Proceedings of the 24^th Paediatric Rheumatology European Society Congress: Part one

Introduction: Juvenile-onset Systemic Lupus Erythematosus (JSLE) is a severe autoimmune disease causing organ damage and long-term morbidity. Impaired clearance of nuclear debris from cells and upregulated circulating damage-associated molecular patterns (DAMPs) and cytokines are thought to trigger cell death and thus, further increase release of pro-inflammatory molecules following the cytosolic assembly of inflammasomes.

Objectives: To investigate the role of pyroptotic cell death in JSLE, which occurs following the assembly and activation of the NLRP3 inflammasome, which may be a promising target in the treatment of JSLE and other inflammatory diseases.

Methods: THP-1 cell line-derived macrophages (Mφs) were primed using lipopolysaccharide (LPS; 10 ng/ml) and interferon (IFN) γ (20 ng/ml) in complete media at 37 °C for 24 hours, and subsequently treated with 10 mM Adenosine triphosphate (ATP) for 30 min. Primed Mφs not treated with ATP were used as a negative control. Some Mφs were incubated with 10% JSLE patient sera or NETosis-derived material (10 ng/ml) from PMA-treated neutrophils. Primed Mφs were tested for cell surface markers, HLA-DR, CD282 (TLR2), and CD68 using flow cytometry. ATP-treated Mφs were collected and either assayed for pyroptosis marker, lactate dehydrogenase (LDH) activity, cleaved caspase-1 with immunofluorescence (IF), or lysed for cleaved caspase-1 using western blotting.

Conclusion: Overall, the results indicate that Mφs undergo pyroptosis via the NLRP3 inflammasome when challenged with a two-signal approach of priming and ATP, and that cytokines, nuclear debris and DAMPs may not only trigger, but amplify the inflammatory response of this pathway. The NLRP3 inflammasome is thought to be an important mediator in the pathogenesis of certain inflammatory diseases, and flare episodes associated with JSLE. Further work is planned to investigate the role of the inflammasome in JSLE, using pharmacological interventions with specific known and novel inhibitors of the NLRP3 inflammasome. This work could prove the NLRP3 inflammasome to be a promising target for future therapy for JSLE.

Disclosure of Interest: None Declared

Introduction: Clinical management of polyarticular JIA with anti-TNF-alpha biologics has been met with significant success, with up to 80% of patients demonstrating clinically meaningful efficacy. Concerns about medium/long term drug toxicities and costs have driven the clinical need to find predictors for successful drug discontinuation. Emerging evidence from previous published data indicate that T cells play a crucial role in the disease progression. Defining the pathogenic subsets and mechanisms within the T cell immunome will likely help stratify patients in terms of therapeutic outcomes.

Objectives: We seek to distill this pathogenic signal hidden within the T cell compartment through the utilisation of a high dimensional platform, CyToF, that is capable of phenotyping up to 41 markers at a single cell resolution. JIA patients treated with anti-TNF-alpha biologics were recruited in the Understanding TNF-alpha trial and segregated into flare, active and inactive arms after drug discontinuation. The central aim of this project is to identify pathogenic immune mechanisms of clinical relapse and signatures capable of distinguishing clinical fates.

Methods: Patients treated with anti-TNF-alpha biologics were recruited into the study (Improved Understanding of the Biology and Use of TNF inhibition in Children with JIA Trial) with clinically inactive disease on treatment (Wallace criteria) and initiated with therapy discontinuation. The patients were followed and evaluated as flare, inactive and active based on 6 JIA core set parameters; number of joints with active arthritis and/or loss of motion, MD global assessment of current disease activity, patient/parent global assessment of overall disease severity in prior week, a validated measure of physical function and ESR. Healthy paediatric controls without any inflammatory diseases were recruited from the day surgery during intravenous plug setting pre-operatively after informed consent.

Conclusion: There exists a group of patients (flare) for which biologic therapy with anti-TNF-alpha is merely controlling the disease activity but not curative. The persistence of CD4 memory cells are likely to play a pivotal role in disease relapse, that may be partially explained by a weaker control through immune checkpoints (CD152/PD1) or interaction with B cells. These results suggest that clinical fate is immunologically predetermined and patients who will develop different clinical fates can be identified from prior biologic sampling.

Disclosure of Interest: None Declared.

Introduction: Systemic Lupus Erythematosus (SLE) is a multi-factorial autoimmune disease and the conventional oligo-dimensional investigative approach involving one or a few cell types or analyses at a time is inadequate for its study. We hypothesize that abnormalities within multiple components of the immune system contribute to lupus pathogenesis and hence, there is a need for a comprehensive interrogative analysis.

Objectives: We aim to employ a multi-dimensional holistic approach using mass cytometry to study the immunome of childhood onset SLE (cSLE) patients and unravel the immune derangements involved in its pathogenesis. This will address the critical unmet need for a simultaneous and holistic interrogation of the different immune cell subsets in cSLE.

Conclusion: A holistic multi-dimensional approach was able to distill multiple derangements in the cSLE immunome with clinical and mechanistic significance. The identification of a B cell subset with phenotypic markers indicative of its ability for antigen presentation (HLA-DR, CD86) and T-B cell interaction (CD25, CD40) in the cSLE cohort highlights that the immunopathogenic role of B cell in SLE goes beyond antibodies production and immune regulation. Additionally, the concurrent demonstration of an increase in memory CD4 regulatory cells and B regulatory cells in the diseased cohort is consistent with our hypothesis that multiple immune abnormalities are involved in SLE pathogenesis. These findings have the translational potential to unravel the pathogenesis of lupus and identify the cellular subsets for further in-depth mechanistic and functional studies for the eventual goal of developing novel therapeutics.

Disclosure of Interest: None Declared.

Objectives: Our group has collected blood for RNA-Seq analysis from children diagnosed with AAV from centres around the world. Transcriptome analyses were conducted in an attempt to detect biomarkers for MPA and GPA that will help determine disease etiology and assist physicians in patient classification.

Results: Hierarchical clustering based on Euclidean distances between samples placed samples into three clusters. Cluster one is composed of only three samples, while clusters two and three are composed of 14 and 15 samples, respectively. Cluster two contains primarily samples from individuals who were classified (via the EMA algorithm) as having MPA or unclassifiable SVV (10/14 samples), while cluster three contains primarily samples from individuals who were classified as having GPA or unclassifiable SVV (14/15 samples). DE analysis between clusters two and three showed 3,198 differentially expressed genes. The MPA cluster is enriched for pathways including interferon signaling, the ISG15 antiviral mechanism, TCR signaling and adaptive immunity. Conversely, the GPA cluster is enriched for pathways including interleukin signaling, TLR4 signaling, and phagosomal maturation. These enriched pathways suggest a viral and adaptive immunity signature for MPA and a bacterial and innate immunity signature for GPA.

Conclusion: The identification of preliminary etiologies for GPA and MPA is the first step toward assisting clinicians in developing improved molecular diagnostics for disease classification, and suggest an opportunity for seeking different treatment paradigms for the management of these two diseases.

Disclosure of Interest: None Declared.

References 1. Barut, K. et al. 2016. Curr Opin Rheumatol 28:29.

Introduction: Childhood onset SLE is a lifelong heterogeneous autoimmune disease that follows a more severe clinical course than adult-onset SLE. Previous studies have shown that HRQoL is impaired in cSLE, little is known which factors influence HRQoL. Fatigue, depressive symptoms and skin/mucosal symptoms (leading to changed physical appearance and potential lower self-esteem) may play an important role for a patient’s HRQoL.

Objectives: To determine the prevalence of fatigue, depressive symptoms and skin/mucosal symptoms in adults with cSLE and examine the relation with HRQoL

Methods: 106 adults with cSLE were included in the CHILL-NL (CHILdhood Lupus-NetherLands) study including a single study visit for structured history, physical examination and SLEDAI-2 k. HRQoL was assessed with SF-36. Fatigue was assessed with Fatigue Severity Scale (FSS) with scores range from 1 to 7. FSS score ≥4 defines abnormal fatigue. Beck Depression Inventory (BDI) was used for depressive symptoms. BDI score ≥14 is indicative for major depressive symptoms.

Results: 92% of cSLE patients were female and white (73%). The median age at study visit was 33 yrs, median disease duration was 20 years, 61% had developed damage (SDI ≥1). HRQoL of cSLE patients was impaired (7/8 domains SF36), remarkably mental health was similar between patients and Dutch norm data. Patients with damage (SDI ≥1) scored remarkably similar on all HRQoL domains, except for the domain ‘physical functioning’. 68% of cSLE patients were abnormal fatigued (FSS score ≥4). 15% were depressive (BDI-score ≥ 14). HRQoL (6/8 domains SF36) was lower in all patients with fatigue but also in those with major depressive symptoms. The median SLEDAI-2 k score was 4, 31% of cSLE patients had ≥ 1 skin/alopecia/mucosal ulcers and its presence was associated with lower HRQoL.

Conclusion: HRQoL in this large cohort of adults with cSLE was not associated with disease damage, but self-reported fatigue- and major depressive symptoms were. Additionally physical appearance (skin/alopecia) and mucosal symptoms had a clear impact on HRQoL.

Disclosure of Interest: None Declared.

Introduction: A proportion of patients with Juvenile-onset Systemic Lupus Erythematosus (JSLE) will have lupus nephritis (LN) as part of their initial presentation, but others will go on to develop this manifestation later [1, 2]. Early recognition and appropriate management of LN is important as early response to treatment is known to be associated with better renal outcomes [3]. Identifying those with or at risk of developing LN is important, so that clinicians can be extra vigilant in monitoring for LN development.

Objectives: (1) To characterise patients with LN at baseline, and how they differ from patients without LN in terms of clinical and demographic factors. (2) For those without LN at baseline, who develop it at a later stage, to determine (a) when they develop LN and (b) whether there are clinical and demographic predictors at baseline which can predict subsequent development of LN.

Methods: Participants of the UK JSLE Cohort Study, between 2006-2016, were included if they had active LN at the time of their initial presentation to paediatric rheumatology care (referred to as ‘baseline’ throughout), or subsequently developed LN. Univariate logistic regression modelling compared clinical/demographic factors of patients with/without active LN at baseline. Those without LN at baseline were followed longitudinally, monitoring for LN development. The association between outcome (time from baseline visit to the development of LN) and clinical/demographic variables at baseline was tested univariately using Cox Proportional hazard modelling. Covariates with a p < 0.2 on univariate analysis were included in a multiple regression model and backward stepwise model selection applied. HRs, 95% CIs and p-values were summarised for covariates present in the final model and the results were displayed graphically with Kaplan-Meier curves and risk tables.

Results: 331 JSLE patients were included in the study. A total of 121/331 (37%) of UK JSLE Cohort Study patients were found to have active LN at baseline. Of the 210/331 patients without LN at baseline, 13 only had a single study visit and were therefore excluded from further analyses. A further 34/197 (17%) patients were found to develop LN after a median of 2.04 years [IQR 0.8-3.7]. Six clinical/demographic factors were found to differ significantly between those with/without LN at baseline. These included the patient’s first ACR score (p = 3.6 x10-6), presence of severe hypertension (p = 0.0006), level of proteinuria (p = 5.7x10-12), serum creatinine (p = 0.00024), ESR (p = 0.00075) and C3 (p = 1.3x10-7). Within the multiple regression model, both ACR score (p = 0.014) and C3 levels (p = 0.0082) at baseline were also significant predictors for subsequent LN development. Patients with a higher ACR score and a lower C3 value at baseline were at greater risk of developing LN at any point in time (ACR score: HR 1.45, 95% CI 1.08-1.95 and C3: HR 0.27, 95% CI 0.10-0.68).

Conclusion: Using clinical data from the UK JSLE Cohort Study, this study has explored the ability of basic clinical and demographic factors at baseline for stratifying JSLE patients as ‘high or low risk’ for LN development at baseline or during their subsequent disease course. Consideration of such factors may help the clinician when considering the individual patients LN risk.

Introduction: Reactive oxygen species (ROS) were primarily considered as harmful mediators of inflammation due to their ability to damage proteins, lipids, nucleic acids and matrix components. However, accumulating evidence point towards an immune-regulatory role of ROS with inflammation-limiting effects and the ability to prevent autoimmune diseases. Thus, a deeper analysis of ROS induced pathways in different immune cells is crucial to understand the ambivalent role of ROS molecules.

Objectives: The aim of our study was to analyse the effects of ROS and oxidative stress on the immune response by deciphering the role of Nrf2 – the key transcription factor of the oxidative stress response – in immune cells.

Conclusion: Thus Nrf2 is a critical transcriptional regulator for a myeloid cell population that plays a major regulatory role in inflammation and infections. Modulation of MDSCs via targeting of Nrf2-dependent metabolism provides ample opportunities for therapeutic manipulation of MDSCs depending on clinical necessities.

Disclosure of Interest: None Declared

Introduction: Juvenile dermatomyositis (JDM) is a complex heterogeneous autoimmune disease. Clinical markers are imperfect to correlate with disease activity. Broad proteomic analysis with high sensitivity and reproducibility may be used biomarker discovery. Novel biomarkers from peripheral blood may help characterize pathogenesis and improve disease monitoring and treatment.

Objectives: To define protein biomarkers dysregulated in JDM and better understand JDM pathogenesis using novel aptamer-based proteomic technology proteome in a well-characterized JDM cohort.

Methods: Unbiased internal discovery and validation analysis was done using broad proteomic analysis of 1306 protein targets using SOMAscan assay of slow off-rate modified aptamers (SomaLogic, CO) which generates simultaneous quantitative results with high sensitivity and reproducibility. In a discovery cohort, 27 JDM patient sera (prevalent cases on variable treatment, average physician global activity or PGA mean 3.9/10 visual analog scale, with 14 anti-p155/140 or TIF1, 6 NXP2, and 7MDA5 myositis specific autoantibodies or MSAs) was compared versus 19 age and gender-matched healthy controls or HC sera using Mann Whitney U FDR <0.10 cutoff. Resulting protein targets were subsequently analyzed in validation cohort sera (14 prevalent JDM cases with similar characteristics including MSA distribution vs 9 HC) using the same cutoff. Resulting proteins with expression ratio of >1.3 were analyzed using Ingeunity Analysis or IPA (Qiagen, CA). The top 10 pathways were then manually clustered to minimize protein overlap with at least 1 unique protein per pathway cluster. Exploratory analysis of the same set of significant upregulated proteins in JDM were analyzed for correlation with PGA by Spearman rank test.

Results: 311 protein targets met above criteria from the discovery cohort; 166 unique proteins met criteria after analysis in the validation cohort. 80 of these proteins were upregulated in JDM versus HC and 59 had expression ratio of >1.3. From IPA analysis, 28 proteins fit into 6 pathway clusters: type I IFN notably including IFN beta, granulocyte/agranulocyte adhesion and diapedesis, remodeling/damage, acute phase response, Th1 pathway, and adipokines. There were between 1-7 unique proteins per pathway cluster but many proteins fit into more than 1 pathway cluster. Among the 10 most highly expressed proteins, the most common associated pathway cluster is type I IFN with granulocyte/agranulocyte adhesion as the second most common. 13 proteins had significant moderate correlation with PGA in JDM from varied pathway clusters with Spearman r values of 0.32-0.41. Further analysis by MSA group is ongoing.

Conclusion: Broad quantitative proteomic analysis in a well-characterized JDM cohort identifies key differentiating pathway clusters as above in JDM versus HC including many novel proteins, 13 of which have moderate correlation with PGA. Top upregulated proteins are most commonly associated with type I IFN pathway cluster, with granulocyte-agranulocyte adhesion and diapedesis as the second most common pathway cluster. Further analysis by MSA group is ongoing. While in need of confirmation in other cohorts, these proteins identified through a high-throughput screen bring to light new pathways that may be important in JDM.

Disclosure of Interest: H. Kim Grant/Research Support from: Cure JM Foundation, A. Biancotto: None Declared, F. Cheung: None Declared, T. O’Hanlon: None Declared, I. Targoff: None Declared, Y. Huang: None Declared, F. Miller: None Declared, R. Goldbach-Mansky: None Declared, L. Rider: None Declared.

Introduction: Because of the large number of common variants or polymorphisms in genes related to hereditary periodic fevers (HPF), genetic results often require an high clinical discrimination. The Infevers database is a large international registry of the different variants described for genes associated to autoinflammatory diseases. Due to the nature of this registry no genotype-phenotype correlation are provided, except for the clinical phenotype of the first patient(s) described for each mutation.

Objectives: Aim of this study was to elaborate a registry of genotype-phenotype correlations derived from the patients with HPF enrolled and validated in the Eurofever registry.

Methods: We created a table for each HPF describing the genotype-phenotype correlations observed in all the patients enrolled in the Eurofever registry. For autosomal dominant diseases (CAPS, TRAPS), all mutations were analyzed individually. For autosomal recessive diseases (FMF, MKD), homozygous and all combinations of compound heterozygous are described. For each mutation or combination, the following items are shown: number of patients, mean age of onset, disease course (recurrent or chronic), mean duration of fever episodes, clinical manifestations associated with fever episodes, atypical manifestations, complications and response to treatment.

Conclusion: We provide a useful tool for all the physicians, creating a registry of genotype-phenotype correlation of HPF based on the patients enrolled in the Eurofever registry. This tool is complementary to the Infevers database and will be available at the Eurofever and Infevers websites.

Disclosure of Interest: None Declared.

Conclusion: Ikaros and PKCδ dysfunction demonstrate that monogenic lupus can occur as a consequence of distinct anomalies of B cell development underlining the fact that SLE should be considered as a syndrome rather than a single homogenous disease.

Disclosure of Interest: None Declared.

Introduction: The measurement of the level of disease activity plays a pivotal role in the care of patients with ju-venile idiopathic arthritis (JIA). To serve this purpose, the Juvenile Arthritis Disease Activity Score (JADAS) was developed in 2009. More recently, a version excluding the acute phase reactant was tested (cJADAS). Cutoff values for the state of remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) were recently developed for the original JADAS score and for the clinical version. These cutoff values are ideally suited for pursuing tight disease control in a treat-to-target strategy, with treatment escalation if the desired JADAS score is not reached. However, although cut-offs were validated in a large and multinational cohort of patients, they were developed in a dataset of patients from a single pediatric rheumatology center an partly before the advent of the so-called biologic era.

Objectives: To develop the JADAS and cJADAS cut-off values of remission, LDA, MDA, and HDA for oligoarthritis and RF-negative polyarthritis in a large multinational cohort of JIA patients.

Methods: The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) study is aimed to obtain information on the frequency of JIA subtypes in different geographic areas, the therapeutic approaches adopted by pediatric rheumatologists practicing in diverse countries or continents, and the disease and health status of children with JIA currently followed worldwide. More than 9.000 patients with JIA from 118 pediatric rheumatology centres in 49 countries were collected so far. For the development of cut-offs, patients with oligoarthritis and polyarthritis followed in the 20 Centres with the highest frequency of these 2 subtypes were retained. In each centre, the 75th centile of JADAS and cJADAS distribution in patients who were subjectively rated by the attending physician as being in remission and LDA, and the 25th centile of JADAS and cJADAS in patients rated as in HDA, were calculated. The obtained values at each centre were then averaged to obtain the prelimary cut-offs for each disease activity state.

Conclusion: New JADAS and cJADAS temptative cut-offs for remission, LDA, and HDA were calculated. Obtained values will be tested in the validation analysis. The preliminary values are higher than currently available cut-offs.

Disclosure of Interest: None Declared.

Introduction: Pediatric systemic lupus erythematosus (pSLE) is a rare autoimmune disorder with onset before 18 years of age and characterized by heterogeneous clinical manifestations, unpredictable courses and a substantial risk of morbidity. There is no targeted treatment available for pSLE. In the last decade, several gene expression profiling and protein studies showed an up-regulation of genes typicallyinduced by type I interferons (IFNα/β) in the peripheral blood and tissue samples of pSLE patients. Although blood expression levels of IFNα/β-related genes were also correlated with disease activity of pSLE patients, the mechanism by which type I IFN contribute to pathogenesis has not yet been elucidated.

Objectives: In this study, we aim to investigate the role of type II IFN, IFNγ, in the pathogenesis of pSLE evaluating: 1) the expression levels of IFNγ-related genes in the peripheral blood of pSLE patients; 2) the relationship between type II and type I IFNs; 3) the correlations between the expression levels of IFNγ-related genes in peripheral blood and the clinical features of pSLE patients.

Conclusion: Taken together, these data indicate a possible role of IFNγ in the pathogenesis of pSLE. Both types of IFNs potentiate each other effect on tissues by affecting their reciprocal biological activity. IFNγ correlates with disease activity in pSLE, IFNγ-induced gene expression may represents a promising biomarker in this autoimmune disease. The potential pathogenic role of IFNγ in SLE remains to be elucidated.

Disclosure of Interest: None Declared.

Introduction: One of the open issues for Juvenile Localized Scleroderma (JLS) is the assessment and monitoring over time of the extent of inflammation and tissue damage. The lack of reliable and standardized outcome measures has represented, over the years, a significant limitation for both clinical monitoring of the disease and development of therapeutic trials.

Objectives: We assessed the reliability of Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) clinical score in comparison with contemporary thermographic analysis. Secondary aim was to evaluate and compare the sensitivity to change of LoSCAT and thermography over time.

Methods: A longitudinal observational analysis of patients with JLS, consecutively evaluated at our Paediatric Rheumatology Unit, has been performed by using the LoSCAT clinical score and infrared thermography.

Conclusion: LoSCAT appears as a promising outcome measure in JLS, distinguishing the different aspects of activity and damage. LoSCAT is not influenced by the experience of the examiner. Infrared thermography confirms to be a very helpful tool for detecting disease activity and reliable in monitoring lesions over time.

Disclosure of Interest: None Declared.

Introduction: Juvenile localised scleroderma (jlSc) is an orphan disease. Most patient respond to treatment ot methotrexate or mycophenolate. In case of nonresponse or partial response, based on the promising tocilizumab (TOC) data of adult systemic sclerosis studies, TOC seems to be a promising option. There is no publication regarding the effectiveness of tocilizumab in jLS.

Objectives: To assess the effectivity of TOC in jlSC patients, who had nonresponse or partial response on conventional therapy.

Methods: Participants of the pediatric rheumatology email board were asked, if they follow patients with jlSc, who are treated with TOC. Clinical characteristics and the response to TOC was assessed.

Results: Six centers responded to the survey from the email board, with around 800 participants, and reported 11 patients. The mean age of the patients at disease onset was 5.5 years. Disease duration at time of the initiation of TOC was 53.5. months (range 9 to 109). 5 patients had linear subtype, 3 of them with facial involvement, 2 of them Parry Romberg and one of them coup de sabre. Three had generalized subtype, 2 mixed subtype and 1 limited subtype/morphea. Before starting TOC patients received 10/11 Methotrexate, 7/11 Mycophenolate, 1 abatacept and 1 anti-TNF therapy. Reason to start TOC was in 9 patients increase in Localised Scleroderma Activity Index[1] (mLoSSI). In two patients increased extracutaneous activity was the indication, in one increased activity of arthritis and in the other increased activity of the central nervous system involvement.

Conclusion: Conclusion:

1. Arkachaisri T, Vilaiyuk S, Torok KS, Medsger TA, Jr.: Development and initial validation of the localized scleroderma skin damage index and physician global assessment of disease damage: a proof-of-concept study. Rheumatology (Oxford) 2010, 49(2):373-381.

Disclosure of Interest: None Declared.

Introduction: We have recently demonstrated that synovial fluids of JIA patients contain elevated levels of proNGF, the immature form of the Nerve Growth Factor (NGF), and not mature NGF as believed in the past. Moreover, mononuclear cells of JIA patients show a reduced expression of TrkA, the specific receptor of mature NGF, and an enhanced expression of p75NTR, the specific receptor for proNGF. This results in an inverted ratio of TrkA and p75NTR in JIA patients compared to healthy donors. How this altered proNGF/p75NTR axis can influence the inflammatory response is at present unknown.

Objectives: In this study, we focused on the involvement of p75NTR and its ligand proNGF in regulating inflammatory responses in the inflamed synovia and in synoviocytes of arthritis patients.

Methods: Fibroblast-like synoviocytes (FLS) were obtained by synovial tissue of rheumatoid arthritis patients (RA FLS) after enzymatic digestion. Osteoarthritis fibroblasts (OF) and skin fibroblasts (SF) were used as control. Using Realtime-PCR and western blot, we evaluated TrkA, p75NTR, sortilin, NGF mRNA expression and protein levels. Realtime-PCR and ELISA were used to evaluate cytokine production.

Conclusion: These preliminary data suggest that the proNGF found in synovial fluids of chronic arthritis patients is produced and released principally by FLS. The accumulated proNGF binds to its specific receptor p75NTR, which is highly expressed by both FLS and SFMC, inducing pro-inflammatory cytokine expression. Inflammatory stimuli further enhances the expression of p75NTR in FLS, creating a vicious circle that amplify the inflammatory response. The use of p75NTR inhibitors might represent a new therapeutic approach for the treatment of JIA and RA.

Disclosure of Interest: None Declared.

Introduction

Methods

Conclusion: Although our study did not meet its primary end point, treat-to-target treatment in this cohort of children with recent-onset JIA resulted in high frequencies of clinical inactive disease and adjusted ACRpedi30/50/70 scores in all three arms. In clinical trials inactive disease seems a feasible goal in juvenile idiopathic arthritis patients.

Disclosure of Interest: None Declared.

Introduction: MRI studies on RA patients showed that subclinical synovitis is often present in patients in clinical remission and is responsible for progression of joint damage. A high frequency of MRI-detected inflammation in JIA patients with clinically inactive disease was also reported. Due to the lack of longitudinal studies in JIA, it is unclear whether this phenomenon entails a risk of progression of joint damage and whether it should affect the therapeutic decisions.

Objectives: To assess the prevalence of subclinical synovitis as detected by MRI in a cohort of JIA patients in clinical remission and to evaluate its association with disease flare and structural damage progression.

Methods: All JIA patients who met the Wallace criteria for clinical remission and underwent contrast-enhanced MRI at the Study Unit between 2007 and 2015 were included. MRIs were scored by two independent readers according to the Outcome Measure in Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Scoring System (RAMRIS). Joint damage progression was assessed by conventional radiography (CR) according to the adapted versions of the Sharp/van der Heijde score and to the Childhood Arthritis Radiographic Score of the Hip. The concordance between the readers was assessed using kappa statistics. Categorical data were analyzed using chi-squared test and Fisher’s exact test. Comparison of quantitative variables was performed by the non-parametric Mann–Whitney U-test. A logistic regression model was applied to perform multivariate analysis of the radiographic damage risk factors.

Conclusion: A sizeable proportion of patients in clinical remission had MRI evidence of persistent joint inflammation. Subclinical synovitis was significantly associated with disease flare, while BMO showed remarkable promise in predicting joint destruction. These findings support the utility of MRI for the assessment of JIA patients in clinical remission and may have important clinical implications for their management.

Disclosure of Interest: None Declared

Introduction: Baseline clinical predictors on long-term outcome, not only regarding remission but also on functional ability, may enable assessment of prognosis and guide early treatment decisions in juvenile idiopathic arthritis (JIA).

Objectives: To evaluate potential baseline clinical predictors of functional ability assessed by the Childhood Health Assessment Questionnaire (CHAQ) eight years after disease onset.

Methods: Consecutive cases with newly diagnosed JIA from defined geographical areas in Denmark, Finland, Sweden and Norway were included and followed over eight years. Logistic regression was performed to assess potential baseline predictors of disability in terms of CHAQ (or HAQ for participants ≥18 years of age) score >0 at the final study visit.

Conclusion: A higher cumulative joint count, and specifically symmetric arthritis in finger joints, morning stiffness and higher pain score, higher patient/parent and physician global VAS score at baseline, predicts functional disability eight years after disease onset in a population-based Nordic JIA cohort.

Disclosure of Interest: None Declared.

Introduction: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease that affects children and adolescents and shows many differences in clinical manifestations, assessment and management compared to adult-onset arthritis. The transition from the child-centered to the adult-oriented care is a challenging multidimensional process that emphasizes a lot of aspects that need to be addressed.

Objectives: To describe the long-term outcome of JIA.

Methods: Four-hundred and fifteen patients affected by JIA and referred to a transition care rheumatology tertiary centre were considered between 1999 and 2016. The outcome assessment included disease activity, mean disease duration, medications, number of prosthesis implantation, pregnancies, mortality, social integration (mobility, employment status and educational level).

Results: A hundred and twenty (28.9%) males and 294 (71%) females were included; 58 (14%) patients were lost to follow up. The median age of the patients was 25 (18-57) years, the median age at onset was 9 years and the average disease duration was 17 years. Subtypes of JIA at disease onset included oligoarthritis 212 (51.2%), polyarthritis 98 (23.6%), systemic arthritis 51 (12.3%), psoriatic arthritis 11 (2.7%), enthesitis related arthritis 41 (9.9%) and undifferentiated arthritis 1 (0.2%). Seventy-one (17.1%) patients had persistent uveitis. Eighty-five implant prosthesis and 15 arthrodesis were recorded. Sixty-eight patients (16.4%) were also referred to the ultrasonography-guided infiltration clinic, to receive either intrarticular steroids or hyaluronic acid. At follow up 180 (43.5%) had low active disease activity, 84 (20.3%) had moderate disease activity, 14 (3.4%) had a high disease activity, 72 (17.4%) were on remission on medication and 64 (15.5%) off medication. Among the 350 patients still on medication, 75 (21.4%) were under treatment with oral steroids, 200 (57.1%) with sDMARDs and 225 (64.3%) with bDMARDs. Five deaths (1.2%) occurred in this cohort. A hundred and eighty-one (43.7%) subjects had a higher educational level (university), 294 (71%) had an employment, 243 (58.7%) obtained a driving license. Twenty-one (5.1%) pregnancies were registered. The transition age was considered after the age of sixteen years old. Particular attention was brought to the multidisciplinary approach towards each patient, that was realized with the collaboration of other specialists (ophthalmologist, orthopedic, dermatologist, gastroenterologist, obstetric and psychologist).

Conclusion: In the era of biologic therapy the long-term outcome of JIA underwent an outstanding improvement regarding a lot of variables. Two hundred and twenty-five (54.3%) patients were still on tight control, not only because of the continuation of the biological therapy, but also owing to the multidisciplinary care carried out even during remission. JIA often persists over the adulthood, therefore the long term follow-up and care of these patients needs to be conducted by a rheumatologist expertized in JIA in collaboration with other specialists.

Disclosure of Interest: None Declared.

Introduction: Currently all children with oligo and polyarticular JIA have to be screened by ophthalmologists for years in order to ensure that this completely asymptomatic disease is not missed. If missed or inadequately treated, some 50% of these children can go functionally blind. The only useful biological marker currently available is ANA status. However this is neither sensitive nor specific enough to significantly alter regular clinical screening. It does however suggest that autoantibodies, as yet undiscovered, may be important in the pathophysiology of this disease.

Objectives: To Identify novel antibodies that predict the development of uveitis in children with JIA.

Results: NAPPA image analysis revealed distinct signals from plasma antibodies of JIA patients with Uveitis which had reacted with specific array proteins. Hierarchical clustering heat maps were used to visualize clusters of proteins with higher array reactivity for JIA or Uveitis samples, realtive to controls. ELISA's were developed for nine highly reactive proteins including BATF, FO5, PROSAPIP1, CCND1, NOUFV3 and SSB. Antibodies specific for single-stranded DNA-binding proteins (SSB) were confirmed to be at significantly higher concentrations in the plasma of JIA patients with uveitis, relative to JIA patients without eye disease.

Conclusion: These results indicate that the NAPPA technique is a sensitive tool for screening antigens including specific nuclear antigens which distinguish JIA patients with uveitis. We plan on developing a nuclear antigen array with over 2000 features to determine further uveitis patient reactivity. Prospective studies are also required to establish if these immunoglubulins are present at detectable levels in JIA patients prior to development of uveitis and to assess their predictive utility.

Disclosure of Interest: None Declared.

Disclosure of Interest: None Declared

Introduction: Microparticles (MPs) are irregularly shaped submicron vesicles, which are released from plasma membrane upon cell activation and during the early phase of apoptosis. Increased levels of circulating MPs (mainly of endothelial cell origin, but also platelet derived) correlates with autoinflammatory disease activity, such as anti-neutrophil cytoplasm antibody (ANCA) – associated vasculitis (AAV).

Objectives: To evaluate levels of activity markers expressed on surface of MPs, during active disease and remission, compared to healthy control subjects.

Methods: Our study included 48 AAV patients (24 with active and 24 with inactive disease) and 23 healthy control subjects (age and gender matched). We analyzed the number and phenotype of MPs in plasma identified by flow cytometry, via labeling with following monoclonal antibodies: CD142 (tissue factor-TF), anti-H3cit (citrulinated H3 directed against neutrophil extracellular traps-NETs), anti-pentraxin3 (pentraxin3), HMGB1 (high mobility group box 1 protein-HMGB1), anti-TWEAK (tumor necrosis factor-like weak inducer of apoptosis-TWEAK), anti-plasminogen (plasminogen), anti-C3a (C3a) and anti-C5a (C5a). The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS), while active disease was defined as BVAS ≥1 and inactive (remission) as BVAS = 0. Statistical analysis was performed using GraphPed software.

Conclusion: Our results support recently postulated potential role of complement system in AAV pathogenesis and disease activity. Evaluated proteins expressed on MPs, especially C5a, could be used as potential biomarkers which might reflect inflammation and disease activity in AAV patients. Further investigations are necessary to confirm our preliminary results and to validate the most promising biomarker in AAV.

Disclosure of Interest: None Declared.

Introduction: The endothelial protein Plasmalemma Vesicle-associated protein 1 (PV-1) is the main component of stomatal and fenestral diaphragms of blood vessels. It regulates permeability, leukocyte migration and angiogenesis [1]. Considering the central role of the endothelium in vasculitis pathogenesis and the lack ofspecific biomarkersfor the clinical diagnosis and management of this group of complex disorders, we have investigated the levels of PV-1 among children with vasculitis and their association with disease activity or remission.

Objectives: To determine, for the first time, serum levels of endothelial protein PV-1 in a population of patients with vasculitis and healthy controls and possibly to assess the role of PV-1 to serve as a diagnostic biomarker in vasculitis disorders in childhood and/or to monitor disease activity and severity.

Methods: A case-control matched for age study was conducted including 62 healthy young people and 35 children with active vasculitis and other inflammatory diseases with vascular involvement: 18 patients with Pediatric Systemic Lupus Erythematosus (pSLE), 9 with Juvenile Dermatomyositis (JDM), 2 with Kawasaki Disease, 2 with leukocytoclastic vasculitis, 2 glomerulonephritis, 1 Central Nervous System Vasculitis, 1 Henoch-Schönlein Purpura (HSP). PV-1 serum levels were also measured in 9 children in clinical remission (2 SLE, 2 JDM, 3 HSP, 1 Kawasaki disease, 1 Hughes-Stovin Syndrome). Measurement of PV-1in blood serum (expressed in ng/ml) was performed using ELISA assay following the manufacturer’s (Biomatik) instructions.

Conclusion: PV-1 could represent a specific marker of disease activity in vasculitis disorders in childhood.

1. Guo L, Zhang H, Hou Y, et al. Plasmalemma vesicle–associated protein: A crucial component of vascular homeostasis (Review). Exp Ther Med 2016; 12:1639–44.

Disclosure of Interest: None Declared.

Introduction: Takayasu arteritis (TAK) is an idiopathic large-vessel vasculitis affecting the aorta and its major branches. Although the disease rarely affects children, it does occur, even in infants. The untreated inflammation often leads to narrowing or ectasias of aorta and its direct branches with or without pulmonary and coronary involvement. It’s a rare medical condition but we in our tertiary care center have collected the second largest single center series of patients over the past 16 years.

Objectives: To evaluate the clinical features, disease activity, treatment and outcome of childhood TAK in a tertiary center in South India

Methods: We analyzed a retrospective case series of children fulfilling the TAK classification criteria of the European League against Rheumatism and the Paediatric Rheumatology European Society. Data has been collected in a retrospective manner from our institute’s electronic medical records (EMR) for childhood onset TAK. Data regarding demographics, clinical features, treatments, and outcomes were recorded. Baseline data including age, gender, disease duration, angiographic type, the extent of clinical disease using DEI.Tak, CRP, and ESR were collected. Disease activity was assessed by a composite clinical score namely ITAS-A (CRP). At each visit, active disease was defined as

1. Clinical activity by the presence of any one of the following:

2. Activity by imaging by presence of de Novo lesion on follow-up angiography or stenosis of the same vessel extending beyond stent margins

3. Laboratory criteria of activity were defined by persistently raised CRP as well as ESR on 2 consecutive visits without any alternative explanation like infection

Results: 100 children with juvenile-onset TAK were included in this study over the past 16 years. Out of 100 children with TAK, 30 were male and 70 were female. Median age at onset was 14 years and mean duration of delay in diagnosis was 7 months (4-24 months). The most common clinical features at presentation were pulse abnormality (67%) followed by arterial hypertension (62%), claudication (40%) and systemic symptoms like fever and fatigue (36%).

Conclusion: Improved awareness of TAK is essential to secure a timely diagnosis. The initial symptoms and signs are non-specific, and a high index of suspicion is needed if the diagnosis is to be made. The investigation and management of Takayasu’s disease can prove difficult.

Disclosure of Interest: None Declared.

Introduction: Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (SJIA), characterized by activation and expansion of cytolytic lymphocytes and macrophages with hemophagocytic properties. Recent work by us and others has shown that emergence of MAS is associated with a surge in IFN-gamma and IFN-induced chemokines; however, previous gene expression studies failed to demonstrate this IFN-induced signature in peripheral blood cells. However, prior studies in SJIA and MAS have been limited by a failure to examine key myeloid effector cells, specifically activated macrophages or histiocytes which traffic to tissue including bone marrow during MAS.

Objectives: Utilize single-cell RNA-sequencing to identify specific gene expression signatures of bone marrow macrophage populations in SJIA and MAS.

Methods: Cell sources include unused portions of bone marrow aspirates obtained as part of a diagnostic workup and interpreted as normal were obtained from the Cincinnati Children’s Hospital Immunopathology lab, as well as cells obtained from a bone marrow biopsy from a newly diagnosed SJIA patient. Macrophage single cell suspensions were obtained using cell sorting for populations expressing the monocyte and macrophage surface markers CD14 and CD163 while excluding cells expression the granulocyte/monocyte marker CD15, prior to loading onto the Fluidigm C1 Single-Cell Auto Prep System. Extracted RNA was converted into cDNA and sequenced as a pooled library, and aligned to the human Ensembl transcriptome using Kallisto through AltAnalyze version 2.1.1.

Results: Three independent control samples yielded 180 single cells which passed quality-control filtering. While there was substantial inter-individual variability, using principle component analysis and Iterative Clustering and Guide-gene Selection, a core set of approximately 1400 genes were identified that contributed to the heterogeneity of normal bone marrow macrophage population. Control macrophages formed at least three primary cellular clusters, which were distinguished based on expression of genes associated with inflammatory responses, GM-CSF signaling, and aurora B signaling. 61 single bone marrow macrophages were captured from a patient with newly diagnosed SJIA with active systemic features, arthritis, marked anemia and relative thrombocytopenia, but lacking other overt signs of MAS, who underwent bone marrow biopsy as part of the diagnostic evaluation. Expression profiles were broadly similar to control macrophages by PCA, and all macrophage clusters were represented. However, a distinct subpopulation of bone marrow macrophages from the SJIA patient was identified that exhibited markedly altered transcriptional profiles. Compared to other macrophages within the cluster, this SJIA macrophage population showed alterations in gene pathways including cellular response to interferon gamma (adjusted p = 1.35e-14), endocytic vesicle membranes (p = 8.44E-14), phagosome (p = 2.98e-9) and vesicle-mediated transport (p = 1.05E-07). These cells showed a proinflammatory gene expression signature, including significant enrichment for genes regulated by NF-kB and STAT1. This included S100A12, which is highly expressed in patients with SJIA and MAS and was markedly elevated in serum from this patient.

Conclusion: We identify a distinct subpopulation of bone marrow macrophages in an SJIA patient with features associated with emergence of MAS, including interferon response, phagocytosis and vesicular transport. This demonstrates the importance of studying these effector cells at the sites of inflammation, and suggests that tissue macrophages may be a key source of IFN-induced products during MAS. Together, these data show that single cell gene expression profiling of bone marrow macrophages can identify reproducible cellular clusters as well as potential biologically relevant subpopulations and pathways perturbed during inflammatory disorders.

Disclosure of Interest: G. Schulert Consultant for: Novartis, N. Salomonis: None Declared, S. Thornton: None Declared, A. Grom Grant/Research Support from: NovImmune, AB2Bio, Consultant for: Novartis, Juno.

Introduction: Pharmachild is a pharmacovigilance registry on children with JIA treated mainly with biologics ± methotrexate (MTX). Little evidence exists in literature about the role of JIA or its immunosuppressive therapy in determining infections, especially caused by opportunistic pathogens.

Objectives: To provide an update on opportunistic infections (OI) revised by an independent Safety Adjudication Committee (SAC) (3 pediatric rheumatologists and 2 pediatric infectious disease specialists).

Conclusion: Our preliminary analysis showed a significant number of opportunistic infections in JIA patients on immunosuppressive therapy, which was mostly confirmed in the list of opportunistic infections approved by the experts. Further analysis on the correlation with medications is ongoing.

Disclosure of Interest: G. Giancane: None Declared, J. Swart: None Declared, E. Castagnola: None Declared, A. Groll: None Declared, G. Horneff: None Declared, H.-I. Huppertz: None Declared, D. Lovell: None Declared, T. Wolfs: None Declared, M. Hofer: None Declared, E. Alexeeva: None Declared, V. Panaviene: None Declared, S. Nielsen: None Declared, J. Anton: None Declared, F. Uettwiller: None Declared, V. Stanevicha: None Declared, M. Trachana: None Declared, F. De Benedetti: None Declared, C. Ailioaie: None Declared, E. Tsitsami: None Declared, S. Kamphuis: None Declared, T. Herlin: None Declared, P. Dolezalova: None Declared, G. Susic: None Declared, B. Flato: None Declared, F. Sztajnbok: None Declared, E. Fueri: None Declared, F. Bovis: None Declared, F. Bagnasco: None Declared, A. Pistorio: None Declared, A. Martini Grant/Research Support from: Starting from 1 march 2016 I became the Scientific Director of the G. Gaslini Hospital, therefore my role does not allow me to render private consultancies resulting in personal income. I perform consultancy activities on behalf of the Gaslini Institute for the following companies: Abbvie, Boehringer, Novartis, R-Pharm The money received for these activities are directly transferred to the Gaslini Institute's bank account., N. Wulffraat: None Declared, N. Ruperto Grant/Research Support from: The G. Gaslini Hospital, which is the public Hospital where I work as full time public employee, has received contributions from BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer and Sobi for the coordination activity of the PRINTO network. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Speaker Bureau of: Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb,, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi.

Introduction: Whole-body magnetic resonance imaging (WBMRI) is a fast and accurate method to detect diseases throughout the entire body without exposure to ionizing radiation. Possible emerging applications for this technique include rheumatologic field and evaluation of fever of unknown origin (FUO).

Objectives: To evaluate the ability of WBMRI to identify significant potential diagnostic clue(PDC) in patients presenting a non specific inflammatory clinical picture.

Methods: We retrospectively collected cases of pediatric patients followed in a single pediatric rheumatology center who underwent WBMRI between January 2010 and December 2015 for the following indications: i) FUO(temperature greater than 38.3 °C for more than three weeks or failure to reach diagnosis after one week of investigations), iii) recurrent fever, iii) persistent low grade fever with evidence of elevation of acute phase reactants and/or other clinical symptoms.WBMRI studies were acquired with coronal and sagittal planes (slice thickness 5 mm) with acquisition of several image sets with automatic direct image realignment after acquisition creating a whole-body scan.Sequences include short τ inversion recovery (STIR) and T1-weighted. All studies have been evaluated twice, the second time according to a predefined checklist, defined by an experienced radiologist, considering systematically single/multifocal bone lesion, bone marrow, joint effusion, soft tissues, adenopathies, parenchymal and vessels looking for PDC.

Results: We collected 105 patients who underwent WBMRI; 24 (23%) of them presenting FUO, 29 (28%) presenting recurrent fever and 52 (49%) presenting persistent low grade fever.The mean age of onset symptoms was 7 years and seven months (range: 2 weeks old- 17 years and 6 months). The mean age of execution of WBMRI was 9 years (range: 5 months old- 19 years and one month). After the whole diagnostic work-out a final diagnosis was achieved in 34 patients (32%).

Conclusion: WBMRI can be a powerful diagnostic tool in patients with FUO. A predefined checklist increase sensitivity of WBMRI in the identification of PDC.

Disclosure of Interest: None Declared.

Introduction: Low back pain (LBP) is a common complaint in adults that often begins in childhood. Despite the increasing frequency, it is estimated only 24% of children with LBP visit a doctor. Nevertheless, those patients are often seen in pediatric rheumatology clinic. Although most of the LBP cases after exclusion of trauma are caused by benign musculoskeletal disease, a history of sacroiliac (SI) joint tenderness and/or inflammatory lumbosacral (LS) pain is one of the ILAR classification criteria for enthesitis related arthritis (ErA), a form of juvenile idiopathic arthritis (JIA) that includes most of the patients with juvenile spondyloarthritis (jSpA). Recognition of jSpA particularly early in the course of the disease represents a unique set of challenges and therefore all of the patients with inflammatory back pain (IBP) and arthritis or enthesitis should be suspected for jSpA with possible involvement of SI and other vertebral joints. Since magnetic resonance imaging (MRI) is the preferred method of assessment both for axial inflammation and other possible musculoskeletal, infectious and malignant causes of LBP in children, it might be advisable to use it in the initial assessment of suspected IBP in children.

Objectives: To evaluate the usefulness of early MRI in discovering inflammation of spinal joints and other possible causes of LBP in children with suspected IBP not fulfilling ILAR classification criteria for ErA at the time of investigation.

Methods: Thirty five children referred to our pediatric rheumatology clinic due to LBP lasting for more than three months, who meet ASAS criteria for IBP and had SI joint tenderness and positive FABRE test on physical examination, participated in the study. Their average age was 14.2 years (6-18) and 11 (31.4%) of them were boys. Five study participants (14.3%) had arthritis and 19 (54.3%) had enthesitis confirmed by physical examination and ultrasound, but none of them meet ILAR criteria for ErA at the time. Twelve (out of 15) were HLA-B27 positive and 13 (37.1%) had a history of SpA related disease in a first degree relative. One of the patients had a diagnosis of ulcerative colitis (UC), and one of psoriasis. All of the participants had normal CBC and CRP values, with negative ANA and RF. None had neurological symptoms. Contrast enhanced MRI of SI joints and thoracolumbar spine was performed according to recommended protocols for the assesment of inflammatory changes within one week after initial visit on a 1.5 T machine and interpreted by experienced musculoskeletal radiologist.

Results: Nineteen (54,3%) patients had various pathological findings detected by MRI. Four (11,4%) had signs of inflammation with one having an active sacroiliitis according to ASAS criteria. Schmorl nodes were discovered in six patients and three of them, including one with the signs of inflammation, had Scheuermann disease. Two patients had stress reaction in LS region. Five patients had incipient degeneration of intervertebral discs. Three patients had disc protrusion without and one with radial nerve compression. After three months of follow up, 19 patients (54.3%) meet ILAR criteria for ErA, one for psoriatic arthritis and one, who also had UC, meet criteria for undifferentiated arthritis.

Conclusion: Differential diagnosis of LBP in children is very wide and it is difficult to distinguish inflammatory and other causes upon the first encounter with pediatric rheumatologist based on history and physical examination alone. In our study, all of the patients with LBP had some characteristics of IBP and ErA, while definite diagnosis of jSpA was subsequently established in almost 60% of the patients. Interestingly, 20% of them already had inflammatory changes of LS and SI joints discovered by MRI, while many others had signs of other LBP causes. Therefore, MRI performed early after referral to pediatric rheumatologist, in all children with suspected IBP, can be very useful in elucidating the cause of LBP and differentiation of those who need only symptomatic relief, orthopedic consultation or further follow up in pediatric rheumatology clinic. High cost of this approach can be justified with the benefit of early therapeutic intervention in those with established axial inflammation and the avoidance of unnecessary treatment in those with other causes.

Disclosure of Interest: None Declared.

Objectives: Primary objective was to demonstrate that CAN 150 mg every 4 weeks (q4w) was superior to placebo (PBO) in resolving flare by Day 15 with no new flares over 16 weeks (wks). Secondary objectives included: proportion of pts who maintained optimal control of disease activity (absence of new flares) between Wk 16 and Wk 40 after dose prolongation; evaluation of pharmacokinetics (PK), pharmacodynamics (PD) and safety of CAN in the HIDS/MKD pts.

Conclusion: CAN (150 mg q4w) was efficacious in resolving flare by Day 15 and preventing new flares in HIDS/MKD patients over 16 weeks. Approximately 23% pts did not flare with a prolonged dose interval (q8w) at the end of E3 compared to 14% pts who did not flare when CAN was completely withdrawn. No new safety issues were reported over 40 weeks of treatment; the safety profile was not distinct from previous controlled studies. The PK/PD results observed with the liquid-in-vial form of CAN were similar to those observed in CAPS and SJIA.

Disclosure of Interest: J. Frenkel Grant/Research Support from: Novartis and SOBI, J. Anton: None Declared, P. Hashkes Grant/Research Support from: Novartis, M. Cattalini: None Declared, T. Constantin: None Declared, A. Livneh: None Declared, B. Lauwerys: None Declared, S. Bensler Consultant for: Novartis, SOBI, AbbVie, P. Miettunen: None Declared, T. Kallinich: None Declared, J. Kummerle-Deschner Grant/Research Support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, Y. Gong Employee of: Novartis, E. Vritzali Employee of: Novartis, G. Junge Employee of: Novartis, F. De Benedetti Grant/Research Support from: Pfizer, AbbVie, Roche, Novartis, Novimmune and BMS, A. Simon Grant/Research Support from: Novartis, Xoma/Servier, CSL Behring, Consultant for: Novartis, Takeda, SOBI, Xoma.

Objectives: The primary objective was to demonstrate that canakinumab (CAN)150 mg every 4 weeks (q4w) is superior to placebo (PBO) in achieving a clinically meaningful response [resolution of flare at Day 15 and no new disease flares over 16 weeks (wks) of treatment] in TRAPS patients (pts). Secondary objectives included: the proportion of pts who maintained optimal control of disease activity (absence of new flares) between Wk 16 and Wk 40 after dose reduction; evaluation of pharmacokinetics (PK), pharmacodynamics (PD) and safety of CAN in TRAPS pts.

Methods: The study comprised 4 epochs: a 12-wk screening epoch (E1), a 16-wk randomised treatment epoch (E2), a 24-wk randomised withdrawal epoch (E3) and a 72-wk open-label treatment epoch (E4). TRAPS pts with a flare during E1 were randomised in E2 to receive CAN 150 mg q4w or PBO. Pts who did not flare in E2 in the CAN group were re-randomised to CAN 150 mg q8w or PBO/CAN withdrawal in E3. In E3, for pts with a flare, dose could be escalated up to 300 mg q4w. For PK/PD assessments, CAN concentrations and total IL-1β at baseline (Day 1), and trough concentrations at Wk 16 were assessed. Safety assessments included adverse events (AEs) and serious AEs (SAEs).

Conclusion: CAN (150 mg q4w) was efficacious in resolving flare by Day 15 and preventing new flares in TRAPS patients over 16 weeks. The prolonged dose interval (150 mg q8w) was sufficient to maintain disease control in approximately 50% TRAPS patients at the end of epoch 3. No new safety issues were reported over 40 weeks of treatment; the safety profile was not distinct from previous controlled studies. The PK/PD results observed with the liquid-in-vial form of CAN were similar to those observed in CAPS and SJIA.

1.Gattorno M, et al. Ann Rheum Dis. 2016;76(1):1738

Disclosure of Interest: M. Gattorno Grant/Research Support from: Novartis and SOBI, Consultant for: Novartis and SOBI, R. Hara: None Declared, A. Shcherbina: None Declared, L. Obici: None Declared, S. Bujan: None Declared, G. Hoerneff Grant/Research Support from: AbbVie, Chugai, Novartis, Pfizer, Roche, A. Jansson: None Declared, R. Brik: None Declared, I. Rosner: None Declared, A. Tomassini: None Declared, Y. Gong Employee of: Novartis, E. Vritzali Employee of: Novartis, G. Junge Employee of: Novartis, F. De Benedetti Grant/Research Support from: Pfizer, AbbVie, Roche, Novartis, Novimmune and BMS, H. Lachmann Consultant for: Novartis, SOBI, Takeda, GSK, Speaker Bureau of: Novartis, SOBI.

Introduction: At present no clear evidence based guidelines exist to standardize the tapering and discontinuation of corticosteroids (CS) in juvenile dermatomyositis (JDM).

Objectives: To provide evidence-based recommendations for CS tapering/discontinuation through the analysis of the patients in the PRINTO new onset JDM trial. Secondary objective of the study was to identify predictors of clinical remission and CS discontinuation.

Methods: New onset JDM children were randomized to receive either prednisone (PDN) alone or in combination with MTX or CSA. All children were given initially intravenous methylprednisolone, and then PDN starting with 2 mg/kg/day. Gradual tapering according to a specific protocol could lead to the safe dose of 0.2 mg/kg/day by month 6, then discontinued at month 24. Major therapeutic changes (MTC) were defined as the addition or major increase in the dose of MTX/CSA/other drugs or any other reasons for which patients were dropped from the trial. Patients were divided according to clinical remission (CMAS = 52 and MD global = 0 for 6 continuous months) into two major groups. Group 1 included those on clinical remission, who could discontinue PDN, with no MTC, and represented the reference standard for the best clinical outcome. Group 1 was compared with those who did not achieve clinical remission, without or with MTC (group 2 and 3, respectively). JDM core set measures (CSM) were compared in the 3 groups. We also calculated the gold standard group (group 1) median change in the CSM in the first 6 and over 24 months and applied a logistic regression model to identify the predictors of clinical remission with PDN discontinuation.

Conclusion: We propose evidence based specific cut-offs for corticosteroid tapering/discontinuation based on the change in JDM CSM of disease activity, and to identify the best predictors for clinical remission and corticosteroid discontinuation.

Disclosure of Interest: G. Giancane: None Declared, C. Lavarello: None Declared, A. Pistorio: None Declared, F. Zulian: None Declared, B. Magnusson: None Declared, T. Avcin: None Declared, F. Corona: None Declared, V. Gerloni: None Declared, S. Pastore: None Declared, R. Marini: None Declared, S. Martino: None Declared, A. Pagnier: None Declared, M. Rodiere: None Declared, C. Soler: None Declared, V. Stanevicha: None Declared, R. Ten Cate: None Declared, Y. Uziel: None Declared, J. Vojinovic: None Declared, E. Fueri: None Declared, A. Ravelli Grant/Research Support from: BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi, Speaker Bureau of: AbbVie, BMS, Pfizer, Hoffman LaRoche, Novartis, Centocor., A. Martini Grant/Research Support from: Starting from 1 march 2016 I became the Scientific Director of the G. Gaslini Hospital, therefore my role does not allow me to render private consultancies resulting in personal income. I perform consultancy activities on behalf of the Gaslini Institute for the following companies: Abbvie, Boehringer, Novartis, R-Pharm The money received for these activities are directly transferred to the Gaslini Institute's bank account., N. Ruperto Grant/Research Support from: The G. Gaslini Hospital, which is the public Hospital where I work as full time public employee, has received contributions from BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer and Sobi for the coordination activity of the PRINTO network. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Speaker Bureau of: Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb,, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi.

Introduction: In immunocompromised patients, varicella zoster virus (VZV) infection can have a very severe clinical course. There is scarce evidence that in adult and paediatric population with rheumatoid or juvenile idiopathic arthritis and other rheumatic diseases the treatment with biologic agents may impair the antibody response to vaccines. However, there is no evidence on whether the use of biologic agents affects in children the VZV IgG levels acquired after natural infection.

Objectives: The aim of the study is to investigate whether children with a rheumatic condition treated with biologic agents have a change in their VZV immune status.

Methods: We performed retrospective case notes review of children presenting with any rheumatic diagnosis requiring treatment with a biologic agent to the Paediatric Rheumatology services at Great Ormond Street Hospital NHS Foundation Trust between 2009 and 2017, identified from the biologic database. We included in the study the children with positive VZV IgG prior to the treatment with a biologic agent and with a minimum of one repeat VZV IgG measurement post initiation of the treatment. A sensitive VaccZyme

Results: Sixty four patients treated with biologic agents and with two measurements of VZV IgG prior and post biologic were identified. Forty three patients had positive VZV IgG acquired prior to treatment and were included in the study. None had received the VZV vaccine, which is not part of the routine childhood vaccination schedule in the United Kingdom. After initiation of treatment with biologics, 10/43 (23%, 2 males and 8 females) had a change in VZV IgG, of which 5/43 (11.6%) had negative VZV IgG, and 5/43 (11.6%) equivocal. Four had a diagnosis of JIA, 2 systemic vasculitides, and 4 other rheumatic conditions. Seven patients were treated with anti-TNF agents, 2 patients with Tocilizumab and 1 received Abatacept. Nine patients received concomitant treatment with other disease-modifying anti-rheumatic drugs (7/9 Methotrexate, 2/9 Azathioprine). For the 10 patients, the median age at the measurement of a positive VZV IgG pre-biologic was 7 years (range 1-12), median time between the two assessments was 40.5 months (range 9-105), and the median time between the initiation of the biologic agent and the post-biologic measurement of VZV IgG was 24 months (range 11-68).

Conclusion: We describe the changes in the VZV immune status post treatment with biologics in the first cohort of paediatric patients with initial seroconversion following natural infection. Although limited by the size of the study population, observational nature and other concomitant medications, our results indicate that biologic agents can affect the VZV immune status of patients with rheumatic conditions, making them susceptible to re-infection. Therefore we suggest that all patients on biologic agents should have the VZV IgG levels re-tested regularly to identify whether the VZV IgG levels are protective and give prophylaxis as required in the event of varicella contact.

Disclosure of Interest: None Declared.

Introduction: Aerobic fitness may serve as an important health-related outcome measure in Juvenile Idiopathic Arthritis (JIA). Reduced aerobic fitness is associated with cardiovascular morbidity, mortality and osteoporosis in adult patients with chronic diseases. However, in adolescents and young adults, long-term outcome of aerobic fitness is unknown. Reduced aerobic fitness was described previously in cross-sectional studies in children and adolescents with JIA and was more impaired in active disease.

Objectives: Our objectives are to describe the course of aerobic fitness in a longitudinal cohort of adolescents and young adult JIA-patients who are intensively treated and to identify the association of clinical variables.

Results: Paired Z-scores were available from 35 patients. 40% were male, median age at baseline was 13,0 yrs (IQR 4,1), disease duration 7,8 yrs (6,4), JADAS27 3,7 (6,4), DAS28 1,8 (1,0). 79% of the patients were in DAS28-remission. 17% had systemic JIA, 6% persistent oligoarticular and 74% had a polyarticular course. Baseline and end Z-scores were reduced compared to healthy controls (ZAbs_base -0,68, IQR2,3 p = 0,01; Zrel_base -1,33, IQR 2,0, p < 0,01; Zabs_end -1,33, IQR 1,7, p < 0,01; Zrel_end -0,70, IQR 1,8, p = 0,01) and did not change significantly over time (change Zabs_change 0,65, p = 0,34; Zrel_change 0,63, p = 0,31). At baseline, a higher DAS28 (p = 0,01), higher JADAS27 (p < 0.01), ESR (p < 0,01), higher thrombocytes (p < 0.01) and the use of MTX (p = 0.01) were associated with a worse outcome of aerobic fitness. The greatest improvement of aerobic fitness over time was seen in male patients (p < 0.01) at baseline. Multivariate analysis showed that a higher DAS28 and male gender were the most important variables for worse aerobic fitness at baseline, a higher ESR at baseline was the most important predictor for improving aerobic fitness over time.

Conclusion: Aerobic fitness is significantly reduced in adolescents and young adults with JIA and does not improve over time, despite intensive treatment. Be aware of a reduced health outcome into adulthood due to a persistent reduced aerobic fitness during disease course of JIA, despite low disease activity.

Disclosure of Interest: None Declared.

Introduction: Periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome is an auto-inflammatory condition of unknown etiology. It is the second most common auto-inflammatory disease in our country, following familial Mediterranean fever. The strong familial clustering suggest a potential genetic origin of the syndrome but none of single genetic variants seem to be relevant for the disease etiology. Previous studies showed that tonsillectomy represents efficient treatment options.

Objectives: Our aim was to explore the main clinical features, response to tonsillectomy and long–term outcome of PFAPA pediatric patients in a single cohort. We assessed association of MEFV gene mutation with disease characteristics and treatment response.

Methods: We reviewed medical records of patients who were diagnosed with PFAPA syndrome between the January 2010 and June 2016. All of the recorded 562 patients were called by the telephone and 359 (64%) of them were reached. Demographic, clinical and therapeutically features were taken from the patients’ medical records. Data on clinical course and the disease outcome were collected by using a structured questionnaire, which was fulfilled during the phone conversation between investigator and patient’s parents.

Conclusion: Although PFAPA symptoms usually resolve before age of eight, some patients’ complaints persist. FMF should be considered in tonsilloadenoidectomy unresponsive PFAPA patients, especially in endemic regions like Turkey. Tonsilloadenoidectomy seems to be an effective treatment option for pediatric PFAPA patients.

Disclosure of Interest: None Declared.

Introduction: Provisional Eurofever evidence-based classification criteria for inherited periodic fever (TRAPS, FMF, MKD and CAPS) have been recently developed and other diagnostic criteria are available for FMF, CAPS and PFAPA. However, no consensus on how to combine clinical criteria and results of molecular analysis has been reached so far. We have recently identified, through a process based on the Delphi techniques (2 subsequent Delphi surveys), those variables the expert, clinicians and geneticists, consider as important for the diagnosis of each monogenic periodic fever syndrome and PFAPA. We also obtained, trough a web-based evaluation a consensus >80% among clinicians and geneticists on the diagnosis for 269 over 360 patients with monogenic periodic fever, PFAPA and undefined periodic fever (UPF) randomly selected from the Eurofever Registry.

Objectives: To identify candidate set of classification criteria for monogenic periodic fever and PFAPA and to test their sensibility and specificity on the subset of patients having reached a consensus among experts. To select the best sets of criteria for each disease to be discussed in a Consensus Conference

Methods: We selected for each disease the clinical variables corresponding to the 3rd quartile considering the total score obtained after the second Delphi survey. Performing univariate statistical analysis, we subsequently assess the ability of these variables to classify individual patients as having or not FMF, MKD, TRAPS, CAPS, PFAPA or UPF according to consensus classification of experts. These variables could be associated both in a positive or negative way to each disease. At the same time we assigned to each genotype presented by our patients a score from 5 to 1 on the basis of the evaluation done by the experts to be able to include the results of genetic testing in the statistical analysis. In a second step, multivariate statistical analysis has been performed to obtain different sets of criteria including only positively associated or positively and negatively associated clinical variables with and without genetic data. For each criteria the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) were calculated. The best performing criteria for each disease have been selected and presented to the expert for voting in a consensus Conference held in Genova in march 2017.

Results: A total of 98 clinical variables derived from the second Delphi survey has been tested. The univariate analysis identified 15 variables significantly associated with FMF (6 positively and 9 negatively), 20 with CAPS (12 positively and 8 negatively), 9 with TRAPS (6 positively and 3 negatively), 13 with MKD (11 positively and 2 negatively) and 15 with PFAPA (5 positively and 10 negatively). 193 criteria derived from the statistical analysis have been selected (45 for FMF, 50 for CAPS, 44 for TRAPS, 32 for MKD and 22 for PFAPA) to be discussed and voted at the consensus. In addition criteria already published in the literature and criteria directly proposed by experts were included for discussion.

Conclusion: Our process led to the identification of the best variables to be included in the multivariate analysis for the identification of the candidate criteria for monogenic periodic fever and PFAPA. Next, the ability of candidate criteria to classify individual patients as having FMF, MKD, TRAPS CAPS or PFAPA have been assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The best classification criteria for each disease in term of sensibility and specificity have been shown and voted by a panel of Experts during the Consensus Conference held in Genoa. For CAPS, FMF and MKD a consensus >80% has been reached for the best genetic/clinical criteria and for the best clinical criteria while for TRAPS the consensus has been reached only for the best clinical/genetic criteria. A new round of web-based evaluation is now ongoing to try to reach a consensus on the clinical criteria for TRAPS as well. Moreover a consensus has been reached for PFAPA clinical criteria.

Disclosure of Interest: None Declared.

Introduction: Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis, is a rare, noninfectious inflammatory disorder that causes multifocal lytic bone lesions with swelling and pain characterized by periodic exacerbations and remissions of unclear/unknown pathogenesis.

Objectives: To describe a case of CRMO in a 10 years old girl.

Methods: A 10 years old girl came to our department because of pain in her right shoulder since the age of 9 years. She did not recall a precipitating event or a trauma, reported no fever or weakness. There was no relevant personal or family history. Before coming to our observation an X-ray of her right shoulder revealing an osteolytic lesion and a PET-CT showing the presence of a pathological high-uptake of the lesion were performed, and a biopsy of the lesion of the right shoulder was done to exclude a neoplastic lesion, a bone infection, or a Langerhans cells histiocytosis (LCH). Patient’s bone biopsy showed infiltration by lymphocytes and neutrophils. No neoplastic cells were identified. All cultures were negative. LCH was excluded since immunohistochemical evaluation of bone marrow for CD1a and S100 expression was negative. When she was admitted to our department she had pain in her right arm and shoulder. Laboratory results showed a modest increase of inflammation parameters (ESR 34 mm/h, CRP 0,88 mg/dL) with normal complete blood count, liver and renal function. The abdominal ultrasound and the chest X-ray were normal so we performed an MRI. On MRI the lesion was hypointense in T1 and hyperintense in T2 and STIR, suggesting an inflammatory process.Suspecting a CRMO, anti-inflammatory treatment with naproxen was prescribed and the symptomatology disappeared. Five months later the patient came back to our department because of pain and swelling in her right clavicle. The physical examination showed a painful swelling of the sternal end of the right clavicle. Laboratory results indicated a modest increase of inflammation parameters (ESR 29 mm/h, CRP 0,98 mg/dL). Clavicle X-ray showed an osteolytic lesion, ultrasound of sternoclavicular joint revealed articular effusion. On MRI this lesion was hyperintense in T2 and STIR.

Results: Clinical history, physical signs, instrumental investigations and histopathological pattern were highly suggestive of CRMO. Anti-inflammatory treatment with naproxen was started again and the symptoms disappeared. After six months was performed a whole-body MRI to evaluate the status of disease. The MRI did not show new lesions and previous bone lesions disappeared.

Conclusion: In a patient with recurrent bone pain CRMO should be considered. The diagnosis is of exclusion and it is based on the clinical and radiological data. Biopsy is needed to exclude infectious osteomyelitis, malignancy, LCH. Some authors suggest that biopsy is not necessary if a patient has classical radiological findings of CRMO, or comorbidities, such as Crohn's disease. Skeletal manifestations are unifocal or multifocal, and the involvement of clavicle, sternum or mandible suggest a CRMO diagnosis. Extra-articular manifestation are gastrointestinal and skin involvement (acne, pustolsis, psoriasis).The SAPHO syndrome seems to be an advanced state of CRMO. The treatment of CRMO has been mostly empiric; NSAIDs are the first choice for CRMO treatment. When disease activity is high or there are complications therapy with bisphosphonates or biologic drugs such as TNF antagonists (etanercept) or inhibitors of IL-1 (anakinra) should be considered.

Disclosure of Interest: None Declared.

Objectives: To elucidate the mechanisms of autoinflammation in Blau syndrome, we sought to clarify the relation between disease associated-mutant NOD2 and the inflammatory response in human samples.

Conclusion: Our data support the significance of ligand-independent autoinflammation in the pathophysiology of Blau syndrome. Our comprehensive isogenic disease-specific iPSC panel provides a useful platform for probing therapeutic and diagnostic clues for the treatment of Blau syndrome patients.

Disclosure of Interest: None Declared.

Introduction: Clavicular cortical hyperostosis (CCH) is a rare inflammatory bone disorder of unknown aetiology represented by pain and swelling of the clavicle. Although similar to chronic nonbacetril/recurrent multifocal osteomyelitis (CNO/CRMO), due to lack of recurrence and additional inflammatory sites, it can be considered separate disease in the spectrum. In our previous study microarray gene expression profiling of CCH patients revealed 974 differentially expressed genes involved in various inflammatory processes (1). Subsequent qRT-PCR in additional number of patients confirmed significantly lower expression of ERBB2 gene and higher expression of TRPM3 and TPRM7 transient receptor potential (TRP) channel genes. Additionally, immunofluorescence microscopy showed high signal of TRPM3 in blood cells of one CCH patient. Based on described findings and other studies which showed TRP channels are involved in inflammasome activation, while ERBB activation promotes protective cellular outcomes during inflammation, we hypothesized CCH could be autoinflammatory disease, but the mechanisms responsible for observed expression alterations remained unclear.

Objectives: Identify possible disease causing gene variants in CCH patients using whole exome sequencing (WES).

Methods: Genomic DNA was extracted from peripheral whole blood samples of three CCH patients. Targeted exome sequencing was performed using the Nextera Rapid Capture Exome Kit (Illumina). The sequence library was constructed with 50 ng of genomic DNA and 100-bp paired-end reads were sequenced on HiSeq 2000 next-generation sequencer (Illumina). The extracted variants were annotated and filtered using the Variant Studio software (Illumina) and Variant Interpreter (Illumina).

Conclusion: In this comprehensive study “bottom-up” approach was used in order to elucidate the molecular disease mechanisms of what we believe could be a new disease entity. Previously performed diligent transcriptome analysis and proof-of-concept experiment which confirmed the results on a protein level indicated CCH could be induced by sternoclavicular joint overuse, TRP channel overexpression, inflammasome activation and reduced protection during inflammation. Interestingly, WES analysis identified majority of likely pathogenic variants in ZNF717 gene. This gene encodes a Kruppel-associated box (KRAB) zinc-finger protein, which belongs to a large group of transcriptional regulators and is therefore involved in the regulation of crucial physiological and pathological processes (2). Many aspects of these proteins are still essentially unknown, as is their role in the inflammation, yet it is speculated they increase DNA accessibility and inflammatory gene transcription (3). Together with possible influence on observed expression patterns, all of these processes could contribute to CCH evolution.

Disclosure of Interest: None Declared.

Introduction: ADAM17 is an important shedding enzyme that regulates the response to tissue injury and inflammation. Only 2 cases of ADAM17 mutations in humans have been described thus far: siblings with a homozygous ADAM17 deletion resulting in a severely truncated protein causing autosomal recessive neonatal inflammatory bowel and skin disease.

Objectives: The aim of this study was to discover the genetic cause affecting a child with a novel inflammatory phenotype.

Methods: Whole Exome sequencing was performed using DNA extracted from peripheral blood for a trio analysis. The Nextera Exome Capture and Hiseq sequencing platforms were used in this process.

Results: A four-year- old girl presented with extreme photophobia, bloody diarrhoea, anal fissures from the first weeks of life, and intermittent fevers. Examination revealed blepharitis, perioral rash and gingival inflammation with hyperthrophy. Feeding difficulties attributed to gastro-oesophageal reflux led to oral aversion and poor weight gain. Inflammatory markers were moderately elevated (mean CRP-22 mg/L and ESR-32 mm/h) in between fevers, and higher (CRP > 150 mg/L) during fevers. Upper gastrointestinal endoscopy at 10 months of age showed gastritis and duodenitis. Brain MRI showed cerebellar hypoplasia; corneal biopsy revealed an abnormal cornea and conjunctival epithelium. Extensive neuro-metabolic investigations performed were normal. Whole exome sequencing revealed 2 rare heterozygous missense mutations in the ADAM17 gene (p.I50V and p.R215V). Sanger sequencing confirmed these results, and carrier status in the parents. Both these mutations were absent from our in-house exome database of 120 exomes; were not seen in homozygous state in population databases; and were predicted damaging in silico. Biopsies of oral mucosa, tonsillar and skin tissue were then assessed by electron microscopy showing patchy structural changes in hemidesmosomes.

Conclusion: We describe the third case of human disease associated to ADAM17, but with a novel phenotype, similar to conditional knock-out mouse models with severely reduced ADAM17 sheddase activity, which develop opaque eyes, skin and heart defects as well as increased susceptibility to dextran sulfate induced colitis. This is in-keeping with the mutations found in our proband, since they are unlikely to result in the complete absence of the protein described in the other human cases.

Disclosure of Interest: None Declared.

Introduction: The spectrum of autoinflammatory diseases (AID) is continuosly expanding and significant delay in diagnosis may occur if those rare entities are not promptly identified.

Objectives: To assess the impact and significance of gastrointestinal (GI) clinical manifestations in a broad cohort of AID patients.

Methods: The web-based international Eurofever registry containing data retrospectively collected about patients enrolled by 108 partecipating centres from November 2009 to June 2016 was evaluated. When present, each GI manifestation was ranked as occasionally or persistently present during flares. Development of severe GI complications was also assessed. To then identify subsets of patients featured by homogeneous patterns of clinical features, the unsupervised Latent Class (LC) analysis was applied to the cohort featured by GI manifestations (GI cohort) in the attempt to assign mutually exclusive class membership based on latent patterns among the observed variables.

Conclusion: These data unveiled the unforeseen significance of GI involvement in AID with implications in the daily clinical management. GI specialists should be aware of these rare diseases in order to avoid delayed diagnosis and joined work-up protocols should be developed in order to monitor these signs and prevent potential complications. A prospective analysis is needed in order to delineate the disease history and potential evolutions (if any) into more defined GI diseases in the contest of autoinflammation.

Disclosure of Interest: None Declared.

Introduction: Monogenic autoinflammatory disorders (AID) and some primary immunodeficiencies can present early in life with Behçet-like symptoms, and may be mistaken for Behçet’s disease (BD). Most of these monogenic conditions require alternative treatments than typically required for BD, and are associated with high morbidity and mortality if diagnosis and appropriate treatment are delayed. Next generation sequencing (NGS) undoubtedly offers the opportunity to screen for these diseases more efficiently, and greatly facilitates diagnosis in this context.

Objectives: To retrospectively describe the clinical and laboratory features, and molecular diagnoses of 11 paediatric cases referred for suspected BD.

Methods: Retrospective, two-centre, case series. A combination of NGS or conventional candidate gene screening approaches were utilised to ascertain genetic diagnoses, facilitated in some cases by functional immunological screening assays. NGS approaches utilised included targeted exome sequencing (the “Vasculitis and Inflammation Panel”, VIP); or whole exome sequencing (WES).

Results: Eleven children referred with suspected BD underwent further molecular testing because of incomplete or atypical BD features, and presentation under the age of 5 years. Seven/11 patients (58%) were Caucasian; the remaining 4/11 were Asian; 64% were female. Two cases were siblings from a consanguineous kindred with “familial” BD; and another had a maternal history of BD. The median age of disease onset was 1.0 (range 0.5-3.0) years. All had systemic inflammation and oral ulceration; 4/11 had genital ulceration; 4/11 had ocular involvement; and 8/11 had cutaneous manifestations. Nine out of 11 were considered to have a monogenic cause: the final genetic diagnoses were: A20 haploinsufficiency (n = 1); Hyper IgE syndrome (n = 1); LYN associated AID (n = 1); TRAPS (n = 1), Chronic Granulomatous Disease (n = 2), Periodic Fever Immunodeficiency and thrombocytopenia Syndrome (PFIT; n = 2), and pustular psoriasis caused by mutation in AP1S3 (n = 1). The remaining two cases had a suspected atypical AID caused by a novel variant in MEFV (n = 1); and a STAT1 variant, as the suspected but as yet unproven monogenic cause (n = 1).

Conclusion: Rare monogenic disorders can mimic BD, particularly when the presentation is under the age of 5 years. These data are now informing a strategy to begin to explore screening for genetic mimics of BD in a UK cohort of children and adults to better understand the proportion of UK BD patients who may in fact have an underlying genetic diagnosis.

Disclosure of Interest: None Declared.

Introduction: Autoinflammatory diseases are a group of inherited diseases characterized by early onset and systemic inflammation, often manifesting with unexplained fevers. These pathologies are usually caused by mutations in genes involved in the regulation of innate immune response with consequent inflammatory phenotype. The mechanism that lead to the development of this diseases are not still clear and part are however genetically undefined.

Objectives: Our aim is to evaluate the differences in the expression of proteins or pathway in monocytes, and plasma metabolites of patients with some of the best-known autoinflammatory diseases (CAPS, TRAPS, FMF and MKD) and healthy subjects. The purpose is clusterize the different disorders to better characterize each pathology and try to distinguish the genetically undefined pathologies.

Methods: Monocytes (purified form peripheral blood and incubated for 4 hours with or without LPS) and plasma were collected from patients and healthy donors. The samples were processed and proteins or metabolites expression evaluated by an High Resolution/Mass Accuracy Liquid Chromatography Tandem Mass Spectrometry (HR/MA LC MS/MS). PCA analysis and Person’s correlation were used as quality control of experimental design, while the statistical analysis was performed with the Perseus software.

Results: We analyze the monocytes and plasma of patients with CAPS, TRAPS, FMF and MKD. We identified about 4000 proteins of each 3500 are quantified by LFQ approach. PCA analysis and Person’s correlation show a good reproducibility of data and a good separation between the different groups. In synchronous way using a cluster analysis and heatmap, based on a machine learning protein selection, we observed a protein signature specific for each group of pathology and for each condition of monocytes treatment. Furthermore we used a supervised multivariate analysis to try to identify a more specific list of proteins for each pathology: at the moment we obtained a list of about 40 protein per disease, significantly modulated if compared with healthy controls and comparing each pathology with the other.

Conclusion: Here, we addressed how an high resolution proteomics approach could be used to better understand the biology of autoinflammatory diseases. The characterization of a broad spectrum of proteins and metabolites and their interaction network will allow us to identify new biomarkers for the different pathologies and better comprehend and recognize the genetically undefined disorders.

Disclosure of Interest: None Declared.

Introduction: Provisional evidence-based classification criteria for inherited periodic fever (TRAPS, FMF, MKD and CAPS) have been recently developed. However, no consensus on how to combine clinical criteria, laboratory test and results of molecular analysis has been reached so far. Moreover, no validated evidence based set of classification criteria for PFAPA has been established so far. We conducted a multistep process, based on a combination of expert consensus and analysis of real patient, to develop new criteria for inherited periodic fevers and PFAPA syndrome.

Objectives: To obtain a consensus > 80% among experts on the diagnosis of a group of patients with inherited periodic fevers, PFAPA and undefined periodic fevers.

Methods: A panel of experts (25 clinicians and 8 geneticists) was asked to evaluate, via a web-based system on the basis of clinical and laboratory data, 360 real patients affected by AIDs (60 FMF, 60 TRAPS, 60 MKD, 60 CAPS, 60 PFAPA and 60 undefined periodic fever) randomly selected from the EUROFEVER Registry. PFAPA patient were evaluated only by clinicians. Experts were asked to classify each patient as having FMF, TRAPS, MKD, CAPS, PFAPA or undefined periodic fever syndrome. The criterion for agreement used was 80% consensus among raters.

Results: After four round of evaluation, 281 over 360 patients (78%) were classified with a consensus > 80% for a specific disease: 36 as FMF, 32 as CAPS, 56 as MKD, 39 as TRAPS, 37 as PFAPA and 81 as undefined periodic fever. In 50 cases the diagnosis changed respect to the diagnosis of the enrolling center. 25 over 36 FMF patients were homozygous or compound heterozygous for high penetrance variants while 4 over 36 patients were compound heterozygous with one high penetrance mutation associated with E148Q variant. 6 over 36 were heterozygous for high penetrance mutations and 1over 36 patients carried only the E148Q variant. Over the 32 CAPS patients, 28 had a genotype consistent with the disease while 4 patients carried a variant of unknown significance (V198M). None of the patients showing the Q703K variant or with negative genetic test was classified as CAPS by the experts. Regarding TRAPS only 1 over 15 patients carrying a low penetrance variants (R92Q, P46L) reached the consensus; none of the 2 patients with negative genetic analysis reached the consensus. Among MKD patients, 4 carried the V377I variant in heterozygous date and among these 2 reached the consensus.

Conclusion: Our process led to a consensus on the diagnosis for 281 patients affected by inherited periodic fevers and PFAPA. In the subsequent phase we had performed statistical analysis in which variables coming from the EUROFEVER Delphi survey will be tested on these patients, to identify the best sets of classification criteria (in term of sensitivity and specificity) for inherited periodic fever and PFAPA that have been discussed in the consensus conference held in Genoa in March 2017.

Disclosure of Interest: None Declared.

Introduction: Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by irregular periodic attacks of serosal inflammation. The gold standard in treatment is colchicine and it is very potent both in preventing attacks and subsiding inflammation and by that way avoiding emergence of amyloidosis.

Objectives: There is a hypothesis pointing out to the negative influence of colchicine on the intestinal absorption of vitamin B12. As colchicine treatment should be used lifelong, vitamin B12 deficiency due to malabsorption may ensue during the course of treatment. Although there is an adult study, there is no data for children with FMF under colchicine treatment.

Methods: Forty-six children with newly diagnosed FMF were enrolled to this prospective study. They were all started colchicine according to their age (0-5 years:0.5 mg, 5-10 years:1 mg, >10 years: 1.5 mg - maximum 2 mg). Vitamin B12 and folic acid levels were obtained at the first day of colchicine treatment, 3rd month and 6th month of the treatment. Mutation analysis of the patients and their clinical findings were also reported.

Conclusion: There was significant vitamin B12 and folate level decrease on the 6th month of colchicine therapy in the children with newly diagnosed FMF. This may be related to ileal malabsorption of vitamin B12 and jejunal malabsorption of folate. Although the study was performed among a small number of children with FMF and a limited time period was reported, prolonged periods may show more significant decrements in the levels of vitamin B12 and folate.

Disclosure of Interest: None Declared

Introduction: Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease, characterized by recurrent fever and self-limited paroxysmal attacks of serosal inflammation.

Objectives: The aim of this study was to evaluate whether iron homeostasis parameters in patients with AAA was improved by treatment with colchicine or not.

Conclusion: In conclusion, we think that colchicine may be effective in balancing the iron homeostasis that is disturbed by chronic inflammation in FMF.

Disclosure of Interest: None Declared

Introduction: The Familial Mediterranean fever (FMF; OMIM 249100) is the most common autoinflammatory syndrome in the group of hereditary periodic fever syndromes, widespread in Armenia. The existing information on frequency of carrying the mutations of FMF gene is hospital based data with subsequent recalculations. To our best knowledge this is first epidemiological population based study in Armenia.

Objectives: The objective is revealing the frequency of MEFV gene mutations and genotypes in Armenian female population in Republic of Armenia.

Methods: The proportionate random sampling technique was performed to select 173 females aged 18-19 years from Yerevan and all marzes (regions) of Armenia. Absence of history or clinical manifestation of FMF or any autoimmune inflammatory disease/syndrome was the premium inclusion criteria. Venous blood samples were taken in EDTA containing vials. Genomic DNA was isolated by means of “Puregene kit” (Gentra System, USA). Molecular-genetic testing performed in the laboratory of auto inflammation diseases of the Center of Medical Genetics and Primary Health Care that has an international certificate and is the best in the region. The most common for Armenian ethnicity 12 mutation were analyzed: M694V, M694I, M680I (G/C), M680I (G/A), V726A, E148Q, K695R, F479L, R761H, A744S, P369S, 1692del.

Results: 53 (30.6%) of females from total 173 carry at least one mutation of FMF gene. From tested 12 mutations only 9 were detected: M694V, M680I, V726A, E148Q, K695R, F479L, R761H, A744S, and P369S. The most frequent finding was M694V: 19 cases (38.8%), followed by V726A: 11cases (22.4%) and E148Q: 9 cases (18.4%). These three mutations cumulatively comprised almost 80% of all. Out of 53 carriers 49 were heterozygous and four carries two mutations. No homozygous were observed. E148Q mutation was presented in all four compound heterozygote carriers, two in combination with V726A and two with P369S.

Conclusion: The frequency of carrying of FMF gene mutation in Armenian non-symptomatic female population is 30.6%. The most common mutations are M694V, V726A, and E148Q. The M694V reported as the most frequent mutation in hospital settings as well, causing the most sever course of disease. Asymptomatic carrier of compound heterozygous genotype is rare, 2.3% only.

Disclosure of Interest: None Declared

Introduction: Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory disease in the world. Although FMF is inherited autosomal recessively, some heterozygotes may express disease phenotype and require therapy. On the other hand, some of the patients presenting manifestations evocative of FMF might happen to be heterozygotes coincidentally due to the high frequency of MEFV variants in at-risk populations.To date, there is no study in the literature about how to follow-up MEFV heterozygotes who do not fulfil FMF criteria.

Objectives: To share a single-center experience of the long-term clinical and laboratory follow-up of paediatric MEFV carriers.

Methods: The hospital charts of 240 children who were heterozygous for MEFV variants were retrospectively reviewed. Among them, 119 heterozygous patients fulfilled paediatric FMF diagnostic criteria and were started colchicine in the first 6 months of follow-up. Ten patients who fulfilled PFAPA syndrome with one MEFV mutation were excluded. 42 patients did not continue to be followed-up at our unit. So, the rest 69 heterozygotes were included in this study. Families were advised to record an FMF diary; including presence of fever, abdominal pain, chest pain, arthritis, arthralgia, myalgia, and erysipelas like erythema and also were asked to record the duration of these symptoms. Patients were asked to admit to hospital in case of any advocative FMF symptom lasting at least 6 hours in order to check acute phase reactants. The children were also followed-up with their routine analysis and serum amyloid A (SAA) levels every 6 months. The data of the visits in which an infection was reported were not included. The averages of all laboratory parameters were then calculated.

Results: 39 children had pathogenic mutations and 30 children had MEFV variants of unknown significance. The most common MEFV variants were M694V (n = 24) and E148Q (n = 16). The mean age at admission was 7.3 ± 3 years. The mean follow-up was 3.2 ± 1.6 years (min:2 max:6 years).

Conclusion: The results of this study suggested that routine clinical follow-up is useful; however, routine periodic laboratory work-up is not necessary among MEFV carriers. To the best of our knowledge, this is the first study about the long-term periodic clinical and laboratory follow-up of MEFV carriers in the literature.

Disclosure of Interest: None Declared

Objectives: We aimed to investigate the prevalence of psoriasis among FMF patients and their relatives.

Methods: FMF patients followed at Hacettepe University Adult and Pediatric Rheumatology Departments between January and August 2016 were included. FMF patients/their relatives were accepted to have psoriasis if the diagnosis was made by a dermatologist.

Results: 351 FMF patients (177 adults; 174 children) were included. The median (min-max) age of adult and pediatric patients was 35 (19-63) and 10 (2-18) years, respectively. Thirteen (3.7%) FMF patients (11 adults, 2 children) had psoriasis. Psoriasis was more common in adult than pediatric patients (p = 0.02). Psoriasis was present in 22 (12.4%) of adult and 9 (5.2%) of pediatric patients’ relatives (p = 0.023). The frequency of psoriasis in ≥1 relatives of FMF patients was found to be 8.8%. Abdominal pain and fever were significantly higher and arthralgia, arthritis, pleural chest pain, pericarditis, and erysipelas-like erythema were significantly less frequent in the pediatric group than adults (p < 0.05).

Conclusion: In our study, psoriasis was more common in FMF patients than the normal population. Thus, FMF patients should be questioned and carefully examined for psoriasis lesions and psoriasis family history. Prospective multicenter studies may be important to find the incidence of psoriasis in FMF.

Disclosure of Interest: None Declared

Introduction: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a fairly common autoinflammatory disease. Still, knowledge of the effects of the recurrent fever episodes on the child and its family situation are limited.

Objectives: To examine the experiences of parents regarding the impact of the disease on the child's general well-being, the family's situation and how the family handles the associated challenges.

Methods: A qualitative approach was used, applying a modified version of Grounded theory for design, data collection and analysis. Data was collected from two different sources:

Uncertainty (Harmlessness - severity)

Assurance (Establishment of diagnosis)

Gradually managing (Regularity - unpredictability)

Conclusion: Getting a diagnosis becomes very important for parents since this reduces uncertainty and feelings of guilt

Disclosure of Interest: None Declared

Objectives: To identify the genetic cause for a phenotype associating severe encephalopathy and chilblain skin lesions in a twenty years old male.

Methods: A twenty years old male presented since early infancy with violaceous, scaling lesions of the fingers and toes, resorption of distal phalanges, dystrophic nail changes and, violaceous lesions on the nose that worsened during the cold season. He was diagnosed at the age of 7 years with Cornelia de Lange syndrome (CdLS) based on the phenotype associating severe somatic and psychomotor retardation, microcephaly, hypertrichosis, synophrys, arched palate, strabismus, hearing loss, cryptorchidism and unilateral vesicoureteral reflux with kidney scarring. Laboratory investigations showed mild thrombocytopenia and positive anti-thyroid antibodies. No cerebral imaging was ever performed. The patient consulted in our Clinic because of his severe peripheral vasculopathy. The interferon type I signature was determined in the peripheral blood of the patient and four age/sex matched healthy controls by quantitative PCR for 3 interferon-stimulated genes (ISGs) (MX-1, IFIT-1 and IFI44); a type I interferon score was calculated as previously described (Nezos et al. J. Autoimmunity, 2015). For disease gene identification, a next-generation sequencing (NGS) panel followed by Sanger sequencing were performed.

Disclosure of Interest: None Declared

Objectives: We present a 4 year old boy with a genetically confirmed diagnosis of CANDLE after presenting to our clinic with the typical clinical and laboratory features of the syndrome.

Methods: The patient was born at full-term and after uneventful pregnancy, to unrelated parents. At 20 days postnatal age a maculopapular rash appeared, initially confined to the extremities, and accompanied by fever. Over the next two years the rash spread to involve the face and body. He developed periorbital swelling, splenomegaly, leucocytosis, iron-deficiency anemia and thrombocytopenia. Fever, reaching up to 40 °C, was a consistent features of disease flares. Three skin biopsies were performed and showed evidence for perivascular and periadnexial infiltrations, consisting mainly of neutrophils. Bone marrow biopsy and immunologic investigations were unremarkable. Treatments with Hydroxychloroquine, Methotrexate and short courses of corticosteroid were tried with little to no effect.

Results: The patient has since been on treatment with oral Methylprednisolone that proved to be effective in controlling his skin rash and systemic inflammation at the cost of systemic side effects. Regular follow-up during the next two years showed nephrocalcinosis, which resolved with symptomatic therapy, and arterial hypertension, controlled by dual antihypertensive therapy. Preliminary reports in the literature showed that JAK-inhibitors might be very effective in controlling the disease activity and we hope to obtain this therapy for our patient.

Conclusion: CANDLE should be considered in patients who present with early-onset severe inflammation, typical skin rash, and lipodystrophy. Genetic testing is already available and although therapy is currently challenging, treatment with JAK-inhibitors holds promise for the future.

Disclosure of Interest: None Declared

Introduction: The complement system represents a major part of the innate immune system, consisting of more than 30 different proteins in plasma and on cell surfaces and can be activated through three different pathways. Inflammasomes are also part of the innate immune system. A group of disorders in inflammasomes have been associated with autoinflammatory diseases (AIDs). Familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular syndrome/neonatal onset multisystem inflammatory disease (CINCA/NOMID) were originally described as three distinct diseases. After the identification of their common genetic origin, i.e. mutations in the NLRP3 gene on chromosome 1q44, they are perceived as a continuum of one disease entity and labelled cryopyrin-associated periodic syndromes (CAPS). Aim of this preliminary study in a patient with MWS was to find a correlation between the complement system and a disorder of autoinflammation.

Objectives: Aim of this preliminary study in a patient with MWS was to find a correlation between the complement system and a disorder of autoinflammation.

Methods: PBMCs (peripheral blood mononuclear cells) were isolated from blood of a healthy donor and of an individual suffering from MWS by density gradient centrifugation using a Ficoll Paque Premium (GE Healthcare). After washing, PBMCs were incubated with anti-human CD14 Magnetic Beads (BD) to obtain CD14+ monocytes. These were stimulated by addition of cytokines (IL-4 and GM-CSF) for five days to generate immature moDCs (iDCs), which were used for cytokine ELISAs and flow cytometric analyses. IL-6 and IL-1β cytokine ELISAs were performed according to the manufacturer (Biolegend) following stimulation of cells using either LPS or differentially complement opsonized HIV-1. Phenotypical characterization of pathogen-exposed DCs was performed by analyzing characteristic surface markers (CD11c, DC-SIGN (C-type lectin receptor on DCs, characteristic marker for iDCs), CD86) by multi-color flow cytometry.

Results: IL-1β production of iDCs is higher in the patients cells than in the cells of the healthy donor. However, the most significant difference was shown in complement opsonized iDCs. DC-SIGN is higher expressed in complement opsonized iDCs in patient cells compared to cells of a healthy donor (37,12% v28,64%). DC-SIGN is also higher expressed in the iDCs of the MWS patient after stimulation with LPS.

Conclusion: The complement system may play an important role in the development of an proinflammatory milieu in patients with disorders of autoinflammation. The phenomenon shown in a patient with MWS has to be reproduced in more MWS patients a well as in patients with other disorder of autoinflammation.

Disclosure of Interest: None Declared

Introduction: Recurrent pericarditis is a common complication of acute pericarditis and affects 15-30% of patients after an initial attack. The etiology is poorly understood and about 80% of these recurrent pericarditis are "idiopathic". However, some data suggest an autoimmune or autoinflammatory mechanism. Colchicine associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice and the use of other treatments remains exceptional.

Objectives: To analyze the clinical findings, course and treatment of pediatric patients with recurrent pericarditis.

Methods: Retrospective monocentric study. Inclusion Criteria :1) patients with at least twice recurrence of recurrent pericarditis (RP) ; 2) followed at Necker hospital between 2006 and 2016. Exclusion Criteria : 1)Known history of autoimmune or autoinflammatory disease.

Results: Thirteen patients (10 F and 3 M) with recurrent pericarditis were included. The median age at disease onset (first episode of pericarditis) was 11.3 years (range 8 - 17). Two groups of patients could be identified: In group 1 (6 patients), the recurrent pericarditis occurred after surgical correction of cardiac malformations; in group 2 (7 patients), there was no history of cardiac disease. During the episodes of pericarditis, all patients showed fever, chest pain, electrocardiographic changes and increased white blood cell counts and C reactive protein (CRP median 181 mg/l, polymorphonuclear cells 13619 g/l,) without differences between the two groups. A family history of recurrent pericarditis was noted in 2 patients from the first group. Six patients had pleuritis and/or pneumonia with concomitant pleural effusion (3 patients in each group). Patients in group 1 had more recurrences than in group 2 (median 2.8 vs 1.5) during the same follow-up period (one year). ANA > 1/640 (Anti-nuclear autoantibodies) and anti-DNA were present in 2 patients of each groups. The pericardial biopsy was performed in 5 patients and displayed fibrosis and showed[an inflammatory tissue with predominance of neutrophils. Initial treatments was aspirin with anti-inflammatory dose, alone (5 patients) or in combination with Colchicine (4 patients), colchicine alone (1 patients) or in combination with ibuprofen (1 patient) and antibiotic therapy (2 patients). To prevent recurrence, six of patients were treated with NSAIDs associated to colchicine or indomethacin alone. Corticotherapy was required in 2 patients in group 2 . Anakinra was introduced in one of them because of corticodependence. Clinical remission was obtained in all patients after discontinuation of the treatment (10 patients) or under treatment (3patients). A heterozygous mutation of R92Q for the TRAPS gene was found in 1 of the 6 patients studied. No mutation in the MEFV gene was found.

Conclusion: Recurrent pericarditis can develop after cardiac surgery or can be isolated. The presence of fever, inflammatory syndrome, pericardial neutrophilic infiltrate, and the efficacy of anti-IL1 in some patients suggests that some recurrent pericarditis could be considered as auto-inflammatory disease. Furthermore the existence of familial cases in two patients suggests a genetic susceptibility. In conclusion early anti inflammatory treatment should be considered in recurrent pericarditis associated with an inflammatory syndrome, after rulling out an infection.

Disclosure of Interest: None Declared

Introduction: Sinusitis is a rare cause of intracranial infection in children. The morbidity and mortality remains high in reported series.

Objectives: We report two cases of sinusitis complicated with intracranial empyema in patients treated with tumor necrosis factor-alfa monoclonal antibody (Adalimumab) for CRMO.

Methods: Case report

Results: The two girls were 11 years old when the infectious complication developed.

Conclusion: Tumor necrosis factor-alfa monoclonal antibody is an efficient anti-inflammatory drug used in treatment of several inflammatory diseases. The increased risk of infections is well known. Special attention should be drawn towards symptoms of chronic rhinitis/sinusitis, as severe intra cerebral complications, such as subdural empyema, may develop. Children with sinusitis and any neurologic finding, signs of complicated sinusitis such as Pott's puffy tumor or orbital cellulitis, or persistent headache, fever, or nausea and vomiting should have additional evaluation for sinogenic subdural empyema.

Disclosure of Interest: None Declared

Introduction: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare auto-inflammatory disorder, characterized by recurrent episodes of bone pain. Diagnosis can be challenging and is based on exclusion. Laboratory investigations, radiology and histology are necessary to make a differential diagnosis with malignancy, infectious osteomyelitis and juvenile idiopathic arthritis.

Objectives: To document clinical characteristics of pediatric patients diagnosed with CRMO. To collect data on outcome and management of the disease.

Methods: We reviewed clinical characteristics, radiological data and treatment in pediatric CRMO patients, followed at the pediatric rheumatology department of the University Hospital of Leuven.

Results: Twenty-five patients were enrolled, with a mean age of 10.1 years at onset of the disease. The mean age at diagnosis was 11.2 years, with a mean diagnostic delay of 14 months. Bone pain was the leading symptom (24/25 patients). On imaging, 148 lesions were identified with an average of 5,9 lesions per patient. The most common sites of involvement were the vertebrae (37%) and lower limbs (31%), followed by the pelvis (10%) and clavicle (9%). In almost half of patients (12/25) monotherapy with NSAIDs was sufficient to obtain remission. The remaining 13 patients received bisphosphonates as 2nd-line therapy. Methotrexate was prescribed in 5 patients. Two patients needed further therapy with biologicals: etanercept (n = 2) and tocilizumab (n = 1). Disease was in remission in 15/25 after a mean time of 22.7 months. The prognosis was worse in patients with spinal involvement, resulting in more long-term sequelae

Conclusion: We present a unique pediatric cohort of 25 CRMO patients. A typical pattern of bone involvement could be found on MRI. Lesions presented as areas of bone marrow edema, with an abnormal hyperintensity on STIR images and/or abnormal hypointensity on T1-weighted images and/or areas of contrast enhancement. NSAIDs were administered as first-line treatment. Second-line strategies included bisphosphonates, glucocorticosteroids, methotrexate, etanercept and tocilizumab

Disclosure of Interest: None Declared

Conclusion: The disease phenotype is more severe in patients with high-risk mutations. Therefore, close follow-up is critical for these patients.

Disclosure of Interest: None Declared

Introduction: Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease which is characterized by recurrent, self-limited flares of fever associated with polyserositis. The association with infectious disease is not clear except for the association with helicobacter pylori infection.

Objectives: In this study, the aim was to assess whether there was a tendency to infections.

Methods: 197 children with FMF who were followed at the Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey between May 2016 and October 2016 were included in the study. In immunodeficiencies, the tendency for infections are defined as acute otitis media, sinusitis and pneumonia frequencies in a year, intravenous antibiotic requirement, presence of abscess, presence of recurrent urinary tract infections and acute gastroenteritis. We have assessed these frequencies in our patient groups according to mutations and attack frequencies.

Results: 30.4% of the patients were in the M694V homozygote group and 42.1% were in high-risk mutation(M694V/M694V, M680I/M680I, M694V/M680I) group. When examining M694V homozygous patients; 3% of patients had more than 4 acute otitis media per year, 6.7% had sinusitis more than 4 per year, and 1.7 had more than 4 per month of upper respiratory tract infection. All of the patients had less than 2 pneumonia per year. Only 6.7% of patients needed intravenous antibiotics. Recurrent urinary tract infection was present in 3.3% and abscess was 1.7% of patients. 13.4% of the patients had a history of acute gastroenteritis.

Conclusion: FMF patients are not inclined to develop infections as in immunodeficiencies. It may be speculated that the abnormality in the innate immune system in these patients does not significantly inpair host defense. More extensive work on this issue may be needed.

Disclosure of Interest: None Declared

Introduction: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease in the world. The disease course could be different in different age groups.

Objectives: In this study, we aimed to study the disease characteristics, treatment compliance and need for additional treatment according to age groups of FMF patients.

Methods: 378 FMF patients (0-18 years) followed at the Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey, between January 2005 and October 2016 were included in the study. The patients were evaluated in three groups according to their age at disease onset; 0-5, 6-11, 12-18 years. The treatment compliance was evaluated in 199 out of 378 patients according to their present ages.

Conclusion: The disease course may be different in different age groups in FMF. FMF may present with less typical phenotype when the symptoms start at an older age (less fever symptom in adolescent. Treatment compliance is very critical in FMF patients and our results have emphasized that poor compliance is an important problem in especially adolescent patients.

Disclosure of Interest: None Declared

Introduction: Familial Mediterranean fever (FMF) is the most common auto-inflammatory disease which is characterized by recurrent, self-limited flares of fever associated with polyserositis. Oral apthosis and periodontitis may be seen in the course of the disease. However we lack studies on the dental care in pediatric FMF patients.

Objectives: In this study, the aim was to report the oral findings and to check the effects of tooth decay on disease course in children with FMF.

Methods: 199 children with FMF who were followed at the Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey between May 2016 and October 2016 were included in the study.

Conclusion: The frequency of the tooth decay was higher in our patient group compared to previously reported Turkish figures(91.5% vs 69.8-73.1%; respectively). The attack frequency at the last six months was higher away patients with tooth decay. Our results may suggest that dental problems may be a trigger for inflammatory attack in FMF. On the other hand, the chronic inflammation itself may be a risk factor for tooth decay in FMF.

Disclosure of Interest: None Declared

Introduction: In 2008 the Paediatric Rheumathology European Society (PReS) promoted an International Project (EAHC, Project No2007332) for the study of Autoinflammatory Diseases (AIDs) named Eurofever, whose main purpose is to create a web-based registry for the collection of clinical, laboratory, instrumental and response to treatment information in patients with AIDs.

Objectives: To implement the Registry with the new recently described AIDs and to increase the collection of longitudinal data, particularly regarding treatment and safety.

Results: Up to date 3648 patients (M:F = 1799:1849) have been enrolled in the Registry from 60 different countries (all of them with available baseline demographic information). In 3183 pts (87%) complete clinical information and response to treatment data from disease onset to diagnosis are also available. For each disease the number of enrolled patients is: FMF 1012 pts (877 with complete clinical data); CAPS 289 pts (268 with complete clinical data); TRAPS 272 pts (254 with complete clinical data); MKD 203 pts (188 with complete clinical data); Blau’s disease 50 pts (26 with complete clinical data); PAPA 35 pts (all of them with complete clinical data); NLRP-12 mediated periodic fever 13 pts (10 with complete clinical data); DADA2 10 pts (6 with complete clinical data); SAVI 3 pts (all of them with complete clinical data); DIRA 3 pts (all of them with complete clinical data); Majeed 3 pts (all of them with complete clinical data); CANDLE 1 pt (with complete clinical data). Among multifactorial autoinflammatory diseases: PFAPA 653 pts (530 with complete clinical data); CRMO 535 pts (513 with complete clinical data); 340 pts with undefined periodic fever (269 with complete clinical data); Bechet disease 215 pts (186 with complete clinical data) and Schnitzler syndrome 11 pts (all of them with complete clinical data).

Conclusion: The enrolment in Eurofever Registry is still ongoing. The longitudinal collection and analysis of data coming from the Registry will improve our knowledge both on the natural history of the single disease and on the efficacy/safety of treatment commonly used in the clinical practice.

Disclosure of Interest: M. Finetti: None Declared, S. Federici: None Declared, J. Frenkel: None Declared, S. Ozen: None Declared, H. Lachmann: None Declared, F. De Benedetti: None Declared, J. Swart: None Declared, L. Cantarini: None Declared, R. Gallizzi: None Declared, M. Cattalini: None Declared, R. Cimaz: None Declared, D. Rigante: None Declared, J. Anton: None Declared, M. Alessio: None Declared, A. N. Olivieri: None Declared, P. Dolezalova: None Declared, A. Jansson: None Declared, G. Fabio: None Declared, J. Sanchez Manubens: None Declared, E. Hachulla: None Declared, R. Consolini: None Declared, K. Krause: None Declared, Z. Ekinci: None Declared, J. Brunner: None Declared, I. Koné-Paut: None Declared, G. Filocamo: None Declared, M. D. C. Pinedo: None Declared, E. Papadopoulou-Alataki : None Declared, L. Bezrodnik: None Declared, A. Martini Grant/Research Support from: Starting from 1 march 2016 I became the Scientific Director of the G. Gaslini Hospital, therefore my role does not allow me to render private consultancies resulting in personal income. I perform consultancy activities on behalf of the Gaslini Institute for the following companies: Abbvie, Boehringer, Novartis, R-Pharm. The money received for these activities are directly transferred to the Gaslini Institute's bank account., N. Ruperto Grant/Research Support from: The G. Gaslini Hospital, which is the public Hospital where I work as full time public employee, has received contributions from BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer and Sobi for the coordination activity of the PRINTO network. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Speaker Bureau of: Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb,, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi., M. Gattorno Grant/Research Support from: Unrestricted grant from SOBI and NOVARTIS

Objectives: Here we present the findings of eye involvement in a family whose 11 members have MWS.

Methods: Clinical data was collected during the course of ongoing patient care.

Results: We evaluated the clinical features of 11 patients who were referred to a tertiary care center. The median age of the patients was 25 years (range: 9-65). The ratio of females/males was 1.2 (6/5). All patients had arthritis with exacerbation on exposure to cold and recurrent episodes of pink eye. The median age of onset of ocular involvement was 8 years (2-45). We observed severe eye involvement in 27% of our cases, including band keratopathy, severe damage of corneal stroma and neovascularization. Corneal involvement and clouding was detected in four patient. Two of those had the diagnosis of keratoconus as well. Patients with keratoconus had corneal scarring due to corneal hydrops verified with corneal topography. The other two patients with corneal clouding had bant keratopathy. One of those patient was a 17 year old girl who had recurrent uveitis with hypopyon which necessiated the use of intravitreal dexamethasone implant. She also had posterior synechia of the iris to the lens. The other eye of that patient had signs of phthisis bulbi. The other patient with bant keraopathy was 46 years old male who had optic atrophy and tractional fibrovascular membranes at the posterior pole of the eye. Anakinra was used for treatment of 5 cases, and canakinumab of 3 cases. It was observed that the frequency of conjunctivitis decreased after anti IL-1 therapy. There was no mutation detected in the study of MEFV (all exons), TNFRSF1A (exons 2 to 7), MVK (all exons), NLRP3 (all exons), NOD2 (exons 4, 8 and 9) and PSTPIP1 (exons 10 and 11) genes.

Conclusion: In this study, it has been shown that eye findings related to MWS can vary from conjunctivitis to severe uveitis. We want to emphasize that ocular involvement in MWS should be carefully assessed, since it can lead to visual impairment.

Disclosure of Interest: None Declared

Objectives: To describe clinical phenotype of an Irish cohort of patients with CRMO and compare those with unifocal and multifocal disease.

Methods: This study was a retrospective chart review of a prospectively gathered cohort of patients attending a single paediatric rheumatology centre.

Results: Since 2006, 42 patients have been diagnosed with CRMO at the National Centre for Paediatric Rheumatology (NCPR) and 5 of these have unifocal disease. Patients with unifocal disease had a single site involved throughout the disease. Three patients with unifocal disease had a single symptomatic episode. All patients met the diagnostic criteria proposed by Jansson et al and are ethnically Irish. Overall the mean age at diagnosis was 10.4 years, diagnostic delay was 0.78 years and number of physicians seen prior to referral to paediatric rheumatology was 3.5. All patients with unifocal disease and 68% of patients with multifocal disease were female (overall F:M = :1). The distribution of lesions was similar in both groups. In patients with unifocal disease, all underwent biopsy to confirm the diagnosis, none had systemic symptoms at presentation, synovitis at any stage or a personal history/first-degree relative with an associated autoimmune disease. In patients with multifocal disease, 81% underwent biopsy, 24% had systemic symptoms at presentation, 21% had synovitis and 38% had a personal history/first-degree relative with autoimmune disease. 1 patient (20%) with unifocal disease was refractory to NSAID treatment and received methotrexate. 14 patients (38%) with multifocal disease were refractory to NSAID treatment and received methotrexate, corticosteroids, anti-TNF, pamidronate or a combination of these.

Conclusion: The clinical phenotype of patients with unifocal CRMO appears to be different to those with multifocal disease. It may be less frequently associated with other autoimmune or autoinflammatory conditions and more frequently responsive to NSAID treatment alone. However, the number of patients with unifocal disease in this cohort was low.

Disclosure of Interest: None Declared

Introduction: Bone marrow oedema in a child is a rare and uncommon condition associated with joint and bone pain exacerbated by weight bearing.

Objectives: We re-evaluated in the period of 2015-2016 seven pediatric patients referred to our Rheumatology Clinic for persistent foot pain with MRI oedema of the feet bones (interpreted commonly as algodystrophic syndrome manifestation); they had all been misdiagnosed in other institutions as affected by algodystrophy of the ankle/feet or complex regional pain syndrome (CRPS).

Methods: All the patients were re-evaluated with clinical examination, blood samples of bone turnover and vitamin D levels.

Results: Mean age of the 7 patients (F:M 6:1) was 11 years. 3 of the patients (43%) had a previous diagnosis of oligoarticular juvenile idiopathic arthritis ANA+ with the disease in complete remission at the moment of the clinical evaluation; 4 patients did not suffer from any chronic disease.

Conclusion: Symptoms and disability out of proportion to the clinical findings is a clinical key feature of MRI bone oedema of painful skeletal sites in children; differential diagnosis with the multifacet pediatric CRPS is possible when bone oedema is associated with limited clinical findings; it may be secondary to underestimated articular microtraumatisms in a bone turnover milieu of vitamin D deficiency; we underline the importance of supplementing vitamin D until the age of 18 as daily drops, in order to avoid its deficiency, which, in combination with other environmental and predisposing factors, could be the cause of invalidating clinical complaints.

Disclosure of Interest: None Declared

Introduction: Chronic non-bacterial osteomyelitis (CNO) is a rare non-infectious inflammatory bone disorder that affects young children and adolescents. It usually affects multiple sites and most commonly the metaphyseal regions of long bones in the lower limbs, pelvis and clavicles.

Objectives: We aimed to compare the diagnostic yield of bone scan to WB-MRI in CRMO in relation to clinical symptoms and location of lesions on imaging.

Methods: A retrospective review of clinical notes of children with CNO/CRMO was performed. 7 patients with paired BS and WB-MRI performed less than 9 weeks apart between September 2009 and October 2015 were analysed. Patients were excluded if both scans were done more than 9 weeks apart or if there was treatment change between scans.

Results: Four sets of scans were performed at diagnosis and 3 sets after initiation of treatment. BS and WB-MRI detected a total of 29 and 40 lesions respectively. 6 out of 7 patients had asymptomatic lesions. 17/29 (58.6%) and 27/40 (67.5%) were found on BS and WB-MRI respectively.

Conclusion: Whole body bone scan performs comparably to MRI in detecting inflammatory bone lesions in CRMO, both symptomatic and asymptomatic. Bone scan remains an appropriate and accessible imaging modality in the evaluation of CRMO, particularly in institutions where resources are limited.

Disclosure of Interest: None Declared

Introduction: The decrease in mineral bone density (BMD) is one of the main manifestations of juvenile idiopathic arthritis (JIA).

Objectives: To evaluate indicators of bone metabolism in patients with articular JIA.

Results: The results of densitometry showed a reduction in BMD in the range Z = -1,1 -2,6 SD up to 40% of cases with oligoarticular the form of JIA and in 57,7% of cases, polyarticular JIA variant. Deficiency of 25(Oh)D in blood serum of examined children with oligoarthritis and polyarthritis detected at 23.3% and 50%, respectively, and the failure is at 76,7% and 50%, respectively. In the control group, these figures were 10% and 75%, respectively. The ratio of RANKL/OPG in children with oligoarthritis were 0.17 and polyarthritis - 0,22 in the control group - 0,07. Indicators of CL, indicating bone resorption in the group of oligoarthritis was increased at 93.3%, in the group of polyarthritis in 100%.

Conclusion: Thus, in patients with JIA is a decrease in BMD, with changes in biochemical parameters outstrip the capabilities of the method of instrumental diagnosis (densitometry) and can be recommended for research on early stages of osteopenia providing for timely correction of bone metabolism.

Disclosure of Interest: None Declared

Introduction: Several studies investigated the accuracy and efficacy of IACI for the treatment of TMJ involvement in JIA. However, the impact on patients’ daily activities and patients’ acceptance of TMJ IACI has been scarcely studied.

Objectives: To detect variations in daily activities involving TMJs in patients with JIA, before and after TMJ IACI, through a Juvenile Arthritis TMJ self-reported Assessment (JATA) questionnaire, developed for the purpose. Second aim: to assess the patients’ acceptance of the TMJ IACI procedure at the study center.

Methods: Patients with JIA and clinical involvement of TMJ consecutively seen at the study center in September-December 2016, with at least 8 years of age, were asked to identify the daily activities most affected by TMJ arthritis. From the collected items, we asked them to select the most relevant and representative of “TMJ well-being/worsening” in their daily life. We included in the JATA the items most frequently selected and a patient’s global assessment (GA) of their TMJs (VAS 0-10; 0 = worst; 10 = best). Then, a subgroup of patients, who underwent to intraarticular corticosteroid injection (IACI) of one or both TMJ, was asked to complete the questionnaire (VAS 0-10; 0 = totally unable, 10 = fully able) and TMJ-GA, before and after the therapeutic intervention. Further, we asked the patients to provide a global assessment of the TMJ IACI procedure performed at the study center (VAS 0-10; 0 = worst; 10 = best). Statistical analysis was performed using GraphPad Prism 5 software. Scores of each item and JATA-score were compared between pre- and post-TMJ IACI (Wilcoxon matched pairs test, statistical significance: p <0.05).

Conclusion: The JATA questionnaire demonstrated to be easily applicable and showed significant improvement of each item, after TMJ IACI. TMJ IACI procedure at the study center was well accepted. Further studies are planned to confirm these results and investigate the applicability of JATA in clinical practice and research.

Disclosure of Interest: None Declared

Introduction: Persistent course oligoarticular juvenile idiopathic arthritis (JIA) has the best prognosis of all JIA categories. One third of children with oligoarticular onset will, however, develop oligoarticular extended JIA or other JIA categories during the course of the disease with outcome similar to polyarticular disease (1). Therefore it is important to look for early predictive factors to define long-term outcome for these children. Pain is a frequent complaint, and knowledge of pain and its relevance for disease outcome is limited.

Objectives: To study if self-reported pain early in disease course can predict long-term disease outcome among children with oligoarticular JIA.

Conclusion: Early pain report among children with oligoarticular JIA seems to predict development into prognostically more unfavourable JIA categories, more pain persistence and more severe long-term disease outcome.

Disclosure of Interest: None Declared

Introduction: Temporomandibular joint (TMJ) involvement with both active and chronic signs of arthritis is seen very often (17-87%) in children with juvenile idiopathic arthritis. Contrast enhanced MRI is the golden standart for diagnosis of TMJ arthritis. There are data that specific HLA II class alleles can be asociated with more severe disease course and radiologic progression in patients with rheumatoid arthritis.

Objectives: To identify HLA II class alleles of risk and protection in JIA patients with chronic arthritis signs in temporomandibular joints evaluated with contrast enhanced MRI.

Methods: We performed retrospective study with 72 JIA patients treated at Childrens university hospital in whom TMJ MRI was performed and acute or chronic or both signs of arthritis were detected. Patients were genotyped for HLA- DRB1; DQB1; DQA1- using RT-PCR with sequence-specific primers. Associations of DRB1; DQB1; DQA1 alleles in patients were examined individually using the Chi-square test and Cochran-Mantel-Haenszel test.

Results: 72 JIA patients with mean age of 13.9 years (range 6.0-17.9 yr); 48 (77%) girls and 14 (23%) boys. The mean duration of the disease from the time of diagnosis till performing TMJ MRI was 1.5 years (range 0.2-8.0 yr). JIA subtypes were as follows: seronegative polyarthritis 60%, seropositive polyarthritis 8%, peristant olygoarthritis 2%, arthritis with enthesitis 9%, undifferentiated 3% and 2%for systemic arthritis.

Conclusion: Alleles DRB1*14 and DQA1*05:01 are possibly protective for development of structural damage in temporomandibular joints in JIA patients and is not dependent on duration of the disease.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) consists of an auto-immune condition with several subgroups with distint clinical, laboratory features and therapy response. Although antinuclear antibody (ANA) positivity can be found in all subtypes, a higher prevalence in the oligoarticular form is well known. Recently, its association with the remission rate has been studied, but few data are available.

Objectives: To evaluate the clinical response based on ANA status in JIA patients.

Methods: We performed an observational retrospective study with all children diagnosed with JIA followed in our Rheumatology Pediatric Unit until april 2017. Demographic and clinical data were colleted from medical records. JIA subtypes were categorized according to the classification of the International League of Associations for Rheumatology 2001. ANA were considered positive when at least 2 titers were ≥ 1/100. Remission status at follow-up was defined using the Wallace preliminary criteria. Parametric and non-parametric test were used for statistic analysis (SPSS 20.0). P-values <0.05 were considered statistically significant.

Results: A total of ninety-four patients were enrolled. Sixty-three were female (67%). The mean age at time of diagnosis was 7.2 years (SD 4.4) and the mean follow-up was 8.9 years (SD 6.6). The most common subgroup was oligoarticular persistent JIA (38.3%), followed by polyarticular (25.5%), systemic (13.8%), psoriatic (10.6%), enthesitis-related arthritis (7.4%) and oligoarticular extended JIA (4.3%). Extra-articular manifestation as uveitis was seen in 14 patients. Both rheumatoid factor and anti-citrullinated peptide antibody were positive in 37.5% of the polyarticular JIA. ANA positivity was presented in 41.5% of all patients, in which was found a significant predominance of the oligoarticular form, female gender, earlier onset of disease and increased risk of developing chronic anterior uveitis during the course of the disease (p = 0.001, p = 0.025, p = 0.001, p = 0.015, respectively). The mean joint count at diagnosis was 3.9 (SD 5.0). At the last follow-up evaluation the mean joint count was 0.32 (SD 0.7), almost 59% of the patients were in remission (25.5% on medication for at least 6 months and 33% off medication for ≥ 12 months) and 41.5% had active disease. 6.4% of the patients were treated with biologic monotherapy, 37.2% were receiving classic DMARDs while 14.9% were under combination therapy. In the group of patients in remission on medication >6 months, 8.3% and 45.8% of the patients were treated with biologic and classic DMARDs respectively, and combination therapy was observed in 37.5% of them. In the group with active disease, biologic monotherapy, classic DMARDs or combination therapy use was seen in 10.3%, 61.5% and 12.8% of the patients, respectively. No significant diferences were found in what concerns clinical outcome when comparing ANA-positive and ANA-negative patients (p = 0.091).

Conclusion: Our study demonstrates once again the association between the ANA positivity and the oligoarticular subtype, female predominance and the presence of uveitis. It also supports the late literature that didn’t find a relationship between the remission rate and ANA status.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is the childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle. JIA combine with muscle weakness, poor flexibility, atrophy, pain, and decreased proprioception of the affected joints, abnormal biomechanics, articular cartilage damage.

Objectives: We aimed to observe the effects of knee Q deformity on postural stability of children with pes planovalgus having JIA.

Methods: Twenty participants as age range 4-16 years (4 female,16 male) were enrolled this study. New York Posture Rating Scale were used to evaluate the posture of participants. Hand held dynamometry was used to assess the strength of the lower extremity muscles. Their static balance evaluated with Flamingo balance test. Their dynamic balance evaluated with Prokin balance system. Q angle was calculated by Universal desktop ruler. Universal Desktop Ruler allows you to measure not only a straight-line distance but any curved distance on the screen. For statistical analysis SPSS Version 21.0 program was used.

Results: For our statistical evaluations, abduction, adduction, knee flexion and extension negatively, knee flexion angle and addiction angle positively may affect static balance(p < 0,05). In addition to that, dynamic balance related to power of plantar flexion positively, knee extension, inversion, abduction angle positively. The results of this study showed that knee flexion angle and plantar flexion angle may affect Q angle negatively. There is statistically significant effect between Q angle and posture deformity (p < 0.05).

Conclusion: In this study, power of hip flexion structure and function of the foot and ankle, and there is preliminary evidence that foot problems impair balance. Balance has often been used as a measure of lower extremity function and is defined as the process of maintaining the center of gravity within the body's base of support. These results are supported by evaluating more children with juvenile idiopathic arthritis with pesplanovalgus.

Disclosure of Interest: None Declared

Introduction: Pediatric immune-rheumatologic diseases are rare, characterized by chronic course and significant impact on patient’s life. Recent developments have significantly improved the prognosis of these diseases, but a close follow-up of patients’ cohorts is essential to evaluate the long- term outcome. The JIRcohorte is an international platform developed to follow pediatric immune- rheumatologic diseases, and evaluate the long-term tolerance and efficacy of immunosuppressive and biological therapies. The challenge was to develop a tool with items both common for all patients and specific for each disease.

Objectives: Describe the multi-module tool implemented in the JIRcohorte platform and the collective of patients included in the different modules.

Methods: For each of the eCRF, an expert group has defined the items to be collected for prospective follow-up of patients with a specific disease. A first comparison was done to highlight the identical items from the different eCRF and the items specific to each one. For all the items reported in more than one module in a similar but not identical way, a negotiation between the experts made it possible either to find a common item or to clearly define the difference between them. We describe the patients of 45 centers (in Belgium, France, Maroc and Switzerland) included in the JIRcohorte between 2014 and 2017.

Results: Thanks to the development of a multi-module tool, we were able to reduce the number of items to insert in the JIRcohorte from 3860 to 2188, by keeping the same level of information. A total of 3266 patients and 10733 visits were collected. The number of patients and visits per module are as follows: Juvenile Idiopathic Arthritis (1371 patients, 4782 visits), Temporomandibular Arthritis (64, 156), Juvenile Dermatomyositis (18, 61), Juvenile Systemic Lupus (121, 369), Juvenile Periodic Fever Syndrome (450, 803), Still Disease (54, 176), Uveitis (142, 1409) and Vaccination (2251, 6924).

Conclusion: JIRcohorte collects follow-up data on pediatric patients with different immuno- rheumatologic pathologies. Thanks to its structure, with both common and specific items in each module, it can be used as a valuable tool to compare pediatric patients with different inflammatory rheumatic diseases.

Disclosure of Interest: None Declared

Methods: Molecular analysis by Whole Exome Sequencing and homozygosity mapping was performed on the proband and other affected and non affected relatives.

Conclusion: The reported family underscores the importance of recognition of this unique skeletal dysplasia by clinicians, and especially by pediatric rheumatologists and orthopedic surgeons.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability [1]. It is essential to know the prognosis for the individual patient early in the course of disease and preferentially at the time of diagnosis in order to start the right treatment immediately [2].

Methods: The study included 255 patients with JIA who were divided into 4 subgroups according to the severity of the disease course: mild (N = 33), moderate (N = 58), severe (N = 68) and very severe (N = 96). The grouping was performed depending on the number of affected joints, the presence or absence of high laboratory activity, systemic features, uveitis, early radiologic progression, functional disability and the need for early "aggressive" therapy. Genotyping was performed using real-time PCR method. Statistical analysis was performed using two-tailed Fisher's exact test (p), odds ratio (OR) and 95% confidence interval (CI).

References. [1] Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007 Mar 3;369(9563):767-78.

Disclosure of Interest: None Declared

Introduction: Survivin is an anti-apoptotic protein and its circulating levels were associated with joint destruction and erosions in rheumatoid arthritis (RA). Recently it was suggested to be a marker of severe disease course in adult patients with RA as well as juvenile idiopathic arthritis (JIA). Three single nucleotide polymorphisms (SNPs) can affect the normal protein and its concentration. Methotrexate (MTX) is an important drug in treating JIA, but markers to predict its efficacy are needed.

Objectives: To evaluate the effect of SNPs in survivin gene on methotrexate efficacy in JIA.

Methods: The data of 119 consecutive patients with JIA treated with MTX at the University Children’s Hospital Ljubljana from June 2011 to January 2015 have been retrospectively reviewed. The disease activity was measured using JADAS 71 score. Non-responders were defined as patients not reaching 30% improvement in JADAS 71 score 6 months after the beginning of treatment with MTX. Genotyping of SNPs in the genes for survivin was performed using real time PCR methods. The following SNPs were analyzed: BIRC5 G692C rs8073069, BIRC5 T241C rs17878465 and BIRC5 G692C rs8073069. Two-tailed Fisher exact test was used for statistical analysis.

Conclusion: Our results suggest that SNPs in survivin gene, BIRC5 rs17878465 and BIRC rs9904341 could be markers of MTX response in JIA.

Disclosure of Interest: None Declared

Introduction: European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) proposed validated classification criteria for Henoch-Schönlein purpura (HSP). However, there are rare studies reporting initial risk factors to HSP nephritis (HSPN) and outcomes using these new criteria. In addition, these studies generally included small samples, and none of them were evaluated in Latin American population.

Objectives: To evaluate risk factors associated with HSPN and outcomes in children and adolescents of a tertiary center in Latin America.

Methods: Two hundred ninety six patients with HSP were retrospectively assessed by demographic data, and initial clinical manifestations, laboratory exams and treatments evaluating in the first three months of disease. All of them fulfilled validated EULAR/PRINTO/PRES criteria for HSP. They were also divided in two groups: with and without nephritis. Additional, persistent non-nephrotic proteinuria, nephrotic proteinuria and renal insufficiency were also evaluated at 1, 5, 10 and 15 years after diagnosis.

Results: Nephritis was detected in 139/296 (47%) at first 3 months. The median of age at diagnosis was significantly higher in HSPN patients compared to those without this complication [6.6(1.5-17.7) vs. 5.7(0.9-13.5) years, p = 0.022]. The frequencies of persistent purpura (31% vs. 10%, p < 0.0001), recurrent abdominal pain (16% vs. 7%, p = 0.011), gastrointestinal bleeding (25% vs. 10%, p < 0.0001) and corticosteroid use (54% vs. 41%, p = 0.023) were significantly higher in the former group. In the multivariate analysis, logistic regression demonstrated that the independent variables that predicted HSNP were persistent purpura (OR = 3.601; 95%CI 1.605-8.079; p = 0.002) and gastrointestinal bleeding (OR = 2.991; 95%CI 1.245-7.183; p = 0.014). Of 139 HSPN, further analysis revealed that persistent non-nephrotic proteinuria, nephrotic proteinuria and renal insufficiency occurred during follow-up: at 1 year [46/88 (52%), 1/88 (1%) and 2/88 (2%)], at 5 year [25/47 (53%), 1/47 (2%) and 1/47 (2%)], at 10 year [9/20 (45%), 1/20 (5%) and 1/20 (5%)] and at 15 years [1/6 (17%), 0/6 (0%) and 0/6 (0%)]. In addition, in patients without HSPN at disease onset: 29/118 (25%) had persistent non-nephrotic proteinuria and/or hematuria only at 1 year of follow-up, 19/61 (31%) at 5 years, 6/17 (35%) at 10 years and 4/6 (67%) at 15 years of follow-up.

Conclusion: Persistent purpura and gastrointestinal bleeding were initial predictors for HSPN. Persistent non-nephrotic proteinuria and/or hematuria may occur during the disease follow-up, even in patients without previous HSPN, and rigorous monitoring of renal involvement should be performed.

Disclosure of Interest: I. Buscatti: None Declared, B. Casella: None Declared, N. Aikawa: None Declared, A. Watanabe: None Declared, S. Fahrat: None Declared, L. Campos: None Declared, C. Silva Grant/Research Support from: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 472155/2012-1)

Introduction: Arthritis of the temporo-mandibular joint (TMJ) is often responsible for severe osteo-articular damage in patients with juvenile idiopathic arthritis (JIA). Early diagnosis of TMJ involvement remains difficult, due to the lack of reliable clinical or imaging parameters. However, magnetic resonance imaging (MRI) is regarded as the most sensitive tool for the detection of TMJ involvement in JIA.

Objectives: To develop and validate a MRI score for early detection of TMJ disease activity and damage in children with JIA.

Results: A total of 35 TMJ MRIs performed between December 2013 and December 2016 were evaluated. The analysis of the absolute agreement in score assignment among specialists revealed substantial agreement, with greater concordance between the dentist and the radiologist. The rheumatologist tended to assign lower scores. Among disease activity parameters, the lowest agreement was seen for bone edema, whereas the most challenging joint damage parameter was disc abnormalities. There was a moderate agreement between the CE recorded by the study assessors and that obtained through the ROI calculation, especially for the rheumatologist and the dentist.

Conclusion: We have developed a new simple and feasible MRI score for the detection and quantification of disease activity and damage of the TMJ in children with JIA. Although the overall score proved reliable across different specialists, further work is needed to increase concordance for assessment of bone edema and disc abnormalities.

Reference: 1. Resnick CM et al. Quantifying Temporomandibular Joint Synovitis in Children With Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2016;68:1795-1802.

Disclosure of Interest: None Declared

Introduction: Phagocyte recruitment and migration to the site of inflammation are key events in the early phase of inflammation. They are indispensable for pathogen elimination, tissue repair and restoration of tissue homeostasis. However, dysregulated phagocyte infiltration and a subsequently overwhelming immune response can also cause severe inflammatory disorders. Therefore, targeting and modulation of phagocyte infiltration represents a promising new approach to fight inflammatory disorders and diseases, such as rheumatoid arthritis. Furthermore, non-invasive tracking of phagocyte migration to the site of inflammation could extend both scientific knowledge as well as the repertoire of diagnostic strategies in clinical use.

Disclosure of Interest: None Declared

Introduction: Diagnosis of juvenile Sjögrens syndrome (jSS) although rare seems to be underestimated in pediatric patients. Especially in patients with undifferenciated mixed connective tissue disease (MCTD) secondary jSS is frequently present but missed in the diagnostic work-up.

Objectives: Our intend was to characterize distinct, ultrasonographic (US) findings in a cohort of primary- and secondary jSS patients, the latter with a focus on MCTD and attribute these findings to US scores defined in adult SS.

Methods: A single-center study collected data from clinical charts of jSS-patients admitted to the GCPAR. According the EULAR/ACR criteria 8 patients with primary jSS, 8 patients with secondary jSS and MCTD and 9 patients with secondary jSS and other collagenoses were included. All ultrasonographic (US) findings were performed by two experienced investigators between 5/2014 and 3/2017 using a GE logic 8 system. Different scoring systems from the literature were compared for accuracy for gland echostructural abnormalities.

Conclusion: In patients with pjSS and sjSS salivary gland ultrasound is a helpful, first-line tool not only to detect salivary gland involvement but to score the severity of inflammation as well. As sjSS is supposed to be underestimated in collagenoses and MCTD, screening of salivary gland by US is usefull even in patients without sicca-symptoms to identified typical, inhomogeneous parchenchymal appearance with hypoechoic lesions suggestive for jSS.

Disclosure of Interest: None Declared

Introduction: The ankle is a complex anatomical structure owing to the multiple joint recesses and surrounding tendons. The clinical examination of this joint is a challenging task even for the expert physician. Ultrasound (US) is becoming a useful adjunctive tool to clinical evaluation for the assessment of children with juvenile idiopathic arthritis (JIA). Disagreement between clinical and US examinations in the assessment of the ankle region has been shown in some studies.

Objectives: The aims of the study were: 1) to assess the frequency of clinical signs of articular and periarticular involvement and of US abnormalities in the different joint recesses and tendon compartments of the ankle region; 2) to investigate the correlation between clinical signs of articular involvement and US abnormalities in the different joint recesses of the ankle region.

Methods: Twenty-seven ankles of 19 patients with JIA with a clinical suspicion of disease involvement were included in the study. At the same consultation, the ankles were scanned by a physician with experience in the US assessment of children with JIA, who was blinded to clinical findings. Clinical and US evaluations focused on tibiotalar and subtalar joints, the tarsal area and on tendon compartments. For each of the joint recesses the presence of swelling, pain on motion and restricted motion and the detection of joint effusion (JE), synovial hypertrophy (SH) and power Doppler (PD) signal inside the area of SH were recorded on clinical and on US evaluation, respectively. US abnormalities were graded on a 4-point semiquantitative scale. Correlation between clinical signs of articular involvement and US abnormalities in the different joint recesses of the ankle region was estimated using the Kendall’s tau (τ) coefficient.

Results: Overall, on clinical assessment swelling was found more frequently in the tibiotalar joint (52%), whereas both pain and restricted motion were documented more commonly in the subtalar joint (44% and 41%, respectively). On US assessment JE and SH were detected more frequently in the tibiotalar joint (56% and 67%, respectively); PD signal was displayed more commonly in the subtalar joint (44%). Among tendon compartments, both clinical and US assessments documented a more frequent involvement of flexor tendons (11% and 52%, respectively). Correlation was found between presence of pain or restricted motion on clinical evaluation and detection of PD signal on US in the tibiotalar joint (τ = 0,58, p = 0,002 and τ = 0,57, p = 0,002, respectively). In the tarsal area correlation was found between presence of restricted motion on clinical assessment and detection of PD signal on US (τ = 0,43, p = 0,024) and between presence of pain on clinical assessment and detection of SH on US (τ = 0,41, p = 0,033). No correlation was found in the subtalar joint between any clinical sign of articular involvement and US abnormalities.

Conclusion: Tibiotalar and subtalar joints are more commonly affected than the tarsal area on both clinical and US assessment in case of ankle involvement in JIA. Flexor tendons are more frequently inflamed than the anterior and lateral tendon compartments. On clinical examination, pain or restricted motion, but not swelling, in the tibiotalar joint and in the tarsal area seem to correlate with the presence of synovitis on US in these joint recesses of the ankle region. The assessment of the subtalar joint remains a challenging task for the physician without the use of US.

Disclosure of Interest: None Declared

Introduction: Kawasaki disease (KD) is an acute febrile systemic vasculitis that affects blood vessels of small and medium calibre. With the availability of intensified treatments for most severe patients, it is crucial to early identify patients at high risk for coronary artery aneurysms (CAA). However, the available risk scoring systems from Japan have not been validated in European populations. There is little data concerning the link between initial echocardiogram findings and cardiac prognosis.

Objectives: To investigate the first echocardiogram can predict resistance to conventional therapy and/or subsequent development of CAA

Methods: We retrospectively analysed demographic, clinical, biological, echocardiographic and therapeutic data from children diagnosed with KD between 2006 and 2016 at the Robert-Debré University Hospital, Paris, France.

Results: A total of 157 children with KD were included. Initial echocardiogram was performed after a median of 6 days of fever and was abnormal in 48 cases (31%). The initial presence of any echocardiographic abnormality was strongly associated with resistance to intravenous immunoglobulin (p = 0.005) and development of coronary artery lesions within the first six weeks of disease (p = 0.01). All patients (n = 7) with persistent coronary abnormalities at one year already had an abnormal initial echocardiogram. In contrast, severity scores had low sensitivity (24-33%) and low specificity (72-81%) to predict immunoglobulin resistance or cardiac involvement.

Conclusion: Abnormalities in the initial echocardiogram can be used to early identify patients with severe Kawasaki disease in populations with mixed ethnic backgrounds.

Disclosure of Interest: None Declared

Introduction: Takayasu arteritis is a chronic granulomatous vasculitis that effects primarily aorta and its main branches and rarely seen before the age of 18. Delay in diagnosis and treatment is a common feature due to the nonspecific systemic features. There is limited data on clinical features and long-term outcome of Takayasu arteritis. Also, there is need to evaluate efficacy of current therapies, since the spectrum of treatment options have been increased compared to the past.

Objectives: We aimed to report our referral center experience on the clinical features and treatment options of Takayasu arteritis. In addition, we have evaluated the correlation of various activity and damage scores with eachother

Methods: We performed a retrospective chart review for Takayasu arteritis between October 2002 and October 2017 at our tertiary referral pediatric rheumatology center. In addition to the current cases that are followed-up, we have comprehensively searched the hospital database for the ICD-9 code 446.7 and ICD-10 code M31.4 to identify Takayasu arteritis patients.

Results: Overall, 16 patients (12 female) have been diagnosed with Takayasu arteritis in last 15 years. Mean age of the patients at disease onset and diagnosis were 10.9 ± 4.8 years and 11.5 ± 4.7 years, respectively. While the median duration from the onset of first symptom until the diagnosis was 2.4 months (range 0.1-65 months), the mean disease duration was 6.1 ± 5.9 years. The most frequent manifestation at admission was nonspecific systemic features (fever, fatigue, anorexia, weight loss) (n = 13, 81.2%) followed by hypertension (n = 10, 62.5%) and neurologic findings (n = 4, 25%). Tuberculosis disease was also detected in 4/16 subjects (25%) at disease onset and anti-tuberculosis therapy initiated concomitantly with immunosuppressive drugs. All patients had met the ACR 1990 criteria for the classification of Takayasu arteritis. The most common angiographic type was Numano’s type IV seen in 5 patients, followed by type V in 4, type III in 4, type IIa in 2, type IIb and type I one patient each. Subjects had extensive disease at presentation with mean DEI.Tak (±SD) of 13.8 (±6); All of the subjects had elevated acute-phase reactants, and were active at presentation [mean ITAS2010 score (±SD): 18.7 (±7.1) and mean PVAS score (±SD): 14.0 (±4.4)). These three activity scores correlated with each other both at disease onset and last visit (p < 0.05). The most frequently used immunosuppressive drug in therapy was corticosteroids (n = 16/16, 100%), followed by azathioprine (n = 15/16, 93.7%), cyclophosphamide (n = 10/16, 62.5%), methotrexate (n = 6/16, 37.5%) and tocilizumab (n = 6/16, 37.5%). The rate of angioplasty and/or bypass was not rare (n = 7/16, 43.7%). Despite the high frequency of surgical procedure, there was no deceased patient with Takayasu arteritis in the last 15 years.

Conclusion: There is no deceased Takayasu patient in the last 15 years. Fairly good clinical outcomes compared to the past may be due to new biologic drugs and/or improved surgical techniques. Three different disease activity scores were in a great concordance with each other.

Disclosure of Interest: None Declared

Introduction: Development of coronary artery abnormalities (CAA) is the hallmark of Kawasaki disease (KD) and accounts for most of the morbidity and mortality associated with the disease. Concerns have been raised as to whether patients with KD are really at risk for premature atherosclerosis later in adulthood. With advancements in technology, dual-source computerized tomography (DSCT) coronary angiography can be developed as a low radiation imaging paradigm for patients with KD. Advantages over echocardiography include the ability to visualize middle and distal coronary segments with little or no inter-observer variability. Unlike catheter angiography, DSCT angiography is non-invasive and clearly delineates calcification and intraluminal abnormalities.

Objectives: This study is designed to evaluate whether KD is a risk factor for premature atherosclerosis by calcium scoring (Agatson’s algorithm) and to detect the CAA (aneurysm/thrombus/stenosis/ectasia) using DSCT with low radiation protocols.

Methods: In this prospective study, 21 patients (male: female- 15:6) with KD in convalescence for more than 10 years were enrolled (mean: 15.76 years). Diagnosis of KD was based on the 2004 American Heart Association (AHA) Criteria for KD. Written informed consent was taken from all the patients prior to the enrolment. Patients were scanned during a single breath-hold with a customized protocol designed to minimize the administered radiation dose. Non-ionic contrast (Omnipaque 350, GE Healthcare, Ireland) 2-4 ml/kg was injected at a rate of 4-5 ml/s (through 20G cannula), in the right antecubital vein, followed by a saline push (1-2 mL/kg at a rate of 1.5 mL/second) with a dual head power injector. An 128 slice SOMATOM Definition flash DSCT scanner (SIEMENS HEALTH CARE; Germany) was used for coronary angiography. The data acquisition parameters were 80-100 KVp voltage, tube current (mAs) (care dose 4D), detector configuration 128x0.6 mm, gantry rotation time 0.28 seconds, and the scan length was adjusted from the scout image to encompass the entire heart. The scan was taken from carina till the apex of heart. Images were analyzed on dedicated work station using proprietary soft ware (Syngovia). Coronary arteries was evaluated using the 13 segment model proposed by the AHA. The calcium score was calculated by determining the density of the highest density pixel in each plaque taking the threshold of 130 HU and applying a weighting factor to each plaque, depending upon the peak density in the plaque. Heart rate at which data was acquired, was recorded along with electrocardiogram tracing.

Results: Mean age of the patients at the time of diagnosis was 3.21 years and mean time interval time interval between diagnosis and imaging 12.59 yrs. At the time of data acquisition the mean heart rate of the patients were 80 beat/min, mean tube current 2417.66 mAs, median scan time 2.5 seconds and median effective dose 2.52 mSv. CAAs are seen in the form of aneurysms and ectasias in two patients (9.52%) in our study. No patient with significant stenosis was seen. The aneurysms were detected in proximal segments of RCA (Saccular, medium sized) and LAD (fusiform, small sized). The ectasias were detected in one patient (4.76%) in LAD and LCx. Raised calcium score is seen only one (4.76%) patient with abnormal coronary arteries. The calcium deposition is seen in only in abnormal segments.

Conclusion: Our study suggests that KD itself may not be a cause for premature atherosclerosis unless the coronary arteries are involved in form of aneurysms. However, the results of this preliminary study done in a small population size has to be replicated in larger cohorts to make a firm conclusion.

Disclosure of Interest: None Declared

Introduction: Coronary artery abnormalities (CAA) develop in 20-25% of untreated cases and 3-5% of treated cases of Kawasaki disease (KD), that accounts for most of the morbidity and mortality associated with the disease. Although, transthoracic 2-D Echocardiography (2DE) is the initial preferred modality for imaging coronary arteries, it has several inherent limitations- unclear views of middle and distal segments of coronaries, chances of inter-observer variation, and poor acoustic windows in older children to view the coronaries. Dual source CT (DSCT) coronary angiography has recently emerged as an non-invasive tool that has low radiation exposure and can accurately demonstrate the coronary wall anatomy and intraluminal abnormalities like thrombosis, stenosis, calcification. It has several advantages over echocardiography including the ability to visualize middle and distal coronary segments with little or no inter-observer variability.

Objectives: To evaluate the role of DSCT coronary angiography in detecting CAAs in children with KD who were not treated with intravenous immunoglobulin during acute stage and its comparison with 2DE.

Methods: Nineteen (19) children (M:F = 15:4) with KD who did not receive intravenous immunoglobulin and are on regular follow up in Pediatric Rheumatology Clinic were enrolled (median age: 11.03 years; range: 3.7-23 years). Diagnosis was based on diagnostic criteria given by AHA. All of the patients were the cases of incomplete KD and were not given IVIg because they either presented late in convalescent phase or when then presented to us, they were afebrile and ESR, CRP were not raised. Mean duration since diagnosis of KD to the time when study was conducted was 3.84 ± 2.27 years. The study was approved by the Ethics Committee of the Institute. A written informed consent from the parents was obtained prior to enrolment. Children underwent both SOMATOM 128-slice Definition flash DSCT coronary angiography (SIEMENS HEALTH CARE; Germany) and 2DE on the same day. Diameters of major coronary arteries were measured and presence of any coronary artery lesions was looked for. Results of 2DE carried out at the time of diagnosis were also taken into account. Student paired T test was used to compare the average diameter of coronaries obtained by two imaging modalities.

Results: None of the patients showed any coronary artery abnormalities by both DSCT and 2DE. All coronary arteries were well visualized by DSCT and even LCX branches and distal RCA was also well visualized. However, coronary artery could not be visualized in 7 patients out of 19 by 2DE. In 3 patients, even main arteries were also not seen due to poor acoustic window. However, in 4 cases, RCA and LMCA were well visualized, but it was difficult to visualize left circumflex artery clearly. The 2DE and DSCT had almost the same results of proximal coronary artery especially LMCA, proximal RCA, and LAD. However, DSCT provided the more accurate visualization of distal coronary artery than 2DE. The average diameter of coronary artery measured by 2DE and CT angiography was almost similar. 2DE at the time of diagnosis showed dilatation of coronaries in 3 children (2 LMCA, 1 LAD) which were not seen in current echo and DSCT.

Conclusion: DSCT coronary angiography more accurately delineated the anatomy and lumen of coronary arteries especially in older children with KD when compared with 2DE. DSCT is superior to echo for distal coronary artery visualization. It can reveal coronary artery lesions in patients with KD in timely manner and help with therapeutic decision making to improve the prognosis.

Disclosure of Interest: None Declared

Introduction: Kawasaki disease (KD) is usually considered as an acute, self-limited vasculitis of childhood. However, of late, several long-term complications including development of major coronary events and premature atherosclerosis have been recognized in patients with KD. The evaluation of vascular endothelial function is important in predicting several long-term complications in patients with KD. Flow mediated dilatation (FMD) of the brachial arteries is considered one of the non-invasive ways to study the vascular endothelial dysfunction.

Objectives: To study the FMD of brachial artery (BA) and evaluate for endothelial dysfunction in children with KD in both acute and convalescent phases.

Results: Mean age of the study population was 4.8 years in cases (n = 16; M:F- 12:4) and 5.75 years in control population (n = 16; M:F- 10:6). The baseline BA diameter in acute phase of KD children is 2.3 ± 0.34 mm and that of convalescent phase is 2.49 ± 0.35 mm. Healthy control population had a mean baseline BA diameter of 2.35 ± 0.46 mm. Maximum dilatation was 2.56 ± 0.36 mm in the group of acute KD, 2.93 ± 0.31 mm in the group of convalescent KD and 2.95 ± 0.56 mm in healthy controls (p- 0.02). Children with KD had FMD of 12.32 ± 6.2% in acute phase and 17.99 ± 8.13% in convalescent phase, whereas, the control population had FMD of 26.88 ± 12.76% (p <0.01).

Conclusion: Our results suggest that FMD is significantly reduced in children with KD in acute phase and convalescent phase as compared to healthy controls. To the best of our knowledge, ours is the first study done in both phases of KD and suggests that endothelial dysfunction starts as early as in the acute phase of KD.

Disclosure of Interest: None Declared

Introduction: With the increased use of imaging as a supportive tool for starting or intensifying treatment in JIA patients, discrepancy between the MR imaging and clinical assessment will pose a dilemma.

Disclosure of Interest: None Declared

Introduction: The acute phase of Kawasaki disease (KD) involve endothelial damage and activation of platelets. Markers of platelet activation were found to be elevated in adults with coronary artery disease (CAD) and venous thromboembolism. The actual evidence for platelet activation in KD, however, is limited to platelet aggregation studies and few studies on platelet activation markers and circulating microparticles. Monocyte-platelet aggregates (MPA), one of the most sensitive markers for activated platelets has not been studied in the acute phase of KD.

Objectives: To assess platelet reactivity by flow cytometry based measurement of MPA in children with KD.

Conclusion: MPA% as an objective measure of platelet activation was significantly elevated in children with acute stages of KD when compared with age and sex-matched febrile and normal controls. Elevated levels of MPA% in patients with KD 3 months post diagnosis suggest that the endothelial inflammation or damage in KD persists for a longer duration even after control of symptoms and signs of systemic inflammation. Long-term studies on platelet activation markers in a larger multicentric cohort would conclusively establish the role of platelets in acute and long-term cardiac morbidity in KD.

Disclosure of Interest: None Declared

Introduction: Chronic active EBV (CAEBV) infection is a rare condition associated to a chronic activation of Epstein Barr virus and therefore to a chronic and potentially life-threating lymphoproliferation. The prognosis is poor: most of the patients not treated with bone marrow transplantation die for lymphatic malignancies and the common immunosuppressive and antiviral therapy are usually not effective. Even if with a wide heterogeneity, most of the patients with CAEBV present severe clinical manifestations with early onset and poor prognosis; the presence of an underlying immunodeficiency causing an unusual EBV replication is therefore reasonable.

Objectives: To describe the clinical course and the genetic characterization of a patient with CAEBV mimicking PFAPA at disease onset.

Methods: In a patient with CAEBV infection a whole exome sequencing (WES) approach was undertaken and variants were prioritized with a custom pipeline to identify the genetic cause of his condition that was validated through Sanger Sequencing in the trio.

Results: The patient, born of consanguineous parents, at the age of 15 months presented, in complete wellbeing, a not-complicated infectious mononucleosis; in the following months he presented recurrent episodes of high fever with exudative tonsillitis, adenitis, splenomegaly and sweating, lasting 3-5 days and treated with NSAIDS or antibiotics. Blood examinations revealed neutrophilic leukocytosis and elevation of acute phase reactants; plasmatic immunoglobulins were within the normal range. An autoinflammatory condition with periodic fever was suspected and therefore on-demand steroidal treatment was suggested, with good response. The child continued to present periodic fever, associated to the occurrence of respiratory infections requiring antibiotics, and recurrent episodes of cheratitis. Several destructive dental caries were found as well as hyper sensibility to mosquitoes bite.

Disclosure of Interest: None Declared

We report the case of a 6-year-old boy with pain in the right knee and both ankles after a 10-day course of oral amoxicillin-clavulanate completed three weeks earlier; at the same time he developed diarrhea with positive culture for Clostridium difficile (CD). Three days later the knee and ankles arthritis resolved spontaneously but appeared in the right shoulder and homolateral hip with a migratory pattern and with fever. Synovial fluid and blood cultures, rheumatoid factor, ANA and HLA-B27 antigen were negative. The improvement of colitis and the negativity of fecal calprotectin at follow-up allowed to exclude an inflammatory bowel disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) and metronidazole completely resolved pain, joint swelling and diarrhea. After 24 months of follow-up there has been no recurrence.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is most common chronic rheumatic disease in childhood. The upper extremity involvement in JIA causes muscle imbalance, joint destruction, pain, stiffness and limitations on activities of daily living (ADL) in varying degrees. However, the information about prevalence of symptoms, disorders, ADL limitations, participation restriction and options of treatments for upper extremity involvement in JIA are limited. It has been reported that improvements of upper extremity functions were achieved by video-based games (VBG) in various disease groups. However, in the literature, no study has been found about effectiveness of VBG in children with arthritis.

Objectives: The aim of the study was to investigate the effects of two different task-oriented activity training to activity performance and participation in children who have involved upper limb with JIA.

Methods: 62 patients included in the study were randomized into two groups as group I (patient-centered task-oriented activity training in daily living conditions) and group II (patient-centered task-oriented activity training with VBG). The patients’ pain, by “Numeric Rating Scale (NRS)”, range of motion (ROM) by “goniometer”, muscle and grip strengths by “dynamometer”, activity performance and participation by “Childhood Health Assessment Questionaire (CHAQ)”, “Duruoz Hand Index (DEI)”, “Jebsen-Taylor Hand Function Test (JTHFT)” and “Nine Hole Peg Test (NHPT)” were evaluated. In group I, ADL were trained with real materials used in daily life and various rehabilitation products. In group II, ADL were trained with VBG. We have created training protocol with Xbox 360 games for patient-centered task-oriented activity training with VBG. We prefered ‘Dance Central2’, one of the Xbox 360 games, for warming (macerana dancing, 10 minutes). Other games, ‘Fruit Ninja’, ‘Table Tennis’, ‘Boxing’, ‘Volleyball’, ‘Darts’ and ‘Bowling’ were selected appropriately according to patients performance. All the patients completed 8 weeks (45 minutes for every session, 3 times in a week) of client-centered treatment.

Results: After treatment in both groups, significant changes were found in NRS, ROM, muscle strength, grips strength, CHAQ, DEI, JTHFT and NHPT (p < 0,05). Table 1 shows comparison between the groups for the activity performance, pain severity, hand grip and pinch grip strengths. After the treatment, group II was statistically more superior than group I in changes of wrist extension ROM and DEI (p <0.05). In addition to, almost all changes of muscles strength in group II were statistically more superior than changes of group I (p < 0.001).

Conclusion: In our study, two different task-oriented activity training provided significant changes in pain, ROMs of upper extremity, muscle strength, grip strength, activity performance and participation and patient-centered task-oriented activity training with video-based games has been proved as an alternative treatment in children who have involved upper limb with JIA.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is an important cause of short-term and long-term disability. Many children appeared to have elbow, hand- and/or wrist-related symptoms and impairments, with resulting moderate to severe levels of activity limitations and participation restrictions at daily living. However, in the literature, no study has been found about variety of activity performance problems in patients with JIA. The Canadian Occupational Performance Measure (COPM) is a client-centered, patient reported outcome measure with which clients evaluate their activity performance and satisfaction with performance in areas of self-care, productivity and leisure. COPM is generally used for analyzing activity performance problems in many chronic diseases.

Objectives: The aim of the study was to analyze the activity performance problems of patients with JIA.

Methods: 50 patients with JIA (42 Female, 8 Male) were included in the study. Inclusion criteria consisted of a diagnosis of JIA according to the International League of Associations for Rheumatology criteria, being aged between 6–18 years, having at least one affected joint in upper extremity (shoulder, elbow, wrist, and finger joints). Activity performance problems as perceived by the individual were measured using face to face interview by the Canadian Occupational Performance Measure (COPM). During the interviews, the patients were encouraged to identify any daily activity that they would like or need to do but found difficult to complete because of their rheumatic diseases. Patients then identified the five most important daily activities and rated, first, their current level of performance, and then, how satisfied they were with this current level of performance. These performance and satisfaction scores were rated by on a 10-point scale, with higher scores indicating better performance and satisfaction. The statistical software SPSS 21.0 was used for the analyses.

Conclusion: Our results showed that patients with JIA, who have at least one affected joint in upper extremity, reported problems with a wide range of activities. We suppose that the COPM can be a useful tool for identifying activity performance problems as a patient-focused outcome measure and also, it could provide information about patient centered management for patients with JIA.

Disclosure of Interest: None Declared

Introduction: The evidence of vaccine safety and efficacy in patients with rheumatic diseases is increasing. However, the data on vaccination status in children with rheumatic diseases remain scarce. So far, only few smaller studies were published that found suboptimal vaccination coverage in patients with rheumatic diseases.

Objectives: To assess vaccination status in a cohort of children with rheumatic diseases followed at the University Children's Hospital Ljubljana and to evaluate the most common reasons for vaccination dropout.

Methods: All consecutive patients with rheumatic diseases evaluated at the rheumatology outpatient clinic between 1 January 2015 and 15 January 2017 received a questionnaire about their vaccination status and reasons for potential vaccination dropout. Descriptive statistics were used to analyse the proportion of children with full vaccination status at 5, 10, 18 years and at their last clinic visit. The study was approved by the national ethics committee.

Results: By May 2017 the data were received from 125 out of 422 enrolled patients (29.6%). Among included patients 64.8% were female, median age was 12.3 (1.5-22.9) years and median age at diagnosis 5.8 (0.7-16.6) years. The majority of included children had JIA (n = 114), followed by SLE (n = 5), CRMO (n = 2), JDM (n = 2), MCTD (n = 1) and systemic sclerosis (n = 1). Vaccination coverage was complete in 92.1%, 81.3%, 72.2% and 71.2% of patients at 5, 10, 18 years and at their last clinic visit, respectively. Most commonly omitted vaccines were Hepatitis B (22.9%) and second dose of Measles, Mumps and Rubella vaccine (18.3%). Most common additional vaccine was against tick-borne encephalitis (26.4%), which is an endemic disease in Slovenia. Most common reasons for vaccination dropout were suggestion of the treating rheumatologist and active disease.

Conclusion: We experienced a low initial response rate of 30%, which might be due to increasing parents' vaccine hesitancy. In our sample we found an approximately 10% decrease in complete vaccination coverage between consecutive age cohorts. Overall vaccination coverage in children with rheumatic diseases is lower than in general population in Slovenia. Parent and patient education on vaccination remains crucial and when possible, vaccination catch-up plans and booster vaccinations should be advocated on an individual basis.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood (4/1000 children) and untreated, can lead to significant morbidity including joint deformities, loss of function and blindness (uveitis). Guidelines for the management of JIA have been created for use in the developed world. Challenges in diagnosis and management arise when these guidelines are applied in low-resource settings given different endemic diseases, access to care, and sociocultural practices.

Objectives: We performed a needs assessment of clinicians managing JIA in low-resource settings with a view to applying our findings to recommendations for JIA management in developing countries.

Methods: An anonymous needs assessment regarding the management of JIA in developing countries was developed based on four areas of attention identified by rheumatologists in the developing world: patient management (access to care and medications, clinical work-up, transition); education (to the health professions and the public); advocacy, networks and policy; and research. The survey (available in English and Spanish) was tested, validated and electronically circulated to healthcare practitioners who see children with JIA in developing countries. Contacts were acquired through pediatric rheumatology professional networks

Results: The survey was distributed to 502 practitioners, with 116 responses from clinicians in South America (50%), Africa (28%), Asia (12%), the Middle East (1.5%), Central America (1.5%) and other countries (7%). Respondents were pediatric rheumatologists (66%), adult rheumatologists (22%), allied health professionals (7%), general pediatricians (4%) and general practitioners (1%); median age 40-50 years, median 10-15 years in practice. The percentage of time devoted by these clinicians to pediatric rheumatology in their practice was: <25% (29%), between 26-50% (19%), between 51-75% (13%), >75% (17%) and 100% (22%).

Conclusion: Management of JIA remains a challenge in the developing world; is rooted in educational gaps in the medical and general community; and complicated by endemic disease and insufficient access to resources. Guidelines specific to low-resource settings, and informed by research exploring the local burdens of disease and experiences of stakeholders, may serve as a powerful educational document to advocate for policy change and best practices.

Disclosure of Interest: M. Chan Grant/Research Support from: International League Against Rheumatism Grant, R. Russo Grant/Research Support from: International League Against Rheumatism Grant, L. Okong'o Grant/Research Support from: International League Against Rheumatism Grant, C. Scott Grant/Research Support from: International League Against Rheumatism Grant

Introduction: Many studies in pediatric rheumatology underline the concept of « window of opportunity », early in the disease course to prevent joint or ocular damage in the context of juvenile idiopathic arthritis (JIA). In Europe, despite facilitated access to health care, children with JIA are referred to pediatric rheumatology centres with significant delay. This delay is closely linked to the organization of the country’s health care delivery system. In France and Switzerland nothing is known about diagnostic delay and little about access to remission in JIA.

Results: We included 709 JIA patients (50% oligoarthritis, 17% RF– polyarthritis, 15% enthesitis-related arthritis [ERA], 10% systemic JIA [sJIA], 3% RF+ polyarthritis, 3% psoriatic arthritis, and 2% undifferentiated arthritis).

Conclusion: The diagnostic delay and treatment delay in France and Switzerland are too long. Strong efforts have to be made to understand the underlying factors to suggest improvements in care pathway organization and practices by the elaboration of care course management guidelines. The JIR network permit to design a prospective study to identify these factors and improve the short-term prognosis of JIA, in the context of national and European rare disease health programs.

Disclosure of Interest: None Declared

Introduction: The transition from pediatric to adult healthcare is a vulnerable time for adolescents and young adults (AYA) with chronic conditions. Thie year the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology European Society (PReS) jointly offered expert-opinions regarding transitional care of AYA with juvenile-onset rheumatic diseases and the American College of Rheumatology (ACR) developed a toolkit. For these guidelines to be implemented or for these resoures to be utilized, adult and pediatric rheumatologists need to understand their application. Nevertheless, there are no published curricula for teaching transition skills to rheumatologist-in-training.

Objectives: We sought to develop and assess the impact of a workshop designed to help adult rheumatology fellows learn key skills for providing effective transition care to transferring young adult patients.

Methods: A 1-hour skills-based workshop on transition and transfer best practices was developed alongside an objective standardized clinical examination (OSCE) station in which trainees were given 12 minutes to welcome a young adult with lupus – and her parent – to a first visit in an adult clinic and perform a full history. The OSCE evaluation rubric assessed five transition/transfer skills (skills 1-5) and one “control skill” (skill 6), on a Likert scale of 1-5, with 5 being the best performance. Adult rheumatology fellows (n = 19) from 5 institutions were evaluated with the OSCE; 12 were tested with the OSCE de novo, whereas 7 were tested with the OSCE after participating in the workshop. Unpaired, aggregated OSCE scores were complemented with unpaired pre- & post-survey data in which fellows reported their self-assessed level of preparation for 12 transition and transfer skills.

Conclusion: A brief educational intervention successfully increased adult rheumatology fellows’ perception of their proficiency with key transition/transfer skills. In addition, fellows who participated in the educational intervention had significantly higher scores on their OSCE performance. It is likely that the “control skill” score was lower in the post-workshop group owing to more time being spent on newly acquired peri-transfer skills: during the 12-minute OSCE scenario, discussing disease pathogenesis took a backseat to conversations about expectations in the adult care model, self-management skills, and goal setting. Making this curriculum available to all rheumatologists-in-training would likely improve the care young adult rheumatology patients receive when transferring from pediatric to adult rheumatology. A complementary curriculum for pediatric rheumatology fellows could further improve the care of AYA rheumatology patients.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is characterized by chronic inflammation of the joints which can lead to structural bone damage.

Objectives: The primary objective of this study was to evaluate response of newly diagnosed JIA patients to an early aggressive treatment by conventional radiography. Secondary objective was to compare Poznanski and BoneXpert methods to evaluate presence and progression of radiological damage in wrists of JIA patients.

Methods: JIA patients participating in the BeSt for Kids study (NTR 1574) were eligible in case of wrist involvement at inclusion if conventional radiographs were available at baseline or within 6 months before/after study inclusion. Follow-up radiographs after 12-36 months were available for comparison. Radiographic bone damage as reflected by carpal length was assessed using Poznanski score. BoneXpert method was used to determine bone age and bone mineral density (BMD).

Results: Forty JIA (27 female) patients were evaluated for Poznanski score and BMD (mean age 7.2 ± 3.4 years), 26 patients (15 female) were evaluated for bone age (mean age 9.3 ± 2.2). At baseline mean Z-score of RM/M2 was 0.047. At follow-up mean Z-score changed to 0.055 (p = 0.937). Baseline and follow-up Z-scores were not different from a healthy population. Bone age did not significantly differ at baseline (Z-score 0.08) and follow-up (Z-score 0.25). At baseline BMD was significantly diminished compared to healthy controls (Z-score -0.71) and improved significantly (Z-score -0.44 (p = 0.032)).

Conclusion: In this cohort of JIA patients treated early and aggressively we have detected no radiographic damage in the wrist at baseline or follow up. BMD was significantly diminished at baseline but improved significantly after follow-up.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis, JIA, is classified into seven categories; systemic-onset type, persistent and extended oligoarthritis, polyarthritis with rheumatoid factor negative, polyarthritis with rheumatoid factor positive, psoriatic arthritis, enthesitis-related arthritis and undifferentiated arthritis classified by the International League of Associations for Rheumatology. As each category of JIA has different features in clinical phenotypes, precise subtyping is required for research and management. Due to inclusion and exclusion criteria, some patients is ended up in the undifferentiated category. Undifferentiated arthritis includes patients who do not meet criteria for any category. Or, they meet the criteria for more than 1 category but with either a close relative who has psoriasis or the presence of RF. The prevalence of subtypes of JIA was reported; Oligoarticular JIA occurs most frequently (50% to 60% of cases), followed by polyarticular JIA. However, there is not enough information in the literature about the undifferentiated arthritis group.

Objectives: We aimed to analysis the characteristic findings of the undifferentiated arthritis group in JIA patients.

Methods: This was a retrospective longitudinal cohort study of patients with JIA at a tertiary care pediatric rheumatology clinic. Subjects were included if they were evaluated at our pediatric rheumatology clinic between June 2016 and May 2017, had a diagnosis of JIA according to ILAR criteria.

Results: During the study period there were 215 JIA patients evaluated at 640 visits. 180(84%) of patients had newly-diagnosed JIA.

Conclusion: Since distribution of the JIA category is different upon ethnicity, this study showed that percentage of undifferentiated JIA patients in our cohort was found higher reported from other studies in the literature. This is a single center, referral-based cohort study. As such, it might not represent the entire population of Turkey. In our conclusion, to clarify characteristics of undifferentiated JIA patients, need large cohort and multicenter study.

Disclosure of Interest: None Declared

Introduction: Uveitis is the most common form of extraarticular organ involvement in juvenile idiopathic arthritis (JIA). The onset of chronic anterior uveitis in JIA is insidious and often entirely asymptomatic. Children with JIA must be subjected to periodic eye examinations with slit lamp according to the different risk of developing this complication. The decision to undertake a screening program depends on the cost-benefit balance. To date, however, there is uncertainty about the optimal frequency of eye examinations. Although guidelines for ophthalmologic surveillance have been proposed, none of them is universally embraced.

Objectives: To evaluate the time of the occurrence of uveitis after the onset of arthritis in children with JIA

Methods: The clinical charts of 1425 patients with JIA by ILAR criteria followed at study centers from January 1987 to October 2016 and with a follow-up of at least 6 months after disease onset were reviewed to identify those who had uveitis. In all patients, the diagnosis of chronic anterior uveitis was confirmed by an ophthalmologist and was defined according to the Standardization of Uveitis Nomenclature Working Group criteria. Children with systemic arthritis, rheumatoid-factor positive polyarthritis and enthesitis-related arthritis were excluded. Patients who developed uveitis before the onset of arthritis were also excluded. Patients who developed uveitis at the same time of the arthritis onset were included. Through the construction of a cumulative frequency curve, we defined the risk of developing uveitis for each year of disease, starting with the onset of arthritis.

Conclusion: Our study shows that nearly half of JIA patients with uveitis developed this complication in the first year after onset of arthritis and around two-third within two years. Less than 5% of patients had uveitis after 7 years from disease onset. These findings underscore the need for tight ophthalmologic monitoring in the first 2 years of disease and support the recommendation of current guidelines to lengthen ophthalmologic screening after 7 years of disease without ocular involvement.

Disclosure of Interest: None Declared

Introduction: A Phase 3b, open-label (OL), multicenter study (CLIPPER) has shown efficacy of etanercept (ETN) in pediatric patients (pts) with extended oligoarticular (eo) juvenile idiopathic arthritis (JIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA). CLIPPER2 is an ongoing OL extension study assessing long-term safety and clinical benefits of ETN in this population.

Objectives: Describe safety and clinical benefit of 6 yr of ETN treatment in CLIPPER (2 yr) and CLIPPER2 (4 yr) studies.

Methods: 127 pts with eoJIA (2–17 yr), ERA, or PsA (12–17 yr) who received ≥1 ETN dose (0.8 mg/kg QW [max, 50 mg]) in CLIPPER were eligible to enter CLIPPER2. Efficacy endpoints included proportions of pts achieving JIA ACR30/50/70/90/100 and Wallace/Juvenile Arthritis Disease Activity Score (JADAS) inactive disease/clinical remission criteria. Time to disease flare for pts who met predefined study criteria for withdrawing from ETN treatment was assessed by Kaplan-Meier (KM) analysis. Safety was assessed from CLIPPER baseline (BL) to month (m) 72.

Results: 109/127 (86%) pts entered CLIPPER2. At m72, 46/127 (36%) were taking ETN (39 [31%] ongoing, 7 [6%] restarted treatment), 44 (35%) had stopped ETN treatment, and 37 (29%) had discontinued the study. Improvements in disease activity seen in CLIPPER (m0–24) were largely maintained at m72 (Table; observed cases). Proportion of pts achieving JIA ACR30/50/70 responses at m24 (% = 99/98/93) was maintained to m72 (% = 96/96/88). Proportion of pts achieving JIA ACR90/100/Wallace inactive disease at m24 (% = 65/54/34) was maintained to m60 (% = 71/51/31) but afterwards decreased (% = 50/26/10 at m72). Sustained remission (≥12 continuous months) was achieved by 7/98 (7%) pts. 22/127 (17%) pts withdrew from ETN treatment due to low/inactive disease; 13/22 (59%) experienced disease flare (median time to flare [KM] = 190 days).

Conclusion: OL ETN treatment to m72 was effective and well tolerated in pts with eoJIA, ERA, and PsA. Majority of pts who withdrew from ETN treatment experienced disease flare. TEAE frequency decreased over time.

Disclosure of Interest: I. Foeldvari: None Declared, T. Constantin: None Declared, J. Vojinovic Speaker Bureau of: Abbvie, G. Horneff Grant/Research Support from: Pfizer, Abbvie, Roche, Novartis, J. Dehoorne Consultant for: Abbvie, Speaker Bureau of: Abbvie, G. Susic Grant/Research Support from: Pfizer, K. Kobusinska: None Declared, V. Panaviene: None Declared, Z. Zuber: None Declared, V. Stanevica Grant/Research Support from: Pfizer, Consultant for: Abbvie, V. Chasnyk: None Declared, R. Pedersen Shareholder of: Pfizer, Employee of: Pfizer, J. Bukowski Employee of: Pfizer, T. Hinnershitz Employee of: Pfizer, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, A. Martini Consultant for: Abbvie, Boehringer, Novartis, R-Pharm, N. Ruperto Grant/Research Support from: BMS, Hoffman-La Roche, Janssen, Novartis, Pfizer, Sobi, Speaker Bureau of: Abbvie, Ablynx, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Gilead Sciences, Janssen, Medimmune, Novartis, Pfizer, Rpharm, Roche, Sanofi

Introduction: Methotrexate (MTX) is commonly used in the treatment of children with juvenile idiopathic arthritis (JIA). Frequently it is discontinued due to intolerance with anticipatory and associative gastrointestinal symptoms. Eye Movement Desensitization and Reprocessing (EMDR) is a therapy where non-processed and dysfunctional experiences and memories are reprocessed by intensive recall combined with eye movements. This leads to selective processing of the negative affect.

Objectives: Objective of this study was to investigate effectiveness of EMDR in the treatment of MTX intolerance in JIA patients, with the underlying hypothesis that intolerance occurs due to dysfunctional memories and expectations.

Methods: An open prospective study on consecutive JIA patients with MTX intolerance was performed. Intolerance was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire and health-related quality of live was determined using the PedsQL, at 3 time points: directly before and after treatment (after treatment: MISS only), and 4 months after treatment. Patients were treated using a standardized EMDR protocol with 8 sessions over a time period of 2 weeks. Changes in MISS and PedsQL were compared using descriptive and non-parametric methods.

Results: 14 patients with MTX intolerance (median MISS at inclusion: 13.5, range: 6-26) were included. Directly after treatment, all patients reported marked improvement of MTX intolerance symptoms (median MISS: 0.5, range: 0-3, p = 0.001). After 4 months, lasting reduction of MTX intolerance symptoms was observed (n = 5, median MISS: 5, range: 0-10, p = 0.068). However, 2/5 patients (40%) showed MISS >6. The health-related quality of life showed a trend towards improvement 4 months after treatment (n = 5, median pedsQL prior to treatment 84.4%, 4 months after treatment 92.4%, p = 0.46).

Conclusion: MTX intolerance in children with JIA can effectively be treated using an EMDR protocol, with lasting effect over 4 months. This intervention could potentially increase quality of life in affected patients and enable continued treatment with MTX.

Disclosure of Interest: None Declared

Introduction: Juvenile idiopathic arthritis with systemic onset (soJIA) is the most striking form of JIA with combination of arthritis and systemic features. The acute lung involvement (ALI) is not frequent manifestation of soJIA but often influence on disease course, outcomes and treatment. The mechanisms of lung involvement are still unclear.

Objectives: The aim of our study was to compare clinical and laboratorial features of patients with soJIA with and without ALI.

Methods: In the study were included retrospective data of 82 children with soJIA. ALI was described if patient had at least one: dyspnoe, shortness of breath, signs of respiratory distress syndrome, interstitial lung disease, pulmonary arterial hypertension.