Proceedings of the 24th 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. Results: Primed Mφs showed an M1 phenotype with geometric means ± SEM of HLA-DR, TLR2 and CD68 expression respectively of: 1177 ± 1.15, 613 ± 0.9, and 1549 ± 0.9 gMFI, respectively compared with un-primed Mφs of 597 ± 1.0, 122 ± 0.88, and 1225 ± 0.9 gMFI, respectively (n = 3; p < 0.05). ATP-treated Mφs showed increased LDH activity compared to controls (3.4x10 ± 0.12x10) compared to 0.00 milliunits/ mL, respectively; n = 3; p < 0.05). Furthermore, a greater increase in LDH activity was observed in Mφs that were incubated with JSLE serum and NET material (3.7x10 ± 0.5x10 and 7.6x10 ± 0.5x10, respectively, compared to 0.00 milliunits/mL; n = 3-6; p < 0.05). IF was positive for cleaved caspase-1 in ATP treated Mφs; and this was confirmed in lysed cells, using western blotting.

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. Methods: Peripheral blood mononuclear cells (PBMC) from 14 cSLE patients and 14 healthy paediatric controls, were stained for 37 immune phenotypic markers after 72 hours of culturing with and without Class B CpG oligodeoxynucleotide stimulation followed by interrogation with mass cytometry. Blood from healthy paediatric subjects without any inflammatory diseases were obtained prior to their elective day surgical procedures during intravenous plug setting after informed consent. Subsequent analysis of the data was done using a machine learning approach with dimensional reductions followed by automated cell classification, clustering and visualization. Unique nodes representing immune subsets enriched in cSLE patients were statistically evaluated with reference to the healthy cohort and its clinical and mechanistic significance inferred from their phenotypes (Wilcoxon rank-sum test, p < 0.05). Results: A statistically significant enrichment of a class-switched memory B cell subset (CD19 + CD27 + IgG + ) with CD11c + CD25 + HLA-DR + CD40 hi CD86 hi was found in the SLE cohort, suggesting its pathologic mechanistic role in lupus. Intriguingly, CD25 (IL-2α chain) expression was found in this population, indicative of its potential responsiveness to IL-2 secreted T cells. This observation was coupled with a reciprocal increase in the transitional/naive B cell population that was negative for CD11c, CD25, CD40 and CD86 in the healthy cohort. Next, a significant enrichment of the memory regulatory T cell population (CD4 + CD45RO + CD25 + Foxp3 + ) was present in the diseased cohort with a small population of these cells expressing CXCR5. CXCR5 is a homing chemokine receptor to the lymph node germinal centre, an important lupus related microenvironment, and its presence may signify a potential regulatory role of these cells. In the healthy cohort, a reciprocal enrichment in the naive regulatory T cell population was found instead. Lastly, the B regulatory compartment of the PBMC was interrogated after CpG stimulation demonstrating an enrichment of IL10 secreting B regulatory cells with the naive and transitional B cell phenotypes (IgM + IgD +/-CD27 -) in the cSLE patients. These populations of T and B regulatory cells may be involved in the amelioration of the lupus disease activity during different phases of the illness. 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.
Introduction: Primary vasculitis encompasses a number of life threatening diseases. The different clinical manifestations and classification framework is partly determined by the size (small, medium, large) of the predominantly inflamed blood vessels. Among small vessel vasculitis (SVV) the Anti-Neutrophil Cytoplasmic Antibody (ANCA) -associated vasculitis (AAV) subtype includes, Microscopic Polyangiitis (MPA) and Granulomatosis with Polyangiitis (GPA) that are difficult for physicians to differentiate because of their many overlapping clinical features 1 . In the absence of biomarkers, classification algorithms (European League Against Rheumatism (EULAR 2 ) and European Medicines Agency (EMA 3 ) algorithms) exist to distinguish these diseases in adults and have been adapted for use in children. Although rare in childhood, the study of AAV in pediatric patients provides opportunity for biomarker discovery in individuals with a relatively naïve immune system and limited comorbidities. 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. Methods: Briefly, blood was collected in Tempus tubes, RNA was extracted, enriched for mRNA and RNA-Seq libraries were prepared using standard methods. Sequencing was performed on an Illumina HiSeq 2500. fastq reads were mapped to the human genome using STAR 4 . DESeq2 5 was used for differential expression analysis while pathway overrepresentation analysis was conducted via innateDB 6 using the Reactome 7 pathway annotation system. Samples from 32 patients at the point of diagnosis or flare-up at blood draw were included in the analysis. All 32 patients were classified using the EMA algorithm, although the EMA classification was not used in the analysis. 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.
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. BDI: Exel E, Lupus 2013;22(14):1462-FSS::ad hoc committee on SLE response criteria, ArthrRheum2007;57(8):1348 Conclusion: HRQoL in this large cohort of adults with cSLE was not associated with disease damage, but self-reported fatigue-and major 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 Nrf2the key transcription factor of the oxidative stress responsein immune cells. Methods: We generated mice with a constitutive activation of Nrf2 in immune cells. Emerging CD11b + Gr-1 + cells were analysed by flow cytometry, whole transcriptome analysis and metabolic assays and compared to wildtype and LPS induced MDSCs. Finally functionality of CD11b + Gr-1 + cells was tested in vivo by means of a transfer colitis model and in an acute lung injury model. Results: Activation of Nrf2 in immune cells induced a massive expansion of splenic CD11b + Gr-1 + cells, which exhibited characteristics of myeloid derived suppressor cells (MDSCs) such as suppression of T cell proliferation in vitro and amelioration of T-cell mediated colitis in vivo. Whole transcriptome analysis revealed Nrf2 dependent activation of cell cycle and pentose phosphate pathway, which closely resembled pathways in MDSCs induced by the TLR4 ligand LPS resulting in higher metabolic turnover and cell proliferation. In addition constitutive activation of Nrf2 was protective in LPS induced acute lung injury. 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 Nrf2dependent 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 wellcharacterized 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.
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. Results: We analyzed the genotype-phenotype correlations of 718 patients (313 FMF, 133 CAPS, 114 MKD, 158 TRAPS) already reported in specific papers and validated by at least two experts for each disease. A total of 152 variants were described: 48 variants of TNFRSF1A, 30 NLRP3, 57 different combinations of MVK and 42 MEFV for compound heterozygous are available. For each HPF, a table with all the variables described has been established. 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.
Introduction: Next generation sequencing (NGS) represents a revolution in the field of molecular medicine, and offers a new approach to deciphering the pathogenesis of complex diseases. Paediatric-onset SLE (pSLE) is a very rare and more severe phenotype than its adultonset counterpart, and is possibly associated with a greater contribution of genetic aetiological factors. We have in the past described a B cell-related Mendelian form of lupus due to a deficiency of PKCδ. Here, we identified and characterized a new B cell-related Mendelian lupus secondary to IKZF1 mutation and compared this novel monogenic disease with PKCδ deficiency. Objectives: The aims of the study were to characterize the molecular impact of a new B cell related variant in IKZF1 encoding the protein IKAROS, and to study the B cell landscape of two distinct monogenic forms of SLE using mass cytometry (Cytof®). Methods: We designed an NGS panel comprising 200 genes including proven disease-associated as well as prospective candidate genes, and analysed 132 patients. We identified a family with three affected individuals carrying a previously unreported mutation in IKZF1. We set up functional assays including oligonucleotide pulldown, B cell phosphorylation and deep B cell immunophenotyping by mass cytometry. Results: We identified a heterozygous missense mutation in IKZF1 c.359A > T (p. D120V) in three affected patients in a single family. IKZF1 encodes IKAROS, a key transcriptional factor in B cell development. Functional assays showed that protein stability was not impaired, but DNA-binding was partially impacted. We performed mass cytometry comparing SLE patients carrying a homozygous loss-offunction mutation in PRKCD and our newly identified IKZF1 mutation. We identified B cell clusters, and unsupervised analysis underlined the wide differences between two monogenic diseases leading to SLE. 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.

New insights into the pathogenesis of systemic lupus erythematosus (SLE)
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. LoSCAT score is composed of two indexes: the modified Localized Scleroderma Skin Severity Index (mLoSSI) which measures disease activity considering any new/enlarged lesion, erythema and thickening, and the Localized Scleroderma Skin Damage Index (LoSDI) which measures tissue damage as dermal atrophy, subcutaneous atrophy and depigmentation. Infrared thermography is a non-invasive imaging technique detecting the thermal energy emitted from the skin providing a graphical representation of its distribution on the body surface. Three examiners with different experience in Paediatric Rheumatology blindly evaluated all patients twice, at baseline and at least three months later. At each visit, thermographic analysis and LoSCAT score were performed by each examiner. The inter-rater reliability was assessed by the Intraclass Correlation Coefficient (ICC) and interpreted as follows: ICC values range 0.75-1 excellent reliability, 0.4-0.74 good reliability, <0.4 poor reliability. All statistical analyses, including the analysis of variance (ANOVA), were performed by using IBM SPSS (Vers. 18.0). Results: Forty-seven patients (129 lesions) entered the study, and 26 (79 lesions) were reassessed by same examiners with the same modality after 4.5 (+1.5) months. As for LoSCAT, mLoSSI showed excellent inter-rater reliability expressed by ICC 0.895 (95% CI 0.846-0.931); the analysis of variance (ANOVA) confirmed that values indicated by In the group of 79 lesions examined twice an improvement for all anatomic sites for both evaluations of the three examiners and thermographic detection was observed. Moreover, thermographic analysis showed statistically significant correlation in different anatomic sites with domains of erythema, dermal atrophy and subcutaneous atrophy of LoSCAT.
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.

O14
Tocilizumab is a promising treatment option for therapy resistent juvenile localised scleroderma patients Ivan Foeldvari 1 , Jordi Anton 2 , Mark Friswell 3 , Blanca Bica 4 , Jaime de Inocencio 5 , Angela Aquilani 6 , Nicola Helmus 1 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. The mean duration of tocilizumab therapy was 14.75 months. 2 patients received s.c. according the poly JIA dosing and all other i.v.. There were different i.v doses applied, 5 of them 8 mg/kg every 4 weeks, one of them 8 mg/kg every three weeks, 1 every two weeks and 1 patients received 10 mg/kg every 3 weeks. 3/11 received TOC as monotherapy. 8/ 11 as combination therapy, 6 of them with Methotrexate and one of each with Mycophenolate or Tacrolimus. Therapy success was reflected by a decreased mLoSSI in 8/11 patients and in 6 patients by a decrease in the Localosed Scleroderma Skin Damage Index [1] (LoSDI). No new lesion occurred during the treatment and in the patients with Parry Romerg subtype(n = 2) no increase in the facial atrophy occurred. In 8/8 patients physician global (VAS 0-100) decreased and in 8/8 the patients global disease activity (VAS 0-100) decreased. In 3/3 patients, were it was applicable, the number of active joints decreased, in one patients the limb discrepancy decreased. The mean modified Rodnan skin score assessed in 8 patients decreased from the mean value of 9.6 to 5.5.

Conclusion: Conclusion:
In this small cohort of patients TOC seems to be a promising rescue medication in methotrexate/mycophenolate nonresponsive patients. A prospective controlled study would be important to prove the seen effect in a controlled way.

Pathogenesis of juvenile idiopathic arthritis (JIA)
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. Results: Our preliminary data show that, similarly to JIA SFMC, p75NTR is significantly upregulated in FLS of RA patients, while TrkA is much less expressed than p75NTR. Instead, OF and SF showed a higher expression of TrkA than p75NTR. Moreover, FLS express NGF mRNA and release high amounts of proNGF, but not of mature NGF, in the conditioned media. Inflammatory stimuli, such as IL-1b, further upregulate p75NTR expression in FLS and induce the expression of p75NTR in control fibroblasts. In vitro, the addition of proNGF to FLS induces the expression of pro-inflammatory cytokines. This effect is abolished when p75NTR activity was inhibited using LM11A-31, a non-peptide ligand that blocks the binding site of p75NTR for proNGF. 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
The BeSt treatment strategy for children with juvenile idiopathic arthritis (JIA) has not been determined as of today. Objectives The aim of the BeSt for Kids study was to investigate, which of three treatment strategies is most effective and safe, by comparing them directly. The therapeutic target in all arms was inactive disease by rapid reduction of disease activity and repeated monitoring and revision of therapy in case of insufficient response. We hypothesized that early treatment with etanercept and methotrexate (arm 3), compared to initial monotherapy (arm 1) or initial combination therapy with methotrexate and prednisone (arm 2), would lead to significantly earlier clinical inactive disease.

Methods
We conducted a randomized, single blinded, multicenter, treatment strategy study with 24 months of follow up. Disease modifying anti rheumatic drug (DMARD)-naive JIA patients were randomized to 1. sequential DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX), 2. combination therapy: MTX and prednisolone-bridging, 3. Combination-therapy MTX with etanercept. For all arms, the treatment protocol described a number of subsequent treatment steps in case medication failed. After reaching remission for 3 (oligoarticular) or 6 months (polyarticular) medication was tapered and stopped as dictated per protocol and flare frequency was observed. Missing data were imputed. Primary outcome was time to inactive disease and time to flare after tapering and stopping DMARD therapy, both calculated using Kaplan Meier method with log rank test. Secondary outcomes are adjusted ACRPedi 30/50/70 scores, toxicity, functional ability and quality of life. Generalised Estimating Equations were used for longitudinal data analyses. In this abstract we share the first 24 months results. Results: Ninety-four patients were randomised, 32 in arm 1, 32 in arm 2 and 30 in arm 3. Two patients received a different diagnosis during follow-up and were left out of all analysis. Two patient were lost to follow up but were analysed due to intention to treat principle. Overall baseline median (InterQuartileRange IQR) age was 9.1 (4.6-12.9) years. 37% were ANA positive, 11 patients had oligoarticular disease, 66 patients polyarticular JIA and 15 patients juvenile psoriatic (polyarticular) arthritis. Baseline median (IQR) ACRpediscores: VAS physician 50 (39-58) mm, VAS patient 54 (37-70) mm, ESR 6(2-14) mm/hr, active joint count 8 (5-12), limited joint count 2.5 (1)(2)(3)(4)(5), CHAQ score 0.9 (0.6-1.5). Inactive disease occurred overall after mean 9.8 months (8.5-11.1). Time to inactive disease was not significantly different in all three arms (log rank test p = 0.23). Outcome measures after 24 months of therapy are summarised in the Table 2.

T2
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. Trial registration identifying number: NTR1574 Disclosure of Interest: None Declared.   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.
Results: A total of 90 patients (15 M, 75 F; mean age 13.8 years; mean disease duration 8.5 years; mean follow-up duration 2.9 years) were included. Fourteen out of 90 patients (15.6%) were in remission off medication, while 76/90 patients (84.4%) were in remission on medication. Forty-five patients were assessed by MRI in the wrist, 30 in the hips, 13 in the ankle and 2 in the knee. Fifty-seven patients (63.3%) had evidence of subclinical synovitis on MRI. The interobserver agreement for presence/absence of synovitis was good (k = 0.74; 95% CI: 0.5-0.9). Forty-three out of 57 patients (75,4%) with subclinical synovitis experienced a disease flare versus 11 out of 33 patients (33.3%) who hadn't any synovial inflammation (P < 0.0001). Radiographic damage progression was assessed in 54/90 patients for whom follow-up CRs were available and was detected in 19/54 patients (35.2%). A significant association between systemic JIA subtype and deterioration of joint damage was found (P = 0.027, Fisher's exact test). MRI-detected bone marrow oedema (BMO) score and the baseline radiographic damage score were also significantly related to structural progression (P = 0.002, Mann-Whitney U-test). The multivariable logistic regression analysis showed that only baseline BMO score ≥3 independently contributed to explain radiographic damage progression (OR 4.82; 95% CI: 1.0-23.2; P = 0.035). 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.
Results: At follow-up 98 months (median, IQR 95-102) after disease onset, CHAQ/HAQ was available in 352 (80%) of the total 440 participants. A CHAQ/HAQ score of 0 was found in 239 (68%) of these. The following characteristics at the first study visit 7 months (median, IQR 6-8) predicted CHAQ/HAQ > 0 eight years after disease onset: higher cumulative joint count, symmetric arthritis in wrists, fingers, or ankles, higher score on physician and patient/parent global assessment of disease activity, pain, CHAQ and morning stiffness (Table 3).

T3
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 childcentered 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  Values are the median (IQR) unless otherwise indicated; OR, odds ratio; CI, confidence interval. * Symmetric finger arthritis: bilateral arthritis in 1 or more of the 14 finger joints; GA, global assessment; VAS, visual analogue scale range 0-10 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.

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Identification of novel antibodies predictive of the development of uveitis in jia using high-density nucleic acid programmable protein arrays Madeleine Rooney 1  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. We undertook this proof of concept study to see whether a novel technique capable of producing multiple proteins could be used to screen for autoantibodies that are associated with uveitis development in JIA patients. This could enable us to identify children, at the time of diagnosis of arthritis, who are highly likely to develop uveitis. Objectives: To Identify novel antibodies that predict the development of uveitis in children with JIA.
Methods: Nucleic Acid Programmable Protein Arrays (NAPPA) enable the in situ production of multiple proteins from DNA templates which are immobilised on a solid phase. Methodology is described in detail elsewhere [1]. NAPPA slides with 2200 genes were produced. Pubmed search identified~60 genes associated with uveitis pathology and~30 genes associated with arthritis development. The remaining~2100 genes were randomly identified from a~12000 human gene collection (http://dnasu.asu.edu). The arrays were then probed using plasma from JIA patients with (n = 20) and without uveitis (n = 20) and from healthy age and sex matched controls (n = 20). Proteins with higher levels of antibody detected were confirmed by ELISA.
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 DNAbinding 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.
Reference [1]: Bian, X., Wiktor, P., Kahn, P., Brunner   Introduction: Biological agents (BA), especially TNF inhibitors, are high efficacy options for current therapy for patients (pts) with juvenile idiopathic arthritis (JIA). They are successfully used not only for the arthritis but also for JIA-associated uveitis, however, development of uveitis de novo in pts treated with BA is a well-established paradoxical adverse event. Objectives: to evaluate the frequency of new onset (no-) uveitis, occurring under BA therapy in JIA pts, to establish clinical features, which may be associated with development of such phenomenone. Methods: retrospective cohort study involved all JIA pts (760) who were treated with BA in our clinic from 2004 to 2017. All cases of nouveitis were collected for the describing of their clinical features in disease onset and course, activity level, JIA category, exposure to Methotrexate (MTX) and BA, presence of ANA, HLA B27. Results: among of 760 pts treated with different BA we identified 22 (2.9%) pts (12 female/10 male) with no-uveitis under BA, mostly during etanercept (ETA) therapy (22 cases from 302 ETA courses, 6.6%), 1/120 -in abatacept (ABA) and 1/249 -in adalimumab (ADA). There are no cases of no-uveitis under other BA Frequency of no-uveitis is much higher in ETA group (2.46 events per 100 patient-year (PY) vs 0.31 in ABA, and 0.15 in ADA. ETA exposure was 14.7 ± 9.7 months (mo).. A case of no-uveitis under ABA was observed after 5 mo of therapy in a girl previously treated with infliximab. 1 boy with early JIA onset (in age of 18 mo) developed no-uveitis after 71 mo of ADA 71 mo simultaneously with general response decreasing and successfully switched to ABA. JIA subtypes were as follows: RF-neg polyarthritis 6 (27%), persistent oligoarthritis 3 (14%), extended oligoarthritis 11 (50%), enthesitis-related arthritis (ERA) -2 (9%). Average age at JIA onset was 4.5 ± 3.9 yrs. 19/22 patients had high laboratory activity (CRP 54 ± 23 mg/l; ESR 41 ± 19 mm/h) and severe arthritis before BA initiation. However most of pts (18/22) achieved 90-100% ACRpedi-response by the uveitis development. 14/22 pts were ANA-positive, 11/22 pts had HLAB27, including 3 pts who had the both features. Uveitis was occurred earlier in ANA plus HLAB27 positive pts (mean exposure -10.7 mo) than in only ANA-positive or HLAB27-positive pts (27.4 mo and 21.6 mo accordingly). 19/22 (86%) of pts received methotrexate (MTX) in mean dosage 11.5 mg/m 2 / week. There are no differences in time of uveitis development depending of MTX. In all cases of no-uveitis BA was switched. Conclusion: Our study suggested that new onset of uveitis is rare adverse event during BA therapy in JIA without any known predisposing risk factors.. Such paradoxical effects may reflect not so much therapy complications, but the delayed implication of natural character of disease. Development of no-uveitis is more often observed in pts receiving ETA, especially in pts with early age of JIA onset. High activity aggressive manifestations at the disease onset and good initial response to BA are typical features for all pts, who developed this paradoxical effect under BA therapy.

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Microparticles as potential biomarkers of disease activity in anti-neutrophil cytoplasmic antibodyassociated vasculitis Milena Kostić 1 , Fariborz Mobarrez 2 , Jelena Vojinović 1 , Iva Gunnarsson 2 , Aleksandra Antović 2 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 antineutrophil 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. Results: Half of the patients group (24) had active vasculitis (mean BVAS 6,69 ± 8,76) and 24 had inactive disease. Plasma levels of MPs expressing TF, NETs, pentraxin3 and HMGB1 in active patients were significantly higher than in those in remission and healthy controls (p < 0.01, p < 0.0001, respectively). MPs expressing C5a and C3a were significantly higher in both patients groups compared to controls (p < 0.001). Additionally, levels of MPs expressing C5a strongly correlated with BVAS (r = 0.78, p < 0.0001), while there was no significant correlation between other explored markers and BVAS. Data presented in Table 4.

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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.  , 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.   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 antirheumatic 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 Introduction: Aerobic fitness may serve as an important healthrelated 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 JIApatients who are intensively treated and to identify the association of clinical variables. Methods: In a longitudinal cohort, all consecutive patients aged 10-24 years were included after informed consent. Annual examinations were obtained from demographic and disease-related items. At baseline and at study-end, aerobic fitness (VO 2 peak) was assessed using a graded cardiopulmonary exercise test (CPET) to volitional exhaustion performed on a cycle ergometer. Absolute and relative VO 2 peak values were measured and related to reference values of healthy controls (Z-scores), using one-sample T-tests. 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. 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 highuptake 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 Xray 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. 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.
Methods: Blau syndrome-specific induced pluripotent stem cells (iPSCs) lines were established. To precisely evaluate the in vitro phenotype of iPSC-derived cells, the disease-associated NOD2 mutation of iPSCs was corrected using a CRISPR-Cas9 system. We also introduced the same NOD2 mutation into a control iPSC line. These isogenic iPSCs were then differentiated into monocytic cell lineages, and the status of NF-κB pathway and proinflammatory cytokine secretion were investigated. Results: IFN-γ acted as a priming signal through the up-regulation of NOD2. In iPSC-derived macrophages with mutant NOD2, IFN-γ treatment induced ligand-independent, NF-κB activation and proinflammatory cytokine production. RNA-seq analysis revealed distinct transcriptional profiles of mutant macrophages both before and after IFN-γ treatment. Patient-derived macrophages demonstrated a similar IFN-γ-dependent inflammatory response. 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.  (Table 11).
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 Kruppelassociated 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.
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 inhouse 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.
Ongoing functional work will provide further information on how these mutations affect ADAM17 activity and impact on hemidesmosome structure. Disclosure of Interest: None Declared.

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The  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.
Results: The cohort included 1655 patients with confirmed diagnosis of AID. At least 1 GI manifestation was reported in 52.32%. Interestingly, the latter had earlier onset compared to cohort that did not show GI involvement (5.18 ± 8.18 vs 9.11 ± 10.25, mean years ± SD). As expected, the majority of FMF, MVK and TRAPS were affected by GI symptoms whereas CAPS and CRMO were mainly represented in the subset lacking GI involvement. In the GI cohort (Table 12), during flares LC1 (13%) displayed persistent abdominal pain together with prolonged diarrhea, and it mainly included majority of MVK. LC2 (7%) was affected by occasional abdominal pain together with occasional vomiting, diarrhea and hepatosplenomegaly. LC3 represented the majority of GI cohort (72%) and presented only occasional abdominal pain while LC4 (8%) was characterized by persistent abdominal pain occasionally associated with vomiting, diarrhea, and sometime developing complications such as septic peritonitis and peritoneal adhesions. As expected, the latter was mostly represented by FMF. 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.

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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.

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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. 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. 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.
Methods: Forty-six pediatric patients with newly diagnosed FMF were included into the study. All patients were assessed in the attack-free periods for hemoglobin, hematocrit, platelet, serum amyloid A, iron, total iron binding capacity, and ferritin before the colchicine treatment, and on the 3 rd and 5 th months of colchicine treatment. Results: We have found that there was a significant increase in mean hemoglobin values when compared the results of hemoglobin levels before the treatment and on the 5 th month of the treatment (p = 0,048; <0,05). Also, we have observed the same increase in iron levels (p═0,004). We have seen that there was a significant decrease in ferritin and SAA levels and platelet counts, reflecting the control of ongoing inflammation. However, no significant difference was found between mean total iron binding capacity value, mean hematocrit values ( 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 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). The median of average SAA level was 3.5 (3-38) mg/L and the median of average CRP level was 0.1 (0.01-1.8) mg/dl and mean of average ESR was 11.3 ± 5.4 (5-27) mm/hour. The children with pathogenic mutations had significantly higher mean SAA levels than the children with variants of unknown significance (p = 0.018), however; the mean CRP and ESR were similar. Besides, the children with pathogenic mutations had significantly more fever episodes than the children with variants of unknown significance (p = 0.04). None of the children had persistent proteinuria in the follow-up. We started colchicine in only 2 patients who were M694V heterozygous because of initiation of typical disease symptoms accompanied by at least one increased acute phase protein during an attack. Both patients had family history for FMF and fulfilled the disease criteria after 2 years of follow-up. Neither of these patients had persistently elevated acute phase reactants in their routine follow-up.

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. 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. 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: · Face-to face interviews with one of the parents of children diagnosed with PFAPA (n = 10, 6 mothers and 4 fathers) · Communication between parents of children with PFAPA in a closed Facebook group Results: The child´s well-being was highly affected by the symptoms during episodes. Parents experienced increased stress with constant fatigue, social constraints of family life and restricted career opportunities. Hope of a recovery was constantly present. Parents described a lengthy process, depicted in the following Grounded Theory core category: From uncertainty to gradually managing and awaiting recovery. Subcategories (below) describes illness trajectory, illness representation and the experiences/impacts of the periodic condition: Uncertainty (Harmlessness -severity) ·Worries · Fear · Frustration Assurance (Establishment of diagnosis) ·Relief · Reassuring · Explaining · Guilt reducing Gradually managing (Regularity -unpredictability) ·Suffering · Exhaustion · Isolation · Work-related limitations Recovery ·Outgrowing PFAPA · Surgery (tonsillectomy) Conclusion: Getting a diagnosis becomes very important for parents since this reduces uncertainty and feelings of guilt Disclosure of Interest: None Declared Introduction: Type I interferonopathies are a clinically heterogeneous group of Mendelian disorders characterized by constitutive upregulation of type I interferon activity. Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy and sometimes mimics a congenital viral infection. Over time, as many as 40% of patients develop chilblain skin lesions on the fingers, toes, and ears. Classical AGS phenotype was associated with mutations in seven genes encoding proteins involved in nucleotide metabolism and/or sensing: , and IFIH1 (AGS7). Mutations in these genes result in the induction of type I interferon production and upregulation of interferon stimulated genes. However, the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
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 nextgeneration sequencing (NGS) panel followed by Sanger sequencing were performed. Results: The type I interferon score was markedly higher (98 times higher) in our patient compared to healthy controls. Using a nextgeneration sequencing panel, followed by Sanger confirmation, the patient was found to be homozygous for a novel c.66delC/ p.SerGlnfs*43 variant in SAMHD1. Although not seen before, considering that this lesion is predicted to act as a biallelic nonsense mutation, and in light of the clinical features, this result confirmed the diagnosis of an Aicardi-Goutières syndrome. A cerebral MRI will be performed to evaluate the cerebrovascular involvement in this patient, considering the risk of intracerebral large vessel involvement with catastrophic cerebral vascular accidents associated with mutations in SAMHD1. Introduction: Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) is a rare recessively inherited autoinflammatory syndrome, characterized by early-onset recurrent fevers, skin lesions, periorbital swelling, lipodistrophy, arthritis, myositis, short stature and hepatomegaly. It is caused by defects in assembly of the proteasome complex. Thus far, mutations have been identified in 5 genes although most commonly they are found in the PSMB8 gene.
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. At the age of 2 years and 10 months, the boy presented to our Clinic. Lipodystrophy, short stature (-4 SDS), typical facial features, longer IV-th and V-th fingers of both hands and hepatomegaly were noted in addition to the above features and a clinical diagnosis of CANDLE syndrome was made. Blood samples from the child and both parents were sent to NIH for genetic testing, revealing compound heterozygous mutations in the patient's PSMB8 gene. The two mutations, p.A92V and p.K105Q, were previously associated with CANDLE. Each parent is heterozygous for one mutation.
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. 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 pathogenexposed 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. 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. 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. Patient 1 had been treated with adalimumab for 15 months, as she developed fever, acute pansinusitis and orbital cellulitis and abscesses during vacation. She was treated with intravenous antibiotics and drainage. The treatment was continued after returning home, and clinical improvement and normalisation of C-reactive protein (CRP) was achieved. Mild and unspecific symptoms of headache, double vision and swelling of the forehead remained and was initially thought of as sequela after surgery. Upon further investigation papilloedema was recognised and a CT scan of the brain showed subdural empyema, intra cerebral oedema located in the frontal lope, abscesses intra orbital and in the forehead, continued sinusitis and subperiosteal abscess and osteomyelitis (Potts puffy tumor). An aggressive rhino-and neuro-surgical approach combined with longterm broad-spectrum antibiotic treatment was initiated. Despite this, osteomyelitis in the frontal bone reoccurred several times, latest 1½ year after the initial infection. Immunosuppressive drugs have been discontinued at the beginning of the infectious period. Patient 2 was treated with methotrexate for a year and received adalimumab for a period of 3 months. In these months she developed chronic rhinitis and allergy was suspected but not confirmed. When psoriasis appeared adalimumab was stopped, but the chronic sinusitis persisted. Two months later she was admitted with high fever and convulsions. She had discrete increased white cell count in the spinal fluid and a CT scan showed pansinusitis but no ostitis or intra cerebral changes. Broad-spectrum antibiotic treatment was started together with drainage of the sinuses. She improved clinically but CRP remained elevated. A MRI of the head was planned, but before it was performed another convulsion occurred. MRI showed pansinusitis, osteitis and subdural empyema. Functional endoscopic sinus surgery (FESS) was performed and the girl is now improving on longterm antibiotic treatment. Methotrexate treatment was stopped at the initial symptoms of meningitis. 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. Written consent for publication has been obtained from the parents. 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. were significantly younger at disease onset than other patients (3 years vs 4 years, respectively; p = 0,021). In addition, the disease duration, disease activity, acute phase reactants, and AIDAI(auto-ınflammatory disease activity index) values were higher and need for additional therapy was more frequent among patients with M694V/M694V compared to others.The disease activity, acute phase reactants were higher and need for additional therapy was more frequent in patients with high-risk mutations than others (Table 14).

Conclusion:
The disease phenotype is more severe in patients with high-risk mutations. Therefore, close follow-up is critical for these patients. There was no statistically significant difference in the incidence of infection between mutation groups. When the patients who had an attack in the last 6 months were examined, there was no significantly difference in infection status.
When the patients, who had increase in any infection frequency, were evaluated according to the mutation groups and attack status in the last 6 months, there was no significantly difference between the groups. Results: The disease onset was ≤5 years in 69%, 6-11 years in 26%, and ≥12 years in 5% of patients. Fever symptom was significantly less frequent in the ≥12 years group than the other age groups. The characteristics of patients according to age groups (at symptom onset) are presented in Table 15. The disease onset was significantly younger in patients homozygous for M694V mutation than patients who were negative for M694V (p = 0.021). 64,6% of 199 patients were compliant to colchicine treatment. When we grouped these patients according to their present age, ≤5 years group was the most compliant and the adolescent patients (≥12 years of age) was the less compliant to treatment (p < 0.05).
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.   Introduction: Bone marrow oedema in a child is a rare and uncommon condition associated with joint and bone pain exacerbated by weight bearing.

Disclosure of Interest: None Declared
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. Physical examination did not reveal any skin color change (rubor) but intense pain limited to the skeletal sites of feet and ankles; only two patients (28%) had a slight swelling of the feet. 6 of the patients suffered from joint hypermobility with recall of minor ankle strain prior to the symptoms onset as precipitating event after meticulous history; 1 was a football player and reported recurrent feet microtrauma. 1 patient had been treated in another institution with bisphosphonates without any improvement. Bone turnover markers were normal in the 6 patients not treated previously with bisphosphonates; vitamin D was below the lower limits in all patients (72% < 20 ng/mL). All Patients were treated with an adequate daily vitamin D intake and symptomatic pain relief was achieved with low dose NSAIDs (ibuprofen) or a short course of steroid treatment (prednisone); rest and physical therapy were recommended; vitamin C was added when diet intake was too low according to minimal daily diet recommendations. Clinical improvement appeared within a 2 to 3 month treatment period in all patients; MRI performed in the 3 patients with over 6 month of treatment documented complete regression of bone marrow oedema. 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. 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).
Results: Twenty (77%) out of the 26 eligible JIA patients identified daily activities most relevantly affected by TMJ involvement. Thereafter, the items most frequently selected were included in the JATA: 1.ability to bite a sandwich/an apple/a "bombolone"; 2.ability to eat a pizza or a steak; and 3.ability to accurately wash the teeth. Eight patients (100% female, 62.5% with persistent oligoarthritis and 12.5% with extended oligoarthritis, polyarticular RF-negative, and polyarticular RF-positive, respectively) filled the JATA questionnaire, reporting their abilities and global assessment of TMJ before and after TMJ IACI. Each questionnaire was completed in about 3-5 minutes. We observed a statistically significant improvement in the scores, both of the single items and the TMJ-GA, prior and after TMJ IACI (Table 17). The procedure was evaluated with a median score of 8 (IQR: 7.8-10).
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.
Methods: Consecutive cases of JIA from defined areas of Norway, Denmark, Sweden and Finland with onset in 1997 to 2000 were prospectively included in a population-based cohort study (1). Selfreported pain was measured on a 10 cm visual analogue scale (VASpain ). The Finnish participants were excluded due to lack of pain scores. Remission at 8 years follow-up was defined according to Wallace (2). We used binomial regression in STATA for multivariable analyses.
In the oligoarticular onset group, we analyzed associations between early pain reports and outcome at 8 years follow-up. Children reporting pain 6 months after disease onset developed oligoarticular extended or other JIA categories more often compared to those reporting no pain at 6 months (percent point difference 19%, 95% CI [1-37%]). Among those reporting pain at 6 months, a higher proportion reported pain also at 8 years, compared to children with no pain at 6 months (percent point difference 35%, 95% CI [16-53%]. Pain at 6 months was associated with not being in remission off medication at 8 years compared to no pain at 6 months (percent point difference 36%, 95% CI [19-54%]. After adjustments for age and sex, the results were similar. 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. 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 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 de- 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].
Objectives: The goal of the study was to determine whether the TNFA gene -308A > G, IL1B gene -511C > T and IL6 gene -174G > C single nucleotide polymorphisms (SNPs) are associated with the disease severity in patients with JIA. 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 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. Nonresponders 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. Results: A total of 119 patients were included in the analysis, 91 (76.5%) girls and 28 (23.5%) boys. Ten (8.4%) patients had systemic arthritis, 41 (34.5%) RF negative polyarthritis, 5 (4.2%) RF positive polyarthritis, 24 (20.2%) persistent oligoarthritis, 24 (20.2%) extended oligoarthritis, 11 (9.2%) juvenile psoriatic arthritis, 2 (1.7%) patients suffered from enthesitis related arthritis and 2 (1.7%) had undifferentiated arthritis. Mean time of disease duration before MTX was started was 13 months in the whole cohort and 6.9 months in the subgroup of patients with polyarticular disease (RF positive and RF negative). Mean starting dose of MTX was 10.3 mg/m 2 and mean dose at 6 months was 12.0 mg/m 2 . Forty-two (35%) patients were switched to subcutaneous MTX to achieve higher efficacy. At 6 months 30/116 (25.8%) of patients were defined as nonresponders. BIRC5 rs17878465 (p < 0.0001) and BIRC5 rs9904341 (p = 0.0272) were associated with achieving 30% improvement in JADAS 71 after 6 months. BIRC5 rs9904341 was also associated with 70% improvement in JADAS 71 score (p < 0.0001) after 6 months of treatment. 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 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. Methods: After a review of the most recent literature on MRI of the TMJ in JIA and based on their experience, three specialists in different fields (a rheumatologist, a dentist and a radiologist) devised the score for the assessment of activity and damage of TMJ shown in Table 18. The score consists of 3 parameters of arthritis activity (joint effusion, contrast enhancement (CE) and bone edema), and 4 parameters of joint damage (erosion/irregularities of the mandibular condyle, disc abnormalities, flattening of the condyle, mandibular asymmetry). The activity score ranges from 0 to 6 and the damage score from 0 to 9. After a series of training sessions aimed to reach consensus on the definition of the score features, each specialist assigned independently the MRI score to an unselected sample of TMJ MRIs of JIA patients followed at our center. The inter-and intra-observer reliability were calculated through the weighted kappa. The CE parameter was also compared with a recently validated score calculated on a specific region of interest (ROI) of the TMJ MRI in JIA patients 1 . Agreement was considered acceptable for a k value > 0.60. 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.  Viability and functionality of labeled cells were confirmed by in vitro assays. In several mouse models -particularly in a collagen induced arthritis (CIA) mouse model -we investigated the ability and specific properties of different cell populations to migrate to sites of inflammation in vivo via fluorescence reflectance imaging (FRI). Using CRISPR-Cas9 technology we introduced targeted gene deletions for main adhesion molecules.
Results: ER-HoxB8 monocytes and neutrophils could effectively be labeled with DIR or DID. In vitro assays confirmed that viability and functionality of ER-HoxB8 cells was not affected by cell labeling. Subsequent in vivo imaging experiments allowed the visualization of migrated labeled phagocytes in different murine disease models, thereby cells could be detected at sites of inflammation with high sensitivity and specificity. In a CIA mouse model the amount of immigrated cells could even be associated closely to disease score and disease severity. Thus, the detection of immigration of labeled cells might also give hints about new inflammatory spots that are about to settle up before they can be detected macroscopically. Furthermore, differential cell labeling allowed direct quantitative comparison of differences in migration rates of wildtype and CD18 or CD49d knockout cells in vivo.  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.
Results: A total of 25 patients (22 females, 3 males) with a mean age of 15,8 years have been included. All 9 pjSS patients had sicca symptoms, this was present in only 56,3% of sjSS. Swelling or pain in major salivary glands occurred in 7 of 9 pjSS but only 5 of 16 sjSS (including MCTD). US scoring of salivary glands according to Hocevar [1] which had been proven to be accurate in jSS as well [2] showed a mean score of 26 in pjSS and 18,28 in sjSS patients. We could not correlate US score (Hocevar) with the duration of the disease (Pearsons r =0.197) (Table 19).
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 siccasymptoms to identified typical, inhomogeneous parchenchymal appearance with hypoechoic lesions suggestive for jSS.  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. 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. 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.  (Table 20).

Conclusion
Nearly 35% of the JIA patients showed discordant findings between clinical assessment and MRI. Clinically active patients without synovial hypertrophy on MRI were significantly older at the time of MRI than the clinically active patients with synovial hypertrophy on MRI.
In the clinically inactive JIA patients, the discrepancy between clinical assessment and MRI was especially seen in younger patients. The meaning of synovial hypertrophy in the clinically inactive patient is still unknown, but it might indicate an incomplete disease remission.

P57
Flow cytometry based assay of platelet reactivity in children with Kawasaki disease-a preliminary study Pandiarajan Vignesh 1 , Surjit Singh 1 , Amit Rawat 1 , Man Updesh S. 555466). Following incubation for 20 minutes at room temperature, the cells were acquired on the flow cytometry (Beckman coulter, Navios). The monocytes were gated from the lymphocyte side scatter plot and MPAs was identified from the monocyte population that had expressed both CD14 (monocyte marker) and CD41 (platelet marker) using the Kaluza software.
Results: The median age group (inter-quartile range) in the cases, febrile controls, and normal controls were 6 (3.0, 7.25), 5 (3.6, 9.0), and 5.5 years (4.15, 6.5), respectively. Male to female ratio among the groups were 12:2, 13:2, and 11:2 respectively. Echocardiographic abnormalities were detected in 3 children (2-   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. Immunologic test revealed then a reduction in the level of plasmatic immunoglobulins. The detection of EBV DNA with quantitative PCR revealed 21935 copies for 100000 leucocytes with prevalence of infection in the B cells. Whole body positron emission tomography revealed a retroperitoneal formation of about 35 mm with an increased metabolism that, at biopsy, revealed a reactive lymphadenopathy with paracortical involvement associated with EBV infection. Genetic conditions associated to chronic EBV infection and immunodeficiency were ruled out: the genetic tests for SAP, XIAP, BAFF-R and ICOS were negative and the cytofluorimetric analysis of perforin, CD107 and 2B4 receptor were normal. In light of these findings a CAEBV was suspected.
Being the patient in good general conditions and in light of the prevalent involvement of CD20+ lymphocytes, on demand treatment with rituximab was started. The clinical response to treatment was initially very satisfying; however after two years the child presented severe infections requiring prolonged hospitalisation; stem cell transplantation was then performed with a complete normalization of both clinical and immunological features. Among variants identified through a WES analysis of the patients and his parents, a homozygous mutation of the CD70 gene appeared to fit the recessive model of inheritance. The variantc.163-2A > G affects the exon2AG-acceptor splice site of the CD70 gene (NM_001252) leading to a deficiency in CD70, the ligand of CD27, a gene involved in isolated immunodeficiency. In the meantime our analysis was ongoing, CD70 mutations were reported in a few patients with a similar condition. At the protein level, the anti-CD70 antibody failed to detect CD70 by flow cytometry at the cell surface of PHA-stimulated T and EBVtrasformed B cells of the patient. In contrast, expression of CD70 was detectable on cells from healthy donors. 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 antiinflammatory drugs (NSAIDs) and metronidazole completely resolved pain, joint swelling and diarrhea. After 24 months of follow-up there has been no recurrence. Reactive Arthritis (ReA) is an aseptic acute inflammatory arthritis occurring after an intercurrent infection in which the causative organism is outside from the joint. It is typically an asymmetrical oligo/polyarthritis predominantly in the lower limbs large joints (knee, ankle, hip) and present approximately 2-4 weeks following infection. Several patients present a migratory pattern and acute arthritis is often characterized by severe pain and sometimes erythema over the affected joints; enthesitis/tenosynovitis may occur. Most frequent causes are Salmonella, Shigella, Yersinia, C. jejuni, group A Streptococcus and C. trachomatis. CD is the most common cause of diarrhea after antibiotic therapy but CD ReA is rare and its pediatric epidemiology is poorly known; it was generally migratory and polyarticular, involving large joint and tipically with a good outcome and self-limiting course.
For the diagnosis of ReaA following CD enterocolitis there are criteria established by Putterman and Rubinow [1], but basically a history of diarrhoea after a course of antibiotic with the exclusion of other causes of gastroenteritis or noninfectious arthritis is essential. Jacobs et al [2] documented until 2001 35 cases of CD ReA in adults; epidemiology in child instead is rare and unknown, but incidence of CD infection has increased among children. We performed a literature search of MEDLINE, Google Scholar, and Cochrane Reviews computerized databases using the keywords "Clostridium difficile", "arthritis", and "child" to identify all papers reporting CD enterocolitis-associated ReA in childhood. Six papers met our review's inclusion criteria with a total of 32 pediatrics cases of CD ReA. The most recent study identified, from 2004 to 2013, 26 cases with acute arthritis/tenosynovitis after CD infection and authors estimate that CD ReA affected 1.4% of child with CD infection; only 35% of CD ReA were correctly diagnosed, occasionally misdiagnosed as septic arthritis [3]. Conclusion: CD infection should be suspected in children presenting with an acute inflammatory arthritis following an episode of diarrhea, especially when culture for common enteric infection are negative and the patient has received antibiotic therapy before the onset of diarrhea. Written informed consent for the publication of patient details was obtained. 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.

Disclosure of Interest: None Declared
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 taskoriented 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 patientcentered 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. 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. Results: The mean age was 12,76 ± 3,16 and the mean disease duration was 5,92 ± 3,82 years. 8% of patients had involvement shoulder joint, 74% of them had involvement elbow joint, 88% of them had involvement wrist joint and also 64% of them had involvement finger joint. The patients with JIA described 36 different types of problematic activities and identified 30 of them as the five most important daily activities. Table 22 shows frequencies of five most important daily activities of patients with JIA. The five most identified problems were "carrying something" (66%), "writing" (50%), "opening a bottle cap" (48%), "dressing" (38%) and "opening a door with handle/knob" (38%) according to COPM. The mean of COPMperformance scores was 3,99 ± 1,72 and the mean disease COPMsatisfaction scores was 2,56 ± 1,70. 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 patientfocused outcome measure and also, it could provide information about patient centered management for patients with JIA. 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%). Barriers to accessing care for children with JIA identified by respondents were: insufficient training in JIA among pediatricians (74%), lack of awareness of JIA in the healthcare community (73%), long referral pathways (67%) and few pediatric rheumatologists (63%). Endemic diseases that complicate the management of JIA in participants' settings were: tuberculosis (84%), HIV (41%), sickle cell anemia (31%), malaria (19%) and diarrheal disease (19%). Transition planning was not a programmed strategy in >40%; and nonadherence to uveitis screening guidelines was reported in >40%. Education on JIA was available to 71% of pediatrics trainees, 50% of adult rheumatology trainees and <50% of medical students in participants' settings. Established pediatric rheumatology training programs were unavailable to 40%; access to educational resources and educating the public on JIA was available to only one third of respondents. Policy and advocacy interventions felt to potentially improve access to care for JIA patients were: increasing the availability of pediatric rheumatologists (79%) and jobs for them (50%), better training on managing JIA (74%), formulation of clear referral channels (65%), formation of patient support groups (62%) and availability of management guidelines (49%). One third of participants were not involved in research. Epidemiological and clinical research were felt to be research priorities in JIA by 75% and 62% of participants to ascertain local burdens of disease. Major barriers to performing research include: lack of funding (79%), lack of time (58%), lack of support systems, e.g., laboratory (52%), lack of trained personnel (46%) and lack of experience (26%). 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. The median diagnostic delay of the whole cohort was 17 weeks (interquartile range (IQR) 9-48). The patients with ERA had the longest delay: 45 weeks (13-104), whereas children with sJIA had the shortest delay: 9 weeks (4-21). The median diagnostic delay was not correlated with parents' home distance from the diagnostic center. 59% and 57% of the patients were in remission and 57% at 1 and 2 years of follow-up, respectively. The median delay between diagnosis and treatment onset was 3 weeks (IQR 0-34) for oral corticosteroids, 8 weeks (IQR 0.3-30) for intra-articular corticosteroids, 9 weeks (IQR 0-52) for DMARDS and 52 weeks (IQR 19-147) for biologics. The diagnostic delays for the whole cohort and for the different JIA subtypes are in line with the international literature. JIA with indolent symptoms as ERA had the longest diagnostic delay whereas sJIA associated to overt manifestations including fever had the shortest delay. In France and Switzerland, there are no guidelines about diagnostic delay but UK guidelines advocate a diagnostic delay inferior to 10 weeks. According to these guidelines, 68% of our patients exceed this delay, which is shlighly lower than previous studies. The absence of correlation with parents' home distance from the diagnostic center is also described in other countries. Our remission rate at 1 year is higher than described in other studies but it decrease at 2 years. The treatment delay is longer in our cohort than in other studies. 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 lupusand her parentto 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.
Results: Fellows' self-assessed proficiency with 12 key transition/transfer skills increased significantly with participation in the workshop and accompanying OSCE, including fellows' confidence in their ability to discuss the needs of the transferring patient with the pediatric rheumatologist (p < 0.01). In addition, OSCE performance (see Table 23) was greater in the group of fellows that participated in the workshop prior to the OSCE ("post-workshop" -average score of 4.3) than in the group that took the OSCE de novo ("pre-workshop" -average score of 3.3, p = 0.01). The skills demonstrating statistically significantly higher scores post-workshop were: skill 1) highlighting differences between adult and pediatric care and setting expectations (p < 0.01); skill 2) placing the patient in the primary role and utilizing the parent for corroboration (p < 0.05); and skill 4) performing a confidential adolescent social history. There was a trend towards improved performance for skill 3, assessing self-management skills, whereas there was no significant change in skill 5, assessing barriers to transition and medication adherence. Performance on skill 6, the control skill of assessing patient and parent understanding of the disease process, was lower in the group of fellows' that participated in the workshop prior to being tested with the OSCE (p = 0.01).
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.  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.
Results: A total of 336 patients (23.6%) had uveitis a median of 1.1 years after onset of arthritis. The cumulative frequency curve showed that 47.6% and 67.3% of patients developed uveitis in the first 1 and 2 years of illness, respectively, and that less than 5% of all instances of uveitis occurred after 7 years from the onset of arthritis (Table 24). 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.     Introduction: Systemic-onset juvenile idiopathic arthritis (SoJIA) is a rare paediatric rheumatic condition with unclear pathogenesis, challenging diagnosis and treatment. Objectives: The aim of our study is to describe the epidemiology, clinical presentation and biologic treatment of SoJIA patients registered in the JIRcohorte. Methods: This is a multicentre, observational, retrospective and inception cohort study, through an international platform: JIRcohorte. Patients with SoJIA, diagnosed and followed in one of the participating centres in the JIRcohorte project in Switzerland, France, Belgium and Morocco are enrolled in the registry. Results: 212 patients with SoJIA have been included; 119 were girls with a female: male ratio of 1.3:1. The median age at diagnosis was 5.4 years and the median diagnostic delay was 40 days. Data for initial systemic manifestations were available in 57 patients: 96% presented with typical fever (55/57), 56% with rash (32/57), 32% with lymphadenopathy (18/57), 21% with splenomegaly (12/57), 21% with hepatomegaly (12/57), and 16% with serositis (9/57). Data for joint involvement were available in 46 patients: arthritis was reported in only 61% of them during the first year of disease evolution, with a poly-articular predominance (61%). 169 out of 212 patients (80%) had a biologic treatment at least once during their disease course. Before 2008, anti-TNFa agents were more frequently used (69%), followed by anti-IL-1 agents (30%), with a very few patients receiving anti-IL-6 agent (1%). Since 2008, anti-IL-1 agents became the most common biologic treatment (46%), followed by tocilizumab (36%), with fewer patients under anti-TNFa agents (18%). Higher rate of infectious adverse effects was reported with Tocilizumab, while Anakinra was associated with skin and administration site effects.

Conclusion:
We describe here the main epidemiologic and clinical characteristics, as well as the treatment of patients with SoJIA included in our international JIRcohorte platform. Biologic therapies, in particular anti-IL1 agents, are widely used in the treatment of this disease throughout the last years. Further prospective data analysis is required to evaluate the long-term efficacy and the safety of these treatments. Results: One hundred and one patients were included (76 girls). 61 oligoarticular JIA, 20 rheumatoid factor (RF) negative polyarticular JIA, 19 extended oligoarticular JIA and 1 RF positive polyarticular JIA. Fifty patients were ANA positive. At least one variation was identified in 26.7% of our patients. Accumulated probability of having some variation in these genes in our JIA series was statistical significant greater than healthy Iberian population (20 vs 8.2% respectively, p = 0.01). Table 28 describes identified genetic variations. Variations in all searched genes were detected except for MVK. Oligoarticular extended JIA was the more affected subtype (47.4%, p = 0.082). We did not find differences according to ANA. Based on the presence of a genetic variation we did not find differences in age at onset disease, presence of extra-articular symptoms, laboratory parameters at diagnosis. Conclusion: Variations on all AID studied genes were detected except for MVK. We found greater prevalence of genetic variations in JIA patients than described in healthy Iberian population. We did not find differences according ANA. We did not find clinical nor laboratory predictors of presence of a genetic variation Disclosure of Interest: None Declared Objectives: The aim of this study is to describe the demographics and diagnostic classification of children with rheumatic conditions followed up in the clinic. Methods: Methods: a retrospective cohort was conducted. All the files from August 2013 to July April 2017 were reviewed. Case description and diagnosis were captured. Standardized description of diagnosis was used. All patients were screened for uveitis by ophthalmologist using slit lamp examination Results: Results: rheumatic conditions were diagnosed in 130 subject. JIA was the most frequently encountered rheumatic condition 44% (n = 58), followed by FMF 10% (n = 14) and SLE 9% (n = 12). Among JIA group oligoarticular JIA was the most common subtype 60% (n = 35), 10% (n = 10) of the cases were complicated by anterior uveitis. The remaining 37% of patients had a variety of other conditions. MTX was used to treat 38% (n = 51) of the cases. Biologics were started in 20% (n = 25) cases. Conclusion: Conclusion: this is the first cohort that describes the epidemiology of rheumatic conditions among UAE children, it highlights the rheumatologist conditions and their frequencies among pediatric population, however continuos prospective data is needed to confirm our initial observation. Introduction: The ankle-foot complex (AFC) is a commonly involved joint site in children with Juvenile Idiopathic Arthritis (JIA) that requires special attention from clinicians due to the complexity of its anatomical structure and the recognized association with a more severe disease course. Some patients experience recurrent, treatment refractory involvement of this region, posing unique challenges for therapeutic management. Little information concerning the longitudinal course of AFC arthritis in relation to treatment and its predictors is available to date to guide treatment strategies for JIA patients. Introduction: Camptodactyly-Arthropathy-Coxavara-Pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by mutations in the PRG4 (proteoglycan 4) gene located on chromosome 1q31.1 (OMIM:*604283). Hallmarks of the syndrome include congenital or early-onset camptodactyly and arthropathy with synovial hyperplasia, progressive coxa vara deformity and noninflammatory pericarditis. Patients affected by CACP syndrome lack the glycoprotein lubricin, a major lubricant expressed mainly in joints and in pericardial and pleural cavities. Features of CACP syndrome mimic juvenile idiopathic arthritis (JIA) and children with CACP are often misdiagnosed as JIA. To date, twenty-two homozygous mutations and 1 case of CACP syndrome resulting from uniparental disomy of chromosome 1 have been reported in different ethnic populations, none from Greece.

Disclosure of Interest: None Declared
Objectives: To report the mutations in the PRG4 gene in 2 siblings with CACP syndrome in one family from Greece. Methods: A 6 years old boy suffered from congenital camptodactyly and progressive non-inflammatory arthropathy from the age of 2 years (knees, ankles, elbows, wrists, and cervical spine). Radiographs, ultrasound and MR images revealed features of CACP syndrome. He was diagnosed with juvenile idiopathic arthritis at the age of 3 years and received corticosteroids, methotrexate, and anti-TNF treatment without efficacy. The patient's younger brother, aged 2 years, had a similar history, albeit more severe, starting at the age of 2 months. The family consulted in our Clinic for a second opinion at the age of 6 years. Molecular genetic studies were done for all coding exons and the exon-intron boundaries of the PRG4 gene. NGS was performed on hybridization-captured region of interest. All variants were confirmed by Sanger sequencing. Results: The 2 siblings were found to be compound heterozygotes for c. Introduction: Previous studies suggest that children with Juvenile Idiopathic Arthritis (JIA) have poorer oral health compared to their healthy peers despite adequate knowledge of appropriate dental care. We hypothesised that this may be due to dental anxiety and that there may be specific dental and/or disease related factors which predict dental fear in this population Objectives: We aimed to determine the prevalence and predictors of dental fear in a single centre population of JIA patients. Methods: JIA patients aged 5-18 years attending the rheumatology clinic at the Women's and Children's Hospital in Adelaide, South Australia completed a questionnaire regarding dental visit frequency, past dental experiences, oral health behaviour, self-rated dental health, assessment of dental anxiety using the Modified Child Dental Anxiety Response Scale (MCDAS f ), their cognitive vulnerability-related perceptions of dental treatment-related events and the degree of pain and reduced movement in upper limb and temporo-mandibular joints (TMJs). Clinical data relating to JIA subtype, medications, arthritis activity in upper limbs and TMJs and JADAS score on the day of questionnaire completion were also documented. Results: Ninety four patients, (24 boys, 25.5%) participated. Average age was 12.3 years (SD = 4.3), average disease duration 5.6 years (SD = 4.3) and median JADAS score 1 (range 0-17.2). Thirty eight (40.4%) had oligoarticular and 33 (35.1%) had polyarticular onset disease. Nine (9.6%) had examination findings of TMJ involvement and four (4.3%) had active arthritis in upper limb joints of the dominant hand. Mean MCDAS f score (Cronbach's alpha = 0.93) was 2.97 with 50.5% of children having a score above the cut point for classifiable high dental fear. While dental fear was not related to having received any specific previous dental treatment, those who had not received any treatment had higher dental fear than those who had experienced at least one treatment (3.61 cf 2.87, p = 0.002). There was no statistically significant association between having had a previously unpleasant dental experience and dental fear (F = 2.06, p = 0.112). However, dental fear was associated with anxiety related to receiving blood tests (r = 0.32, p = 0.002) and injectable medications (r = 0.34, p = 0.001). Vulnerability-related cognitions, ie perceptions of the dental visit as dangerous, disgusting, uncontrollable and unpredictable were significantly correlated with dental fear (r = 0.44, p < 0.001) and in a multivariable stepwise regression model accounted for a statistically significant amount of variance in dental fear (adjusted R 2 = 31.1%) after controlling for participant demographics, medically-related fears, and having received a past dental treatment. Conclusion: In a single-centre cohort of JIA, approximately 50% reported high levels of dental fear associated with procedures related to their arthritis care rather than a previously unpleasant dental experience. Those who had not yet visited a dentist had higher dental fear with vulnerability-related cognitions of the dental visit contributing most significantly to dental fear. These results may explain poorer dental health reported in JIA patients. Objectives: To describe a large cohort of patients with JIA from several regions of Colombia that are followed in a specialized private medical center. Methods: A cross-sectional study was conducted in 366 patients who were enrolled in the registry between December of 2011 and August of 2016. There were 342 patients who met the International League of Statistical Associations for Rheumatology criteria who were included in the analysis. Association was examined by means of Chisquare tests, Kruskal-wallis test, and logistic regression analyses (to adjust for possible confounders). Results: Analysis of clinical characteristics by subtypes showed differences in gender, rheumatoid factor positivity, bone erosions, axial and peripheral involvement (Table 29). Hand and/or feet deformities were present in 21,3% of the patients, bone ankylosis of the wrist in 9,6%, asymmetric extremities in 2,9%, and ankylosis of the hip in 1,2%. Complications such as uveitis, delayed growth and osteoporosis presented in 4,7%, 7,9% and 5,5%, respectively. Three cases of avascular necrosis and one case of macrophage activation syndrome were registered during follow up. No significant differences in DMARD and biologic therapy were found among groups, but less use of steroid therapy in oligoarthritis (OR 0,24 95%CI 0,09-0,91) and enthesitis related arthritis (OR 0,05 95%CI 0,02-0,16). Conclusion: Polyarthritis was more common in preadolescent females while enthesitis related arthritis in preadolescent males. Bone erosivity was particularly conspicuous in polyarticular and systemic JIA, which implies a great risk of deformities and ankylosis, and could justify a more agressive and early management. The definition of regional epidemiological profiles in JIA helps to understand differences in disease patterns, that allow both the development of personalized interventions and resources optimization. Missing data on primary outcome variable. Protocol: Patients with infant-juvenile AIJ treated with TCZ. They are reviewed during every infusion of TCZ. Before age of 14 years old, patients are derived to Rheumatology Unit to be reviewed in adult unit and then they are followed each time they receive an infusion of the drug in day-hospital or every three months if they are in sc therapy (sc biological therapy clinic). Outcomes: Mean changes from baseline in DAS28, HAQ and activity level at 3rd month from change to sc TCZ and at 6 months from the reduction; count and description of serious and non-serious side effects during the follow-up. Other variables: Demographics, therapeutic and clinical-analytical data: tenderness joint count (TJC), swollen joint count (SJC), CRP, ESR, physician VAS, patient VAS, adverse events. Statistical analysis: Paired t test or Wilcoxon signed rank between the first and last TCZ administration, between the dose reduction and after 6 months, and between switching to sc administration and after 3 months Results: The main baseline characteristics of patients with JIA during last administration of TCZ are shown in Table. The mean of DAS28 was higher in JIA adults in the last administration of TCZ (p = 0.028).During the exposure to TCZ three non-severe adverse events were recorded. Three patients switched to sc. At 3 months after to start sc TCZ, no differences were observed in effectiveness outcomes and any adverse effect with sc TCZ was recorded. There was not any switch to sc TCZ in patients with infant-juvenile JIA, compared to patients older than 14 years where 70% of them changed to sc TCZ (p = 0.022).Seven patients reduced doses: 6 with iv and 1 sc. Six months after the reduction, no difference was observed in effectiveness outcomes; only trend to fewer non-severe adverse effects in patient with reduced doses (3 with full doses versus none patient in dose reduction;p = 0.07). Only one patient returned to full dose because inefficiency.  Table 30. The most frequent subtype was oligoarticular JIA (16.3% extended, 47.5% persistent) followed by polyarticular JIA (25.1%). Twenty-five percent had uveitis. Fifty percent had inactive disease with treatment, 26% had activity and 23% were inactive without treatment. 52.5% had methotrexate and 30% had a biological drug (22.5% antiTNFα, 5% antiIL-1, 2.5% antiIL-6), with an average disease duration of 6.6 years (±3.7DE).They had mean scores of JADAS27 of 2 (± 4DE), PCR of 4.7 mg/l (± 9,5DE), VSG of 8.7 mm (± 7,2DE) and CHAQ of 0.17 (± 0,38DE). The anthropometric parameters are shown in Table 30. The mean of JADAS27 in patients with normal BMI, was lower than 1.7 (± 3.6 SD) for those who were overweight or with obesity 3.3 (± 6.0 SD), although not significant (p = 0.255 In bivariate analysis we found direct association between hypovitaminosis D and Body Mass Index percentile (BMIp)(p = 0,05), received dose of prednisone (p = 0,03) and clinical activity duration (p = 0,04); and an inverse relation with physical activity level (p = 0,04). In multivariate analysis, relationship between hypovitaminosis D and BMIp (B 0,024; p 0,016) and with disease activity (B 0,015; p 0,01) were maintained. Moreover, we found an inverse association with biological disease-modifiying antirheumatic drugs (B-4,69; p 0,048), specifically with anti tumoral necrosis factor α (antiTNFα) (B -4,7; p 0,042) Conclusion: Hypovitaminosis D prevalence in our population is similar to previously described. JIA patients with higher BMIp have more hypovitaminosis D, as it has been reported in other inflammatory diseases. A direct relationship exists between inflammatory activity and hypovitaminosis D, but we need more studies to asses if one is cause or consecuence of the other. Introduction: Juvenile idiopathic arthritis (JIA) is one of the most common pediatric chronic illnesses. A remarkable number of patients need long term or lifelong treatment. In 'biological era' many publications have strengthened the safety and effectiveness of TNF inhibitors and some of them noticed psychological or neuropsychological (NP) adverse events (AE). The relationship of these AEs with the treatment is unclear. There is no evidence available if these skills vary in different therapy and change during JIA therapy.
Objectives: Our aims are to estimate NP state in JIA treatment groups and specify NP state influencing factors. The next step was to compare NP state in different treatment groups. Methods: Descriptive statistics and exploratory analysis were completed. 120 patients were examined at the Paediatric Rheumatology Unit (Semmelweis University, Budapest) between 01.01.2015 -31.12.2016. 68 patients received combined therapy (TNF inhibitor + methotrexate (MTX) and/or salazopyrin (SSZ)), 42 patients received DMARD: MTX +/-SSZ, 18 patients were on only TNF inhibitor therapy. After a formal psychological assessment, all patients were tested with age specific questionnaires as well: Infant Behaviour Questionnaire, Children's Behaviour Questionnaire, Child Behaviour Checklist. Furthermore, by using Woodcock Johnson III Tests of Achievement, three NP variables were compared in treatment groups: attention, learning, and working memory. In addition, current and baseline disease activity, duration of therapy and demographic parameters were assessed in each group. These parameters were stratified, and NP variables were compared in these strata. Comparison of NP variables of different treatment groups were age-, age at diagnosis-, gender-, duration of treatment-, current and baseline JADAS disease activitymatched.
Results: In the analysis of each treatment groups we did not observe any significant deviation of all NP variables based on age, gender, duration of treatment, current JADAS disease activity. All NP variables were the highest in patients whose JIA was diagnosed between 3,1-5,25 years of age. In combined therapy group attention was significantly (p < 0,05) higher in patients whose baseline disease activity was low. In the analysis of comparison of treatment groups the following differences were observed: learning score was significantly lower (p < 0,05) in male patients in MTX group than in the combined therapy group. Working memory score was significantly (p < 0,05) higher in patients whose JIA was diagnosed between 3,1-5,25 year of age, and whose treatment duration was longer than 3 years in combined therapy group. Attention score remained stable in age-, age at diagnosis-, gender-, JADAS disease activity-matched treatment groups. There was no significant discrepancy in all three NP variables between disease activity-matched treatment groups. Conclusion: We have not observed any clinically significant difference in the neuropsychological state in different treatment groups assessed only at a definite date. Age, age at diagnosis, gender, duration of treatment, current and baseline JADAS disease activity were not clinically influencing factors of NP variables in this study. The analysis of cognitive function has already been assessed, but has not been analysed yet. In a prospective study we will follow patient's psychological changes before and during therapy in order to observe if different therapies have any effect on psychological functions in JIA patients. Methods: 146 treatments were started for 116 patients with polyarticular course JIA. The following variables were assessed: Giannini improvement and JADAS-71 score every 3 months, the time for achieving at least 90% Giannini improvement, reason for treatment discontinuation, relapse rate. We estimated the alteration of Giannini improvement and JADAS-71 disease activity in patients treated for at least 24 months. Finally, we analysed the features of patients achieved inactive disease. Paired Wilcoxon test, Kaplan-Meier survival analysis, log rank test, chi square test, Fisher's test, T test were used with SPSS statistics program. Results: Statistically significant (p < 0,05) alteration was detected in achieving ever higher improvement of the Giannini's criteria in the first 12 months of treatment, afterwards this alteration remained in tendency but not statistically. The JADAS-71 disease activity significantly decreased in the first 6 months of the treatment, afterwards the decline remained in tendency. Giannini 90% improvement was achieved significantly more frequently in those who received etanercept treatment, first-line TNF inhibitor treatment and any first-line biological. Among those who achieved inactive disease, there were significantly more of those, who started treatment with fewer active joints, lower JADAS score and CHAQ values, and were significantly younger at diagnosis. Biological therapy was discontinued due to inefficacy in 50,8%, remission 28% and adverse events 10,5% of cases. In addition, 37,5% of patients had relapse whose treatment was  Anti-IL1 4 (5,2)
Conclusion: Giannini's criteria improved significantly over the first 12 months, the disease activity decreased significantly in the first 6 months, afterwards these observations remained in tendency in our cohort. Approximately one-third of treatments were discontinued due to remission almost two-third of these patients have not experienced relapse during our observation period. Introduction: Juvenile Idiopathic Arthritis (JIA) is the most frequent disease in pediatric rheumatology. There are few studies about body composition in these population, most of them suggest they have excess fat. Sarcopenia in children and young adults is pathologic and constitute a risk factor of morbi-mortality due to its association with alteration in immunologic function, decrease strength muscle and thermoregulation capacity, exercise tolerance and functionality, all of them affect articular function and preservation. Additionally, bone mass accretion and bone mineral density are related proportionally direct to muscle mass. Also patients with sarcopenia could present an increase in the fat mass known as sarcopenic-obesity.
Objectives: To describe body composition alterations in a cohort of children diagnosed with JIA in Bogota, Colombia.
Methods: Cross-sectional study where a cohort of children with JIA was assessed the anthropometry and densitometry measured by dual-energy X-ray absorptiometry (LUNAR iDXA). It was evaluated stature and weight. The fat mass was evaluated through Fat Mass Index (FMI): Kg/m 2 , subtotal percentage body fat for age and gender, and subtotal trunk fat mass. To measure lean mass was used: lean mass index (LMI): Kg/m 2 , appendicular lean mass (arm and leg lean): Kg/m 2 , and total bone mineral density less head (TBLH) The statistical analysis was only descriptive where it involved measurement of central tendency and dispersion.
Results: Thirty children were included in the study. Fifty three percentage were female with average age of 13.8 years (ranked from 5 to 22 years).All subtypes of arthritis were included, 56% had systemic and polyarticular subtypes. The average of onset of the disease was 5 year (ranked from 2 to 14 years).
In this cohort 33% of the patients had short stature. 36% patients had compromise in fat mass. FMI median z-score was -0.57 (ranked from -1.66 to 1.11), 26% of children presented fat deficiency (12.5% of them had severe fat deficit), and 10% excess fatobese. In 20% of patients the percentage of fat was above of expected and trunk fat mass was higher in 16% of the studied children; the last measure is related to cardiovascular risks. 80% of the patients had low LMI z-score that is considered as low lean mass-sarcopenia. LMI z score median was -2.17 (ranked from -4.56 to 0.36). 58.6% presented low appendicular lean mass. 30% of patients had compromise in two compartments (FMI and LMI). 100% of patients with Fat deficit had low lean mass -sarcopenia, while 33% of patients had sarcopenic-obesity (fat excess with sarcopenia) which is associated to decrease in lifeexpectancy.
The median z score for Total bone mineral density less head (TBLH) was -1.25 (ranked from -3,8 to 1,5 . The TBLH density was low in a 30% of patients, from which 100% had low lean mass-sarcopenia. Conclusion: The included children diagnosed with JIA presented high percentage of disorders of body compositions characterized by sarcopenia 80% followed by fat mass compromise in 36% (low fat mass 26% and excess fat 10%) and low bone density in 30%. The abnormalities in the lean mass could be explained due to the increase in metabolic rate and catabolism which lead to skeletal muscle consumption. It has been described "rheumatic cachexia" in 67% of adults with rheumatoid arthritis, affecting bone mineralization, strength muscle loss, and is associated with cardiovascular risk increase, but there is not any data in children with JIA. This is the first study which measure sarcopenia by DEXA in this population, additional studies including more patients are necessary to validated these results and establish opportune interventions to improve their nutritional status and quality of life. Disclosure of Interest: None Declared 44 JIA children had clinically detectable TMJ involvement (32%), but the percentages were rather different across the ILAR sub-groups : TMJs were symptomatic in 12 ERAs (19%), in 9 oligoarticular JIAs (27.3%), in 18 polyarticular JIAs (66.7%), in 3 psoriatic arthritis (30%) and in 2 systemics (50%) ; moreover, within the oligoarticular group, the most affected category was the oligo-extended group with 6 out of 7 patients having TMJs involved (85.7%). Interestingly, the clinical manifestations were not the same since half of the oligoextended JIA patients reported no pain, no chewing difficulty, no evidence of mouth opening limitation but insidiously developped facial asymetry due to unilateral TMJ inflammation. In all cases, the spreading of the arthritic process happened before 5 of age. In contrast, ERA patients manifested pain and reduced mouth opening much more frequently and at a later age, prompting to a quick therapeutic answer. Conclusion: In conclusion, TMJ arthritis might have severe consequences in those patients starting agressive disease early in life, as many extended-oligoarticular as well as part of polyarticular JIAs and systemics. Detecting the patients at high risk for structural damage in TMJs should be a major goal in the coming years. This preliminary study also shows that a significant proportion of ERA patients suffer from TMJ inflammation during the course of their disease. The limited number of patients is the drawback of this preliminary study and larger prospective studies are required to validate these data. Introduction: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. In clinical practice it is occasionally difficult to assess the real inflammatory activity. Physician's assessment of global disease activity (PGA) is a holistic assessment and it is always available. The myeloid-related protein complex 8/14 (MRP8/14, calprotectin) secreted by infiltrating phagocytes in synovial inflammation has been suggested to function better than conventional acute-phase reactants as a marker of low inflammatory activity and to be more sensitive and reliable indicator of disease activity.
Results: During TCZ course NSAID were discontinued in all studied population, decreased part of children who were treated with combination of non-biologic DMARDs from 37.5% to 2.5% and proportion of whom were treated with MTX from 92.5% to 75.0%, and leflunomide up to 2.5%. The discontinuation of the second DMARD, corticosteroids, cyclosporine and NSAIDs were due to achievement of remission and rare due to intolerance. In first 6 months of therapy was revealed impressed decreasing of ESR (p = 0.000002), CRP (p = 0.00002), WBC and (p = 0.001) PLT (p = 0.00002) up to normal ranges during whole TCZ course. Number of active joints decreased gradually (p = 0,00002), reached the median = 0 to 24 th month, 15.3% obtained inactive disease status in 6 months and 80% in 42 months. During the study inactive disease status was reached totally in 60.5% patients and in 3 patients TCZ was discontinued due to persistent remission. The main predictors of achievement inactive disease were WBC < 9.0 x 10 9 /l (HR = 1,92, p = 0.16), absence of previous biologic treatment (HR = 1.92, p = 0.16). The absence of previous biologic treatment was also predictor of low disease activity status (HR = 2.4, p = 0.01). Among adverse effects were transient hypercholesterolemia and hypertriglyceridemia and single episode of grade II neutropenia which not lead to TCZ discontinuation infection side effects and antibiotic treatment. Introduction: Juvenile arthritis is a broad term that describes heterogeneous group of a chronic inflammatory joint disease which characterized by progressive course leading reduced mobility and function. Progressive chronic arthritis of an unknown cause lasting for at least more than three months are the main diagnostic criteria of JIA. A typical classic variant of oligoarticular JIA (oligo-JIA) is well known. Monoarthritis of the elbow joint is atypical onset oligo-JIA. It's difficult to differentiate of elbow chronic synovitis due to clinically heterogeneous. The instrumental and specific diagnostic tests are great assistance to determine cause of synovitis.
Objectives: Chronic synovitis in children arises from several causes. There are inflammatory, infectious, traumatic, reactive, hemorrhagic, neoplastic and undifferent etiologies of synovial diseases. Usually chronic elbow monoarthritis associated with tumor-like conditions (pigmented villonodular synovitis, synovial haemangioma and chondromatosis), osteomyelitis, tuberculosis arthritis, osteochondropathy and rare JIA. The aim of the present study was to determine diagnostic and treatment strategies of elbow monoarthritis manifested like oligo-JIA. Methods: We carried out a retrospective review of sixteen children with chronic undifferentiated elbow monoarthritis which were hospitalized at Children Orthopedics Institute, Saint-Petersburg (rheumatology department) between 2011 and 2016. The data of clinical, serological, x-ray, ultrasound, MRI, arthroscopy and synovial fluid were analyzed. Detected atypical/diffuse form synovial proliferation or limited to a well-defined single nodule were recommended for arthroscopy and biopsy. Six children were excluded from study due to verification of cause elbow monoarthritis: 6-yr-old girl -PVNS, 10yr-old boy cavernous haemangioma and 17-yr-old boy -synovial chondromatosis, 2 small girls and 1 boy -osteoid osteoma. Ten children were study group (median age 5,8 ± 2,5, range 3-11 years; female 90%, male 10%). Children with post-traumatic elbow joint transient effusion were controls. Results: Trauma of elbow joint related to onset chronic arthritis, progressive flexure contracture with dry synovitis, low activity and the long-term period absence of clinical involvement of other joints were occurred in all children. Asymptomatic early-stage, progressive flexure/combined contracture less joint effusion and morning stiffness were cause of late diagnosis of oligo-JIA. Only seven children (all girls) were ANF positive ≥ 1:160, two HLA-B27 positive. Radiographic finding of early-stage JIA were accelerated cartilage model ossification of distal humeral epiphysis and trochlear, osteoporosis with subchondral bone sclerosis and cyst-like deformation. The MR imaging were non-specific inflamed elbow synovium. Overgrowth of epiphysis and trochlear with joint space narrowing, deformation articular surfaces with erosive changes were radiographic findings of latestage JIA. MR imaging revealed significance multiple erosive synovitis with bone cyst-like deformation. Ultrasound wasn't show elbow synovitis at half of the study children. 70% children were negative effect of monotherapy NSAID. Positive treated effect was achieved after intra-articular triamcinolone injection (20-40 mgs) and methotrexate therapy (15 mg/m 2 /week) > 6 months, splinting and physiotherapy. After 2-3 years 30% children were persistence oligo-JIA (involved wrist or knee), 40% -extended oligo-JIA, 30% -isolated monoarthritis. Children with post-traumatic elbow joint deformation haven't revealed chronic synovitis. Conclusion: Monoarthritis of elbow joint are rare atypical manifestation of pauciarticular JIA. Non-specific clinical signs and instrumental imaging may contribute to diagnostic problems of elbow chronic synovitis. Therapy of elbow chronic idiopathic monoarthritis must be coincide treat-to-target strategy in juvenile arthritis. Ultrasound can't be the decisive diagnostic method of chronic elbow pathology. Objectives: The primary aim is to document demography, disease profile and medical management of patients attending the Tygerberg Paediatric Rheumatology clinic. The secondary aim, based on these findings, will address the need of specialized services and subspecialty training posts.
Methods: Retrospective folder review, electronic data search and use of bivariate and multivariate statistical tools used for analysis to outline the disease profile of JIA (Juvenile Idiopathic Arthritis), other autoimmune (AI) or auto-inflammatory diseases and miscellaneous musculoskeletal conditions and management thereof. Results: 450 patients were reviewed between March 1995 and March 2017. Referrals were derived from secondary and tertiary hospitals (68%), general and private practitioners (13%) and 8.2% by primary healthcare centers. 60% of referred patients resided in the greater Cape Town region and 40% in rural-country regions, depending on availability of public health transportation services. Most of the patients (74%) were from a family income bracket of less than 7700 USD per year. Gender distribution reflected 56% female and 44% male. The most common age of presentation was between 10-14 years (46%) with a range of 0 to19 years. Racial distribution was Mixed Racial 79%, Blacks 16%, Whites 4% and Asians 1%. JIA (38%) was most common rheumatological condition. Reactive Arthritis (23%), autoimmune and autoinflammatory conditions (11%), vasculitides (2%) and miscellaneous musculoskeletal conditions (39%) e.g. growing pains, Raynaud's, infection related arthritis, malignancies etc. comprised the rest. Common presenting symptoms were tender joints (71%), stiffness after rest (46%) and swollen joints (44%). Uveitis was present in 9% at initial diagnosis or during follow up. Delay in diagnosis was up to 9 years. Ibuprofen (42%) was the most commonly used NSAID. Most frequently used DMARD's were methotrexate and hydroxychloroquine. Intra articular steroid injections were frequently indicated and biological therapy accessed by selected patients. Referral to ancillary services included physiotherapy (51.6%), imaging predominantly X-rays (41%), ophthalmology (47.1%), orthopedics (37%), occupational therapy (27%) and dermatology (16.7%). 46.5% were offered social grants. 14.7% recorded, achieved remission. Remission could not be established in most patients due to high rate of patients lost to follow up (50%). 3.5% transitioned to adult Rheumatology services. Conclusion: Patients reviewed were mainly of mixed racial origin from low-income homes. JIA was the most common paediatric rheumatological condition seen. Delay in diagnosis and late referrals were frequent. Increased awareness, education and training, early diagnosis of disease and appropriate funding for these neglected diseases could dramatically improve outcome. Addressing challenges unique to a developing country and resultant complexities of management are essential for advocacy and planning of such services. Objectives: Long-term assessment of recurrent unilateral perichondritis in patients with systemic diseases, for the development of RP diagnostic criteria. Methods: We retrospectively identified the cases of unilateral recurrent ear perichondritis in the patients with suspected polychondritis in the last 15 years in a tertiary referral adult Rheumatology department. The patients then fulfilled a questionnaire and were seen prospectively for two years. All chondritis episodes and the Mc Adam and Damiani-Levine polychondritis criteria were assessed. Laboratory tests for inflammation, immunology, uric acid, ENT examination, cartilage biopsy whenever accepted and an extensive search for infection,vasculitis, hematologic malignancies, as well as complications of other organs classically involved by polychondritis were recorded, as part of the regular screening for polychondritis. Results: We identified 3 cases of recurrent unilateral chondritis, all occuring in spondylarthritis patients, that were followed up for 3 to 12 years for other polychondritis features, without development of RP criteria. None of these patients developed ulcerations or crusting to suggest Winkler's disease, either. Case 1: A 26-years female patient with a juvenile extensive oligoarthritis since the age of 5 and psoriasis since 11, on methotrexate, presented with recurrent episodes of right ear swelling and inflammation, healing within three days, not altered by empiric antibiotic short courses, accompanied by transient mild leukocytosis with neutrophilia. An active follow-up for 12 years did not reveal other chondritis sites. NSAIDs helped to alleviate the attacks, which became less frequent with time. Case 2: A 48-year male patient with aseptic abscesses syndromes, Crohn's disease and spondylarthritis with bilateral coxitis diagnosed for 3 years had a recurrent left ear upper lobe inflammation since the first visit. The nodular chondritis, with low-level local inflammation generally lasting for one week, independent from the joint flares, responded to the addition of NSAID and sulfasalazine to adalimumab and azathioprine. No progression to polychondritis was noted in 3 years. Case 3: A patient with undifferentiated spondylarthritis and a history of treated medullar thyroid carcinoma presented with recurrent right ear painful inflammation. No signs of tumoral dissemination or relapse were detected in 6 years. The cartilage biopsy was normal. The attacks' frequency decreased after leflunomide. Conclusion: Unilateral recurrent ear perichondritis may not always herald polychondritis, at least in spondylarthritides. It can be speculated that local triggers (pressure on the ear, etc) may activate the innate immunity through danger-associated molecular patterns, however, the progression to polychondritis probably requires activation of certain Toll-like receptors. An active search for an RP is nevertheless worthed in the unilateral chondritis, as RP requires a more aggressive therapy. Informed consent to publish has been obtained from the patient/parent/guardian.
Objectives: It was aimed to evaluate the dental and temporomandibular status in children with GJH. Methods: Sixty two children with GJH and age-sex match sixty two healthy children as a control group were enrolled to the study. The GJH was assessed by the Beighton Hypermobility Score (BHS). The subjects screened for dental and TMJ status. Assesment included index for 'Decayed' , 'Missing' and 'Filled Teeth' (DMFT), visual plaque index (VPI) and gingival bleeding index (GBI) scores, tooth mobility and TMJ evaluation. The Mann-Whitney U and chi-square tests were used to evaluate the data. Results: Mean BHS score was found 6.3 ± 1.2 in GJH group. VPI and GBI scores were found significantly higher in children with GJH then control group (p < 0.05). No differences were found regarding the DMFT scores between GJH and control groups (p > 0.05). Temporomandibular disease (TMD) frequency was significantly higher in children with GJH compared to the control group (p < 0.001) ( Introduction: IgG4-related disease (IgG4-RD) is relatively a new growing entity of immune mediated origin, characterized by a unique pathological feature that affect a wide variety of organs with infiltration of IgG4-positive plasma cells and occasionally elevated serum IgG4. It is both a systemic inflammation and a sclerosing disease. The most common manifestations are parotid (14-26%) and lacrimal swelling (4-13%), lymphadenopathy and autoimmune pancreatitis. Several studies have examined orbital adnexal IgG4-related disease or IgG4-related orbital inflammation. The diagnosis should be proven histopathologically but other conditions such as lymphoma should be carefully excluded. Patients with IgG4-RD respond beneficially to glucocorticoid therapy especially when administered at early onset stages. In some cases, the combination of immunosuppressive agents is required.
Objectives: To describe a pediatric clinical case with orbital IgG4 related disease with an excellent response after immunosuppresive treatment.
Methods: We present a 16-year-old girl with IgG4-RD during one year with left ocular pain and eye inflammation, diagnosed as bacterial conjunctivitis and trated with ophtlamic antibioticoteraphy, with no improvement. Weight loss and increased acute phase reactants (erythrocyte sedimentation rate and C-reactive protein). On ocular computed tomography. Histopathology clearly defined the mass to be IgG4 related fibrosis with focally arranged fibrosis in a storiform pattern, and positive CD20 deposit ++++, positive IgG4 +++ in plasmatic cells and lymphocytes, positive CD38 deposit ++. Biopsy report: Autoimmune Dacryoadenitis Associated with IgG4 Disease. IgG4 serum normal level 9 mg/dl. Ocular Magnetic resonance imaging was performed in which volume and lacrimal gland intensity is identified, which displaces the rectus and oblique muscle causing proptosis, the lacrimal gland presented an increase in it's dimensions with measures of 23x8x10mm in its posterior axes, posterior No abnormal reinforcement is identified in the contrast medium. Infectious serological test were negative (EBV, CMV, HBV, HCV, toxocara and toxoplasma).
Results: The patient was started on oral corticosteroids and mycophenolate mofetil, which resulted in significant clinical improvement after 3 months of treatment, the mass became smaller and the patient was asymptomatic.
Conclusion: IgG4-RD remains a field not yet fully explored or understood. Early and efficient therapies aiming to achieve a beneficial outcome, and to improve prognosis are still required.  Introduction: Acid ceramidase deficiency (Farber disease; Farber lipogranulomatosis) is caused by mutations in both alleles of the ASAH1 gene, resulting in deficiency of acid ceramidase and accumulation of the pro-apoptotic and pro-inflammatory sphingolipid, ceramide. It is considered an ultra-rare disease, with only 109 cases reported in the medical literature since 1952. However, since 2014, we have identified a cohort of 45 patients (some of whom are since deceased) from 30 countries on 6 continents, which indicates a much broader phenotypic spectrum and potentially higher incidence than previously thought. The information collected from this cohort demonstrates that there are patients diagnosed in late adulthood with attenuated forms, as well as patients for whom years elapse between the appearance of the three typical Farber symptoms: joint disease (arthritis and/or contractures), subcutaneous nodules, and hoarseness (due to laryngeal involvement). Moreover, there is wide intra-and inter-patient variability of symptom severity.
Objectives: To develop a natural history study structure and design that would enable systematic collection of information on deceased patients using medical records, as well as on living patients who have or have not undergone hematopoietic stem cell transplantation (HSCT). In addition, the study will evaluate clinical assessment tools used for other diseases with similar symptoms, as well as those developed specifically for Farber disease. Methods: We designed a cross-sectional cohort study with a unique data collection instrument, including sections for the collection of retrospective data on disease-specific and general medical history, as well as data from clinical assessments to be performed at prospective visits.
Results: The pre-existing clinical assessment tools include (among others) the Childhood Health Assessment Questionnaire (CHAQ), and Wong-Baker Faces Pain Rating Scale, 6-minute Walk Test, Pulmonary Function Testing, and Joint Range of Motion measurements. We also developed a unique patient reported outcome measure related to Farber disease symptoms including physical impairment, pain, and emotional distress, and a method for the assessment of change in size of subcutaneous nodules. Conclusion: Consideration of the broad spectrum of ages and heterogeneous phenotypes in a small population of patients available to participate in a study of the natural history of acid ceramidase deficiency led to the design of a cross-sectional cohort study with retrospective and prospective components. By including deceased patients and patients having undergone HSCT in the study design, the amount of data that can contribute to the understanding of this very rare disease is substantially increased. Furthermore, the specific prospective assessments will allow us to follow disease progression over time, and to evaluate the degree to which the assessment tools and techniques may be appropriate measures to use to register change in certain symptoms. It is our hope that this unique design will provide data which is sufficiently robust to serve as the basis for preventing misdiagnosis of acid ceramidase deficiency as JIA, provide an indication of the most appropriate methods for measuring efficacy in future therapeutic trials, and serve as a potential point of reference in the design of similar studies in rare disease populations. Results: Activities of PPC representatives include attendance several face-to-face and teleconference meetings each year. This is an essential activity that enables researchers and healthcare professionals to actively interact with PPCs as equal partners, in order to shape ongoing and future research activities. This approach also emphasises the importance of physical meetings in fostering collaborative and participatory approaches to research. In addition, PPC represenatives bridge the gap between the research community, patient groups and charities, facilitating communication between individuals and teams.
Conclusion: By widely accepting and embracing the PPC voice as a catalyst for high quality, young person-and family-focused research, it is hoped that the often negative experiences of living with an RMD can be used positively to shape research, so as to be able to provide the best possible care, treatment and support for young people and their families living with RMDs in the future. Results: Eight interviews were conducted with 4 caregivers and 4 patients. Included were: 2 adult patients (attenuated phenotype); 1 caregiver of deceased child (severe phenotype); 1 transplanted adult patient (moderate phenotype); 1 caregiver of transplanted pediatric patient (moderate phenotype); 1 caregiver of a pediatric patient (moderate phenotype); and 1 caregiver/patient dyad of a nontransplanted pediatric patient (moderate phenotype). Interviews revealed the symptoms of acid ceramidase deficiency have measurable clinical impact across a broad spectrum of phenotypes and symptom severity. In general, all participants found the questionnaires and assessments relevant to their condition. Feedback was provided by the participants to improve the formulation and scope of questions. With regard to the relative impact of symptoms, the ability to move joints had an average impact rating of 6.6 (range 1 to 10), followed by ability to perform daily activities and subcutaneous nodules with 5.9 (range 1 to 10 for daily activities and 3 to 9 for nodules), voice impact was rated 5 (range of 3 to 9). The remaining symptoms (arthritis, overall pain, level of tiredness, and other symptoms) all yielded lower levels of impact. In the cases where the SF-36 and CHAQ were completed, scores demonstrated significant impact and disability in the population of patients with acid ceramidase deficiency. Conclusion: In spite of the small number of participants, the information gathered provides a better understanding of methods useful for measuring symptom impact, potentially in the context of future therapeutic trials, and may allow better discussion of symptom impact between physicians, patients and caregivers. This type of qualitative study can be particularly useful in rare disease populations, and may also help interpret the utility of both new and established patient reported outcomes in cases when the size and variability of the available population prohibits traditional methods of validation.  Introduction: RAiISE is a user-led research project inspired by the negative experiences that young people face while studying and living with an invisible illness. Many young people who live with chronic illnesses look no different to their healthy peers. The invisible nature of some illnesses can often lead to an invisible struggle, leading to misunderstandings, particularly in the case of young people. It can be a huge burden on the chronically ill to make the invisible, visible to others. Objectives: The main objective of RAiISE is to improve the standard of care given to young people with invisible illnesses in school, college and university and to create a resource to teach education professionals a series of strategies and techniques to support their students. RAiISE will also offer support to young people with invisible illnesses and aim to empower them to take control of their own health.

Disclosure of Interest: None Declared
Methods: A young patient of Alder Hey NHS Children's Foundation Trust decided to raise awareness of living with an invisible illness. A network of young people, parents, education and health professionals was created and a series of workshop and focus groups allowed each stakeholder to share their experiences and expertise as they inspired and advised the production of the RAiISE information pack. It is important that young people are able to shape research based on their lived experiences. Several international charities and organisations have offered support and knowledge in advising the process.
Results: At early workshop meetings, young people with invisible illnesses and their parents were able to offer personal accounts and experiences which highlighted that the most common themes were problems with communication and trust, as well as difficulty in understanding the erratic nature of many chronic illnesses. From this research, a draft information pack was written by the RAiISE committee, which was later presented to young people, parents, health and education professionals and charity representatives. All stakeholders were able to offer their expertise from their respective fields. Feedback was overwhelmingly positive and any adjustments are to be made in the coming weeks. The final pack will be completed and ready for distribution by the end of summer 2017. Conclusion: The project has been a successful example of young patient led research and highlights the importance of self-management in young people living with invisible chronic illnesses. The collaboration between young people, parents, and education and health professionals has highlighted the necessity for cooperation between all stakeholders for the benefit of the young person. The project comes from a long journey undertaken by our association in order to be closer to people affected by chronic pathologies during their daily lives, defining strategies of inclusion in order to create an understanding atmosphere about Rheumatic Pathologies, who unfortunately are still not very well known nowadays. Some of these pathologies are diagnosed at a later stage, resulting in a late treatment and in some cases in a great degrade in selfsufficiency.
Objectives: The aim of our project is to offer support for families and develop empowerment over chronic and rare Rheumatic Pathologies in children; giving easier access to information, promoting actions in order to offer an early diagnosis, helping families face the new challenges they will be inevitably exposed to Methods The method is to create a partecipative process by involving all possible factors in an active process regarding chronic and rare rheumatic pathologies in children. We have involved, over the course of the years and through the help of educational and informational workshops, various family members, journalists and paediatricians. Results: We have therefore been able to build a social window, in collaboration with professional staff, that works overall to make the journey that these families will have to face easier. With the use of this social window, the family nucleus can find information as well as a place to be heard and guided. Moreover, available to them is also a psychotherapist psychologist, both over the phone or in the form of a private meeting. The clinical instrument used here is the meeting with our staff (both hearing and empathy), and with the use of monitoring sheets, drawings and illustrations according to the age of the child. At the end of this formative journey, the family will be asked to fill out a survey in order to rate our project. Our social window is also available online in the form of a blog. Other communication and participation activities take place in local doctor's surgeries, schools, and with the collaboration of Rheumatology Paediatricians. We have also developed a comic, 'A new challenge together' , in order to inform young adults and children on these issues.

Conclusion:
The presence of a Rheumatic Pathology can result in heavy effect on the life of a child and its family. These impacts vary depending on the resources that they might have available. May these be 'external' (financial and economical, available treatments, network support) or 'internal' (the possession of medical and bureaucratic information useful to the management of the problem, the relationship between the members of each family and their degree of flexibility).
Our project, 'A Smiling Childhood' has kept many families informed, emotionally supported and aware of their internal resources. The most frequent type of JIA was polyarticular and enthesitisrelated arthritis (64%), followed by systemic (16%), oligoarticular (16%) and psoriatic arthritis (5%). In terms of anxiety, 46% of parents reported having moderate anxiety. Similar results related to stress were observed. Mild depression symptoms were found in 18% of parents and moderate in 9%. Severe and moderate familiar dysfunctionality were reported by the parents in 14% and 36%, respectively. There was not association of familiar dysfunctionality and the number of years living with the disease. However, those parents of children with more than two years of disease present an increase in moderate symptoms of depression. Perception of uncertainty was moderate with mean score of PPUS of 83.85 (SD 15.66). Parents of children with recent diagnosis(less than 2 years) presented higher scores than parents of children which had been diagnosed longer than two years (mean score 88.5 (SD 8.70) vs 80.75 (SD 18.68), respectively). Among parents with higher PPUS score: 89% reported severe or moderate anxiety, 66% reported moderate symptoms of depression, and 44% informed moderate or severe familiar dysfunctionality.
Being optimistic, learning about the diseases and treatment, and interactions with their ill child were the most frequent coping strategies used by the parents. However, parents of children with recent diagnosis are more optimistic and interact more with their ill child compared with parents of children which had been diagnosed longer than two years.
Conclusion: This study shows that anxiety and stress in parents of children with JIA is present frequently. Perception of uncertainty, anxiety, and familiar dysfunctionality were observed more frequent and severe in parents of children with recent diagnosis(less than two years). Considering the limitations of the study, in order to alleviate anxiety and depression symptoms on parents, and prevent family dysfunctionality, psychological intervention and participation in group support are recommended strategies for parents of children with recent JIA diagnosis.

P117
Rehabilitation games for juvenile idiopathic arthritis. Focus on hand and wrist. 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. Physiotherapy and occupational therapy, with the aim to keep or restore joint function and to achieve a normal pattern of mobility, are important components of the therapeutic approach. In standard physical therapy patients tend to lose interest in the treatment, due to the monotony of the exercises, and as a consequence, patients either perform their exercises irregularly or quit the physical therapy. In recent years, the introduction of new gaming input devices, such as Nintendo's Wii Remote™ and Microsoft's Kinect, and the development of games that involve physical activity, induced the researchers to consider the possibility of using videogames to perform physical therapy. Objectives: To design a set of rehabilitation games that could help patients affected with Juvenile Idiopathic Arthritis performing their physical therapy. Methods: A multidisciplinary study group involving paediatric rheumatologists, physiotherapists and engineers of the Department of Electronics, Information and Bioengineering of the Politecnico of Milan was created. During the first meeting, the rheumatologists explained the basic aspects of disease and the principal physical problem observed in patients with JIA; the therapists introduced how the physical therapy for JIA works. In order to improve the final outcome, engineers used an iterative design approach, that is, they designed the games, and then they followed a cyclic process of prototyping, testing and analyzing designs.
The key points on which engineers focused were: the ability of the game to adapt to the capabilities of the patient, the possibility for the therapists to create custom game levels, the need to save every information about how the patient performs during the exercises and the possibility to see again the exercise carried out by the patient. For this study, the attention was focused on hand and wrist. Four different games to play were developed. For each game was defined a rewarding system that increases the score when the player does something good, but does not decrease it when he/she makes a mistake. The scoring system was also a useful first qualitative feedback for the therapist about the patient's performance. The therapists were asked to create a custom level for the flight simulator game, so she could simulate an exercise performed in a typical training session. Results: Three poliarticular JIA patients took part to the first experimental session. Ten, fifteen and twenty-one years old respectively. The first patient had ankle involvement, while the last two had wrist and small joints of the hand involvement.
Two games were tested on the 3 patients; a flight simulator and a Flappy Bird-like game. The flight simulator, in particular, was tested both with the hands and with the feet. The feedback from the subjects was quite good; The therapists' feedbacks were also good. The patients enjoyed the exercises much more and "it did not look like they were doing exercises". The subjects were doing without complaint the same exercises that they found to be boring and difficult during standard physical therapy. Conclusion: The feedbacks received during the experimental sessions validated the work. The patients liked the games and suggested some additional changes to make them more appealing. The therapists also were satisfied with the study design. They were glad to see how easily the patients performed their exercises by playing the games. In future work it should be possible t dynamically adapt the difficulty during the game in relation to the patients' performances. It would be consider also the possibility to use a webcam to see live the patients while they are playing and to record the patient's performance, giving the therapist a second visual feedback in addition to the replay. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and a cause of short-term and long-term disability. Physiotherapy is an important component of the therapeutic approach. The rehabilitation process is developed through a series of simple, repetitive exercises to be performed frequently and for a long time. Often patients lose interest and stop performing them before the results have been accomplished. Recently a new frontier in the design of videogames has been explored: the games for rehabilitation. The development of this research field has been limited by the cost, technical limitations and technical expertise needed to use the products and the sensors needed. The introduction of new gaming input devices and the development of games that involve physical activity, induced the researchers to consider the possibility of using videogames to perform physical therapy. Objectives: To design a set of rehabilitation games for children with JIA, that would be considered amusing by the largest part of players, while helping them in performing their rehabilitation exercises for the mobility of knee and ankle. Methods: The project was conducted in collaboration between pediatric rheumatologists, physiotherapists and engineers researchers of the Politecnico of Milan. The specific rehabilitation principles were applied to the ones of the common game design, to obtain games both medical relevant and fun to play. The iterative design approach, a methodology based on a cyclic process of prototyping, testing, analysing, and refining of the games was applied by the researchers. Four different games were designed, one for the ankle, three for the knee. The third and the fourth games were redesigned to perform two types of exercises. The first exercise prescribe the use of a wobble board, a board mainly used to perform equilibrium exercises. During the exercise the patient had to tilt on all four different directions the board by performing the deflection of the extension of the ankles, if the patient is seated on a chair, or by changing the position of the whole body. The second exercise prescribed to perform the extension-deflection movement of the knee while the patient was seated from the rest position to the maximum angle reachable by the patient. For each of this games the therapist could completely personalize the parameters of the game in order to personalize the experience of the patient and make it suitable for his/her clinical condition. Experimental sessions were performed to validate the result of the system. The interaction of the patient with the games were tested, and it was verified how they react to the different type of experience. Results Tuning session. Tuning session was completed by testing the games with 2 JIA patients, 15 and 12 years of age respectively, with predominant involvement of ankles (patient 1) and ankles and right knee (patient 2). Therapeutic sessions. Two therapeutic sessions were performed on 4 (3 female and 1 male) and 3 (female) patients respectively. Median age 7 years (5-15 years) Feedbacks received from patients and therapists were good, and all the patients completed easily their sessions. Conclusion: Four rehabilitation games for the mobility of knee and ankle were developed. The feedbacks received from the patients and therapists were very good. The rehabilitative sessions were easily controlled, the patients enjoied the sessions and the therapists appreciated also the possibility to monitor the patient even in remote.

Disclosure of Interest: None Declared
Introduction: Requests of rheumatologic visits for lims arthralgia are more frequent in these last years, expecially in adolescents. Functional Pain (without demonstrable organic cause), is often associated with psychological problems. Objectives: to differentiate organic articular pain from functional pain; to evaluate the real incidence of functional pain in healthy school students; to investigate the correlation between functional pain and psychological disagreement, in a series of school students. Methods: A questionnaire was given to a group of students of primary school; the following data were collected: a) sex, age; b) functional pain; c) relation with relatives, teachers and schoolfellows; d) failure in school-studies. Results: 809 students, 354 females, 455 males, median age 14 years, participated to the study. Functional Pain was referred from 537/809 students: 265 Females, 272 males: p = 0,155. Pain episodes showed a different incidence between females and males (p = 0,511). Pain intensity vs. number of episodes in females showed a statistically significant correlation (p = -0,001). Most frequently abdominal pain was recorded in females and limbs pain was selectively described in males. Psychological disagreement was referred from 513/809 students: 260 females, 253 males (p = 0,150). Psychological disagreement was reported with: parents in 15; with siblings in 59; with other relatives in 45; with teachers in 42, with schoolfellows in 356. The correlation disagreement vs. functional pain in all the students included in the study was statistically significant (p < 0,001).
Introduction: Juvenile Idiopathic Arthritis (JIA) is the more frequent rheumatologic disease in paediatric age with a possible worsening on posture in a vulnerable period of life. This condition can show a negative impact on balance and on activities of daily life. Objectives: The aim of the study is to evaluate the efficacy of regular physical activity on posture and balance deficit in children and adolescents affected by JIA. Methods: We enrolled 56 patients (17 patients affected by JIA: JIA group; and 39 healthy control subjects, of comparable age: CG). Furthermore, JIA group was stratiphied in two subgroups: inactive (AIG-SED) and active (AIG-ACT). All the patients were tested by a computerized analysis of posturography, by a new-generation stabilometric platform (Sensor Medica; Guidonia Montecelio, Roma). Results: The group AIG-SED showed statistically significant differences vs. the group CG on the following indexes: ellipse surface (p < 0,05), ball length (p < 0,0001) e Y mean (p < 0,05). At the opposite, no statistically significant difference was relieved between the AIG-ACT and the CG, with the exception of the ball length (p < 0,05), which is reduced respect the CG. Conclusion: This pilot study confirms the relieve of regular physical activity on the motor deficit, on balance and posture secondary to JIA, especially in evolutive age. Disclosure of Interest: None Declared Introduction: Children's experience of moving from children's hospital department to adult department in hospital care are often related to increased stress and anxiety. The transition period could also be very demanding for the parents. Studies show that preparing the children from early age could prevent most of the stress and anxiety. By starting the transition process several years before the child's move to adult care we presume the parents gets educated and supported for letting their child take more responsibility for its own illness. At the pediatric reumatology department, Astrid Lindgrens Childrens hospital we are working with a transition program inspired by Janet McDonagh. The program consists three meetings with the rheumatology nurse.
Objectives: To prepare and facilitate the child and its parents for the child's transition to adult care. Methods: The children and their parents are called to three meetings over a period of 5 years. The first meeting are placed when the child is 14 years old. Before the meeting the child and its parents filled in different transition formula. To evaluate the child's knowledge about its disease and treatment we used the questionnaire MEPS abbreviation for medical issues, exercise, pain and social support. Results: To evaluate if the child and its parents found it valuable to participate in the transition program, we did a pilot study. After the visit to the nurse the child got a evaluation formula. The results showed that 86% of the participants should totally recommend this to other children with rheumatic disease and the remaining 14% recommended it. Neither of the children found it embarrassing or hard to fulfilled the transition formula. Conclusion: Both the children and their parents found the first transition meeting with the nurse very educational and valuable. The meeting with the nurse seems to facilitate the transition process for the child and its parents. By offering a structured transition program to the children and their parents the fear of moving to adult care can be reduced. Introduction: Transition for patients with chronic diseases is defined as the purposeful, planned movement of adolescents and young adults from child-centered to adult oriented health care system. 1 Rheumatic diseases of childhood extend to adulthood as active diseases in 30-70%, which is the reason for requiring rheumatologic care into adulthood. First coordinated transition of pediatric rheumatologic patients in Croatia was organized in 2012 as developmental type of transition, where patient is gradually prepared for the transition by a pediatrician rheumatologist throughout years preceding transfer. The moment of final transfer to adult care is organized in the pediatric rheumatology clinic, where patients and their parents are meeting adult rheumatologist in known environment (pediatric rheumatology ambulance). At the transfer, patient's history is being presented to the adult rheumatologist and afterwards patient is examined by both of the specialists. At the end of the examination, patient is given next checkup date at adult rheumatologist clinic, where the patient will continue with regular follow up visits. Objectives: Our objective is to verify successfulness of organized transition of pediatric rheumatologic patients to adult care. Introduction: According to the Referral Center's policy regarding the patients' psychomotor rehabilitation, a summer camp program is annually offered to children with Chronic Rheumatic Diseases (CRD) in clinical remission and ability for self-care.They attend a sport camp addressed to healthy children, where the CRD group participates in various camp activities (handicrafts, arts, games, sports and swimming), accompanied by a specialized physiotherapist and a pediatric rheumatologist. During their 2-week camp life, they additionally receive education and practice on maintaining group and personalized physiotherapy. Objectives: To evaluate the psychomotor impact of organized summer rehabilitation program on children with CRD, in a setting away from the caregiver protection, for 5 consecutive years. Methods: A 28-item questionnaire was created pertaining 5 domains: physical activity, self-care, pain, socialization and psychology and a score range 1-4 (4 the best). The questionnaire was annually completed by the children after the end of the camp and the responses were evaluated in respect to the participants' age and their experience in the camp setting. Results: Replies of 69 campers with a mean age of 11 yrs were analyzed. A mean total score of 54/65 was found, which was positively correlated with the participants age (p < 0.001). Campers with no previous experience had a significantly median lower score (48), after age adjustment (p = 0.05). The domains of physical activity and psychology had the worst scores for the naive campers (p = 0.018, and p = 0.027, respectively). Socialization was positively correlated with age (p = 0.008) and especially among the naïve young participants (p = 0.005). There was no correlation between pain and activities' restriction. Home sickness regarding either the family, or peers or TV watching was reported by 82%, 74% and 37.5%, respectively. Noteworthy, 88% expressed the desire to become future camp teamleaders. Conclusion: These findings indicate that the aforementioned kind of camp life offering a rehabilitation program for children with CRD has a beneficial impact on their quality of life. The valuable effect was found to be correlated with the campers' age and was more prominent, in those with the least experience. The reported home sickness by the majority of children did not affect their active participation in the program. Moreover, they expressed the wish to gain more camp experiences and take future camp responsibilities as leaders. Methods: A retrospective study of patients with jSLE (age of onset: 0-18y) and aSLE (age of onset: >18y) seen in our center during the period 1988-2016 was performed. Case definitions of the American College of Rheumatology were used to identify NPSLE manifestations. Demographics, clinical and serological data were obtained through a review of their medical records.

Disclosure of Interest: None Declared
Results: A total of 69 patients with NPSLE were included, aSLE 41 (59%) and jSLE 28 (41%), the comparison of groups is presented in the table. Most of them were Caucasian (92%), mean age at diagnosis in adults was 36.4 years (range: 19-68) and 13.9 years (range: 8-18) in children. The proportion of males was higher in the latter group. The mean duration of the disease was significantly greater in adults, as well as the time from SLE diagnosis to NP manifestation onset, although without significant difference. Central NP manifestations were the most frequent in both groups (aSLE 93%, jSLE 96%) regarding to the peripheral manifestations (aSLE 12%, jSLE 11%). The most frequent manifestations in aSLE were headache (29%), cerebrovascular disease (27%), seizures (17%) and myelopathy (15%), whereas in jSLE were seizures (46%), headache (29%), mood disorder/depression (25%), psychosis (18%) and autonomic disorders (18%). A significant group of patients presented ≥ 2 central manifestation during their evolution (aSLE 32%, jSLE 41%), with the mean number of manifestations in adults being 1.36 (range: 1-3) and in children 1.44 (range: 1-4). Patients with jSLE developed lupus nephritis with a significantly higher frequency, as well as higher titres of anti-DNA antibodies, erythrocyte sedimentation rate (ESR) and hypocomplementemia. During the study period there was mortality in 2 cases of aSLE and 2 jSLE (5% and 7%, respectively). Conclusion: Our results corroborate that juvenile patients with NPSLE present higher disease activity compared to adults. There was no significant diference in the time from SLE diagnosis to NP manifestation onset, but tended to be shorter in jSLE. The spectrum of NPSLE was varied both groups and an important proportion of them developed ≥ 2 manifestation. Mortality continues to be important in NPSLE in both age groups.   treatment with immunomodulating agents. Demographic, clinical and laboratory data as well as data regarding immunization status, vaccine history and mean time between the doses of the vaccine were collected. Seroprotection rates and rubella-IgG titers were measured at enrollment and at specific intervals afterwards(0,12,36 months). Total IgG levels were measured simultaneously. Rubella-IgG antibodies were assessed by ELISA. The cutoff value for seroprotection was deemed at 200mIU/ml. The Hospital's Research and Ethics' Committee approved the study; written informed consent was obtained. Statistical significance was set at p < 0.05 and analyses were conducted using SPSS.
Results: The two groups had similar demographic characteristics, vaccination history and immunization status. No significant differences were detected in terms of vaccine type, time interval between the two groups as well as mean time from last vaccination to blood sampling. Seroprotection rates were adequate for both groups. Nonetheless, the jSLE group had consistently inferior (but not statistically meaningful) seroprotection rates at all time-points. Mean rubella-IgG antibodies were significantly lower in the jSLE compared to the control group(p < 0.01). Similar results were found at one and three years' follow up (Table 37). None of the participants had hypogammaglobulinaemia at the time of blood sampling. During the follow up period, the jSLE group had greater decrease in antibody levels as indicated from the significant interaction effect of analysis. There was no association detected between the degree of antibody loss and type of jSLE treatment received or jSLE disease activity.
Conclusion: Although seroprotection rates were similar between the two groups, mean rubella-IgG titers were significantly lower in the jSLE group at all time-points. Further studies are required to address the question of long-term immunity conveyed by immunizations given at an early stage in children with rheumatic diseases. However, evaluation of immunization status against all vaccine preventable diseases in such patients may be beneficiary.  Introduction: Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder characterized by immune cell dysregulation, chronic inflammation and increased cardiovascular risk. Disease onset dominates mid-puberty and the female to male ratio is 4.5:1, suggesting a hormonal importance in disease pathogenesis. JSLE patients have more aggressive disease, more major organ involvement and increased standardised mortality ratios compared to patients with adult-onset SLE yet research into JSLE is uncommon. Our previous findings show that defects in immune cell lipid metabolism contribute to disease pathogenesis in adult-onset SLE. However, in JSLE little is known about the immune profile or whether abnormal lipid metabolism also contributes to pathogenesis. Objectives: Since altered metabolism plays a role in adult-onset SLE our objective was to explore this in JSLE through in depth immune and metabolic phenotyping of a cohort of JSLE patients and age and gender matched healthy donors (HCs). Methods: Flow cytometry was carried out using two 15-colour panels to immune-phenotype peripheral blood mononuclear cells from 39 healthy donors (HCs, 17 male, 22 female, mean age 18) and 35 JSLE patients (12 male, 23 female, mean age 19). Data was analysed by cluster and phenotype-phenotype correlation. Flow cytometry was also used to measure functional and metabolic marker expression on immune cell subsets. Data was correlated with clinical assessments of disease. Results: Patients with JSLE were characterised by increased naïve and decreased memory B-cell and T-cell subsets and increased monocyte frequency (p = 0.0013) compared to HCs. Furthermore, phenotype-phenotype correlation analysis identified differential associations between naïve and memory immune cell subtypes when comparing the HC and JSLE cohorts. CD4 + and CD8 + T-cells from JSLE patients had elevated membrane lipid raft (p = 0.0185, p = 0.0087) and glucose transport receptor (GLUT-1) (p = 0.0205, p = 0.0017) expression suggesting that they were more metabolically active. Metabolic defects were also found in monocytes and plasmacytoid dendritic cells. The expression of these metabolic markers on different subsets correlated with cell frequency suggesting a role of cell metabolism in driving the JSLE phenotype. Furthermore the metabolic immune-phenotype in JSLE correlated positively with disease activity, erythrocyte sedimentation rate and dsDNA titre and negatively with complement protein C3 supporting the hypothesis that altered metabolism is associated with JSLE development and severity. Unsupervised hierarchical cluster analysis of patient clinical data revealed that JSLE patients in this cohort could be stratified into 5 groups each with a unique clinical identity mainly associated with disease activity markers and the presence of anti-cardiolipin antibodies. Each group had a unique immune-phenotype and metabolic profile. Conclusion: Differences in the metabolic profiles of immune cell subsets in JSLE contribute to disease pathogenesis and severity. Cellular metabolic regulators may therefore have therapeutic benefit for JSLE patients. Defining these patient groups further may help to determine the therapeutic benefit of these and other therapeutics and allow for the treatment patients in a more effective and personalised manner. Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease and various infections play significant roles in flares of this chronic remitting-relapsing disease. Hepatitis A virus is one of these infectious agents that has high endemicity particularly in developing countries and countries with poor sanitary conditions. Hence, immunization via vaccination against this infectious agent would provide a better management of the disease. However, both immunosuppressive drugs and the disease itself are believed to impair the normal functioning of immune system. Little is known regarding the safety and immunogenicity of vaccinations in SLE patients. Moreover, to the best of our knowledge safety and efficacy of hepatitis A vaccination were not studied in children with SLE.
Objectives: In the present study, we aimed to compare the antibody titers and seropositivity in juvenile SLE and healthy subjects after hepatitis A vaccination. Besides, we examined the effect of immunosuppressive drugs and disease activity on antibody responses. Methods: Sixty-nine juvenile SLE patients were enrolled in the study. Initially, we evaluated anti-HAV IgM and anti-HAV IgG titers in juvenile SLE patients. Of the 69 subjects, 37 patients were seronegative and eligible for hepatitis A vaccination. However, 7 juvenile SLE patients refused to participate to the study. Finally, anti-HAV Ig G negative 30 patients and 39 healthy subjects were vaccinated with two doses of hepatitis A vaccine (at 0 months and at sixth months). After vaccinations, anti-HAV Ig G titers were measured and compared between two groups. Results: Anti-HAV Ig G concentrations were measured after vaccination in 30 patients with juvenile SLE and 39 control subjects. Anti-HAV Ig G titer of the juvenile SLE patients was significantly lower than that of the healthy controls (median 4.6 versus 11.9 IU/L, p = 0.02). Although the rate of seropositivity was lower in juvenile SLE patients (n = 24/30, 80%) compared to healthy controls (n = 33/39, 84.6%); this was not statistically significant (p = 0.6). No adverse reaction was reported after vaccination. Conclusion: Although anti-HAV Ig G antibody titers after vaccination have found to be somewhat lower than that of the healthy subjects, significant portion of juvenile SLE patients were seropositive. According to these results, we conclude that hepatitis A vaccine is adequately immunogenic and quite safe in juvenile SLE patients.
Introduction: Capillaroscopy findings can be qualitatively described as: normal, microangiopathy (non-specific abnormalities) or scleroderma pattern. Capillary abnormalities, described in varying prevalence in patients with systemic lupus erythematosus (SLE), are mainly described as microangiopathy with nonspecific capillary morphologic changes Objectives: To describe the capillary morphologic abnormalities in a cross-sectional tertiary cohort of patients with childhood-onset SLE (cSLE) by a detailed quantitative assessment Methods: Nailfold videocapillaroscopy (NVC) was performed in cSLEpatients (onset < 18 years) with a x200 magnification lens (Optilia). All fingers except the thumb were examined with four images per finger. The following capillaroscopic characteristics were evaluated per millimeter: density (compared to mean density known for age, sex and ethnicity), number of abnormal shapes (as defined by the EULAR study group on microcirculation in Rheumatic Diseases), giant capillaries (defined as apical diameter >50 mcm), maximum apical diameter (dilatations defined as apical diameter 20-50mcm) and microbleedings (categorized by large hemorrhages and small multiple point-shaped hemorrhages surrounding the capillary loop) Results: This cohort of cSLE-patients was predominantly female (n = 19/22, 86.4%), with a median age of 14 years at onset of disease. At time of capillaroscopy, the median age was 17 years with a median disease duration of 29.3 months (IQR* 25-75: 12.7-56.5 months). Thirteen patients (59.1%) had an African/Afro-Caribbean ethnic background and seven (31.8%) a Caucasian. Median SLEDAI-score** at diagnosis was 11, and median SLEDAI-score at moment of capillaroscopy was 4. In total, 4607 capillaries from 22 patients were analyzed. By qualitative analysis, 81.8% (n = 18) showed a pattern of microangiopathy. Quantitatively, all of these patients showed a specific combination (observed per finger) of three specific morphological capillary abnormalities: apical dilatations, small point-shaped hemorrhages and abnormal shapes. Looking at frequency and localization of these combined capillary abnormalities, three patients ( Introduction: Induction therapy combined with corticosteroid and immunosuppressant from the acute phase improves long-term outcome in people with systemic lupus erythematosus (SLE). The prognosis of SLE is significantly improved by intravenous cyclophosphamide (IVCY) and mycophenolate mofetil (MMF). According to major guidelines for lupus nephritis (LN), IVCY and MMF are recommended as the first line remission induction therapy for adult proliferative LN (type III or IV), but the use of this strategy in childhood LN is not well established.
Objectives: To investigate if early remission induction therapy using IVCY can improve long-term outcome in childhood proliferative LN (type III or IV), by comparing patients treated with IVCY at onset versus later at disease flare. Methods: Thirty-four children with SLE who were admitted to our institute from April 1997 to April 2016 were enrolled. Diagnosis of SLE was based on 1987 ACR criteria and diagnosis of LN was based on WHO classification or 2003 ISN/RPS classification. Patients were divided into two groups; group A: IVCY was used at the time of onset (n = 22), and group B: IVCY was used at the first recurrence (serological and/or clinical flare of SLE/LN) (n = 12). All patients successfully achieved remission once. We retrospectively evaluated parameters before and after IVCY including renal pathology, period to the first recurrence after IVCY, dose of prednisolone at the last observation, SLE disease activity index (SLEDAI), anti-double-strand DNA antibody (anti-dsDNAab), complement, urinary protein, estimated glomerular filtration rate (eGFR) and immunosuppressant as remission maintenance therapy.
Results: There was no significant difference in patient's characteristics between the two groups. Type IV LN was more common than type III in both groups. The median number of IVCY was 8.5 (6)(7)(8)(9)(10)(11)(12) in group A and 8.5 (6-9) in group B (p = 0.83). Eleven of 22 patients had recurrence in group A (50%) and 8 of 12 patients had recurrence in group B (67%) after IVCY. The median period to the first recurrence after IVCY was 74 months in group A and 47.5 months in group B (p = 0.34, log-rank test). At the last observation, daily dose of prednisolone did not differ between groups A and B (0.100 vs. 0.155 mg/kg, p = 0.15). Additionally, there was no significant difference in titer of anti-dsDNAab, complement, SLEDAI, urinary protein, or eGFR. Regarding remission maintenance therapy after IVCY, 26 patients were treated with MMF (16 group A, 10 group B), and 8 patients were treated with other immunosuppressants such as azathioprine and mizoribine (6 group A, 2 group B). Of note, 12 of 26 patients treated with MMF (46%) and 7 of 8 patients on non-MMF immunosuppressants (88%) experienced recurrence (p = 0.039, log-rank test). Six of 16 patients on MMF in group A and 6 of 10 on MMF in group B experienced recurrence (p = 0.47). There were no deaths during the observation period. Conclusion: In this study, timing of IVCY did not affect either prevention of recurrence or recurrence-free survival. Despite IVCY as induction therapy at onset, half the patients later had recurrence. Surprisingly, choice of MMF as maintenance therapy after IVCY is one factor to achieve longer remission. A recent meta-analysis showed that MMF was the most favorable maintenance therapy for adult SLE/LN 1) . Our results were consistent with this finding and IVCY followed by MMF could be a favorable treatment for childhood proliferative LN. However, to avoid gonadal toxicity and malignancy due to IVCY, remission induction therapy with MMF for childhood proliferative LN should be evaluated by a prospective randomized-control trial in the future.

P137
Sexual differences in TLR7 driven interferon alpha production may explain the increased prevalence of JSLE in females after  Introduction: FMF is a hereditary autoinflammatory periodic fever syndrome that is caused by mutations in the MEFV gene. It is common in Mediterranean countries and the carrier rate in MEFV gene in Turkey is reported to be around 20%. It has also been reported that in many chronic inflammatory diseases, the frequency of MEFV mutations is increased and the course of the disease may be altered.
Objectives: The aim of this study was to assess the frequency of MEFV gene sequence variants in patients with juvenile SLE and compare the clinical features, disease severity and course of the patients with or without MEFV sequence variants. Methods: MEFV gene analysis was studied in 40 jSLE patients that were being followed in 2 pediatric rheumatology centers in Istanbul and Kayseri. None of the patients in the cohort had diagnosis of FMF.
Results: The frequency of MEFV polymorphisms and mutations in juvenile SLE patients was found to be 35% (Table 39). The most common of these was R202Q polymorphism (50%). The significance of the R202Q and E148Q sequence variants is controversial. After the exclusion of these variants, re-analysis revealed that the carrier rate was 12.5%. Age at onset of the disease, duration of the disease, SLICC and SLEDAI scores did not differ between the carrier and non-carrier groups. Hepatic involvement was found to be more frequent in MEFV mutation carriers (p = 0.037). There was no difference regarding fever, hematologic involvement, renal involvement, serositis, neuropsychiatric involvement, mucocutaneous findings, and vascular involvement in between the two groups. Conclusion: In conclusion, we have seen that MEFV carrier rate was high in SLE patients. But we did not observe any differences in both clinical findings and disease damage in SLE patients with MEFV variant carriers except for hepatic involvement.

Disclosure of Interest: None Declared
Introduction: Childhood Systemic Lupus Erythematosus (cSLE) is a multisystemic chronic autoimmune disease characterized by a wide spectrum of clinical manifestations. Renal involvement is one of the most common manifestations of cSLE, reported in 40-80% of patients. Growth failure and delayed puberty are features of cSLE, Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that is more severe in pediatric population than in adults. Biological therapy with anti-CD20 (rituximab) is an option in patient that do not respond to conventional therapy.
Objectives: The aim of this study is to determine the clinical and immunological response in 9 patients with childhood-onset systemic lupus erythematosus (cSLE) that received treatment with rituximab in a third level hospital. Methods: This is a retrospective observational study. 9 patients treated with Rituximab between November 2007 and October 2016 were included and their medical records were reviewed. The response to treatment at 6 months and one year after the first infusion of Rituximab were assessed. Patients with overlap syndromes were excluded. All patients fulfilled four or more of the 1982 revised American College of Rheumatology criteria for the diagnosis of SLE (< 16 years).
Results: Nine pediatric patients with SLE treated with rituximab were included, all of them were female. The age at diagnosis of SLE was a mean of 15,22 years. The mean time duration of disease was 87,55 months (5-255 m). 7 patients were caucasians. Rituximab was indicated in 6 patients with class IV of lupus nephritis (LN) 1/9 with class III LN, 1/9 with severe cutaneous lupus, and with severe hematological manifestations in 1 case (haemolytic anemia). In addition, 6/9 patients had mucocutaneous and articular manifestations. The disease activity of all patients was assessed using SELENA-SLEDAI index pre rituximab infusion, the mean was 17,11 (8-33). All patients had low level of complement C3 and C4 and 8/9 increased anti-DNA. In 8/9 patients Rituximab was used as a rescue treatment and in a single case as a first line. 3/6 patients with renal involvement were previously treated with cyclophosphamide (CF) iv and mycophenolate, 2/6 CF. In case of cutaneous involvement the previous treatment was methotrexate, azathioprine (AZA) and dapsone and in case of hemolytic anemia was AZA.The treatment protocol was 1 gram x 2 (1 cycle) in 7/9 patients, 375 mg/m2x 4 in 1/9 cases and 600 mg monthly for 5 months in the case of hemolytic anemia. Five patients received more than 1 cycle. After the administration of Rituximab, the SELENA-SLEDAI activity index was 4.5 points. At 6 months a complete response was obtained in the case of hematological and cutaneous manifestations, in 2 cases of lupus nephritis (proteinuria <0.5 g/day) and partial response was obtained in 2 cases. Data were not analyzed in 2 patients (death and less than 6 months of the first dose of rituximab). Patients with partial response and lack of response achieved complete response at 12 months. 2/9 patients had side effects (Rituximab pneumonitis in 1 case and infections in 2 cases). Mortality was 11.11% (1/9 patients, per infection and lupus activity, SLEDAI pre rituximab = 33) Conclusion: In our study, although it consisted of few patients, it was objected that Rituximab therapy in patients with cSLE is effective, reduces lupus activity index, especially in cases of renal, cutaneous and hematologic involvement, that don't respond to conventional therapy. It may be consider in the future as an effective alternative treatment at first line treatment.

Disclosure of Interest: None Declared
In the 23 patients enrolled, the female-to-male ratio was 2,6:1, the mean age at onset was 11.75 ± 3.2 years. The mean disease duration up to renal biopsy was 15 and 19 months for mild and severe involvement respectively. ACL and LAC screening record were found for 21 and 20 patients respectively. LAC was present in 19,1% of patients and IgM and IgG anti-cardiolipin were present in 40% of patients. ENA were positive in 13 out 23 patients (56.5%). Overall the patients enrolled, the most common positive ENA subtypes were, anti-Ro/SS-A (38%), followed by anti-Sm and anti-RNP(22,7%). The prevalence of ENA in patients with mild and severe renal involvement are reported in Table 41. Results: A cohort of 150 patients with a mean age at diagnosis of 11.3 ± 3.13 years and a mean period of follow-up of 3.34 ± 2.14 years were analyzed. One hundred thirty-one (87.3%) patients were female. The most common manifestations were mucocutaneous (74.7%), hematological (56%) and musculoskeletal (39.3%) abnormalities. Upon diagnosis, renal damage was found in 56 patients (37.3%), of which 28 (18.3%) were diagnosed with lupus nephritis. Antinuclear and double-stranded anti-DNA antibodies were positive in most patients, 96.7% and 77.3%, respectively; antiphospholipid antibody positivity was observed in 40.7%. During follow-up, immunosuppressive management consisted of azathioprine in 54%, cyclophosphamide in 66.6%, mycophenolate mofetil in 31%, a combination of more than one of the above in 56.7%, being the most frequent azathioprine and cyclophosphamide; 22 individuals (14%) were only treated with hydroxychloroquine as an immunomodulator. Objectives: Identify NL cases, describe the clinical manifestations and its course, evaluate the presence of the most important antibodies and the history of mother's disease.
Methods: Retrospective review of case files of all patients diagnosed with NL in the last eight years, admitted to the Neonatal Unit and/or followed at the outpatients department of a tertiary teaching hospital.

Results
The authors present a case series which includes eight cases diagnosed with NL and a brief review of the literature (Table 42). Conclusion: Underdiagnosis might explain the reduced number of patients identified. The positivity of anti-Ro/SSA and anti-Sa/SSB seems to be associated with higher prevalence of neonatal cardiac manifestations. Early detection of this condition is paramount since treatment may reverse lower grade HB. Also, adequate maternal treatment can reduce the likelihood of NL. Disclosure of Interest: None Declared  Introduction: Children and adolescents diagnosed with Juvenile Idiopathic Arthritis (JIA) often exhibit lower physical activity level and poorer aerobic and anaerobic exercise capacity when compared to their non-JIA counterparts. Mild intensity exercise regimen has been proven to be safe in children with JIA and may produce significant improvements in overall physical function. Inadequate adherence to the treatment prescribed by paediatric rheumatologists, could also have a detrimental impact towards different clinical outcomes and possibly increased disease activity. This includes symptoms such as pain, fatigue, quality of life, longer term outcomes including joint damage, as well as increase of healthcare associated costs. Low adherence to medications such as methotrexate and biological-drugs remains a significant issue in paediatric rheumatology, with evidence that less than half of the children with JIA are actually compliant to their drug-therapy. The recent advances in smart technology resulting in a variety of wearable user-friendly interactive devices may become a key solution to tackle important challenges in JIA clinical management.
Objectives: The aim of this review was to explore the current use of modern interactive technologies in the provision of health care Methods: A litterature review was performed using MEDLINE, PUBMED and CINAHL. This review focused in 4 main topics: monitoring symptoms and disease progression using interactive technologies, adherence to prescribed medications using smart devices, available app to encourage physical activity and data protection.
Results: The recent advances in smart technology resulting in a variety of wearable user-friendly interactive devices may become a key solution to tackle important challenges in JIA clinical management. Fully understanding the impact that JIA and treatment complications have upon patients and their families has long been a challenge for clinicians. Modern interactive technologies can be adapted to the individual requirements and accessed directly in the hands or wrists of children with JIA. These secured networks could be accessible 'live' at anytime and anywhere by the child, parents and clinicians. Multidisciplinary teams in paediatric rheumatology may benefit from adopting these smart devices to enhance the understanding in different aspects, such as: patient's biological parameters, symptoms progression, and adherence to drug-therapy, quality of life, and participation in physical activities. Most importantly the use of interactive technologies may also promote more timely clinical decisions, improve self-management and parents active involvement with their child's disease. Paediatric rheumatology research could also further advance from the use of these smart devices, as they would enable real-time access to meaningful data to thoroughly analyse the disease-patterns of JIA, such as pain and physical activity outcomes. Data collection that typically occurs once every 1 or 3 months in the clinical setting could instead be gathered every week, day, minute or virtually live online. Many limitations in wearing such interactive technologies still exist and require further developments and investments.  Introduction: Juvenile idiopathic arthritis (JIA) is one of the most frequent rheumathologic conditions in childhood. The most common extra-articular manifestation of JIA is chronic anterior uveitis (CAU). It usually has an insidious, asymptomatic onset, with a chronic and recurrent course, being blindness its major complication. Several risk factors to develop CAU has been reported, including early age at the onset of arthritis (before 6 years), short disease duration and some JIA subtypes (oligoarticular-persistent and extended-oligoarticular JIA, psoriatic arthritis, undifferentiated arthritis). The presence of positive antinuclear antibodies (ANA) tests is one of the most important risk factors. In some cases ANA are present at the onset of the disease, subsequently becoming negative. Objectives: To determine if the presence of steadily ANA positivity (>2 determinations) throughout disease course is associated with an increased risk of developing chronic anterior uveitis Methods: We performed a retrospective study including JIA patients with high-risk to develop CAU and at least one positive ANA determination during the follow-up at the Pediatric Rheumatology Unit of our center. A cut-off point titer of 1/80 was considered for ANA positivity. The χ 2 test was performed with Fisher's adjustment. The level of significance was set by the 95% confidence interval (CI) and p <0.05.
Results: A total of 53 JIA patients were included, 48 (90.5%) of them are girls, with a mean age at diagnosis of 3 years. 16 patients developed CAU (31.3% of the girls and 20% of the boys), without a statistically significant difference in the percentage of patients who developed CAU between the genders or age. When dividing into groups, 52% of the girls had 1or 2 positive ANA determinations and 48% had ≥3 positive determinations; 40% of the boys had 1or 2 positive ANA determinations and 60% had ≥3 positive determinations. Analysing by groups, patients with 3 or more determinations an OR: 4.93 (95% CI: 1.32-18.31) to develop CAU compared to those with 1or 2 positive determinations. Conclusion: Our results are similar to others studies previously published regarding the absence of association of chronic anterior uveitis with the female sex, based on the frequency difference in the largest Introduction: Juvenile idiopathic arthritis (JIA) is commonly complicated by chronic uveitis. Therapy of JIA-associated uveitis is guided by the severity of inflammation and complications. When the standard anthireumatic drugs and the local eye therapy are insufficient we need to consider immunosuppressive or biological agents. Objectives: Observation was aimed at assessing the effectiveness of adalimumab (ADA) in the treatment of juvenile idiopathic arthritis associated uveitis in children with disease resistance to standard antirheumatic therapy. Methods: 7 patients with JIA (5 oligoarticular, 2 polyarticular) and who experienced eye problems were included in the study, 6 girls and 1 boy. Mean age was 6.  Introduction: Tubulointerstitial Nephritis and Uveitis syndrome (TINU) is a rare disorder characterized by inflammation of the tubulointerstitium associated with recurrent unilateral or bilateral uveitis. Since TINU syndrome may not be obvious at initial presentation, it remains often underdiagnosed.
Objectives: To report a case of recurrent bilateral optic disc edema in a definite TINU syndrome with limited responsiveness to corticosteroid therapy and immunosuppressants. An anti-TNF-α blocking agent was added in order to control the inflammation.
Methods: Observational report about a 13-year-old Caucasian boy diagnosed with TINU syndrome and bilateral papilledema. An extensive general and ophthalmological workup confirmed the diagnosis of TINU.
Results: A 13-year-old boy diagnosed with TINU syndrome, was referred to our department with a bilateral papilledema. In a 25months follow-up 4 episodes of bilateral anterior uveitis were observed. At the 2nd episode the anterior chamber inflammation was accompanied by bilateral optic disc edema. The ocular inflammation responded initially well to systemic corticosteroids but after a recurrence-free period of 1-year, bilateral papilledema recurred. At referral ocular examination showed mild anterior chamber reaction with bilateral optic disc edema. Visual field testing was normal and optical coherence tomography showed a thicker peripapillary retinal nerve fiber layer (PPRNFL). Immunosuppressive therapy with mycophenolate mofetil and methotrexate failed to control the inflammation. A treatment with infliximab, an anti-TNF-α blocking agent, was initiated. Initially remission with a recurrence-free period of 7 months was achieved but papilledema recurred. Conclusion: TINU syndrome may rarely manifest with optic disc edema. To our knowledge, this is the first case of TINU syndrome with bilateral papilledema treated with infliximab. Despite a recurrence-free period of 7 months, the anti-TNF-α blocking agent failed to control the papilledema. Since the limited responsiveness to anti-TNF-α blocking agents, alternative treatment options need to be explored.

Disclosure of Interest: None Declared
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