Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part one

P381 Transient periosteal hyperostosis with dysproteinemia (Goldbloom syndrome): two cases report Riccardo Papa, Alessandro Consolaro, Francesca Minoia, Roberta Caorsi, Gianmichele Magnano, Marco Gattorno, Angelo Ravelli, Paolo Picco Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy; Radiologia, Istituto Giannina Gaslini, Genoa, Italy Presenting author: Riccardo Papa Pediatric Rheumatology 2017, 15(Suppl 1):P381

Introduction: Periodic fever syndromes (PFS) are rare autoinflammatory conditions that include, among others, cryopyrinassociated periodic syndromes (CAPS), familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) [1]. Canakinumab (CAN), a fully human, highly specific anti-IL-1β neutralising monoclonal antibody, is effective in CAPS [2].  has been shown to be involved in the pathogenesis of FMF, HIDS/MKD and TRAPS, for which no or limited treatment options exist [1]. Open-label studies have suggested the efficacy of CAN in colchicine-resistant/intolerant FMF (crFMF), HIDS/MKD and TRAPS [3][4][5]. We report the efficacy and safety of CAN from a randomised treatment epoch of a Phase 3 pivotal study in patients (pts) with crFMF, HIDS/MKD or TRAPS. Objectives: Primary objective was to demonstrate that CAN 150 mg (or 2 mg/kg for pts ≤40 kg) sc q4w is superior to placebo (PBO) in achieving a clinically meaningful response defined as resolution of the index flare at Day 15 and no new disease flares over 16 weeks (wks) of treatment. Secondary objectives included proportion of pts who achieved a physician global assessment (PGA) of disease activity <2 (minimal/none) and proportions of pts with C-reactive protein (CRP) ≤10 mg/L and serum amyloid A (SAA) ≤10 mg/L at Wk 16. Methods: The study consists of 3 disease cohorts (crFMF, HIDS/MKD and TRAPS) and 4 study epochs: a screening epoch (E1) of up to 12 wks, a randomised treatment epoch (E2) of 16 wks, a randomised withdrawal epoch (E3) of 24 wks and an open-label treatment epoch (E4) of 72 wks. Pts (aged ≥2 years) with a flare during E1 were randomised (1:1) in E2 to receive CAN or PBO. Safety assessments included adverse events (AEs) and serious AEs (SAEs). Results: Of 181 pts (crFMF, n = 63; HIDS/MKD, n = 72; TRAPS, n = 46) randomised in E2, 6 discontinued (5 PBO; 1 CAN). In all 3 disease cohorts, the proportion of responders for the primary outcome at Wk 16 was significantly higher with CAN vs PBO (Table). At Wk 16, a significantly higher proportion of pts achieved a PGA score <2, CRP ≤10 mg/L and SAA ≤10 mg/L in the CAN group vs PBO in all 3 cohorts. The most frequently affected system organ class across 3 cohorts was infections and infestations typically involving the upper respiratory tract. The incidence of SAEs was 8.6%, 4.7% and 11.8% in crFMF, TRAPS and HIDS/MKD cohort, respectively. Conclusion: These results demonstrated superior efficacy of canakinumab after a 16-week treatment period compared with placebo. The overall safety profile was not distinct from those reported in previous controlled studies.
Introduction: Gain-of-function mutations in TMEM173 encoding STING (Stimulator of Interferon Genes) underlie a novel type I interferonopathy, minimally responsive to conventional immunosuppressive therapies and associated with high childhood morbidity and mortality. A newly emerging treatment strategy in STING-related inflammation aims to control interferon (IFN) signalling post-binding of the IFN receptor, by targeting JAK1/2. We hypothesized that inhibition of IFN production itself might represent an alternative therapeutic approach in this disease. Objectives: To evaluate the effect of BX795, a TBK1 inhibitor, on constitutive production of type I IFN in TMEM173-associated vasculopathy. Methods: Human embryonic kidney 293 cells (HEKs) transfected with wild-type (WT) or mutant STING, and peripheral blood mononuclear cells (PBMCs) from three patients were treated with BX795 2 μM. The effect of BX795 on TBK1 signalling cascade was assessed in HEKs by western blotting and IFNβ reporter assay. In patient cells, IFNα production was assessed by ultra-sensitive digital ELISA, STAT1 phosphorylation status by flow cytometry and RNA expression of IFNstimulated genes (ISG) by qPCR.
Results: In HEKs, BX795 inhibited the phosphorylation of IRF3 and IFNβ promoter activity induced by cGAMP or mutant STING. In patient-derived PBMCs, exposure to BX795 inhibited IFNα production measured by digital ELISA, and was associated with a decrease of STAT1 phosphorylation and reduced ISG transcription. In addition, BX795 decreased the positive feedback loop of STING on the type I IFN pathway. Conclusion: Our findings demonstrate that inhibition of IFNα secretion is a potential approach to control disease-associated inflammation in patients with gain-of-function mutations in TMEM173, and may also be relevant in other monogenic type I interferonopathies.
Disclosure of Interest None Declared O4 NLRP3 inflammasome activity in monocytes is regulated by 12/15lipoxygenase Yvonne Kusche 1 , Johannes Roth 1 , Katarzyna Barczyk-Kahlert 1 Introduction: We present a novel syndrome characterised by both lymphoproliferative and autoinflammatory features, due to a PIM-1 kinase gene mutation (PIM-1 associated Lymphoproliferative Autoinflammatory Syndrome, PLAS). Objectives: To describe clinical and genetic features in two cases with PLAS. Methods: Whole exome sequencing (WES) analysis with trio based strategy in the first case and direct sequencing of candidate gene in the second one. Results: A 35-year-old man was referred to ophthalmologist's evaluation for blurry vision in his left eye. The fundus examination showed confluent, yellowish choroidal lesions in both eyes. During childhood, his past medical history was relevant for a diagnosis of celiac disease, recurrent episodes of protracted unexplained fever and skin rashes. He also referred unexplained inflammatory lesions of the osteoarticular and muscular system, one episode of aseptic meningitis, an intracranial granuloma with features of vascular proliferation and two episodes of anterior uveitis. In adulthood, his medical history included episodes of fever with urticaria and subcutaneous nodules. The histological examination of two skin lesions showed a reactive angioendotheliomatosis and a leukocytoclastic vasculitis, respectively. At the age of 30 he underwent splenectomy because of car accident and the subsequent biopsy revealed the incidental finding of noncaseating granulomas. Brain TC also founded multiple lytic and sclerotic skull lesions. He was diagnosed with atypical sarcoidosis (normal thorax X-ray, ACE) and started oral steroid and methotrexate. Since childhood its laboratory data ever showed persistent elevated erythrocyte sedimentation rate (100-112 mm/h), strong positive Creactive protein (60-80 mg/l) and polyclonal gammopathy (IgG Introduction: Autoinflammatory diseases are caused by mutations in genes regulating innate immune responses. More than 20 genes have been associated with various monogenic autoinflammatory disorders, however there is a significant number of undiagnosed patients including familial cases.
Objectives: To identify a disease-causing gene in two inbred families presenting with a neonatal-onset systemic inflammatory disease. We expected to find homozygous pathogenic mutations and subsequently to screen other undiagnosed patients who present with similar disease.
Methods: We performed whole-exome and candidate gene sequencing in the patients and their unaffected family members. NFκB luciferase assay and overexpression experiments in HEK 293 cells were used to confirm the causality of the mutations. Patient samples were analyzed using immunoprecipitation, immunoblotting, gene expression and cytokine profiling. Results: We studied 3 unrelated patients, one of Pakistani and two of Turkish ancestry, with early-onset systemic inflammation and generalized erythematous rash diagnosed as neutrophilic dermatitis/ panniculitis, lipodystrophy, failure to thrive, and without obvious primary immunodeficiency. We identified three novel homozygous mutations in the FAM105B gene, which encodes OTULIN, the deubiquitinase that specifically hydrolyzes Met1-linked ubiquitin chains (Ub) from target proteins. Post-translational modifications by ubiquitination are important for the regulation of many signaling complexes including the NF-kB pathway. Met1-Ub chains are generated by the linear ubiquitin assembly complex (LUBAC). OTULIN is an evolutionarily highly conserved protein and in mice complete deficiency is embryonically lethal. The p.Leu272Pro and p.Tyr244Cys mutations are located near the linear ubiquitination binding region, while the p.Gly174Aspfs*2 mutation truncates the protein. Cells transfected with mutated versus wildtype OTULIN had decreased enzyme activity and showed a substantial defect in the linear deubiquitination of target molecules NEMO, RIPK1, TNFR1 and ASC. Stimulated patients' cells, fibroblasts and PBMCs, showed increased phosphorylation of IKKα/β, IκBα, JNK, P38 and a higher linear-ubiquitinaton level of the target proteins.
These results indicate that inefficient deubiquitination of OTULIN target proteins might explain increased NF-κB activity in mutant cells. Levels of many proinflammatory cytokines including IL-1β, TNF, IL-6, IL-18, IL-12, and IFN-γ were substantially increased in patient serum samples and stimulated cells. Cytokine profiling in serum samples was consistent with disease activity. Transcriptome profiling of patient whole blood samples and stimulated fibroblasts showed similar results. One patient had excellent response to treatment with the TNF inhibitor, infliximab. Two other patients have been treated with either etanercept or anakinra, but they still have an active disease requiring steroids.
Conclusion: Loss-of-function mutations in OTULIN result in increased linear ubiquitination of signaling molecules and lead to enhanced TNFR1, NF-κB, and ASC-dependent inflammasome activity. This new disease, which we named otulipenia, adds to the emerging spectrum of human diseases caused by defects in the ubiquitin pathway and suggests a role for targeted cytokine therapies. is well supported by randomized trials, however, there is controversy about the best dose of acetyl salicylic acid (ASA). Consequently, there is worldwide difference in the current ASA dose used. Concerns regarding gastrointestinal side effects of ASA have prompted use of moderate doses (30-50 mg/kg) in some parts of the world, supported by evidence from meta analyses. The use of high dose ASA (80-100 mg/kg/day) in the initial phase of KD, at one Canadian Centre, as opposed to low dose ASA (3-5 mg/kg) at another centre with a similar patient population, led to this retrospective study Objectives: To determine if low dose ASA in initial phases of KD at one Canadian centre leads to worse short term outcomes compared to higher doses of aspirin used at another centre. Primary Outcome: IVIG resistance Secondary outcomes:1. Duration of hospital stay 2. Incidence of coronary artery abnormalities Methods: Retrospective chart review of patients admitted with a diagnosis of Kawasaki disease at 2 Canadian centres. 150 charts from centre 1 and 178 charts from centre 2 were reviewed. Inclusion criteria: 1. Definitive diagnosis of KD as per AHA guidelines2.

Disclosure of Interest
Received IVIG at AHA recommended dose 3. Received ASA (3-5 mg/kg at centre 1 and 80-100 mg/kg in initial phase at centre 2)Charts with incomplete information were excluded. Data from both centres was entered into the REDCAP database and exported to SPSS version 22.0 for analysis. Data analysis: Baseline characteristics were compared with descriptive statistics. Chi square test was used to compute p values for the primary outcome. Multiple logistic regression analysis was used to adjust for potential confounders. Duration of hospital stay was compared with ANOVA to adjust for confounders.p value of <0.05 was considered significant.
Results: 122/150 and 127/178 patients from centre 1 and 2 respectively were included for the final analysis. There were no significant differences in baseline characteristics between the two groups. IVIG resistance was seen in 28/122 patients in Centre 1 vs 11/127 in centre 2 (p = 0.030). There was no significant difference in the duration of hospital stay between the two groups (p: 0.375) The differences in coronary artery abnormalities between the two groups did not reach a significant p value after adjusting for confounders (p = 0.075).
Conclusion: In this retrospective study, a lower dose of ASA led to an increased risk of IVIG resistance without a significant difference in coronary artery outcomes. The 154% increase in the use of IVIG translates to potential increase in health care costs. Given that IVIG is a scarce resource worldwide, this justifies conducting larger multi centric trials to explore cost benefit ratio of high versus low dose aspirin. Introduction: Systemic-onset juvenile idiopathic arthritis (sJIA) is considered to follow a biphasic course with an initial systemic disease phase driven by innate immune mechanisms and interleukin (IL)-1β as a key cytokine, while a second chronic arthritic phase may be dominated by adaptive immunity and cytokines such as IL-17A.

Disclosure of Interest None Declared
Objectives: A recent sJIA mouse model points to a critical implication of IL-17A expressing γδT cells (Tγδ17) in disease pathology [1]. In this model, IL-17 expressing γδT cells drive a phenotype that resembles arthritis-prominent sJIA in an environment of low interferon (IFN)γ. However, human data on the role of IL-17 expressing γδT cells in sJIA are lacking. Methods: Paired serum samples of sJIA patients (n = 12) during active and inactive disease as well as sera from healthy children (n = 10) were analyzed for expression of IL-1β, IL-6, IL-17A, IL-23, IFNγ and S100A12 by bead array assay. Ex vivo T cellular cytokine expression was assayed in whole peripheral blood samples collected from active and inactive sJIA (n = 12) as well as healthy children (HC, n = 13). Cells in whole peripheral blood were stimulated with phorbol 12myristate 13-acetate (PMA) and ionomycin and were stained for expression of CD3, CD4, γδTCR, IL-17A and IFNγ before analysis by flow cytometry. Finally, CD4 + and γδTCR + T cells were isolated from sJIA patients' as well as healthy control PBMCs (both n = 5) and cocultured with healthy control monocytes under different stimulating conditions. IL-17A and IFNγ expression was quantified.
Results: Particularly in active sJIA patients' serum IL-17A expression was significantly increased. Ex vivo T cellular cytokine expression analysis revealed sJIA γδT cells to over-express IL-17A compared to cells in whole blood obtained from healthy donors. This was not observed with CD4 + T cells. During active disease peripheral Tγδ17 cell frequencies were decreased and appeared to recover in patients with no clinical disease activity. IL-17A over-expression by sJIA γδT cells was confirmed in in vitro studies on isolated cell level and found to occur particularily upon stimulation of monocyte:γδT cell co-cultures with TLR4 ligands such as LPS or S100A12. On the contrary to γδT cellular IL-17A over-expression, IFNγ expression by sJIA CD3 + CD4 + cells was strikingly low, both in ex vivo analysis of patients' whole blood as well as in vitro T cell cultures. Finally, in our assays particularly therapeutic IL-1 blockade appeared to expand peripheral IFNγ + CD4 + cells and restore intracellular IFNγ levels, while γδT cellular IL-17A expression and release normalized to that of healthy donors.
Conclusion: An sJIA serum factor environment with elevated levels of endogenous TLR4 ligands such as S100 proteins and increased expression of cytokines like IL-1β can result in IL-17 over-expression by sJIA γδT cells. As already suggested from the sJIA mouse model, this may be promoted by impaired IFNγ expression as we observed with CD4 + T cells. During active disease Tγδ17 cells may migrate from the periphery to inflamed tissues to drive local inflammation and promote downstream differentiation and expansion of Th17 cells. As a cell-type bridging innate and adaptive immunity, γδT cells may thus play a key pathological role in tilting systemic to arthritis-prone disease in men and mice.
Introduction: The human body is home to a myriad of nonpathogenic bacteria, the so-called microbiota. It has been hypothesised that the gut microbiota plays a role in the pathogenesis of autoimmune diseases, such as RA. Its role in the pathogenesis of JIA needs further investigation.
Objectives: To study differences in the composition of the gut microbiota in patients with JIA compared to healthy controls. Methods: A prospective follow up study was initiated in October 2013, in which untreated patients were enrolled with a new onset of JIA according to ILAR criteria and a duration of symptoms of at most 6 months. Patients were followed for 2 years. At baseline, and if ever a patient presented with inactive disease according to Wallace criteria or a disease flare, a faecal sample was collected and stored at -80°C. Operational taxonomic units were pyrosequenced targeting 16S ribosomal RNA. Additionally, faecal samples were collected from age-, gender-and geography-matched healthy controls and processed as above.
The microbial composition of the faecal samples was analysed using compositional data analysis. The relative abundance was visualised using ternary plots. Differences between healthy controls and patients, as well as between Italian and Dutch patients were tested using MANOVA. Paired baseline, inactive disease and flare samples were analysed using Hotelling's T 2 paired sample test. Association with various clinical parameters was tested using MANOVA. Finally, a random forest algorithm was used to distinguish Italian patients and healthy controls based on their microbiota composition.
Results: Overall, 307 samples were available for analysis. Of these, 100 belonged to patients at baseline (72 Italian samples and 28 Dutch samples). These were matched 1:1 with 107 healthy control samples. Moreover, 100 samples were obtained during follow-up: 70 in inactive disease and 30 in persistent activity or disease flare. There was strong evidence the composition of the microbiota at the phyla level was different in patients at baseline with respect to healthy controls, when analysing Italian and Dutch patients both separately and jointly, taking into account the different age at onset of Italian and Dutch patients (p ≤ 0.003). There was no evidence of differences between patients at baseline and in inactive disease, or between patients at baseline and in persistent activity (p 3 0.048). There was evidence that the composition of the microbiota at the phyla level was different in ANA positive patients with respect to ANA negative patients, even when taking the nationality of patients into account (p = 0.02). There was no evidence for an association with uveitis at baseline (p = 0.18) and only weak evidence for an association with the number of active joints (p = 0.07).
Visualisation of the results, as well as compositional Principal Components Analysis showed that the relative abundance of Proteobacteria and Tenericutes contributed the most to the differences between the groups in all comparisons. The random forest algorithm separated patients and healthy controls well, using only the microbiota composition at the species level. The Introduction: Behçet's disease (BD) is a variable vessel vasculitis characterized by recurrent oral and/or genital aphthous ulcers accompanied by cutaneous, ocular, articular, vascular, gastrointestinal, and/or central nervous system inflammatory lesions. The most widely used diagnostic criteria for adult onset disease is the International Behçet's Study Group (ISG) critera. An international expert consensus group (the pediatric BD [PEDBD] group) has recently proposed a new set of criteria for the classification of Behçet's disease (BD) in children. To evaluate the disease activity in the follow-up; there are mainly two severity scores Behçet's disease dynamic activity measure (IBDDAM) and Behçet's disease current activity form (BDCAF).
Objectives: Our aim was to test the performance of the PEDBD criteria compared to the ISG criteria. Our second aim was to check the correlation between the severity score systems and physician global assessment (PGA) in pediatric BD patients. Methods: Two centers from Turkey and one center from Israel participated in this study. The disease onset was ≤16 years of age. As controls, pediatric patients with other diseases such as primary vasculitides, periodic fever syndrome, or systemic lupus erythematosus were included.
Results: Sixty eight BD (44.1% male) patients and 93 control patients were included. The median age at symptom onset was 132  months and the median time to diagnosis from symptom onset was 12 (0-108) months. Acneiform lesions were significantly associated with female gender (18.4% in females versus 0% in males; p = 0.015). The sensitivity and specificity of the PEDBD and the ISG criteria and revised ICBD criteria were 73.5%/ 52.9% and 98.9%/100% respectively. Thirty two (47%) patients with BD failed to fulfill the ISG BD criteria. However, almost all of these patients met the PEDBD criteria. For systemic therapy, 62 (91.2%) patients received oral colchicine, 15 (22.1%) prednisolone, 16 (23.5%) azathioprine, 6 (8.8%) methotrexate, 5 (7.4%) antitumor necrosis factor alpha treatment, and one patient received cyclophosphamide. The median (min-max) IBDDAM and BDCAF scores at diagnosis were 6 (1-23) and 4 (1-7) and significantly decreased to 1 (0-8) and 1 (0-4) respectively at latest follow-up (p < 0.001 for both). The median (min-max) physician global assessment score at diagnosis was 5 (2-9) and significantly decreased to 1 (0-7) at latest follow-up (p < 0.001). IBDDAM score had a strong positive correlation with BDCAF score (r = 0.637; p < 0.001). PGA positively correlated with BDCAF and IBDDAM scores (r = 0.502; p < 0.001 and r = 0.624; p < 0.001, respectively). Conclusion: In our pediatric series, the PEDBD criteria showed better sensitivity (73.5%) than the ISG criteria and the specificity was close. The higher sensitivity of the PEDBD criteria set is a big advantage for pediatric patients since early diagnosis and timely treatment is very important. Currently, BD patients are treated according to the physician's judgement of disease activity. Our study demonstrated that the severity scores were positively correlated with each other and PGA and thus may be used in clinical practice.

Disclosure of Interest None Declared
Introduction: ADA2 Deficiency is a new autoinflammatory disease characterized by systemic vasculopathy and episodes of strokes, but some patients can present mild immunodeficiency. The defect is due to a loss of function mutation of CECR1 gene, coding for Adenosine Deaminase 2 protein. This protein regulates the catabolism of extracellular adenosine, which we have shown is an important regulator of Class Switch Recombination in B lymphocytes.
Objectives: As some DADA2 patients show hypogammaglobulinemia and recurrent infections, we investigated the role of CECR1 mutation on adaptive immunity. Therefore we decided to characterize peripheral B and T lymphocytes of DADA patients to directly address if ADA2 mutation affects B-cell and T cell function.
Methods: 9 patients carrying mutations in CECR1 were examined. They showed clinical history with livedo reticularis, fever, vasculitis and neurological symptoms. 2 patients presented hypogammaglobulinemia, whereas others 2 patients present recurrent infections. We analyzed peripheral B and T cell phenotype by flow cytometry. B cells isolated from healthy donors and DADA2 patients have been cultured alone or in coculture with CD4+ T cells and in vitro B cell proliferation has been evaluated by CFSE dilution. In vitro B cell differentiation to Immunoglobulin secreting cells in response to TLR9 agonist and T cell help has been evaluated by ELISA/ELISPOT assay. Moreover ex vivo and in vitro cytokines production from T cells has been evaluated.
Results: Flow cytometric analysis showed a significant reduction of total B cells in adult population compared with age matched controls. Intriguingly, a significant decrease in the proportion of memory B cell compartment (CD19+CD27+) was observed in DADA2 patients. Moreover we observed a reduced frequency of CD4+ and CD8+ cells, whereas the subpopulations of T cells resulted normal. To investigate B cell function in DADA2 patients, B cells were isolated from patient's peripheral blood and cultured in vitro with TLRs and CD40L stimulation. Under these conditions, the rate of proliferation of B cells has resulted strongly abrogated as compared to normal controls. We addressed the interaction of B and T cells, essential for generation of memory B and for T cell dependent response of B cells. To this end, we isolated simultaneously from DADA2 patients CD19+ B cells and CD4+ T cells.

Analysis of proliferation and differentiation showed that in vitro proliferation of B cells is not sustained from patient's T cells and
IgM and IgA secretion is significantly reduced with respect to HD B lymphocytes in the presence of CD4 helper T cells obtained from DADA2 patients. Moreover intracellular IFNg, TNFa and IL17 did not differ between controls and DADA2 patients, whereas the evaluation of IL4 and IL21 are ongoing.
Conclusion: Our findings suggest that CECR1 mutation could lead to a defect in B cell function and to a reduced T cell help of B cells.

Disclosure of Interest
None Declared n number of patients who satisfy the criteria, m number of patients with an assessment in the time period Introduction: Gain-of-function mutations in TMEM173 encoding STING (stimulator of interferon genes) underlie a very recently described type I interferonopathy referred to as SAVI (STING Associated Vasculopathy in Infancy ). Thirteen patients belonging to ten different families have been published so far, all carrying heterozygous substitutions involving one of three residues at positions 147, 154 and 155, located in a small linker region connecting the N-terminal transmembrane domain of STING to the C-terminal cyclic dinucleotide-binding domain.
It has been shown that the constitutive activation driven by these mutants is mediated by exit of STING from the endoplamic reticulum (ER) and stable sequestration within the ER-Golgi intermediate compartment (ERGIC)/Golgi compartment. This triggers the downstream protein kinase TBK1, which then phosphorylates IRF3 and induces the transcription of interferon stimulated genes (ISGs).
Objectives: To report three new individuals variably exhibiting the core features of SAVI including systemic inflammation, destructive skin lesions and interstitial lung disease. Methods: One patient was studied by exome sequencing and all three by Sanger sequencing of the candidate gene TMEM173. Interferon alpha titres were assessed by Single Molecule Array (Simoa™) technology and ISGs were measured by qPCR on PBMCs. Functional studies were performed using site-directed mutagenesis, studying the response to cGAMP in a HEK 293 T transfection system. TBK1, IRF3 and STAT1 phosphorylation were also studied. Results: Although all three patients demonstrated characteristic features of SAVI, in two individuals the disease was essentially limited to the skin. Furthermore, none of the three experienced recurrent fevers, and bacterial infections were seen, thus perhaps broadening the phenotypic spectrum. All three patients demonstrated high interferon alpha titres in serum and / or increased expression of ISGs. Molecular and in vitro data revealed that the pathology in these patients is due to missense substitutions at positions 206, 281 and 284 of the human STING protein. These mutations confer cGAMP independent constitutive activation of type I interferon signalling through TBK1, and independent from the alternative STING pathway triggered by membrane fusion of enveloped RNA viruses. Structural analysis indicates that these three amino acids lie in a discrete region of the protein -thereby providing a physical explanation for the human genetic findings, and implicating a novel cluster of amino acids in STING as functionally important in the regulation of type I interferon signalling. Conclusion: Our data clearly implicate a novel region of STING as important in type I interferon signalling, leading us to speculate that the surface-exposed arginine residues at 281 and 284 may be involved in ER retention or in binding to a negative regulator of STING signalling. Thus, the findings presented here suggest a previously unappreciated aspect of the control of STING.

Disclosure of Interest
None Declared

O19
Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in three children Marie-Louise Frémond 1 , Mathieu P. Rodero 1 , Nadia Jeremiah 2 , Alexandre Belot 3 , Eric Jeziorski 4 , Darragh Duffy 5 , Didier Bessis 6 , Guilhem Cros 7 , Gillian I. Rice  Introduction: Gain-of-function mutations in TMEM173 encoding STING underlie a novel type I interferonopathy, minimally responsive to conventional immunosuppressive therapies and associated with high childhood morbidity and mortality. Objectives: We hypothesized that inhibition of interferon (IFN) signaling could be used as a therapeutic approach in this disease. We describe here the medical and molecular consequences of treatment with ruxolitinib, an oral JAK1/2 inhibitor. Methods: During follow-up of three children over a period of between 12 to 24 months, clinical data were collected and disease activity scores were determined for systemic, skin and lung manifestations. The effect of ruxolitinib on JAK-STAT signaling was assessed in vitro and ex vivo by transcriptomic analysis and STAT1 phosphorylation status. Results: We observed marked clinical improvement in all three children in each of the central aspects of the phenotypenamely, destructive skin lesions, interstitial lung disease and systemic inflammation. This clinical effect was mirrored by in vitro and ex vivo data, where we recorded decreased STAT1 phosphorylation and reduced expression of both IFN-stimulated genes and a subset of genes associated with fever and vasculopathy. Tolerance of treatment was good without an obvious infectious risk. Conclusion: These results suggest that JAK1 inhibition represents a promising therapeutic approach in TMEM173-mutated patients and may be also relevant to the treatment of other type I interferonopathies.

Disclosure of Interest None Declared
Introduction: Autoinflammatory diseases cause systemic inflammation which can result in damage to multiple organs. A validated instrument to measure damage is essential to quantify damage in individual patients, and to compare disease outcomes in clinical studies. At this moment, there is no instrument to qualify damage in autoinflammatory diseases. Objectives: Our objective was to develop a common autoinflammatory disease damage index (ADDI) for Familial Mediterranean Fever (FMF), Cryopyrin Associated Periodic Syndromes (CAPS), Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) and Mevalonate Kinase Deficiency (MKD). Methods: We have developed the ADDI by consensus building based on the Delphi method. The top 40 enrollers of patients in the Eurofever registry and nine important experts from the Americas participated in multiple rounds of online surveys to suggest and select items and definitions. Patients fulfilled a role in this project in order to develop a damage index that represents what is important for patients. Further, 22 patients and parents of patients rated damage items and suggested new items. A consensus meeting was held to finalize the items and definitions. Lastly, we decided the scoring of each item based on the results of a decision making survey (1000minds), which was completed by experts and (parents of) patients. Results: More than 80% of the 49 experts and 22 patients completed the online surveys. At the consensus meeting, 31 experts and a patient representative reached consensus on the inclusion and definition of the items. The scoring of each item was based on the 1000minds program, which was completed by 37 experts and fourteen patients. The preliminary ADDI contains eighteen relevant damage items, categorised per organ system. The damage items are considered relevant by the experts and all cause an important burden for patients according to the experts and (parents) of patients. Examples of damage items of the preliminary ADDI are hearing loss, amyloidosis, infertility and serosal scarring. It will take approximately five to ten minutes to complete the ADDI. Conclusion: An instrument to measure damage caused by autoinflammatory diseases is developed based on consensus building with multiple rounds of online surveys and a consensus meeting. Patients fulfilled a significant role in this process. were not present at the meeting and did not have influence on the selection of experts/patients, the content of the meeting or the ADDI itself.
Introduction: Autoinflammatory disorders (AIDs) are an expanding group of complex diseases marked by periodic or chronic systemic inflammation. Mutations in approximately 25 genes have been associated with autosomic recessive or dominant autoinflammatory AIDs. Genetic analysis of based on the candidate gene has a low efficiency and it is expensive and time consuming. Next Generation Sequencing (NGS) has emerged as a new diagnostic tool in this field, with the goals of allowing for faster genetic diagnosis and of providing a better comprehension of the phenotype/genotype correlation in AID patients. Objectives: To evaluate the results obtained by the application of NGS in a cohort of patients affected by undefined AIDsevaluated at our center Methods: In this study we enrolled 242 patients evaluated at our center from 2010 to march 2016 affected by undefined AIDs. In the first 4 years of the study, we performed Targeted resequencing on 179 patients using a panel including 11 AIDs related genes (MVK, MEFV, NRLP12, NRLP3, NOD2, TNFRSF1A, PSTPIP1, IL1RN, LPIN2, IL36RN, PSMB8). The customized panel was subsequently implemented, adding 14 genes more recently demonstrated to as involved in AIDs, used to analyse 63 additional patients. Sequencing analysis were performed on MiSeq® sequencing platform (Illumina, San Diego, CA) and all variants identified have been confirmed by Sanger sequencing. Validated variants were studied by in silico analysis using SIFT and PolyPhen softwares in order to predict their possible functional impact. Results: NGS analysis led to the identification of 80 patients with different variants in the typically AIDs-associated genes: MVK, MEFV, NRLP12, NRLP3, NOD2, TNFRSF1A, PSTPIP1, with a detection rate of 31%. We took into account only variants with a frequency in the global population <1%, as reported in dbSNP and Ensembl databases. 25% of patients showed monogenic variants, both novel or already known, while variants in two or more genes were found in 5% of patients. In details, 33% of total variants was found in NOD2 gene, 19% in MEFV, 16% in NLRP12, 12% in NLRP3, 9% in PSTPIP1 and 5% in both TNFRSF1A and MVK. Several of these variants do not have a clear functional significance yet, while some of them are described as risk factors. We performed 19 familial study to unravel the segregation of some variants. Conclusion: NGS allowed the identification of a large amount of genetic variants in different genes. The major challenge is represented by the interpretation of the clinical relevance of the identified variants, particularly of variants that are found at low, but >1% frequency in various populations. These may indeed function as susceptibility alleles to inflammation rather than disease associated mutations. Some patients show variants in different genes that may cooperate to cause a clinical phenotype or, on the other hand, may be irrelevant. Therefore large-scale population studies, in vitro functional assays and careful correlation between genetic information and phenotypic data are needed. Cooperations with clinicians as well as collaborations with different laboratories using NGS is crucial in order to generate information that are scientifically rigorous and relevant for patient management. Introduction: Canakinumab (CAN) has been shown not to impair antibody production following vaccination in children in an openlabel phase 3 study (NCT01302860) [1]. Here we present the results from the extension of this study. Objectives: To evaluate the presence of protective antibody levels following immunisation with inactivated vaccines in CAPS patients during extension study. Methods: Patients who completed the core study were allowed to continue into the extension study on the standard dosing regimen of 2 mg/kg subcutaneous CAN every 8 weeks or on last dose/dosing regimen received in the core study. Vaccination response was evaluated using post-vaccination antibody titres at 4 and 8 weeks after immunisation. Patients were considered assessable for an antibody response to a specific vaccination if they had a measurement of antibody titre 0-14 days post-vaccination (pre-vaccination assessment) and at least 1 subsequent measurement of antibody titre at 4 weeks and/or 8 weeks postvaccination. However, for patients with adequate pre-dose antibody titres and maintained during the trial, the specific patient vaccination was deemed non-assessable. Results: During the extension phase, of 17 patients (≤6 years), 4 received 8 types of vaccinations against Corynebacterium diphtheria, Bordetella pertussis, Neisseria meningitidis, Clostridium tetani, influenza type A and type B, Haemophilus influenza B, Streptococcus pneumoniae, or hepatitis B. Of 20 unique patient-vaccination cases, 17 were assessable for a vaccination response, whereas for the remaining 3, pre-dose antibody titre was not available. For 16 (94.1%) assessable cases, post-vaccination antibody titres increased above protective levels. For one patient who received Tetravec formulation (diphtheria, tetanus and acellular pertussis combination), the response observed for 1 (vaccination against Clostridium tetani) of the 3 vaccines included in Tetravac represented optical density rather than antibody concentrations and hence considered non-evaluable. For 19/20 patient-vaccinations, including those without pre-dose antibody titres, protective levels were observed during the study, which were maintained throughout the extension. Conclusion: Canakinumab appeared to have no effect on postvaccination antibody production following the administration of nonlive vaccines in CAPS patients.
Introduction: Chronic nonbacterial osteomyelitis (CNO) is one of the most common autoinflammatory bone disorders in childhood. Until now few data are available about the treatment and outcome of these patients. Several studies, all uncontrolled, have suggested the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, methotrexate, bisphosphonates and tumour necrosis factor α (TNF-α) inhibitors. These drugs are differently used with variable degree of response Objectives: To evaluate demographics, clinical features, laboratory and radiological assessment, therapeutic response in a large cohort of Italian CNO patients Methods: Since 2015 CNO patients from 8 Italian centers were included in the new longitudinal section of the Eurofever registry. Demographic data, clinical manifestations and response to treatment were analysed. Results: baseline data from 116 patients are so far available. 72 (61%) females, 111 (95.7%) Caucasian with a median age at disease onset of 10 years (IQR 7.8-11.7). Disease duration at diagnosis was 7.1 months (IQR 3.1-18.5). Disease course was continuous in 73 patients (62.9%), recurrent in 35 (30.2%) and continuous and recurrent in 8 (7%). All patients presented with musculoskeletal involvement at the onset of disease (bone pain 91.4%, arthralgia 84.5%, bone alteration 55.2%, osteitis 55%, osteolytic lesions 48.3%, myalgia and arthritis were found in a minority of the patients). Other features include constitutional symptoms in 64 patients (55.2%), muco-cutaneous manifestations in 17 (14.7%), gastrointestinal involvement in 10 ( 8.6%) and neurological manifestations in 4 (3.4%). At diagnosis erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated respectively in 84 (72.4%) and 62 (53.4%), with 26 (22.4%) patients having ESR and CRP both normal. Serum amyloid A was elevated in 34 out of the 50 patients tested (68%). MRI/CT was performed in 107 patients (56 Whole Body MRI, 52 local MRI, 19 CT), while bone scintigraphy in 90 patients, leading to the detection of a median of 4 lesions (range 1-21). A bone biopsy was performed in 52 patients. At the baseline visit, thirty-one (26.7%) patients had received NSAIDs, 8 (7%) were treated with pamidronate, 29 (25%) with glucocorticoids, 8 with anakinra (7%), 7 (6%) with sulfasalazine. Etanercept was used in 5 patients, Methotrexate was used in 4, adalimumab, colchicine in 1 patient Conclusion: In this study we describe the baseline demographic, clinical, laboratory and radiological findings and therapy in a cohort of patients affected by CNO [1]. Results: Out of the 268 patients in the Eurofever database registered with an undefined AID, 21 were excluded from further analyses because of incomplete clinical data (20) or a positive mutation for TRAPS (1). The median age of disease onset was 4.2 years (interquartile range 1.3-12.8). Patients had a median of 12 (5-15) episodes per year with a median duration of 4 (3-7) days. In 47 patients relatives were affected as well. In 204 patients analysis of one or multiple genes was performed. In 31 patients genetic variants, excluding benign polymorphisms, were found in the MEFV (12), TNFRSF1A (8), NOD2 (9), NLRP3 (6), MVK (3) and NLRP12 gene (3). None of these variants were confirmative for diagnosis of a known AID. Patients with positive genetic screening more often had relatives affected (p < 0.001, Chi-squared) and had more episodes per year (p = 0.035, Mann-Whitney U). Clinical manifestations are shown in the table below. NSAIDs were beneficial in 108/128 patients, but rarely completely effective. Corticosteroids were beneficial in 109/118 patients (51 complete, 58 partial response). Of 50 patients treated with colchicine, 10 had a complete response and 22 had a partial response. Of 15 patients treated with anakinra, 7 had a complete response and 6 a partial response. There was no correlation between the response to medication and presence of genetic variants (Mann-Whitney U). When applying the clinical classification criteria [1], 22 patients were classified as CAPS, 37 as TRAPS, 15 as MKD and 12 as FMF. Seven patients scored positive for multiple diagnoses. Patients classified as TRAPS had a better response to anakinra (p = 0.036, Mann-Whitney U). There were no correlations between the disease classified by the clinical criteria and the presence of specific gene variants (Fisher's exact).
Conclusion: This study describes the clinical features of a group of patients with undefined periodic inflammation. Almost one third of the patients (32%) had a positive clinical classification score for a hereditary AID.  , showed that patients with bone malignancies (but not Langerhans cell histiocytosis patients) displayed a significant higher incidence of systemic symptoms: elevated fever (>38°C) and malaise in fact resulted prevalent in hemato-oncological cohort than in the other two categories (P respectively: <0,0001 and <0,01). CRP and LDH levels were significantly higher and hemoglobin levels lower in patients with bone malignancies than in patient with CRMO or LCH, whilst arthritis signs (pain, swelling and functional limitation) were more frequent in CRMO patients (P: <0,007). Comparing only CRMO with LCH patients, some differences in the onset variables were observed: onset age was higher in CRMO than in LCH patients (P <0,001). Some differences have also been detected in the radiological distribution of bone localizations: clavicle, distal fibula and foot were exclusive for CRMO. Moreover, patients with CRMO displayed a greater number of lesions than LCH. (Table) Conclusion: Our study shows that some clinical manifestations and laboratory data could be useful for differential diagnosis between CRMO and bone malignancies. However, LCH represents the most difficult disease implicated in differential diagnosis with CRMO. Biopsy still represents the gold standard examination for a correct diagnosis.  (Table 7),

Conclusion:
In this cohort, a risk stratification method that used variables usually available at diagnosis accurately estimated the risk of a severe JIA course during the following 5 years. Knowing the probability of a severe disease course at diagnosis will help parents and physicians better tailor the optimal aggressiveness of treatment for each child with JIA.

Disclosure of Interest None Declared
Introduction: Vasculopathy is considered central to the pathogenesis of Juvenile Dermatomyositis (JDM). Moreover, the interplay between persistent JDM-vasculopathy, traditional cardiovascular risk factors, exposure to corticosteroids, and chronic inflammation could create a perfect storm for early atherogenesis. One major hurdle to the study and detection of the vasculopathy of JDM, monitoring of its trajectory over time and contribution to excess cardiovascular disease has been a lack of non-invasive biomarkers. Recently, we described a number of methods for detecting endothelial cell components in blood which allow non-     We also analysed mRNA expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). For each patient charts were reviewed to record clinical features at diagnosis, physician's global assessment of the patient's overall disease activity, serum levels of muscle enzymes (CK, ALT, AST, LDH), erythrocyte sedimentation rate (ESR), C-reactive protein level, antinuclear antibodies status, time to inactive disease, number of immunosuppressants used over disease course and relapses. We also evaluated typical histological aspects of JDM (inflammatory infiltrate, necrosis, perifascicular atrophy and fibrosis) on tissue sections of the muscle biopsies.
Results: Since glucocorticoid therapy strongly reduced muscle expression of cytokines, JDM patients treated before biopsy were excluded from analysis.  Introduction: Children with rheumatic diseases have reduced bone density and increased vertebral fracture rate compared to controls and that children on high dose steroids have twice the fracture risk of those on low dose. Despite the widespread use of biologics some 30% of children with JIA for example remain on steroids. There is ample evidence base for the treatment of adults with low bone density (BMD); there is none for children and adolescents. Objectives: To investigate whether the bisphosphonate risedronate was superior to 1-alfacalcidol or placebo, in increasing BMD as a surrogate for reducing fracture risk Methods: Children and adolescents with JIA, JDM, JSLE or vasculitis, commencing or receiving steroids were eligible. Patients were stratified using a minimisation technique according to: disease type; Tanner score: and low /high steroid dose. They were randomised to receive: Group 1. Risedronate 1 mg/kg per week; Group 2 1alfacalcidol 15 ng/kg/day; Group 3 Placebo. Groups 1,2 and 3 all received nutritional supplements of Calcium 500 mg /day as well as Vit D 400 IU/day. All were followed for 1 year. Clinical and biochemical measurements were performed every 3 months; DXAs every six months; X rays at T0 and one year. Statistical analysis was undertaken using ANOVA. Primary Outcome. Change in lumbar spine BMD Z score (LSBMDz) at one year. Results: At analysis there were 58 in Group 1; 67 in Group 2 and 72 in Group 3. There were no significant differences in SAEs between the groups. There were highly significant differences in the changes in LSBMDz at one year between the three groups; risedronate vs 1-alfacalcidol (difference 0.34; p < 0.001) and risedronate vs Placebo (difference 0.27; P < 0.01). There was no significant difference in LSBMDz between the 1-alfacalcidol and placebo groups (0.07; p = NS). Conclusion: The bisphosphonate risedronate results in significant improvement in LSBMDz at one year and likely associated reduction in vertebral fracture risk. Clinicians should be advised to consider using risedronate in young people with rheumatic diseases on steroids. In contrast 1-alfacalcidol should not be used as it has no impact on improving LSBMDz Trial registration identifying number: Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritides with different prevalence and distribution of joint involvement. Ultrasound (US) is a powerful tool for the assessment of joint disease and has been shown to be more accurate than clinical examination in detecting synovitis. However, assessment of a large number of joints is tedious and time consuming in daily practice, making the feasibility of US questionable. Objectives: To evaluate the prevalence of clinically active joints in different JIA categories, to propose a core set for reduced joint assessment for US (rUS), and to provide preliminary evidence of validity of rUS. Methods: The data collected in a large multinational study (the EPOCA study) were analyzed to evaluate the prevalence of active Conclusion: Although descriptive, these data unveiled the unforeseen significance of GI involvement in AIDs. These findings have threefold implications in the daily clinical management of AIDs. 1) GI specialists should be aware of these rare diseases in order to avoid delayed AID diagnosis in case patients come to their attention first; 2) pediatric rheumatologists and GI specialists should develop standardized work-up protocols in order to monitor these signs and prevent potential complications; 3) these data strongly address the need of a prospective analysis in order to delineate the disease history and potential evolutions (if any) into more defined GI diseases in the contest of autoinflammation. Introduction: The deficiency of adenosindeaminase 2 (DADA2) is a recently described autosomal recessive autoinflammatory disease, caused by mutations of CECR1 and characterized by early onset vasculopathy with livedoid skin associated to systemic inflammation. In some patients, the disease is mild and skin-limited, in others is severe, with multi-organ involvement including ischemic or hemorrhagic strokes. In some DADA2 patients a mild immunodeficiency was detected involving adaptive immunity. TNF inhibitors are very efficacious. Recently, an upregulation of type I interferonstimulated gene transcripts, so called interferon signature, was described also in two DADA2 patients. Objectives: To describe the clinical course of a 4 patients with CECR1 mutations and to assess the role of interferon type I signature as marker of disease's activity Methods: Molecular analysis of CECR1 was performed using next generation sequencing and confirmed by sanger sequencing. Blood was collected into PAXgene tubes and expression levels of IFI-27 IFI-44 L IFIT-1, ISG-15, RSAD-2 and SIGLEC-determined. The IFN score was derived as described [1]. The mean interferon score of the controls plus two SD was calculated: 1.62  Results: PedsQL™ self-report scores of pre-school age children (2-7 years) with PFAPA were significantly lower than FMF peers for general quality of life, physical and psychosocial functioning (Table). The parent proxy-report did not find a significant difference even though scores were systematically lower in PFAPA patients. The parent proxy-report and child self-reported PedsQL™ scores of school age children and adolescent patients (8- HEK293FT. In almost all cases, mutated alleles have been identified not only in all the cell population from the blood but also in ectodermal tissues, suggesting that the event has been established very early in development. DNA from the remaining patients have been subjected to WES in search of novel candidate genes. Unfortunately, same SNPs or different variants at the same genes have not been identified in at least two different patients. Subsequent analysis has been conducted considering single family or trio. A de novo mutation has been identified in a transcription factor belonging to the FOX gene family. Preliminary functional tests confirm a causative role of this amino acid substitution. In a family, the disease segregates with a novel variant in a protein sensor of viral RNA. Finally, in a patient an immune receptor displays impaired membrane expression in white blood cells, due to the coupling of an allele with low frequency from the mother and a non-functional one from the father. Conclusion: CAPS are widely associated with mutations in the NLRP3 gene, being mutated in mosaic status in the most severe patients, and only a small percentage to private mutations that arise in individual patients. Although these changes have apparently a very rare frequency, only an analysis of the genes identified in this study in more patients with CAPS resembling symptoms can definitively assess their actual impact.  Methods: Two following Delphi surveys were sent to health professionals working in the field of autoinflammation.

Disclosure of Interest
In the first open survey 124 experts belonging to the PRINTO Network were asked to list as many variables they wanted they consider as important for the diagnosis of patients with PFAPA. The variables may be of any type (clinical, laboratory, instrumental variables, genetic tests etc). In the second survey 162 experts (also American experts were involved in this phase) were asked to select, from a list of items coming from the first survey, the 10 top variables and to rank them by assigning a score from 10 to 1 in order of importance. There was no possibility to assign the same rank to multiple variables. This process has been conducted in parallel with an analogous process for the monogenic periodic fevers.

Results:
The overall rate of response to the first and second Delphi, including monogenic periodic fevers, was respectively 86% (107/124 experts) and 87%(141/162 experts). For PFAPA, the rate of response to the first and second Delphi was respectively 55% (68/124 experts) and 70% (101/162 experts). We obtained 92 variables from the first survey among which 62 were selected in the second survey. Table 15 shows the total score obtained and the rate of selection of the top variables (3 rd quartile). Conclusion: Our process led to the identification of those features that are considered to be the most important as candidate variable to be included in a new set of evidence based classification criteria for PFAPA. The next step of this project (now ongoing) is the evaluation by a panel of experts of 360 real patients affected by AIDs (PFAPA, monogenic periodic fever and undefined periodic fever) randomly selected from EUROFEVER Registry. Those patients reaching the 80% of consensus among experts in the evaluation process will be used for the subsequent statistical analysis aimed at identified the best evidence-based classification criteria (in term of sensitivity and specificity) for PFAPA. The process will end with a consensus conference that will be held in Genoa This abstract is not included here as it has already been published. Introduction: The Gaslini Diagnostic Score (GDS) is a differential diagnostic score intended to determine a patient's risk of having genetic factors contributing to PFAPA syndrome (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis). The GDS is calculated based on the following criteria: age at onset, positive family history of periodic fever, chest pain, abdominal pain, and diarrhea. While the presence of any of the clinical symptoms is associated with an increased likelihood of a genetic basis, a child with a GDS of 1.32 or higher is considered likely to be at high risk of having a hereditary periodic fever syndrome. When applied in European countries, the GDS showed very high sensitivity (>90%) and a specificity of 59% to 82% .
Objectives: To investigate the utility of GDS in Japanese children diagnosed with PFAPA.
Methods: Children 5 years old or younger who had been diagnosed with periodic fever were enrolled in this study. The observed clinical symptoms for each subject were used in determining his or her GDS, in order to compare the score to the presence or absence of polymorphisms in 10 genes that are frequently implicated in autoinflammatory diseases. Each patient's genomic DNA was isolated from peripheral blood and subjected to polymerase chain reaction (PCR) to amplify selected exons of the genes of interest. The three genes most frequently reported as being associated with PFAPA (and the exons amplified for each in this study) include: pyrin/marenostrin (MEFV, exons 1 to 10), tumor necrosis factor receptor superfamily member 1A (TNFRSF1A, exons 2, 3, 4), and mevalonate kinase (MVK, exons 9, 10, 11). The PCR products were purified, sequenced using the BigDye® Terminator v3. Introduction: PAPA syndrome, is a rare autosomal dominant autoinflammatory disorder and its management still represents a challenge Objectives: Our goal is to present our only experience in the treatment of PAPA syndrome. Methods: We report the case of a 13 year old boy who was referred to our hospital with two weeks history of swollen and painful left knee and right ankle. Since the ages of 2 he was treated in another hospital for recurrent sterile arthritis and skin ulcer; last two years he was treated with Etanercept. His first relative suffers from recurrent sterile arthritis, skin ulcers and acnae. Although genetic analysis not made, arthritis of boy was suspected associated with PAPA syndrome. On examination, left knee, right ankle were swollen, painful with limitation of movement, right elbow with the flexion contracture. A rough scars on the skin above elbows, ankles, right knee, lower legs and on the back were present. Laboratory findings were abnormal with the ESR of 110 mm/h, CRP of 90.0 mg/l, mild anemia, and sterile culture of an aspirate from left knee.
Results: The boy responded well to start treatment with Infliximab, pulses and intra-articular steroides, in terms that after a few days the swelling and pain diminished, movements was better also; in addition, laboratory results returned to normal. In the following months the disease was partially controlled considering that after 7 months of treatment the boy had skin manifestations (ulcer and milde acne), so tetracycline were added. After   Introduction: The proinflammatory cytokine IL-1β has significantly increased the understanding of the pathogenesis of many autoinflammatory diseases (AID), including cryopyrin-associated periodic syndromes (CAPS), hyper IgD syndrome (HIDS), familial Mediterrenan fever (FMF), and systemic onset Juvenile idiopathic arthritis (sJIA). Canakinumab is a fully humanized monoclonal antibody (mAb) specific for IL-1β that has been indicated for a wide range of inflammatory disorders. Based on data from the treatment-withdrawal phase III trial, canakinumab was approved for use for the treatment of children aged >4 years for CAPS and >2 years for SJIA indications.
Objectives: The aim of this case report is to verify the efficacy and safety of canakinumab in patients younger than 2 years old. Methods: Eight unrelated AID patients (4 sJIA, 2 NOMID/CINCA, 1 HIDS and 1 FMF and inflammatory bowel disease) are reported from two pediatric rheumatology centers. All patients were younger 24 months old and obtained their drugs off-label by approval of Ministry of Health.
Results: The results of eight patients (5 female, 3 male) are analyzed in this study. All patients were younger 24 months old (9 to 23 months; mean age = 18,6 months), and had canakinumab (3 mg/kg up to 6 mg/kg) s.c. every 4-8 weeks. Six out of eight patients were previously treated with anakinra for a median period of 55 days (range 1 to 150 days). The median follow up time was 20 months. Seven patients achieved a complete response while one patient was switched due to adverse event. Of the seven patients with the sJIA, HIDS and NOMID/CINCA, four (patients 1,2,4 and 5) did not require any adjustment of the therapy due to a persistent optimal control of both clinical and laboratory parameters during the whole follow-up period. Three others required at least one modification of the treatment schedule due to a persistent elevation of acute phase reactants. Compliance with treatment was good, and no reactions at the site of the injection were recorded. A patient (number 2) had pneumonia at month 20 who treated ambulatory with antibiotic. The administration of canakinumab was postponed until the complete resolution of the infection, which occurred without complications.
Conclusion: In this case series, we report the response to canakinumab in a AID pediatric patients. canakinumab was an effective treatment for patients with ADIs younger than 24 months old and well tolerated. WB MRI (1,5 Tesla) short tau inversion recovery (STIR) and T1weighted images were performed at baseline (median -1 month, range -6-0), after one year (median 12 months, range 9-19) and two years (median 24 months, range 22-26). Clinical assessments, medical history and inflammatory biochemistry were obtained. For data not following a normal distribution Wilcoxon rank signed tests were used to assess change in number of bone lesions.

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The study was performed according to Danish law after approval by institutional innovation board. Results: Six children had elevated sedimentation rate at baseline, all normalized during the first year. Comorbidities were JIA (n = 3) and IBD (n = 1) no children had psoriasis. All children were treated with NSAID as first line treatment and further medical history was antibiotics 6%, methotrexate 41%, steroids 41%, anti-TNFα treatment before PAM 18% and 18% had anti-TNFα treatment added during PAM due to persistent symptoms and progression on WB MRI. The total number of lesions pre-treatment was 112, median 6 (range 2-14) and median number of clinical symptomatic lesions was 3 (range 1-8).
Seven children had axial lesions median 1 (range 1-4) and six had lesions in relation to SI-joint median 1 (range 1-2). There were no erosive changes in the SI-joints. After one year the total number of lesions was 71, median 2 (range 0-21), seven had no lesions. Ten children had new or persisting lesions median 4 (range 1-15). One active spinal lesion and one SI-joint lesion persisted. Two children had deformation of vertebrae without persistent sign of inflammation on STIR-imaging. None of the data followed a normal distribution. There was a statistically significant change in number of bone lesions from baseline to year one (p = 0.047), particularly change in number of spinal lesions from baseline to year one (p = 0.016).
The clinical response after one year was complete pain relief 41%, partial pain relief 48% and no pain relief 11%. In six children the lesions resolved completely as assessed by WB MRI, but pain was still reported.
We evaluated preliminary data of 9 children after two years treatment. Introduction: Marshall syndrome (PFAPA) is characterized by recurrent episodes of fever associated with aphthous stomatitis, cervical adenitis or pharyngitis. It is relatively frequent in children, but the diagnosis is rarely established. Objectives: The aim of this study was to establish the clinical and laboratory characteristics in Marshall syndrome. Methods: Methods included: anamnesis, clinical examination, determination of ESR, PCR, TNF-α and other laboratoty tests. The treatment consisted in Prednison 1 mg/kg p.o. Results: The age at the onset was 1.9 years and at diagnosis was 4.8 years. The mean interval between episodes was 4.1 weeks and the mean duration per febrile episode was 3.6 days. The patients presented: pharyngitis (100%), adenitis (100%) and aphthous lesions (60%). The mean value of ESR was 35 mm/hour, PCR was 9.2 mg/dL and leucocytes were 15.500/mm 3 . TNF-α was elevated during the febrile episodes (14.35 pg/mL) and remained high between them (11.3 pg/mL). Procalcitonin has normal values during flares. Family history revealed the presence of autoimmune diseases in 20% of patients. The patients were treated with Prednison with favorable evolution. Tonsillectomy was performed in three patients with remission of the symptoms. Conclusion: Marshall syndrome should be suspected in children with periodic fever associated with pharyngitis, cervical adenitis and aphthous stomatitis. Although this is the most common cause of recurrent fever in children, the diagnosis is rarely established. Introduction: Pustular psoriasis is uncommon in children. The presentation is characterized by sudden flares of skin and extracutaneous manifestations, which is suggestive of an autoinflammatory syndrome. Adult case reports have suggested use of topical corticosteroids, phototherapy, dapsone, methotrexate, cyclosporine, retinoids, and biologics (TNF-alpha antagonists) but there is no standardized or approved course of treatment. Objectives: To describe a clinical course of a pediatric patient with severe pustular psoriasis with extracutaneous manifestations to sequential treatment course with topical and systemic therapies, utilizing Auto-Inflammatory Diseases Activity Index (AIDAI) to document treatment response. Methods: A 3-year old Caucasian male was diagnosed with pustular psoriasis and prospectively followed from 2014 to 2016. He initially presented with a 6-month history of recurrent generalized pustules which were accompanied by high fever, conjunctivitis, myalgia, headache, anorexia and malaise. There was associated mild dactylitis, but no overt arthritis. HLA-B27 and ANA were negative. During flares, CBC revealed normal hemoglobin with leukocytosis and thrombocytosis and elevated serum C-reactive protein (CRP). The patient had several inpatient hospital admissions for suspected bacteremia with the febrile episodes but septic work-up was consistently negative. Family history included psoriasis, uveitis, and rheumatoid arthritis. Due to severity of skin disease and systemic features, genetic screening for an auto-inflammatory syndrome was considered but declined by the family as a skin biopsy confirmed psoriasis and did not reveal features suggestive of a hereditary recurrent fever syndrome. He was treated with numerous topical and systemic therapies as well as phototherapy. The response to treatment was assessed according to visual skin score for psoriasis along with sequential clinical photographs and an AIDAI score. AIDAI contains 12 items as follows: (1) fever ≥ 38.5°C;(2) overall symptoms; (3) abdominal pain; (4) nausea/ vomiting; (5) diarrhea; (6) headaches; 7) chest pain; (8) painful nodes; (9) arthralgia or myalgia;(10) swelling of the joints; (11) eye manifestations; (12) skin rash. The validated modified scoring system was used for each item with no (0) = absence of symptoms or yes (1) = presence of symptoms, with a total maximum score of "12". Results: Pre-treatment, he had 80% of his skin surface area involved with AIDAI score of 7/12. The following medications were ineffective: topical and oral corticosteroids (oral pednisone 1 mg/kg/day) and UVB phototherapy, followed by oral methotrexate (1 mg/kg once weekly) and colchicine (0.6 mg/day). Oral cyclosporine (3 mg/kg/day) was added to colchicine and methotrexate and resulted in approximately 50% improvement in cutaneous disease between flares, but systemic flares with skin involvement persisted with AIDAI score unchanged at 7/12. Due to incomplete response, subcutaneous etanercept was added (0.8 mg/kg once weekly). Within 2 weeks of initiation, the patient experienced complete remission of skin and extracutaneous manifestations with AIDAI score of 0/12. Methotrexate, colchicine and cyclosporine were subsequently tapered over 4 weeks. He remains in complete remission with etanercept monotherapy at one year follow-up. Conclusion: Pustular psoriasis is challenging due to its rareness, severity and lack of uniformly effective treatment. In this case report, the patient's severe skin and extracutaneous manifestations resolved once Etanercept was added to existing therapy, allowing rapid discontinuation of other therapies. AIDAI score was helpful in documenting treatment response.

Disclosure of Interest
None Declared Lochal Ethics Committee approval was given by the Clinical Research Ethics Committee of the Adnan Menderes University before starting this study. Signed informed consent was obtained from all participants for genetic analysis. A questionnaire was administered to all children for the symptoms of FD. And also, all participants are examined by the same ophthalmologist for FD. The urine analysis and FMF gene mutations of the patients were recorded. 24-hour urine protein was evaluated for each child. The renal ultrasound was done for renal cysts. For the measurement of AGALA enzyme activity in FMF children, the blood drops were smeared onto a dry filter paper, and the meausrement of AGALA activity was performed by the dried blood spot method, with minor modifications. The cut-off value for the lysosomale enzyme activity was 1.2 μmol/l/h. Childrens who have low AGALA enzyme activity were screened for mutation analysis of the GLA gene. Results: The patients' clinical and demographic dates are given in Table 17. The female/male ratio was found to be 1. 3. The mean age of FMF was 12.3 ± 3.9 years. Clinically positive patients with/without MEFV mutation were defined as phenotype I. All of the children were receiving colchicine treatment. The heterozygous mutation was detected in the MEFV gene was 51.3% (39/76), this rate was 19.7% (15/ 76) for the homozygous mutation and 14.5% (11/76) for both negative and combined heterozygotes mutation. Childrens were questioned for clinical signs of Fabry disease.51.3% of patients had longterm abdominal pain, 19.7% of patients had acroparesthesia and 9.2% of patients had skin angiokeratoma like lesion. In the eye examination, corneal opacity is not diagnosed in any of participitants. In the renal examination, 11.8% of patients had proteinuria and 5.3% of patients had renal cyst in the ultrasound. A total of 4 children (2 males) had decreased AGALA enzyme activity (<1.2 μmol/l/h). In those four cases, we determined M694V heterozygous mutation in one patient, M94I/V726A combined heterozygotes mutation in one patient and also negative mutations in two patients. Sequence anlysis of whole exons of GLA gene was performed for patients who have low enzyme activity, but any mutation was not found. Conclusion: Fabry disease is a rare disorder, in which the clinical findings are confused with various systemic and rheumatic disorders, including FMF. Our study includes the most number of cases in the literature which the incidence of Fabry Disease in Familial Mediterranean Fever childrens are investigated. Fabry disease can cause serious complications and renal failure in adult life for the diagnosis of these disorders, we think the risk groups must be scan in childhood.  (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and 30.09 ± 8.9 years (19-54) in children and adults, respectively. Three patients were excluded from the study, as their medical records were not available. The patients were classified according to the final diagnosis as FMF in 39 patients (30.6%), Henoch-Schonlein purpura in 10 patients (7.8%), PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome in 6 patients (4.7%), juvenil idiopathic arthritis (2 oligoarticular onset, 1 enthesitis-related arthritis) in 3 patients (2.3%), Chron's disease in 2 patients (1.6%), celiac disease, ulcerative colitis and mixed connective tissue disease in one patient each. 57 patients (44.6%) had FMF-like symptoms, without a diagnosis of FMF. Four asymptomatic patients (3.2%) were identified during family screening. A female adult patient was dignosed as FMF at the age of 22 and needed biological treatment (anakinra) at 27 years old due to colchicine resitance. Five patients had a history of appendectomy. In the study population, two patients developed chronic renal failure (CRF). One of them was diagnosed as CRF at 15 years old, when he had 3.2 gram/day proteinuria, without a spesific etiology. Another patient had CRF secondary to nephrolithiasis at the age of 42. Conclusion: R202Q alteration of MEFV gene may lead to symptoms consistent with FMF in some cases. Also, this alteration may present with varied distinct clinical conditions other than FMF.  to body weight, and were estimated to be 0.14 ± 0.04 L/day and 4.96 ± 1.35 L, respectively. The estimated half-life of CAN was 25.6 ± 6.4 days. CAN minimal concentration at Week 16 following 150 mg sc q4w dosing was estimated to be 15.3 ± 6.6 μg/mL. The estimated steady-state area under the serum concentrationtime curve from time zero to the end of the dosing interval tau (AUCtau) was 648 ± 202 μg.day/mL. Similar results were obtained in all 3 diseases. CAN binding to circulating IL-1β was demonstrated by increase in total IL-1β following CAN dosing in all 3 diseases. In pts requiring uptitration to 300 mg, levels of total IL-1β were higher, suggesting higher production of IL-1β, and therefore the need for a higher dose.

Disclosure of Interest None Declared
Conclusion: This was the first study to evaluate the PK of canakinumab given in the LIVI form. The results observed in crFMF, HIDS/MKD and TRAPS pts were similar to those observed in other indications (CAPS and SJIA) using the lyophilisate form. These data suggested that the new formulation did not affect the PK/PD of canakinumab and similar to CAPS, patients with higher levels of IL-1β require canakinumab uptitration to achieve optimal disease control. We have a lot of different ethnicities in Iran like Armenians, Turks, Arabs and Jews and also consanguineous marriage is common among Iranian people. These lead to more frequent diagnosis of genetic disorders like FMF in our country. We aim to identify the distribution and the frequency of the Mediterranean Fever (MEFV) gene mutation among FMF patient in the pediatric population in Tehran -Iran.
Methods: This study is a prospective cross sectional study of patients diagnosed with Familial Mediterranean Fever (FMF) who was registered in the autoinflammatory computer database registration through periodic fever clinic, which was established for this reason, in the medical center of children in 23.09.2012 in Tehran-Iran and data were collected with standardized forms. Of the total 102 FMF pediatric patients (68 male, 34 females) with a mean age of onset of disease 4.2 years, were screened for mutation in four exons (2, 3, 5 and 10) of MEFV gene. Genomic DNA was extracted from whole blood and entered in ARMS-PCR and PCR-RFLP reactions. When cases were negative in ARMS-PCR and PCR-RFLP, the exons were amplified and subjected to direct sequencing. The tested individuals were screened for the most common 12 MEFV mutations. Introduction: Chronic Non-Bacterial Osteomyelitis (CNO) is a rare inflammatory disorder that primarily affects children, characterized by insidious onset of pain, local bone expansion and radiological findings suggestive of osteomyelitis at single or multiple sites. The aetiology is unclear. Recent evidence strongly supports a genetic susceptibility, considering CNO a disease in the spectrum of autoinflammatory disorders.

Results
Objectives: The aims of the study are to investigate the role of autoinflammatory candidate genes in a subgroup of patients of the Italian Cohort of CNO patients and to find possible correlation with clinical phenotype.
Methods: Blood samples were collected from 51 CNO patients of the cohort upon informed consensus. We selected 112 genes involved in autoinflammation and we used an Ion Torrent platform to sequence the coding regions. All the annotations and pathogenic prediction were performed with VEP (http://www.ensembl.org/info/docs/tools/ vep/index.html) and all the potential pathogenic variants will be confirmed using Sanger sequencing. Laboratory data, diagnostic imaging, histological features and clinical course are also collected and all the data are stored in a relational database.
Results: Clinical data of 116 patients with CNO diagnosis and included in the Italian Cohort were collected. DNA samples from 51 patients were available. They were the only patients included in the present study. The patients were 33 females (65%) and 18 males (35%). Median age of first complaint was 10 years (range 4-16). Median sites number was 5 (range 1-26 sites). The majority of bone lesions was located in the long bones 63%, followed by pelvis (59%), column (43%), thorax (26%), clavicle (24%), extremities (17%), skulls (6%) and mandible (4%). Blood examination revealed increased erythrocyte sedimentation rate and C-reactive protein in 82% and 65% of cases respectively. In 36/51 (70%) patients the diagnosis was formalized after biopsy. At diagnosis X-ray was performed in 32 (63%) of patients and resulted positive for lesions in 17 of them (53%). Computer tomography was used in 12 patients (23%) and was negative only in one. Magnetic resonance (MRI) imaging was performed in 47 patients (90%) and was always positive. Radionuclide bone scanning was performed in 30 patients (59%) and was negative only in one case. All patients received non-steroidal antiinflammatory drugs (NSAIDs) therapy, only 12 (23%) reached remission. About the other therapies: 9/18 reached remission with oral steroids, 3/11 with methotrexate, 4/8 with sulfasalazine, 10/17 with biologic therapy and 14/24 with bisphosphonates. Currently 43 patients (84%) are in clinical remission (16 on medications, 27 out of medications). All the 51 patients underwent sequencing of the selected genes. In the majority of cases, one or both parents were available for the analysis and were sequenced in order to exclude inherited variants. We are currently evaluating each variant with Sanger sequencing in order to assess their pathogenicity and have a clearest picture of CNO genetics.
Conclusion: This study confirms some findings already known of the disease: the prevalence of lesions in long bones, the high sensitivity of MRI and the high clinical remission rate. We have also sequenced the selected genes involved in autoinflammation. If the variants found and selected for big impact on the protein structure, will be confirmed with Sanger sequencing, we will try to find a correlation with clinical phenotypes.   [3,4] attacks of fever and painful serositis. There are described some case reports of FMF with hyperbilirubinemia. Objectives: We present FMF Armenian patient with a single MEFV gene mutation and hyperbilirubinemia during the attacks, with the interesting family history. Nevertheless high incidence of FMF in Armenia, the case with hyperbilirubinemia in Armenian children have not yet been described. Conclusion: This is a rare case of mild hyperbilirubinemia with family history of FMF with interesting family tree. There is no doubt, that display of heperbilirubinemia during the attack is mediated by the effect of cytokines on the liver. As evidenced by a number of literature these cytokines decrease bile excretion and increase serum level of bile acids. It is not excluded that these mechanism operates mainly in cases, when there are changes of bile excretion and some changes of metabolism of lipids in the family history of FMF patients. For more detail evaluation of hyperbilirubinemia in FMF, should be necessary to have large number of group with investigations their family tree. of disease began from the infancy period only with fever, but from the 8-9 years it was accompany with abdominal and chest pains. Family history: father has FMF with M694V/M694V mutation and gold bladder stone. There are too some cases of FMF from the mother and father relatives, including secondary amyloidosis also which whom conducted transplantation of kidney. The attacks of patient was 1-3 times per month each lasting typically for 3-4 days. Examinations; skin with yellow coloration. RBC results showed leucocytosis with elevated CRP and ESR. Chest X-ray reviled exudates in the costophrenic angle from the two sites, ultrasound investigation -splenomegaly. Genetic investigation of MEFV-M694V/N mutations. We established the diagnosis of FMF (according criteria Tel-Hashomer) and Gilbert syndrome (according clinical feature and genetic homozygotes mutations (UGT1A1). At the same time we rule out other conditions with similar symptoms. Conclusion: According the literature data and our long work in this field, we can conclude, that liver has very important role in the development of FMF attack which is trough hepatomegaly and biochemical deviations in some cases. We can presume, that coexistence of two diseases due to the affection of cytokines which are more producing during the attacks of FMF and which are decreasing the activity of uridine 5-diphospho-glucuronosyltransferase (mutation in this enzyme cause Gilbert's disease), It is not excluded some interaction of genes of above diseases. Introduction: Behçet's disease is a chronic, recurrent and multisystemic disease that can involve the skin, mucosal surfaces, eyes, joints and other organs. Behçet's disease, which progresses with flare and remissions, can limit individuals' daily activities, disturb their psychological well-being and ruins the quality of life.

Disclosure of Interest
Objectives: In this qualitative part of the study, it is primarily aimed to enrich the item generation for the multidimensional assessment of juvenile Behçet's disease.

Methods:
The research was conducted in the Pediatric Rheumatology Department of Gulhane Military Medical Academy and Hacettepe University in Ankara, Turkey. Twenty children with Behçet's disease and fourteen of their parents were enrolled in this qualitative study. In this study, we used a qualitative study design and a grounded theory approach. The first step was data collection, through individual in-depth interviews. From the collected data, the key points were marked with a series of codes, which are extracted from the text. The codes were grouped into similar concepts. From these concepts, categories were produced, which were the basis for the creation of a theory. The data were collected using both a demographic data form and a semistructured interview form. The interview form was developed by the authors based on the literature search, the theoretical framework, expert opinion, and included open-ended items to gather data regarding the experiences of the participants with respect to their diseases. The study was performed on individual patient face-to face interview. Data were analyzed by grounded theory and the N Vivo 9 software program. Results: Four categories were obtained. These categories were (i) physical effects of the illness, (ii) emotional effects of the illness, (iii) social effects of the illness and (iv) experienced challenges related to treatment process. In the physical effect category there are two themes; symptoms and the limitations about the illness.
In the symptoms theme there are aphthous lesions, genital lesions, pain, visual problems, and in the limitations about the illness theme there are speaking and feeding difficulties related to aphthous lesions and walking difficulties related to genital lesions. The emotional effect category includes two themes, psychological impacts, coping and support. In the psychological impacts theme there are anger, disability to cope, rebellion against disease and emotional exhaustion. In the social effects category there are three themes; school-related problems, problems with peer relations and problems with social life. In the school related problems theme, decrease in academic performance, absenteeism to school and concealing the sickness from friends; in the problems with peer relations theme, fighting with friends, reduction in peer relationships; in the problems with social life theme, social isolation, inability to adapt to their peers, hide the illness were the most common features. The fourth category includes three themes; lack of knowledge about the illness, problems with medication and reaching the health facility.
Conclusion: These results provide us evidence-based data and necessity for the assessment of children with Behçet's disease with multidimensional approach including physical, emotional and social aspects as well as treatment process. Our study also contributes the basis and/or justification for selecting the domains that the developing multidimensional instrument should include. Introduction: Familial Mediterranean Fever (FMF) is an autoinflammatory disease causing overt or subclinical inflammation likely associated with insulin resistance. Various nail fold capillary changes were described and used to identify several rheumatic disorders such as scleroderma and dermatomyositis. In adults, nail fold capillary abnormality has been described in FMF. however, there is no enough study in children with FMF Objectives: The aim of this study: 1) to investigate whether children with FMF have nail fold capillary abnormalities in both active or/and remission period or not. 2) To assess the insulin resistance in children with FMF in both active or/and remission period of the disease and compare to control group. Methods: Ninety-two patients with FMF, including 25 patients in active period and 67 patients in remission period and 33 apparently healthy children were enrolled in the study. Nail-fold capillary examination was done by dermatologist who was unaware of subject's details such as patient or control group. Groups were compared for inflammatory markers (ESR, CRP and SAA), insulin resistance (HOMA-IR) and nailfold capillary abnormalities. The relationship among the nail fold capillary abnormalities, insulin resistance and inflammatory markers were evaluated.

Disclosure of Interest
Results: Overt nail fold capillary abnormality was found in 20% of patients at the attack period and in %2.9 of patients in remission. There was no nail fold capillary abnormality in control group. HOMA-IR was higher at the attack period than attack free period and control. But this did not reach statistical significance. However, HOMA-IR was positively correlated with serum AA. Nail fold capillary abnormality was significantly positively correlated with increased levels of acute phase reactants and was significantly negatively correlated with serum HDL levels.

Conclusion:
-There are apparent nail fold capillary abnormalities in children with FMF especially in the active period of the disease.
-There is insulin resistance which is likely associated with inflammation.
-Nail fold capillary abnormality become overt in active period of disease as insulin resistance. Introduction: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), formerly known as familial Hibernian fever, is an autosomal dominant autoinflammatory disease, resulting from mutations in the TNFRSF1A gene, encoding tumor necrosis factor receptor. Its most common clinical features include recurrent long-lasting fever episodes usually persisting 1-3 weeks, periorbital edema, conjunctivitis, a migratory erythematous skin rash with underlying fasciitis and myalgia, arthralgia or arthritis and polyserositis. Even if headaches are frequently described, no case has been reported until now with documented inflammatory neurological involvement. However, an interesting association has been hypothesized with multiple sclerosis and the R92Q mutation. The R92Q is a TNFRSF1A variant of unclear significance, which has been associated with cases of TRAPS but its actual pathogenic contribution should always be interpreted in the appropriate clinical context. Objectives: To describe a case of R92Q positive TRAPS patient with documented inflammatory neurological involvement.

Disclosure of Interest
Methods: Case report.
Results: 4-year-old girl, originated from Switzerland, presenting with recurrent episodes of fever and gastrointestinal symptoms beginning within the first 2 weeks of life, later on associated with arthralgia, pharyngitis, periorbital lilaceous discoloration and atypical febrile seizures. The patient had a normal growth and development; the family history was unremarkable. Laboratory findings showed intermittent increased levels of acute phase reactants. Imaging studies revealed normal cerebral MRI and abdominal ultrasound. After exclusion of an infectious origin as well as an immunodeficiency, an autoinflammatory disease was suspected. Genetic analysis was performed in the 4 major genes associated with periodic fever syndromes (NLRP3, MEFV, TNFRSF1A, MVK) and the R92Q variant was found in the TNFRSF1A gene suggesting the diagnosis of TRAPS. A treatment with Canakinumab, an IL-1 blocking agent, was introduced with partial response. In spite of the uptitration of its dosage to 6 mg/kg, arthralgia and monthly episodes of fever persisted. Moreover, the patient developed progressive headaches with vomiting and fluctuant level of consciousness. Cerebral MRI was repeated and was normal. Lumbar puncture showed high opening pressure suggesting intracranial hypertension. Analysis of the cerebrospinal fluid reveled pleocytosis with sterile cultures, indicating the presence of aseptic meningitis. The patient experienced resolution of the headaches after the evacuating lumbar puncture, but neurological symptoms rebounded two days later. Canakinumab treatment was, therefore, replaced with Anakinra, another IL-1 blocking agent which seems to be more efficient in treating autoinflammatory neurological symptoms following previous experience in CAPS patients. Acetazolamide therapy was also started to lower intracranial pressure. Conclusion: We report here the first case of TRAPS with documented inflammatory CNS involvement. This observation could suggest that thorough cerebral investigations should be performed in TRAPS patients presenting with persistent headaches or other neurological symptoms. Anakinra, a smaller molecule inhibitor of IL-1 with a better blood brain barrier permeability than Canakinumab, might be considered in these patients.

Disclosure of Interest None Declared
Introduction: Osteopetrosis is an extremely rare inherited disorder, characterized by an increased bone density and caused by a defect in osteoclasts formation and function. Clinical presentation varies greatly ranging from very early onset bone marrow failure, neurological problems, hearing or vision problems to the incidental finding of osteopetrosis on classical X-ray at a later age.
Objectives: To create awareness that osteopetrosis need to be included in the differential diagnosis of a limping child and to demonstrate the usefulness of classical X-ray in the differential diagnosis of limping.
Methods: Retrospective review of pediatric cases with limping and on X ray diffuse sclerosis.
Results: Two patients of 3 and 5 years old, were referred to our pediatric rheumatology outpatient clinic with limping since 2 months. The 1 st patient is a 5y old girl from consanguineous parents. She presented with persistent limping without fever or previous trauma. Clinically we saw a girl with macrocrania, frontal bossing and hypertelorism. Mobilisation of the left hip was slightly painful and limited in endorotation and abduction. Previously this girl was followed at the neurology department with a discontinue nystagmus and a bombing fontanel where additional imaging revealed a triventricular hydrocephaly with a coronal synostosis. Decompressive craniectomy and the placing of a ventriculo-peritoneal drainage was done before the age of 1y. Afterwards she had several revisions of the ventriculo-peritoneal drain because of recurrence of increased intracranial pressure. The 2 nd patient is a 3y old boy, born from consanguineous parents, that consulted because of painful limping since 2 months without any trauma. Symptomatic treatment partially improved pain symptoms. Clinically we saw a limping boy with macrocrania and hypertelorism, bilateral genu valga and a painful mobilization of the right hip, limited in exo-and endorotation. This boy had a normal psychomotor development and no hearing or vision problems. Classical X-ray of the hip in both patients showed sclerotic bone with extreme coxa vara and the impression of sliding of the left and right femoral head respectively. Further imaging confirmed diffuse sclerosis of the skull, the pelvis and several long bones and "sandwich" vertebrae. None of the patients had signs of bone marrow suppression, nor hypocalcemia. Genetic analysis in the 1 st patient revealed a missense substitution in the CLCN7 gene, which is compatible with an intermediate form of osteopetrosis. Genetic analysis of the 2 nd patient is ongoing.
Conclusion: Limping is a frequent presenting symptom at the pediatric rheumatology outpatient clinic with a broad differential diagnosis. Classical X-ray in the present patients revealed extreme coxa vara with increased bone density in the context of osteopetrosis. Limping may be the only symptom or accompanied by small stature, neurological manifestations, signs of cranial nerve compression, bone marrow failure and/or renal tubular acidosis. This is the first report that describes limping in pediatric patients as a first presentation of osteopetrosis. Diagnosis is important as the prognosis (development of haematological problems, blindness, hearing problems and neurological complications) is determined by the underlying genetic defect and therefore also the treatment strategy. Treatment varies from merely symptomatic to haematopoeitic stem cell transplantation (HSCT) in case of bone marrow failure.  Table 20. None of them had osteoporosis. The population prevalence estimation of low BMD was lower than 3%, with a confidence interval of 95% In multiple linear regression analysis we found a model with R 2 = 0.4, with significant correlation between BMD Z-score adjusted for height (ZAH) and lean mass index (LMI) (g/m 2 ) (B:0.14; p:0.03), body mass index (BMI) percentile (B: 0.024; p < 0.01); height percentile (B:-0.09; p < 0.01) and fat mass index (FMI) (g/m 2 ) (B:-0.135; p < 0.01). We found no relation between BMD ZAH and other studied parameters.

Disclosure of Interest
Conclusion: Low BMD prevalence in our population is lower than previously described in other studies. Different dietary and cultural habits and an unequal access to therapeutic resources could explain these results. Higher values of LMI and BMI seems to be a protector factor to the bone, while a higher FMI acts as a risk factor for the development of low BMO for chronological age in JIA paediatric patients as it has been described in similar research in other countries.
Influence of diet, physical exercise, inflammatory activity and treatment with glucocorticoids and synthetic and biologic diseasemodifying antirheumatic drugs (DMARDs) could not be demonstrated, probably because of a low sample size, because their effects might be scarce and because of the low prevalence of low BMD in our sample.

Disclosure of Interest
None Declared Introduction: Musculoskeletal ultrasound (MSUS) is an important tool for evaluating disease activity, therapeutic progress, and remission status of rheumatic diseases in children. Knowledge of age-related normal findings is essential when interpreting pathological findings such as those seen in juvenile idiopathic arthritis.
In juvenile spondyloarthritis and in the JIA category enthesitisrelated arthritis the affection of the Achilles tendon is very common.
Objectives: To evaluate normal findings and sizes of the Achilles tendon (AT), we recorded age-related grey-scale findings in 438 healthy children between 1 and 18 years of age using high-resolution Bmode MSUS Methods: We determined approximate age-and sex-related norms for the AT (sagittal and transverse diameter) at two predefined positions (middle part at the end of the tibia and distal part at the beginning of the calcaneal back). Ultrasound measurements were performed in the longitudinal and tranversal plane.
Results: 438 probands (243 girls) were bilaterally examined. 6 age groups were created for analyses. In the youngest age group (1-3 years) the mean sagittal diameter was 3.4 mm (middle part boys), 3 6.43% of the explored knees, respectively). Interestingly, the joint with the greatest clinical-US discordance was also the knee (5.55% discordance), followed by the wrist and ankle. The joint with the lowest discordance (0.58%) was the 2nd MCP. The GS score and PD score were significantly higher in patients with active disease compared with patients with inactive disease (p = 0.000 and p = 0.017, respectively). The GS score was significantly changed (p < 0.05) with the following variables:physician's VAS, parent's VAS, CHAQ, ESR, number of limited, swelling, tender, and active joints, JADAS10/27/71, cJADAS, JADAS-PCR, and active disease status. The PD score was significantly changed (p < 0.05) with the same variables, except for CHAQ and ESR. The GS score was moderately correlated with physician's VAS, number of active, swelling, limited and tender joints, JADAS10/27/71, cJADAS and JADAS-PCR, but the PD score showed no correlation with any of the clinical variables studied.
Conclusion: Subclinical synovitis detected by US is not uncommon in children with JIA. However, US scores changed significantly, mirroring most of the clinical variables. US scores could help physicians to determine the inflammatory activity of JIA more accurately. However, GS and PD US of the joints previously involved seem to be more useful than the comprehensive US score. Following the GRADE method for the elaboration of recommendations, they formulated a series of research questions according to the PICO process. Systemic JIA, as a specific entity whose course and prognosis differ from the other categories of JIA, was ruled out. An exhaustive literature review was performed by one junior investigator (MP) using MEDLINE and EMBASE. The keywords "juvenile idiopathic athritis", "juvenile chronic arthritis", "juvenile rheumatoid arthritis", "juvenile psoriatic arthritis", "enthesitis-related arthritis", "juvenile spondyloarthritis/spondylarthropathy", OR "radiography", "X Ray" OR "radiographic assessment" were used, and completed by a manual search. We considered articles in English describing structural damage (ca, joint space narrowing, erosions, growth abnormalities). Then, several assessments were proposed, following evidence-based data when available, and expert opinion. The draft was submitted for evaluation to a group of 14 independant french-speaking reviewers. Final guidelines then underwent a second round of reviewing by the two groups of experts, with evaluation by a numeric scale according to a Delphi process. Results: Of over 900 publications identified initially, 117 underwent full-text review, and 72 were included. One poster was also considered along with one online national recommendation. For sructural damage, most studies considered JIA as only one entity or are based on polyarticular forms of JIA. The task force produced four general statements, and twenty-seven recommendations about CR at diagnosis and follow-up in the different subsets of JIA . The Delphi process was under progress at submission of this abstract. We recommend systematic CR of hands, wrists and feet at diagnosis and follow-up when the structural threat is high. In the oligoarticular form, CR should be based on clinical justification. CR plays a minor part in axial imaging.

Disclosure of Interest
Conclusion: Few publication have evaluated structural damage in JIA. Polyarticular and extensive oligoarthritis were the most studied. CR are frequently neglected in JIA, however, they are accessible and the less expensive imaging procedure. Hoowever they are of prime nterest in polyarticular subtype. Ultra sound and magnetic resonnance imagery will probably take an increasing part in diagnostic and therapeutic decisions but studies are also needed.

Disclosure of Interest
None Declared Results: Labeling of monocytes or neutrophils with DIR or DID did not affect viability or cellular functions like phagocytosis, ROS production, adhesion or transwell migration in vitro. Furthermore, FRI allowed the quantitative visualization of directed migration of phagocytes towards an inflammatory stimulus, i.e. endotoxin in the cutaneous granuloma model, in vivo with high sensitivity and specificity. In addition, in CIA the amount of immigrated monocytes showed a close correlation to disease score and severity.
Using genome editing techniques we knocked out the adhesion receptors CD18 and VLA-4 (knockout of the α4 subunit of VLA-4). Differential cell labeling and parallel injection allowed direct quantitative comparison of two distinct phagocyte populations within the same animal. This method revealed significant differences in recruitment of wildtype and CD18 and VLA-4 knockout phagocytes in vivo.
Conclusion: Specific and distinguishable labeling of diverse phagocyte populations (e.g. wildtype versus specific knockouts) allows in vivo tracking and subsequent quantification of migrated cells within the same animal. Targeted deletion of specific genes and correlation of the amount of immigrated cells to disease severity offers new opportunities to investigate and monitor inflammatory mechanisms of arthritis at a cellular and molecular level in vivo.

Disclosure of Interest
None Declared

P42
Impact of S100A12 proteins quantification and MSUS in treatment management of JIA patients with complete remission on treatment; a pilot study in 13 patients We reviewed the clinical information regarding reasons for MSK-US request, that were divided into 1) confirmation of joint disease activity in children with a known inflammatory rheumatic disease; 2) local diagnosis at the joint level in patients with either mechanical disorders or for confirmation of arthritis in children without a defined diagnosis; 3) evaluation of response to a specific treatment. We also reviewed the diagnostic and therapeutic changes that were taken by the pediatric rheumatologist following the result of the MSK-US.
Results: A total of 67 patients were included and 82 MSK-USs were performed, completing a total of 185 anatomic regions assessed (median: 2). Fifty-five patients (82%) were female. Ages ranged between 12 months and 17 years old (mean age: 10.5 years; median: 10 years    Results: VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (▫▫ < 0.05). The same sequence was observed for ANG -1. We found large variation in serum ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 54 (90%) examined JIA children.
Conclusion: In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA. Introduction: Since the dawn of the medicine, heat (lat. calor) is one of the four main signs of inflammation. Although it is recognized more than 2,000 years ago, there is still no reliable, simple and objective method to measure the warmth of inflamed joint, which is therefore most often assessed only by clinical examination, with very low validity and reliability.

Disclosure of Interest
Objectives: To investigate the use of smartphone attached mobile thermography for the assessment of joint inflammation.
Methods: Twenty participants with various forms of arthritis and/ or arthralgia participated in this pilot cross-sectional observational study. Average age of the participants was 10 years (2,5 -17,5).
In all of the participants Power Doppler vascularization signal of both knee joints was graded from 0-3 by EULAR certificated instructor in MSUS. FLIR ONE smartphone connected device was used to obtain infrared thermal image of every patient's knee joint prior to the MSUS examination, without clothes and with same environment conditions (room temperature was set to 20°C ). Acquired images were analyzed using FLIR Tools software for thermal image analysis with automatically set range of temperatures. On every image, both knee joints were selected using manual ellipse measurement tool and the data on average, minimum and maximum temperature inside the circle was collected. Subsequent statistical analysis of selected data was performed with Graphpad Prism software. Results: In sixteen knee joints of nine patients a PD signal was above 0,5 (0,5-2,5), which was defined as an active inflammation, while in twenty-four knee joints of thirteen patients PD signal was 0, which was defined as no inflammation. Average value of average temperature in knee joints with inflammation was 33,72°C (31,3°C -35,4°C) and in patients without inflammation 29,81°C (23,9°C -31,9°C), average value of maximal temperature was 34,98°C (32,7°C -36,9°C) and 31,08°C (25°C -33,3°C), while average value of difference between maximal and minimal temperature was 4,73°C (2,6°C -7,7°C) and 2,96°C (1,2°C -5,7°C) respectively. Statistical analysis revealed significant difference in all of the measurements between knee joints with and without active inflammation (p < 0,05). Conclusion: In our proof of concept study we investigated the usefulness of thermography with FLIR ONE, a cheap, portable and easy to use compact device, in joint inflammation assessment. For objective evaluation, MSUS with Power Doppler scoring of synovial vascularization was used. This method is almost a gold standard in joint inflammation assessment and it effectively measures increased blood flow inside the joint, which is one of the main causes of higher temperature. Preliminary results of our study suggested FLIR ONE thermography can be used as a bedside screening tool for joint inflammation, with a potential in assessing and quantifying degree of inflammation. This is in consistence with the results of a recent study which indicated the described method has a sufficiently high validity and reliability to be recommended for assessment of subclinical inflammation in patients with pressure ulcer and diabetic foot [1]. After confirmation in a larger cohort, our results could facilitate this innovative technique as a tool for joint inflammation assessment in everyday clinical practice. T-test was used for potential differences in DEMRIQ scores between the visits (p ≤ 0.05 = statistically significant, p ≤ 0.25 = clinically meaningful). Pearson's correlation coefficient was used to show any decrease or increase in DEMRIQ over time (r 3 0.80 = very strong, r 3 0.60 = strong, r 3 0.40 = moderate, r 3 0.20 = weak). Results: At 3 and 6 months all patients showed statistically significant and/or clinically meaningful changes in ALL and SING DEMRIQ scores (Table 21). In 6 patients clinical improvement was found at 3 and 6 months. In 5 of these patients a persistently high or worsening DEMRIQ-Inflammation was correlated with a clinical flare within 2-6 months after the last DCE-MRI. In one patient, clinical worsening was seen despite DEMRIQ-Inflammation improvement, but that was followed by the clinical improvement over time.
Overall, SING DEMRIQ scores showed a higher percentage of inflammation in the MCP joints compared to the clinical scores. Introduction: According to a clinical registry frequency of cardiovascular system diseases ranged from 51% to 81% among 327 children with systemic diseases of connective tissue (SDCT). Injury of the heart is potentially life-threatening. Their initial signs cannot be detected by traditional diagnostic methods. Objectives: improving early diagnosis of cardiac lesions in children with rheumatic diseases Methods: There are 25 healthy and 31 sick children of 10-17 years with SDCT (SLE, JDM, MCTD), in which are absent active inflammation, endocrine pathology, and arterial hypertnsion, clinical and laboratory signs of carditis or cardiomyopathy were examined. Patients underwent magnetocardiographic examination, i.e. registration of heart magnetic field by SQUID-magnetometer at 36 points above the chest with 4 sm step, during 90 sec at single point. The inverse solution, i.e. reconstruction of current density vectors maps based on MCG-curves was done. The leading quantitative indicator of current density vectors maps is abnormal index (AI) the ratio of the total length of vectors directed in the "proper" direction to that have a different direction (%). To evaluate the processes of ventricular de-and repolarization this index was calculated during QRS complex and ST-T interval (AIQRS total and AIST-T total . Besides, some other parameters were calculated, namely the ratio of the actual duration of each QRS phase to its "proper" duration (Duration Ratio -DR) for each of four depolarization phases (DR1-4) separately and for the whole process of depolarization (DR total ), duration of complex QRS -DurQRS, the correlation coefficient C cor between all maps during each interval, duration of ST-T curve area from its beginning to the inflection point in percentage to the overall length of the ST-T interval (A Dur ). Results: Statistically significant differences of average values of MCG indicators characterizing QRS complex were not found in the examined groups. However, individual analysis of normalized indicator of anomalous ventricular depolarization showed that it significantly deviates from the normal range in patients with active inflammatory process, mostly in front-apical area of myocardium (AI QRS2 70,15 ± 2,94% in patients, 56,4 ± 4,12% in healthy). This was accompanied by a reduction in the total duration of the QRS complex and the portion of normal complexes in the corresponding time intervals DRtotal 1,02 ± 0,04 s and in healthy 1,2 ± 0,09 s (by Dr1) respectively. DurQRS in patients with rheumatic diseases equal 0,089 ± 0,003 s (0,1 ± 0,04 s in healthy), Auto-CorrQRS 80,43 ± 0,73% (84,14 ± 1,5% in healthy). Correlation coefficient decreased in patients with rheumatic diseases insignificantly (CorrQRS 34,85 ± 1,01% in patients, 37,29 ± 7,01% in healthy). The analysis of the ST interval indicators showed reliable abnormalities in early repolarization of the ventricles (increasing Adur 19,85 ± 1,61% (11 ± 6,1% in healthy), reducing CorrST 63,85 ± 7,61% (82 ± 4,1% in healthy), downward trend in AI ST-Ttotal in patients 53,85 ± 3,35% (91 ± 0,4 in healthy children)). Comparing the results with standard ECG data it was revealed that the changes of repolarization processes are visualized up to 35% more frequently by MCG. Instant maps of current density vectors that obtained by MCG are more convenient for on-line visual assessment. Conclusion: Non-invasiveness and sensitivity of MCG allow recommend it as a screening method for early detection of the heart injuries. The ability to visualize of electrophysiological active substrate makes the MCG as effective way to detect local changes into myocardium. Absolute safety of method makes possible its use for dynamical investigation.

Disclosure of Interest
None Declared Introduction: Ultrasonography could be an helpful screening method for the detection of TMJ involvement in children with JIA. It can be used and well tolerated even in very young children (2 years) without sedation or radiation risk. Objectives: The aim of this work was to evaluate the usefulness of high-resolution ultrasound (US) in the early detection of temporomandibular joint (TMJ) alterations and to show normal and pathological imaging appearance of the TMJ in patients with Juvenile Idiopathic Arthritis (JIA). Although TMJ arthritis in JIA is frequently asymptomatic, the TMJ is particularly susceptible to damage. The TMJ is commonly involved in JIA and can lead to malocclusion, condylar alterations, facial deformity and restricted mouth opening. Methods: High-resolution US examinations were performed in 130 patients with JIA. 34 patients (34%) had normal US appearance on both side. The sonograms were done using General Electric LOGIQ E9 equipment using real-time linear-array transducers with variable frequencies (9-18 MHz) by an experienced radiologist. Longitudinal and transverse view images were obtained. Dynamic video clips demonstrated condylar translation from "closed mouth" position to "open mouth" position. The movements can be recorded and compared between the left and the right side. Color Doppler US images furnish diagnostic information regarding hyperemia and synovial vascularity, thus allowed to study vascular signals in the soft tissues around the TMJ. Each joint was analyzed with regard to condylar irregularity, capsular thickness (effusion/synovial thickness), condylar disk dislocation, vascular increasing on Color-Doppler examination and symmetry in condylar translation between open-and closedmouth position. Results: In our clinical cases capsular thickness, enlargement of the intra-articular space, joint effusion, osteophytes, irregular condyle shape, disc displacement, erosions, increased color Doppler signals were detected. Limitations were especially related to the scarce accessibility of the medial part of the TMJ structures, and the need for trained operators. An important advantage especially in the case of Introduction: Primary immunodeficiency (PID) and autoimmune phenomena may occur concomitantly in the same individual. The most common forms of PID disease with articular involvement are those associated with humoral defects such as X-linked agammaglobulinaemia, common variable immune deficiency and selective IgA deficiency.
Objectives: The aim of our study was to systematically track a comprehensive array of PID in a cohort of 286 children with a presentation of chronic arthritis followed at the Immunology and Rheumatology outpatient clinic in Children's Hospital Zagreb.
Methods: Patient's charts were reviewed for the following immunological investigations performed as a part of the diagnostic algorithm for juvenile idiopathic arthritis: IgG, IgA, IgM, IgE, IgG subclasses, C3, C4, CH100, ANA, ANA, ENA-profile, antiphospholipid antibodies, rheumatoid factor (RF) and HLA-typing. Additional screening and specialized laboratory tests were performed in patients who presented with the recently revised warning signals for primary immunodeficiency.
Results: Six patients were identified with immunity defects compatible with classical PID. Two patients had selective IgA deficiency (sIgAD), while one patient with the following PIDs in each group was found: ataxia teleangiectasia (AT), autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and familial Mediterranean fever (FMF). Majority of patients presented as RF-negative polyarthritis (see table). Conclusion: Our findings further emphasize that PID and JIA may coexist and patients with autoimmune diseases should be carefully monitored for the presence of PID and vice versa. To the best of our knowledge, we also describe a first case of a child with typical ataxia telangiectasia who developed JIA. Aicardi-Goutières Syndrome (AGS) is a rare genetic disorder with broad phenotype spectrum. Access to molecular investigation confirmed AGS for different clinical manifestations in 2 sisters of nonconsanguinous parents Objectives: The value of a confirmed molecular diagnosis for a rare disease which would otherwise have remained undiagnosed is illustrated in our patients Methods: We describe 2 sisters with unusual clinical features resembling childhood SLE and targeted molecular investigation. The index patient presented with hemiplegia and complex partial seizures in infancy, diagnosed as moyamoya syndrome on imaging. At 4 years of age she was referred to the paediatric rheumatology service with interface dermatitis, vasculitic lesions on her ears and fingertips and deteriorating gait. She tested negative for antinuclear antibody (ANA) and anti double-stranded DNA (dsDNA) but had positive antiphospholipid serology. She was anticoagulated with Warfarin, responded well to Chloroquine and Azathioprine for control of extensive vasculitic rash and Sodium Valproate for her seizure control. She was then diagnosed with multidrug resistant Tuberculosis and superficial staphylococcal abscesses of the spine which resolved on antituberculous and antibacterial treatment. The unusual combination of her clinical findings prompted molecular investigation. The older sister was found to have a longstanding history of vasculitic skin lesions and threatened gangrene of fingertips on presentation. She was severely stunted with delayed puberty, a feature not typically described with AGS. Skin biopsy showed perivascular-interface dermatitis. Antiphospholipid antibody screen and ANA were negative. She responded well to Nifedipine, Chloroquine and low dose Aspirin. She was subsequently diagnosed with glaucoma, which is associated with AGS and developed progressive contractures of interphalangeal joints with bone resorption on X-Ray.  Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University. Since this mutation had not been described previously, 322 normal South African mixed racial population controls were genotyped by HRM and 63 of these were sequenced. No other chromosomes contained this mutation, the frequency of this 'likely pathogenic' mutation is <0.31% and therefore considered causative and consistent with a diagnosis of AGS.

Disclosure of Interest
Conclusion: Great intra-familial phenotypic variability of AGS, previously described in other publications, was documented in these two siblings with confirmed mutations of the SAMDH1 gene. The molecular investigation yielded a unifying diagnosis for an unusual combination of physical findings and different phenotype expression of AGS.
Other benefits of a confirmed diagnosis were the genetic counseling which could be offered to the family and targeted investigation and treatment for complications such as glaucoma in the sister of the index patient. Although the parents are not related it was interesting that they were both heterozygous for the SAMDH1 mutation.
Whether this AGS mutation results in increased susceptibility to tuberculosis, as a result of impaired interferon production, may need to be investigated further as a potential novel finding.

Disclosure of Interest
None Declared Results: Among 901 children with joint syndrome in 21,97% its character at a pre-hospital stage was regarded incorrectly. Hyperdiagnostics was frequent in JIA (11,09%). In 13 cases (1,4%) the diagnosis of PIDS was established after an additional clinical examination. Most often (7 cases) joint lesions were observed at selective immunoglobulin A deficiency. Previous infectious was not revealed in these cases. Manifestation of joint syndrome 2-11 y., its features corresponded to JIA: 2 entezit-arthritis with inflammatory bowel diseases, 3 oligoarthritis, 1 sacroileitis, 1 sJIA. Immunological examinations: serum IgA ≤ 0,05 g/l, IgM, G, subclasses, B-cells within age values, was found depression of T-cytotoxic cells, in 4 cases -ANA, RF and HLA B27 weren't taped. Were observed 3 cases of Bruton disease (3-6 y). In anamnesis occurred infectious syndrome (repeated pneumonia in 3 cases, pyelonephritis, chronic pyoderma), 2 patients had died sibs. Duration of joints lesions was 3 m -2 y, it was characterized as exudative oligoarthritis of knee joints. X-ray examination didn't reveal osteal destructions. In 2 cases were reported movement restrictions and extremity elongations. Laboratory data: leukocytosis 12,5-17,2 × 10 9/ l, ESR 15-40 mm/h, IgG 0,2-2,5 g/l, Ig A 0-0,1 g/l, IgM 0,1-0,2 g/l, AB weren't revealed, B-cels 0,02-0,85% (12-38 in mcl), CD19 + CD5 + 0-1,1%. In 2 cases the diagnosis was confirmed with genetic research. Dee-Georgie syndrome was established in child (4 y) with physical and psychomotorical development retardation. In his anamnesis were described cramps, repeated operations on cleft palate and interventricular septum defect.  Objectives: The multinational study of the EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA study) is aimed to obtain information on the variability of JIA phenotypes in different geographic areas, the therapeutic approaches of pediatric rheumatologists practicing in diverse countries, and the disease status and outcome of children with JIA currently followed worldwide.
Methods: Participation in the study was proposed to all pediatric rheumatology centers that are part of the Pediatric Rheumatology International Trials Organization (PRINTO), and to several centers in the US and Canada. Each center was asked to enroll 100 consecutive JIA patients or all consecutive patients seen within 6 months. Each patient received a retrospective and cross-sectional assessment. Parent-and child-reported outcomes were recorded through the administration of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Participating countries were grouped into 6 geographic areas.
Results: Currently, 8,325 patients from 44 countries have been entered in the web database. Comparison of main epidemiology, treatment, and outcome features across the different geographic areas is presented in the table.
Conclusion: These results provide further evidence of the wide difference of JIA characteristics across geographic areas in terms of age at disease onset, subtype prevalence, and frequency of anterior uveitis. Overall, patients living in non-Western countries had higher levels of disease activity and cumulative damage than patients followed in North America and Western Europe. This disparity in disease outcomes may be partially due to differences in the availability or affordability of biologics, as usage of these medications was more common in Western pediatric rheumatology centers.  Introduction: Despite the efficacy of current biologic agents for the treatment of juvenile idiopathic arthritis (JIA) in many children, for others, treatment is ineffective and they continue to suffer active disease and disability. There are an increasing number of biological agents available but we have no validated biomarkers of treatment response with which to predict response and guide therapy choices. In order to develop a rational, evidenced-based approach to support choices of therapy for these children (stratified medicine), multi-center, international collaboration is vital.

Disclosure of Interest
Objectives: An international working meeting focused on stratified medicine in JIA, was held. The objectives of which were to reach consensus on how to overcome barriers and hurdles to robust, collaborative, clinical/translational research, and to foster effective and successful collaboration.
Methods: An international group of experts (paediatric rheumatologists, epidemiologists, geneticists, immunologists and translational scientists), from 8 countries and 17 institutions, representing major national and international networks, recently came together for two days to drive progress in stratified medicine in JIA. Prior to the meeting all investigators contributed to a priority-setting exercise to define the most important and feasible research questions, hurdles and possible solutions. These responses were grouped into themes, for both questions and hurdles, and then participants were asked to rank each theme in order of their perceived importance. Currently available tools, such as appropriate biobank protocols from previously established networks within pediatric rheumatology were collated.

Results:
The key elements of a new framework to guide processes for working together were agreed, a new International collaborative study was proposed, and a declaration on principles of Research Collaboration for Stratified Medicine in Childhood Rheumatic Disorderstermed the London Declaration, was agreed and signed by all.  Introduction: Inflammation has been associated with a marked increase in the production of nerve growth factor (NGF) in tissues of patients with a variety of chronic inflammatory diseases, including rheumatoid arthritis and juvenile idiopathic arthritis (JIA). However, the effects of NGF, its immature form proNGF, and their receptors, TrkA and p75NTR, in regulating cells and mediators during inflammatory responses and their contribution to the pathogenesis of arthritis are not yet defined. Objectives: To evaluate the role of proNGF, mature NGF and their receptors in the modulation of inflammatory response in chronic arthritis patients. Methods: Seventy-five JIA patients, according to the International League of Associations for Rheumatology classification criteria, were divided in persistent oligoarticular, extended oligoarticular or polyarticular subtypes. The expression of the NGF receptors, p75NTR and TrkA, in peripheral blood (PBMC) and synovial fluid (SFMC) mononuclear cells from JIA patients and healthy children was analyzed using real time-PCR and Western Blot. In ex vivo experiments JIA SFMC were treated with mature NGF or proNGF and the effects on intracellular signaling pathways and cytokine production were assessed by Western Blot, real time-PCR and ELISA Results: p75NTR is the main NGF receptor expressed in JIA PBMC and SFMC while TrkA is the prevalent NGF receptor in healthy donor mononuclear cells. The increased expression of p75NTR and the concomitant decrease in TrkA, at both the mRNA and protein levels, resulted in a highly abnormal ratio between p75NTR and TrkA in JIA cells. The highest expression of, not only p75NTR, but also sortilin, the p75NTR co-receptor, was found in JIA SFMC. When patients were divided according to JIA subtypes the highest p75NTR expression levels were found in SFMC of patients with polyarticular JIA. The lowest p75NTR expression levels characterized SFMC from persistent oligoarticular patients while patients with extended oligoarticular JIA showed intermediate p75NTR levels. A significant correlation was found in JIA patients between the p75NTR mRNA expression levels in SFMC and the number of active joints at sampling and the levels of C-reactive protein. In the synovial fluid of JIA patients the concentration of proNGF, the specific ligand of p75NTR, far exceeded that of mNGF. In ex vivo experiments, LPS-stimulated SFMC of JIA patients were treated with proNGF. We found that proNGF specifically enhanced phosphorylation of p38, JNK and IkB, all involved in inflammatory cytokine production in immune cells. The addition of NGF did not induce the activation of these pathways and proNGF, but not mNGF, induced in SFMC a higher production of pro-inflammatory cytokine. This production was blocked using p75NTR inhibitors. Conclusion: Our results show that high levels of p75NTR mRNA expression in the SFMC of JIA patients are associated with the most severe subtype and with disease activity. We also found that proNGF is the predominant form of NGF in the synovial fluid of JIA patients. Blocking of p75NTR in ex vivo experiments with JIA SFMC showed that proNGF acts through p75NTR. Altogether these results suggest that an active proNGF-p75NTR axis is involved in sustaining inflammatory production and may provide the rationale for specifically targeting p75NTR in chronic arthritides. Introduction: Vaccination can be beneficial in children with pediatric rheumatic diseases (PRD), who are prone to infections. However, due to the disease itself as well as due to the use of immunosuppressive drugs, the vaccine-induced immune response of these patients can be impaired. Additionally, vaccines should be safe: they should not induce a disease flare, and, when the vaccine contains a liveattenuated pathogen, it should not induce an infection. One of the possibly beneficial vaccines for PRD patients is the varicella zoster virus (VZV) vaccination which can be used to prevent chickenpox and shingles. An adequate cellular immune response is especially important for effective protection against VZV.  (Table 26). There were no disease flares or overt varicella infections reported after vaccination. Antibody concentrations of 35 patients and all healthy controls were determined. Responders were defined as having VZV-Ab levels of >0.26 IU/ml after vaccination and/or as a 4-fold or higher increase in VZV-Ab after vaccination. Responder status did not differ between patients and healthy controls (odds ratio (OR) 1,9; 95% Confidence Interval (CI) [-0.08; 1.35  Participants were asked to order these areas in terms of which should receive the most funding. All focus groups were audiotaped and transcribed for thematic analysis.

Disclosure of Interest None Declared
Results: 12 focus groups (11-15 years (n = 5) and 16-24 years (n = 7)) have been held with 58 participants. Young people's research priorities were influenced by whether they felt that investment in a particular area was likely to: 1. Achieve benefits for all patients, 2. Achieve long term or short term goals (finding a cure versus improving quality of life). Other influences on participants' priorities were their beliefs about whether research areas are already well funded and whether increasing funding could lead to faster results. Basic Science was considered to be a key priority. Participants were especially interested in understanding the genetic basis of their condition and how this could affect their prognosis and treatment side effects. However, there was an appreciation that progress in this area was unlikely to happen overnight, and that for this reason a steady stream of funding was likely to be important. Participants also felt that psychosocial research currently did not receive considerable investment. However, there were varying views on whether it should. Those who felt that the psychosocial aspects of their condition had been neglected tended to feel that Psychosocial research should be a priority. However, a number expressed uncertainty as to who could provide this support believing their doctors were already overstretched. Finally, some participants expressed a wish not to focus too much on the psychosocial aspects of their condition as part of their overall coping strategies. Health Services Research was considered by many to be a low priority, as for the majority of participants, consultant care was their preferred option. GPs were considered not to be a viable support option. However, participants were interested in transitional care arrangements between paediatric and adult care. For many, the development of new treatments was a low priority, because they were currently happy with their treatment regime, or because they felt uncomfortable with the risk of trying an experimental treatment.
Finally, for all groups Public Health was ranked low. There was a need identified to provide education to a range of audiences about their conditions, e.g. GPs, schools, workplaces, but scepticism existed as to whether or not such educational materials would be utilised.
Conclusion: Understanding the research priorities of young people with rheumatic conditions is important to ensure that research strategies are developed that are in tune with their needs and wants. The findings from this work will feed into the research strategy of the BANNAR. Results: We analyzed data on 34 patients, 9 with leukemic arthritis and 25 with JIA. The mean age at diagnosis was significantly lower in the group of leukemic arthritis 7.56 vs 10.76 years (p = 0.045), female gender prevailed in both groups (66% and 76%, respectively, p = 0.586), time of onset of symptoms it was lower in the group of leukemic arthritis. Pain intensity, night sweats, weight loss, fever, lymphadenopathy, hepatosplenomegaly and night pain was higher in the group of leukemic arthritis. Remission of pain with analgesics was significantly lower in patients with leukemic arthritis As for laboratory parameters, rheumatoid factor positivity was higher in the group of AIJ without showing statistical significance. The hemoglobin level, the leukocyte and neutrophil count was lower in patients with leukemic arthritis, the lymphocyte count was similar in both groups. The platelet count was higher in JIA patients, the VSG was similar in both, the difference between the value of the PCR was not the value of the DHL was higher in the group of leukemic arthritis without showing statistical significance. Conclusion: Leukemia is an important diferential diagnosis in children presenting with arthritis. In this study it was found that the presence of pain disproportionate to the degree of arthritis, fever, night pain, which does not yield to the use of analgesics, weight loss and lymphadenopathy, help to discriminate clinically between leukemic arthritis and juvenile idiopathic arthritis. Useful laboratory parameters are leukopenia, neutropenia, and anemia, the mean platelet count was in low normal value, but lower than in juvenile idiopathic arthritis. The laboratory parameter with most higher relative risk was neutropenia.

Disclosure of Interest
None Declared Objectives: To describe the case of a young girl with juvenile idiopathic arthritis and pulmonary LCH and to discuss the possible common pathogenetic mechanism for both diseases.

Methods:
A 10 year old girl was symptomatic for past 1 year. Her illness started with left ankle swelling with pain, redness, restriction of movement and early morning stiffness. Over the next 5 months she had progressive involvement of right ankle joint, small joints of bilateral foot and bilateral wrist joints. On examination, she had swelling in bilateral ankle and wrist joints. There was redness and increased temperature over the surface associated with synovial thickening and restriction of passive range of movement. Her investigations revealed (Table 29) thrombocytosis; elevated ESR and C-reactive protein; positive antinuclear antibody (ANA) and positive rheumatoid factor (RF). Chest X-ray revealed cystic changes in bilateral lung fields which were confirmed on CT chest which showed multiple well defined cysts with variable sizes distributed throughout the parenchyma in bilateral lung fields. An open lung biopsy was performed to confirm the diagnosis. Histopathology examination of the resected lung tissue revealed lymphomononuclear inflammatory infiltrate in the interstitium with collection of large atypical cells around the peribronchiolar region which were showing oval to round nuclei and moderate to abundant vacuolated cytoplasm, these cells were positive for CD1a. Skeletal x-ray revealed no lytic lesions and bone marrow examination was also normal.
There was no evidence of any other organ involvement with LCH.

Results:
For arthritis, she was initiated on oral naproxen, a short course of oral prednisolone and subcutaneous methotrexate; which led to marked improvement in her joint symptoms. For management of LCH, as she was asymptomatic with predominantly cystic lung changes and no nodular changes on CT chest; hence a possibility of chronic fibrotic disease was considered and a decision not to give any specific therapy for LCH was taken    (1-3)).
The delay to diagnosis did not vary depending on the parents' socioeconomic groups or their education level. Semi-structured individual interviews have been done with 9 families (13 parents) and pointed out that this waiting time was very stressful for each family with a fear of irreversible process with ankylosis. 8 families used complementary and alternative medicines (7 homeopathy, 2 acupuncture and 2 osteopathy). 8 families needed help in the day-today life, 2 mothers stopped their jobs and one got a partial time work.
Conclusion: In spite of the fact that patients have quickly recourse to health care, delay to diagnosis for JIA remains very long: strong efforts have to be made to organize targeted training programs for all practitioners involved in the care pathway of these children and to communicate on the on-going national program on rare diseases in France.
The identification of the various components of the delay to diagnosis may enable practitioners to elaborate care course management guidelines and public governmental bodies to set up adapted program for rare disease. By the mean of the JIR cohort (juvenile inflammatory rheumatism cohort), we intend to carry out a broader study about delay to diagnosis and access to healthcare and treatment for JIA in France and in Switzerland.

Disclosure of Interest
None Declared The knees were injected with Triamcinolone Hexacetonide 20-40mgs according to size. A cylindrical fibreglass cast with a reinforced back slab was then applied under anaesthetic, with the knee held in the greatest achievable level of extension. The splints were opened, secured, and left in place for 24 hours. They were worn nightly thereafter. Parents were taught a daily physio regime for strengthening and stretching, and physio treatment was provided on a weekly basis for up to 6 months. Knee extension was measured at various time points -actively pre-theatre, passively in splint and actively post treatment.
Results: 9 patients and 10 joints were included in the review. Ages ranged from 1-6 years, with a mean age of 2.5 years. Of the 10 patients, 7 had a diagnosis of Oligo JIA and 3 of Poly-Articular JIA, with a mean disease duration of 2.5 years (ranging from 6 months to 6 years). All 10 of the knees treated showed significant improvement in active extension post injection / splintage. The mean improvement was 83%, and this improvement was maintained unless the knee flared.  Introduction: Juvenile idiopathic arthritis (JIA) is the most common connective tissue disease in the pediatric population with a prevalence of approximately 1 in 1,000 children younger than 16 in North America, and girls being more frequently affected than boys. JIA predominantly involves the large joints, most frequently the knees, wrists, and ankles. Magnetic resonance imaging (MRI) is a relatively new imaging technique to confirm the internal derangement of the joints on patients affected with JIA. Moreover, MRI has the advantage of displaying both soft tissue and bone and we found to be very accurate in the assessment of disease activity and to depict the more frequent pitfalls encountered on these patients, which can lead to a misdiagnosis.
Objectives: 1. To describe the more frequent diagnostic pitfalls on patients with JIA on imaging, especially on MRI. 2. To illustrate the radiographic appearance of JIA patients from head to toe, highlighting the differences between active and chronic disease. 3. To review the MR protocol and imaging techniques to study patients with JIA. Results: 88 patients were enrolled, 70,5% female with an average age of 11 years old. Their epidemiological, clinical and regarding treatment received characteristics are recorded in Table 33.
The IR prevalence was 24.4%. Regarding classical CDRF, 6 (7.5%) were obese, 12 (15%) overweight, 16 (18.3%) arterial hypertension (AH), 14 (16.8%) dyslipidemia, mainly HDL About the diet and physical activity surveys, 41.3% followed an optimal Mediterranean diet (KIDMED score ≥ 8), being the most of the cases improvable (score 4-7). Our patients performed moderate physical activity during free time (PAQ-C/PAQ-A score > 3), however, statistical differences were not significant between JIA subtypes. A linear multivariate regression analysis was performed. IR was associated (R 2 = 0,512) with hip circumference (cm) (β = 0.04; p 0.008), HbA1C% (β = 2.845; p 0.008) and leptin (ng/ml) (β = 0.036; p 0.007). Clinical activity duration was the only predictor factor, not having significant correlation with the subtype, received treatment or disease activity during the study. Conclusion: Our data suggest that the patients with JIA have an IR prevalence similar to the Spanish healthy children (adjusted by age, gender and pubertal stage). The only factor related to the disease which directly influenced the IR grade was the clinical activity overall duration, hence the importance of an early control of the disease to avoid this CDRF in future. Introduction: There is some evidence that clinical response in patients with chronic arthritis treated with antiTNF agents can be influenced by their immunogenicity. This particular has not been fully studied in patients with juvenile idiopathic arthritis (JIA).

Disclosure of Interest
Objectives: To evaluate the immunogenic response against antiTNF agents and its possible impact on treatment efficacy in patients with JIA.
Methods: Seventy-three patients (40 children and 33 adults) fulfilling ILAR criteria of JIA were included. All of them were on treatment with Etanercept (ETN), Adalimumab (ADA) or Infliximab (IFX) +/-Methotrexate (MTX). Demographical and disease characteristics were recorded at baseline. Clinical outcome was prospectively assessed every 6 months (JADAS10/27/71, patient or parents VAS, physician's VAS, CHAQ/HAQ, ESR, CRP, number of swollen, painful and limited joints). Patients were tested for the presence of both, serum drug levels and antidrug antibodies levels at baseline and every 6 months.
Results: Thirty-one paediatric patients (77.5%) needed combined treatment (antiTNF + MTX) vs 18 patients (54.4%) in the adult group. Furthermore, paediatric patients followed an intensified antiTNF therapy protocol more frequently than adult patients (54% vs 39.33%; p = 0.044). A total of 189 determinations for the assessment of immunogenic response against antiTNF therapy were analysed. No differences were found between children and adults in the prevalence of antidrug antibodies or in the circulating antiTNF levels. No antidrug antibodies were found neither in the 107 determinations of patients following ETN treatment nor in the 6 determinations of patients on IFX. Just 5 (17%) of the 29 patients on ADA treatment produced anti-ADA antibodies at least once during the follow-up period. Regarding the 77 ADA determinations, patients who were on monotherapy with ADA produced antidrug antibodies with a significant higher frequency than patients on combined treatment with MTX (37.5% vs 8.7% of them respectively; p = 0.016). Patients on monotherapy with ADA also exhibit a significant reduced serum ADA levels than patients on ADA + MTX (4.73 μg/mL vs 12.73 μg/mL respectively; p = 0.019). However, no significant differences were observed in the ETN concentration between patients on monotherapy or on ETN + MTX treatment (1.50 μg/mL vs 1.77 μg/mL respectively).
No correlation was observed between drug levels or the presence of antidrug antibodies and any of the clinical or biological parameters.
Conclusion: JIA paediatric patients needed intensified and combined with MTX antiTNF therapy more frequently than adults. In spite of this, no differences were found regarding antiTNF levels between children and adults. This fact suggest that children need more therapy to maintain antiTNF concentrations to control the disease activity. No antibodies antiETN were detected in our patients. ADA in monotherapy seems to be more immunogenic than in combined therapy in JIA. We found no correlation between antiTNF levels or the presence of anti-antiTNF antibodies and the clinical outcome of JIA patients.

Disclosure of Interest
None Declared  There was no other clinical involvement, no biological inflammation and no auto-antibodies. Search for urinary mucopolyaccharidosis was negative. In both patients, MRI of the wrist showed no joint effusion, no bone erosion, absent or mild synovial thickening with a slight enhancement after gadolinium infusion. One patient underwent a synovial biopsy which showed a dense fibrosis with a sparse inflammatory infiltrates, similar to the pathological pattern observed in the skin biopsy. With methotrexate and systemic steroids, joint contractures slowly improved in the first patient, remained stable in the second. Conclusion: These two cases suggest that fibrous synovitis should be considered in children with acquired diffuse, symmetric and painless contractures, without elevation of acute phase reactants even in absence of extra-articular manifestations. Articular MRI with gadolinium and careful cutaneous examination at onset and during the follow-up should provide clues for diagnosing this entity.

Disclosure of Interest
None Declared Because CV events are rare in the young, surrogate markers of atherosclerosis such as carotid intima-media thickness (IMT) are valuable to detect early subclinical atherosclerosis. Objectives: To assess subclinical atherosclerosis in patients with JIA and to compare it with disease duration, subtype of arthtritis and the principal outcome measures of disease activity Methods: Patients with JIA consecutively hospitalised in our center were included in the study. IMT of the common carotid artery was determined by ultrasonography. The serum levels of atherosclerosis-related biomarkers, such as homocistein, triglicerid, cholesterol and sistemic blood pressure were measured. The Juvenile Arthritis Disease Activity Score (JADAS) was used to measure JIA disease activity. Results: 134 patients were included. Sixty one percent were female. The mean age at diagnosis was 8.3 years. The distribution of patients by subtype was: Oligoarticular 36%; RF + Polyarticular 2%; RF -Polyarticular 25%; Systemic 7%; Enthesitis Related 9%; Psoriatic 7% and Undifferentiated 13%. Eighty nine percent of patients achieved a zero joint count at least once in the first year of follow-up, however, just 66% had a zero joint count at 1 year. The mean time to a zero joint count was 4.3 months in patients achieving this outcome in the first year of follow-up. The systemic subtype had the shortest time to zero joint count at 2.7 months, psoriatic the longest at 6.2 months. For the 11% of patients who did not achieve a zero joint count in the first year of follow-up, the mean time to this outcome was 17.4 months. Sixty three percent of patients were commenced on a conventional DMARD (cDMARD), most commonly methotrexate. The mean time to commencement of a cDMARD was 2.2 months. 15% were commenced on a biologic DMARD (bDMARD). The mean time to commencement of a bDMARD was 6.3 months. 55% were treated with oral corticosteroids. 19% were on oral corticosteroids at 1 year. 62% were treated with intra-articular steroids, most commonly the oligoarticular subtype, of whom 94% had at least one joint injection. 7% of children developed uveitis, with the highest incidence in the oligoarticular subtype, 17%. Of patients with inactive arthritis at 12 months, 41% were on and 25% were off treatment.
Conclusion: This study demonstrates that children with JIA in Australia have demographic features and short-term outcomes similar to those described in international cohorts. At twelve months, two thirds of the cohort had a zero joint count and over a third of these were on no medications. When compared to international cohorts there was some variation in management, with a higher proportion having intra-articular steroid therapy.

Disclosure of Interest
None Declared We estimate the prevalence of each type of JIA. The immunological characteristics (RF, ANA and Anti-CCPA) were assesed and compared by type of JIA (Kruskal Wallis or Chi-square). Spearman correlation coefficients between age and assessments were calculated. Results: The analysis included 50 patients, 29 (58%) female and 21 (42%) male, aged 10.56 ± 3.39 years old, 34% seropositive polyarthritis, 28% seronegative polyarthritis, 16% systemic arthritis, 14% oligoarthritis, and 8% enthesitis related to arthritis. Association between sex and type of JIA (p = 0.014) was detected. Only one patient had positive ANA. There was significant difference in Anti-CCPA levels by JIA type (p < 0.001); higher leveles in patients with seropositive polyarticular JIA. High correlation between RF and Anti-CCPA (r = 0.63, p < 0.001) was detected. It was identified that age correlated with RF (r = 0.40, p = 0.004), and with Anti-CCPA (r = 0.29, p = 0.041). Conclusion: Our data suggest that there is a positive correlation between RF and Anti-CCPA in patients with JIA. The elevation of Anti-CCPA and RF seem to be an early form of adult RA. Patients who have positive Anti-CCPA and RF have a higher degree of severity of the disease with a poor response to the conventional treatment and early biological therapy is required. The presence of Anti-CCPA and RF in a pediatric patient may be a criterion for making a decision on treatment. Multicenter studies that support these findings are required.

Disclosure of Interest
None Declared Objectives: In this context, we have decided to develop a framework of the necessary skills needed for children suffering from JIA (REAJI) in order to improve their quality of life (knowledge, know-how, know-how-to-be). Methods: The steering committee is composed of health professionals involved in paediatric rheumatology and patients' associations. Different stages are scheduled: 1. Literature review 2. Setup of four focus groups (FG) with different facilitation methods: 2 patient FGs (8-12 year olds and adolescents), 1 parent FG, 1 health professional (HP) 3. Analysis by the steering committee et production of a first skills list. 4. Submission of the list to a panel of patients and to the national JIA competence centres for further information. 5. Submission of the completed list to the same participants for ranking (primary and secondary objectives). 6. Validation of the final list by the committee. Results: The steering committee is made up of two rheumatologists, two paediatricians, and two patients associations, ANDAR (association of patients suffering from RA) and KOURIR (association of parents whose children suffer from JIA).
The press review highlights a number of works, mainly on adolescents and outside the French territory. The HP FG is composed of 1 rehabilitation doctor, 1 rheumatologist, 1 paediatrician, 1 psychologist, 1 occupational therapist, 1 nurse and 1 pain nurse. The parent FG is composed of 10 people (6 mothers, 1 aunt, 3 fathers). The 8-12 year olds FG had 3 children and the adolescents FG 4 teenagers. The committee gathers to establish the initial skills list and then proposes to complete it via an online questionnaire to a selection of HPs from the 38 French centres listed by the FRancophone SOciety of Rheumatology and Internal Paediatric Medicine (SOFRE-MIP) and an equal number of patients/ parents. This expanded list is sent back to participants using the same method in order to rank it and lastly to be validated in its final version by the committee.

Conclusion:
The collectively-developed REAJI framework is a consensus-based support tool that anyone will be able to call upon: not only individual families but in particular teams working on educational projects. This multidisciplinary participative, national effort is an example of health democracy, the results of which will be made available to all.

Disclosure of Interest
None Declared Introduction: Clinical experience is that inflammations and pain in hand/finger joints affects grip strength in children and adolescents diagnosed with JIA which also affects their activities in daily life. Occupational therapist's at Astrid Lindgren's Childrens's hosptital, has measured grip strength with Grippit TM electronic hand grip measure for the last 20 years. Grippit TM has now been computerised. Results from Grippit TM gives objective measurment in Newton presented in maximum, average and sustained grip strength after 10 seconds. The results are compared with norms for typical children age 4-16 years 1 . It is known that grip strength for children and adolescents with JIA is generally lower compared to healthy population 2 . With medical treatment, e.g. joint injections, and hand training programs grip strength and hand function will improve and can affect the performance of daily activities.
Objectives: To evaluate the computerised Grippit TM and analyse data from children and adolescents with JIA and compare relation between grip strength, pain and activitites in daily life.
Methods: A clinical pilot study on 12 participants, 10 girls and 2 boys age 10-18 years. Grip strength was measured at 2-3 occasions per individual. Grip strength data was correlated to age and/or length of hand. Pain in the hand during the grip assessment was meassured with Visual Analogue Scale (VAS 0-100). Performance in activities in daily life (ADL) was measured with Childhood Health Assessment Questionnaire (CHAQ) for items concerning hand function. Results: Eight participants had a lower grip strength compare to typical children. Pain in hand/fingers during the assessment was reported to mean 40 at VAS. Eleven participants reported a negative impact on ADL. Even for those (n = 4) with normal grip strength, the majority (n = 3) reported a negative performance on ADL and 2 of those reported pain in hand/fingers during the evaluation. Conclusion: It is important to measure grip strength for children and adolescents with JIA to get a better understanding how the disease affects activity functioning and in order to conduct adequate interventions. The computerised Grippit TM is as good and useful instrument for measuring grip strength.
Introduction: Physical activity (PA), health related quality of life (HRQoL) and exercise capacity are decreased in patients with Juvenile Idiopathic Arthritis (JIA) and do not restore after clinical remission has been obtained. Considering the impact of JIA on daily life, the long-term health risks of the disease, the sedentary habits, and the potentially favorable effect of PA, it is important to promote an active lifestyle in children with JIA. Therefore, we developed a 14-week, cognitive behavioral program, Rheumates@work, which was a combination of internet-based and in-person instructions supplemented with four group sessions to improve PA in children with JIA.
Objectives: The aim of this multicenter study is to determine the effects of Rheumates@work, on PA, exercise-capacity, HRQoL and participation in school and physical education class in children with JIA. Methods: Patients, aged 8-13 years, were recruited from three pediatric-rheumatologic-centers in the Netherlands to participate in an observer blinded, randomized controlled multicenter trial. Rheu-mates@work started either in winter or in summer. Primary outcome was PA, assessed with a diary and an accelerometer (Actical) during 7 days, expressed as PA level (PAL), time spent in rest, light PA and moderate-to-vigorous PA (MVPA), before the intervention, after the intervention (intervention and control group), and after 3 and 12 months follow-up (intervention group only). Secondary outcome parameters were; exercise-capacity (assessed with a Bruce treadmill test expressed as endurance time), HRQoL (with the Pediatric Quality of Life Inventory Generic-core-scale) and participation in school and sports (assessed by questionnaires).
Results: Twenty-eight children (median age 9.69, 21 girls) participated in the intervention and 21 as controls (median age 10.2, 12 girls). No significant differences between groups were found. None of the PA outcomes measured with the Actical had changed significantly within groups. A significant median difference of MVPA of 31 minutes (p = .04) has been found in the intervention group. Exercise-capacity improved in the intervention group with a median of 57 seconds (p = .02) and decreased in the control group by 46 seconds (not significant). Participation in school improved significantly in the intervention group. Children that missed at least one day of school due to JIA decreased from 43% to 14% (p = .02). Participation in physical education class increased in the intervention group from 57% to 71% (p = <.01). HRQoL improved in the control group (p = .01), not in the intervention group. Improvements on PA and exercise-capacity persisted in the 12 months follow-up period. Improvements in rest (median decrease of 54.17 minutes, p = .01), MVPA (median increase of 12.72 minutes, p = .03 (Actical)) and PAL (increase of 0.07, p = .02) (Actical)) were better for the intervention cohort starting in winter compared to the cohort starting in summer.
Conclusion: Rheumates@work exerted no significant differences between groups. Small positive effects on PA, exercise-capacity, and participation in school and physical education classes in the intervention group were found. Improvements lasted up until 12 months of follow-up. Participants who started in winter showed most improvements. Rheumates@work showed no effect on HRQoL. Introduction: Lipoma Arborescens, is a diffuse villous proliferation of the synovium characterized by replacement of subsynovial tissue by mature adipocytes. The etiology is not exactly known. Usual presentation is on the middle-aged men and knee joint especially on the suprapatellar bursa. A few cases in childhood have been reported in the literature.
Objectives: In this report, we describe an unusual case of Lipoma Arborescens in a child who was initially diagnosed as oligo articular juvenile idiopathic arthritis (JIA) in the elbow without any response to JIA treatment. Methods: Case: A 16-year-old boy was admitted to our hospital with the complaint of the swelling and limitation in the movement of the right elbow for the last 5 months. He had no history for trauma. Physical examination revealed swollen and limited range of motion of the right elbow without redness and warmth. Laboratory tests showed normal acute phase reactants; negative antinuclear antibody (ANA) and Purified Protein Derivative test. MR examination of the right elbow demonstrated joint effusion and synovial hypertrophy consistent with juvenile idiopathic arthritis. He was treated with ibuprofen and then intraarticular steroid injection was performed. Upon no response, methotrexate treatment was initiated. On the third month of the treatment, since no ACR paediatric 30 response was received, etanercept was added to treatment. On the sixth month of follow up another MR was performed based on his ongoing complaints and revealed dense effusion, synovial hypertrophy and contrast involvement consistent with active synovitis and also cystic destructive fields in his elbow.
Results: Having these findings, the patient was referred to the orthopedics department. A synovectomy was performed to the anterior and posterior compartments of elbow joint via anterolateral approach. A sample of biopsy was also taken from the lytic lesion in the distal humerus. Histologically, synovium and perisynovium had increased adipose tissue with occasional lymphoid aggregates. Humerus biopsy revealed an osteoblastic tumor consistent with osteoblastoma having hemorrhagic cystic areas. The first MR was revaluated and T1-weighted sequences revealed frond-like synovial proliferation with high signal density where fat-supressive sequences revealed partial suppression in this formation. The diagnosis of Lipoama Arborescens was confirmed. The limitation range of motion was resolved in time. He is now on follow up for osteoblastoma.
Conclusion: This case has been assessed worthy to report because it was seen in the elbow joint together with osteoblastoma. This rare disease should be kept in mind where joint is severely swollen with limited range of motion, negative ANA and acute phase reactants and unresponsiveness to the oligo JIA treatment. Introduction: Juvenile arthritis often associate with bone mineral density (BMD) decrease which can lead to osteoporosis onset and fractures. Determination of risk factors of BMD decrease will help to prevent these complications.

Disclosure of Interest
Objectives: To determine risk factors of BMD decrease in children with juvenile arthritis. Methods: Bone mineral density (BMD) was investigated in 32 children from 6 to 17 years with juvenile chronic arthritis by means of dual-energy X-ray absorptiometry method according to program 'The whole body'. The duration of the disease was from 2 to 14 years. Twenty three children had polyarthritis and 9 children had oligoarthritis. Using multiple regression analysis, the relationship between BMD and idiopathic arthritis (JIA) form, therapy, the age of disease onset, disease duration and the level of C-reactive protein (CRP) at the time of investigation, was estimated. All regressive models were adjusted for the age and child growth percentiles.
Results: The children age (p = 00006), child growth percentiles (p = 0,005) and the age of disease onset (p = 0,029) were determined to be the most associated factors to BMD. Disease duration, JIA form, the level of CRP at the moment of investigation, history of intra-articular injection of glucocorticosteroid (GC), treatment with biologic medicines and even orally intake of small doses of GC at the present have not shown significant associations with BMD. Conclusion: Early onset of juvenile arthritis can be the risk factor of systematic decrease in BMD among children.

Disclosure of Interest None Declared
Introduction: Large population-based studies have shown the association between rheumatoid arthritis (RA) and chronic kidney disease [1]. In juvenile idiopathic arthritis (JIA) renal manifestations have been rarely observed [2]. Serum cystatin C (CysC) has been proposed as a novel biomarker of the renal function and microalbuminuria is regarded as the gold standard for diagnosing the onset of pediatric diabetic nephropathy. The resistive index (RI), a measure derived from an arterial Doppler sonographic waveform, provides information about arterial impedance; it is especially important for the evaluation of the blood flow in renal parenchymal diseases [3].
Objectives: To investigate the presence of renal damage in a group of children with JIA and to establish the possible relationship with treatment.
Methods: Blood urea nitrogen (BUN), serum creatinine, cystatin C (CysC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), microalbuminuria, glomerular filtration rate (eGFR), and renal resistive index (RI) were assessed in 46 children with JIA (9 boys and 37 girls, mean age 10.3 ± 3.8) and compared with 51 healthy controls (M/ F:26/25, mean age 11.5 ± 3.5 years). 20 patients were on methotrexate (MTX group) therapy (M/F = 2/18; mean age 9.1 ± 3.1 years) and 26 were treated with biologic drugs (BD group) (M/F = 7/19; mean age 11.2 ± 4.1 years). Renal RIs were measured from pulse Doppler waveforms obtained from interlobar and arcuate arteries in three different regions from upper, middle and lower third of the kidney. Also a mean RI was calculated for each child by averaging mean RI of the right and left kidney.
Results: Creatinine, CysC and BUN were significantly higher in patients compared to controls; besides eGFR was lower in JIA subjects respect to healthy patients (p < 0.001) (tab 36). In details, the right, left and mean RI values were significantly increased in JIA subjects compared to controls (p < 0.001). Of note BD group showed significantly higher values of the mean RI compared to MTX group (tab 36); however disease duration in the BD group tends to be higher than the MTX group.
Conclusion: The results of our study suggest that eGFR is reduced in children with JIA. Moreover RI values are impaired in subjects with JIA compared to healthy controls and are significantly higher in those treated with BD compared to MTX group. IR values are directly related to indexes of inflammation suggesting a direct effect of disease. In the pediatric population, anti-synthetase autoantibodies are rare and found in less than 5% of patients with Juvenile DM (JDM) but occur in 9% of patients with JPM and 13% of patients with juvenile overlap myositis, with the peak age at disease onset being 14 years 2 . They appear to have a similar disease phenotype to adults and are at risk of developing ILD, which has been found to be the most common cause of death and were consequently associated with an increased risk of mortality. Objectives: The aim of this study was to define the frequency and investigate the clinical associations of anti-synthestase autoantibodies in a large cohort of patients with JDM, the UK JDM Cohort and Biomarker Study (JDCBS). Methods: Serum samples and clinical data were obtained from 386 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-synthestase autoantibodies was determined by immunoprecipitation. Due to the small number of patients with the autoantibody in the study, descriptions of common features are given. Results: Anti-synthestase autoantibodies were identified in only 6 (1.5%) patients with JDM within the cohort. All patients were female and all bar one were considered to have JDM overlap. 50% were of black origin, they were all non-anti-Jo1 positive and had ILD. The details of their diagnoses and clinical features are demonstrated in Table 37. Conclusion: Anti-synthestase autoantibodies can be identified in a small proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-synthetase autoantibodies especially non-anti-Jo1 antibodies may identify patients at risk of ILD. This mirrors the adult presentation where ILD is the predominant manifestation of non-anti-Jo1 anti-synthestase autoantibodies.   In group 1, patients had a greater degree of weakness at diagnosis (median MMT score 42 versus 63, p =0,01; median CMAS score 3 versus 38, p =0,001) and more frequent vasculopathy-related features, especially gastrointestinal involvement, (p = 0,007) than in group 2. Conversely, the percentages of patients who developed calcinosis did not differ between the two groups (20% in each group). At diagnosis, CPK values were > 5 000 IU/L in 88% and 43% of patients from group 1 and 2 respectively. All the patients underwent a muscle biopsy. Histological features revealed typical lesions of dermatomyositis in all cases: inflammatory and perimysial myopathy with ischemic lesions, perifascicular atrophy and necrosis, expression of HLA ABC class I, C5b9 capillary and sarcolemal deposits. Group 1 displayed more frequent ischaemic punch-out vacuoles associated with microinfarcts (p = 0,022) and capillary dropout (p = 0,01). At 6 months, 80% of the group 1 patients required more than two lines of treatment (including plasmapheresis or immunoadsorption) versus 45% in group 2 (p = 0,01) Conclusion: Anti-NXP2-positive patients demonstrate a greater disease severity and a more prominent ischemic pattern than other JDM. Histopathological investigation can contribute to the classification of inflammatory myopathies in assocation with the MSA screening. Introduction: The course of juvenile dermatomyositis has improved greatly over the last 70 years with the aggressive use of corticosteroids, immunosuppressive medication, and biologics. Yet it is often difficult to detect disease flare in these children. Symptoms may be mild, signs of the rash and muscle disease can vary widely and are often equivocal. Lab tests including muscle enzymes are often normal. EMG and muscle biopsy are invasive and not reliable. New disease outcome measures are in development. Other tools may be helpful to determine if more treatment is needed. Objectives: To determine if a muscle MRI is useful in detecting a JDM disease flare-up and affecting physician decision-making. Methods: Approval was obtained from the IRB of Nationwide Children's Hospital (NCH). Subjects were identified by US ICD10 and ICD9 codes and only included if they met the modified Bohan and Peter DM criteria and were seen at NCH between 1/2005 and 6/2015. Each child had to be in remission for 6 months prior to flare-up. Data collected included demographics, clinical presentation at onset, clinical features at time of repeat MRI, lab test and imaging results at presentation and flare-up, and treatment before and after flare-up MRI. The MRI was performed on both lower extremities without contrast with the following sequences: Axial T1, axial T2 fat saturation, axial and coronal inversion recovery, and axial diffusion weighted. The physician decision that a child with JDM was in a flare-up was the gold standard, using rash, muscle weakness (CMAS), muscle enzymes, and myositis on MRI. We compared the MRI result with the physician's decision of relapse or not and evaluated whether there was a concordance or discordance between MRI findings and the subsequent treatment decision. Cohen's kappa test was used for chance-corrected agreement between physician decision and MRI findings, Bayes' rule for conditional probability  Table 38 for details) and 54 (65%) were still taking immunosuppressive medication for myositis. Among respondents at school or higher education, 13 out of 29 (44.8%) reported that their academic results were adversely affected by myositis, and. that time missed due to myositis, muscle weakness and fatigue were all significant contributors.         There was no difference in racial distribution (p-value = 1), age at disease onset (p-value = 0.87) and disease duration prior to treatment initiation (p-value = 0.75) between patients who had clinically active and inactive disease. The demographic characteristics of children with JDM were similar to that from most other regions of the world with female predominance and similar age at onset. The median delay in diagnosis (4 months) was not longer than that reported in most other studies. However, some children had prolonged delay of up to 7 years due to misdiagnosis that denied them appropriate treatment in a timely manner. Majority (60%) of the patients also remained with clinically active disease, which put them at risk of further disease complications including calcinosis. Even though the mortality rate was low (8%) this was still more than double that reported in most recent large studies especially from the resource rich countries. Conclusion: Long term follow up of JDM patients is advisable since majority of patients seem to have clinically active disease many years after disease onset despite treatment. Formulation and use of appropriate treatment guidelines and protocols may aid in the early diagnosis and appropriate management for optimum outcomes.

Disclosure of Interest None Declared
Methods: Children with a diagnosis of CTD or receiving methotrexate or biologic drugs for more than two years who were followed-up at Hacettepe University Department of Pediatric Rheumatology and referred to the Department of Pediatric Pulmonology were included into this study. Medical history, physical examination, chest radiography (high resolution computerized tomography [HRCT] in selected cases), and pulmonary function tests such as spirometry, whole-body plethysmography and carbon monoxide (CO) diffusion test were evaluated in all patients. Results: There were 33 children with CTDs (21 with juvenile dermatomyositis [JDM], 2 polymyositis [PM], 5 systemic lupus erythematosus, 4 systemic sclerosis, 1 mixed CTD). Female-to-male ratio was 2/1 and the median (min-max) age at diagnosis was 96 (11-186) months. CO diffusion capacity was low (<80%) in two patients (one with PM and one with JDM) and spirometry showed restrictive changes in these patients. HRCT was normal in the patient with PM. The patient with JDM had features suggesting interstitial lung disease (ILD) in HRCT and she was positive for anti-MDA5 autoantibody. As for the second part of the study, there were 50 children who received biologic/nonbiologic DMARDs (44 methotrexate, 12 etanercept, 4 adalimumab, 4 anakinra, 1 tocilizumab, 1 canakinumab, 2 abatacept, 1 infliximab) for more than two years. The median (minmax) duration of treatment was 36 (24-180) months. During the routine evaluation for tuberculosis in 25 patients receiving biologics, 12 (48%) received isoniazid prophylaxis for nine months since their PPDs were ≥10 mm. However, no active tuberculosis was diagnosed during a follow-up of 36 (24-71) months. Only three patients had ILD who were using anakinra for ≥2 years for the treatment of systemic juvenile idiopathic arthritis. Both the disease itself and anakinra treatment might be contributing to the etiology of ILD in these children. Conclusion: Pulmonary disease should be assessed carefully in children with CTD especially JDM/PM. ILD has been associated with several rheumatic diseases in children and whether this is a complication of the biologic/nonbiologic DMARD treatment. Thus, the routine follow-up of pulmonary functional status in children treated for rheumatic diseases is crucial to diagnose and treat pulmonary disease in the early phases. Methods: We experienced three cases of the JDM with anti-TIF1 antibodies. In previous reports in Japan, 7 cases have been reported so far (Nagoya: 3 cases, Kanazawa: 4 cases). We analyze the clinical characteristics of these 10 patients in Japan categorized as JDM with anti-TIF1 antibodies. Results: Three patients with active JDM with anti-TIF1 antibodies were observed in our hospital. All patients reported skin lesion. Two patients had elevated muscle enzymes aldolase. Only one patient has exhibited a severe systemic symptoms (fever, general fatigue, myositis). Ten patients with active JDM with anti-TIF1 antibodies were observed in Japan. There was no trend in the age of onset. No patients reported malignancy. Incidence of JDM with anti-TIF1 antibodies in Japan was 29% of whole JDM. Conclusion: JDM with anti-TIF1 antibodies exhibited different clinical features. To establish the clinical significance of myositisspecific antibodies, the accumulation of cases is indispensable. In the near future, not only the tendency of each region, it is expected that the differences between all regions of the world will become apparent. Results: A total of 89 JDM patients (55 girls) from Saudi Arabia (65.2%), Jordan (18%) and Oman (16.9%) were included. The mean age at onset was 6 years (±3), the mean age at diagnosis was 6.6 years (±3), and with mean follow up duration of 5 years (±4.4). Fifty patients had active follow up, 27 patients transferred to adult rheumatology service and 12 patients had lost follow up. Forty patients had polycyclic disease course, 34 had monocyclic course while 15 had continuous progressive course. Seventy-four patients had organ involvement, arthritis (48%), upper airway and dysphagia (14%), gastrointestinal (13%) and lung involvement (10%). Seven patients admitted to intensive care unit (ICU), 4 of them required mechanical ventilation. Dysphagia, upper airway and lung involvement were all statistically significant associated with ICU admission. All patients received corticosteroids; while methotrexate was the most frequently used immunosuppressive drugs (86%) and rituximab was used in 8 patients. Additionally 31 patients received IVIG. Twelve patients received pamidronate mainly for calcinosis. Most of the patients achieved complete clinical response but 16 ended with permanent skin changes and 12 had residual muscle weakness. Twenty-seven patients developed calcinosis, 15 had osteoporosis, and 3 had lipodystrophy while 37 patients had growth failure. One patient developed mucinous cystic ovarian tumor. There were two deaths due to infection during the follow up period. Conclusion: Arab patients with JDM have similar characteristics to previously described cohorts. However, compared to our previous experience, a steadily improvement in outcome particularly calcinosis which probably related to better therapeutic approach.

Disclosure of Interest None Declared
Introduction: Juvenile dermatomyostis (JDM) is a systemic inflammatory microvasculopathy that primary affects skin and muscle The clinical course of JDM is variable and correlates with severity of vascular disease and vascular alternations taking place in the muscle, skin and diverse organs The microangiopathy characteristic of JDM can be confirmed by nailfold capillaroscopy(NC). NC is an important tool for noninvasive study of peripheral microcirculation in children with dermatomyositis.
Objectives: The aim of study was to comparison disease activity and nailfold capillaroscopy findings in children with juvenile deramatomyositis. Methods: 13 children with diagnosed dermatomyositis (3 -17 years old, 6 girls and 7 boys were included in the study. Age of the patients at the time of diagnosis was: 4 -14 years, duration of illness at the time of study: 4 -79 months. The evaluation of capillaries was performed using a stereoscopic microscope, the measurements were done using the program AxioVision. The capillary system was evaluated by assessesmant of number or loss of capillaries, the number of enlarged and giant capillaries, haemorrhages, neoangiogenic capillaries and their disorganization. The evaluation was made using the scoring system of the capillaroscopic parameters 1  Results: A total of 14 children (8 boys and 6 girls) were diagnosed as SSc between 1990 and 2014. Diffuse and limited cutaneous SSc were seen in 10 and 4 patients, respectively. Median age at symptom onset and diagnosis was 7 years (range of 4-14 years) and 10 years (range 6-15 years), respectively. Progressive skin tightening (78%) and Raynaud phenomenon (71%) were the most common presenting manifestations. Raynaud phenomenon as the only presenting manifestation was present in 21% patients. Other common presenting features included restriction of joint movements due to skin tightening (57%), hyperpigmentation of skin (21%), arthritis (14%), dysphagia (30%) and dyspnoea on exertion (14%). Calcinosis and palpitation were the presenting manifestations in 1 patient each. On evaluation, skin involvement [digital tip ulcers (50%), calcinosis (21%), salt-pepper pigmentation (14%), telangiectasia (14%) and acro-osteolysis (7%)] was present in all patients. Median Modified Rodnan Skin Score (MRSS) at presentation was 18. Skin biopsy was done in 8 patients and was suggestive of sclerodermatous skin changes in all. Capillaroscopy was done in 3 patients and was suggestive of capillary drop outs and tortuous loops. Pulmonary involvement was seen in 10 patients. Only 2 of these were symptomatic at presentation. One patient developed ILD after 2 years of initial diagnosis of SSc. Pulmonary function test (PFT) was suggestive of restrictive pattern in 9/13 patients. Gastrointestinal tract involvement was seen in 30% patients with dysphagia as the most common clinical manifestation. Median juvenile Systemic Sclerosis Score (JSSS) was 6.5 at presentation (range 3-12). ANA was positive in 10/14 patients [speckled (4), nucleolar (4), mixed (1) and diffuse (1)]. RA factor was positive in 3/14 patients. CT chest showed features of ILD in 6/9 patients with ground glass opacity and honeycombing being common abnormalities. Mean follow up was for 2.07 years (3 months to 6 years). In majority of patients with major organ involvement, the treatment regimen included cyclophosphamide pulse therapy followed by oral azathioprine. No mortality was reported in our cohort of patients; however recent follow up was available for only 7 patients. Conclusion: In our cohort, we found a significant male preponderance. Progressive skin tightening and Raynaud phenomenon were the most common presenting manifestations Disclosure of Interest None Declared Morbidity was defined as: unsightly effects (dyscromic, disfigurement lesions and/or alopecia). Sequela was defined as functional joint involvement and growth disturbances (longitudinal, circumferencial or mixed). Results: n = 88. Mean age at diagnosis 6.9 years (0-14 years) with a sex ratio F:M 2,1:1. The mean follow up time was 43 months (6-243 months). Mean time between symptoms appearance and diagnosis was 16,5 months (1-96 months). AAN were positive in 42% of patients. According to PRES criteria the distribution was: circumscribed morphea (33%), mixed (32%), linear (22%), generalized (11%) and panesclerotic (2%). The clinical phenotypes of the predominant subtypes are described in Table 41. 67% developed multiple lesions. 22% had extra cutaneous involvement (neurological, ocular and articular) and 13% had another autoimmune disease. Circumscribed was the most common type, morbidity was related to unsightly effects. In mixed type the association between linear and circumscribed lesions account for 75%. This type had multiple complications (unsightly and functional effects). Linear lesions induced the three types of morbidity and showed the higher polyautoimmunity rate. The coup du sabre type had the longest duration between symptons and diagnosis, the higher extra cutaneous involvement and a significant morbidity. Generalized scleroderma developed important unsightly and functional effects. Pansclerotic was the least common, 2 girls being affected by a severe crippling disease. The frecuency of functional joint involvement, growth disturbance and multiple complications was higher in the mixed, linear and generalized types, being statistically significant. Conclusion: JSC is a polymorphic and unpredictable disease that determines important morbidity. Late diagnosis is common and might have a negative impact on prognosis because it allows the progression of the lesions, their size, depth and number. The high number of extra cutaneous complications reflects that this is not a disease limited to the skin. Polyautoimmunity reflects an immune system dysregulation. An early diagnosis and a more dynamic immunosuppressive treatment may improve the prognosis. Patients need a regular and extended follow up. Introduction: Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Currently just retrospective data exist regarding evolvement of organ involvement. In the retrospective studies assessment of the organ involvement is not standardized. Our project is the first project, where prospectively and with a standardized assessment data of jSSc patients are collected. We present the data of the patients at the entry into the cohort.

Disclosure of Interest
Objectives: to learn about the characteristics and evolvement of jSSc Methods: Patients with jSSc, according the PRES criteria, were recruited worldwide and were prospectively assessed, using the proposed standardized patient assessment protocol. Results: 26 centers from 17 countries applied to participate on the project. The assent and consent forms were translated into the local native languages. Up till now 80 patients were enrolled. Sixty-six (82.5%) of the 80 patients were female. The mean age of the onset of Raynaud symptomatic was 9.4 years (0.2 -15.9). The mean age at the onset of the non-Raynaud symptomatic were 9,9 years (0.3 -15.9). 58 (72.5%) had diffuse subtype and 22 had limited subtype (27.5%). 11 (14%) of them have an overlap symptomatic, in 6 (10%) in the diffuse and 5 (23%) in limited subtype.  Introduction: Evidence of premature atherosclerosis and systemic arterial stiffening in follow up patients of Kawasaki disease (KD) and coronary artery abnormalities is accumulating. Diminished flow-mediated dilatation (FMD) and increased carotid artery stiffness index (SI) have been used as surrogate markers of premature arteriosclerosis. Both of these indices have been shown to correlate with late cardiovascular events and/or mortality in adults. Because of their noninvasive nature these parameters have recently been studied in children as well. There is paucity of studies in endothelial dysfunction in children with KD and transient coronary artery abnormalities.
Objectives: In the present study, we assessed the risk of atherosclerosis by noninvasive methods (FMD, cIMT and carotid artery stiffness index) in children of KD with transient coronary artery abnormalities at least 1 year after resolution CAA of KD. Methods: Twenty children with KD (mean age 11.5 ± 3.7 years) and transient coronary artery dilatation which had resolved within 1 year of diagnosis were studied at least 1 year of after resolution of CAA. All had received intravenous immunoglobulin except one during the acute phase of the disease. High-resolution ultrasonography was used to analyze brachial artery responses to reactive hyperemia and sublingual nitroglycerine. Flow-mediated dilatation was also studied in an equal number of healthy age-and sex-matched controls. Carotid artery intima-media thickness and stiffness index was calculated using B mode ultrasound and compared in all subjects using previously published equations. Results: No statistically significant difference was noted in the percent flow mediated dilatation of the brachial arteries in response to reactive hyperemia among the cases (13.31 ± 10.41%) compared with controls (12.86 ± 7.09%; p = 0.874). Sublingual nitroglycerine-mediated dilatation in children with KD was 14.88 ± 12.03%. Mean carotid intima-media thickness was found to be almost same in both cases (0.036 ± 0.015 cms) and controls (0.035 ± 0.076 cms; p = 0.791). Also, no significant difference was noted in the carotid artery stiffness index among the cases ( 1.153  Introduction: Kawasaki disease (KD) is the most common medium vessel vasculitis in children. It has a predilection to involve coronary arteries, leading to several long term cardiovascular sequelae. In addition to coronary artery abnormalities (CAAs), premature atherosclerosis, endothelial dysfunction and lipid abnormalities are seen in children with KD. Despite prompt treatment with intravenous immunoglobulin in the acute phase, these complications ensue.
Objectives: At our institute in Chandigarh, Meena et al. in 2009 studied carotid intima media thickness (cIMT) and lipid profile in 27 children with KD after 1 year of the acute episode of KD. This study was planned to follow-up the same cohort of children at least 5 years after the acute episode. Methods: All the 27 children previously enrolled by Meena et al. were followed-up in the present study. cIMT, being a surrogate marker for premature atherosclerosis and fasting lipid profile were evaluated. Diagnosis of KD was based on the American Heart Association criteria. All patients had received 2 gm/kg of IVIg at the time of diagnosis. Age and sex matched healthy children were enrolled as controls from the out-patient department of the institute for cIMT. For lipid profile, comparison was made with published data on this subject. cIMT was measured in the Echocardiography lab of Advanced Cardiac Centre, PGIMER by Acuson Sequoia C-512 Siemens Limited with 7-12 MHz linear array transducer. All children with KD were asked to fast for 8 hours overnight and 2 ml blood sample was collected. Total cholesterol, HDLC, triglycerides were estimated using standard laboratory kits manufactured by Siemens Healthcare Diagnostics. Cholesterol levels < 170 mg/dL were considered desirable and > 200 mg/dL were considered undesirable. Cholesterol levels in between these limits were considered borderline. Low-density lipoprotein cholesterol (LDL-C) levels < 110 mg/dL were considered desirable, and > 130 mg/dL were considered undesirable. LDL-C levels in between these limits were considered borderline. High-density lipoprotein cholesterol (HDL-C) levels > 35 mg/dL were considered desirable, and < 35 mg/dL were considered undesirable. For triglycerides, levels < 150 mg/dL were considered desirable and > 150 mg/dL as undesirable.
Results: Mean duration between onset of fever and IVIg treatment was 14.3 days with a range of one to 90 days. At the time of diagnosis, 10 patients (37.03%) had CAAs in the form of dilatation. There was significantly higher mean cIMT in children with KD (0.54 ± 0.087 mm) as compared to controls (0.42 ± 0.036 mm), however there was no significant difference in cIMT at 1 and 5 years of followup. There was no statistically significant difference among cholesterol, HDLC, LDL-C and triglyceride levels between cases with CAAs at diagnosis as compared to children without CAAs at diagnosis. Abnormal lipid profile was seen in 7 out of 27 children in the present study (1 child-borderline serum cholesterol levels, 4 children-undesirable serum HDL-C levels, and 2 children-undesirable serum triglyceride levels), 5  Introduction: Plasma exchange (PE) is a renal function preserving and potentially life-saving therapy in children and adults with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). The therapeutic mechanisms of PE in AAV are poorly understood, but it is likely that PE removes autoantibodies and other plasma constituents involved in AAV. We have previously shown that circulating neutrophil microparticles (MP) are key inflammatory mediators underpinning the pathogenesis of AAV. Objectives: The aim of this project was to investigate whether MP are removed from the circulation of patients with AAV by PE, and therefore are potentially an important therapeutic target. This was an ancillary study of a major international clinical trial of therapeutic PE in AAV, the PEXIVAS trial (NCT #NCT00987389). Methods: Patients with AAV undergoing PE for active disease measured by the Birmingham Vasculitis Activity Score (BVAS) were recruited from the Royal Free Hospital and Great Ormond Street Hospital NHS Foundation Trust. Annexin V+ MPs were isolated from platelet poor plasma, cellular origin defined (neutrophil, platelet, endothelial) and MP quantified using flow cytometry. The soluble inflammatory mediators in EDTA plasma were measured using multiarray electrochemiluminescence (MSD). Results were expressed as median and range. Results: A total of seven patients undergoing PE at diagnosis of AAV were recruited: median age 64 years (range 17-22 years old); 4 male. Median BVAS was 15/63 (12-18/63); all patients studied had rapidly progressive glomerulonephritis. The number of total circulating AnV + MP reduced by~60% after 3 cycles of PE from a median of 5.1 × 10 6 /ml (range of 11.2 -4.78 × 10 6 /ml) to a median 1.97 × 10 6 /ml (0.36 × 10 6 -3.7 × 10 6 /ml), p = 0.04. Neutrophil MP identified as CD66b + AnV + were reduced from a median of 58 × 10 3 /ml (range of 88 × 10 3 -40 × 10 3 /ml) to a median of 15 × 10 3 /ml (range of 17 × 10 3 -11 × 10 3 /ml), p = 0.02. Angiogenic factors (VEGF and Ang-1) were lower in patients with active AAV, comparing with health control, but no change after PE. In patients with active AAV, significantly increased level of Ang-2 was detected, comparing with healthy control, furthermore, levels of Ang-II declined from a median of 8179 pg/ml (range of 3440-17313 pg/ml) to median of 3776 pg/ml (range of 775-12143 pg/ml), p = 0.03, similar to normal values (median of 2747 pg/ ml, range of 1063-9296 pg/ml). Similarly, the plasma level of sICAM (a soluble marker of endothelial activation) were increased in patients with active AAV, and there was a significant reduction pre and post PE, p = 0.01. Conclusion: Our preliminary results suggest that PE is an effective method to remove these circulating mediators of inflammation and endothelial injury. It remains to be elucidated if the removal of excess injury factors is crucial to ameliorate endothelial damage in patients with AVV. Introduction: Kawasaki disease (KD) is a leading cause of acquired heart disease in children in developed countries mostly because of its coronary artery complications. Still there is controversial data about the influence of patient's age on the clinical features and outcomes of KD Objectives: Medical records of 168 KD aged from 1 month 13 days to 13 years 6 months treated in the University Children's Clinical Hospital from 2003 to 2014 were reviewed. 24 (14,3%) of them were <6 months, 31 (18,4%) -6-< 12 months, 94 (56%) -12 months-< 5 years, 19 (11,3%) -≥5 years. To evaluate the contribution of patient's age to the development of coronary artery aneurysms (CAA) clinical, laboratory data and IVIG treatment were analyzed Methods: Patients' data were compared between four groups: children <6 months of age, 6-< 12 months, 12 months -<5 years, ≥5 years at the time of the disease onset. The presence of CAA was measured using 2-DE performed at 8 weeks after disease onset. Differences were tested using the Mann-Whitney test, Fisher's exact test, Chi-square, Student's t-test. The odds ratios (ORs) with 95% confidence intervals (CIs) of explanatory variables for the presence of CAA were determined by multiple logistic regression models Results: The high degree of statistical significance for different age groups of children with KD was revealed for the frequency of the cervical lymphadenopathy, articular and abdominal syndromes, vomiting (as a gastrointestinal damage manifestation), meningeal and urinary syndromes, erythema of the BCG area (P < 0,05). It was shown that patient's age influenced the clinical and laboratory phenotype of KD determining the frequency of non-basic symptoms which could be very prominent and often defined an incorrect diagnosis. CAA were found in the group of children younger 6 months of age significantly more often even if they were treated with IVIG before the 10 th day of illness: 60% vs 11,6-12,5% of children treated with different doses of IVIG before the 10 th day of illness in three other age groups (P < 0,05); 50% vs 9-11% of children treated with IVIG 2 g/kg before the 10 th day of illness in groups 6-< 12 months and 12 months -<5 years and 20% in children ≥5 years (P > 0,05). Conclusion: Patient's age influences the clinical phenotype of Kawasaki disease and has to be taken into account while making the diagnosis. It also influences the outcome of the disease even if a child is treated with IVIG before the 10 th day of illness Disclosure of Interest None Declared Objectives: Case report of early onset BD. Methods: A 13 year-old boy was admitted to our hospital to investigate the presence of recurrent oral aphthosis, acneiform and papulopustular skin lesions, bronchiectasis associated to recurrent respiratory infections, arthritis, and growth retardation. His family history showed recurrent oral aphthosis in his mother. He was born after 36 weeks of gestation via vaginal delivery, with APGAR score 9/10. Birth weight was 3,450 Kg. At the third month of age, oral candidiasis associated to perioral and genital papulo-pustular skin lesions appeared. After 6 months, he developed recurrent fevers (T°max 39-40°C), monthly. At 3 years of age, the papulo-pustolar skin lesions spread to buttocks and ears and, after one year, the boy developed anterior uveitis. Since he was affected by growth delay associated to increase of fecal calprotectin, he underwent an EGDS, that showed features of autoimmune enteropathy (mucosal architectural changes including villous atrophy, increased intraepithelial lymphocytes and 10 or more eosinophils per high power field); autoantibodies (transglutaminase ab, ANA, p-ANCA, c-ANCA, anti-dsDNA, anti-Jo1, ant-Sm, anti-RNP, anti-Scl70, anticentromere and anti-SSA) were negative. At 5 years of age, genital ulcers and erythema nodosum on legs (anterior tibial regions), hands and elbow appeared. Results: He was then admitted to our hospital for further investigations. On physical examination, he presented rather good general conditions, oral aphthosis, acneiform and papulo-pustular skin lesions son perioral, ears and genital regions. Blood tests revealed an increase of inflammatory markers (ERS 35 mm/1 h, CRP 4.51 mg/L, SAA 70 mg/L). Liver and renal functions were normal. Autoantibodies (ANA, p-ANCA, c-ANCA, anti-dsDNA, anti-Jo1, ant-Sm, anti-RNP, anti-Scl70, anticentromere and anti-SSA) were performed as well, and resulted all negative except for ANA (1:1280). Genetic tests for MEFV, MVK, CIAS-1 and TMEM173 were negative. HLA-B51 was positive Cerebral MRI, MR angiography and echocardiography were performed, and resulted normal. He started Colchicine (1 mg/die), topical corticosteroids, antimicrobial prophylaxis and airway clearance techniques. Conclusion: The diagnosis was confimed according to the criteria of the "International Study Group for the Diagnosis of Behçet Disease" (Recurrent oral aphthosis, genital ulceration, skin involvement, anterior uveitis). Looking at the early onset of disease and the positive family history we have also considered the monogenic disease with A20 haploinsufficiency, recently described and caused by highpenetrance germline mutations in TNFAIP3, which encodes the NF-kB regulatory protein A20, leading to a Behcet-like disease with early-onset systemic inflammation. Genetic test results are pending. Henoch-Schonlein purpura (HSP) is the most common systemic vasculitis of childhood with an incidence of 10-20 cases per 100,000 children per year. Generally the prognosis is good, with exception of those with significant renal involvement. The principal aim of HSP follow-up is mostly to detect persistent renal inflammation that could progress to renal damage. It was our observation that the weak link in the care of these children at our institution was urinalysis (UA) follow-up after the first patient contact with the Nationwide Children's Hospital (NCH) medical system. In the long-term, the HSP renal disease may be serious in these children and a simple cost-effective intervention may detect HSP renal disease earlier in the disease process and improve outcomes.

Disclosure of Interest
Objectives: This quality improvement (QI) project's overall objective was to design an intervention that might improve the followup with UA screenings by educating families and asking care providers to do the urinalyses on schedule. The specific aim was to increase the performance of follow-up urinalyses from baseline by 21% over 6 months and by 30% over 12 months by use of this QI intervention. Methods: Approval for this study was obtained from the Institutional Review Board of NCH in 2014. We identified HSP patients in our electronic medical record (EMR) EPIC using the US codes ICD 9 and ICD 10 for HSP. 105 HSP patients were identified retrospectively who had a diagnosis of HSP from July 1, 2014 to December 31, 2014. Their records were reviewed for diagnosis, date of diagnosis, location of clinic visit, new or old HSP diagnosis, dates and results of urinalyses at diagnosis and on follow-up, and diagnosis of renal disease by nephrologists and results of kidney biopsy. Similarly patients were identified and charts reviewed prospectively from January 1, 2015 to December 31, 2015 for the same data. The review of the 2014 charts helped identify the QI key drivers of provider factors, process factors, and patient factors that informed the intervention. The authors agreed on a consensus schedule for follow-up UA's. A dot phrase was developed and inserted into the EMR of NCH which contained education about HSP, the rationale for the follow-up urinalyses, and our suggested schedule. The availability of the dot-phrase was advertised widely to all care providers in the NCH system before January 1, 2015. The data was collected month to month in 2015 on 239 HSP patients and UA results obtained from the EMR and primary care providers.
Results: Follow-up urinalysis performance for the HSP patients in 2014 was 21%. The AVS was given out to families in 2015 at rates from 75-95% in different outpatient sites. With the intervention during 2015, the urinalyses were performed at the rate of 61% from January 1 to June 30 th and 55% over the second 6 months. The changes were statistically significant (for mean change p = .0075). Four children initially had a normal urinalysis at their first visit and then developed an abnormal UA; 3 patients' abnormal UA resolved over the next 8 months but one developed chronic renal disease. Overall, 2 children developed chronic renal disease with IgA nephropathy on kidney biopsy. Conclusion: Our QI intervention was successful in achieving our goal of increasing follow-up urinalysis performance in HSP patients seen at HSP in 2015. We believe such an inexpensive QI intervention is beneficial to the HSP patients but further study in a collaborative network is needed to determine if it actually detects renal disease earlier and improves outcomes. Introduction: Polyarteritis nodosa is a rare necrotizing vasculitis which affects small and medium-sized arteries and characterized by multi-organ involvement. Gangrene digitale and extremity loss via necrotising vasculitis have been reported in polyarteritis nodosa. Although immunosuppressive agents, vasodilatators, anticoagulants are used, there is no definitive treatment protocol. Objectives: . Methods: A 15 year old male was admitted to our hospital with paleness, redness, bruising on both the fingers, toes and redness on the cheeks. The complaints of paleness, coldness, redness at fingertips began five days before admission to hospital. In a few days bruising, more prominently on toes, appeared on fingers and toes. Anamnesis and the family history was not significant. In the first examination, vital signs were stabile, growth and development were compatible with the age, 2 nd 3 rd and 4 th fingertips of left foot's color were black and necrotising. Capillary refilling time was apparently prolonged. Laboratory analyses showed WBC of 15,040/mm 3 (5,000-14,500), hemoglobin of 14 gr/dL (12-16), platelet of 387,000/mm 3  Urinalysis, creatinin levels, serum levels of transaminase were normal and anti-HIV, anti-HAV, anti-HBV, and anti-HCV antibodies were negative. Anti-nuclear antibody (ANA) titre was 1/100. Anti-ds DNA, profile of Anti ENA, p-ANCA, c-ANCA, Anti cardiolipin IgM and IgG antibodies, lupus anticoagulant and crioglobulin were negative. C3, C4, Protein C, Protein S, antitombine III, vWF, homocysteine levels were normal. FVIII and FIX levels were increased. Enhanced CT angiography demonstrated narrowing and contour irregularities at left kidney, mesenteric and both tibialis posterior arteries. PA lung and sinus graphies were normal. Patient was screened for MEFV mutation and homozygous R202Q/R202Q and M694V/N were detected. The patient was homozygous for MTHFR C677T. With these findings, patients was diagnosed as poliarteritis nodosa (PAN). Methylprednisolone 1gr/day was given in three consecutive days and 1gr/month cyclophosphamide was started. After these treatment, 60 mg/day orally prednisolone therapy and simultaneously, 30 sessions of hyperbaric oxygene therapy was applied. Treatment of the first five days of hyperbaric oxygene therapy, ilioprost (0,5 ng/kg/min) was given with IV infusion. Low molecular weight heparin (enoxaparin) (2 mg/kg/day) was administrated for 6 months. Mycophenolate mofetil (1200 mg/m 2 /day) was added to therapy at the end of the cyclophosphamide pulse. After 30 sessions of hyperbaric oxygene therapy, the patient was discharged.

Results:
Conclusion: Vasculitis which can lead to loss of extremity, hyperbaric oxygene therapy that might be considered as a concomitant treatment with drugs has an important contribution to the preservation of tissue and extremity.

Disclosure of Interest None Declared
Introduction: Idiopathic retroperitoneal fibrosis (RPF) is a rare disease characterised by development of fibro-inflammatory mass in retroperitoneum. RPF is very rare among children and is considered a subtype of chronic periaortitis that might be associated with large-vessel vasculitis or other autoimmune disorders. Objectives: To analyse an unusual case of retroperitoneal fibrosis in a teenage girl progressing towards predominantly large vessel vasculitis and to review existing paediatric literature. Methods: Case report and literature review Results: A 13-year-old previously healthy Caucasian girl presented with recurrent fever, elevated inflammatory markers and back pain that initially mimicked pyelonephritis. Recurrence of symptoms and later development of supraclavicular lymphadenopathy promoted imaging (ultrasound US, MRI) which confirmed presence of large lymph node (LN) packet with inflammatory rather than malignant appearance on PET-CT. Transient partial spontaneous regression of her symptoms as well as non-specific inflammatory histopathology changes of her cervical LN supported conservative watch-and-wait approach by the paediatric oncology team. The third relapse with systemic hypertension as an additional new symptom led to the open biopsy from the retroperitoneal mass which excluded lymphoma. Repeated MRI revealed new involvement of aorta at the level of renal arteries and supported suspicion of vasculitis. Review of the history, imaging and biopsy results led to the diagnosis of RPF with progression to secondary vasculitis. General symptoms improved on corticosteroid (CS) therapy, but systemic hypertension as a consequence of the right renal artery occlusion progressed and resulted in nephrectomy. Aggressive immunosuppression with CS and i.v. cyclophosphamide did not abate the process which eventually affected abdominal aorta, iliac, renal and pulmonary arteries. Postcontrast gadolinium enhancement was noticed in the wall of these large vessels corresponding to persistent inflammatory activity despite the disappearance of the fibrous/LN retroperitoneal mass. After introduction of rituximab and later also low-dose weekly methotrexate (MTX) disease activity slowly diminished. After 18 months of this therapy she has been able to reduce her CS dose to 0,1 mg/kg/day and is doing well clinically, laboratory and imaging-wise. Literature search of the PubMed database from 2003 revealed 31 cases of RPF in children with typical onset age between 10 and 15 years, but none of them presented with arterioocclusive process. Around half of the patients presented with an associated autoimmune condition, and in two cases the association with malignancy was described. Majority of patients with RPF responded well to CS therapy, in refractory disease B cell-depleting therapy with rituximab was successful. Conclusion: We present an unusual paediatric case of an overlap between RPF and large vessel vasculitis. This case is in accordance with the published adult case series demonstrating that chronic periaortitis as a component of RPF is not limited to the abdominal aorta and displays the features of primary large vessel inflammatory disease. Our choice of initial cytotoxic therapy was driven by the severe clinical picture. We have learnt that rituximab time to clinical effect may by as long as 18 months and that combination with MTX has brought additional benefit. Despite that, the long-term prognosis is warranted. Introduction: The mainstay of treatment for Takayasu arteritis (TAK) is high-dose corticosteroid. However, the addition of immunosuppressive agents such as methotrexate and cyclophosphamide is usually needed. Besides, several studies have shown favorable effect and good tolerance of tocilizumab (anti-interleukin 6) treatment in TAK patients. Objectives: Our aim was to describe our experience with tocilizumab treatment in children with TAK and to review previous studies regarding tocilizumab use in TAK patients. Methods: We reviewed the charts of all pediatric TAK patients followed between 2000 and 2015 in Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey and we present the patients who were treated with tocilizumab. We screened PubMed and MEDLINE for articles involving TAK patients treated with tocilizumab.
Introduction: Behçet's disease (BD) is a chronic multisystemic vasculitis that can affect arteries or/ and veins of any size and is characterized by triple -symptom complex of recurrent oral and/ or genital aphthous ulcers and uveitis. It can also involve gastrointestinal tract, pulmonary, musculoskeletal, cardiovascular and neurological systems (neuro-Behçet). Neurological involvement is one of the most devastating manifestations, with rare reports in pediatric age range Objectives: Report a case of pediatric neuro-Behçet, emphasizing the importance of including vasculitis in the differential diagnosis when neurological disorders are associated with systemic manifestations. Methods: Chart review, checking medical history, laboratory tests and imaging of a child with Behcet's disease, according to the criteria of the International Study Group (ISG). A informed consent form was signed. Results: M.E.S., four years old, female, admitted with headache associated with dilatation of the veins on the forehead (capitus medusa), erythema nodosum and history of recurrent oral ulcers. Added to this, it was observed bilateral papilledema and thrombosis of the superior sagittal sinus extending to the left transverse sinus, suggesting a diagnosis of Behçet'disease. Corticosteroid and anticoagulation were introduced. The patient progressed with completed resolution of the signs and symptoms. Conclusion: Behçet's disease should be always considered in the presence of neurological manifestations associated with systemic involvement, avoiding permanent sequelae that affect quality of life.

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Associatiom between pediatric cutaneous polyarteritis nodosa and streptococcal infection -a single tertiary center experience Isabela H. Introduction: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of the wall of small and medium-sized arteries. Cutaneous Polyarteritis nodosa (cPAN) is the most common in pediatric population. Its etiology is unknown, but the association with streptococcal infection has been described, which suggests the indication of antimicrobial prophylaxis similar to that made in rheumatic fever. There are few studies addressing this, what motivated this study.
Objectives: Aim to evaluate the association between cPAN and streptococcal infection. Results: Fifteen patients were evaluated in this period. Two children were excluded because they did not have investigation about streptococcal infection. Thirteen patients had PAN diagnosis, three (23%) with systemic and 10 with cPAN (77%). Three patients out of four (75%) had clinical recurrence with streptococcal evidence. The number of reported cases in our service was similar to that found in the literature. Conclusion: The evidence of streptococcal infection was found in patients with cPAN at diagnosis and relapse. If the association between streptococcal infection and patients with cPAN is confirmed, prophylaxis is suggested.
Introduction: Cogan syndrome (CS) is a rare autoimmune vasculitis affecting vision by non-syphilitic interstitial keratitis and hearing by sensorineural hearing loss, tinnitus, and vertigo. Typical CS affects cornea and inner ear. However, the "atypical" variants of CS can involve kidneys, CNS and other eye structures. Objectives: A case report of a young girl with the background of episodes of ketotic hypoglycaemia, who then developed typical features of CS with significant behavioural changes and sleep disturbance, is presented. Methods: A 5 years old, Caucasian girl presented with a four week history of being unwell, red eyes, vomiting, reduced appetite and behavioural changes including sleep disturbance and keeping head tilted to left side. She was noted to be Ataxic on examination. She has been under follow up by Paediatric Metabolic team from 10 months of age, for recurrent episodes of ketotic hypoglycaemia presenting in mornings. Almost a year before presenting with CS, her sleep pattern changed markedly from prolonged sleep episodes to sleeplessness. Following this, she developed vertigo and hearing difficulties which were initially felt to be related to ear wax and episodes of otitis media. Her symptoms of sleep disturbance and behavioral changes such as reduced apetite, tiredness and tendency to keep head down and tilted to a side progressed slowly. She was originally admitted and treated as incomplete Kawasaki disease. Results: Following an ophthalmology review due to persistence of red eyes, CS was considered as a differential diagnosis due to bilateral inferior corneal epitheliopathy. Diagnosis of CS was confirmed by an MRI of head showing an enhancement of the inner ear structures, abnormal FLAIR signal and a subtle enhancement of the right iris. Her audiometry revealed high frequencies hearing loss which was in keeping with CS. The infection screen including lumbar puncture was negative except raised antistreptococcal antibody titres (ASOT). However, she did have raised inflammatory markers during her admission. Her autoantibody screen including ANA and ANCA was negative. Treatment: She received 2 doses of intravenous immunoglobulin (2 g/kg/dose) for suspected incomplete Kawasaki disease, however, it failed to resolve her symptoms leading to further investigations. Following a diagnosis of CS, she was treated with high dose intravenous methylprednisolone (30 mg/kg/dose) for 3 days, followed by a weaning course of oral prednisolone over 3 months at 2 mg/kg/day initially. She was commenced on methotrexate subcutaneously in dosage 15 mg/kg/week. A very good clinical response has been observed on this treatment. Conclusion: CS in paediatric population has been reported in the literature. However association of CS with non-ketotic hypoglycaemia has not been reported yet. Some of her symptoms associated with non-ketotic hypoglycaemia, very young age and significant procedural anxiety posed diagnostic challenge. It was classical MRI finding supported by typical ophthalmic signs which helped to prove the diagnosis. CS is usually treated by corticosteroids, followed by disease modifying agents (DMARDs) (1). The similarities between Cogan's syndrome and Kawasaki disease should be considered in differential diagnosis (2). Use of anti TNF or Rituximab to treat resistant cases has been reported (3), however, there are no guidelines available and the treatment remains experimental. We suggest collaboration with other centres to develop a data base on such a rare disease to increase awareness and develop consensus guidelines.

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Sensitivity of four criteria for Behçet's disease in Japanese pediatric patients Ken-Ichi Yamaguchi 1 , Satoshi Fujikawa 1,2 , and Working Group of Behçet's Disease, Pediatric Rheumatology Association of Japan (PRAJ) Introduction: Quadrivalent Human Papillomavirus (HPV) vaccine has been reported to be significantly associated with Behçet's disease (BD). However, no reports have described HPV infection as a possible cause for the development of BD. Objectives: The objective of this study was to evaluate whether anti-HPV antibody titer is increased in BD. Methods: Sera from 93 Korean BD patients, who fulfilled the diagnostic criteria of the International Study Group for BD, were used in an enzyme-linked immunosorbent assay (ELISA). The clinical activity of BD was evaluated at the time of blood sampling. HPV-16 L1 virus-like particle (VLP) antigen was used in this study for the ELISA. Results: Patients with BD had significantly higher antibody titers against HPV-16 (optical density [OD]: 0.210-3.675; mean 0.992) than that of healthy controls (OD: 0.248-0.762; mean 0.517; p < 0.001). Using a receiver operating characteristic (ROC) analysis, a cut-off value of 0.578 OD for the anti-HPV antibody titer was determined that differentiated BD patients from healthy controls. When we compared the clinical features of BD between the two groups, articular involvement of BD was more likely in patients with an anti-HPV-16 antibody titer <0.578 OD (p = 0.035). In addition, patients with an anti-HPV-16 antibody titer <0.578 were significantly younger than patients with a titer ≥0.578 OD. Introduction: Churg-Strauss syndrome, also known as allergic granulomatous angiitis, is extremely rare in children and is associated with higher cardiopulmonary disease and mortality rates compared to adult patients. Here, we report a twelve year-old girl with a diagnosis of CSS, who presented with prominent pulmonary involvement accompanied by eosinophilia, two-year history of asthma, peripheral neuropathy but without anti-neutrophil cytoplasmic antibody (ANCA). Objectives: A twelve year-old girl presented to our clinic with a two months history of periodic fiver, weight loss, productive cough, breathlessness, arthralgia, myalgia, muscle weakness, paresthesias of right extremities. She has a two-year history of asthma, sinusitis, urticaria, allergic rhinitis, gastrointestinal bleeding. On examination she had skin nodules on her extremities and purpuric lesions on her uncles. Methods: We present a case report of a 12 year old girl with Churg-Strauss syndrome, who were treated in a Pediatric Rheumatology outpatient center.
Results: Blood tests revealed eosinophilia, ESP-61 mm/h, CRP-192 mg/l. Chest-x ray and CT demonstrated cardiomegaly, pulmonary infiltrates in right lung andbilateral pleural effusion. Echocardiogram showed aortic and mitral valve insufficiency, EF-31%, bronchoscopy demonstrated 15% of eosinophils on BALF. Skin biopsy demonstrated necrotizing granulomatous inflammation with eosinophils. Electromyography has shown a gross violation of n. peroneus. She was treated with prednisolone (2 mg/kg -reducing with appropriate scheme) with good clinical response. ESP, CRP and eosinophil levels were normalized, but cardiopulmonary involvement sustained. Cyclophosphamide was not used (parents decision). Conclusion: Presenting case demonstrates the importance of considering the diagnosis of CSS in children with eosinophilia, uncontrolled asthma, sinusitis, skin lesions and cardiomyopathy. Sever organ involvement and delayed diagnosis may worsen prognosis and even lead to a fatal outcome. If started early, treatment with corticosteroids is often successful. Introduction: Cutaneous polyarteritis nodosa (cPAN) is a form of necrotizing vasculitis of small and medium sized arteries without visceral involvement. cPAN has often relapsing and chronic course. Some patients with cPAN are resistant to various immunosuppressive treatments and have repeated exacerbations over prolonged periods. Objectives: To report the effectiveness of tumor necrosis factor alpha (TNF-a) blockade as a therapeutic alternative for refractory cPAN. Methods: We report the patient of cPAN refractory to various immunosuppressive treatments and tonsillectomy, who was successfully treated with etanercept (ETA). We also present a review of 3 similar cases of cPAN reported in the literature. Results: Case presentation: An 8-year-old girl was referred to us with fever, erythematous papules and painful subcutaneous nodules located over her extremities and arthritis of bilateral ankles and knees. Laboratory findings revealed leukocytosis (13410/mm 3 ), elevated levels of CRP (1.4 mg/dl) and ESR (61 mm/hr). Antistreptolysin O (ASLO) titer was found to increase (2380 IU/ml). Magnetic resonance image of the thighs revealed multiple high signal nodular lesions throughout the subcutaneous tissue and subfascial muscle tissue of the thighs. A skin biopsy of a subcutaneous nodule revealed a necrotizing vasculitis. The diagnosis of cutaneous polyarteritis nodosa (cPAN) was made. She was treated with prednisolone and maintained on cyclosporine and monthly infusions of cyclophosphamide. However, flare of cPAN with fever, myalgia and painful subcutaneous nodules occurred 5 times with steroid withdrawal. Tonsillectomy was performed but flare occurred again with steroid withdrawal. ETA (12.5 mg 2 times/week) was started and led to a marked improvement of her symptoms within 3 weeks. The patient presented complete clinical remission of cPAN and continues to receive ETA and cyclosporine. Review of the literature: Three cases of cPAN successfully treated with TNF-α blockade have been reported. Two cases were treated with ETA and one patient was treated with infliximab. ETA and infliximab attenuated their symptoms and showed a corticosteroid sparing effect and no adverse effects. Conclusion: The significant improvement observed in this patient. ETA could be an effective alternative treatment for cPAN. Further larger studies is desired to establish the effectiveness of ETA as therapeutic alternatives for cPAN. Introduction: Henoch-Schönlein purpura (HSP) is the most common childhood systemic small-vessel vasculitis with skin, joint, gastrointestinal and renal involvement. Uncommon gastrointestinal complications are: intussusception, bowel perforation and rarely appendicitis. Other rare complications are: ureteritis, orchitis, pancreatitis, severe intestinal bleeding. Objectives: We evaluated complicated HSP children and followed them until remission. Methods: In the last 3 years we followed in our Paediatric Unit 90 children (age: 4-14 years) with SHP, presenting with classical signs (cutaneous vasculitis, arthralgia and/or arthritis of limbs, abdominal pain, without a complicated picture of intussusception and/or perforation and/or severe bleeding. Among these children 10/90 patients (11%) (age: 5-10 years) showed a complicated HSP with a recurrent form and an organ involvement. Results: 7/10 patients showed an intestinal involvement with severe abdominal pain and persistent bleeding; 4 patients had severe and prolonged intestinal bleeding, resistant to steroids. 2/7 patients developed a persistent nephritis with proteinuria and hypertension. One patient with intestinal bleeding developed a pancreatitis with persistent and significant amylase and lipase increase; 4 patients had orchitis. All the patients were treated with methylprednisolone (1-2 mg/kg/ day), with a mild tapering of steroids. In the 2 children with nephritis amlodipine was associated. All the patients had a slow and progressive ameliorating outcome, with a complete remission. Clinical presentation and biochemical parameters at the disease onset were not predictive of a poor outcome. During the acute phase of the complications, factor XIII of the blood coagulation system was detected: it was in the normal range in 6/7; it was reduced in one. Conclusion: Most of the children affected by HSP have an excellent prognosis, however a few cases develop a complicated form, witch need steroid and/or a combined treatment with anti-hypertensive and immunosuppressive drugs. In our population, 8% showed a complicated form, however all the patients did not show long-term sequelae.

Disclosure of Interest None Declared
Introduction: The etiology of Immunoglobulin A vasculitis (IgAV), the most common childhood vasculitis in western countries, remains unclear. Changes over time in its epidemiology could guide in the search of a causal pathway. Objectives: We aimed to describe the epidemiological characteristics of childhood IgAV in a large French population. Methods: Cases were prospectively collected in Val de Marne county, a southeastern suburb of Paris, with 263 874 residents <15 years old. Children with incident IgAV living in this area from 2012 to 2014 were identified by 4 sources of case notification (emergency departments, pediatrics departments, private practice pediatricians, general practitioners). We calculated 95% confidence intervals (95% CIs) for incidence rates under the assumption of a Poisson distribution. Foursource capture-recapture analysis was performed using log linear modeling to estimate the completeness of case finding. Socioprofessional factors, ethnicity, seasonal and geographic variations in IgAV incidence were investigated. Results: The survey identified 147 incident cases meeting the study criteria, including 78 (53%) boys and 69 (47%) girls with a mean age of 6.5 years (2.2-14.7 years). The overall annual incidence (per 100,000 children) was 18.6 (95% CI 13.6-24.5), with 19.3 (12.6-28.3) for boys and 17.8 (12.8-26.7) for girls. The capture recapture analysis estimate the completeness of case finding at 62% (95% CI 50-81) with an annual incidence of 29.9 (95% CI 23.7-37.3). The annual distribution of diagnoses significantly deviated from a random distribution and indicated a nadir in summer months. Neither socioeconomic factors nor environmental factors like industrialization or pollution appear to play a role. Conclusion: Our annual incidence rate of 18.6 to 29.9 per 100,000 children, gender distribution and seasonal variation are in line with data reported worldwide and show no significant periodic or secular variation over time. IgAV seems to be trigger by an indeterminate infection shared by children in community. The impact of genetic, as predisposing factor, need to be more explore in particular the role of innate immunity.

Disclosure of Interest
None Declared Introduction: In paediatric rheumatology practice, systemic vasculitides associated with primary immunodeficiency disorders are highly challenging conditions.

Objectives:
The aim of this presentation is to report the clinical course and response to treatment in two sisters suffering from systemic vasculitis associated with unclassified hypogammaglobulinaemia. Methods: We retrospectively evaluated the medical records of both sisters. Results: The first case was a girl, born from non-consanguineous parents. At the age of 1.66 years old, she suddenly presented high fever, nonspecific maculopapular rash, athralgia, myalgia with elevated levels of acute phase reactants and prompt response to steroids. One year later, the above manifestations relapsed. A skin biopsy showed interstitial granulomatous dermatitis in association with vasculopathy. At 3 years old she developed recurrent cranial nerve palsies and livedo reticularis and then two stroke events at the age of 4 (one ischemic and the other hemorrhagic). Magnetic resonance angiography showed no evidence of cerebral vasculitis and the biopsy of the brain performed as part of the surgical procedure for the hemorrhagic stroke showed only extravasation of erythrocytes and fibrin deposition around small vessels, without significant inflammation. The antibody profile (including antiphospholipid antibodies) and clotting tests were negative. Hypogammaglobulinemia with global Ig deficiency was present from the onset of the disease and persistent in time. She could not be considered common variable immunodeficiency disorder because total serum IgG levels were not constantly reduced below 500 mg/dl. As part of a research study, she was also diagnosed with complete C4B deficiency. At the age of 5 years old she developed moderate thrombocytopenia which persisted for the next 3 years. At 5.5 years old she was also diagnosed with nodular regenerative hyperplasia (NRF) of the liver. For the first 2 years of evolution, only high dose of corticosteroids was able to control the disease manifestations. Methotrexate, azathioprine, cyclosporine, cyclophosphamide were ineffective. Conversely, mycophenolate mofetil (MMF) associated with high monthly doses of IGIV provided prompt and persistent improvement of clinical symptoms and acute phase reactants and also tapering of steroid dose. Till now, under MMF, no recurrences have been observed, but the NRH was slowly progressive. No portal hypertension has been developed so far. Case 2, the older sister of the above patient, had the first disease manifestations at 6.8 years old. Since then, she developed the following disease features: fever, myalgia, painful subcutaneous nodules, livedo reticularis, low serum IgM and IgG4, elevated acute phase reactants, negative antibody profile, recurrent abdominal pain, systemic arterial hypertension, one episode of massive intestinal bleeding which had no obvious source at total colonoscopy, upper endoscopy and computed tomography angiography. The biopsy of a subcutaneous nodule revealed leukocytoclastic vasculitis. In her case, MMF induced only a partial remission. The association of tacrolimus permitted rapid control of the disease activity. Up to now, no neurological signs were present. The recently described genetic disorder "deficiency of ADA2" is being considered in both sisters, but yet unproven. Conclusion: Aggressive medical management is often necessary and therefore the rate of drug related morbidity in high. The response to the various treatments is variable, even between siblings.

Disclosure of Interest
None Declared Introduction: Henoch-Schönlein purpura is the more often vasculitis in pediatric population, it is characterized for being a small vessel leucocitoclastic vasculitis; it has an incidence between 10 to 20.4 cases per 100,000 children, with a predominance of male sex 2:1. Etiology remains unknown. Given the tendency for spontaneous resolution of disease treatment in most cases will be supportive. There is no evidence of the benefits of renal disease treatment, mainly because few patients have severe disease at baseline. Objectives: Identify factors of poor renal prognosis in mexican children with Henoch-Schönlein purpura diagnosis. Methods: A transversal comparative study in a cohort of 79 patients diagnosed with HPS over a 5 years period in Hospital Infantil de Mexico, Federico Gomez. We realized parametric, descriptive, comparative, correlation and likehood ratio test were performed Results: In this study, they were evaluated a total of 79 files of patients with this diagnosis; 47 female patients and 32 male patients, with a 1.6:1 relation women dominate; the mean age presentation was 82 months, predominating in autum with 34.7% and spring with 27%. 100% of patients debuted with characteristic purpuric rash, gastrointestinal symptoms were presented in 35%, 76% presented joint disease during the disease onset; as to kidney disease nephritis was found during the debut in 19% (n = 15) and elevated creatinine in 5.1% (n = 4), to which were subsequently performed renal biopsy, histological lesion more frequently found was mesangial proliferation glomerulonephritis in less than 50% of glomeruli (grade IIIa) that was found in 4 of 4 patients, currently a patient is on replacement therapy with hemodialysis, with an average of 0.5 mg / dL ± 0.11 with a maximum of 13 mg found / dL. Conclusion: Statistical correlation tests of our study are consistent with other studies published in the literature, finding a statistically significant correlation between the presence of elevated at diagnosis and relapse with p = 0.011 creatinine. As prognostic factors for relapse reported in the literature we found that the presence of initial nephritis is a prognostic factor p ≤ 0.001 relapse and complications with a value of p = 0.025. In that order we can extrapolate the results of international studies to our population.

Disclosure of Interest
None Declared Introduction: The Henoch-Schönlein Purpura (HSP) is the most common vasculitis in children, mainly involving the skin vessels, joints, gastrointestinal tract and kidneys. Kidney involvement remains the main cause of morbidity and mortality in children. Nephritis occurs in 30 -50% of patients during the first 4 to 6 weeks, but with a risk of appearance during the first 5 years. The spectrum of kidney involvement ranges from mild manifestations until the development of a nephrotic and/or nephritic syndrome or kidney failure. Some predicting risk factors have been identified for the development of nephritis: persistent or recurring purpura, severe abdominal symptoms, older age at debut and disease relapse. Renal prognosis has been associated with kidney biopsy findings. The aim of the study is to determine the clinical features and kidney involvement during the first year of follow-up.
Objectives: Determine the clinic features at debut and kidney involvement of patients with a final diagnosis of HSP during the first month, 3 months and until the first year of follow-up. Methods: Retrospective study of patients with a final diagnosis of HSP in a Pediatric Rheumatology service. A single form of data collection was applied in an institution of Bogota, Colombia during the period comprised between 2010 and 2016 Results: N = 86 patients, 42 girls and 44 boys. Median age at disease onset was 5.3 years SD 2.4 years (range 1 -14 years). At HSP diagnosis all the patients had palpable purpura,70.9% abdominal pain and 88.4% arthritis. Kidney involvement was present in 39/86 patients (45%). 22/39 (56%) patients had renal involvement at diagnosis: Isolated proteinuria was the most frequent finding 10/22 (45.4%) and 3 patients had nephrotic syndrome.12 patients (31%) had kidney involvement within the first month (50% had isolated proteinuria and 50% proteinuria/hematuria). Between the first and third month 2 (5%) patients had renal manifestations (all isolated proteinuria). Between 3 months and 12 months follow-up 3 patients (8%) had kidney compromise: one hematuria, one isolated proteinuria and one hematuria/proteinuria. A trend was observed to kidney involvement in patients with abdominal symptoms (p = 0,053). Renal biopsy was performed in 8/39 patients with HSP nephritis. Mesangial proliferation was the most common finding in 6/8 patients, sclerosis in 3/8 patients (1 patient with nephrotic syndrome and 2 patients with proteinuria/hematuria). There was no evidence of crescents in any of the biopsies. The mean follow-up was 26.8 months SD 17 months (range 1 -72); there was no evidence of kidney damage in the last assessment in any of the 39 patients with kidney involvement. Conclusion: In this group of patients, kidney involvement was more severe and common in the first weeks of the disease onset. The active search and education of families during the first 4 weeks of HSP onset is essential. In severe forms, it is important to conduct a kidney biopsy in order to document poor prognostic factors and adjust treatment.

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T helper 17 (Th17) and T regulatory (Treg) cells in children with Kawasaki diseaseexperience from a tertiary care centre in North India Sagar Bhattad 1 , Amit Rawat 1 , Biman Saikia 2 , Ranjana Minz 2 , Jitendra Shandilya 1 , Surjit Singh 1 and Pediatric Allergy and Immunology Unit, PGIMER, Chandigarh 1 Pediatrics, PGIMER, Chandigarh, India; 2 Immunopathology, PGIMER, Chandigarh, India Presenting author: Sagar Bhattad Pediatric Rheumatology 2017, 15(Suppl 1):P153 Introduction: Kawasaki disease (KD) is an acute necrotizing vasculitis with predilection for coronary arteries. Acute KD has been associated with abnormalities in T-helper 17 (Th17)/ T-regulatory (Treg) cells and a high Th17/low Treg profile predict poor outcome in acute KD Objectives: To assay Th17 and Treg cells in children with acute KD Methods: Ten children with acute KD diagnosed at the Advanced Pediatrics Centre of our institute during Jan-Dec 2015 were enrolled after obtaining written informed consent from parents/guardians. Diagnosis of KD was based on American Heart Association (AHA) criteria. Children were treated with 2 g/kg of intravenous immunoglobulin (IVIg) which was given over 12-24 hours. Aspirin was administered at a dose of 50 mg/kg initially until the children were afebrile for atleast 48 hours and later changed to anti-platelet dose. Seventeen healthy children and 9 febrile patients (not suffering from KD) were enrolled as controls. Th17 and Treg cells were estimated at admission (pre-IVIg) and at 4-8 weeks of follow-up in cases. Samples for febrile controls were drawn only at the first instance. Estimation of Th17 and Treg cells was carried out by flow cytometry using the Th17/Treg phenotyping kit-catalog no. 560762 (BD Biosciencies) as per manufacturer's recommendations. This kit contains PerCP-Cy5.5 labeled anti-CD4, Phycoerythrin (PE) labeled anti-IL-17 and AlexaFluor labeled anti-FoxP3 antibody Results: Male: female ratio amongst cases was 4:1. Mean age at onset of KD was 4.45 years and the youngest child was 6 months old. Mean duration of fever at presentation was 10.7 days and 60% of children presented beyond 10 days of onset of fever. Conjunctival injection and oral mucosal changes were noted in 50% and 70% respectively while cervical lymphadenopathy and rash each occurred in 60% of our cohort. Extremity edema was noted in 50% while periungual/ perineal peeling of skin was noted in all. 40% of the children had incomplete KD. Coronary artery abnormalities (CAA): coronary dilatation was noted in 3 cases at admission (left anterior descending artery in 2, left main artery in 1), which resolved at follow-up of 6 weeks. Two amongst these were subjected to CT-coronary angiography during follow up, which were normal.
Proportions of Th17 and Treg cells in cases and controls have been tabulated below. Th17 cells were increased in acute phase of KD as compared to febrile controls (2.58% vs 1.57%, P = 0.27) and healthy controls (2.58% vs 2%, P = 0.21). Treg cells were decreased in children with KD during acute phase as compared to febrile controls (0.99% vs 1.96%, P = 0.62) and healthy children (0.99% vs 2.37%, P = 0.45). Following treatment with IVIg, Th17 cells decreased (2.58% vs 1.88%, P = 0.13) and Treg cells showed an increase (0.99% vs 2.64%, P = 0.07), however, this difference was not statistically significant. No significant difference was noted in Th17 and Treg % between cases who had CAA and those who did not.
Conclusion: Th17 cells were elevated and Tregs were reduced during acute KD as compared to febrile and healthy controls; the difference, however, was not statistically significant. A larger study to assess the same differences is recommended to confirm the differences of statistical significance. Introduction: Majority of patients with Kawasaki disease (KD) are believed to have subclinical myocardial involvement that predispose to an increased risk of developing ventricular arrhythmia resulting from inhomogeneous ventricular repolarization. This inhomogeneous ventricular repolarization manifests as increased QT dispersion on electrocardiography. Though there are a few studies on QTd in patients with KD and persistent coronary abnormalities, there is paucity of literature on QTd in children with KD and transient coronary abnormalities. Objectives: The present study was undertaken to study QT dispersion in children with KD and transient coronary artery abnormalities during follow-up. Methods: Twenty children with KD and transient coronary artery dilatation that resolved within 1 year of diagnosis (mean age 11.5 ± 3.7 years; range between 5.1 to 19.6 years) were studied at least 1 year after resolution of coronary artery abnormalities. Diagnosis of KD was based on standard guidelines of the American Heart Association. As per unit protocol, treatment included intravenous immunoglobulin (IVIg) infusion (2 g/kg) along with aspirin (30-50 mg/kg/day during acute stage followed by 3-5 mg/ kg/day for 4-6 weeks or until resolution of CAA, whichever was later). Mean interval between onset of KD and IVIg infusion was 11.05 ± 6.24 days. 20 healthy controls, matched for age and sex, were also enrolled. 12 lead ECG was done in all cases and controls. A single blinded observer used the digital caliper to measure the intervals with least count of 0.01 mm. The difference between the maximum and minimum corrected QTc intervals was calculated as the QTc dispersion. As only two of the six extremity leads are recorded and the remaining 4 leads are mathematically derived, QTc dispersion was also calculated in 8 leads. These included the 6 precordial leads, shortest extremity lead, and median of other 5 extremity leads. Results: Mean follow up of patients was 53.70 ± 22.52 months after acute episode. Mean interval between normalization of transient coronary dilatations and enrolment in this study was 50.55 ± 22.67 months (range of 12 -79 months). Mean QT dispersion (QTd) in cases calculated from 12 leads was 0.057 ± 0.018 seconds compared to 0.059 ± 0.015 seconds in controls (p = 0.785). Mean QT dispersion in cases calculated from 8 leads (QTd8) was 0.052 ± 0.017 seconds in cases and 0.056 ± 0.017 seconds in controls (p = 0.442). Corrected QT dispersion in 12 leads (QTcd) was 0.079 ± 0.028 seconds and 0.081 ± 0.028 seconds in cases and controls respectively (p = 0.747). Corrected QT dispersion in 8 leads (QTcd8) was also not found to be significantly different between cases (0.072 ± 0.022 seconds) and controls (0.078 ± 0.026 seconds; p = 0.441) Conclusion: QT dispersion in children with KD and transient coronary artery abnormalities was not found to be significantly affected in long term follow up.  Introduction: Fibromuscular dysplasia (FMD)hyperplastic disease, is caused by a mutation in the gene of type III collagen (135580, 2q31, COL3A1), characterized by lesions of the kidney, at least -carotid and other major arteries. According to the literature the FMD of renal arteries is second (10-15%) in the structure of renovascular hypertension (RVG). In some cases, clinically FMD may be asymptomatic. However, the possibility of RVG, the instrumental detection of the deformation of large arteries is the reason for the conversion to a rheumatologist and a cardiologist with the assumption TA the patient. Objectives: Common to FMD and TA are gross vascular murmur in the projection of the large arteries, the possibility of VAG, deformation and thickening of the large arteries, detected by instrumental research. In contrast to TA, while no FMD laboratory signs of inflammatory activity. Angiography can reveal a kind of defeat of large arteries throughout the "string of pearls", "rosary" -thick, hardened areas of the arteries with hyperplasia interspersed with less altered areas, while at TA, affects primarily the mouth of the large arteries and possibly the aorta. Methods: We observed 7 children with FMD -4 girls and 3 boys ranging in age from 11 to 17 years (mean age at the time of detection of arterial hypertension 13.5 years -13.4 ± 1.05). Compared the results of clinical, laboratory and instrumental (Doppler ultrasound, MRI, angiography) examinations in 6 patients with FMD and 38 with a documented diagnosis of TA.

Disclosure of Interest
Results: at the onset in all children with suspected FMD TA in identifying RVG, not amenable to standard anti-hypertensive therapy, the presence of vascular noise in the projection of the large arteries and the data of instrumental examination (Doppler ultrasound -thickening of artery walls and increased linear velocity of blood flow). However, all patients were not inflamatory syndrome at the beginning, typical for the acute phase of TA and laboratory signs of activity throughout the observation period. For differential diagnosis, along with named above instrumental methods of examination, and in 4 children was used positron emission tomography, allowing to estimate objectively the absence of active inflammatory process in the walls of arteries. Surgical treatment was performed 5 of the 7 patients with FMD. In 2 patients, in marked stenosis of the renal arteries, attempt balloon angioplasty did not lead to the desired effect. Only autovenous bilateral aortorenal prosthesis has allowed everyone to stop RVG. Conclusion: Deformation of the aorta and its branches with vascular dysplasia leads to difficulties of differential diagnosis with nonspecific aortoarteritis. The lack of inflammatory syndrome at disease onset and laboratory signs of activity during the whole follow-up period in the presented clinical case are not allowed to confirm the diagnosis of Takayasu arteritis. Revealing as a new differential diagnostic method of research is positron emission tomography, allowing to estimate objectively the absence of active inflammatory process in the walls of arteries. Introduction: Childhood polyarteritis nodosa (cPAN) is a systemic inflammatory disease characterized by histopathological evidence of necrotizing vasculitis or angiographic abnormalities. The classification criteria for cPAN involve the angiographic detection of visceral aneurysms and conventional angiography remains the overall gold standard. There are limited numbers of publications about the use of noninvasive imaging modalities in the diagnosis of cPAN.

Disclosure of Interest
Objectives: The aim of this study was to present the clinical and imaging findings of the patients with cPAN who were diagnosed with non-invasive imaging techniques. Methods: Files of patients who had been diagnosed as cPAN in our department from 2005 to 2015 were evaluated, retrospectively. Demographic, clinical, laboratory and imaging findings of the patients were evaluated. Results: Nine patients (8 M, 1 F; age at disease onset: 12,5 years (7-16)) had been diagnosed as cPAN in our clinic with non-invasive imaging techniques within the last 10 years. Abdominal pain, fever, fatigue and myalgia were the most frequent complaints. Doppler ultrasonography (US) was used in the diagnosis of 7 patients and computerized tomography (CT) angiography was done in 4 patients. Duration between admission to our center and diagnosis was median of 5 days, including 4 patients who were diagnosed within 24 hours of admission. Approximately 80% of our patients with cPAN had MEFV mutations and 90% had elevated ASO levels. All of them had the involvement of the gastrointestinal tract. Hepatic and cystic arterial involvements were detected in 7 and 6 patients, respectively.
Conclusion: This report included the largest cPAN series that were diagnosed with noninvasive imaging modalities. We suggest that noninvasive modalities, especially Doppler US should be considered in first line approach in the diagnosis of these patients, particularly in children.  Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a severe immune-inflammatory childhood disease characterized by arthritis and systemic features, such as quotidian fever, rash, lymphadenopathy and serositis.

Disclosure of Interest
Objectives: The role of natural killer (NK) cells in sJIA pathogenesis remains unclear. Therefore, we investigated the phenotype, functionality and gene expression of NK cells in sJIA patients.  Introduction: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions that are unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA that is characterized by episodic systemic inflammation and chronic arthritis. Approximately half of children with sJIA go on to develop destructive, life-long arthritis that has phenotypic similarities with the oligoarticular/seronegative polyarticular (polygoJIA) or seropositive polyarticular (RFpolyJIA) forms of JIA. Importantly, elevated until month 3. The patient remained free from clinical symptoms for now 3 months. Thus, the patient remained in clinical remission after a single injection of canakinumab without any antirheumatic treatment. Conclusion: First experience with first line treatment with canakinumab for systemic JIA is presented. A single sq. injection of canakinumab, a monoclonal anti-IL-1ß antibody with prolonged plasma half life, completely suppressed disease activity in a toddler with systemic JIA and normalized inflammatory parameters and biomarkers . This treatment clearly showed advantage over daily sq. injections. Early steroid free treatment with canakinumab may lead to long lasting remission via decreased inflammasome activation and reconstitution of NK-cell function, and eventually cure of the disease. Aside, unwarranted effects of long lasting steroid application was avoided.