons of the patient and control groups are given in Table 1 in detail. When patients with FMF were compared according to the presence of attacks in the last year, presence of exertional leg pain as well as their mutation types, no differences were found in terms of inattention/hyperactivity scores. However, patients whose FMF symptoms were onset before the age of 6 had significantly higher inattention/hyperactivity subscale scores (4.21 ± 2.42) when compared to patients whose symptoms started after 6 years of age (3.42 ± 2.02; p =0.016).

Conclusion: This research demonstrated that FMF patients had increased inattention/hyperactivity, similar across all ages and genders, which was unaffected by FMF-related variables, except for age of onset. The FMF-inattention/hyperactivity relationship may be due to a common etiology in which proinflammatory cytokines play a role.

Disclosure of Interest None declared Introduction: Undifferentiated systemic autoinflammatory diseases (uSAID) are diverse syndromes characterized by acute flares of fever and inflammation, which do not meet clinical criteria for known disorders like Familial Mediterranean Fever (FMF). As part of the uSAID workup, many patients undergo genetic testing, sometimes revealing variants of uncertain significance in genes associated with autoinflammation. E148Q is a common polymorphism in exon 2 of the MEFV gene, which is not thought to be a disease-causing variant for FMF. The contribution of E148Q mutations in patients with uSAID is poorly understood, and it is unknown how it may respond to empiric treatment with colchicine, which is first line for FMF.

Objectives: To compare the clinical characteristics and colchicine response of children with uSAID identified to have E148Q vs non-E148Q mutations in the MEFV gene. Methods: Children with uSAID ≤18 years old at initial evaluation seen at a single-center during 2000-2019 were included if they received ≥3 months of colchicine therapy and carried at least one MEFV mutation but did not meet clinical criteria for FMF (n = 25). Data on demographics, clinical features, laboratory/genetic studies, and treatment responses were collected. Results: Results: In our cohort of 25 children with uSAID and MEFV mutations, 8 (32%) were heterozygous for E148Q mutations. Half of these patients also carried another non-exon 10 MEFV mutation (2x 369S, 1x L110P, 1x I591T). Distribution of the remaining variants on MEFV gene is shown in Figure 1 . Introduction: Interleukin 1 (IL-1) induced proinflammatory signals were discovered as a causative aetiology in a spectrum of diseases. Efficacy and safety of the recombinant IL-1 receptor antagonist anakinra across autoinflammatory and autoimmune diseases has been demonstrated in many studies. Despite the recommended dosage in patients above 8 months and weighing more than 10 kg, use of higher doses or earlier onset of therapy have been occasionally reported.

Objectives: To an institutional review of data on efficacy, safety and tolerance of anakinra in patients with autoinflammatory diseases (AID).

Methods: A single-centre retrospective review of electronic records of patients treated with anakinra between August 2007 and May 2021.

Results: A total of 47 patients (30 children, 17 adults) were identified. The median follow-up was 35 months (range 1-165 months). Patients have been treated for diagnosis of systemic juvenile idiopathic arthritis (sJIA) (n = 18; 38%), cryopyrinopathy (CAPS) (n = 10; 21%), mevalonate-kinase deficiency (MKD) (n = 7; 15%), undifferentiated AID (uAID) (n = 6; 13%), PIMS-TS (n = 3; 6%), NLRC4-GOF (n = 1, 2%), PAPA syndrome (n = 1; 2%) and polyarticular JIA (n = 1, 2%). The most frequent indication for starting anakinra was macrophage activation syndrome (MAS) (n = 20; 42,5%) which occurred in patients with sJIA (n=14, 70%), uAID (n=3, 15%), PIMS (n=1, 5%), NLRC4-GOF (n=1, 5%) or polyarticular JIA (n=1, 5%). Fourteen patients with sJIA (78%) received anakinra due to macrophage activation syndrome. MAS was the first manifestation of sJIA in 6 patients (33%). Recommended dosing of anakinra (1-4 mg/kg/day) was exceeded in 44,6% of patients (n=21) with the following dose range: 4-6 mg/kg (n = 8; 38%), 6-9,9mg/kg (n = 4; 19%), ≥10 mg/kg (n = 9; 43%). Paediatric cohort received anakinra in very wide dosing range of 1,4 -26,1 mg/kg (average 5,59 mg/kg, median 4,15 mg/kg). The highest dose (10-26mg/kg) was required by patients with uAID (n=1, 8 days of age), sJIA/MAS (n=2, 3 and 5 years of age), CINCA (n=1, 4 years of age) and NLRC4-GOF (n=1, 4 weeks of age). The median dose of anakinra in adult patients was 1,6 mg/kg (range 0,9-7,7mg/kg). In severely sick patients the daily dose was divided into 2-4 intravenous applications, one patient received continuous anakinra i.v. infusion. Rapid therapeutic effect (within 24-48 hours from starting anakinra) was observed in all patients. The most frequent recorded adverse effects were already well-known injection-site reaction in 25,5% (n = 12) of patients which disappeared within one month in all of them. Persistent eosinophilia (highest values 3,6 and 2,3x10*9 cells) was documented in 2 sJIA patients. Mild asymptomatic neutropenia (ANC min 0,8 x10*9/L) and transient liver transaminase elevation (up to 3-times ULN) both occurred in 4,2% (n = 2) of patients each.

Conclusion: Use of anakinra in a wide dosing range was reported.

Our observation illustrates the need as well as safety of higher anakinra dosing in younger age groups including 2 newborns. No serious adverse effects that would require discontinuation or termination of anakinra were observed at all dosing regimens. Introduction: The recognition of adenosine deaminase-2-(ADA2)-deficiency (DADA2), a monogenic vasculitis syndrome, is important due to the significant morbidity associated with the increased risk of stroke and vasculopathy.

Objectives: DADA2 has a highly variable clinical presentation including signs of vasculopathy (e.g. livedo reticularis, vasculitis, stroke), systemic inflammation and musculoskeletal findings e.g. arthritis and myositis, which is not widely recognised to be a typical finding associated with the diagnosis. Methods: We report the diagnostic work-up and management of two patients with DADA2, where myositis was a key symptom to reaching the diagnosis. Results: Patient 1 and 2 (both female, Turkish-German ethnicity), presented aged 5 and 10 years respectively, with muscle and joint pain, a history of fever attacks and livedo reticularis beginning in infancy. Inflammatory markers including serum amyloid A, were persistently elevated in both patients. Diagnostic tests ruled out HIDS, Blau Syndrom (Patient 1), as well as Bechet's Disease (negative HLA-B51 and Pathergie test), CAPS, TRAPS and FMF. However, Patient 2 was positive for the non-pathogenic FMF heterozygous mutation A744S. Initial therapy for both patients was colchicine with varying compliance and effectiveness. In patient 1, therapy was extended to include azathioprine and due to minimal effect, oral cortisone. Unfortunately, both patients attended sporadically and were non-compliant with therapy. In this time, Patient 1 was found to be a distant relative of Patient 2. Ten years after initial presentation, Patient 1 complained of muscle pains in the thighs. CK was normal, PM-Scl antibodies were positive and whole-body MRI showed muscle oedema and inflammation particularly affecting the vastus medialis and gracilis muscles.

In combination with a history of trochlear nerve paralysis, the diagnosis of DADA2 was suspected. Once confirmed with genetic testing, treatment was initiated with the TNF-Inhibitor adalimumab. Fever and inflammation episodes did not reoccur, and the muscle pain resolved. Patient 2 was invited for re-evaluation after being lost to follow-up. However, before attending, she suffered Introduction: Familial Mediterranean Fever (FMF) is characterized by severe systemic and organ inflammation. Successful treatment with rapid remission of symptoms and normalization of laboratory parameters was achieved in most patients with the interleukin-1β inhibitor canakinumab (CAN) in clinical trials. Objectives: The aim of the present analysis was the evaluation of long-term efficacy and safety of CAN in pediatric (age ≥2 years) and adult patients with FMF with respect to weight-dependent CAN dosing in routine clinical practice. Methods: RELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confirmed diagnoses of autoinflammatory periodic fever syndromes routinely receiving CAN are enrolled. Efficacy-and safety-parameters, CAN dosing as well as weight were recorded at baseline and assessed at 6-monthly intervals within the 3-year observation period of the study. Results: The interim analysis of the RELIANCE Registry comprises data of 54 FMF patients enrolled by December 2020. Of these, the % of patients reported to receive standard dose CAN (SD CAN; 150 mg or 2mg/kg respectively per 4 weeks) halved from 77% at baseline to 36% at month 18 in favor of less than SD CAN (<87.5% of SD) and higher than SD CAN (>112.5% of SD). Patients´and physicians´rating of disease activity was higher in patients receiving SD CAN and higher (table 1), even though CRP was equally well controlled in all three dosing groups. A total of 11 serious adverse events was reported, of which 1 case of tonsillectomy was classified as drug-related. The interim analysis of the RELIANCE Registry comprises data of 54 FMF patients enrolled by December 2020. Of these, the number of patients reported to receive less than standard CAN dose* (SD CAN; <87.5% of SD) / SD CAN / higher than SD CAN (>112.5% of SD) were 2/36/9 at baseline, 10/13/9 at 6 months, 11/7/8 at 12 months and 5/ 5/4 at 18 months. Even though CRP was equally well controlled in all three dosing groups, disease activity was rated higher by patients and physicians in patients receiving SD CAN and higher (table 1). A total of 11 serious adverse events was reported, of which 1 case of tonsillectomy was classified as drug-related.

The present interim data from the RELIANCE study confirm efficacy and safety of long-term CAN treatment in clinical routine. CRP levels were well controlled in all dosing groups. Remaining disease activity was mainly observed in patients under SD CAN and higher than SD CAN. There was no joint swelling, recurrent abdominal, chest pain or fever in his past medical history, and there were no signs of uveitis. His parents were first degree cousins. Physical examination was normal.

Acute phase reactants (APRs) were high at admission (erythrocyte sedimentation rate (ESR) 50 mm, normal range 0-20, and C-reactive protein (CRP) 3 mg/dl, normal range 0-0.5). Neutropenia (1100/mm 3 ) was detected with normal white blood cell (WBC) count. Antinuclear antibody (ANA) and extractable nuclear antigen antibodies (ENA) were negative. The local pediatrician initially started him on colchicine treatment, suspecting familial Mediterranean fever. However, MEFV gene variant analysis did not reveal any mutations. After two years of colchicine treatment, his family discontinued the drug since there was no response. The patient was then referred to our center. A periodic fever gene panel analysis (including LPIN2, MEFV, MVK, NLRP3, PSTPIP1 and TNFRSF1A genes) was performed with next generation sequencing and homozygous mutation was detected in exon 4 of the LPIN2 gene; c.589C>T (p. Arg197*). Both his parents were carriers for this variant. The whole body musculoskeletal system magnetic resonance imaging (MRI) was normal. After the diagnosis of Majeed syndrome, recombinant IL-1RA (anakinra) treatment was initiated at a dose of 2 mg/kg/day via the subcutaneous route. The patient has remained free of symptoms on anakinra treatment. However, neutropenia did not improve as of yet.

The sister of patient 1, presented to our department with recurrent joint and bone pain, fatigue, and anemia in the last six months. Physical examination was unremarkable. APRs were elevated at admission (ESR 120 mm and CRP 14 mg/dl). Severe neutropenia (600/mm 3 ) with normal WBC count, microcytic anemia (Hb 8.6 mg/dl), and thrombocytosis (700x10 3 /mm 3 ) were detected. She was consulted to the pediatric hematology department. Her bone marrow assessment revealed a normocellular bone marrow with megaloblastic changes. The whole body musculoskeletal system MRI demonstrated osteitis at the distal femur, proximal, and distal tibia, bilaterally. The periodic fever gene panel analysis revealed homozygote mutations in exon 4 of the LPIN2 gene; c.589C>T (p. Arg197*), like her brother. After the diagnosis of Majeed syndrome, anakinra was initiated at a dose of 2 mg/kg/day at the same time with her elder brother. Patient 2 has also remained free of symptoms with normal APRs on anakinra treatment. However, she still has neutropenia (900/ mm 3 ) four months after the diagnosis. Conclusion: Majeed syndrome should be considered in children with joint and bone pain, anemia, and neutropenia especially in the presence of parental consanguinity or positive family history. Anti-IL-1 drugs seems to be effective in treating of Majeed syndromerelated inflammation while neutropenia seems to be unresponsive to this treatment. Although it has been more commonly reported in cases with rheumatoid arthritis, multiple myeloma and in those on chronic hemodialysis programme, it has rarely been reported in cases with familial mediterranean fever (FMF). Objectives: Here we report a case with FMF complicated with aymloid arthropathy. Methods: An 18-year-old girl was admitted with bilateral knee swelling. Her past medical history was remarkable for recurrent fever, abdominal pain and joint pain beginning at the age of 3 and was diagnosed with FMF at the age of 6. Genetic analysis revealed M694V homozygous mutation. Renal biopsy performed at the age of 10 upon proteinuria revealed amyloidosis. She had attacks every two weeks which were resistant to colchicine, thus canacinumab was initiated. Despite canacinumab, chronic kidney disease developed and she was put on peritoneal dialysis programme at the age of 13 and two years later she received a living unrelated kidney transplant. At admission, she had bilateral swollen knees without warmth or hyperemia. All other physical examination findings were normal. Results: Laboratory parameters were as follows: WBC 10,500/mm 3 , Hb 9.7 g/dL, MCV 66.3 fL, RBC 4.68 x 10 6 , plt 412,000/mm 3 , urea 25 mg/dL, serum creatinine 1.06 mg/dL, CRP 0.3 mg/L, ESH 14 mm/h, serum amyloid A: 0.75 mg/L (N<6). Knee MRI revealed widespread irregularity in the bony cortex at the level of the lateral malleolus of the femur and millimetric degenerative bone cysts in the tendency to merge were observed. There were heterogeneous contrast enhancements in degenerative bony cysts. Effusion was observed in the suprapateller bursa and intraarticular area. The findings were compatible with amyloid arthropathy. Non-steroid anti-inflammatory drugs were prescribed and colchicine dose was tried to increase. Conclusion: The typical radiological findings should suggest amyloid arthropathy in cases who have predisposition to amyloidosis. This is the first case with amyloid arthropathy associated with FMF in the literature. Objectives: This study aimed to present the demographic, clinical, and laboratory features of children clinically diagnosed with FMF and had a defined variant in at least one allele. The secondary aim was to predict more severe mutations by evaluating clinical findings. Methods: We enrolled cases diagnosed with FMF according to Tel-Hashomer criteria and a defined variation in at least one allele, being followed up for at least 6 months. The medical charts of the patients were reviewed retrospectively. The patients were grouped as homozygous, compound heterozygous, and simple heterozygous cases with and without M694V mutation and the data were compared between the groups.

Results: A total of 263 (M/F:109/154) cases were included. The mean age at the onset of symptoms, follow-up duration, and time to diagnosis was 81.10±47.00 , 51.78±39.31 (6-166), and 9.23±14.44 (1-132) months, respectively. The rates of parental consanguinity, positive family history, and FMF in a first-degree relative were 15%, 42%, and 31.4%, respectively. The most common symptom was abdominal pain (85%). There was no difference between the growth parameters of the cases during the initial and final control periods. The most frequent alleles were M694V, E148Q, V726A. The most common accompanying disease was IgA vasculitis (20%). Almost 90% of the cases fulfilled all the defined criteria. Hb values were lower and the ESR and CRP values were higher during the attack period; ESR and CRP values were higher in the attack-free period; Pras scores were higher and the use of high dose colchicine was more frequent in homozygous and compound heterozygous cases carrying M694V. The presence of FMF in a first-degree relative increases the probability of this genetic predisposition 2.63 times; and each 1 unit increase in Pras score increases this probability 1.63 times. The threshold Pras score for this possibility is 5.5 (sensitivity: 65%, specificity: 55%). Conclusion: M694V is the most common and severe mutation in our cohort. First degree relative with the disease and Pras scores ≥5.5 may predict an M694V homozygous or a compound heterozygous mutation. Methods: Patients diagnosed with PFAPA syndrome and FMF and followed up at Pediatric Rheumatology and Pediatrics outpatient clinics between March 2016 and March 2021 were included in the study. Patients were diagnosed with PFAPA syndrome regarding modified Marshall's criteria, while patients with FMF were diagnosed using Yalçınkaya-Özen criteria. Regardless of their primary diagnosis, all the patients and their primary caregivers were exposed to a questionnaire including demographic and clinical data. MEFV gene mutations of the cases with FMF were noted. Homozygous or compound heterozygous pathogenic MEFV gene variants were defined as "confirmatory" and heterozygous pathogenic MEFV mutations, or compound heterozygous for one pathogenic MEFV variant and one variant of unknown significance (VUS), or biallelic VUS were defined as "non-confirmatory" genotype. Patients with heterozygous VUS or benign variants were defined as "nonpathogenic" and were not taken into consideration for Eurofever/ PRINTO "genetic and clinical (CG)" criteria. The consistency between Eurofever/PRINTO "clinical only (CO)" and (CG) criteria was established. The effectivity of the CO criteria to differentiate cases with FMF from those with PFAPA, sensitivity, specificity, negative and positive predictive values (NP and PP, respectively) and accuracy of the CO criteria were calculated. Results: 407 patients (M/F: 200/207) were included. Of those patients, 230 were diagnosed with FMF and 177 were diagnosed with PFAPA. In patients with FMF, 80 had confirmatory, 97 had non-confirmatory, and 53 had non-pathogenic mutations. When patients with FMF and PFAPA were compared, age at disease onset and diagnosis were significantly younger, male gender, pharyngotonsillitis, aphthous stomatitis, lymphadenitis, rinorrhea, cough, and febrile convulsion were more prevalent in cases with PFAPA, while abdominal and chest pain, maculopapular rash was more prevalent in cases with FMF (p<0.01). Disagreement between CO and CG criteria was established in only 5 of 177 (3%) patients with pathogenic mutations. The sensitivity, specificity, PP, NP and accuracy levels of CO criteria to differentiate FMF cases from PFAPA were 98.26%, 63.84%, 77.93%, 96.58%, and 83.29%, respectively. When evaluated considering MEFV gene groups, the highest sensitivity, specificity, PP, NP and accuracy were found in cases with "non-confirmatory" genotype. Since not all PFAPA cases have MEFV gene analysis, these values for CG criteria could not be defined for the whole group. Conclusion: The sensitivity is higher, whereas the specificity and accuracy was lower for CO to differentiate FMF from PFAPA in our series when compared to the values established by Eurofever/ PRINTO to differentiate FMF from other autoinflammatory diseases. Also, CO shows the best performance for cases with nonconfirmatory mutations, which may cause diagnostic challenge for clinicians. Introduction: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a periodic fever syndrome. No universally accepted criteria for PFAPA hasbeen developed yet. An international consensus has been established recently to define a new set of classification criteria for PFAPA syndrome. Objectives: We aimed to evaluate the diagnostic validity of four different criteria for the diagnosis of PFAPA. Methods: The patients diagnosed with PFAPA syndrome and Familial Mediterranean fever (FMF) and followed up at Pediatric Rheumatology and Pediatrics outpatient clinics of Tepecik Teaching Hospital, İzmir, Turkey between April 2016 and April 2021 were included in the study. Patients who fulfilled the modified Marshall's criteria irrespective of age and responded to steroids during the follow up were recruited for PFAPA syndrome. Patients with FMF were diagnosed using Yalçınkaya-Özen criteria and were included as the control group. All the patients and their primary caregivers were exposed to a questionnaire including demographic and clinical data mentioned in the criteria sets. The agreement between the four criteria was established. In addition, the sensitivity, specificity, positive predictivity (PP), negative predictivity (NP) and accuracy levels were calculated for each criteria set. Introduction: Chronic inflammatory era may result in cardiovascular changes. Objectives: We aimed to evaluate whether children with familial Mediterranean fever (FMF) have increased blood pressure (BP) values, higher arterial stiffness or left ventricular mass index (LVMI). Methods: Patients diagnosed with FMF who have homozygous or compound heterozygous mutations in the exon 10 of the MEFV gene and being followed up between April 2020 and April 2021 were included in the study. Demographic data, office blood pressure (OBP) measurements were recorded at the first visit. Ambulatory blood pressure monitoring (ABPM), central BP (cBP), pulse wave velocity (PWV), and augmentation index (AIx@75) values recorded within the same device and LVMI calculated with echocardiographic measurements were recorded in the following visit. The same tests were performed for a sex and age-matched control group. Results: Finally, data would be collected for 26 cases with FMF and 26 cases as the healthy controls. Body weight, height, body mass index SDS values were similar between the groups (p>0.05). Both systolic and diastolic OBP SDS values were similar as well (p>0.05). 24-hour, daytime and nighttime systolic and diastolic BPs and 24hour mean arterial pressure (MAP) SDS and nighttime mean MAP SDS levels were similar between the groups (p>0.05). However, daytime MAP SDS was significantly higher in FMF patients (p:0.033). Both daytime systolic and diastolic loads were significantly higher in FMF cases (p=0.005 and p=0.034, respectively), whereas nighttime systolic and diastolic loads and systolic and diastolic dips were similar between the groups. 24-hour, daytime and nighttime AIx@75 and PWV levels, and systolic and diastolic central BP levels were similar between FMF patients and the control group (p>0.05).

The results of this preliminary study suggested that FMF cases with confirmatory mutations were prone to have higher daytime systolic BP and MAP, however negative effects of these disorders on the left ventricle and arterial stiffness could not be established. Evaluation of these parameters in larger patient groups and re-assessment of the same patients in the follow-up would be rather valuable. Introduction: The number / phenotype of DADA2 continues to expand rapidly though series from Asia are scant. Objectives: Share experience with 10 DADA2 patients (9 unrelated families) identified over 2 years. Methods: We diagnosed the first case in April 2019 following which we recalled and diagnosed 4 more patients on renewed suspicion. In 2, their phenotypes did not match the initial provisional diagnosis of primary CNS vasculitis and inflammatory bowel disease (IBD) respectively while 2 had been treated as classic PAN. 4 patients were diagnosed prospectively on clinical suspicion and 1in whom we suspected syndromic bone dysplasia with inflammatory features was a diagnostic surprise. Results: 7/10 are males. Age of onset ranged from 4 months -17 years 9 months. Referrals were by varied specialists including primary pediatrician, pediatric hematologist, ophthalmologist, adult neurologist and urosurgeon. Medium-vessel dominated disease was seen in 6 patients and in 3 we suspected a systemic autoinflammatory disease (SAID) {1-febrile relative of a previously diagnosed DADA2 patient, 1-IBD-like with cutaneous vasculitis,1-early onset prolonged fever with granulomatous mediastinal adenitis suspected Blau syndrome} and 1 patient with progressive deforming symmetric inflammatory arthropathy and acquired micrognathia. Cutaneous features were the commonest; seen in 7 patients and stroke was seen in 3. Other systems involved were musculoskeletal (5including the bone dysplasia mimic described above),renal (4-notable were renal artery stenosis and perinephric hematoma), gastrointestinal (2-notable was bowel perforation), while ocular involvement was seen in 2 (notable being central retinal artery occlusion and episcleritis). Hematological features were seen in 5 and included pure red cell aplasia, persistent leucopenia and thrombocytopenia in 1 patient each and anemia in 2 (notable-unexplained anemia of infancy). None of the patients had exclusive hematological disease or immunodeficiency. 5 were homozygous for p.G47R variant and 2 are compound heterozygous with p.G47R and splice mutation c.753+2T>A and p.G47R and p.H219P respectively. Of those with p.G47R variant 4 belong to Agarwal community in whom endogamy is known. 2 patients born of a first cousin marriage (and even related three generations higher) have a homozygous pathogenic variant p.G358R. The patient with symmetrical skeletal affliction has a homozygous pathogenic variant in p.R169Q. All 4 patients in whom ADA2 enzyme assay was performed were deficient. 4 patients are on etanercept originator molecule and 6 on etanercept biosimilar with treatment duration varying between 2 weeks to 116 months and no drug side effects. 9 patients are in clinical remission off steroids and growing well with no restriction of activities of daily living. 2 have residual hypertension. 1 unvaccinated patient contracted COVID 19 and recovered uneventfully. Conclusion: Since our first case in 2019, DADA2 is now the commonest SAID in our cohort (10/44). Due to its initial presentation to varied specialists we need to spread awareness to increase diagnosis. We report an unusual phenotype mimicking a bone dysplasia and alert colleagues that the classic phenotype originally described is being overshadowed by a wide spectrum. The p.G47R mutation is the commonest in our series and seen in the endogamous Agarwal community. The disease is very responsive to etanercept and treatment is progressively affordable with etanercept biosimilar. Residual hypertension may be seen with renal involvement and 1 patient with COVID19 on etanercept recovered uneventfully. Results: The present interim analysis comprises baseline data of 7 HIDS/MKD patients enrolled by December 2020 as well as preliminary 12-month data. Of these patients, 4 (57%) were females and median age at baseline was 7 years (2-39 years). The median duration of prior CAN treatment at baseline was 2.0 years (0-5 years). Standard, low, and high dose CAN treatment was evenly distributed at every interval. Preliminary results indicate stable remission and disease control by physicians´and patients´assessment as well as laboratory parameters (table 1). In total, 3 patients were affected by adverse drug reactions, however, none of these events was classified as serious. Conclusion: Baseline characteristics and preliminary data of HIDS/ MKD patients from the RELIANCE study indicate good clinical and laboratory disease control and no unexpected safety concerns at the 12 months interim analysis. Introduction: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory condition characterized by severe systemic and organ inflammation. In a phase 3 pivotal trial 1 , TRAPS patients have been successfully treated with the interleukin-1β inhibitor canakinumab (CAN). 45% of patients reached clinical remission after 16 weeks (primary endpoint) 1 Methods: RELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed diagnosis of TRAPS who routinely receive CAN are enrolled in order to evaluate efficacy and safety of CAN at baseline and at 6-monthly intervals.

Results: The interim analysis of TRAPS patients enrolled by December 2020 includes baseline (N=16, 1 patient with atypical TRAPS) and preliminary 18-month data. Of these patients, 11 (69%) were females and median age at baseline was 23 years (3-43 years). 10 (62.5%) patients had been pre-treated with anakinra and 1 (6.3%) with tocilizumab.

Preliminary results indicate stable remission by physiciansá ssessment and laboratory parameters. Disease control by patients´a ssessment showed no major changes (table 1) . In total, 7 adverse drug reactions where observed, of which none was classified as severe.

Conclusion: Baseline characteristics and interim data of TRAPS patients are available from the RELIANCE study. Further interim and end-of-study data will be analyzed to assess efficacy and safety of long-term treatment as well as dosing effects in TRAPS patients. Objectives: The RELIANCE registry is designed to explore long-term safety and effectiveness of canakinumab under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA).

Methods: This prospective, non-interventional, observational study with a 3-year follow-up enrolls patients with clinically confirmed diagnoses of CAPS routinely receiving canakinumab. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline with last update at 30 months of follow-up in the total cohort including the cohort with severe subtypes (NOMID/CINCA Thirteen of 48 (27%) patients underwent MRI brain due to neurological involvement, mainly due to recurrent headaches, with no abnormalities identified in 9/13 (70 %); whereas 4 patients (3 with CINCA) had changes on their MRI brain. None of the patients experienced deterioration neither in their clinical symptoms nor in MRI brain scans after starting anti-IL1. Conclusion: Anti-IL1 treatment has had a major impact in paediatric patients for the prevention and treatment of CAPS symptoms. Treatment efficacy was observed by improved CAPS clinical disease activity scores; and normalised inflammatory markers. In our cohort, neurological symptoms including sensorineural hearing problems improved and MRI brain scans have remained stable with anti-IL1 therapies. Introduction: A20 Haploinsufficiency (HA20) is a recently described autoinflammatory disease (AID) caused by a loss-offunction mutation in the TNFAIP3 gene. HA20 can be described like rare autosomal-dominant syndrome with early onset of systemic inflammation. Clinical manifestations of HA20 are similar to Behҫet's disease (BD) and represented by periodic fever, recurrent oral aphthosis and genital ulcers, arthralgia/arthritis, uveitis. In world practice there are a few described cases of gastrointestinal involvement (abdominal pain, diarrhea, vomiting, rectorrhagia). Elevated acute-phase markers and immune reactants (ANA, anti-dsDNA, anti-Sm, RNP) and positive HLAB51 have been observed in some patients.

Objectives: To present clinical manifestations of Behҫet-like syndrome (HA20), initially diagnosed as an rheumatic disease.

Methods: Case report of patient with HA20 genetically confirmed by high-throughput DNA sequencing and detection TNFAIP3 gene mutation.

Results: An adolescent girl (16 у.о.) was examined in our Federal Rheumatologic Centre. From the age of 14, disease manifested with repeated episodes of oral and genital ulcerations, arthritis of proximal and distal interphalangeal joints (PIP, DIP), CRP was 124 g/l (Normal=0-5 mg/l). Initially diagnosis was verified as juvenile idiopathic arthritis (JIA). The treatment included subcutaneous methotrexate (MTX) 15 mg/week, NSAID courses without positive respond. Since 15 y.o., hips and ankles arthritis were developed, deformation of PIP, DIP joints were getting worse. BD, JIA were included in differential conditions. Because persistence of symmetric polyarticular damage, increased ESR, CRP -abatacept was prescribed, without any response. Gastrointestinal involvement (erosive enteritis, endocolitis), loss of 9 kg weight for 6 months and diffuse alopecia were detected after 1.5 years from the onset of the disease. A lot of laboratory disturbance including ESR-46 mm/h (N= 2,0-30,0); ANA-1/2560 (N<1/160); anti-dsDNA-23.9 IU/ml (N= 0,0-20,0); lymphopenia (0,72x109/l, N= 1,20-3,00), anemia (HGB 111 g/l, N=120-140) was preserved. Methods: Retrospective case notes review.

Results: A 21 month old girl presented with a 9 month history of recurrent fevers lasting 3-5 days, approximately every 14 days, associated with arthralgia, urticarial rashes, blistering panniculitic lesions on hands, legs and face and irritability. She had mild delay in gross motor skills and speech. She had been born to Caucasian non-consanguineous parents at 35+4 weeks gestation. She developed a persistent cough from five weeks of age and and was treated for bilateral lower respiratory tract infections secondary to pseudomonas aeruginosa. Subsequently unsafe swallow was noted and she was fed via a nasogastric tube. Bronchoscopy, video fluoroscopy, bulbar EMG, and cystic fibrosis screening were performed, all with negative results. There was a family history of chilblains in father and paternal grandmother. Laboratory parameters revealed normal full blood count and elevated inflammatory markers during the episodes with CRP 24 mg/ L (reference range [RR] < 20 mg/L), erythrocyte sedimentation rate (ESR) 45 mm/hr (RR < 10), serum amyloid A 100mg/L (RR < 10), with normalisation between episodes. A skin biopsy of the rash showed features of urticaria and septal panniculitis, but no vasculitis. An extensive work up for infections, autoimmune diseases and common immunodeficiencies was negative. Ophthalmic examination was normal. Echocardiogram and magnetic resonance imaging of brain were normal, and an ultrasound of the abdomen showed a mildly coarse liver. CT scan brain showed left frontal lobe calcification. A systemic neuro-autoinflammatory disease was suspected, leading to genetic screening with targeted next-generation sequencing. Empirical treatment with colchicine 0.5mg/kg/day was commenced and subsequently azathioprine 2 mg/kg/day pending genetic results. No benefit was observed from the treatment with colchicine or azathioprine, and oral prednisolone (1mg/kg for 3 days) was introduced with improvement in shortening duration of fever episodes. Motor skills and language remained delayed, and there was a decline in neurological function with mild spasticity in the lower limbs. Genetic studies revealed a heterozygous c.G217A mutation (p.D73N) in TREX1 gene confirming a diagnosis of AGS. Expression of interferon-stimulated genes was found to be upregulated. Treatment with baricitinib (2 mg three times a day (0.34mg/kg/day)), a selective JAK1/2 inhibitor, was initiated at age 4 years. At 5 months follow up post initiation of baricitinib there was significant improvement in the clinical features, with only one episode of fever and mild rash which lasted 2 days over a 5 month period. The neurological function remained stable. Conclusion: We describe a rare autoinflammatory phenotype as the predominant manifestation of AGS caused by a heterozygous mutation in TREX1 and highlight the response to baricitinib. Recognition of this phenotype and early diagnosis is of outmost importance as prompt initiation of treatment may be of greatest benefit in the early stages of the disease. The patient has shown clinical response to JAK inhibition, although we cannot comment on the long term benefits at preventing progression of neurological Introduction: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare mostly multifactorial autoinflammatory disease. It is characterized by non-infectious recurrent bone lesions, usually manifesting in childhood. There is no standard and universal treatment approach that is able to control disease progression in all patients with CRMO. Objectives: We aim to report our positive experience with treatment of a refractory CRMO case with tocilizumab. Methods: We describe clinical, laboratory, imaging characteristics and treatment response of a CRMO patient. Known genetic defects, leading to CRMO, were excluded via whole exome sequencing. The diagnosis was confirmed histologically, bone tumors and infections were excluded.

Results: A 7-year-old girl was admitted to our hospital because of pain in the right knee and left ankle, accompanied by fever and increased laboratory inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR). Treatment with NAID, antimicrobial therapy was not effective. She was started on bisphosphonate therapy, with minimal reduction of the clinical symptoms. TNF-α inhibitors (adalimumab, then infliximab) were ineffective. Steroids (2 mg/kg/day) + methotrexate relived her pain, as well as led to normalization of CRP levels, yet all the symptoms relapsed with steroids tapering. Therefore, she was started on anakinra with partial effect. Two days after cessation of anti-IL-1 therapy she relapsed with exudative and proliferative lesions in the knee, ankle joints, joints of the wrists, and palmar-plantar pustulosis (erythema) on the feet Canakinumab 150 mg, later 300 mg every 4 weeks, was initiated and the patient's general condition improved, but increased acute phase reactants and pain persisted. Denosumab, nuclear factor kappa-B ligand (RANKL) inhibitor, had been added to the сanakinumab and MTX therapy, without. MRI and bone scintigraphy showed persistent inflammatory changes in the bones. She was then started on tocilizumab and MTX. Now the patient is 8 months on treatment, is clinically asymptomatic, has no fever and pain. Laboratory tests showed decrease inflammatory activity. Introduction: Blau Syndrome is a rare dominantly inherited autoinflammatory disease resulting from a mutation of a pattern recognition receptor NOD2 gene and typically manifest as a triad features of arthritis, dermatitis and uveitis with a paediatric onset. Several case series have reported that ocular manifestation is a frequent presentation (70-80%) and is often a bilateral disease with progression towards panuveitis in a long run. Management of uveitis in Blau Syndrome has been particularly challenging due to the chronicity and persistent uveitis despite systemic corticosteroids and institution of immune modulatory and biologic treatments. Combination of persistent active ocular disease, with postinflammatory ocular complications and long term topical steroids, inevitably result in progressive decrease in visual acuity. The visual burden of patients suffering from Blau-associated uveitis is essentially unknown. There is lack of a published data assessing long term visual outcomes of patients with Blau-associated uveitis and the data published so far are based on case series without a standardized follow up.

Objectives: Sight threatening complications remains as one of the major factor of long term morbidity in patients with Blau syndrome.

In this review, we aim to identify and quantify the visual prognosis of Blau syndrome uveitis in a retrospective longitudinal review of a single centre study. Methods: Clinical data were collected retrospectively from patients with a diagnosis of Blau Syndrome associated uveitis with a proven NOD2 mutations attending the regional South West of England Paediatric Rheumatology Haploinsufficiency of A20 (HA20) decreases the NF-kB regulatory protein A20 and thereby amplifies action of the transcription factor NF-kB, a central mediator within inflammatory and innate immune signaling pathways.

Objectives: This review/case report is to provide additional information on clinical presentation and genetic findings in a rare, only recently, described autoinflammatory disorder.

Methods: A 10y/o girl repeatedly presented with severe oral ulcers, gingivitis, lymphadenopathy and occasional fevers. Serum levels of C-reactive protein (CrP) and erythrocyte sedimentation rate (ESR) were mildly increased, Immunglobulin E levels considerably elevated. No ulcers were found by endoscopy in stomach and colon, but few intramucous lymphoid follicles were seen. Interestingly, her mother also suffers from recurrent oral ulcers in addition to lung emphysema, autoimmune hepatitis of unknown origin, and scleroderma. Results: Whole exome sequencing in the index patient revealed a novel heterozygous mutation in the TNFAIP3 gene (NM_006290.4:c.176_177delAG, p.Gln59fs). This variant leads to a frameshift and a premature STOP codon at the beginning of exon 2 and thereby most probably to nonsense mediated decay. Mutations in this gene can vary in location and usually lead to STOP codons or frame shift mutations. Due to the decreased A20 levels and hence reduced inhibition of NF-kB, patients with HA20 suffer from episodes of fever, recurrent oral and genital ulcers, skin rashes, and polyarthritis, as well as from gastrointestinal and neurological symptoms. Ocular manifestations are far less frequent than in Behcet's disease, and age at manifestation is usually earlier.

Conclusion: In patients with severe "familial" aphthosis and unexplained fever, genetic testing may guide clinical treatment decisions as exemplified in this family with unexpected monogenic disease. Our patient is presently stable under colchicine (1 mg/d) and on-demand steroid treatment. TNF-alpha-inhibitors and IL-1 antagonists may control ulcers, arthritis and sterile abscesses in patients with HA20. In the presence of systemic autoimmunity and an elevated interferon signature, JAK-inhibitors are a therapeutic option as stated by Schwartz et al. (2) .

Consent for publication was signed by the patient's parents. Introduction: TRNT1 is a nuclear gene encoding a ubiquitous enzyme (CCA-adding tRNA nucleotidyltransferase enzyme) necessary for aminoacylation of both mitochondrial and cytosolic tRNA. Mutations of that gene were firstly associated to SIFD but over the years phenotypic heterogeneity was described.

Objectives: To expand autoinflammatory phenotype of SIFD and to report a novel mutation of TRNT1 gene. Methods: Case report of a 10-years-old female admitted to our Rheumatology Pediatric Unit of Santobono Children's Hospital of Naples due to febrile illness associated with vomit and diarrhoea, evolved in shock, treated with broad spectrum antibiotics and cardiovascular support in Intensive Care Unit. No infective causes were found. Results: At the admission, the anamnesis revealed recurrent episodes of fever since the second month of life treated with antibiotics even without evidence of infection, with poor clinical response. She underwent to haematological investigations due to microcytic anaemia requiring blood transfusions. Bilateral cataract was diagnosed at the age of one years, ascribed to perinatal infection of Cytomegalovirus.

Physical examination evidenced facial dysmorphisms, brittle hair, intellectual disability, failure to thrive. Laboratory assessment showed microcytic anemia (Haemoglobin 9.4 g/dl, MCV 60.9 fL, RDW 43 fL), lymphopenia (Lymphocytes 619/uL), elevated inflammatory markers (C-Reactive Protein 324 mg/L, Procalcitonin 610 ng/ml, Ferritin 2071 ng/ml). Immunological assessment was performed, showing hypogammaglobulinemia with IgA <0.22 g/l (0.5-3) and IgG 6,3 g/dl (7) (8) (9) (10) (11) (12) (13) (14) (15) , low levels of CD3+ T cells 49% (55-78%). The clinical history plus the phenotype and the laboratory data, led us to assume mutations of TRNT1 gene. Genetic analysis was done, confirming our suspicion. Sanger sequencing was performed for genetic confirmation, resulting for TRNT1 mutations in SFID in compound heterozygous status in the proband: c.1205_1206dupAA (p.Glu403Lysfs*27) and c.1246A>G (p.Lys416Glu), the first mutation never described in literature, the second one already reported as pathogenic. She required low-dose prednisone to control a new febrile episode and then she started on anti-TNFα therapy (Etanercept), with resolution of recurrent fever and improvement of laboratory inflammation. Conclusion: Since the first publication on SIFD, several studies have described patients with heterogeneous phenotypes and systemic involvement of variable severity and progression. Our patient presented a clinical picture characterized by several features which until the age of ten had not been considered as a part of a single disease. Currently, about 50 cases are outlined in literature. We also reported a novel mutation in the TRNT1 gene (c.1205_1206dupAA) and even if functional analysis of the protein expression was not performed, the in-silico prediction led to consider the mutation as pathogenic. Taking into account the clinical and immunological phenotype altogether with the found mutations and response to treatment, we conclude that the patient is affected by SIFD syndrome. Due to the rarity of that syndrome, diagnostic delay is observed, as in our patient. Early diagnosis of this condition would enable patients to promptly access to therapies thus allowing the opportunity of a better outcome. Written informed consent for the publication was obtained. Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinfammatory disease manifesting with phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. Objectives: We aimed to determine the clinical findings, phenotypegenotype correlation and treatment outcomes within a large pediatric FMF cohort. Methods: The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. Results: A total of 3454 children (1755 girls, 1699 boys) were involved in the study. The mean±standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1±5.2, 5.1±3.8, and 7.3±4.0 years, respectively. Of 3454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (n=3373, 55.3%), M680I (n=782, 11.3%), V726A (n=529, 7.6%) and E148Q (n=503, 7.2%). Children carrying homozygous or compound heterozygous mutations had an earlier age of disease onset (4.6 vs 5.6 years, p=0.000) and a higher number of attacks per year (11.1 vs 9.6, p=0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n=11) had presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% (n = 145) of our patients. Conclusion: In this largest pediatric cohort studied and presented since now, it has been demonstrated that exon 10 mutations, particularly the M694V homozygous mutation, are important in disease severity and outcome. Although E148Q is considered as a polymorphism in some populations, it was identified as a diseasecausing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control and the availability of anti-IL1 agents in colchicine-resistant cases. Introduction: To date, fewer than 20 variants with demonstrated pathogenicity in the NLRC4 gene associated with the development of autoinflammatory syndrome due to gain-of-function (GoF) of the NLRC4 inflammasome have been described. This autosomal dominant disorder encompasses a spectrum,from cold-induced relapsing fevers (FCAS) to neonatal-onset multisystem autoinflammatory disease (NOMID), autoinflammatory syndrome with infantile enterocolitis (AIFEC) or macrophage activation syndrome (MAS). In most cases, the onset of the disease occurs during early infancy with recurrent fever, and rash Treatment varies according to the degree of presentation, being key the identification of severe forms, associated with macrophage activation and secretion of pro-inflammatory cytokines (IL-1β and IL-18) for disease control with targeted drugs.

Objectives: In this study, we report two clinical cases in which the genetic study revealed two novel variants in NLRC4 Methods: 23-year-old woman with a history of self-recurrent episodes of oral aphthous ulcers and odynophagia treated with antibiotics since the age of 4 years. At age 21, she presented mononucleosis followed by a generalized skin rash, pharyngotonsillitis, fever of 39°C, being diagnosed with scarlet fever. Currently, she refers to have recurrent episodes, usually 2 or 3 a month, of oral aphthous ulcers, abdominal pain and pharyngotonsillitis, along with increase of acute phase reactants, treated with glucocorticoids. They are mainly associated with stress. Girl aged 2 years and 5 months, with recurrent fever every 15 days (fever up to 39-40°C for 4-5 days) with pharyngotonsillitis in the last 11 months. The febrile episodes are associated with a marked elevation of acute phase reactants. She had experienced an immediate response to methylprednisolone in two of the three episodes in which they were administered. Her father had similar symptoms during childhood that disappeared with tonsillectomy Results: The genetic study revealed two heterozygous variants not previously described in NLRC4. Case 1 carried the p. Cys258Arg variant (Allelic Freq<0.01%), absent in her asymptomatic mother, located within the NACHT-NBD domain, in which the presence of GoF variants has not been statistically associated with mild or severe forms of the disease. Case 2 carried the p. Glu311Lys variant (Allelic Freq. unknown), inherited from the affected father during childhood and absent in her asymptomatic mother, which is located within a region of the NACHT domain (between NACHT-NBD and NACHT-WHD), in which the presence of GoF variants has been found in a more significant number of patients with severe forms of the disease (AIFEC/MAS). Conclusion: Nowadays, these two variants remain uncertain clinical significance, although potentially associated with the development of NLRC4 inflammasomopathy. Nevertheless, the genetic study has been of prognostic utility to identify genotype-phenotype correlations in other cases in the scientific literature with variants in NLRC4, because of that, if its pathogenicity is confirmed in these two cases, its result allows us to anticipate severe forms of the disease and to evaluate targeted treatment options. Introduction: Case 1 -A systemically well 7 year-old girl presented with 5-weeks of right calf tenderness and swelling following a short episode of pharyngitis and generalised maculopapular rash. There was no gait abnormality, focal neurology or restriction in activity aside from fatigability on walking distances. There were no skin rashes, joint involvement, eye changes or involvement of other muscles. She had a raised creatine kinase, plasma viscosity and lactate dehydrogenase. Her other blood results were normal including an extended autoimmune screen, immunoglobulins, complement levels, ASOT and titres of mycoplasma, EBV and CMV. MRI showed evidence of extensive inflammation of the gastrocnemius and soleus. A muscle biopsy showed heavy interstitial inflammatory cell infiltrate of predominantly lymphocytes, features of fibre necrosis including phagocytosis and hyalinisation with concurrent fibre regeneration (figures 1+2). She was initially managed with physiotherapy and anti-inflammatory medications but then developed intermittent right calf pain, restriction in activity and tiptoe walking due to gastrocnemius contractures. She was commenced on an 8-week tapering course of oral steroids and is improving with weekly methotrexate. Case 2-A systemically well 14-year-old presented with 6-months of leftsided hip pain, weight loss and inability to weight-bear without crutches. On examination there was painful fixed limitation of the left hip to 45 o on abduction and external rotation with bilateral mild swelling of the proximal interphalangeal (PIP) joints on both upper limbs. Otherwise, there was a full range of movement in all joints, with no rashes or other joint swelling or inflammation. Her blood tests were ANA positive 1:6000 and MRI of her hips demonstrated high T2 signal intensity in the left gluteus minimis and medius, obturator internus, obturator externus in keeping with myositis ( figure 3 ). She received a pulse of corticosteroids followed by a course of methotrexate. There was immediate improvement in her PIP joint swellings and within a few weeks she was able to walk without crutches for the first time in 6 months. Unfortunately, 18 months after her diagnosis, she had developed anterior uveitis of her left eye with posterior synechiae; this responded well to steroid and cyclopentolate eye drops. Objectives: . Methods: . Results: . Conclusion: Summary-Focal myositis is a rare immune-mediated pseudotumour of a single skeletal muscle group (1) . Only around 200 cases have been described in the literature so little is known on incidence, prevalence, patient management and outcomes (2) . This differs and should not be confused with post-viral myalgia which bears neither the histological changes nor chronicity of focal myositis. Treatment options are centred on immunomodulation and in severe cases surgical management of contractures (3) . We emphasise that clinicians should bear this rare differential diagnosis for in mind for consideration of early conservative management, assessment for uveitis, immunomodulation and possibly surgical correction to improve patient outcome. magnification (right). Heavy interstitial inflammatory cell infiltrate of predominantly lymphocytes, features of fibre necrosis including phagocytosis and hyalinisation with concurrent fibre regeneration is shown. Figure 3 Introduction: Pathogenic heterozygous variants in PSTPIP1 lead to excessive IL1 mediated inflammation, which is the cause of rare autoinflammatory syndromes: PAPA (pyogenic arthritis, pyoderma gangrenosum, acne) and the more recently described PAMI (PSTPIP1associated myeloid-related proteinemia inflammatory) (1). Gene expression characterization may lead to better understand the molecular pathogenesis of these diseases. Objectives: We investigated the gene expression pattern in two patients with familial PAPA syndrome (father and son, pt1 and pt2), two siblings with PAMI syndrome (pt3 and pt4) and a sporadic case of PAMI syndrome in a girl who presented an atypical clinical picture (pt5). Methods: Gene expression studies of whole blood cells of patients with PAPA and PAMI syndrome compared to a group of healthy subjects and pathway over-representation analysis to investigate the main biological processes involved. Table above describes the analyzed families including the results of target sequencing panels and pharmacological treatments. Gene expression analysis highlighted the heme metabolism pathway which is over-expressed among all the patients compared to controls already known to be involved in physiological and pathological processes (4). Only patients with PAMI syndrome showed among the over-represented signaling pathways the neutrophils degranulation pathway probably due to neutrophiles hyper-activation. Interestingly, only pt5 presented a high interferon signature score that recovered after therapy with HCQ.

The presence of lupus-like manifestations in PAMI has never reported so far. Even if only one of our patients with PAMI displayed interferon-related-inflammation, we can speculate a possible cross-talk between IL1 and interferon pathways. A possible hypothesis, which could be worth investigating, is that the increased neutrophil activation pathway found in PAMI could be associated to the release of neutrophil extracellular traps and to the activation of interferon signaling. (Table 1) . MRI presented bilateral signs of myositis of the lower limbs. He subsequently developed nocturnal fever, multiple inguinal, axillary lymphadenopathy and splenomegaly. Infectious workup, the autoimmunity panel including myositis specific and associated autoantibodies, and serum markers of malignancies were all negative. PET-scan showed multiple tracer uptake in axillary, inguinal and abdominal lymph nodes (SUV max 2.2). A myogenic pattern of active denervation was confirmed by electromyography. Muscle biopsy did not reveal clear sign of vasculitis, only showed non-specific signs of inflammation with scarce macrophagic infiltration; no alteration of muscle fibres or perifascicular atrophy. Bone marrow and lymph node biopsy with flow cytometry were negative for malignancy. Symptomatic treatment with indomethacin was started because of extremely painful musculoskeletal involvement associated to the development of recurrent infiltrative burning nodular skin lesions of both hands and feet. The result was a dramatic and prompt relief, but persistence of elevated acute phase reactants. Genetic sequencing of ADA2 revealed compound heterozygosity for a novel frameshift deletion in the catalytic domain, c.1100_1113del:p.I367Tfs*41, inherited from the father, and a maternally inherited missense variant, c.1148G>A:p.G383D, previously described in compound heterozygosity in two patients with DADA2. ADA2 functional analysis confirmed pathological low activity of the enzyme. Brain angio-MRI was unremarkable. Etanercept treatment was deployed with rapid response of muscoloskeletal and skin involvement, normalization of inflammatory markers and regression of lymphoproliferation. Conclusion: Here, we report a case of an unusual presentation of DADA2 with myositis and an optimal response to the anti-TNF α therapy. We described a new compound mutation with a novel ADA2 deletion leading to premature protein truncation in heterozygosity with the recently described c.1148G>A mutation. The pathogenic role of the latter, so far reported in only two siblings in compound heterozygosity, is supported by our data. DADA2 phenotype spectrum is constantly increasing and description of peculiar cases and new mutations could improve genotype/phenotype correlation leading to significant progresses in diagnosis, management and prognosis of these patients. Introduction: SAVI-syndrome -STING-associated vasculopathy with onset in infancy, a rare monogenic autosomal-dominant autoinflammatory disease associated with a mutation in the TMEM173 gene; belongs to type 1 interferonopathies. It is characterized by an early onset, fever, skin rashes (vasculopathy), arthritis, interstitial lung disease (ILD), increased levels of acute phase markers, and presence of autoantibodies (ANA, RF and other antibodies). The main treatment: glucocorticoids (GC), JAK inhibitors Objectives: To present a family case of SAVI-syndrome in the practice of a rheumatologist and pulmonologist Methods: Family case: three patients from the same family were sequentially hospitalized at the federal rheumatology center and diagnosed with SAVI-syndrome: 2 children-twins (2018 y.o.b.), the 1 st pregnancy (IVF), the 1 st cesarean operation (the girl was examined at the age of 1 year and 7 months, the boyat the age of 2 years and 3 months), the children's father (1980 y.o.b.) was diagnosed at the age of 41. All the three of them were revealed to have a genetic mutation in the TMEM173 gene c.463G> A, p.V155M in a heterozygous state. No mutation was found in the mother. Prior to the diagnosis, all these patients were monitored by a pulmonologist Results: The main characteristics of the pts are presented in Table  1 . Earlier than all, the manifestation of the disease was noted in the boy: shortness of breath from the birth, ILD, up from 1.5 months -skin rash, up from 2 years -ankle arthritis, changes in fingers like drumsticks and nail plates like watch glasses. The girl from the age of 1.5 years has suffered from skin rash, arthritis of the knees, ankles, small joints of the hands, fever, lymphadenopathy, enlarged liver, spleen, ILD in the absence of shortness of breath and manifestations of a respiratory failure. The father had a manifestation of a pulmonary pathology in the form of shortness of breath, decreased exercise tolerance from 9 years old, cutaneous vasculopathy up from 20 years old, arthritis of the knee, ankle, hand joints up from 24 years old, interstitial pulmonary involvement, fibrosis established at the age of 29. Treatment: prednisolone (Pr), cyclophosphamide, rituximab without any effect. Results: A 4-year-old boy, first born of non-consanguineous marriage, presented with skin rashes during the winter season from age of 2 years. The rashes were macular, red in color not associated with itching lasting for 12-24 hours. He complained of similar episodes on travelling to areas with low temperatures that resolved spontaneously. He had no history of any joint complaints or any other systemic involvement.

He had a strong family history involving at least 10 members across four generations of family members on the paternal side. All these family members reported rash during the winter season or on travel to areas with low temperature. The father had had macular rashes on the lower limbs and arms on exposure to low temperature during winter season followed by pain in ankles, knees, elbows, and small joints of fingers. Similar history was reported by the grandfather with rashes and joint pains during winters. On examination, the boy was healthy looking, having multiple blanching macular rashes on his lower limbs on both flexor and extensor surfaces and on the soles of his feet. Systemic examination was normal. Inflammatory markers were slightly elevated, however immunological evaluation showed normal immunoglobulin levels.

In view of the strong family history, an autosomal dominant pattern of inheritance was suspected, and genetic evaluation was carried out. A pathogenic heterozygous mutation c.13222C>T (p.Ala441Val) was identified in exon 3 of the NLRP3 gene by whole exome sequencing. Father was also noted to have the same mutation. A diagnosis of FCAS was established and they were started on colchicine for the persisting complaints and are under close followup. FCAS is characterized by early onset fever, urticarial rashes, and joint pains after 1-3 hours of generalized cold exposure. Cold sensitivity is unique to FCAS among the autoinflammatory disorders and has been shown to increase the activity of the transcription factor AP-1, which increases synthesis of secretory proteins from inflammatory cells. Mean age of presentation in a large series, was 47 days, with a range of 2 hours to 10 years. The most consistent finding in all affected subjects included recurrent fever and chills (93%), arthralgia (96%) and recurrent conjunctivitis (84%). Amyloidosis was reported only in 2% among those affected. In the index family, none of the family members developed amyloidosis, suggesting a milder phenotype. Hoffman et al studied the benefit of the IL-1 receptor antagonists in patients with FCAS. Unfortunately, IL-1 blockers are not readily accessible in our subcontinent. There are case reports of thalidomide being used, however, prolonged exposure to thalidomide is known to cause peripheral neuropathy. We chose colchicine as it seems to be least toxic among the choices available. As majority of patients with FCAS seem to have a milder phenotype especially in tropical countries, it is often a clinical dilemma deciphering the choice and duration of therapy. Conclusion: Cold induced urticarial rashes, arthritis and fever must make one think of FCAS especially in the setting of a positive family history. To the best of our knowledge, this is the first Indian family to be reported with FCAS type Introduction: Sideroblastic anemia associated with immunodeficiency, fevers and developmental delay (SIFD) is a newly described inborn error of immunity caused by TRNT1 deficiency. Not many cases have been described in literature. Objectives: To describe a case of TRNT1 deficiency. Methods: Retrospective review of clinical records was performed. A detailed clinical history including the age of presentation, symptoms, family history, findings on physical examination, laboratory findings and treatment details were recorded. Whole exome sequencing was performed on Next generation sequencing (NGS) platform. Results: A 3-year-old boy born to a non-consanguineously married Indian couple, developmentally normal, presented with recurrent fevers from 6 months of age. Fever was intermittent, high grade; each episode lasting for 4-7 days and recurred 2-3 times a month occasionaly associated with loose stools and vomiting. He was also treated for pneumonia with intravenous antimicrobials twice in the past. Family history was significant as the boy had lost two elder brothers within the first 2 years of life. Both had recurrent fevers from 6 months of age. While the first boy did not receive any blood transfusion, the second boy was transfused blood only while he was critically ill. No immunological or genetic studies had been performed in either of the children. Both parents and three daughters were healthy. Systemic examination was normal. Immunological work up showed panhypogammaglobulinemia and low B cells. This in the setting of a family history suggestive of X-linked inheritance, a provisional diagnosis of X-linked agammaglobulinemia was made and he was started on monthly intravenous immunoglobulin (IVIG) transfusions. Despite which, he continued to have episodic periodic fevers and intermittent episodes of diarrhea, with no response to antibiotics. Inflammatory parameters were found to be elevated during the febrile episodes and they were normal while he was afebrile. Genetic evaluation showed compound heterozygous mutation in TRNT1 gene: exon 2c.143_144insTT and exon 7-c.1043A>T on whole exome sequencing. A diagnosis of SIFD was established and the family has been counselled for bone marrow transplant. TRNT1 is an enzyme necessary for mitochondrial and cytosolic tRNA function. A deficiency of TRNT1 disrupts the protein synthesis machinery, leading to multi-organ involvement. The death of two boys in the index family, misled us to think on the lines of a possible X-linked disease. However, occurrence of periodic aseptic febrile episodes with no respite despite regular IVIG infusions, pointed towards an alternate diagnosis such as TRNT1 deficiency. In a recent study on TRNT1 deficiency, hypogammaglobulinemia was detected in 7/9 with persistent B-cell lymphopenia in a few patients. Index case was noted to have panhypogammaglobulinemia and was treated with regular IVIG infusions. He, however, did not have severe anaemia warranting transfusions, retinitis pigmentosa (RP) or developmental delay, highlighting the heterogeneity of mitochondrial diseases. Of late, TNF blockers have been effectively used to treat periodic fevers in SIFD. However, bone marrow transplant offers a more definitive therapy in these patients. Long term neurological outcome in transplanted patients remains undetermined as of now. Sensorineural hearing loss, nephrocalcinosis, panniculitis, myofascitis, hemophagocytic lymphohistiocytosis, thromboembolism have been reported in a few cases of TRNT1 deficiency. Fortunately, index case has none of the above mentioned manifestations and is under close follow-up. Conclusion: TRNT1 deficiency must be considered as a differential diagnosis in children presenting with periodic fevers and hypogammaglobulinemia. We describe a 3-year-old boy with periodic aseptic febrile episodes, hypogammaglobulinemia and low B-cells due to TRNT1 deficiency. Methods: Analysis of 28 childhood cases SD/SS was done. All patients (pts) had satisfacted for disease criteria (Sjogren's International Collaborative Clinical Alliance = SICCA, 2012г). All children carried out physical examination, salivary glands ultrasound investigation, sialometry, sialography, tests for xerophthalmia. Lab test included the measuring of CBC, total protein (TP), α-, βand γglobulins, IgA, IgM, IgG, rheumatoid factor (RF), ANA, ENA-profile with anti-SSA/Ro and anti-SSB/La detection. Results: we observed 28 pts, aged from 3.5 to 17 years, the mean age 10.5 years, 24 girls and 4 boys (girls/boys = 7:1). SD was diagnosed in 13 girls. SS was diagnosed in 15 pts. Systemic lupus erythematosus (SLE) and SS -11 pts ( 9 girls, 2 boys), systemic scleroderma (SSD) and SS -2 girls, juvenile rheumatoid arthritis (JRA) and SS -1 boy, juvenile dermatomyositis (JDM) and SS -1 girl. Pts with SD (13) more often had mild course of the disease. Arthralgia, fatigue and low subfebrile temperature after acute respiratory infection was common complaints in all 13 pts (100%). Two girls had hemorrhagic nonspecific rush. Lab investigations revealed increased ESR in all pts (100%), leukopenia in 6 (46%) pts. Due to prolonged arthralgia, fatigue and subfebrile fever subsequent studies revealed hyper γ-globulinaemia (100%), ANA and RF in unexplained high titers (100%), and SSA/SSB antibodies (100%). Only two girls complained of dry mouth. And also two girls had episodes of recurrent parotitis. So the diagnosis was made on average 6-12 months after the onset by excluding other systemic diseases and by instrumental investigations. Salivary glands ultrasound investigation revealed initial stage of parotitis in all pts (100%) that was suggested by sialometry and sialography. As to xerophthalmia no one of patients complained of dry eyes. Low lacrimation was detected in 5 girls (38%). Low dose of prednisone and micophenolate mofetil (MF) have been used for treatment in all patients. In compare with SD course SS depend on associated rheumatic diseases and seems more aggressive. Strong fever up to 38C had all pts with SLE, one of with SSD and one pts with JRA. This two pts demonstrated high level of TP, significant hyper γglobulinaemia with polyclonal secretion that required excluding lymphoma. Body weight loss had 6 children (40%). Generalized lymphoadenophaty had 8 pts (40%). Purpura and nonspecific rash registered in 9 (60%) children. Seven pts (46%) demonstrated Raynaud phenomenon. Six pts complained of dry mouth and 5 pts complained of dry eyes in disease onset. Twenty six pts (90%) with SS/SD demonstrated good response for immunosupressive treatment with reducing of clinical symptoms (fever, arthralgia, rush, function of salivary glands, lacrimation) after six month of treatment but not for lab parameters. Objectives: Here we describe a 13-year-old patient with recurrent attacks of fever, pleural effusion, and chronic periodontitis, whose genetic workup for autoinflammatory diseases revealed polymorphism in genes coding for the inflammasome proteins. Methods: Genetic workup for autoinflammatory diseases revealed NLRP3 (c.2113 C>A, p.Q705K) heterozygous polymorphism located in axon 5, SH3BP2 (c.1429 C>T, p.R477W) heterozygous polymorphism in exon 11 and MEFV (c.605 G>A), p.R202Q) heterozygous polymorphism in exon 2. Results: A 13-year-old male patient, with a history of chronic periodontitis, was hospitalized with fever, chest pain, shortness of breath and fatigue. A computed tomography (CT) scan of the thorax revealed atelectasis at lower lobes of the left lung and left-sided pleural effusion. Two years later, recurrent symptoms with left sided pleural effusion led to the second and third hospitalisation of the patient. On the second attack, the MEFV genetic analysis revealed c. 605 G> A (p. R202Q) (p. Arg202Gln) heterozygous polymorphism, which has not been reported so far with such severe symptoms. However, colchicine 1.5mg/day was initiated. The patient was hospitalised again with recurrent symptoms on the third month of colchicine treatment. Genetic testing for the autoinflammatory diseases revealed polymorphism in genes coding for the inflammasome proteins. Clinical symptoms such as recurrent fever, myalgia, pleural effusion, and chronic periodontitis in our patient were atypical compared to the CAPS forms described at present. Therefore, canakinumab treatment was initiated. He remains symptom-free at one year on canakinumab and colchicine treatment. Conclusion: The relationship between clinical heterogeneity and weak genotype phenotype in CAPS has been previously reported, and it has been shown that disease expression may be affected by other factors in addition to specific gene polymorphism. It is proposed that NLRP3 variants with unknown clinical significance may be associated with atypic inflammatory presentation. In our case, we presumed that the associations of NLRP3 Q705K polymorphism with R202Q and SH3BP2 polymorphisms have aggravated the clinical presentation and caused the resistant findings. Objectives: We aim to describe NLRP3 gene mutations clinical presentation and relationship of phenotype and genotype. Methods: The data of 320 patients from next generation sequencing genetic database of autoinflammatory diseases, Umraniye Training and Research Hospital, Department of Pediatric Rheumatology, were included in the study. Patients with VUS-likely pathogenic or pathogenic mutations in the NLRP3 gene were collected from these patients. In at least three months of follow-up, patients with autoinflammatory disease (AID) compatible recurrent episodes (with high acute phase response) were included, in which other etiological reasons (infectious, autoimmune, malignant diseases) were excluded. Demographic, clinical and laboratory data, treatments and responses of patients were presented Results: 23 patients (16 male, 69.6%) were included in the study. The median age (IQR) at disease onset was 29 months ( 9 months -5 years) and the median disease duration (IQR) was 33 months (14-40 months) . The mean number of febrile episodes was 11.2±7.3 per year and the mean duration of fever attacks was 4.45±2.50 days. The history of AID in family members was in 6 (26%) patients and consanguinity was in 3 patients. All patients were characterized by symptoms consistent with recurrent inflammatory syndrome. 52.2 % of patients (n= 12) presented with urticarial rash, 39% (n=9) with tonsillitis, 82.6% (n= 19) with arthralgia, 30.7 % (n=7) with conjunctivitis, 17.4 % (n=4) with headache. In 11/23 patients had worsening symptoms with cold contact. The phenotypes of PFAPA (n=5,21.7%), CAPS (FCAS and MWS) (n=11,47.8%) and undifferentiated AID (uAID) (n=7, 30.4%) were determined . There was no statistical significance between phenotypes in terms of median age at onset of attacks (>0.05). The most of patients (n=19, 82.6%) had Q705K variant in NRLP3 gene. Patients carrying the q705k variant had 26.3% PFAPA, 42% FCAS and 31.6% uAID phenotype. In 13 (59%) patients responded to colchicine treatment. Remained 9 (40.9%) patients had partial response or unresponsive to colchicine, were achieved to inactive disease with anti-IL 1 treatments. Conclusion: We suggest that the Q705K variant causes autoinflammatory syndromes in a variety of phenotypes. Introduction: Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome is the most common periodic fever syndrome in children. It is a benign self-limiting multifactorial disorder with an estimated incidence of 2.3/10000 children up to 5 years of age. Year 2020 was dramatically affected by the Covid-19 pandemic, with a yet undefined impact on several aspects of child health. Objectives: To describe the demographic and clinical features of pediatric patients with recurrent febrile episodes referred to a single centre, with a focus on cases with onset in 2020. Methods: Patients referred to the Pediatric Immunology and Pediatric Rheumatology departments between 01/01/2015 and 01/ 05/2021 for recurrent fever without an infectious cause were included in the study. Demographic, clinical and laboratory features were retrospectively reviewed and compared between patients with fever onset before and after January 1st, 2020. For the classification of PFAPA, both the modified Marshall criteria and the Eurofever/ PRINTO criteria were used. Resolution of PFAPA was defined in presence of a 3-month fever-free interval. For statistical analysis, Mann-Whitney U test and Fisher's exact test were used as appropriate.

Results: 84 patients were included; 33 were female, 82 were white. Median age at onset was 3.7 years (IQR 2-4.6, range 0.3-12.9). Median length of follow-up was 1.3 years (IQR 1.1-2.3, range 0.5-6.4 years). 57/84 (68%) patients met the modified Marshall criteria, 72/82 (88%) patients met the Eurofever/ PRINTO criteria for PFAPA. Thirty-nine patients had disease onset between 01/2015 and 12/19, while 45 patients in 2020. One patient with onset in 2015 and resolution in 2018, restarted presenting recurrent fever in January 2020. In 29 patients recurrent fever resolved during the follow-up, 39 in the 2015-2019 cohort and 10 in the 2020 cohort. Median follow-up since onset was 2.4 years in the 2015-2019 group and 1.1 years in the 2020 group. While median age at onset was not significantly different in the two groups (3.2 vs 3.8 years), in patients with onset in 2020 median time to referral was shorter (14.3 vs 7.5 months, p<0.0001) and recurrent fever episodes tended to resolve faster (median 2.3 vs 0.9 years, p<0.0001). Aphtous stomatitis and lymphadenitis appeared more common in patients with onset before 2020 (64% vs 32%, p=0.0062 and 84% vs 58, p=0.0322 respectively). Duration of fever episodes and intercritic interval, periodicity, prevalence of pharyngitis, abdominal pain and arthralgia were not significantly different between the two cohorts. 

We observed an increase in referrals for recurrent fever with onset during 2020. Demographic and clinical features did not significantly differ between patients with onset in 2015-2019 and patients with onset in 2020, with the exception reduced occurrence of aphtous stomatitis and lymphadenitis, and faster referral and resolution for the latter. Whether an increase in parental attention and concern for fever episodes, or environmental factors, including SARS-CoV-2, contributed to the increase of referrals for recurrent fever still needs to be clarified. Introduction: Chronic non-bacterial osteomyelitis (CNO) and its severe form chronic recurrent multifocal osteomyelitis (CRMO) are considered as rare autoinflammatory diseases. It is a heterogeneous condition and is characterized by recurrent attacks of localized bone pain, swelling or loss of function in any area, mainly affecting the metaphysis of the long bones, clavicles, vertebrae, and pelvis. The pathophysiology of the disease is not fully understood, but it has been shown that there is unbalanced cytokine expression and increased inflammatory activation in patients' monocytes, a proinflammatory response contributing to osteitis. Results: The child attended the emergency department with difficulty in breathing (respiratory rate > 60/min, Paco2= 55mmHg), and low fever. Radiograph of lung demonstrated diffuse lung opacities and initial impression was of bacterial infection, so antibiotics were administered, without improvement. During her hospitalization, she entered a state of complete oxygen dependency, with increasing needs of high flow oxygen supply and occasionally fever spikes accompanied by elevation of acute inflammatory indexes: WBC (max 29.000/μl), CRP (130mg/L), ESR (51mmHg), Ferritin (360ng/ml) and SAA (30,7mg/L). While none of pathogen was identified by laboratory investigation, administration of corticosteroids was attempted with good treatment response (1-2 mg /kg/d). CT lung scan revealed diffuse lung disease and whole exon sequencing confirmed the cause. Until now, the identified mutation has been described in 8 children, all of whom of Arabic ethnicity [2] . Treatment with baricitinib, a JAK-1, 2 inhibitor, was commenced in increasing dose with impressive response (max dose: 10mg per day). As a result the deterioration of the disease stopped and at the same time the status of our patient improved: needs of oxygen supply decreased to 2 liters normal flow, oral steroids tampered (0,2mg/kg/d) and the respiratory status improved. Conclusion: Interferonopathies are the newly added subject of current inflammatory syndromes uncovering decisive steps of etiological pathways and treatments [1] . One of them is SAVI, recognized in 2014. SAVI is formally presented as peripheral necrotizing vasculitis on which lung fibrosis and end stage respiratory failure develops [3] . There are a few cases in literature with initial lung involvement and vasculitis development under environmental circumstances [4] . Our patient never developed any kind of skin involvement, even if she had past exposure to cold. Diagnosis was challenging. Early diagnosis and treatment are of vital importance in order to avoid progression to pulmonary failure, which is the first cause of death in SAVI [3] . Clinical suspicion of SAVI among infants, presented with severe, intractable respiratory distress, is of prime importance in order to diagnose the disease, using whole exon sequencing test examination. 'Chance favors the prepared mind', Louis Pasteur. Introduction: Mutations in the phospholipase C gamma 2 (PLCG2) gene are typically associated with a spectrum of diseases ranging from allergy and immunodeficiency to autoimmunity and autoinflammation [1] . PLCG2 gene variants can cause the PLCG2associated antibody deficiency and immune dysregulation (PLAID) and the autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. In recent years, awareness for monogenic syndromes with concomitant symptoms of autoinflammation and immunodeficiency has expanded. However, making a diagnosis is still challenging. Objectives: To elaborate phenotype and genotype characteristics of five patients with suggestive history for autoinflammation and immunodeficiency.

Methods: This is a single center case series of five patients (P). P1 is a 44-year-old mother of 14 (P2) and 11 year (P3) old boys and twins (male/female) aged 4 years (P4, P5). They presented with recurrent fevers, episodes of conjunctivitis, lymphadenopathy, headaches, myalgia, abdominal pain, cold induced urticaria and upper airway infections. In P1 symptoms appeared in early adulthood. P2-P5 are affected since infancy. Family history was unremarkable. Parents were not consanguineous. Work-up included physical and laboratory examinations (genetic panel test, flow cytometry for lymphocyte subsets, expression of Interleukin (IL-)2, IL-4, IL-17, IFNγ, and CFSE proliferation of T cells. High-frequency pure tone audiometry (HF-PTA), ophthalmology examination and skin biopsy were performed. Results: Examination confirmed conjunctivitis (P1-5) and mild hearing loss (P1, P2). Skin biopsy in P1 indicated urticaria. Serum amyloid A and S100A8/A9 were slightly elevated during flares. Unswitched B-cells were decreased. Naive IgD + CD27 -B-cells and unswitched IgD + CD27 + B-cells were decreased, switched IgD -CD27 + B-cells were slightly increased (P1-5). T-cell function was normal. Genetic testing revealed a new heterozygous missense variant (c.77C>T, p.Thr26Met) in the PLCG2.

A literature search in Pubmed and Infevers yielded reports on PLAID patients with cold-induced urticaria, recurrent infections, signs of autoimmunity, allergic diseases and granulomatous dermatitis along with immunologic findings (reduced immunoglobulins (Igs), low circulating class switched memory B cells, reduced NK cells). In APLAID patients, rash, granuloma, cutis laxa, eye inflammation, recurrent infections, abdominal pain/inflammatory bowel disease, musculoskeletal complaints and immunologic findings (reduced/normal Igs, reduced circulating class-switched CD27 + memory B-cells, decreased/ normal NK-cells) were reported. P1-5 showed similarities to both, PLAID (cold-induced urticaria) and APLAID (eye inflammation, musculoskeletal complaints, no circulating antibodies). In addition, they displayed PLAID and APLAID symptoms (recurrent infections, abdominal pain/diarrhea, normal T-cell function). Sensorineural hearing loss (P1, P2) was reported in one APLAID patient [2] . Conclusion: This case series describes a new heterozygous missense PLCG2 variant (c.77C>T, p.Thr26Met) which might cause a phenotypical overlap of PLAID and APLAID disease patterns.

Introduction: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common recurrent fever syndrome in children. PFAPA has often a good prognosis, but disease activity dramatically impacts health-related quality of life, family and psychological wellbeing. Thus, disease control is imminent. Colchicine may be effective in reduction of disease activity in PFAPA. Objectives: To evaluate the effectiveness of colchicine for PFAPA in children.

Methods: A cohort study of consecutive children diagnosed with PFAPA treated with colchicine was performed between 03/2012 and 12/2020. Patients were excluded if (i) genetic AID testing revealed any gene variant, (ii) they had elevated liver enzymes or decreased kidney function. Demographics, clinical features, inflammatory parameters and PGA/PPGA were collected. Disease activity was defined as patient/parent (PPGA) and physician (PGA) global assessment recorded on a 10 cm visual analogue scale, with 0 representing no and 10 maximal disease activity. PPGA/PGA was captured at baseline (colchicine start) and at follow-up. Primary outcome was colchicine effectiveness defined as improvement of disease activity (PPGA or PGA ≥2). Results: A total of 30 PFAPA patients were included, 50% were female, median age was 5.2 years (1-10.75). At baseline, the median PPGA was 4 (0 -9) and median PGA was 3.5 (0 -6). All patients had fever (mean 40.08°C, ± 0.58°C). Median flare frequency was 4 weeks (1 -6); flares lasted 3 to 6 days. Lymphadenopathy (100%), pharyngitis (97%) and aphthous stomatitis (47%) were commonly reported. During flares, serum amyloid A (mean 423 mg/l, SD ± 327) and C-reactive protein (mean 5.05 mg/dl, SD ± 4.8) were elevated. In the past, 11 patients (37%) were treated with corticosteroids (CS). CS reduced flare intensity in all, but increased frequency in 9 patients (82%). Median follow-up time was 3.9 months (2 -10.6). Primary Outcome: colchicine was effective in 19 patients (63%). Of these, 13 patients (43%) achieved a PPGA reduction ≥2 and 14 patients (47%) a PGA improvement ≥2. No PPGA or PGA changes were seen in 4 and 3 patients, respectively. Secondary Outcome: Children with CS mediated increased flare frequency experienced on colchicine PGA (100%) and PPGA (55%) improvement. At follow-up, a total of 17 patients (57%) experienced any PPGA improvement and 25 (83%) had any PGA improvement. Median PPGA and PGA decreased to 2 (0 -8 and 0 -4, respectively). Conclusion: Colchicine was effective in controlling disease activity in PFAPA patients. More than 60% of PFAPA patients had a PPGA or PGA improvement ≥2. In patients with CS mediated increased flare frequency colchicine effectively reduced disease activity. Taken together, colchicine is an effective treatment in PFAPA and a potent alternative to CS, particularly in PFAPA patients with CS mediated increased flare frequency. Susanne M. Benseler and Jasmin B Kuemmerle-Deschner have contributed equally to this work and should be therefore be considered as co-senior authors. Introduction: IgA vasculitis (IgAV, Henoch-Schoenlein purpura, HSP) is the most common form of childhood vasculitis. The Paediatric Vasculitis Activity Score (PVAS) is an objective tool used for scoring all types of vasculitis in clinical trials and it includes 64 manifestations of various active vasculitides. However, the inclusion of some subsystems such as chest, cardiovascular and ENT suggest it may not be specific enough for evaluating IgAV disease activity. Objectives: The aim of this study was to develop and perform preliminarily validation of a vasculitis activity scoring tool designed specifically for IgAV (the IgA-VAS) and compare performance to the PVAS. Methods: A cohort of children with IgAV were retrospectively scored in February 2021 using both the IgA-VAS and the PVAS. Test validity, concurrent validity and inter-rater agreement were assessed. A randomly selected subgroup were also scored using a physician visual analogue scale as a marker of global disease activity. Any domains which scored 0 for all patients were excluded from the analysis. Results: The IgA-VAS consists of 40 manifestations, each with a score from 0-10, divided into 5 domains: cutaneous, gastrointestinal, musculoskeletal, renal and other. For preliminary validation, retrospective scoring was performed in a single tertiary centre over a 5-year period. 196 children were identified; 153 met inclusion criteria. 54% were male with a median age of 5.7 years (range 0.6-16.7). Median total scores for the IgA-VAS were 7/125 (range 2-31) and 5/125 (range 2-29) for rater 1 and rater 2 respectively. Median PVAS scores were 6/63 (range 2-25) and 5/63 (range [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] . Correlation between all overlapping domains of the two tools was strong (all r>0.5,p< 0.001). Inter-rater reliability overall was low for both tools (0.131 and 0.225, p<0.001). For the IgA-VAS, inter-rater reliability was low for the cutaneous, renal and other domains (0.332, 0.237, 0.288 p<0.001) and high for the gastrointestinal and musculoskeletal domains (0.543 and 0.667, p<0.001). The general, cutaneous and renal subsystems in the PVAS had a low inter-rater reliability (0.347, 0.213, 0.304, p<0.001) and was better for the abdominal domain (0.579, p<0.001). The IgA-VAS moderately correlated with the visual analogue scale for both raters (r=0.482, r=0.362, p<0.05), however the PVAS strongly correlated with rater 1 (r=0.504, p=0.004) and moderately correlated with rater 2 (r=0.372, p=0.043). Conclusion: The IgA-VAS has improved since its initial circulation however further work is needed to optimise the tool before prospective validation. Introduction: Familial Mediterranean Fever (FMF) is a prototypic autoinflammatory disorder associated with MEFV pyrin-encoding gene mutations, characterized by unprovoked episodes of inflammation. In a substantial number of patients with familial Mediterranean fever (FMF) only one mutation within the MEFV gene (MEditerranean FeVer gene) can be found. Objectives: To analyse whether colchicine can be terminated in a subgroup of these patients without reoccurrence of symptoms and/ or inflammation. Methods: All FMF-patients registered in the German AID-registry (Autoinflammatory Disease registry) and the international Juvenile Inflammatory Rheumatism cohort (JIRcohort) with a heterozygous MEFV-genotype and confirmed clinical FMF diagnosis, that stopped colchicine treatment during follow-up, where enrolled. Duration of colchicine withdrawal, reasons of re-introduction, and epidemiologic characteristics of the patients successfully terminating colchicine in comparison to patients re-introducing the medication where analysed. Results: We identified 169 heterozygous pediatric FMF patients, in 44 of them colchicine therapy was discontinued. Among those, 27 stayed in colchicine-free remission during a follow-up of 2,04 ± 1,55 years after discontinuation. Compared to heterozygous FMF patients continuously taking colchicine (n=125) and patients who had to resume colchicine after temporary discontinuation (n=17), these patients were treated with lower initial colchicine dosages, 0,7 ± 0,32 mg/day vs 0,77 ± 0,38 mg/day (not significant). They were older at disease onset (4,84 ± 3,15 years vs 4,04 ±3,86 years) and in tendency they had lower initial CRP-levels during subclinical disease (15, Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. It was recently shown that the most common additional two diseases were juvenile idiopathic arthritis (JIA) and immunoglobulin (Ig) A vasculitis in children with FMF. Furthermore, it was demonstrated in the studies involving all age groups that the frequencies of spondyloarthropathies, Behçet disease, Sjögren disease, polyarteritis nodosa (PAN), inflammatory bowel diseases, multiple sclerosis (MS), and psoriasis were increased in patients with FMF. Objectives: Given the strong genetic background of FMF, the diseases that have been previously demonstrated as co-exists in children with FMF should also be investigated in the other family members. Therefore, we aimed to examine the diseases of first-degree relatives (FDRs) of our pediatric patients with FMF in the present study. Methods: In total, 449 patients with FMF and 147 patients with JIA who are being followed up at Istanbul University-Cerrahpasa Department of Pediatric Rheumatology and 93 healthy controls were interviewed between March 2019-November 2019 during routine outpatient visits. The medical conditions of their FDRs were asked. Among the FDRs of index cases, those with FMF were excluded from the study. Results: The mean age of healthy children (n=93), patients with FMF (n=449), and patients with JIA (n=147) were 7.7 ± 4.6 years, 12.6 ± 4.8 years, and 11.6 ± 5.2 years, respectively. A total of 3071 FDRs (FMF:1975, JIA: 690, Healthy Children: 406) were included in the study. While the most common medical conditions reported among the FDRs of the patients with FMF were asthma (n=90, 4.5%), tonsillectomy history (n=66, 3.3%) and type 2 diabetes (n=59, 2.98%), the most common medical conditions detected among the FDRs of the patients with JIA were type 2 diabetes (n=17, 2.4%), asthma (n= 15, 2.1%) and tonsillectomy history (n=13, 1.8%). Among the FDRs of the healthy children, asthma (n=15, 3.69%), tonsillectomy history (n= 12, 2.95%), and type 2 diabetes (n=6, 1.47%) were the most commonly detected ones. The frequencies of acute rheumatic fever (ARF), asthma, allergic rhinitis, and appendectomy history were significantly higher among the FDRs of the patients with FMF compared to other FDRs (all <0.05). Conclusion: This is the first study evaluating the FDRs of patients with FMF. ARF, asthma, allergic rhinitis, and appendectomy history were found to be significantly more frequent in FDRs of the patients with FMF compared to the FDRs of healthy children and the patients with JIA. Introduction: We describe a case of non-specific colitis as the first manifestation of an autoinflammatory disease. Objectives: A., 12 months old, comes to our attention for severe normocytic anemia, without signs of hemodynamic failure. From 3 months of age, A. had a history of bloody diarrhea during exclusive maternal breast-feeding. This condition was diagnosed as allergic proctitis and maternal diet free of milk and derivatives was started. The weaning was conducted in a diet free from milk too. Despite a reduction in bloody diarrhea complete resolution of the symptom never occurred. At admission to our Center, the patient performed a colonoscopy, which revealed the presence of small, eroded translucent nodules and bleeding mucosa suggestive of nodular lymphoid hyperplasia throughout the colon. Histological examination showed active colitis without signs of colitis IBD or allergic colitis. After discharge, we began oral steroid therapy and gastroenterological follow-up. Two weeks later, during steroid withdrawal, A. came to Emergency Room for acute panniculitis of the limbs for which we prescribed an anti-inflammatory therapy. After 48 h the skin condition worsened and she was febrile and suffering. Therefore, A. was hospitalized for further investigations. Blood tests showed a rise in inflammation indexes. Given the inflammatory status, intravenous steroid therapy was started with rapid response. At each attempt to stop steroid treatment, the same symptoms recurred. We also noted the presence of adverse effects related to therapy (Cushing-like aspect and irritability). Methods: In differential diagnosis, the following hypotheses were evaluated and relative tests were performed. 1) Haematological disease: bone marrow aspirate negative for neoplastic conditions. 2) Infectious disease: swabs for viruses and bacteria, as well as serological tests all negative. No history of COVID19 or contact with COVID19 patients. 3)Immunological/inflammatory disease: family history of autoimmune conditions (father with recurrent oral aphthosis, vitiligo and thyroiditis) and unkown diseases with earlyonset (paternal grandfather with liver disease started when he was young, brother of paternal grandfather died at 16 years old due to unexplained causes). Therefore, first level autoimmune tests were done, resulted all normal. Then the possibility of early-onset chronic inflammatory bowel disease (VEO-IBD) were evaluated but genetics was negative. Finally, since autoinflammatory genesis was suspected, interferon signature and molecular investigations of the main known genes responsible for auto-inflammatory diseases were performed. These tests revealed mutation in TNFAIP3, leading to the diagnosis of haploinsufficiency A20 (HA20). In view of this diagnosis, therapy with a biological drug, IL1 receptor antagonist (Anakinra), was started. Results: HA20 is an autoinflammatory disease due to a loss of function of A20 protein, whose role is to down-regulate the proinflammatory pathway of NF-kb. It is autosomal dominant, with earlyonset and with very heterogeneous manifestations even within the same family. This condition is often called Behcet-like, with which it shares some features (oral ulcers, gastrointestinal and skin involvement). Regarded A., the disease appeared at 3 months of age with ulcerative colitis and later skin manifestations started. Probably father and paternal grandfather have the same condition but with milder manifestations. Conclusion: This case taught us that HA20 should be considered in patients with very early-onset inflammatory disease, characterized by colitis as the first manifestation and cutaneous involvement, often with positive family history. Introduction: Intermediate uveitis (IU) is described as inflammation in the anterior vitreous, ciliary body and the peripheral retina. The diagnostic term pars planitis should be used only for that subset of IU where there is snow bank or snowball formation occurring in the absence of an associated infection or systemic disease (that is, "idiopathic"). It is usually bilateral and is usually asymmetric in severity. Pars planitis is a chronic condition that may reoccur for many years. Hereby, we are presenting one rare case report of a 13-year Libyan girl who was diagnosed with intermediate uveitis Objectives: illustrating importance of not considering all types of uveitis as pars planitis, and the need to rule out sarcoidosis, multiple sclerosis and Lyme disease as possible causes. Methods: case report study Results: A 13-year-old Libyan, female presenting to our Rheumatology clinic, Dec/2020 with blurred vision and floating objects for one month involving her Lt > than Rt eye, not associated pain nor irritation, with history of previous episodes of bilateral uveitis in 2017 and 2018. Managed with topical steroids and mydriatics under ophthalmology care. There was no history of trauma, headaches, tick bites, fever, rash, joint pain or swelling, cough, respiratory distress, oral ulcer, no weakness, numbness, or clinical features suggestive of enthesitis or other organ system involvement. There was significant family history of autoimmune diseases (vitligio, psoriasis, her father has vaculitis churge Strauss syndrome). Neurological examination was free with pain free eye movement, no diplopia . On detailed ophthalmological evaluation, she was found to have the presence of vitreous reaction more on left eye suggesting inflammatory exudates, predominantly near pars plana region (vitritis), thereby diagnosis of bilatral intermediate uveitis (pars planitis) was established, with no retinal (no macular edema), corneal, or choroidal involvement. She was evaluated to exclude other systemic associations such as JIA, sarcoidosis, TINU and MS. Blood tests, CBC with differential, ESR, CRP, Toxocara, CMV and Toxoplasma titres, ACE level, serum creatinine, ANA, (HLA) B27, testing for syphilis, TB, hepatitis, HIV, c-ANCA, p-ANCA and RF all were within normal limits, chest X-ray and MRI brain were within normal limits, urinary β2-microglobulin also normal . Diagnosis was consistent with idiopathic pars planitis with no macular oedema and minimal visual acuity involvement. She was started on local therapy, followed by oral steroid (prednisolone) 1 mg/ kg/day for 2 weeks, tappered over the next 4 weeks. Her vision improved dramatically, with V/A 10\10 bilaterally. A relapse after few months bilateral pars planitis affecting Lt eye more (moderate vitritis and minimal decreased in visual acuity of left eye 6\10). She was started a short course of repeat oral prednisolone for 4 weeks and on methotrexate injection at 15 mg/m2/week in April 2021, with consideration of Humira (40 mg/every other week) according to her response. Conclusion: To highlight the importance of the detailed description of type of uveitis by ophthalmologists considering that they are playing a major role and can guide the rest of work up and management in such cases. Objectives: To evaluate visual function (VF) and QoL in children with JIA-U and idiopathic uveitis. Methods: A cross-sectional study was conducted in two tertiary Pediatric Rheumatology Centres, enrolling all patients seen with JIA-U, JIA without uveitis and idiopathic uveitis. VF was assessed by a translated form of the available EYE-Q, adapted for cross-cultural feasibility into a 10-question tool, while QoL was evaluated by the Italian version of the Pediatric Rheumatology Quality of Life scale part of the Juvenile Arthritis Multidimensional Report (JAMAR), shortened for feasibility to an 8-question tool. JAMAR section on treatment compliance and school attendance was also included. Parents, and patients when appropriate, were asked to complete each patient/parent-reporting outcome measure, answering on a 4-point Likert scale, with a total score ranging from 0 to 72 (worst condition). Medical charts were reviewed regarding JIA and uveitis features and outcome. Quantitative and qualitative variables were compared by means of Mann-Whitney U test or chi-square/Fisher exact test, as appropriate; correlations among quantitative nonparametric variables were evaluated by Spearman's test. Results: We describe results from 170 patients enrolled (72.9% female), with a median age at study time of 12.9 (9.3-16.4) years. Seventy-seven had JIA-U, 72 JIA without uveitis and 21 idiopathic uveitis. Uveitis was active in 22/98 patients (22.4%), with a median of uveitis duration of 8.0 years (3.7-13.0). Almost all children with uveitis were on systemic treatment (89/98, 90.8%) at the time of interview; 48.0% of patients presented an ocular damage, with 7.1% having a best corrected visual acuity (BCVA) < 4/10. Total score, VF and QoL scores resulted significantly higher in JIA-U patients compared to JIA without uveitis, while no differences were noticed among children with uveitis with or without JIA (Table 1) . VF was significantly worse in patients with ocular damage and BCVA < 4/10 (p 0.0242 and 0.0039, respectively). In patients with uveitis, VF and QoL showed a significant correlation (r 0.47, p <0.0001) especially in patients with idiopathic uveitis (r 0.61, p <0.0001). Conclusion: Visual function is a crucial component of QoL in children with uveitis and it correlates with ocular damage. Since eye involvement significantly affects QoL in patients with JIA, a specific tool widely validated and cross-cultural adapted is highly demanded in the clinical care of JIA-U patients.

Disclosure of Interest None declared Introduction: Nonetheless the most frequent form of uveitis in paediatric age, there is fair evidence regarding chronic idiopathic uveitis (CIU) in childhood Objectives: To describe the demographic, clinical, laboratory and ophthalmological characteristics of children with CIU Methods: This is a multicentre retrospective chart review observational study recruiting children affected by CIU, who attended the uveitis clinic of Bristol and Firenze Children Hospital (1 st Jan2019 -31 st Jan 2020). Demographic, clinical and laboratory data of enrolled children were collected at disease onset, and at 3, 6, 12 months, and the last available follow-up Results: Data of 126 (61 F) children with diagnosis of CIU were entered. The median age at diagnosis was 9.3 years (3-16 years), median time of follow-up 46 months (4-149 months). 111 (88.8%) were Caucasian, 5 (4%) African, 5 (4%) Asian, 3 (2.4%) Arab and 1 (0.8%) mixed. Uveitis was bilateral in 106 patients (84.1%). Sixty-eight patients had an anterior involvement (54%), 29 intermediate (23%), 15 anterior plus intermediate (11.9%), 13 panuveitis (10.3%) and one a posterior involvement (0.8%). Ocular signs and symptoms at onset have been reported in the 77.9% of patients (95), of whom 31.6% reported ocular pain (30), 57.9% ocular redness (50) and 55.8% blurred vision or floaters (53). The mean of ESR was 11.9 mm/ h (SD ±12) and of CRP was 0.47 (SD ± 0.92). ANA positivity was reported in the 26.1% of patients, ANCA in the 5.5%. ANA positive patients were younger than ANA negative (F18.1, p< 0.001), as well as ANA positivity was more frequently in female gender (χ 2 3.9, p 0.04). At the onset, the 54.7% of patients (47) had normal VA, while impaired visual acuity and blindness were reported respectively in the 31.4% (27) and 14% (12) . The mean value of best corrected visual acuity (BCVA) was 0.425 LogMAR (SD ± 0.63). At the last available follow-up, the 83.2% had a normal VA (99) while impaired VA and blindness were reported in the 12.6% (15) and 4.2% (6) respectively. The mean value of VA in LogMar was 0.14 (SD ± 0.42). A significant improvement in VA logmar was observed in all patients at the last available follow-up (p <0.001). The 85.6% of patients (89) showed at least one complication at onset, while 46.8% (59) at the last follow-up. Stratifying by different anatomical subtypes, anterior uveitis was more frequently in Asians (χ 2 : 4.5 p= 0.034). ANA were significatively more frequently positive in patients with the anterior subtype (χ 2 : 15.1 p= 0.002). No differences have been detected in age at onset. At the onset, panuveitis had worse BCVA (0.9, p=0.03), an increased number of complications (4, p=0.011), and was associated with the presence of retinal vasculitis (χ 2 36.1, p<0.0001). Conversely, anterior uveitis presented more frequently posterior synechiae (χ 2 19.1, p <0.000) and band keratopathy (χ 2 15.8, p =0.001). At the last available follow-up, a significative proportion of cataract were observed in panuveitis (χ 2 The role of potential predictors for lack of response to treatment has been assessed at bivariate and multivariate levels. Furthermore, a multivariable logistic model has been applied in order to estimate the strength of association between predictors and outcome, adjusting for potential confounders. Results: Data from 152 JIA-U patients were analysed (82.2% female), with a median follow up of 12.0 years (IQR 9.9) and a median age at uveitis onset of 4.8 (4.1) years. In 72 patients (43.4%) at least one biologic DMARD (bDMARDs) to control uveitis was required. Compared to patients responsive to a monotherapy with a DMARD (n=38), children requiring a bDMARDs for uveitis had a lower median age at uveitis onset, a longer disease duration and a greater frequency of bilateral uveitis at onset (Table) . No difference was observed in uveitis activity grade at onset. Despite similar frequency of ocular damage at onset, patients not responsive to DMARDs showed a higher percentage of ocular damage at last visit (66.7% vs 39.5% p=0.011). Multivariable analysis confirmed younger age at disease onset as an independent factor for lack of response to DMARDs (p 0.018). Male gender is associated with higher frequency of ocular surgery (33.3% vs 12.4%, p=0.043), and, despite the inaccuracy of the estimate due to limited sample size, acts as an independent factor in multivariable analysis with an almost 9 times higher risk to lack of response to DMARDs (p=0.049). Introduction: Paediatric-onset granulomatous uveitis (PGU) is rare. In addition, the lack of awareness often leads to diagnosis delay and poor visual outcome. Determining the underlying cause is essential and challenging. In addition, the care of these patients still lies on very little data.

To evaluate the demographics, aetiologies, complications, treatments and visual prognoses of paediatric noninfectious granulomatous uveitis Methods: Retrospective chart review of PGU occurring in children before 16 years of age and recruited from the paediatric rheumatology department at Bicêtre Hospital, France from 2001 to 2021. Our study excluded infectious uveitis. Our definition of inactive disease and remission followed the Standardization of Uveitis Nomenclature criteria. (1) Results: We included 43 patients with 80 affected eyes: 24 had idiopathic uveitis, 13 had sarcoidosis-associated uveitis, 3 had NOD2 mutation-associated uveitis, 2 had juvenile idiopathic arthritisassociated uveitis, and one had Vogt-Konayagi-Harada disease. The median age at diagnosis was 10.2 years. Sex-ratio M/F was 0.72. Features of PGU were mostly: panuveitis (63%), bilateral (84%), and evolving chronically (84%). Granulomatous features consisted in mutton-fat keratic precipitates (65%) in all aetiologies. Choroidal granulomas and iris nodules were present more in sarcoidosisassociated uveitis than in idiopathic uveitis (31% vs 17%, p=0.4 and 38% vs 8%, p=0.07). All but 5 patients with sarcoidosis had ocular symptoms before other manifestations, which included mainly lung damage in 38%, then liver damage (23%), lymph node involvement (23%), lymphocytic meningitis (23%), arthritis (15%), hearing loss (8%), and cutaneous lesions (8%). Features leading to diagnosis of sarcoidosis were mainly lymphopenia, hypergammaglobulinemia, elevated lysozyme and ESR. None of the investigations were relevant for the diagnosis of Blau syndrome, excepted screening for NOD2 mutation. None of the patients with NOD2 mutation exhibited neither granulomatous polyarthritis and dermatitis, nor extraocular symptom. Ocular complications at diagnosis and/or during follow-up were present in 62 eyes out of 80 (78%). The most used treatments were systemic corticosteroids (79%), methotrexate (79%), TNF-alpha monoclonal antibody (42%), and azathioprine (16%). Twenty-seven per cent of eyes were on remission at last follow-up, 67% were inactive and 5% remained active. The median duration of follow-up was 4.8 years. Conclusion: We report herein the first significant cohort focused on paediatric non-infectious granulomatous uveitis. PGU are idiopathic in most cases. Sarcoidosis-associated uveitis are associated to laboratory tests abnormalities. A high rate of complications is associated with PGU. However, a significant proportion of uveitis became inactive or achieved remission, following the use of systemic treatments as corticosteroids, immunosuppressants and/or biologics. patients treated with both biologics and MTX, in 65% of eyes there was no need for TGC therapy. Overall, in the 48th month of followup, in 50% of eyes there was no need for TGC therapy, and the rest required 1-2 daily doses of TGC. At the end of the first year, with MTX and biological therapy 75% of eyes had grade 0 of inflammation in AC and in 48th month 61.1% of eyes achieved grade 0 of inflammation. In the 12th month of application of biological therapy, in addition to MTX, in our study in 75% of eyes a grade 0 of inflammation was achieved with ≤2 doses of TGC, and in the 48th month in 61.1% of eyes. If the results are presented according to milder criteria, then in the 12th month of follow-up 90% of the eyes have a degree of inflammation ≤0.5+ with ≤2 doses of TGC, and in the 48th month all patients achieved a degree of inflammation ≤0.5+ with ≤2 doses of TGC. Conclusion: It was shown that the results of treatment outcomes during follow-up largely depend on the selected outcome measures, i.e. the criteria for the effectiveness of therapy. This will be important for future research because it suggests caution that in the pursuit of better results, setting different limits can lead to a more favorable outcome. Table 1) . None of them presented RF-positive polyarthritis, nor systemic JIA (sJIA). In JIA-U cohort, 60% (35/58) presented isolated joint involvement at onset. Median time from diagnosis to uveitis was of 19 months. Articular and ocular inflammation occurred simultaneously in 19 children; uveitis preceded arthritis in 6.9%. Each uveitis episode was initially treated with topical steroids and mydriatics. Most of JIA-U patients (87.9%) were already on c-DMARDs at ADAstart. Compared to the cohort without uveitis, they were younger both at onset and at baseline and started TNF-α inhibition later. Forty-five (77.6%) experienced recurrent uveitis (median frequency of 3 episodes) before starting ADA. Among JIA-U patients, there were no differences in gender, age at disease onset, ILAR JIA subtype and ANA positivity between active disease (AD) and clinical remission on therapy (CM) cohorts at 6 and 12 months from baseline. At baseline, 32 of the JIA-U children showed ocular complications, including posterior synechiae (n=29), visual loss (n=10, BCVA 20/40), cataract (n= 9), band keratopathy (n=6) and glaucoma (n=1). Uveitis flares between 12-24 months were mostly bilateral, as well as at baseline; those occurred by 6 months from ADA start and after withdrawal were more frequently unilateral. There was no joint effusion on ultrasonography of the left knee and right wrist. Ophthalmologic and cardiac evaluations were normal. He was treated with non-steroidal anti-inflammatory drugs (NSAI Ds) and on day 7 metronidazole was started with impressive clinical improvement. On day 12, a single dose of intramuscular benzylpenicillin was administered. One month later, he was asymptomatic and laboratory values were normal. When re-evaluated 3 years later, the patient was still free of symptoms. Conclusion: Parasitic rheumatism is a rare condition characterized by inflammatory aseptic joint manifestations due to a parasitic infestation. The clinical presentation of this reactive arthritis may be very heterogeneous and can mimic the clinical picture of different inflammatory rheumatic diseases making it a challenging differential diagnosis. It seems to rely on genetic predisposition, which may explain its uncommon occurrence despite the high prevalence of parasitic infestation worldwide. The failure of NSAID's, along with the notable efficacy of specific anti-parasitic treatment in a patient with a parasitic infestation, are the main hallmarks. When caring for a patient coming from an endemic area of parasitosis with osteoarticular complaints, even with none or mild gastrointestinal manifestations, a high index of suspicion is suggested, and when correctly treated, the prognosis is excellent. (Table) . She met the HLH-2004 primary HLH criteria and she was treated with emapalumab in the context of the primary HLH trial. She had complete remission with normalization of CXCL9. In June 2018 (after 10 months from last emapalumab) she presented a progressive increase in liver enzymes (ALT 1333 UI/l, AST 851 UI/l, LDH 822 UI/l), with no other HLH features. The liver biopsy was suggestive for autoimmune hepatitis. Treatment with oral prednisone (1 mg/kg/die) was started with progressive normalization of liver enzymes and continued for 8 months up to February 2020. During these months she presented recurrent episodes of fever with thrombocytopenia, increased levels of inflammatory markers, transaminases, LDH with mild hyperferritinemia (< 1500). All these episodes were managed with transient increase in GCs. In February 2020, she developed arthritis (wrists and knee) and she was referred to our attention. At this time she met the ILAR criteria for sJIA and the EULAR/ACR MAS criteria (ferritin 3.460, PLT 64.000, triglyceride 220; fibrinogen 385, AST 100). Abdominal CT showed splenomegaly and hepatomegaly, with disseminated round lesions. Chest CT showed initial signs of interstitial lung disease. Intravenous methylprednisolone (3 pulses of 30 mg/kg) followed by oral prednisone (0.5 mg/kg) and anakinra (5 mg/kg) were started without significant improvement. She then presented a further episode of MAS with severe marrow and liver involvement. CXCL9, neopterin and IL-18 levels were persistently elevated. Emapalumab was started, on compassionate use regimen. After 5 months of emapalumab she achieved complete clinical remission with normalization of laboratory parameters. GCs were tapered to <0.2 mg/Kg after 4 months and discontinued after 7 months. After 13 months of emapalumab, CT showed complete resolution of the liver nodular lesions, of splenomegaly and of lung involvement. CXCL9 and neopterin levels normalized, while IL-18 levels decreased, but remained persistently elevated. Regarding the complete hematic biometry, the presence of cytopenias is describen in 1 line in two patients (11.7%), two cell lines in eight patients (47%) and three cell lines in seven patients (41.3%). A finding of hemophagocytes in bone marrow was evidenced in 12 patients (70.5%) The JIAs an SLE groups are compared by analyzing each of the criteria individually, finding statistical significance in the cytopenia criterion, with 100% of the patients with SLE presenting affection of three cell lines (p 0.001) codition explained by the pathophysiological bases of each of the diseases described above.

The score was given to each variable determined by de HScore with a mean of 272.9, median of 271 an mode of 297 points respectively. Concluding that it is possible to diagnose MAS with HScore variables in 100% of the studied patients. When comparing the JIAs and SLE groups, no statistical significance is found in the final absolute value of the HScore, with which it is possible to conclude that the Hscore has no variation in terms of the associated base pathology, establishing then, that obtaining the necessary score allows to do diagnose of Macrophage Activation Syndrome and therefore its application is possible in the face of the different associated comorbidities. Conclusion: The high mortality rate of these conditions highlights the importance of early and timely recognition to establish treatment strategies. This being the main reason why it seeks to establish new criteria that facilitate its application and that in turn have high sensitivity an specificity for the diagnosis. The objective of applying these criteria is to simplyfy laboratory tools using more widely available markers.

Considering that at this time, the HScore criteria have not yet been validated in the pediatric population, however, the study and application of them in our population establishes the possibility of diagnosing Macrophage Activation Syndrome from the initial or early stages, a situatioin that allows to implement early and aggressive treatment of the underlying disease. Normalized NanoString counts were used for comparisons. Groups were compared using non-parametric statistics. Correlation analyses and hierarchical clustering analyses were performed. Gene expression signatures were derived by using the geometric mean of normalized NanoString counts of the respective gene sets.

Results: On an individual gene level, there were substantial differences in expression between HC and AD, pre-MAS and MAS samples for many genes, with highest expression levels in MAS samples. In contrast, for CIITA, lower expression levels were seen in these disease states, compared to healthy controls. Conspicuously absent were significant differences in CXCL9 expression between disease states. Using correlation analyses across different disease states and using hierarchical clustering analysis, distinct gene expression signatures were identified, which we termed type 1 IFN, IFNγ and innate immunity signatures. While there was a probable gradient of expression levels, with a more prominent type 1 IFN signature in MAS > pre-MAS > AD > CID > HC, and a consistently elevated innate immunity signature in AD, pre-MAS and MAS, differences were not seen for an IFNγ signature (Table) . On the 17 th day, the fever pattern changed and became persistent; hepatosplenomegaly became more evident, and he developed distributive shock. Analytically, there was a decrease in hemoglobin and leukocyte count, a slight decrease in platelet count, severe hyperferritinemia (> 54 000 ug/L), elevation of aspartate transaminase, elevated triglycerides, and a decrease in ESR. The diagnosis of MAS was made and he started methylprednisolone pulses. He completed 5 pulses of methylprednisolone, maintaining high dose corticotherapy and initiated anakinra 3 mg/kg/day with marked clinical, inflammatory and MAS markers improvement. On the 8 th day of anakinra, the clinical and analytical condition worsened and, despite raising anakinra to 5 mg/kg/day, a second MAS was diagnosed. Due to raised liver enzymes (> 5 higher than the upper normal limit), anakinra was suspended two days later, he repeated pulses of methylprednisolone and started IV cyclosporine with clinical and laboratory improvement allowing to restart anakinra.

One year later, he is off steroids, symptom-free, maintains therapy with anakinra, and is suspending cyclosporine. HLH, primary and acquired immunodeficiency genetic panels revealed no pathogenic mutations.

Conclusion: Among pediatric rheumatic diseases, MAS is most commonly seen in patients with sJIA. 1,2 It is characterized by the acute onset of persistent high fever, pancytopenia, hyperferritinemia, hepatosplenomegaly, liver dysfunction, and coagulation abnormalities. 1, 2, 3, 4 Regardless of the criteria used, if sJIA is suspected, sudden worsening of the clinical condition should raise a high suspicion of MAS. 5 If left untreated, MAS can progress to multiorgan failure and be fatal. 1, 3 In this case, rapid recognition and prompt therapy were critical to this child's survival and good outcome. Heterozygous perforin-pathway mutations and mutations of other immune pathways that result in cytokine storm syndrome have been described in MAS patients. 3, 4 Despite a difficult-to-treat MAS, no pathogenic mutation was found in this patient. Introduction: Magnetic resonance imaging (MRI) can detect musculoskeletal inflammation in patients with juvenile idiopathic arthritis (JIA). Whole-body MRI (WBMRI) is a promising imaging technique as it enables us to assess multiple joints in one examination. However, less is known about young people's experience of undergoing MRI scans and their willingness to have these tests. Objectives: To describe the experience of young people who underwent a WBMRI scan for research purpose, designed to assess joints for inflammation, and their willingness to have this investigation again in the future. Methods: Sixty patients, 47 JIA and 13 controls with noninflammatory musculoskeletal pain, aged 14-24 were recruited in a tertiary hospital for a prospective study which measured the prevalence of subclinical synovitis on WBMRI. The scan was performed with gadolinium in a 3 Tesla scanner and lasted 45-60 minutes. All participants completed an anonymised questionnaire, immediately after the MRI examination. The age, gender and presence or absence of JIA diagnosis were recorded. Fivepoint smiley face Likert scales were used to rate anxiety and pain levels during the scan. The likelihood of agreeing to undergo a repeat WBMRI scan for clinical reasons in 6 months' time was recorded as definitely not, not likely, likely, or definitely. The mean ± standard deviation was calculated for age, and absolute and relative frequencies (%) were calculated for ordinal data. The chi-square test was used to compare ratings and t-test for the comparison of numerical data between groups. Results: Forty female and 20 male participants completed the survey. Two male patients with JIA did not complete the second page of the questionnaire, which included the question of having a repeat scan. The mean age of JIA patients and controls in years was 18.3 ± 2.4 and 16.5 ±1.2 (p=0.012), respectively. The pain and anxiety ratings in young people with JIA and controls are shown in the Table. A higher proportion of JIA patients rated their anxiety levels as 'okay' or 'totally fine' compared to controls (83% vs 54%, p=0.028). Male patients reported more frequently that they felt 'totally fine' in terms of anxiety, compared to female patients (65% vs 28%, p=0.005). There were no significant differences in the pain levels experienced during the scan between males and females, or between JIA patients and controls. Almost all patients (57/58, 98%) answered that they were 'likely' (24/58, 41%) or would 'definitely' agree (33/58, 57%) to have a repeat scan in 6 months if advised by their doctor. Conclusion: The majority of young people, predominantly patients with JIA, who underwent a research WBMRI scan for the assessment of synovitis, reported either mild or absent symptoms of anxiety and pain during the scan. Almost all patients would likely or definitely be agreeable to undergo a repeat scan in 6 months, for clinical reasons. In conclusion, WBMRI appears to be an acceptable imaging technique amongst young people who received this test. Introduction: Computerized color telethermography (CCTT) is an established diagnostic procedure in clinical practice that is used for assessment and follow-up of patients with microcirculatory disorders in adult population, such as Raynaud's phenomenon (RP). However, CCTT is still not validated in pediatric patients with RP. Objectives: To analyze the CCTT findings in children and adolescents with clinically suspicious RP and its relationship with age, gender and season as well as with biochemical and immunological laboratory findings. Methods: Retrospective study included pediatric patients with suspected RP who underwented CCTT diagnostic procedure at the University Hospital Centre Zagreb from 2010 to 2019. Laboratory findings included inflammatory parameters, complete blood count, renal function tests and immunological tests (ANA, ENA screen, ANCA, RF, antiphospholipid antibodies, serum IgG and complement levels). Differences between categorical variables were examined using Chi-Square test and among numerical using t-test, followed by logistical regression analysis. Results: Out of 225 patients with suspected RP, 176 were females (78.2%) and 49 were males (21.7%) giving a female to male ratio bigger than 3:1. In 44 patients (19,6%) CCTT was compatible with the diagnosis of primary RP, 68 patients (30,2%) were classified as In these two categories, estimation of patients who were able to achieve clinical disease remission at 12 months since disease onset was evaluated. Reliability of US was assessed on still images by the two sonographers who performed US examinations and was calculated using kappa (k) statistics. Any discrepancies on US findings were then resolved through a discussion between the sonographers before data analysis.

Results: Twenty-seven new-onset JIA patients were found to have clinical involvement of the ankle among the joints affected. Nine of them (33.3%) showed on US isolated arthritis of the ankle, whereas US-detected tenosynovitis with or without arthritis was found in 18 (66.7%) patients. The percentage of patients who were able to achieve disease remission at 12-months was the same (66.7%) for patients with and without US-detected tenosynovitis in the ankle (12/ 18 and 6/9 patients, respectively). Seventeen patients were not treated with biologics: also in this subgroup no difference was found in the rate of clinical remission at follow-up between patients who had isolated arthritis (8/17) and patients who had tenosynovitis (9/ 17) with or without arthritis at US baseline assessment (5/8 and 4/9 patients in clinical remission, respectively). In patients with USdetected tenosynovitis and clinical remission at 12 months, the lateral tendon compartment (LTC) was the tendon site more frequently affected by pathology (75%). Patients with US-detected tenosynovitis that did not achieve clinical remission at follow-up had the highest frequency of tendon pathology on US in the medial tendon compartment (MTC) (83.3%). The anterior tendon compartment was the less frequently affected in all patients (33.3% both in patients with and without clinical remission at the follow-up visit). Intraobserver reliability of US was excellent for both the sonographers (k=0.92 and k= 1.00). Interobserver reliability of US was moderate (k=0.65). Conclusion: US-detected tenosynovitis of the ankle is common in patients with new-onset JIA with ankle clinically active disease and is more frequent than the detection on US of isolated arthritis. The MTC and LTC are the tendon compartments more commonly affected. The detection on US of tenosynovitis at disease onset in ankles with clinical disease activity does not seem to affect the chance to achieve the overall clinical disease remission compared to patients without tendon pathology but with joint disease in the ankle region. Methods: Children with clinically inactive and clinically active JIA who underwent static CE-MRI of the knee were included. Synovial SI was evaluated on post-contrast T1-weighted fat-saturated images using a 0.02 cm 2 region of interest drawn in the area of the synovium that contained visually the highest SI. To control for time-dependent postcontrast enhancement variability, a ratio between the SI of the synovium to the musculus gastrocnemius was calculated. Objectives: To compare knee joints of JIA patients with and without arthritis using pD and bM to determine the most sensitive US views in an international multicenter study. Methods: Patients aged ≤ 18 years attending with clinical symptoms of arthritis of 1 or both knee joints in 6 participating centres were recruited. Standardized US examination was performed (Table 1) using a linear transducer and bM and pD findings were graded 0 (normal)-3 (severe) according to the adapted OMERACT-US score.

Results: A total of 75 individual knee joint examinations in 53 patients were performed, knees without arthritis were controls. Patient reported symptoms of arthritic knees were swelling (98%), loss of function (85%) and pain (83%). At the time of scanning, 57% of patients were using NSAR therapies, 23% methotrexate, 2% biological and 2% oral steroids. In BM, the commonly used anterior longitudinal standard view performed in 30°remained the most sensitive for assessing effusion when used as independent view. However, PD in lateral parapatellar and lateral longitudinal views were more sensitive than the typically evaluated anterior longitudinal and transverse in neutral view. The highest sensitivity for hypervascularization was seen in the parapatellar views, the lateral longitudinal and the anterior transverse and longitudinal views performed at 30°. and transition clinic (7.9; SD 2.6) were higher than satisfaction with adult care (7.7; SD 2.2). Satisfaction with preparation for transfer (6.8; SD 3.0) was the lowest score but showed negative correlation with time since transfer (beta -0.34).

Low physician global assessment (PGA) at time of transfer was associated with high HR-QoL after transfer. Conclusion: The long-term HR-QoL in our cohort is lower than that of the general population, although problems with self-care (8.8%), mobility (31.6%) and pain/discomfort (56.1%) of JIA patients are comparable to literature (10.7%; 25.2%; 56.4%) (2). Continuity of care was higher than in similar studies (74.0%) (3). Satisfaction with the HCT program was high, including a recent significant increase in satisfaction with preparation for transfer. While the burden for rheumatic long-term patients remains elevated, a structured interdisciplinary HCT program can improve patient satisfaction and soon, hopefully, long-term HR-QoL. Introduction: Children with cancer often present with diffuse signs which complicates the diagnostic process, especially if musculoskeletal symptoms are the initial manifestation of malignancy. Arthritis and arthropathy are the most frequent symptoms leading to cancer misdiagnosed as rheumatic disease. Joint involvement, although well-recognized in children with acute lymphoblastic leukemia, has only rarely been described in children with other types of cancer. Yet, limited data exist on the prevalence of musculoskeletal diagnoses prior to cancer diagnosis in children. Objectives: Our objective was to identify the prevalence of musculoskeletal diagnoses leading to hospital contact within six months preceding cancer diagnosis in children. Secondarily, to evaluate whether preceding musculoskeletal diagnoses affected survival. Methods: Design, Setting, and Participants: We used data from population-based medical registries covering all Danish hospitals to identify a cohort of children diagnosed with cancer over a 23-year period . We compared children with musculoskeletal diagnoses recorded within six months preceding the cancer diagnosis and children without musculoskeletal diagnoses using prevalence ratios and 95% confidence intervals (CI). Exposure: A musculoskeletal diagnosis (ICD10 codes, M00-M99) recorded in the Danish National Patient Registry within six months before cancer. Main Outcome and Measures: Survival measured as five-year overall survival, crude, and adjusted hazard ratios. Results: Among 3,895 children with cancer, 7% (n = 264) had at least one musculoskeletal diagnosis recorded within six months preceding cancer diagnosis. These 264 patients had a total of 451 visits across Danish hospital departments with a median of two visits (range 1-10). The overall median physician's diagnostic interval from first musculoskeletal diagnosis to cancer diagnosis was 15 days (IQR 7-47). The five-year overall survival did not differ for children with a prior musculoskeletal diagnosis 84.5% (95% CI 79.2-88.6) compared to those without 84.2 (95% CI 82.9-84.4), except for spinal tumors being favorable for those with a prior musculoskeletal diagnosis: adjusted hazard ratio: 0.23 (95% CI 0.05-0.98). Conclusion: A preliminary musculoskeletal diagnosis occurred in 7% of children with cancer but did not affect overall survival. Furthermore, this study provides an insight into musculoskeletal diagnoses prior to cancer diagnosis. Introduction: It is estimated that juvenile idiopathic arthritis (JIA) persists into adulthood in at least one-third of patients, but it is not clear how frequently hospital services are used beyond age 16. Objectives: To describe characteristics related to disease persistence in young people (YP) with JIA using electronic health records (EHR) in England. Methods: YP with JIA were identified from primary care EHR (Clinical Practice Research Datalink GOLD and Aurum databases) between 2003 and 2018. JIA was identified if they had a Read code for JIA and either >=3 Hospital Episode Statistics (HES) outpatient specialist care (rheumatology/ophthalmology) appointments or a HES inpatient admission coded with JIA, prior to age 16. Further, cases needed to have linkage to HES data, registration at the same GP for >1 year beyond age 16. Cases were followed from the earliest of first Read code or first HES outpatient appointment until leaving their GP or end of 2018. YP with >=1 specialist care outpatient appointment beyond age 16 were considered to have "persistent disease". YP were considered discharged from specialist care (a proxy for disease remission) if they had >=1 year between the last appointment and end of study follow-up. For both databases, patient characteristics and characteristics of discharged are presented, stratified by disease persistence. Results: Of 192 and 903 YP eligible for the study, 135(70.3%) and 639(70.8%) had persistent disease in GOLD and Aurum, respectively. Those with persistent disease were older at first JIA code and more likely to be female compared to those without persistent disease (Table 1) . Overall, 90/192(46.9%) and 453/603(50.2%), in GOLD and Aurum respectively, remained in specialist care after age 18. Of those with persistent disease, approximately 41% were discharged prior to the end of study follow-up, with 33% and 29% discharged between ages 16-18 in GOLD and Aurum respectively. The median age of the last visit was 14 for those without persistent disease and 18 for those discharged after the age of 16. Disease duration was longer in those discharged after age 16. Conclusion: Over two-third of patients with JIA continue to have hospital visits beyond age 16. Of those, however, approximately 4 in 10 were discharged from specialist care by the age of 18. These data provide important information for YP with JIA and their families, as well as clinicians running, developing and planning young adult services in paediatric and adult rheumatology. Concerns about their long-term safety in children and young people has prompted many clinicians to consider tapering or stopping these treatments in patients who have achieved remission, but currently it is unclear whether this is an effective decision and what proportion of children will flare and require further biologic therapy.

Objectives: This analysis aimed to estimate the proportion who stop biologic therapy for remission, how long they were on therapy prior to stopping, how many then re-start biologic therapy and after how long.

Methods: All children and young people with JIA registered on their first biologic without a history of uveitis into the UK JIA Biologic Registers from 1-Jan-2010 up to 1-Feb-2021. Systemic JIA patients were only included if they were starting either IL-1 or IL-6 inhibitors. Other JIA patients were only included if they were starting a TNF inhibitor. Time on drug prior to remission was calculated from the original start date of the biologic therapy, until the date the therapy was stopped for remission, regardless of interim episodes of stopping due to non-remission reasons. Tapering could not be identified, only stop of therapy. Results were stratified by systemic and non-systemic JIA to account for the differences between ILAR subtypes. Results: A total of 878 children and young people with JIA were included. Of the 793 non-systemic JIA patients starting TNF inhibitorsthe majority polyarticular RF-(37%), extended-oligoarticular (19%), and ERA (15%) -131 (17%) patients stopped their first biologic for remission after a median of 2.2 years (IQR 2.0, 2.9). However, 44% later re-started biologic therapy, usually the same biologic (84%), after a median of 4.7 months. Of the 85 systemic JIA patients starting IL-1 or IL-6 inhibitors, 25 (29%) stopped their first biologic for remission after a median of 2.2 years (IQR 1.5, 3.2). However, 20% later re-started biologic therapy, usually the same biologic (80%), after a median of 4.4 months. There was no evidence to support that more systemic JIA patients were stopping for remission; age and gender adjusted hazard ratio 1.3 (95% CI 0.8-2.0) compared with non-systemic JIA patients. Conclusion: In this large UK study, around 1 in 5 children had their biologic stopped following achievement of remission. For children with non-systemic JIA, almost half restarted their biologic within 2 years, although this proportion was lower for systemic JIA. These data suggest that tapering biologics rather than stopping completely should be explored in some children to minimise biologic exposure without triggering a flare. [10] [11] [12] [13] [14] [15] years, and at evaluation was 36 [28-43] years. Of the 55 cases, 45 (82%) were employed, four were students, four were mainly housekeeping with no remuneration, and the remaining two cases were unemployed. Of the 45 employed patients, 36 (80%) were fulltime and 9 (20%) were part-time. The employment rate was 82%, which was similar to the women's rate in Tokyo for the same age group (76-81%). The type of jobs was categorized into three types. Patients who have mainly engaged in a sedentary job (e.g., administrative work, accounting work) were 35 (71%), a job that mainly a walkaround (e.g., salesperson, nurse) were 7 (14%), and a job that requires much standing (e.g., teacher, shop clerk) were 3 (6%). Significantly more patients with a disability certificate were engaged in sedentary work than those without (95% vs. 52%, p<0.01). The median [IQR] time since their first job was 15 [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] years, 28 (57%) patients had changed jobs at least once, and of these, 8 (16%) patients had changed jobs because of JIA. However, there was no difference[MH1] in the era of onset or disease duration between patients who changed jobs and not. The most common method of commuting was public transportation with 24 (49%) patients. Regarding commuting time, 23 (47%) patients took less than 15 minutes, 11 (22%) took 15 to 30 minutes, and 6 (12%) took more than 60 minutes. These results tended to be slightly shorter than the average commute time of 44 minutes in Tokyo. There were 27 (59%) patients with an annual income of fewer than 4 million yen. Among them, 11 (24%) had an annual income fewer than 2 million yen. Moreover, none had an annual income of more than 10 million yen. This result was similar to women's average annual income of 2.8 million yen in Tokyo. Regarding to academic background, 95% of patients had graduated high school, and 49% had a college degree. Conclusion: In the long-term disease course, the majority of the adult JIA patients were working, and the impact of the disease on work productivity was limited, despite some patients changed jobs because of the JIA. The commuting time was shorter compared to the general population of the region. Furthermore, the patients tended to be engaged in mainly sedentary office work, especially patients with functional disability. Objectives: This study aimed to evaluate which JIA patient disease characteristics might lead to self-management skills improvement in the transition readiness process. We also wanted to explore the readiness of JIA patients and their families for the transition process into the adult health care system. Methods: We have recruited different JIA patient subtypes and their parents from a single study center. Demografic data were collected and Transition Readiness Assessment Questionnaire (TRAQ) was applied to all patients and their parents at one time point. Results: A total of 44 JIA patients (9 males and 35 females; median age 15.12 years, range 12.33 to 19.33 years; median disease duration 4.29 years, range 0.42 to 17.5 years) and their parents were enrolled. Fourteen (31.82%) of 44 JIA patients had a concomitant disease while 10 (22.73%) of them had uveitis. Eleven (25%) of them had a family history of autoimmune diseases. In total, 21(47.7%) of JIA patients were receiving biologics. There was a strong correlation between older patient age and total TRAQ score among patients (ρ= 0.799, p<0.0001) and a moderate correlation between older patient age and total TRAQ score among parents (ρ=0.522, p<0.0001). Total TRAQ score has a strong correlation between patients and parents (ρ=0.653, p<0.0001). We could not find any association of JIA patient characteristics (JIA disease subtypes, disease duration, gender, concomitant diseases, uveitis, family history of autoimmune diseases, number of hospitalizations, and treatment with biologics) with TRAQ scores and JIA patients' and parents' readiness for transition. Conclusion: Transition readiness of JIA patients increase with advancing age. There is no difference between transition readiness for JIA patients and their parents. Future studies with a larger sample size and new insights are needed in order to facilitate this challenging transition process. Results: All of our patients were girls. The median age at diagnosis was of 11-year-old, with extremes of 9 and 14-year-old. The interval between onset of symptoms and diagnosis was of 2 months. One of the cases was treated at first as tuberculosis and another one was treated as systemic juvenile idiopathic arthritis. Prolonged fever and arthritis were a revealing pattern in all cases. Meanwhile, we found uveitis in one case, lymphadenopathies in 3 cases, hepatosplenomegaly in 2 cases, interstitial lung disease in 4 cases, and liver failure with cholestasis in one case. Macrophages activating syndrome was a revealing pattern in one case. Acute phase reactants were high in all cases, with medians of ESR of 23 mm the first hour, CRP of 31 mg/L, and ferritin of 340 ng/ml. Meanwhile, hematological involvement was in the form of microcytic anemia in one case, leucopenia in 3 cases, lymphopenia in 2 cases, thrombocytopenia in one case, and aregenerative normocytic anemia in one case. High angiotensin 2 conversing enzyme level was found in all cases, with a mean of 181 ui/L. Biopsy of the lymphadenopathies showed granulomas in one case. Treatment was based on steroids alone in one case. Meanwhile, associated immunosuppressive therapy was needed in the remaining cases. Azathioprine was prescribed in 2 cases, methotrexate in one case, and mycophenolate mofetil in one case. The mean treatment period was of 42 months. Evolution was marked by complete remission in one case, and recurrence of the symptoms after treatment withdrawal in the remaining cases. One child had blindness after a severe refractory uveitis. Conclusion: Sarcoidosis symptoms are nonspecific and often lead to misdiagnosis. Management can be difficult in the pediatric population, and recurrence of the disease after treatment withdrawal is frequent. Objectives: The purpose of this study was to answer the following questions: 1. Which are the most informative questions to infer patient's disease activity? 2. Are these informative questions the same for JIA children and parents? Methods: We included 71 children with JIA according to ILAR criteria, all of them receiving treatment and we followed them up for a year. JAMAR questionnaires were answered by both children and parents at baseline, 6 and 12 months. Also, a thorough clinical examination was performed in every visit: all the joints were clinically assessed for swelling, tenderness, and limited range of motion, Juvenile Arthritis Disease Activity Score (JADAS), disease activity state, parents and patients assessment through Visual Analogue Scale (VAS), physician's VAS, Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) were recorded. We applied state of the art machine learning methods in order to find the most relevant questions in JAMAR. The objective was to predict if a patient was clinically active or inactive according to the clinical criteria. Each question from the JAMAR was treated as a potential feature. Additionally, we utilized tensor decomposition to identify relevant patient clusters. Furthermore, we correlated these critical questions with clinical and biological parameters recorded. Results: A total of 374 JAMAR questionnaires were analyzed with our Machine Learning algorithms. First, we trained and evaluated several classifiers and identified those that performed the best. Second, in order to understand better how our features (questions) are performing in our algorithm we calculated and plotted the weight of each question. Finally, we identified a small group of questions as the most relevant for patients and parents. The identified questions exhibited better correlations with the JADAS scores than the nonrelevant ones. Not all the most informative questions were the same for JIA children and their parents, highlighting the need of considering these discrepancies when interrogating the parents or JIA patients. Conclusion: In this study, we revised the JAMAR questionnaire by applying modern data mining techniques in a longitudinal dataset. Our results suggest that a small number of questions in the JAMAR questionnaire provide significant information and correlate well with the JADAS scores. We argue that this reduced set of questions could make the data collection easier by trading off the number of questions for frequency and ease of self-reported data collection. More work is needed to make the best use of the information and capabilities that JAMAR offers to physicians. Introduction: Parent-and child-reported outcomes (PCROs) are measures that reflect the parent and child perception of rheumatic disease course and effectiveness of therapeutic interventions. Among PCROs for the assessment of patients with juvenile idiopathic arthritis (JIA), the most widely adopted is the parent/patient global evaluation or well-being visual analogue scale (WB-VAS). Several studies in JIA have highlighted the discrepancies in the assessment of the disease status between the physician and the parent/patient. This difference might be due to the WB-VAS measuring a broader construct than the physician global assessment (PGA). Objectives: To evaluate, in a large multinational sample of JIA patients, the disease characteristics of subjects considered as inactive by the physician with an increased WB-VAS score. Methods: Data from the multinational dataset of patients enrolled in the Epidemiology Treatment and Outcome of Childhood Arthritis (EPOCA) study were analyzed. We have included only subjects with a PGA score of 0. PCROs were collected through the juvenile arthritis multidimensional assessment report (JAMAR). We compared demographic features, socio-economic status, level of education, subtype of JIA diagnosis and the main PCROs (pain level, presence of morning stiffness, count of joints with swelling or pain, functional ability, disease activity level, ongoing therapy, presence of medications side effects and health related quality of life measured with the pediatric rheumatology quality of life (PRQL) scale) between subjects with WB-VAS ≤ 1 and > 1. Results: A total of 3537 patients were sorted into two groups according to the WB_VAS score: 2862 subjects were included in a first group (WB_VAS ≤1); 675 in a second one (WB-VAS >1). Respectively, 17,6% and 18,1% of families belonged to the lower socio-economic status, 70,5% and 71% to the intermediate, 11,9% and 10,8% to the higher. The percentages of patients in the three levels of education was not different in the two groups:20,2% and 22% in the lower, 48,9% and 50,1% in the intermediate, 30,8% and 27,9% in the higher level of education. No significant difference was observed in the distribution of JIA categories in the two groups. Subjects in first group were younger at disease onset (5.6 vs 6.4 years). Comparison of main PCROs results is presented in the 

We have analyzed the variables that might determine a difference between the physician's assessment of inactive disease and the parent's/patient's perception of well-being. In particular, socio-economic status, level of education, and gender representation seem not to impact on the general perception of well-being, while pain seems to have the greatest influence on the parent/patient quality of life assessment. Finally, children with lower WB-VAS score were younger at disease onset. Introduction: Rheumatic diseases (RD) are a group of diseases characterized by the development of a wide range of comorbid conditions, primarily of the cardiovascular system. In routine practice, the state of the heart is usually assessed by the work of its left ventricle. However fibrosis of the lung tissue often develops with the involvement of the pulmonary artery system in the process. Therefore, the study of the right ventricle is important in RD. According to the consensus on the use of biomarkers, the N-terminal inactive fragment (NT-proBNP76), which accumulates in specific granules of cardiomyocytes, is currently of great importance in the diagnosis of heart failure.

In the presence of symptoms, in adults its level is more than 125 pg / ml and in children from 1 to 16 years old more than 83 pg / ml, should be regarded as a diagnostically important criterion.

Objectives: To study the systolic function of the right ventricle (RV) myocardium in adolescents with rheumatic diseases, taking into account the level of NT-proBNP in the blood. Methods: 52 adolescents with RD at the age of 13.11 ± 0.89 years were examined. This group included 9 patients with systemic lupus erythematosus (SLE) and 43 with juvenile idiopathic arthritis (JIA). The control group consisted of 44 healthy peers aged 14.73 ± 0.32 years, comparable in age. In order to determine the functional state of the RV of heart, an ultrasound examination was carried out on the LOGIO V2 apparatus by General Electric (USA), with a 3Sc-RS transducer in M-and B-modes. The ejection fraction of the right ventricle (EFRV), minute (MV) volumes, heart rate (HR) were determined. The study of NT-proBNP in blood was carried out by the method of competitive immunoassay on the analyzer IMMULITE 2000, Siemens. Statistical processing of the obtained data was carried out using the SPSS17 software package (license 4a180844250981ae3dae-s/nSPSS17) on the PC / Pentium-4 computer.

Results: The level of EFRV in patients with RD was significantly lower than in adolescents in the control group (46.99 ± 2.92 % versus 58.51 ± 1.77 %; p < 0.001), but at the same time, the minute volume (MVrv) in children of this group was higher than in children in the control group (MVrv 1.05 ± 0.10 l/min versus 0.48 ± 0.03 l/min; p < 0.001). The increase of MVRV in adolescents with RD was due to their higher heart rate (81.67 ± 2.37 beats/min versus 66.61 ± 1.65 beats/ min; p < 0.001). The level of NT-proBNP in the blood of adolescent patients was significantly higher than in the control group (45.71 ± 6.39 pg/ml versus 18.38 ± 0.94 pg/ml; p < 0.001). Correlation relationships between RV systolic function and NT-proBNP level have not been established. Conclusion: In adolescents with rheumatic diseases a significant decrease in the pumping function of the right ventricle of the heart was established with an increase in its minute volume due to the higher heart rate. This occurs against the background of a significantly increased level of natriuretic peptide in them. 1 . The transfer from pediatric rheumatology care to adult rheumatology care is often perceived as difficult and creates a great deal of concern for the adolescents and their parents. 2 To facilitate the transition process, it´s important that both the adolescents and their parents have good knowledge about the disease and treatment. 3 If the adolescent has good knowledge about the disease and treatment it increases the opportunity to take an active role when visiting the rheumatology clinic and to take a greater reasonability for the disease and treatment 3 .

Objectives: The purpose of the study is to investigate how ready adolescents with Juvenile Idiopathic Arthritis (JIA) are to transfer to adult care and to take responsibility for their own health. The purpose is also to investigate parent's perspectives in these issues. Methods: Members, aged 14-18, of Young Rheumatic's, Sweden was invited to participate in the study by responding to the questionnaire "Readiness for transition questionnaire". 4 All patients at the pediatric rheumatology clinic at Astrid Lindgren´s Children´s hospital in Stockholm Sweden aged, 14-18 also received an invitation to participate in the study. Parents of these adolescents were also invited to participate. Results: During the period April 2020 to March 2021, 59 adolescents (girls n= 58, boys n= 10, did not state gender=1) and 58 parents (women n= 44, men n= 14) answered the questionnaire. Preliminary result demonstrates that about half of the adolescents responded that they were the ones taking the greatest responsibility for their health but only 24% of the parents experienced the same. Furthermore, adolescents take responsibility to book visits to the pediatric rheumatology clinic to a small extend, 52% of the adolescents and 54% of the parents stated that the adolescents didn't take any responsibility at all for booking visits. Furthermore, the result show that 48% of the adolescents experienced that they took responsibility to talk to the staff when visiting the clinic, the parents had the same experience. Half of the parents felt that their adolescents was not at all ready to transfer to adult care compared to almost half (46%) of the adolescents. Very few of the adolescents (4%) felt completely ready to be transferred to adult care, which corresponded the parent's experiences (2% There was a significant correlation between low drug level and the presence of ADAb (p<0.05) and between the absence of DMARD and the presence of ADAb (p=0.032). Disease activity is also correlated with low drug level (p: 0.028).

Conclusion: This small real-life pilot study suggested a correlation between disease activity, and low anti-TNF drug levels with detectable ADAb. TDM may contribute to the optimisation of patient care, leading to a personalised medicine approach but for the time being, there are no standardized therapeutic drug levels to aim for. The next goal will be to set optimal drug levels to be targeted on induction and maintenance treatment for patients on ADAL.

None declared Introduction: TNF alpha inhibitors (TNFi), are widely used to treat juvenile idiopathic arthritis (JIA) and usually well tolerated. Among the side effects of these agents, many paradoxical events have been reported such as psoriasiform skin reactions, uveitis and granulomatous diseases (sarcoidosis and Crohn's disease) 1 . Herein, we report the case of 16-years-old girl with oligoarticular JIA (oJIA) who developed SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) as a paradoxical adverse event during adalimumab treatment.

Objectives: Describe the first case of ADA-induced SAPHO-like syndrome in a paediatric patient with JIA. Methods: Case report.

Results: A 14 years-old girl affected by oJIA since the age of 2 years with recalcitrant uveitis was started on adalimumab (ADA) at a standard dose of 40 mg every 2 weeks with progressive improvement of ocular inflammation. Seven months later, the patient presented swelling and pain of the proximal part of left clavicle associated with palmar-plantar pustular rash. She had no history of trauma or recent infections. Laboratory test showed a mild elevation of CRP (7,5 mg/L) and ESR (62 mm/h) with normal white blood-cell count. X-rays showed enlargement of the medial third of the left clavicle with irregular structure with periosteal reaction and, in the same site, MRI showed a spongy bone oedema with osteitis and intense periosteal reaction. Tc 99 bone-scan ruled out other possible sites of bone involvement. Considering the close temporal relationship with the start of ADA, the working diagnosis was ADA-induced SAPHO syndrome. ADA was therefore discontinued and the skin lesions were successfully treated with topical corticosteroids. The bone symptoms did not improve with non-steroidal anti-inflammatory drugs (Naproxen) therefore, 3 monthly infusions of pamidronate were administered with success. Six months later MRI showed a reduction of cortical bone thickening and oedema of the clavicular spongy bone. Because of poor control of ocular inflammation with just MTX, 15 months later, abatacept was added. Almost three year since Sapho syndrome onset, the patient is on stable articular, ocular and bone remission. Conclusion: Since the introduction of biological agents, such as TNFi, treatment options have increased in children with JIA and its prognosis has significantly improved. However, unexpected side effects have been reported, particularly dermatological, intestinal and ophthalmological paradoxical adverse events (PAEs) 3 . To our knowledge, this is the first case of ADA-induced SAPHO-like syndrome in a paediatric patient with JIA. Our experience also suggests that Abatacept may represent an effective treatment option in patients requiring biological treatment in case of PAEs secondary to TNFi. Introduction: Children with pJIA present with five or more joints affected by pain, swelling and stiffness. Untreated, joint inflammation can lead to irreversible joint damage and disability. Corticosteroids have been used for treatment of JIA since the 1950s. Current clinical practice for treatment of pJIA involves high-dose corticosteroids for a limited period in order to decrease inflammation. The aim is to induce remission whilst systemic treatment, commenced alongside corticosteroids begins to work. No standardised, evidence-based approach currently exists to guide corticosteroid induction regimens in pJIA. Objectives:

1. Describe corticosteroid regimens in children newly diagnosed with pJIA. 2. Compare disease activity at diagnosis, with follow-up review after treatment with corticosteroids.

Retrospective chart review of children newly diagnosed with pJIA, January 2019 to December 2020, inclusive. Demographic data collected and steroid regimens documented. Disease activity recorded pre-instigation of corticosteroids, and then at a follow-up appointment on average 5.5 weeks into treatment (range 3-12 weeks). Modified JADAS-27 created using active joint count (AJC), Creactive protein (CRP) and ESR, as physician and patient/parent global assessment scores were missing from the majority of charts. Total score achievable using modified JADAS-27 (mJADAS-27)=47.

Results: Sixteen-children were diagnosed with pJIA between January 2019 and December 2020, (male = 5,15%). Eleven-children (69%) had polyarticular RF-negative JIA (RF-), 3(19%) polyarticular RF-positive JIA (RF+), 1(6%) Psoriatic-JIA (PsA) and 1(6%) HLA-B27 positive enthesitis-related arthritis (ERA). All children were commenced on non-steroidal anti-inflammatory drugs (Naproxen, n=11; Ibuprofen, n=5) and subcutaneous Methotrexate (15mg/m 2 ) alongside corticosteroids.

A three-day course of intravenous methylprednisolone (ivMP) was the initial corticosteroid of choice in 12/16(75%) children. Six children were given a dose of 30mg/kg (maximum 1gram), two children 20mg/kg and four 500mg (weight 30.9-44.2 kg; two children were on oral prednisolone (POPred) prior to admission for ivMP; one child had T1DM). Following 3-days of ivMP, all 12 children were commenced on POPred. The children that did not receive ivMP were commenced on POPred at a dose of 0.5-1mg/kg, with an initial weaning plan of 5mg/week. Two of these children had RF+, one had ERA and the other PsA. AJC ranged from 5-12.

Starting dose of POPred following 3-days of ivMP ranged from 7. Introduction: Despite early intensive treatment with DMARDs (Disease -Modifying Antirheumatic Drugs) for the last twenty years, many pediatric patients are followed up with chronic active disease in the rheumatic diseases such as juvenile idiopathic arthritis (JIA), Chronic nonbacterial osteomyelitis (CNO), Uveitis. Therefore, biological drugs have been used in the treatment of childhood rheumatic diseases in order to decrease the frequency of chronic sequelae and achieve complete remission. Biological drugs are effective in various pathogenetic pathways. Therefore, the choice of medication should be based on the subgroup of the disease. Anti-TNF agents are one of the most commonly used drugs in practice. It is important to know the side effects of these drugs in order for the treatment to be effective and continuous.

Objectives: Anti-TNF agents are used for the treatment of various rheumatologic diseases. We aimed to study the hematological side effects of anti-TNF agents, including infliximab, adalimumab, and etanercept.

We evaluated the patients followed up between December 2019 and December 2020 in the Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey, retrospectively. 93 pediatric patients who were treated with anti-TNFs were included in the study. The demographics, follow up duration on treatment, dose, drug side effects were analyzed. Patients with anemia, thrombocytopenia, and leukopenia (Hb<10.5 mg/dl, WBC<4000 /uL, plt<250.000/mm 3 ) at drug initiation were excluded from the study. Results: 93 pediatric rheumatology patients including 42 juvenile idiopathic arthritis, 29 enthesitis-related arthritis, four CRMO, six DADA2, one PAPA, two UAID, one Behçet' s disease, and 2 psoriatic arthritis were included in this study. The mean age of the study cohort was 14.7±4.1 years. Among our patients, 59 of them (63%) were treated with etanercept, 28 of them (30%) with adalimumab, and six patients (6%) were treated with infliximab. No allergic reactions to adalimumab and etanercept were detected. On the other hand, one patient developed a hypersensitivity reaction against infliximab; thus the treatment was switched to adalimumab. Among all patients, 11 of them (11.8%) had thrombocytopenia, seven (7.5%) of them had leukopenia, and only one of them (1%) had anemia during anti-TNF treatment. 23.7 % of the patients treated with etanercept (15.2% had thrombocytopenia, 6.7% had leukopenia and 1.6% had anemia), %16.6 of the patients with infliximab (thrombocytopenia) and 14.2 % of the patients with adalimumab (10.7% had leukopenia and 3.5% had thrombocytopenia) developed drug-related hematological side effects during follow-up. The mean total duration of anti-TNF drug treatments were 4.6 ± 2.1 years, 5.1 ± 2.5 years, 3.7 ± 0.5 years, for etanercept, adalimumab, infliximab, respectively. Among those who developed hematological side effects, the mean delay between the onset of biologic agent and the onset of the side effects were 11.5 months (range=3-33) for leukopenia and 29.4 months (range=13-48) for thrombocytopenia. And it was one month who developed anemia with etanercept. Conclusion: Anti-TNF agents are being used effectively in daily pediatric rheumatology practice. In this study, we observed that anti-TNF drugs could affect the blood cells, with etanercept bearing the greatest risk in our population. Pediatric rheumatologists and to this day there are no consensus on the best modality for treatment. Objectives: The aim of this study was to search of predictive biomarkers of ineffective treatment by early intra-articular steroid injections in oligoarticular onset juvenile arthritis. Methods: Efficacy of early isolated intra-articular injections (is-IAI) of triamcinolone acetonide in 120 children (met ILAR criteria for JA; 89% girls /11% boys) aged median (IQR) 4,2 (1,6 -7,6) years with oligoarticular onset juvenile arthritis without extra-articular manifestations (oligo-JA) were collected retrospectively and analyzed. Clinical data, radiology and laboratory results (blood and synovial fluid) were evaluated. Triamcinolone acetonide (TA) was administered intraarticular at a dose of 20-40 mg with an injection interval of 3-6-12 months which was depended on the activity of the disease. All children were divided into two groups: active / inactive arthritis based on the effectiveness of is-IAI. The average follow-up was 48 [38; 62] months. Results: 42 children (35%; all girls) were achieved remission oligo-JA after is-IAI of TA with mean of 2 injection per joint (inactive arthritis > 24 months). The mean interval between two consecutive is-IAI was 7 [5,25; 10] months. Other children (54% girls; 11% boys) did not achieve inactive oligo-JA after is-IAI of TA with mean of 3 [2; 4] injection per joint. The mean interval between first two consecutive injection was 5,5 [4,25; 7] months and other injections -2 [2; 3] months. All children who did not achieve remission of oligo-JA for is-IAI were treated by DMARDs. Statistical analyses were performed to determine the relationships between clinical, instrumental, laboratory signs and efficacy is-IAI of TA. In addition to routine studies measures were included cJADAS10 and biological inflammatory markers [interleukin 6 (IL6), tumor necrosis factor alfa (TNF-α) and calprotectin in serum and synovial fluid]. Efficacy is-IAI of TA was no associated significantly with number of active joint of onset oligo-JA, cJADAS10, titer of ANF, serum level of CRP mg/ml, ESR mm/h, IL6 pg/ml TNF-α pg/ml and Calprotectin. 6; 3,7] pg/ml at onset of inactive and active oligo-JA were not significantly differ. The analysis revealed a correlation between a short phase of beneficial effect after is-IAI of TA and risk of activity disease (with an inactive phase of arthritis less than 3 months, the risk activity was OR = 2.09, p <0.001; with an inactive phase less than 2 months -OR = 8.9, p <0.001). Conclusion: TA is an effective and safety treatment in children with oligoarticular juvenile arthritis. Research was revealed that about a third of children with oligo-JA achieved inactive arthritis of average after two intra-articular injections of TA (all girls). There are no biomarkers for prediction of poor treatment response in oligo-JA to early steroid injections. But a short phase of beneficial effect after is-IAI of TA may be sign of risk activity disease. In addition boys with oligoarticular onset juvenile arthritis may be considered like potentially ineffective for local steroid therapy. . Results of proliferative hyperactivity are formed multinucleated giant cells, foam cells and hemosiderophages with thickened synovial membrane to nodules and greatly elongated villious leading to damage joint. Usually only one joint is affected of PVNS, the knee is the most common site involved in 80 percent of cases. There are localized (tenosynovium, giant cell nodule) and diffuse form. There is not a standard method of treatment for PVNS, especially in pediatric patients. Use of radiotherapy in children is controversial due to the possibility of post-irradiation sarcoma.

Objectives: The aim of this study was to investigate of feasibility and efficacy of surgical treatment of PVNS in children.

Methods: Retrospectively were analyzed clinical history, histologic features and radiographic images of 25 children with PVNS (9-17 years old, boys ≈ girls). 10 children were with single nodular, 14diffusing form of PVNS. Chronic monoarthritis of knee had 87% (diffuse, nodular), elbow -12% (diffuse), ankle -4% (nodular) children. All children were insensitive to anti-rheumatic therapy (methotrexate, steroids, anti-TNF). Surgical treatment of PVNS was removal of the nodule by means of arthroscopy and total synovectomy or synovial capsulectomy in case of diffuse form. PVNS was confirmed by the results of the characteristic histological picture of the pathology. Results: During 5-year follow-up period after orthopedic surgery relapse of PVNS was noted in two children with a diffuse form. A feature of these forms of PVNS was the total involvement of the synovium, including the posterior area of the knee. There were no relapses among children with nodular PVNS. A specific feature of the recovery period after orthopedic-surgical treatment of children with PVNS of the elbow joint was the formation of yearly arthrosis-arthritis with reduced range of motion. Conclusion: PVNS is a rare condition in pediatric rheumatology. Arthroscopy -useful method of treatment nodular PVNS in children. Conclusion: In paediatric patients with chronic rheumatic diseases, immunological I level tests and serological analyses to screen the protection against the common childhood pathogens are suggested before starting an immunosuppressive drug. These patients should also complete the vaccination schedule.

According to our clinical observation, in patients treated with MMF a strict monitoring of Ig values is required during treatment and after discontinuation of the drug. Introduction: Most Juvenile Idiopathic Arthritis (JIA) patients use weekly methotrexate (MTX). The risk of MTX causing liver injury has been a great concern [1]. Due to potential hepatotoxicity, guidelines for monitoring MTX treatment were proposed by the American College of Rheumatology (ACR). The ACR guidelines recommend laboratory testing every 12 weeks. Especially alanine aminotransferase (ALT) is regarded as an important test to screen for liver damage. [2] The ACR guidelines have never been formally validated in children. Studies have suggested that hepatotoxicity and substantial abnormalities in liver enzymes are rare in JIA patients when compared to adults [3] [4] [5] .

Objectives: To gain more insight into the outcomes of surveillance laboratory ALT testing in JIA patients and to assess predictors for ALT elevation in MTX treated JIA patients. This in order to progress towards a MTX monitoring guideline that reflects the specific risk of hepatotoxicity in JIA patients more accurately. Especially considering the burden of three monthly laboratory testing for pediatric patients and their families. Methods: Analyses were made in a prospectively collected clinical database for 844 JIA patients. Follow-up was at least 3 months, regarded from the moment of first visit until the last available normal ALT test or the first ALT elevation. An ALT value higher than 1.5 times the upper limit of normal (ALT>1.5x ULN) was considered clinically relevant. The patient was marked as a MTX treated JIA patient, if they used MTX either orally or subcutaneously at the time of the first significant ALT elevation, or at the last normal ALT value if never significantly elevated. Mann Whitney U and Chi square tests were used for comparisons between patients with and without significant ALT elevation. Numbers needed to harm (NNH) were calculated using 2x2 contingency tables. Predictors for ALT>1.5×ULN were identified using univariate and multiple regression analysis in MTX treated JIA patients. Results: 597 JIA patients were included with 6078 ALT tests. 452 (76%) of patients were ever treated with MTX and 253 (42%) patients were treated with MTX at the moment of an ALT test. ALT>1.5xULN was observed in 92 (15%) of all JIA patients and 65 (71%) of these were MTX treated JIA patients at the moment of ALT elevation. Therefore ALT>1.5xULN was observed in 65 (26%) of JIA patients treated with MTX at the moment of an ALT test. MTX treatment was significantly associated with ALT elevation (p=0.000). Associations were observed between ALT>1.5xULN and the female sex (p=0.005), younger age (p=0.018), lower BMI (p=0.005), oJIA and pJIA subtypes (p=0.021) and ANA positivity (p=0.042). The association with the female sex, JIA subtypes and ANA positivity were not found in the MTX treated patients subanalysis. A NNH of almost 6 JIA patients was calculated to be treated with MTX to achieve significant ALT elevation in one patient. No predictors could be identified for ALT>1.5×ULN in the MTX treated JIA patients subanalysis. Conclusion: This study underlines the importance of the surveillance laboratory ALT testing in MTX treated JIA patients. A relatively high incidence of 15% in ALT elevation is found in all JIA patients, but with 26% in MTX treated JIA patients in particular. The NNH is almost 6 patients to be treated with MTX to achieve ALT elevation in one extra patient. No predictors for ALT elevation are identified in MTX treated JIA patients. The combination of high occurrence and difficult prediction, imply that surveillance ALT testing for all MTX treated JIA patients is more effective then hypothesized. Further research should be conducted to identify predisposing factors for elevated ALT and to explicitly evaluate the optimal frequency of ALT testing. Introduction: Growth and the skeletal system status are the factors that determine the prognosis of consequences in JIA course. Also, a series of recent studies has indicated that vitamin D deficiency and the presence of antibodies to adalimumab (ADA) can worsen the JIA patient condition. Objectives: To evaluate the growth parameters, the skeletal system status, the vitamin D serum level, the anti-adalimumab antibodies (AAA) levels in JIA patients. Methods: We assessed the data from 47 patients aged 3 to 17 years. All children were divided into 2 groups depending on the therapy type. Group I included patients treated exclusively with methotrexate (MTX) for 1 year or more (26), group II consisted of patients treated with MTX and ADA for at least 6 months (21). The frequency of growth disorders, muscle strength changes, serum calcidiol level, dual-energy X-ray absorptiometry (DXA) data, and AAA serum level in JIA patients were analyzed. Results: 8.5% of our JIA patients demonstrated less than -1 SD score compared to 39% in previous years. According to manual dynamometry data, there was a decrease in muscle strength compared with healthy peers, that was especially prominent in patients with polyarticular (49.0%) and systemic (54.5 %) forms. Depending on group affiliation, it was 66.7 ± 9.4% in group I and 32.0 ± 9.5% in group II. Assessed vitamin D status revealed that 68% of patients with JIA required vitamin D level correction: 52% have mild vitamin D deficiency (serum 25(OH)D3 level is below 30 ng/ml), the remaining 16% have severe vitamin D deficiency (serum 25(OH)D3 level below 20 ng/ml). DXA data showed the signs of secondary osteopenic syndrome in 38% of patients from both study groups and significantly higher of bone mineral density (BMD) scores in children treated with MTX and ADA simultaneously (χ2 = 20.28; p <0.001). Also, in patients of group II (25.1 ± 0.9 ng/ml), the serum osteocalcin level was significantly higher (t = 4.22, p <0.001) compared with group I patients (19.4 ± 1.0 ng/ml) who took MTX exclusively. There was a positive, almost strong correlation (r-Spearman's = 0.69) between the osteocalcin and BMD values. According to our multiple regression analysis results, it is the total disease activity indicator that reliably has an inverse correlation with the growth indicator expressed in SD (β = -0.45, p = 0.003) and the indicator of the relative growth rate per year (β = -0.62, p = 0.000009). It was revealed that patients with a pronounced decrease in BMD were more likely to have increased AAA level, with the highest detected level 1153.6 AU/ml. Conclusion: Simultaneous treatment MTX and ADA in JIA patients is associated with a positive effect on both growth parameters and skeletal system. The decrease in bone mineral density is strongly associated with elevated titers of anti-adalimumab antibodies. Objectives: to conduct a correlation analysis between the levels of serum calprotectin and pro-inflammatory cytokines -IL-6 and TNF-α. Methods: We evaluated serum calprotectin levels (sCal) in 28 patients (including 18 girls and 10 boys). The mean age was 11.1 ± 0.8 years, and the duration of the disease was 5.8 ± 0.7 years. IL-6 level was determined in 13 patients with systemic form of JIA (5 of them took MTX exclusively, 7tocilizumab, 1 -MTX and adalimumab) and in 15 patients with polyarticular form -TNF-α level in blood serum (10 patients who took MTX, 3adalimumab, 2adalimumab with MTX). Results: The median serum IL-6 concentration was 23 [5; 125] pg/ml, respectively, are equal to the median sCal level of these patients -3200 [1100; 25900] mg/l. Only in 2 patients from group II, who were in the stage of drug remission, IL-6 concentrations were within the reference values (below 7.1 pg/ml). With regard to serum TNF-α levels, the median of its concentration was 8 [3, 34] pg/ml, and the median sCal level was 5500 [900; 24900] mg/l, respectively. In 8 children (4 from group I and 4 from group II), TNF-α levels were within the reference values (below 8.1 pg/ml), although all these patients had the JIA active course (1 st or 2 nd stages of activity). When conducting Spearman's rank correlation, a significant direct strong correlation of moderate strength was found between the levels of serum calprotectin and IL-6 (r-Spearman's = 0.88, p = 0.00006), and there was found no significant correlation between the values of sCal and TNF-α (r-Spearman's = 0.41, p = 0.13). Conclusion: IL-6 concentration is an informative laboratory marker for assessing the inflammatory activity process in JIA patients. Introduction: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatological disease (1: 1000 children). In Ukraine, the prevalence of JIA among children 0-17 years old over the past 5 years was 0.32-0.42 cases per 1000 children. The involvement of the temporomandibular joints (TMJ), depending on the diagnostic methods, the studied population and the JIA subgroup, varies from 17% to 87%. Unfortunately, detection of TMJ arthritis in children with JIA is difficult due to the absence of early signs and symptoms. Therefore, the diagnosis of TMJ involvement often occurs late, when the growth disorders of the mandible are already evident. Objectives: To determine the diagnostic measures according to a multidisciplinary approach in the early manifestations of JIA. Methods: The analysis of clinical, laboratory data and TMJ MRI studies of 11 children with JIA (10 girls/1 boy) aged 8-18 years was carried out. All children are on medication. Results: JIA manifested as polyarthritis (with positive rheumatoid factor (RF)) in 5 our patients, polyarthritis (with negative RF)in 4 children, enthesitisin 1 child, and undifferentiated arthritis in 1 child. According to radiological criteria, changes in joints were detected: stage I in 54.5%, stage II -27.3%, stage III -9.1%, and in 1 (9.1%) child with undifferentiated arthritis no radiological changes were found. The manifestations of the TMJ arthritis were mouth opening limitation, pain in the TMJ and limitation of lower jaw movement in 91% of patients, which appeared already in the first year of illness in 36% of children and in 45% in the third year. Long-term absence of complaints of TMJ pain was identified in all children with positive RF. Changes in the TMJ tissues were found to correspond to complaints presented by children in 82% of cases. Adhesion of articular discs to the posterior slope of the articular tubercle was diagnosed in 27.3% (n = 3) children. Bilaminar zone with edema and intra-articular effusion -in 9.1% (n = 1) of the child. The MRI stage of changes in the TMJ coincided with the general stage in 36% (n = 4) cases and in 27.3% (n = 3) children it was higher than in other joints. No chronic changes in the TMJ structures were found in a child with undifferentiated arthritis. The revealed changes in the muscular system of the TMJ in JIA showed that on the side of the affected joint m.pterygosdeus lateralis tended to shorten its length. M.pterygosdeus medialis lengthens from the side of the affected joint compared to the opposite side and the norm, according to 3.73 ± 0.11 cm; 3.64 ± 0.12cm and 2.91 ± 0.27cm. Such a compensatory-adaptive reaction of the masticatory muscles provides protection for the intra-articular disc, ligaments and capsules. The data obtained on changes in the structures of the temporomandibular joint and the masticatory muscles around it indicate that in the first year of the JIA disease course they are included in the symptom complex and are a component of the disease diagnostic measures. Conclusion: Examination of the temporomandibular joint with the determination of anatomical and functional changes according to MRI indicators is a mandatory diagnostic test for correcting the treatment of chronic temporomandibular arthritis. Children with JIA need a multidisciplinary approach by rheumatologists and maxillofacial surgeons. Introduction: Higher dosage regimes for Infliximab (IFX) have been described to be effective in partial-or non-responding adults and children with rheumatic disease and appear to be safe. To optimize IFX treatment in juvenile idiopathic arthritis (JIA) patients, therapeutic drug monitoring (TDM) might be beneficial. To support routine TDM of IFX and regimen optimization in JIA patients, more in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. Ultimately, as soon as the optimal therapeutic drug ranges will be known, PK model-based simulation can be used to individualize drug dosing recommendations. In this study, a population PK model for IFX is described for JIA patients. Objectives: Our hypothesis is that optimizing dosage and frequency of IFX administration for individual patients will improve treatment outcome. Individual dosages may be optimized by taking specific patient characteristics into account that explain inter-patient variability in pharmacokinetics (PK). Inter-patient variability can be quantified and investigated by the population approach. Ultimately, as soon as the optimal therapeutic drug ranges will be known, PK model-based simulation can be used to individualize drug dosing recommendations for these patients, based on their characteristics. In this current study, the population PK for IFX are described for JIA patients (which to our knowledge have not been described before). Methods: Data including IFX trough concentrations and anti-IFX antibodies of 27 JIA patients on IFX maintenance treatment were retrieved from electronic charts. Three population pharmacokinetic models from literature were validated for our dataset using nonlinear-mixed effects modeling program NONMEM. A novel population pharmacokinetic model was developed based on our study data. Results: A total of 65 obtained blood samples after a median of 32 days after the last IFX infusion (IQR 28-42) were analyzed. The three published models underpredicted the observed trough concentrations. A newly developed one compartment model best described the IFX serum concentration over time data in JIA patients. Conclusion: Our study shows a novel and the first PK model for IFX in JIA patients. Our main finding was that a one-compartment model best described the IFX serum concentration over time data. Predictive performance of the literature models was insufficient for our patient data. Our data also show that different PK models are needed for different age categories (children or adults) and in different diseases. Introduction: Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic condition which causes by a ACVR1 gene mutation responsible for the activity of BMP and uncontrolled osteogenesis. According to its mechanism, this disease has a classic autoinflammatory pattern and after the manifestation of the first flare, usually provoked by mechanical trauma, a cascade of inflammatory reactions is triggered, ending with the development of large heterotopic ossifications Objectives: To analyze the use of Janus-kinase inhibitor Tofacitinib (TOFA) as a new therapy approaches in most severe cases of FOP Methods: 35 patients (pts) (17 males/18 females) with verified FOP for the period from 1998 to 2020 were analyzed. In 9 pts with severe course of FOP TOFA administration were evaluated Results: We observed 35 pts with definite diagnosis FOP. Among them 9 pts (5 males/4 females), from 2 to 16 y.o. with extremely severe course of FOP and steroid addiction received TOFA. All pts have «classic» FOP stigmas and confirmed mutation in the ACVR1 gene (8 pts have classic mutation c.617 G> A (p.Arg206His), 1 pt has с.983 G>A (p.Gly 328 Glu). Multiple heterotopic ossifications were detected in all pts (neck, back, upper and lower limbs with significant limiting of motion in large joints). All pts had synovitis mostly of the low limb (hip -8, knee-7, ankle -4) with ultrasound and MRI evidences. Active bilateral sacroiliitis with bone edema was detected in 2 of 3 patients who were able to perform MRI. In another patient sacroiliitis verified by CT. The most pts at the age after 5 years had ankylosis of the facet joints and vertebral bodies by the type of syndesmophytes (6 pts). Presence of axial skeletal damage with sacroiliitis and gradual development of ankylosis of facet joints of cervical spine, synovitis of large joints makes it possible to justify the diagnosis of juvenile ankylosing spondylitis (5 pts) or JIA (4 pts) as concomitant condition. It was done for the "organizational" reasons to facilitate the availability of the drug therapy. All patients received NSAIDs and steroids (9-per os, 5-intravenous pulse therapy), 6 pts -bisphosphonates (infusions of pamidronic acid 2-3 courses of 30-60 mg depending on weight). Due to the severe uncontrolled course of FOP with continuous flares, formation of new nodes and steroid addiction targeted anti-inflammatory therapy with the Janus kinase inhibitor was prescribed. We use the similar dose to randomized trial for JIA (up to 5 mg twice a day) after the approval of the local Ethic Committee. The first patient was 16 y.o. at the time of TOFA administration in December 2019, the age of the others pts was from 2 to 12 y.o. Duration of TOFA therapy is from 7 to 17 months. Compare to previous 6 months, the average number of new flares significantly decreased from 8,1 (Me 9) to 0,9 (Ме 0) in after 6 months of TOFA treatment. Only in one youngest patient of 2 y.o. the number of flares decreased from 10 to 4 per the same period. In the most of children was achieved an improvement of movements in large joints (shoulder, elbow). In one patient with severe course of FOP and localization of the inflammatory focus in the temporomandibular joint area, a rapid regression of changes with restoration of the mouth opening aperture was obtained. In all 9 pts we stopped the steroids. Drug tolerance was good in all pts, no AE were registered Conclusion: The anti-inflammatory effect of TOFA allows to stop the recurrence of new flares of FOP and restrain the progression of heterotopic ossification. An additional advantage of TOFA is an oral method of use, taking into consideration contraindications for using of injections in patients with FOP. Objectives: to present a rare case of successfully application of abatacept in an jSLE+SS in a boy who had two episodes of macrophage activation syndrome (MAS). Methods: Case report. Results: 4-year-old boy admitted to our clinic for the first time in 2010 presenting the 6-month history of disease. There were fever up to 39°C, polyarthritis, anemia, trombocytopenia, hyperIgG-emia, increase TA (2N), CRP (20 mg/l), RF 30 mg/l at the disease onset. Initially JIA, polyarthicular sybtype, RF+ was diagnosed in regional hospital. Treatment with NSAIDs, GC iv 125 mg №3, methotrexati 7,5 mg weekly was started. During the next 3 weeks laboratory results were constantly getting worse (Нв 80 г/л, trombocytes 145000, leucocytes 1000, increase TA 10N) and new clinical symptoms occurred (maculopapular rash with itching; splenomegaly; febrile fever). He received GC iv + per os 1 mg/ kg with a short-term effect. On 1 st admission in our clinic in September of 2010, he had general fatigue and tiredness, classic malar rash, severe cutaneous vasculitis (palpable purpura and digital capillaritis), Raynaud's syndrome, enanthema, myopathy, lymphadenopathy, hepatosplenomegaly, polyarthritis. Data of laboratory tests: Hb 96g/l, ESR 27 mm/h, ANA titer 1:640 h+sp+cytopl, anti-SS-A(Ro)>200 U/ml, RF 230 ME/ml, C4 0.07 g/l. The revision of bone marrow biopsy showed changes typical for MAS. So jSLE was diagnosed as with SLICC criteria, 2012 with MAS at onset according the preliminary diagnostic criteria for MAS Complicating SLE. The initial SLEDAI was 29. Patient failed to respond to GC iv repeating courses, GC per os max 0.7 mg/kg, IVIG repeating courses, DMARDs consequentially: cyclophosphamide iv, azathioprine, mycophenolate mofetil (MMF) + hydroxychloroquine. Rituximab (RTX) was introduced in November of 2013 due to inefficiency of prior therapy in dose 375mg/m2 weekly N2 on course. Concomitant therapy: GC per os 0.5 mg/kg, MMF 500 mg/day, hydroxychloroquine 200 mg/day. Treatment with RTX allowed to decrease the dose of GC to 0.2 mg/kg, to reduce the activity of the disease (SLEDAI=4), but relapses of the disease required a repeat of RTX therapy every 6 months (5 courses in total). Patient developed a recurrent episode of MAS on 6 th years of disease (the 8 th day after RTX -5 th course, 1 st infusion). Therapy of RTX was discontinued. In June 2016 Sjogren's syndrome has been verified (according to parotid sialography, unstimulated sialometry in combination with clinical signs of dry mouth, anti-SS-A(Ro)+, RF+). Correction of therapy was carried out at the expense of the change a dose of GC, the dose of MMF was increased to 750 mg per day. Patient received repeat courses of IVIG due to recurrent infections of mouth. Since October 2017 flare due to fever, polyarthritis, skin and mucosal lesions. The dose of GC has been increased to 0.5 mg/kg. In November 2017, abatacept therapy with 10 mg/kg was started with good safety. Inactive status of the disease was achieved after 12 months of therapy. Now boy receives abatacept during 42 months, continues GC 5 mg per day, hydroxychloroquine 100 mg per day, MMF 750 mg per day. In November 2020, he underwent COVID-19 with minimal manifestations (runny nose, fatigue, positive PCR test) without reactivation of rheumatic disease. Introduction: Cryopyrin associated periodic syndromes (CAPS) are a group of ultra-rare autoinflammatory diseases caused by mutations in the NLRP3 gene, leading to overproduction of IL-1β. CAPS includes the following subdiagnoses: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological cutaneous articular syndrome/neonatal-onset multisystem inflammatory disease (CINCA/NOMID), where FCAS is the mildest form of CAPS and CINCA/NOMID the most severe. A graduated pre-filled syringe of the IL-1 receptor antagonist anakinra was introduced to meet the need of smaller and varying doses when treating children with CAPS. Objectives: To evaluate the safety of anakinra in CAPS patients using the novel pre-filled syringe. Methods: Investigators managing patients with CAPS treated with anakinra were identified via the Eurofever registry. Follow-up data of at least 3 years for each patient were prospectively collected and analyzed (EUPAS6366). The primary study endpoints were the occurrence of adverse events (AEs) with focus on serious infections, malignancies, injection site reactions, allergic reactions and medication errors, including re-use of the syringe. Secondary endpoints included dose at specific time points, discontinuations, and switch to other IL-1 blocking treatment. Results: 12 patients with CAPS were included in the study, 8 with MWS, 2 with FCAS and 2 with CINCA/NOMID. The majority were male (75%) and white (83.3%). At baseline, all but one patient were already using the graduated prefilled syringe with anakinra. 5 patients required a median dose of 2 to 3 mg/kg/day and 6 patients below 2 mg/kg/day. During a total of 26.1 patient years of treatment, there were 7 AEs with rate of 26.8 (95% CI 4.2-169.6) per 100 patient years. All AEs were infections from 1 patient with CINCA/NOMID and were considered unrelated to anakinra by the investigator. Two of the AEs were considered serious as hospitalization was required (1 tonsillitis and 1 urinary tract infection). No AEs were severe, 6 of the AEs were of moderate severity and 1 was of mild severity. In total, 6 patients discontinued anakinra permanently, 2 during the first year of treatment, 3 during the second year and 1 after the third year of follow-up. The reasons for discontinuation included switch to canakinumab (4 patients), switch to canakinumab and inefficacy (1 patient) and non-compliance (1 patient). The remaining 5 patients continued anakira until the end of the study. 1 patient discontinued anakinra temporarily during the second year of treatment due to noncompliance. No deaths, malignancies, injection site reactions, allergic reactions or medication errors, including re-use of the pre-filled syringe, were observed. Results are shown as number (%) unless stated otherwise. In the second year of biological therapy, against the background of maintaining a persistent effect within the framework of the minimal clinical and humoral activity of the disease, the patient was verified to have focal hair loss on the head. The child was comprehensively examined in accordance with clinical guidelines in cases of development of unspecified alopecia, including an immunological and endocrinological examination. Taking into account the peculiarities of the course of the underlying pathology, further decisions on the genesis of alopecia were made within the framework of a consultation of university clinics with the participation of rheumatologists, dermatologists and a clinical pharmacologist. After excluding other causes, the genesis of alopecia was verified as a side effect of the ongoing biological therapy with recombinant monoclonal antibodies to TNF-α. The biological therapy was changed to a drug with a different effect. Against this background, over the next 6 months, regression of the pathological symptom, partial restoration of the hairline was noted. Introduction: Achievement of a normal peak bone mass is an especially important consideration in young adults with juvenile idiopathic arthritis (JIA), because interference with attainment of peak bone mass may not be repaired later in life. It has been suggested that children with JIA cortical appendicular skeletal bone is more affected by disease activity than axial trabecular bone. To evaluate bone mineral density (BMD) DXA measurements are widely used. Although, DXA is limited to two-dimensional evaluation of integral BMD and cannot differentiate between trabecular and cortical bone compartments. Alternatively, 3D-DXA analysis is a new method based on DXA scans of proximal femur that provides accurate estimates of trabecular and cortical volumetric BMD.

Objectives: The aim of the study was to analyze the trabecular and cortical bone using 3D-DXA in young adults with JIA compared to age-matched healthy controls. Methods: This cross-sectional study was aimed to analyze the differences in 3D-DXA proximal femur compartments. The patients were recruited from the specialized transitional unit of the Vall d'Hebron University Hospital. JIA patients older than 18 yo without previous bisphosphonates intake were included. Age and sex-matched healthy controls were selected. Risk factors for OP were assessed in all participants, suptype of JIA and disease activity was evaluated. DXA scans (Lunar Prodigy, General Electric Medical Systems, v.15) were acquired to both patients and controls. OP was defined according to the WHO criteria. The 3D-DXA software was used to assess in 3D the trabecular density and cortical thickness from DXA scans as reported previously [1] . Quantitative variables were described using means and standard deviations (SD) whereas frequencies and percentages were reported for qualitative variables. The 3D-DXA and DXA measurements were compared using Student's t test. Categorical variables were compared using Chi-squared test. All hypothesis tests with p value lower than 5% were considered significant. Results: Forty-six patients and 46 age and sex-matched controls were evaluated. The mean time of disease's duration was 7.37 years, and the most frequent JIA subtype was Oligoarticular ANA positive. More than 21% of the patients had an active disease. OP was present in 5 patients and 1 control. Despite not finding significant differences in the prevalence of osteoporosis, JIA patients had lower aBMD at total hip by DXA (0.932 ± 0.02 g/cm 2 in patients and 1.001 ± 0.01 g/cm 2 in controls, p-value=0.008) and and lower cortical sBMD by 3D-DXA than controls (147.23 ± 3.41 mg/cm 2 A similar pattern was found in the subgroup with active disease versus controls with ≥0.4-fold increase in TNF-α, S100A12, FGF-21, CCL20, IL-6, SIRT2, 4E-BP1 and a ≥0.4-fold decrease in IL-13. In the subgroup with low versus high BMD Z-score, TNF-α and TNF-β were ≥0.4-fold increased, while OSM, S100A12 and IL-5 were ≥0.4-fold decreased.

Conclusion: In this explorative study on inflammatory biomarkers, we found characteristic changes in several inflammation-related proteins in JIA versus controls. We also found similar characteristics in JIA with active disease versus controls, while children with low versus high BMD Z-score had a slightly different profile. Several of these proteins have not previously been studied in JIA.

Bone fragility risk factors in a pediatric rheumatology department -data from a single-center A. Introduction: Low bone mineral density (BMD) is an underrecognized complication of chronic illness in childhood. Reducing the frequency of fragility fractures requires increased attention to risk factors, early intervention, and additional research to optimize therapy and potentially prevent their occurrence. Objectives: To identify and characterize children with risk factors for low BMD followed in a Paediatric Rheumatology unit.

Methods: A retrospective observational study was conducted by consulting all the clinical records of patients followed at a Pediatric Rheumatology Unit, from January 1st 2020 to April 30th 2021. The following criteria were considered risk factors for low BMD: active chronic inflammatory disease (defined as moderate or high disease activity for at least 3 months duration), corticotherapy (>3month duration), reduced mobility, puberty disorders, metabolic diseases and previous fractures. Results: Five hundred and sixty-six patients were analyzed, 71 (12.5%) of whom had risk factors for low BMD. Forty patients (56.3%) were female, with a median age of 13.7 [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] years. Nine patients with osteogenesis imperfecta (OI) were identified (2 of whom had also reduced mobility). Four other patients had reduced mobility (all had Duchenne muscular dystrophy diagnosis and all medicated with corticosteroids); a malabsorption syndrome was identified in 6 patients (half of them had a metabolic genetic disease diagnosis). Active chronic inflammatory diseases were identified in 41 patients. From those, 37 were also exposed to corticosteroids. The most frequent active chronic inflammatory diseases identified were juvenile idiopathic arthritis (n=12) and juvenile systemic lupus erythematosus (n=12), followed by idiopathic uveitis (n=3), juvenile dermatomyositis (n=3) autoimmune hepatitis (n=2), mixed connective tissue disease (n=2), and ANCA vasculitis (n=2). If possible, patients were stimulated to practice physical exercise. An adequate dietary calcium intake and vitamin D supplementation were advised. Nineteen patients (26.7%) had at least one fragility fracture identified of whom 10 patients had a Z score of -2. Four of these patients were currently treated with alendronate, 5 with zoledronic acid (4 biannually and 1 annually) and 1 patient was treated with denosumab. None of these patients had subsequent fractures, except a girl with OI type VI that had previously been treated with pamidronate, but maintained repetitive fractures and for that reason was started on denosumab.

Conclusion: In our cohort, inflammatory chronic diseases were the main risk factors for low BMD, demonstrating the impact of inflammation on bone, potentiated with steroid intake. An adequate treatment of the underlying illness, exercise, a sufficient calcium intake and vitamin D status are essential to prevent osteoporosis. If general measures fail to prevent further bone loss and fracture, pharmacologic therapy may be considered. Introduction: A 10 year-old girl was referred to paediatric rheumatology with a six-month history of a painful, swollen left wrist associated with functional limitation and disturbed sleep. She initially had a minor fall, X-rays at the time showed no bony abnormalities.

Objectives: Blood tests were normal including inflammatory markers and autoimmune screen. Wrist MRI showed significant synovial thickening and avascular necrosis of the left lunate (figure 1). Methods: Our patient received non-steroidal anti-inflammatories and physiotherapy, but a year later continued to have chronic regional pain with allodynia and hyperalgesia. Despite this, she remains upbeat and continues to live a normal childhood and has coped well with the recent increase in computer usage and typing associated with remote-schooling as a consequence of closures during the COVID-19 pandemic. Results: Kienböck disease; an eponym for avascular necrosis of the lunate bone, is of unknown aetiology and incidence [1] . The proposed trigger is trauma in those with a susceptibility due to natural skeletal and vascular variations [2] . It is the commonest cause of adult aseptic osteonecrosis of the upper extremity, usually in dominant hands of men aged 20-40 [3] . Paediatric Kienböck is rare; presenting as pain, stiffness, swelling and reduced power often after an innocuous fall. Diagnostically this is challenging because the mechanism suggests a soft-tissue injury whereas the chronicity mimics Juvenile Idiopathic Arthritis. Radiographic severity is defined by Lichtman classification and used to guide non-curative surgical or conservative management [4] . This aims to relieve pressure on the lunate bone and restore perfusion. Anti-inflammatory medications are offered prior to surgical jointlevelling to reduce pain, swelling and deformity [5] . Conclusion: We emphasise that clinicians consider this rare, destructive pathology in their differential diagnosis for paediatric chronic wrist pain and swelling, especially in those presenting weeks after a seemingly innocuous hand trauma. Before referral to our institute, 40% of children were misdiagnosed as cases of JIA and were managed with anti-inflammatory and immunomodulatory drugs. In 11 (68.75%) patients, mutation in WNT1-inducible-signaling pathway protein 3 (WISP3) gene was detected. We also noted a novel pathogenic variant in one patient. Four patients with CACP syndrome were identified based on typical clinical findingsnon-inflammatory nature of joint pain and synovial enlargement, camptodactyly, and constrictive pericarditis. All had pathogenic variation in the plasticity-related gene (PRG) gene. One patient was misdiagnosed as rheumatic fever and had been on penicillin prophylaxis for 6 months. Pericardiectomy was required in two patients to relive the features of congestive cardiac failure. Two patients with MONA syndrome were identified based on extensive symmetric joint deformities involving small and large joints and presence of osteopenia in radiographs. Pathogenic variant in MMP2 gene was detected in both of them. In one patient with progressive joint stiffness and flexion contracture of hips, autosomal dominant epiphyseal dysplasia was identified based on positive family history and skeletal radiographs. Mutation in Exon 53 of COL2A1gene was documented in this patient. Fifteen (65.21%) patients already had joint deformities at the time of presentation. Twenty-one patients were alive at the times of this study whereas 3 patients were lost to follow-up. Conclusion: Noninflammatory arthropathies are distinct group of musculoskeletal disorders. PPRD is the most common noninflammatory arthropathy found in our cohort. As these group of musculoskeletal disorders mimic JIA, and there is a lack of awareness among clinicians, a considerable delay in diagnosis was observed. There is also a need of increase awareness among clinicians and rheumatologists about these groups of musculoskeletal disorders in order to initiate appropriate therapeutic and rehabilitative measures. , with "0" being "no-pain" and "10" being "the worst possible pain" was administered at baseline, 3, 6 and 12 months and yearly. The radiologic outcome was assessed by serial WB-MRIs and serial joint radiographs. All patients with ON were evaluated for bone turnover and BMD at set intervals. Introduction: The function of the leading proinflammatory cytokines interleukin 6 (IL6) and tumor necrosis factor-α (TNF-α) in patients with JIA may depend on their structure, which is due to the characteristics of allelic polymorphism of their genes, which in the case of autoimmune inflammation may lead to pathomorphosis of disease.

Objectives: To study the allelic polymorphism of IL6 and TNF-α genes in JIA depending on the peculiarities of its course. Methods: 52 patients with JIA (14 oJIA, 2 pJIA RF +, 11 pJIA RF-, 15 entJIA, 2 psJIS, 5 sJIA, 3 undifferentiated) were examined. In addition to standard examination, allelic polymorphism of TNF-α G308A & IL-6 G-174C genes using polymerase chain reaction (PCR) using specific oligonucleotide primers and subsequent analysis of restriction fragment length polymorphism, and of IL-6 and TNF in blood serum using chemiluminescence immune assay (CLIA) and the electrochemiluminescence immune assay (ECLIA) were determined.

Results: The population of JIA patients with GG (wild allele) of IL-6 G-174C gene was characterized by a higher frequency of registration of hyperthermia, anemia and osteoporosis, GC (heterozygous mutation) IL-6 included all cases of pJIA RF+, CC (homozygous mutation) -predominance of ANA-positive cases, uveitis, hip joint damage, cardiometabolic changes and higher level of IL6 and immunoglobulin M in the serum. A significant statistical relationship was found between the unfavorable course of the disease and the allelic variant of the IL-6 GC gene (Pearson Chi-square = 6,165, df = 2, p = 0,045). Significant differences in JIA activity depending on the allelic polymorphism of the TNF-α G308A gene (JADAS GA (heterozygous mutation) = 4.5 vs. GG (wild allele) = 12.71) were revealed by the ttest (p = 0.027). Patients with GG TNF-α are more likely to be ANApositive, carriers of GA to have sacroiliitis. It should be noted that carriers of the GG allele were found three times more often than carriers of the GA allele, and there was only one carrier of AA (homozygous mutation) allele, which could affect the results. One third of JIA patients were children with a combination of GC IL-6 and GG TNF-α (mainly oJIA and entJIA), of which 76% had an unfavorable course of disease, 73% had changes on standard 12channel ECG, 53% secondary osteoporosis, 17.6% gastrointestinal lesions. The combination of GG IL6 + GG TNF-α had 21.15%, halffever at the onset of the disease, 40% polyarthritis. 7 children were included in the group with GC IL6 + GA TNF-α (all with an unfavorable course, included all pJIA RF + cases, sacroiliitis, 57% received biological DMARDs).

Patients with CC IL6 + GG TNF-α were characterized by a higher incidence of uveitis, hip joint damage, ANA-positivity (70%) and HLAB27 + (56%). Conclusion: Changes in the sequence of nitrogenous bases in the genes of proinflammatory cytokines can lead to changes in the sequence of amino acids in the cytokine, changes in its functional ability, which leads to changes in course of JIA. The presence of a mutant allele of the IL-6 GC gene causes a more severe course of JIA, the wild GG allele of the TNF gene -higher inflammatory activity. Cluster analysis of the data showed that the combination of two heterozygous gene mutations leads to the least favorable course of disease. Introduction: Scurvy is the disease generated by the lack of vitamin C, although it is considered a rare and past disease, scurvy continues to be detected in children with neurodevelopmental disorders and with restricted and selective diet habits. Clinical features are hypertrophy, swelling and bleeding of the gums, follicular hyperkeratosis, lower limbs swelling and tenderness. Identifying scurvy could be demanding due to the perceived rarity of the condition, and it could become a tricky diagnostic question given to the variety of nonspecific symptoms, including gingival manifestations.

Objectives: Here we present a case report of Scurvy in a 4 year-old child.

Methods: A 4 year-old child presented to our Department with lower limbs pain and refusal to walk for about 4 months. The symptoms were partially managed with Non Steroidal antinfiammatory Drugs. Patient's mother did not refer ferver, skin rash or weight loss. Patient psychomotor development was referred in the norm up to 7-8 months of age, then patient presented a delay of psychomotor and language development. Dietary history reveals highly selective eating since the second year, based exclusively on ham and white meat homogenized, with refusal of fruits and vegetables. Since about 1 year the mother reports difficulty in eating, and several episodes of gengivitis with antivirals and topical antifungals with partial benefit. When patient came to our department he was in fair general conditions, his weight was 17 kg (25-50 th), his height was 105 cm.(25-50 th). Physical examination althought difficult because of the patient's developmental delay revealed :pale and dry skin, corkscrew hair, signs of follicular hyperkeratosis in the lower and upper limbs. Child refused to walk, with legs fixed in flexion at hips and knees ("Frog legposition"). Both legs were diffusely tender to palpation. The child was uncooperative for oral examination but erythematous, hemorrhagic, and swollen gums in maxillary anterior region were noted. Blood examinations revealed low iron and vitamin D level, inflammatory parameters (C-reactive ptotein and erythrocyte sedimentation rate) were normal. Hips, knees and ankle ultrasound did not revealed joints effusion. X-ray of the lower limbs did not revealed fractures, but generalized osteopenia and typical features of malnutrition, including a ground glass appearance, Pelkan spur, which represents a healing metaphyseal pathologic fracture, and a Wimberger ring sign, which denotes a thin sclerotic cortex surrounding a lucent epiphysis.

Periosteal new bone formation secondary to subperiosteal, hemorrhage, a dense provisional calcification immediately adjacent to the physis (Frankel line), and an adjacent lucent band more, diaphyseal in location (Trummerfeld line). Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with strong genetic component, which determines the relevance of research on the contribution of various genetic factors to this disease. These studies are of particular importance in the SLE with juvenile onset (jSLE). Objectives: To study the hypothesis of the association of some polymorphisms of the STAT4, CRP, and IRF5 genes with susceptibility to jSLE and the effect of the revealed correlation on the severity of the disease. Methods: The case-control pilot study included 50 patients (pts) with jSLE (38 girls) with an average age of 12.1±2.85 years at onset and 103 healthy individuals (controls). Diagnosis of SLE was reviewed based on 2012 SLICC criteria. 80.0% of pts had acute cutaneous lupus at the onset, 46.0% -nonscarring alopecia, 76.0% -arthritis, 22.0%oral and nasal ulcers, 22.0% -serositis, 44.0% -renal involvement, 28.0% -neuropsychiatric disorders. Leucopenia was found in 68.0% of pts, thrombocytopeniain 28.0%. ANA were detected in 100% pts, anti-dsDNAin 90.0%, anti-Smin 22.0%, antiphospholipid antibodies -in 20.0%, hypocomplementemiain 38.0%, positive direct Coombs testin 30.0 %. STAT4 (rs7574865, G/T), CRP (rs1205, C/T) and IRF5 (rs2004640, G/T) gene polymorphisms were genotyped using allele-specific RT-PCR assay. Results: The distribution of GG, GT and TT genotypes of the STAT4 gene polymorphism rs7574865 differed statistically between jSLE and controls (36.0%, 54.0%, 10.0% and 63,1%, 33.0%, 3,9 respectively, χ 2 =10.42, p=0.005). The minor T allele was associated with the development of jSLE (OR=2. Conclusion: Our preliminary study in small groups of jSLE pts revealed that STAT4 (rs7574865) and IRF5 (rs20004640) gene polymorphisms are associated with susceptibility to jSLE. At the same time, we did not find a relationship between the CRP gene polymorphism (rs1205, C/T) and the risk of developing jSLE. The rs7574865 STAT4 gene polymorphism had a pronounced relationship with the development of arthritis in our pts with jSLE. The rs1205, C/ T CRP gene polymorphism had a pronounced relationship with the development of nonscarring alopecia. Further investigations are required to clarify the role of genetic markers in jSLE as markers of the risk of developing SLE and its clinical and laboratory phenotypes in large studies in different ethnic and population groups. Objectives: To study whether polymorphisms in apoptosis genes predict course and outcomes of juvenile arthritis. Methods: We conducted for potentially functional single-nucleotide polymorphisms in Fas ligand (CD95L), TRAIL, IL6 and TP53. A total of seven functional SNPs were identified. In the first step, to study whether SNPs in apoptosis genes predict course and outcome of JA were analyzed 116 children. A second step was to assess gene polymorphisms interact with clinical predictors JA. All children were classified according to the ILAR criteria (ILAR 1997; 2001 ; the Edmonton revision 2004). 89 children were with ANF-positive JA (oligo-polyarthritis: ♂25, ♀66), 27 ANF-negative JA (entheso-JA: ♂18, ♀9). 60 healthy children without family history of any autoimmune disease were controls. Statistic analysis was carried out in groups of girls and boys with long active arthritis and remission. Results: For juvenile arthritis genetic predictors there are no identified. Distribution of IL6 C174G, FasL-124A/G, FasL-843C/T, TRAIL-1525G/A, TP53 Arg72Pro genotypes did not differ significantly between the study groups. We identified that 67,6% of ANF-positive girls with long phase of "active disease" (n=34) were with IL6 -174 GC/GG (G allele) genotype and P53 -72 GC/CC (Pro / C allele) genotype (p<0,01; Odd's ratio 9,2; 95%CI: 2,7490 -30,7896). All girls with IL6 -174 GG and P53 -72 CC genotype (n=9) were with severe erosive polyarthritis. 89% ANF-positive girls which achieved early "inactive disease" (n=27) were with IL6 -174 GC/GG (G allele) genotype and P53 -72 GG (Arg / G allele) genotype (p<0,01; Odd's ratio 16,9; 95%CI: 3,347-85,54). Correlation with FasL-124A/G, FasL-843C/T, TRAIL-1525G/A polymorphisms in ANF-positive girls with outcomes of JA didn't revealed. The difference in ANF-positive boys distribution across the genotypes was not significant. ANF-negative boys and gilrs with enteso-JA had a high frequency of P53 -72 GC/CC (Pro / C allele) genotype but this SNP was not associated with the course and outcomes of disease. Conclusion: We observed that polymorphisms of IL6 C174G and TP53 Arg72Pro influence to the course and outcomes of juvenile arthritis. The strongest association was seen P53 Introduction: After spring 2020, a series of reports from Europe and USA described clusters of children, presenting life-threatening multisystem inflammatory syndrome in children (MIS-C), associated with antecedent exposure to SARS-CoV-2 (1). In patients with life threatening COVID-19 3.5% were found to have inborn errors in type I IFN signalling pathway (2) . A case series of 4 young patients with severe COVID-19 reported rare loss-of-function variants in the TLR7 gene associated with impaired type I IFN responses (3). Clinically, MIS-C shares features with secondary hemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD), which were also associated with possible infectious trigger and might share a common genetic cause (4). Objectives: We analysed whether MIS-C patients have an underlying presence of genetic variants in exomes associated with inborn errors of type I IFN immunity, HLH, KD and presence of variants in TLR7 gene. Methods: Blood was drawn from 17 MIS-C patients upon submission into the hospital, DNA from peripheral blood was isolated and whole exome sequencing was performed. Variants in the following genes were investigated: type I IFN immunity (TLR3, UNC93B1, TRAF3, TBK1,  IRF3 Objectives: The research is aimed at establishing the structural and functional features of bone tissue in children during the growth spurt, taking into account the Fokl polymorphism of the VDR gene. Methods: The examination covered 205 children aged from 9 to 17, they were divided into three groups depending on the presence or absence of growth spurt (GS) and its intensity: group 1 included 50 children whose height increased by 8-12 cm for the current year; group 2 consisted of 46 children who grew by 12 cm for the present year, group 3 included 109 children without growth spurt. The eligibility criteria were as follows: no chronic somatic or endocrine pathology. The research required the collection of clinical data, medical history and an objective assessment of the level of physical (according to WHO guidelines "Child Growth Standards", 2007), molecular diagnosis of the Fokl polymorphism of the VDR gene (PCR method, Realtime), ultrasound (Sonost-2000, Korea) and X-ray densitometry (DXA) (HOLOGIC QDR W Explorer, USA). The criterion for diagnosing a decrease in the bone mineral density was considered to be BMDZscore ≤-2 in accordance with the recommendations of The International Society For Clinical Densitometry (ISCD), 2019. Results: A decrease in the bone mineral density (BMD) as observed through ultrasound densitometry (UD) was diagnosed in 24 children (48.0%) of group 1, in 28 children (60.87%) of group 2, and in 43 children (39.45%) of group 3. DXA was used to examine 32 children with a decrease in BMD. In 18 of them (56.25%) a decrease in BMD was diagnosed as shown by ultrasound. The number of children with a decreased BMD in group 1 reached 38.9% while in group 2 it was 50.0% (p<0.05). Spearman's correlation analysis showed that children in groups 1 and 2 revealed a positive relationship between the intensity of the growth spurt and BMD (r=0.40). The frequency of BMD reduction in children of group 2 was significantly higher (p< 0.05) than in group 1. The following variants of the Fokl polymorphism of the VDR gene were detected in all of the examined children: a normal genotype was found in 27.81% of children, 61.95% of children showed a heterozygous mutation, a homozygous mutation was detected in 10.24% of children. A heterozygous mutation of the Fokl polymorphism in the VDR gene proved to bethe most widespread (72.48%) in the group of children without GS with a decreased BMD. Children of groups 1 and 2 showed no significant differences in the prevalence of the heterozygous mutation of the Fokl polymorphism in the VDR gene. Conclusion: The main reason for a decreased BMD in school children during the growth spurt is a delayed bone mass accumulation associated with an intensive linear skeletal growth. Fokl polymorphism mutations of the VDR gene are also relevant, but their negative impact is more pronounced in children without GS. Thus, this process is not of a pathological nature and does not require any treatment. Introduction: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a critical and a very potent inhibitor of T-cell proliferation that serves as a "immune checkpoint". Patients with CTLA4 haploinsufficiency with autoimmune infiltration (CHAI) present with autoimmune cytopenias, hypogammaglobulinemia, organ-specific autoimmunity, lymphadenopathy/splenomegaly and lymphocytic infiltration of non-lymphoid organs.

Objectives: To describe a family with CHAI involving multiple members across 3-generations. Methods: Retrospective review of clinical records was performed. A detailed clinical history including the age of presentation, symptoms, family history, findings on physical examination, laboratory findings and treatment details were recorded. Whole exome sequencing was performed on Next generation sequencing platform. Results: A 10-year-old boy, born to a non-consanguineously married Indian couple presented with history of passing blood in stools from the age of 4-years. He also had had recurrent episodes of wheeze associated lower respiratory tract infections and had received multiple courses of antimicrobials. At the age of 9, he developed chronic diarrhea and was treated with antibiotics on multiple occasions with no relief. He had a strong family history involving his father and paternal grandmother. Father, a 35-year old, developed severe anemia at the age of 13 years and was diagnosed with autoimmune hemolytic anemia (AIHA) that responded to steroid therapy. He has had three relapses so far and the recent episode was treated with intravenous immunoglobulin. At age of 22 years, he developed chronic diarrhea and was treated as a probable case of celiac disease with gluten free diet with no relief. Paternal grandmother, 55-year old, developed AIHA at the age of 42 years and has had multiple relapses requiring steroid therapy. At the age of 45, she developed chronic diarrhea with significant weight loss, possibly autoimmune enteropathy that has partially responded to steroids.

On examination, index case was found to be underweight and had an enlarged right axillary lymph node. Computed tomography abdomen showed multiple enlarged intra-abdominal lymph nodes and endoscopy of the small and large bowel revealed diffuse nodular hyperplasia. Immunological evaluation showed normal serum immunoglobulins. In view of the strong family history,an autosomal dominant pattern of inheritance was suspected,and genetic evaluation was carried out. A pathogenic heterozygous mutation c.416A>G (p. Tyr139Cys) was identified in exon 2 of the CTLA4 gene by whole exome sequencing. A diagnosis of CTLA-4 haploinsufficiency with autoimmune infiltration (CHAI) was established. The index case has been started on steroids and sirolimus and is under close follow-up. A review of literature of 222 CHAI patients reported the median age of onset of symptoms to be 10-years (6-16 years) with median age at diagnosis being 23-years (17-40). Family history of immune deficiency was reported in 62% and autoimmunity was observed to be the most common presentation in these patients. The age of onset of symptoms in the index case was 4 years and age at diagnosis was 9 years, however, it was much delayed in both his father and paternal grandmother. Non-malignant lymphoproliferation as reported in previous cases series was also noted in the index patient. Initially patients with CHAI were treated with rapamycin, however various studies have reported a promising role of abatacept, belatacept and sirolimus as a first-line therapy to control manifestations of immune dysregulation. However, HSCT offers a more definitive therapy in patients with severe disease manifestations or poor control with immuno-modulatory drugs. Conclusion: Poly-autoimmunity with lymphoproliferation is a known presentation of CHAI. We hereby present a family with CTLA-4 haploinsufficiency involving members from 3-generations. Introduction: Childhood skin psoriasis and psoriatic juvenile idiopathic arthritis (psJIA) are poorly understood. Approximately 50% of psJIA patients develop joint disease prior to skin involvement, making the diagnosis challenging. Because psJIA poorly responds to first-line treatments for other forms of JIA, delayed diagnosis frequently contributes to prolonged disease activity.

Objectives: Aiming at the definition of biomarkers and new treatment targets, this study investigated molecular phenotypes of immune cells in psoriasis/psJIA as compared to controls (enthesitis-related arthritis (ERA-)JIA, healthy individuals) using DNA methylation mapping and cytokine expression profiling. Methods: Using biospecimen from patients with psJIA (5), ERA-JIA (6) , and healthy controls (5) DNA and RNA were isolated from CD4+ T cells. DNA Methylation was assessed using Illumina EPIC BeadChips; gene expression was investigated using NanoString Inflammation panels.

Disease-specific gene expression profiles were found in CD4+ T cells from psJIA and ERA JIA when compared to healthy controls. LGAL S3 (20/97, 20 .6%). Twelve children underwent testing for myositis specific autoantibodies in ≤3 years group. Positivity for anti-TIF-gamma positivity, NXP-2 positivity, anti-Jo-1, anti-TIF-gamma with PM/Scl-100, anti-Sm with snRNP with anti SS-A were seen in 3, 2, 2, 1 and 1 respectively. Patients in group 1 took longer time to achieve remission than patients in group 2(median time to achieve remission: 8 months vs 6 months,p-0.011).However,the number of patients receiving methotrexate,pulse steroids,pulse cyclophosphamide, intravenous immunoglobulin and mycophenolate mofetil were comparable between the two groups. The median follow-up duration was 6.35 years and 3.4 years in group 1 and 2 respectively. The number of patients with relapses and episodes of relapses, presence of lipodystrophy and calcinosis were comparable between two groups. In group 1, there was only 1 (2.9%) death (aspiration) as compared to 7 cases (7.2%) in group2. Conclusion: The highlight of the study is that none of the younger children (≤3 years) had severe respiratory muscle weakness or ventilator support requirement. Amyopathic forms of JDM, ILD, overlap syndromes, and Raynaud's phenomenon are much less common in ≤3 years age group. Older children had higher incidence of periorbital edema at presentation as compared to younger ones. Younger patients in our cohort took significantly longer time to achieve remission but mortality rate is less in younger children as compared to older children. Introduction: Juvenile inflammatory myopathies (JIM) are a heterogeneous group of diseases characterized by muscle weakness, skin manifestations, and involvement to different organs 1 . They comprise four groups: dermatomyositis, polymyositis, inclusion body myositis, and immune mediated necrotizing myopathy. Overlap myositis has recently been recognized as an autonomous entity 3 . Juvenile dermatomyositis covers 80% of patients, with an incidence of 4.1 cases per million children per year 1 . Laboratory tests are fundamental to the diagnosis of JIM, more than 80% of patients present increase in muscle enzymes (creatine kinase, lactate dehydrogenase, aspartate and alanine aminotransferase, aldolase) and antinuclear antibodies (ANAs) are found in more than 76% of patients 1 . Myositis-specific antibodies (MSA) and myositisassociated antibodies (MAA) can be present in different groups of JIM and their presence is associated with various clinical phenotypes 2 . There is a lack of information related to serologic profile in Latin-American patients with JIM. Objectives: To describe the clinical and serologic characteristics of patients with inflammatory myopathies in a single Mexican center. Methods: A single-center observational cross-sectional study was carried out, analyzing the clinical records of patients diagnosed and followed with JIM in the pediatric rheumatology clinic of our hospital between May 2008 and April 2021. General demographics, clinical and laboratory criteria at diagnosis, serologic (ANAs, MSA, and MAA), and complementary studies information were collected in order to perform descriptive analysis. Results: Twelve patients were included in the study, 66% female (n = 8), median age of onset 8.5 (2 -14) years, males were younger at diagnosis, diagnosis delay 2.9 (1 -9) months. All patients presented muscular features, 92% (n = 11) cutaneous manifestations, 25% (n = 3) Raynaud's phenomenon, and 33% (n = 4) calcinosis. None of them presents gastrointestinal, neurological, heart, or kidney disease. Three patients presented as overlap with scleroderma. ANA was positive in 6 patients (50%), with fine speckled (n = 3), fine speckled + centriole (n = 1), filamentous (n = 1), homogeneous nucleolar (n = 1) immunofluorescence patterns. Eight patients had a MSA and MAA panel, 3 were NXP2+, 2 MDA5+, 1 PMScl+, 1 Mi2a+ and 1 TIF1g+. The pattern associated with younger age at onset was NXP2, a higher risk of relapses occurs in MDA5 positive patients, calcinosis was frequently found in patients with FIF1g and NXP2, extrapulmonary calcifications in MDA5 and TIF1g. Conclusion: This is one of the firsts reports on clinical and serological findings from JIM Latin-American patients. Presentation has a defined variability in terms of the positivity of antibodies, and there is a need to collect more data to understand MSA and MAA relevance in outcomes of this patients. Results: Twelve cases were identified: 67% female. The median age (IQR) at diagnosis and median time to diagnosis were 3.4 (2-6.5) years and 3.5 (1.2-8) months, respectively. The common clinical presentations were weakness (100%), Gottron papules (75%) and heliotrope rash (42%). Most patients had polyphasic disease course. More than half of the patients (67%) developed calcinosis. Lactate dehydrogenase was elevated in all cases. Muscle inflammation was found in 88% of biopsy, 75% of electromyography and 100% on MRI. The most common myositis specific Ab was anti-NXP2 (60%). Anti-NXP2 positive patients were more likely to have calcinosis. Five of 12 cases received recommended treatment with prednisolone and methotrexate at diagnosis. One patient with calcinosis had a good response with infliximab. Conclusion: Our review underscores that JDM patients with younger age at diagnosis will need to be monitored closely and are likely to need aggressive long-term treatment. Prompt treatment should be managed according to the severity of symptoms in order to improve clinical outcome and prevent serious complication. Introduction: two main mechanisms of pathogenesis have been proposed for juvenile dermatomyositis (JDM), namely, interferon type I-(IFN-I) and antibody-centered. The activity of IFN-I signaling pathway can be measured using IFN-score.

Objectives: to evaluate IFN-score in patients with JDM. Methods: 15 patients (5 boys and 10 girls) were enrolled in the study. Clinical and laboratory parameters including disease activity (CMAS-childhood myositis assessment tool, aCATabbreviated cutaneous assessment tool) and treatment efficiency were assessed. IFN-score was assessed by RT-PCR quantitation of 5 IFN I-regulated transcripts; median relative expression of ≥2 was considered as a cut-off. Results: The median age of patients was 9.0 (5.9-10.8) years ( Table 1) . One of the patients (#15) had widespread soft-tissue calcinosis, another one (#10) had combination of JDM and systemic sclerosis. The median time to IFN-score assessment was 21 (4; 51) months. Patients were divided into groups with high (n=12) and normal IFN-score (n=3). The first group had higher aCAT activity index -3 (2-6) vs 0 (0-0), p=0.012. Positive correlations with IFN-score value were found for aCAT activity (p= 0.014) and arthritis (p=0.018). IFN-score was 11.6 (3. Introduction: Juvenile dermatomyositis is an inflammatory autoimmune disease that mainly affects the skin and muscles. Some autoantibodies may help predict damage to other organs and establish the prognosis.

Objectives: To present a case of juvenile dermatomyositis with anti-MDA5 and lung involvement. Methods: Case report. Results: A 9-year-old boy presented with constitutional symptoms of one month of evolution and skin rash (face, hands, elbows, knees). He also had aphthous stomatitis and limiting pain in the knees, ankles, wrists and fingers. No gastrointestinal or respiratory symptoms. Physical examination revealed a heliotrope rash, Gottron's papules and inverse palmar Gottron sign over the finger flexor tendons.

Wrists and thumbs were swollen, with limitation in range of motion. Only neck flexion weakness was found, with no findings in the rest of the muscle and joint examination.

In the laboratory test we found mild lymphopenia and elevated aldolase, CK, LDH, ferritin, and transaminases levels. CRP 1.8 mg/L. Weak positive anti-nuclear (ANA 1/80) and anti-MDA5 antibodies were detected. His pulmonary function tests were normal as well as his chest x-ray. When anti-MDA5 antibodies positivity was confirmed and because of its association with interstitial lung disease, a highresolution computed tomography was performed, and ground-glass opacities were revealed. The skin biopsy showed vacuolar interface, perivascular infiltrate, and leukocytoclasia, compatible with dermatomyositis. The magnetic resonance of the shoulder girdles showed patchy muscle involvement, and the electromyogram demonstrated a myopathic pattern. The capillaroscopy showed a group of capillaries with dilation (4th finger, left hand). Synovitis during the ultrasound assessment was observed, with effusion and Doppler signal in radiocarpal joints and in the left 4th metacarpophalangeal.

After confirming the diagnosis of juvenile dermatomyositis treatment was started with hydroxychloroquine, corticosteroids, methotrexate and tacrolimus. The PNEUMOVAX 23 was completed and infection prophylaxis was started with Trimethoprim/sulfamethoxazole. Two months later the arthritis and blood test were resolved, he continues with skin inflammatory activity. Without any respiratory symptoms, the pulmonary function test remains normal. Conclusion: The diagnosis of juvenile dermatomyositis is based on the Bohan and Peter criteria. Our patient presented muscle weakness, typical skin rash, elevated muscle enzymes and a myopathic electromyographic pattern. It may be accompanied by constitutional symptoms, skin ulcers, calcinosis, arthralgia/arthritis or periungual capillary alterations (1, 2) . Anti-MDA5 antibodies are associated with a poor prognosis, with the development of skin ulcers and rapidly progressive lung interstitial disease. Its prevalence in Europe reaches 12-40% in adults and children with dermatomyositis. In Great Britain it is estimated to occur in 7% of juvenile dermatomyositis (3). Chest CT is essential for the early detection of lung involvement, even in the absence of respiratory symptoms (3, 4) . The treatment is based on high-dose corticosteroids and immunosuppressants. The therapeutic response is determined by the symptomatic improvement and the laboratory (muscle enzymes) and pulmonary tests (1, 2) . There is no clear consensus on the radiological follow-up of lung involvement.

Disclosure of Interest None declared Introduction: Juvenile dermatomyositis (JDM) is the most common paediatric inflammatory myopathy and it is characterized by distictive skin rashes and symmetrical proximal muscle weakness. The most widely used diagnostic criteria are those suggested by Bohan and Peter, although they have not been tested for sensitivity or specificity against all appropriate disease confounders. Recently, myositis specific antibodies (MSA) have been detected in patients with dermatomyositis. Among them, the presence of anti-MDA5 antibodies is associated with an increased risk of skin and oral ulceration, arthritis, milder muscle disease and interstitial lung disease (ILD). However, few data concerning presentation, treatment and follow up are available on anti-MDA5 antibodies JDM patients.

Objectives: To describe the first patient with anti-MDA5 antibodies JDM and associated periostitis Methods: We performed a full blood count, liver and muscle enzymes. MSA has been detected by immunofluorescence assay. A whole body (WB) MRI was used to highlight muscle inflammation. A CT-chest scan was required to rule out the presence of Interstitial Lung Disease (ILD) Results: A 10 years old boy was admitted to our Pediatric Unit because of a three month story of pain of the wrists and legs and asthenia associated to the presence of erythematous-xerotic lesions of hands, elbows, knees and ear auricles. On physical examinations, he presented both hand arthritis, pain at digitopression of the left tibia, Gottron's papules, heliotropic rash and erythematous-xerotic lesion of elbows. No muscle weakness was noted (MMT8 78/80, CMAS 48/52). His blood count revealed mild lymphopenia (L 1260/mmc) and an increase in liver exams (ALT 180 U/I), with normal values of CPK and LDH. CRP, ESR, C3 and C4 were in ranges too. Infective and paraneoplastic causes were ruled out; a punch biopsy of the skin of the elbow was obtained to exclude psoriasis and cutaneous sarcoidosis. The autoimmune panel was negative for ANA antibodies. Due to the presence of Gottron's papule, MSA were performed, revealing the positivity of anti-MDA5 auotoantibodies. The boy underwent a WBMRI that enlightened the presence of inflammation of both peroneal muscles and left tibia periostitis, which was very painful. No signs of calcinosis were found. A diagnosis of anti-MDA5 autoantibodies JDM was held. Because of a suspicious of ILD, a CT chest scan was made, but it was negative. He started three glucocorticoid pulses (20 mg/kg) later tapered orally, intravenous immunoglobulin (2 g/kg) and subcutaneous methotrexate, which was dismissed 2 weeks later due to an increase in liver enzymes. Mycophenolate mophetile (600 mg/mq every 12 hours) was preferred with good response on both arthritis and skin lesions. Conclusion: Anti-MDA5 autoantibodies identify a distinct clinical phenotype of children affected by JDM. Data from the Japanese and English cohort differ in prognosis: Caucasian children seem to have less likely ILD than the East-Asians. In particular, English JDM patients reached remission according to PRINTO criteria after 2 years of treatment, although this is not clearly defined. To the best of our knowledge, this is the first case of anti-MDA5 positive JDM patient with associated periostitis. We described periostitis as a potential novel feature of anti-MDA5 autoantibodies JDM. Moreover, mycophenelate could be used in children as a first line therapy, even in those that present with arthritis. Our case expands the phenotype of anti-MDA5 autoantibodies JDM and supports the evidence that mycophenolate could represent a good therapeutic choice in these patients. Introduction: Anti-Melanoma differentiation associated gene 5 (MDA5) autoantibody (Ab) was identified in a small population of patients with juvenile dermatomyositis (JDM) in Caucasians and was associated with skin ulceration and arthritis. Whereas anti-MDA5 Ab was reported to be related to rapidly progressive (RP)-ILD and a poor prognosis in East-Asian patients with JDM. Objectives: We aim to report a case of 4-year-old boy diagnosed with JDM complicated with RP-ILD who was successfully treated with Mycophenolate mofetil (MMF) and Tacrolimus (Tac). Methods: A case report and a literature review. Parental informed consent was obtained.

Results: A 4-year-old boy was referred to our hospital for eruption and fever. At the first visit, he exhibited Gottron's sign on the dorsum of his hands, periungual erythema, auricular ulcer, and symmetric muscle weakness of the proximal lower extremities. The level of anti-MDA5 Ab was high (138 index), where the cut-off value is 32 index in the EIA. His chest CT demonstrated ground-glass opacities in the right upper lung lobes. He was diagnosed as JDM complicated with interstitial lung disease, and we initiated treatment with methylprednisolone (PSL) pulse, cyclosporine (CyA), and intravenous pulse administration of cyclophosphamide (IVCY). Just after the 2nd IVCY, he had syndrome of inappropriate secretion of antidiuretic hormone and posterior reversible encephalopathy syndrome, and so we had to alternatively treat him with PSL, MMF, and Tac. His myositis and interstitial pneumonia significantly improved six months after the first administration of MMF. Forty-eight months later, he achieved drug-free remission. Introduction: Lupus erythematosus tumidus (LET) is a rare type of cutaneous lupus erythematosus (CLE), which has commonly, been under-estimated, and neglected in clinical practice. LET is generally, an independent disease, although it has been reported to co-exist with discoid lupus erythematosus (DLE), and SLE. Herein, report a case of 11-year-old female child diagnosed as of LET associated with alopecia significantly improved after treatment with hydroxychloroquine in combination with oral corticosteroids and MMF. Objectives: We report a case of LET converted from DLE with diverse clinical manifestations and unusual pathologic findings. Methods: case report study Results: An 11-year-old female child born of consanguineous marriage was brought to our Rheumatology clinic with the complaint of erythema and rashes present on the face her cheeks, bridge of the nose and forehead. Subsequently, spread too much of the similar lesions were present over the extremities since 3 months. Gradually, which healed with hyper-pigmentation. Lesions occur in hairy areas such alopecia. Along with the skin lesions, the child also developed painful oral ulcers, which caused considerable difficulty in eating, poor appetite and weight loss, there was a significant history of worsening of facial skin lesions during sun-exposure and discoloration of both hands and feet on prolonged cold exposure. She later developed low-grade fever, which was not associated with chills or rigor along with joint pain over large joints (fingers of her both hands, knee and ankle). She had undergone some local treatment but was not relieve. On general examination, the child was thin-built (30 kg). Generalized pallor and no cervical lymphadenopathy were present. Her developmental milestones were normal. Cutaneous examination showed diffuse hair loss (lupus hair) and at some places patchy alopecia Erythematous rash was seen all over the face with (malar rash/butterfly rash) involving both cheeks and bridge of the nose and forehead. Showed post hyperpigmentation, Photosensitivity and Reynaud's patches were seen on the both hands and foot. Laboratory investigations revealed WBC = 3.600cells/mm3 (58% neutrophils, 28% lymphocytes), hemoglobin = 10.5g/dL, platelets = 313,000/mm3, erythrocyte sedimentation rate (ESR) was elevated 90 mm/h, CRP was negative; specific tests -ANA was positive with ANA titer = 1:160 though anti-double stranded DNA (dsDNA) was positive with titer 554 IU\ml, anti-Sm AB was positive >330 U\ml (REF <7), U1-snRNP was positive 88U\ml (REF <5), Scl70 was positive 10 U\ml (REF <7), anti-Ro/SS-A, and anti-La/SS-B antibodies were undetectable serum complement levels were normal. LFT and renal function tests and urinalysis were within normal limits. Chest X-ray and electrocardiography revealed no abnormality. Ophthalmologic tests were also normal. Systemic examinations were within normal limits. The histopathological examination of skin biopsy specimen showed dermis thinking in the blood vessels wall due to fibrin, mild papillary oedema, perifollicular and interstitial inflammatory cell infiltrate predominantly of lymphocytes and histocytes. On base of the clinicopathologic findings, a diagnosis of LET was made. Treatment was initiated with prednisolone (1 mg/kg. d), combined with hydroxychloroquine (6.5mg/kg/d) MMF and vitamin D supplements were further added to the patient Conclusion: Considering the history of LET being transformed from DLE, we speculate that a continuous spectrum may include DLE, LET, and SLE, and these 3 entities could potentially, convert between each other. Introduction: Systemic lupus erythematosus (SLE) is the prototypic multisystem autoimmune disorder with apparent shift to Th2 immune responses leading to B cell hyperactivity and production of autoantibodies. Psoriasis, on the other hand, is a predominantly Th1 immune response. The coexistence of SLE and PS is considered unusual and very rare. However, treatment is also challenging, as medications used to treat one condition exacerbate or even trigger the symptoms of the other. Worldwide, therefore. We herein report first Libyan female a child with pSLE who develops Ps; illustrate the dilemma of diagnosis and therapeutic management in such case. Objectives: to present the clinical problem of SLE and Ps coexistence Methods: case report presentation Results:

We have a 12-year-old Arab Libyan female child born by parents of non-consanguineous marriage. There was no family history of neither autoimmune nor metabolic diseases. She had history of progressive dyspnoea, periorbital edema, and fatigue over the past few months.

Her physical examination showed pericardial rub, short for her age height 113.5cm (<0.4 percentile). Investigations showed marked hypothyroidism with echocardiogram confirming severe pericardial effusion and a tamponade phenomenon. Urgent pericardiocentesis relieved her acute symptoms and prompt treatment with thyroxine replacement .one month later was referred to our Rheumatology clinic with history of malar rash and mild alopecia,diagnosed as SLE at the age of 10 years old according to American college of Rheumatology (ACR) criteria. The diagnosis of SLE was based on the presence of constitutional symptoms, malar rash, photosensitivity, serositis, hepatomegally, ANA was positive, antids-DNAab was positive 144.8 IU\ml, antiSMA was negative, anticardiolipin IgG positive 15.2 normal range <10, anticardiolipin IgM was positive 340 MPL-U\l, lupus anticoagulant was positive, C3 was low 0.3 g\l, C4 was normal 0.1, AST was very high 93.0 IU\L, ALT was very high 185 IU\L,TSH 0.09 uIU\ml very low (normal range 0.27-5) free T4 was high 31.9 pmol\l (normal range 12-22), serology test for autoimmune hepatitis and anti-tissue transglutaminase IgA,IgG were negative,).She had been in prednisone intake 10mg\day, L-thyroxin, added hydroxychloroquine 200mg since March 2019 prior to appearance of lesions and subsequent one-year history of severe skin lesions over her body. Which presented as erythematous, well-defined scaly plaques on the scalp, behind ears, trunk, extremities and buttock. The dermatologists were treated her as infectious eczematous dermatitis however, the malar rash persisted. Psoriatic skin changes became more frequent and worsening. Skin biopsy revealed the presence of psoriasis vulgaris. Other laboratory parameters (CBC, ESR, CRP, urinalysis, chemistry) were normal. ANA was positive 1:160; anti-dsDNA was negative, ENA was negative, APL-antibodies were negative, anti thyroid peroxidise AB was negative 9 IU\ml normal ranges <35. C3 was normal, C4 8 mg/dl (N: 14-44), C1q level: 15.1 (5-25), CH50: 80: (N: 60-130). Since her C4 level is low while C3 level is normal and the absence of lupus nephritis, we considered the possibility of C4 mutation. WES test has not resulted yet. Considering her SLE is inactive and her psoriasis is stable after discounted hydroxycholoquine, immunosuppressant (MMF, azathioprin that used for a while without any benefits) and prednisone was slowly tapered until discontinuation. The goal was to manage her with methotrexate if she will have flare skin lesions Conclusion: We need to consider the potential development of GPP when administering HCQ to patients with SLE even though it is rare; it is a severe adverse event.

Introduction: Overlapping JIA and JSLE is a rare clinical condition in children. RHUPUS syndrome has been defined as a Rhupus is an overlap syndrome of rheumatoid arthritis and systemic lupus erythematous (SLE) in adult patients. To diagnosis a patient with Rhupus present with clinical symptoms of SLE with positive ANA, antiDNA or antiSm, associated with clinical symptoms of JIA Objectives: Describe clinical and serological findings of a Libyan male child diagnosed with Rhupus Methods: case report Results: An 8 year-old Libyan black boy was referred with history with clinical manifestation (fever, fatigue, pallor, jaundice, and LL oedema), hepatosplenomegally, ascites and arthritis in the left elbow and left shoulder. At that time, laboratory results revealed anemia (Hb: 9.7 g/dL), thrombocytopenia (30,000/mm3) and normal leukocytes (WBC count 8000/mm3) (predominant lymphopenia) high elevated ESR 100ml\hr, positive CRP . Coomb's test was negative, elevated liver enzymes AST was 134 U\L, ALTI was 136 U\L, TB 4.2, BD 2.5, total protein 8, S. Albumin was low 3.2, viral screen (HIV, HBSAg, HCV) was negative, serology tests to exclude Wilson disease was negative, serology tests for AIH were negative, CTscan chest, abdomen pelvis revealed hepatomegaly with normal parencyhmal density, moderate ascites with minimal right pleural effusion, bone marrow aspiration was normal, ANA was positive (1/60, anti-dsDNA level was positive 1/80, anti-SM was negative, rheumatoid factor level (RF) was 7.88 IU/mL (0-14IU/mL), and C3 (65.7mg/dL) and C4 (4.4mg/ dL) levels were low. Antiphospholipid antibodies (aPL) level was negative and urinalysis was negative. He was diagnosed as JSLE, with more than five criteria,. Treatment was started with new diagnosis of SLE with Prednisolone (1mg/kg/day), Azathioprine (50 mg/d), and Hydroxycholoroquine (200/mg/day). After two years of ongoing chronic polyarthritis MRI both hips revealed a vascular necrosis of both femoral heads with subsequent changes, that needs to doing hip total or subtotal replacement in future. The main symptom lately was erosive arthritis, polyarticular, and morning stiffness and decreased joint range of motion; there was evidence of multiple joints erosion in radiologic evaluation of elbows, shoulders, hips and both knees. After 5-year followup, he is 17 years old and he is under observation and he was on low dose prednisolone (0.5 gr/kg/day), azathioprine (50 mg/d), and hydroxycholoroquine (400/mg/day) and methotraxte. The patients met 6 classification ACR 1997 criteria for SLE. All of the patients met ILAR 2001 criteria for JIA diagnosis. Joint manifestations were treated with methotrexate, the patient required etanercept therapy for persistent joint disease but unfortunately not available in Libya Conclusion: The coexistence of two JIA and JSLE in the same patient is a very uncommon finding. It is very important to recognize the Rhupus in order to make a prompt diagnosis and intervention that assures a better outcome for patients Patient Consent Received Yes Introduction: Systemic Lupus Erythematosus (SLE) patients are at risk for premature atherosclerosis at relatively young age. Endothelial dysregulation is one of the pathophysiologic mechanisms that lead to higher risk for cardiovascular disease in SLE. Objectives: To perform a systematic literature review on endothelial markers that are dysregulated in SLE and investigate potential associations with disease activity. Methods: Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of endothelial cell (EC) markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. Results: From 1892 hits, 124 eligible articles were selected. The identified endothelial markers were involved in endothelial cell (EC) activation, endothelial cell apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, GAS6, Thrombomodulin, VEGF, ICAM-1 and MCP-1. Other dysregulated markers, without associations with disease activity, were: Angiopoeitin-2, Neopterin, vWF, P-Selectin, VCAM-1, TWEAK, IP-10 and E-Selectin Conclusion: We provide a complete literature overview for dysregulated endothelial markers in SLE comprising a wide range of different endothelial functions. SLE-induced endothelial marker dysregulation was seen with and without association with disease activity. Longitudinal data on endothelial markers in SLE are now needed to guide us in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients in young adulthood. Methods: A national retrospective multicenter cohort study was performed between 2007 and 2020, including cSLE patients who presented symptomatic pulmonary features. Results: Forty-six patients, with a median age at diagnosis of 12.7 years, were included from 10 French centers. Lung features prevalence in cSLE, estimated from available data (38 of the 46 included patients, from 5 centers), was 10.1%. Acute manifestations (78%) included: pleuritis (39%), diffuse alveolar hemorrhage (DAH) (22%), acute lupus pneumonitis (22%), infections (20%). Chronic manifestations (33%) associated: interstitial lung disease (17%), pulmonary hypertension (13%) and shrinking lung syndrome (9%). Severe forms, defined as the need for intensive care or third-line therapies, were frequent (n=15/46, 33%) but no death from pulmonary manifestation was observed. Children with severe lung features had a lower female to male ratio (1.1:1 versus 5.2:1, p=0,038), presented more renal manifestations (73% versus 45%, p=0,047) and less serositis (13% versus 52%, p=0,013) in comparison to non-severe patients. DAH was more prominent in the severe group (47% versus 10%, p=0,008), while pleuritis was more frequently reported in non-severe patients (7% versus 42%, p=0,018). Conclusion: With one of the largest cohorts reported, we observed that pulmonary features in cSLE are varied and often severe. These manifestations should actively be assessed, with extensive paraclinical tests such as pulmonary function tests (associated with DLCO), computed tomography or bronchoalveolar lavage, if necessary. Early diagnosis enables adequate, aggressive treatment of severe forms, and long-term follow-up is necessary for those patients. Introduction: Angioedema is a rare phenomenon in patients with Lupus. It usually results from acquired C1-inhibitor deficiency due to antibody formation directed against this molecule. Some reports also describe patients with severe forms of Systemic Lupus Erythematous, classical pathway-mediated hypocomplementemia and presence of anti-C1q antibodies. Herein we report a case of Juvenile Systemic Lupus Erythematosus presenting with recurrent angioedema, normal C1q and C1 inhibitor antigen levels and positive anti-C1q antibodies, with an excellent response to rituximab. Objectives: -Methods: -Results: A previously healthy fifteen-year-old girl was referred to a Paediatric Rheumatology clinic due to recurrent episodes of facial and acral angioedema without urticaria or pruritus, accompanied by asthenia and painless cervical lymphadenopathy with 2 months duration. She had no family history of angioedema or rheumatic/autoimmune diseases. Type I and type II hereditary angioedema, lymphoproliferative and infectious causes were excluded. Complementary investigation identified hypocomplementemia (C3 -41mg/ dl, C4 -6 mg/d and CH50 -23.8 U/ml), positive antinuclear antibodies (1/160, fine speckled pattern), positive lupus anticoagulant antibodies and anti-C1q antibodies (237 U/mL; normal <15), with normal C1q (23.7 mg/dl) and C1 inhibitor antigen (23.5 mg/dl) and functional levels (99,5%). It was not possible to test for anti-C1 inhibitor antibodies in our institution. Acquired angioedema, associated with systemic lupus erythematous, was strongly suspected. However, the patient lacked clinical criteria for systemic lupus erythematous thus far. Hydroxychloroquine and oral prednisolone (0.75 mg/kg/day) were initiated with a fairly good response (less frequent and milder episodes). One year later, daily, severe headaches, without response to painkillers, started. Neuroimaging (MRI) was normal. Pseudotumor cerebri was excluded and a mild elevated protein CSF level was found (92 mg/dl), with negative CSF cultural results and negative anti-NMDA, anti-AQ4 and anti-MOG antibodies. Mycophenolate mofetil (600 mg/m 2 /dose) was added to therapy with a very significant clinical response.

A formal diagnosis of systemic lupus erythematous was finally established two years after angioedema presentation, with the addition of the following clinical and immunological manifestations: alopecia, malar erythema, Raynaud phenomenon, cutaneous vasculitis, polyarthritis, lymphopenia, persistent microscopic haematuria, non-nephrotic proteinuria, leukocyturia and positive anti-dsDNA antibodies. Blood pressure and renal function were normal. Due to increased frequency of angioedema episodes, poor lupus disease activity control (SLEDAI>10) with optimized conventional therapy, and inability to taper glucocorticoids, rituximab was started with excellent results (375mg/m 2 , weekly, four doses). After the first dose, the patient remained asymptomatic with sustained remission of angioedema, allowing safe tapering of glucocorticoids. Conclusion: There are scarce reports of angioedema as a presenting symptom of systemic lupus erythematous. Our patient had several atypical findings for acquired angioedema, including a normal C1-inhibitor antigen and its functional activity. Patients with classical pathway-mediated complement consumption, presence of autoantibodies against C1q and systemic autoimmune manifestations have been seldom described. The pathophysiology in most of these cases is still poorly understood and diagnosis is usually established on clinical grounds. Rituximab seems to be a safe and effective treatment in cases of Systemic Lupus Erythematosus with angioedema. Introduction: Juvenile systemic lupus erythematosus (jSLE) is a chronic multisystem autoimmune disease. Around 15 to 20% SLE patients are diagnosed before the age of sixteen. Disease severity and outcome are more serious in childhood. 1 Objectives: To analyze the pattern of disease expression, laboratory data, treatments used and outcome in pediatric patients diagnosed with jSLE, followed in a tertiary care Hospital in Spain. Methods: Medical charts of all the pediatric patients younger than 16 years old, diagnosed with jSLE between January 2008 and December 2020, according to revised 1997 American College of Rheumatology (ACR) criteria 2 and followed at the pediatric rheumatology clinic in our hospital were retrospectively reviewed. Results: We describe a cohort of 17 patients with a mean age at disease onset of 10.8 ± 2.63 years (mean ± 1SD, range 3-14 years), thirteen were female (76%), follow-up time was a mean of 3,5 ± 2 years (mean ± 1SD, range 0,6-7 years). 24% had first-degree relatives with autoimmune diseases. Arthralgia was the most prevalent clinical feature with a frequency of 76%, followed by mucocutaneous involvement (malar rash and oral aphthosis) and constitutional manifestations like fever or asthenia. Ten (59%) developed renal involvement, eight of which showed the latter at the time of diagnosis. Renal biopsy was performed in all of them, showing nephritis class II in 3/10 (2/3 evolved to IV), class III in 3/10, class IV in 3 and class V in 1/10. Neuropsychiatric manifestations developed in 6 patients. Headache (4 patients) was the most common symptom. One patient presented paresthesia and one suffered from seizures due to cerebral ischemia. Serositis was found in three (18%) patients, and pulmonary involvement appeared in two, as pulmonary hemorrhage and decreased lung function.

Hematologic abnormalities were found in 76% patients. Anemia (53%) followed by thrombocytopenia (41%) were the most common findings at diagnosis. Antinuclear antibodies (ANA) were detected in all patients, but anti-dsDNA and anti-ENA were both found in 82%. Hypocomplementemia (low C3 and C4) was detected in 15 patients (88%) at diagnosis. Some type of antiphospholipid antibody was positive in 7 patients (41%) and aCL IgM was the most antiphospholipid antibody detected at diagnosis. At the follow-up period, one patient developed renal venous thrombosis and other developed cerebral venous thrombosis. All patients received hydroxychloroquine and oral corticosteroid. Ten (59%) were treated with intravenous pulse corticosteroid, mycophenolate mofetil in 71%, cyclophosphamide in 35%, methotrexate in 41%, rituximab in 24%, tacrolimus in 12% and azathioprine in 6%. 59% received antiplatelet or anticoagulants. At the end of the study, 59% patients had an SLEDAI score of 0 (complete remission) whilst receiving treatment. 13% (2 patients) had a mild SLEDAI score (≤3), 13% had a moderate SLEDAI (>3 and ≤12) score and 13% had a severe SLEDAI score (>12) 3 . One patient required a renal transplant and two had dialysis requirement. Two patients died, one because of cerebral venous thrombosis and other died of cause nonrelated of jSLE. Conclusion: Our patients were similar to jSLE patients from other series 3, 4 . Although jSLE is uncommon in childhood, disease activity tends to be greater in pediatric patients, increasing morbidity. A multidisciplinary approach including early treatment approaches is necessary to offer the best possible outcome of this patient group. Objectives: The aim of this work is to investigate how the clinical features at disease onset impact the time to diagnosis in a monocentric cohort of patients with jSLE. Methods: The clinical records of patients were retrospectively reviewed. Patients were included in the study in case of i) diagnosis of SLE according to 1997 American College of Rheumatology (ACR) or the 2012 SLICC classification criteria for SLE and ii) disease onset before 18 years of age. Clinical data at disease onset were retrospectively collected. Continuous data are expressed as median (interquartile range [IQR]). Potential differences in continuous variables between two or more subgroups were investigated using Mann-Whitney U test or Kruskal-Wallis (KW) test, respectively. Dunn's correction was applied for multiple comparisons. Statistical analysis was performed using GraphPadPrism v6. P values <0.05 were regarded statistically significant. Results: One hundred seventy-seven patients (155 females, 87.6%) fulfilling the inclusion criteria were recruited in the study. The median age at disease onset was 12.2 years (10-14.5). The diagnosis of jSLE was made at a median age of 12.9 years (10.6-15.2), with a median delay of 2 months (1-8). A significant difference in the time to diagnosis emerged when patients were classified in 3 groups upon the age at diagnosis (before 10 years, between 10 and 15 years, after 15 years of age; KW=7.65, p=0.021). In particular, patients diagnosed after 15 years had a time to diagnosis significantly longer compared to those receiving a diagnosis of jSLE before 10 years (median 1.4 and 4.0 months, respectively; p=0.01). No difference in the time to diagnosis (months) emerged when patients were subgrouped upon the presence of renal, articular, cutaneous, neurological and haematological involvement at disease onset. In particular, patients with anemia (hemoglobin<12g/dL), thrombocytopenia (platelets<100,000/mm 3 ), leukopenia (white blood cells<4,000/mm 3 ), had a time to diagnosis not statistically different from patients with normal hemoglobin, white blood cell or platelet count, respectively. Time to diagnosis was similar in patients stratified upon anti-dsDNA antibody positivity, increased ESR or CRP levels, low serum C3 or C4. Conclusion: Age at disease onset is the main determinant of the time to diagnosis in patients with jSLE in our large cohort. In particular, subjects presenting the first clinical manifestations when aged more than 15 years were diagnosed significantly later. ) and categorical data as percentages. The association between categorical variables was assessed by chi-squared test or Fisher exact test, as appropriate. Statistical analysis was performed using GraphPadPrism v6. P values <0.05 were regarded as statistically significant. Results: One hundred seventy-seven patients (155 females, 87.6%) fulfilling the inclusion criteria were recruited in the study. The median age at disease onset was 12.2 years (10-14.5). The diagnosis of jSLE was made at a median age of 12.9 years (10.6-15.2), with a median delay of 2 months (1-8). Hematologic involvement was the most common disease manifestation (133 patients, 75%), followed by joint and cutaneous involvements (124 patients, 70% and 101 patients, 57%, respectively). Renal disease was observed in 58 patients (32.8%) while neurological complications were diagnosed in 26 cases (14.7%). Table 1 reports the immunological profile and laboratory data of enrolled patients. The only difference in disease manifestations between genders related to the higher prevalence of anemia observed in males (χ 2 : 10.4; p=0.0012). Patients with positive anti-dsDNA antibodies had a higher rate of renal involvement (χ 2 : 21.4; p<0.0001), neurological manifestations (χ 2 : 6.58; p=0.010), skin lesions (χ 2 : 54.1; p<0.0001), joint involvement (χ 2 :7.64; p=0.0057), leukopenia (χ 2 : 14.8; p=0.0001), low C3 (χ 2 : 13.08; p=0.0003) and low C4 (χ 2 : 42.95; p<0.0001). Patients with positive anti-Sm antibodies had a higher rate of leukopenia (χ 2 :4.96; p=0.0259). Complement levels were inversely related with leukopenia (χ 2 : 6.9; p=0.0086) and joint involvement (χ 2 :5.42; p=0.02). Conclusion: These data on manifestations at onset of jSLE in a large monocentric cohort allow togain further insights into a rare disease with a still high morbidity burden. Introduction: Juvenile Systemic Lupus Erythematosus (jSLE) is a rare systemic autoimmune inflammatory disease that usually presents in early adolescence. jSLE is characterized by a severe clinical course and by a higher prevalence of lupus nephritis, haematological anomalies, neurological and cutaneous involvements. Objectives: The aim of this work is to investigate the different patterns of organ involvement in a monocentric cohort of patients with jSLE. Methods: The clinical records of patients were retrospectively reviewed. Patients were included in the study in case of i) diagnosis of SLE according to 1997 American College of Rheumatology (ACR) or the 2012 classification criteria for SLE and ii) disease onset before 18 years of age. Clinical data at disease onset were retrospectively collected. Results: One hundred seventy-seven patients (155 females, 87.6%) fulfilling the inclusion criteria were recruited in the study. The median age at disease onset was 12.2 years (10-14.5), with only one child being diagnosed before the age of 5 years. Anti-nuclear antibodies tested negative in 5 subjects (2.8%). Complement serum levels were decreased in 138 patients (78%, C3 in 128 patients and C4 in 110). In 128 patients (74.6%), ESR was raised, in 21 cases with a concomitant CRP increase. Patients presented most commonly with 3 disease manifestations (58, 32.8%), while 2 organ involvements were identified in 54 patients (30.5%) and 4 in 25 subjects (14.1%). As presented in Table 1 , the most frequent pattern of disease manifestation consisted in the combination of hematological, cutaneous and articular involvements (29 patients, 30.5%). In 26 cases (14.7%), the disease started with the association of hematological abnormalities and joint involvement. Nineteen patients (10.7%) had at disease onset 4 lupus manifestations consisting in hematological, skin, neurological and renal involvements. Only few patients (6, 3.4%) had a SLE onset with 5 manifestations (hematological, cutaneous, neurological, articular and renal involvements). Conclusion: The combination of hematological and joint involvements, alone or in association with other manifestations, provides the most frequent pattern of disease presentation in our large monocentric cohort of jSLE, being identified in more than half of cases (94 patients, 53%). Methods: We performed Ped-ANAM and formal neuropsychological testing on 23 children with SLE and on 12 healthy children. All participants were assessed by a child and adolescent psychiatrist with Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime Version, DSM-5 November 2016 -Turkish Adaptation (K-SADS-PL-DSM-5-T). Participants with any current psychiatric diagnosis on the K-SADS-PL-DSM-5-T and intellectual deficits were excluded clinically. PedANAM is a computerized battery which is consisted of 10 subtests and 4 performance parameters.

Cognitive Performance Scores (CPS) were adjusted for age and sex. Higher CPS PCA levels indicate a lower probability of NCD and higher CPS multiscore kevels indicate a higher probability of NCD. If a lupus patient's CPS PCA < 0.25 and CPSmultiscore > 4.62 during follow-up, a formal neurocognitive test and neuroimaging are suggested. The software can be obtained from Vista Life Sciences (Parker CO, USA). Results: Twenty-three patients with cSLE and 12 healthy children were recruited into the study. There was no statistical difference between 2 groups in the mean of age and gender (p>0.05 Introduction: In systemic lupus erythematosus, the presence of antibodies against complement C1q (anti-C1q) in combination with anti-dsDNA and low complement has a strong serological association with lupus nephritis [1, 2, 3] . There is paucity of data on the clinical significance of anti-C1q in juvenile systemic lupus erythematosus (jSLE), particularly with non-renal lupus.

Objectives: This retrospective study aimed to identify clinical and laboratory associations of anti-C1q in a large single centre UK based paediatric cohort with jSLE and determine the value of anti-C1q as a marker in patients without lupus nephritis. Methods: Patients seen in the connective tissue disease (CTD) clinic at Great Ormond Street Hospital from May 2014 to July 2019 were included. The following characteristics were collected: sex, age, ethnicity, organ system involvement at presentation and follow-up, presence of anti-C1q, anti-dsDNA antibodies, anti-nuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA) and its subtypes, antiphospholipid antibodies, complement C3 and C4 levels, immunoglobulins levels, urine albumin/creatinine ratio. Therapies used were also recorded. Measurement of anti C1q is part of the routine assessment at presentation and follow-up for all patients with a possible or established diagnosis of CTD in our centre. Data were analysed using Statistica. Differences between groups were tested using Mann-Whitney U-test for non-parametric variables and Chi-square and Fischer Exact for parametric variables. P-values less than 0.05 were considered statistically significant.

Results: 128 patients were included (20% male, 80% female), the median age at diagnosis was 10.0 years (range 0.9-15.9 years). 73% met the 1997 American College of Rheumatology criteria for jSLE diagnosis, and 27% had other CTD diagnoses. 46% of patients tested positive for anti-C1q and 54% tested negative. Anti-C1q positive patients were more likely to have a diagnosis of jSLE compared to negative patients (75% and 39%, respectively; P= 0.01). Nephritis, anti-dsDNA positivity, low C3, low C4 were more common in anti-C1q positive compared to negative patients: 42% compared to 12%, P=0.0001; 67% compared to 32%, P=0.0002; 62% compared to 15%, P=<0.0001; 65% compared to 34%, P=0.001, respectively. Positive anti-C1q patients were more likely than negative patients to have arthritis, (71% compared to 44%, P=0.002), oral or nasal ulcers (47% compared to 29%, P= 0.03) and they were less likely to have neurological disorder (18% compared to 42%, P=0.004). 85% of the 46 cases with jSLE had positive anti-C1q and polyarthritis at presentation; of this subgroup 46% had no nephritis at any time during follow-up. From that group of patients, 22% had anti-C1q positivity, arthritis and no renal involvement, despite negative anti-dsDNA antibodies at presentation. Other differences between groups of patients did not meet the significance threshold once remaining clinical and laboratory features were considered. Conclusion: Previous paediatric studies investigated the association of anti-C1q with lupus nephritis and SLE disease activity markers and we supported this association. In addition, our results highlight an association between anti-C1q positivity and arthritis and mouth ulcers in jSLE. Interestingly, the anti-C1q antedated the anti-dsDNA positivity for a minority of patients with arthritis. Larger prospective studies are needed to confirm our observations. Nevertheless, these data support screening for these antibodies in paediatric patients presenting predominantly with arthritis.

Having a child with a chronic disease is stressful for all members of the family, and especially for the primary caregiver (in most cases, the mother). Caregiver burden is used to identify physical, psychological, social or financial problems that may occur while providing care to another person with a physical or mental disability.

Objectives: There is no documentation about the association between caregiver burden and psychological status in caregivers of patients with childhood-onset systemic lupus erythematosus (SLE). The aim of this study was to evaluate the associations between caregiver burden and both the caregiver's and child's psychological symptoms in a cohort of children with SLE. Methods: Thirty-four patients (aged 9-18 years) with childhood-onset SLE and their caregivers participated in this study. The control group (n=34) was composed of healthy children and their caregivers. The Zarit Burden Interview (ZBI), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to assess caregiver burden and the caregiver's psychological state. The Strengths and Difficulties Questionnaire (SDQ)-parent form was completed by the caregiver to assess the psychological state of children and adolescents.

Results: The mean age of the children and caregivers in the patient group was 14.35 ± 2.83 and 39.91 ± 5.19 years, respectively, and it was 15.62 ± 1.46 and 42.44 ± 7.12 years in the control group. There was no difference between the groups in terms of the ages of the children and caregivers. No significant difference was found between the study and control groups for caregiver burden, anxiety and depression in parents, and psychological status in children. Objectives: To explore, in-depth, the views of CYP on a proposed animation and voice-over, which will help to explain the concept of T2T to eligible JSLE patients in a future T2T clinical trial.

Methods: An illustrated animation story board was developed on PowerPoint, to be used alongside a contemporaneous voiceover which allowed the animation to be simulated for CYP participating in three established young person's research advisory groups (Generation R, Lupus UK young person's group, and YOUR RHEUM). Topic-guided discussion was used to generate feedback on both the storyboard and voiceover. Meetings were recorded, transcribed and analysed for key areas of improvement. Changes were made iteratively to the resources, based on participant feedback. Participants completed pre/post workshop questionnaires to assess the impact of the resources on their understanding of T2T. . The majority of CYP (76%) felt that the concept of T2T is best communicated using an animation and accompanying participant information sheet. 19% felt the animation could be used alone, and 5% stated they would prefer a written description alone. Participants liked that the animation followed the journey of a patient participating in a T2T study. They liked the use of a graph which showed progress towards the target. CYP made the following suggestions for improvement; (1) a slide showing a clearer side by side comparison T2T and standard care, using key words and pictures to demonstrate the differences, (2) involving different characters in the voiceover (patient, doctor, narrator), (3) inclusion of a parent in the animation rather than a patient alone, (4) emphasising that it isn't the patients fault if they haven't met their target, (5) changes to terminology. Conclusion: Involvement of CYP in research is crucial to help improve the design and delivery of studies, ensuring that it is relevant to CYP/families. In the current study, involvement of CYP has greatly improved the animation explaining the concept of T2T, leading to important changes to the visuals, terminology and content, and significant improvements pre/post-test survey scores. These resources will be of benefit in a future JSLE T2T study, supporting study recruitment. Trial registration identifying number:

Introduction: Wilson's disease (WD) is a rare, recessively inherited disorder of copper metabolism with its accumulation in multiple organs particularly in the liver and brain. Systematic lupus erythematosus (SLE) is an autoimmune disease, and like WD, it involves multiple organs and systems. The combination of WD and SLE is not usual apart from iatrogenism. Objectives: we present a pediatric case of concurrent WD and primary SLE not induced by penicillamine. After extensive research in the literature, this is the only male case described so far. The other seven reported cases are female. Methods: Case presentation: A previously well 12-year-old boy was admitted at the University Hospital Center of Batna (Algeria) with acute haemolysis (pallor, subictereus, and red urine). There was no consanguinity, or family history. Physical examination revealed normal development and growth, no fever, and no signs of swelling in the liver, lymph nodes and spleen. A complete blood count (CBC) revealed normochromic normocytic anemia, Thrombocytopenia, and Leucopenia. His blood biochemistry showed Hepatic cytolysis, and Hepato-cellular insufficiency. WD was suspected because of the combination of the impaired liver function, hemolytic anemia, and normal alkaline phosphatase levels. Serum ceruloplasmin and copper levels were decreased, while urinary copper was elevated confirming the diagnosis of WD. There was no neurological or ophthalmological involvement. Family investigation revealed WD with cirrhosis in a 9-yearold brother. The onset of nephrotic syndrome and the presence of inflammatory syndrome cannot be explained by WD. The kidney biopsy histopathology revealed nephritis lupus class II (WHO classification). Subsequent serum analysis also revealed positive native anti-DNA and anti-PCNA antibodies verified on a second sample. Based on all the findings, the final diagnosis for this patient was Wd combined with SLE. We started therapy with bolus of corticosteroids and Cyclophosphamide, relayed by Mycophenolate Moftil and hydroxychloroquine Cooper chelation has also been initiated. Improvement in renal and even hepatic damage was noted. Unfortunately, after two years, the patient presented abnormal movements with dysarthria. Brain MRI showed abnormal signals of the basal ganglia consistent with neurological damage in WD. Results: Discussion : Concomitant SLE and WD without penicillamine treatment is rare (7 cases reported in the literature with 3 children). To our knowledge, this is the first report of an association between WD and SLE in a male. In our patient, SLE and WD were diagnosed simultaneously as 4 other described cases. WD was first suspected due to unexplained impaired liver function with hemolytic anemia. Copper Tests confirming the diagnosis. At that time, there was no neurological or ophthalmological impairment. In our patient, the worsening of the hematological involvement (pancytopenia) in an inflammatory context, with installation of a nephrotic syndrome cannot be explained by WD. SLE was evoked despite the fact that it was a child and male. Renal biopsy as well as the immunological workup were in favor of SLE disease. Treatment of SLE improved symptoms but later chelation could not prevent the usual neurologic complication of WD at this age. Neurological involvement appeared at the age of 14 as described in the literature with the common sign of dysathria, followed by the installation of abnormal movements due to the impairment of the basal ganglia seen on MRI.

Conclusion: WD and SLE not induced by penicillamine can co-exist. As there is no pathophysiological explanation, it's probably a simple fortuitous association. Introduction: Rasmussen's encephalitis (RE) is an immune-mediated disease characterized by resistant focal epileptic seizures, progressive hemiplegia, cognitive impairment, and unilateral inflammation of the cerebral cortex. Both RE and systemic lupus erythematosus (SLE) have common autoimmune markers suggesting the existence of common immune mechanisms in the pathogenesis. Objectives: To describe the coexistence of RE and SLE. Methods: Case report Results: An eight-year-old girl was admitted to the hospital with a right-sided focal motor seizure and right-sided weakness. Electroencephalography (EEG) showed rare sharp wave discharges in the left frontocentral region. Brain magnetic resonance imaging (MRI) and computerized tomography were normal. The patient was treated with levetiracetam. However, focal seizures and unilateral deficits persisted for two months. A repeat MRI revealed a signal increase in the left frontal lobe, the cortical-subcortical area of the insula and the putamen, and volume loss in the left frontal lobe on the FLAIR sequences. With MRI and the EEG findings of slowing bioelectric activity in the left hemisphere, a diagnosis of RE was made. Despite treatment with levetiracetam, oxcarbazepine and topiramate, seizures persisted. At the pediatric intensive care unit, 20 mg/kg pulse methylprednisolone for three consecutive days and 2 g/kg intravenous immunoglobulin (IVIG) were administered. Since the patient's mother had SLE and her aunt had lupus nephritis, the patient was searched for other autoimmune disorders that may accompany RE. ANA, which was tested before IVIG infusion, was positive. A detailed history concerning SLE revealed constitutional complaints such as hair loss, fatigue, anorexia, and cognitive changes such as excessive aggression and introversion. She also had intermittent arthritis of hands with morning stiffness in the last year. ANA was positive at a titer of 1/1000 -1/3200 with a speckled pattern, anti-RNP/ Sm, and direct coombs were positive. The patient was diagnosed as SLE.

The treatment was aimed to cover both disorders. Methylprednisolone 2 mg/kg and monthly IVIG infusions for RE were continued, and cyclophosphamide (500 mg/m2/month for six courses) with hydroxychloroquine was added. Cyclophosphamide induction therapy was switched to azathioprine. No new organ or system involvement developed, and the frequency of seizures decreased. Results: A total of 17 children (female: male-7.5:1) with SLE were analysed. Median age of symptom onset was 13 years (range 8-17 years). The initial manifestations at the time of presentation were fever(59%), joint involvement(59%), malar rash(47%), renal involvement(35%), photosensitivity(30%), alopecia(19%), headache(19%), body ache(19%) Raynaud's phenomenon(12%) and gastrointestinal complaints(12%). Atypical presentation included isolated peripheral arthritis(6%) and B/L pleural effusion(6%). Lupus nephritis was present in 6 (35%) children. Renal function tests were deranged in only 1 case. Out of 6, 66.67% (4) patients with lupus nephritis were diagnosed to have hypertension. Urine examination revealed proteinuria and microscopic haematuria in 6 patients. Renal biopsy was done in 5 patients, 2 had class III and other three had class II, class IV and class V lupus nephritis respectively. ANA, Anti dsDNA positivity and hypocomplementemia were present in 94%, 45% and 75% of patients respectively. One patient had positive Anti Smith,U1RNP,SSA,RO 52,SSB antibodies. AVN of hip joint was detected in 2 of our SLE patients (12.5%).Both the patients required core decompression of femoral head. One patient developed osteonecrosis B/L hip joints on prolonged steroid therapy 7 years after diagnosis of disease whereas the other patient developed symptoms 1 year after diagnosis and steroid intake. In our study, there was an association between intravenous pulse methylprednisolone and AVN. It highlights the value of screening lupus patients by MRI to rule out the presence of AVN. All patients were started on hydroxychloroquine and photoprotection. Children with renal involvement were given pulse methylprednisolone followed by tapering doses of oral prednisolone and intravenous, monthly cyclophosphamide. Azathioprine or Mycophenolate Mofetil were used as maintenance therapy in all. Subcutaneous weekly methotrexate was used in 2 patients. Two children died during the disease course. Cause of death was Macrophage Activation Syndrome (MAS). The case fatality rate was 12% in our centre. Disease continues to be in remission in rest.

The current study reveals complications and few atypical presentations in children with SLE. There is a significant female preponderance in our study group. Joint involvement followed by renal was the commonest presentation. We believe that the aetiology of AVN in SLE is multifactorial. Corticosteroid is the main predisposing factor for AVN in SLE patients and its use should be judicious. Early recognition of SLE is critical for timely initiation of appropriate treatment. Introduction: Anti-C1q has been associated with systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis in previous studies Objectives: Aim of this study was to determine the prevalence of anti-C1q antibodies in the pediatric SLE population and to determine clinical associations of elevated anti-C1q antibody levels especially with lupus nephritis Methods: Sera of 150 pediatric SLE patients who fulfilled ACR criteria for SLE were recruited. After obtaining informed consent, blood samples were tested for anti-C1q antibody by commercially available ELISA kit. Prevalence of anti-C1q and its association with lupus nephritis were determined Results: Out of total 150 children with SLE, anti-C1q positivity was present in 95 children (64%), at a cut off value of 20U/ml. Children with proteinuria, low C3, low C4 and anti dsDNA positivity had were significantly more likely to have anti-C1q antibody positivity. Children with lupus nephritis were significantly more likely to have anti C1q antibodies positive than children without renal involvement (74% vs. 51%, p= 0.02). Among the children with lupus nephritis, children with active renal disease were more likely to have anti-C1q positivity than in children with quiescent disease (88% vs. 53%, p= 0.002). Anti-C1q antibodies had a sensitivity of 74% and specificity of 54% at a cut off value of 22U/L, for renal disease in pSLE Conclusion: Out study confirms previous findings of the association of anti-C1q antibodies with nephritis and disease activity in pSLE. Anti-C1q antibody titers were found to have positive correlation with renal disease in children with pediatric SLE, and could be used as an adjunctive biomarker in monitoring disease activity in children with lupus nephritis General Paediatrics, Infectious Disease and Internal Medicine; 2 Child and Adolescent Psychiatry; 3 Objectives: Describe thoroughly j-NPSLE features and try to identify specific markers. Methods: Retrospective (January 2017 to December 2020) monocentric study including any patient followed for j-SLE (onset < 16 years) meeting the 2019 European League Against Rheumatism (EULAR) American College of Rheumatology (ACR) Classification Criteria for SLE. Neuropsychiatric events were attributed to SLE using ACR NPSLE criteria (isolated headaches excluded) after multidisciplinary evaluation by a psychologist, a child psychiatrist, and a paediatric rheumatologist.

Results: Among 39 patients included, 44% (n=17) presented with j-NPSLE. J-NPSLE was diagnosed at the onset of j-SLE in 59% and was most often associated with active lupus disease. Patients with j-NPSLE had frequent kidney involvement (76%). All had psychiatric symptoms: hallucinations (71%), psychomotor retardation (71%), cognitive symptoms (59%), depressed mood (35%), catatonia with agitation (12%). Headache (53%) and hyperreflexia (41%) were often associated. The main signs noted on brain MRI were T2/FLAIR white matter hypersignals (71%), often considered as non-specific, and cerebral atrophy (88%), sometimes following corticotherapy. Neopterin and interferon-alpha (IFN-α, quantified by Simoa) in CSF were higher at j-NPSLE diagnosis than during partial or complete remission of j-NPSLE (respectively p=0.01 and p=0.001). During the acute phase steroid shots followed by oral corticotherapy were initiated in 15 patients (88%), cyclophosphamide in 9 patients (53%) while 13 patients (76%) were treated by mycophenolate mofetil in the maintenance phase. Under immunosuppressive treatment, clinical improvement of neuropsychiatric symptoms was observed in all patients. Conclusion: Clinicians should be aware of the unique presentation of j-NPSLE (predominantly psychiatric manifestations). CSF IFN-α (Simoa) and neopterin levels may be new significant biomarkers. Nevertheless, prospective investigations are warranted to assess the specific link between these biomarkers and active NPSLE. Introduction: Pediatric SLE (pSLE) represents 15% of all patients with SLE. Renal and neuropsychiatric involvement is more aggressive in pSLE, with single-organ involvement being the most common clinical form of appearance. Forms of presentation such as cerebral infarction and serositis are uncommon presenting manifestations in pSLE. Treatment of pSLE does not differ from that of adults and the therapeutic arsenal is the same as in adult forms. Rituximab (RTX) is a biological agent used worldwide in SLE with excellent results, however, there is still no consensus on its real efficacy in SLE.

Objectives: Presentation of 2 cases of pSLE with infrequent forms of presentation (cerebral infarction and serositis), which did not respond to conventional therapy but did respond to rituximab. Methods: Case report, with a description of the clinical picture, diagnostic method and form of treatment.

Results: First case: a 16-year-old woman presented with a progressive headache with a tonic-clonic seizure. The brain scan shows a left frontoparietal cerebral infarction. On physical examination, he found livedo reticularis in the lower limbs, joint pain, hair loss, and oral ulcers. Tests reveal normocytic anemia, thrombocytopenia, decreased complement, 1/320 ANA with homogeneous pattern, and 3,200 mg of protein in a 24-hour urine sample. Diagnosis of pLES is made and it is pulsed with methylprednisolone 1 g EV daily for 3 days, then cyclophosphamide 1 g EV monthly. After 3 months, proteinuria, fatigue and arthralgia persist. For this reason, it was decided to use rituximab at a dose of 375 mg / m2 on days 1 and 15 every 6 months. After 4 infusions, the proteinuria disappeared, as well as the arthralgias and general malaise. She currently maintains SLEDAI-2K in remission score, maintaining low doses of prednisone. Second case: a 10-year-old boy, diffuse abdominal pain with associated distension begins more or less abruptly. Tiredness, shortness of breath, and palpitations are added. A plain abdominal X-ray does not show air-fluid levels, but the chest plate shows bilateral pleural effusion with enlargement of the cardiac silhouette. An abdominal echocardiogram and ultrasonography show pericardial effusion and ascites respectively. Physical examination reveals general paleness, translucent lower limb edema, pericardial rub, and decreased vesicular murmur in both lung bases. Laboratory tests show leukopenia, lymphopenia, normocytic anemia, elevated acute phase reactants, ANA 1/560, anti-DNA 280 U / mL, decreased complement, elevated urea, creatinine, and transaminases. SLE is diagnosed and it is pulsed with methylprednisolone 30 mg / kg / dose for 4 days, to then go on to mycophenolate 600 mg / m2 daily. Initially there is improvement, but after 2 months initial serositis reappears. It was decided to use rituximab 375 mg / m2. After the second infusion, serositis improved, but maintained elevated creatinine levels. He is currently in low activity, with lupus nephritis and slightly elevated creatinine values. , dermatology (4/112, 4%) or by a multi-speciality team (all involving rheumatology or nephrology) (9/112, 8%). Most patients (82/112, 73%) were seen by at least one other hospital team prior to diagnosis and 25/112 (22%) were seen by two or more other hospital teams prior to diagnosis. The diagnosing clinicians felt that patients had not been referred appropriately, despite seeking medical review, in 15/112 (13%). Table 1 shows the five individual factors reaching statistical significance as potential predictors of shorter time to diagnosis. When combined within a multivariate model, the only factor that retained significance was overnight admission at diagnosis. Interestingly, length of stay did not reach statistical significance, perhaps implying that the importance of admission is not solely related to the patient being more unwell at diagnosis. Conclusion: There remains a marked delay in achieving diagnosis for CYP presenting with JSLE. In the UK and Ireland, overnight admission at diagnosis appears to be the strongest predictor of shorter time to diagnosis. This may relate to the patient being more unwell (and therefore warranting admission) or by accessing a more expedient diagnostic work-up through elective admission to hospital. Future studies should focus on understanding whether novel care pathways, including routine admission for patients with possible JSLE to facilitate diagnostic work-up could lead to earlier diagnosis and treatment. The boys more often had acute cutaneous lupus at the onset (95% boys and 68% girls, respectively) (p = 0.0084). We did not find a statistically significant difference between other manifestations of jSLE depending on sex, but boys were relatively more likely to have non-scarring alopecia (33% and 16%, respectively), involvement of nervous system (38% and 20%) and leukopenia (81% and 60%). Assessment of the immunological features had no statistically significant differences depending on sex, but anti-Smith antibodies (24.4% and 14.3%) and hypocomplementemia (53.3% and 33.3%) were more presented among girls. Evaluation of disease activity at onset did not reveal sex differences (12 [8; 17] in girls and 14 [8; 19] in boys). Therapeutic options were comparable depending on sex. The use of biologics (B) (rituximab/belimumab/abatacept), including sequential Introduction: Systemic Lupus Erythematous (SLE) is a chronic autoimmune disease that can involve any organ system with a wide range of disease manifestations, and can lead to significant morbidity and even mortality.

Objectives: This series describes the epidemiology, common clinical features, complications of disease, and the management of SLE in children.

Methods: A single center retrospective descriptive study of 35 children with SLE.

Results: There was 27 (77%) girls and 8 (22.9%) boys. The mean age at diagnosis was of 9±2 years, with extremes of 3 and 15-year-old. Systemic involvement was in the form of protracted fever in 62.8%, nephrotic syndrome in 37%, nephritic syndrome in 40%, thrombotic microangiopathy in 8.6%, isolated proteinuria in 25.7%, acute kidney injury in 25.7%, malar rash in 48.6%, arthritis in 57%, neurolupus in 17%, serositis in 11.4%, and hemolytic anemia in 28.6%. Autoimmune conditions associated with SLE were systemic sclerosis, antiphospholipid antibodies syndrome and Gujerat-Sjogren syndrome in one case each. Two cases had severe pancreatitis as a revealing pattern. Posterior uveitis was present in one case. Meanwhile, pulmonary involvement was seen in two cases (interstitial lung disease and recurrent pneumonia). Proliferative lupus nephritis was found in kidney biopsy in 48.6%. Four cases had an end stage kidney disease and were put under hemodialysis. Management consisted on hydroxychloroquine at 5 mg/kg/day and oral steroids at a starting dose of 2 mg/kg/day in all cases, while pulses of methylprednisolone were prescribed in 57% of our cases. Other immunomodulatory treatments used were IV cyclophosphamide in 34.4%, mycophenolate mofetil in 51.4%, azathioprine in 8.6%, tacrolimus in 5.7%, rituximab in 11.4%, and methotrexate in 2.8%. Evolution was marked by stabilization of the disease activity in 42.8% and recurrent flares in 28.6%. Meanwhile, six cases were lost to follow-up, and four cases died. The main reason of death was the disease activity (seen in two cases), followed by infection and macrophages activation syndrome (in one case each Results: Our patient was referred with 48-hours of behavioural change: confusion, agitation and aggression. There were no physical symptoms or history of infection and her physical examination was normal. Baseline investigations were unremarkable and the following morning her symptoms had largely recovered. The Child and Adolescent Mental Health Service (CAMHS) team's initial diagnosis was acute stress reaction. It was not until she presented with catatonia 2 months later and previous investigations reviewed, that they noted an unexplained raised ESR so further autoimmune bloods were sent, including Anti-dsDNA which was positive. The patient required inpatient psychiatric treatment and then was safe for transfer to a medical paediatric hospital to begin JSLE treatment. During her follow up, the patient continued to have psychiatric symptoms however bloods normalised with an unremarkable repeat MRI brain. As a result, it is difficult to establish how best to monitor response to treatment in this patient.

Recent studies state that catatonia should be considered a red flag for autoimmune conditions(1) and may also be useful as a marker of severity (2) . As a result we continue to monitor closely. The most helpful clinical information has been from reported changes in behaviour by her mother and psychiatric reassessment. There are also side effects of psychiatric medications to consider and at times it has been difficult to differentiate behavioural changes secondary to medication changes or increasing inflammation. Ongoing care requires close work alongside psychiatry to monitor symptoms and her response to any medication changes with regular mental state examinations.

Conclusion: This is a rare presentation with primary psychiatric symptoms, posing many challenges to the team throughout. It is not uncommon for JSLE patients to have neurological involvement but this is not common at presentation(3) and is usually accompanied by signs in other organ systems. It is rare to have pure psychiatric symptoms, therefore in these patients we must look carefully for associated physical symptoms or signs for evidence of wider systemic inflammation. We must also look further into the required follow up for patients where imaging and serology do not correlate with our clinical suspicions of ongoing inflammation. How can we best measure ongoing inflammation and inform the next treatment decisions? It is our responsibility as a paediatric rheumatology community to share knowledge with our colleagues in other specialties, learn from each other's experiences and build strong cross team working relationships so that we support each other with the problem solving approach required for difficult or rare presentations. Introduction: SDI score measures irreversible damage in 12 organ systems, present for at least 6 months resulting from cSLE or its treatment.

Objectives: To measure SDI and analyse some associated factors which may contribute to long term damage. Methods: After ethics approval 50 patients with cSLE regularly following up for at least a year at the first study visit were identified and damage was measured using SDI at two separate visits six months apart. Patients with monogenic lupus, mixed connective tissue disease, drug-induced lupus, were excluded.

Demography of our patients, SDI and its damage associations and comparison with other cross-sectional studies appear in Table 1 . 28% (14/50) of patients had damage in one or more organ systems, with 20% showing damage in 1, 6% in 2 and 2% in 3 organ systems. Damage was observed in ocular (9/50;18%), neuropsychiatric (NPS) (7/ 50;14%), renal (2/50;4%) and in musculoskeletal (1/50;2%) systems respectively; and was absent in pulmonary, cardiac, gastrointestinal, peripheral vascular, and cutaneous systems. Growth failure was observed in 9 (18%) patients and none had delayed puberty. A high SDI score was associated with NPS involvement (p-value 0.002), prolonged steroid usage (p-value 0.04) and growth failure (p-value 0.04).

No corelation was observed with gender, age at diagnosis, time to diagnosis, disease duration, number of diagnostic criteria, renal disease and cyclophosphamide use. Conclusion: A striking feature is the progressive reduction in the number of patients with damage since Ravelli's first study in 2003 with the rest of the studies comparing similar numbers and similar or even longer times to SDI evaluation. SDI scores were lower in our patients compared to other studies probably due to inclusion of only regularly visiting (and thus probably adherent) patients. Using steroids in lowest possible doses, greater vigilance towards patients with NPS involvement, and growth monitoring are crucial for best outcomes. Our study additionally examined diagnostic delay as an associated factor and did not find corelation with SDI. Genetic studies revealed a substantial number of genomic loci linked to SLE susceptibility. Objectives: to evaluate IFN-I score and lupus-associated genetic variants in pediatric SLE patients. Methods: 40 SLE patients (33 girls, 7 boys) under 18 years old were enrolled in the study. The data on clinical manifestations, laboratory findings at the onset of the disease and at the point of interferon signature assessment were evaluated. Interferon score was assessed by RT-PCR quantitation of 5 IFN I-regulated transcripts; median relative expression of ≥2 was considered as a cut-off. Genetic analysis was performed in 21 patients using clinical exome sequencing (CES, Roche IDP panel). Results: 31 (77.5%) patients had increased IFN-I score, which was associated with nephritis (28% vs 0%, p=0.036) and ANA-positivity (87% vs 56%, p=0.043). Patients with increased IFN-I score needed more aggressive treatment (rituximab or cyclophosphamide, 71.0% vs 33%, p=0.040). There was no correlation between IFN-score and disease activity indexes (SELENA-SLEDAI, ECLAM). CES revealed rare pathogenic/likely pathogenic variants in 11 (52.5%) patients. Of those, 7 children had mutation in genes associated with nucleic acid sensing and IFN-signaling, two carried variants of genes associated with apoptotic and immune complex (IC) clearance and two had mutations in both groups (Table 1) . All the patients with mutations had elevated IFN I score.

Conclusion: the majority of pediatric SLE patients have hyperactivation of IFN-I pathway. IFN-I score was associated with nephritis and aggressive treatment, but not with disease activity. Half of the patients had pathogenic/likely pathogenic mutations in SLErelated genes. 

Methods: A previously healthy 12-year-old female with no personal or family history of bleeding disorders presented with hemodynamically relevant anemia (hemoglobin 48 g/l) due to menorrhagia and moderate thrombocytopenia. Laboratory investigations revealed markedly reduced Factor VIII, reduced von Willebrand Factor (vWF) ristocetin cofactor, reduced vWF activity and vWF antigen leading to the diagnosis of AvWD. Screening for underlying disease was negative for malignancy and primary or acquired immunodeficiencies. Further investigations found non-neutralizing anti-vWF IgG and a mildly elevated antinuclear antibody (ANA) titer (1:640; <1:320). Initial response to infusion of plasma-derived vWF and immunoglobulins was poor, and menorrhagia was controlled with a combined hormonal contraceptive pill and tranexamic acid. Six weeks later, the patient developed proteinuria in the nephrotic range while maintaining normal renal function leading to consultation of the rheumatology department. Further investigations showed decreased complement, increased ANA titer (1:1280) and positive double stranded DNA antibodies. Renal biopsy confirmed mesangial proliferative lupus nephritis (ISN/PRS Class I/II). Retrospectively, the patient described a malar rash.

Results: jSLE was diagnosed, based on the ACR/EULAR as well as the SLICC criteria. First-line treatment with intravenous steroid pulse and oral maintenance therapy with mycophenolate mofetil and steroids was introduced. Four weeks later, the proteinuria completely resolved and vWF levels increased significantly.

Conclusion: This case illustrates once more that jSLE can present with a wide variety of symptomsin this patient with menorrhagia due to an acquired bleeding disorder caused by autoantibodies against vWF. AvWS likely occurs in association with an underlying disorder, and search for an immune-mediated pathogenesis should be included in the workup. Keeping the differential diagnosis of jSLE in mind, even when faced with unusual clinical symptoms, can facilitate early recognition of the disease. Early specific jSLE treatment can decrease the risk of long-term organ damage and, as seen in this case, it can lead to normalization of vWF. Objectives: Here, we report on four patients with pathogenic variations in DNASE1L3, including 2 previously undescribed causal variants, and expand the phenotype from SLE to vasculitis with gut involvement. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. We also review previous reports highlighting the spectrum of DNASE1L3 deficiency. Methods: Identification of disease-causing variants was based on NGS sequencing in 3 out of 4 patients, and for one patient, coding regions of the DNASE1L3 gene were directly sequenced by Sanger sequencing. Type I interferon signature was determined using either quantitative reverse transcription polymerase chain reaction or nanostring technology, and serum IN-α2 concentrations was measured using simoa assay. Results: Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Conclusion: Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

Disclosure of Interest None declared Introduction: Childhood-onset systemic lupus erythematosus (cSLE) is a lifelong and potential life-threatening multisystem autoimmune disease. cSLE generally has a more severe course than SLE in adults with higher cumulative disease activity and earlier accrual of damage over time. Therefore, achieving and maintaining disease remission is specifically important for children with cSLE. Lupus Low Disease Activity State (LLDAS) is a disease index describing a state of low lupus activity in adults and could be a useful tool for a treat-to-target approach in cSLE as well. Objectives: To investigate the course of disease activity in a prospective cohort of Dutch cSLE patients focused on achieving disease remission and medication use. Methods: All patients fulfilled the Systemic Lupus International Collaborating Clinics classification criteria. Clinical characteristics and medication use were prospectively collected. Disease activity was measured with BILAG-2004, SELENA-SLEDAI and Physician Global Assessment (PGA). In short, LLDAS is defined by SELENA-SLEDAI ≤ 4 without an increase since the previous visit, SELENA-SLEDAI-PGA ≤1.0, and treatment with maintenance dose of immunosuppressants and/or prednisone ≤ 7.5 mg/day. Clinical remission (CR) is defined by PGA and SELENA-SLEDAI equal to 0. For CR with treatment (Tx), patients are allowed hydroxychloroquine, low dose prednisone (≤5 mg/ day), maintenance dose of immunosuppressants and biologicals. For CR without Tx, patients are allowed hydroxychloroquine. Disease flare is defined as increase of 1 point in the PGA and/or score ≥12 or increase of >4 points in the SELENA-SLEDAI and/or having A or B in any domain of the BILAG-2004 since the previous visit. Results: 54 patients (85% female, 52% white) with a total of 550 visits (median 10 per patient) were included. Organ system involvement was most often found in the hematological (69%) and mucocutaneous (67%) domains, 33% had renal involvement. BILAG-2004, SELENA-SLEDAI and PGA at diagnosis had a median of 10 (2-42), 9 (1-29) and 2.0 (0.5-3.0). After 6 months of follow-up, BILAG-2004, SELENA-SLEDAI and PGA had decreased to a median of 2 (0-13), 2 (0-16) and 0.3 (0.0-2.0). 49 children ever achieved LLDAS in a median of 179 days. 20 children ever achieved CR with Tx in a median of 406 days, and 12 ever achieved CR without Tx, median of 485 days. 28 children ever had a disease flare, median of first flare at 237 days. 87% of children were treated with hydroxychloroquine within 3 months after diagnosis. Mycophenolate mofetil (MMF) was the most frequently used immunosuppressant, 55% of children were treated with MMF within 6 months after diagnosis. 50% of children were treated with prednisone at diagnosis, median dose 0.76 mg/kg/ day, 51% still had prednisone after 6 months but with reduced doses (median dose 0.16 mg/kg/day). At 1 year after diagnosis, 21% used prednisone (median dose 0.21 mg/kg/day). Conclusion: In this cSLE cohort, LLDAS was a realistic goal, achieved in almost all children within 6 months after diagnosis and a useful (additional) guide for a treat-to-target approach. In concordance with European guidelines, prednisone use could be decreased significantly within 6 months after diagnosis, however paralleled with equal increase in use of immunosuppressants. We are currently extending this study in multiple Dutch centers to validate these results and relate achieving disease remission and prednisone use to damage accrual over time. Introduction: Recently, plasminogen, its activators, and its receptors have gained more attention in inflammation regulatory processes, including release proinflammatory signaling molecules, and thus its role has implications for a wide spectrum of clinical manifestations. Objectives: To present a case of homozygous plasminogen variant managed initially as periodic fever syndrome. Methods: A retrospective report of a child who presented with a constellation of findings; which cannot fully be explained by one classified autoinflammatory disease. Results: A 9-year-old boy presented at the age of 18-months with periodic fevers and vomiting every 3 weeks, lasting for 48-72 hours. Heterozygous variant of MEFV gene was detected (c.442G>C; p.E148Q). Over a period of 7 years he developed recurrent headaches, abdominal pain, dysphagia, failure to thrive, eosinophilic esophagitis, recurrent otitis media, pneumonias, bronchial asthma like exacerbations, eye redness, tearing, delayed wound healing, periodontitis, and loss of teeth. Also, he was found to have Pseudotumor cerebri. Immunological and infectious work-up were inconclusive. Colchicine and short courses of steroids were initiated. However, anakinra was added with a partial response. It is worth mentioning that his parents are first-degree cousins; he has a twin sister with severe cyclic GI manifestations, with remarkable response to anakinra. Other siblings had sickle cell disease suffered from similar complaints as the index case with varying degrees in severity. With the constellation of findings and the inadequate response to therapies, wholeexome sequencing was obtained revealing homozygous variant in plasminogen gene; coding for plasminogen. However, his twin was found to have heterozygous plasminogen variant. Introduction: ARPC1B deficiency is a rare syndrome caused by mutations in this gene, which consists in an actinopathy and which clinically combines immunodeficiency, allergy and autoinflammation. Objectives: To present the case of a child with a rare disease such as ARPC1B deficiency. Methods: Male with consanguineous parents and disease onset at 27 days of life with deep oral ulcers that progressively worsened, fever and papulo-purpuric skin lesions that appeared spontaneously or in the context of trauma and that subsequently were ulcerated. He associated progressive anemia, receiving several transfusions, and severe bloody liquid stools. Blood tests showed elevated CRP, procalcitonin and ferritin, platelets in the lower limit and high leucocytosis with neutrophilia. It was performed lumbar puncture (with negative cultures), brain ultrasound and cardiology study (without significant pathological findings), abdominal ultrasound (findings suggestive of colitis were observed), skin biopsy (with pathological result compatible with leukocytoclastic vasculitis) and bone marrow aspirate that ruled out malignancy. Given the significant inflammatory component (and no response to antibiotic treatment), it was decided to administer intravenous immunoglobulin doses and systemic corticosteroid therapy was initiated. Then, the patient improved clinically and didn't required new transfusions. But when reducing corticosteroid dose, there was a point when the symptoms got worse again.

It should also be noted the growth failure that didn't improve as the weeks went by and the presence, during the admission, of several infections, such as a P. aeuroginosa abscess in a vaccination area and CMV primary infection. In one of the skin flares, a biopsy was repeated, and the result was compatible with polyarteritis nodosa. Immunological study was extended: the study for chronic granulomatous disease, leukocyte adhesion deficit and functional study of the IL-10 pathway (related to neonatal Crohn's disease) were normal. An angio-MRI was also performed, in which no other vascular alterations were observed, ADA2 enzyme activity was normal and an interferon signature was also negative. At this time, due to suspicion of a possible autoinflammatory disease, a targeted clinical exome was requested and, given the important vasculitic component of the clinical manifestations, mycophenolate mofetil was associated to the treatment. The patient remained stable with this treatment. Results: It was done an exhaustive genetic study. First, nucleotide variants for recessive and X-linked pattern variants were tested. And later, a copy number variation analysis was made. This last study showed a big deletion in the ARPC1B gene, affecting the exomes 2,3 and 4. During the clinical evolution, the patient has continued presenting serious infections (like skin abscess and CMV reactivations), it was impossible to reduce corticosteroid dose lower than 1.2 mg/kg/day, he needed a nasogastric catheter to improve nutrition and, actually, the hematopoietic stem cell transplantation has been turned on. Conclusion: ARPC1B defiency is characterized by a very early onset and clinical presentation includes growth failure, fever, vasculitic skin lesions, infections and gastrointestinal symptoms. Platelet alterations are characteristic of actinophaties. The autoinflammatory manifestations seem to respond to treatment with corticosteroids, mycophenolate mofetil and sirolimus, although hematopoietic stem cell transplantation is considered the only curative option. Objectives: We aimed to explore the influence of SARS-CoV-2 pandemic among patients with JSS. In this context, we performed a web-based survey by focusing on patients' complaints, accessibility to health care and compliance of routine treatment.

The questionnaire including 28 questions was send by the telephone or by the e-mail to patients diagnosed with JSS. The first part of the form included questions regarding the demographic characteristics of patients. The second part included multi-choice of questions regarding the clinical characteristics of patients, treatment they used for the JSS and the continuation and/or discontinuation of regular follow up during the pandemic. Results: Of the 27 responders, 22 (81.5%) were females. The mean age at the time of the study was 17.3 ±3.5 years. Five patients (18.5%) responded that they had deterioration of the disease during the last 6 months. Six patients (22.2%) reported the irregular usage of their routine scleroderma treatment during pandemics. Nine patients (33.3%) missed their routine clinic control since the proclamation of the SARS-CoV-2 pandemics: 2 patients due to a lockdown, 4 patients were afraid to be infected by the SARS-CoV-2 if they go to hospital, 1 patient was feeling well so she decided to postpone the visit and 1 patient took the advantage of telemedicine. Seven patients (25.9%) had a contact with family member diagnose as COVID-19. A total of 4 patients (14.8%) were diagnosed as COVID-19 and only 1 (3.7%) of them was hospitalized. All of those 4 patients had symptoms of fever, fatigue, myalgia and headache but they completely recovered. Nine patients were under biological treatment (tocilizumab) but only one of them was diagnosed as COVID-19. Conclusion: This is the first study evaluating the impact of COVID-19 on patients with JSS. The COVID-19 hasn't significantly disrupted the medical care in JSS patients. The telemedicine could be an acceptable option for patients disenabled to come to hospital due to different reasons. Introduction: Juvenile systemic sclerosis is a rare chronic and autoimmune rheumatic disease ; whose symptoms begin on average at age 11 affecting the skin and other organs. It has a high morbidity and mortality, being a disease of which there is no consensus of treatment, so it becomes a challenge for the specialists who manage it . Objectives: To report clinical manifestations, management and outcome of systemic sclerosis in children. Methods: We conducted a retrospective descriptive study including 9 cases of juvenile systemic sclerosis. Results: All our patients were girls. The mean age at onset was of 10year-old, with extremes of 6 and 14-year-old. The mean interval between disease onset and diagnosis was of 9 months. Telltale symptoms of systemic sclerosis were tightening of the skin in all cases, protracted arthritis in 6 cases, lower-limb functional capacity impairment in two patients, recurrent skin ulcers in one patient, dysphagia in one patient, and prolonged fever in 2 patients. Skin biopsy was performed in all cases and diagnosis was made on the basis of the ACR-EULAR classification criteria for systemic sclerosis. Laboratory work-up found high acute phase reactants (ESR, CRP) in all patients. Meanwhile, three children had microcytic anemia. Electromyogram found peripheral neuropathy in one case. In the other hand, esogastroduodenal fibroscopy found significant thickening of the walls of the upper gastrointestinal tract in one patient. As for the immunological assessment, the antinuclear antibody test was positive in two patients, the anti-double stranded DNA test was positive in one patient, and the anti Scl-70 antibody was present in one case. Systemic lupus erythematosus was associated with systemic sclerosis in one girl. At last, one patient presented with proteinuria above 500 mg/ 24h, and for whom a kidney biopsy was performed and showed focal segmental glomerulosclerosis. Management was based on steroids associated with methotrexate as a first line treatment, and for a minimal period of 24 months in all cases. In one case, mycophenolate mofetil was latter added to obtain remission. All our patients were under physiotherapy and psychological support. Evolution was marked by complete remission in 5 patients and partial remission in 3 patients. Unfortunately, we deplore the death of one of our patients following a septic shock. Conclusion: the delay in the diagnosis and management can lead to permanent sequalae in children affected by systemic sclerosis, as well as a major impact on their quality of life. That is why, more awareness is needed among pediatricians to improve outcome of this disease. Methods: Demographics, organ involvement, laboratory evaluation, patient reported outcomes and physician assessment variables were compared between male and female jSSc patients enrolled in the prospective international juvenile systemic sclerosis cohort (jSScC) at their baseline visit. Results: 175 jSSc patients were evaluated, 142 female and 33 male. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. The composite pulmonary involvement was also more frequent in males, though not statistically significantly. Conclusion: In this cohort, jSSc had a more severe course in males. This reflects the adult-onset SSc cohort data and parallels it in regards to increased digital ulcers, interstitial lung disease, and global severity. Differences from adult findings include no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in jSSc need to be identical for males and females, our findings suggest a higher index of suspicion of certain organ involvement in males. Introduction: Juvenile systemic scleroderma (jSSc) is a rare, but potentially life-threatening disease. Around 45% of the patients develop interstitial lung disease and this can lead to relevant mortality. Pulmonary function tests (PFT). Including forced vital capacity (FVC) and lung carbon monoxide diffusion (DLCO), are key for the screening of interstitial lung disease. PFT require an optimal patient cooperation and coordination. For example, the patient has to hold the breath for 10 seconds. Additionally, the graph of the breath holding maneuver has to be carefully observed, if there is a premature expiration, numbers have to be judged with suspicion. We were interested how in the real world these problems are addressed in children.

Objectives: to assess how PFT is assessed in the participating pediatric rheumatologic centers in the juvenile scleroderma inception cohort Methods: We conducted a survey among the pediatric rheumatologists and associated pediatric pulmonologists, who are participating in the prospective juvenile scleroderma inception cohort (jSScC). We asked them some simple questions about the standard of care regarding assessment of the PFT. Results: 65% (26/40) of the surveyed participants of jSScC responded. From the participating centers 96%(25/26) assess the pulmonary function test in a specific pediatric setting. 65% (17/ 26) regularly assess DLCO. In 77% (20/26) of the centers the respiratory technician that conducts the PFT judges the level of cooperation of the child and the pediatric pulmonologist, who evaluates the results, also makes a judgement on the reliability of the test. We asked a specific question regarding the duration of the breath holding time setting in the lung function system. 32% (8/25) set the breath holding time under 7 seconds and 8% (2/26) at 7 seconds and 20% (5/25) between 7 and 10 seconds and 28% (7/25) exactly 10 seconds. Conclusion: We could demonstrate that in 96% of the responding centers PFT are carried out in specialized pediatric pulmonology departments, which are aware of the methodological problems and change their breath holding time to an appropriate time to gain as many reliable tests as possible. There is still a wide range of the applied breath holding time and even in centers carrying for jSSc patients, 23% do not assess DLCO. Introduction: Juvenile systemic sclerosis (jSSc) is a rare disease with a prevalence of around 3 in 1,000,000 children. To better capture the clinical manifestations of jSSc the juvenile systemic sclerosis inception cohort (jSScC) has been prospectively enrolling patients with predetermined clinical variables over the past 12 years. One of the goals is to study the demographic, clinical features, and physician and patient reported outcome differences between those with juvenile limited cutaneous (lc) compared to diffuse cutaneous (dc) disease subtypes, to determine if characteristics are similar or different between dc and lc jSSc. Objectives: Evaluation of the baseline clinical characteristics of jSSc patients in the jSScC. Compare clinical phenotype between diffuse (dcjSSc) and limited cutaneous (lcjSSc) subtypes. Methods: Demographic, physical examination, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were evaluated from the jSSc Inception cohort and summary statistics applied using chi-square test and Mann Whitney U-test comparing lcjSSc and dcjSSc subtypes. Results: At the time of data extraction, 187 jSSc patients were enrolled in the cohort, 80% were Caucasian and 80% female. Diffuse cutaneous jSSc subtype predominated (72%). Median Disease duration was 2.5 years (1 -4.4) . Median age at Raynaud´s was 10.4 years (7.2 -13.1) and median age of first non-Raynaud´s was 10.9 (7.4 -13.5 ). Significant differences were found between dcjSSc versus lcjSSc, regarding several clinical characteristics. Patients with diffuse cutaneous subtype had significantly higher modified Rodnan skin score (p<0.001), presence of sclerodactyly (p=0.003), presence of Gottron's papules (p=0.008), presence of telangiectasia (p=0.005), history of digital tip ulceration (p=0.001). Cardiac involvement was significantly higher in limited cutaneous jSSc subtype (p=0.001). Diffuse cutaneous jSSc patients had significantly worse scores for Physician Global Assessment of disease activity (35 vs 20; p<0.001) and disease damage (30 vs 15; p<0.001). Conclusion: Results from this large international cohort of jSSc patients demonstrate significant differences between dcjSSc and lcjSSc patients. According to the general organ involvement and physician global scores, the dcjSSc patients had significantly more severe disease. These observations strengthen our previous findings of the unique organ pattern of pediatric patients. Introduction: Juvenile localised scleroderma is a rare autoimmune disorder causing functional disability and aesthetic sequelae (1, 2) . It is usually considered a disease confined to skin and subcutaneous tissue but can extend to bones and has been linked to extracutaneous features, without development of systemic sclerosis (3) . Objectives: We present a rare case of juvenile localised scleroderma with acute myositis and bony changes on magnetic resonance imaging (MRI) who initially presented with blaschkoid hyperpigmentation. Methods: A case report is described. Results: A 4 year old girl was referred with knee swelling and a limp. The mother described a 2 year history of rash spanning her right leg with review by dermatology in 2019 suggesting a diagnosis of atrophic lichen planus. Over time, the rash became increasingly hyperpigmented, was spreading and her right knee appeared more prominent with a limp. There were no systemic features. Examination revealed extensive linear skin changes to her right leg from the dorsum of her foot over her buttock and hip, classical of linear scleroderma. There was accompanying muscle and fat loss, reduced strength and restriction of movement at the right ankle, knee and hip. The clinical diagnosis prompted a range of investigations revealing the extent of fibrous bony change, acute myositis, muscle and fat atrophy. (4) . Due to the progressive nature of this disease, early recognition and treatment has been proven to have better long-term outcomes (1, 4) . In this patient, delay in diagnosis led to significant contractures, weakness, muscle and fat wasting which may cause complex functional and aesthetic sequelae into adult life.

We are currently unsure of the relevance of the positive Ku antibody and bone changes. Introduction: Localized scleroderma (LSc) is a chronic inflammation in the skin and soft tissues associated with autoimmunity, which subsequently leads to fibrosis. Fibrosis of the skin of the extremities induces joint deformity and contracture and inhibits normal growth of the affected limb. Although the clinical features of childhood-onset LSc have been well studied, optimal treatment has not been established at present. In recent years, several case reports have suggested the effectiveness of biological agents for LSc. It has been reported that interleukin-6 acts on fibroblasts to promote synthesis of collagen and differentiation into myofibroblasts, which strongly induces fibrosis. We experienced a case of LSc successfully treated with tocilizumab (TCZ), a humanized monoclonal anti-IL-6 receptor antibody.

Objectives: To evaluate the effectiveness of TCZ on skin sclerosing lesions and secondary dysfunction in a pediatric case of LSc during the adolescent growth spurt.

Methods: Case report.

Results: An 11-year-old girl presented with skin sclerosis of body trunk and lower extremities. Especially severe sclerosis spread from the thigh to the lower left leg at the age of three. The findings of skin biopsy were consistent with LSc. She also manifested limited flexion in her left knee, and MRI revealed arthritis in her left knee joint beneath the sclerotic lesion. Methotrexate ameliorated sclerosis, however joint symptoms and observations did not improve.

Therefore, adalimumab and tacrolimus were applied at the age of four, and were very effective against arthritis. She achieved medication-free remission after the age of 8, and both joint and skin symptoms were stable without treatment. At the age of ten, the sclerotic lesion on the right thigh enlarged, and her left knee joint pain and limited flexion flared up. Knee MRI and ultrasound findings did not dipict any results that would explain arthritis this time, and her arthralgia and limited flexion were attributed to skin sclerosis around the knee. There was an 18 x 6 cm of skin sclerosis on the right thigh and brown spots with atrophy from the left thigh to the lower leg. In addition, multiple skin sclerosis on the left axilla, back, left side abdomen, left upper arm, and right dorsum of the foot was newly identified. Skin re-biopsy of her right thigh showed increased collagen fibers in all layers of the dermis and fatty tissue, lymphocytic infiltration to blood vessels and skin appendages. These findings suggested relapse of LSc. There were no serological markers reflecting the disease activity. After methylprednisolone pulse therapy, intravenous TCZ (8 mg/kg/4 weeks) was started and her pain disappeared. She has received treatment with TCZ for seven months, and no new skin lesions appeared so far. The patient's height is increasing at a high rate of 1 cm per month; nevertheless, the skin sclerosis lesions showed improvement and reduction in size, her skin sclerosis have been gradually softened, the right thigh lesion diminished to 15 x 5.5 cm, and no secondary leg length difference appeared. Although limited flexion of left knee remained slightly, she can now crouch with her knees folded and ride a bicycle sitting down instead of standing up. Conclusion: TCZ is widely used in juvenile idiopathic arthritis patients who require a biological agent in Japan. IL-6 activates innate immunity via T cells and B cells, which is involved in the pathogenesis of LSc. It is desirable to confirm the effect of blocking activity of IL-6 on skin lesions of LSc in vivo and to establish biomarkers that reflect the pathophysiology and therapeutic effects of TCZ. infection was common complaints in all 13 pts (100%). Two girls had hemorrhagic nonspecific rush. Lab investigations revealed increased ESR in all pts (100%), leukopenia in 6 (46%) pts. Due to prolonged arthralgia, fatigue and subfebrile fever subsequent studies revealed hyper γ-globulinaemia (100%), ANA and RF in unexplained high titers (100%), and SSA/SSB antibodies (100%). Only two girls complained of dry mouth. And also two girls had episodes of recurrent parotitis. So the diagnosis was made on average 6-12 months after the onset by excluding other systemic diseases and by instrumental investigations. Salivary glands ultrasound investigation revealed initial stage of parotitis in all pts (100%) that was suggested by sialometry and sialography. As to xerophthalmia no one of patients complained of dry eyes. Low lacrimation was detected in 5 girls (38% In addition to localized scleroderma, one (6.6%) patient had puberty precox, one (6.6%) patient had juvenile idiopathic arthritis and Reynaud's phenomenon, one (6.6%) patient had vesicoureteral reflux and renal scar. Systemic lupus erythematosus developed in the follow-up of two (13.2%) patients. One (6.6%) patient also had Crouzon syndrome and vitiligo diagnoses. In addition, growth retardation was detected in the follow-up of one (6.6%) patient. Joint involvement such as arthritis and arthralgia were detected in 6 (40%) patients, gastrointestinal (gastroesophageal reflux) findings in 1 (6.6%), and neurological findings (headache) in 1 (6.6%) patient. One patient (6.6%) with vesicoureteral reflux also had a renal scar.

Ocular, respiratory, and cardiological involvement was not seen in any of the patients.

In the laboratory examinations, no patient was found to have an acute phase reactant (white blood cell, sedimentation, C-reactive protein) elevation in the follow-up. Antinuclear antibody was positive in nine (60%) patients, anti-dsDNA in two (13.3%) patients, and rheumatoid factor in one (6.6%) patient. Thyroid function tests (TSH, T3, T4), thyroid antibodies were normal in all patients. Ten (66.6%) patients were using disease-modifying antirheumatic drugs (methotrexate or mycophenolate mofetil), and two patients were using biological agents (Etanercept, Tocilizumab collaborating. An initial survey was generated aimed at understanding the jSSc prevalence in our community, and most commonly used assessments and treatments for cardiopulmonary disease. It will be soon widely distributed amongst CARRA and PReS members and will serve as an opportunity for members, including fellows and junior investigators, to engage in this international collaborative effort at a range of levels Conclusion: A wide gap on defining optimal care for jSSc patients exists worldwide. Developing consensus tools to assess patients and evaluate treatment response is essential for conducting treatment studies to enable generation of jSSc evidence-based recommendations and improve outcomes. An international collaborative effort is needed, expanding beyond the 9 countries and 14 collaborators currently involved His chest X-ray showed an interstitial pattern. His first echocardiographic evaluation only showed a minimal pericardial effusion, and normal coronary arteries. The patient received two consecutive intravenous infusions of immunoglobulins (2 g/kg), associated with 2 mg/kg/day methylprednisolone, with consequent apyrexia and reduction of CRP (4,5 mg/dl). He also started 3 mg/kg/day aspirin. After two days from the second infusion, fever reappeared together with coronary dilatation: diameter was 2,4 mm for LCA (z-score 3,16); 2,4 mm for LAD (z-score 4,49); 2,5 mm for RCA (z-score 4,13). Exams showed CRP 6,57 mg/dl; leukocytes 62860/mm3 (73% neutrophils); platelets 1532000/mm3. The child then received Intravenous pulses of 30 mg/kg/day methylprednisolone in three consecutive days, and started 4 mg/kg/day anakinra. The pulses were followed by apyrexia, with CRP 6,54 mg/dl. Four days later CRP was 8,96 mg/dl, so anakinra was interrupted, and 5 mg/kg infliximab was started. Echocardiogram showed rapidly evolving giant coronary aneurysms: diameter was 6 mm for LCA (z-score 15,79); 6,5 mm for LAD (z-score 16,41); 5 mm for RCA (z-score 11,72). Due to the rapid evolution of aneurysms and an elevated z-score (> 10), 1 mg/kg/dose enoxaparin was started, according to the Kawasaki disease guidelines of the American Heart Association (AHA) (Circulation, 2017). The patient also started ECG, troponin and BNP monitoring. Three days later, the coronary arteries showed further dilatation. Seven days after infliximab infusion, RCA developed a "rosary beadlike" pattern. There was a gradual improvement of general clinical conditions with reduction of inflammatory markers (negative CRP, ESR 22, leukocytes 28580/mm3, platelets 800000/mm3 after ten days from infliximab infusion), so steroid tapering was started. Because of an increased thromboembolic risk (due to thrombocytosis and to the accelerated blood flow in stenotic coronary traits), clopidogrel 0,5 mg/kg/day was added, according to AHA guidelines. Thirty days after symptom onset, also LDA developed a "rosary bead -like" pattern. CRP was 1,27 mg/dl and ESR was 37. The patient was then transferred to Pediatric Cardiac Surgery, started 5 mg/kg/day cyclosporin and, after further coronary dilatation (LDA 11 mm; RCA 9 mm), 3 mg/kg/day propranolol and warfarin. A CT angiogram confirmed the aneurysms, and excluded any aortic dilatations. Epiaortic vessels were spared. An increase of cyclosporin dose to 8 mg/kg/day was followed by stabilization of coronary aneurysms. Conclusion: The extreme refractariety of coronary disease, despite aggressive therapy and biologics, is rather clear. The rapid evolution could be explained, though only in part, by a few risk factors such as age below 12 months and elevated CRP. These factors are well known, even though they are not mentioned in guidelines. Written informed consent for publication was obtained. Introduction: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium/small arteries. It is a rare condition, especially in the pediatric age group. Cutaneous PAN (cPAN) is recognized as a separate entity. It is characterized by disease affecting the skin with no major organ system involvement. Objectives: Chronic polyarthritis is much less observed and can simulate juvenile idiopathic arthritis, which can delay diagnosis, as was the case with this patient. Methods: We report a 14-year-old boy, who presented to us with polyarthritis and myalgia as a first manifestation of cPAN.

Results: This 14-year-old male adolescent presented with a history of arthritis in right shoulder, ankles, knees, elbows, fingers and toes, associated with myalgia, with partial improvement after the use of non-hormonal anti-inflammatory drugs. Two months later, he was diagnosed with juvenile idiopathic arthritis. Corticosteroids were prescribed in a dose of 20 mg/day, methotrexate 7.5 mg/week and folic acid. There was no clinical improvement. At this time, he start with fever and the appearance of a painful erythematous lesions in the lower limbs and arms, difficulty in walking, which were progressively getting worse, anorexia and weight loss during this period. He also had a history of oropharyngeal infection prior to beginning of these symptoms. At that time, he was treated with azithromycin for 5 days.

As there was no improvement in his clinical condition, he sought the Emergency Room where he was admitted for investigation 3 months after the beginning of his symptoms. On physical examination, we found arthritis in the elbows, knees, ankles and joints of the hands, maculopapular rash in the ankles, muscle atrophy in the arms and legs, palpable and painful nodules on the right leg and right foot. Several laboratory tests were requested. Blood investigations showed anemia, leucocytosis, elevated CRP, ESR and ASLO titres, with normal liver and kidney functions, and normal urine 1. Syphilis, HIV, serology for Mycoplasma pneumoniae, leishmaniasis, Paracoccidioides brasiliensis, Epstein-Barr virus, cytomegalovirus, Zika and Chikungunya viruses, dengue, and parvovirus B19 were negative. HBsAg, hep c were negative. CRP and serology was negative for . Chest Xray, echocardiogram, and ultrasound of the abdomen were normal. Lupus anticoagulant, and FR were negative. Other autoantibodies were negative. p-ANCA and c-ANCA were negative. Myelogram with normal immunophenotyping was found. A skin biopsy was suggestive of PAN showing perivascular lymphomononuclear inflammatory infiltrate, sometimes permeating the vascular wall. The presence of eosinophils and neutrophils with outbreaks of leukocytoclasia was noted, an absence of malignancy was also shown. With infectious, hematological and oncological causes aside, pulse therapy with methylprednisolone was started. After the first infusion, a significant improvement in myalgia and arthritis was observed, in addition to the disappearance of febrile peaks. Then, he started a monthly pulse therapy with cyclophosphamide and methylprednisolone. Four months after start this therapy, we observed improvement of skin lesions and in laboratory exams. Conclusion: Cutaneous PAN is a rare disease, especially in the pediatric age group. Its clinical manifestations are quite varied, making early diagnosis difficult. Joint involvement, when it occurs, is characterized by an acute and oligoarticular pattern in the knees and ankles. Chronic polyarthritis is much less observed and can simulate juvenile idiopathic arthritis, which can delay diagnosis, as was the case with this patient. We must consider the diagnosis of PAN in those patients with chronic polyarthritis, associated with cutaneous vasculitic manifestations and increased ASLO. Introduction: Kawasaki disease is an acute vasculitis of childhood that carries a risk of developing coronary artery aneurysms in up to 25% of cases without treatment. Prompt treatment with IVIG and additional therapies can lower risk to less than 4%. In the past decade, the bibliography reports the contraindication of IVIG administration after the acute phase of disease. Currently, the therapeutic goal of treating Kawasaki disease with IVIG even after day 10 of evolution, is to reduce inflammation limit arterial damage, and prevent thrombosis. Objectives: To describe the presentation of a clinical case that describes the complications associated with the previous indication for not administering IVIG after the acute phase of the disease. Methods: Case Description: a 3-year-old male sent to a third-level hospital for a 30-day fever, meets the criteria for incomplete Kawasaki disease, so an echochardiogram was performed to corroborate the presence of a 6 mm aneurysm in the right coronary artery. Because it is in the subacute phase of the disease, IVIG administration is deferred. During his followup, progression to a giant saccular aneurysm was documented and in the last control of myocardial perfusion tomography, data of mild ischemia in the affected artery territory was reported; being a candidate for management with interventional hemodynamics. Results: Not administering IVIG and additional therapies, even after the acute phase of the disease, entails an increased risk of aneurysm development and their progression, which determines the need for invasive revascularization procedures. Conclusion: 10 years ago IVIG was indicated only in the acute phase of the disease, currently the benefit of its administration is documented, as well as additional therapies even after this time has elapsed to improve prognosis and function. Because of the development of coronary disease in the acute and subacute phase of the disease, the administration of IVIG is currently indicated during this period and not limit its indication to the first ten days of the disease, since this situation conditions the presence of coronary lesions and/or progression thereof. Heart disease can cause coronary artery occlusion, ischemia, and rupture, even disability or death. Shock is not a common presentation of the disease; it rarely occurs in the acute phase. In recent years, cases of patients with KDSS have been reported, which is characterized by presenting hemodynamic instability during the acute phase of the disease. Despite the continuous advances underdiagnosed by pediatricians, due to erroneous diagnoses. Objectives: Describe a case of shock syndrome due to Kawasaki disease (KDSS) Methods: We present the case of a 4-month-old boy who presented KD complicated by shock syndrome (KDSS), treated with intravenous immunoglobulins (IVIG) and methylprednisolone pulses. Results: 4-month-old male. Healthy preview. Clinical picture: persistent fever for 20 days (40°C), changes in the oral mucosa with cheilitis, conjunctival injection, maculopapular rash, edema of the hands and feet, cervical adenopathy> 1.5cm, for which he was hospitalized outside the institution, receiving multiple treatments of antibiotics for a week. Referred to our center for treatment of long-standing fever. At his evaluation drowsy, irritable, with shock data (tachycardia of 220 beats per minute, generalized paleness, diminished peripheral pulses and capillary filling 3 seconds), seizure. Kawasaki disease shock syndrome was integrated, he was admitted to the emergency room where he required oxygen, loads with crystalloids and aminergic support with dobutamine, he was transferred to intensive care (PICU). It has a HARADA score of 5 points. Laboratories: leukocytosis, thrombocytosis, anemia, hyponatremia, hypoalbuminemia. High acute phase reactants (CRP and ESR). Electrocardiogram with sinus tachycardia, an echocardiogram was performed with aneurysm of the left coronary 4.4x5.3 mm, right coronary 4.8x4.6 mm and 2.5x3.2 mm anterior descending coronary artery. Renal and liver function without alteration, negative blood and CSF cultures. Treatment: gamma globulin (2gkgd), methylprednisolone (20mgkgd) for 3 days, acetylsalicylic acid (10mgkgd) and enoxaparin (1mgkgd). Cefepime during his hospital stay. He was discharged with a decrease in the aneurysms and without neurological sequelae, with an antiplatelet dose of ASA (3mgkgd) due to clinical improvement after 7 days of hospitalization. Conclusion: We report a case of Kawasaki disease shock syndrome (KDSS). This entity is characterized by tachycardia, hypotension, and signs of poor perfusion. The relevant clinical finding in this case was hemodynamic instability, as well as the typical KD clinical presentation. Shock, a rare but serious complication of Kawasaki disease, should be considered as a differential diagnosis of toxic shock. Timely diagnosis is imperative to initiate adequate treatment, thus reducing the risk of developing coronary artery aneurysm. We emphasize that fever for more than 5 days with no apparent cause can be suggestive of Kawasaki disease and according to the 2017 AHA recommendations, it is imperative to perform an echocardiographic study, a situation that can avoid sequelae such as KDSS in this patient. Introduction: Behçet's disease (BD) is a polygenic multisystemic autoinflammatory disorder and vascular involvement is one of the major causes of morbidity and mortality of the disease. Objectives: We aimed to define whether vascular involvement of pediatric BD is a risk factor for hypertension and cardiovascular dysmorphology. Methods: Thirty-one BD patients who followed at pediatric rheumatology clinic, were enrolled to the study. The pediatric patients (<16 years of age at disease onset and diagnosis) were classified as having BD according to the Pediatric Behçet's Disease (PEDBD) classification criteria. Demographic data, clinical manifestations, laboratory and radiological findings and outcomes were documented from patient charts. Patients with other known risk factors for cardiovascular disease as obesity and hypertension were excluded. During the same week, carotid intima-media thickness (cIMT) measurement and echocardiography and 24-hour ambulatory blood pressure monitoring (ABPM) were performed. Physical examination and blood tests were also performed on the same day with cIMT. Results: Thirty-one children with pediatric BD (16 female, 51.6%; F/M: 1.06) were enrolled in the study. Based on the cumulative disease characteristics; oral ulcer was the most common clinical finding (100%), followed by skin involvement (78%, n=25), arthritis (56%, n= 18), genital ulcers (47%, n=15), ocular involvement (28%, n=9) had and vascular involvement (18%, n=6). We grouped patients into two groups as patients with and without vascular involvement. The mean age at disease onset and at the time of BD diagnosis was 8.79 ± 4.23 years, and 11.62 ± 3.22 years, respectively. The median follow-up duration was not statistically different between two groups (59.63 months (IQR: 58.38-63.57) vs 40.28 months (IQR: 11.30-75.47)). All patients underwent cIMT measurement, echocardiography and 24-hour ABPM. The mean value of right cIMT, left cIMT and echocardiograpy measurements were not different between two groups. Although the prevalence of abnormal ABPM, non-dipping, and ambulatory hypertension was higher in patients with vascular involvement, they did not reach to statistical significance (Table) . Renal biopsy was performed in 8 patients in each group (c-IgAVN and a-IgAVN). Five patients in each group had undergone an upfront renal biopsy before commencing immunosuppressive treatment, while in 3 patients it was done after failure of initial treatment. We found that ISKDC class 3a and 3b were the most common ISKDC classes found in both groups. There was no significant difference in individual scores (MEST-C scoring) for mesangial proliferation, endothelial proliferation, segmental sclerosis, tubular atrophy, or crescents between the two groups. We did not have any patient with CNS involvement or angioedema. There was no significant difference in other traditional laboratory markers.

Conclusion: In our study, we found that among all the prognostic factors analysed, most of the risk factor like GI bleed were present in both groups; however, the central distribution of purpuric lesions, bullous skin lesions and renal insufficiency at presentation were more prevalent in a-IgAVN patients as compared to c-IgAVN patients. These findings concur with more aggressive nature of adult-onset IgA vasculitis-nephritis. Initial treatment was with aspirin as patient was outside thrombolysis window, followed by dual anti-platelet therapy as evidence of occluded left common carotid artery and nearly occluded right common carotid and internal carotid artery on Carotid Ultrasound. Methods: Further investigation with CT angiogram aorta and carotid revealed evidence of large vessel vasculitis involving the aortic arch, its branches and descending thoracic aorta,which would support a diagnosis of Takayasu's arteritis. No evidence of truncal end-organ ischaemia or other sites of arterial occlusion apart from common carotid arteries was seen.

Results: Multidisciplinary team approach was adopted. Upon discussion no surgical intervention was advised by vascular surgery.

Clopidogrel was advised to stopped after 4 weeks and aspirin to continue long term. Rheumatology team was involved and patient was started on IV methylprednisolone for 3 days followed by weaning dose of oral prednisolone with view of starting on Rituximab as outpatient. Physiotherapy input was valuable and helped her with improving her mobility.

Takayasu arteritis can have stroke as its rare initial manifestation in young people (2) . In dealing with young people, neurological symptoms should be taken seriously and acted promptly upon, followed by urgent investigation to rule out any underlying serious problem. Diagnosis of stroke in young patient should raise concern of ruling of Takayasu arteritis as a potential cause.

The Conclusion: Cogan's syndrome should be in our differential when a young patient presents with sudden onset hearing loss. The major morbidity of the disease is hearing loss, which will become irreversible if treatment is delayed. Early diagnosis and treatment can prevent irreversible hearing loss. Methods: Sixteen KAWAKINRA patients with KD that failed to respond to one or more courses of IVIG received daily subcutaneous injections of anakinra for a total treatment duration of 14 days 1 . Serum samples for biomarker analyses were acquired during screening visit prior to first anakinra treatment as well as on days 3 and 14 in course of the study. Biomarker levels in serum or cell culture supernatant were assessed by multiplexed bead array assay. S100A12 serum levels were quantified by inhouse ELISA.

Results: Levels of most analyzed inflammatory serum markers predominantly linked to either innate (IL-1b, IL-6, IL-10, IL-18, TNFa, MCP-2, S100A12) or adaptive (IFNg, IFNg-signaling: CXCL9, CXCL10; IL-17A) immune mechanisms declined significantly in course of anakinra treatment but remained elevated over healthy pediatric controls. Similarly, serum concentrations of markers linked to immune cell or endothelial cell activation (sICAM-1, soluble VCAM-1, LRG1) were reduced upon IL-1 blockade. Hierarchical clustering analysis of all quantified serum biomarkers detected prior to anakinra treatment revealed the cohort to separate into two distinct clusters, which was predominantly driven by differing levels of IL-1b, endogenous IL-1Ra and LRG1. Following 3 days of anakinra treatment, we still observed a distinct clustering of patients, primarily driven by LRG1 serum levels. Increased concentrations associated with the necessity to adjust anakinra dosage. Following 14 days of daily anakinra injections a clustering of patients according to significant differences in serum biomarker levels was no longer evident. Throughout, LRG1 blood levels were tightly associated with circulating IL-1b and inversely correlated to hemoglobin concentrations. In line with these in patient observations, LRG1 release from human coronary artery endothelial cells or monocytes following inflammatory in vitro challenge was quenched by the inhibition of IL-1 signaling, but promoted by stimulation of cells with IL-1b.

In the investigated KD study population LRG1 as possible trigger of endothelial activation, neovascularization and cardiac re-modelling 2 appeared tightly associated with IL-1 signaling. Besides a potential pathomechanistic implication of these findings our data suggest monitoring of LRG1 serum levels alongside with blood leukocyte counts to support steering of IL-1R1 blocking KD treatment.

Introduction: Macrophages frequently infiltrate injured glomerular and tubulointerstitial tissue, and it is possible that the degree and subtype of macrophage infiltration (M1 macrophages, which show proinflammatory features, and M2 macrophages, with their immunosuppressive features) varies depending on the type and severity of renal injury. Although renal involvement in patients with Henoch-Schönlein's purpura (HSP) is the main cause of morbidity and mortality and a significant prognostic determinant for the disease outcome, a reliable prognostic factor for severe forms of HSP nephritis (HSPN) is yet to be determined. KD and compared them with healthy and febrile age-matched controls. Early and late activation markers (CD69 and HLA-DR, respectively) in different monocyte subsets was also assayed using flow cytometry. Plasma levels of monocyte activation markers (sCD14, sCD163, MCP-1/ CCL2) in children with KD (n=16), age and sexmatched febrile (n=16) and healthy controls (n=16) were assayed using Quantikine® ELISA kits (R&D Systems® USA). Analysis was performed in a fully-automated ELISA machine (Infinite200 pro) and results were read in the ELISA reader (Tecan). Monocyte activation markers were also assessed after intravenous immunoglobulin (IVIg) infusion and 3 months after the acute episode of KD. Results: Median (IQR) duration of fever among children with KD and febrile controls were 9 (7-15) and 7.5 (6.5-18) days, respectively. Children with acute KD and febrile controls had a significant elevation in absolute monocyte counts as compared to healthy controls (p-0.007 . Time to seek consultation ranges from 1 day to 1.5 months after appearance of first symptom/sign with mean duration of 13 days. Pain abdomen was the initial manifestation in 50% of patients followed by skin rash (29%) and arthritis (21%). However skin rash which was present in all brought them to hospital. Gastrointestinal involvement was seen in 57%, in form of pain abdomen (57%), bloody stools (29%), hematemesis (7%) and intussusception in 8 years old male child (7%). Renal involvement was seen in 43% in form of combination of hematuria and proteinuria. Hypertension was present in 21%. Other manifestations were arthralgia (40%), arthritis (29%), fever (29%), scrotal swelling (14%), swelling hands and feet (14%). None of our patients had nervous system involvement. There was significant difference in clinical presentation of patients with and without nephritis. The mean age of presentation was higher in patients with nephritis (12 years) as compared to patients without nephritis (8 years). Pain abdomen with bloody stools was main presentation (83%) in patients of HSP nephritis while other patients without nephritis mainly had arthritis (62.5%) and fever (50%). Recurrence of skin rash was present in 83% of children with HSP nephritis. Older age of presentation with abdominal symptoms were found as risk factor for HSP nephritis. Renal biopsy was done in 2 patients with renal involvement and showed fibrocellular crescents in one and mesangioproliferation in another patient. Patients with HSP nephritis were treated with high dose pulse steroid therapy followed by oral prednisolone and azathioprine or mycophenolate mofetil and were followed up. 83% of these patients continued to have proteinuria and hematuria on follow up (range11 months -25 months). However no abnormality was detected in their renal function tests. Presently 50% of these patients are on antihypertensive drugs. Conclusion: Pain abdomen may be the initial symptom of HSP which may be a risk factor for development of HSP nephritis along with older age of presentation. In our study we found persistent renal involvement even after early use of high dose pulse corticosteroids along with immunosuppressive drugs. So renal monitoring for prolonged periods is required along with renal biopsy. Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a genetic disorder caused by mutation in the Proteoglyacn PRG4 gene on chromosome 1 (Online Mendelian Inheritance in Man OMIM number 208250). The syndrome is characterized by congenital or early-onset camptodactyly and childhood-onset of non-inflammatory arthropathy, coxa vara deformity, or other dysplasia associated with progressive hip disease and non-inflammatory pericardial effusion. It has an autosomal recessive mode of inheritance and the causative gene is located on chromosome band 1q25-31.We present a case of a female child who presented with early onset camptodactyly, non-inflammatory arthropathy, and short femoral necks, with pericardial effusion. Objectives: We describe a case of a 6-year -old female with features of CACP syndrome and with chronic nonspecific constrictive pericarditis. Methods: Molecular genetic sequencing analysis were enriched using ROCH\KAPA sequence captured technology and sequenced on an illumina system (NGS) identified the homozygous variant c.3507T>Gp.Tyr1169 in the RAG4 gene is classified as likely pathogenic Results: A 6-year -old female child,born of consanguineous healthy parents. Presented with a 3-month history of swelling of both knees and wrists. The parents also stated that they had noticed bent fingers for nearly and 4 years. On examination, the child had camptodactyly of the fingers with swelling of both knees, ankles and elbows without [1] . CNO usually affects the metaphyses of tubular bones of lower extremities, followed by other parts of the body [1] . The involvement of the cranial and facial bones is rare in CNO. The mandible is the most reported facial bone in the literature [2] . Objectives: We present a rare case of CNO affecting facial and cranial bones (apart from the mandible) presenting as facial palsy with a review of the literature about similar affection. Methods: A 10-year-old female with left side facial swelling and pain associated with elevated inflammatory markers initially assumed due to infectious osteomyelitis. Her imaging of the face and brain showed a destructive osseous process involving multiple cranial and facial bones. Bone biopsy of the left maxilla showed fibrous dysplasia with abscess formation. On empirical antibiotic treatment (Clindamycin), she developed a right-sided facial palsy. Toward the end of the antibiotic course, she developed another skeletal bone lesion at the right radius bone. Imaging showed multifocal lesions with mixed sclerosis and lucency. Bone biopsy of the right radius showed similar findings of destruction with no evidence of malignancy which helped towards the diagnosis of (CNO). Non-steroidal anti-inflammatory drug (NSAID) was started with regular follow up. Over more than a year of follow-up, the patient's inflammatory markers remain normal and joint swelling/limitation have remained in remission.

PubMed was used to search for articles using specific keywords. We found 5 cases in addition to our case (Table 1) .

The affection of the cranial & facial bones in CNO is very rare, but awareness of such presentation by the clinician is an important aspect of reaching the diagnosis. Trial registration identifying number: None. Introduction: Diffuse lung disease (DLD) in children with rheumatological disease (RD) represents a heterogeneous group of autoimmune disorders that lead to significant morbidity and mortality due to chronic inflammation and immune dysregulation. (1) Data on the incidence and prevalence of pulmonary involvement in children with RD is scarce. (2) Objectives: Describe the experience of the "Hospital Infantil de México Federico Gómez" regarding the pulmonary manifestations of rheumatological diseases in pediatric patients. . The main pulmonary manifestation in the patients was serositis (pleural effusions) in 11 patients (25%), followed by ground glass in seven patients (16%), fibrosis in five patients (12%), nodules in four (9%), two patients with hemorrhage (5%), two with pulmonary embolism, two with pulmonary arterial hypertension, one patient with emphysema and spontaneous pneumothorax, one patient with pulmonary infarction and eight patients (17%) with mixed pattern. The patients received treatment according to the activity of the RD and the type of pulmonary manifestation they presented. All patients received as initial therapy intravenous pulses of methylprednisolone at 30 mg / kg for 3 to 5 doses and subsequently prednisone 2 mg / kg per day with gradual reduction until its suspension. The DMARD most used was mycophenolate mofetil in 25 patients (58%), followed by methotrexate in 10 patients (23%) and azathioprine in 8 patients (19%). 38 patients (88%) also received cyclophosphamide 750 mg / m2 monthly for 6 to 9 doses as multi-target therapy. 7 patients (16%) required biological therapy (5 patients with anti-CD20 and 2 with anti-IL-6), 16 patients (37%) received 2 g / kg of intravenous immunoglobulin and 9 required plasma exchange as a second and third line of treatment. Two underwent autologous hematopoietic stem cell transplantation for refractory disease. 33 patients (77%) are in partial remission. 5 patients died (12%); the main cause was pulmonary hemorrhage (80%). Conclusion: Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of severe autoimmune disorders. Pulmonary manifestations of rheumatologic require a multidisciplinary and collaborative approach for optimal diagnosis and management. Introduction: The Paediatric Task Force for Musculoskeletal Health (TF) was established in 2018 in order to foster global co-operation and address gaps in education and care delivery, especially in underserved communities. TF activities have focused on creating a network of regional leaders who work "better together" in order to achieve the aims of the task force. Objectives: To describe recent TF activities and initiatives and report on growth in membership. In addition, we will highlight models of best practice and propose new projects for the future. Methods: The TF has created a network of regional MSK leaders accross the globe. Newsletters and ad hoc communications are used to identify projects which have the potential to influence global MSK health. Task Force working teams are established on a volunteer basis to collaborate on tasks and complete objectives. Results: The TF has grown in terms of membership and influence, including novel partnerships in areas of the globe where engagement with global rheumatology has been suboptimal. The total number of countries included now number 44 (Fig 1) . Our 'call to action' has been published to address the needs of children with MSK conditions. The regular TF e-newsletter has highlighted regional and country specific updates on rheumatology services, including sharing models of care and education, conference and funding opportunities as well as educational clinical vignettes. TF activities include applications to amend the WHO Essentials Medicine List for Joint Diseases in children and include medications integral to JIA treatment (Triamcinolone, Tocilizumab and Anakinra). Future plans include a bespoke virtual rolling paediatric rheumatology Continuing Medical Education (CME) program catering for the needs of healthcare workers in underserved areas; entitled SPRINT (Sharing Paediatric Rheumatology INternationally Together) as well as an overlapping multi-media awareness and "branding" campaign entitled RUN (Rheumatology Unmet Needs Introduction: Raynaud's phenomenon (RP) is a vasospastic disorder characterized by recurrent transient vasospasm in the small arteries of the fingers and toes that results in triphasic color changes. According to etiology, RP can be primary (%80 of cases) or secondary. There is no associated disease in primary RP. Secondary RP is attributed to an underlying disease, most commonly connective tissue diseases. The difference of secondary RP from primary RP is related to its severity and complications. Antinuclear antibody (ANA) positivity, changes in capillaroscopy and digital ulceration are suggestive of secondary RP. Patients with primary RP may show signs of collagen tissue disease over time.

Objectives: The aim of this study is to evaluate the clinical, laboratory and capillaroscopic findings of patients with primary and secondary RP. Methods: Patients who were diagnosed RP in the pediatric rheumatology department between January 2014 and January 2021, were retrospectively reviewed. Demographic data of patients, laboratory parameters and capillaroscopic findings were recorded. Capilleroscopy findings of the patients were classified as normal (capillary count> 7, capillary morphology normal, no capillary enlargement, no avascular area), nonspecific abnormalities (one of them; decrease in capillary number, capillary enlargement, abnormal morphology or microhemorrhage) and scleroderma pattern (presence of giant capillaries or the combination of abnormal shapes with an extremely lowered number of capillaries). Results: Ninety-five patients with RP, of which 68 (71.6%) were females (female-to-male ratio= 2.51:1) were enrolled. The median age was 15.5 years (range 13.9-16.5 years) at the onset of disease. Color changes were biphasic in 69 (72.6%) patients, and triphasic in 26 (27.4%) patients. Twenty-one (22.1%) of the patients had pain and 40 (42.1%) had numbness. Primary RP was present in 84 (88.5%) patients and secondary RP in 11 (11.5%). In patients with secondary RP, the associated disease was systemic lupus erythematosus in 3 (27.2%) patients, scleroderma in 2 (18.2%) patients, juvenile dermatomyositis in 1(%9.1) patient, and juvenile idiopathic arthritis in 5 (%45.5) patients. Arthralgia, arthritis, rash and recurrent fever were significantly more common in secondary RP cases (p=0.001, p=< 0.001, p=0.01, p=0.035, respectively). Pattern of color changes, age of onset hemogram parameters, acute phase reactants do not show a significant difference in primary and secondary RP cases. ANA was positive in 40 (42.6%) patients. ANA positivity >1/320 was significantly higher in patients with secondary RP (p=0.01). Two patients had scleroderma pattern, 19 patients had nonspecific changes, and 19 patients had normal capillaroscopy findings of 40 patients who could be reached capillaroscopic findings. Capillary irregularity, tortuous capillaries and increased branching were significantly higher in secondary RP cases (p=0.015, p=0.015, p=0.003, respectively). Conclusion: In addition to capillaroscopy findings, patients with joint complaints, rash, fever, high titer ANA positivity should be examined in detail in terms of underlying diseases. Introduction: Immunocompromised children (ICC) are at increased risk for vaccine preventable infections and complications from these infections. However, for unclear reasons, vaccination of these highrisk patients remains suboptimal. Objectives: Our primary aim was to assess vaccine knowledge, comfort, and vaccination practices among parents of and primary care physicians caring for children with c-SLE and IBD. In order to better identify barriers preventing the vaccination in this patient population, we performed a needs assessment survey. Methods: We created and administered two needs assessment surveys: One was distributed to community primary care providers (PCP) at their monthly hospital meeting followed by an email survey to PCPs not present at the meeting. The second survey was administered to patients with c-SLE or IBD receiving care at the rheumatology and gastroenterology clinics at NCH or their caregivers, between January 1 to August 31, 2018, during routine scheduled visits for disease management. Surveys were completed by patients 18 years or older or by their parent or caregiver. We reviewed electronic medical records of the surveyed patients for demographics, medication exposure, and diagnosis. Responses were recorded in a Redcap database for statistical analysis. Since the study was performed as an internal quality improvement project to improve processes of care, it was deemed exempt from review by the Institutional Review Board. Results: We surveyed 31c-SLE and 26 IBD patients. Patient characteristics and medications are noted in Table 1 . Most patients received their vaccines from their primary care provider (PCP) or the Health Department and a minority (16%) stated they usually received vaccines from their subspecialist. The vast majority of patients (96%) felt that their PCP was well informed about vaccines. Notably, 91% of patients reported that their subspecialist discussed vaccines in the past year, most commonly Influenza, Human Papilloma Virus, pneumococcal vaccine and Hepatitis B. Only 2 parents expressed concerns for vaccine adverse effects and triggering a disease flare. Among the 30 PCP who responded to the survey, 70% had over 20 years' experience and 50% preferred to provide all vaccines. However, barriers to completing vaccines included: 14 of 16 (85%) stated they did not stock the 23-valent pneumococcal vaccine. Further, PCPs felt "very confident" about providing vaccines in their ICC) only 40% of the time. Practitioners cited not feeling well informed about their patient's immunosuppressive medications and reported concern for exacerbating the patients underlying illness as the main reason for their lack of confidence. SLE (n=31) IBD (n=26) All subjects (n=57) Age: Median (Range) 16 (8- (100) 14 (54) 44 (77) Biologic DMARDs 4 (13) 9 (35) 13 (23) Conclusion: In our survey of patients and PCPs, there was discordance between patient's feeling confident in their PCP being aware of vaccine recommendations and PCP comfort in vaccinating their ICC patients, due to lack of knowledge of medications and concern for triggering a disease flare. While most ICC received vaccines at their PCP's office, most of these offices did not carry the 23-valent pneumococcal vaccine and did not routinely recommend the vaccination of other household members. Access to recommended vaccines and lack of education about ICC vaccination schedule remain significant barriers and continued areas for improvement. Introduction: The evidence base underlying the management of children and young people (CYP) with paediatric rheumatic diseases (PRD's) is inadequate, with many outstanding questions. Objectives: The main objective of this study was to elicit PRD's research priorities, through collaborative consultation of patients, carers and healthcare professionals. Methods: This study was led by the UK NIHR CRN Children/Versus Arthritis Paediatric Rheumatology CSG ('the CSG') and its Topic Specific Groups (TSG's) 1. The CSG is a multidisciplinary group with strong patient/parent representation, supporting the development of UK clinical studies. Research priority ideas were sought from paediatric rheumatologists, trainees, AHP's, nurses, patients, parents and charities, through on-line surveys and face-to-face meetings. Research ideas were categorised as disease specific or broad/general. They were grouped into sub-themes, duplicates, previously answered questions, and similar submissions combined. A modified on-line Delphi survey was initally used for research priority ranking, followed by an on-line consensus workshop to derive top research priorities. Results: The initial consultation yielded 304 research priority ideas; 25% from patients/parents, 22% from the CSG, 18% from TSG's, 13% from AHPs, 11% from trainees, 11% from nurses. 55 disease specific and 37 broad/general research priorities were voted upon in Delphi survey 1. A top 11 general broad research priorities were agreed. The top 10 disease specific priorities were discussed at the online Delphi workshop, and two online surveys held to determine their final ranking (see Table) . Globalization was based on existing frameworks for internationalizing medical school curricula. Content was rephrased to ensure clear, simple language as many future users may have English as a second or additional language. Other adaptation strategies include: removing cultural identifiers, using generic drug names, and including reflection and conversation prompts around practice in specific healthcare systems and cultures. These working strategies were discussed and agreed upon by the team. Our strategies were refined after we piloted our updating and adaptation processes with an initial review of 3 learning modules (out of 37). Each member did an initial review of one module, provided feedback, updated content and learning objectives, as well as references. Proposed changes were then independently reviewed by each group member; if universally agreed upon, they were accepted prior to a monthly meeting. Discrepancies were discussed by the group with all final accepted changes requiring 75% consensus. All work has been facilitated through online platforms including monthly virtual meetings, cloud-based file sharing, and real-time group file editing. Results: To date the working group has met five times and fourteen topics have been reviewed and updated. Project completion is expected in the coming months with plans for dissemination thereafter. Our collaboration allows team members to challenge each other professionally and academically, share practice and cultural insights, and develop both clinical and cultural competency. Conclusion: Our virtual working group is an example of a successful cross-cultural collaboration to develop a high-quality evidencebased educational resource to address the needs of diverse stakeholders. Making this resource freely available may help address inequities in PR education worldwide. Evaluation of this resource and its applicability in different contexts will further inform the development of educational materials relevant to other healthcare systems and cultures.

None declared

The shift to pediatric rheumatology telemedicine practice impacts the ability to assess and document critical JIA outcome data: a survey within the PR-COIN network Introduction: The COVID-19 pandemic disrupted the traditional inperson healthcare delivery model, prompting a shift to telemedicine to ensure continuity of care for pediatric rheumatology patients. The change to virtual practice affected healthcare provider's assessments of disease activity in patients with juvenile idiopathic arthritis (JIA) as they were unable to perform hands-on physical assessments. Understanding the impact of this shift is critical to help address any care gaps that are faced during virtual visits for patients with JIA. Objectives: The objectives of the survey were four-fold: a) understand the impact of the switch from in-person to telemedicine visits from the healthcare provider perspective; b) identify the barriers and facilitators to collecting critical data elements that are important in monitoring JIA disease activity and outcomes; c) identify tools that providers are using during their telemedicine visits to perform disease activity assessments; and d) examine the impact of the telemedicine healthcare delivery on clinical research. Methods: A cross-sectional survey sent to members from all Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) centers (n=21) with total number of targeted respondents of 121. The survey was sent out for completion between 08/17/2020 -09/ 02/2020. Quantitative responses were analyzed using descriptive statistics. Qualitative responses were analyzed by content and theme. Results: Survey ersponse rate was 98% (n=119) 90% fully completed. Most respondents (99%) indicated that they documented six critical data elements [CDE] (physician global assessment, patient global assessment, active joint count, morning stiffness, arthritis-related pain, and completion of uveitis screen) in 75% of telemedicine visits. Most respondents (74%) indicated that they documented active joint count over 70% of the time, while 30% of respondents reported barriers to documenting active joint count such as inability to palpate joints and the inability to visualize all joints on virtual examination. Identified barriers to assessment and visit documentation included challenges with assessing joint disease activity and platform technical issues. Ten percent of the respondents reported they often forgot to document CDE during telemedicine visits, indicating that setting up automated reminders in their electronic medical records may help with increasing their likelihood of documentation. A few centers reported having processes to assist with the collection of patient data in advance of the visit, such as pre-visitquestionnaires and planning. The ability to perform research activities was significantly impacted with only 37% of centers reported participating in research activities via telemedicine, and 29% reported their ability to consent patients via telemedicine visits. Conclusion: There are multiple barriers and facilitators to conducting successful clinical visits as well as performing clinical research over telemedicine. Our data suggests variation in telemedicine practice and process across centers, as well as within each center, reflecting the need to standardize the process of telemedicine visits. Given that a portion of patients with JIA will likely continue to be serviced over telemedicine post-pandemic, teams need to adapt their existing practices to continue providing quality care and integrating clinical research over this platform where appropriate. Introduction: When a child is diagnosed with childhood rheumatism, such as Juvenile Idiopathic Arthritis (JIA), it is often a turbulent time with a lot of anxiety and stress, not only for the child but also for the parents. 1 Information given directly after the notification of the diagnose can be difficult to comprehend and remember. 1,2 The child and parents often need repeated information to understand the disease to ensure compliance with treatment. 3 Therefore, we anticipate that it is important that the child and the parents establishes a contact in care enabling close communication and supportive care. 4 Objectives: To improve quality of care for children who is newly diagnosed with JIA and their parents by developing and implementing a team-based one-year support-program. Furthermore, the objectives are to investigate satisfaction levels of children and parents by comparing experiences between care received during the support-program and standard care. Methods: The support-program has been developed by our rheumatology team including physicians, registered nurses (RNs), physiotherapists, occupational therapists and an external organizational coach. Children diagnosed with JIA and their parents are offered to participate in the support-program from the time of diagnose and one year ahead. During the program the children and their parents are invited six times to structured appointments with the team. The appointments are person-centered, thus flexible according to individual needs. For example, one visit may focus on physical activity and is led by the physiotherapist and the RN. Continuous telephone contact with the RN on demand, is scheduled over the whole year. To measure satisfaction-levels with care the participants (children/parents) in the support-program and children/parents who have received the standard care are invited to answer a study-specific questionnaire. For children younger than 8 years old the parents are invited to answer the questionnaire. For children 8-17 years old both the child and the parents are invited to answer the questionnaire. Results: So far, totally 42 children and their parents have been included in the program, none have declined to participate. Of these, 14 have completed the support-program and 8 children and 6 parents have answered the questionnaire. Four children and 6 parents who have received standard care have answered the questionnaire enabling comparative data. Preliminary results show that most participants included in the support-program where satisfied with the care. Answers to the question regarding "Do you know where to turn to for help?" indicate that the support-program assists the child in everyday life. Almost all children and their parents (93%) in the support-program answered that they did know where to turn to for help, compared to 50% in the group of children and parents receiving standard care. Moreover, almost all parents (87%) in the program answered that they had received information about how the disease can affect their child's everyday life, compared to 40 % in the group receiving standard care. Conclusion: There seems to be a great interest in and need for the support-program. Participants in the support-program are satisfied with the team-based person-centered care during the first year ahead of diagnoses. Overall, children and parents included in the support-program are more satisfied than children and parents receiving standard care. Introduction: Juvenile fibromyalgia syndrome (JFS) is a chronic disabling condition characterized by widespread musculoskeletal pain associated with several somatic symptoms including fatigue, non restorative sleep and headaches. Although gastrointestinal (GI) symptoms are common in fibromyalgia (FM), there is a lack of studies primarily focusing on GI disturbances in children with JFS. Objectives: 1) To describe prevalence of GI symptoms and functional gastrointestinal disorders (FGID) in patients with JFS 2) To explore the impact of GI involvement on the global JFS severity. Methods: We included 26 patients (24 females, 2 males, median age 15) diagnosed with JFS according to the 2010 criteria of the American College of Rheumatology. 23 patients had a primary JFS while the remaining had secondary JFS. Gastrointestinal symptoms were explored using a specifically devised questionnaire. The GI manifestations were classified according to Rome IV criteria of FGID. A 0-10 visual analogue scale was used to quantify the severity of GI symptoms. The global JFS severity was assessed using the J-FIMAR which includes comprehensive patients self-report questionnaires and numerical rating scales to quantify musculoskeletal pain, fatigue, headache, sleep quality, physical function, psychological state, health-related quality of life, and satisfaction with illness course. Correlations between GI symptoms and global JFS severity were tested using the Spearman's rank order correlation coefficient (rs). Results: Twenty out of 26 (77%) patients complained of GI symptoms and 11 (42%) perceived them as invalidating. None of the 3 patients with secondary JFS showed GI involvement. Gastrointestinal reflux disease (GERD) was present in 11/26 (42.3%) patients. The incidence of FGID is reported in Table 1 . Significant correlations were found between the intensity of GI involvement and the Widespread Pain Index (WPI) (rs = 0.54; p= 0.046) and the musculoskeletal pain severity (rs = 0.52; p0.045). FGID were not associated with higher rates of sleep problems, chronic fatigue, headache and comorbid anxiety, and/or depression. Thirteen out of 26 (50%) patients presented a stool consistency indicating moderate/severe constipation according to Bristol stool charts; 10/26 (38.4%) referred inconstancy in daily number of evacuations. Conclusion: GI symptoms are common features in primary JFS patients and may impair patient's activities of daily living. Irritable bowel syndrome and functional dyspepsia are the most frequently reported FGID. In our patients GI symptoms significantly correlated with the extent and intensity of musculoskeletal pain. Our results confirm the link between FM and the gastrointestinal system and highlights the need of a multidisciplinary approach for optimal management of JFS. Experiences around medication administration route 6. Tolerability of side effects. Both parents and young people identified a harmful effect on body image from glucocorticoid medication. Side effects such as facial swelling, weight gain and increased appetite were repeatedly identified as the most severe. This influenced selfesteem and perception from peers. The effect became more evident around puberty and was noted by some families to be of particular relevance in adolescent girls: "At her age, she was worried about what people thought of her." Changes in mood & cognition included difficulty concentrating, hyperactivity and mood swings. Parents reported difficulty in managing behavioural effects, particularly in younger children. Families reported glucocorticoid treatment led to a rapid improvement in mobility and pain, "After he was put on the steroid drip, he went, "Look mummy, I can run," and I just cried." However, families reported toxicity from the physical effects of treatment e.g. poor immunity, skin changes and muscle weakness. Glucocorticoid medication changed the way CYP participated in daily life, including social relationships. Families reported poor body image and feelings of isolation related to "being different", resulting in withdrawal from peers. Some effects were related to particular administration routes, e.g. anxiety with general anaesthesia. Tolerability related to duration and effectiveness of glucocorticoid medication in controlling the primary condition. Many families felt rapid onset of action was tempered by limited duration of effect, with concern about long-term toxicity. Conclusion: Glucocorticoid medication has a diverse and marked impact on HRQOL for patients with JIA, JSLE and JDM. The benefits result in rapid improvement of pain and mobility, but the varied psychosocial impact of glucocorticoid toxicity remains concerning.

Introduction: Presence or development of the pain syndrome, that standardly localized in extremities, muscles, near joint regions is very common cause of the patient's admission to the general practitioners, orthopaedics, surgeons and rheumatologists as well. This pain usually presents spontaneous sudden onset and makes parents to find reason of its development and start treatment anyhow, even if its not needed with a situation above. The most common reason of such pain episodes is musculoskeletal syndrome and not an onset of the infectious disease or manifestation of the rheumatological process.

Objectives: The goal of the study is to analyse the most common reasons of patient's admission to the paediatric rheumatologist with noninflammatory musculoskeletal pain syndrome in children.

Methods: To evaluate the meanings we analysed literature data, summarized experience of the outpatient consultation within passed 2 years of work in Vinnytsya regional children's hospital. Results: The most common reason of the doctors admission (up to 35%) is a development of the periodic arthralgias, "knocking" in the joints in patients with hypermobility syndrome. For the differential diagnose we used modified criteria of Carter and Wilkinson. In such patients very important to remember that cause of their pain at the periarticular tissues is increased stiffness of the ligaments. That's why optimal treatment strategy is modification of physical activity with stretching training instead of nonevidential usage of NSAIDs. The next frequent cause of the arthralgias and stiffness in the knee joints (22 %) after physical activity that occurs with patella-femoral syndrome. Typical patient is a girl of 10 -14 y.o. with complains on pain after physical activity, climbing stairs, prolonged sitting during classes. Additional investigations are sufficient for differential diagnose and final its confirmation, that allows to start rehabilitation in time and exclude unnecessary drugs prescription. Up to 15% of all cases .025* 100 90.9

Note. AUC area under curve, CI confidence interval. *P < .05 are met in young sportsmen with iliotibial tract syndrome that manifests with pain in knees and calve muscles. As well 11% of sport active boys shows signs of Osgood-Schlatter that doesn't require any special treatment, just lifestyle and sport activity managing. And the separate group of the conditions that require special attention is growth pain that causes majority of the stressful situation, associated with restless leg syndrome, that are very common (40 %) in Ukrainian paediatric population at the age 3 -12 y.o. All the mentioned diagnoses can be ruled out after thorough differential diagnose and exclusion of other possible organic and structural causes. They may require short-term anti-inflammatory therapy, modification of the sport and rest activity. Conclusion: Routine work of the paediatric rheumatologist in developing counties may include up to 30 -35% of the patients that don't require specific observance even though they present syndrome of musculoskeletal pain. Theoretical knowledge and practical skills allow provide correct differential diagnose and avoid polypharmacy prescription and quickly resolve situation with adequate physical and social adaptation. Methods: A systematic review was conducted in accordance with the PRISMA guidelines for Scoping Reviews. PubMed and Embase were searched from inception to April 20th, 2020. Inclusion criteria were studies in children (≤18 years) with established JIA on clinical factors associated with the development of chronic pain. Pain had to be measured at multiple moments in time Studies focusing on psychological behavior and coping rather than on clinical factors were excluded. Primary outcomes were Visual analog scale for pain (VAS), Numerical Rating Scale pain (NRS) and pain trajectories described in terms of VAS or NRS.

Results: Search resulted in 292 references. After title & abstract screening, 49 articles were read in full-text and five studies were eventually included in the review. Baseline characteristics are presented in Table 1 . Due to large variability in methodology and outcome measurements, meta-analyses of combined results were not valid. Therefore, a qualitative review was conducted, including results and individual statistical models. Three studies showed a positive relation with female gender and chronic pain: 3 or pain at a single visit 1 .

Association of age at onset of JIA, disease duration, JIA subtype and treatment with chronic pain were non-significant or contradictory across included studies. Conclusion: Despite diverse outcome measures and limited studies available, female patients with juvenile idiopathic arthritis seem to be at a higher risk for developing chronic pain than their male counterparts. Higher disease activity is likely to increase the risk of chronic pain for children with JIA. Thus, controlling disease activity appears the most important preventative measure regarding the development of chronic pain. No specific treatment was significantly associated with the development of chronic pain. We hypothesize that a treat-to-target approach would be well-suited in this regard. For age, age at onset, and disease duration, evidence remains inconclusive.

Disclosure of Interest None declared

Telemedicine appointments offer substantial benefits for families, but parents report they are not as good as in-person appointments and most want their child's next appointment to be in-person Results: A total of 133 CYP were included (66% female, median age 12). The majority were from the UK, Ireland and Greece (53%, 26%, and 9% respectively). Over half of respondents (53%) reported that it takes over an hour to travel to in-person appointments with their paediatric rheumatologist, 51% reported an appointment usually takes over three hours in total, and 45% take a full day out of school to attend. Parents reported taking time off work to attend appointments (41% take a full day, and 4% take two days off per appointment). Prior to COVID-19, 47% visited their paediatric rheumatologist four times per year. Overall, this represents a significant time burden for families. Prior to COVID-19, 92% had never had a telemedicine appointment. Since March 2020, 71% had at least one telemedicine appointment (median 2, range 0-20). Table 1 shows the scores (1 worst, 5 best) given by parents about their telemedicine experience. Overall, most aspects scored positively (p<.05). However, parents felt telemedicine was not as good as in-person appointments (mean 2.2, 95% CI 1.96-2.46). 56% of respondents reported telemedicine appointments had saved them time. 50% said it enabled them to have an appointment and 47% felt that it made the appointment safer. However, 76% felt that their consultant could not properly assess their child, 27% were concerned that the doctor could not identify changes in their child's condition, 26% said it was hard to explain their child's condition, and 27% of parents and 23% of CYP disliked telemedicine. Overall 82% said they would prefer the next appointment to be inperson.

Conclusion: Whilst there are advantages to telemedicine, notably saving time and making appointments accessible, parents reported concerns about the ability to assess their child. There may be value in providing training to parents to allow for homebased assessments, particularly when the disease is stable. However, parents continue to report the value of in-person appointments. Introduction: Patient and public involvement (PPI) in paediatric rheumatology extends beyond clinical research and review of healthcare provision, and includes patient organisations working in partnership with clinicians and professional bodies to help ensure the needs of patients, parents and families are represented. The European Network for Children with Arthritis and Autoinflammatory Disease (ENCA) is a network of paediatric patient organisations across the continent of Europe and beyond, and since 2020 have been involved in reviewing abstracts for the joint PReS / ENCA annual congress.

Objectives: To develop a standardised tool to allow reviewers to consistently score abstracts submitted to international conferences. Methods: Three members of the ENCA Board were invited to review abstracts ahead of the 2020 PReS Congress. Each reviewer received different abstracts, in line with standard PReS review practices. Abstracts were reviewed individually by reviewers using their experience, skills and expertise. During this process, each reviewer collated a list of questions and their own scoring system for each question. Once all reviews were complete, a single combined scoring system was developed, and checked against the processes followed by each individual. This scoring system was presented back to the PReS Scientific Committee for feedback and update. Results: A single combined scoring system was developed, verified by the three reviewers and accepted by PReS as an example of best practice. The tool asks a total of 20 questions, with a maximum possible score of 20 points. Topics cover all parts of a standard abstract, and draw attention to scientific rigour, research methods, communication, impact on clinical care, validity of conclusions drawn, and involvement of patients and parents in the work. Conclusion: The development of a standard tool has enabled reviewers to adopt a consistent approach to reviewing abstracts, giving a fair and balanced weight to a wide range of important considerations needed in the process. This tool can be used by patient organisations involved in abstract reviews as well as clinicians and researchers, and helps reduce potential bias or inconsistencies. It also helps new reviewers to become involved in the process as they have clear guidelines to follow. Introduction: Children and young people (CYP) with juvenile idiopathic arthritis (JIA) face many burdens associated with their disease that their peers, teachers and communities often fail to understand. Sharing information about their condition and its impacts can be difficult, particularly in busy environments lacking privacy such as school classrooms and sports halls.

Objectives: To develop a resource to enable CYP to highlight they have JIA, allowing them to explain what that means for them in a simple way without the need for further explanation or details. The resource is designed to be small, accessible and transferable, allowing CYP to share with teachers and peers when necessary.

Methods: CYP with JIA asked for a resource to help them explain their condition, noting the variability of disease can appear paradoxical to others. A specific challenge for many CYP is that they can be active and appear well one day, but experience intense pain and loss of mobility the next. This can make explaining their condition in their own words more difficult.

A resource was developed with input from CYP with JIA, highlighting the key points about their condition. Printed out as business-card sized resources, these double-sided cards state 'I have JIA' on one side, with a summary of important information on the reverse. They are branded by an official JIA charity, giving a greater level of authority than a CYP can express on their own to teachers. The cards are available as printable resources from www.jarproject.org/teen, and are provided in support packs provided by Juvenile Arthritis Research (a UK charity) to CYP and their families.

Results: Prior to launch, information about the cards was shared on social media resulting in considerable interest from CYP with JIA and their families around the world. The printable version has been downloaded and shared widely, and the copies provided by the charity have been used across the UK. CYP and their families have reported that the cards have enabled them to tell others about their JIA, that the information has helped explain the impact and variability of their condition to teachers (particularly sports teachers to whom a CYP experiencing physical limitations needs to be able to share this information), that the cards are accessible and light-hearted whilst answering the key questions teachers and peers express, that they help outline why they need to attend medical appointments that may appear to be unrelated to their condition (such as ophthalmology assessments for uveitis), and that the use of the term 'I have JIA' reduces the stigma attached to the term 'arthritis'. Conclusion: CYP with JIA value the awareness cards which provide a new and simple way to share information about their condition, allowing them to explain it to others. Introduction: Your Rheum is a UK young person's research advisory group, for those aged 11-24 years and diagnosed with a rheumatic condition. Prior to the COVID-19 pandemic, Your Rheum mostly engaged with its members and researchers at face-to-face meetings twice a year, offering online activities to potentially enable broader involvement.

Objectives: To explore the advantages and disadvantages of conducting research involvement activities virtually, from the perspectives of both young people and researchers. Methods: Online surveys were only sent to Your Rheum members and researchers, who have engaged with the Group virtually over the past 12 months. 8/16 of these young people responded; 1 male, 7 female; age range 16-22 years and 3/6 researchers representing different research projects. Results: Many young people commented on the convenience of meetings taking place virtually, allowing more young people to be involved regardless of location. Some highlighted that face-to-face meetings were often too far to travel to and therefore required a significant commitment to attend. For example as one young person highlighted in regards to virtual meetings, "no travel is required so it is much less of a whole-day commitment, meaning it is much easier and more likely that I will be able to attend." Similarly, researchers who responded also stated the convenient aspect to conducting virtual activities. Additionally, for some young people, speaking online is easier and more comfortable than face-to-face communication; with some expressing, it is not such an intimidating environment and there is less pressure to contribute to discussions. Using interactive tools on virtual platforms, such as breakout rooms, is another positive aspect of online meetings. One researcher noted a positive feature was the ability to switch cameras off, helping younger or quieter members to participate. However, a number of young people felt the opposite was true and have found virtual meetings difficult to contribute to, "it is more stressful … as everyone is looking at you and no one else is speaking. The format of having meetings online also makes the whole event feel much more formal … which means that it can be quite intimidating to speak." Difficulty building virtual relationships and connections was a significant disadvantage. This was highlighted by over half of respondents, who reported that it is easier to get to know others in person as you have the opportunity to deviate from the topic being discussed, allowing for natural conversations to occur. As one young person poignantly noted, online meetings seem to be "lacking true human connection". From a researcher perspective, the subtle insights gained from face-to-face interactions were missing.

Conclusion: This study has highlighted strengths of conducting research involvement activities virtually. For example, logistics and convenience, and for some young people, the development of personal skills such as speaking to others and contributing to group discussions. However, the formal and rigid nature of virtual meetings makes interacting and connecting with other young people difficult. Moving forward, a blended approach to Your Rheum activities is proposed ie the inclusion of frequent virtual meetings, as well as regular bi-annual face-to-face meetings (COVID-19 restrictions permitting). However, when planning virtual meetings, consideration to social interactions and opportunities to get to know one another remains important for young people. Introduction: Patients and public involvement (PPI) events allow families to use their own experience to contribute meaningfully to health research, as well as learn more about research processes and findings. Glucocorticoid medications, or steroids, and their side effects remain a central part of the patient experience across a range of paediatric rheumatic diseases. The research team hosted a virtual PPI event around the use of glucocorticoid medication in children and young people (CYP).

Objectives: The aims of the virtual event were to share experiences of glucocorticoid treatment, provide education about the research team's work, and to identify future key CYP/parents that would continue to be involved in a smaller that PPI group to co-develop glucocorticoid associated clinical studies. Methods: The event was advertised to CYP with experience of glucocorticoid medication use and their parents through clinicians (n=4), charities (n=9) and patient groups (n=2), including their associated social media channels. The event was held virtually on Zoom due to Covid-19 restrictions. During the session, the research team shared findings from four on-going studies involving glucocorticoid medications. Interactive polls and structured discussion were used to help participants share their experiences of steroids. Pre-and post-attendance online questionnaires were used to collect quantitative and qualitative feedback about the event.

Results: 11 families with a range of conditions necessitating glucocorticoid medication (JIA, Behcet's, Lupus, Nephrotic Syndrome, Allergic Bronchopulmonary Aspergillosis) participated from across the UK. The ages of CYP ranged from 2-26. Participants had used glucocorticoid medication through a variety of administration routes (oral, intravenous, intra-articular, topical, inhaled). The duration of use varied from <1 year to >10 years. Online pre-attendance and post-attendance questionnaires showed an improvement in mean self-reported confidence [1 = not at all confident, 5 = very confident] in the following: what steroid medications are (pre = 3.9, post = 4.8), steroid side effects (pre = 3.8, post = 4.6), patient-reported outcome measures (pre = 2.0, post = 4.5), available research on steroids (pre = 2.2, post = 3.5). Most participants (86%) reported that they were likely or very likely to attend future PPI events. Diversity was seen in the experiences and views of CYP in relation to glucocorticoid medication. Many reported several benefits including rapid improvement in their disease, reduced pain and improved mobility. However, there were a greater number of negative effects reported, impacting upon health-related quality of life, including effects on body image, school, mood and relationships with others. A number of participants reported the most enjoyable part of the event was hearing other participants' experiences. This suggests that PPI events offer avenues for insight and therapeutic benefit through sharing common experiences. Conclusion: PPI initiatives provide a valuable forum for both researchers and families to share their perspectives. They can be a useful educational tool to disseminate research findings that are relevant to patients and improve health research knowledge. Families found the experience to be beneficial and enjoyed the opportunity to share experiences on the effect of glucocorticoid medication on health-related quality of life. Five families opted into further PPI group work to engage in the co-development of future glucocorticoid studies. Introduction: The issues of medical supervision of children with rheumatological diseases are key and priority, but not the only ones when observing patients of this group in real clinical practice. A serious problem in the solution of which the participation of medical personnel is also necessary is the problem of social adaptation of young patients with such a serious pathology. Social adaptation issues include psychological, moral, ethical, deontological and other problems that may arise both in organized groups and in the families of these children.

Objectives: In the Saratov region of the Russian Federation, a regional patient organization has been functioning for almost 10 years, uniting the parents and children of JIA patients themselves.

Methods: The public association of parents whose children are sick JIA "Life Without Pain" was created in August 2011 and when it was created, it aimed to provide maximum assistance in the implementation of the treatment process to achieve the best result. Results: During its work, the methods and operational goals of the association have undergone certain changes. Taking into account the successfully functioning all-Russian patient organizations capable of having a significant impact on the organization of care for children at the federal level, a natural revision of the goals of the regional patient structure took place. So, as the most relevant were preservedthe possibilities of operational interaction with regional health authorities (regional ministry), operational monitoring of drug supply, as well as educational programs and socio-cultural programs for sick children and their parents. One of the areas of socio-cultural activities of the regional patient association has become the organization of traditional regular events, most often timed to coincide with significant dates in the medical calendar -Word Arthritis Day, World Young Rheumatic Diseases Day and Children's Day. The material component of these events is based on the principles of fundraising, as well as with the sponsorship of the Russian Children's Fund. These events are very popular among children with JIA, especially taking into account the presented possibility of independent performances in various genres (painting, diclomation, choreography, original genre and others). During the COVID-19 pandemic, taking into account the needs of children, all these activities were saved and transferred to an on-line format. A separate aspect of the relevance of these events was the involvement of volunteers from among the students of the medical university.

Conclusion: The feasibility of maintaining and functioning of small regional patient organizations is determined by the allocation of a rational segment of their activities in which the efficiency of their work will be maximum. In our case, such a segment is social and cultural events, educational and training activities and interaction with local health authorities. In the majority of patients elevated levels of inflammatory biomarkers, D-dimer, troponin, ferritin were found. Most of patients had a tendency to anemia (median hemoglobin 105 g/l). Platelet levels varied greatly (8-919*10 9 /l), 37.5% of patients had thrombocytopenia. Carditis and coronary artery dilatation were found in 48.9% and 22.7%, respectively. Arterial hypotension/shock was in 52.5%. Heart MRI showed signs of myocarditis (n=5): Т1 prolongation (n=2); signs of myocardial edema, pericarditis, severe arrhythmia, and a tendency to diastolic overload (n=1), but no signs of ischemic or non-ischemic myocardial damage, and the global systolic function stayed normal. Patients were treated with high-dose glucocorticoids (93.6%), low-weighted heparin (100%), low dose of aspirin (64.4%), intravenous immunoglobulin (37.8%); Tocilizumab was used in three patients (6%). The median duration of hospitalization was 22 days, and 65.9% of patients required an ICU admission. Some of the most informative indicators for the differential diagnosis of MIS-C and KD are shown in the Introduction: Increase in cases with chilblain-like acral lesions has been observed during the pandemic period. Epidemiological data suggest that children have different immunological responses to SARS-CoV-2 virus, which can cause mild respiratory illness but more frequently involve other organ systems. Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae has been described both in adults and pediatrics (1) . Objectives: To analyze clinical features, laboratory and instrumental findings of a group of patients with chilblain-like lesions during SARS-CoV-2 pandemic period. Methods: Retrospective analysis of 4 patients with chilblain-like lesions. Results: We present 4 patients with chilblain-like acral lesions (2 female and 2 male). The median age was 15.5 years (13 to 16 years old). Two patients had lesions only in toes whilst others had both hand and feet perniosis. All patients had no laboratorical signs of inflammation (CRP, ESR, WBC, neutrophil, and lymphocyte count were in normal range) and markers for rheumatic and connective tissue diseases (cryoglobulins, antinuclear antibodies, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor) were negative. Levels of serum complement C3 (mean value 0.775 g/l) and complement C4 (mean value 0.1425 g/l) was reduced in all cases. Two patients had positive Chlamydia pneumonia antibodies (IgM titers of >12 were defined as positive), others were not tested. The first patient had lesions in toes and for the second patient, both hands and feet were damaged. All patients underwent ultrasound of affected sites. One of 4 patients was diagnosed with reactive arthritis in metatarsophalangeal joints in ultrasound and MRI. There was no epidemiological anamnesis or clinical manifestation or any evidence of SARS-CoV-2 infection (SARS-CoV-2 antibodies were negative) for all patients. Also, there was no anamnesis of any respiratory tract symptoms or diagnosed infection in the last 4 months in all patients. Patients with C. pneumoniae IgM antibodies positive were given a course of clarithromycin. Despite the prescribed course of antibiotics, the skin lesions remained. One patient with arthritis was treated with NSAIDs. Others resolved by themselves without requiring any treatment. Conclusion: Chilblain-like lesions in the skin can be one of the signs of previous SARS-CoV-2 infection despite negative virus antibodies (2) . Possible hypothesis is a high production of type I interferon (IFN) associates with early viral control and suppression of antibody production. A strong IFN response can cause skin manifestations (3) . Coinfection with other atypical bacteria can intensify immune complexes formation and skin injury (4) . This phenomenon can be observed with low levels of C3 and C4 in blood samples. 0.801, p=0.125, respectively). All the types were treated with antibiotics (till negative bacteria culture tests), glucocorticoids, and anticoagulants. Treatment with intravenous immunoglobulin was administered with Kawasaki-like disease (80 %) and toxic shock syndrome (33.33 %). Vasoactive support was received by 2 from 3 patients with toxic shock syndrome. 13 patients of 15 came to followup after 6 weeks, no residual symptoms were found. All the patients, who had any cardiac system involvement, had no changes in echocardiography and cardiac markers during the follow-up. Conclusion: Manifestation of MIS-C is nonspecific and there is a wide variety of symptoms, but we observed that all of the patients had a fever, laboratory signs of inflammation, coagulation disorders, almost all of them had gastrointestinal symptoms, moreover mucocutaneous system and lymphadenopathy involvement also was a common sign. All patients, that came to follow-up, had no lasting effects of MIS-C. and more frequent lymphopenia (89.5% vs 34%; p< 0.001) than those in KD group. Only 40/72 (55.6%) patients in the cohort had either a positive RT-PCR and/or positive antibodies to SARS-Cov-2 and/or a contact with confirmed or suspected infected individual. These proportion increase to 18/19 (94.7%) in the TSS group (p < 0.001). Twenty-three patients (31.9%) required ICU hospitalization including 17 on 19 patients in the TSS group (89.5%; p < 0.001). Cardiac involvement was the most frequent complication either as coronary aneurysm, (15/72 -20.8%) mainly in patient with KD presentation or as cardiac dysfunction (24/72 -33.3%), mainly in patient with TSS presentation. Patient received intravenous immunoglobulins (69/72 -95.8%), steroids (49/72 -68.1%), sometimes both (48/72 -66.7%). Five patients (6.9%) required biotherapy: 1 with Enbrel and 4 with Anakinra. Patient received a treatment 6.6 days after the beginning of the symptoms. After 3 months, 4 patients (0.5%) had persistent coronary dilatation and 2 (0.3%) had mitral insufficiency. Conclusion: This cohort study enables a better description of PIMS clinical and biological presentation, which can sometimes be confusing. It also highlights the importance of fast and adequate diagnosis and treatment to avoid the risk of acute and chronic complications, especially cardiac complications. Introduction: Vaccination of children and young people (CYP) with rheumatic and auto-inflammatory diseases is reported to be lower than amongst healthy peers. Whilst vaccination to confer protection against COVID-19 is now underway amongst adults, vaccination of children under 16 years is not yet available. Objectives: To understand the views of parents/carers regarding vaccination against COVID-19 for CYP with rheumatic and autoinflammatory diseases. Methods: An online survey was developed, translated into multiple languages and shared via social media and patient organisations, targeted at parents of children and young people (CYP) with rheumatic, autoimmune and autoinflammatory conditions. Fieldwork took place between 2 and 22 April 2021. Consent was provided during enrolment. Results: A total of 133 CYP were included (66% female, median age 12). The majority were from the UK, Ireland and Greece (53%, 26%, and 9% respectively). The primary diagnosis for the majority was Juvenile Idiopathic Arthritis (JIA; 46% polyarticular, 16% oligoarticular, 13% enthesitis-related JIA, 7% psoriatic, and 7% systemic), although no significant differences in outcomes between any diagnoses were identified. At the time of completing the survey, the majority of CYP had received no vaccination against COVID-19 (93%), although 5% had received one dose and 2% had received both doses; those receiving any vaccination were all aged 16 and over. The majority of parents/ carers (65%) would agree for their child to be vaccinated to prevent COVID-19 if the vaccine was approved and available at no cost, with only 8% saying they would not agree, and 21% unsure. Overall, 45% would allow their child to have the vaccine as soon as it was available, with a further 20% who would prefer to wait, and 11% who will allow their child to have the vaccine only when required to. Reasons given by parents choosing not to vaccinate their child against COVID-19 focussed on perceived safety, apparent lack of testing, and alleged potential damage caused by vaccines. When asked about the sources of information most likely to influence their decision about vaccination against COVID-19 for their child, the majority (90%) cited their doctor or health professionals; however this varied significantly (p=.015, chi-square) based on whether they currently would agree to have their child vaccinated, with only 64% of parents who would not vaccinate their child saying their healthcare professional would influence their decision. Around one-third of parents would be influenced by information from their patient organisation. Unsurprisingly, parents who indicated they would not be vaccinated themselves were less likely to agree for their child to be vaccinated (p<.001, chi-square). Conclusion: Healthcare professionals and patient organisations play a key role in supporting, advising and influencing parental decisionmaking with regards to COVID-19 vaccination amongst CYP with rheumatic and autoinflammatory conditions, particularly amongst parents/carers who are currently undecided whether to vaccinate or not. As vaccines become available for CYP there is a need for accurate, reliable and clear information for parents and carers to make informed decisions. Results: During the time period, 70 children had confirmed MIS-C and 27 suspected MIS-C cases had an alternate diagnosis including typhoid, tuberculosis, sepsis and appendicitis among others. Sixty five percent of children with MIS-C had no SARS-CoV2 contact but all had evidence of SARS-CoV2 exposure by antibody (90%) or Polymerase Chain Reaction (PCR) tests (14%). There was no difference in age, sex or ethnic distribution between children with MIS-C and inflammatory controls ( Table 1 ). The most common presenting features of MIS-C were fever (100%), tachycardia (99%), rash (86%), conjunctivitis (79%), and abdominal pain (60%). Compared to inflammatory controls, the presence of tachycardia, abdominal pain and conjunctivitis resulted in 96%; 93% and 91% respectively increased odds of a diagnosis of MIS-C after controlling for all other presenting features. Compared to inflammatory controls, children with MIS-C had lower platelets, sodium and albumin and higher troponin-T and pro-brain natriuretic peptide (pro-BNP) ( Table 1 ). The median minimum ejection fraction in MIS-C was lower than inflammatory controls (52% vs 63%, p=0.048). Ninety four percent of MIS-C patients received at least one dose of intravenous immunoglobulin (IVIG), 63% required methylprednisolone and 6% received IL-6 inhibition. Children with MIS-C were more commonly admitted to ICU compared to inflammatory controls (38% vs 12.5%, p=0.013) although there was no difference in mean hospital stay which was 8.2 days in MIS-C. There was no difference in requirement for inotropes (p=0.142) or ventilation (p=0.493). No children died. Conclusion: Distinguishing MIS-C from acute infectious or inflammatory causes of childhood fever may be challenging. The presence of conjunctivitis, tachycardia or abdominal pain associates with higher odds of MIS-C in this population. Differences in widely available blood tests like sodium, albumin and platelets may be useful to differentiate MIS-C in the acute setting.

Disclosure of Interest None declared Results: a first survey between centers members of PRINTO network identified 365 patients from 51 centers (43 countries). Currently, 180 patients have been enrolled in the registry from 25 centers worldwide. Moreover, 11 additional centers have been activated and are ready to start enrollement. Ethical committee submission or activation procedures are ongoing in 36 more centers. 31 European countries and 12 extra-European countries are actively involved. Conclusion: After some interesting national initiatives, the HyperPED-COVID registry will give the chance to analyze the impact of Multisystem Inflammatory Syndrome Children at the European and extra-European level, giving the possibility to analyze the distribution, clinical presentation and long-term outcome of this condition in different countries. The registry can also represent the basis for further biological and genetic studies in these patients. -19) . Its rapid spreading all over the world has caused a pandemia that has a deleterious impact on public health worldwide. The COVID-19 is associated with cytokines dysregulation, increased IL-1β tumor necrosis factor (TNF) and IL-6 release with hyperinflammation and risk of cytokine storm syndrome. Autoinflammatory diseases (AID) are rare, potentially life-threatening conditions caused by pathogenic gene variants encoding for inflammasomes leading to excessive production of pro-inflammatory cytokines. The innate immune system that plays a critical role in the pathogenesis of Familiar Mediterranean Fever (FMF) is also essential in antiviral defense. Colchicine is the main drug therapy for FMF and fulfills its role with the inhibition of microtubule polymerization and pyrin inflammasome. Colchicine effects on COVID- 19 have not yet been evaluated in trials, but some studies on COVID-19 patients under colchicine treatment for FMF arouse interest. Anti-SARS-COV-2 vaccination is of key role for COVID-19 eradication worldwide, few data are available for AID patients.

Objectives: This study aims to describe the COVID-19 impact on patients under regular treatment for AID and their outcome after anti-SARS-COV-2 vaccination. Methods: An observational monocentric study has been conduct on a cohort of Italian AID patients who were under regular follow up for their disorders. Data have been collected both retrospectively and prospectively. Results: Seventy-eight adult AID patients (65 FMF, 5 PFAPA, 3 FCAS, 2 TRAPS, 2 Behcet Disease, 1 SAPHO,) followed at Center for Primary Immunodeficiency and Autoinflammatory disorders have been considered. Among FMF patients, eight communicated to the center when they got COVID-19 and were followed by regular phone calls. The mean age was 36.9 years, (range 27-60) and they had no other comorbidities. All the patients were on regular colchicine therapy and were on complete remission before COVID-19. They were started with azithromycin (with precaution for colchicine interference) and four were treated also with low-weight heparin prophylaxis. None of the patients need oxygen or hospitalization. Two sisters (MEFV genotype M694V/V726A) had FMF attack relapsing during COVID-19 disease, despite regular colchicine therapy. All the cases recovered from COVID-19 without complications. None of the other AID patients declared to have COVID-19, and all the swabs, that they did when they had symptoms suspected for, were negative. Genetics of FMF patients' with COVID-19 -2 M694V/V726A -2 M694V -1 M694V/M694V -1 M680IGC/E148Q -1 R761H/E148Q -1 -/-Till now 31 AID patients have been vaccinated (22 FMF, 4 PFAPA, 3 FCAS, 2 Behcet disease). No adverse reactions were observed. All the patients who had COVID-19 have been vaccinated (Pfizer/ Biontech or Moderna), two had FMF attack. Two patients with PFAPA had a mild attack. Post-vaccination titre was checked after 4 week since 2nd dose for those patients who were under anti-IL inhibitors (n=5) or anti-TNF (n=1). Conclusion: In this study, the FMF patients who had COVID-19 under chronic colchicine treatment had a mild/moderate disease and recovered without consequences. According to other studies, FMF under colchicine treatment seems not to be a risk factor for severe COVID-19 and colchicine anti-inflammatory effect worths to be considered for treatment in COVID-19. Anti-SARS-COV-2 vaccination in AID patients of this study has been observed to be safe and effective. Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) was initially described during the first phase of COVID-19 pandemic as a severe clinical condition with systemic inflammation and multi-organ involvement. We previously published the results of the Italian multicenter survey of MIS-C, launched by the Rheumatology Study Group of Italian Pediatric Society We suggested that SARS-Cov-2 might determine two types of inflammatory diseases in children: the classic KD, that could be triggered by the coronavirus, and the multisystem inflammatory syndrome, which has some specific clinical peculiarities. Objectives: The aim of our study was to analyze clinical features, laboratory findings and treatment strategies in patients diagnosed with MIS-C in Italy during SARS-CoV2 pandemic and evaluate if different outcomes may be related to different disease phenotype in order to establish specific prognostic criteria. Methods: This is an observational, retrospective, multicenter study. We enrolled the children hospitalized between September 1 st 2020 and April 30 th , 2021 with clinical diagnosis of multi-inflammatory syndrome (MIS-C). For each patient who received MISC diagnosis, we collected demographic, clinical, laboratory data, imaging findings, and treatment information in an online anonymized database (RED-Cap). We focused on the following main outcomes: the presence of heart abnormalities at dischargement, ICU admission, need of respiratory support or vasoactive agents and number of IVIG cycle administered analyzing a possible relationship with different disease phenotype. Results: 186 children were included in the study. The median age at presentation was 8 years (4-11), 103 (55%) patients were male and 83 (45%) female. 23 (12%) patients had pre-existing comorbidities. 130 (70%) patients presented a positive IgG serology for SARS-CoV-2 and 51% of patients reported a close contact. Markers of systemic inflammation at onset was elevated in all patients: CRP 143,2 mg/dl (111,0-156,3), ESR 51,5 mm/h (51,0 -54,5), neutrophils 8200/mmc (6490-9011), D-dimer 2175 ng/ml (1076 -2814). 16 (8%) children needed oxygen supplementation at baseline. 129 patients showed cardiac involvement characterized by myocarditis (23%), valve dysfunction (20%), hypotension (19%) and heart failure (15%). MAS was a complication in 11(6%) patients. ICU admission was required in 40 patients (22%). In our study, a majority of patients were treated with glucocorticoids (77%) and intravenous immunoglobulin (91%), of which 9% receveid two doses of IGEV. At dischargement heart ultrasonography showed valvular insufficiency (19%) and coronary abnormalities (8%). Conclusion: MIS-C has an extensive clinical spectrum that led to serious and life-threating illness. Systemic inflammation and specific organ involvement of cardiac and gastrointestinal involvement are the hallmarks. Good outcomes depends on prompt recognition and timely treatment, based on the combined use of glucocorticoids, high-dose immunoglobulins and anti-cytokine therapy.

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is a known severe condition affecting children previously exposed to SARS-CoV-2. Cardiovascular manifestations in MIS-C are quite common and include myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. Severe cases can present even with cardiogenic shock. To date, little is known about the very early myocardial abnormalities in pediatric patients with MIS-C. The Speckle Tracking Echocardiography (STE) and cardiac MRI (cMRI) have shown to be potential candidate for identifying regional ventricular dysfunctions in early stages of inflammatory COVID-related conditions [1, 2] . Objectives: To describe the early cardiac findings in patients with MIS-C, evaluated by two advanced cardiovascular imaging, STE and cMRI. Methods: Consecutive patients with MIS-C underwent standard transthoracic echocardiography (TTE), speckle-tracking echocardiography (STE) with analysis of left ventricle (LV) global longitudinal strain (GLS) and cardiac MRI (cMRI). Clinical and laboratory data, including markers of systemic inflammation, Troponin I (TnI) and Brain Natriuretic Peptide (BNP) were also collected at onset and during follow up. All patients received intravenous immunoglobulins (IVIGs), intravenous corticosteroids (methylprednisolone) and antiplatelet therapy (aspirin). The use of biological agents (Anakinra) was reserved to patients with severe or critical illness. The need for Intensive Care Unit (ICU) was based on clinical and hemodynamic status at presentation. Results: Twenty-three patients (13M, 10F), mean age 8.1±4years (range 5.4-15.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. The majority (78.2%) was caucasian. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular symptoms, as hypotension, thoracic pain or dysrhythmia, were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission and 3 required inotropic support. Short-term survival was 100%. All patients showed an hyperinflammatory state with elevated CRP, ESR, and D-Dimer. Tn-I was abnormal (>34 ng/L) in 15 patients (65.2%), BNP was significantly elevated in 20 (86.9%). Median time to STE evaluation was 8 days and to cMRI was 18 days since fever onset. Mean LVEF and RVEF were respectively 59±10% and 45±7%. Coronary dilation was observed in 6 (26.1%) patients. STE showed reduced mean LVGLS (-17±4.3%). LVEF on cMR was 60±13%, LGE with non-ischemic pattern was evident in 6/16 patients (37.5%) and pericardial effusion in 2 (12.5%). Conclusion: MIS-C can occur in a small but not negligible proportion of children previously affected by COVID-19 and affects the heart in a significant proportion of them. STE and cMRI were shown to be very sensitive tools to evaluate and monitor the early cardiac dysfunctions in patients with MIS-C. The elevation of myocardial necrosis markers, the myocardial injury confirmed by reduced LVGLS and presence of LGE on cMR in about a quarter of the patients support the pathogenetic hypothesis of a post-viral immuno-mediated myocarditis.

Introduction: Since April 2020, Multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide and associated with a different spectrum of symptoms. Although mild neurological manifestations in SARS-Cov2 infection and MIS-C have been reported, severe involvement with brain abnormalities, is rare 1 . Objectives: Describe a child with MIS-C presenting non-convulsive status epilepticus associated with abnormal cerebral magnetic resonance (MR), never previously reported. Methods: Case report. Results: A previously healthy 19-month-old girl presented to our emergency department after a prolonged febrile seizure involving the right side of her body lasting about 25 minutes. She presented with fever lasting more than 24 hours. On physical examination, abdominal distention and tenderness and altered mental status with irritability were detected. RT-PCR for SARS-CoV-2 on nasal swab was negative but her parents had SARS-CoV-2 infection four weeks earlier. Laboratory showed elevated CRP (35 mg/L), while all microbiological analyses in blood, urine and CSF were negative. Computerized tomography (TC) showed a doubtful left temporal hypointensity, and cerebral MRI displayed cytotoxic oedema in left temporal mesial area of the brain on diffusion-weighted imaging (DWI). Few day later, her clinical conditions worsened with irritability and drowsiness associated with persistent abdominal distention, diarrhoea, and high fever. The EEG revealed a pattern suggestive for non-convulsive status epilepticus responsive to benzodiazepines and loading dose of Levetiracetam. Consensually, an increase of inflammatory markers (CRP 153 mg/L, procalcitonin 114 ug/L) was observed. Chest X-ray, EKG, troponin and BNP levels were normal, whereas echocardiogram demonstrated left ventricular diastolic dysfunction and mild pericardial effusion. In the suspicion of MIS-C with abdominal, cardiac and neurological involvement, she was treated with intravenous immunoglobulin (2g/kg), methylprednisolone (2 mg/kg) and acetylsalicylic acid (5mg/kg). Serum SARS-Cov2 antibody test resulted positive for previous infection, confirming the diagnosis of MIS-C. Neuronal antibodies for immune-mediated CNS disorders tested negative. Within 36 hours from therapy start, a significant improvement in general conditions, along with stable apyrexia and decreasing in inflammatory markers were observed. She was discharged two weeks later on oral steroids, ASA and Levetiracetam; the physical examination was normal, and EEG showed a global improvement in brain electrical activity. Conclusion: Neurological symptoms secondary to SARS-Cov2 infection and MIS-C have been reported in children (1) but only a few present severe neurological complications such as status epilepticus. Non-convulsive status epilepticus has been previously described in an adult with acute COVID19 2 but has never been reported as presenting sign of MIS-C. The current case illustrates the need of a careful neurological evaluation in children with MIS-C, as CNS involvement can represent the main clinical presentation thus underlining the need of an appropriate diagnostic and therapeutic approach. Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is an emerging clinical condition, similar to the hyperinflammatory response seen in adults with COVID-19 1 . To date, little is known about the natural history of the disease and the long-term monitoring of MIS-C patients. Positron emission tomography PET/MRI is actually used to identify active inflammatory or neoplastic sites using [ 18 F]fluorodeoxyglucose (FDG) due to the high glycolytic metabolism of inflammatory/neoplastic tissues 2 . Therefore, it could be indicated to evaluate and monitor the inflammatory disease state 2 . Objectives: To describe the PET/MRI findings for the evaluation of the minimal residual disease in a cohort of patients with MIS-C. Methods: Consecutive patients with MIS-C underwent a whole body FDG PET/MRI by 2 weeks, when possible, and at 6 weeks after the onset of fever. Each patient, after a 36 hours of fasting and high-fat low carbohydrate (<5g/day) diet preparation, was scanned using 3 MBq/kg FDG to minimize the radiation exposure. Clinical and laboratory data were also collected at onset and during follow up. Results: Ten patients (7M, 3F), mean age 10.2 years (range 5.4-17.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular involvement, as hypotension, significant myocardial dysfunction and increased myocardiolysis markers, were also present in half of them. Only one patient needed intensive care support for five days. Systemic inflammatory and prothrombotic markers were elevated in all patients on admission (mean CRP 166.3 mg/L; procalcitonin 11.8 ug/L; D-dimer 2348 ug/L, ferritin 1135 ng/L). All patients were treated, 4.5 (± 1.5) days from fever onset with pulse IVIG (2 g/ kg) and IV methyprednisone (MPDN 2 mg/kg/day, max 80 mg) for 2 weeks then with oral PDN tapered down to 0 in further 4 weeks. PET/MRI was performed 13.3 days (± 1.5) after fever onset in three patients and 48 days (± 10.6) in 8. During the acute phase, all patients showed pelvic effusion and edema of the abdominal wall tissues at the total body MRI, not seen in patients during the late phase. Lymph node involvement was present in 81% of MRI findings. The cervical district appeared to be the most involved one as compared to the thoracic, mesenteric and retroperitoneal ones (72% vs 45, 36 and 45% respectively). However, a residual mesenteric lymphadenopathy was exclusive to the late phase (5/8 patients). Conclusion: PET/MRI confirms the good metabolic response to treatment in patients with MIS-C. The abdominal region is more intensively involved in the early stage of the disease, likely related to the hyperinflammatory state. A slow normalization through the lymph node compartment is present in the late stage. PET/MRI is a highly sensitive and specific tool for assessing minimal residual disease in MIS-C and should be indicated for patients with incomplete clinical response to treatment.

Introduction: Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS) or can have an acute abdominal presentation. Objectives: We report the demographic profile, clinical presentation, management, and outcome of this emerging syndrome in 15 children in Switzerland. Understanding these parameters will enable streamlining of early diagnosis and treatment, thus leading to a favorable outcome. Methods: Our clinical study is a case series that includes patients identified during the study registration period (consecutive, formal) at Geneva, Zurich and Lausanne. The data for most of Lausanne patients were extracted from JIR cohort database. This is an observational (descriptive research design), retrospective, multicentric study of a case series. Results: The socio-demographic profile showed male predilection (12 male patients (80%) and 3 female), with no significant racial predisposition. Concerning the symptoms, fever was always present (15/15, 100%). A high incidence of gastrointestinal (10/15 with abdominal pain (67%), 10/15 with emesis (67%) and 9/15 with diarrheas (60%)-these symptoms did not necessarily overlap) and mucocutaneous symptoms (rash 9/15 (60%), conjunctival ejection 11/15 (73%), cheilitis 3/15 (20%)) and extremity changes 9/15 (60%)) was noted. Other manifestations included adenopathy (6/15, 40%), neurological symptoms (6/15, 40%), respiratory insufficiency (10/15, 67%), shock (8/15, 53%), cardiac abnormalities (9/15, 60%)-either like coronary artery anomaly (5/15, 33%) or left ventricular dysfunction (7/15, 47%). Concerning the biological profile, serological evidence of SARS-CoV-2 was present in all our patients (15/15, 100%) as was also the case for the elevated inflammatory markers (C-reactive protein and sedimentation rate). Serum cytokine profile investigations showed increased IL1RA levels in all tested patients (6/6 patients, 9 patients had not been tested) and increased IL6 levels for 3 patients (3/7 patients tested). Concerning the treatment, 13/15 patients (87%) received at least one dose of intravenous immunoglobulins (IVIG), while 8/15 (53%) patients also had a steroid treatment. One patient did not need any treatment except from supportive care. One patient received only anakinra with favorable evolution, and five combined with other treatments (6/15 in total, 40%). The treatments combined with anakinra were: IVIG for all the 5 patients; 4 of them received additionally corticosteroids, while 2 patients further needed one dose of Tocilizumab (anti-IL6 treatment, because of their cytokine profile demonstrating high levels of IL6). Nine out of 15 (60%) patients were transferred to the PICU (pediatric intensive care unit), and there were no deaths. Most of the patients (14/15) recovered fully and only one showed long COVID symptoms. Conclusion: Awareness about post COVID inflammatory syndrome should be raised among pediatricians because early diagnosis and management of this syndrome by a multidisciplinary specialized team can lead to a favorable outcome. In conclusion, our case series reports on clinical and laboratory findings, as well as on the management of Swiss cases with MIS-C. Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first reported from the Wuhan city of China in December 2019, swept the world in a few months and became a global health emergency of primary international concern continues to be a priority health problem. Recent studies suggest that subjects with autoimmune disorders (JIA, RA, SLE) do not have an increased risk to get Sars-Cov2. Juvenile Idiopathic Arthritis (JIA) is an inflammatory chronic disease concerning joints and others structures. According to International League of Association for Rheumatology (ILAR) seven subtypes of arthritis can be defined in relation with the number of joints and the extra-articular involvement occurring in the first six months of disease. NSAIDs and intra-articular steroids represent the first line treatment for JIA. Systemic steroids, disease modifying antirheumatic drugs (DMARDs) and biologic drugs are used in children with severe disease. Objectives: To evaluate the incidence and the impact on the disease course of Sars-cov2 infection in a group of children affected from juvenile idiopathic arthritis in treatment with Methotrexate and/or biological drugs. Methods: This study includes 77 children affected from JIA (55 females, 22 males). JIA diagnosis was made according to ILAR criteria and treatment was assigned with recommendations of the American College of Rheumatology. For each patient we recorded the type and the duration of pharmacological treatment, JIA subtype and relapses (defined according to Wallace criteria). During follow up visit from Nov 1st, 2020 to April 30th, 2021 we investigated in each patient history of Sars-Cov2 infection and related symptoms, diagnostic tests for Sars-Cov2. Results: The mean age at the last follow-up visit was 13.3±5.61 years. Thirteen out of 77 patients was affected Sars-Cov2 infection, none of them needed to be hospitalized. The most common symptom was headache (8 of 13 patients), followed by myalgia (6 of 13), fever (4 of 13), anosmia or dysgeusia (3 of 13), upper respiratory tract symptoms (3 of 13) and nausea (3 of 13). Five out of 13 patients were asymptomatic (38,5%). The mean duration of Sars-Cov2 infection was 12,5 days (confirmed with nose pharyngeal swab). In the group of patients with Sars-Cov2 infection 4 of 13 (30%) were in treatment with MTX, 2 of 13 (15%) with both MTX and biological drugs, 5 of 13(38%) with biological drugs, 2 of 13 (15%) with NSAIDs. In the group of patients without Sars-Cov2 infection 37 of 64 (48%) patients were in treatment with MTX, 32 of 64 (41,5%) with biological drugs, 18 of 64 (28%) with both MTX and biological drugs, 10 of 64 (15,6%) with NSAIDs. We didn't find a higher risk to contract Sars-Cov2 infection in patients under MTX treatment (48% vs 46.15 %; p value 0.6416), in ones under MTX and biological drugs (28.1% vs 15.4%p value 0.543) or in ones under only biological therapy (50% vs 53.8% ; p value 0.231). We found that in patient with JIA the risk to get Sars-Cov2 infection is not related to the treatment. The percentage of JIA relapses was higher in patients with Sars-Cov2 infection than in the ones without infection (53,8% vs 9%; p value 0.0004). Conclusion: Treatment with MTX or biological drugs did not increase the risk to get Sars-Cov2 infection. The frequency of JIA relapses was higher in patients who got Sars-Cov2 infection than in ones who didn't get it.

Disclosure of Interest None declared flowed by bilateral nonpurulent conjunctivitis (47%). Gastrointestinal tract involvement was the most common internal organ manifestation. Treatment included corticosteroids (15 patients), intravenous immunoglobulin (1 patient) and two patients received nonsteroidal anti-inflammatory drug in anti-inflammatory dose, while the rest were only treated symptomatically. Favorable outcome was achieved in all patients with no morphological changes observed on echocardiography during the hospitalization and 2 weeks after discharge. Conclusion: Our findings suggest connection between infection and occurrence of the disease in susceptible children. Yet, a large portion of the population had contact with SARS-CoV-2, thus the exact role of infectious agent and pathophysiological mechanisms have to be determined. Gender distribution with male dominance among our patients is expected. Still, average age at diagnosis was bit higher than what is usually observed in classic KD and is more in line with characteristics of MIS-C. Further research are to be done in order to define what determine progression of the disease and are there any signs that may point in which way it will develop. Only in that way the clinicians would made right choices regarding the patients treatment. lethal outcome in a patient with underlying ALL. Those with higher procalcitonin levels at admission were found to stay longer in the hospital (r=0.254, p=0.027). Older age (aOR: 1.277; 95%C.I.: 1.089-1.498; p: 0.003) and lower initial albumin levels (aOR: 0.105; 95%C.I.: 0.029-0.378; p: 0.001) were found to be significant associated factors for predicting PICU admission in multivariate linear regression analysis. Conclusion: Although there is wide clinical variability among the patients with MIS-C, we suggest that those with older age and lower initial serum albumin levels merit closely monitoring due to their higher risk for PICU admission.

Disclosure of Interest None declared MIS-C (multisystem inflammatory syndrome in children); PIMS-TS (pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection) Introduction: MIS-C is a hyperinflammatory syndrome that follows exposure to SARS-CoV-2 by 2-6 weeks. However, some aspects remain unclear, such as cardiac involvement. Objectives: to evaluate the role and effectiveness of cardiac magnetic resonance (CMR) in heart involvement in children affected by MIS-C; to review the expert groups' clinical experience in the field. Methods: we describe a case series of 7 children (age: 2-11 years), admitted to the tertiary care Children Hospital "G. Di Cristina", Palermo, between December 2020 and May 2021 with clinical symptoms meeting the criteria for the diagnosis of MISC-C. All the patients showed findings of cardiac involvement without coronary artery lesions. Transthoracic echocardiography demonstrated temporary systolic dysfunction that lasted for 2-5 days. CMR was performed during the recovery phase or after the discharge (the median time to CMR was 10-30 days after the onset of illness). CMR was performed with a 1,5 Tesla scanner (GE Signa Explorer). 5/7 didn't undergo CMR study during the acute phase because they were clinically unstable and needed general anesthesia or sedation. The protocol included, before intravenous contrast media injection, retrospective ECG-Gated fiesta cine sequences (short axis, 4, 3 and 2 chamber views), sequences for edema, and hyperemia T2 -short tau inversion recovery (Stir) (repetition time =1689ms, echo time55.10 ms). Myocardial edema was evaluated by following the Lake Louise criteria. Because normal value in native T1 mapping and T2 relaxation time in children have poor reference, myocardial edema was characterized by increased signal intensity on T2-weighted imaging and myocardial damage by non-ischemic patterns late gadolinium enhancement.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of COVID-19 infection, typically evidenced 4-6 weeks after the infection. The debated pathogenesis is a dysregulation of inflammatory response to SARS-CoV-2 infection ad a cytokine hyperexpression. Persistent fever, respiratory and gastrointestinal symptoms are the most common manifestations, associated with typical clinical signs described in Kawasaki Disease (KD). Furthermore, pleiomorphic cardiac manifestations are described, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, conduction abnormalities and pericardial effusion. These manifestations are a strong link with KD, even if in MIS-C they are more frequently documented. Severe cases can present as Toxyc Shock Syndrome (TSS) with vasodilatory or cardiogenic shock, requiring treatment with plasma expanders, inotropic drugs, diuretics, albumin and -in the more severe patients-extracorporeal membrane oxygenation and mechanical ventilation. KD experience guided the clinicians to treat these children with intravenous immunoglobulin (IVIG), steroids, aspirin (ASA) and, in refractory cases, anti-IL-1 monoclonal antibodies.

Objectives: Most patients recover within days to a couple of weeks and mortality is rare, although the medium-and long-term sequelae, particularly cardiovascular complications, are not yet known. Methods: We describe the short-term outcome in a case series of 12 Sicilian children (4M; 8F; age: 1.4-14 years) with MIS-C and a documented recent or actual infection by SARS-CoV-2 who showed cardiac involvement.

tolerability. All patients were given a diary card to record the occurrence of local symptoms or systemic symptoms for the following 14 days. The symptoms were classified as mild or severe (requiring medical attention). Adverse reactions were defined as any reaction that lasted for more than 7 days after the vaccination and serious adverse reactions as any reaction that required medical attention or hospitalization during the study period. Disease activity was evaluated by using the JADAS-27 score at all planned assessments performed so far. The ESR and CRP levels were measured simultaneously. Data were analysed using SPSS 18.0. Results: All subjects were seronegative at baseline. All participants tolerated both doses of the vaccine well. Local reactions were frequent (74%) in the majority of participants, no difference was noted between patients on etnanercept (71%) versus adalimumab (75%)(p=0.09). Localized erythema(73%), pain(72%) and swelling(68%) were among common side effects. There were no differences noted in patients with different JIA types. In addition, systemic reactions [headache (34%), myalgias(23%), tiredness(12%), transient arthralgia(11%)] were relatively infrequent (18%). The type of JIA or medication received did not reveal any differences in the rates of systemic reactions. Most localized and systemic reactions were noted after the second dose of the vaccine (p= 0.02). One patient developed an allergic reaction (hives) after the second dose, which was alleviated with anti-histamines. Finally, there were no significant changes in 27-JADAS or laboratory tests as noted at 2 the months' follow-up. Conclusion: The mRNA vaccine seemed safe and well tolerated in adolescents with JIA on TNFi. Although our sample size was small and a restricted number of patients were included within each JIAtype and treatment groups, it can be concluded that the vaccine assures an adequate safety and tolerability profile and not provoking disease flare. Further studies are needed to evaluate the immune response of patients receiving biological agents in more detail, analyse the immunogenicity of the two-dose schedule, and determine the real duration of immune protection as well as the potential use of a booster dose. A diffuse coronary artery ectasia was found in 1. All children completely recovered with a timely immunomodulatory treatment with intravenous immunoglobulins, steroids and, in case of severe cardiac involvement, anakinra. Nasopharyngeal swabs and serological test for SARS CoV-2 resulted positive in 5/13 and 14/14 respectively. The MIS-C incidence rate, adjusted for the 5,170 children hospitalized, resulted 0.27% and represented the 13.9 % of paediatric COVID 19related hospital admissions in Tuscany. Conversely, the number of observed KS significantly reduced comparing to the first six months of COVASAKI survey: 3 cases, 0.5 incidence/month vs 11 cases, 1.8 incidence/month (p <0.03, RR 0.27, 95% CI 0.06 to 0.92). Comparing the 2.7 incidence/month of the 165 diagnosed KS from 1st January 2015 to 31th January 2020, a statistically significant difference has been detected (p <0.0005, RR 0.24, 95% CI 0.07 to 0.59). The same result has been found limiting the analysis to the 92 children with KS diagnosed during the same corresponding 6 months of the last 5 years: 3.0 versus 0.7 incidence/month (p <0.0002, RR 0.21, 95% CI 0.06 to 0.53). Conclusion: Our results seem in accordance with the hypothesis of an infectious trigger in KS pathogenesis. The stay-home imposed by pandemic and the extensive adoption of barrier protection devices have concomitantly reduced the incidence of respiratory infections among general and paediatric population. At this regard, the massive drop in the number of influenza and Syncytial Virus infections during the winter months results emblematic. From this point of view, it could be hypothesized that, in contrast to what had been previously reported in the early stages of its outbreak, the SARS CoV-2 pandemic could lead to a reduction rather than a substantial increase in the number of KS cases. Although indirectly, the behavioural measures adopted to contain the contagion or maybe further mechanisms not yet identified might be the reason.

Disclosure of Interest None declared 1 patients received IVIG and systemic corticosteroids. Four patients (20%) received high dose methylprednisolone pulse therapy. Biologic therapy with anakinra was started in 2 patients. Nineteen patients (19/20, 95%) received acetylsalicylic acid and prophylactic anticoagulation was prescribed in 15/20 (75%) of patients. The mean follow up was 50 days (14 -122) . At the last follow-up visit all patients had normal laboratory parameters of inflammation, troponin, pro-BNP, ddimer values and normal heart function. Non MIS-C group. Thirteen patients (6M, median age 7.5 years), referred as MIS-C and later diagnosed with a different disease were included. The final diagnoses were: Campylobacter gastroenterocolitis (3), staphiloccocal sepsis (2), urinary tract infection (2), renal abscess (1), appenditicis (1), adenovirus tonsilopharyngitis (1), streptococcal faringitis (1), pancreatic mass (1) and TNF receptor-associated periodic syndrome (1) . Group characteristics are shown in Table 1 . The main differences between the groups hystory of SARS-CoV-2 infection, lip/mouth changes, conjunctivitis and later the presence of myocarditis. The initial inflammatory parameters did not differ between groups, but in the MIS-C group significantly lower values of platelets, sodium and albumins and higher values of troponin, pro-BNP and ferritin were noted at admission.

Non Cardiac involvement 20 (100) 0 (0) < 0,0001 ocular surgery more frequently. These patients received more systemic steroids, but no difference in regard to DMARD use rate. Conclusion: Our data suggest that differences in outcome may correspond partially to differences in treatment approach depending on the origin of the uveitis. Surprisingly, JIAu patients sowed the best prognosis, despite its chronicity, in comparison with the other groups, traditionally considered mild self-limited diseases. Awareness of ophthalmologists and rheumatologists on these observations may ameliorate the burden of disease by inducing rheumatology referral for early treatment.

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Physical activity for paediatric rheumatic diseases: standing up against old paradigms

Körperliche Aktivität von Kindern und Jugendlichen in Deutschland -Querschnittergebnisse aus KiGGS Welle 2 und Trends

Employee of: Syneos Health Inc, A. Blum Shareholder of: Pfizer Pharma GmbH, Employee of: Pfizer Pharma GmbH, P. Klaus Shareholder of: Pfizer Pharma GmbH, Employee of: Pfizer Pharma GmbH, A. Shapiro Shareholder of

Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey

Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature

Concurrence of Juvenile Idiopathic Arthritis and Multiple Sclerosis

The profile of polyunsaturated fatty acids in juvenile idiopathic arthritis and association with disease activity

Recent advances in our understanding of the pathogenesis of juvenile idiopathic arthritis and their potential clinical implications

Fatty acid oxidation compensates for lipopolysaccharide-induced Warburg effect in glucose-deprived monocytes

The rheumatoid synovial environment alters fatty acid metabolism in human monocytes and enhances CCL20 secretion

Consultant for: BMS, Pfizer and Novartis, B. Vastert Grant / Research Support from: Sobi, Consultant for: Sobi and Novartis References

Cetin Gedik: None declared, G. Materne: None declared, G. Montealegre Sanchez: None declared, A. Ortega-Villa: None declared

Single amino acid charge switch defines clinically distinct proline-serinethreonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases

Abnormal production of tumor necrosis factor (TNF) -alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome

Haematological involvement associated with a mild autoinflammatory phenotype, in two patients carrying the E250K mutation of PSTPIP1

Heme Catabolic Pathway in Inflammation and Immune Disorders

Interferonopathies de type I

A Novel biallelic STING 1 Gene Variant Causing SAVI in two siblings, Frontier in immunology

Adult -onset ANCA -associated vasculitis in SAVI: Extension of the phenotypic spectrum, case report and review of literature, Frontier in Immunology

Lung involvement in monogenic interferonopathies

Patient Consent Received Yes Disclosure of Interest T. Welzel: None declared, L. Oefelein: None declared, U. Holzer: None declared

379-83. 3. Finzel et al. Rheumatology

Childhood Arthritis Rheumatology Research Alliance et al. American college of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis

S100A12 facilitates osteoclast differentiation from human monocytes

Trajectories of disease courses in the inception cohort of newly diagnosed patients with JIA (ICON-JIA): the potential of serum biomarkers at baseline

Psychiatric autoimmune conditions in children and adolescents: Is catatonia a severity marker

2.6 CATATONIA AND AUTOIMMUNE CONDITIONS IN CHILDREN AND ADOLESCENTS: A DIAGNOSTIC AND THERAPEUTIC CHALLENGE

Pattern of neuropsychiatric manifestations and outcome in juvenile systemic lupus erythematosus

Division of Pediatric Rheumatology, Children's Hospital at Montefiore, Albert Einstein College of Medicine

United Kingdom; 3 Pediatric Rheumatology

Riley Hospital for Children, Indianapolis; 12 Pediatrics, Division of Pediatric Rheumatology

Takayasu arteritis in paediatrics

Malignant ischemic stroke in a young female: A rare primary manifestation of Takayasu arteritis

Correlation of neurological manifestations of Takayasu's arteritis with cerebral angiographic findings

Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms

Clinical features and outcome of Cogan syndrome

Cochlear implantation in patients with Cogan syndrome: long-term results

Disclosure of Interest None declared P293 Macrophage polarization in Henoch-Schönlein's purpura nephritis N. Kifer 1 , M. Sestan 1 , M. Held 1 , D. Kifer 2 , M. Frkovic 1 , E. Babarovic

Chronic Recurrent Multifocal Osteomyelitis: review

Pediatric Chronic Nonbacterial Osteomyelitis

Skull involvement in a pediatric case of chronic recurrent multifocal osteomyelitis

Chronic Recurrent Multifocal Osteomyelitis

Unusual onset of a case of chronic recurrent multifocal osteomyelitis

Osteosclerotic bone lesions of the skull

Chronic Recurrent Multifocal Osteomyelitis involving the skull

Consultant for: No conflicts of interest, Employee of: No conflicts of interest, Paid Instructor for: No conflicts of interest, Speaker Bureau of: No conflicts of interest, C. Aguiar Shareholder of: No conflicts of interest, Grant / Research Support from: No conflicts of interest, Consultant for: No conflicts of interest, Employee of: No conflicts of interest

Type I interferon signature in Sjögren's syndrome: pathophysiological and clinical implications

Validation of EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)

Epidemiology of Juvenile Idiopathic Arthritis in a Multiethnic Cohort. Arthritis and rheumatism

Disclosure of Interest None declared P326 Economic impact of juvenile idiopathic arthritis

Pediatric Rheumatology; 2 Pediatrics, Hospital Universitario

Gait Adaptations in Youth with Juvenile Idiopathic Arthritis

DeepLabCut: Markerless Pose Estimation of Userdefined Body Parts with Deep Learning

DeeperCut: A Deeper, Stronger, and Faster Multi-person Pose Estimation Model

ImageNet Large Scale Visual Recognition Challenge

2D Articulated Human Pose Estimation and Retrieval in (Almost) Unconstrained Still Images

Correspondence: M. C. Maggio Pediatric Rheumatology

Ponte de Lima; 8 Hospital Garcia de Orta, Almada; 9 Instituto Português de Reumatologia, Lisbon; 10 Hospital Divino Espírito Santo, Ponta Delgada; 11 Centro Hospitalar Lisboa Ocidental, Lisbon; 12 Centro Hospitalar Universitário do Algarve, Faro; 13 Centro Hospitalar do Baixo Vouga, Aveiro; 14 Hospital Central do Funchal

After 48 hours, if CRP increases and/or fever persists, the treatment is intensified either with a MP dose increase or with subcutaneous Anakinra 5 mg/ Kg/day. IVIG is reserved for patients with suspected CAA at any ultrasound evaluation (defined according to American Heart Association 2017 Guidelines for KD), or presenting persistent symptoms despite defervescence and CRP reduction. We retrospectively collected and analyzed clinical data of a cohort of consecutive MIS-C patients treated with MP mono-therapy between the 1st of April and the 31st of

Conclusion: Despite some limitations, including the sample size and the absence of a control group treated with IVIG, our data suggest that early administration of MP together with fluid restriction can rapidly decrease the inflammation and restore myocardial contractility in MIS-C, considerably reducing the need of ICU admission and/or inotropic support

Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature

Chilblain-Like Lesions (CLL) Associated With COVID-19

COVID toes: where do we stand with the current evidence?

P: Skin and Mucous Membrane Eruptions Associated with Chlamydophila Pneumoniae Respiratory Infections: Literature Review

Methods: A monocentric retrospective study was done, including hospitalized children who met the criteria for the MIS-C. We analyzed clinical features, laboratory and instrumental examinations, treatment, and duration of hospitalization in the intensive care unit (ICU). identified as Kawasaki-like disease, 3 as toxic shock syndrome, and 1 as secondary HLH. The longest duration of fever (6.33 ± 3.21 days) and hospitalization in ICU (5.67 ± 3.21 days) was in cases with toxic shock syndrome

The mean value of PLT was low in HLH (67 x 10 9 /l ) and toxic shock syndrome (88.6 ± 12.6 x 10 9 /l) (p=0.260). Low Hgb was pre

Children (Basel)

Patient were included if they were less than 18 years old, had at least 2 days of fever, had multisystemic involvement (at least 2 systems) and had a temporal association with COVID 19. This temporal association was defined as: positive reverse transcription (RT)-PCR or antibodies to SARS-Cov2, history of contact with a confirmed or suspected SARS-Cov 2 infected individual or symptom appearance during the pandemic. Patient were excluded if they had an alternative diagnosis that explained the symptoms. Patient were sub categorized into two categories depending on their clinical presentation: 1-Complete or incomplete Kawasaki disease (KD), following the American Heart Association Criteria; or 2-Toxic shock syndrome (TSS). Data were collected during the hospitalization and the follow up. Results: Between

An international registry on COVID-19 related hyperinflammation in children and young adults

Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Roma; 3 DiNOGMI, Università di Genova, Genova; 4 Pediatric rheumatology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico

Giovanni XXIII" Pediatric Hospital, Bari; 5 Division of Rheumatology, Bambino Gesù Children's Hospital IRCCS, Rome; 6 Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan; 7 Department of Pediatrics and Public Health

COVS-2 must be thorough. PIMS is associated with: lethargy and drowsiness

Department of Women's and Children's Health

Department of Women's and Children's Health, Pediatric Rheumatology; 3 Institute of Radiology

Disclosure of Interest None declared P360 Non convulsive status epilepticus as ongoing symptom of multisystem inflammatory syndrome in children

Department of Women's and Children's Health; 2 Pediatric Emergency Department, Department of Women's and Children's Health; 3 Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua

Neurologic and Radiographic Findings Associated With COVID-19 Infection in

Non-convulsive status epilepticus in a patient with COVID-19 infection

COVID-19 and multisystem inflammatory syndrome in children and adolescents

Diagnostic Performance of 18 F-FDG PET/CT in Infectious and Inflammatory Diseases according to Published Meta-Analyses

HUG, Geneve; 3 HUG, Genève; 4 Kinderspital Zürich, Zurich; 5 Bellinzona Hospital, Bellinzona; 6 CHUV

Vojinovic Clinic of Pediatrics

SARS-CoV-2) infected individuals experience life-threatening events, children are most likely to have a significantly milder COVID-19 disease course. However, they might have a pivotal role in the transmission. Raised concerns regarding the vulnerability of those with several comorbidities led to studies evaluating the patients with rheumatic diseases, but they were not found to be significant risk factors for a severe disease course, neither in childhood nor in adulthood. Objectives: We aimed to find out the asymptomatic SARS-CoV-2 seroprevalence among pediatric patients with rheumatic diseases and healthy children and to compare them with each other. Methods: Patients with familial Mediterranean fever (FMF), juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (jSLE) and healthy children (HC) who remained asymptomatic during the pandemic are examined by ELISA Immunoglobulin (Ig) A and IgG tests in this cross-sectional study. Results: Overall, 149 subjects (90 females) were included in the study

Both IgA and IgG positivity were not found to be related to age, sex, underlying rheumatic diseases and received treatments of the patients. Conclusion: We revealed that patients with childhood-onset rheumatic diseases, even if they receive immunosuppressive medication such as bDMARDs or cDMARDs, might have an asymptomatic SARS-CoV-2 infection, similarly to their healthy peers. Patient Consent Received No Disclosure of Interest None declared P366 Clinical features and outcomes OF 76 patients with COVID-19-related multi-system inflammatory syndrome in children F

Pediatric Rheumatology; 2 Pediatric Intensive Care; 3 Pediatric Emergency, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty; 4 Pediatrics, Cam and Sakura Hospital; 5 Pediatrics; 6 Pediartric Cardiology; 7 Pediatric Intensive Care, Bagcilar Education and Training Hospital; 8 Pediartric Cardiology

Correspondence: F. Haslak Pediatric Rheumatology

All patients had SARS -CoV-2 N-protein IgG antibodies but without history of disease symptoms and had positive contact four weeks prior to the onset of MIS-C symptoms. First symptom of MIS-C was fever (over 38C) which lasted in average for 4.4 days (3-7 days). Muco-cutaneous and gastrointestinal manifestations were most common. All patients had bulbar conjuctivitis, rash was present in 8 patients (80%), hand/foot oedema in 6 cases (60%), anterior cervical lymphadenopathy and cheliitis in 4 cases (40%) and periobital oedema in one case (details presented in Table 1. Clinical features of MIS-C patients). Nine patients (90%) presented with gastrointestinal and hypoproteinemia, low levels of serum potassium and sodium were present during ten days after the onset of symptoms. Troponines were elevated in 4 cases, proBNP in 5 cases. Abdominal ultrasound was performed and 6 patients presented with hepatoplenomegaly, 3 with enlarged spleen, one with enlagred liver and 4 had ascites. All patients were treated with combination of two antibiotics till cultures were proven negative, corticosteroid therapy and antiaggregation therapy. Three patients received a IVIG in a single dose (2gr/kg). All patients had good response to corticosteroid therapy (2mg/kg). Corticosteroid therapy was continued for four weeks (tapering)

It has been suggested that the syndrome results from an abnormal immune response to the virus and it is not considered an autoimmune disease. 2 boys with MIS-C/ PIMS-TS, aged 4 and 5 years, also fulfilled diagnostic criteria for Kawasaki disease. Autoantibodies were detected in 2 patients, in a 15 years old boy with Miller Fisher syndrome (anti GQ1b antiganglioside antibodies) and in a 13 years old girl with Henoch-Schonlein purpura (antinuclear antibodies, ANA). Most of our patients had positive COVID-19 serology (10 patients, 83.3%), negative PCR swab for COVID-19 (9 patients, 75%) and had a family history of COVID-19 (9 patients, 75%)

COVID-19 and autoimmune diseases

COVID-19 and autoimmune diseases. A systematic review of reported cases

COVID-19 and autoimmunity

Bambino Gesù Children's Hospital, Rome; 3 Anna Meyer Children's Hospital, Florence; 4 Policlinico Federico II, Naples; 5 Giovanni XXIII Pediatric Hospital, Bari; 6 Santobono-Pausilipon Children's Hospital, Naples; 7 Cà Granda Ospedale Maggiore Policlinico, Milano; 8 Spedali Civili

MIS-C) 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 (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

9%) in non-ICU settings (Group B). Epidemiological, clinical, and laboratoristic features at ANK prescription are described below

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%)

Cattalini: None declared, A. Taddio: None declared, R. Caorsi: None declared, G. Marseglia: None declared, F. LaTorre: None declared, A. Campana: None declared, G. Simonini Consultant for: SOBI, A. Ravelli: None declared, D. Montin: None declared P372 COVID-19 temporally related multisystem inflammatory syndrome (MIS-C): an early window of opportunity is a good treatment strategy? The experience of the paediatric

Via dei Benedettini 1, 90100 Palermo; 2 U.O.C. of Paediatric Infectious Diseases, Paediatric COVID Center

Via del Vespro 129

Methods: We describe a cohort of 16 Sicilian children (6M;10F; age:1.4-14 years), with MIS-C, with clinical features compatible with classical or incomplete KD, in some cases with MAS and/or TSS. Demographic, clinical, laboratory, echocardiographic and imaging findings, treatment strategy and outcome were collected. Results: Common presenting symptoms included: fever (94%), abdominal pain or vomiting (50%), mucocutaneous rash (50%), conjunctivitis (44%), latero-cervical lymphadenitis (63%), cheilitis/ pharyngeal hyperaemia (81%), hands and feet oedema (13%)

High doses of steroids and IVIG were promptly started with a significant improvement of the clinical course. In all the patients, treatment was started within 72 hours of admission, with IVIG (2 g/ Kg/dose), methylprednisolone (2mg/Kg/day in 56% of patients; 30 mg/Kg/day for 3 days, followed by 2 mg/Kg/day in 38% of patients). 2 patients were treated with enoxaparin. TSS was described in 2 patients, who received additionally vasoactive drugs, albumin and diuretics. Conclusion: In our series, most of patients received a prompt treatment with IVIG and steroids. This approach could explain the good outcome in all the cases and the rapid restoring of cardiac function also in patients with MAS or TSS. Patients showed a wide spectrum of presenting signs and symptoms; evidence of inflammation with pathological values of CRP, ESR, D-dimer, ferritin, pro-BNP, troponin, transaminase, pancreatic amylase and albumin; a multi-organ involvement was documented in a high percentage of cases, inducing the clinician to perform a multi-specialistic approach. Patient Consent Received Yes Disclosure of Interest None declared P373 COVID-19 temporally related multisystem inflammatory syndrome (MIS-C) and cardiovascular involvement assessed with cardiac magnetic resonance (CMR). Experience of the children hospital of Palermo F. Finazzo 1 , A. Alaimo 2

of Paediatric Infectious Diseases, Paediatric COVID Center

P374 Livedo reticularis as a late sign of COVID-19 temporally related multisystem inflammatory syndrome (MIS-C): a case series

Di Cristina"; 2 U.O.C. of Paediatric Infectious Diseases, Paediatric COVID Center

IgG were detected 1-2 months after the resolution of the clinical manifestations of MIS-C. Results: 8/14 children (58%) showed livedo reticularis at the legs, arms, trunk. The livedo was more evident at the legs in all the patients. The livedo started at the remission, after normalization of CRP, ESR, D-Dimer; the sign lasted also for 1-2 months after the discontinuation of steroids and the normalization of haematochemical parameters. 4/8 showed low-title positive autoimmune tests (ANA in 2; ENA anti-Sm in 2; anti-cardiolipin IgG in 1; ASCA in 2). Conclusion: In our series, 8/14 patients showed a livedo reticularis, more marked in the legs, however in some cases with a wide distribution to arms and the trunk. Low-title autoantibodies were transiently positive in 50% of these cases, negative in later detections. Livedo reticularis was a late sign, linked to MIS-C related vasculitis, persisting 1-2 months after the resolution of MIS-C. A different treatment regimen (IVIG plus steroids at 1-2 or 30 mg/Kg/day) did not influence the progress of this clinical manifestation. In 50% of children we documented a transient autoimmune response. Patient Consent Received Yes Disclosure of Interest None declared P375 Acute cardiovascular manifestations in children with multisystem inflammatory syndrome associated with COVID-19 infection in a Sicilian case series A

P376 Step-by-step surveillance in children with multisystem inflammatory syndrome associated with COVID-19 infection: proposal of a cardiologic follow-up F. Finazzo 1 , A. Alaimo 2

Di Cristina"; 2 U.O.C. of Paediatric Cardiologic Division

P379 Multisystem inflammatory syndrome in children related to COVID-19 in Hospital

Introduction: It was recently observed and described an association between a pediatric hyperinflammatory state and the infection by SARS-CoV-2 which was named Multisystem inflammatory syndrome in children related to COVID-19 (PIMS-TS) or Multisystem inflammatory syndrome (in children) MIS-C. Objectives: We aimed our study at describing the clinical features, epidemiologic characteristics, management, and prognosis

Abbreviations: PIMS-TS pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 a Data showed as median and inter Quartile Range

Université Claude Bernard Lyon 1 -Hospices Civils de Lyon -bioMérieux; 7 Cellular Biotechnology Department and Biobank, Hospices Civils de Lyon, Lyon; 8 Réanimation Pédiatrique Hôpital Femme-Mère-Enfant Hospices Civils de Lyon, Bron; 9 Service de pédiatrie, Centre Hospitalier de Valence, Valence; 10 Unité medico-chirurgicale des cardiopathies congénitales, hôpital Louis-Pradel, hospices civils de Lyon, Bron; 11 Pediatric intensive care unit -University hospital of

5-15; females 74.8%). The most frequent JIA subtype was the oligoarticular one (53.6%), followed by polyarticular (23.1%) and the systemic (10.2%) JIA. There were 35 (23.8%) patients presenting contact histories with confirmed COVID-19 cases. 18 patients had a positive polymerase chain reaction test for SARS-CoV-2 at the nasopharyngeal swab, resulting in a COVID-19 prevalence of 12.2% in our cohort. No statistical difference was observed with regard to age and sex patients with or without SARS-CoV-2 infection. No patient with polyarticular JIA presented COVID-19, resulting in a statically significant difference compared to patients without COVID-19 history (0% vs 25.6%, p=0.013). 3 patients presented remission off-medication at the time of COVID-19 and 1 patient was in monotherapy with NSAID. 4 patients were treated only with methotrexate, while 5 only with a biotechnological disease modifying anti-rheumatic drug (bDMARD). 4 patients were on combined therapy with both MTX and a bDMARD. 9 out of the 18 patients with COVID-19 presented symptoms during the infection: fever, musculoskeletal pain and cough were the most frequent (27.8%), followed by headache (22.2%). 3 patients were hospitalized during COVID-19, 2 of them in order to undergo the periodic drug infusions for JIA (tocilizumab and infliximab); the third was hospitalized for clinical observation since the parents reported cough with dyspnea and desaturation at home, which were not confirmed during her stay in hospital. No one of our patients with SARS-CoV-2 infection presented a severe COVID-19 requiring oxygen or developed a multisystem inflammatory syndrome, irrespective of the ongoing treatment for JIA. Conclusion: We found a COVID-19 prevalence of about 12% in our cohort of patients with JIA and reported no cases of severe SARS-CoV-2 infection or COVID-19-related complications in our patients. P387 A rapid review and meta-analysis of the laboratory phenotype of multisystem inflammatory syndrome in children W

P388 Introduction: Multisystem inflammatory syndrome in children

The Centers for Disease Control and Prevention case definition for MIS-C is used to define a confirmed case of MIS-C. Demographic, clinical, laboratory results and follow-up data were collected through the electronic patient record system and analyzed. Results: A total of 67 patients with MIS-C were included in to the study. Fever was detected in all patients; gastrointestinal system symptoms was found in 67.2% of the patients

In 21 (31.3%) patients, a pediatric intensive care unit (PICU) was required in a median of 2 days. The first finding to improve was fever, while the first parameter to decrease was ferritin (median 6.5 days (IQR, 4-11.2 days)). Sixty-five patients were discharged home with a median duration of hospital stay of 10 days (IQR, 7-15 days). Conclusion: The patients with MIS-C may have severe cardiac

Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul; 4 Pediatric Rheumatology, Erciyes University, Kayseri; 5 Pediatric Rheumatology, Şanlıurfa Research and Training Hospital, Şanlıurfa; 6 Pediatric Rheumatology, Karadeniz Technic University, Trabzon; 7 Pediatric Rheumatology, Dr Behcet Uz Children's Hospital, Izmir; 8 Pediatric Rheumatology

The median exposure time of a biologic drug was 13.5 months. Additionally, 66 patients were using DMARD, and 27 patients were also receiving corticosteroid. 70 (63.6%) patients had at least one COVID-19-related symptom (fever, cough, diarrhea, myalgia, anosmia and/or rash), while 40 (36.4%) patients were asymptomatic. Respiratory findings were seen in 26% of all patients, 7 patients also had pathology in computed tomography. Hospitalization was required in 25 patients (22.7%) at median of 6 days (IQR: 4-10). Five patients developed MIS-C and 2 of these patients were followed up in the pediatric intensive care unit. Laboratory tests revealed that fourteen patients had elevated acute phase reactants, ten had elevated D-dimer levels, 5 had lymphopenia (< 1000/mm 3 ), and five had hyperferritinemia. Conclusion: In patients with underlying comorbidities, COVID-19 can have a severe course regardless of the use of bDMARD. In the light of these findings, it would not be correct to say that the currently used bDMARDs worsen the course of COVID-19 infection or to say whether they affect the severity of the disease, but still, the disease findings-modifying effects of these drugs, especially high fever and myalgia, have been observed

Kozhikode; 3 Pediatric pulmonology and critical care; 4 Pediatric cardiology; 5 Pediatrics; 6 Microbiology, Amrita Institute of Medical Sciences

to University Medical Centre Ljubljana, Slovenia. The inclusion criteria for the study was suspected MIS-C on referral. Inclusion criteria for MIS-C group was meeting the WHO criteria and serology was used to confirm SARS-CoV-2 infection. Results: MIS-C group. 23 patients (14male, median age 12.4 yrs), all Caucasian were enrolled and prevalence of MIS-C was 5.8/100 000 persons younger than 19 years of age. Detailed analyses were available in 20 patients. Two patients were treated in ICU and none died. Four patients had symptomatic SARS-CoV-2 infection, all had positive serology

All had elevated levels of D-dimer with no signs of thrombosis

Anjan Trikha, Sushil Kumar Kabra Division of Pediatric Rheumatology, Department of Pediatrics

University Children's Hospital, Lubliana, Slovenia; 6 Allergy and Clinical Immunology

Information and Operation Branch; 10 Endocrinology Metabolism and Hypertension

HLA-typing was available in 94/131 subjects. European descent Still's-DRESS cases were ancestry-matched to INCHARGE pediatric Still's cases 3 (n=550) and compared for HLA allele frequencies. HLA association also was analyzed using Still's-DRESS cases (n=64) compared to drug-tolerant Still's controls (n=30). Results: In cases with HLA typing available, DRESS features included eosinophilia (89%), AST-ALT elevation (75%), and non-evanescent rash (95%; 88% involving face)

months (range 3-40) after drug withdrawal, significant improvement (symptoms and imaging) or resolution of lung disease occurred. Conclusion: DRESS-type delayed reactions occur among Still's patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes across ancestries. These haplotypes are not associated with Still's disease itself. MAS during drug treatment, a known feature of DRESS reactions 5 , should raise suspicion of DRESS to IL-1/IL-6

Pulmonary Manifestations of DRESS Syndrome: A Systematic Review

Emergent high fatality lung disease in systemic juvenile arthritis

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

High-resolution HLA alleles and haplotypes in the United States population

Overlap between hemophagocytic lymphohistiocytosis and drug reaction and eosinophilia with systemic symptoms: a review

Pediatric Rheumatology; 2 Pediatric Ophtalmology, Hospital Clínico Universitario Virgen de la Arrixaca; 3 Centro Tecnológico de las tecnologías de la información y comunicaciones (CENTIC)

Pediatric Rheumatology; 6 Reumatologia, Hospital Niño Jesús, Madrid; 7 Pediatric Rheumatology, Hospital Virgen de las Nieves, Granada; 8 Pediatric Rheumatology; 9 Pediatrics

Pediatric Rheumatology, Hospital Son Espases

Pediatric Rheumatology, Hospital Cruces, Bilbao; 12 Pediatric rheumatology

Hospital Universitario Alicante, Alicante; 16 Pediatric rheumatology, Hospital Cabueñes Gijón, Gijón; 17 Pediatric rheumatology

Pediatric rheumatology

Hospital Universitario Vinalopó, Elche; 23 Reumatologia, Hospital Marina Baixa, Villajoyosa; 24 Pediatric rheumatology; 25 Ophtalmology, Hospital Gregorio Marañón; 26 Pediatric rheumatology

Introduction: Pediatric multisystemic inflammatory syndrome (PIMS) is characterized by the appearance of persistent fever associated with hypotension and multisystem compromise. SARS-COV 2 is a neuroinvasive virus with neurological manifestations, caused by the cytokine storm, which causes an exaggerated response such as meningoencephalitis.Objectives: Describe a case of pediatric multisystemic inflammatory syndrome with neurological involvement due to SARS-COV-2 Methods: We present the case of a 4-month-old girl who presented a pediatric multisystemic inflammatory syndrome with neurological involvement due to SARS-COV-2, treated with intravenous immunoglobulins (IVIG) and methylprednisolone pulses. Results: 4-month-old female. Epidemiological contact: maternal grandfather with COVID-19 4 weeks previously. Clinical picture: 5-day fever (40°C), irritability, sporadic cough, generalized maculopapular rash, non-suppurative conjunctivitis, edema of the hands and feet. On admission irritable, drowsy, bulging anterior fontanelle, tachycardia, bulging pulses, flash capillary filling. He required oxygen, crystalloid charges, and admission to intensive care. It was integrated (PIMS) and meningoencephalitis. Cerebrospinal fluid (CSF): protein spinal cord and leukocytosis, SARS COV2 positive in CSF and serum. Echocardiogram, chest X-ray and skull tomography without alteration. Treatment: gamma globulin (2gkgd), methylprednisolone (2mgkgd) and enoxaparin (1mgkgd). Discharged without sequelae 6 days after hospitalization. Conclusion: We report the exceptional case of SARS-COV-2 meningoencephalitis with positive CRP in the CSF. The comprehensive evaluation of the patient with neurological compromise due to SARS-

Results of the PedsQLTM 4.0 generic core scales in children with juvenile idiopathic arthritis L. Bohmat 1,2 , A. Fadieieva 1 , N. Shevchenko 1,2 1 Department of Rheumatology and Comorbid States, SI Institute for Children and Adolescents Health Care of NAMS of Ukraine; 2 Department of pediatrics № 2, V. N. Karazin Kharkiv National University, Kharkiv, Ukraine Correspondence: L. Bohmat Pediatric Rheumatology 2021, 19(Suppl 1):P324 Introduction: According to the "Treat to target" strategy, the aim of JIA management in children is both clinical remission/low disease activity and reaching the best indicators of the patient`s quality of life that it determines his social status in the future 1 . However, there is no optimal tool for assessment and control quality of life in this category of patients. Objectives: To identify the quality of life in patients with JIA according to the results of the PedsQLTM 4.0 Generic Core Scales taking into account the variant of the disease. Methods: 41 children with JIA were investigated ( 22 with polyarthritis -53,66%, 14 with oligoarthritis -34,17%, and 5 with undifferentiated -12,19%), 3 -17 years old (26 girls and 16 boys), 37 were treated by methotrexate, 5by sulfasalazine. The duration of the disease was 40,22± 6,21 month. Disease activity was determined corresponded to JADAS27, and functional state to CHAQ. Validated for Ukraine questionnaire PedsQLTM 4.0 Generic Core Scales was used for quality life evaluation during the last week. The questionnaire consists of 4 scales (physical, emotional, social, and school functioning), 33 questions, and has 4 age versions (for children from 2 to 18 years). The results were evaluated according to the method of the Likert scale 2 (the highest score of 100 points demonstrates the best quality of life). The survey was conducted by children from 8 years and older and parents of children up to 8 years.Results: It was found that the activity of JADAS27 in the children with polyarthritis was 11,20 ± 7,04, with oligoarthritis -9,80 ± 4,23. High degree of JIA activity was in 12 patients with polyarthritis and 9 persons with oligoarthritis. Functional status (CHAQ) was estimated as 0.23 ± 0.17 indicating minimal functional impairment (0.22 ± 0.14 in children with polyarthritis and 0.18 ± 0.12 with oligoarthritis). The overall level of quality of life in patients with JIA was 50,11 ± 6,20. This indicator had a strong relationship with the value of the score on the JADAS27 (r=0,784) and a weak relationship with the duration of the disease (r=0,272), p<0,05. The overall level of quality of life in patients with polyarthritis was lower (38,41 ± 3,40) than with oligoarthritis (54.1 ± 2,81; p<0,05). The physical scale of the questionnaire showed the highest results among other scales (corresponding to the minimum functional impairment according to CHAQ) -76,21 ± 3,41; in children with polyarthritis -62,71 ± 8,61 and with oligoarthritis -80,51 ± 6,20. The lowest indicators were the results of subscales of emotional and school functioning (58.35 ± 3,67 and 44,24 ± 6,11 respectively), the same in children with polyarthritis (57,61 ± 7,34 and 42,42 ± 6,21) and with oligoarthritis (68,21 ± 8,71 and 64,60 ± 4,51 respectively). At the same time, the results of social functioning were quite high in both groups (82,45 ± 4,11) . Conclusion: The indicators of the quality of life of children with JIA were reduced, especially according to the data on the emotional and school functioning subscales. The results of the PedsQLTM 4.0 Generic Core Scales allow assessing the additional social and emotional sphere of children's life, which is important for their active socialization. This problem requires further study to understand possible actions to improve the situation in the cohort of children with JIA.

Introduction: Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of diseases, which are characterized by chronic arthritis before the age of 16, and require prolonged treatment and follow-up. The treatment is multidisciplinary, with multiple appointments, laboratory studies and medications, this approach represents a high economic cost.Objectives: The objective of this study is to systematically review the relevant literature on the socio-economic burden on direct and indirect costs of the JIA. Methods: The PRISMA recommendations were followed, an unlimited search was made in different databases from January 2000 to July 2019, updated on May 2020. Reviewers worked independently and in duplicate, with good agreement (kappa 0.61) . The reported costs were converted from the original currency to US dollars (USD) for the year of publication, and inflation adjustment was made as of December 2019. Results: REFID Introduction: The past decade in rheumatology has seen tremendous innovation in digital health technologies. With a limited number and distribution of pediatric rheumatologists, telemedicine has been proposed as one way to meet this mission, yet the adoption of this modality has been slower than expected. The current global COVID 19 pandemic has triggered a paradigm shift in many centers to use telemedicine more widely Objectives: We report on the implementation of a telemedicine program in Russian Federation for the evaluation and treatment of patients with rheumatic diseases. Provide an overview of the use of telemedicine consultations in rheumatology department at the Federal Center. In 2021 (from January to April) the number of applications increased 3 times in comparison with 2020. From April 2020 to April 2021, 44 initial applications and 19 repeated applications were received with a referral diagnosis of COVID 19, multisystem inflammatory syndrome. COVID 19 were confirmed in 10 patients. Other diagnoses were exposed: 6 -sepsis, 2 -PID, 1thrombophilia, 1 -relapse of leukemia, 5 -infection and 2 -deaths. 17 patients were admitted: sJIA were diagnosed in 8 patients, SLE -2, large B-cell lymphoma-1, colitis-1, Kawasaki-4, polyarthritis-1. There were patients from the remote regions: 30 were from Sakhalin Republic, 25 -Republic of Bashkortostan, 25-KhMAO, 28 -Orenburg Region, 14-Amur Region. Conclusion: Telemedicine is becoming more widespread, and the number of applications is increasing every year. We report the successful use of this service to assess the solution to the issue of hospitalization of children with rheumatic diseases for the initiation of DMARD in a region with limited access to rheumatological care. (5) was applied as metric to evaluate the performance of our proposed approach. PCP measures a part prediction as correct if the pixel distance between the predicted part location and the manually labelled part is less than a fraction of the limb length in pixels. Despite the large age range of participants, we can correctly track pixel location of 99.6% of the body parts in the test videos according to the PCP metric with threshold set to 0.1. Furthermore, we evaluated our joint angle estimations by computing the mean absolute error (MAE) between angles estimated from predicted landmarks and those from manually labelled markers. For the front limb, MAE for the knee and ankle was 3.9°and 3.2°, for the rear limb, MAE was 6.4°and 3.5°r espectively. Conclusion: Our approach represents a marker-less, robust, low-cost and adaptable method for gait analysis at any age. It will therefore help to understand gait in a broader spectrum of disease courses and can efficiently increase our knowledge of the functional gait and movement abnormalities in individuals with JIA, thereby improving further outcomes. Literature Introduction: The recent epidemic strongly evidenced the necessity of reorganizing physician work, patients' access to clinics and patient support, especially for chronic diseases.In this field, a good strategy must consider the integration between department pediatricians, multidisciplinary specialists and pediatricians in private practice. Besides, adequate standards of care must be ensured especially for children affected by chronic diseases, as Autoinflammatory syndromes.Objectives: These children need to monitor clinical manifestations, attacks-free intervals, treatment adherence and response, onset of short-and long-term complications. This surveillance is a fundamental step to guarantee the best and personalized therapeutic choice, to update the therapeutic plan and to monitor adverse events.In this framework, a cutting-age strategy must adopt web applications, running on personal devices as tablet or smartphone. Methods: SAIApp is a web application written in Python using the Django framework. The app's data layer relies on a relational DBMS implemented in SQLite, while its presentation layer makes use of Bootstrap to guarantee full responsiveness even for small-screen devices. The mobile version has been designed just as a "webapp" that is a mobile app that simply shows a frame where HTML browsing still takes place. This choice is due to the very low computational load involved in SAIApp: it does not use any sensor of the mobile device, and no particular time constraints are required for the user interaction thus allowing for the use of web GUI widgets. The application considers three main actors: the patient or her/his family, the department pediatrician, and the pediatrician in private practice that has been appointed by the patient as her/his reference physician. All of them are registered users of the application but with different roles and grants on the database. The patient can only specify her/his health status by answering a series of simple Yes/No questions about the presence of some symptoms like fever, headache, vomit, constipation, and so on. Moreover, the patient can provide a qualitative evaluation of the overall health status through an easy GUI made by a list of emoj expressing increasing levels of satisfaction. Each health status report has a timestamp, and it is the main source of information to be stored in the database. Introduction: Young children with JIA have to cope with pain and fatigue during schooldays, facing problems with writing, climbing stairs, physical education and playing outside. 1 They need to develop age-appropriate self management skills, encouraged by their parents and teachers in a therapeutic alliance with the health professional team. 2 For this purpose a personal plan for managing pain, fatigue and limitations is made during outpatient rehabilitation treatment in Reade by the physiotherapist and the occupational therapist and noted in a shared management tool, called the "Back and Forth Schoolbooklet"(B&FS). This tool contains diary pages with 1) a colourin puppet for expressing location and amount of pain, 2) spaces for suggested alternatives for limited activities, 3) feedback spaces for comments of parents and teachers and 4) a self-evaluation scale of general well-being for the child. Children, parents and teachers are educated and instructed how to use the booklet in the context of the child's personal pain and fatigue management plan at school. Structured evaluation of the use of the instrument is necessary to improve its applicability and effectiveness during rehabilitation treatment.Objectives: To study the feasibility, defined as practical and experienced applicability and effectiveness, of the B&FS. Methods: Pilot feasibility study with a mixed-method design. Parents, teachers, therapists and children with JIA(4-8 years) were invited to fill in questionnaires after using the booklets in school during their rehabilitation treatment. Practical applicability was assessed by multiple choice questions on duration and frequency of use. Used diary items and pages were counted in returned booklets. Experienced applicability and effectiveness were assessed by open-ended questions. Topics were experienced barriers, facilitators and benefits using the mentioned items of the booklets. Practical applicability was analysed descriptively. Atlas-ti8 was used for analysing and coding the answers on the open-ended questions using a thematic approach. Results: Eight children used the booklets. Six booklets were returned. Six parents of six children, four therapists and four teachers signed informed consent and answered questionnaires. Practical applicability: Five children used booklets for a period of 2 to > 12 week, almost every day. One child stopped in the first week. Counting diary pages confirmed every day or every second day appropriate use of the colour-in puppet and spaces for parents and teachers. Experienced applicability: Identified themes were: child-friendly, easy and providing a clear guide for managing symptoms in the daily school situation. Themes as: daily obligation, unwillingness of the child, lack of motivation or time of the parents or teachers and insufficient instruction illustrated experienced barriers for the use of the booklet. Effectiveness: Identified themes: 1) Children express themselves better about feelings of pain and fatigue, 2) Parents and teachers appreciate more insight into how the child feels and 3) Teachers feel provided with guidance in the interaction with the child 4) Children feel more secure to express themselves at school and 4) Parents are more relaxed about the school situation. year-old enrolled in RESRIP (2013-2020) were included in the study. At enrollment visit (EV): sociodemographic/ clinical characteristics, ongoing medications were inquired from the patients or their parents. Actions to be implemented by RESRIP (paramedical and school level) were also collected. Perceived physical health and social life were reported using a standardized questionnaire set up by RESRIP for the follow-up of patients, at EV and every 6 months. A "well-being score" was then calculated ranging from 0 to 18, with 0 corresponding to absolute well-being. Patients were followed up from their inclusion till June 2020.Results: A total of 406 patients were enrolled and followed up for 36 months in average: 205 juvenile idiopathic arthritis, 68 connective tissue diseases, 81 auto-inflammatory diseases and 52 other diseases. The well-being score did not differ between the groups of diseases. At EV, use of homeopathy, need for implementation of hypnosis or psychological support and need for adjustment of school exams were associated with worse well-being score, and this, whatever the diagnosis. Over time, well-being score improved significantly by 0.04 score unit every 6 months (95%IC [-0.06; -0.03] p<0.001).

Well-being appears to be associated more with the impact of chronic illness than with the type of disease itself. Chronic pain, psychological suffering or functional failure are probably factors associated with this uneasiness, as described in the literature. This result underlines the importance of a healthcare network such as RESRIP who is responsible for the overall care of patients. In the future, it would be interesting to compare these results with patients with CIR not included in a healthcare network. Among JIA patients, a significantly higher negative affect score in PANAS was found compared to controls (mean 22.1 vs. 18.9, p=0.009). However, no difference was seen in the positive affect score, nor the scores in total SCAS and WHO-5 well-being index. A significantly higher positive affect score and lower negative affect score were found in children participating in club sports or always participating in edu-PA, regardless of study group. However, the anxiety score and WHO-5 well-being index were not significantly different between JIA patients whether or not participating in edu-PA or club sport, as it was for the control subjects. In controls recording zero days with pain, a significantly higher positive affect score, lower negative affect score, lower anxiety score (SCAS-C) and higher WHO-5 were found, compared to those with pain. However, in the JIA group we observed no significant difference in these scores, regardless the presence of pain. Conclusion: By using the pain app How-R-You, we found that subjects with JIA recorded pain more often and more intense than healthy age-related controls. Psychological well-being was positively related to participation in educational PA and club sport in both study groups. Psychological well-being was also positively related to pain-free days in the control group, but not in the patient group.

Potential disparity between patient and physician priorities for glucocorticoid medication in relation to HRQOL needs to be addressed in order to improve acceptability and tolerability of glucocorticoid medication in patients. Introduction: Since up to 60-76% of patients with (inactive) juvenile idiopathic arthritis (JIA) suffers from fatigue, leading to significant impairments including increased school absences and decreased physical functioning, an item to screen specifically for fatigue in JIA patients should be added to the Juvenile Arthritis Multidimensional Assesment Report (JAMAR).

Objectives: The first aim is to examine whether two items of the JAMAR "Evaluation of Quality of Life" (JQL) section are sufficiently able to detect fatigue, namely item 3 "difficulty carrying out activities that require a lot of energy such as running, playing football, dancing etc." and item 9 "any difficulty concentrating or paying attention". If not, the second aim is to discover which item of the Checklist Individual Strength-8 (CIS-8), a validated questionnaire for measuring fatigue, is most associated with the presence of fatigue in JIA patients. The most distinctive item will be recommended as addition to the JAMAR to assess whether further evaluation of fatigue would be required. Ultimately, the most distinctive item was CIS-8 item "I feel weak", given that this item was least associated with disease activity. Conversion to 4-Likert scale did not alter sensitivity and specificity of the cut-off value (≥1; i.e. "sometimes") (CIS ≥35; sensitivity 92.5% specificity 85.0%, CIS ≥40; sensitivity 100% specificity 77.2%). Similar results were found when stratifying based on age and gender (see Table  1 ).

The two JQL items could not detect fatigue excellently for the entire cohort, contrary to the CIS-8 items. CIS-8 item "I feel weak" would be most suitable to recommend as addition to the JAMAR to detect fatigue. Scores of ≥1 would indicate that the CIS-8 should be completed by JIA patients to assess to which extent fatigue is present. Male to female ratio was 2:1 and mean age at diagnosis was 6.5 years (min. 8 months; max. 17 years). In fourteen cases current or recent COVID-19 infection or confirmed COVID-19 exposure was observed. When only these patients are analyzed average age was 8.2 years. Antibodies against SARS-CoV-2 were confirmed in seven patients, three had positive PCR test for COVID-19 and one had close contact with someone who has COVID-19 but COVID-19 was not proved. Interestingly, three patients that were antigen positive had respiratory organ involvement. In the reaming seven cases all the other possible causes of symptoms were ruled out and possible contact with SARS-CoV-2 was assumed.In addition to prolonged fever, that was present in all patients, polymorphous rash (95%) was the most common clinical feature Introduction: Given the recent data regarding a broad spectrum of variabilities in clinical and immunologic findings, a complex immune mechanism probably influenced by geographical and ethnic circumstances was thought to play the role in the pathogenesis of COVID-19 related multi-system inflammatory syndrome in children (MIS-C Introduction: Although it is known that COVID-19 related diseases are less frequent and less aggressive in children, pediatric patients with rheumatic diseases are at higher risk for infections due to immunomodulatory therapy and illness itself.Objectives: The objective was to assess clinical features and outcomes of COVID-19 among pediatric patients with rheumatic diseases being treated with biologic (bDMARD) and nonbiologic (nbDMARD) therapy. None of 27 patients diagnosed with COVID-19 required hospitalization. Seven were completely asymptomatic (25,9%), 10 (37,0%) had mild symptoms such as cough, headache or anosmia, without fever, 6 patients (22,2%) had only subfebrile episodes for a day or two, 3 patients (11,1%) were febrile less than 5 days and only one patient experienced dyspnea but without objective signs of lung involvement. One JIA patient with cough during COVID 19 was treated with azitromicin, while others received only symptomatic therapy or no treatment at all. Ten patients (37,0%) continued receiving bDMARs and nbDMARDs, all of them asymptomatic and diagnosed due to epidemiological screening (3 by serological and 7 by PCR test). NbDMARD was paused for 1 or 2 weeks (5 and 7 patients respectively) and bDMARDs were paused in 3 patients for2 weeks in agreement with pediatric rheumatologist. Both bDMARD and nbDMARD were paused in 2 patients (1 and 2 weeks respectively). Decision regarding duration of therapy intermission was based on COVID-19 symptoms and due to parents concern in two occasions. No flares of rheumatic diseases were noticed, only 2 patients with active disease previous to infection needed therapy readjustment. Conclusion: Data on COVID-19 in pediatric patients with rheumatic diseases is still scarce. Our group of patients receiving bDMARD and nbDMARD had mild presentation of COVID-19, not requiring hospitalization. According to our data, treatment with bDMARD or nbDMARD does not pose risk for more severe COVID-19 disease. Due to small sample size more studies are needed for definite conclusions.

Disclosure of Interest None declared

The clinical course and short-term health outcomes of multisystem inflammatory syndrome in children in the single pediatric rheumatology center B. Sozeri 1 , S. caglayan 1 4 Pediatric Intensive Care Unit; 5 Pediatric Infectious Disease, University of Health features of incomplete Kawasaki disease, and macrophage activation syndrome. As it is a new disease there is a paucity of literature on medium-term and long-term outcomes hence this study was planned.Objectives: To study medium-term outcomes in cases of MIS-C from two tertiary care centers from south India. Methods: MIS-C cases diagnosed from March 2020 to February 2021, who had completed three months from acute illness of MIS-C by May 2021, were enrolled in the study. At the time of follow-up at three months, their baseline characteristics, clinical features, laboratory parameters, echocardiographic findings, and ongoing treatment were noted.Results: A total of 37 MIS-C cases had completed 3 months follow-up by April 2021 from both centers. Residual sequalae were cardiac and detected only on follow-up echocardiography. All discharged patients were clinically well and echocardiographic changes were also on improving trend. However, 6 (16%) patients had some echocardiographic changes. Coronary abnormalities were noted in a total of 4 (11%) cases; coronary dilation and small coronary aneurysm were noted in one patient each and two patients had hyperechoic/non-tapering coronaries. Left ventricular dysfunction and pulmonary arterial hypertension were present in one patient each. Patients with persistent coronary abnormalities were on Aspirin and the other two patients required treatment of left ventricular dysfunction and pulmonary arterial hypertension respectively. Conclusion: Medium-term outcomes in MIS-C patients are favorable; provided optimum treatment, follow up with clinical, laboratory, and echocardiographic assessment. Sequalae at 3 months follow up were cardiac and were only detectable by echocardiography, this emphasizes the need for subsequent echocardiogram during follow-up periods to decide the appropriate treatment. All echocardiographic parameters were on improving trends hence these cases are required to be followed up for long-term outcomes. Methods: This is a partially retrospective study with prospective follow-up of disease activity and serology after SARS-CoV-2 infection. We collected children with RD, treated at UCH Ljubljana, Slovenia, who were exposed to SARS-CoV-2. If a member of the same household had a confirmed SARS-CoV-2 infection, we performed a serology test even if the patient had no symptoms. We collected demographical data, clinical presentation of infection, diagnosis of RD, therapy and disease activity at the time of infection and location of the contact with SARS-CoV-2. Serology for SARS-CoV-2 was tested several times during the follow-up.Results: From July 2020 to May 2021, we identified 36 children with RD, who had been exposed to SARS-CoV-2 (31 female; median age 14.8 years, range 2.5-23 years). The majority (28/36; 77%) had juvenile idiopathic arthritis. Introduction: Nailfold videocapillaroscopy (VCP) is an in vivo, noninvasive, rapid, and inexpensive imaging technique that allows quantitative assessment of microcirculation. Pediatric Multisystem inflammatory syndrome in children temporally associated with COVID-19 (MIS-C) affects small, medium and large vessels. Nailfold capillaroscopy findings as pericapillary edema, meandering capillaries and reduced capillary density has been described in adults patients with COVID-19. Case report shows non specific alterations however quantitative microcirculatory impairment has not been clearly documented in MIS-C. Objectives: To describe qualitative and semi-quantitative and quantitative nailfold videocapillaroscopy assessment in Mexican patients with pediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2.Methods: The present study was a cross-sectional observational study that analyzed 40 images from 5 patients with Pediatric Multisystem Inflammatory Syndrome according the case definition published by Cattalini et al. VCP was performed by the same examiner (AVT), images were obtained from all fingers except thumbs of both hands using a videocapillaroscope equipped with a 200x optical probe. The images were collected, coded, and stored using OptiPix software (version 1.7.16), 2015 Optilia Instruments. Qualitative and semi-quantitative assessment were realized according Cutolo classification. Quantitative assessment consist in the measurement of the number of capillaries per millimeter, capillary loop length, capillary width in micron (μm). Results: 2 patients had coronary abnormalities, 1 valvular insufficiency, 1 myocarditis all patients received intravenous Immunoglobulin. 40 images of 5 patients with MIS-C (Image 1) were included in this series, all patients with Hispanic ethnicity and 60% male (n=5). The qualitative assessment did no reveal images with normal capillaroscopy pattern, nonspecific alterations were found in 100%, no pictures suggestive of sleroderma pattern-like have been observed. The semi-quantitative and quantitative assessment. Lower capillary density (4.8 capillaries/mm), increased capillary width in all patients 2 nd Left medium 24.6μm, moderate edema in 90% (n= 36) of images, altered architecture 75% (n=30), peri-capillary stripping hemosiderin deposits probably due capillary leak 60% (n=24), tortuous capillaries 40%(n=16), bizzare capillaries 40% (n=16), meandering 75%(n=30) and irregular ectasias 90% (n=36). Conclusion: This study found qualitative and quantitative abnormalities in VCP suggesting systemic microvascular damage. Further studies are needed to asses the clinical relevance of VCP and its relationship with cardiac alterations and multisystemic damage in MIS-C.

Disclosure of Interest None declared Introduction: The spectrum of clinical manifestations of COVID-19 in children is expanding since the global emergence of the COVID-19 pandemic from early reports in January 2020 depicting respiratory distress to a severe multisystem inflammatory syndrome (MIS-C) within various pediatric clusters. There is a paucity of data from resource-poor countries with respect to follow-up outcomes, particularly for coronary artery abnormalities. Considering this, we conducted a single centre prospective longitudinal study to describe the clinical, laboratory,echocardiographic findings and follow-up of children with MIS-C. Objectives: To study the clinical and laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Methods: All children meeting the WHO case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the SPSS version 12 software. Results: 31 children with MIS-C were enrolled in an eleven-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight % of children presented with shock, and 22.5% required mechanical ventilation. The median (IQR) duration of hospital stay was 9 (6.5-18.5) days. Four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in nonsurvivors as compared to survivors [1061 (581,2750) vs 309.5 (140,720.08), p value=0.045] (table 1) . Six children had coronary artery involvement: 5 recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome (table 1) . Conclusion: Most children with MIS-C present with acute hemodynamic and respiratory symptoms. The outcome is favourable in children without preexisting comorbidities. Raised ferritin level may be a poor prognostic marker. The coronary outcomes on followup were reassuring. Trial registration identifying number: Not applicable Disclosure of Interest None declared Methods: This prospective multicenter study examined the safety and immunogenicity of the two-dose regimen BNT162b2 mRNA vaccine in adolescents aged 12-18 years diagnosed with juvenile-onset AIIRD including Juvenile Idiopathic Arthritis (JIA), connective tissues diseases (CTD) including systemic lupus erythematosus (SLE), systemic vasculitides and uveitis. Patients were evaluated 2-10 weeks after the second dose of the vaccine. Safety and post-vaccination COVID-19 infection were evaluated, as well as disease activity prior and following the vaccine. Post vaccination serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured. Seropositivity was defined as IgG ≥15 binding antibody units (AU/ml). Anti-Nuclear (N) IgG antibodies were measured for evidence of past COVID-19 infection (level above 1.4RLU was considered positive).Results: 71 adolescents with AIIRD patients and 28 controls from 2 countries, 4 centers, participated in the study. The most common diagnosis in the AIIRD cohort was JIA (N=27), followed by SLE (N=14 Introduction: Most children who contract SARS-CoV-2 infection are asymptomatic or mildly symptomatic. However, a subset go on to develop a potentially life-threatening hyperinflammatory condition called multisystem inflammatory syndrome in children (MIS-C) 4-6 weeks after COVID-19. The mechanisms by which MIS-C occurs are not yet clear, resulting in hesitation to vaccinate this subset of children against SARS-CoV-2 due to concerns for a reoccurrence of hyperinflammation.Objectives: To evaluate outcomes following SARS-CoV-2 vaccination in patients who were previously diagnosed with MIS-C after COVID-19. Methods: Medical records of patients who were treated for MIS-C at our institution were retrospectively reviewed. Details for those who were subsequently vaccinated against SARS-CoV-2 were extracted.Results: A total of 164 patients were treated for MIS-C between May 2020 and May 2021. 22 patients were 16 years of age or older and an additional 30 patients were age 12-15 years, resulting in a total of 52 patients eligible for SARS-CoV-2 vaccination. 10 (19%) of these patients were vaccinated using the Pfizer-BioNTech product in our COVID-19 vaccine clinic. The age of the patients ranged from 12 to 17 years. 8 were male, and 8 were from racial/ethnic minority groups. All were generally healthy (3 asthma, 1 repaired congenital heart disease) prior to their MIS-C diagnosis. The patients presented between July 2020 and February 2021 with a febrile illness, and fulfilled the case definition for MIS-C established by the Centers for Disease Control and Prevention, including all 10 having positive SARS-CoV-2 serologic testing and 9 with myocarditis or coronary changes (measured by troponin elevation and/or electrocardiographic or echocardiographic evidence). 8 presented in shock or with hypotension, and 6 were admitted to the intensive care unit (ICU), among which 3 required vasoactive medications and 2 intubation. ICU length of stay ranged from 2-15 days, and total hospital stay from 2-23 days. All 10 patients were treated with corticosteroids, 8 received intravenous immunoglobulin, and 5 anakinra. All patients had normal cardiac function without coronary artery dilation at the time of last cardiology follow-up. The patients were vaccinated an average of 199 days from MIS-C hospitalization discharge (range 83 to 337 days). Thus far, a median of 57 days (range 1 to 117 days) has elapsed since 9 of the 10 patients completed the second vaccine dose. None has developed a recurrence of MIS-C or a hyperinflammatory condition. No significant adverse events have occurred following vaccination. Conclusion: These 10 patients who experienced MIS-C after COVID-19 have tolerated vaccination against SARS-CoV-2 without the subsequent development of a similar hyperinflammatory state providing critical information as the COVID-19 pandemic continues to rage across the globe. As we move toward vaccination for children younger than 12 years, a growing number of prior MIS-C patients (average age 8-9 years) will become eligible for vaccination. Given the risk of re-infection with SARS-CoV-2 and the known additive protection from re-infection provided by vaccinating previously infected individuals, it is imperative that patients with a history of MIS-C be offered vaccination against SARS-CoV-2.

Introduction: Pediatric noninfectious uveitis is a mayor challenge for Pediatric ophthalmologist and rheumatologist. Objectives: Describe a large cohort of spanish pediatric onset uveitis. Methods: A cross sectional and retrospective cohort study was conducted from october'19 to march'21. Multidisciplinary participation was mandatory for entering the study and only fully completed patients were included for analysis. Three distinct groups were made for comparison: Juvenile Idiopathic Arthritis related uveitis (JIAu), Idiopathic childhood uveitis (ICU) and Pars Planitis (PP).Results: A total of 501 patients from 20 centers were included in the analysis, 310 (61.9 %) with an associated immune disease, 91 (18.2%) ophthalmologicaly defined and 100 (20%) idiopathic. JIAu accounted for 54.8 % (275), 259 (51.6%) non B27 related; 67 patients (13.3%) had PP. JIAu was significantly associated to females, younger at uveitis onset, ANA positive, anterior location and insidious presentation, with less ocular complications, systemic corticoid use and ocular surgeries. DMARD exposure was longer and started earlier after uveitis onset with less unilateral severe visual loss. ICU tended to present as panuveitis an associated to males, older age at onset, ANA negative, panuveitis, acute presentation and acute clinical course. Ocular complications were higher, mainly synechiae at onset and cataracts. Exposition to DMARD was significantly lower for both synthetic and biologic agents. PP showed the highest complication rate within the groups (71.6%), specially cataracts during the follow up and greater tendency to present vitreoretinal complications (macular edema, epiretinal membrane and retinoschisis), requiring