key: cord-0033363-w4t99f62
authors: nan
title: Proceedings of the 25th European Paediatric Rheumatology Congress (PReS 2018): Lisbon, Portugal. 5-8 September 2018
date: 2018-08-22
journal: Pediatr Rheumatol Online J
DOI: 10.1186/s12969-018-0265-6
sha: 7e3c984696e22074f3f05acff1865c6d54d35a65
doc_id: 33363
cord_uid: w4t99f62

nan

Introduction: Accurate estimates of the likelihood of attaining early remission with conventional treatment escalation may help target aggressive treatment to children with juvenile idiopathic arthritis (JIA) who have a low chance of remission. Objectives: To develop a clinical prediction tool to estimate the chance of early clinical remission with conventional treatment for each child at the time of JIA diagnosis. Methods: Prediction models were developed using data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort diagnosed 2005-2010. Treatment was compatible with the 2011 recommendations of the American College of Rheumatology. The predicted outcome was clinical inactive disease for 6 or more months starting within one year of the diagnosis in patients who did not receive early biologic agents or triple DMARD therapy. Models were developed in 200 random splits of 75% of the cohort, and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and cindex values. Results: A Cox-logistic model combining 18 clinical variables at a median of 2 days after diagnosis had a c-index of 0.69 (95%CI: 0.67-0.71) and performed better than JIA category alone (0.59, 0.56-0.63). Table 1 lists the top 8 variables included in the final model. Using the model, an online calculator (https://andrew-j-henrey.shinyapps.io/JIA_Remission_Calc/) produces estimates of the chance of remission for each child with JIA at diagnosis. Children in the lowest decile of probability of remission according to the model had a 20% chance of remission and 21% of them remitted; children in the highest decile had a 69% chance of remission and 73% remitted. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of the cohort as having a low chance of remission (<0.25 probability of remission), of whom 77% failed to attain remission within one year of diagnosis. Conclusion: Although the model did not meet our a priori performance threshold (c-index>0.70), it identified three times more subjects with low chance of remission than JIA category alone, and it may serve as a benchmark for judging the value added by future biomarkers. Introduction: Immune cells are constantly confronted with intracellular and extracellular radical oxygen species (ROS) under steady-state and even more under inflammatory and pathogenic conditions. To investigate the effects of oxidative stress and ROS molecules in regulatory T cells (T regs ), we deciphered the role of Nuclear factor Introduction: An atlas of the developing immune system is key to understanding its normal maturation and identifying diseaseassociated cell subsets. The availability of high dimensional mass cytometry, in comparison to traditional oligo-dimensional approach such as fluorescence-based flow cytometry, provides an opportunity for the creation of this reference. However to date, the power available from these big data has not been fully harnessed due to the absence of clinically relevant and standardised datasets. This results in issues of fragmentation by focusing on individual cell subsets and lack the ability to transverse the whole developmental gradient from neonatal to adult age. There is a critical unmet need for standardised datasets depicting at single cell level and with high dimensionality the entire human immune system. These limitations hamper translational and clinical research.

Objectives: To address this need, we aim to construct a mass cytometry based immune atlas from healthy peripheral blood mononuclear cells (PBMC) samples ranging from cord blood to adult age and make this dataset available to the research community via an interactive web portal to enable its mining and comparison with diseased dataset. Methods: The mass cytometry data from 113 healthy individuals (cord blood, newborn to adult) using 63 immune markers encompassing the major immune lineages were obtained. Quality control was performed before dimensional reduction and clustering to identify the cell subsets using our in-house analysis and visualisation pipeline. Their frequencies across the ages were presented as 3-D frequency histograms to create the immune landscape. This database and the analytic pipeline were incorporated into a web-based portal allowing users to interact and upload their own data for comparison.

Results: Here, we described EPIC with examples of its potential by exploring the evolution of some representative immune subsets over the full gradient of ages. Three developmental trajectories made up the healthy immune landscape with the most distinct being an increase or decrease in the cell populations with age. The last trajectory constituted an increase in population size in early childhood followed by a region of levelling. There was a distinct segregation of the naive T cell subset enriched in the cord blood/newborn period with the memory T cell subset enriched in adulthood. The naive IL8+ and TNFα+ CD4+ T cells were prominent peaks in the landscape and were found in higher frequency in the cord blood/newborn period. In contrast, the memory IFNɣ+ and TNFα+ CD4+ T cells were enriched in adulthood. For specific cell subsets, transition developmental milestones were observed in the TNFα+ CD4+ T cells where the size of its memory subset would exceed its naive subset at 8 year old. There was a significant reduction and increase with age in the frequency of the naive and memory TNFα+ CD4+ T cells with a Spearman's correlation coefficient, rho, of -0.4662 and 0.4164 respectively (p<0.0001). A similar intersection was present for the naive and memory regulatory T cell (CD4+, CD25+, Foxp3+, CD152+) subsets at 14 year old with a rho of -0.537 and 0.5034 respectively (p<0.0001).

Conclusion: A holistic description of the developing immunome was obtained with key developmental milestones in the T cell compartment identified. This atlas has the translational potential of helping us define the stage of immune maturity and identify the pathological cell subset in both paediatric and adult immune mediated diseases by the direct comparison with this reference atlas using the webbased portal that will be made freely available. Table 1 . Overall, their performance was superior (accuracy ranging from 0.81 to 0.98) to the already published literature's criteria (accuracy 0.56-0.94) with a very high specificity and a variable sensitivity. Most of the patients not classified with the new criteria were negative for genetic analysis or carriers of low-penetrance mutations with an inconsistent clinical phenotype.

Conclusion: The validation of the new Eurofever classification criteria in a large group of unselected patients coming from the registry confirms their high specificity and overall better performance in comparison to other criteria available in the literature. It is recommended to use them as classification rather that diagnostic criteria, for clinical trials and pathogenic studies. Introduction: AIDAI is a novel and unique, validated patient (pt)-reported assessment tool to evaluate disease activity in familial Mediterranean fever (FMF), hyper-IgD syndrome/mevalonate kinase deficiency (HIDS/MKD) and TNF receptor-associated periodic syndrome (TRAPS). 1 Objectives: To perform an external validation of AIDAI, we calculated scores over 40 weeks (wks) of canakinumab (CAN) treatment in pts enrolled into the CLUSTER trial and assessed correlation between AIDAI and disease/response characteristics. Methods: CLUSTER consisted of one cohort per disease (crFMF, HIDS/ MKD and TRAPS). 2 AIDAI was calculated as the sum of 12 items (Yes=1; No=0) 1 for 30 consecutive days. AIDAI score was calculated if the first score was recorded before ≥29 days. Missing items beyond last evaluable measurement were imputed by last observation carried forward (LOCF). Inactive disease (ID) was defined as AIDAI score <9. Correlation analysis of AIDAI with Sheehan disability score (SDS), child health questionnaire-psychological/physical ( (Table 1) . Conclusion: AIDAI scores decreased markedly over 40 weeks of treatment with canakinumab in crFMF, HIDS/MKD and TRAPS, with a relevant percentage of patients having inactive disease score. AIDAI improvements at Week 40 correlated with patient-and physician-driven evaluations. AIDAI is a validated patient-reported tool to assess disease activity and appears to have good sensitivity to change to be used in comparative trials. Patient's experience on disease activity does not strictly correlate with CRP and SAA, as these reflect more closely biological inflammation than clinical symptoms. 1 Methods: Eleven pediatric radiologists, each with at least 5 years of experience reading musculoskeletal MRI from seven different pediatric hospitals in North America and Europe, discussed definitions and grading of signal intensity, extent of signal abnormality within bone marrow and surrounding tissue, physis damage and vertebral fracture on MRI through monthly conference calls and an in-person meeting (Seattle, July 2017). Nine sets of whole body MRIs were used as a pilot reading session at the conference that demonstrated greater than 70% of agreement among the radiologist attendees. Fifty sets of pre-existing WB MRI scans between Jan 2013 and August 2016 from children with CNO at the University of Iowa Children's Hospital were anonymized and used for an interrater reliability study. Inter-rater agreement of presence of abnormal signal and severity were assessed using Fleiss kappa analysis. Results: Signal intensity was rated as absent, < fluid signal or similar to fluid signal within bone marrow. Extent of abnormal signal intensity within bone or surrounding tissues were scored according to the relative affected proportion. Long bones were divided into proximal epiphysis, proximal metaphysis, diaphysis, distal metaphysis and distal epiphysis. Complex bony regions such as the pelvis were divided into easily identifiable anatomical subareas. The agreement among 11 radiologists in readings of femur and tibia were shown in Table 1 . There was moderate to substantial agreement (0.44-0.63) in all parameters except the sizes of femoral proximal epiphyseal and femoral proximal metaphyseal lesions (0.28-0.34). There were 38 tibias and 30 femurs identified as active inflammation by at least 9 of 11 radiologists. Data from other bones are being analyzed. Conclusion: A comprehensive standardized scoring tool for MRI in children with CNO was developed. There was moderate to substantial agreements among radiologists in majority of parameters of femur and tibia. If proven reproducible, this tool can be validated in a prospective study and will become a key element of disease activity assessment in CNO. This study was funded by CARRA-AF small grant. Introduction: Systemic onset JIA (sJIA) is a multifactorial autoinflammatory disease. Historically, the prognosis of sJIA was very poor. The use of interleukin (IL)-1 and IL-6 blockade improved outcome, but still most studies report inactive disease in only 30-50% of patients within one year. It is hypothesized that innate immune activation is most prominent in the early phase of sJIA. To make use of this 'window of opportunity' , we started a prospective cohort with recombinant IL-1 receptor antagonist (rIL-1RA) as first-line monotherapy in new-onset sJIA patients (Vastert et al. AR 2014). Objectives: To analyse the long-term efficacy of this therapeutic strategy and to separately analyse a subset of sJIA patients without arthritis at disease onset. Methods: In this single centre, prospective cohort study, new-onset sJIA patients with an unsatisfactory response to NSAIDs received rIL-1RA 2mg/kg. Inactive disease (ID) was defined according to the Wallace criteria. In patients reaching ID, rIL-1RA was tapered after 3 months and subsequently stopped. In patients with an incomplete response to rIL-1RA, our protocol directed to increase rIL-1RA dose, add prednisolone or switch to alternative therapy. Clinical data including damage (JADI) and patient reported outcomes (CHAQ and/or JAMAR) were completed in a standardized way. Cytokine profiling was performed using Luminex multiplex immunoassay. Results: Forty-two patients were analysed, with a median follow-up of 5.8 years. At 3 months, 30/42 patients (71%) had ID with rIL-1RA monotherapy and another 6 had ID with rIL-1RA and prednisone. At one year, 32 patients (76%) had ID, of which 22 (52%) were off medication. Twelve patients had no arthritis at onset; 4 of them developed arthritis during flares. The clinical phenotype, inflammatory parameters and cytokine profile of patients without arthritis at onset was similar to patients with arthritis. Hence, after extensive ancillary investigations to exclude other diseases, these non-arthritic patients also received rIL-1RA as first-line therapy. After 3 months, 11/12 nonarthritic patients had ID (10 on rIL-1RA monotherapy), at 1 year all 12 had ID (8/12 off medication). Long-term outcome reflected the high efficacy of first-line rIL-1RA: 95% of all patients had ID and 72% had ID off medication at 3 and 5 years follow-up, only 5% reported articular damage and 5% extraarticular damage, no patient developed growth failure and only one developed obesity during follow-up. Moreover, around 60% of patients reported complete absence of pain and disease, no limitations in daily life and the highest possible score on well-being. One patient died due to MAS. In total, 24 patients (57%) never used other medication besides rIL-1RA and NSAIDs and only 14 patients (33%) used glucocorticoids.

Patients who achieved ID at one year were younger and had a significantly shorter disease duration, less active joints and higher neutrophil and leukocyte count before start of rIL-1RA. Multivariate analysis confirmed high neutrophil count as a significant predictor for ID at one year. Furthermore, ID at one year was highly associated with a good response at 1 month. Conclusion: First-line, short course monotherapy with rIL-1RA is a highly efficacious strategy to induce and sustain inactive disease and to prevent disease-and glucocorticoid-related damage. Our data on sJIA patients without arthritis plea for leaving out arthritis as a prerequisite criterion in future disease classification criteria.

Introduction: Long-standing debate continues on the factors and potential etiological agents of vasculitides and rheumatic diseases, such as Kawasaki disease (KD). Together with the genetic predisposition to suffer the condition, hitherto undefined environmental factors have been suggested to contribute to the onset of autoimmune vasculitis in susceptible individuals. A combined approach integrating research on atmospheric circulation and wind dynamics with a time-series study on Kawasaki disease epidemiology in Japan and the US led to Objectives: The hypothesis of a windborne role in the generation of KD etiology is further tested in this study for a series of other world locations where the disease is also prevalent and along the suspicion that the interaction between bioaerosols, the air chemistry and predisposed or genetically susceptible patients might similarly be associated with KD incidence there. Recovery of land source regions is attempted with the aim of exploring similarities/differences with those found for Japan. Exploration of the phenological status of vegetation in each of those region is performed to seek further mechanistic explanations on the epidemiological links to KD. Methods: In this study, a retrospective time series analysis of historical daily hospital admissions of KD and reconstruction of air movements and source regions is presented for several locations in all continents (US and Canada, Chile, France, the United Kingdom, Catalonia, South Korea, India and Thailand). The FLEXPART v9 atmospheric particle dispersion model is used and land-surface cover and high-resolution vegetation data employed to explore relationships to stages of vegetation development.

Results: Source regions and their land-cover typology is reconstructed for all major KD world sites in terms of disease incidence. Similar strong relationships emerge to cereal croplands in all the different continents.

The phenological cycle of vegetation in those areas shows a link to the stages where vegetation is decaying, indicating that a relationship between the major KD season and some kind of agricultural byproducts or remnants might play a role in the onset or exacerbation of this disease. An application of a statistical model integrating the air physics ssociated to the movement of winds from these sources further demonstrates predictive capacity to anticipate peaks in KD incidence.

Conclusion: Long-standing debate continues on the factors and potential etiological agents of vasculitides and rheumatic diseases, such as Kawasaki disease (KD) in susceptible children. Together with the genetic predisposition to suffer the condition, hitherto undefined environmental factors are now suggested to contribute to the onset of autoimmune vasculitis in susceptible individuals. The role of bioaerosols and air chemistry and physics is presented pointing to a much clearer combination of factors ultimately appearing to be crucial to the manifestation of epidemiological clusters of this pediatric vasculitis. A computational model integrating all this new environmental information in combination with epidemiological dynamics proves successful in predicting KD incidence in Japan.

Introduction: Juvenile dermatomyositis (JDM) is a rare, severe autoimmune disease characterised by proximal muscle weakness and skin rash. While JDM and adult-onset dermatomyositis (DM) share similar clinical and biological features, there are differences in prevalence of these features, including cancer, calcinosis and myositis-specific autoantibodies, suggesting a possible influence of age on pathogenesis.

Objectives: To investigate genetic risk factors for JDM and age of disease onset. Methods: Caucasian JDM cases from the UK (n=312) were genotyped (Illumina HumanCoreExome). Caucasian control data (n=2808) were obtained from the Wellcome Trust Case Control Consortium (Affymetrix 500K). Following quality control, classical human leukocyte antigen (HLA) alleles and HLA amino acids were imputed using SNP2HLA. Logistic, linear and Cox regression were performed using PLINK and R package GenABEL, with adjustment for the first two principal components. Genome-wide association was set at P<5×10 -8 and suggestive association at P<1×10 -5 . We subsequently built an international consortium to create a replication cohort of Caucasian cases (n=479). Genotyping of the replication cohort is ongoing using the HumanCoreExome array.

Results: Case-control analyses confirmed involvement of HLA including multiple loci within HLA-C (p=1.35×10 -8 , OR=2.49, 95% CI = 1.82-3.42) and HLA-DRB1 (p=2.73×10 -8 , OR=0.56, 95% CI=0.46-0.69). Outside the HLA region there was suggestive evidence of association at ZNF337 (p=7.49×10 -6 , OR=1.81, 95% CI=1.40-2.34). Analyses of association with age of disease onset did not implicate HLA involvement, suggesting age does not influence the association between HLA and JDM/ DM. Analysis of age of onset as a quantitative trait revealed suggestive associations at PDE1A (p=1.56×10 -6 , β=-1.61, 95% CI = -2.26-0.97) and AGPAT3 (p=2.26×10 -6 , β=1.63, 95% CI = 0.97-2.30), genes involved in regulating intracellular cyclic nucleic acid concentrations and phospholipid biosynthesis/Golgi-to-endoplasmic reticulum retrograde transport, respectively. In addition, we now have a replication cohort via our international consortium to validate these findings. Genotyping of the replication cohort is ongoing using the HumanCoreExome array.

Conclusion: This study confirms previous findings regarding HLA involvement. Analyses of associations with age of JDM onset identified novel loci, PDE1A and AGPAT3, which if validated in an independent replication cohort could suggest novel processes involved in pathogenesis. Together with the replication cohort, this study will be the largest GWAS of JDM to date.

Introduction: Innovative changes towards targeted treatment have improved the outcome dramatically for juvenile idiopathic arthritis (JIA) during the last two decades. The question remains how well these children perform during long-term follow-up.

Objectives: To study the disease activity, remission rate and damage 18 years after JIA onset. The distribution of the JIA categories was as follows: 3% systemic, 27% persistent oligoarticular, 20% extended oligoarticular, 16% polyarticular RF negative, 1% polyarticular RF positive, 7% psoriatic, 10% enthesitis-related arthritis (ERA) and 15% undifferentiated JIA. For all 329 patients attending a clinical visit the median active joint count was 0 (range 0-15), however during the 18 years of disease course the median cumulative joint count was 8 (range 1-59). 66 participants (15 %) received disease-modifying anti-rheumatic drugs (DMARDS) and 84 patients (19%) were treated with biologics at the last follow-up. At the final study visit the median composite juvenile arthritis disease activity score JADAS71 was median 1.5 (range 0-31.6) with the ERA category having the highest median score of 4.5 (range 0-16.5) (p=0.003). In the follow-up cohort 48% had a JADAS71 score <1 indicating inactive disease. Articular damage (JADI-A) was found in 20% of the patients who had a follow-up visit and 12.5% had developed extra-articular damage (JADI-E), most commonly ocular damage, found in 26/41 (63%). The highest JADI-A and JADI-E scores were found in the polyarticular RF negative and psoriatic categories. Less than half (44%) of the participants were in remission off medication 18 years after disease onset, but 39.8% had active disease. Achievement of remission off medication was observed in the following order: persistent oligoarticular 39/72 (54%), systemic 7/13 (54%), psoriatic 9/22 (41%), undifferentiated 21/55 (38%), extended oligoarticular 19/66 (29%), RFneg poly 16/59 (27%), RFpos poly 1/5 (20%), and ERA 4/37 (11%), the latter being significantly different from the other categories (p<0.001).

Conclusion: A significant proportion of the JIA cohort do not reach remission despite new treatment options and notably more than one third receive systemic treatment even 18 years after disease onset. The worst outcome was evident in the ERA category and in general the JIA disease burden in adulthood remains extensive.

Introduction: Reaching early inactive disease is the goal in Juvenile Idiopathic Arthritis (JIA) patients. How to proceed after reaching inactive disease is subject of ongoing research. Tapering and stopping disease modyfying anti-rheumatic drug (DMARD) therapy, including observation of subsequent flares, was applied in all three arms of the BeSt for Kids study.

Objectives: The aim of the BeSt for Kids study was to investigate, which of three treatment strategies was most effective and safe, by comparing them directly. The therapeutic target, in all arms, was inactive disease. If inactive disease was reached and maintained for a specific period of time, medication was tapered and stopped. Methods: We conducted a randomized, single-blinded, multicenter, treatment strategy study with 24 months of follow-up. DMARD-naive JIA (oligoarticular, rheumatoid factor negative polyarticular, and juvenile psoriatic arthritis patients) were randomized to 1) sequential DMARD monotherapy, 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 inactive disease for 3 (oligoarticular) or 6 (polyarticular) months, medication was tapered and stopped according to protocol. Flare frequency was observed. Missing data were imputed. In case of drug-free clinically inactive disease often intentionally no blood was drawn causing non-random missing ESR, and here '0' was imputed for the analysis of inactive disease. Primary outcome was time to inactive disease and time to flare after tapering and stopping DMARD therapy calculated using Kaplan Meier curve with log rank test. Secondary outcomes are adjusted ACRPedi 30/50/70/90 scores, toxicity, functional ability and quality of life. Generalised Estimated Equations were used for longitudinal data analyses.

In this abstract we share time-to-flare, flare frequencies and flare characteristics in all three arms. Flares were characterised by JADAS-10 of 9.7 (8.1-11.3), which improved 3 months after restart of treatment to JADAS-10 of 3.9 (1.8-6.0). Conclusion: During 24 months of treatment to target inactive disease, including tapering and stop-strategies, flare frequency was 26% after median 18 months. After 24 months, 71% of patients had inactive disease and 39% were in drug-free inactive disease. It is feasible to incorporate strategies for tapering and stopping DMARD-therapy in juvenile idiopathic arthritis patients, when tight control is maintained. Trial registration identifying number: Trial registration number: Dutch trial register 1574

Introduction: The measurement of disease activity plays a pivotal role in the care of patients with juvenile idiopathic arthritis (JIA). To serve this purpose, the Juvenile Arthritis Disease Activity Score (JADAS) and its clinical version excluding the acute phase reactant (cJADAS) were developed. Cutoffs for the state of remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) are necessary to interpret the scores and are ideally suited for pursuing tight disease control in a treat-to-target strategy.

Aiming to obtain cutoffs suitable for any clinical setting, new values were recently developed for JADAS10 and cJADAS10 in oligoarthritis and polyarthritis, based on a large multinational dataset of JIA patients ( Face validity was assessed in dataset 1) by plotting the proportion of patients in remission and LDA against the values of the 6 parameters in the ACR JIA core set. Discriminative ability was assessed in datasets 2) and 3) by comparing the percentage of patients below the cutoff values in the different ACR pediatric categories of response. In dataset 1) we compared in each disease activity state, the level of pain (0-10 VAS), functional ability impairment, and number of restricted joints and the frequency of patients satisfied with disease outcome, starting a new medication for JIA, and having morning stiffness. Predictive ability was assessed in dataset 4) by calculating the sensitivity and specificity of the cutoffs for remission and LDA after 3 months for treatment response after 12 months.

Results: Only most relevant results are described. JADAS10 and cJA-DAS10 cutoffs for remission allowed up to 1 active joint for polyarthritis and 0 for oligoarthritis. In dataset 2), 42% and 63% of patients achieving an ACRp70 response met the JADAS10 cutoffs for remission and LDA, respectively. In dataset 3), these percentages were 48% and 82%, respectively. In dataset 1), the median level of pain was 0, 1.5, 3, and 5.5 for polyarthritis patients in cJADAS10 remission, LDA, MDA, and HDA, respectively (Kruskal-Wallis p<0.001). The frequency of satisfaction with disease outcome was 94%, 76%, 56%, and 24% for oligoarthritis patients in cJADAS10 remission, LDA, MDA, and HDA, respectively (Chi2 test p <0.001). In dataset 4), 100% and 71% of patients with oligoarthritis classified as non-responders after 12 months had JADAS levels after 3 months above the cutoffs for remission and LDA, respectively. For polyarthritis, 90% and 80% of non-responders had JADAS levels after 3 months above the cutoffs for remission and LDA, respectively. Conclusion: New JADAS cutoffs showed good face and content validity; achievement of remission and LDA defined by the cutoffs predicted the response to therapy. Cutoffs were developed and validated in a large multinational dataset and they are ready for use in clinical trials and routine practice. Methods: Retrospective and prospective study of patients fulfilling Bohan and Peter criteria for JDM and Troyanov for OM, aged less than 16 years at diagnosis, ascertained from 3 French paediatric rheumatology reference centres between 2013 to 2018. Severe forms were defined as requiring ICU management, and/or more than 3 treatment lines and/or with fatal outcome. Muscle biopsies were reviewed. Type I interferon pathway activity was assessed by dosage of interferon alpha (IFNa) through digital elisa (Simoa) with a Pan-IFNa antibody in patient sera and myoblast lysate, mRNA expression of interferon stimulated genes (ISGs) by RTqPCR and phosphorylation of STAT by flow cytometry on whole blood. Results: 67 patients were included, 12 (group 1) and 54 (group 2) with and without anti-MDA5 antibodies respectively. Group 1 demonstrated more arthritis (100% vs 24%), cutaneous ulcerations (42% vs 26%), interstitial lung disease (ILD) (33% vs 14%) and a milder muscular involvement (median of CK: 96 vs 149 UI/l), with better preserved muscular function (MMT and C-MAS, respectively 79/80 vs 70/ 80 and 50/52 vs 38/52). Total muscle biopsy scores were lower for group 1 than group 2 (respectively 5.5 vs 20). Group 1 included more severe forms (36% vs 19%). 133 IFN signatures (ISGs) and 210 IFNa Simoa measurements were assessed. Correlation between ISG expression and protein at 79 simultaneous data points was high (Pearson: r = 0,74 ****). ISGs and IFNa (signature and dosage) were higher in group 1 than 2 (median of ISGs 21 vs 7.4 and median of Simoa 3807.5 vs 49.6 fg/ml). In contrast, IFNa levels in patient myoblasts were similar to controls for group 1 (1 patient), whilst those in group 2 were higher (10 patients). A constitutive phosphorylation of STAT1 and STAT3 was observed in T and B lymphocytes and monocytes of 5 patients, including one from group 1. Treatment with steroids, tacrolimus, rituximab and immunoadsorption in one group 1 patient correlated with the disappearance of MDA5 auto-antibodies, the normalisation of IFNa levels and the induction of complete remission (normalisation of clinical, laboratory and radiological parameters).

Conclusion: This study indicates a higher frequency of cutaneous ulcerations, arthritis and ILD, and milder muscular involvement in JIM with positive MDA5 auto-antibodies compared to other JIM. These data suggest an important role of systemic IFNa in the pathology of the disease. In severe and refractory forms, IFNa may be a potential therapeutic target.

Introduction: Juvenile onset systemic lupus erythematosus (jSLE) is characterised by a type 1 interferon (IFN) transcription signature. Up to 80% of patients with jSLE of varying severity express a predominant IFN signature which correlates with disease activity, and is abrogated by steroids. Investigating the IFN signature outside of a flare may provide insight into the true prevalence of high IFN signature disease, and underlying differences in disease pathogenesis, that may be masked by steroid or disease activity. Objectives: To investigate the prevalence of high IFN signature in low disease activity jSLE, and to assess whether toll like receptor (TLR) 7 or 9 dependent IFNα production pathways differ between high and low IFN signature patients.

Methods: Blood was collected, with consent, from healthy volunteers (n=24:10 female; 14 male, age=12-19) and young people with jSLE (n=29:20 female; 9 male, age=14-21). Clinical data were recorded. Peripheral blood mononuclear cells (PBMC) were separated by Ficoll gradient centrifugation. Ex vivo RNA was assessed by Nanostring Plex Set. IFN score was calculated from counts of 5 IFN inducible genes (MX1+BST2+MCP1+ISG15+ IFIT1/5). Samples were classed as IFN positive (IFN+) if >2SD from the healthy mean. Separately, PBMC were stimulated with TLR7 agonist, R848, or TLR9 agonist, CPGODN2216, before assessing for secretion of IFNα and TNFα by luminex. Statistical analysis was performed using SPSS with linear regression.

Results: There was a significantly higher IFN score in jSLE than healthy controls (p=0.001). 14/29 (48.27%) jSLE patients were IFN+ vs 1/23 (0.04%) healthy controls (p=0.005). Patients with jSLE had a mean SLEDAI of 3.0 (range=0-12); 15 (52%) were on prednisone (mean= 6.9mg). In patients with jSLE, the only autoantibody that significantly predicted IFN score was towards RNP (p=0.018). There was no association between any specific organ involvement and IFN score. Four patients with jSLE were B cell depleted (<2%), with no effect of B cell depletion on IFN score. There were no significant differences in markers of disease activity (SLEDAI, CRP, ESR, C3, C4 and double stranded DNA antibodies) between IFN+ and IFN-jSLE patients. Only jSLE patients who were IFN+ produced significantly more IFNα (p=0.046) and TNFα (p=0.031) than healthy controls after TLR7 stimulation. After TLR9 stimulation, however, IFNα production was decreased in jSLE compared to healthy, regardless of IFN score. IFN+ patients with jSLE had significantly higher PBMC RNA expression of TLR7 than those who were IFN-(p=0.001), and healthy controls (p=0.04). IFN+ patients with jSLE showed a significant decrease in TLR9 expression when compared to healthy controls (p=0.023). We confirmed that TLR7 was not an IFN inducible marker, by assessing expression in healthy controls with and without IFNα pre-stimulation, which showed no significant difference. Conclusion: We present novel data, showing that, in non-flaring patients with jSLE on low doses of steroid, half are IFN signature positive. This is lower than reported in studies that include flaring patients and may better represent prevalence of high IFN signature disease at baseline. In jSLE, IFN signature score associates with autoantibodies to RNP. PBMC from IFN+ patients produce more IFNα after TLR7 stimulation, and have a significantly higher expression of TLR7, along with a decrease in TLR9 expression compared to samples from patients with a negative IFN signature, and healthy controls.

Introduction: The granulocytic protein S100A12 is expressed at high levels in Kawasaki Disease (KD) but it is unclear whether S100A12 does actively participate in KD pathology or is a bystander of neutrophil activation.

Objectives: Kawasaki disease (KD) is an acute vasculitis of childhood, predominantly affecting coronary arteries. S100A12 is an endogenous pattern recognition receptor (PRR) ligand, which is strongly upregulated in KD and S100A12 serum levels track with KD disease activity and response to intravenous immunoglobulin (IVIG) treatment. While S100A12 was originally described as agonist of the multi-ligand receptor for glycation endproducts (RAGE), we described human monocytes to respond to S100A12-stimulation in an exclusively TLR4-dependent manner. Here, we aimed to investigate whether and how serum S100A12 might be actively involved in inflammatory processes in KD.

Methods: Serum samples (n=75) from patients with KD at different stages pre-and post-intravenous immunoglobulin (IVIG) treatment were analyzed for S100A12, cytokines, chemokines and soluble markers of endothelial activation. Primary human coronary artery endothelial cells (HCAECs) were analyzed for responsiveness following direct stimulation with S100A12 or lipopolysaccharide (LPS). Alternatively, HCAEC were cultured in conditioned medium obtained from primary human monocytes stimulated with LPS or S100A12 in the absence or presence of IVIG or cytokine antagonists. Results: Multiple correlation analyses revealed, that in KD patients' sera in course of IVIG-therapy soluble vascular cell adhesion molecule-1 (sVCAM-1) titers as indicator of endothelial activation exclusively associated with pre-treatment S100A12 levels. Yet, in contrast to stimulations with LPS, HCAECs were not responsive to direct treatment with S100A12, despite the presence of appropriate receptors (RAGE, TLR4). Unresponsiveness of HCAECs to S100A12 was due to lack of membrane CD14 expression. Addition of recombinant soluble CD14 or human serum benefitted LPS-but could not establish response to S100A12. Instead, HCAECs strongly responded to supernatants obtained from S100A12-stimulated primary human monocytes, as evidenced by expression of inflammatory cytokines and adhesion molecules. Inflammatory activation of HCAECs by S100A12stimulated monocytes required monocyte-co-stimulation with ATP. Endothelial cell stimulation was completely abrogated upon IL-1β blockade but remained unaffected by treatment with IVIG or anti-TNFa and IL-6 receptor blocking antibodies. Conclusion: We identified IL-1β-signaling in coronary artery endothelium as particularly relevant in course of sterile inflammation as induced by damage associated molecular pattern (DAMP) molecules such as S100A12. These data are in support of a potential key role for IL-1 in KD pathology but also highlight the coronary artery endothelium, which is critically involved in early KD pathology and aneurysm formation as particularly sensitive to IL-1β blockade during DAMP-induced sterile inflammation.

safety of CAN dosing regimens of every 4 weeks (q4w) and every 8 weeks (q8w) in patients with crFMF, TRAPS or HIDS/MKD from the epoch 4 (E4 up to week 112) of CLUSTER. Methods: CLUSTER comprised 4 epochs (E1-E4). After lead-in E1, efficacy of CAN 150/300 mg q4w to induce complete response was assessed in E2, a 16-week randomised, double-blind, placebo (PBO)controlled epoch. E3, a 24-week randomised withdrawal epoch, evaluated whether responders to CAN 150/300 mg q4w in E2 could maintain clinical efficacy on 150/300 mg q8w or PBO. In E4, a 72week, open-label epoch, the long-term maintenance of efficacy and safety of CAN 150/300 mg q4w or q8w in patients with crFMF, TRAPS or HIDS/MKD was evaluated. Patients who did not maintain clinical response on q8w could be uptitrated to 150/300 mg q4w. Safety assessments included incidence of adverse events (AEs) and serious AEs.

Results: Five patients discontinued from the study in E4 (one TRAPS patient discontinued due to AE). A substantial proportion of patients maintained optimal control of disease activity following treatment with 150/300 mg q4w or q8w in all 3 cohorts at week 112 (Table 1) . HIDS/MKD patients more often required uptitration to 300 mg q4w. Conclusion: Long-term treatment with canakinumab 150/300 mg q4w in epoch 4 of the CLUSTER study showed that optimal control of disease activity can be maintained in patients with crFMF, TRAPS or HIDS/MKD. There were no new or unexpected safety issues reported over 112 weeks of treatment.

Introduction: Regulation of IL-18 gene expression by primary human monocytes is poorly understood but may provide insights into the cytokine's still unclear role in autoinflammation.

Objectives: The interleukin (IL) 1 family cytokine IL-18 is overabundant in plasma and serum of familial mediterranean fever (FMF) and systemic juvenile idiopathic arthritis (sJIA) patients and its levels coincide with hypersecretion of the damage associated pattern (DAMP) proteins S100A8/A9 and S100A12. Comparable to IL-1b it is thought to require caspase-dependent processing to render an immature pro-form into bioactive mature IL-18. Yet, in stark contrast to IL-1b, it seems largely unknown whether and how IL-18 gene expression is regulated.

Methods: Primary human monocytes isolated from healthy donors were analyzed for kinetics of cytokine expression on gene and protein level following different stimulations and drug treatments.

Results: Initially, we performed endotoxin desensitization experiments on primary human monocytes, which suggested TNFa, IL-6 and IL-1b but not IL-18 gene expression to be subjected to LPStolerance. However, when studying time kinetic gene expression of cytokines, we found that IL-1b and IL-18 followed identical secretion but completely different gene expression patterns. In contrast to IL-1b, we observed human monocytes to maintain a cytoplasmic store of mature, bioactive IL-18 from which it could be readily secreted upon LPS stimulation and, following the observed attenuated IL-18 gene expression, this intracellular bioactive IL-18 store replenished. Importantly, colchicine as the mainstay of todays FMF-therapy, as well as the the microtubule polymerisation inhibitor nocodazole abrogated IL-18 expression, while IL-1b gene expression was massively enhanced. Conclusion: We propose monocytic IL-18 transcription to be subjected to negative feedback regulation by an intracellular store of IL-18 protein. The cellular efforts to maintain such a store may suggest IL-18 to rather operate as DAMP than classical cytokine. This may explain the orchestrated hypersecretion of IL-18, S100A8/A9 and A12 in diseases such as FMF or sJIA. Introduction: Juvenile Idiopathic Arthritis is hallmarked by a disturbed immunological balance between regulatory T-cells (Treg) and effector T-cells (Teff). Restoring this balance by either enhancing the suppressive function of Treg or inhibiting activation and proliferation of pro-inflammatory T-eff is therefore a promising therapeutic strategy. Previously we demonstrated that inhibition of the lysine deacetylase SIRT1 resulted in an increase in FOXP3 positive cells in vitro. Since the transcription factor FOXP3 is essential for Treg differentiation and function, this approach could positively influence immunological tolerance. Interestingly, SIRT1 can be inhibited by the well known food additive, Vitamin B3, also known as Nicotinamide (NAM). We therefore aim to translate these laboratory findings into clinical practice and envision a role for NAM as a novel therapeutic strategy in maintaining the immunological balance in patients with JIA. We demonstrated a distinctive effect of NAM on Treg, however the effect of NAM on the other side of the balance; Teff cells is still unexplored. Objectives: To investigate the effect of SIRT1 inhibition on proliferation, activation and cytokine production of Teff cells.

Methods: T-cells were isolated from the blood of healthy controls and JIA patients as well as the synovial fluid from JIA patients. Cells were stimulated with aCD3/aCD28 and cultured in the presence of increasing concentrations of NAM (0-9mM) for 1-4 days. Proliferation and expression of activation makers were determined using flow cytometry. Cytokine production was determined by qPCR, luminex and flow cytometry. The specific SIRT1 inhibitor EX-527 was used as a control to determine the pathway involved.

Results: In vitro NAM treatment of human CD4+ T-cells significantly decreased the production of the pro-inflammatory cytokines IL-2 and IFNy measured both on mRNA and protein level. In line with this, surface activation markers were downregulated after NAM incubation. Furthermore proliferation of both CD4+ and CD8+ T-cells was inhibited with NAM treatment in a dose dependent manner in both PBMC from HC and SFMC from JIA patients. Results were verified by using another SIRT 1 inhibitor; EX-527.

Conclusion: In addition to the previously demonstrated increase of Treg numbers and function, these data demonstrate that NAM treatment in vitro inhibits proliferation and activation of Teff cells. Therefore NAM treatment could modulate the immunological balance by both increasing tolerance and suppressing immune activation. We envision that NAM treatment as an adjuvant therapy has the potential to benefit JIA patients and potentially other autoimmune diseases. To translate these findings to clinical practice and determine if NAM treatment is useful as a strategy to maintain disease remission after stopping DMARD or biologicals we are in preparation of a phase III clinical trial.

Introduction: Macrophage activation syndrome (MAS), a severe complication of paediatric rheumatic disease, is currently classified among the secondary forms of HLH (sHLH). Primary HLH (pHLH) are caused by mutation of genes coding for proteins involved in cytotoxic functions. Mice carrying heterozygous mutations in more than 1 pHLH gene carry a higher risk to develop HLH following viral infection, suggesting that accumulation of partial genetic defects may be relevant in HLH.

Objectives: To analyse, with next generation sequencing (NGS), genes involved in pHLH in MAS in the context of different rheumatic diseases and in sHLH. Methods: We performed Targeted resequencing on all patients using a panel including the 7 principal HLH-related genes (PRF1, UNC13d, STX11, STXBP2, Rab27a, XIAP, SH2D1A) on MiSeq® and NextSeq550® platforms (Illumina, San Diego, CA); all variants identified were confirmed by Sanger. We took into account variants with an allelic frequency in the global population up to 5% in the dbSNP and Ensembl databases. Results: We analysed 125 patients: 47 MAS (40 developed this complication in the context of systemic Juvenile Idiopathic Arthritis (sJIA) and 7 in the context of different rheumatic diseases), 32 sHLH, 22 sJIA (without history of MAS) and 24 with different autoinflammatory diseases (AID). sJIA and AID patients were used as control groups. We identified at least 1 heterozygous variant in one of the pHLHrelated genes in 41 patients with a detection rate of 52%, 45% of MAS and 62% of sHLH patients. More than one variant was identified in 37% patients from both groups, with 19% of both MAS and sHLH patients carrying polygenic variants. In control groups, 54% of sJIA and 33% of AID patients carry at least a variant in the analysed genes, while polygenic variants have been detected in 14% and 8% of control patients, respectively. The most involved genes in both MAS and sHLH groups were PRF1 and UNC13d, while variants in RAB27a and XIAP have been found only in sHLH patients. The most frequent variants identified in both groups were A91V in PRF1 gene and R928C in UNC13d gene. The A91V variant in PRF1 gene was identified in 19% of both MAS and sHLH patients, while this variant was present, respectively, in only 5% of sJIA and 4% of AID patients. The R928C variant in UNC13d gene was identified in 32% of MAS and 18% of sHLH patients, and in the control group in 9% of sJIA and 17% of AID patients. Considering the patients' clinical characteristics, relapse, CNS involvement, ICU admission and death, in sHLH we observed that three of the 6 patients (50%) carrying multiple variants had recurrent episodes of HLH and that two of them (33%) presented a severe disease with exitus. Conclusion: Monoallelic variants in pHLH-related genes are more frequent in MAS, sHLH and sJIA and less in AID patients, suggesting different molecular mechanisms involved in the diseases. Re-occurrence and severity of disease seem to be more frequent and more severe in patients who carry mutations in two genes in sHLH group. These data may support a polygenic model of sHLH.

MAS is still significantly high. A score that identify sJIA patients who are at high risk to develop MAS would be useful in clinical practice. There are no parameters available to identify from onset sJIA patients with high risk to develop MAS in their disease course. Objectives: To evaluate whether routine laboratory parameters at disease onset may predict the development of MAS in patients with active sJIA. To define a risk score of MAS for sJIA patients using these parameters.

Methods: Laboratory parameters of disease activity and severity (WBC, N, PLT, Hb, ferritin, AST, ALT, gGT, LDH, TGL, fibrinogen, D-dimer and CRP), were retrospectively evaluated in 56 sJIA patients referred to our Division of Rheumatology from 1998 to 2016 with at least one year of follow-up. Laboratory parameters were evaluated during active sJIA, without MAS, at time of hospitalization (T1) and before treatment for sJIA was started (T2). Patients were divided in two groups: group 1 (patients without history of MAS), group 2 (patients with at least one MAS episode during disease course). To calculate a MAS risk score, laboratory parameters, collected at T2, with a statistical significant difference between the two groups of patients were selected. Results: Fourteen patients, that fulfilled the 2016 classification criteria for MAS [1] at time of sampling, were excluded from the analysis. Therefore, we analyzed laboratory parameters of 42 patients with sJIA, 27 of whom without history of MAS (group 1) and 15 who developed at least one episode of MAS during disease course (group 2). Levels of ferritin, AST, LDH, gGT and TGL, collected at T2, were statistically significant higher in patients with a history of MAS compared to those without a history of MAS. For each of these parameters an arbitrary cut-off was defined. In order to define the final score an arbitrary rate was attributed to each parameter. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were calculated to define the best scoring system. The scoring system with the best sensitivity was chosen (Table 1) . A MAS risk score >3 identified 14 out of 15 sJIA patients with a history of MAS and 3 out of 27 sJIA patients without history of MAS.

Conclusion: In conclusion we developed a MAS risk score based on routine laboratory parameters that are available worldwide, that can help clinicians to identify these patients early in the disease course.

Our results need to be validated in a larger population.

The efficacy and safety of intravenous (IV) tocilizumab (TCZ) were demonstrated in patients (pts) with systemic juvenile idiopathic arthritis (sJIA) in the phase 3 TENDER study. 1 Objectives: To investigate dosing regimens of subcutaneous (SC) TCZ in pts with sJIA by bridging from TENDER data for TCZ IV to identify the optimal SC regimen through characterization of the pharmacokinetics (PK), pharmacodynamics (PD), and safety of TCZ SC in pts with sJIA; efficacy was an exploratory objective.

Methods: This was a multicenter, open-label, phase 1b study to evaluate the PK, PD, and safety of TCZ SC in pts aged 1-17 years with sJIA and inadequate response to glucocorticoids. Interim analysis was conducted after 24 pts had received TCZ SC for 14 weeks. Pts could be TCZ naive or could switch from TCZ IV to SC. TCZ SC was administered for 52 weeks according to body weight: pts <30 kg received either 162 mg every 10 days before interim analysis or 162 mg every 2 weeks (Q2W) after interim analysis; pts ≥30 kg received 162 mg every week (QW). Results: We enrolled 51 pts, including 25 weighing <30 kg (8 before and 17 after interim analysis) and 26 weighing ≥30 kg. Twenty-six pts (51%) were TCZ naive and 25 (49%) switched from TCZ IV. Median steady state C min was similar for pts <30 kg receiving TCZ 162 mg Q2W and pts ≥30 kg receiving TCZ 162 mg QW; the ranges largely overlapped (Table 1 ). More than 95% (49/51) of pts treated with TCZ SC had steady state C min higher than the 5th percentile achieved with TCZ IV. The median and range of AUC 2weeks were similar for both body weight groups (Table 1) . Changes in interleukin-6, C-reactive protein, and erythrocyte sedimentation rate were similar for both body weight groups. Almost all pts had ≥1 adverse event (AE; n = 50; 98.0%). Injection site reactions (ISRs) occurred in 21 pts (41.2%); most were mild, and none led to treatment interruption or withdrawal. The AE rate was 1200.3/100 pt-years (PY) (909.3/100 PY, excluding ISRs). The most common AEs were viral upper respiratory tract infection (13; 25.5%), neutropenia (13; 25.5%), and cough (12; 23.5%). Nine serious AEs occurred in 7 pts (13.7%; 19.3/100 PY); 5 were infections, all in the <30 kg group. Two deaths occurred, both in the <30 kg group. Median JADAS-71 improved from baseline to week 52 for TCZ-naive pts (<30 kg, -13.9; ≥30 kg, -12.4) and was maintained or improved further for pts who switched from TCZ IV (<30 kg, -0.7; ≥30 kg -0.2). At week 52, 29/43 pts (67.4%) had inactive disease (JADAS-71 <1.0). Conclusion: A PK-based strategy was successful in bridging TCZ SC to TCZ IV in pts with sJIA. Dosing regimens of 162 mg Q2W in pts <30 kg and 162 mg QW in pts ≥30 kg provided adequate exposure to support efficacy comparable to that of TCZ IV. Except for ISRs, safety results were consistent with the known safety profile of TCZ in sJIA. Introduction: An increasing body of evidence obtained both in patients and experimental models of secondary hemophagocytic lymphohistiocytosis (sHLH), including macrophage activation syndrome (MAS), supports the pathogenic role of Interferon-gamma (IFNγ). Nevertheless, to date, few data demonstrating the activation of the IFNγ pathway in target tissues of patients with sHLH during the active phase of the disease are available.

Objectives: In this study, in order to further clarify the involvement of IFNγ in the pathogenesis of sHLH, we investigated the activation of the IFNγ pathway in the affected liver of patients with active sHLH. In addition, we evaluated the circulating levels of IFNγ inducible chemokines CXCL9 and CXCL10 and assessed the activation of the IFNγ pathway in peripheral blood mononuclear cells (PBMCs) of patients collected during the course of the disease. Methods: We analysed by real-time PCR the mRNA expression levels of IFNγ and IFNγ-inducible genes in the liver and in peripheral blood mononuclear cells (PBMCs) from two patients with active sHLH and one patient with active MAS, in which the disease was limited to the liver, without systemic involvement. Moreover, both in liver and PBMCs protein lysates, we evaluated by Western Blot analyses the levels of total and Tyrosine (701)-phosphorylated Signal transducer and activator of transcription 1 (STAT1), the transcription factor mainly involved in the activation of the IFNγ signaling pathways. Circulating CXCL9 and CXCL10 have been measured by ELISA.

Results: The expression levels of IFNγ and IFNγ-inducible genes were markedly up-regulated in livers from all three patients, compared to control livers. Conversely, slight differences in the expression levels of Type I IFN-inducible genes and other classical pro and antiinflammatory cytokines were found. Further supporting the activation of the IFNγ pathway, higher protein levels of phosphorylated and total STAT1 were detected in patient livers. Accordingly, we found that mRNA levels of IFNγ-regulated genes and phosphorylated STAT1 protein levels were markedly increased in patient PBMCs collected during the active phase of the disease. Finally, circulating levels of IFNγ-inducible CXCL9 and CXCL10 were markedly increased during the active phase of the disease, paralleling the ferritin's trend. Conclusion: Our data provide evidence of selective and marked upregulation of the IFNγ pathway in liver tissue as well as in PBMCs and blood of patients with active sHLH, further supporting the key role of IFNγ in the pathogenesis of the disease, and provide the rationale for the therapeutic use of an anti-IFNγ antibody in sHLH.

Introduction: Systemic onset juvenile idiopathic arthritis (SoJIA) is a potentially severe disease with both systemic and joint inflammation; different evolutive forms were described (monophasic, polyphasic or persistent), but the outcome is hardly predictable at diagnosis.

Objectives: This study aims to identify early predictors of disease evolution within the SoJIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohorte), an international prospective cohort study. Methods: 152 SoJIA patients with a minimum of two-year follow-up were enrolled. 5 patients were excluded due to missing data on diagnostic visit. Demographics and clinical data were collected (retrospectively if diagnosis < 2015 and prospectively if diagnosis ≥ 2015) and described for 147 patients. At diagnosis, median age and disease duration was 5.3 years and 1.9 months, respectively, male to female ratio was 1:1.2. Median follow-up was 6.7 years. 123 and 98 patients were treated with biologics and DMARDs, respectively. Monophasic evolution is determined by the occurrence of active disease (systemic symptoms and/or arthritis) followed by inactive disease. No recurrence of active disease is observed, and remission is obtained. The polyphasic course is defined by the recurrence of active disease at any time after having achieved remission. A persistent evolution is characterized by the persistence of systemic symptoms and/or arthritis and/or abnormal laboratory results (for at least 24 months). We present the preliminary results in 30 patients with complete data for disease activity and medication use.

Results: Corresponding to their evolution, patients were classified in the monophasic (n=10; MONO), polyphasic (n=14; POLY) or persistent group (n=6; PER). Females were predominant in the MONO and POLY group with 80% and 79%, respectively. No female patient was in the PER group. At diagnosis, all patients in the PER and POLY group had arthritis; only 80% did in the MONO group. Hepatomegaly and splenomegaly was present in 30% and 50% of MONO patients versus 17% and 0% of PER patients, respectively. Joint count during first 6 months was ≥ 5 joints for 83% of the PER population compared to 30% for the MONO. Four patients in the MONO group (40%) did not have any biologics, whereas all patients from the other groups had one or more (POLY: 7 patients had one, 5 patients had two and 2 patients had three different biologics). Disease Modifying Anti-Rheumatic Drugs (DMARDs) were used in 4 patients of the MONO (40%), 13 of the POLY (93%) and 5 of the PER group (83%). Median duration of corticoid-use for the MONO group and the POLY group was 0.3 years and 2.68 years, respectively. Conclusion: Systemic presentation seems to be more prevalent in the MONO group whereas arthritis in the POLY and PER groups. Polyarticular arthritis at 6 months is suggesting persistent disease evolution. Biologics, DMARDs and corticoids are more often and longer used in the POLY and PER groups correlating with a more severe disease course. Early recognition of a monophasic evolution could help the physician to limit the use of treatments, in particular steroids.

Data are under completion for all 152 patients. Precise description of disease evolution and deep phenotypic analysis will be performed.

Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a severe childhood immune-inflammatory disorder with unknown etiology. Objectives: One of the concepts is that the disease results from an inappropriate control of immune responses to an initially harmless trigger. In the current study, we investigated whether sJIA may be caused by defects in IL-10, a key cytokine in controlling inflammation. Methods: IL-10 production was analyzed in a sJIA mouse model, which relies on injection of Complete Freund's Adjuvant (CFA) in IFNγ deficient mice. Corresponding wild type (WT) mice develop a subtle and transient inflammatory reaction and were used to study the effect of IL-10 neutralization. Cytokines and CRP were analyzed in plasma of sJIA patients (active: n=10; inactive: n=8) and healthy controls (n=15). Their PBMCs were used to study cell-specific defects in IL-10.

Results: Diseased IFN-γ deficient mice showed a defective IL-10 production in T reg cells, B cells and NK cells, with B cells as the major source of IL-10. Neutralization of IL-10 in WT mice resulted in a chronic immune-inflammatory disorder clinically and hematologically reminiscent of sJIA. In sJIA patients, IL-10 plasma levels were strikingly low as compared to pro-inflammatory mediators. In addition, B cells from sJIA patients showed a decreased IL-10 production, both ex vivo and after stimulation. Conclusion: Cell-specific IL-10 defects in sJIA mice and patients result in an insufficient IL-10 production to counterbalance their proinflammatory cytokines. IL-10 neutralization in CFA-challenged WT mice converts a transient inflammatory reaction into a chronic disease and represents a model for sJIA in IFN-γ competent mice.

Introduction: Systemic juvenile idiopathic arthritis (SJIA) accounts for 10-20% of all JIA patients. It is characterized by findings of systemic inflammation such as fever, rash, serositis, lymphadenopathy, and hepatosplenomegaly, and arthritis. Arthritis may develop later in life with variable clinical features. Macrophage activation syndrome is the most life threatening complication. Progress in the understanding of pathogenesis has led to the development of cytokine-targeted therapies, biologics.

Objectives: This study aims to evaluate the treatment options in SJIA, particularly effect of methotrexate prior to biologics. Methods: A retrospective review of 52 cases of systemic JIA in the last 20 years was performed.

Results: Thirty one (59.6%) of the patients were female. The mean age of diagnosis was 89.8 ± 7.88 months and the mean follow-up was 32 ± 18.5 months. Twenty seven (51.9%) had monocyclic, 9 (17.3%) had polycyclic and 16 (30.8%) had polyarticular course. All of the patients had intermittant fever at onset, followed by rash and arthritis, and the least common symptom was serous involvement. Ten (19.2%) cases had macrophage activation syndrome (MAS). Four of them presented with MAS as the initial diagnosis. The laboratory values of MAS cases were significantly lower in ESR, platelet and fibrinogen levels and higher in ferritin and triglyceride levels when compared with other cases. Eight of the MAS cases (80%) had monocyclic, 1 (10%) had polycyclic and 1 had polyarticular course. In 8 of the MAS cases (80%) the disease was controlled by pulse steroid followed by methotrexate alone. Fifty (96.2%) cases received pulse steroids. Methotrexate (MTX) treatment was added in 47 (88.5%) cases. Thirty two (61.5%) cases were in remission with methotrexate treatment, whereas 14 (27%) cases required an additional biological agent. Majority of patients with biologics (56.3%) had polyarticular course. Adalimumab (1), anakinra (3), tocilizumab (6), etanercept (8) and canakinumab (9) were the biologics. In 4 cases, cyclosporin was added to control the disease. Eight patients (15.4%) were transferred to adult rheumatology clinic for persisting arthritis. Two (4.3%) of the patients died due to sepsis and MAS, respectively. Seventeen (32.7%) were in remission under medication, and 25 (48.1%) were in remission without medication. Conclusion: Randomized controlled trials have evidence about effectiveness of biologics, particularly IL-1 and IL-6 inhibitors, in treatment of SJIA. However, this study shows that methotrexate could control the disease in about two thirds of patients, particularly in "monocyclic" SJIA. Biologics such as anakinra, canakinumab, or tocilizumab could be preferred in cases with systemic onset and polyarticular course. Multicentered studies with more patients are needed to support this "real-world data".

Introduction: Monogenic primary HLH (pHLH) are caused by mutations of genes coding for proteins involved in cytotoxic activity or occur in the context of immunodeficiency.

Objectives: To demonstrate that the evidence of unusual clinical and laboratory findings in a well-known condition needs further investigations to rule out a different diagnosis. Methods: Serum CXCL9, CXCL10 and IL-18 levels measured using ELI-SA.T cell proliferation was assessed stimulating PBMCs with either anti-CD3 or PMA/ionomycin for five days.

Results: A 14 months old Caucasian male was admitted with a history of persistent fever, small palpable cervical lymphnodes, rash, pericardial effusion and arthralgia. He developed overt swelling of wrists and ankles. Laboratory findings showed: elevated CRP and ESR, neutropenia, lymphopenia and anaemia, with normal platelet count. Serum ferritin levels were markedly elevated and lactate dehydrogenase aspartate aminotransferase and triglyceride were also elevated. Fibrinogen was normal. Bone marrow biopsy showed haemophagocytosis. Based on the presence of arthritis in a child with fever and rash a diagnosis of sJIA was made with onset complicated by MAS. Treatment with glucocorticoid was started. Functional tests and genetic analysis of pHLH related genes were negative. After two weeks the patient presented normalization of laboratory parameters except for persistent anaemia and profound lymphopenia. Moreover, a mild muscle hypotone became apparent. These features, unusual in sJIA, triggered additional investigations. These revealed: reduced aptoglobin, high reticulocyte count and positive Coombs test, all suggestive of haemolytic anaemia. Immunological phenotyping revealed a reduced number of B cells, CD4 + T cells, CD8 + T cells and a defective proliferative response of T cells to phytohemagglutinin (PHA) and anti-CD3 (OKT3). A metabolic screening showed an increase in urine orotic acid, with normal citrulline serum level and low serum level of uric acid. Based on the presence of haemolytic anaemia, T lymphocyte defect and increase in urinary orotic acid, purine nucleoside phosphorylase (PNP) deficiency was suspected. The diagnosis was confirmed by marked reduction of enzymatic activity of PNP and by genetic analysis. The patient received an haplohydentical bone marrow transplantation (BMT) with a subsequent progressive clinical improvement. Serum levels of CXCL9 and CXCL10, two chemokines directly induced by IFNgamma (IFNγ) and of IL-18, were found markedly elevated at disease onset during active phase of MAS. Cytokines levels decreased progressively during disease course and completely normalized after the BMT.

Conclusion: This patient with a clinical presentation highly suggestive for sJIA onset complicated by MAS was later diagnosed with PNP deficiency with HLH. The diagnostic process was driven by some unusual features that became apparent when HLH clinical and laboratory features were controlled with glucocorticoids. Low T cells and profoundly defective response to mitogens suggested an immunodeficiency, low haptoglobin with positive Coombs test suggested an haemolytic anemia and increased urinary orotic acid suggested an alteration of the pyrimidine biosynthetic pathway. These findings were consistent with a diagnosis PNP-deficiency. CXCL9, CXCL10 and IL-18 levels suggested that patients with PNP-deficiency may have a subclinical activation of the IFNγ pathway and indeed they are predisposed to develop sHLH. Informed consent to publish had been obtained from the parents.

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood, divided into several subgroups. The sJIA could be presented by monocyclic, polycyclic or persistent polyarticular clinical course. Macrophage activation syndrome (MAS) represents the most devastating complication that could appear during the disease course. Studies on follow up, treatment response and disease complications of the sJIA patients are spare and rare. Objectives: To evaluate demographic and clinical characteristics and to explore the long-term treatment response and disease complications in a large cohort of sJIA patients from the single center. Conclusion: Systemic JIA is a subtype of JIA characterized by significant morbidity and mortality rate with macrophage activation syndrome being the most severe disease complication. Corticosteroids represent the main treatment modality. Biological agents should be considered in the steroid-resistant patients. The clinical remission could be achieved and chronic arthritis sequelae could be prevented in a majority of patients with biological agents.

Introduction: The optimal initial treatment for systemic juvenile idiopathic arthritis (sJIA) is unclear. Uncontrolled reports suggest that early treatment with biologic agents likely produces superior shortterm clinical outcomes, but many patients may respond well to nonbiologic therapies. To further study the initial treatment of sJIA, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed Consensus Treatment Plans (CTPs) to formalize and Pericarditis, pleuritis 12(7.1), 3(1.8) standardize current treatment practices. Subsequently, 4 CTPs were developed: initial systemic glucocorticoid (GC); initial methotrexate (MTX) +/-GC; initial IL-1 inhibition (IL-1i) +/-GC; and initial IL-6 inhibition (IL-6i) +/-GC. Objectives: The FiRst Line Options for Systemic JIA Treatment (FROST) is an observational study designed to assess the effectiveness and safety of each of the 4 CTPs and to the compare the CTPs containing initial biologic therapy (IL-1i and IL-6i) to those that do not contain initial biologic therapy (GC and MTX). Methods: Patients with recent onset sJIA who are initiating therapy are considered for enrollment in FROST. In order to be eligible for FROST, participants must have fever for ≥2 weeks, arthritis for ≥ 10 days, and at least 1 of the following: evanescent rash, generalized lymphadenopathy, hepatomegaly, splenomegaly, or serositis. Treatment assignment is at the discretion of the treating physician and family. All data are collected in the CARRA Registry. To date, 43 CARRA Registry sites have been activated to enroll FROST patients.

Biosamples are collected at baseline and at 6 months. Patient reported outcomes (PRO) of presence of fever and rash and pain scores are collected at home using mobile devices every 2 days during the first 2 weeks of the study. The primary study outcome is clinical inactive disease (Wallace ACR provisional definition) and cessation of glucocorticoid therapy at 9 months. Results: Enrollment in the FROST study began in November 2016. As of April 2018, 26 patients have been enrolled at 13 sites, and their baseline characteristics are shown in Table 1 . The proportion of patients with specific SJIA disease manifestations was: rash 89%, lymphadenopathy 31%, hepatomegaly 15%, splenomegaly 23%, serositis 8%, polyarthritis 46%. Overall, 15 participants (58%) have completed every requested home PRO during the first 2 weeks of the study, and 19 (73%) have completed ≥50% of the requested home PRO. Study follow-up continues to accrue. Eight patients (31%) have completed the 9-month study visit when the primary study outcome is assessed. Conclusion: Enrollment in the FROST study has begun. Participants enrolled thus far appear to be representative of the general population of patients with sJIA. Home PRO collection is feasible through the CARRA Registry. Additional time is needed to enroll and observe a sufficient number of patients to assess the comparative effectiveness of initial treatments for sJIA. Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a multisystemic disease characterized by fever, rash, arthritis and polyserositis. The most dreadful complication of sJIA is macrophage activation syndrome (MAS) that is seen in 10-25% of the cases. sJIA cases may follow monocyclic, polycyclic and chronic polyarticular course.

Objectives: The aim of this study was to demonstrate the frequency of MAS in sJIA cases and to see whether sJIA cases complicated with MAS follow a more severe course in the long term.

Methods: Files of sJIA cases that were followed in our clinic between May 2010 and September 2017 were reviewed. To be included in the study, the patient had to be coming regularly to follow-up visits and had to be completed the first six months of the disease.

Results: The cohort consisted of 53 sJIA cases. Mean duration of follow-up was 39.0 ± 24.1 months. Mean age at the time of diagnosis was 7.9 ± 4.5 years. There was a female predominance in the cohort (32 females, 21 males). The frequency of MAS was 33.9% (18 cases). MAS was observed much more common in male patients than female patients; 42% vs 28%, respectively. Bone marrow aspiration was performed to all patients to exclude malignancy. In 27.7% of MAS cases hemophagocytosis was not observed and hemophagocytosis was observed in 8.5% of cases without MAS. Initial laboratory test at the time of diagnosis of sJIA (leukocyte, hemoglobin, platelet, ferritin, triglyceride, ESR, CRP, fibrinogen, AST, ALT, albumin, and LDH) were compared in between patients with MAS and without MAS. Only ferritin and fibrinogen levels showed significant difference in between the groups (p<0.01). Patients that developed MAS had higher ferritin (4482 mg/dl) and lower fibrinogen (371 mg/dl) values than patients without MAS (ferritin 2060 mg/dl, fibrinogen 466 mg/dl) at the time of diagnosis of sJIA. When these laboratory parameters were compared at the time of diagnosis of sJIA and at the time of diagnosis of MAS, all parameters showed significant differences except CRP. Long term follow-up results showed that monocyclic course was observed in 45%, polycyclic course in 32% and chronic polyarticular course in 23% of the cases. We have observed that patients with MAS segregated equally into three groups. All MAS patients were initially treated with high-dose methylprednisolone and intravenous immunoglobulin. Additional treatments in MAS were cyclosporine (12 cases), anakinra (7 cases) and plasmapheresis (4 cases). Biologics were used in 38.8% of all cases. Biologic treatments were needed in 12.5% of monocyclic cases, in 50% of polycyclic cases and in 77% of chronic polyarticular cases. At the time of enrollment, 58% of patients were under remission without medication and 38% were under remission with medication. Only two cases were active and both cases were in the group of chronic polyarticular course.

Conclusion: All sJIA patients should be followed for the development of MAS. High ferritin and relatively lower fibrinogen levels at the time of diagnosis of sJIA may be early warning signs of impending MAS. sJIA patients that develop MAS do not seem to portend more guarded prognosis in the long term follow-up. sJIA patients that follow a chronic polyarticular course are possibly one of the hardest group of patients to treat in pediatric rheumatology.

None Declared This study was a retrospective chart review conducted in the pediatric department of a tertiary level teaching hospital from 2002 through 2016. The ILAR criteria were identified in each patient at the time of first presentation to our hospital. Seventy-four patients were diagnosed with sJIA. 12 boys and 15 girls formed this study cohort. A comparison of the baseline laboratory characteristics of patients who fulfilled the ILAR criteria and those with suspected sJIA has been shown in Table 1 .

Results: Diagnosis of MAS is confirmed by presence of haemophagocytic histiocytes in bone marrow. Bone marrow biopsy confirmed activated histiocytes engulfing a band neutrophil. Conclusion: A cytokine storm is a consistent feature in patients with MAS, and it is a potentially life-threatening complication of rheumatic diseases. The fact that highly effective treatment is needed in the early stage. So do that, early diagnosis is necessary. The conduct of the new 2016 classification critieria for MAS also underscored potential limitations. Additional validation of these criteria will be necessary. The BM biopsy will make up the weakness of limitation and early diagnosis will be more possible. The questionnaires focused on the incidence of Flu infection and Flu vaccination, and the efficacy and side effects of Flu vaccination. The frequency of each item was compared to that in the general population. Multivariable logistic regression analysis was performed to determine the risk factor on the Flu infection. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in the pediatric population. These patients coexist with the chronic disease, and present to a greater extent negative outcomes such as osteoporosis and cardiovascular diseases.

Objectives: To describe the biomarkers of lipid metabolism related to the cardiovascular risk of children and adolescents with JIA and to relate them to variables of the disease, lipid and glucose profile, nutritional status and food consumption.

Methods: Cross-sectional study with 62 JIA patients. The following were evaluated: disease activity and medications used, body mass index, height for age (z score), food intake (24 hour recall), lipid profile (total cholesterol -CT, low density lipoprotein -LDL, high density lipoprotein -HDL, triglycerides -TG and non -HDL), lipid markers such as apolipoproteins A-I and B (Apo A-I and Apo B). The association analyses were stratified as follows: HDL-c and Apo A-I into adequate and borderline/low; LDL-c, CT, TG, NHDL-c and Apo B into adequate and borderline/high; levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). For statistical analysis: Exact Fischer, Chi-square, Mann-Whitney and Spearman Correlation tests; p <0.05. Results: The mean age and time since diagnosis were 7.7 years (± 4.3) and 5.0 years (± 3.4), respectively. Active disease was observed in 33.9% of the patients and the prevalence of dyslipidemia was 62.9% overall when we considered lipid profile alone (CT, LDL-c, HDL-c, non-HDL-c and TG) and 82.3% when we included altered apolipoproteins (Apo A-I and Apo B). HDL-c and Apo A-I were the most frequently altered lipid markers. When comparing the subtypes, the systemic subtype had a higher value and higher frequency of altered LDL-c and NHDL-c and increased Apo B/Apo A ratio, when compared to the polyarticular subtype (p = 0.017, 0.042 and 0.03, respectively). When we cross-referenced the adequate or borderline/low HDL-c variable against other variables, patients with borderline/low HDL-c presented lower values and higher frequency of altered Apo A-I (p<0.001 and 0.001, respectively). There was no significant correlation between us-CRP and variables related to lipid metabolism. However, ESR showed a negative correlation with Apo A-I levels (r = -0.25, p = 0.047).

Conclusion: We conclude that dyslipidemia and alteration of lipid biomarkers are common in patients with JIA. The systemic subtype and elevated ESR were associated with lower concentrations of Apo A-I, indicating the participation of the inflammatory process in this alteration. Furthermore, the systemic subtype presented higher value and frequency of atherogenic particles, suggesting that patients with this subtype are at increased risk for the development of cardiovascular disease. Introduction: Increased ferritin is considered biomarker highly suggestive of primary and secondary HLH and it is one of the HLH-2004 diagnostic and MAS guidelines (1, 2) , nevertheless it could also be elevated in other inflammatory conditions. Interferon-gamma (IFNγ) and IFNγ induced chemokines, particularly CXCL9, have been demonstrated to be markedly elevated in patients with primary and secondary HLH. Objectives: To describe eight patients with hyperferritinemia who fully or partially met the HLH-2004 diagnostic guideline, but in which the subsequent clinical course and further investigations led to different diagnosis that required different therapies and to investigate the CXCL9 levels in identify diseases that may mimic HLH. To be noted that soluble CD25 was not measured in these patients. Methods: Serum CXCL9 levels were analyzed by DuoSet ELISA KIT DY392 (R&D Systems, Minneapolis, Minn). Normal values of CXCL9 are lower than 700 pg/ml. Results: We identified 8 patients with laboratory features suggestive of HLH, included high ferritin levels (>500 ng/ml). Three of these patients met five of the HLH-2004 criteria, two of them met four criteria and the others two met three criteria. One patient presented only high serum ferritin level and cytopenia. CXCL9 levels were <300 pg/ ml in seven of them and approximately 600 pg/ml in one patient. The clinical disease course and the other investigations ruled out the diagnosis of HLH and every patient received a different diagnosis. None of them received treatment for HLH (Table 1) . Conclusion: Since HLH is a life-threatening condition, early recognition and promptly therapy are essential to modify the disease course. One of the most typical feature of primary and secondary HLH is high ferritin levels. Due to the severity of the disease, sometimes patients need to be treated before all criteria are fulfilled. The eight patients reported had features highly suggestive of HLH and met the HLH-2004 criteria, or part of them. However they all received a different final diagnosis. Despite all presented with high ferritin levels, CXCL9 was low in all. CXCL9 is a chemokine specifically induced by IFNγ, and has been demonstrated to be markedly elevated in patients with primary and secondary HLH due to the activation of the IFNγ pathway. In these cases CXCL9 was able to differentiate diseases with high ferritin that mimics HLH. High CXCL9 levels appear to be a potential specific biomarker for HLH diagnosis. Early dosage of CXCL9 levels in patients with hyperferritinemia and with clinical suspicion of HLH may be helpful for a timely differential diagnosis. Introduction: Macrophage activation syndrome (MAS) is part of the spectrum of hemophagocytic disorders and is a serious complication of rheumatologic conditions, mainly systemic juvenile idiopathic arthritis (sJIA). Thrombotic microangiopathy (TMA) is a heterogeneous group of life-threating diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury. The association between TMA and hemophagocytic syndromes has been described only in single reports in adult renal transplant recipients and in two pediatric cases of virus-induced hemophagocytic lymphohistiocytosis. TMA complicating MAS has never been reported so far Objectives: To describe clinical and laboratory features, treatment and outcome of a cohort of patients with MAS complicated by TMA Methods: The clinical charts of patients with MAS and TMA seen at 3 Italian tertiary-care pediatric rheumatologic centers were reviewed retrospectively. Demographic, clinical and laboratory data at the time of TMA diagnosis were collected. Therapeutic intervention and outcome were also recorded Results: Five patients who met the criteria for MAS and developed TMA during the course of MAS were identified; one patient was excluded due to insufficient data. The underlying disease was sJIA or a sJIA-like disease in all patients. The median age at MAS onset was 8.6 years (4.2-12.8 yr), and the median interval between onset of MAS and occurrence of TMA was 13.5 days. TMA was characterized in all patients by renal failure with hematuria, and presence of schistocytes in blood smear. Three of the 4 patients experienced severe CNS involvement, with lethargy, seizures, or coma. The main laboratory features at TMA onset are shown in Table 1 . For the management of MAS, all patients received high-dose corticosteroids and cyclosporine; in 3 cases anakinra was added. All TMA episodes were treated with plasma-exchange; two patients were also given biologics (rituximab or eculizumab) with good results. During the course of TMA, aggressive and prolonged management in the Intensive Care Unit was required in all cases. All patients survived Conclusion: TMA is a dreadful complication of MAS, which is likely under-recognized. If not diagnosed timely and treated appropriately, TMA may precipitate the course of MAS and lead to a fatal outcome. Clues to suspect TMA in a patient with MAS are the increase in lactic dehydrogenase and decrease in platelet count out of proportion of the other laboratory abnormalities, the drop in haptoglobin level, the finding of schistocytes in blood smear, and the new onset of hematuria. Biologic medications, particularly rituximab and eculizumab may offer an adjunctive therapeutic option for refractory cases Introduction: There is no internationally agreed definition of 'JDM-Scleroderma overlap' in children and little data on the clinical characteristics, laboratory features and outcome in this specific group of JDM have been published. The goal of this survey is to achieve consensus on a meaningful definition of JDM-Scleroderma overlap in paediatric population and to determine whether overlap features affect outcome and management. Objectives: To develop criteria for the diagnosis of JDM-Scleroderma overlap using an international consensus process. Methods: A survey was circulated to all investigators in the Juvenile Dermatomyositis Cohort and Biomarker Study and Repository (JDCBS) and extended to other members of the Network for JDM in Paediatric Rheumatology European Society (PReS JDM working party) through a Delphi survey. Each individual was asked to identify those clinical manifestations that were felt to be most characteristic to enable them to make the diagnosis of JDM-Scleroderma overlap. The opinions on the importance of identification this subtype of JDM ware collected and the role of myositis autoantibodies has been mentioned in the questionnaire. Results: The survey had a response rate of 26.9% (41 individuals) from both JDCBS and PReS JDM working party. The most common clinical features identified by survey responders as found in JDM patients with scleroderma overlap were sclerodactyly, sclerodermatous skin change proximal to MCP joints, Raynaud phenomenon and ulceration at the tip of fingers, respectively. 95.1% of responders though the scleroderma overlap presentations influence the outcome of JDM, while 86.4% agreed that these features influence the choice of treatment. Interestingly, all of responders (100%) thought that negative myositis autoantibodies could not exclude the diagnosis JDM-Scleroderma overlap, but almost 11% used positive myositis autoantibodies to diagnose this subgroup of JDM. Myositis associated autoantibodies occurring in systemic sclerosis overlap (anti PM-Scl, anti U1-RNP and anti Ku) were thought to be the most commonly associated autoantibodies with JDM-Scleroderma overlap (78%), followed by systemic sclerosis specific autoantibodies (anti Scl70, anti RNA polymerase III) (44%). Although 83% felt that autoantibody profile influences the outcome, only 49% thought that autoantibody profile would influence the choice of medication. 89% of participants in this survey have seen patients with JDM-Scleroderma overlap.

Conclusion: This process identified clinical features that clinicians felt to be helpful or important in the diagnosis of JDM-Scleroderma overlap. A further process of secondary survey is necessary to agree an internationally acceptable, clinically usable set of classification criteria. Introduction: About 10-20% of patients with Kawasaki disease (KD) are resistant to intravenous immunoglobulin (IVIg) and are at increased risk of coronary artery abnormalities (CAAs). Early identification is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Japanese populations.

Objectives: We investigated the accuracy of 2 Japanese scoring systems and studied factors associated with IVIg resistance in a large multiethnic French population of children with KD to build a new scoring system. Methods: Children admitted for KD between 2011-2014 in 65 centers were enrolled. For patients fulfilling American Heart Association (AHA) criteria, we identified factors predicting resistance to IVIg by multivariate regression analysis. The performance of our score and the Kobayashi and Egami scores were compared in our population and in ethnic subgroups.

Results: Overall, 465 children were reported by 84 physicians; 355 (76%) fulfilled AHA criteria (55% European Caucasian, 12% North African/Middle Eastern, 10% African/Afro-Caribbean, 3% Asian and 11% mixed). Eighty patients (23%) needed second-line treatment. Japanese scores had poor performance in our whole population (sensitivity 52-44.5%). Predictors of IVIg resistance were ALT≥30 IU/L, hemoglobin level <10 g/dl, lymphocyte count <1500/mm 3 , modification of extremities, CAAs at initial echocardiography, and time to treatment <5 days. The best sensitivity (80%) and specificity (65%) of this model was with weighted variables and cut-off ≥ 17.5/50 points. The sensitivity remained good in our 3 main ethnic subgroups (78-83%). Conclusion: We identified predictors of IVIg resistance and built a new score with good sensitivity and specificity in a non-Asian population. Introduction: Persistent fever and inflammation after infusion of 2g/ kg of IVIG, the standard treatment of KD represents a high-risk situation for coronary aneurysms in Kawasaki disease. Identifying patients at risk for IVIG resistance is difficult outside the Asian population, and there remains a critical unmet need to identify an anti-inflammatory treatment that is efficacious in all KD patients. Recent evidence from studies in animals and humans suggest a critical role for interleukin-1 (IL-1) α and β in the pathogenesis of KD. Objectives: To identify the clinical characteristics, reasons for use and response to treatment with anakinra in a retrospective series of patients with Kawasaki Disease (KD). Methods: A retrospective chart review of patients treated with anakinra for KD diagnosed according to the AHA criteria. We compared clinical, biological and echocardiographic characteristics of KD before and after anakinra use. We analysed reasons for use of anakinra, and compared treatment regimens used in 7 European KD referral centres. Results: Eight boys and 3 girls with treatment-refractory KD, aged 4 months to 9 years old, received at least 2 different KD treatments prior to anakinra, which was given on mean at 25 days after disease onset (8 to 87 days). The main reasons for use of anakinra were clinical and biological inflammation, progression of coronary dilatations, and severe myocarditis with cardiac failure. Doses of anakinra ranged from 2 to 8 mg/kg and duration varied from 6 to 81 days. On anakinra treatment, fever disappeared within hours (<24 h) in 3 patients, and within 2 and 6 days in two patients respectively. Six others patients were not febrile at onset of anakinra. In addition, CRP levels fell two to three fold within 48 hours in 7/9 evaluable patients. In terms of its effect on coronary artery dilatation, Z scores decreased in 10/ 11 patients and increased in one who died suddenly of pericardial hemorrhage. Conclusion: Anakinra used late in the disease course led to a rapid and sustained improvement in clinical and biological inflammation. However, our retrospective analysis did show neither a striking nor a rapid decrease of coronary dilatations and we cannot determine if anakinra itself had an effect on coronary artery dimensions. More robust data will be available soon from the two Phase II ongoing trials, KAWAKINRA using anakinra treatment early after one failure of IVIG treatment (European Clinical Trials no. 2014-002715-41) and ANAKID (ClinicalTrials.gov identifier: NCT02179853), focused on patients with coronary giant aneurysms.

Introduction: Takayasu arteritis (TA) is a chronic large-vessel vasculitis affecting the aorta and its major branches. Glucocorticoids (GCs) can achieve remission in most patients with TA. As most patients suffer relapse after reducing GCs, additional therapy such as methotrexate, azathioprine and intravenous cyclophosphamide (IVCY) has been applied. Recently, the efficacy of TNF-α inhibitors or tocilizumab (TCZ) has been reported. However, there remain insufficient data on clinical characteristics and outcomes of patients with childhoodonset TA, including recent therapeutic advances. Objectives: We aimed to retrospectively analyse the characteristics and outcomes of patients with childhood-onset TA in two tertiary centres in Japan. Methods: Subjects were 24 patients with TA diagnosed when younger than 18 years. Follow-up duration was more than 2 years. Diagnosis of TA was based on the EULAR/PRINTO/PRES criteria. We divided the subjects into two groups: those who did and did not experience relapse. Relapse was defined as NIH criteria for active disease in TA. We analysed the patients' background, treatment and complications. We additionally compared two groups according to prednisolone (PSL) reduction rate and whether or not they carried HLA-B52. Binary data were analysed by Fisher's exact test, and quantitative data by Mann-Whitney U test. The cumulative relapse rates after the diagnosis were estimated using the Kaplan-Meier method; differences between two groups were assessed by the log-rank test. Results: Median age at onset was 13.0 (range; 0.5-18.0) years old (male:female, 11:13). Thirteen patients (54%) had HLA-B52. Period from onset to diagnosis was 1 (0-66) months. Angiographic classifications were I, IIa, IIb, III, IV and V (n=3, 2, 4, 1, 2 and12), respectively. Four patients and one patient had pulmonary artery involvement and coronary involvement, respectively. Three patients achieved drug-free remission. Median dose of prednisolone (PSL) was 0.8 (0.4-2.4) mg/kg/day at initiation of treatment and 0 (0-0.3) mg/kg/day at the last visit. Immunosuppressants were used in 13 (54%) from the onset and in 21 (88%) at the last visit. IVCY was used in 10 patients (42%) from the onset, and 4 after the relapse. Some biologics were used in 4 (17%) from the onset, and in 12 (50%) at the last visit. Twelve patients (50%) experienced relapse, and median number of relapses was 3 (1-6) times. The ratio of relapse was not significantly different between the HLA-B52 positive and negative patients (69% vs 27%, P=0.099). However, median duration from diagnosis to the first relapse was significantly shorter in HLA-B52 positive patients than negative patients (6 vs 51months, P=0.016). The reduction pace of PSL was significantly greater in relapsed patients than nonrelapsed patients (0.058 vs 0.025 mg/kg/month, P=0.017). The cumulative relapse rates after the started IVCY or TCZ were not significantly difference between the patient who introduced IVCY (n=14) and TCZ (n=12) (P=0.10). Nine patients (38%) had cardiovascular complications (aortic valve regurgitation (AR) (n=4), annuloaortic ectasia (AAE) (n=1) and AR+AAE (n=4)). Two patients underwent cardiac surgery. Ten patients had osteoporosis, 2 had surgery for glaucoma and 5 had some mental disorders in their clinical coarse.

Conclusion: Approximately half of the patients with childhood-onset TA experienced relapse despite using immunosuppressants and/or biologics. HLA-B52 positivity and rapid reduction rate of PSL significantly increased risk of early relapse. Furthermore, cardiovascular involvement and GCs-related complications were common. Our study suggests the outcome of childhood-onset TA remains unfavourable. structured separately for pediatrics and adults, to provide consistency in myositis outcomes. The MDI documents persistent changes in 11 organ systems thought to be related to damage. There is a dearth of studies on damage caused by Juvenile Dermatomyositis (JDM) especially from less resourced countries and hence our study. Objectives: Primarily to assess the myositis damage index in a cohort of children with JDM from a single centre in Mumbai, India and secondarily to study associations of factors leading to long term damage in these children. Methods: After ethics approval and consents, a total of 23 patients with JDM under regular treatment and at least a 2 year follow up, at first study visit were identified. Specifically excluded were children with overlap syndromes eg scleromyositis. The MDI was assessed as severity of damage and extent of damage at the first study visit and reassessed at a second visit at least six months later and only damage present at both visits were scored to give a final severity and extent of damage score. There were no drop outs. Results: 23 children with age range at disease onset 1y -17.9 y (mean 6.9 y, median 6.8 y, IQR 3.5-8.8) were diagnosed as JDM after a duration of symptoms ranging 1m-30 m (mean 6.8 m, median 5 m, . Their age at the study visit ranged from 5.5 y -24.8 y (mean 13.4 y, median 12.9 y, IQR 10.4-15.3) after a follow up duration ranging from 2 y -20.1 y (mean 5.9 y, median 4.2 y, IQR 2.6-8.5, Total 136.5 patient years). The disease course was monocyclic in 14, continuous in 6 and polycyclic in 3. The total MDI extent of damage score ranged from 0-8 / 35 (children) or 37 (adolescents) (mean 2.04, median 2.0, IQR 0.5-2.5) and severity of damage score ranged from 0-24.7 /110 (mean 4.7, median 3.5, IQR 1.3-6.4). 17/23 children had damage in one or more organ systems, with 9 showing damage in one organ system, 4 in two organ systems, 3 in three organ systems and 1 child showed damage in six systems. Cutaneous (16/23), endocrine ie growth retardation (6/23) and muscle (5/23) were the most commonly damaged organ systems with 2 children showing skeletal damage while ocular, gastrointestinal and cardiac domains were involved in one each. Importantly, over this duration of follow up there were no children with infection, pulmonary, peripheral vascular disease or malignancy. Correlation between age at onset, gender, time to diagnosis, course of disease and duration of follow up did not yield statistically conclusive results. Conclusion: This is amongst the earliest studies to report damage due to JDM from less resourced countries. Over the median follow up period of 4.2 years about 75% of the children suffer damage in one or more domains, cutaneous damage being the commonest. Uniquely despite high infection rates in the community, this domain was unaffected in our population. Continued enrolment with longer duration of follow up are needed to shed light on factors influencing damage. Introduction: The first composite disease activity score for juvenile dermatomyositis (JDM), named JDMAI, has recently been developed and validated in retrospective patient datasets. It is composed of 4 domains and takes into account the parents' perception of disease status. The 6 preliminary versions of the tool performed similarly in previous validation analyses. Objectives: To test prospectively the validity of the JDMAI in a sample of JDM patients seen in daily practice. Methods: A total of 53 JDM patients seen consecutively at 2 tertiary-care paediatric rheumatology centers, either at disease onset or at a follow-up visit, a median of 2.3 years after disease onset, were enrolled. Each patient received a retrospective assessment and a cross-sectional evaluation at study entry. Twenty-two patients also underwent a second (prospective) assessment after a median of 3.5 months from study entry. Physician-centered evaluations included assessment of muscle, skin and overall disease activity on a visual analogue scale (VAS) or through the Disease Activity Score (DAS), rating of disease state and course and measurement of disease damage with the Myositis Damage Index (MDI). Laboratory data comprised muscle enzymes and ESR. Parent-reported outcomes were collected through the administration of the Juvenile Dermatomyositis Multidimensional Assessment Report (JDMAR). Validation analyses included assessment of construct validity, internal consistency (with Cronbach's α), discriminant ability, and responsiveness to change in disease state over time (with standardized response mean, SRM). Results: All JDMAI versions showed strong (r>0.7) correlations with muscle disease activity VAS (0.85-0.87), muscle section of DAS (0.81-0.83), total DAS (0.89-0.92), pain VAS (0.72-0.75), and fatigue VAS (0.92-0.93). The correlations of the different JDMAI versions with the skin index not contained in the specific version (skin disease activity VAS or skin section of DAS) were strong (0.74-0.79). As expected, JDMAI correlations were moderate (r=0.4-0.7) or low (r<0.4) with laboratory parameters (CK, LDH, AST, ALT, and ESR) and with the MDI (0.1-0.11). The SRM was greater in patients judged as improved by the physician or the parent (1.26-1.56) than in those judged as not improved (0.88-1.11). Cronbach's α was very high (0.89-0.91) for all JDMAI versions. All JDMAI versions discriminated strongly between patients classified in different disease activity states by the physician (p<0.0001) or by the parent (p=0.002-0.005), and between patients whose parents were satisfied or not satisfied with their children's disease status (Mann-Whitney U test, p=0.0005-0.0008). Conclusion: Validation analyses in this prospective patient sample confirmed that the JDMAI possesses good measurement properties and is a suitable and reliable tool for the assessment of disease activity in children with JDM both in clinical practice and research. Importantly, the new tool revealed a strong capacity to capture the improvement of disease activity over time. Introduction: Juvenile dermatomyositis (JDM) is the most common of the pediatric inflammatory myopathies characterized by inflammatory microvasculopathy. Nailfold videocapillaroscopy (VCP) is an in vivo, rapid, and inexpensive imaging technique that allows quantitative assessment of microcirculation. VCP has demonstrated a key role in diagnosis and disease monitoring. The most severe videocapillaroscopy semi-quantitative changes previously reported as loss of capillaries, enlarged loops and brushy capillaries are associated with longer disease duration 1 . There is a lack of specific quantitative measures of the capillaries during disease curse. Objectives: To describe qualitative and semi-quantitative VCP assessment in Mexican patients with JDM . Methods: The present study was a cross-sectional observational study that analyzed 192 images from 24 patients with JDM during different of the disease course, form 3 diferent centers in Mexico. VCP was performed by the same examiner (AVT), images were obtained from all fingers except thumbs of both hands using a videocapillaroscope with a 200x optical probe. The images were collected, coded, and stored using OptiPix software (version 1.7.16).Semi-quantitative assessment for architecture were scoredfollowing the international definitions for the capillary abnormalities.2 Quantitative assessment consist in the measurement of the number of capillaries per millimeter, capillary loop length, capillary width, intercapillary distance in micron (μm) 3 . Results: Twenty four patients with JDM were included, 62.5% female. The qualitative assessment reveal only 4 images with normal capillaroscopy pattern, nonspecific alterations were found in 31.2%. Conclusion: VCP is a noninvasive image method that's provides a window to microcirculation and allows quantitative assessment of nailfold capillaries with a grave reliability and gave reproducible results. This study found more quantitative alterations than previously reported. A combination of qualitative and quantitative measures can be used for JDM diagnosis, monitoring and response to treatment. To our knowledge this study is the first in measuring quantitative, semi-quantitative and qualitative parameters of the microvasculature in juvenile dermatomyositis. Introduction: The inflammatory idiopathic myopathies (IIM) are a rare group of myopathic autoimmune diseases diagnosed in both adults and children. Patients' present with proximal muscle weakness with associated skin changes in dermatomyositis. Immunohistochemical analysis of muscle tissue from these patients has identified immune cell infiltrate and the expression of pro-inflammatory cytokines however, little is known about the peripheral immunological profile in juvenile and adult patient groups. Objectives: To identify specific immune cell signatures and cytokine profiles for disease subtypes and correlate this data with measurements of disease activity. Methods: 44 adult myositis (AM) patients, 15 Adolescent-onset juvenile dermatomyositis (JDM) patients, 25 age-matched adult healthy controls (AHC), and 15 age-matched teenage healthy controls (THC) were recruited with appropriate ethical approval after obtaining written informed consent. Peripheral blood mononuclear cells (PBMC) were isolated from patient and control samples. PBMC from all groups were analysed by flow cytometry to quantify 32 lymphocyte populations including; T-cell, B-cell and monocyte subsets. The AM patients were grouped according to myositis subtype; 19 dermatomyositis (DM), 9 polymyositis (PM), 7 DM + overlap, 4 DM + cancer and 5 PM + overlap). Disease activity was determined by MITAX score and clinicians' decision on treatment; remission off treatment, remission/mildly active/active on treatment. Cell populations were analysed by group for differences in fold change/adjusted p value (1-way ANOVA with Tukey's multiple comparison). Results: There was an idenified T cell signature in ADM (increased Th17, Tregs and CD4+ naïve), a B cell signature in APM (CD27+/-B cell ratio) and a T cell signature in JDM (CD4/CD8+ T cell ratio). A decrease in CD8+ central memory T-cells was observed in both AM and JDM patients compared to healthy controls, this reduction was most significant in active disease. AM patients also had reduced CD27+ memory B-cells compared to both JDM patients and healthy controls.

AM patients in remission off treatment had increased non-classical monocyte subset frequencies, whereas JDM patients off treatment had elevated CD8+ EMRA T-cells. Th17 cells were significantly increased in ADM compared to JDM samples (mean = 3.68 vs. 0.64, adjusted p value = 0.0032). More specifically increased Th17 cells were found in ADM but not APM (mean = 3.67 vs. 0.68, adjusted p value = 0.0019). However, the Th17 population was highest in AM patients that were in remission on treatment (remission on treatment vs AHC, mean = 2.68 vs. 0.84, adjusted p value = 0.038). Conclusion: This group of diseases are notably heterogeneous both clinically and immunologically as shown by the complex immunophenotyping patterns identified within myositis subgroups. This study identified signatures unique to adult compared to juvenile disease, and between AM patients on treatment and during remission. The Th17 signature concurs with studies pinpointing these cells within the muscle tissue. This data supports the need for further investigation for the use of IL-17A inhibitors in the treatment of the IIM.

Introduction: There are various diagnostic and classification criteria for myositis, but they are not always suitable for juvenile idiopathic inflammatory myositis (JIIM). To establish standard diagnostic criteria, the International Myositis Classification Criteria Project (IMCCP) published the EULAR/ACR classification criteria for idiopathic inflammatory myositis (IIM) in 2017. Objectives: To evaluate the validity of the EULAR/ACR classification criteria with JIIM cases in Japan. Methods: We used clinical and laboratory data from a group of JIIM patients and a comparator group comprised of non-JIIM patients with mimicking conditions collected at seven major pediatric rheumatology centers in Japan between 2008 and 2015. A diagnostic confirmation made at least 6 months prior to the study by a pediatric rheumatologist was used as the inclusion criterion for this study. Results: The total of 117 patients (68 JIIM patients and 49 non-JIIM patients) were included to the study. For the validation analysis, we applied 55% probability cutoff, which corresponds to "probable IIM", based on the IMCCP study. The IMCCP's diagnostic standard gave us an almost equivalent sensitivity (86.7% without muscle biopsies; 92.1% with muscle biopsies) and a higher specificity (100% without/ with muscle biopsies) compared to the data reported in the IMCCP study. We also confirmed an improved sensitivity with the EULAR/ ACR classification criteria, compared to other traditional diagnostic criteria (e.g. 86.7 % with the EULAR/ACR criteria vs 80.9% with the Bohan and Peter criteria). In terms of the diagnostic accuracy, the 

Enlarged capillary Introduction: Juvenile dermatomyositis (JDM) is a rare and heterogeneous inflammatory myopathy. Clinical features may be severe and disease course refractory to standard treatment with corticosteroids and methotrexate (MTX). Evidence for a critical role of the type I interferon (IFN) pathway in the pathophysiology of dermatomyositis exists in both childhood and adult forms of the disease. Objectives: To report the first case of severe vasculopathic JDM successfully treated with the JAK 1/2 selective inhibitor ruxolitinib. Methods: Retrospective chart review from initial presentation to last follow-up. We assessed type I IFN status by IFNα digital-ELISA quantification in serum, STAT1 phosphorylation and RNA expression of IFNstimulated genes in whole blood. Results: A previously healthy 13-year-old girl presented with cutaneous lesions and a severe proximal muscle weakness (Childhood Muscular Assessment Score, CMAS 2/52, and Manual Muscle Testing, MMT 38/80) characteristic of JDM. CK level was elevated and anti-NXP2 antibodies positive. Muscle biopsy revealed severe vasculopathic lesions. Despite treatment with prednisone (1.2mg/kg/day) and MTX, she developed tetraplegia, dysphonia, dysphagia, intestinal involvement, and new skin lesions. Treatment escalation with IVIG, plasma exchange (5/week), rituximab, and increased prednisone resulted in clinical improvement. Thus, plasma exchanges were subsequently spaced out and discontinued 6 months after diagnosis. However, three weeks later, recurrent muscle weakness necessitated the restart of plasma exchanges, increase of prednisone, a 4 th dose of rituximab, and initiation of mycophenolate mofetil (MMF). While prednisone and the frequency of plasma exchanges were slowly tapered, she developed two further muscular, cutaneous and intestinal relapses, as well as a diffuse fascia calcinosis, at 12 and 18 months after diagnosis. High levels of IFNα protein in the serum (238, 75, and 46 fg/mL, normal < 10 fg/mL) and an increased expression of ISGs were documented. A constitutive phosphorylation of STAT1 and STAT3 was recorded in T lymphocytes and monocytes from the patient compared with controls. Considering these results, ruxolitinib was started (10mg x 2/day). Rituximab and MMF were discontinued. Within 2 months, CMAS and MMT scores increased from 47 to 52 and from 57 to 79, respectively. Plasma exchanges were discontinued and prednisone decreased. Eight months post initiation of ruxolitinib, JDM was clinically inactive according to the PRINTO criteria and prednisone was tapered (0.15mg/kg/day). Ruxolitinib was well tolerated. Serum levels of IFNα stabilized and STAT1 phosphorylation in monocytes was comparable to a control 4 hours after drug intake. Informed parental consent was obtained for the use of ruxolitinib on a compassionate basis and for conducting the experiments. Conclusion: Efficacy of JAK1/2 inhibitors has previously been reported for severe dermatomyositis in adults and for certain monogenic interferonopathies in children. Our findings suggest that JAK inhibition may also represent an efficacious and well-tolerated therapeutic option in a subset of patients with recalcitrant JDM. Informed consent for publication had been obtained from the parents.

Introduction: Juvenile Dermatomyositis (JDM) is a rare, potentially life threatening condition. Beginning with mild fatigue and weakness, the condition can occur at any age, and currently there is no known cure. Some children and young people can experience fluctuations between remission and relapse throughout their childhood, into adolescence and beyond. There is very little evidence about the psychological impact this condition has on children and young people, and none that has asked them directly, however, through experience from clinical practice and conversations with those affected, we know the effects can be profound. Objectives: The aim of this study was to identify the lived experience of children and young people between the ages of 8 and 19 years of age diagnosed with JDM. This study constitutes the first part of a larger mixed-methods study. Methods: Ethical approval was gained to interview children and young people who were enrolled in a wider cohort study. Young people were interviewed either using creative arts based methods, such as drawing in a comic book and parallel discussion, or with a standard verbal interview. Young people were all asked: 'what it is like to have JDM?' Further questions were used to probe or to add clarity. Interviews took place when attending a specialist Rheumatology clinic or the inpatient Rheumatology Ward of a tertiary specialist Rheumatology Centre or during a specially arranged home visit. Results: Fifteen young people offered to share their story, their demographics are shown in Table 1 . The interviews lasted between 18 to 130 minutes and all, with permission, were audio recorded. They were transcribed verbatim and analysed using Interpretive Phenomenology. The overarching metaphor of a 'Rollercoaster' was developed from the interview transcripts, to depict the ups and downs of having JDM. From initial difficulties with diagnosis by local health professionals of a rare disease to feeling comfort at getting a diagnosis, to the low of not being able to walk, to the relief when medications start to work and some improvement is felt. The 'Rollercoaster' metaphor is visual, easy to explain and understand, and will allow young people to feel some support from seeing the journey ahead. Within this overarching construct, there are five themes which emerged from the data. These are: being-confused in the beginning; being-different; sick-steroidal-and-scared of the medicines; beinguncertain; and having-acceptance, as the JDM journey continues for many years. Conclusion: This study is the first to ask children and young people what it is like to have JDM, and to recount the 'ups and downs' of their lives and describe the ways that JDM affects them. The results from this study will lead to a wider study asking young people all over the United Kingdom to share their story through surveys examining aspects which have been highlighted so far, this will lead into dissemination workshops to share the results found not only with children, young people and their families, but also with health professionals. Table 1 reports the clinical characteristics for both groups. Adult DM had a significantly higher proportion of lung involvement and ANA positivity compared with JDM (p=0.002 and p=0.02, respectively). Dilated capillaries, giant capillaries, hemorrhage and neovascular pattern were found in 86%, 0%, 29% and 14% of JDM patients, respectively, and in 71%, 26%, 43% and 29% of adult patients, respectively, but with no statistically significant difference between children and adults. Clinically inactive disease was found in 38% and 10% of JDM and adult DM patients, respectively. All of those children have stopped medication. There was one case of malignancy in an adult DM patient. Conclusion: Nailfold microvascular abnormalities were found in most of the NFC parameters, in JDM patients assessed for after a median of 8 years of disease, which might reflect the long-term microangiopathy associated with this disease. Regarding the studied clinical features, in our cohort, the adult DM patients have higher lung involvement when compared to JDM. Introduction: Idiopathic myopathies are heterogeneous disorders characterized by muscle weakness and inflammation. Dermatomyositis is the most frecuent subgroup in pediatrics. Juvenile Dermatomyositis (JDM) in addition to muscle involvement is characterized by typical skin rashes (Gottron´s sign and heliotrope rash). Recently, a new proposal of diagnostic criteria was The unit followed 119 children with poststreptococcal reactive musculoskeletal symptoms: 61 rheumatic fever, 55 poststreptococcal reactive arthritis and 3 had only diffuse myalgia -acute onset, incapacitating and severe pain (one girl and two boys). The mean age at diagnosis was 5,7 years. Tonsillitis was the previous streptococcal infection in all patients (one scarlet fever). The time span between the infection and myalgia presentation had a variation between 25 and 30 days. The longest myalgia duration was nine weeks and the shortest was one week and four days. Lower limbs were involved in all patients and upper limbs in two. Arthralgia without arthritis was present in two patients. At diagnosis visual analog score (VAS) of muscle pain was ≥ 80 mm and all patients had elevation of inflammatory markers (erythrocyte sedimentation rate between 86 and 102mm/h and C-reative protein between 4,9 and 6 mg/dl) and normal creatine kinase (CK) values. The antistreptolysin O titre (ASLO) performed in all patients were strongly positive (≥ 800 U/l and ≤ 1820 U/I) and echocardiography was normal. Two patients had full recovery with NSAIDs but one refractory patient also needed prednisolone (1mg/kg) during four weeks. Conclusion: Severe diffuse pain and tenderness of skeletal muscles without accompanying arthritis is an under-recognized feature of post-streptococcal disease. High ASLO titre with normal CPK in a child with myalgia should alert PSPM diagnosis. We propose the Coimbra diagnostic criteria for PSPM.

Introduction: Juvenile dermatomyositis (JDM) is a systemic autoimmune capillary vasculopathy that predominantly affects the muscles and cutaneous tissues. In JDM cases, myosonography can reportedly be used to evaluate disease activity and perform followup monitoring. However, the effectiveness of myosonography in clinically amyopathic JDM (CA-JDM) is undetermined. Objectives: To investigate the myosonographic findings in patients with CA-JDM. Methods: Myosonography was performed in three patients with CA-JDM. Case 1 was a 2-year-old male with full range of motion in manual muscle testing (MMT), positive anti-TIF-1γ antibody results, and superficial perivascular dermatitis; case 2 was a 4-yearold male with full range of motion in MMT, negative myositisspecific autoantibody results, and superficial perivascular dermatitis; case 3 was a 14-year-old female with full range of motion in MMT, positive anti-MDA5 antibody results, interstitial pneumonia, and superficial perivascular dermatitis. Case 3 had minimal evidence of myositis on MRI and in a biopsied specimen. Laboratory testing revealed normal creatinine kinase concentration in all three cases. The ultrasonographic assessment was performed in the bilateral biceps brachii and quadriceps femores.

Results: In case 1, the right biceps and quadriceps had increased echo intensity compared with the left side, and the power Doppler signal was positive on the perimysium in the left biceps and quadriceps. In case 2, the echo intensity was increased in the bilateral biceps and quadriceps, and there was a positive power Doppler signal on the perimysium in all muscles. In case 3, there was a high echo intensity and positive power Doppler signal on the perimysium in the left quadriceps, and there was a suspected positive power Doppler signal on the epimysium in the left quadriceps. Objectives: A 10-year-old boy consulted with a 6-days history of fever, abdominal pain, vomiting and a scarlatiniform rash. Initial blood tests showed Hb 9.7 g/dl, WBC 14.2 × 10 9 /L, platalet count 442 ×10 9 /L, C-reactive protein 68.8 mg/L, erythrocyte sedimentation rate 65 mm/hr, albumine: 2.8 g/dL, increased amylase of 639 U/L and lipase 2056 U/L. In echocardiographic examination myocarditis was seen and pro-BNP level was 11418 pg/ml. Intravenous immünoglobulin (IVIG) at a dose of 2 g/kg and aspirin 40 mg/kg/day was given with a preliminary diagnosis of atypical Kawasaki disease. The patient became afebrile 24 hours later. In the second week of the disease thrombocytosis (platelet count, 780 ×10 9 /L) and periungual desquamation of his fingers and toes were observed. Coronary arteries were normal and cardiac contractions were good in echocardiography. His pancreatitis had resolved with a normal amylase of 97 U/L and lipase of 29 U/L within two weeeks. Methods: A 6-year-old girl was referred with a 4-days history of vomiting and abdominal pain. Her physicial examination was normal except abdominal tenderness. Initial investigations showed Hb 14.4 g/dl, WBC 41.8 × 10 9 /L, platalet count 443 ×10 9 /L, Creactive protein 50.6 mg/L, erythrocyte sedimentation rate 1mm/ hr, albumin: 1.9 g/dL. In abdominal ultrasonograpy hydrops of gallbaldder was detected. Few days later purpuric rash on her legs was observed. She was diagnosed as HSP and prednisolone at a dose of 2 mg/kg/day was given to her. Despite steroid treatment, back and chest pain added to abdominal pain. Increased amylase of 344 U/L and lipase 294 U/L levels were detected at the seventh day of disease, but ultrasonographic pancreatitis was not observed. In addition to fat free diet intravenous fluids and pulse steroid treatment (30 mg/kg, for 3 days) was given. In the second week of the disease proteinüria was detected in 24 hour urine testing, and mesengioproliferative glomerulonephritis was diagnosed in renal biopsy. Pulse cyclophosphamide treatment was started her for HSP nephritis. Her pancreatitis resolved within a month Results: HSP and KD are most common types of vasculitis in children. But, HSP and KD associated pancreatitis is uncommon. There are autopsy studies about KD associated pancreatitis. The association between pancreatitis and HSP is rare. Conclusion: In conclusion HSP and KD related pancreatitis is rare. HSP-related pancreatitis should be considered when abdominal pain is prolonged and present with changing character of pain. KD should be considered in the presence of acute pancreatitis and prolonged fever even the patient does not meet all the criteria. Informed consent to publish had been obtained.

Introduction: Kawasaki disease (KD) is one of the most common vasculitis of childhood. Coronary artery involvement is the most important complication of the disease and the major cause of the mortality. IVIG resistance is defined as persisting or recurring fever at least 36 hours after the end of intravenous infusion of immunoglobulin (IVIG).

Although there are some scoring systems trying to predict, it is not always possible to forsee the IVIG resistance and coronary artery involvement.

Objectives: The aim of this study is to assess the success of the Kobayashi scores and other parameters in predicting IVIG resistance and coronary artery involvement in Turkish population. 1686ng/L and NT-proNBP 14800pg/mL. Tryptase was normal (3.9mcg/L). Bilateral pulmonary insterstitial infiltrates with bilateral pleural effusion were identifed on chest x-ray and ECG and echocardiogram were suggestive of myopericarditis. The patient was admitted to the pediatric intensive care unit. Antibiotherapy was switched to vancomicin plus meropenem and anti-inflammatory drugs, furosemide, espironolactone and immunoglobulin were started. Due to hemodinamic instability, mechanic ventilation and aminergic support were needed. Further exams were performed: bronchoalveolar lavage was negative for bacteria and fungi; myelogram showed hypercellular medulla with increased non-clonal eosinophils (41%); skin biopsy revelead leukocytoclastic vasculitis with eosinophils and direct immunofluorescence compatible with vasculitis. Anti-myeloperoxidase (MPO) antineutrophil cytoplasm antibodies (ANCA) were negative. The genetic analysis for hypereosinophilia syndrome mutations was negative. The pediatric rheumatology team was called to observe the patient and, according to the clinical presentation and laboratory results, the diagnosis of EGPA was made. The patient was started on methylprednisolone i.v. 1 g per day for three days. A fast clinical, laboratory and radiological improvement occurred, including complete regression of eosinophilia. Currently, more than six months after this episode, the patient is followed at the pediatric rheumatology outpatient clinic and there are no signs of disease activity under therapy with azathioprine (2mg/kg) and prednisolone in progressively lower doses. Conclusion: We present a patient with EGPA, fulfilling 5 of 6 criteria (asthma, eosinophilia exceeding 10% of the total white blood cell count, history of allergy, pulmonary infiltrates, extravascular eosinophils), associated with musculoskeletal and cardiac abnormalities and negative anti-MPO ANCA. In conclusion, EGPA is a potentially life-threatening condition, clinical suspicion and early treatment of these patients are thereby crucial. For this case submission written informed consent was obtained from the patient and family.

Introduction: Henoch-Schönlein purpura nephritis (HSPN) is the most severe complication of Henoch-Schönlein purpura (HSP) that can occur at any time of the disease process and includes isolated microscopic or macroscopic hematuria, mild or heavy proteinuria with or without nephrotic syndrome, renal failure and hypertension. Objectives: To determine a possible prognostic factor for earlier HSPN onset, to explore indications for kidney biopsy according to urine analysis and the correlation between 24-h urinary protein levels and biopsy findings, as well as biopsy findings and patient outcome. . No significant differences were found concerning age at baseline (3.6 ± 0.6 vs. 2.1 ± 0.5 years old), sex ratio (0.9 vs 0.5 M / F, p> 0.05) respectively in cKD-ICU and iKD-ICU patients; total duration of fever, initial biology or extreme values (hemoglobin, platelets, leucocytes, CRP, ASAT, ALAT, natremia) were also similar in both groups. iKD-ICU patients were more frequently hospitalized in ICU before onset of fever (43.4 vs 8%, p = 0.01). The delays between onset of signs or hospitalization in ICU and the first course of IGIV were similar in both groups. Intravenous corticosteroid therapy was used in 36% of cKD-ICU vs 20% of iKD-ICU patients (p = 0.2); a second course of IGIV was used in 52% of cKD-ICU vs 47% of iKD-ICU patients (p = 0.7). All patients received a broad-spectrum antibiotic. Other therapeutics and evolution features were not significantly different between 2 groups. Conclusion: KD-ICU patients had no initial or evolutive differences whether they met complete or incomplete AHA criteria. The strong suspicion of KD is therefore enough to initiate specific therapeutics These patients would likely benefit from an early  and aggressive treatment, although the most appropriate treatment  strategy remains unknown. To date 3 cases of pediatric patients with  giant aneurysms have been published showing a good response to anti IL-1 (anakinra). In addition, 3 clinical trials with antiIL-1 are currently ongoing. Abciximab (monoclonal antibody against the GPIIb / IIIa glycoprotein receptor located on the surface of platelets) has been used in cases with giant aneurysms and preliminary data suggests a positive effect on the vascular remodeling. Objectives: We highlight the favorable medium term outcome and suggest the potential benefit of anti-Il-1 therapy and abciximab in this clinical setting. Methods: We report the case of KD with a severe clinical course and the development of multiple, large CA despite an early and aggressive treatment.

Results: A 6 months-old male Asian infant was admitted with high fever for 4 days, submandibular adenopathy, conjunctival injection, red lips and macular rash. He was initially treated as a bacterial infection but lack of clinical improvement despite empirical intravenous antibiotic therapy and the development of clinical symptoms suggestive of KD lead to the performance of a trans-thoracic echocardiogram revealing a dilatation of the left coronary artery and an aneurysm of the anterior descending coronary artery. Treatment with intravenous immunoglobulins (IVIG) 2 mg/kg and ASA 50 mg/kg/d was initiated (day 6). Due to the persistence of fever and raised acute phase reactants a second IVIG dose was administered at day 8. Given the severity of symptoms, laboratory tests (49160/mcl leukocytes, PCR 295 mg/l, proBNP 1261pg/ml), the patients' age and the echocardiographic findings, corticosteroids (30mg/kg/dose) were prescribed (day 8, 9 and 10) without clinical improvement and the patient was therefore transferred to our center. Because of the refractory clinical picture and the remarkable coronary findings(multiple CA, the highest in right coronary artery:14mm, z-score: 39.89) anakinra(4mg/kg/day) was started on day 11. The dose was increased to 8mg/kg/day, and abciximab(initial dose of 2 mg/kg/day followed by a 12 hour intravenous infusion of 1.6 mg with ICU monitoring) was added to the treatment plan on day 14 with resolution of the clinical symptoms and normalization of the laboratory parameters (except trombocytosis 1295000/mm3). He was discharged 1 month after the onset of symptoms and managed as an outpatient with anakinra (8mg/kg/day), ASA, heparin and tapered corticosteroids. At discharged the ecocardiogram showed a significant dilation of the coronary aneurysms, with 2 giant aneurysms of 9.7 mm, z-score 26.17 and 12 mm, z-score 33.59 in the right coronary artery. Anakinra was stopped one month after discharge. Subsequent echocardiographic controls (seven months later), showed a significant improvement (largest aneurysm 2.5 mm, z-score: 2.93). Current treatment is limited to AAS and heparin. Conclusion: Despite adequate initial KD management, there remains a group of patients which develop serious cardiac complications. The identification of these high risk patients and the establishmentof guidelines forrisk-adjusted therapy are needed in order to optimize the management and subsequently the outcome of these patients. Informed consent had been obtained from the parent. Introduction: Fever of unknown origin (FUO) in children is defined as fever >38.3°C (101°F) at least once per day for ≥8 days with no apparent diagnosis after initial outpatient or hospital evaluation that includes a detailed history, thorough physical examination, and initial laboratory assessment. The most common causes are infectious diseases, rheumatologic diseases and malignant diseases. This case is presented to emphasize that Takayasu Arteritis should be considered in patients examined for FUO.

Objectives: An 11-year-old girl presented with a fever increasing up to 38.3°C 1-2 times a day for one month, and up to 39°C for the last five days, despite continued antibiotic therapy. It has been learnt that she had a pain in the upper abdominal region for a week and she had lost 10 kilograms in the last two months after using a teeth retainer. On physical examination, body weight was under 3th percentile, while height was at 25-50 percentile. Vitals were normal except a fever reaching up to 38.5°C. There was no finding in systemic examination except general sensitivity in the abdomen. Hemoglobin was 8.1 g/dL. Biochemical values, immunoglobulin levels, and complements were normal. C-reactive protein (14.9 mg/dL) and erythrocyte sedimentation rate (140 mm/h) were high. Rheumatoid factor and viral serology were negative. No microorganism was yielded in the blood, throat or urine cultures. There was no sign of active tuberculosis on chest X-ray and PPD evaluation. Anti-nuclear antibody, anti-dsDNA, and p/c-anti-cytoplasmic antibodies were negative. Ophthalmologic evaluation, echocardiography and abdominal USG were normal. No additional features were found in peripheral smear and bone marrow examination. Methods: Abdominal Doppler USG was performed upon ongoing fever, abdominal pain and high levels of acute phase reactants. The patient was diagnosed with Takayasu Arteritis due to the wall thickening in the first 4-5 cm proximal segment of the anterior mesenteric artery and severe thickening in the left carotid artery wall. We report a case of sixteen year old girl with refractory Takayasu arteritis to standard treatment who entered remission and could stopped steroids after inducing tocilizumab Results: Sixteen year old girl was treated with antibiotics as having pneumonia due to fever and cough. After two weeks she was admitted to the pulmology department of our hospital due to prolonged fever, dizziness and weakness, but without reporting other symptoms. After excluding respiratory tract infection and tuberculosis she was transferred to the department of pediatric rheumatology and immunology. Possible infection causes were ruled out as procalcitonin, all cultures, virusology and atypical infections testing were negative. Bone marrow biopsy, detailed immunological and endocrinological laboratory testing were not proved hematological, immunodeficiency or autoimmune disease background. Due to persistently elevated inflammatory markers we suspected on autoinflammatory disease, but feritin was mildly elevated. Slit lamp examination and angiotenzin converting enzym have excluded possibile diagnosis of sarcoidosis. Abdominal ultrasound and echocardiography were normal. After the treatment with non-steroid anti-inflammatory drugs (NSAIDs) fever has gone, but elevated inflammatory markers persisted with profound feeling of fatigue, weakness, and dizziness. Physical examination has revealed less palpabile right radial pulse and higher blood pressure on the same side. F-fluorodeoxyglucose positron emission tomography (PET-CT) have confirmed diagnosis of Takayasu arteritis of thoracic and abdominal aorta. Magnetic resonance angiography (MRA) of the brain was normal. Methyl-prednisolon pulses were induced with gradually steroid tappering and metotrexate treatment, but unfortunately this could not stopped inflammation. Six months later she was steroid dependent with chronic fatigue and persistently elevated inflammatory parameters. MRA of the heart and large blood vessels have revealed evidence of still active inflammation in the thoracic aorta. Decision was made and tocilizumab was added on regular basis treatment. Four months after inducing tocilizumab she was without any symptoms with normalized inflammatory markers and steroids could be tapered and stopped. Introduction: Cutaneous sun exposure is an important determinant of circulating vitamin D. Both sun exposure and vitamin D have been inversely associated with risk of autoimmune disease, including multiple sclerosis and rheumatoid arthritis. In children with juvenile idiopathic arthritis (JIA), low circulating vitamin D is reportedly common, but disease-related behavioural changes may have influenced sun exposure behaviours (reverse causation). Objectives: We aimed to determine whether sun exposure across the life-course prior to diagnosis is associated with JIA. Methods: Using validated questionnaires, we retrospectively measured sun exposure for 202 Caucasian JIA case-control pairs born and living in Victoria Australia and recruited to the CLARITY JIA Biobank. Cases and controls were matched for year of birth and time of recruitment. All subtypes of JIA were included in the analysis. Measures included maternal sun exposure at 12 weeks of pregnancy, and child sun exposure across the life-course pre-diagnosis. We converted sun exposure to UVR dose using location-specific (Melbourne Australia, latitude 37.5°S) UVR data. We looked for case-control sun/UVR exposure differences at various ages pre-diagnosis, and cumulatively across the pre-diagnosis life-course, using logistic regression, adjusting for potential confounders. Results: Higher cumulative child pre-diagnosis UVR exposure was associated with reduced risk of JIA (e.g. total UVR dose quartile 1 vs 4, adjusted odds ratio (AOR) 0.19, 95% CI 0.04 -0.85, p = 0.030), with a clear dose response relationship (test for trend p=0.025). UVR exposure at 12 weeks of pregnancy was similarly inversely associated with JIA (e.g. UVR quartile 1 vs 4, AOR 0.32, 95% CI 0.13 -0.80, p = 0.014) with evidence of a dose response (test for trend p=0.031). Associations were robust to sensitivity analyses for disease duration, and for pre-diagnosis behavioural changes and knowledge of the hypothesis as collected by parent questionnaire. Conclusion: Increased UVR exposure across the pre-diagnosis lifecourse is associated with reduced risk of JIA in our setting. This suggests lower circulating vitamin D in JIA may be causative, but prospective studies that directly measure pre-disease vitamin D in JIA are required. If confirmed, the associations point to an environmental factor amenable to intervention that may reduce risk of JIA in the population. Introduction: In addition to its well-known neurotrophic activity, the nerve growth factor (NGF) is involved in the immune regulation. Our previous studies showed that the immature NGF, proNGF, is the prevalent form in synovial fluids of patients with juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). The distinct roles of NGF, pro-NGF and their different receptors (TrkA and p75NTR) in the regulation of the inflammatory response are still unclear. Objectives: To investigate if p75NTR and its specific ligand proNGF modulate the activity of synovial fibroblasts and mononuclear cells playing a role in the inflammatory response in the synovia of arthritis patients. Methods: Mononuclear cells (MNC) were purified from blood and synovial fluids of JIA patients. Fibroblasts-like synoviocytes (FLS), obtained from synovial tissue of RA patients (RA FLS), were used to evaluate pro-inflammatory activity of proNGF. Skin fibroblasts (SF) from healthy donors (HD) were used as controls. TrkA, p75NTR, Sortilin, NGF, and cytokines expression were evaluated by quantitative PCR (qPCR). Specific ELISA were used to analyze NGF, proNGF and cytokine concentrations. p75NTR was inhibited using a synthetic inhibitors (LM11A-31) or by small interference RNA in order to evaluate how its inhibition can modify proinflammatory pathways. Results: Our data showed that p75NTR expression was significantly up-regulated in MNC purified from blood and synovial fluid of JIA patients and in FLS of RA patients. TrkA expression was highest in HD cells and down-regulated in patient cells. Patient FLS but not MNC expressed high levels of NGF mRNA and high amounts of proNGF. On the contrary, low levels of mature NGF were detected in their conditioned media. Inflammatory stimuli, such as IL-1β, IL-6, LPS, TNFα, further up-regulated both p75NTR expression and proNGF production in synovial FLS. The inhibition of the binding of proNGF to its specific receptor p75NTR using synthetic inhibitor LM11A-31 in synovial FLS resulted in a marked reduction of IL-6 release induced by either IL-1β or other inflammatory stimuli. Conclusion: The abnormal p75NTR expression levels and the modified p75NTR/TrkA ratio observed in JIA and RA patients might have a crucial role in the chronicity of the inflammatory response. In addition to inducing p75NTR up-regulation, inflammatory stimuli increased the release of proNGF in synovial FLS. ProNGF further enhances pro-inflammatory cytokine production, creating a vicious circle that amplify the inflammatory response. Blocking the binding of endogenous proNGF to its receptor p75NTR, using a specific p75NTR inhibitor, strongly reduces the production of inflammatory mediators and suggests the use of p75NTR inhibitors as a new therapeutic approach to chronic arthritis. Introduction: Down syndrome (DS) is a common chromosomal disorder associated with the development of a range of medical and immune abnormalities such as haematologic malignancies, increased susceptibility to infections, and a high incidence of autoimmune diseases, including Down's Arthritis (DA). Previous work by our group suggests that the prevalence of DA is 18-21 fold greater than JIA, much higher than the previously reported DA prevalence of 8.7/ 1000. Children with DA most often follow a polyarticular course of disease, with erosive joint damage observed more frequently in this cohort when compared to a cohort of children with JIA. Small joint involvement is frequently observed, again in a significantly greater proportion (p<0.01) of children with DA than expected in a typical JIA cohort. These characteristics suggest that DA may be distinct from JIA, however little is known about the differences in synovial pathology or immunological regulation. Indeed no studies to date have examined synovial pathology in DA Objectives: -To examine B-cell and T-cell subsets, and cytokine profiles in children with DA and JIA -To characterise & compare the synovial membrane immunohistochemistry in DA & JIA. Methods: Multicolour flow cytometry was used to analyse the phenotype of B and T cells in peripheral blood mononuclear cells (PBMCs) from 40 children (n=10 per group; Healthy Control (HC), JIA, DS, DA). Cells were stained with the following panels; Panel 1 B cells (CD38, CD24, CD20, CD80, CD27, IgM, CD138, CD45, CD19, MHCclas-sII, BCMA, CD40, CD86, IgD); Panel 2 T cell cytokines analysed after 5hours PMA/Ionomycin stimulation (CD3, CD8, CD161, IFN-γ, TNF-α, IL-17a, GM-CSF). Flow cytometry data was assessed by Flowjo software analysis. Synovial tissue obtained through ultrasound guided biopsy and analysed by immunohistochemistry for CD3, CD20, CD68, Factor VIII (DA n=3; JIA n=6). Synovial Inflammation and lining layer thickness were also scored. Analysis was performed using semiquantification scoring method. Flow cytometry was performed on PBMC samples from 4 distinct gps; HC (50%F, age 9.2y (2.5-15.6)), JIA (91%F, age 13.2y (8.2-16.1)), DS (45%F, age 6.5y (1-11.9)) & DA (60%F, age 11.4y (3.8-17.8) Introduction: We have previously published and identified two dichotomous dysregulated populations within the Teff (CPLs) and Treg (iaTreg) compartments that are inflammatory, antigen experienced, correlating with disease activity and exhibiting similar TCR oligoclonality with synovial T cells. Their commonality in phenotype despite being in two functionally distinct compartments, signal the possibility of a common pathogenic origin during active disease manifestation. Objectives: To determine the common transcriptomic drivers influencing dysregulation in both Teff and Treg compartments during active disease in JIA patients. Methods: Next generation RNA sequencing was performed on sorted CPLs (CD3 + CD4 + CD14 -HLADR + CD25/CD127 Teff gate) and iaTregs (CD3 + CD4 + CD14 -HLADR + CD25 hi CD127 lo Treg gate) from 16 active disease JIA PBMCs, 8 age-matched healthy PBMCs, and 8 paired SFMCS. The corresponding total pool of Teff (Non-CPLs) or Treg (Non-iaTreg) was also sorted as a comparative control. Sorted cells were lysed and extracted for RNA, and cDNA conversion/amplification were then carried out using SMART-seq v4. Libraries are prepared and multiplexed using Nextera XT DNA library preparation kit, and ran on the Illumina HiSeq High output platform. RNA-Seq raw reads were mapped to human genome using STAR aligner with default options and reads were counted/summarised at gene level by feature Count programme. Differential expression analysis were performed using edgeR package, and pathway enrichments were done under R statistical environment and Reactome. Results: Comparative differential gene expression (DEG) reveal strong transcriptomic convergence between CPLs and iaTregs as compared with the common pool of Teff and Treg. Phylogenetic analysis indicate the convergence has uncoupled the CPLs or the iaTregs away from their respective original compartments (Teff or Treg) into a common branch point. Restriction in TCR sequence oligoclonality in CPLs/iaTregs versus that of the common Teff/ Treg pool reinforce the possibility of a common selection pressure. Pathway enrichment analysis reveal similar dysregulated pathways (IFN-g, PD1, CD28 costimulation) within T cell signalling for both CPLs and iaTregs. Furthermore, Weighted gene correlation network analysis (WGCNA) identified strongly coordinated HLA-DR gene network module and suggests its potential role as the driver of pathogenic T cell subsets away from conventional subsets. Gene set enrichment analysis (GESA) suggest that HLA-DR module genes are involved in TNFA signalling, inflammatory response, complement, and apoptosis. Global transcription factors gene regulatory network (TF-GRN) analysis identified several key regulatory molecules (FOXP3, CEBP, SPI and E2F1) driving the convergence of pathogenic CPLs and iaTreg populations. Taken together , we have shown that reveal several layers of mechanism operate to drive the convergence of CPLs and iaTregs, suggesting the possibility of common disease drivers in active JIA patients. Conclusion: Overall the transcriptomic data indicate strong similarity in both pathogenic populations and underscore a potential mechanistic role of the inflammatory microenvironment in shaping two functionally dichotomic populations. None Declared   P057  ASSOCIATION BETWEEN THE IL2-IL21 RS6822844 LOCUS  POLYMORPHIC VARIANTS AND AGE AT JUVENILE IDIOPATHIC  ARTHRITIS Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in pediatrics and is characterized by marked clinical heterogeneity, including the age-related features of the disease onset [1, 2] . Objectives: The aim of the study was to analyze the relationship between the IL2-IL21 rs6822844 locus polymorphic variants and age at JIA onset. Methods: The study included 328 patients with JIA from the Republic of Bashkortostan, Russia. Genotyping was performed by real-time PCR method and statistical processing of the resultswith the Mann-Whitney U test. Results: The study of the IL2-IL21 rs6822844 single-nucleotide polymorphism showed, that in the carriers of the GG genotype (n=271), JIA developed statistically significantly earlier than in the carriers of the T allele (4.16 (2.14;8.09) vs 6.00 (3.03;8.78) years respectively, p=0.045). In contrast, patients with the GT genotype (n=54) tended to have a later onset of the disease than the other patients had (6.00 (3.01;8.78) vs 4.19 (2.19;8.09) years respectively, p=0.072). In a sexstratified analysis, similar patterns for the GG and GT genotypes were found only for girls with JIA, being even more pronounced and in both cases reaching a statistical significance level (GG (n=174) vs GT +TT (n=42): 3.19 (1.90;6.79) vs 4.97 (3.01;9.65) years, p=0.008 and GT (n=41) vs GG+TT: 4.64 (3.01;8.25) vs 3.21 (1.90;6.99) years, p=0.013 respectively). It should be noted, however, that there was only one girl with the TT genotype in the studied JIA patients' sample, and age at the disease onset of this girl was 9.65 years. Conclusion: In this study, the association between the IL2-IL21 rs6822844 locus polymorphic variants and age at JIA onset in girls was established. articular inflammation that persists for more than 6 weeks, while SA is caused by bacterial infection in children joints. Although these diseases have different physiopathological basis and involve different treatments and prognoses, they share clinical similarities. Objectives: To date, there are no markers sufficiently reliable to discriminate between these two forms of arthritis at the onset of the disease. Our goal is to respond to this clinical need by identifying diagnostic biomarkers capable of discriminating between JIA and SA. To that end, we focused on microRNAs (miRNAs) and myeloid cell subsets, both playing a major role in inflammation and autoimmune disorders. Methods: We analyzed serum and synovial fluid (SF) samples from patients with inflammatory or septic arthritis using a miRNAs Whole Transcriptome Assay associated with a next-generation sequencing detection technology to measure the expression level of 2083 miR-NAs in a pilot study (oligoarticular JIA (oJIA): n=5; SA: n=3) and validated using RT-qPCR in a replicative study (oJIA: n=9; SA: n=9). In parallel, we performed a phenotypic characterization of peripheral blood (PB) and SF myeloid subpopulations using a flow cytometer in order to identify cellular biomarkers (oJIA: n=9; SA: n=8). Results: Principal component analysis and hierarchical clustering characterizations did not show significant differences between serum miRNAs of oJIA and SA patients. However, we observed a distinct miRNA profile signature in SF between the two diseases with 16 upregulated miRNAs and 5 down-regulated that perfectly discriminates oJIA and SA (p<0.01). In addition, phenotypic characterization revealed the existence of 5 myeloid cell subsets with distinct accumulation profile between the SF of oJIA and SA (p<0.05). A study of their activation profile indicated differences in the expression of cellular markers between the two groups. Conclusion: In this study, we propose for the first time a synovial fluid-based miRNA signature as well as 5 myeloid cell subsets that discriminate between oJIA and SA and might be used as potential diagnosis markers in juvenile arthritis. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and its etiology is unknown. Microribonucleic acids (miRNAs) are small (16-24 nucleotides), noncoding RNA molecules that have roles on the regulation of gene expression at the post-transcriptional stage. It is also known that microribonucleic acid (miRNA)s play a role in immunoregulation. Objectives: We aimed to evaluate plasma expression of some candidate miRNAs that associated with pathogenesis of autoimmunity. Methods: Thirty-one patients diagnosed with JIA and age-sex matched 31 healthy children were enrolled for the study. Plasma levels of four candidate miRNAs (miRNA-16, miRNA-155, miRNA-204 and miRNA-451), which is known to be associated with autoimmunity were examined in all subjects. Plasma levels of miRNAs were measured with Real Time PCR in patients in active and inactive period and in healthy controls. Groups were compared with each other.

Plasma miRNA-155 levels were found to be increased in JIA patients compared to the healthy controls and it was statistically more significant in inactive period. We found that JİA patients had higher levels of miRNA-16 and lower levels of miRNA-204/miRNA-451 expressions compare with the control group, but there was no statistically significant difference. A statistically significant decrease in plasma levels of miRNA-204 was found in patients that were in inactive disease with only methotrexate therapy. Plasma miRNA expressions were compared in JIA subtypes and it was observed that miRNA-204 levels were higher in polyarticular JIA and miRNA-451 levels were higher in entesitis related arthritis without statistical significance. Conclusion: Significant alterations in the plasma expression of miRNA-155 and miRNA-204 suggest to us that these molecules may be related to pathogenesis of JIA. More comprehensive and functional researches about the role of this molecules are needed in this regard. Introduction: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency affecting T regulatory lymphocytes caused by FOXP3 mutation and is associated with multiple autoimmune disorders including enteropathy, diabetes and atopic dermatitis. Kidney involvement is uncommon but has been already reported. Little is known regarding the impact of Tregs deficiency on renal tolerance. Objectives: This study is intended to describe the renal phenotype of IPEX patients and to determine the self reactivity of patient's sera using a protoarray assay enabling the detection of the autoimmune repertoire across 8000 peptides. Methods: We retrospectively collected clinical, histopathological and immunological data from IPEX patients seen in French pediatric immunology, rheumatology or nephrology centres. We retrieved patients sera and analyse the autoimmune repertoire targeting the kidney with a combined strategy of immunofluorescence crossreactivity on rats cell lines and direct crossreactivity on 8000 peptides (Protoarray, Thermofisher). Results: In the index case, immunofluorescence staining showed linear deposits along the tubular basal membrane suggesting a B-cell mediated immunopathogeny. The patient serum was tested Introduction: Juvenile idiopathic arthritis (JIA)is a chronic immunemediated inflammatory joint disease in children under the 16 years. The peculiarities of JIA pathogenesis depend on JIA category and related to autoimmune or autoinflammatory mechanisms. Currently there are no unique approaches to evaluate JIA activity. The classical clinical and laboratory test, such as ESR and CRP no always correlate with local inflammation, joint erosions and so on. The finding of new biomarkers is actual, because can help more precise evaluate JIA activity, choose the appropriate treatment and better prognosis of outcomes. Objectives: The aim of our study was to demonstrate possibility using of calprotectin, 14-3-3η and butirylcholinesterase (BUCHE) as a potential JIA biomarkers. Methods: in pilot study were included 13 patients with JIA (4 boys and 9 girls) with enthesitis-related (n=3) and oligoarticular (n=9) JIA categories in whom calprotectin and 14-3-3η levels and activity of BUCHE in blood plasma -BP (n=12) and synovial fluid -SF (n=7) were measured. The onset age of patients was 3.9 (3.1; 8.9) years, disease duration -3.7 (1.3; 6.6) years. Plasma and synovial fluid supernatant were used to determine the content of interleukin-6, calprotektin, protein 14-3-3η by the ELISA. Statistical analysis of data was carried out with the program Statistica 10.0. We utilized descriptive statistics (Me; IQR), Mann-Whitny and Wilcoxon tests, Pirson's and Spearmen's correlation analysis. Results: Obtained data showed that the content of calprotectin in JIA in SF -57.3 (47.3; 102.8) ng/ml was higher than in blood plasma -5.8 (3.6; 15.0) ng/ml (р=0.02). It was shown that the content of 14-3-3η protein in JIA SF -66.7 (56.4; 98.6) ng/ml is also higher than in BP-46.4 (37.1; 53.1) ng\ml (р=0.02) that is also coincides with literature data obtained for blood plasma 14-3-3η levels in adult persons with rheumatoid arthritis (Walter P. et al., 2014). Activity of typical fraction of BUCHE was higher in BP -47.3 (39.8; 60.6) U/l than in SF -30.2 (22.8; 39.1) U/l (р=0.027). Activity of atypical fraction of BUCHE was 14.2 (11.6; 16.7) U/l and 6.2 (5.0; 9.1) U/ l in BP and SF, relatively (р=0.046), and activitiy of minor fraction of BUCHE was 0.46 (0.1; 1.1) U/l and 14.7 (12.2; 15.5) U/l in BP and SF, relatively (р=0.027). There weren't found correlation between studied biomarkers and JIA measures, such as onset age, JIA duration, active joints count, ESR, CRP, JIA category, beside positive correlation between minor fraction of BUCHE in BP and active joints count (r=0,998; r<0,05) and negative correlation between CRP and 14-3-3η (r=-0.999; p<0.05) in SF. It was found that levels of calprotectin, 14-3-3η and minor fraction of BUCHE more effective reflect local inflammation than routine markers. We have found positive correlation between BP and SF for calprotectin (r=0.997; r<0.05) and 14-3-3η (r=0.958; r<0.05), but not for minor fraction of BUCHE. Conclusion: We suppose that calprotectin and 14-3-3η in BP can be used as possible non-invasive biomarkers of JIA activity. Further investigations required. Introduction: One of the key elements of immune pathogenesis of human autoimmune arthritis is the resilience of pathogenic T cells. We have previously described that CD4+ T cells in patients with arthritis have an increased level of autophagy than their healthy equivalents. Here, we sought to explore at epigenetic and transcriptional levels the concept of persisting increased autophagy as the consequence of "autophagic memory", as one of the mechanisms conferring resilience to pathogenic T cells, in particular to a subset of CD4+ T cells (CPL: Circulating Pathogenic-like Lymphocytes), which are significantly more represented in patients with active arthritis and resistant to therapy with biologics Objectives: T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis Methods: Autophagy was assessed in CD4+ T cell subsets from autoimmune arthritis pateints and healthy subjects using flow cytometry. RNA sequencing and methylation array analysis was performed to understand the molecular mechanism of autophagic memory. Transcription-factor gene regulatory network analysis was build to identify key regulators. qPCR was used to confirm the gene expression level of key regulator Results: We demonstrate "Autophagic memory" as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD4+ T cells subsets from autoimmune arthritis patients. Using RNA-sequencing, transcription factor gene regulatory network and methylation analyses we identified MYC as a key regulator of autophagic memory. We validated MYC levels using qPCR and further demonstrated that inhibiting MYC increased Conclusion: The present study proposes the novel concept of autophagic memory and suggests that autophagic memory confers metabolic advantage to pathogenic T cells from arthritis and supports its resilience and long term survival. Particularly, suppression of MYC imparted the heightened autophagy levels in pathogenic T cells. These studies have a direct translational valency as they identify autophagy and its metabolic controllers as a novel therapeutic target. Introduction: Our group has recently described that the majority of polyarticular juvenile idiopathic arthritis (pJIA) and a large fraction of extended oligoarticular JIA (oJIA) patients fulfil classification criteria for rheumatoid arthritis (RA) in adulthood. B cells play several important roles in RA pathogenesis, but it is still unclear if the pattern of B cell involvement in pJIA and extended oJIA follows what has been described for adults with RA. Objectives: The main goal of this study was to characterize peripheral blood B cell phenotype and cellular activation in pJIA and extended oJIA patients when compared to established RA. Methods: Blood samples were collected from JIA patients (N=10; mean age 10 ± 4 years), established RA patients treated with synthetic DMARDs (N=10; mean age 72 ± 7 years) and two corresponding groups of age-and sex-matched healthy donors. B cell phenotype was characterized by flow cytometry and B cell apoptosis was assessed after 48H of in vitro cell culture. Results: JIA patients recruited in this study were either classified as extended oJIA (N=6) or pJIA (N=4). Seven JIA patients (4 extended oJIA and 3 pJIA) were treated with methotrexate and three patients (2 extended oJIA and 1 pJIA) were untreated. We found that JIA patients had similar CD19+ B cell levels in circulation when compared to controls, but significantly higher CD19+ B cell frequencies in comparison to established RA. In addition, increased frequencies of transitional (IgD+CD38++) and naïve (IgD+CD27+) B cell subpopulations were observed in JIA patients when compared to RA. However, established RA patients had significantly higher levels of CD21 low C-D38 low , post-switch (IgD-CD27+) and IgD-CD27-memory B cell subsets when compared not only to controls, but also to JIA patients. No significant differences were detected in pre-switch (IgD+CD27+) memory and plasmablasts (IgD-CD38++) levels in JIA patients when compared to both controls and RA. Furthermore, the frequency of CD5+ B cells, CD5 median fluorescence intensity (MFI), CD40 MFI and CXCR5 MFI B cell expression levels were significantly increased in JIA patients when compared to established RA, but not to controls. No significant differences were observed between JIA and established RA patients in BAFF-R, FcgRIIB, CD21, CD23, CD38, CD86, CD95, HLA-DR, TLR9 and RANKL expression on B cells. After 48H of in vitro cell culture a significantly higher B cell death was found in JIA in comparison to RA patients. Conclusion: The increased frequencies of transitional, naïve and CD5 + B cells in circulation and reduced levels of memory B cell subpopulations in JIA patients when compared to established RA are probably related to an immature immune system present in children when compared to adults. Nevertheless, the similarity in B cell phenotype found between extended oJIA, pJIA and established RA patients suggests an early B cell involvement in the pathogenesis of these two categories of JIA.

Introduction: The australian arthritis and autoimmune biobank collaborative = a3bc a national paediatric and adult rheumatology clinical research network Objectives: The A3BC seeks safer, more effective and evidence-based prevention, diagnosis, treatment and prognosis strategy in arthritis and autoimmune disease. Key A3BC aims are to Develop a higher level of capability by collaborating across multiple disciplines and sector Progress precision medicine by growing capacity in open-access, data-linked biobanking Innovate preventive medicine by forming unique partnerships with population health research Demonstrate a new era of data linkage and use to inform policy and practice decision-making -Methods: The A3BC protocol was developed in consultation with leading researchers, clinicians, industry and best practices. A3BC processes will initially run parallel to the Australian Rheumatology Association Database (ARAD), but will merge in the future. The initial A3BC disease focus is Rheumatoid Arthritis, Juvenile Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis. Recruited through over 40 sites nationally, participants donate blood (20-53mls) and synovial tissue/fluid, stored across 10 biobank nodes as plasma, serum, PBMCs, DNA and RNA. On a project basis, newborn screening cards, urine and/or faeces are accessed. These samples are accompanied by standardised pre-analytical variables and clinical data, and linked datasets including the ARAD, electronic medical records, Commonwealth health (e.g. Pharmaceutical Benefits Scheme, Medicare)), registries (e.g. cancer, death), longitudinal/lifecourse data (e.g. Juvenile Arthritis national CLARITY project), and consumer entry (My Health Record). Using cutting-edge capture, real-time analytics and dashboarding processes and systems, all data is integrated and mined for patterns and associations, then effectively communicated to practitioners and policy-makers.

The A3BC protocol will result in new dataset integration systems, new multidisciplinary collaborations, and identification of new risk factors, biomarkers and cross-dataset associations. It will improve research by enabling innovative research questions and faster translation. And facilitate health policy/practice decision-making in precision and preventive medicine. Conclusion: The A3BC protocol provides best-practice, quality assured and validated methods to realise its aims. Current experience from recruiting and processing participants demonstrates that the protocol's methods and technologies are fit-for-purpose. Introduction: Neither genetic, epigenetic nor environmental factors alone have been able to unravel the pathogenesis of autoimmune and autoinflammatory diseases in children and adolescents. The specific aspects which determine the individual susceptibility to the development of a rheumatic disease are still to be elucidated. As of now, these conditions are seen as multifactorial in respect of pathogenesis. The microbiome has been under discussion as a contributing factor. Microbial communities who play an important role in the physiological development of the immune system may turn into "false friends" leading to the state of dysbiosis. Objectives: We aimed to gain new data in this context via examing the oral microbiome in patients with different rheumatic diseases in children and adolescents. Methods: We examined the oral microbiome by obtaining oral swabs of 11 patients with juvenile idiopathic arthritis and 20 patients with chronic non-bacterial osteomyelitis (CNO). The hypervariable region V6-V7 of the 16S rRNA gene was amplified and subsequently sequenced. The following bioinformatic analysis was performed with QUIIME (Quantitative Insights Into Microbial Ecology). Results: In accordance to previous studies we were able to identify Actinobacteria and Fusobacteria on the phylum level as microbiota only present in our JIA cohort. In the CNO cohort so far no distinct microbiotic players could be detected. For this entity the only data so far describe an advantage in mice who were fed with a high-fat diet resulting in a shift in the microbial environment leading to a better course of the disease. These mice data could -as of now -not be shown in our patients.

The microbiome may open a new door to a better understanding of multifactorial autoimmune and autoinflammatory disease. In accordance to previous studies we were able to identify specific microbiota present only in JIA patients. However, the clinical consequence and the exact immunological effects of dysbiosis are still to be unravelled. As of now, studies of the microbiome may enhance the pathophysiologic understanding of these diseases.

Introduction: Juvenile idiopathic arthritis (JIA) is a disease that begins in patients under sixteen years of age, continues longer than six weeks, and diagnosed with arthritis in at least one joint. Other causes of arthritis should be excluded for diagnosis of JIA. The etiopathogenesis is still unclear and it is thought that it is the result of the immunological response due to environmental and genetic factors. Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor)-like domain-containing protein (SCUBE) is a newly defined, secreted cell surface protein. SCUBE1 and SCUBE2 have been shown to play a role in various pathophysiological processes such as vascular endothelial cells, inflammation, cancer metastasis, and vascular diseases. Objectives: We aimed to research whether there is a relationship between SCUBE1 and SCUBE2 proteins, and JIA. Methods: Between January 2016 and May 2017, the patients admitting to outpatient clinics in Pediatric Department of Farabi Hospital in Karadeniz Technical University and diagnosed with JIA according to ILAR criteria were included. Patients who used steroid or nonsteroidal anti-inflammatory drugs in last three months were excluded. Blood samples collected from patients who were in active and recovery phases of their diseases and healhty control group. IL (interleukin)-1, IL-6, TNF (tumor necrosis factor)-α, SCUBE1 and SCUBE2 levels were studied by ELISA method. Patients with oligoarticular JIA were classified as Group 1, patients without oligoarticular JIA as Group 2 and these two groups were compared according to the blood results of cytokines and SCUBE's mentioned above. Results: A total of 24 patients, 11 (45.8%) were male and 13 (54.2%) female, aged between 2 and 17 years old, who were diagnosed with JİA, were included in the study. Fifteen (62.5%) patients were diagnosed as oligoarticular JIA, eight (33.3%) patients polyarticular JIA and one (4.2%) patient systemic JIA. İn the active phase of disease, IL-1 and IL-6 levels found significantly higher in Group 2 than in Group 1 (p=0.01 and p=0.004, respectively). TNF-α and SCUBE1 levels were higher in healing phase of the disease than in active phase (p=0.03 and p=0.01, respectively). TNF-α levels were higher in the active period of the disease than in the control group (p=0.02). SCUBE1 levels in the healthy control group were found to be significantly higher than the active period of the disease (p=0.009). TNF-α levels were higher in the recovery period of the disease than in the control group (p=0.004). SCUBE1 and TNF-α levels were found to be higher in the healing period of disease than in the active period (p=0.02 and p=0.03, respectively). SCUBE2 levels were found to be higher in patients with thrombocytosis in acute period (p= 0.01). Conclusion: These results concluded that SCUBE can not be used as early biomarker in JIA, but SCUBE may has a role of JIA pathogenesis. We believe that this situation can be elucidated by studies on more patients in this regard. Methods: The study involved 78 children, aged 1.1 years to 16.11 years. A group of children with a verified diagnosis of JIA consisted of 56 patients -30 patients with an oligoarticular variant of the course of the disease and 26 with a polyatricular variant, an average age of 10.2 ± 3.8 years, a group of ReA -22 children an average age of 7.49 ± 3.95 years. To compare the revealed relationships, a similar analysis was carried out in the group (n = 20) of relatively healthy children, the average age was 9.2 ± 3.99 years. The concentration of interleukins in the blood serum was determined by ELISA using ready-made commercial kits for the detection of IL-1β IL-4 IL-6 INF-γ from Vector-Best Europe (Novosibirsk, Russia) and IL-17 firm "eBioscience" (Vienna, Austria).The work was carried on the automated enzyme immunoassay analyzer "Lazurite" (Dynex Technologies Inc., USA). Results: In children with JIA, a higher concentration of Th1-associated cytokines was observed with respect to similar parameters in children with ReA and from the comparison group, so the concentration of IL-1β was 1.5-2 times higher than in patients with ReA and in relatively healthy children , INF-ɣ was 1.9 times higher than in patients with ReA and 3.5 times higher than the values in the comparison group. At the same time, the concentration of Th2-associated cytokine (IL-4) in the blood serum of children with JIA was practically the same as for the comparison group and children with ReA. In patients with ReA, in the absence of significant differences in the concentration of IL-1β, IL-6, IL-4 in the blood serum from similar parameters in relatively healthy children, 1.8-fold increase in the INFотмеча level and a 1.5-fold decrease concentration of IL-17. In children with articular form of JIA and ReA, there was a mixture of immune responses toward the activation of Th1-associated cytokines relative to the parameters of the comparison group, but with JIA this imbalance was greater than in patients with ReA. A key role in mixing immune responses towards the activation of Th1 cells in patients with ReA was played by a change in the ratio INF-ɣ / IL-4. A change in the balance in the Th1 / Th17 cell system was due to a change in the INF-ɣ / IL-17 ratio. When performing the correlation analysis in patients with different variants of articular pathology, the following significant correlation pairs were obtained: for the oligoarticular version of JIA-INF-ɣ and IL-4; polyarticular JIA-IL-1β and IL-4, IL-1β and IL-17, IL-6 and IL-17; ReA-INF-ɣ and IL-17, 1β and IL-17. Conclusion: The course of JIA and ReA is characterized by a definite unidirectional disorder in the Th1-and Th2-associated cytokines, which fits into the overall picture of the deployment of the cascade of immunoinflammatory reactions, which is relatively universal, but both by the severity of the established imbalance and by the nature of the revealed relationships immunological parameters has its own characteristics. The most informative at the stage of the differential diagnostic process of the joint form of JIA and ReA can be considered an interrelated analysis of the immunological activity of the inflammatory reaction. Introduction: Autoantibodies targeting cytosolic 5′-nucleotidase 1A (cN1a) were first identified in adults with inclusion body myositis but have subsequently been reported in a variety of other autoimmune diseases. They have recently been described in patients with Juvenile Idiopathic Arthritis (JIA) but to date clinical associations are unknown [1] . Objectives: We aimed to determine the prevalence and clinical associations of anti-cN1a in a UK cohort of patients with JIA. Methods: We screened sera from 227 patients with JIA enrolled in the Childhood Arthritis Prospective cohort study for anti-cN1a by ELISA (16 systemic, 98 oligoarthritis, 52 rheumatoid factor negative polyarthritis, 12 rheumatoid factor positive polyarthritis, 9 enthesitis related arthritis, 16 psoriatic, 12 undifferentiated). In addition, sera from 45 healthy juvenile controls, 52 patients with Juvenile-onset myositis (JDM) and 20 patients with Juvenile onset Systemic Lupus Erythematosus (JSLE) were also screened. The negative cut-off was defined as more than 5 standard deviations above the mean of 34 normal healthy (adult) serum controls. Results: Anti-cN1a were not identified in any healthy controls nor children with JDM but were present in 3 (15%) of patients with JSLE. Anti-cN1a were present in 19 (8%) of children with JIA. They were present in all ILAR defined subgroups with the exception of systemic-onset JIA and were most common in those with enthesitis related JIA (22% anti-cN1a positive). JIA patients with anti-cN1a were typically older at disease onset, although the age range was wide, median 8.8 years (IQR 2.7-12.1) versus 5.5 (IQR (2.0-11.0). The proportion of females was similar in both groups (74% anti-cN1a positive and 66% anti-cN1a negative). Patients with anti-cN1a were more likely to be ANA positive 84% versus 53% (p=0.02) a dense fine speckle or homogenous immunofluorescence pattern was most common but different immunofluorescence patterns and ANA negative individuals were found in both groups. Data on uveitis was limited to 139 JIA patients (10 patients with anti-cN1a). Three patients with anti-cN1a had a history of uveitis (one each of rheumatoid factor negative polyarthritis, enthesitis related arthritis and psoriatic arthritis) compared to 56 of 129 patients with available data who were anti-cN1a negative. Of the 68 patients with oligoarthritis with uveitis data, 10 were anti-cN1a positive and this group were less likely to develop uveitis than oligoarthritis patients who were anti-cN1a negative (p=0.03). Conclusion: cN1a is a common target of circulating autoantibodies in UK children with JIA and are seen in all subtypes except systemic JIA. In patients with oligoartiuclar JIA, who are at a higher risk of uveitis, the presence of anti-cN1a was negatively associated with a history of uveitis. Further work is needed but patients with oligoarticular JIA and anti-cN1a may be at a lower risk of uveitis and may therefore not require as frequent ophthalmological screening.

Introduction: Literature showed the importance of classifying patients into the right Juvenile Idiopathic Arthritis (JIA) category to provide them with optimal treatment 1 . However, a substantial amount of patients were classified as 'undifferentiated JIA' (UJIA) due to the strict exclusion criteria, harbouring the risk of losing the indication of the preferred treatment. Objectives: The aim of this study was therefore to investigate the influence of 'a first-degree relative with psoriasis' , which is an inclusion criterion for psoriatic arthritis and an exclusion criterion for the 'remaining five JIA categories'. This results in more insight in the accuracy of the classification system for JIA from the International League of Associations for Rheumatology (ILAR). Methods: Analyses were made in a retrospective and prospective cohort of 8,309 patients with JIA. 606 patients were classified as UJIA, 303 patients as 'psoriatic arthritis' (PSA) and 7,400 patients as one of the 'remaining five categories'. Results: 225 (37.1%) patients with UJIA had 'a first-degree relative with psoriasis'. No significant difference was found between the PSA and UJIA category in the number of patients with 'a first-degree relative with psoriasis'. None of the abovementioned 225 patients developed psoriasis during the observation period. Only 60 (20.8%) patients were classified as PSA because of the inclusion criterion of having 'a first-degree relative with psoriasis' in the PSA category. Conclusion: The exclusion criterion 'a first-degree relative with psoriasis' increases the number of patients classified as UJIA. No significant difference was found between the PSA and UJIA category in the number of patients with 'a first-degree relative with psoriasis' , suggesting this criterion is not of added value for the ILAR classification system for JIA. We conclude that 'a first-degree relative with psoriasis' is not a necessary inclusion criterion for psoriatic arthritis. For these reasons, we suggest removing the inclusion and exclusion criterion 'a first-degree relative with psoriasis' for all the JIA categories.

Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized with fever, recurrent episodes of self-limiting polyserositis and arthritis. FMF arthritis is generally acute monoarthritis especially in the larger joints of the lower extremities, healing without a sequelae. However some of the patients develop different type of chronic arthritis, predominantly oligoarticular juvenile idiopathic arthritis (JIA) and juvenile spondyloarthropathies (JSpA). Studies on JSpA among childhood FMF patients are scarce. Objectives: To evaluate the frequency of JSpA in a large childhood FMF cohort. Furthermore, we aimed to define main characteristics of JSpA among childhood FMF patients. Methods: A total of 320 juvenile FMF patients were blindly questioned according to recently proposed criteria for JSpA by 3 researchers (EO, DS, ET). A standardized case report form including demographic data, clinical features, MEFV mutation and treatment was prepared and completed for each patient. Patients fulfilled the JSpA criteria were previously classified as probable JSpA. Afterwards, an expert in pediatric rheumatology (OK) reevaluated the classified patients and some of them were confirmed to be a definite while some of them were accepted as potential JSpA patients. Results: 37 patients (11.5%) were initially classified as potential JSpA: 32 (10%) were accepted as definite and 5 (1.5%) as probable JSpA. Demographic, clinical and treatment data of definitive JSPA patients are shown in Table 1 . Conclusion: Articular involvement compatible with JSpA could be seen in childhood FMF patients. Spondyloarthropathies were detected in 10% of childhood FMF cases. The M694V mutation is the most common MEFV mutation among JSpA patients with FMF. JSpA should be considered in childhood FMF patients, especially in those chronic arthritis, axial involvement and enthesopathy. Introduction: The OMERACT JIA Core Set Working Group formed in 2015 as an international initiative to revise the existing Core Set with relevant patient/caregiver input. In efforts to develop an updated, patient-centered Core Outcome, virtual focus groups (VFGs) to identify main patient/caregivers-valued themes regarding the physical, mental, and social impact of JIA disease activity states were conducted.

Objectives: To identify and prioritize key features defining patientperceived inactive disease state and to examine possible crosscultural differences in the main domains Methods: Two sets of paired VFGs were conducted with JIA patients (adolescents and young adults) and parents (split by ages of their children) in two clinics, in the US and in Italy respectively. Eligibility included prior or current experience of JIA disease inactivity (>3 months). A 3-day facilitated online board was held per group, focusing on the impact of JIA on physical, mental and social health, and the perceived differences between active and inactive JIA. Participants were asked to identify and rank their five top priority features defining inactive disease. Content analysis of transcripts was conducted independently in the two centers and compared. Coded transcripts were further analyzed using network analysis, an approach that allows to study the structure of the connections between domains and the impact of specific items, measured by centrality indexes.

Results: 86 subjects were included. Caregiver were split by ages of their children (under and over 15 years old in the US sample; under and over 10 years old in the Italian sample). Patients were split in adolescents (15-17 years old in the US sample, 15-18 years old in the Italian sample) and young adults (18-24 years old in the US sample, 19-25 years old in the Italian sample). Qualitative analysis revealed psychosocial impact and limitations in daily activities emerged as main domains in both samples; fear of relapses and burden of medications were indicated as concerns mostly by Italian patients and caregivers, while the impact on children's activities and family life appeared relevant in US groups. Network models of ranked "top five" remission-defining items identified absence of pain as the single item with the highest degree, closeness and between centrality, indicating high relevance; others central themes in both samples were absence of functional limitations, improved engagement and autonomy. When comparing network models by the two populations, reduction of anxiety and absence of uveitis showed the greatest differences in centrality across the samples, respectively showing higher centrality in the Italian and in the US groups.

Conclusion: Data analysis revealed several domains that need to be evaluated for the development of patient/parent-centered outcomes assessment instruments. Network models revealed the central role of pain, functional limitation and restricted participation in patientperceived remission in both populations. Main differences in the two populations include the role of relapses, treatments and secondary demands in the impact of disease. Further analysis and cross-cultural validation of the results is planned to inform the development of patient/parent-centered outcomes measures. Twenty-one patients (45,6%) had an elevation of acute phase reactants at disease onset. Eight patients (17%) had erosive arthritis within the first year of evolution. The first line treatment was METHO-TREXATE for 34 patients (74%) alone in 11 patients (32%)) or in association with anti-TNF in 23 patients (67%)). Twenty-four/27 patients (88%) were treated by anti-TNF: ETANERCEPT (74%), ADALIMUMAB (11%), and INFLIXIMAB (3.7%). Other biologic agents were RITUXIMAB (n=2), TOCILIZUMAB (n=4). ABATACEPT (n=6). Sixteen patients (35%) received short or sustained treatment with corticosteroids. Primary or secondary resistance for the first biological agent occurred in 3 (6.5%) and 4 patients (8.6%) respectively. Seventeen out of 35 patients (48%) were on remission on treatment or off treatment (mean follow-up without relapse: 7 and 8 years respectively). Four patients (15%) who were treated by at least one biological agent presented side effects, which required to stop the treatment. Conclusion: Our study confirms the severity of RF positive polyarticular JIA and emphasizes its demographic and immunological heterogeneity. This first report of bronchiectasis in this population emphasizes the need for a careful pulmonary evaluation. The frequency of family auto-immunity history and the occurrence in two siblings suggest that some FR positive polyarticular JIA might be monogenic diseases. of controls always participated in physical education, thus JIA patients were significantly less active than controls. Pain did not reduce physical activity in JIA, but pain significantly lowered the level of activity in controls (p<0.001). No significantly relation between neither sleep disturbances and study groups nor sleep disturbances and pain was found. Disease activity (JADAS-27) in JIA was significantly positively correlated to pain intensity, and significantly related to reduced physical activity (p<0.05). Conclusion: Pain is common in JIA patients and controls. JIA patients are significantly less active compared to controls. Low physical activity in JIA is not related to pain, but to increased disease activity. Higher pain intensity is related to higher disease activity in JIA. In controls, pain is related to reduced activity. 02. An abnormal pGALS was associated with longer duration of ART (median duration: 9.9 years vs 8.7 years with normal pGALS, p=0.01).

Amongst the 23 participants with abnormal pGALS, 2 PHIVA were diagnosed with Osgood-Schlatter Disease, 6 (4 PHIVA and 2 controls) with orthopedic conditions including scoliosis or osteochondroma, 9 PHIVA had underlying neurological conditions including cerebral palsy or a prior stroke and 6 PHIVA had mechanical joint conditions. Conclusion: There was a low prevalence of musculoskeletal abnormalities in this group of PHIVA established on ART. Advanced HIV stage and longer exposure to ART were associated with musculoskeletal abnormalities. Screening for musculoskeletal abnormalities may target these subgroups of PHIVA. Introduction: Patients with autoimmune diseases are susceptible to infections due to their defective immune system and the receiving immunosuppressive treatment. Juvenile spondylarthritis (jSpA) often requires life-long treatment with biologics, which manage to fully control the disease. However, data regarding response and long-term immunological memory to specific vaccines are lacking. Objectives: We aimed at a comprehensive assessment of how anti-TNfα therapy interferes with vaccine-specific-IgG titers in children with jSpA. Methods: Prospective controlled study including 41 patients with jSpA and 149 matched-healthy controls. All patients had received two doses of MMR vaccine in early childhood. Demographic, clinical and laboratory data were collected. Type and duration of treatment was recorded. Samples were collected at diagnosis and at one and two years' follow-up. Seroprotection rates as well as measles and rubella-IgG titers were measured and expressed as GMC's. 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 STATA (version 13.0). 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 vaccines as well as mean elapsed time from last vaccination to blood sampling. All patients in the ERA group were HLA-B27 positive. Seroprotection rates were adequate for both groups at all times. Both rubella and measles GMC's were significantly lower in the jSpA compared to the control group (p<0.01) at one and three years' follow up but not at diagnosis. During the follow-up period, the jSpA group had greater decrease in antibody levels as indicated from the significant interaction effect of analysis. Subgroup analysis showed that longer disease duration was directly correlated to lower antibody concentrations (p<0.01). Subgroup analysis on other parameters tested such as uveitis, sacroileitis, enthesitis, JADAS scores and type of anti-TNFa treatment did not specifically correlate with antibody loss. The same was true for comcommitant use of synthetic DMARD's. Conclusion: Ant-TNFα treatment seems to reduce measles and rubella GMC's. Further studies are required to assess long-term immunity conveyed by immunizations given at an early stage in children with rheumatic diseases, especially the ones receiving biologics. However, evaluation of immunization status against all vaccine preventable diseases in such patients may be beneficiary.

The parent global assessment of disease activity (PDA) has been suggested to replace the parent global assessment of overall well-being (PWB) as the main patient-reported outcome incorporated in the Juvenile Arthritis Disease Activity Score (JADAS). JADAS is an important tool in a treat-to target-strategy in children with juvenile idiopathic arthritis (JIA).

Objectives: To investigate any discordance between PDA and PWB among children with JIA. Methods: The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) study collected information on the health status of children with JIA currently followed worldwide. More than 9137 children with JIA from 118 pediatric rheumatology centers in 49 countries were included, and we analyzed the PDA and PWB reported by the parents. The differences between the visual analogue 10-cm scale (VAS) (range 0-10) of PDA and PWB were assessed. Discordance was defined moderate for a VAS difference >1 and ≤3, high for a VAS difference >3, and agreement if VAS difference was ≤1.

Results: PDA and PWB were available in 8615/9137 (94.3%) of the EPOCA participants. Mean (SD) PDA was 2.1 (2.7), while mean (SD) PWD was 2.0 (2.6). Among the one-fourth of patients with a VAS difference >1, the number of active joints, percentage of children with morning stiffness, and pain scores were significantly higher in the group assessing PDA higher than PWB. In contrast, there was a higher score indicating impaired quality of life when PWB was higher than PDA (Table 1) . Also, in parents assessing PWB higher than PDA, the number of girls and the age at visit were significantly higher. Conclusion: Overall,there is a high rate of agreement between PDA and PWB. In parents rating PDA higher than PWB, patients have higher number of active joints and pain scores, and more morning stiffness, while parents rating PWB highest had lower quality of life scores.

Introduction: Up to now, few studies have been addressed to the natural history of uveitis associated to Juvenile Idiopathic-Arthritis (JIA-U) in order to properly select the treatment approach since the early disease manifestations.

Objectives: Aim of the present study was to identify the clinical characteristics of patients with benign course JIA-U in order to early select the appropriate treatment and predict the final outcome. Introduction: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease of unknown origin which can be considered as an autoimmune disease. Objectives: The aim of this study was to evaluate the frequency of symptomatic autoimmune thyroid disease (AITD) in children with JIA and to investigate if there are any factors contributing to a higher risk of developing AITD. Methods: 8,309 patients, with a total observation time of 51,324 patient-years, were studied. PharmaChild, the largest JIA-registry was used for this, containing clinical and laboratory data. Patients who were members of the Paediatric Rheumatology INternational Trials Organisation (PRINTO) were enrolled for the registry. Numerous patient characteristics and the family history were calculated separately for the JIA patients with AITD and the patients without AITD. Results: 96 of the 8,309 patients had AITD, which provided a prevalence of 1,2%. The median age of onset was significantly higher in the children with AITD (9,1 versus 7,1). Furthermore, significantly more females (84,4% versus 67,3%), ANA positivity (51,7% versus 40,8%), rheumatoid factor (RF) positive JIA (9,4% versus 3,8%) and psoriatic JIA (7,3% versus 3,4%) were seen in the AITD group. Additionally, the AITD group had significantly more first degree relative with any autoimmune disease (26,4% versus 13,4%), or more specific Introduction: The role of the gastrointestinal tract in pathogenesis of JIA has raised attention since some of the risk factors for JIA relate to an altered gastrointestinal immunological situation. Early introduction of cow's milk is one such risk factor. Cow's milk includes more than 25 different proteins. In bovine milk β-lactoglobulin is the main whey protein, but antibodies against α-lactalbumin are more common in cow´s milk allergy in children. IgG antibodies against cow's milk antigens are produced in plasma cells in the intestinal canal. The role of these antibodies is unclear, they have been elevated in cow´s milk allergy but not in cow´s milk intolerance. IgG4 antibodies against a specific food antigen mainly relates to the degree of exposition. Antibodies against nutritional antigens in children with JIA are only scarcely studied. Objectives: We wanted to investigate levels of antibodies against cow's milk antigens in children with JIA, at high compared with low disease activity, and compare the results with antibody levels in healthy controls. We also wanted to evaluate whether a history of milk intolerance affected the results. Methods: We investigated levels of IgG and IgG4 antibodies against β-lactoglobulin, α-lactalbumin and casein in serum of 65 children with different categories of JIA, at high and low disease activity, and in 30 healthy controls. The analyses were performed with an automated FEIA method, ImmunoCAP ThermoFisher. At low disease activity the majority of children were treated with metotrexat and/or biological agents. Disease activity was assessed by analysis of calprotectin by ImmunoCAP in plasma and E-SR. In the group of children reporting milk intolerance, IgE antibodies against milk antigens were analysed with ImmunoCAP.

Results: Analyses revealed a significantly higher concentration of IgG antibodies against all three milk antigens in high compared with low disease activity, Md 4.7 mgA/L compared to 3.4 (p=0.001) for IgG βlactoglobulin, Md 2.2 mgA/L compared to 0.0 (p=0.032) for IgG αlactalbumin, and Md 7.3 mgA/L compared to 6.9 (p=0.003) for IgG casein. There was no difference between high and low disease activity in concentration of IgG4 β-lactoglobulin. When comparing children in high disease activity with children in the control group, there was no difference regarding levels of β-lactoglobulin (p=0.29), αlactalbumin (p=0.14) or casein (p=1.0). The levels of β-lactoglobulin in serum correlated with the levels of calprotectin in plasma in all samples at high and low disease activity, r s = 0.26 (p=0,004), as well as with E-SR, r s = 0.24 (p=0,007). There was a high correlation between E-SR and calprotectin, r s = 0.82 (p<0.001). None of the eight children with current or earlier milk intolerance had positive IgE antibodies against milk antigens and the milk intolerance did not influence levels of IgG antibodies against milk antigens. Conclusion: In this study children with high disease activity in JIA had the same degree of antibody-production against milk antigens in serum as healthy children, but the levels were significantly decreased in lower disease activity. The stable concentration of IgG4 βlactoglobulin was considered a sign of unchanged exposition of cowś milk at high compared with low disease activity. Our results support influence on the gastrointestinal immune system by disease activity and treatment in JIA. Introduction: The ILAR consensus establishes classification criteria, dividing the JIA into 7 subcategories, with juvenile psoriatic arthritis (APsJ) being one of them. In the adult population, the CASPAR classification criteria are usually used to classify a patient with psoriatic arthritis. However, the two classifications have some differences that sometimes produce confusion Objectives: To assess the applicability of the CASPAR classification criteria in a series of patients previously diagnosed in pediatric age of JPAs or undifferentiated arthritis by exclusion criteria to be male> 6 years old and HLA B27 positive, comparing these with the ILAR classification criteria, through the study of clinical features Methods: Retrospective cross-sectional observational study. Clinical, epidemiological, sociodemographic and analytical variables were collected from 30 patients previously diagnosed with JPAs (6 years in HLA B27-carrying male. It was assessed whether the patients met the ILAR classification criteria as well as the CASPAR classification criteria, which, unlike the previous ones, did not exclude HLA B27 positive patients, considered the family history of the 2nd degree and added a test radiographic Results: The mean age at diagnosis was 11.23 ± 4.6 years; 15 of them being women and 15 men. 15 (15/30) patients presented cutaneous psoriasis at some point during the follow-up, in 5/15 patients psoriasis began before arthritis while 7/15 patients were previously diagnosed with arthritis than cutaneous psoriasis; in 3/15 patients the diagnosis was simultaneous during the medical visit. 9 (9/30) patients presented a family history of 1st degree cutaneous psoriasis and 7/ 30 of them had a family history of 2nd grade psoriasis. Of the total number of patients, 10 of them would not meet the ILAR classification criteria, 8 because they presented as exclusion criteria being male, HLA-B27 positive and> 6 years of age, among which, 7/8 would fulfill CASPAR criteria, and 2 other patients who were not classified according to ILAR criteria, did meet the CASPAR classification criteria, given the presence in these criteria of negative RF, family history of the 2nd degree and typical radiological alterations, which are not present in the ILAR criteria. 1 (1/30) patient did not meet CASPAR criteria, and belonged to the group of patients excluded from the ILAR criteria for being male> 6 years HLA-B27 +. If we did not take into account the negative FR of the CASPAR criteria, 14 patients would not meet these criteria and if we eliminated the 2nd grade AF, 5 patients would not be classified (among them 2 who meet CASPAR and do not ILAR) Conclusion: In our series of patients despite the fact that the presence of current skin psoriasis contributes 2 points in the CASPAR criteria, only 1 patient would not meet the CASPAR criteria, since the majority of patients present other clinical or analytical manifestations, such as the presence of negative rheumatoid factor or 2nd degree family history. Patients who do not meet criteria for PsA by exclusion criteria, practically all of them would be diagnosed with psoriasic arthritis by CASPAR criteria.

Introduction: Methotrexate (MTX) is a second line drug in the treatment of juvenile idiopathic arthritis (JIA), either alone or in combination with biologic agents. However, there is variation in the clinical response to MTX. Objectives: The aim of this study was to investigate the role of factors such as age, gender, ANA status, number of active joints, and JADAS-10 in predicting MTX response. Methods: Clinical and laboratory data of oligoarticular and polyarticular JIA patients diagnosed according to the International League of Association for Rheumatology (ILAR) criteria, who had received MTX treatment between January 2012 and March 2017, and continued MTX treatment for at least 12 months were evaluated retrospectively. The age at diagnosis, gender and ANA status were recorded. The number of active and tender joint and levels of acute phase reactants were assessed at baseline, and 3, 6, and 12 months. Disease activity score (JADAS-10) was calculated at onset of MTX and at months 3, 6 and 12. Patients' responses to MTX treatment were assessed according to the American College of Rheumatology Paediatric (PedACR) improvement criteria. At each time the patients were divided into responders and non-responders according to Ped-ACR 30 and 70 Results: This study included 55 JIA patients (40 female). Thirt-four were oligoarticular (2 extended oligoarticular) and 21 were polyarticular (5 rheumatoid factor positive) JIA. The mean age at onset of the disease was 7.71± 4.83 years.(mean age was 6.75 ± x4.99 years in patients with oligoarthritis, 9.27 ± 4.21 years in polyarticular patients). The median JADAS 10 at beginning for all 55 children was 19 (10-40), and 16 (10-27) for oligoarticular, and 28 (19-40) for polyarticular JIA. At month 3, 45% of all patients, %41 of oligoarticular, and 52% of polyarticular JIA patients had a minimum PedACR 30 response. 13 patients (2 at 4 th and, 11 at 7 th months) received biologic agents along with MTX. These patients were not included in the evaluation of treatment responses at 12 th month. The remaining 42 patients had PedACR 30 response at month 12. Moreover 81% of these patients (% oligoarticular, % polyarticular JIA) reached pedACR 70 response at month 12. Patients who had PedACR 30 response at 3 months had a higher rate of reaching the Ped ACR 70 response at 12 months (p=0.009). In patients with oligoarticular JIA, the 12 th month Ped ACR response was negatively correlated with the number of involved joints (OR). The initial JADAS 10 did not effect the PedACR response at 3 months (OR), but it was found that the 6 th month of JADAS 10, had a significant effect on PedACR 70 response at 12 th month (p<0.05). Age, gender and ANA status had no effect on PedACR responses. Conclusion: PedACR 30 response at the 3 rd month, JADAS-10 at 6 th month and number of active joints in oligoarticular JIA were found to be predictors of the ACR response at 12 th month. Introduction: There is an association between juvenile idiopathic arthritis (JIA) and chronic lung disease. These pulmonary disorders are multiple -interstitial (ILD) or non-inflammatory -depending on the type of underlying JIA -mainly polyarticular or systemic. In children, because of absence of accurate and multi-center data, the management of these chronic lung diseases remain difficult. Objectives: This work aimed to constitute a national cohort of JIA patients presenting chronic lung disease. Methods: A retrospective multicenter study was conducted. The cases between 2007 and 2018 were obtained from appeal of French Medical societies (SOFREMIP, RespiRare, SFR, CRI, database of pediatric pulmonary arterial hypertension). JIA was defined according to ILAR criteria; all had to have chronic pulmonary disease. Exclusion criteria were: age at onset> 18 years old, systemic JIA, other documented auto-immune or auto-inflammatory disease, asthma, cystic fibrosis, bronchopulmonary dysplasia, chronic lung infection, pulmonary primitive malformation. Data regarding clinical, paraclinical, therapeutic and evolution items were collected. Results: 8 files were selected; 4 met the study criteria. All patients had positive rheumatoid factor polyarticular JIA, with female predominance (3/4), mean age at rheumatism onset of 11.5 years (7.5-16) . They all had disabling polyarthritis, involving small/big articulations, mostly symmetrical, involving neck in 3/4 and hips in 1/4 patients, Xray erosions in 2/4 patients. All had markedly erythrocyte sedimentation rate (32-107 mm, mean=65), hypergammaglobulinemia (14.8-30.8 g/l, mean=22.5), high titers of CCP antibodies, elevated antinuclear antibodies (>1/320) -with specificities in patient 4 (SSA/SSB/ RNP without criteria for any connective tissue disease); patient 2 had positive TRAK antibodies without functional consequences. Each patients had different subtypes of ILD (Table 1) . Pulmonary symptoms at diagnosis were: cough (2/4), exercise dyspnea (2/4), dyspnea at rest (1/4), hemoptysis (1/4patient 4), digital clubbing (1/4patient 2), auscultation abnormalities (2/4). In patient 2, ILD/fibrosis was related to SFTPC mutation. She had familial history of dominant inheritance of lung fibrosis and 2 ascendants with inflammatory rheumatic disease (rheumatoid arthritis, unclassified). Treatment was based on oral steroids, that could be associated with variable immunomodulation. In contrast to methotrexate -used in all patients, Etanercept was associated in patient 2 with ILD worsening, that improved at treatment discontinuation. Among all patients at last visit, patient 2 was the only who needed nutritive and respiratory support, and died at age of 15 years old, 13 years after lung disease beginning, on a graft waiting list. Conclusion: The chronic pulmonary diseases related to JIA are extremely scarce. In this cohort only ILD form was observed in positive rheumatoid factor polyarticular JIA patients. Treatment strategies of both combined diseases were heterogeneous: oral corticosteroid was used in all, methotrexate did not seem to aggravate ILD, conversely to etanercept. The long-term interest will be to propose consensual recommendations for management of these patients. Informed consent had been obtained from the parents.

Introduction: Digital, remote, mobile health (mHealth) pain assessments are increasingly used in the research and care of children and young people (CYP) with long-term conditions, such as Juvenile Idiopathic Arthritis (JIA). However, little is currently known about the influence, impact or patient preference for particular ecological momentary assessment (EMA) techniques in pain reporting. Objectives: To explore patient preferences of different pain assessment timing and frequencies in CYP with JIA remotely monitoring pain at home. Methods: The study was a randomised n-of-1 crossover trial. Participants aged between 5 and 16 years of age were recruited from The Childhood Arthritis Prospective Study, UK. Participants were loaned an iPad for the duration of the study. The iPads were uploaded with My Pain Tracker (MPT), a valid and acceptable multi-dimensional pain assessment application for CYP with JIA. MPT collects information about pain intensity, severity, location, qualities and interference and can be used by CYP to track their pain independently. Participants were randomised into one of four groups. Each group followed different administrative patterns of pain assessment reporting. Four different timing schedules (once-a-week, once-a-day, twice-a-day and asand-when pain occurred) were randomised within the groups to occur twice within an eight-week data collection period. Semi-structured interviews were conducted over the telephone at the end of the study to explore which timing schedules participants and their parents preferred and why. Questions about subjective measurement reactivity (whether participants or parents noticed a change in pain or emotion in response to particular pain reporting schedules) were also included.

Results: Fourteen CYP took part in the study (M=11.93, SD=2.65). An equal number of CYP reported that they preferred once-a-day and as-and-when reporting schedules (42.9%). As-and-when reporting facilitated flexibility in pain tracking. Some participants considered this an advantage and others, a burden. Flexibility was problematic because participants did not know what level of pain was sufficient to report or how to report when they were in school. Furthermore, CYP were not able to record and review 'good' or pain free days with this schedule, which CYP found valuable for evaluating the contrast with 'bad' pain days. Creating habits or routines was one of the most important factors for successfully remembering to report pain. A priority for CYP was capturing comprehensive information about recent pain which they could still remember. The once-a-day schedule accommodated these advantages. Higher frequency of pain reporting (more than once-a-day) was perceived to affect mood and fatigue by some participants and their parents. One parent reported a perceived physical change in their child's pain as a response to more intense pain reporting schedules. The majority of participants and their parents did not report any subjective measurement reactivity, with some suggesting frequent assessment served as a distraction from pain. Conclusion: To our knowledge, this is the first study to investigate the impact of different EMA schedules with CYP with JIA and persistent pain. Findings suggest that daily reporting of pain using multi-dimensional mHealth assessment tools is feasible, sustainable and a reporting preference for CYP with JIA. Findings are important for the development of administrative guidelines for new mHealth pain assessment tools. In a multivariable analysis we found female sex (p = 0.021), increasing number of joints with active arthritis (p < 0.001) and antinuclear antibody (ANA) positivity (p = 0.023) were significantly associated with TMJ involvement. In the oligoarticular group (persistent and extended) was a positive association of TMJ involvement and age (OR = 1.07, p < 0.001), while this association was negative in the enthesitis related arthritis group (OR = 0.94, p = 0.015). A significant correlation revealed between pathological MRI results and laterotrusion of the chin (p = 0.012) and pain on palpation (p = 0.020).

Conclusion: Based upon our data we cannot recommend one unique clinical parameter to diagnose TMJ involvement, and MRI is still the gold standard to assure the diagnosis. Female sex, ANA positivity and disease activity were correlated significantly with an increased OR for TMJ involvement, and a significant interaction between age and JIA categories (oligoarticular and enthesistis related arthritis) was found. Further prospective controlled studies are still needed. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatologic disease in children and adolescents with a prevalence of 1 in 1000 children in Germany. An early referral of children suspected to have JIA to a pediatric rheumatologist is essential for an early diagnosis and starting treatment in the therapeutic window to reach a better outcome. An easy-to-use and time efficient questionnaire originally developed by a Brazilian study group led by Claudio Len may detect children and adolescent under risk for JIA. Objectives: To determine, whether the German version of the screening tool is reliable for the early diagnose of JIA and secondly, whether a weighting scheme of individual questions improves its diagnostic performance. Methods: The original questionnaire was translated into German by Dr. med Ivan Foeldvari. The questionnaires were distributed among patients at the first clinical visit at the Hamburger Centre für Kinder-und Jugendrheumatologie. The questionnaire includes 12 disease-orientated questions each with three possible responses, either: "Yes", "No" or "I don't know". A retrospective evaluation of patients diagnosed with JIA or with a noninflammatory joint pain (NJP) was performed later on. The sample consisted of patients seen between August 2015 and July 2017. All patients were at least older than 2 years and younger than 17 years at the time of evaluation. Only questionnaires, which were fully answered, were evaluated. Subsequently, a weighting scheme (based on the factor loadings from a confirmatory factor analysis) of individual questions was applied in order to increase the sensitivity of the tool. Standard statistical techniques were used to find associations between the sum scores and clinical characteristics and to compare the weighted and non-weighted sum scores. Results: In total 165 of 800 questionnaires could be evaluated for the study. 133 (81%) were diagnosed with JIA and 32 (19%) with NJP. The group of JIA patients consisted of 79 (59%) girls, whereas the control group consisted of 21 (66%) girls. The analysis of the individual questions was performed by comparing the rate of a positive response to the questions ("Yes") between the two groups. Four questions showed a highly significant difference by comparing answers of the control group with a subgroup of JIA patients having at least one active inflammatory joint. In particular, questions regarding physical constraints (p= 0.20; AUC= 0.62), joint pain (p= 0.040; AUC = 0.61), swelling in the joints (p= 0.040; AUC =0.60) and stamina (p= 0.047; AUC = 0.60) seem to be relevant in the diagnostic approach. A weight of 3 was assigned to the first and seventh, 2.5 to the fourth and sixth, and 1.5 to the third and fifth item. The diagnostic accuracy of the respective weighted sum score increased from 64% to 68% to discriminate between patients with JIA with at least one active joint and the control group in comparison to the ordinary sum score. An optimal cutoff of 6.0 for referral to a pediatric specialist was calculated.

Conclusion: The validation of the questionnaire showed a discriminative difference in patients with clinical diagnosed JIA and a control group diagnosed with NJP. Furthermore, the weighted sum score performed better to differentiate between JIA and NJP patients. The modified questionnaire can be useful to screen for JIA and speed up the referral to a pediatric rheumatologist.

None Declared Introduction: Juvenile arthritis (JA, JIA) is an umbrella-term describing a heterogeneous group of musculoskeletal diseases characterized by chronic synovitis of unknown etiology. Typical classic forms of JIA (oligo, poly, psoria, entheso) are well known. Genetic disorders with musculoskeletal involvement that mimic chronic arthritis should be considered in the differential diagnostics of JIA. The topically of the problem in children is determined by frequent cases of treatment of skeletal dysplasia by the DMARDs.

Objectives: The goal of this study was to improve the diagnosis of skeletal dysplasia manifested as JIA.

Methods: We carried out a retrospective review of more than fifty children with past-onset chronic undifferentiated arthropathy (low laboratory activity; progressive idiopathic contracture with entheso/ synovitis) which were hospitalized at Children Orthopedics Institute, Saint-Petersburg between 2006 and 2016. The data of clinical of joint involvement, laboratory, x-ray, ultrasound, MRI were analyzed. Results: All children were divided into two groups based on their disease. The first group (large) consisted of children with recessive multiple epiphyseal dysplasia (rMED/MED4, gene SLC26A2 Mut, OMIM 226900) characterized by abnormal development of the bone and cartilage of the epiphyses. A second group (small) was children with JIA. Children with congenital or early-onset forms of skeletal dysplasia and other monogenic arthritis-like diseases were excluded from study. 1. Less of morning stiffness, bilateral painless joint contractures and axial deformation of the lower limbs were the main finding of children with pseudo-rheumatoid pathology. Most children with rMED in the early childhood were characterized by a lack of signs of physiological hypermobility, reduced daily motor activity and treated of bilaterally delayed ossification of femoral heads. Morning stiffness and painful joint contractures were actually for children with JIA. 2. Radiology of JIA was characterized by inflammatory dynamic picture: overgrowth of metaepiphysis and joint osteoporosis at onset of disease, development dystrophic and erosive changes of osteochondral tissue at progressive durated and arthros-arthritis deformation like outcome. Symmetric flattening of epiphyses of hands, hips, knees and feet, double-layered patella were x-ray hallmarks of rMED. Avascular necrosis may be superimposed on rMED. Dystrophic spondylolisthesis at the L5-S1 vertebrae to 10-12 years of life was a frequent sign of epiphyseal dysplasia. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder of childhood and encompasses a complex group of disorders comprising several clinical entities with the common feature of arthritis. Calprotectin is a calcium-and zinc-binding protein that belongs to the S100 protein family and is released during the interaction of leucocytes with inflammatory activated endothelium at the sites of inflammation as occurs in JIA. We undertook this study to assess the usefulness of Calprotectin as a marker of disease activity in Indian children with JIA.

Objectives: To assess the effetiveness of serum Calprotectin levels as a marker of disease activity in children with JIA. Methods: Children who fulfilled the International League of Associations For Rheumatology (ILAR) criteria for JIA were recruited into the study. Baseline demographic details were collected and Blood counts, ESR, CRP and Calprotectin levels were analyzed in all children after obtaining consent. Children were then divided into 2 groups based on disease activity as per Wallace criteria. Calprotectin levels were also analysed in 10 normal healthy children. Calprotectin levels were measured by using a "Human Calprotectin Kit" which works on the basis of sandwich-enzyme linked immune sorbent assay technology (ELISA).

Results: 121 children with JIA were recruited into the study, 63 had active disease and 58 had inactive disease. Systemic onset JIA constituted 42% of the study population and was the predominant disease subtype. Calprotectin levels were elevated in children with active disease compared to those with inactive disease. Mean Calprotectin value in active disease (3954ng/ml) was 2 fold higher than those with inactive disease (1899ng/ml) (p value ˂0.001) and 16 times higher than children who were normal healthy controls (mean of 233ng/ml). Area under curve for Calprotectin was 0.744. For a cut off value of 1760 ng/ml, Calprotectin had a sensitivity of 77% and specificity of 61% for assessment of disease activity in JIA. Conclusion: Serum Calprotectin levels was found to be a good marker of disease activity in children with JIA. However, further studies which involve serial monitoring of Calprotectin levels in a study population will provide additional information about accuracy of these markers. There was no difference between the proportion of patients with abnormal titres in those who reported recent illness (7 of 16, 44%) compared to those without (8 of 20, 40%; p = 1). Furthermore, reporting recent illness was not associated with antibiotic use (6 of 16 (38%) compared with 4 of 20 (20%) without; p = 0.29).

In total 10 patients received antibiotics after initial serology results. 10-14 days of penicillin was always given when both ASOT and anti-DNase B titres were raised, but the decision to treat when only one titre was raised was variable. 6 of 11 (54%) patients with one abnormal titre were given antibiotics. Antibiotics were not given to patients with normal serology, or borderline ASOT alone.

No patients had repeat serology within 10-14 days. 5 patients had serology repeated, varying from 5 weeks to 14 months later.

Conclusion: This cohort consisted of patients with JIA and did not include those diagnosed with reactive arthritis, which would be valuable. ASOT typically rises 1 week after a streptococcal infection, falling between 2-8 months to baseline. Anti-DNase rises 2 weeks after infection and returns to baseline from 3-12 months.

(2) A fourfold rise in titres taken 10-14 days apart provides evidence of recent streptococcal infection. However, taking repeat blood tests in young children can be both traumatic and practically difficult, with limited access to age-appropriate phlebotomy. A history of recent illness is not predictive of a raised titre in the context of JIA. A pragmatic approach, therefore, is to treat a single abnormal titre. Results: Of 1241 respondents 19 were young adults with JIA (range 16-30 years), 89% were female and 84% had university or equivalent qualifications. Due to incomplete responses there is missing data on all 19 young adults. 4/13 young adults were studying at university, 9/13 were in paid employment. 9/17 respondents reported their school did not offer additional workrelated activities to students with disabilities and/or additional needs. 10/14 young adults felt their school did not provide advice about coping with possible limitations on placements/traineeships due to their arthritis. 11/14 respondents thought about their condition when thinking about future career plans e.g. "I wanted to work as a ranger or similar for the National Trust but it's a fairly physically demanding job and I knew my joints would suffer so I changed track slightly". However, 8/14 felt their career advisors did not take their arthritis into account e.g. "I had to cease my physiotherapy master's degree as my arthritis got too bad to continue and change career choice. I wish there would have been more discussion about it not being a reasonable choice for me at the time as we just didn't have the information then". 8/14 young adults changed their career plans because of their arthritis. Managing JIA symptoms and a physically demanding role, as well as wanting to stay healthy, were the main reason for changing career. Important aspects of employment included: good relationships with your line manager, work you like doing and a job you can use your initiative.

Conclusion: Despite small numbers these results highlight potential current unmet vocational needs of young adults with JIA in the UK and the need for further research with this age group. There appears to be a lack of structured support within schools and universities offered to students with disabilities and/or additional needs, about work-related activities and careers. Young adults with JIA actively consider their condition whilst thinking about career opportunities and value a productive and challenging job with a good working environment, including relationships with colleagues and supervisors. Introduction: There is evidence that obesity could be a risk of factor for the development of RA due both to the mechanical effect of overweight and to the potential pro-inflammatory effects of cytokines produced by adipose tissue.

Objectives: To evaluate the role of overweight and obesity in a cohort of JIA patients, in terms of incidence, disease activity, outcome and response to treatments.

Methods: This single-center retrospective cohort study evaluated 125 children affected by JIA under treatment with anti-rheumatic agents (NSAIDs/IAS, DMARDs, biologic agents). Change from baseline in ERS, CRP, number of active joints (with distinction between upper and lower limb joints), and BMI was analysed under each treatment until last visit. BMI categories of 5-84th (normal weight), 85-94th (overweight), and ≥ 95th (obese) percentile were used. Patients with systemic JIA or chronic comorbidity under potentially confounding systemic treatments were excluded. Informed consent was obtained by the patients and their family. Results: One hundred twenty-five JIA patients (36% oligoarticular JIA, 42,4% RF-negative polyarticular JIA, 0,8% RF-positive polyarticular JIA, 8% enthesitis related arthritis, l'11,2% psoriatic JIA, and 1,6% undifferentiated unclassified arthritis) were enrolled in the study, 76,8% girls, 23,3 boys. The mean age was 5,9 years (± 3,8). Baseline BMI was ≤ 84th percentile in 73,22% of patients, 85-94th in 19,64%, and ≥ 95th in 7,14%. We did not observe a significative association between BMI and ERS (p=0,29), CRP (p=0,24), or number of active joints (p=0,45) at baseline, while the involvement of the joints of lower limb was significantly greater (p=0,025) in overweight/obese patients. We also demonstrated a substantial equality in remission and relapse rates in subjects with different BMI.

Conclusion: This study focuses on the complex relationship between overweight/obesity and JIA. A significant correlation between obesity and a greater involvement of the joints of the lower limbs was observed at baseline. Furthermore, we observed that obesity does not influence the course of the disease nor treatment response. These data seem to suggest a prevalent mechanical effect of ponderal excess on JIA, rather than a biochemical influence due to proinflammatory cytokines released by adipocytes. At the posturography test, the distribution of the weight between left and right was pathological in 15 (4 sJIA; 9 polyarticular JIA; 2 oligoarticular JIA). The load distribution between forefoot and hindfoot was pathological in all the patients, with a more severe overload in polyarticular JIA patients.

Hand-grip test in 8 patients was <3°Centile; in 11 was < 20°Centile. The patients who performed a regular physical activity program showed fitness test in the normal range, and these parameters were not correlated with the type of JIA and/or the treatment for the arthritis.

Among the patients evaluated in follow up, 2 (1 with sJIA and 1 with polyarticular JIA) maintained an asymmetry in the weight distribution between left and right and a reduced fitness. 5 patients (2 M with sJIA and 3 F with polyarticular JIA) normalized their parameters. Conclusion: The persistent asymmetry of the load distribution between left and right foot and the persistent pathological distribution between forefoot and hindfoot was more frequent in patients with polyarticular JIA. A regular physical activity program is the best strategy to maintain an adequate fitness and the best control of the disease. Introduction: We present the development of an evidence based online learning resource for rheumatologists who manage adolescents and adults with JIA as part of their routine practice, including translation of a learning needs analysis into learning activity design and the creation of three interactive learning modules. Objectives: Many children and young people with JIA will continue to have active disease as adults and will need treatment delivered by adult rheumatology services. A learning needs analysis of the UK adult rheumatology community identified key areas where further training in the management of JIA is required: -Knowledge about JIA, including understanding JIA subtypes, how JIA manifests in adults, and how JIA differs from adult onset arthritis.

-Knowledge, skills and guidance for the management of adolescents and young adults with JIA. -Approaches to management in adults with JIA. The JIA in Adults e-learning series was developed with the British Society for Rheumatology (BSR) to target these educational needs.

Methods: The content and format were informed through our research to gather opinion from adult and paediatric rheumatologists in the UK (Smith et al, 2017). A PACT analysis (People, Activities, Context, Technology) informed the design process. Learning activities were based on constructivist learning theory with cognitive considerations for online learning activity design: activation of prior knowledge, construction of new knowledge and knowledge transfer. Results: The 'People' element of the PACT analysis was an essential considerationexperienced clinicians with a varied prior exposure to adolescent and young adult (AYA) rheumatology, both through formal training and clinical practice. Therefore, learning activities designed to activate prior knowledge and therefore optimise the foundation for further leaning were key. Social considerations and the wider, National and Global view were used to define purpose, motivate and prepare for learning. New knowledge was presented around clinical cases so that key concepts could be explored in depth and related back to prior experience. A series of interactive cases with questioning focusing on evidence, explanation, hypothetical reasoning, cause and effect and synthesis of understanding were used to develop clinical reasoning skills and to facilitate knowledge transfer to new clinical scenarios. The inclusion of the 'more knowledgeable other' in the form of feedback from an expert in the field of AYA rheumatology further enhanced the development of advanced clinical reasoning.

The learning needs analysis demonstrated that many find managing the complex psychosocial needs of AYA to be particularly challenging, therefore the cases explored these particular elements in more depth. Further cognitive considerations in the module design included enhancing learning through the use of video media, data interpretation, interviews, pictures and quizzes, and through the reduction and segmentation of text.

Conclusion: An e-learning series for adult rheumatologists who manage JIA in adults as part of their routine clinical practice was successfully created through the application of an evidence-based learning needs analysis to inform learning activity design, appropriate to the prior experience of the learners through interactive case-based learning. Introduction: Children with one or more subtypes of juvenile idiopathic arthritis, such as enthesitis-related arthritis (ERA), often exhibit growth impairments.

Objectives: To explore the impact of adalimumab (ADA) on growth in pediatric patients (pts) with ERA.

Methods: Pts aged 6-<18 with ERA were enrolled in a phase 3, multicenter, randomized, double-blind, study. Following 12 weeks of treatment with ADA (24 mg/m 2 BSA up to 40 mg every other week [eow]) or placebo, pts were eligible to enroll in an openlabel extension and receive ADA eow for up to an additional 192 weeks. For this analysis, all pts who received ≥1 dose of ADA were included, and pts were grouped by baseline height percentiles into 2 categories: ≤25 th and >25 th percentiles based on the World Health Organization (WHO) growth charts. Mean WHO percentile changes in height, weight, and body mass index (BMI) percentiles were calculated through 204 weeks. Per protocol, bone age and familial height were not collected. Growth and efficacy data were analyzed as observed.

Results: Among the 46 pts who received ≥1 dose of ADA in this study, 67% were male with a mean age of 12.9 years; no pts had associated IBD. Eleven pts (24%) were in the ≤25 th height percentile, and these pts had a numerically lower baseline height (147.7 cm) and weight (42.5 kg) compared with those pts who were in the >25 th height percentile (156.0 cm and 51.5 kg, respectively). Additionally, numerically higher proportions of pts in the ≤25 th percentile received concomitant corticosteroids than did the >25 th percentile group (54.5% vs 28.6%). Pts in the ≤25 th percentile group experienced a larger change in mean height percentile through 204 weeks of ADA treatment (70.3 vs 20.5 for the >25 th percentile), a finding that was evident within the first 6 months of treatment. Juvenile males in the ≤25 th baseline height percentile demonstrated the numerically highest rates of growth, although similar levels of growth improvement were observed for the lowest quartile of females as well. None of the 11 pts in the ≤25 th baseline height percentile remained in this category at their final study visit (Table 1) . Similar percentile increases were observed for BMI percentiles between groups. ACR Pedi90 response rates improved over time in both ≤25 th and >25 th percentile groups, reaching approximately 80% at the end of 3 years treatment with ADA.

Conclusion: Long-term ADA treatment was associated with growth improvement and maintenance in children with ERA. These improvements among children in the lowest WHO quartiles at baseline may improve their quality of life and psychosocial environment. ADA treatment improved ERA signs and symptoms, regardless of baseline growth status. In IBD group the frequency of small, coxo-femoral and sacroiliac joints complain was higher in the arthritis than arthralgia patients(p=0.006;p=0.001;p=0.001,respectively). CD patients in both arthritis and arthralgia groups, showed a higher prevalence of the Ileum-colon involvement (L3)(63%vs52%) than ileum (L1)(15%vs27.7%) and colon disease (L2)(22%vs20.7%). Also in the subgroup of sacroileitis in CD the L3 involvement was higher(73%) than L1(18%) and L2(9%). The joint remission was higher in arthritis patients on top down treatment than those on step up and the difference was already statistically significant at follow up at times 6 and 12 months(p=0.043,p=0.036,respectively).The peripheral arthritis group showed a higher frequency of remission at the follow up at 6,12 and 24 months compared with the sacroileitis. Conclusion: Arthritis is an earlier extraintestinal manifestation in pediatric IBD compared to arthralgia, and sacroileitis is more frequent in CD. Otherwise UC and CD have the same frequency to develop arthritis or arthralgia. The L3 localization in CD may be related itself to the development of joint involvement. The top down therapy in case of joint manifestation showed a higher frequency of remission. Introduction: juvenile idiopathic arthritis (JIA) is not uncommon disease among aboriginals in Sakha Republic (Yakutia) -SR(Y), which can be related to high spreading of HLA B27 antigen. Aboriginals in SR(Y) have higher prevalence of enthesitis-related category of JIA and juvenile ankylosing spondylitis, increased family history of rheumatic diseases, especially arthritis and have higher requirement in biologic medicine (anti-cytokine antibodies) for arthritis control compare to Caucasians.

Objectives: The aim of our study was to evaluate cytokine profile in aboriginals in SR(Y) and compare to Caucasians have been living in the same area. Methods: In continuous study were included 108 JIA patients before age 18 consisted of 96 SR(Y) aboriginals and 12 Caucasians with JIA whom have been living in SR(Y). All patients have an active disease course. In children HLA B 27 and interleukin-1β, interleukin-6, interleukin-10, interleukin-4, tumor necrosis factor-α, γ-interferon levels were detected.

Results: The prevalence of HLA B27 antigen was 50% in RS(Y) aboriginals. We have found differences in cytokines levels between aboriginals and Caucasians: inerleukin-10: 3.75±1.7 and 3.24±0.9 pg/ml (р=0.038), inerleukin-1β: 2.9±8.4 and 2.0±0.9 pg/ml (р=0.0000001), tumor necrosis factor-α: 6.3±9.1 and 4.9±2.2 pg/ml (р=0.00001), γinterferon: 22.7±11.4 and 20.1±3.5 pg/ml (р=0.007). No differences were observed in inerleukin-4 and inerleukin-6 levels between groups. Inerleukin-6 positively correlated with ESR (r=0.72, p<0.05). There was not found correlation between cytokines level and presence of HLA B27 antigen. Conclusion: the prevalence of pro-inflammatory cytokines were observed in aboriginals in SR(Y) compare to Caucasians. Further investigations required to validate these data in clinical practice. Introduction: Although predictors for the development of uveitis in patients with juvenile idiopathic arthritis (JIA) are well known, uveitis regarded as a separate, parallel disease has its own models of disease course, and accordingly, its own trends for remission. Adalimumab (ADA) is a highly effective anti-TNF drug having a strong therapeutic effect on both JIA and uveitis.

Objectives: This study aimed to assess the parameters associated with achieving remission of uveitis as a comorbid disease in JIA during ADA therapy. Male and female ratio was close to each other in the whole cohort (26 males, 28 females) and in JIA cases (12 males, 15 females). While idiopathic uveitis cases (6 males, 11 females) had female predominance, BD (5 males, 1 female) and TINU (3 males, 1 female) cases had male predominance. Mean age at the time of diagnosis of uveitis was 9.1 years (1-17.5 years) in the whole cases and this number was 5.0 years in persistent oligoJIA cases, 11.8 years in idiopathic uveitis, and 13.7 years in BD. Bilateral anterior uveitis was observed in 20 (74%) of JIA cases. Six JIA patients had unilateral anterior uveitis and one case had intermediate uveitis. Anti-nuclear antibody was positive in 90.4% of oligoarticular JIA-uveitis cases and 95.2% of oligoJIA associated uveitis cases were asymptomatic. Idiopathic uveitis cases had unilateral anterior uveitis (6 cases), bilateral anterior uveitis (5 cases), bilateral intermediate uveitis (5 cases), and bilateral panuveitis (1 case). All of the idiopathic uveitis cases were symptomatic as red eyes being the most common symptom. Three BD patients had bilateral panuveitis, 2 cases had unilateral anterior and 1 case had bilateral anterior uveitis. Only one BD case was asymptomatic. TINU cases had bilateral anterior uveitis (3 cases) and unilateral anterior uveitis (1 case) and all of them had red eyes. At the time of enrollment 45 uveitis cases (83.3%) were under remission while 9 cases (5 idiopathic uveitis, 2 JIA, 1 BD, and 1 TINU) had active uveitis. Biologics were used in 14 cases of methotrexateresistant JIA-related uveitis (adalimumab in 11 and tocilizumab in 3 cases). Half of BD uveitis patients were treated with biologics (2 cases with interferon-alpha, 1 case with adalimumab).

Complications of uveitis were observed in 10 cases (18.5%) such as intraocular hypertension (5 cases), adhesions (2 cases), band keratopathy (2 cases) and decreased visual acuity (1 case). Conclusion: Patients with JIA and BD should be regularly checked for uveitis. It is hard to find an etiology in uveitis cases that were sent from ophthalmologist if initial examination and questioning do not reveal an overt rheumatologic disease but simple urine test may help in diagnosis of TINU. Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood and uveitis is one of the major extraarticular manifestations. Uveitis occurs more frequently in children with antinuclear antibodies (ANA) positive disease and is often asymptomatic and may lead to permanent visual impairment, if not treated properly. ANA is the only biomarker that currently guides uveitis screening in JIA but it remains not conclusive. Among various ANA patterns, anti-DFS70 antibodies has been proposed as a novel biomarker for uveitis screening, being positive in children likely to develop uveitis. By contrast, in adults these antibodies seem to identify healthy individuals among asymptomatic ANA positive subjects.

Objectives: Aim of this observational study was to evaluate the correlation between uveitis and anti-DFS70 antibodies in children affected by JIA.

Methods: A total of 34 children (22 females, 12 males; median age 13.3 years) admitted to Rheumatology Unit of Verona and affected by JIA were enrolled. Following data were recorded retrospectively: JIA subtype, ANA positivity, anti-DFS70 positivity, presence of uveitis, diagnosed by a well-trained ophthalmologist.

Results: In our series oligoarticular ANA+ JIA was the predominant subtype (23 cases, 67.6 % of total), followed by oligoarticular ANA-subtype (6 cases, 17.6 % fo total), polyarticular ANA-JIA (3 cases, 8.8% of total), and lastly polyarticular ANA+ JIA (2 cases, 5.9% of total). 23 (67.8% of total) patients presented a DFS/homogeneous ANA pattern. 6 out of 34 patients (17.6%) developed mono-or bialteral uveitis and all of them were ANA positive, confirming that DFS/ homogeneous ANA pattern is the most common pattern associated to uveitis. None of patients presented antibodies anti-DFS70, regardless of clinical history of uveitis. Conclusion: DFS/homogeneous ANA pattern remains the most common pattern seen in JIA patients and seems to be an hallmark of uveitis. In our series, we found that neither JIA nor uveitis risk in JIA patients correlate with anti-DFS70 positivity. The role of these antibodies in children remains thus unclear. Further studies are needed to identify a reliable biomarker to guide ophthalmologic screening in JIA patients and to identify children likely to develop uveitis. Introduction: Non-infectious uveitis is a leading cause of blindness in the developed world. Juvenile idiopathic arthritis associated uveitis (JIA-U) is one of the most commonly reported immune mediated cause of uveitis in children. However, as in other developing countries, infectious uveitis is more common in Africa and there is a paucity of data on the epidemiology of non-infectious uveitis in children in this setting. To our knowledge, this is the first description of noninfectious uveitis managed at a tertiary paediatric rheumatology service from sub-Saharan Africa.

Objectives: To describe the disease characteristics and treatment of children with non-infectious uveitis at a tertiary paediatric rheumatology service in Cape Town Methods: A retrospective analysis of children managed by the paediatric rheumatology and ophthalmology service for uveitis from 1 January 2010 to 31 December 2017, was conducted. Ethics approval was obtained, and relevant data extracted from patient medical rheumatology and ophthalmology case files. Descriptive statistics were employed and comparisons between JIA-U and idiopathic uveitis groups were made, with p-values < 0.05 considered significant.

Results: Thirty-four children (60 eyes) were reviewed -18 boys and 16 girls with a median age at first visit of 76 months (age range 25 to 156 months).

Chronic anterior uveitis predominated in 23 (68%), acute anterior uveitis occurred in 3 (9%), panuveitis in 4 (14%), followed by 3 (9%) posterior, and 1 (3%) intermediate uveitis.

Fourteen (41.1%) were associated with juvenile idiopathic arthritis (JIA), 12 (35.3%) were considered idiopathic, while 2 (5.8%) were due to sarcoidosis, 1 (3%) to Behcet's, 2 (5.8%) to human immune deficiency virus (HIV), 2 (5.8%) post streptococcal and 1 (2.9%) to toxocara. The JIA-U group were characterised by a female preponderance, median age of onset of 56 months and chronic anterior uveitis. Further review according to the International League of Association for Rheumatology (ILAR) classification showed 10 (71,4%) to be oligopersistent antinuclear antibody (ANA) positive while 3 (21,4%) were poly-articular rheumatoid factor negative and 1 (7,1%) had psoriatic-JIA. 9 (64.2%) of the JIA-U group and 8 (73%) of the idiopathic group presented with complications, predominantly cataracts, followed by band keratopathy and posterior synechiae. There was no significant difference in age and complications at presentation, between the two groups, p-values 0.4 and 0.62 respectively, though a male preponderance was evident in the idiopathic group. All children were treated with standard initial therapy which included steroids (topical, oral and/ or intravenous) and methotrexate, of which 21 (61.7%) achieved remission. Thirteen children required the addition of a tumour necrosis factor (TNF) inhibitor, due to failure of Mycophenolate Mofetil in 2 and Azathioprine in 7. Eight (61.5%) achieved remission (Table 1) .

Conclusion: Here, JIA-U appears to have similar disease characteristics as previously described. However, the high rate of complications at presentation, requires further review of overall visual outcomes and the effectiveness of current screening and treatment strategies. Optimum management of non-infectious uveitis therefore necessitates a close relationship between paediatric rheumatologists and ophthalmologists. Introduction: Biosimilar infliximab (Remsima®) has been introduced in our country, together with other European countries in 2014. Information regarding the use in child age group is limited but it is reported that its therapeutic efficiency and safety is similar to the reference molecule regarding the pediatric Chron disease Objectives: In this study, our aim was to reporte the efficiency and safety of BI used for children with non-infectious uveitis.

Methods: In this study, there were 13 subjects (9 boys, and 4 girls) diagnosed with non-infectious uveitis. BI (Remsima9 treatment had been given in 5 mg/kg in 0.,2.,4 th week and then every 8 th week. Ophthalmic assessment of disease activity and ocular complications were measured throughout the trial with the use of slit-lamp biomicroscopy for uveitis activity, according to Adalimumab N= 6 (Remission)

the SUN criteria. The Drug exposure has been evaluated by calculated of patient year (HY), adverse event (AE) was assessed using the CTCAE criteria. The median values due to the small number of patients are considered.

Results: The patients who were include the study, 5 had diagnosed extended oligo JIA, 2 with enthesitis-related arthritis (ERA) ,2 with persistent oligo JIA, 2 with pars planitis and one of them Behcet's disease. At the time of evaluation, the median age was 10 years (3-13), age at diagnosis of their disease 8 years (1-13), respectively. The median age of uveitis diagnosis was 8 years. The median disease duration before BI was 10 months. All of the patients had methotrexate therapy with BI and BI before. Only one patient used a different biological agent prior to BI, and revealed they were determined that considered unresponsive. Other patients (n=12) had biosimilar infliximab as first biologic drug due to the activation of disease after using the drug methotrexate.

After therapy of BI, in all of the patients, joint and eye symptoms were improvement. The systemic steroid therapy was cut down in the first month in all patients, 2 of them continue prophylactic topical steroids. The median duration of BI therapy was 10 months. There was one case of anaphylaxis in all the patients, whereas five of them frequent upper respiratory tract infection have been observed as side effect. Conclusion: In this preliminary report, This biosimilar infliximab treatment appears to be safe and effective in pediatric age group on the pediatric patients with non-infectious uveitis. These results must be supported by multicenter studies and registries. Introduction: There are no established treatment guidelines for patients with juvenile idiopathic arthritis-associated uveitis (JIA-U).

Objectives: Therefore, multi-center survey was conducted to examine the present treatment status for JIA-U in Japan to establish treatment guideline in the future. Methods: Questionnaires were sent to medical centers with pediatric rheumatologists at April in 2016 to investigate the patients' profile and how JIA-U was treated in each center. Results: Of 726 patients involved in this study, 44(6.1%) had JIA-U and 36/44 (81.8%) was oligoarticular onset. Of 40 JIA-U patients recruited by the 2 nd detailed survey, 23 (57.5%) had been treated with NSAIDs in 13 (32.5%), MTX in 16 (40.0%), glucocorticoids (GCs) in 1(2.5%), and etanercept (ETN) in 1 (2.5%) by the time when JIA-U was diagnosed. After JIA-U was diagnosed, topical GC was started in all cases in combination with MTX in 3(7.5%) and/or systemic GC in 2(5.0%). Some biologic agents (infliximab (IFX) and adalimumab (ADA)) were used more frequently in JIA-U patients than non-uveitis patients (P <0.0001, P = 0.0029). Of 40 JIA-U patients, 22 patients (55.0%) were treated with biologic agents such as IFX in 9(22.5%), and ADA in 11 (27.5%). Surgical treatments for JIA-U such as intraocular lens implantation underwent in 15 cases (37.5%). Symptoms and findings related to uveitis improved with treatment in all 40 JIA-U patients, and no blindness was observed in this survey. Conclusion: Treatment for JIA-U in real clinical settings in Japan was similar to that of previous reports from other countries. Higher incidence of JIA-U onset in MTX treated patients in Japan may be explained by the differences in administration dose or method. Further investigation with larger scale is essential to establish the evidencebased treatment recommendation for JIA-U. Introduction: In 2014 the Region of Southern Denmark created the application (app), "Mit forløb" ("My Pathway") giving the different departments at the hospitals, the option to create their own specific section of the app. The app is available for everybody but using the communication and registration tools requires access granted by the relevant department. "My Pathway" is patient empowerment put into practice because the patients can be more involved in their own treatment and gain knowledge about different aspects of their disease and management thereof.

Objectives: To provide the young patients with JIA an easy and accessible way to find information on their disease, treatment and rights before and during transition to adult medicine a smart phone app was created.

Methods: The information in the app was written in collaboration between health professionals from the pediatric department and the department of Rheumatology, securing a uniform structure and language. It covers JIA, pain management, treatments and their side effects. Also included is general information on the department, its structure and staff. A chat function was developed which enables communication with the hospital in a flexible way; the patient can write whenever the question occurs and the hospital staff can answer when they have the time and have looked into the patient journal. "My Pathway" meets the young patient where they are; online anytime and anywhere via the smartphone in their pocket. Regarding transitioning focus was put on patients' rights and the app was created to it could be accessed both as a patient at the pediatric department and the department of Rheumatology.

Results: The app is still a very new initiative and has not yet been widely spread to the young patients. Around 30 young patients have been granted access to the app, and the feedback has been positive. Feedback from the patients has been a wish for more personalized information, regarding treatment and consultations, and to be able to see future appointments.

As of yet the chat feature has not been in much use probably due to reduced awareness among families and staff.

The pediatric team succeeded in creating an app geared towards informing the young patients about JIA, medication, painmanagement, transfer to the department of Rheumatology etc. As the app is a new implementation there must be expected a period of time for adjusting, both for patients and health professionals.

There is need for further development for the app to achieve full potential. Adapting the feedback from the young patients and the health professionals working with the app is an ongoing process.

The app is planned to include all rheumatic diagnoses and also access for younger children and their parents in the future. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood requiring long-term treatment. JIA has an fluctuating and unpredictable course. The fluctuation of disease activity, asks for continuous monitoring by a pediatric rheumatologist to achieve good health outcomes. Children with JIA live with chronic or recurrent pain and disability, which can severely limit their ability to complete daily physical tasks and participate in school and social activities.

An app was developed with input of patients, parents and caregivers to help close the gap between hospital care and the normal daily life activities of children with JIA in between hospital visits. Objectives: To create an ehealth platform (Reuma2GO) that aims to significantly improve the care for children with JIA and the dialogue between children with JIA, their parents and team of caregivers and hence, to advance true patient participation both in care and research. Methods: We performed a two-day workshop which was attended by patients, parents, app developers and caregivers about the added value of eHealth for the JIA patient and their parents. The participants were asked what they wanted from an app in their therapy that they are not currently finding. The workshop participants then worked together to come up with design and concept features that their ideal app should have and identify the critical success factors giving app developers a clear, clinically-approved model to work to. The Reuma2GO app tracks joint pain, fatigue, morning stiffness, daily activities and manages appointments and medication. Patients can communicate with health professionals in the app for advice or questions. Weekly feedback is sent on the self-reports by the care team to support patients and parents. The patient-generated data in the app will be integrated into the EMR in the near future.

Results: The Reuma2GO app is developed and tested among patients and care professionals according to the agile scrum method. 180 JIA patients and 7 rheumatologists/immunologists are using the Reuma2GO app. The app was evaluated as helpful in selfmanagement and recommended by patients. The app generates a dynamic reflection of the daily life of a JIA patient. This allows patients to efficiently monitor the impact and actual status of their disease. Conclusion: Reuma2GO is an eHealth platform that enables JIA patients to better understand and monitor the burden of the disease and thereby providing patients a way to become more actively involved in their disease management. By sharing their data in between hospital visits both patients and care professionals should benefit by offering more personalized care and using monitored data for research. Planning is to scale up the app to other hospitals in Europe that participate in the PRES network in the coming period. Introduction: From the patients perspective, the big promise of health apps (mHealth) is to increase self-awareness and self-care. For chronic conditions such as juvenile idiopathic arthritis (JIA), mHealth may provide a way for patients to become more actively involved in their disease management. With input of patients, parents and caregivers the Reuma2GO app was developed in 2017. It was intended to close the gap between hospital care and the normal daily life activities of children with JIA. The Reuma2GO app creates insights for patient, parents and caregivers into all aspects of JIA that influence the burden of disease (e.g. joint pain, fatigue, morning stiffness, daily activities, medication use, side effects). By offering the possibility of instant reporting about health issues one does not have to rely on their memory for conditions that were present weeks before the routine visit. Moreover the app allows for built-in thresholds with automatic alerts to physicians. A closed communication system allows the patient to open discussions with their physician. We feel that some routine visits of JIA patients, when in a stable inactive episode (either on or off medication), can be skipped as long as the patients agree that they are still doing fine. Objectives: To evaluate if patients/parents are capable of selfmonitoring with the Reuma2GO app when they feel the disease is quiet in order to skip future hospital visits. Methods: Data from the Reuma2GO-app, the JAMAR at the hospital visit (question 6: "Considering all the symptoms…. evaluate the level of activity of your child's illness at the moment") and the physician's global assessment of disease activity (PGA) were compared. The data used from the Reuma2Go app were the following (total score 0-40) 1: How much pain did you have in the past week (0-10)? 2: Do you have pain and/or swelling in your joints today (max 10 joints)? 3: Did you suffer from morning stiffness in the last week (5 stepscale; 2 points per step)? 4: How active is your illness at this moment (0-10)?

We only included those patients that had completed the abovementioned questions in the Reuma2Go-app 0-3 weeks before the routine visit and scored a maximum of 1 point in total and only allowed for question 1 and 4 (=Wallace's criteria for inactive disease according to parent/patient). Results: 186 (128 Female) patients aged 12.07±4.27 years use the Reuma2GO app. The distribution of JIA categories was: 19.4% polyarticular RFnegative, 6.9% enthesitis-related arthritis, 3.5% polyarticular RF positive, 11.8% extended oligoarticular, 40.3% persistent oligoarticular, 5.6% systemic JIA, 4.9% artritis psoriatica and 7.6% had undifferentiated arthritis. Preliminary data show that 17 patients completed the questions and considered the JIA to be inactive. In 16 (94%) of the cases the physician confirmed that the JIA was inactive and the JAMAR question on disease activity reflected the same. Only one patient score a 1/10 at the JAMAR during the visit, while the app scored a 0 before. This patient was suspected to have still a bit of unilateral TMJ arthritis and received a PGA of 1/10 as well, although no change in medication was performed Conclusion: The Reuma2Go-app creates a continuum of care by which the physician does not need to make treatment plans depending on one-point in time conditions at prescheduled visits. Moreover 94% of the patients that felt their disease was quiet were right about it. The only one that changed his/her mind at the visit was backed up by the physician, although no treatment change was needed. Future studies will look into the safety of giving autonomy to patients when they feel a visit can be skipped. Introduction: Identifcation of a need to replace a paper based activity diary used as part of pain management intervention with a more accessible and user friendly smart technology resource. Researchers within the field of E-technology have demonstrated the use of smart phones for self-monitoring pain and symptoms preferable to paper based forms noting that the information recorded was more accurate and time efficient. Pain diary apps exist however they tend to focus on reporting and recording pain rather than activity levels. At the time of development there were no activity diary apps specifically aimed at children and young people. Objectives: To develop an interactive user-friendly e-diary app that is accessible on android and iOS smart mobile phone. Methods: At concept a business plan was submitted to secure financial funding and obtained authorisation clinical design group within NHS trust. Consultation with multi-disciplinary team and user groups on the style, content, usability. This led to consultations with the nominated app developer to bring the concept to wireframe draft format. Educational content was then researched and drafted. Further consultation with user-groups to sign off the final draft of the app. Results: The development process was initially estimated to be completed within 12 months. In fact the entire process was 3 years in duration, underestimating the volumes of work and time that would be involved. A particularly steep learning process for the therapist who was a novice to app development. Despite this editing drafts and trailing the app was required to ensure that all glitches were identifeid and rectified the app is now a the point of final sign off. The app is at point of release on app store(s). The next phase is to research the efficacy of the app in the following 12 months. Conclusion: Many challenges emerged during the app development process, with important lessons learnt. Technology is ever-evolving at a fast pace. Ensuring the app was relevant was a key driver in the development process, the additional time taken to complete this project increased the risk that the app would be out of date or other activtiy diary apps may become available before the completion date was reached. Having to use an external organisation to develop the app had limitations in being able to communicate quickly and easily to ensure alterations to the drafts were completed in a timely manner. Future updates that may be required to the app will be limited as this will have to go through the app developer and will have a cost implication. Improvements emerged during the development phase that were beyond the scope of the app and were not included in the original costings therefore could not be included. It is hoped once the efficacy of the app is researched that further funding can be secured to include the additional functions to the app to build of the scope. Engagement with user groups was a vital part of the development process providing opinions on the look, and userability of the app interface. The focus group contributed significant modifications to the final app and included setting reminders and a notification facility as well as assisting with naming the app. The next phase is to research the efficacy of the app in the following 12 months. An essential part of the process is making links with other researchers in this field to continue to the build on the access to evidence-based e-technology tailored specifically for young people. Introduction: Genia is an app created as a patient support system for improved communication and collaboration with patients, families and the health care team. Its designed for IOS so far and is available in app store in both Swedish and English. Objectives: Through the app, patients can take notes and track selfassessed observations in daily living, which could include Visual Analog Scale trackers on various symptoms, activities and other areas reflecting quality of life. Automatic data collection, such as Steps from Apple eHealth, is also included. In addition users can send Pre-Visit report to health care to help both patients/families and care team to prepare for meetings as well as to help understand patients needs and preferences. Methods: A pilot project using the app has been driven by a physiotherapist, occupational therapist and the head physician of the Childrens rheumatology department in Karolinska University Hospital in Stockholm. Currently 56 patients at the clinic have Genia. Results: The feedback on experience from both patient/families and the clinic include that the app: 1. helps patients/families remember, reflect and prepare 2. support clinic visits 3. support patient activation and communication Conclusion: As health professionals we see great potential in the app to get the patient more active, understanding their disease and aware that their behavior and selfcare can make a different in how they feel. Genia is co-designed with JIA patients, families and members of the care team and continues to be iterated with feedback and ideas provided by stakeholders. There are further opportunities to co-develop the app to be helpful to patients and clinics, for example the creation of different types of reports, new or improved trackers that could support patients or/and assist care teams to support patients in self-care, etc. Introduction: The Juvenile Idiopathic Arthritis (JIA) chronicity, combined with the psychosocial effects of the entire therapeutic process on children and parents, often leads to non-compliance and a significant financial burden. These parameters, in the era of the economic crisis, are an incentive to seek new approaches to physiotherapy. Objectives: To investigate the applicability of a physiotherapy telerehabilitation program on children with JIA and to explore the program's impact on children and their families. Methods: Thirty JIA patients, with Medical Doctor's global assessment (MDVAS) <2, who applied a home-exercise program, were selected and randomly divided in the tele-rehabilitation (TRG, n=15) and the control group (CG, n=15). Each child from the TRG participated, additionally at home-exercise program, in a 30-minute tele-session (using personal computers, at home) with a qualified pediatric physiotherapist, twice a week, for 12 weeks, performing their exercises under the supervision and guidance of the specialist. Before and after the tele-rehabilitation program (T1 and T2, respectively), TRG and CG patients and a parent/guardian completed the Juvenile Arthritis Multidemensional Assessment Report questionnaire (JAMAR) and a relevant one for the implementation and compliance on the homeexercise program. Residual disease was estimated at T1 and T2 from a physiotherapist, different from the one performing the telerehabilitation program. At T2, TRG patients and their parents completed a questionnaire, evaluating the tele-rehabilitation program. One month after T2, a reassessment of compliance with the homeexercise program was performed. Results: The children's median (range) age was 12.8 (8) (9) (10) (11) (12) (13) (14) (15) (16) years. Nineteen children (63%) had JIA with poly-articular course and 11 (37%) with oligo-articular. All TRG children completed the tele-rehabilitation program. At T2, the TRG children performed the home-exercise program more frequently (p=0.023), for a longer time (p=0.034) and with less promoting (p=0.004), compared to T1. Moreover, there was increased compliance with the home-exercise program (p=0.001), functionality (p=0.008) and quality of life (p=0.007) and less pain due to JIA (p=0.017). In the CG children, there was no statistical significant change in the abovementioned parameters. The residual disease was improved in both groups (TRG: p=0.002, CG: p=0.018), but the improvement in TRG children was greater (p=0.043). The applicability of the telerehabilitation program was rated in a 0-10 VAS scale with a median (range) of 10 (7-10) by children and 10 (9-10) by their parents. The telerehabilitation program's total benefit was rated with a median of 10 (8-10) by TRG children and 10 (9-10) by their parents. Finally, one month after T2, the compliance with the home-exercise program was still greater, compared to T1 (p=0.001). Conclusion: The implementation of an interactive physiotherapy tele-rehabilitation program, is applicable and effective in children with JIA, providing an additional tool in their rehabilitation. Introduction: Ongoing proteinuria causes long term damage to the kidney. This is reflected by a change in estimated glomerular filtration rate(eGFR) over a period of time. A fall in eGFR is a poor marker and heralds damage. There is paucity of data about eGFR in children with lupus nephritis. We undertook this study to add to the existing data Objectives: To estimate the eGFR by using the bedside Schwartz formula at the onset of nephritis,at one year after treatment and at last follow up Methods: Charts were reviewed retrospectively of 82 children with lupus nephritis. Height records at disease onset were available for 69 and these were included for analysis. eGFR was calculated using the bedside Schwartz formula: 0.413*(Height/Creatinine). Results: 69 children with lupus nephritis were included for the analysis of eGFR. Two children did not complete one year of treatment and were thus not included for analysis of eGFR at one year and at last follow up. Median age at onset of nephritis was 12 years. Median duration of follow up of the cohort was 55 months(9-164months). Median eGFR at onset of nephritis prior to treatment was 82ml/min./ 1.73m 2 (IQR 63-115). Median eGFR at one year after treatment was 127ml/min/1.73m 2 (IQR 89-150).eGFR at last follow up was 128ml/ min/m 2 (IQR 101-145) The change in eGFR from baseline to one year was statistically significant (p =<0.001) and the change at last follow up visit from baseline was also better and was statistically significant (p=<0.001). However there was no statistically significant change in eGFR from one year to last follow up value (p=0.72). 39 children had eGFR less than 90ml/min/m2 at onset of nephritis and of these 14 had eGFR <60ml/min/m2.After one year of therapy one child had eGFR< 60ml/min./m2 and 18 had eGFR <90ml/min/m2. 39 children had eGFR less than 90ml/min/m2 at onset of nephritis and of these 14 had eGFR <60ml/min/m2.After one year of therapy one child had eGFR< 60ml/min./m2 and 18 had eGFR <90ml/min/m2. This could imply that aggressive treatment early on led to a significant improvement and there was not much deterioration subsequently. Conclusion: Stringent follow up is practiced at our unit and a tight treat to a target approach is employed. Early aggressive therapy is the norm. This is probably a reason for better outcomes. Another possibility is that many children have not spent a long time in the disease course and a longer follow up is needed to actually determine the renal damage. Introduction: Juvenile systemic lupus erythematosus (jSLE) is a multisystemic disease that has its onset in childhood. It is accompanied by an important morbidity related to the disease and its therapy. Ped-SDI index is used to measure the organ damage in these patients. Morbidities and comorbidities can impact this index in a positive or negative way. Objectives: To evaluate the relationship between morbidities and comorbidities with the ped-SDI damage index in patients with juvenile systemic lupus erythematosus being followed up in 2 paediatric rheumatology clinics in Bogotá, Colombia. Methods: A descriptive, cross-sectional study of a retrospective cohort of patients evaluated between 1997 and 2016. Morbidities, comorbidities and treatment were identified and the ped-SDI damage index was measured in the last visit. The statistical analysis was done using Stata V12. Results: 112 participants with juvenile systemic lupus erythematosus were included, the female: male ratio was 5,2:1. Sixty-two percent were 12 years or older at the diagnosis. The mean time of follow up was 49,3 months (6-161). Seven patients (6,25%) died during follow up with variable causes of death. The most frequently involved organs were musculoskeletal, mucocutaneous and hematologic. Patients who have taken 3 o more different immunosuppressive drugs (excluding antimalarial and steroids) during their disease, had a statistically higher damage index at last visit. Medication non-adherence was found in 40% of patients, being this related with a higher damage index at last visit. The morbidities associated with a higher organ damage index were acute kidney injury (p=0,0277), chronic kidney disease (p=0,0275), dialysis requirement (p=0,0072), neuropsychiatric (p=0,0020), cardiovascular (p=0,0000), pulmonary (p=0,0000), gastrointestinal (p=0,0082) and ocular involvement (p=0,0001). The presence of polyautoimmunity was also associated with a higher index (p=0,003). In contrast, the presence autoimmune thrombocytopenia was associated with a lower damage index (p=0,0378). Conclusion: These findings showed that morbidities and comorbidities can impact the prognosis of juvenile lupus patients in a positive or negative way. These findings help to understand some different factors that can contribute to organ damage in these pediatric patients. Searching for these conditions and starting an early and directed therapy would impact the prognosis in a positive way. Introduction: Although hepatic disease is not a significant cause of morbidity/mortality in jSLE,it is now considered to have greater clinical significance. Objectives: To report two cases of SLE who presented with abnormal liver function tests several months before the onset of the rest clinical manifestations. Methods: The first case is a 12,5 years old girl who presented with a one month history of malar rash and joint pain (ankles and knees). One and a half year before, elevated transaminases (2fold above the upper normal limit) were noticed during a routine exam. An extensive laboratory work up for viral hepatitis A,B and C,Wilson disease, celiac disease, hepatotropic viruses (EBV),a1 antithrypsin level and autoimmune hepatitis (ASMA,AMA.anti LC-1) had failed to reveal any kind of hepatic disease. Antinuclear antibodies were positive (1/320). Liver elastography was normal. The second case is a 15,5 years old girl who came to our department with the diagnosis of autoimmune hepatitis (AIH).8 months earlier, laboratory exams done due to a persistent maculopapular rash of hands and feets had revealed a significant increase of transaminase levels (4fold above the upper normal limit). Based on positive serological markers (positive antinuclear, smooth muscles and anti liver cytosol type 1 antibodies) the diagnosis of AIH had been considered as most probable although liver biopsy was normal. Results: On physical examination the first girl had malar rash and arthritis of both knees and ankles. Blood examinations showed leucopenia (3370/μL),low C3 (32,3mg/dl),ANA positive (1/640),anti DNA positive (254units) and mild proteinuria (120mg/24h).The diagnosis of jSLE was set and treatment with hydroxychloroquine and steroids was started. Transaminases level returned to normal quickly after the initiation of treatment. The second girl had on physical examination reticular peliosis, arthritis of metatarsophalangeal joints and a papular rash of hands and feet. Supplemental laboratory exams revealed low C3 and positive anti Ro antibodies and Coombs test. JSLE was diagnosed while the diagnosis of autoimmune hepatitis was considered as less probable based on normal liver histology. She started hydroxychloquine and prednisone leading to a complete resolution of hepatitis. Nine months later, while receiving a low dose of steroids, she developed a typical malar rash and nephritis with significant proteinuria and hypoalbuminemia. A renal biopsy showed early membranous nephritis. Treatment with pulses of methylprednisolone followed by per os steroids and azathioprine leaded to a complete resolution of symptoms. Conclusion: A wide spectrum of liver disorders is associated with SLE classified as liver parenchymal injury associated with SLE ("lupus hepatitis"),overlap syndromes with autoimmune liver disease and nonautoimmune hepatopathy (drug induced, viral hepatitis, fatty liver, thrombosis). Although abnormalities of liver function are not included in the diagnostic criteria, hepatitis is frequently noticed at disease onset. The diagnosis of SLE should be kept on mind in every child who presents with asymptomatic biochemical liver abnormalities (even if it doesnot fulfill the diagnostic criteria) and proper clinical and laboratory examination should be done towards this direction. Informed consent to publish these case reports has been obtained from the patients and their parents. Introduction: The association between systemic lupus erythematous (SLE) and early onset atherosclerosis has been widely accepted. In 2006, childhood-onset SLE (cSLE) was included by the American Heart Association and the American Academy of Pediatrics in the list of pediatric diseases with an increased risk of cardiovascular diseases (CVD). Carotid intima-media thickness (IMT) is frequently used as a precocious marker to detect early subclinical atherosclerosis and to identify higher risk patients. Objectives: To assess early subclinical atherosclerosis in patients affected by cSLE, and to investigate its possible correlation with disease related parameters and traditional cardiovascular risk factors Methods: Patients with diagnosis of cSLE by ACR classification criteria, followed at our center were included in the study. Demographic, clinical and laboratory features and therapeutic interventions were retrospectively collected from clinical charts. In all patients IMT of the distal 10mm of the far wall of common carotid artery was determined by ultrasonography with an highly automated method (qIMT). Concurrently with carotid IMT measurement, atherosclerosis-related biomarkers, such as plasma lipid levels and blood pressure were measured, and an accurate evaluation of traditional clinical CVD risk factors (smoke, exercise, familiar history of CVD, renal disease and hypertension) was performed. The SLEDAI was used to measure the disease activity. Correlation between carotid IMT and disease related parameters and traditional CVD risk factors was calculated by means of Spearman's test or Mann-Whitney U test as appropriate. Results: We present the preliminary data on 15 cSLE patients (12 females, 3 males) enrolled so far. The median age at time of IMT evaluation was 15 years. The median SLEDAI was 7 at cSLE onset and 4 at time of IMT evaluation. Median lipid and apolipoprotein plasma levels, uric acid, and renal functional index were in range with age related references. Measured carotid IMT values observed in our 12 patients were in range with age and sex matched published values. In three patients an IMT >75°centile was detected: all of them had a higher SLEDAI at onset and a short disease course (< 3 years). IMT values according to ENA profile and treatment are shown in Table 1 .

No traditional blood marker of dyslipidemia nor other disease related features nor therapeutic intervention were associated with IMT in our cohort. Conclusion: Carotid IMT is a non-invasive marker for subclinical atherosclerosis that should be considered in the follow up of cSLE patients. Our data suggest that patients with short disease duration could be at higher risk of having higher IMT values. The correlation with short disease duration may be due to the burden of the induction steroidal therapy or to the effect of new onset uncontrolled disease. Our results are preliminary from a small cohort and needed a further confirmation in a larger prospective sample with a control group. Introduction: Drug induced-lupus erythematosus (DILE) is an autoimmune disorder characterized by typical lupus-like symptoms in the setting of drug exposure. Genetic factors, including differences in drug metabolism and immunologic features, affect the risk of developing the disease. Recently, it was found that DILE might also be associated with epigenetics, since some drugs known to induce a lupus-like phenotype inhibit DNA methylation. Lamotrigine is used as an anticonvulsant and mood stabilizer drug. Between 5 to 10% of the patients develop a skin reaction to the drug, which, infrequently, can be life threatening, namely Stevens-Johnson syndrome, DRESS syndrome and toxic epidermal necrolysis. DILE associated with lamotrigine has been, very rarely, described. Objectives: Describe a patient with lamotrigine-induced systemic lupus erythematosus in order to improve our knowledge of the drugs and phenotypes associated with DILE. Methods: Clinical description of a patient with more than two years of follow up. Results: CASE DESCRIPTION: 17-year-old female, with panic and generalized anxiety disorders, treated with quetiapine, propranolol and lamotrigine. The latter was started four days before the beginning of the symptoms. The patient presented to the emergency room with a three week history of daily fever, fatigue, odynofagia, arthralgias and myalgias. On physical exam it was identified a non-pruritic diffuse erythematous maculopapular rash, vasculitic lesions on the fingers and lips and vulvar edema. There were no manifestations of serositis or neurological involvement. Alopecia, oral and nasal ulcers, organomegalies and arthritis were not detected. It was identified leukopenia (3920/μL), lymphopenia (880/μL) and a slightly elevated C-reactive protein (2.9mg/dL), with normal hemoglobine and platelets count; serologies were negative for cytomegalovirus, epstein barr, parvovirus, coxsakie, echovirus, herpes virus, Mycoplasma pneumoniaeand Chlamydia. The patient was admitted to the hospital and treatment with lamotrigine was immediately stopped. There was a significant clinical improvement including apirexia and regression of the maculopapular rash in less than 24 hours after withdrawal of the drug. Positive antinuclear antibodies (1/80), positive anti-double stranded DNA (anti-dsDNA) antibodies (50.5 UI/mL), positive anti-Ro (SSA) antibodies (163.2 UQ) and low serum C3 (59 mg/dL) and C4 complement level (9 mg/dL) were found; antibodies anti-histones were negative (<1.1 U/mL). The patient remained asymptomatic for two years under therapy with hydroxychloroquine (6.5mg/kg/day). C3 and C4 remained below normal ranges and anti-dsDNA antibodies persisted elevated. Recently, the patient developed photosensitivity and had a new vasculitic rash on the fingers, which improved with a short course of steroids. Conclusion: We describe a rare case of lamotrigine DILE, who presented with a diffuse erythematous rash, leukopenia, lymphopenia, low serum C3 and C4 and antinuclear and anti-dsDNA antibodies, thereby fulfilling the SLICC criteria. The withdrawal of the drug was essential for clinical improvement. In conclusion, DILE should always be included in the differential diagnosis of a patient with systemic lupus erythematosus and the medical community should be aware of the drugs that might cause it. Drug withdrawal is a fundamental step for a favourable outcome. For this case submission written informed consent was obtained from the patient and family. Results: Women's 5 years previously healthy age with symptoms of fever and arthritis 5 months of evolution, admitted to the institute by the presence of generalized edema and decrese output urine, elevated serum creatinine, proteinuria, metabolic acidosis and hypertension, presenting a rapidly progressive glomerulonephritis requiring renal replacement therapy with hemodialysis, renal biopsy was performed finding diffuse proliferative glomerulonephritis endocapillary, class IV lupus nephritis and thrombotic microangiopathy and hypertensive; The antibody profile denote ANA, antiDNA, anti B2-IgM glycoprotein and anticoagulante lupic positiv. For a history of seizures (7 days prior to admission) craneal MRI showed consistent data are with periventricular ischemia, ultrasound doppler renal absence of arterial and venous flow in both kidneys was performed and required anticoagulation heparin infusion for 21 days. She was presented persistent thrombocytopenia, elevated DHL, 1% schistocytes peripheral smear and Ac IgG Anti ADAMS 13 positive (activity normal limit) in addition to histological finding of renal biopsy thrombotic microangiopathy integrated diagnostic thrombotic thrombocytopenic purpura, was administered treatment with methylprednisolone, gamma globulin, monthly cyclophosphamide, and plasmapheresis every 48 hours (first sessions entirely with albumin later albumin and plasma 1: 1), requiring 17 sessions, after which presented remission, with platelet count in 150,000, improvement of renal function and neurological status.

Conclusion: The incidence of SLE and PTT is unclear, lower incidence of 0.5% reported being more common in adult patients with prolonged evolution of SLE, it is difficult to establish the diagnosis because the two entities have laboratory findings in common, being key finding schistocytes in peripheral blood smears, and antibodies ADAMS 13. There are no clear for the number of sessions of plasmapheresis patients requiring these guidelines, however The British Committee for Standards in Hematology (BCHS) guidelines recommend continuing the sessions at least two days after having a platelet count above 150.000, normal neurological status, hemoglobin levels and lactic dehydrogenase normal. The diagnosis of thrombotic thrombocytopenic purpura in patients with SLE is underdiagnosed, it´s essential to consider no matter the time of diagnosis of SLE if there is presence of persistent thrombocytopenia, neurological and kidney disease or histological findings compatible with thrombotic microangiopathy. Informed consent for publication has been obtained from the parent. Objectives: The aim was to study the relationship between the activity indices of the process (C-reactive protein (CRP), complement titer, circulating immune complexes (CIC)) with lipid profile (total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol), the clotting system (prothrombin index, fibrinogen) and the functional state of the kidneys and liver (serum creatinine, glomerular filtration rate).

Methods: 35 children with SLE at the age of 7-18 years were examined, of which 4 (11.4%) were boys and 31 (88.6%) were girls. The majority (in 74.29%) patients was diagnosed with comorbid pathology. In the structure of comorbid conditions, violations of the functional state of the liver (in 40%) and kidneys (in 80%), pulmonary lesions (in 20%) and hip joint prevailed (in 20.0%), as well as cardiovascular disorders (in 11 %). Changes in the lipid spectrum of atherogenic orientation and signs of osteoporosis were recorded in half of patients (in 51.43% and in 50.0%, respectively), and changes in the coagulogram with signs of hypercoagulability occurred in 35.7% of the examined patients.

Results: In patients with SLE and comorbid conditions, an inverse correlation was established between the values of CRP and the level of complement (r = -0.477, p <0.05), the complement level was inversely correlated with the level of triglycerides (r = -0.744, p <0.05), and triglyceride levels correlated closely with the level of circulating immune complexes (r = 0.896, p <0.01), which confirms the interdependence of atherogenesis and immunocomplex inflammation. The level of triglycerides of blood also had an inverse correlation with the parameters of the glomerular filtration rate (r = -0.892, p <0.05) and the straight line with serum creatinine (r = 0.834, p <0.05, and transaminases, in particular with ALT (r = 0.848, p <0.05).

With the help of multiple regression analysis it was found that an increase in the activity of the disease with an increase in the level of circulating immune complexes in children suffering from SLE and comorbid conditions is accompanied by an increase in the level of total cholesterol and triglycerides, a decrease in the complement titer, which is represented by the equation:

Conclusion: Thus, changes in the lipid spectrum of atherogenic orientation in patients with SLE of childhood not only take place against the background of the disease, but also contribute to the development of comorbid pathology there were signs of irreversible damage to certain organs and systems, namely, the nervous, cardiovascular systems, the lungs, the kidneys, the bone and muscle system, and the eyes. The duration of the disease in these patients varied from 3 to 113 months, on average 47 ± 6.9 months. In 15 cases the IP was equal to 1 point. These patients had an irreversible damage to the nervous (9 persons) and cardiovascular systems (1 person), as well as the kidneys (1 person) and lungs (4 people). In 5 patients, PI was 2 points due to irreversible damage to the organ of vision (4 persons) and musculoskeletal system (1 child).

In one patient, the injury index was 4 points due to persistent damage to the organ of vision as a cataract of both eyes and the nervous system in the form of convulsive seizures requiring prolonged use of anticonvulsants. The most commonly damaged CKD was the damage to the nervous system, which was observed in 25.6% of patients and in all cases was represented by cognitive impairment, and only one patient had convulsive seizures. In the second place, the frequency of occurrence was damage to the organ of vision (in 12.8% of patients). This kind of damage was due to the presence of cataracts of both eyes. Somewhat less frequently, lung damage was detected (10.3% of the subjects) in the form of pleural fibrosis according to the X-ray examination. Irreversible damage to the kidneys, cardiovascular and musculoskeletal systems was noted at the same frequency (2.6%). Damage to the kidneys was represented by the development of massive proteinuria, cardiovascular system -cardiomyopathy, and damage to the musculoskeletal system is due to avascular necrosis of the femoral head. Conclusion: Thus, the obtained results testify to the expediency of the use of PI in systemic lupus erythematosus in childhood in order to clarify the nature and degree of damage to organs and systems, which will allow timely correction of treatment. Introduction: The antiphospholipid syndrome (APS) is a multisystem and autoimmune disease, which is mainly characterized by the presence of thrombotic events, gestational morbidity, in the presence of high titers of antiphospholipid antibodies. It can present as a primary entity, or secondary to another autoimmune disease. The understanding of this pathology is still evolving and even more in its presentation in the pediatric patients. The presence of antiphospholipid antibodies has been widely reported in pediatric patients with thrombosis. APS is considered the most common acquired cause of a prothrombotic state. At the moment, there are no reliable data of its presentarion in pediatrics. The long-term morbidity and mortality associated with thrombosis events in pediatric population may be minored by determining prognosis and select patients for prophylactic treatment and more rigorous follow-up. Objectives: To describe the clinical presentation and evolution, in addition to laboratory findings, in Mexican pediatric population with diagnosis of APS. Identified patients with arterial or venous thrombosis and its relation with laboratory findings. Introduction: Pleural pulmonary manifestations in patients with systemic lupus erythematosus are reported in approximately 5% of cases. Presenting as pleural effusion, alveolar hemorrhage, diffuse interstitial lung disease, pulmonary infections and pulmonary arterial hypertension, among others, they are a manifestation difficult to diagnosis. Pulmonary arterial hypertension is defined as a pressure greater than or equal to 25mmHg. The world health organization has classified pulmonary arterial hypertension into five categories, the first group being associated with connective tissue disease such as systemic lupus erythematosus. Pulmonary arterial hypertension is a rare condition, usually occurring 3 to 5 years after the diagnosis of systemic lupus erythematosus and conditioning a high risk of morbidity and mortality. Initially, the majority of patients with SLE and PAH are asymptomatic and as the disease progresses, they present with progressive dyspnea, fatigue, intolerance, exercise, chest pain and non-productive cough. Objectives: We report the case of a 7-year-old male patient who presented with pulmonary arterial hypertension as the initial manifestation of systemic lupus erythematosus. Methods: Case report.

Results: Clinical case A 7-year-old male patient who was admitted to the Pneumology Department at Children's Hospital of Mexico Federico Gómez due to respiratory distress. In emergency assessment, pulmonary arterial hypertension of 66mmHg was identified, of unknown cause. The patient did not have significant medical background, having enjoyed of good health up to 6 months prior to his admission. He presented with a history of non-quantified fever, as well as episodes of fatigue and dyspnea. Two months before admission, chest pain was added, exacerbated with inspiration. On admission, transthoracic echocardiography revealed severe dilatation of right cavities, moderate tricuspid insufficiency, with left ventricular ejection fraction of 56% and arterial pulmonary pressure of 66mmHg. The diagnostic approach is initiated. Due to a history of pulmonary tuberculosis in the patient grandmother, the patient was studied with BAAR and cervical lymph node biopsy, ruling out the diagnosis. Infectious process causing the manifestations was also ruled out. The patient was discharged with medical treatment, requiring readmission in for 7 days, with facial edema and in lower extremities, generalized pallor, asthenia, adynamia and 4 days before a decrease in urinary volumes and frequency. On admission, right heart failure, secondary to increase of pulmonary hypertension for discontinuation of diuretic administration. A renal biopsy was performed, which was reported as class IV lupus nephropathy, with an index of activity and chronicity of 0. The diagnosis of systemic lupus erythematosus is integrated based on the ACR criteria. Induction of remission of lupus nephropathy based on the CARRA protocol. As treatment was administered the patient showed important clinical improvement. Conclusion: Pulmonary arterial hypertension is a rare condition, usually occurring 3 to 5 years after the diagnosis of systemic lupus erythematosus. In pediatric population, it is reported as a lupus complication in 5 to 14% of patients, and less than 1% as an initial manifestation. It is a clinical complication that gives the patient a high risk of morbidity and mortality. It is important to acknowledge that pulmonary arterial hypertension can be the initial manifestation of lupus in pediatric population. A prompt identification assures a prompt treatment and a better prognosis. Informed consent to publish had been obtained from the parents. . The first organ systems damaged in affected patients were renal (28%), musculoskeletal (22%), ocular (19%), neuropsychiatric (17%), cardiovascular (11%) and peripheral vascular (2.8%), but with no significant statistical difference regarding the type of organ damage. Kendall rank correlation coefficient was used to evaluate the relationship between SLEDAI-2K at the disease onset and SDI, determining a positive correlation which was statistically significant (τb = 0.252, p = 0.003). However, no significant correlation was determined between the duration of the disease and SDI (τb = 0.042, p = 0.628) or follow up period and SDI (τb = 0.111, p = 0.191) nor was there significant difference of SDI in regard to gender (Asymptotic Wilcoxon-Mann-Whitney Test, p= 0.574). Using Kaplan-Meier method we estimated the decrease in ratio of patients without organ damage since diagnosis or the occurrence of the first symptoms. Since the estimated ratio of patients with organ damage at the endpoint was less than 50%, we could not estimate the time required for damage development in 50% of patients. However, we are 95% sure that the damage is not happening in the first 9 or 10 years after diagnosis or the occurrence of the first symptoms, respectively. Conclusion: The high correlation detected between SLEDAI-2K and SDI indicated that the presentation of the cSLE at onset can be prognostic of the course and long-term prognosis of lupus. Our findings suggest that it is unlikely that organ damage will occur in 50% of patients in the first nine years of the disease course. Objectives: The authors present a case of a female adolescent with sickle cell disease and lupus nephritis with a severe presentation and without any serologic markers to corroborate the diagnosis. Methods: A 14-year-old female with Sickle Cell Disease (SCD), born and living in Angola until 3 days before admission, was hospitalized in the past 3 months due to a nephrotic syndrome, complicated with pneumonia with empyema, arterial hypertension, seizures and exacerbations of the SCD requiring frequent red blood cell transfusions and long term corticosteroids. Results: The patient arrived to Portugal for further investigation and was admitted in the Paediatric Intensive Care Unit with respiratory deterioration due to a pyopneumothorax, requiring thoracentesis and intravenous antibiotics. At D13 of hospitalization she presented seizures and neurological deterioration. The magnetic resonance imaging performed was suggestive of a posterior reversible encephalopathy syndrome. The renal biopsy revealed a proliferative glomerulonephritis with mesangial and capillary deposition of several types of immune complexes, mainly IgG, also known as "full-house" immunofluorescence pattern, highly suggestive of a class III lupus nephritis. The laboratory results were inconsistent with the diagnosis of jSLEnegative autoantibodies, mild elevation of complement and a negative direct Coombs test. Treatment with mycophenolate mofetil and prednisolone was started in order to induce remission of lupus nephritis, having attained a clinical remission (without proteinuria, normal renal function and normal blood pressure) in one week. Conclusion: In jSLE, renal involvement compromises the prognosis with significant morbidity and mortality. Few cases of lupus nephritis without serologic markers have been described to date. The literature reports two main presentations of seronegative lupus nephritis: one with a lifelong seronegativity, either with renal-limited or extra-renal manifestations; other with a serologic conversion, latter in the course of the disease. The authors hypothesized if the diagnosis of sickle cell disease and previous corticotherapy are related with this atypical presentation. Regardless of the clinical picture, a prompt and accurate treatment should not be delayed. This is an example of how an association of two complex diseases can present an hard treatment challenge. Informed consent to publish had been obtained from the parent. Introduction: Paediatric onset of systemic lupus erythematosus (SLE) is associated with a high rate of major organ involvement, and patients of African ancestry tend to develop more aggressive SLE than those of Caucasian descent. A particularly severe disease phenotype has been described in this multi-ethnic South African cohort of children with SLE.

Although cardiovascular involvement appears to be common in paediatric SLE, there are few published reports on the subject and none have been conducted in an African paediatric SLE population.

Objectives: This study aims to describe the frequency and characteristics of cardiovascular manifestations of paediatric SLE in a multiethnic South African cohort. Methods: Demographic, clinical, and echocardiographic data were collected from paediatric SLE patients at 2 centres in Cape Town, South Africa. At the time of investigation, this cohort consisted of 93 participants diagnosed with SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) or 1997 American College of Rheumatology (ACR) SLE criteria, prior to the age of 19 years. Individuals with cardiovascular involvement were identified by retrospective chart review. Cardiovascular involvement was defined as presence of: pericardial effusion, myocarditis, cardiomyopathy, cardiac failure, Libman-Sacks endocarditis, myocardial infarction, deep vein thrombosis, pulmonary embolism, sinus thrombosis, stroke, arrhythmia, central nervous system vasculitis, or other vasculitis. Echocardiographic data were included in the analysis, when available. Statistical analysis was performed with R software package version 3.4.1.

Results: Cardiovascular involvement was present in a total of 44 participants, or 47% of the PULSE cohort (Table 1 .) This is much higher than previously published reports of 3-32%. Those with cardiovascular involvement did not differ significantly in gender, age at diagnosis, or race/ethnicity from the overall cohort. Echocardiographic data were available for 23 of these participants. The most common cardiovascular manifestation observed in this cohort was pericardial effusion (n=24), followed by cardiac failure (n=8) and stroke (n=7). Cardiovascular manifestations were frequently severe, with one third of cases of pericardial effusion requiring intervention, and 3 patients presenting with cardiac tamponade. Mortality was high in patients with cardiovascular involvement, at a rate of 20.5%. Conclusion: Cardiovascular involvement was found to be common in this multi-ethnic cohort of South African children with SLE, with pericardial effusion being the commonest cardiovascular manifestation. The mortality rate was high, and severe cardiovascular manifestations including stroke and cardiac tamponade were frequent. Prospective research is required to identify risk factors for cardiovascular involvement, in order to inform practice and improve outcomes for this high-risk population. The aim of this study is to report the first Arab patient with BS who was refractory was conventional therapy but had rapid quiescence after using Tocilizumab. We also conducted a systematic literature review about biologic treatments in BS.

Methods: A 3.5 year old boy was referred at the age of 8 month for evaluation of intermittent fever, rash and polyarthritis that started at the age of 2 months. He also had a granulomatous panuveitis with posterior synchia and lens cataract. Skin biopsy revealed non-caseating epitheloid granuloma. DNA analysis identified a heterogenous missense mutation in exon 4 of the NOD2 gene. Over the course of years, patient had a difficulty stormy course with severe polyarthritis that was refractory to conventional treatment including pulses of methlyprednislone, oral prednisolone, methotrexate, adalimumab and infliximab. Tocilizumab 12mg/kg every 2 week was introduced 8 months ago with rapid improvement of arthritis with ability to taper oral prednisolone to 2mg/day. Introduction: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease with autosomal recessive inheritance. There is MEFV gene mutation encoding the pyrine protein in the short arm of chromosome 16 that leads to overexpression of IL-1. The basic treatment in FMF has been colchicine since 1972. Colchicine is effective both in the prevention and treatment of attacks, and in reducing the frequency of amyloidosis. However, there is resistance to colchicine in 5-10% of FMF cases, and anti interleukin-1 (anti IL-1) is effective in these cases.

Objectives: In this study, we aimed to find out possible risk factors for colchicine resistance in FMF by comparing the clinical and demographic data of patients with and without colchicine resistance, and to examine anti IL-1 effectiveness in patients with colchicine resistance Methods: Data charts of children with FMF from Dokuz Eylul University childrens' hospital and Dr.B.Uz childrens' hospital (n=950) were reviewed. Despite the use of adequate doses of colchicine, the patients with over 3 attacks in last 6 months were considered to be colchicine resistant. Then, colchicine resistant patients were compared with colchicine responsive group. Results: Thirty four (3.6%) of 951 patients had colchicine resistance and all of them used anti IL-1 (canakinumab). 67.7% of these patients were male and 47.1% had positive family history. Median age of symptoms onset was 40 (24-75) months, median age of diagnosis and colchicine onset were 72 (43-115) months. Median diagnosis delay time was 12 (9-47) months and median time of follow-up was 52 (33-99) months. There was not statistically difference between the 2 groups. Most common symptoms were fever, abdominal pain and musculoskeletal symptoms in both groups, while fever (85.3%), arthralgia (53%), arthritis (41.2%) were significantly higher in group with colchicine resistance when compared with other group (p:0.032, p:0.048 and p:0.001 respectively) Other frequent symptoms were myalgia, chest pain and erysipelas like rash in both of groups. The number of attacks in last 6 months after colchicine treatment was statistically higher in group of colchicine resistance than in other group (median numbers of attack: 6(3-10) (p:0,000). Colchicine resistant group response to canakinumab was good; the median number of attacks was 1(0-2) in the last year When the groups were compared in terms of FMF gene mutation, exon 10 mutation was 88.2% positive in-group of colchicine Introduction: Familial cold auto-inflammatory syndrome-2 (FCAS-2) is an autosomal dominant disorder due to the NLRP12 mutation which plays a role in the regulation of proinflammatory cytokines. It is characterized by fever, headache, joint symptoms, urticarial rash that is triggered by cold; usually starting in early infancy. Episodes are generally last for 5-10 days. It can also be accompanied by conjunctivitis, hearing loss and myalgia.

Objectives: Presenting a familial cold auto-inflammatory syndrome case with atypical presentation. Methods: Case presentation.

Results: A 17-year-old girl presented to outpatient clinic with recurrent arthritis, urticarial rash for 6 years. She had no accompanying fever in any of the episodes. The frequency of attacks increased in last 2 years, often lasting for 10 days, which were unresponsive to NSAIDs. Attacks were triggered irrelevant from cold exposure. She also had clinical diagnosis of mature onset diabetes in young (MODY), and autoimmune thyroiditis. On physical examination, she had arthritis and urticarial rash on left ankle. Acute phase reactants were increased. FMF was the initial diagnosis, however no mutation was found in MEFV gene sequencing. Auto-inflammatory next generation sequencing (NGS) panel demonstrated NLRP-12 gene mutation (p.Arg352Cys) compatible with FCAS-2. Colchicine treatment (1.5 mg/day) was able to provide disease control. Conclusion: Familial cold auto-inflammatory syndrome (FCAS) is characterized by recurrent attacks of cold-triggered fever, arthritis and urticarial rash mostly starting in infancy. This case differs from the classical pattern by old age, and it seems fever is not always one of the presenting symptoms. Informed consent to publish had been obtained from the parent. Trial registration identifying number: Note: Followings case report contains a method which in our thought is not appropriate in a case report abstract. Hence, the method was depicted as "case presentation". If committee have any suggestion in following days it could be changed accordingly. Introduction: Abscesses Aseptic (AA) syndrome is an autoinflammatory disorder mostly reported in adult, of unknown etiology characterized by occurrence of fever, AA and elevated acute phase reactants. It responds to steroid treatment. It is either associated with inflammatory diseases, such as Crohn's disease or relapsing polychondritis, or as « idiopathic ». Pediatric-onset AA has been reported in only 8 patients and never in association with JIA.

Objectives: To report the association of JIA and muscle AA. Methods: we retrospectively analyzed the medical notes from patients followed in two pediatric departments from the French FAI2R network for rare autoimmune and autoinflammatory diseases who presented both Juvenile Idiopathic Arthritis and multiple aseptic muscle abscesses. Patients had been included in the CEMARA platform for rare diseases, which benefits from an agreement from the French Commission Nationale Informatique et Liberté. According to the French legislation, no ethics committee agreement was requested for such a retrospective, observational survey. Results: We identified 3 male patients diagnosed with JIA between the age of 4 and 5 years. Patient 1 had systemic-onset with spiking fever, polyarthritis, myalgia, pericarditis; patient 2 had a seronegative polyarticular JIA; patient 3 had Rhumatoid Factor and ANA positive polyarticular JIA. There was no familial anamnesis of interest and the 3 patients were born from unrelated parents. Biological inflammation was present at in all cases with CRP > 70mg/L at diagnosis. Muscle abscesses developed 4, 30 and 48 months respectively after the diagnosis of JIA. At this time, patient 1 was on oral steroids, patient 2 on remission off treatment and patient 3 on oral steroids and subcutaneous etarnercept. Abscesses were revealed by painful tumefactions, associated with fever, flare of polyarthritis and an elevation of CRP. Ultrasound and MRI revealed a collection consistent with abscess in the biceps (patients 1 and 2) or the mesogluteus muscles (Patient 3). Corticosteroids and biologics were stopped and surgical drainage was performed in patient 1 and 2, showing an exudate of polymorphonuclear neutrophils. An extensive microbiological screen for bacteria, fungi and mycobacteria was negative in both cases. We also ruled out in the 3 patients chronic granulomatous disease as well as XIAP and PSTPIP1 mutations. In the 3 patients after 7 to 10 days on large spectrum of antibiotic treatment with no effect on lesions nor on the CRP level, steroid 1 to 2mg/kg/day were re-introduced or initiated, which was associated with quick improvement and a complete resolution of symptoms within 5 to 10 days. After tapering the dose of steroid, patient 1 developed a relapsing-remitting course, with recurrent biceps muscle abscesses that responded each time to increase of the steroid dosage. After 4 to 5 years from the onset of abscesses and the failure of several treatments including, in 2 cases the interleukin (IL)-1 receptor antagonist anakinra, all 3 patients were put on the anti-IL-6 receptor antibody tocilizumab and achieved remission that persisted, off steroid at the latest follow-up, 10 to 12 years later. However, severe bilateral erosive hips arthritis had developed in two patients before the onset of tocilizumab.

The diagnosis of muscle AA should be considered in a patient with abscesses associated with polyarthritis, particularly in the absence of documented infection or response to antibiotics. The association of early-onset polyarthritis, systemic inflammation and aseptic muscle abscess is likely a peculiar autoinflammatory disorder that may respond to anti IL-6 blockade. Objectives: We aimed to compare the demographic, clinical and genetic data of the patients whose symptoms started before the age five and after the age five to see the effect of age to the severity and outcome of disease, to evaluate the presence of mutations according the the age of symproms onset. Methods: Children who are diagnosed as FMF at Sağlık Bilimleri University KSSEAH Pediatric Rheumatology outpatient-clinic according to Tel-Hashomer Criteria were involved to the study. Patients were grouped based to the age of onset of the symptoms related to FMF. In the first group consisted 100 children with the clinical features that began before age of 5 and the second group consisted 100 children with the clinical features starting after age of 5. All the patients were carrying either heterozygous or homozygous MEFV mutations. Retrospective analysis of the files of the patients were done. Demographic data, genetic analysis, consanguinity, family history, age that first symptom ensue, duration passed until the diagnosis was made, frequency of attacks, duration of attacks and the involved sites during attacks, reports of MEFV analysis, laboratory data including CRP, ESR, SAA, blood counts, urinary protein levels were recorded. Severity of the disease were evaluated according to the Pras score. S Results: Mean age of the patients was 11.7±4.04. Mean age of the children whose symptoms began before age of 5 (Group 1) was 9.65±3.83 years, mean age of the children whose symptoms began after age of 5 (Group 2) was 13.7±3.09 years. Group 1 consisted 57 girls, group 2 consisted 46 girls. Consanguinity was 35% for group 1and 21% for group 2 (p<0.05). Clinical features started at the mean age of 2.37±1.19 years in group 1 and 8 ±2.39 years in group 2. The duration that passed till diagnosis was 2.19±1.99 years and was not different between groups. Although group 1 had more frequent attacks than group 2, the duration af attacks were similar in both groups. Colchicine dose was more than the dose needed for age in group 1, 14% of children needed increased doses, while in group 2 only 2% needed higher doses appropriate for their age (p<0.05). Fever and abdominal pain was present in 64% of all patients as the first symptom. Fever only was the presenting symptom in 19 children under age 5, while non of the patienst in group 2 had just fever as the presenting symptom (p<0.05). Artrhitis and chest pain were the presenting symptoms in group 2, but not the first symptom in group 1 (p<0.05). Mean Pras score of patients in group 1 was significantly higher (7.35±1.24) than the mean score of group 2 (6.14±1.55). Homozygous M694V mutations were statistically more frequent in group 1 (p<0.05). Leukocyte counts and CRP levels were higher, hemoglobin concentrations were lower during attacks in group 1 than group 2 (p<0.05).

Conclusion: Age of onset of FMF is an important factor while eavluating clinical features and severity of the disease. Increased doses of colchicine may be needed in children with early onset of disease. Severe disease causing mutations are also frequently seen when the disease starts early. Presence of recurrent fevers even without accompanying symptoms must warn the physician about the presence of FMF that will prevent the delay in diagnosis. So, both the complications like amyloidosis and the severe burden of disease will be avoided Introduction: Misdiagnosis in patients with such autoinflammatory syndromes as juvenile idiopathic arthritis (JIA) occurs rather frequently in routine practice. Because of the heterogeneity of JIA and the lack of widespread genetic testing, children with autoinflammatory syndromes can be treated for many years using the standard protocols before they turn out to be ineffective.

Objectives: The objective of this study was to estimate the incidence of autoinflammatory syndromes among biologic-naïve patients with JIA and those with a long-term disease, as well as the ineffectiveness of therapy with one or more biologics. Introduction: Immunologic processes are altered in patients with autoinflammatory diseases. Little is known about efficacy and safety of vaccinations in these patients, which might affect decision to vaccinate.

Objectives: The aim of this study was to determine vaccination coverage in children with PFAPA syndrome and other autoinflammatory diseases, to find out the reasons for potential vaccination dropout and to assess the frequency and nature of potential side effects after vaccination in these patients.

Methods: All children with PFAPA syndrome and other autoinflammatory diseases who visited rheumatology outpatient clinic at the University Children's Hospital (UCH) Ljubljana since 2008 were invited to participate in the study. They were asked to provide a written vaccination record and they were sent a questionnaire about the reasons for potential vaccination dropout and potential side effects after vaccination. The study was approved by the national ethics committee. Hereby we report the preliminary results of the study. Introduction: Interferon gamma (IFNγ) plays a pathogenic role in primary and secondary HLH. An ongoing phase 2/3 trial with emapalumab in primary HLH provides encouraging preliminary data and a pilot trial in MAS in the context of sJIA has just been initiated. Gainof-function mutations in NLRC4 are associated with a distinct autoinflammatory syndrome, with recurrent HLH. Objectives: To report safety and efficacy of emapalumab treatment in two patients carrying de novo missense mutations in NLRC4, with severe early onset HLH. Methods: Cytokine levels were measured by multiplex assay and by specific ELISAs and expression of IFNγ in freshly isolated PBMCs by cytometry.

Results: Pt 1. Caucasian male, presented, at age 20 days, fever and rash and progressively developed clinical and laboratory features of HLH leading to multi-organ failure. A de novo missense mutation in NLRC4 (T337N) was found. High-dose glucocorticoids and cyclosporine-A (CyA) led only to partial improvement. A sepsis triggered HLH reactivation. Emapalumab was started (compassionate use) on background of dexamethasone (13.6 mg/m2) and CyA. After 3 months, the child was discharged in excellent conditions (prednisone 0.3 mg/kg). Infections resolved during treatment with emapalumab. After 7 months of emapalumab treatment, all therapies, including emapalumab, were discontinued, without clinical or laboratory signs of HLH reactivation. Pt 2. This is 16 months old Caucasian boy with recurrent HLH and vasculitic skin lesions, since 1 month of life, secondary to a de novo missense mutation in NLRC4 (I343N). His disease was not controlled despite treatment with repeated methylprednisolone pulses and chronic daily glucocorticoid therapy, CyA (5 mg/kg) and anakinra (ranging from 5 to 25 mg/kg/day). When anakinra was withdrawn prior to start emapalumab he immediately developed highgrade fever, skin rash with vasculitic lesions and diarrhoea with laboratory features of HLH. Emapalumab was started (compassionate use) on background of methylprednisolone and CyA with rapid resolution of fever and improvement in biochemical parameters. During emapalumab treatment the patient resolved his initial HLH flare and presented two HLH episodes of mild intensity controlled with moderate intensification of glucocorticoid therapy. These episodes were triggered by systemic infections caused by pathogens translocated from the gut. His diarrhoea persisted with low grade inflammation; emapalumab was eventually withdrawn after 3 months. His subsequent course was characterized by additional mild episodes of MAS. Introduction: NLRP1-associated autoinflammation with arthritis and dyskeratosis (NAIAD syndrome) is a monogenic autoinflammatory syndrome caused by mutations in NLRP1 gene. It was first reported in 2016 and described as a complex syndrome of inflammasome hyperactivation with release of pro-inflammatory cytokines, dyskeratotic and papilloma-like skin lesions, arthritis and features of antibody-mediated autoimmunity with impairment of B-lymphocyte maturation.

Objectives: To report a case history of an 8-year-old Russian girl with some clinical features of NAIAD syndrome who was referred to our Center. Methods: genetic defect was confirmed via exome next generation sequencing; lymphocyte immunophenotyping was done according to the standard flow cytometry protocols. Results: We identified a heterozygous mutation in NLRP1 c.160 G>A, p.Ala54Thr in the patient, presenting with severe anemia (hemolytic and chronic inflammation anemia), thrombocytopenia, hyperkeratotic skin rash, dyskeratotic nail changes, additional auricular appendages, alopecia, arthritis and short episodes of alveolitis. The clinical feature that had not been previously described in NAIAD patients was corneal opacity with severe vision impairment. Until 8 years of age the patient suffered mostly from skin and eye sympthoms and cytopenia, that was treated by regular blood transfusions but otherwise had stable clinical condition. While in the process of clinical evaluation in our Center the patient deteriorated rapidly and developed a lifethreatening condition with respiratory and acute kidney failure and secondary HLH, requiring artificial lung ventilation. Features of respiratory distress was found on CT-scans. The blood tests showed highly elevated inflammatory serum markers (CRP up to 220 mg/l), hypergammaglobulinemia. Peripheral blood B-cells predominantly consisted of transitory forms with decrease of the post-switch B-cells. Urine tests showed proteinuria and hematuria. After the evaluation of potential clinical significance of the discovered mutation, the patient was started on IL-1R inhibitor (anakinra) and rituximab (N=4) with dramatic improvement in a matter of days. We further enhanced her therapy with ruxolitinib addition, hoping to curb IL-18 hyperproduction. Currently the patient is at home and well, on ruxolitinib and anakinra therapy. Introduction: ADA2 gene (previously named CECR1 gene), located on chromosome 22q11.1, encodes for adenosine deaminase 2, an enzymatic protein also involved in the homeostasis of endothelial and hematopoietic cells. Loss of function mutations in ADA2 gene are responsible of a rare autosomal recessive condition, named DADA2, characterized by a broad clinical spectrum ranging from a systemic inflammatory disease with vascular and multiorgan involvement, resembling Panarteritis Nodosa, to clinical conditions associated to a variable range of immunodeficiency and immune-deregulation. A certain percentage of patients, despite a consistent phenotype and lack of the ADA2 enzymatic activity, have an incomplete or negative genotype. Objectives: to define the genetics underlying a patient with a clinical phenotype consistent with DADA2 and a deficient enzymatic activity but without any mutation in the coding region of the CECR1 gene. Methods: Whole exome sequencing (WES) was performed in a 9 year old patient with a clinical phenotype consistent with DADA2 (fever, livedo reticularis, hypertension, hypogammaglobulinemia and two episodes of ischemic stroke) and a complete lack of ADA2 activity in circulating monocytes. In particular, we analyzed the proband and the asymptomatic parents by using Illumina's Nextera Rapid Capture Expanded Exome libraries and Illumina Hiseq2000 Instrument with 75bp paired-end reads. Since no coding mutation was identified as potentially candidate to account for the clinical phenotype, whole Genome Sequencing (WGS) was performed in the proband by TruSeq Nano DNA Library Prep kit and HiSeq 3000 Instrument with 150bp pairedend reads. Structural variants were identified with Manta.

Results: a homozygous tandem duplication of the genomic region encompassing exons 3 and 4 (involving 12895 bases), generated by two breakpoints in intron 2 and intron 4 respectively, was assessed by the WGS data. This has led to a gene transcript postulated to contain 1967 instead of 1536 nucleotides, due to an in tandem duplication of the sequences corresponding to exons 3 and 4, thus leading to a frameshift starting from codon V252 followed by a premature stop codon after 11 aminoacid residues (p.V252Gfs11*). Conclusion: The structural variation identified in the patient represents the first evidence of a genetic defect, different from the presence of biallelic loss-of-function point mutations, involving the ADA2 gene. A timely identification of ADA2 enzymatic impairment in the presence of a phenotype clearly consistent with DADA2 should lead to a careful and extensive molecular approach in all patients presenting a monoallelic variant or even in the absence of any mutation at standard DNA sequencing. Introduction: Autoinflammatory diseases are a group of immunological disorders characterized by 'seemingly unprovoked' episodes of fever and inflammation without evidence of autoantibodies or antigen-specific T cells, implying the importance of dysregulation in the innate immune system. Objectives: To report a case of severe rheumatic carditis that, in a significant host predisposition, could trigger an underlying autoinflammatory syndrome (associated with a mutation in MVK gene) Methods: M, a caucasian previously healthy 11-years old boy, diagnosed with a rheumatic fever with carditis at the age of 10 (years old) based on the following criteria: fever, polyarthralgia, erythrocyte sedimentation rate > 60 mm/h, C-reactive protein (RCP) > 3.0 mg/dl, increased antistreptolysin O titer (1700), prolonged PR interval on ECG and echocardiography/Doppler evidence of mitral and aortic valve regurgitation. He was treated with steroid therapy and secondary prophylaxis with Benzathine penicillin (every 21 days). After two months of the steroid withdrawal, he presented recurrent fever attacks (every 2-3 weeks). Each attack was heralded by chills, followed by a sharp rise in body temperature and lasted 4-5 days with gradual defervescence. Abdominal pain with vomiting or diarrhea and increased acute phase markers almost always accompanied the fever attack. Laboratory exams such as immunologic tests for autoimmunity as well as serology for CMV, parvovirus B19, EBV, adenovirus, coxsackie virus, and antistreptolysin O titer resulted negative or within normal limits. Common causes of infections were ruled out. Intravenous antibiotics were administered at any episode of fever and induced a partial remission of the disease activity and inflammatory markers, but his heart disease dramatically worsened such he needed to undergo to cardiac surgery (mitral valve repair and aortic valve replacement using mechanical prosthesis). Three days after the surgery, because of hyperpyrexia despite antibiotic therapy, he started corticosteroid therapy again achieving a partial remission in the following three months. When off steroid therapy, he developed four fever attacks lasting 4-7 days in 3-5 weekly intervals accompanied by abdominal pain and recurrent serositis (e.g., pleuritis, pericarditis) with acute phase markers increased and infectious disease tests, immunological and autoimmune exams always negative. SAA (serum amyloid A) levels were reported to be high in the interepisode periods while acute phase markers were negative. Results: Because of the recurrence of pericarditis and steroid dependence, we decided to start the treatment with daily Introduction: Neonatal onset multisystem inflammatory disease (NOMID) is a rare autoinflammatory disease with onset in infancy. Together with familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), they form the spectrum of cryopyrinassociated periodic syndrome (CAPS) with NOMID at the most severe end of the spectrum. CAPS is caused by single heterozygous germline or somatic gain of function mutations in the NLRP3 gene encoding the protein cryopyrin. To date, 209 different sequence variants of the NLRP3 gene and more than 90 heterozygous mutations are identified in patients with CAPS, and the list is expanding [1] . The case report here demonstrates a new sequence variant of NLRP3 gene in a patient with NOMID phenotype of Asian ancestry. Objectives: To report the finding of a new sequence variant c.1568T>A of NLRP3 gene in an Asian infant with NOMID Methods: Case report Results: A 10-month old girl developed a generalized skin rash within hours of birth. The rash was described as "migratory" and "waxes and wanes" every day. A skin biopsy at 7 months of age showed periadnexal and perivascular neutrophilic infiltrates. At 8 months of age she developed a prolonged fever of 2 weeks. Physical examination showed frontal bossing, a mild delay of gross motion function and mild central hypontonia. A generalised macular rash was found and some of them were of urticarial morphology. There was persistent elevation of inflammatory markers with highest Creactive protein (CRP) of 180mg/L (0.1-1.0mg/L), erythrocyte sedimentation rate (ESR) 77mm/h (2-34mm/h), and serum amyloid A greater than 16,000 ng/ml (1000-5000ng/ml). MRI brain showed macrocephaly with prominent supratentorial ventricular and extraaxial cerebral spinal fluid (CSF) spaces with bilateral papilloedema. Lumbar puncture (LP) showed elevation of white cell count (WCC) 38x10^6/L and protein 0.41g/L (0.15-0.4g/L) in CSF. There was no skeletal deformity found on radiographic bone survey. Next generation sequence genetic testing revealed a rare sequence variant of the NLRP3 gene (c.1568 T>A). Genetic testing of the parents were negative for this variant. Thus, it appears to have arisen de novo and is likely pathogenic. Anakinra (4mg/kg/day) was started and the fever and rash resolved within a day. A repeated LP after one year of treatment showed normalization of WCC and protein in CSF. The follow up MRI brain also showed interval improvement of supratentorial extra-axial CSF spaces and resolution of bilateral papilledema. Her development is appropriate to age. Conclusion: NOMID is a severe disease with onset within hours of life. Different systems can be affected and permanent organ damage can occur if treatment is delayed. However, not every feature presents in early infancy and they may appear later in the disease course. The skin biopsy finding of neutrophil infiltrates in our case provides a crucial clue of an autoinflammatory condition. CNS involvement is a unique feature of NOMID in the CAPS spectrum. Treatment with IL-1 blocking agents results in significant clinical and laboratory improvements in NOMID and has become the standard of care [2, 3] . The IL-1 receptor antagonist anakinra can penetrate into the CNS and treatment improves CNS inflammation. Introduction: Lipoid pneumonia (LP) is a rare entity with two clinical forms. Endogenous LP, putting aside cases associated with an obstructive cause, has been reported to be associated with metabolic, infectious or systemic inflammatory diseases. Diagnosis may be challenging as clinical presentation is insidious and non-specific. Radiological findings are well described with an unusually low density on chest CT scan suggesting the presence of fat. Histopathology, when available, describes lipid laden alveolar macrophages.

Objectives: Lipoid pneumonia is scarcely described in pediatric rheumatology and treatment strategy remains unclear. Methods: We report the cases of two patients sharing a similar presentation of auto-inflammatory disease of early onset with the association of arthritis, urticarial eruption and hyper eosinophilia. For both, progression was marked by lung involvement (lipoid pneumonia) with major clubbing in the absence of hypoxia.

Results: The auto inflammatory presentation resembles systemic Juvenile Idiopathic Arthritis (JIA) with a form particularly resistant to biotherapies and hypersensitivity reactions to drugs. Biologically, we did not detect any marker of auto immunity and genetic analysis with whole exome sequencing did not enable us to identify mutations in the genes associated with auto inflammatory diseases nor new variants in a common gene to the two patients. However, it is interesting to point out that under high doses of anti interleukine 1(IL1) therapy (10mg/kg), these patients maintain positive circulating levels of IL1 suggesting a central role of the inflammasome in the presentation of these patients. The early onset of clubbing associated with lipoid pneumonia and in the absence of hypoxia seems characteristic and syndromic of this entity. Results: Patient 1 (P1) was a 12-month-old girl referred because of recurrent attacks of fever with high levels of CRP from the age of two months, with or without documented infections, chronic microcytic anaemia and failure to thrive. Aseptic febrile manifestations included vulvitis, parotiditis, adenitis, and neutrophilic panniculitis. She developed progressive lymphopenia, with undetectable levels of B cells by age 15 months, so that IVIG was initiated at this time. At last follow-up, aged six years, her height and development were normal and she was no longer subject to recurrent infections. However, she continued to experience three to four febrile attacks each month, associated with elevated CRP levels. Whole exome sequencing identified compound heterozygous mutations in the TRNT1 gene (c.1213G>A, p.G405R / c.1057-7C>G). Patient 2 (P2), a girl born at term to first-cousin parents presented with intrauterine growth retardation (IUGR) and severe neonatal anaemia necessitating blood transfusion on the first day of life. During infancy she required regular blood transfusions because of sideroblastic anaemia, which resolved spontaneously at the age of four years. She also demonstrated developmental delay and severe autoinflammatory flares associated with fever and high levels of CRP, diarrhoea and dehydration. Mild T and NK lymphopenia together with a profound B cell defect were evident at four years of age. Sanger sequencing of TRNT1 identified a homozygous mutation in exon 7 (c.977T>C, p.I326T). Using an ultra-sensitive digital ELISA combined with a high specificity pan-IFN-α antibody pair, we observed an increased concentration of IFN-α protein in the serum from P1 (246.44 fg/mL, healthy controls <10 fg/mL) and P2 (108.18 and 38.05 fg/mL, healthy controls < 10 fg/mL), comparable to the levels measured in the context of certain monogenic type I interferonopathies. We also recorded an increased expression of ISGs in the whole blood of P1 and P2 on 3 occasions. In an ex vivo flow cytometry assay, STAT1 and STAT3 were constitutively phosphorylated in T lymphocytes and monocytes from P2. Both patients also displayed a negative IFN score on one occasion, suggesting a fluctuating biological process. Conclusion: These data indicate a constitutive activation of the type I IFN pathway in patients with biallelic mutations in TRNT1, and thus suggest a possible role for type I IFN in the pathogenesis of SIFD. An increase in serum IFN-α protein and an enhanced expression of ISGs have been previously reported in one patient 2 . How aberrant tRNA processing secondary to TRNT1 dysfunction might mediate enhanced type I IFN production and signalling remains to be determined. Informed consent to publish had been obtained from the parents of the two patients. face, alopecia areata, periorbital edema, diffuse arthralgias, poliarticular arthritis and growth hormone deficiency. Another remarkable clinical feature was multiple painful pannicular nodules, which resulted in a severe diffuse lipodystrophy, particularly on the face, with subsequent need to undergo a course of lipofilling. She displayed a highly positive interferon signature, but her genetic evaluation, including whole exome sequencing, performed taking into account the family history of connective tissue disease, was inconclusive. Objectives: Her disease had always showed a moderate response to corticosteroids, while several therapeutic attempts with immunosuppressant drugs (cyclosporine, azathioprine, ciclophosfamide, hydroxychloroquine), intravenous immunoglobulins and biological agents (anakinra, infliximab and abatacept), together with hyperbaric therapy did not lead to significant improvement of her symptoms. Methods: Given the severity of the cutaneous involvement with its related emotional burden and acknowledging the role of interferon in the pathogenesis of the disease, a therapy with 10 mg BID tofacitinib (JAk1-JAK3 inhibitor) was started.

Results: She displayed a prompt improvement of her lipodystrophy and chilblains along with a slow but progressive hair re-growth. An almost complete healing of the panniculitic lesions was observed, along with the halving of her interferon signature score. Introduction: Although histiocytic necrotizing lymphadenitis (HNL) or Kikuchi-Fujimoto disease, which is characterized by self-limiting regional lymphadenopathy with prolonged fever, has a low recurrence rate, this rate appears to be higher and the disease progresses to severe forms associated with autoimmune diseases such as systemic lupus erythematosus (SLE) in some previous reports. Introduction: Behςet's disease (BD) is a chronic, relapsing, multisystem inflammatory disorder classified as vasculitis and characterized by recurrent oral and genital ulcerations, uveitis, and protean clinical signs of skin, central nervous system, musculoskeletal, and gastrointestinal involvements. Oral ulceration is more common in younger patients. However, there are few reports about chronic hypopharyngeal ulceration, are rare involvements in child in early phase. We report the case of a 4year-old Japanese girl with refractory laryngeal edema who was successfully treated with multidrug therapy including infliximab (IFN).

Objectives: This report aimed to scrutinize of BD-related laryngeal and hypopharyngeal manifestations in a Japanese young girl. We show that rare clinical phenotype in early phase of pediatric-onset BD.

Methods: A young girl with multiple ulceration and stenosis of the hypopharynx and laryngopharyngeal involvement at onset.Clinical features, especially laryngeal findings by laryngoscopy in our patient were described in detail about the findings symptoms at onset and during the course. By using the paediatric Behςet's disease (PEDBD) classification criteria, the case was diagnosed.

Results: In a 4-year-old Japanese girl with a 2-year history of recurrent fever, recurrent ulcerative gingivostomatitis, snoring or respiratory disorder during sleeping, was referred to our hospital with the suspicion of rheumatic diseases after tracheotomy was enforced due to the breathing disorder and dysphagia. Before tracheotomy, physical examination revealed that her voice was hoarse and dysphasia. Soft tissue lateral neck film revealed straightening of the cervical spine with edema of the epiglottis and upper airway. Laryngeal endoscopy findings showed that laryngeal and hypopharyngeal involvements were edematous severely. After tracheotomy, the patient received oxygen supplementation, methylprednisolone. Involvement in ulcerative colitis was estimated by using colon fiverscopy. By using the PEDBD classification criteria, the case was diagnosed.Her symptoms except for intestinal involvement did not change with these maneuvers. On admission, the patient showed body temperature of 37°C, heart rate of 107/min, respiratory rate of 28/min, and blood pressure of 108/66 mmHg. Genital ulcers were absent, and repeat ophthalmologic examinations showed no symptoms. Laboratory examinations revealed the presence of nonspecific inflammation: white blood count, 11,100/μL; C-reactive protein (CRP) level, 2.0 mg/dL; electron spin resonance (ESR) level, 20 mm/h. Hypocomplementemia was absent. The results of immunological examinations were negative for specific autoantibodies, including antinuclear antibody, anti-dsDNA antibodies, and anti-neutrophil cytoplasmic antibodies. The test for HLA-B51 was positive. Bone marrow examination showed no evidence of malignancy. Then, colchicine and 1mg/kg/day of prednisolone (PSL) therapy was started. When the dose of PSL was decreased, her snoring and respiratory disorder relapsed. Therefore, infliximab (IFX) therapy was started and the dose of PSL was gradually decreased. For approximately 1 years, she showed a good general condition with laryngeal swelling improved.

Conclusion: There is a case of BD in a child, who has multiple ulceration and stenosis of the laryngeal and hypopharyngeal involve-mentsThe Upper airway manifestations could be critical to identify potentially life-threatening laryngeal involvement at onset by direct laryngoscopy. In our case might deal with the successful treatment of a laryngopharyngeal involvements with IFX as anti-TNF-alpha agents. Informed consent to publish had been obtained from the parent. veloped amyloidosis and MAS before IL1 inhibitor treatment initiation, which led to her death. In patients receiving anti-IL-1 therapy AIDAI index decreased from 58.3±11,2 before to 1,5±1,4 after 6 month of therapy (p =0.003).

Conclusion: MKD symptoms can be variable and sometimes atypical, which requires physician's awareness. In our cohort of MKD patients anti IL-1 therapy was highly effective. Introduction: Although nowadays intraarticular corticosteroid injections may be considered a somewhat obsolete method of treatment of juvenile idiopathic arthritis, they still might serve as an alternative to stronger but more expensive DMARDs/biologic drugs. treated with injection was found to be median 11,5 (range 1-66 ) months. The median interval between repeat injections was 27.5 (6-57) months. Three joints did not respond to IAC injection. Subgroups of the disease and disease duration had no effect on the duration of remission. The duration of remission was longer in boys (11.5 vs 8 months), in ANA positives (13,5 vs 10 months), and in patients with concurrent MTX treatments (12 vs 9 months) . However, the differences were not statistically significant. The level of acute phase reactants had not been shown to correlate with the duration of remission.

No early or late adverse events were observed after the IAC procedure. Conclusion: In single or multiple joints, IAC treatment induced remission in a significant proportion of patients without major side effects. For every infectious side effect, the date, the severity, the need for an hospitalization, the accountability of the treatment on the occurrence, and the consequence of the event on the biologic course were noted. The type of microorgansim and the affected organ were also analyzed. Incidence rates were expressed in number of events per 100 person-years (100p-y), and OR were calculated; for their comparison, we used the Fischer test with a significance threshold at 0.05.

Results: Six hundred eighty-six patients with JIA from thirteen Frenchspeaking rheumatologic reference centers were included in the study. A total of 1095 treatments with biological agent, for 3075.4 personyears of exposure were analyzed. One hundred eighty-four IAE occurring under a treatment with biologics were described, that is to say an incidence rate of 6.0 events/100 p-y, 15.5/100 p-y with Tocilizumab, 9.6/100 p-y with Canakinumab, 7.4/100 p-y with Abatacept, 6.9/100 p-y with Golimumab, 6.7/100 p-y with Aankinra, 6.3/100 p-y with Infliximab, 4.8/100 p-y with Etanercept, and 3.7/100 p-y with Adalimumab. Risk of developing an infection was significantly higher with IL6 antagonists than with TNF-inhibitor (TNFi) ( Ultrasound showed transplanted liver unimpaired, non-biliary oblong vein, portal vein width 6mm, PV vmax 48cm / sec, HAV max 69cm / sec, hepatic flow three-phase normal. In Liver biopsy 01.2018: The organ structure preserved, without features of acute cell rejection. The stipend of fibrous connective tissue with the creation of port-port bridges within the port space (S3 according to Ishak). Discrete inflammatory infiltrates of a chronic nature in the area of the gantry-biliary and focaly intralobulary, no cholestasis, no steatosis, no ductopenia. The hepatologist decided to add to treatment encorton, continue tacrolimus and methotrexat.

Results: The use of methotrexate due to JIA in patients after liver transplantation on tacrolimus treatment allowed for rapid improvement in joints. Conclusion: During 2 years of obserwation frequent laboratory control and liver assessment in USG and liver biopsy showed a stable function of the transplanted organ. Informed consent to publish had been obtained.

None Declared Conclusion: Our study showed that the frequency of CAM use is associated with the nature of the parent/legal guardian's profession, their monthly income, acquaintances who use CAM and their child's diagnosis. CAM was concomitantly used to the standard therapy and medical staff was not informed about it (87%; 68.25%, respectively). Due to rarely documented CAM side-effects and the possible interferences between CAM and standard therapy, it is essential for pediatric rheumatologists and other medical personnel to improve the communication with families in order to achieve optimum disease management outcomes. Therefore, more data on population characteristics and commonly used types of CAM, would allow medical staff to raise awareness of the benefits and consequences that such therapies offer. The numbers of registrations were distributed as follows; start up 92 (9%), controls 901 (86%) and discontinuation of biologics 54 (5%) (18 due to remission, 25 due to insufficient response and 13 due to adverse events). Physicians' assessment of disease activity, number of active joints, number of joints with limited range of motion, CRP, ESR and CHAQ were significantly higher in the "start up medication group" than in the registrations from control visits; all p`s <0.01 (data not shown). When comparing registrations from control visits with those in the discontinuation group, disease variables were significantly better in the 18 registrations from patients discontinuing biologics due to remission"; all p`s<0.05, and significantly worse in registrations from patients discontinuing due to insufficient response; all p`s <0.05 (data not shown). Severe disability (CHAQ score >= 1.5), was found in 146 (14%) of the total registrations; 24 (26%) in the "start up group", 113 (13%) in the "control group", and 9 (17%) of the registrations in the "discontinuation group"; however, no significant differences between the groups were found Conclusion: Registrations on biologic medications consist mainly of patients with polyarticular and extended oligoarticular JIA (55% of registrations), but also a relatively large proportion of systemic JIA (21% of registrations). The most frequently used biologics were etanercept, followed by adalimumab, tocilizumab and infliximab. Disease activity measures, inflammatory parameters and physical status improved from start up registrations to control visits. Severe disability was found in a relatively large proportion of registrations. : 6 (1-12); MTX SC : 9 (4-14); p=0.044). Fifty-six children (73%) had MTX-induced nausea deduced from the diaries (MTX O : 16/27; MTX SC : 40/50; p=0.051). The BAI-Y raw score was higher in the MTX-induced nausea (diary) subgroup compared to all others, but there was no difference in BAI-Y raw scores between the MTX intolerant and MTX tolerant subgroups (Table 1) . Unfavourable coping strategies were used more often in the MTX intolerant subgroup and the MTX-induced nausea (diary) subgroup compared to all others.

[1] The scores of the subscales externalising and internalising/ catastrophizing are summed up, ranging from 10 to 50.

Conclusion: MTX-induced nausea was associated with unfavourable coping strategies (externalizing and catastrophizing) and anxiety in children with JIA, MTX intolerance was associated with unfavourable coping strategies. These psychological factors need attention when children with JIA commence low-dose MTX treatment, in order to intervene when appropriate. [8 -14] . Their body mass index (BMI) was normal and most had been active athletes prior to disease development with normal social contacts but at admittance they were experiencing social isolation and had ceased all physical activities. Ad admittance the children were in severe pain, most frequently the condition involved a lower extremity (86 %) and 59% were depending on a wheelchair or crouches. The time from symptom appearance to diagnosis was 174 days . At discharge, after a median hospitalization of 14 days, all had remarkably pain reduction or were completely free of pain, and everyone was reintroduced to their social life. Using the affected extremity was achieved by 97% at discharge and by the end of the outpatient training program (1 month later) almost half could run and the rest improving. Setbacks were seen in 6 patients (21%), but all, except one, were managed solely at our outpatient clinic. Conclusion: CRPS in children was a rare but invalidating disease. In our material it was most often seen in girls around the age of 11 years affecting a lower extremity. The children were prior to the disease physical active with a normal BMI. Despite the long diagnostic and referral delay great improvement was achieved with our in-patient treatment approach. were enrolled. All were evaluated for pain intensity through the Visual Analogue Scale (VAS) and gait evaluation using dynamic baropodometry (FootWork Pro, AM cube, Gargas, France).

Results: The mean age of the IMSP group was 13.6 years (SD = 2.1, range 9.8 -16.9) and the mean age of the control group was 13.5 years (SD = 2.0, range 9.6 -16.5). The mean pain scale was 5.4 cm in the IMPS group. In gait, the mean right foot velocity of the IMPS group was significantly lower than that of the control group (p = 0.034), the time of the IMPS group step was significantly higher than that of the control group (p = 0.003) and the pace of the IMPS group was significantly lower than that of the control group (p = 0.001).

Conclusion: Children and adolescents with IMPS present gait alterations when evaluated by dynamic baropodometry. Introduction: Rheumatic fever (RF) is an acute immune-mediated consequence of group A beta-hemolytic streptococcus (GABHS) infection. Rheumatic heart disease is the most threatening feature and the main cause of morbidity and mortality. Due to the high risk of recurrence in case of another streptococcal infection, RF patients need a long term secondary antibiotic prophylaxis in order to prevent a relapse. The use of intramuscular benzylpenicillin is still recommended worldwide as the most effective drug for secondary prophylaxis against GABHS. However its effect on health-related quality of life (HRQL) has never been investigated so far.

Objectives: To evaluate the impact of long term prophylaxis with intramuscular benzylpenicillin on the quality of life of patients with rheumatic fever Methods: RF patients in secondary antibiotic prophylaxis for more than 1 year, referring to our pediatric rheumatologic center, and their parents were asked to fulfil a HRQL questionnaire: due to its high face validity the Pediatric Quality of Life (PedsQL 4.0) was chosen. An age-matched group of healthy children and their parents were used as control samples considering the absence of a control group of patients with previous RF off secondary prophylaxis, due to ethical reasons. The Global Score (GB) was calculated as the sum of all the items in the four domains evaluated (physical, emotional, social and school functioning); the Psychosocial Health Score (PHS) was the sum of all items related to emotional, social and school functioning domains. Comparisons between groups were analysed by means of Mann-Whitney U test. Results: PedsQL questionnaire was sent to 28 families of RF patients and 18 controls respectively. The median age of RF patients was 9,8 years with a median duration of secondary prophylaxis of 20 months, and 9,4 years for controls . All the RF patients had a complete adherence to prophylaxis. No relapses were observed. The main results are shown in Table 1 .

Patients with RF and their parents scored lower than controls in school scale domain. Patient with RF had a trend to lower levels of GB and also PHS compared to aged matches controls. No differences were detected between parents and children in control groups Conclusion: Although RF families have a good compliance to long term secondary prophylaxis with intramuscular benzylpenicillin, this prolonged treatment affect the quality of life of both children and parents.

The results of this study are preliminary, but if confirmed on a bigger sample, might stimulate a collaborative effort in reviewing the evidence on secondary prophylaxis in RF patients. Introduction: Chronic red eye is a common cause of paediatric rheumatology consultation to exclude a rheumatic disease. Paediatric ocular rosacea (POR) is a underdiagnosed disease, even by ophthalmologists. Since 1999 twelve cases of POR were diagnosed in our Paediatric Rheumatology Unit and Pediatric Ophthalmology Unit, the majority of which with significant diagnostic delay. Objectives: To alert to clinical features, diagnosis and therapeutic approaches of POR. Methods: Retrospective study. Patients were include based in POR Coimbra criteria: (> 3 criteria): a) Chronic or recurrent keratoconjunctivitis and/or red eye and/or photophobia; b) Chronic or recurrent blepharitis and/or hordela and/or chalazia; c) Eyelid telangiectasia; d) Features of cutaneous rosacea and/or periorifical dermatitis; e) Positive family history of cutaneous and/or ocular rosacea. Results: Twelve children: seven boys and five girls. Mean age at diagnosis was 10,5 years (±4,0); with a median diagnostic delay of 2,5 years (IQR 3, 9) . Bilateral hyperaemia, ocular irritation and eyelid inflammation were found in all patients. Significant improvement occurred with a minimum of three months treatment with oral macrolides (erythromycin or clarithromycin) or topical azithromycin. Leukoma occurred in 6 children and spontaneous corneal perforation in 1.

Conclusion: POR is a disease with high morbidity. POR Coimbra criteria can improve its prompt recognition avoiding treatment delay. A high level of suspicion is needed in patients with red eye when Introduction: Carnitine palmitoyltransferase II (CPTII) deficiency is a long-chain fatty-acid oxidation disorder. Carnitine palmitoyl transferase II is localized in the inner mitochondrial membrane and catalyzes the formation of acyl-coenzyme A. Three phenotypes of CPT II deficiency are known: a lethal neonatal form, a severe infantile hepatocardiomuscular form and a mild myopathic form. The disease follows an autosomal recessive mode of inheritance. Clinical features are attacks of muscle weakness, myalgia, pain and rhabdomyolysis with or without renal failure. Trigger factors are fever, prolonged exercise and exposure to cold.The severity of attacks is highly variable and some of these attacks may be complicated by acute renal failure . The CPTII deficiency is the most common cause of hereditary myoglobinuria and the most frequent disorder of lipid metabolism affecting skeletal muscle. Objectives: To emphasize considering CPT II deficiency in a patient with recurrent episodes of rhabdomyolysis triggered by fever. Methods: A six years old child came to our department because of fever, myalgia and generalized muscular weakness. She had a personal history of diffuse muscular pain and generalized weakness triggered by fever . Before coming to our observation both Duchenne Muscular Dystrophy and Becker Muscular Dystrophy were excluded. When she was admitted to our department she was unable to walk and presented generalized weakness, muscular pain, and fever. Laboratory text showed an increase of serum creatine kinase levels (15,400 U/L, normal value < 190U/L), aspartate aminotransferase (586 U/L, normal value <30U/L), alanine aminotransferase (382 U/ L, normal value< 30U/L). Complete blood count and renal function tests were in normal range. Her urine was brown-colored, while urinalysis was negative for red blood cells. She was managed with intravenous hydration with immediate clinical and laboratory improvements. The recurrence of severe episodes of rhabdomyolysis and normal creatine kinase value between attacks suggested Carnitine palmioyltransferase II (CPTII) deficiency .

Results: The genetic analysis of the CPT II gene revealed homozygosity for the p.Ser1133Leu mutation, so CPTII deficiency was diagnosed. A low-fat and rich in complex carbohydrates diet was prescribed. She was advised to avoid physical exertion and exposure to cold and to receive additional carbohydrates before exercise and during illness.

Conclusion: CPT II deficiency should be suspected in children with recurrent rhabdomyolysis triggered by fever, exercise and exposure to cold . Molecular genetic analysis of the related gene should be performed to confirm the diagnosis. A prompt diagnosis and a careful management are essential to prevent further episodes of rhabdomyolysis. Consent to publish had been obtained. Patients' ages at diagnosis were 3 to 8.5-years-old, the youngest was the only female. Time to diagnosis since first visit in the rheumatology clinic was 7 months to 6.5 years. Symptoms began during the first or second year of life, and consisted primarily of episodic swelling of the knee, along with tenderness and limping, but without fever or any extra-articular manifestation (including uveitis). Some episodes began after minor local trauma and lasted days to months. Physical examination revealed swollen and mildly tender left knee, and mild limitation of the range of motion. Two patients had vascular skin lesions on their left lower limb. Laboratory workup was unrevealing, in general, with the exception of highly elevated C-reactive protein in the female patient, during a single episode (she was later found as heterozygote for the V726A mutation in the MEFV gene). Anti-inflammatory drugs (including colchicine in the girl) and intra-articular corticosteroid injections in 3 patients had no measurable effect on the course of the disease. Bloody fluid was aspirated from the knees of two patients. Differential diagnosis included JIA, familial Mediterranean fever, anatomic disorders of the knee and pigmented villo-nodular synovitis. As radiographs, bone scintigraphy and ultrasonography revealed inconsistent findings, MRI scans were performed, and diagnosis was finally made. At the time of writing this report, two patients were already successfully treated with sclerotherapy. Conclusion: Intra-articular vascular malformation should be suspected in patients with dermal vascular malformations, episodic monoarthritis, without extra-articular involvement, with normal inflammatory markers, history of aspiration of bloody synovial fluid, or when anti-inflammatory treatment fails. MRI is the diagnostic modality of choice, revealing high T2 and low T1 signal intensity and patchy enhancement after intravenous contrast medium injection. Treatment of the vascular lesion depends on the type of malformation and the flow within it and can include excisional surgery, embolization, sclerotherapy and irradiation. Introduction: A large body of evidence demonstrates the pivotal role of interferon gamma (IFNγ) in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH) and macrophage activation syndrome (MAS). IFNγ is a key endogenous activator of macrophages and exerts its biological activities by phosphorylation of the transcription factor Signal transducer and activator of transcription 1 (STAT1).

Objectives: In this study, we aimed to investigate whether the phosphorylation status of STAT1 in whole blood cells represents a good biomarker for the identification of patients at early stages of MAS/ sHLH. Methods: Whole blood samples from patients with suspected untreated MAS/sHLH (n=7) and suspected treated (glucocorticoids) MAS/sHLH (n=9) were collected prospectively. As controls, whole blood samples from patients with active systemic Juvenile Idiopathic Arthritis (sJIA) without MAS at sampling (n=6) and healthy subjects (HS, n=7) were used. Fresh whole blood cells were left unstimulated or stimulated with different concentrations of IFNγ (0.01, 0.1, 1, 10 ng/ml) for 10 minutes. The intracellular phosphorylation levels of Tyrosine (701) STAT1 (pSTAT1) were evaluated by flow cytometry. Results have been expressed as Delta mean fluorescence intensity (MFI), calculated by subtracting the MFI of cells stained with isotype control antibody (Ab) from that stained with anti-pSTAT1 Ab. Anti CD3, CD14 and CD16 staining was performed to discriminate the monocyte, neutrophil, natural killer-and T-cell subpopulations. In addition, western blot (WB) analyses were carried out on unstimulated whole blood cell lysates, in order to further evaluate the basal levels of pSTAT1 and total STAT1. Results: In both treated and untreated MAS/sHLH patients, flow cytometric analyses showed no significant differences in pSTAT1 levels in unstimulated monocyte, neutrophil, natural killer and T cell subpopulations, compared to sJIA and healthy subjects. Interestingly, we found that, compared to sJIA and healthy subjects, in patients with untreated MAS/sHLH, pSTAT1 levels were significantly higher in monocytes (p<0,01 Vs HS, p<0,05 Vs sJIA and p<0,01 Vs HS, p<0,05 Vs sJIA, for stimulation with 1 and 10 ng/ml of IFNg respectively) and neutrophils (p<0,05 Vs HS, p<0,05 Vs sJIA and p<0,01 Vs HS, p<0,01 Vs sJIA) stimulated with the higher concentrations of IFNγ (1 and 10 ng/ml). In contrast, we did not find differences in the levels of pSTAT1 observed in stimulated monocytes and neutrophils from treated MAS/sHLH patients or those observed in cells from active sJIA and healthy subjects. In order to further evaluate the phosphorylation status of STAT1, we also performed WB analyses on patient whole blood cell lysates. We found that pSTAT1 levels were markedly higher in untreated MAS/sHLH patients and also in treated MAS/ sHLH patients, compared to active sJIA patients without MAS. Conclusion: Our results demonstrate that the combined evaluation of pSTAT1 levels by flow cytometry in monocytes and neutrophils stimulated with high doses of IFNγ and by WB in fresh whole blood cell lysates show high levels of pSTAT1 and might contribute to the identification of patients at early stages of MAS/sHLH. WB might be more sensitive and technically simpler approach, although it takes at least 2 days. In addition, our results further support the involvement of IFNγ in the development of the diseases, as suggested by the increased phosphorylated STAT1 levels exclusively in patients with active MAS/sHLH and not in patients with active sJIA. All of the patients were treated with NSAID or corticosteroids at the beginning of the disease. 20% of the patients reached remission with NSAID, corticosteroid or DMARDs however rest of the patients needed at least one biologic drug. Anakinra was the most common first-line biologic treatment choice (n=45). Among the patients whom remission was achieved, 44% of them were treated with anakinra, 12% with canakinumab, 10,7% with tocilizumab. 46% of the patients had recurrent attacks however 54% had one attack (26% monophasic, 28% persistant). 18,7% of the patients had polyarticular joint involvement during the disease course. There was no significant difference between the patients with polyphasic and monophasic course in terms of laboratory and clinical features other than HSM (%42,4 vs %17,1; p=0,016 respectively). 40% of the patients are being followed without any treatment after remission was achieved. Five out of 8 patients who had remission with tocilizumab had polyarticular joint involvement, thus it can be speculated that anti IL-6 treatment is very beneficial in this specific group of patients. Conclusion: sJIA is an important disease with high risk of morbidity and mortality. As our center is one of the most important tertiary referral rheumatology center, we expect to see higher MAS incidence than the previous reported sJIA series. Although 1/5 of the patients achieved remission without any biological agent, they are still the most beneficial treatment in most of the sJIA patients. Anti-IL1 drugs are the mostly preferred treatment choice and they have the highest success rate. Anti-IL-6 agents are very efficient in patients with systemic onset polyarticular course.

Introduction: Serum soluble CD163 (sCD163) level is a valuable diagnostic marker in hemophagocytic lymphohistiocytosis (HLH) and systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS). However, it is still unclear whether serum sCD163 level is useful for the assessment of disease activity of s-JIA. Furthermore, it is unknown whether sCD163 expression is modified by interleukin (IL)-6 blocking.

Objectives: This study aims to investigate the clinical significance of serum sCD163 levels as a predictor of the disease activity of s-JIA.

Methods: In this study, we examined 63 patients with s-JIA, four with Epstein-Barr virus-induced HLH (EBV-HLH), and seven with Kawasaki disease (KD), along with 14 healthy controls. We quantified serum cytokine levels (sCD163, neopterin, IL-18, IL-6) by enzyme-linked immunosorbent assay and compared the results with the clinical features of s-JIA.

Results: Serum sCD163 levels were significantly elevated in patients with s-JIA associated MAS and EBV-HLH compared to those in patients with acute-phase s-JIA and KD. In addition, serum sCD163 levels profoundly increased with the progress of MAS and correlated positively with the disease activity of s-JIA, even in patients receiving tocilizumab. Furthermore, serum sCD163 levels significantly decreased in the inactive phase compared to those in the active phase and normalized in remission.

The correlation between macrophage activation and serum sCD163 levels might be a unique indicator of the disease activity and a potential diagnostic laboratory criterion for clinical remission in patients with s-JIA, including those receiving tocilizumab. Introduction: Severe lung disease including pulmonary alveolar proteinosis (PAP) and interstitial lung disease is an increasingly recognized complication of Systemic Juvenile Idiopathic Arthritis (SJIA). The inflammatory features and patterns of this lung disease are poorly described.

Objectives: To describe the experience of SJIA-associated lung disease in a large US referral center as well as novel immunological and pathophysiological findings. Methods: Informed consent was obtained from all patients and/or their legal guardians through protocols approved by the CCHMC IRB. Clinical data was abstracted from medical records, and cellular, biomarker, and genomic analysis performed as indicated.

Results: Since 2010, we have evaluated 12 patients with SJIAassociated lung disease. The number of new patients evaluated has markedly increased during this timeframe, with 5 newly diagnosed patients evaluated in 2017 alone. Considering only local patients, the incidence of severe lung disease in SJIA patients may be as high as 5-10%. Most patients with SJIA-associated lung disease had refractory disease despite treatment with multiple biologics, predominantly systemic features, and history of overt or subclinical macrophage activation syndrome (MAS). Patients with active SJIA and lung disease also had markedly higher serum IL-18 levels than patients without lung disease (median 45,854ng/ml vs 7,194, p<0.01), levels comparable to that seen in MAS. Chest imaging (CT and MRI) findings included diffuse ground-glass opacities, subpleural reticulation, interlobular septal thickening, and lymphadenopathy. F-18-FDG positron tomography was also performed in one patient, showing multifocal uptake consistent with an inflammatory process.

Five patients had open lung biopsy. While there was substantial variability in findings, typical findings included patchy but often extensive lesions histologically comprised of lymphoplasmacytic (CD4+ and CD8+) infiltrates and mixed features of PAP and endogenous lipoid pneumonia. Air spaces were filled with granular lipoproteineous material typical for PAP, foamy macrophages and cholesterol clefts. Pleural and interlobular septal collagenous fibrosisas well as vasculopathy was prominent is some cases. PAP results from disordered surfactant homeostasis, often secondary to defective alveolar macrophage GM-CSF signaling. However, SJIAassociated lung disease patients had several features atypical for GM-CSF signaling related PAP. Bronchoalveolar lavage (BAL) fluid often did not reflect biopsy findings and typically did not contain the abundant proteinaceous material seen in PAP with only a minority of macrophages being lipid-laden (3-25%). BAL fluid did contain high levels of IFNg-induced chemokines CXCL9-11, observed in serum and tissue during MAS. Whole exome sequencing was performed on seven patients, which failed to reveal any variants associated with familial PAP. Finally, isolated alveolar macrophages showed normal STAT5 phosphorylation in response to GM-CSF, suggesting that this signaling axis is functional. Conclusion: Severe lung disease is increasingly detected in children with SJIA, particularly in association with MAS. Pathologic hallmarks of disease are often absent from BAL fluid, supporting utility of lung biopsy. This entity has distinct clinical and immunologic features from other disorders including PAP, and represents an uncharacterized inflammatory lung disease. Introduction: Early diagnosis and treatment of systemic-onset juvenile idiopathic arthritis (SJIA) are crucial in order to avoid long-term complications. However, the existing International League of Associations for Rheumatology (ILAR) classification criteria for SJIA have been criticized. A substantial percentage of SJIA patients fail to fulfill them, mostly because of the absence of arthritis, or due to the exclusion criteria requiring regular testing of HLAB27, which is often not performed in real-life clinical practice. Objectives: To evaluate and compare the existing Yamaguchi and ILAR classification criteria as well as a new set of ILAR 'modified' criteria without HLAB27 testing, in an international cohort of SJIA patients. Methods: This is a multicentre, retrospective and inception cohort study, through the international platform JIRcohorte. The existing ILAR classification criteria, a new set of 'modified' ILAR classification not including HLAB27 testing and the Yamaguchi criteria were applied in SJIA patients followed in one of the participating centres in Switzerland, France, Belgium and Morocco. 50 SJIA patients with no more than one missing criteria in the database were enrolled (sex ratio 1:1) and compared to a control group of 46 patients with other autoinflammatory and autoimmune diseases presenting with systemic and articular manifestations. Results: Of 50 SJIA patients enrolled, only 56% (28/50) fulfilled the ILAR classification criteria for SJIA, 14% (7/50) were classified in another JIA category and the remaining 30% (15/50) were unclassified. Among the 22 patients who failed to fulfill the ILAR criteria, 4 (18%) had no arthritis, 9 (41%) had no other systemic manifestations than fever at diagnosis, 1 (5%) had family history of psoriasis, and in 8 patients (36%) HLAB27 testing has not been performed. ILAR 'modified' criteria identified 74% (37/50) of SJIA patients (kappa value 0.73). Their sensitivity and specificity in the discrimination of SJIA patients from the control group were of 74% and 100% respectively, their positive predictive value (PPV) of 100% and their negative predictive value (NPV) of 78%. Yamaguchi criteria were accomplished in 46% (23/50) of SJIA patients (kappa value 0.41), with a sensitivity of 44%, a specificity of 98%, a PPV of 96% and a NPV of 62% respectively. Conclusion: A substantial percentage of SJIA patients (44%) followed through the international, real-life JIRcohorte platform, failed to fulfill the existing ILAR classification criteria. The application of Yamaguchi criteria in our SJIA population was no more advantageous. However, ILAR 'modified' criteria had a better diagnostic value raising questions about the usefulness of HLAB27 testing in SJIA. The frequent absence at diagnosis of arthritis or systemic manifestations other than fever, may suggest the need of development of international consensus based strategies for diagnosis and treatment of probable and definitive SJIA. Table 1 . Patient 1 initially treated with steroids (CS) developed 2 MAS events on the 1 st month necessitating IVCS pulses (IVMP). MTX was added; a 3 rd MAS event developed during CS tapering. Anakinra (ANA) was added 4 months after onset and changed to CAN for adverse event-AE. A4 th MAS event developed on CAN-1 year-and MTX-5 months after CS withdrawal. It subsided by IVMP, and cyclosporine. MTX was discontinued after 18 months and CAN after 2,7years remission. Patient 2 initially manifested MAS treated by CS. Disease relapsed 4 months after CS withdrawal;CS were reinitiated along with MTX. 11 months after onset a relapse remitted by CS; ANA permitted CS taper. MTX was discontinued after 3 years for AE; ANA sustained remission for 7 months. Due to poor compliance ANA was changed to CAN. After 1 year CAN was withdrawn. After 21month remission a flare with fever and monoarthritis remitted by CAN reinitiation. Patient 3 suffered 2 relapses during CS tapering in the 1 st month; MTX was added and discontinued in 3 months for relapse during CS tapering; 6 months after onset ANA allowed CS discontinuation. After 3 months ANA was changed to CAN due to AE. ANA washout led to reactivation. Remission was achieved in 8 months. CAN was discontinued after 2 years. Patient 4 suffered 5 years of active disease presenting by CNS insulting MAS. MTX was added and discontinued in 6 months due to flare after CS withdrawal. ANA&CS were added 10 months after onset maintaining minimal activity for 10 months until a 2nd MAS. HLH treatment protocol led to remission for 2 months; for 1 year minimal activity under NSAID persisted. 4 years after onset fever, rash and arthritis remitted by CAN administration 2 mg/kg/month and Intraarticular CS. A flare after 4 months remitted by dose increase. For 1 year transient spontaneously remitting rash and arthritis occurred. The disease remained in remission on CAN for 19 months; it was discontinued due to thrombocytopenia after initiation of Growth Hormone initially considered AE of CAN/ GH, still persisting after 2,8years. Patient 5 manifested fever, rash, polyarthritis and carditis attributed to C.burnettii unresponsive to antibiotics abating by CS. Disease flared 2 months after CS withdrawal necessitating reinitiation. MTX was added 6 months after onset. A flare 10 months after onset off CS remitted by ANA-withdrawn after 2 months for AE; disease flared and was treated by CS& CAN; MTX was discontinued after 6 months. CAN was discontinued by interval-increase after sustaining remission on medication for2,6years and 1year off medication. A flare with systemic manifestations remitted by CAN reinitiation Conclusion: Canakinumab leads into off medication remission highly active SJIA. Informed consent to publish had been obtained. Introduction: The US Food and Drug Administration approved intravenous (IV) administration of tocilizumab (TCZ) for the treatment of patients (pts) ≥2 years (y) of age with systemic juvenile idiopathic arthritis (sJIA) in 2011 based on results of the phase 3 TENDER study. 1 This approval was associated with a postmarketing requirement to investigate the use of TCZ in pts with sJIA <2 y (study NP25737). Results from the 12-week (wk) main evaluation period (MEP) have been reported. 2 Objectives: Safety results following completion of the optional extension period (OEP) of NP25737 (until 52 wk from baseline or 2 y of age, whichever was longer, was reached) are now reported. Methods: NP25737 was a multicenter, open-label, single-arm study to evaluate the pharmacokinetics and safety of IV TCZ 12 mg/kg every 2 wk for 12 wk in pts <2 y with active sJIA for ≥1 month whose treatment with corticosteroids and nonsteroidal antiinflammatory drugs failed and who were receiving stable background therapy. After the 12-wk MEP, pts could participate in the OEP and continue TCZ treatment (without requirement for stable background therapy) to evaluate long-term safety. Cumulative adverse events (AEs) over the entire study period are reported. Results: Seven of 11 pts enrolled in the MEP continued to the OEP and received ≥1 dose of TCZ. Across the entire study period (n = 11), the median number of TCZ doses was 11.0 (range, 2-26) and the median duration of exposure to TCZ was 22.1 wk (range, 4.1-58.1). Most pts (10/11; 90.9%) had ≥1 AE; most AEs were mild or moderate and unrelated to study drug. The most common AEs were upper respiratory tract infection (6/11 pts; 54.5%), hypersensitivity, neutropenia, rash, viral upper respiratory tract infection, and vomiting (3/11 pts each; 27.3%). Seven serious AEs occurred in 5 of 11 pts (45.5%); 2 occurred during the OEP (transaminases increased, histiocytosis hematophagic), 3 occurred during the MEP (hypersensitivity), and 2 occurred during the safety follow-up of the MEP (sJIA flare, hand-foot-and-mouth disease). AEs leading to dose modification occurred in 5 of 11 pts (1 in MEP, 4 in OEP) mostly because of infections, neutropenia, and elevated liver enzymes; all were mild or moderate. AEs leading to withdrawal occurred in 5 of 11 pts (45.5%): during the OEP, 1 pt was withdrawn because of a serious AE of increased transaminases; during the MEP, 3 pts were withdrawn because of serious hypersensitivity reactions to TCZ, and 1 pt was withdrawn because of thrombocytopenia. No deaths were reported during the study. AE rates per 100 pt-y of exposure are ?A3B2 show $132#?>reported (Table 1) . Conclusion: During the OEP, long-term treatment with TCZ was well tolerated in sJIA pts <2 y, and no additional safety signals were reported in the OEP beyond those reported in the MEP or observed previously for pts with sJIA ≥2 y. Introduction: Kawasaki disease (KD) is rarely described in siblings in the same time. In these cases, an infectious trigger must be excluded.

Objectives: We describe the clinical course of two brothers who showed severe KD all at once, secondary to Parvovirus infection. Methods: A 9-month-old female showed fever, pallor, vomiting, bilateral non-secreting conjunctivitis, rash. Anamnesis revealed that 12 days before, she had fever, spontaneously resolved. At admission, 9 days after fever onset, she showed fever, conjunctivitis, pharyngitis, rash, and cervical adenopathy. Haematological parameters showed: leukocytosis, neutrophilia; anaemia; CRP: 2.31; ESR: 120. ECG and echocardiography were normal, including coronary Z-scores. She showed positive Parvovirus IgM. Spontaneous defervescence occurred. Further cardiological evaluation was performed to exclude a pericarditis secondary to Parvovirus, and at day 26 after fever onset, coronary artery lesions (CAL) were documented: proximal right coronary artery Z-score of 6.02; left main coronary Z-score: 5.72; left anterior descending Z-score: 5.78. The child was promptly treated with IVIG plus ASA. A further echocardiographic evaluation showed worsening of CAL, with a sacciform aneurysm in the left anterior descending artery (Zscore:5.08). Laboratory test did not show inflammation; however, the girl was treated with 3 bolus doses of intravenous methylprednisolone (30 mg/kg/dose). The Z-score of CAL did not change and the patient was treated with anakinra (4 mg/kg/day), with a progressive improvement of CAL, and after 2 months, Z-scores normalized. The cardiological outcome revealed a progressive improvement of EF, which reached the 50%. Results: CAL significantly improved after anakinra, at the contrary, the clinical evolution in the brother was different. Conclusion: We describe familial KD in two siblings which had the same infectious trigger (Parvovirus). The brother was diagnosed as a post-viral myocarditis. However, considering the two parallel and different evolution, the girl showed late CAL with aneurisms, and the brother a Kawasaki shock syndrome picture with myocardial dysfunction. Viral illnesses are recognised trigger of KD, and in these cases the rareness is the coincident KD in two siblings, with different and severe clinical course. Noteworthy, the girl had aneurisms which resolved with anakinra, a therapy which has been recently shown to be promising for this disease. Informed consent to publish had been obtained from the parents.

Introduction: Henoch-Schönlein purpura (HSP) is the most frequent vasculitis in children. Typically, it is characterized by palpable purpura, joints swelling, arthralgia, abdominal pain with possible intestinal bleeding. In more severe cases, the patients show acute abdomen. Acute pancreatitis is a rare dramatically evolutive, life-treating manifestation of SHS and it can be associated with a fulminant course. Persistent abdominal pain, need to be investigated by the dosage of serum pancreatic amylase, lipase and by abdominal MRI. In these patients, corticosteroid treatment is recommended and must be associated with parenteral feeding. Objectives: We analysed the full series of children with HSP admitted to our paediatric unit in the period 2011-2018. Methods: We retrospectively collected data of 50 children (age: 4-14 years), with HSP who needed hospitalization. 4/45 patients (9%) developed an acute pancreatitis. All the patients were males, age:3-10 years. All the patients did not show other risk factors of pancreatitis. Results: The treatment was parenteral feeding in 100% of the patients. One patient with pancreatitis and nephrotic syndrome received 3 bolus doses of methylprednisolone (30 mg/kg/dose) followed by prednisolone (2 mg/kg/day) and mycophenolate; one patient with pancreatitis and acute renal failure, received 3 bolus doses of methylprednisolone (30 mg/kg/dose) followed by a single-dose of cyclophosphamide (750 mg/m2), followed by azathioprine (50 mg/day). One patient showed a mild pancreatitis and healed with prednisolone (2 mg/kg/day) and parenteral feeding. One patient showed acute pancreatitis, associated with acute intestinal bleeding, orchitis, was treated with 3 bolus doses of methylprednisolone (30 mg/kg/dose) followed by prednisolone (2 mg/ kg/day). Steroids treatment was progressively tapered until the complete resolution of the pancreatic involvement. Conclusion: Acute pancreatitis is a rare and life-treating manifestation of HSP. High-doses steroids are a recognised and useful treatment, associated with parenteral feeding. In non-responders to steroids, immune suppression treatment is the second-line treatment to induce remission. The choice depends on associated manifestations of HSP and on associated failure of other organs. Methods: We present the case of a one-year-old with persistent fever for six days,a generalized rash,lymphadenopathy,conjunctivitis,cheilitis,swollen hands and feet,diarrhoea and irritability.Blood tests revealed increased C-reactive protein (100.80 mg/L),D-Dimer (532.00 ng/mL) and Fibrinogen (810.00 mg/dL).There was increased platelet count (532,000/ mm3) and hyperneutrophilia (neutrophils 79.80 %);He showed low levels of serum albumin (2.9 g/dl),serum sodium (130 mEq/L) and serum chloride (90 mEq/L).Blood cultures and serological tests for infection were negative.He underwent an echocardiography that showed an enlarged coronary diameter,(right 3.9 mm, left 3.6 mm; circumflex 3.1 mm, proximal anterior inter-ventricular 3.1 mm; worse Z score +5).

Results: From the presence of fever that had lasted for more than five days,the lymphadenopathy,conjunctivitis,the cutaneous rash and the oedema of the hands and feet with cardiac involvement,we diagnosed complete Kawasaki disease and started IVIG (2 g/Kg) and Aspirin (80 mg/Kg).Despite the initial IVIG treatment, the fever,rash,conjunctivitis,cheilitis and mild oedema of hands and feet remained,and additional IVIG doses and three metilprednisolone (30 mg/kg) pulses were administered in the following days.The patient underwent another echocardiography that did not show any changes.Maintenance treatment with oral prednisone (0.5 mg/kg/day) was initiated.The patient became afebrile, and the rash, cheilitis and conjunctivitis gradually disappeared.Serological markers of inflammation returned to the normal range.After ten days, the patient's fever recurred with irritability, exanthema,conjunctivitis, and hand and feet desquamation.Blood tests showed a significant increase of CRP (65.30 mg/L),ESR (50 mm/h);anaemia (Hb 10.4 g/dL) and more platelets (566,000) were also registered.Echocardiography did not show changes.Further Metilprednisolone pulses were administered over three days.After one day the patient repeated the Echocardiography, which showed a worsening of the enlargement of the coronary diameter,(right 6 mm (Z score 13),left 6 mm (Z score 9.9),proximal anterior interventricular 5.7 mm (Z score 15).There was an aneurism in the diagonal branch of left anterior descending coronary (7.2 mm; Z Score >10) with a thrombus inside.After three days, the patient's fever continued.Due to the persistence of the fever,the worsening of the echocardiography features and blood tests,with the agreement of his parents,other intravenous treatments with IL-1RA were initiated (Anakinra 2 mg/kg subcutaneously once a day for two weeks).One day later, the fever disappeared and CRP, ESR, platelet and haemoglobin levels returned to normal in the subsequent blood tests.The Aspirin dose was reduced to the antiplatelet dose and Clopidogrel (5 mg) was added. Conclusion: Treatment with Anakinra was maintained for two weeks, and Prednisone (0.5 mg/kg/dy), Aspirin and Clopidogrel.There were no flares of the disease after discontinuing the Anakinra and blood tests were within the normal range. Echocardiography tests showed an improvement in his coronary enlargement. Written informed consent was obtained from the patients for publication of Case Report. Objectives: We describe a case of HSP presenting with severe skin lesions that did not respond to standard therapy with corticosteroids,and was therefore treated with intravenous immunoglobulins(IVIG).

Methods: An 11-year-old girl was admitted to our department with fever,abdominal pain,arthralgia,severe purpuric palpable rash and haemorrhagic bullae distributed on the buttocks and lowerextremities.Physical examination showed a purpuric palpable rash,multiple haemorrhagic bullae and vesicles ranging in size from five to 30mm on the buttocks and lower limbs.The abdomen was painful but soft.-Blood tests revealed a white blood cell (WBC) count of 20.730/ml with normal differential, platelets (PLT) 336.000/ml,haemoglobin (Hb) 13.3 g/dl,erythrocyte sedimentation rate (ESR) 30 mm/1h (nv 20 mm/ 1h), C-reactive protein (CRP) 13 mg/L.She tested negative for streptococcal tests showed Antistreptolisine (ASLO) 778 IU/mL (nv 0-200) and anti-DNAse 1170 IU/mL (nv 0-200).Microscopic analysis of the patient's urine showed mild proteinuria (30mg/dl) and an occult blood test on a stool sample was negative.Abdominal ultrasound was unremarkable.A skin biopsy revealed peri-nuclear infiltration of polymorphs,nuclear leukocyte and mononuclear cells with IgA deposition in immunofluorescence studies,typical of leukocytoclastic vasculitis. Results: Clinical findings were consistent with HSP and she was started on oral prednisone (1mg/kg/daily),as well as antibiotics with teicoplanin for the super-infection of skin lesions (Staphylococcous Aureus).After ten days she was discharged,with an improvement in skin appearance.She was given a schedule to progressively taper and stop steroid therapy within a month.At the 15-day follow-up,she presented new onset of purpuric rash on her lower extremities and scars of previous bullae.We decided to increase the dosage of corticosteroid therapy from 0.5mg/Kg to 1mg/kg/die.At the one-month followup she presented a new purpuric rash and haemorrhagic bullae on her lower extremities,associated with abdominal pain.She was therefore readmitted to our department.Blood tests revealed WBC 10.730/ ml with normal differential count,PLT 300.000/ml,Hb13.2 g/dl,ESR 40 mm/1h,CRP 15 mg/L;creatinine,were within range.The results of urinalysis,an occult blood test of a stool sample and an abdomen ultrasound were all negative.She started an IVIG infusion (2g/kg),while still on oral prednisone (1mg/kg/daily),progressively tapered.After treatment she showed good improvement in respect of her skin lesions and was discharged.At the 15-30-60 day follow-up visits the patient was in good general condition;she did not have any new lesions but only scars on her lower limbs.

There is no consensus about the management for cutaneous manifestations in HPS.In the case of rare skin complications,such as haemorrhagic bullae lesions,immunosuppression with corticosteroid therapy is often necessary in order to control the inflammation and limit the expanse of necrosis.Unfortunately,our patient gained only partial benefit from corticosteroid therapy.As a consequence,we decided to treat her with an IVIG (2g/kg as a single infusion) associated with oral prednisone (1mg/kg/daily),progressively tapered,which induced rapid and persistent resolution of symptomatology.Written informed consent was obtained from the patients for publication of Case Report.

None Declared Objectives: To report a pediatric-onset HLA-B51 positive case of Beh-çet´s disease.

Methods: Review of the medical records.

Results: An 11-year-old boy with recurrent oral aphthae was referred from the pediatric emergency department to the pediatric rheumatology consultation after two episodes of great saphenous vein superficial thrombophlebitis. He had been experiencing daily oral aphthae with spontaneous resolution after 10 days for the past three years (>3 episodes in a year). Besides, his mother described various episodes of folliculitis with formation of pustules over the previous months. He denied fever, rash, weight changes, sleep disturbance, headaches, abdominal pain, change in bowel habits or diuresis, respiratory symptoms, visual disturbances or fatigue. His physical exam and pediatric gait arms legs spine exam was normal except for two oral aphthae and some acneiform lesions. Laboratory data including complete blood count with renal function, ionogram, reactive c protein, coagulation studies, viral markers for hepatitis B and C and HIV, herpes simplex and varicella-zoster virus serology and calprotectin were negative. Immunglobulin levels were normal and autoimmunity studies with beta 2 glycoprotein antibodies, lupus anticoagulant, anti-HLA-B27, anti-nuclear, anti-SSA and SSB, anti-RNP, anti-SM, anti-Scl-70, anti-JO-1, anti-cardiolipin and anti-ds-DNA antibodies and markers for celiac disease were negative. Urine testing showed discrete proteinuria. A pathergy test was performed, which was negative. His echocardiogram was normal and his ophtalmologic evaluation did not show any signs of uveitis. Thus, a diagnosis of Behçet´s disease was established according to the International Classification Criteria for Behçet´s disease. HLA-B51 testing was later requested, which was positive. According to the EULAR 2008 guidelines, he initiated colchicine without further episodes of oral aphthae. He currently maintains a regular follow-up in the pediatric rheumatology and vascular surgery consultation, without any further occurences except for an episode of self-limited epididymitis.

Conclusion: Although the diagnostic criteria for Behçet´s disease are well-established in adults, diagnosis and treatment is still a challenge in the pediatric population, as there are no pathognomonic laboratory tests and diagnostic criteria are not adapted to children. The consensus classification criteria have been recently developed for pediatric Behçet´s disease in an attempt to increase the sensitivity of the prior criteria. We described a case illustrating that a detailed clinical history and a thorough physical exam associated with a high level of suspicion remains the most suitable approach. These patients require a periodic ophtalmologic evaluation and a close vigilance of prothrombotic states. Written informed consent has been obtained from the legal representative of the subject involved. Methods: We examined medical information that was extracted from patients' charts, such as vital signs, the Indian Takayasu Arteritis Clinical Activity Score (ITAS2010), results of blood examination, echocardiography, vascular ultrasonography and other imaging inspection, and evaluated the change before and after the initiation of scTCZ by the dosage of 125mg once a week.

Results: There are two children with TA treated with scTCZ. Case 1 is a 12-year-old girl who developed reversible cerebral vasoconstriction syndrome combined with cerebral infarction. Because of the upper extremity blood pressure differential and cervical murmurs, contrast CT and vascular ultrasonography were performed that revealed the wall thickening and stenosis of cervical and subclavian arteries. HLA-B52 was positive, but other blood examination shows no abnormality, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin (IL)-6. Oral prednisolone (PSL) was started that resulted in no improvement of artery wall thickening, then intravenous TCZ (8mg/kg, every other week) was initiated 4 months after the onset. The thickening of arteries, blood flow acceleration and ITAS2010 improved, and prednisolone was decreased to 5mg/day. 11 months after the onset, the dosage of TCZ was switched to 125mg subcutaneously once a week and the effect continues. Case 2 is an 11-year-old girl whom complicated with ulcerative colitis and had been treated with azathioprine, prednisolone and infliximab. She complained fever, fatigue, leg pain after exercise, and was accompanied with high CRP level. Positron emission tomography revealed integration at cervical, subclavian, brachial and femoral arteries. The upper extremity blood pressure differential and cervical murmurs were confirmed. The symptoms, the inflammatory response on blood examination and the findings of vascular ultrasonography improved by the administration of systemic PSL, however, serum ferritin level remained high and the thickening of arteries exacerbated as the PSL was tapered. Infliximab was switched to scTCZ 24weeks after the diagnosis and there has been no deterioration of disease activity with the lowest level of serum ferritin. In both cases, vascular ultrasonography and ITAS2010 enabled us to detect disease activity, even if CRP was negative and was not useful as an evaluation means. Introduction: Takayasu arteritis is an idiopathic large-vessel vasculitis that primarily affects the aorta and its major branches. Chronic granulomatous inflammation leads to stenosis and occasionally aneurysms of the involved portions of the arteries, producing a wide variety of symptoms. High-dose corticosteroids are the mainstay of therapy but adjunct immunosuppression is frequently required. TNF-a blocking agents have shown to be effective in refractory cases.

Objectives: Characterization of patient demographics, clinical features, disease extent, treatment and outcomes in children with Takayasu arteritis Methods: Retrospective data analysis of a case series of children fulfilling the EULAR/PRINTO/PRES criteria for childhood Takayasu arteritis in a tertiary hospital setting during a 10-year period.

Results: A total of 4 children (3 female), with a median age at diagnosis of 7 years (5 -10 years) were identified during this period. The most common clinical features at presentation were systemic symptoms and cardiovascular involvement (4/4). Weak peripheral pulses, discrepant systolic blood pressure between limbs and arterial bruits were present in all cases. Arterial hypertension was detected in half of the patients. Neurological manifestations were also very common (3/4), with seizures at the initial presentation in 2 patients and ischemic stroke in 1 case. A minority of patients complained of gastrointestinal (1/4) and respiratory (1/4) symptoms. Acute phase reactants (ESR and CRP) were elevated in all patients. Thrombocytosis (3/4) and chronic disease anaemia (2/4) were also commonly found. The distribution of the involved arteries according to the angiographic classification of Takayasu arteritis showed a pattern type V in 3 cases, one of which was VP+. The remaining case displayed a pattern IIa. First-line treatment in all cases included high-dose corticosteroids and methotrexate. Cyclophosphamide was added in 2 cases. Due to a severe and refractory disease course, TNF-a blocking agents were administered in all patients (Infliximab, 2 cases; Adalimumab, 2 cases). Endovascular procedures were required in 2 patients with irreversible stenosis: renal artery percutaneous transluminal angioplasty (2 cases) and pulmonary artery stenting (1 case). There were no relevant infections or mortality during the followup period. Repeated magnetic resonance angiography to assess disease activity showed improvement in vascular lesions in 3 patients, with remission in 1 case. None of the patients presented disease progression with involvement of new vessels. Conclusion: The diagnosis of childhood Takayasu arteritis remains challenging, mainly due to the insidious clinical course and the lack of specificity of the presenting symptoms. The abnormal peripheral pulses in the setting of elevated inflammatory markers should raise suspicion for this condition. Previous studies found that constitutional features like low-grade fever, weight loss and arthralgia are more frequently found in childhood Takayasu arteritis compared with adult patients. In our series these symptoms were present in all patients. We report a higher frequency of neurological involvement compared with other paediatric reports, perhaps reflecting the severity of the angiographic pattern and the delay in diagnosis. None of our patients achieved stable remission with high-dose corticosteroids and methotrexate only. Anti-TNFa showed to be beneficial in refractory patients with clinical improvement in the majority of the cases, as previously reported in other studies.

None Declared Introduction: Childhood Takayasu (c-TA) as a rare large vessel vasculitis remains challenging from the initial diagnostics to the managment of the disease, accordingly morbidity and mortality remains high. In literature, there exist some promising reports of treating otherwise treatment-resistant systemic vasculitis with autologous peripheral blood stem cell transplantation.

Objectives: To demonstrate the difficulty of managing c-TA after allogeneic stem cell transplantation due to Hyper-IgE Syndrome Methods: Case report Results: Here, we report on the case of a 10 year old boy who developed c-TA several months after allogeneic hematopoietic stem cell transplantation having received for the correction of a severe Hyper-IgE-Sydrome. At the time of diagnosis of c-TA the patient was off systemic immunosuppressive treatment, with stable donor chimerism and without any clinical evidence of graft versus host disease. The management of the immunosuppressive therapy was challenging, but the introduction of infliximab resulted in stabilisation of the disease course.

Conclusion: The difficulty of monitoring disease activity due to lack of specific biomarkers, the importance of radiological follow-up, the common complications and the non-steroidal treatment options will be discussed here. Informed consent to published had been obtained from the parents. Objectives: The identification of regular variability cycles modulating population epidemiology of KD in Japan at temporal scales ranging from seasonality to interanual cycles and their close association to variability in wind dynamics, raised new questions and altered our former understanding of KD. At seasonal timescales,wind intensity and wind direction closely mimick variability in KD. At longer scales, regional climate features, like interhemispheric winds in the north and midlatitude Pacific Ocean and the El Niño-Southern Oscillation (ENSO) phenomena seem to play a dominating role. However, despite daily dynamics were also proved to be related between local winds and hospital case admissions, variability at these fast time scales has never been studied in relation to local air physics and air quality Methods: Machine learning data clustering and a suite of classification techniques were applied to both KD incidence and environmental datasets in Kumamoto (Japan), during two intervals covered with intensive daily surveillance. KD incidence, physical air determinants and air chemistry factors are pooled together in these analyses. Results: Interestingly, new associations emerge that strongly link the nature of air masses to very high frequency cycles in KD. Results are supported by analyses reproduced during different synoptic weather conditions and among typologies of KD epidemiological events, suggesting a clear role of air determinants in the population epidemiology of this vasculitis.

Conclusion: Air quality and its dynamics should be considered as a determinant factor of enhanced KD incidence in Japan. These results may be the basis for widening our long-standing views on this paradigmatic disease, and be useful in the case of other similar diseases. Specific surveys aimed at precisely characterizing these air determinants are urgently needed to unravel what constellation of environmental factors seem to be modulating KD incidence. Results: Flow cytometric analysis showed a significant reduction of memory B cell compartment (CD19+CD27+) in DADA2 patients, in particular in Swich memory B cell subset. We also observed a reduced absolute number of CD4+ and CD8+ T cells, whereas the subpopulations of T cells resulted normal, with the exception of TEMRA CD8+ T cells, significantly expanded in DADA2 patients. Moreover we identified an expansion of circulating Tfh cells in DADA2. Then we investigated a role of ADA2 in B cells: we found that ADA2 is expressed, secreted by B cells, but the enzymatic activity is impaired in patients' B cells that show functional impairment in proliferation and differentiation. We addressed in vitro the interaction of B and T cells, essential for generation of memory. Analysis of proliferation and differentiation showed that proliferation of patients' B cells is not sustained from patient's T cells and IgG secretion is significantly reduced in the presence of CD4+ T cells obtained from DADA2 patients with respect to normal CD4+ T cells. Moreover T cells from DADA2 show an impairment in the production of IL21, key cytokine for B cell help and a significantly downregulation of CD40L. Conclusion: Our findings suggest that CECR1 mutation could affects directly B cell function and leads also to an impairment of T cell help functions. Results: This 4-year-old boy, originating from Portugal, presented with persistent fever in the last 3 months, lower limbs pain, systemic inflammation, anaemia, livedo reticularis, and hypogammaglobulinemia M and A. The personal history showed failure to thrive since the age of 2 years. Family history revealed consanguinity and a fourth degree relative with the diagnosis of DADA2 due to a homozygous R169Q mutation. After exclusion of infectious and oncologic causes, targeted genetic analysis was performed and showed the presence of the same R169Q mutation with enzymatic tests confirming the absence of ADA2 activity. After diagnosis, oral steroids were introduced with remission of symptoms and normalization of inflammatory markers within 3 weeks and was followed by anti-TNF alpha therapy. Genetic testing of the parents is ongoing. Conclusion: DADA2 diagnosis may be challenging with no specific symptoms at presentation; the presence of livedo, hypogammaglobulinemia and thrombotic events should raise the awareness of physicians. We describe here a case of DADA2 promptly diagnosed due to the positive family history. Early diagnosis of DADA2 is essential to prevent serious complications of the disease, highlighting the importance of genetic testing in all family members. However, the management of presymptomatic patients remains a matter of controversy. In the absence of biomarkers predicting the onset of the disease, a close and regular follow-up is recommended in case of the mutation. Written informed consent was obtained from the patients for publication.

Introduction: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are very rare in childhood vasculitides with an increased risk of morbidity and mortality. Five factor score (FFS) is a tool designed to assess prognosis at diagnosis of the patient with systemic necrotizing vasculitides and is found to be a good predictor for survival rate in adult studies. Patients with FFS ≥ 2 had more common crescentic, mixed and sclerotic histopathologic findings in biopsies. By logistic regression analysis forward method, the strongest single-risk factor among all the parameters was the initial level of creatinine in patients with ESRD, compared to the other patients (p = 0,007) Conclusion: We have presented the association between poor histopathologic findings and MPO-ANCA positivity, impaired renal function and FFS ≥ 2 at the diagnosis. The most important predictor factor for renal prognosis was initial serum creatinine level. In conclusion, evaluation of the FFS, ANCA serology and the creatinine levels may help to predict renal prognosis. Introduction: Kawasaki Disease (KD) is a self-limited childhood vasculitis of unknown origin and coronary artery aneurisms are its most significant complication. Timely treatment with Intravenous Immunoglobulin (IVIG) represents the standard care, but more than 10% of children are unresponsive. Many treatment options have been reported, but the most effective therapy for refractory cases is still not defined. Although mice models have suggested a significant role of Il-1 in the pathogenesis of KD and coronary artery aneurisms, treatment with Interleukin -1 Receptor Antagonist (Il -1 RA) has been seldom used. Objectives: We report two patients with refractory KD who achieved remission with Anakinra following IVIG and systemic corticosteroid failure. Methods: Describing case series. Results: Case #1 is a previously healthy four-month-old male, presenting for high fever not responsive to empiric antimicrobial therapy, marked irritability and poor feeding, bilateral conjunctivitis, micropapular rash involving face and extremities, keilitis, perianal hyperemia and mild hand and feet edema. KD was diagnosed and the patient was started on aspirin and IVIG on day 5 th from the onset of fever; a second dose of IVIG was administered two days later because of persistent fever. Despite this treatment, his general conditions deteriorated and cutaneous rash worsened significantly, evolving into necrotic-hemorragic vasculitic lesions. Pulse methylprednisolone was started on day 8 th , followed by high dose oral prednisone. Ten days later the patient relapsed and a third IVIG infusion was administered. Seriated echocardiographies showed from the 23 rd day of illness a marked dilation of both right and left coronary arteries. Case #2 is a previously healthy 4-year-old male who was admitted to General Pediatric Unit because of 4 days high-grade fever, feeding difficulties, conjunctival injection, cervical adenopathy, mucositis, abdominal rash and palm and sole erythema. KD was diagnosed, aspirin was started and 2 IVIG infusions were administered without improvement. Seriated echocardiographies showed coronary involvement with mild dilation of left coronary artery. From the 8 th day of fever, 3 pulses of methylprednisolone were administered, followed by oral prednisone, with initial improvement. Four days later he was febrile again and in poor general conditions with severe irritability.

Given the resistance to IVIG and corticosteroids, IL1 -RA (anakinra) was started in both patients at the dose of 2 mg/kg once a day, subcutaneously. They both showed a rapid improvement; particularly, patient #1 showed a gradual resolution of the severe cutaneous vasculitic lesions. Two weeks after starting biological therapy, both patients could be discharged from hospital on anakinra, tapering oral corticosteroid. Treatment with anakinra was maintained for 1 month in both children and no relapses occurred after its discontinuation; patients did not experience any side effect during therapy. Echocardiographic controls showed progressive reduction of coronary dilation with complete resolution after 5 months in patient #1 and after 6 weeks from the onset of KD symptoms in patient #2. Conclusion: Our case series suggests that treatment with IL-RA may be considered as an effective and safe therapeutic option for refractory KD. Informed consent to publish was obtained from the parents. Renal doppler ultrasonography demonstrated total occlusion of the left renal artery, severe stenosis of right renal artery (nearly occluded) and vascular wall thickening of the abdominal aorta and superior mesenteric artery (SMA). Magnetic resonance (MR) angiography showed wall thickening and perivascular inflammation of aorta and its major branches which is consistent with Takayasu arteritis. Significant narrowing in SMA and right renal artery, total occlusion of left renal artery and T2 signal decrease in left kidney suggested diffuse ischemia and infarct. Accordingly, he was diagnosed as Takayasu arteritis, and given pulse methylprednisolone (PMP) treatment immediately at his first day of admission. However within 12 hours, he became anuric, his edema increased, and creatinine level elevated to 4 mg/dL. Urgent hemodialysis (HD) was performed and due to the rapid progression of the disease intravenous pulse cyclophosphamide (CYC) was added. Despite daily HD and intense immunosuppressive therapy with CYC and 5 day course PMP, creatinine levels continued rising (7 mg/dL). On the sixth day of admission, thoracoabdominal aortography was performed but the attempt for revascularization of renal arteries by balloon angioplasty was unsuccessful. Considering his severe renal failure and inadequate response to the medical and endovascular interventions, RAT was performed. His relatively preserved right kidney was dissected and directly anastomosed to right external iliac artery. Postoperatively, diuresis started immediately, creatinine levels decreased slightly right after surgery, and returned to normal levels (0.99 mg/dL) on post-operative day 10. Immunosuppressive therapy was continued with 60 mg/day oral corticosteroid (CS) and second dose of CYC was given 3 weeks after RAT.

Conclusion: This case shows that early diagnosis and immediate appropriate interventions are life-saving in TA. In experienced transplant centers, RAT performed in selected cases is a kidney-saving method and provides dialysis-free-survival. Informed consent to publish had been obtained from the parents. Introduction: Juvenile idiopathic arthritis (JIA) is known as an autoimmune disease and the severity of inflammation in arthritic joints is thought to be due to the imbalance of pro-inflammatory and antiinflammatory cytokines. Pro-inflammatory type 1 helper (Th1) and anti-inflammatory type 2 helper (Th2) T cell activity are shown as serum levels of soluble CD26 (sCD26) and sCD30.

Objectives: The aim of this study is to assess serum levels and clinical significance of sCD26, sCD30 and sCD30/sCD26 ratio in patients with JIA. Methods: Forty eight JIA patients (19 patients with RF+ poly-articular JIA (p-JIA), 8 with RF-p-JIA, and 21 with oligo-articular JIA (o-JIA)) and 9 healthy controls (HCs) were enrolled. Serum levels of sCD26 and sCD30 were measured using enzyme linked immunosorbent assay. Furthermore, we investigated the correlation between these levels and clinical manifestations.

Results: In JIA patients, serum CD26 levels were lower and serum CD30 levels were higher compared to HCs, although not statistically significant. In RF+ and RF-p-JIA patients, serum sCD30/ sCD26 ratio was significantly elevated compared to HCs in active phase. Serum sCD30/ sCD26 ratio was significantly decreased in inactive phase compared to active phase. Furthermore, in RF+ p-JIA patients, serum sCD30/sCD26 ratio was correlated with arthritic disease activity including tender joint counts, swollen joint counts and serum levels of Overweight was documented in 25% of patients with SLEj, 19% in JIA and 11% of the population without rheumatic disease. 6% of patients without rheumatic disease were classified in the obesity range in contrast to 2% of patients with JIA and SLEj. Conclusion: Both the population with rheumatological diseases and individuals without documented disease have low rates of regular physical activity. In this group of patients with JIA and SLEj the high rates of physical activity are related to lower rates of both disease activity and damage. The analysis suggests more than doubling incidence of JIA in Eastern Denmark over a 21 year period. This could be attributed to increased awareness and centralisation of JIA treatment during the period, but possibly also other factors as gradual introduction of musculoskeletal ultrasound (MSK US) over the observation period possibly resulting in JIA diagnoses in "borderline" mild cases that previously would not have fulfilled the criteria for a JIA diagnosis. An increase in the fraction of very mild cases is consistent with unchanged absolute numbers of patients with TMJ involvement and patients with uveitis. Availability of improved JIA treatment options could potentially also have contributed to an increased fraction of milder cases.

Conclusion: Although the current study suggests dramatically increasing incidence of JIA in Eastern Denmark, the results must be interpreted with great caution due to potential confounding factors including increased JIA awareness and new technological developments in diagnostic tools e.g. MSK US. The data suggests that due to increasing use of MSK US we may be diagnosing many more mild JIA cases that previously would not have been diagnosed with JIA. Methods: Twenty fictive JIA cases were introduced orally and in written to 26 physicians attending an annual national Swedish meeting of pediatric rheumatology. A mentimeter was used to collect information about the physicians and the PGA rating score for the cases presented. In order to mimic ratings on a 10-cm visual analoug scale, participants were allowed to chose a score between 0 and 100, where 0=no activity and 100=maximum activity.

Results: Most physicians were specialists, women, aged > 55 years and worked at county hospitals. Eighteen (69%) had more than 8 years experience of pediatric rheumatology. The PGA scores for some cases presented varied considerably, the median of differences in PGA scores across physicians was 70 (range 5-86). The distribution of the medians of the physicians' individual PGA scores also differed, the mean was 42.5 (range ). An increased but nonsignificant trend for a prolonged work absence >60 hours /month) attributed to JIA (17% vs 0%, p=0.07) in the JIAp was observed. The parental observation or performance of drug administration or home physio-exercise program was not associated with the parental time spent with the affected child (p=0.48). Additionally, the presence of JIA flares or worsening was not associated with an increased duration of home care in respect to the Hp (p=0.68). Conclusion: The contemporary and holistic JIA management did not adversely affect the working state of these Greek parents or their spouses in respect to work performance, the duration of home care of the affected child, regardless of the drug administration or home physioexercise program. Noteworthy, an increased but non-significant chance of retirement was recorded among the parents having a child with JIA. Introduction: Randomised controlled trials (RCTs) are central to improving the clinical care and outcomes of children and young people (CYP) with juvenile idiopathic arthritis (JIA). RCTs have traditionally been designed by research teams with outcomes selected by researchers and healthcare professionals. However, it is children and their families who live with the effects of the illness and its treatments. It is increasingly clear that they can and must be involved in prioritising different outcomes to research teams. Accessing children's and parents' unique perspectives and experiences of JIA can help to inform the selection of outcomes. As part of a wider process, .The total duration of the disease was 3 years 4 months ± 1.3 years, from 2 months to 13 years 2 months.The serum level of vitamin D was measured through blood test by chemiluminescence method. The relationship between the level of vitamin D and disease activity was analyzed based on juvenile arthritis disease activity score (JADAS 27).

Results: The average level of vitamin D in serum was 23,05±6,4 ng/ ml. It was found that the level of vitamin D was correlated with age of patients (r = --0,43; p < 0,05). Using the regression method, a relationship was established between the level of vitamin D in serum and the age of the child, the number of affected joints and the number of active joints (33,48 -0,065*age of the patient -0,55* number of injured joints + 0,37 * number of active joints ).The results of the present study indicated that there was no significant relationship between the level of vitamin D in serum and disease duration and activity. Conclusion: JIA patients are presented with low vitamin D levels. It was found the relationship between the vitamin D deficiency, age of the patient and the number of affected and active joints.

Introduction: The abatacept (ABA) Registry 1 is a medication registry aimed at studying the long-term safety of ABA in juvenile idiopathic arthritis (JIA Physician Global Assessment of current disease activity § 0 0.5 1.5 1 2

*Self-rated: 0=none, 10=extreme; † Self-rated: 0=well, 10=poor; ‡ Physician-rated: 0=unqualified; 10=fully qualified; § Physician-rated: 0=no activity, 10=maximum activity (all 0.5 increments) was 10 years for the <18 cohort, 36 years for the ≥18 cohort and 53 years for the adult RA cohort. Most patients were female. Uveitis was the most frequently occurring AI disease in patients with JIA <18 years of age and SLE was the most common AI disease in patients with JIA ≥18 years of age. Sjögren's syndrome was most common in adult patients with RA. Conclusion: These results show variability in AI prevalence by age group among patients with JIA and separately for patients with RA. Whether this variability is a consequence of the limitations of healthcare claims data requires further investigation. Understanding the coexistence of AI diseases among patients with JIA may play an important role in patient management, treatment decisions and outcomes.

Introduction: Patients with juvenile idiopathic arthritis (JIA) have an increased risk of being infected. Approximately half of all serious infections in children with JIA are associated with airway involvement. Objectives: Our aim was to study the efficacy and safety of the pneumococcal 13-valent conjugate vaccine (PCV) in children with JIA.

Methods: In a prospective cohort study, 5 groups were formed: children with JIA in the remission phase on methotrexate therapy (group Ia) or etanercept (group Ib), with JIA in the active phase prior to the appointment of methotrexate (group IIa) or etanercept (group IIb), control group (conditionally healthy children). 0.5 ml of the 13-valent PCV was administered once subcutaneously during therapy in patients in the remission phase or 3 weeks before the appointment of methotrexate or etanercept in patients in the active phase. The main study outcome was the proportion of patients with a protective (40 mg/L) level of specific anti-pneumococcal antibodies (anti-SPP) IgG to Streptococcus pneumoniae 4 weeks after vaccination. In addition, we assessed the incidence of infectious events before and after vaccination as well as changes in the content of a high-sensitivity Creactive protein, S100 protein, and post-vaccination period.

Results: The study included 125 children. Four weeks after vaccination, the protective level of anti-SPP IgG was established in 21 (84%) patients in the 1st, 23 (92%) in the 2nd, 22 (88%) in the 3rd, 24 (96%) in the 4th and 5th groups (p =1.0). Increase in the concentration of S100 protein and high-sensitivity C-reactive protein after vaccination was not noted. JIA exacerbation episodes were not recorded in any patient. Conclusion: Vaccination with the 13-valent PCV in children with JIA is highly effective and is not accompanied by the flare of JIA. Objectives: The objective was to conduct a participatory plan to build a referential of skills that could help young patients and parents and be useful to healthcare professionnals. (HCP) Methods: On the initiative of an association of patients and a rheumatologist experienced in TPE, a steering committee (COPIL) was constituted bringing together rheumatologists, pediatricians and associative representatives. After a qualitative phase (review of literature and focus groups of children, adolescents and parents), the COPIL identified skills of knowledge, know-how and know-how-to-be in different areas of interest for people affected by JIA. The work by topic allowed the balance between the biomedical and psychosocial. For the quantitative phase, all the French competence centers as well as the KOURIR association and the RESRIP Network were invited to participate in a validation using different online questionnaires. Each center had to involve HCP, children and parents. For each area, the participants had to indicate the three skills that seemed to them to be priorities and could, if they wanted, to propose a competence not listed. The analysis consisted in classifying the answers by type of responder (Children, parents, HCP) to identify the priorities of each group, then to weight the skills of each theme (3 points for skills ranked first, 2 points for second place skills, 1 point for third place skills). Finally an average was made for the overall ranking. Results: 19 competence centers, Kourir and RESRIP contributed to this approach. Thirteen themes were explored (disease, treatment, pain, care, myself, information, relationship to others, relationship to the health care team, schooling, home, living daily, fatigue and sleep, physical activity-sport-rehabilitation). The "children" skills questionnaire brought together 78 respondents (19 children, 22 parents, 37 HCP), the "teenagers" questionnaire 50 respondents (10 teenagers, 17 parents, 23 HCP), the "parents of children" questionnaire 59 answering machines (8 children, 28 parents, 23 HCP) and the questionnaire "parents of adolescents" 30 respondents (6 teens, 14 parents, 10 HCP). Priorities differ among groups. On the subject of treatment in particular, we note a tendency of parents to privilege theoretical knowledge whereas children focus their choices on coping and living with JIA and the HCP put forward intermediate skills.

Conclusion: This collaborative and participatory work makes it possible to identify the children's priorities, without neglecting the expected skills by the parents and the HCP. The classification by theme will allow teams wishing to develop educational approaches to rely on real notions and not only on HCP projections. This repository wants to be closer to problems and expectations of children and their families. It is not, however, a list of ideal skills that all child, adolescent or parent must master but a source of reflection to implement custom actions.

Objectives: The purpose of this study is to present results regarding the functional status, psychosocial status and disease activity of children with JIA, and their effects on the child's family. The second aim is to present the correlations between these parameters. Conclusion: This study concluded that pain and function were affected by disease activity. It was also shown that the psychosocial states that children expressed with their own knowledge are related to their participation in daily living activities. It has been determined that these changes do not reflect in the perspective of the family. It was concluded that the functional and psychosocial aspects of JIA children should also be taken into consideration. Introduction: According to official statistic data in Ukraine there are more than 3 thousand kids suffer from JIA and disease has strong tendency to spreading. The most dangerous, that up to 50% of the patients lose functional abilities within 3 -5 years of life, up to 30% of them has high activity of the inflammatory response on basic treatment. Well known, that pathogenesis of the JIA is mediated by molecular interactions between immune cells, inflammatory cytokines, macrophages, that lead to hyper activation of the inflammation response, somehow connected with NF-kB. Previous in vitro studies presented important role of NF-kB for generation of the active response on the treatment of the process, caused by active inflammation reaction. Goals of the JIA treatment are suppression of inflammation activity, dangerous clinical signs, limit iatrogenic effect of concomitant treatment and support condition of the patient. Ukrainian kids with JIA has limited access to biology treatment, that is why very often we get complicated variants if the disease with significant influence on patients quality of life.

Objectives: The aim of our study was to evaluate efficacy of the standard basic treatment, and in a combination with available biological drugs, its influence on inflammation cytokines, NF-kB in kids with JIA.

Methods: For the achievement of the goals we checked up 78 kids of our center with estimated diagnose of JIA, mid age of them -12,7 years, mid duration of the disease -19 months. Most of the kids had polyJIA (52%) in seronegative subtype, seropostivite variant of poly-JIA was met rarelyin 7,6%, all other cases -40,4% were presented by oligoJIA; we didn't take into account sJIA. For characteristic of the clinical features, we took into account amount of the active joints, results of CHAQ, VAS, ESR value. According to JADAS27-ESR score, most of the patients had moderate disease activity (5,2±0,7) -62,8%. For estimation of the laboratory activity we checked absolute amount of CRP, IL-1β, IL-6 and NF-kB in serum of the patients with JIA, by using of the ELISA method.

Results: Laboratory activity of the inflammatory response was presented by enlarged concentration of CRP (7,2±3,1g/l), ІL-1β (5,8±4,2 pg/ml; N ranges <5 pg/ml), IL-6 (10,2±2,4pg/ml; N ranges <9 pg/ml), and as well high concentration of NF-kB (70,5±3,1pg/ml; N ranges 20 -48 pg/ml). Concentration of CRP, IL-1β was slightly increased through all groups of clinical variants JIA, IL-6 and NF-kB correlated with activity of the clinical signs, were significantly higher in patients with polyJIA. To evaluate efficacy and response on treatment, we checked="checked" the same laboratory parameters in 6 months after the treatment: with methotrexate in 51 (65,3±3,9%) patients, with methotrexate+adalimumab in 17 (21,8±1,9%) and methotrexate+tocilizumab in 10 (12,8±1,4%) patients. In a 6 months after the treatment 66,7% patients with MTX achieved ACR30 response, 76,4% of patients MTX +ADA and 90,0% of patients MTX+TOC achieved ACR50. In a group of MTX patients we didn't observe significant decrease of IL-6 or NF-kB concentration, it was at the equivalent level with primary results. Group of the patients with MTX+ADA showed significant lowering of CRP, IL-1β, and IL-6 on 28,7% to compare with baseline level. In group of MTX-ADA decreasing of NF-kB wasn't clinically significant. Group of the patients that received MTX+TOC presented the best resultswith significant decreasing of CRP, IL-1β and IL-6. As well was observed significant decreasing of NF-kB on 41,7 %, that can be estimated as pathogenically linked therapeutic effect. Conclusion: So, patients with JIA that meet high concentration of IL-6 and NF-kB as laboratory predictors of high clinical activity, are more lucky to get good treatment response in case of start therapy of MTX-TOC to compare with MTX-ADA or isolated MTX treatment. Conclusion: Most patients with LS treated with MTX achieve complete remission without flares and only a minority present repeated relapses and active disease after more than 10 years. The long-term monitoring of the patients even after therapy withdrawal is crucial to promptly identify possible flares and treat them adequately, as they tend to recur. Overall aesthetic and functional sequelae are moderate, probably because tissue damage establishes early in disease course as its severity does not seem to be related to disease duration. Results: Significant increase in expression (see Table 1 ) was found for CD16b, TLR2 and S100A9 mRNA and protein in JSLE patients compared to controls; CD16b was only significant after patients were stratified by their IGS. This profile suggests a strong phagocytic ability which we confirmed with phagocytosis assays. We found IFNa to regulate CD16b expression, while apoptotic supernatant caused CD16b shedding. TNFa increased TLR2. We did not find significant differences in S100A9 protein expression for any stimulation. Conclusion: Expression of PRGs and proteins is strongly up-regulated in JSLE patients and can partly be explained by factors in the lupus environment. A "ready to phagocytose" phenotype could make neutrophils oversensitive to phagocytic triggers or danger molecules. This is further suggested by our metabolomics data indicating that neutrophils are active in patients even in non-flaring patients. Overreactive cells can cause harm to the body once flares occur. The molecules investigated are therefore potential targets for preventive treatment. Introduction: Rituximab (RTX) is increasingly used in rheumatologic [1, 2] , hematologic [3] and renal diseases [4] . The induced B cell depletion can lead to hypogammaglobulinemia and thus an increased risk of infection [5] . B cell depletion is not always achieved, and this has a negative effect on therapeutic response [6]. Anaphylaxis is a frequent side effect of RTX and has been associated with the occurrence of anti-drug antibodies (ADA) against RTX [7] . Objectives: To describe in different pediatric patient groups the pharmacodynamics of RTX in children by outcome variables, i.e.

success of B-cell depletion and time of B cell repopulation, as well as the risk factors for severe infections and anaphylaxis. Methods: Patient data of children who received RTX between 2008 and 2017 at our center were retrospectively collected. Three patient subgroups were defined: autoimmune diseases (AID), immune dysregulation (ID) and renal diseases (RD). B cell repopulation was defined as a number above the cut-off value of B cell depletion (=0.050*10^6/l or <2% of the total amount of lymphocytes Introduction: Subclinically passing endocrine pathology plays an important role in the development and progression of the atherosclerotic process and is often underestimated not only by rheumatologists, but also by endocrinologists. The mechanism of development of autoimmune thyroid pathology, as well as systemic diseases of connective tissue, is closely related to the imbalance of the immune system, mainly with the Th1 immune response. Under the influence of pro-inflammatory cytokines, the expression of receptors activating the apoptosis of follicular cells of the thyroid gland occurs, which ultimately leads to the development and progression of hypothyroidism. Deficiency of thyroid hormones can promote the appearance of hypercholesterolemia, cause disturbances in the state of the autonomic nervous system and energy metabolism.

Objectives: The aim of the study was to evaluate the state of lipid metabolism and thyroid function in children with juvenile scleroderma Methods: 40 children with juvenile scleroderma at the age from 5 to 16 years were examined. The parameters of the immune system, lipid spectrum of blood and thyroid hormone levels were studied. Results: According to the results of immunological examination, a significant increase in the relative amount of B-lymphocytes, a redistribution of immunoregulatory subpopulations of T-lymphocytes by decreasing the number of CD8 + cells against a background of increased number of CD4 + cells, hyperproduction of total IgG and IgM, a significant increase in TNF-α and a decrease in serum IFN-γ was established in children with juvenile scleroderma when compared with the control group (P <0.01). As a result of the thyroid function study, a significant (p <0.05) decrease in the levels of total and free T3 and T4 in the blood serum of children with JS was compared with that in the children of the control group: the mean levels of total T3 in children with JS were 1,4 (0, 8, 1, 9) Introduction: Juvenile scleroderma is a rarely seen chronic connective tissue disorder.The hands are commonly affected in patients with JS, and Raynaud's phenomenon, finger swelling and joint pain are the primary manifestations of the disease. Skin thickening is a manifest consequence of JS. The hands account for only a small fraction of the total skin area of the body, but are necessary for many important functions in daily life.

Objectives: The purpose of our study is to examine the effects of sense and functionality changes in the hands on activity and participation in patients with JS. Methods: 30 patients (26 girls, 4 boys) with JS between the ages of 6-18 and 30 healthy controls (20 girls, 10 boys) with similar age and gender were included in our study. 14 of 30 JS patients were JSS and the rest of them were JLS.The inclusion criterias were to have been diagnosed with Juvenile Scleroderma 6 months prior to the ILAR classification and to be at the mental level that could respond to the assessments to be used in the study. The follow-up form was prepared considering the relevant parameters such as gender, socio-demographic status, clinical family story of JS disease. Children rated their pain severity on a six-item Wong-Baker FACES® Pain Rating Scale (WBS) from none to worst. Hot-cold, pain, and touch sense were evaluated in both groups. Vibration sence is assessed with 256Hz diapozon, light touch-deep pressure sensation is with Semmes Weinstein monofilament (SWMT) test, static-dynamic 2 point 2-point discrimination test is with a discriminator, localization sensation test is with a pencil. In addition moberg pickup test, stereognosis evaluation, wrist joint position sense, sympathetic activation were evaluated. The hand joint range of motion was measured by goniometer , hand grip strength by "Jamar Plus + Hand Dynomometer (JPHD)", the pinch gripping force by "Jamar® Pinch Gauge -Hydraulic" pinchmeter, the hand mobility by modified Hand Mobility in Scleroderma (mHAMIS). Children completed their activtiy and participant performance status with "Childhood Health Assessment Questionnaire (CHAQ)", "Duruoz Hand Index (DHI)", "Jebson Taylor Hand Function Test(JTHFT)", "Community Integration Questionnaire (CIQ)" tests. The quality of life were evaluated with "Scleroderma Health Assessment Questionnaire(SHAQ)". Statistics were analyzed with the SPSS for Windows 21.0 program. Results: The mean age of the JS group was 14.06±3.24, while the mean age of the control group was 12.43±3.24 years. There were significantly differences between the two groups in pain (WBS), light touch-deep pressure sensation, sense of touch localization, range of motion, functional assessment (JTHFT), activity and participation scores (CHAQ, DHI) and quality of life scores (SHAQ)(p<0,05). Almost half of the JS group describes the character of their pain as inflammable or whining.There was a significant correlation between SWMF and CHAQ (r=0,52), SWMF and DEI (r=0,62), SWMF and SHAQ-Total (r=0,57) scores. There was a significant correlation between resting pain and CHAQ-Total (r=0,576) and Resting Pain and DEI (r=0,674) scores. Conclusion: Consequently, sense and functional changes after hand involvement in JS patients cause limitations in daily living activity and negatively affect the effective use of the hands.Assessments of sensation symptoms that affect the functionality, activity level and participation should be taken into consideration in patients with JS.In addition, we think that the use of sensory therapies in JS treatment will be an important factor in increasing the effectiveness of rehabilitation. Introduction: Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence 3 in a 1 000 000 children(1). There is not much published data about the course of jSSc with standardized assessment of the patients. We report our date form juvenile scleroderma inception cohorte with a follow up of 24 months in the cohort.

Objectives: to evaluate the development of the disease during the first 24 months in the cohorte Methods: The juvenile scleroderma inception cohorte is a prospective multicenter registry of patients with jSSc, who fullfill the adult classification criteria, and have age of disease onset of less then 16 years of age and less then 18 years at the time of inclusion in the cohort. We evaluted the patients characteristics of the patients, who were followed 12 months in the registry. Results: 40 patients were followed 24 months in the registry. 80% were female and 77.5% had diffuse subtype. 20% had overlap feutures. Mean disease duration at time of inclusion was 3.2 years. Mean age of onset of Raynauds was 8.2 years and the first non-Raynauds 8.7 years. 73% received DMARDs at the time of inclusion and 95% after 24 months. 85% of the patients were ANA positive, around 25% anti-Scl70 positive and around 3% anticentrome positive. The mean modified skin score decreased from 14.4 to 12.9. The frequency of Raynaud´s stayed around 87.5%. The frequency of the nailfold capillary changes increased from 55% to 62%, but the frequency of active ulcerations decreased from 23% to 20%. The number of patients with FVC <80 % decreased from 42% to 39% (p=0.8). The number of patients with DLCO< 80% decreased from 54 to 44% (p=0.58). The number of patients with pulmonary hypertension assessed by ultrasound increased from 5% to 10% ( p=0.396 Introduction: Juvenile systemic scleroderma (jSSc) is an orphan disease, with an estimated prevalence of 3 per 1000 000 children. Most jSSc patients primarily present with Raynaud phenomenon (RP). Objectives: We investigated in our patient of the juvenile scleroderma inception cohort, how fare patients with (RP+) and without (RP-) RP differed in their clinical presentation at enrolment. Methods: The jSSc is a prospective cohort of jSSc patients. Patients were enrolled who were diagnosed with jSSc, had a jSSc onset age under 16 years and were younger as age of 18 years at the time of inclusion. The patients are prospectively assessed every 6 months according to a standardized protocol. We reviewed the organ involvement pattern of our patients currently followed in the cohort.

Results: 100 patients are currently followed in the cohort and 89 (89%) of them had RP. The female/male ratio was lower in the RP+ group, 3.7:1 compared to 4.5:1(p=0.808). Diffuse subtype was more common in the RP+ group, 72% compared to 63%. Mean age of onset of first non-Raynaud symptomatic was 10.4 years in both groups. Mean disease duration was slightly higher in the RP+ group, 3.4 compared to 2.2 years. ANA positivity was higher in the RP+ group, 88% compared to 70% (p=0.48). Anti-Scl70 was 34% in the RP+ and 20% in the RP-group (p=0.34). Interestingly 7% of RP + but none of the RP+ were anti-centromere positive. The mean modified skin score was lower in RP + group (mean of 14.8 compared to 17.0). There were significantly more nailfold capillary changes (70% compared to 18%, p=0.001) and a higher rate of history of ulceration in the RP+ group (49% compared to 20%, p=0.083). Decreased DLCO and FVC<80% was higher in the RP-negative group with 45%/50% compared to 37.5%/31% respectively. Pulmonary hypertension occurred in 7% in the RP+ group and there was no case in the RP-group (p=0.335). RP-group had a higher rate of urinary sediment changes 18% compared to 4.5% in the RP+ group (p=0.07). No renal crisis or hypertension was reported in neither groups. Gastrointestinal involvement was similar between the two groups with around 35%. Occurrence of swollen joints was similar in both groups as the frequency of muscle weakness with around 20%. The tendon friction rub occurred around 10% in both groups. In the patient related outcomes, there was only a difference in rating of Raynauds activity.

The RP-group differed from RP + group in the clinical presentation at enrolment. The absence of Raynaud phenomenon was associated with a decreased rate of history of ulceration, no occurrence of pulmonary hypertension. Interestingly higher rate of urinary sedimentary changes and no anticentromere positivity was observed in RP-patients.

Introduction: Pulmonary vascular disease and interstitial lung fibrosis are the leading causes of morbidity and mortality in Juvenile Systemic Sclerosis (JSSc Introduction: Juvenile localized scleroderma (jLScle), a limited autoimmune disease, theoretically renders patients susceptible to infections due to their defective immune system and the immunosuppressive treatment. However we lack data regarding response and long-term immunity conveyed by specific vaccines.At present, we are experiencing major measles' outbreaks throughout Europe.Measles infection harbors potentially serious consequences. Rubella infection, on the other hand, may harbor significant long-term sequences for the mother and the fetus. Thus it is critical that we understand the impact of jLScle on young patients' immunity to measles and rubella.

Objectives: In this study we determined the immune status against measles and rubella in previously vaccinated jScle patients, prior to commencement of treatment and at one and three years, and compared this to healthy controls.

Methods: This was a prospective controlled study including 28 newly diagnosed jLScle patients and 56 healthy controls. All participants had two doses of the live attenuated MMR vaccine in early childhood. Demographic, clinical and laboratory data were collected. Type and duration of treatment was also recorded. Seroprotection rates and rubella-measles-IgG titers were measured at enrolment (prior to commencement of treatment) and at 1 and 3 years. Total IgG levels were measured simultaneously. Measles and rubella specific IgG antibodies were assessed by ELISA and were expressed as GMC's. The cut-off value for seroprotection was deemed at 10IU/ml and 120IU/ ml for measles and rubella respectively. 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 STATA 13.0. 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 vaccines as well as mean elapsed time from last vaccination to blood sampling. Seroprotection rates were adequate for both groups. Nonetheless, the jLScle group had marginally lower seroprotection rates at one and three years (both measles and rubella). Measles-specific-GMC's were similar between the patient and control group at all time points. Rubella-specific-GMC's were significantly lower in the jLScle compared to the control group (p<0.01) at one and three years' follow up but not at diagnosis. None of the participants had hypogammaglobulinaemia at the time of blood sampling The use of methotrexate did not seem to exceed any significant effect on seroprotection rates but had a negative impact on rubella-GMC's. The use and duration of systemic steroids as well as topical treatments did not have any effect on rubella or measles-specific-GMC's. Conclusion: In conclusion, although seroprotection rates were similar between the two groups, rubella GMC's were significantly lower in the jSLcle group. 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. Introduction: Systemic sclerosis is an auto-immune disease characterized by small-vessel vasculopathy, dysregulation of innate and adaptive immunity, and extensive fibrosis of the skin and visceral organs which can lead to loss of organ function. However its pathogenesis is not completely understood. In the past few years research in adult patients has focused on the role of type I interferon in the pathogenesis of the disease, with variants in several interferon related genes being identified as a genetic risk factor. Objectives: The aim of this study was to characterize the type I interferon response in paediatric patients with systemic sclerosis as well as to assess the potential contribution of genetic variants in IRF7 to this response. Methods: DNA was extracted from saliva using Oragene saliva collection pods and DNA extraction protocol. Exons 1 to 9 of the IRF7 gene were sequenced by Sanger using an AB1 sequencer. Peripheral blood was collected to PAXgene tubes for RNA stabilization and extraction. RNA was transformed into c-DNA using High Capacity c-DNA Reverse Transcriptase kit. Changes in gene expression were assessed by real-time polymerase chain reaction. The interferon score was calculated by assessing the relative expression of six interferon related genes (SIGLEC1, RSAD2, ISG15, IFI44L, IFI27, IFIT1). Patients' demographics were collected from medical records. Results: Two patients with paediatric-onset systemic sclerosis were recruited into this study. Both patients were female and black British. Patient 1 is 16 years old and has long standing disease with multiple organ involvement diagnosed at the age of 9 years. Patient 2 is 5 years old and has early stage disease (less than 6 months since diagnosis). A high interferon score was detected in Patient 1, with long standing disease, but not in Patient 2. Patient 1 also had a modest increase in expression of IRF7 (2.3 fold), but not in the other interferon related genes tested.

Sanger sequencing of the IRF7 gene revealed the presence of the same variant, p.K192E, in both patients. Although frequent in the general population, this variant has been linked in GWAS studies to increased risk of Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis. Conclusion: Our results show an increased type I interferon response in a patient with long standing disease. A high interferon score has been shown both in long standing disease and early stage disease in adult patients. However, our patient with early stage disease did not have increased expression of any of the interferon related genes tested. Interestingly, both patients presented the same variant in IRF7, which has been linked with disease risk for SLE. Variants in other interferon related genes could eventually have additional relevance to the disease phenotype. Larger studies in paediatric patients with systemic sclerosis are needed to determine the relative importance of type I interferon response in the pathogenesis and progression of this disease. Informed consent to publish had been obtianed. Conclusion: CBCT is an innovative technique that allows to assess the changes of the affected side, usually the non-growth, of LSF in comparison with the healthy side, during the developmental phase of pediatric patients. CBCT represents a reliable and objective tool for monitoring LSF over time in association with the other clinicalinstrumental methods currently in use. Its practical benefit lies in its potential of correctly addressing therapeutic changes including the timing of start the reconstructive surgical process.

Introduction: Raynaud's phenomenon (RP) is a condition characterized by periodical vasospasm in response to cold temperatures or emotional stress exposure, that in the vast majority of patients exists without other disorders, but sometimes is associated with several autoimmune rheumatic diseases and, to distinguish between these two types, clinical examination, laboratory findings, nailfold capillaroscopy and computerized color telethermography (CCTT) are necessary.

Objectives: The aim of this research was to analyze RP features in children in correlation with the most frequently associated laboratory tests, CCTT and nailfold capillaroscopy.

Methods: This retrospective study included children who were clinically recognized as RP in the period from 2011 to 2017 at University Hospital Centre Zagreb. Laboratory data included serum level of IgG, C3, C4, CH50, RF, presence of ANA and ANCAs. Nailfold capillaroscopy and CCTT were utilized to distinguish between primary and secondary RP.

McNemar's test was used to evaluate whether capillaroscopy or CCTT was more effective in the diagnosis of secondary RP and to estimate was there a difference between capillaroscopy and CCTT in matching with the results of immunological laboratory findings.

Results: Out of 224 children with RP, 169 were females (75.4%) and 55 were males (24.6%) with female/male ratio 3:1. CCTT was performed in 188 patients (83.9%), nailfold capillaroscopy in 89 patients (39.7%) and both investigations in 80 patients (35.7%). CCTT classificated 15 patients as primary RP, 57 patients as secondary RP (among them, 33 had at least one pathological laboratory finding), while in 47 patients no classification could be made. In 69 patients clinically recognized as RP, CCTT findings were normal. Among patients classificated as secondary RP on CCTT, the most of them, 14 (24.6%), were diagnosed with juvenile idiopathic arthritis (JIA). There were 5 patients (8.8%) with systemic sclerosis (SSc), 2 (3.5%) with mixed connective tissue disease (MCTD), 1 (1.7%) with systemic lupus erythematosus, 11 (19.3%) with undifferentiated connective tissue disease (UCTD), whilst 24 patients (42.1%) had no evident other disease. The appearance of abnormal capillaroscopic pattern was found in 17 patients (among them, 11 had at least one pathological laboratory finding) and nonspecific capillaroscopic alterations were noticed in 27 patients (among them, 16 had at least one pathological laboratory finding), while 45 patients had normal capillaroscopic findings. Among patients with the appearance of abnormal capillaroscopic pattern, 5 (29.4%) were diagnosed with SSc, 3 (17.6%) with JIA, 2 (11.8%) with MCTD, 1 (5.9%) with dermatomyositis, 2 (11.8%) with UCTD, whilst 4 patients (23.5%) had no evident rheumatic disease. All patients with RP diagnosed with SSc and MCTD had both the appearance of abnormal capillaroscopic pattern and CCTT findings consistent with secondary RP. No statistically significant difference between capillaroscopy and CCTT in predicting the diagnosis of secondary RP was determined (McNemar's test, χ 2 = 0.042, p = 0.838) nor was there significant difference between capillaroscopy and CCTT in regard to the results of laboratory findings (χ 2 = 1.042, p = 0.307). Conclusion: Both nailfold capillaroscopy and CCTT have important role in the diagnosis of RP in children. We found that both methods were equally effective in the diagnosis of secondary RP and that there was no difference between them in regard to the results of immunological laboratory findings distinctive with secondary RP. Introduction: RASopathies are neurodevelopmental syndrome caused by heterozygosity for germline mutations in genes that encode protein components of RAS/MAPK pathway. There are several reports of RASopathies complicated with autoimmune disease, such as Noonan syndrome with germline mutation of PTPN11 or SHOC2 associated with systemic lupus erythematosus (SLE) [1] . Recently, it is revealed that somatic mutations of KRAS and NRAS cause autoimmune lymphoproliferative syndrome (ALPS)-like disease, which called RAS-associated-ALPS-like disease (RALD) [2] . Some patients with RALD showed clinical and laboratory features of SLE. Objectives: We aim to investigate the relationship between BRAF-associated RASopathy and development of SLE. Methods: We present a Japanese case of cardio-facio-cutaneous syndrome with germline BRAF mutation complicated with SLE refractory to conventional treatments.

Results: A 5-year-old girl with cardio-facio-cutaneous syndrome with germline mutation of BRAF was referred to hospital due to recurrent fever and erythema. Laboratory data showed pancytopenia, hypocomplementemia, high erythrocyte sedimentation rate, positive antinuclear antibody, elevation of serum anti-dsDNA antibody, and proteinuria. She was diagnosed as having SLE. The histological findings of renal biopsy showed lupus nephritis ISN/RPS class III. She received three times of methylprednisolone pulse therapy and combination of mycophenolate mofetil and tacrolimus that showed poor response. Interestingly, peripheral blood immunophenotyping by flow cytometry showed increased TCRαβ+CD4-CD8-double negative T cell, which indicate dysfunction of T cell apoptosis such as ALPS.

Conclusion: This is the first report of SLE with germline mutation of BRAF. Introduction: Anti-C1q has been associated with systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis in previous studies Objectives: To determine the prevalence of anti-C1q antibodies in the pediatric SLE population To determine clinical associations of elevated anti-C1q antibody levels especially with lupus nephritis. Methods: Sera of pediatric SLE patients who fulfilled ACR criteria for SLE were recruited. After obtaining informed consent, blood samples were tested for anti-C1q antibody by commercially available ELISA kit. Prevalence of anti-C1q and its association with lupus nephritis were determined.

Results: Out of total 150 children with SLE, anti-C1q positivity was present in 95 children (64%), at a cut off value of 20U/ml. Children with proteinuria, low C3, low C4 and anti dsDNA positivity had were significantly more likely to have anti-C1q antibody positivity. Children with lupus nephritis were significantly more likely to have anti C1q antibodies positive than children without renal involvement (74% vs. 51% , p= 0.02). Among the children with lupus nephritis, children with active renal disease were more likely to have anti-C1q positivity than in children with quiescent disease (88% vs. 53% , p= 0.002). Anti-C1q antibodies had a sensitivity of 74% and specificity of 54% at a cut off value of 22U/L , for renal disease in pSLE Conclusion: Out study confirms previous findings of the association of anti-C1q antibodies with nephritis and disease activity in pSLE. Anti-C1q antibody titers were found to have positive correlation with renal disease in children with pediatric SLE, and could be used as an adjunctive biomarker in monitoring disease activity in children with lupus nephritis. Objectives: To evaluate whether apoptosis-related proteins expressions in NK cells contribute to its defects in JSLE patients and relate with disease activity parameters, neuropsychiatric involvement and nephritis.

Methods: Thirty-five JSLE patients (30 girls, mean age 15.1±2.7 yrs, ACR criteria), 7 sex-and age-matched healthy individuals (6 girls, mean age 13.0±2.9), 4 JIA disease controls (3 girls, mean age 10.7 ±4.8 yrs, ILAR criteria) and 13 JDM controls (8 girls, mean age 13.1 ±3.5 yrs, Bohan and Peter criteria) had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim and Caspase 3 expressions in NK (CD3-CD16+CD56+) cells simultaneously determined by flow cytometry. Disease activity parameters included SLEDAI score, ERS, CRP, anti-dsDNA, C3 and C4 levels. Eleven patients had active disease (SLEDAI ≥4), 21 had positive anti-dsDNA, 9 had neuropsychiatric involvement and 28 had nephritis. Mann-Whitney test was used for two group comparisons and Spearman's rank for correlations. P values <0.05 were considered significant.

Results: Reduced proportion of TRAIL-expressing NK cells was observed in JSLE patients (median 11.4 vs. 51.9%, p=0.03), in those with active disease (median 5.4%, p=0.02), in patients with positive anti-dsDNA (median 6.6%, p=0.009), in those without neuropsychiatric involvement (median 13.8%, p=0.03) and in patients with nephritis (11.4%, p=0.02) compared with healthy controls. Reduced proportion of Bcl-2-expressing NK cells was seen in JSLE patients (median 81.8 vs. 94.3%, p=0.04), in those with inactive disease (83.7%, p=0.04) and in patients without neuropsychiatric involvement (median 80.0%, p=0.03) compared with healthy controls. JSLE patients with nephritis also had increased proportion of caspase 3-expressing NK cells (median 2.5 vs. 1.0%, p=0.03) compared with healthy controls. Surprisingly, proportion of FasL-expressing NK cells positively correlated with SLEDAI score (r=0.6, p=0.002) and with C3 levels (r=0.5, p=0.005). No differences were observed comparing JSLE patients, JIA and JDM disease controls. Conclusion: JSLE patients present altered expressions of TRAIL, Bcl-2 and caspase 3 apoptosis-related proteins in NK cells, particularly in those with active disease, with positive anti-dsDNA, with nephritis and those without neuropsychiatric involvement, which may contribute to NK cells defects and consequently to disease pathogenesis. Introduction: SLE has been mainly associated with primary immunodeficiencies of early complement components and selective IgA deficiency 1,2 . LRBA deficiency leads to immuno-deficiency of heterogenous presentation, as respiratory infections, hypogammaglobulinemia, reduced number of specific B cell subsets, functional T cell defects and aberrant autophagy 3 . LRBA gene mutations have also been associated with autoimmune diseases, including inflammatory bowel disease, endocrinopathy, autoimmune hemolytic anemia and thrombocytopenia, and occasionally arthritis but not SLE. Objectives: To report clinical and laboratory features of a JSLE patient carrying a novel mutation in LRBA gene. Methods: Whole exome sequencing was performed from -80ºC stored genomic DNA (PIDBioRep) 4 . Results: A 10-year-old girl born from healthy consanguineous parents presented with wheezing and cough since 1-year-old, and respiratory infections, arthralgia and chronic bloodless liquid diarrhea since 7 years of age. A sister with bronchitis, few diarrhea episodes and hypertiroidism had been diagnosed with Graves' disease. Our patient initial tests showed normal sodium and chloride sweat dosage, negative stool cultures, non-specific colitis in colon biopsy, increased IgG, decreased IgM that afterwards normalized (39 mg/dL and 130 mg/dL, respectively), normal IgE and decreased IgA (1.0 mg/dL), normal C3, C4 and CH50 levels and immunophenotyping. After 6-month follow-up she had polydipsia and polyuria, serum glucose was 724 mg/dL, anti-insulin antibody was positive while anti-GAD and anti-IA2 were negative. Diagnosis of diabetes mellitus was established and NPH insulin initiated. After 1-year follow-up she presented acute polyarthritis (cervical spine, left elbow, wrists and knees), autoimmune hemolytic anemia (hemoglobin of 7.3 g/dL and positive Coombs test), alopecia, malar rash and pericarditis. Autoantibodies analyzes revealed homogeneous ANA 1/1,280, positive anti-dsDNA (119, normal up to 50 IU/mL), anticardiolipin IgG (13 GPL, normal up to 10 U/mL), anti-TG and anti-TPO with normal free T4 level, and negative anti-Sm, antiSSA/Ro and antiSSB/La. As patient fulfilled criteria for JSLE, prednisone, hydroxychloroquine and cyclosporine were initiated. During follow-up she presented respiratory infections, venous thrombosis, septic shock and died at 20 years of age from pneumonia. The whole exome sequencing identified a novel homozygous 1-bp deletion in exon 44 of the LBRA gene, resulting in a frameshift with introduction of a premature stop codon (p.Trp2248Glyfs*26). This mutation is located in a highly conserved region within the BEACH domain that interacts with CTLA4 and prevents its degradation, and is predicted to result in nonsensemediated mRNA decay of the transcript, leading to absence of protein.

Conclusion: LRBA-deficient patients have been shown to present decreased intracellular and cell-surface CTLA4 and reduced Treg function, which is likely to explain their multiple autoimmune syndromes, now shown to include SLE. Therefore, abatacept might be a therapeutic option for JSLE cases in which LRBA deficiency may be suspected, such as in patients presenting other autoimmune diseases. Informed consent for publication had been obtained from the parents. Methods: Multicenter, descriptive, retrospective study. A unique data collection format was used. Analysis of the information was made with SPSS20 Results: N = 57. Mean age at diagnosis 12 years (SD 2.8 and range 4-17 years), 60%> 12 years. Average follow-up time of 26 months (SD 23m). The commitment by organs /systems at debut was: 1. Skin in 52.6% 2. Oral / nasal ulcers 16% 3. Arthritis 56% (poly 49%) 4. Serositis 32% 5. Renal 68%, kidney biopsy at onset 18/39, 61% class IV nephropathy, 15% required dialysis 6. Hematologic: 21% hemolytic anemia, 19% thrombocytopenia , 33% leukopenia / lymphopenia 7. Neurological 5.3%. Autoantibody profile: 95% positive antinuclear antibodies, titers> 1: 640 63% and 54% mottled pattern. 77% had positive anti-DNA antibodies, 51% positive anti-SM antibodies, C3 hypocomplementemia 95% and C4 hypocomplementemia 97%.Other clinical manifestations at onset: Antiphospholipid syndrome 14%, 7% Hashimoto's thyroiditis, 14% infection (88% pneumonia). All patients received steroid at debut 60% in IV pulses and 53% cyclophosphamide (CFM). During follow-up, 11 patients had renal involvement, 43% had Class IV nephropathy. Immunosuppressants frequency during the course was: 42% CFM, 53% Azathioprine, 30% Mycophenolate mofetil, 10% Methotrexate. 28% used more than one medication. 10% of patients required Rituximab. Complications during follow-up: 23% short stature, 18% pubertal delay, 7% depression, cataract and chronic dialysis, 5% osteoporosis 3.5% fibromyalgia and 2% kidney transplant. Mortality 10%. A statistically significant difference was found between prepubertal disease onset (under 12 years of age) and frequency of short stature (p 0.019). There were no statistical differences in clinical manifestations at onset, autoantibody profile, treatment and other complications between pre-and postpubertal patients. Conclusion: In this cohort of male patients with juvenile SLE the mean age of diagnosis was in early adolescence with a higher frequency of cases in postpubertal patients. The skin, hematological and renal manifestations were the most frequent at debut. The patients required an intensive treatment for the control of the disease and had a high prevalence of complications especially in relation to growth and a mortality of 10%. Lupus in this cohort of males behaves in a similar manner to that reported in the literature of patients with juvenile SLE. Introduction: In recent years, several mutations located in the TREX1 gene have been associated with different disease phenotypes. Aicardi-Goutières syndrome, familiar chilblain lupus (FCL), systemic lupus erythematosus (SLE) and retinal vasculopathy with cerebral leukodystrophy are included among these conditions. Objectives: To describe the clinical and analytical characteristics of a patient with a homozygous mutation in the TREX1 gene. Methods: Clinical chart review Results: We present a boy, of gypsy ethnicity and son of nonconsanguineous parents, who consulted in our unit at 6 years of age due to swelling, limitation and pain affecting knees, ankles and elbows. The child also reported recurrent severe episodes of pallor and erythema involving fingers and toes during several years, which had even led to amputation of the distal phalanx of the second finger of the left hand due to necrosis. Initially he was diagnosed with Juvenile Idiopathic Arthritis (JIA), antinuclear antibodies (ANA) negative, and secondary Raynaud syndrome. Etanercept and methotrexate were started with modest response. However, two years later, several intense chilblain appeared, affecting both auricular pavilions, and all fingers and toes. Given the suspicion of associated vasculopathy, immunological screening was performed, with no relevant findings; and a genetic study of autoinflammatory/autoimmune diseases was carried out by NGS panel, detecting a homozygous mutation in the TREX1 (R97H). This mutation has been previously reported as associated with Aicardi-Goutières syndrome, and also described in one patient with early onset SLE who presented cerebral vasculitis one year after disease onset 1,2 . Nevertheless, the clinical features and the laboratory results of our patient (Raynaud syndrome, chilblain and arthritis with no neurologic symptoms and absence of autoantibody) permit to include him among familiar chilblain lupus phenotype 2 . When the family tree data were collected, a history of chilblain, deafness, abortion due to malformations, neurological delay from the neonatal period, arthritis and amputations were found through both family branches. A genetic study of the patient relatives will be performed in the near future, in order to confirm wether the various familiar antecedents are related to the mentioned mutation as this option seems probable. Conclusion: To our knowledge, this is the first time that a R97H mutation in homozygosis is described in a patient with FCL phenotype. However, the family history suggests that he same mutation may be associated to different phenotypes too, as has been previously described in the literature 2,3. Written informed consent has been obtained Results: A 10-year-old Vietnamese boy was referred to our Pediatric Rheumatology Unit for the third episode of sudden anasarca. He previously presented two steroid-responsive episodes of hypoalbuminemia with oedema, ascribed to nephropathy, even if no nephrotic proteinuria was detected. At the admission, the serum albumin was undetectable and raised levels of acute phase reactants were detected (Erythrocyte sedimentation rate: 75 mm/h; C-reactive protein: 3,85 mg/ dl). Liver and kidney function tests were normal and 24-h urinary protein quantification was negative for proteinuria. An increase of faecal alpha-1 antitrypsin (αAT) was disclosed (7.21 mg/g with normal range 0.38-0.5) and 99m Tc-labelled human serum albumin scintigraphy ( 99m Tc-HAS) confirmed severe PLE, mostly deriving from the duodenojejunal area. Gastrointestinal biopsies revealed gastric and duodenal lymphangiectasias and a colonic mucosal chronic inflammation. Positivity of antinuclear antibody (ANA) with speckled appearance and SSA/SSB antibodies (146 U and 70 U with normal range <20) was detected. Thereby, the diagnosis of LUPLE was suspected. Treatment with intravenous methylprednisolone was started, followed by daily oral prednisone combined to daily oral azathioprine, with a progressive improvement in values of serum albumin and clinical response. Almost two years later, the patient developed other clinical findings that fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) diagnostic criteria for SLE. The systematic literature searching revealed 7 cases of LUPLE in children younger than 16 years. Considering reported cases and the present case, this condition is prevalent in females (6/8) and in Asiatic patients (3/8) . PLE could represent either the first presentation of the collagen disease (4/8) or a successive complication. All the 8 patients showed peripheral oedema but only one patient presented gastrointestinal symptoms, such as diarrhoea and abdominal pain. To identify gastrointestinal protein loss and protein leakage site, αAT faecal clearance and 99m Tc-HAS are respectively the most specific diagnostic methods. As concerned gastrointestinal histology, nonspecific inflammation involving at least one of duodenum and colon was observed in 5 patients and lymphangiectasias were detected in our and in another patient. Concerning autoimmune profile, ANA antibody is usually present; positivity of anti-DNA and anti-SSA/SSB is described in the half of the reported children. All but one reported pediatric cases were treated with both steroids and immunosuppressive treatment in order to control gastrointestinal disease or the other manifestations of the autoimmune disease. Conclusion: The diagnosis of LUPLE has to be suspected in every child with hypoalbuminemia without evidence of renal and hepatic disease, even without gastrointestinal symptoms. It could represent a manifestation of the disease either already diagnosticated or not detected yet. Written consent for publication was obtained from the parents of patient. Objectives: This study evaluated the immune response through antibody profile after Tdap vaccine in juvenile systemic lupus erythematosus (jSLE) and controls. The jSLE group was also monitored for possible disease flares. Methods: We included 21 jSLE and 19 healthy adolescents who had already received three whole-cell DTP vaccine (DTwP) plus two booster doses and had lymphocytes count > 500. Blood samples were collected immediately before the Tdap vaccine and 14 and 28 days thereafter.Tetanus, diphtheria and pertussis antibodies were tested by ELISA. Results: jSLE group median age was 15y (9-18y) and control group, 15y (9-15.6y). The immune response was evaluated according to antibody levels as shown in Table 1 . Both groups had a similar response for antibody levels for tetanus and diphtheria. The opposite was seen for pertussis, with similar antibody levels. In the control group 96.7% on D14 and 100% on D28 seroconverted to pertussis (p=0.012). On the other hand, in the jSLE group, many adolescents did not seroconvert on D14 and D28 (54.5% vs 63.6%, p = 0.581). Protective levels were noted for tetanus (p=0.031) and diphtheria (p<0.001) in jSLE group. No difference was found between groups on the frequency of adverse events (p=0.081), except for local tenderness, which was more frequent in the control group (p=0.042). Disease flares were not observed after the vaccine. Conclusion: In this study, children and adolescents with jSLE and healthy controls showed adequate humoral immune response to tetanus and diphtheria. The response to pertussis after Tdap vaccine seemed to be less evident in jSLE patients. Objectives: We describe this rare variant in a girl who was difficult to treat in the initial weeks but is now in remission. Methods: A 11 year old female initially presented to another centre in June 2017 with arthralgia, hair fall and oral ulcers. She was diagnosed as systemic lupus with no other organ involvement and started on hydroxychloroquine. She presented to us in November 2017 -5 months later, with extensive skin eruptions on face, neck, trunk, extremities and oral mucosa since 3 weeks. On examination, her weight was 54 kg with height of 155 cm, she had tense vesico-bullous lesions filled with clear fluid on face, neck, trunk, extremities and in the oral cavity. Systemic examination was normal. Her SLEDAI score was 4. There was no recent drug ingestion. Her hemogram, erythrocyte sedimentation rate and urinalysis were normal, Direct Coombs Test was 1+ with C3 -53.3 mg/dl, C4-11.5 mg/dl and negative dsDNA, APLA IgG/IgM and lupus anticoagulant. Skin biopsy was performed and immunofluorescence examination showed IgG and C3 positive linear deposits at the dermo-epidermal junction with positive IgM, IgA, C1q and fibrinogen. Results: She was pulsed with methylprednisolone (30mg/kg) for 3 consecutive days, followed by oral prednisolone (1mg/kg/day), dapsone (1mg/kg), hydroxychloroquine and supplements. As the new lesions continued to erupt, dose of dapsone was increased at the end of Week 2 (1.5mg/kg) and methotrexate (10mg /sq m po once weekly) was added. With no change in clinical status, Mycophenolate Mofetil (MMF) (330mg/sq m/dose, twice a day po) was added at the end of Week 4 and titrated upwards (500mg/sq m,twice a day po) in Week 12. By Week 15 there were no new crops and she finally achieved remission with no fresh lesions and normal hemogram and complement levels with residual hyperpigmentation. Steroid tapering has commenced successfully and currently she is on oral prednisolone (0.15mg/kg/day), dapsone (1.5mg/kg), MMF (500 mg/sq m/dose, twice a day po), methotrexate (10mg/sq m po once a week), hydroxychloroquine and supplements. Conclusion: Vesicobullous lesions in lupus may morphologically resemble Stevens Johnson syndrome but are easily differentiated on histology and immunofluorescence. Such cutaneous lesions are rare in childhood and our case was rather severe in the initial weeks, refractory to Dapsone which usually is effective in this form. In our case the SLEDAI does not accurately reflect the true intensity or activity of the skin domain. Informed consent had been obtained. Introduction: Spondyloenchondrodysplasia (SPENCD) is a very rare genetic immuno-osseous dysplasia characterized by skeletal anomalies (short stature, platyspondyly) and enchondromas in the long bones or pelvis. SPENCD may have a heterogeneous clinical spectrum with neurological involvement or autoimmune manifestations, such as systemic lupus erythematosus (SLE). Objectives: We describe an Indian child with SPENCD, who presented with features of SLE , skeletal dysplasia and enchondromas. Methods: A 9 year old male born of second degree consanguineous marriage presented with fever, oral ulcers, leg pain with morning stiffness since 1 month. He was worked up by his primary paediatrician for pyrexia of unknown origin and a summary of laboratory tests performed included, hemogram with hemoglobin 8.7 gm/dl, white cell count 5900 /cu mm, platelet 1.85 x 10 3 cu mm, erythrocyte sedimentation rate 100 mm/hr, antinuclear antibody 4+. Suspecting connective tissue disease child was referred to us for further evaluation. Results: On further enquiry, there was past history of multiple medical visits for poor growth since infancy and a bony swelling of the right forearm leading to incomplete supination for which he was operated at age 5 years. No details were available. His milestones were appropriate for age with normal scholastic performance. His weight (16.9 kg) and height (113cm) were below the 3rd centile. On examination, he had pallor, facial rash, mucositis of the palate, generalised lymphadenopathy, triangular facies, prominent anteverted ears, prominent conjunctival blood vessels, supernumerary teeth, right elbow swelling, paucity of body hair. On systemic examination abdomen was soft with hepatosplenomegaly and other systems were normal. On further investigation his dsDNA was 4+, Direct Coombs test was positive, C3 -19.1 mg/dl, C4 -3.36 mg/dl, urinalysis was normal, Anti Ro and lupus anticoagulant were negative and APLA IgG was positive and APLA IgM negative. The diagnosis of SLE was confirmed. Considering, consanguineous marriage, short stature and right elbow swelling with other subtle dysmorphisms described above, a syndromic form of lupus was suspected and a skeletal X ray analysis showed extensive areas of metaphyseal abnormalities with epiphyseal remodelling changes and platyspondyly. Hence a clinical diagnosis of Spondyloenchrondrodysplasia (SPENCD) was considered. Sanger sequencing of ACP5 encoding the protein TRAP revealed homozygous non sense mutation (c.849T>A, p.(Tyr283stop) confirming the diagnosis of SPENCD. He was further investigated for diseases associated with SPENCD, which revealed normal thyroid function, IGF -1, immunoglobulin levels and 2DECHO. He was started on hydroxychloroquine (5mg/kg/day), oral prednisolone (0.6mg/kg/day), low dose aspirin, supplements and was advised sun protection. On follow up after 2 months, he had gained 1 kg of weight, was afebrile and there was no arthritis, mucositis or rash Conclusion: SPENCD is an immunosseous dysplasia and a very rare cause of monogenic lupus. This, is the second case of SPENCD reported from India. The entity should be suspected in children with SLE with a consanguineous background who have short stature and bony abnormalities. We expand the phenotype here with additional dysmorphic features comprising supernumerary teeth, triangular facies, prominent anteverted ears and prominent conjunctival blood vessels not described before to the best of our knowledge. Informed consent for publication had been obtained. Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multisystem involvement. In pediatric patients, renal disease is higher in comparison with that observed in adults, and it is reported that up to 99% of patients with SLE develop a certain degree of affection throughout the disease. Lupus Nephropathy in Hispanic patients is more aggressive, with reports of failure to first-line treatment in up to 43% of cases, which is why multitarget therapies are currently being studied, the use of two or more immunosuppressants, to achieve a complete remission in patients with lupus nephropathy, specifically class IV.

Objectives: The objective of the study was to evaluate the response to treatment using schemes with double immunosuppressant: intravenous cyclophosphamide associated with mycophenolate mofetil or azathioprine.

Methods: In material and methods, 60 case files of patients treated at this Institution were reviewed, of which only 40 complied with the treatment schedule for at least 6 months and had a written report of renal biopsy for Class IV Lupus Nephropathy performed at the Hospital Infantil de México. Results: From the results it was found that 82% corresponded to female patients and 18% to male patients, the average age during follow-up was 12.4 years. The main pattern reported of ANA antibodies was a homogeneous pattern and 92.5% presented anti-doublestranded DNA by Elisa positive. The response to the treatment was evaluated with 2 parameters, the first one based on renal function (creatinine) and urinary sediment finding that 67.5% had complete remission, while based on the response to 12-hour proteinuria, a complete remission was reported. 46% Improvement was observed in other indices such as hemoglobin, creatinine and complement levels. The adverse effects of infectious type reported were 28% pneumonia and 22% upper respiratory infection, with a mean hospital stay of 5.1 days (3.5). Only 20% of the patients presented vomiting associated with the application of cyclophosphamide. Conclusion: We conclude that our population presented a response greater than 50% with the use of double immunosuppressive scheme, a value that is comparable with that reported in other series and also without presenting a higher rate of associated adverse effects. Although the study presented limitations due to the fact that not all the indices were requested to assess remission according to the current definitions, it is an initial descriptive study that shows that the therapy used in our institution presents good results. Methods: We reviewed our data on seven children with hereditary complement deficiency and obtained a genetic diagnosis in 5 of these 7 patients using next-generation sequencing. Informed consent was taken from the parents and the data was tabulated in the study proforma.

Conclusion: Based on our study and others reported, hereditary complement deficiency (notably C1Q deficiency) is the commonest form of monogenic lupus in our part of the world. Afflicted children present most commonly with rash and mucositis below 5 years of Methods: Multi-center, retrospective and descriptive study. Medical records were reviewed and the information was recollected using a data collection format. The data analysis was performed with SPSS 20. Results: N = 163. Sex ratio F4: M1, mean age was 12 years (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) . 37,4% developed jSLE before their 11th birthday. The most common clinical manifestations were: arterial hypertension 48.5%, mild to moderate proteinuria 34.4%, nephritic-nephrotic syndrome 33.1%, hematuria 24%, nephrotic syndrome 20.9% and nephritic syndrome 13,5%. 19% developed acute kidney injury (AKI) and 8.6% progresses on to early chronic kidney failure. The mortality rate was 13.5%. 18% of patients with class IV nephropathy died during follow-up. 137(84%) biopsies were analyzed. The distribution by nephropathy subtype was: 46.6% class IV, followed by 12,9%class II, 9.2% class V, 6.7% class III and 5.8% presented mixed changes (class IV-V in 6 and III-V in 2 patients) and 3.7% histology was modified by treatment. Patients with class IV nephropathy developed: nephrotic syndrome 46,7% (p=0.002), nephritic-nephrotic syndrome 62% (p=0.032) and AKI 76,9% (p=0.057). 86,6% (p=0.002) of class V patients developed nephrotic syndrome. There were no differences between types of LN and the profile of autoantibodies or levels of hypocomplementemia. Induction treatment: 81,6% received pulses of methylprednisolone plus 76% intravenous cyclophosphamide and 5,5% mycophenolate mofetil (MMF). Maintenance treatment: 32% received MMF and 54% azathioprine. 11.7% required Rituximab, 5.5% intravenous immunoglobulin and 2.5% plasmapheresis. Early dialysis was used for patients with class IV nephropathy and severe deterioration of renal function. Conclusion: In this cohort, LN was severe and associated with significant morbidity which is similar to previously reported studies in medical literature. The most frequent subtype was class IV nephropathy; 64% of them developed nephritic-nephrotic syndrome or nephrotic syndrome with a significant percentage to complications at onset and course of the disease. Second most frequent was class II nephropathy and this one subtype did not have an adequate pathological clinical correlation. The biopsy is essential to classify LN and guide the immunosuppressive treatment. Introduction: Compelling evidence from studies in systemic lupus erythematosus (SLE) demonstrates that Interferonα (IFNα) and type I IFN signaling are implicated in disease pathogenesis; moreover, upregulation occurring in IFNα production/signaling has been linked to a group of autoinflammatory monogenic diseases named type I interferonopathies.

Objectives: The aim of our study was to evaluate type I IFN signaling by assessing two read-outs of IFN activation: STAT1 (both total STAT1 and phosphorylated pSTAT1), and Interferon Score (IS) [1] , mirroring the expression of 6 IFN stimulated genes, in two different populations. In a group of SLE patients we wanted to evaluate if the assessment of type I IFN signaling correlates with clinical phenotype/laboratory inflammatory markers (anti dsDNA antibodies)/disease activity and then could be a useful tool for monitoring treatment response. In a group of undiagnosed patients, strongly suggestive for a systemic autoimmune/autoinflammatory disorder (SAD), we aimed to evaluate if the assessment of type I IFN signaling could help in clustering the kind of disorder. Methods: In the last 3 years we have enrolled 21 patients. 9/21 were diagnosed with SLE (ACR criteria). 12/21 patients were highly suggestive for SAD. During periodical evaluations, disease activity index was performed, blood samples were collected and type I IFN signaling was evaluated as compared to healthy controls. Results: In the 9 SLE patients we detected a strong upregulation of type I IFN signaling. These data are in agreement with recent publications, in which type I IFN is described as a main contributor to SLE pathogenesis. Comparison among controls, SLE and SAD groups at time of first examination (T1), showed a significant increase in IS, pSTAT1 and STAT1 in the SLE group as compared to controls (IS: p<0,0001, pSTAT1 and STAT1: p<0,001). Moreover, in the SLE group, a significant reduction of IS, pSTAT1 and STAT1 was evident by comparing samples collected at T1-T2 (ΔT: 6-8 months) and this mirrored both clinical improvement measured by SLEDAI and lowering of anti-ds DNA antibody titres. Results from the SAD group are apparently heterogeneous: only some patients showed an activation of type I IFN axis, but this was quite expected given the criteria by which the patients were recruited. Conclusion: We noticed a good concordance between SLEDAI, anti dsDNA antibodies and pSTAT1/IS, thus stating that the evaluation of type I IFN signaling can be a useful tool for evaluating therapeutic effectiveness in SLE patients. In the SAD group, the evaluation of type I IFN signaling helped us to discriminate among disorders: when the IFN pathway was inactivated, we could more easily rule out previously hypothesized diagnosis of an autoimmune disorder. In those patients where a strong type I IFN activation was detected without a final diagnosis, a strict follow up has been provided, as the upregulation of the IFN pathway may be an early clue of SAD.

None Declared Methods: Juvenile SLE patients initially were evaluated by ACR-1997, SLICC-2012 and EULAR/ACR classification criteria at baseline, when the diagnosis for the first time had been established by an expert pediatric rheumatologist (OK). All data were obtained from patient records. The diagnostic sensitivity of the three sets of classification criteria were further tested within 1 year of diagnosis and at last patient visit, longitudinally. Subjects with a clinical diagnosis other than SLE for at least 1 year-period, consecutively enrolled as controls.

Since patients with autoinflammatory diseases, particularly with FMF constitute the vast majority of our outpatient appointments, these subjects were excluded.

Results: A total of 104 juvenile-onset SLE patients were enrolled for the sensitivity performance of classification criteria at diagnosis and 104 controls (69 juvenile idiopathic arthritis, 9 juvenile systemic sclerosis, 5 juvenile dermatomyositis, 1 mixed connective tissue disease, 15 vasculitis and 5 other diseases) for specificity at their last visit.

Since the follow-up period was less than 1 year, 12 SLE subjects excluded after baseline evaluation. Finally, 92 SLE subjects were eligible for sensitivity evaluation within 1 year of diagnosis and at last visit. The median age of the SLE patients at diagnosis of clinician was 13.0 years (range 3.1-17.9 years) with a median disease duration of 5.0 years (IQR 3.0-8.0 years). The female-to-male ratio was 4 Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by high-levels of autoantibodies mainly targeting nuclear antigens and loss of self-tolerance. Peroxisomeproliferator activated receptor gamma (PPARγ) and nuclear factorkappa beta (NF-κB) are transcription factors, which, within normal levels, have shown to be crucial in immunomodulation namely, activation and development of normal lymphocytes, negative and positive selection of T and B cells. High-levels of NF-κB has inflammatory properties such as release of autoreactive T cells. On the contrary, PPARγ has anti-inflammatory effects, which has been demonstrated to be effective when used early in prevention of disease in murine models of systemic lupus erythematosus.

Objectives: Herein, we investigated whether NF-κB and PPARγ could exert opposite effects in the immune response and the possible implications in immunomodulation of juvenile systemic lupus erythematosus. Methods: Serum NF-κB and PPARγ levels were measured in 42 juvenile systemic lupus erythematosus. In addition,19 juvenile systemic sclerosis and 25 age-matched healthy children were selected for patient control and healthy control, respectively. We have also assessed the relation of these transcription factors with organ involvement patterns, disease activity, damage scores, autoantibody and acute phase reactant levels.

Results: The control group did not differ from the juvenile SLE patients for age (p>0.05). According to our study, serum NF-κB levels (ng/mL) of juvenile SLE and juvenile systemic sclerosis patients were significantly higher ( (LN) , a major cause of morbidity and mortality. Recent evidence in adult-onset SLE suggests that prompt achievement of proteinuric remission is associated with improved long term renal outcomes. Data on time to proteinuric remission in jSLE are still limited.

Objectives: To describe the clinical course of LN in our cohort of jSLE patients and to analyze potential clinical and laboratory features associated with proteinuric remission.

The clinical records of jSLE patients followed at our centre in the last thirty years were retrospectively reviewed. To be included in the study patients needed to satisfy ACR criteria for SLE, to have an age at SLE diagnosis <18 years, a biopsy-proven LN, and at least 5 years of follow-up. Demographic, clinical, laboratory and histological data at LN onset were collected. Significant proteinuria was defined as proteinuria >0,5 g/day or urine protein creatinine ratio (UPCR) >0,5. To be classified as in proteinuric remission patients needed to achieve a proteinuria under the cut-off in two consecutive visits. Data of patients with and without persistent significant proteinuria at 1 year were compared using Fisher's exact test or Mann-Whitney U test as appropriate. Correlation between time to proteinuric remission and variables at LN onset was calculated by means of Spearman's Rho test or Mann-Whitney U test, as appropriate. Results: Twenty-six patients were included in the study, 22 were females. Median age at jSLE onset was 12,9 years (range 5,1-16,2), and at LN onset 13,6 (range 6,2-23,7). In 19/26 patients (73%) kidney involvement was present at jSLE diagnosis. The majority of patients were histologically classified with LN class III and IV (69,2%). All patients received high dose corticosteroids as induction treatment; in 7 patients cyclophosphamide i.v. pulses were added. Twelve patients (46%) received ACE-inhibitors or angiotensin II receptor blockers (ARB). Proteinuric remission was achieved in 73,9% and in 82,6% of patients at 1 and 5 years from LN onset, respectively. Median time to proteinuric remission was 5,4 months (range 0,2-68,8 months). In two patients (7,6%) a severe renal damage occurred. The main features of patients with and without significant proteinuria at 1 year from LN onset are presented in Table 1 . Although statistical significance was not achieved, persistence of proteinuria seemed associated with a younger age and nephrotic proteinuria at LN onset. No patient with Class II LN developed persistent significant proteinuria. Correlation analyses highlighted that patients treated with ACE-inhibitors/ARB presented a faster remission of proteinuria (p=0,03). Conclusion: Our cohort suggests that younger patients with nephrotic proteinuria at LN onset present a higher risk of prolonged proteinuria and should be carefully monitored. Treatment with ACEinhibitors/ARB could be useful to achieve a faster proteinuric remission. Due to the small size of our population, these results need confirmation in larger studies. Furthermore, a longer follow-up will allow to evaluate the role of time to proteinuric remission on long term renal outcome in jSLE. Introduction: An acquired form of angioedema (AAE) with symptoms of swelling in subcutaneous and mucosal tissues is clinically similar to hereditary angioedema but it is rarer than the hereditary type.

Objectives: The AAE occurs rarely the existence of a systemic lupus erythematosus (SLE). The antibodies in SLE may change the structure of C1-INH or diminish its regulatory capacity.

In this study, we aim to present AAE as the initial presentation of SLE and literature review.

Methods: We presented a case report and provided information about AAE related to SLE. Hence, literature was researched using the keywords "acquired angioedema," "systemic lupus erythematous," and "C1 esterase inhibitor protein." Results: A 16 year old girl was admitted to our clinic with persistent angioedema in the eyelids and lips, alongside polyarthralgia with fatigue. Her family and she had no remarkable history for recurrent angioedema or rheumatological disease. On examination, she had bilateral periorbital and lip swelling without dyspnoea. There was a pain and limitation in the joints of both hands and fingers. The other organ systems were normal on examination. Laboratory investigations showed leukopenia with a white cell count of 2.19 x 109/L, serum C-reactive protein 0.09 mg/dL (<0.5), erythrocyte sedimentation rate 90 mm/h (0-20), IgG 1811 mg/dL (600-1400). Immunological tests showed a major classical pathway-mediated complement depletion with low C3 of 28.1 mg/dl (90-180) and a low C4 of 2 mg/dl (10-40). C1-INH level was normal of 21.70 mg/dL (18-40). There was no hematuria or proteinuria. . In addition, ANA, anti-dsDNA, anti-Smith antibody in high titer and the direct Coombs tests with complements were positive. According to the SLICC criteria, she was diagnosed as SLE and AAE with the presence of polyarthralgia, leukopenia and positivity of immunologic criteria. After pulse methylprednisolone therapy (1 gr/day), the patient received oral prednisolone (2 mg/kg/day), hydroxychloroquine (4 mg/kg/day) as maintenance treatment. After seven days, the angioedema resolved. The patient has been under treatment for 2 years with prednisolone (4 mg/day) and hydroxychloroquine (4 mg/kg/day) and has experienced neither SLE flares nor angioedema. Angioedema can occur as either hereditary or acquired types due to vasodilation and increased vascular permeability resulting from inflammatory mediators, especially bradykinin. Bradykinin production is Introduction: Mutations of CECR1 have been recently reported as causative of an inflammatory condition characterized by an early onset vasculopathy resembling polyarteritis nodosa. The clinical manifestations of the disease are heterogeneous with a wide range of severity. Patients with a more serve phenotype present early onset cerebral stroke, which can be either ischemic or hemorrhagic. Objectives: to describe the neuroradiologic features of patients affected by ADA2 deficiency with central nervous system (CNS) involvement. Methods: We reviewed the contrast-enhanced brain MR, MR angiography (MRA), and digital subtraction angiography (DSA) examinations of 5 patients with a confirmed molecular diagnosis of ADA2 deficiency and CNS involvement. The patients were two brothers (R312X and E328D mutations in compound heterozygosis) and three other unrelated patients: a male homozygous for the T360A mutation, a girl homozygous for the G47R mutation and a girl with a structural variation in 22q11.1 leading to not functional enzyme.

Results: Four patients presented multiple acute and/or chronic small ischemic infarcts involving the basal ganglia and the midbrain, in keeping with small-vessel occlusions (lacunar strokes). One patient additionally presented a large hemorrhagic infarct in the temporal lobe. Areas of focal accumulation of hemosiderin due to intraparenchymal bleeding were also noted. Interestingly, three patients presented an abnormal contrast-enhancing soft tissue in the interpeduncular cistern, encasing the midbrain perforating arteries. These neuroradiological findings regressed after the treatment with anti-TNF agents. The fifth patients presented a large haemorrhagic infarct in the frontal lobe and after few years a subarachnoid haemorrhage due to the rupture of aneurysm of anterior communicating artery; an aneurysm of the left superior cerebellar artery was also detected. Inflammatory alterations of the vessels were not demonstrated. The brain MRA and DSA performed in all patients showed no relevant vascular stenosis of the major arteries of the circle of Willis.

Conclusion: Typical lacunar strokes in patients with ADA2 deficiency are due to occlusion of small perforating arteries, which can be missed on conventional arterial imaging focusing on the vessel lumen of relatively large arteries. We hypothesize that the abnormal soft tissue detected in the interpeduncular cistern in the present patients may represent an abnormal inflammatory perivascular response, leading to small vessel stenosis. The presence of aneurysms in one patient, without signs of inflammation, enlighten a different pattern of vascular involvement of DADA2 mainly represented by structural rather than inflammatory alterations. Wider use of contrastenhanced high-resolution MR examinations may better demonstrate vascular manifestations in patients with ADA2 deficiency. Introduction: Recurrent pericarditis is a complication of acute pericarditis and affects 15-30% of patients after an initial attack. The etiology is poorly understood and about 80% of recurrent pericarditis are "idiopathic". The therapy seems to be very important to avoid the recurrences. Conventional treatment includes NSAIDs, glucocorticoids, colchicine, and in the last years, treatment with Anakina (anti IL-1) became common in the clinical practice Objectives: To analyze clinical findings and treatment in a cohort of pediatric patients presented with recurrent pericarditis. Methods: patients with at least two episodes of idiopathic pericarditis, followed at Necker Hospital (Paris) and at Bambino Gesù Childern's Hospital (Rome) between 2006 and 2016 were included in the study. Patients with a known history of autoimmune or autoinflammatory disease were excluded. Results: Thirty-two patients (19 F and 13 M) with recurrent pericarditis were included. The median age at disease onset (first episode of pericarditis) was 11.8 years (range 8-17). The first episode was treated differently: 15 (46%) patients received NSAIDs, 6 (18.8%) and colchicine, and 11 (34.4%) glucocorticoids. Patients who had received glucocorticoids at the first episode showed relapsed before than the others ,respectively 1.9 vs 6 months with a statistical difference (p<0.02). The first treatment did not influence the number of relapses in our study. Moreover we can divided our study population in two groups: Group 1 (20 patients): recurrence of pericarditis was treated only with NSAIDs, colchicine or glucocorticoid (alone or associated); Group 2 (12 patents) in which the treatment with anakinra (IL 1 inhibitor) was necessary. The group 2 showed a higher number of relapses than the group 1 (median 2.93 vs 1.73 p<0.01). In the group 2, there were more steroid-dependent patients in comparison to the group 1 (respectively 72.7% vs 21.1 ; p<0.005). In the group 2, all patients treated with anakinra showed a complete response within few days (in median after 2-3 days) and were able to discontinue the glucocorticoid therapy. During daily treatment with Anakinra no relapse was reported. In 7 out of 12 patients, the dose of anakinra was tapered and of these patients relapsed. The tapering strategy was to progressively reduce the days of administration during the week. The mean time from the start of anakinra to tapering was 11 ±3,4 months (range 6-15 months) in the 4 patients who experienced relapse versus 17.6 ±4.6 months (range 15-23 months ; p<0.04) in those who did not flare. All the patients who relapsed responded quickly to the reintroduction of anakinra. In 5[IA2] out of 12 patients, anakinra was discontinued after a mean duration on treatment of 32.2 months (range 16-58) ; two patients of these 5 patients relapsed within 2 months, and anakinra was reintroduced with a good response. Conclusion: Our study shows the high variability of treatments of recurrent pericarditis and underlines the importance of a standardized therapy to avoid relapses. Glucocorticoid therapy is associated with a shorter period to flares than the other treatment. Anakinra is an effective treatment; however, discontinuation of anakinra lead to relapses in many cases, principally when it was tapered or stopped within a few months. This study suggests that IL-1 inibithion should be used rather than steroids in patients with inadequate response to NSAIDs and colchicine . Moreover our data suggests also that a longer term therapy with anakinra reduces the risk of relapses. Further experience on larger population is needed to define treatment duration. was considered i)confirmatory, if the patient carries 1 P or LP variant in autosomal dominant (AD) diseases or 2 P/LP variants in autosomal recessive (AR) disease; ii)consistent, in presence of 2 P or LP variants (not phased) or 1 P/LP variant and 1 VOUS or unsolved variant in AR diseases; iii)of uncertain significance, if composed by 1 VOUS variant in AD diseases or 2 VOUS variants in AR diseases.We defined as not confirmatory the genotype of patients carrying 1 or more variants and not included in the previous groups (i.e heterozygous patients for AR diseases) or negative patients for genetic analysis Results: A total of 281 patients reached a consensus during the evaluation by the experts. The majority of patients with consensus obtained the classification as confirmatory or consistent genotype. The most relevant discrepancy observed was the lack of classifications of some heterozygous patients (7 FMF and 2 MKD) for AR diseases in the consensus group. The 2 MKD patients were positive for mevalonic acid in the urine. Only 1FMF, 1 CAPS and 2 TRAPS with uncertain pathogenic variants reached a consensus among the experts (Table 1 ) Conclusion: Generally a good correlation between the two methods of classification was observed. Nonetheless a limitation of this method might be the lack of classification of a subgroup of patients (heterozygous patients in AR disease) that otherwise reached a consensus on the diagnosis when considering both clinical and genetic data.

None Declared Methods: The β-CONFIDENT Registry was a multicenter, long-term, prospective, observational study conducted at 39 sites across 13 countries. Patients with different CAPS phenotypes and those with other autoinflammatory diseases receiving canakinumab at physician's discretion were enrolled in the registry. Cumulative safety data were reported as exposure-adjusted incidence rate per 100 pt-years (IR/pyr) from enrollment of the first pt (November 2009) until the end of study (December 2015). Patients were followed up for at least 1 yr. The protocol did not mandate any visits or procedures. All observed and reported adverse events (AEs) and serious AEs (SAEs) were recorded for the following age groups: <4, 4−<12, 12−<18, 18−<65 and ≥65 yrs. Results: Of the 285 pts enrolled, 21% (n=60) discontinued the study mainly due to loss to follow-up (35%, n=21) followed by AEs (10%, n=6), poor efficacy (8%, n=5) and pt preference (3%, n=2). In total, 1114 AEs and 155 SAEs were reported in 223 pts (110.7 IR/100 pyr) and 83 pts (15.4 IR/100 pyr), respectively. Exposure-adjusted incidence rate of AEs (IR/100 pyr) among pts in the <4 and 4 -<12 yr age group, were lowest in pts who received <2 mg/kg (130.3 and 59.7, respectively) compared with pts who received 2-<4 mg/kg (450.8 and 169.6, respectively) and 4 -<8 mg/kg (121.5 and 90.0, respectively) CAN. In pts aged 12 -<18 yrs, IR/100 pyr were lowest in pts who received 2-<4 mg/kg doses (118.2) compared with pts who received <2 mg/kg (169.6) and 4 -<8 mg/kg (139.4) CAN. Similarly, in the 18 -<65 yr age group, IR/100 pyr were lowest in pts who received <2 mg/kg (93.1) compared to pts who received 2-<4 mg/kg (100.7) and 4 -<8 mg/kg (154.4) CAN. In the ≥65 yr age group, IR/100 pyr decreased with increasing dose (<2 mg/kg: 26, 2−<4 mg/kg: 17). Overall, 5, 13, 19, 84 and 7 SAEs were reported in the <4, 4 −<12, 12−<8, 18−<65 and ≥65 yr age groups, respectively. One death (metastatic rectal adenocarcinoma in a 76-yr-old Muckle-Wells syndrome patient) was reported.

Conclusion: The incidence of adverse events in each dose group increased with age (<4−<65 yrs). No meaningful pattern of AEs was observed, however, with increasing doses. Canakinumab demonstrated a safety profile consistent with previous reports 2, 3 , and is well tolerated in CAPS patients aged <4−65 years.

Introduction: Secondary, AA amyloidosis and infertility are most common and severe complications of Tumour necrosis factor Receptor-Associated Periodic Syndrome (TRAPS) in adults.

Objectives: To define the best treatment approach in patients with TRAPS and the effect on long-term outcomes.

Methods: We reviewed all data of 100 patients carrying a total of 40 TNFRSF1A gene variants who were referred to fever clinic at the National Amyloidosis Centre in London up to January 2018. The Auto Inflammatory Diseases Activity Index (AIDAI) was used to estimate the long-life disease severity. Results: 29 patients had intronic variants of the TNFRSF1A gene and displayed milder disease than the 71 patients with mutations affecting coding regions with an AIDAI score <5 (P<0.005), less abdominal pain and skin rashes but more frequent headache or mouth ulcers during fever attacks (P<0.001 and P<0.05, respectively), none developed AA amyloidosis. Amyloidosis affected 13 patients and the strongest association was duration of untreated disease, independent of the AIDAI score. Almost 70% of patients required maintenance therapy. Anti-interleukin (IL) 1β drugs were the most frequently used, in 53 patients, with the highest efficacy rate (86% complete response), while Etanercept was less effective and discontinued in 72% of 25 patients. No patients on anti-IL1β treatment developed amyloidosis and 10 patients with amyloidosis have been successfully treated with anti IL-1 agents with preservation of native renal function in 7 and excellent long term transplant function in 2. Nine women had a history of failure to conceive and seven had successful pregnancies without fertility treatment following complete disease control with anti-IL1β drugs. Long term safety profiles for anti IL-1 agents were excellent even in the presence of comorbidity. Conclusion: Anti-IL1β drugs are the best maintenance treatment in TRAPS with potential to reverse the most serious disease complications of AA amyloidosis and infertility. The diagnosis of TRAPS should be considered very carefully in patients carrying intronic variants of the TNFRSF1A gene.

Introduction: Blau syndrome (BS) is a rare monogenic form of sarcoidosis with paediatric onset resulting from mutations in the pattern recognition receptor NOD2. It is phenotypically characterized by the triad of granulomatous polyarthritis, uveitis and skin involvement. Although skin involvement occurs in about 2/3 of cases, only very little is known about its initial clinical presentation and evolution during disease course.

Objectives: The aim of this study is to describe skin manifestations of BS. Methods: We retrospectively studied a French national cohort of 20 patients with a genetically confirmed BS. Patients have been identified through a call to SOFREMIP and Dermatology French Society. Epidemiological clinical data have been collected and data about skin involvement (medical record, photographies, biopsies) were analyzed by two independent expert dermatologists. 5 skin biopsies were analyzed by one anatomopathologist.

Results: The mean age at diagnosis was 14.3 (0.25-54) years. Skin involvement, present in 15/20 (75%) patients, was early at a median age of 1.5 (0.25-20) years and always inaugural of BS except in one case. Skin lesions have been initially considered as nonspecific dermatitis in 2/15 patients. Skin lesions were mainly (13/15 patients) diffuse erythematous or flesh-colored micropapules, sometimes with livedoid disposition, or nodules (2/15 patients) which coexisted in one patient. All skin biopsies revealed dermic granuloma without caseous necrosis. 9/15 (60%) of patients got a dermatological consultation and 7/15 (47%) a skin biopsy. Average time before diagnosis was 6.3 (-0.8-41) years and 1 (0-3) in case of skin biopsy. Mean age at diagnosis in patients with skin involvement was earlier (10.6 y vs 14.3y) and significantly lower 2.1 (0.25-4.2) years when a skin biopsy has been realized. Conclusion: Skin involvement in BS is often unrecognized or considered as a nonspecific dermatitis. The skin lesions occur in early childhood, are inaugural with stereotypical clinical manifestations and a dermal granulomatous histology. These observations suggest that a better recognition of evocative lesions and a skin biopsy could allow earlier diagnosis and management of patients. Introduction: STING-associated vasculopathy with onset in infancy (SAVI) is a recently described autoinflammatory disease caused by gain-of-function mutations in the TMEM173 gene (1). Most cases are due to de novo mutations; however, familial cases have been reported (2). Manifestations include progressive interstitial lung disease (ILD), polyarthritis and cutaneous changes including acral violaceous plaques and digital ulceration.

Objectives: To describe a patient with ILD and a pathogenic TMEM173 mutation without the typical features of cutaneous vasculopathy and arthritis.

Methods: The index case presented at 4 months of age with failure to thrive, increasing oxygen requirement, tachypnoea and intermittent fever. Past history was significant for prematurity (28 +5 weeks gestation) and chronic lung disease having been discharged home at 3.5 months of age on low flow oxygen. Progressive deterioration necessitated mechanical ventilation. No infectious agent was identified and antimicrobial therapy failed to alter the disease course. Lung biopsy was non-diagnostic, showing interstitial fibrosis and pneumocyte hyperplasia. The patient's mother and maternal grandmother had been affected by severe arthritis and ILD suggesting a familial syndrome. The patient's mother was diagnosed with rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) aged 2. She developed respiratory issues in young childhood and lung biopsy had shown non-specific changes of lymphoid interstitial pneumonia. Her symptoms had been stabilised with regular rituximab having previously failed treatment with methotrexate, mycophenolate and adalimumab. The patient's maternal grandmother died at the age of 38 having undergone a single lung transplant aged 30. She too had been diagnosed with RF positive JIA and subsequently with rheumatoid arthritis associated pulmonary fibrosis. The family history and clinical features of ILD, fever, acute phase response, positive antinuclear antibodies and non-response to conventional immunosuppressive therapy raised the possibility of SAVI. Results: Bidirectional Sanger sequencing revealed a heterozygous c.463G>A; p.(Val155Met) mutation in the TMEM173 gene in the child and mother. Functional assay confirmed significant upregulation of interferon stimulated genes in both patients. Posthumous genetic evaluation of the patient's grandmother is underway with results awaited. Treatment with baricitinib led to clinical and laboratory improvement. The patient is thriving six months after starting treatment but remains dependent on home oxygen treatment.

Conclusion: SAVI has a varied phenotype and we present a case without the typical cutaneous and articular manifestations. Prompt recognition and treatment is important to prevent irreversible lung disease. This diagnosis should be considered in children with ILD where other more common causes are not apparent; even in the absence of typical cutaneous or joint findings. Accurate identification of rare, inheritable diseases in children can allow for retrospective diagnoses and more precise treatment for family members. Written informed consent for publication of their clinical details was obtained from the parent of the patient. Objectives: We report a single centre experience (GOSH) of the association of CRMO and IBD. Methods: We reviewed reports of whole body MRI scans of 300 children, done in last 5 years between January 2012 and December 2016. Patients with MRI scan results consistent with CRMO were included in the study. Retrospective analysis of electronic clinical records of these patients was done and we recorded their clinical symptoms at presentation, any associated illnesses and Family history. Histopathological/ microbiological findings of bone biopsies were reviewed to rule out haematological, infectious or malignant causes. Results: Twenty three patients were included in the study.Five were male and eighteen female. These children were 8-18 years old with median age of 15 years. The clinical feature of CRMO at first presentation are as under.All patients presented with musculoskeletal symptoms like backache, clavicular involvement, or joint pain.Five patients (21%) presented with abdominal pain and blood in stool. These patients were diagnosed as Inflammatory bowel disease(IBD) on the endoscopic and histopathological findings. Three patients presented with gut symptoms first and later on they developed joint pain and swelling. However one patient presented with joint pain to start with and diagnosed as CRMO. This patient later on developed gut symptoms. One patient presented with simultaneous onset of diarrhoea, blood in stool, abdominal pain and joint pain with swelling.There is significantly more raised inflammatory markers in the IBD/CRMO group than in the CRMO alone groupHistory of trauma was present in 13% of patients who presented with musculoskeletal symptoms.Hyper mobility was present in four patients. Juvenile idiopathic arthritis was an associated diagnosis in three patients. One patient was diagnosed as Enthesitis related arthritis (ERA) and CRMO overlap. Psoriasis, palmoplantar pustulosis , acne, atopic dermatitis, dermatitis artefacta were the skin conditions associated with CRMO but not in IBD/CRMO overlap group.There was family history of connective tissue disorders in six (26%) out of 23 patients, including systemic lupus erythematosus, ankylosing spondylitis, Crohn's disease, rheumatoid arthritis, antiphospholipid syndrome and psoriasis. Only one patient (4%)out of 23 was HLAB27 positive.

Conclusion: CRMO has a varied presentation. We identified that CRMO is associated with IBD in 21% of the patients. Further studies are needed to identify whether the CRMO/IBD overlap group has a separate phenotype.

Introduction: Familial Mediterranean Fever (FMF) patients with a poor compliance to follow-up (FU) appointments and treatment may not only be mischaracterized as resistant to colchicine, but potentially may have an unfavorable long-term disease outcome.

Objectives: Primary objective: To assess the level of compliance in patients with FMF, in respect to the disease outcome and the development of amyloidosis. Secondary objective: To detect the tolerant patients, who need additional treatment for the disease control.

Methods: A retrospective study of all patients with an established diagnosis according to Tel-Hashomer criteria and a minimum FU of 6 months was performed. After 2015, the auto-inflammatory diseases activity index (AIDAI) was given to all patients attending the FU appointments, aiming to the disease self-monitoring. For the purpose of the study, good compliance to the scheduled FU was defined as consistent attendance to all visits (twice yearly). Compliance to treatment was assessed according to the family/patient information given in the FUs. In those with continuous colchicine administration, the presence of clinical or subclinical inflammation was recorded to estimate the disease gravity. . The expression of 28 IFN-related genes was quantified from RNA from whole blood using NanoString technology. Summary scores for IFN6/IFN28/ and a z-score for CXCL10(IP10) were calculated(as described elsewhere) Four of the probable interferonopathy patients had mutations related to the IFN pathway genetic analysis on the other are ongoing. Depending on the features of patients with a significantly high IFN signature, we created a preliminary clinical score to identify autoinflammatory interferonopathies based on literature review and expert opinion (Table 1) .

The median IFN6, and IFN28, scores were significantly higher in the probable interferonopathy cases as compared to healthy controls and oJIAs patients, but did not differ from SLE and JDM patients. Interestingly, CXCL10(IP10) scores were higher in the probable interferonopathy group than the SLE and JDM groups. The mean clinical score was 3(3-5) among these patients. Thus patients with high IFN signature, lacking features of SLE and JDM may be classified to have a autoinflammatory interferonopathy and the suggested clinical score may be helpful to the clinician. Further genetic analysis will enable defining the underlying mutation in the pathway and treatment results on IFN blocking treatments are needed to confirm the pathogenic role of type I IFN in these diseases. Conclusion: We suggest to use this new clinical score for screening patients with undifferentiated inflammatory diseases, and the IFN signature quantified in the 6-gene or 28-gene(preferably) IFN score to identify patients with potential autoinflammatory interferonopathies. The mutation screening for specific mutations is ongoing in these patients.

Introduction: Chronic Non-bacterial Osteomyelitis (CNO) is a rare inflammatory disorder that is characterized by onset of pain, local bone expansion and radiological findings suggestive of osteomyelitis, usually at multiple sites. Although CNO pathogenesis remains still unknown, the hypothesis that CNO might be a genetic disease in the spectrum of autoinflammatory disorders has acquired importance. The strongest evidence comes from the syndromic forms of CNO (Majeed syndrome and Cherubism) and from the presence of chronic inflammatory osteomyelitis in two monogenic diseases caused by mutations of genes involved in the activation of the NLRP3 (pyogenic arthritis, pyoderma gangrenosum and acne: PAPA) and IL-1 beta receptor (deficiency of IL-1 receptor antagonist: DIRA). Although it has been suggested the existence of genes contributing to sporadic CNO, the identification of a gene related to its aetiology has not been identified so far; however it has been recently demonstrated that FBLIM1, a protein involved in the regulation of bone remodeling, could be involved in the pathogenesis of sterile bone inflammation [1] Objectives: To sequence FBLIM1 in a cohort of 83 Italian patients with CNO and correlate the possible results with clinical manifestations.

Methods: The coding regions of FBLIM1 were sequenced in a cohort of 83 CNO patients using DNA purified from blood. PCR products were sent for Sanger sequencing. Only rare (global MAF < 2%), coding variants detected were taken into account. Clinical evaluation between patients with rare variants and those without was performed. Fisher' s exact test was used to compare categorical and ordinal data, and Student' s t test was used to analyze continuous data.

Results: Ten out of 83 patients presented at least one rare coding variant in FBLIM1 gene. One patient was a compound heterozygote (rs114077715/rs146575757), while a patient carried an homozygous mutation (rs540511146). Eight patients presented a heterozygous variants never described before (Table 1 ). All patients presented classical features of CNO and statistical differences between patients with presence of FBLMI1 and those without genetic mutations were not found in terms of gender prevalence, positive family history, age at onset, number of sites involved, presence of fever, arthritis and skin involvement as well as remission prevalence at the end of follow-up. Conclusion: Our data seem to confirm a possible role of FBLIM1 in the pathogenesis of CNO suggesting that CNO is a disorder of chronic inflammation and imbalanced bone remodeling.

Introduction: Children and adults with clinically and genetically defined autoinflammatory diseases (AID) including CAPS, TRAPS and HIDS can receive expensive Interleukin-1 (IL-1) inhibitors in many countries around the world. However, patients suffering from unclassified autoinflammatory conditions characterized by recurrent fevers and organ dysfunction and the absence of a known pathogenic mutation commonly have no access to these treatment options.

Objectives: The aim of this study was to explore the efficacy and safety of colchicine treatment in children and adults with autoinflammatory diseases without pathogenic mutations. Methods: Consecutive children and adults with autoinflammatory diseases without pathogenic mutations treated with colchicine were included in this single centre study and observed for a median of 12,94 months (range 1,25 -66,73). Clinical features, autoinflammatory disease activity indices (AIDAI), inflammatory markers ESR, CRP, SAA and S100, frequency and duration of flares and physician global assessment of disease activity (VAS) were recorded serially and compared at baseline and while receiving Colchicine therapy.

Results: A total of 39 patients were included in the study. These were 16 girls and 23 boys, median age at start of colchicine therapy was 4 years (range 1 -54). The diagnoses included PFAPA in 15, mutationnegative FMF in 11, autoinflammation with low-penetrance variants in nine (all NLRP3) and other unclassified AID in four patients. Recurrent fever was the leading symptom, mostly associated with arthralgia and myalgia. The mean disease activity decreased from 4.4 at baseline to 2.2 on colchicine. Mean SAA-levels decreased from 159 to 63.3mg/l, CRP levels from 6.4 to 2.3mg/dl. Flare frequency was reduced in 72% and remained unchanged in 28% of patients. Flare duration was reduced in 82%, unchanged in 14% and increased in only 4% of patients. Most common adverse events were abdominal pain and nausea in 50% of patients and appeared to be dose dependent.

Conclusion: Children and adults with unclassified autoinflammatory diseases may benefit significantly for colchicine therapy. Control of clinical disease activity and improved inflammatory markers were documented in 59% of patients. Colchicine should be considered in patients with active inflammatory disease with no access to IL-1 inhibitors. Controlled trials are needed to further explore this approach. Results: Four patients (2 female and 2 male) with a mean age of 14 years and 9 months (range 140-179 months) were collected. The median time between disease onset and diagnosis was 9,5 months, with a range of 3-22 months. All four patients had osteoarticular symptoms and skin involvement. Two patients had already been diagnosed with Crohn disease (CD) one, and Ulcerative colitis (UC) the other and were both under infliximab treatment at the time of SAPHO diagnosis. Skin involvement in these two cases was characterized by psoriasis vulgaris and palmoplantar pustulosis psoriasis. The other two patients were under isotretinoin therapy for a severe acne. All patients suffered from back pain, 3 of them complained with pain at sternoclavicular joints, 2 at coxofemoral joints, 1 at shoulders and 1 in the costal, tibial and mandibular bones. Two patients displayed a persistent, low fever. Three patients showed increased ESR and the two CRP. Whole body MRI was performed in three patients and it showed signs of osteitis and synovitis, while bone scintigraphy was performed only in one patient and exhibited an increased uptake in affected bone with the typical "bull's head" appearance in the sternoclavicular region. All patients received NSAID and successively corticosteroid without clinical and radiological response; one was treated with cyclosporine with partial response. All patients finally received an anti-TNFα treatment (3 Adalimumab and 1 Etanercept) with a complete clinical and laboratory recovery in three of them, while one only had a partial improvement because of the brief follow-up. Moreover, two of them received intravenous bisphosphonate (Pamidronate 1mg/kg/day for 3 days) in consideration of a serious involvement of vertebral bodies, but in one of them it was discontinued for side effects.

Conclusion: SAPHO syndrome, as we observed in our patients, has a high impact on general health and quality of life. In two cases we evaluated the association with IBDs, and we observed the disease onset under treatment with anti-TNFα. While in the others two cases the disease onset was under isotretinoin. There is a lively debate if these drugs may be considered triggers or cure. Whole body MRI and bone scintigraphy have been useful tools to define the diagnosis, while no patients needed bone biopsy. Anti-TNFα agents have proven to be effective in our patients, and they could be considered as a standard treatment to control this disease.

Trial registration identifying number:

The treatment with systemic steroids and cyclosporine is well documented in the literature as the first-line treatment. In nonresponders, other treatment lines are indicated, as: corticosteroids and mycophenolate mofetil, mycophenolate mofetil and cyclosporine, tacrolimus, dapsone, infliximab, plasmapheresis. In case reports adalimumab has been used as the treatment for patients who did not respond to other drugs. Objectives: We evaluated the efficacy of adalimumab in PG nonresponder to steroids, steroids plus cyclosporine, dapsone plus cyclosporine.

Methods: We describe the clinical course of a 16-years-old female affected by PG at the left leg since age 13. Autoimmune tests were negative, as abdominal US with evaluation of the thickness of bowel wall, tTG, AGA, IgA, IgG, IgM, IgE, C3, C4, transaminases, ocular study with slit lamp were negative. She showed HLA DQ8, as the mother affected by Celiac disease. Two biopsies studies confirmed the diagnosis of PG, and the treatment with steroids and antibiotics was started. However, the disease gone on and cyclosporine was associated to steroids. In a further line of treatment, she was treated with dapsone plus cyclosporine. PG extended to the right leg and worsened with acute lesions. She was treated with topic steroids and antibiotics, with a further extension of the lesions. We proposed to start adalimumab (40 mg s.c. /14 days) and the tapering of topic steroids.

Results: Skin injuries progressively improved, and after 3 doses of adalimumab PG is limited to the atrophic lesions in the zones of previous ulcerative lesions.

Conclusion: Adalimumab is a safe and promising treatment in isolated paediatric PG and can reduce the use of steroids or other immune suppressive drugs. We highlight the role of accurate diagnostic procedures to primary exclude associated diseases. Informed consent to publish had been obtained from the parents. Introduction: Chronic Non-Infective Osteitis (CNO), is a rare autoinflammatory condition which results in one or more sterile inflammatory lesions of the bony skeleton. The most common presenting complaints are bony pain and swelling. Clinical course varies and diagnostic delay is common, often resulting in significant pain for those affected. It is characterised by a relapsing and remitting course, and long-term outcome is unclear. It is a diagnosis of exclusion with a wide differential including infection and malignancy. It can affect any part of the skeleton but most often affects the metaphyses of long bones, clavicle, pelvis and vertebrae 1 . It has previously been reported that the skull is almost never involved 2 . We report a rare case of multifocal CNO with a large lytic skull lesion which healed following a course of ibuprofen.

Objectives: To describe a rare case of multifocal CNO with a large lytic skull lesion which healed following a course of ibuprofen. Methods: Retrospective case review.

Results: A previously well 9 year old girl presented with a one month history of pain and swelling of the forehead, with associated headaches and lethargy. There was no evidence of rash or fever. Past medical history included two discrete episodes of right foot pain and swelling 10 months previously. X-rays showed expansion and sclerosis of the 2 nd metatarsal, with corresponding cortical thickening with oedema on MRI. Her symptoms resolved spontaneously without treatment and she was kept under clinical surveillance. There was a strong family history of psoriasis affecting her father, maternal aunt and maternal grandmother. There were autoimmune problems including lichen sclerosis, Sjogren's and thyroid problems on her maternal side. On examination she had an obvious soft tissue swelling over the bridge of her nose, which was tender on palpation. Vision, eye movements and cranial nerves were intact. Initial investigations showed mildly raised inflammatory markers (CRP 11 and ESR 45 Introduction: Pyoderma gangrenosum (PG) and Sweet's syndrome (SS) were initially described independently according to their cutaneous elemental lesions. Based on observations in adult patients it was subsequently shown that PG and SS share many diseases characteristics. This led to the development of the current "modern" classification. In this classification PG is considered as the prototypical deep ND, SS as the prototypical dermal ND and sub-corneal pustular dermatosis as the prototypical superficial ND. Furthermore, association of clinical and histological features of two different types of prototypic ND simultaneously or successively in the same patient were called "atypical" forms ND. The validity of these "modern" classifications systems of ND has not been studied in pediatric patients. Objectives: to describe an atypical clinical phenotype.

Methods: A 4 year-old young girl presented since the first months of life with recurrent fevers, arthralgia, persistent cough and failure to thrive (below the 5th percentiles). She never showed skin rash. At the age of 3, she was admitted to our hospital for persistent fever and arthritis of left knee and right ankle; she started ibuprofen without any benefit. Laboratory tests showed persistently elevated CRP and serum amyloid A levels, persistent microcytic anemia and increased IgG levels, highly positive antinuclear antibody (title 1:640, homogeneous pattern) with positive p-ANCA. Immunological and cytogenetic studies performed on bone marrow were normal; both sweat test and genetic test for cystic fibrosis were negative. She started low-dose glucocorticoids with incomplete response, persistent cough and polyarthritis in small joints. Chest radiograph and CT showed features of severe interstitial lung disease (ILD) with bronchiectasis and small nodules. Extensive investigations for bacteria, virus and fungi and cytological tests on blood and bronchoalveolar lavage were negative. A lung biopsy showed desquamative interstitial pneumonia. So, she started high-dose methylprednisolone, subcutaneously methotrexate and rituximab. Whole blood of the patient and healthy donors (HD) (n = 10) were collected into PAXgene tubes. The type I IFN signature was defined by the expression levels of six IFNregulated genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1), measured by quantitative polymerase chain reaction (qPCR). As previously described by Rice GI, the median fold change of each IFNinduced gene, when compared with the median of the combined HD, was used to calculate the type I IFN score. The mean type IFN score of the HD plus two SD was calculated; we considered as positive a type IFN score higher of 1,42.

Results: Because of a persistent inflammatory state, ILD and polyarthritis, an autoinflammatory syndrome was considered and, in particular, Copa syndrome was suspected; however, sequencing of coatomer associated protein subunit alpha (COPα) gene showed no mutations. Molecular analysis of the TMEM173 gene by NGS showed the presence of c.463G>A (p.Val155Met) variant in heterozygotic status. Whole-blood gene expression studies demonstrated increased IFN signature (182,2), well in the range for those reported in the literature in patients with SAVI and other interferonopathies. Elevated levels of CXCL-10 (>1000 pg/ml) were also found.

The clinical picture of SAVI syndrome is characterized by early-onset (before 8 weeks of age) cutaneous vasculitis, recurrent fevers, ILD, and systemic inflammation. Our patient never developed skin rash unlike the cases described in literature. Therefore, lack of typical skin lesions should not exclude this clinical suspicion. The respiratory and systemic inflammatory component of the disease may predominate. In the context of early age of onset, ILD, failure to thrive and recurrent fevers, SAVI must be considered as a differential diagnosis. A better understanding of the genotype-phenotype correlation is needed to improve SAVI management and prognosis. Introduction: Chronic non-infectious osteitis (CNO) predominantly affects patients < 18 years of age. We have previously described shortterm outcome of consecutive pediatric CNO patients treated with intravenous pamidronate (IV-PAM).

Objectives: We now present the long-term clinical, magnetic resonance imaging (MRI), and bone resorption data in this same cohort.

Methods: Patients: All consecutive pediatric CNO patients initially treated with IV-PAM between 2003-2008 at a single tertiary pediatric centre were prospectively followed until 2017. Intravenous Pamidronate (IV-PAM) dosing: 0.5 mg/kg (maximum 30 mg) for the first dose and 1 mg/kg (maximum 60 mg) for all subsequent doses (maximum annual dose 11.5 mg/kg). IV-PAM was administered either as 1 day/month x 9, or as 3-day cycles every 1-3 months if the patient lived far away. Whole body MRI (WBMRI) was performed at baseline, at pain resolution and at 6 and 12 months during the first year, and also at time of suspected flare. In case of WBMRI-confirmed flare unresponsive to non-steroidal antiinflammatory agents (NSAIDs), the patient received a repeat treatment with IV-PAM (discontinued when pain resolved with follow-up MRI at 6 months). Visual analog scale for pain (VAS, 0=no pain; 10=maximum pain) and bone resorption marker urine N-telopeptide/urine creatinine (uNTX/ uCr) were measured at baseline, preceding each IV-PAM, at 12 months, and also at time of WBMRI-confirmed CNO flare. Each patient's uNTX/uCr level was compared to age and sex specific norms. Introduction: Autoinflammatory diseases have revolutionized the concept of classical rheumatic disease. Most of them are produced by a "novo" mutation (only 10% have family history of disease). Haploinsufficiency of A20 was described in 2016, it has dominant inheritance and it is caused by mutations in the TNFAIP3 gene. A20 protein is an inhibitor of transcription factor NF-kB signaling pathway, which is key to inflammatory responses. This new autoinflammatory disease presents high penetration and patients present clinical symptoms at early age with similar phenotypes to Behçet's disease.

Objectives: We present a clinical case diagnosed of Haploinsufficiency of A20 with a mutation not described in the literature. Methods: 7-year-old boy with histamine intolerance and non-IgEmediated food allergies. At the age of 4, pain begins in lower limbs, reason why he attended a Paediatric Rheumatologist. He associated perineal irritation and frequent conjunctivitis, as well as episodes of oral aphthae and recurrent headaches. In addition, he presented abdominal pain, diarrhea, genital aphthae, 3 day self-limiting febrile episodes, asthenia, arthralgia, increased irritability and aggressiveness. Prior to diagnosis, it was considered as an autoinflammatory process and treated with colchicine with partial response. He precised dose increase and association of subcutaneous methotrexate. Among others, Behçet's disease and familial Mediterranean fever were considered as differential diagnosis. He presented normal serum levels of immunoglobulins and complement, negative antinuclear and anticardiolipin antibodies and negative HLA-B51. No mutations in MEFV gene on genetic studies. Analysis of TNFAIP3 gene detected heterozygosis the mutation p.W356R located in exon 7, that confirmed diagnosis of haploinsufficiency of A20. Throughout family history, we found years of evolution of similar symptoms in a sister, his mother and grandmother. Genetic study showed that the mutation p.W356R is segregated with disease because it was only detected in the three affected relatives. Results: We report an haploinsufficiency of A20 case with a new mutation p.W365R, which not described in literature or registered in the database of genome diversity Exome Aggregation Consortium (EXAC). In silic studies of functional damage of the mutation with SIFT applications show a deleterious effect and with Polyphen applications a possible damage. We emphasize that family study was carried out in 3 generations and shows that the mutation is segregated with the autoinflammatory disease. Conclusion: It is important to consider autoinflammatory diseases in differential diagnosis when recurrent symptoms of this type appear, since only its suspicion will enable adequate diagnosis and treatment. Informed consent to publish had been obtained. Conclusion: Conclusion: AID was identified higher in childhoodonset patients compared with adult-onset. In both onset age groups, AID was mostly identified in patients with periodic fever and never diagnosed in patients with persistent fever. Fever pattern is one of useful factors to estimate probability of AID. registry of autoinflammatory diseases (SpRAD). Secondary: To identify patients not currently included in the Eurofever registry and enroll them. Methods: Retrospective cross-sectional study was performed. The study was approved by the ethics committees of all hospitals and, accordingly, the participants had to sign an informed consent prior to inclusion in the registry.

Results: 287 patients from 14 centres in 9 different Spanish regions were identified, 144 were males (50%). Genetic study had been performed in 144 individuals (50%), and 18 inconclusive mutations belonging to 14 patients were found. 106 had a clinical diagnosis of monogenic disease, being the most frequent: familiar Mediterranean fever (FMF) (40%), hyper Ig D syndrome (HIDS) (25%), cryopyrinopathies (11%) and tumor necrosis factor receptor-associated periodic syndrome (TRAPS) (8.5%). As expected, the most common identified mutation among TRAPS patients was p.R92Q (67%). Three patients diagnosed with deficiency of adenosine deaminase 2 (DADA2) were included, all of them with symptoms resembling polyarteritis nodosa. The rest of cohort, 180 patients, were classified as suspected polygenic diseases, including systemic-onset juvenile idiophatic arthritis (34%), periodic fever, aphtous stomatitis, pharyngitis and adenopathy syndrome (PFAPA) (23%), chronic multifocal recurrent osteomyelitis (CMRO) (25.5%), Behçet syndrome (12%) and nonspecific recurrent fever (5.5%). Globally, the most frequent clinical manifestations at onset were fever, cutaneous symptoms, arthritis or arthralgia, lymphadenopathies and abdominalgia. One patient, who was finally diagnosed with chronic infantile neurological, cutaneous, and articular (CINCA) syndrome, showed deafness. Two HIDS patients presented advanced kidney failure due to amyloidosis. 118 patients were still on treatment at the time of the study cut: corticosteroids (46.5%), colchicine (40%), anti IL1 (43%), anti IL6 (23%), anti TNF (23%) and JAK inhibitor in one patient. Conclusion: Autoinflammatory diseases are infrequent diseases. For this reason, registries are necessary in order to gather as many patients as possible, with the aim of improving these diseases description, avoiding misdiagnosis and developing therapy strategies. Introduction: ISG15 is a type I interferon (IFN)-inducible gene, encoding an ubiquitin-like protein which is an effector of IFN-α/βdependent antiviral immunity in mice. Previous reports, based on only 6 reported patients, have suggested that this deficiency does not lead to increased viral infections in humans, but do promote autoinflammation.

Objectives: We present a 6 year old girl, recently diagnosed with this rare disease. We describe the striking presentation of this case, its diagnostic/therapeutic approaches, and clinical outcome. Methods: Medical chart was reviewed.

Results: At the age of six months, the patient showed spontaneous and severe deep and necrotizing ulcerations involving groins, genital area and proximal thighs; with associated fever, increased acute phase reactants, and strabismus corresponding to sequelae of choriorretinitis. After exhaustive study, no infectious/traumatic etiology was found. The biopsy showed necrosis of the epidermis, dermis and upper subcutis and vascular thrombosis in one margin. Despite parenteral antibiotics, surgical debridement and vacuum-assisted wound closure therapy, healing was achieved only after oral steroids treatment. Firstly considered an early onset Behçet disease, etanercept was started with incomplete response, since systemic flares still appeared albeit milder. IL-1 blockade was initiated (anakinra) with persistence of systemic symptoms, and was thus withdrawn. Adalimumab was subsequently started and had to be retired, due to a rapid development of anti-adalimumab antibodies at high levels. The patient had recurrent systemic inflammation flares, becoming steroid-dependent. At the age of 4, a deep and severe necrosis followed by ulceration appeared on her neck, which led to hospital admission for metilprednisolone intravenous pulses. Finally, IL-6 blockade was started with quick and complete response of systemic symptoms. Nevertheless, mild skin flares have appeared twice, being controlled with short courses of oral steroids. In September 2017, a broader genetic study by next generation sequencing (NGS) panel was performed, and two heterozygous mutations affecting ISG15 gene were discovered. After literature review involving 6 patients, skin lesions were interpreted as affecting skin areas specifically above lymphadenopathies. Moreover, the basal ganglia brain calcifications that some of the previously reported patients exhibited led to perform brain CT scan, which demonstrated the presence of striking calcifications. At present, the patient is still on tocilizumab, her growth is normal, and has not presented serious infections.

Conclusion: Data reported so far show that ISG15 deficiency behaves as an autoinflammatory disease but also as an immunodeficiency, due to its involvement in type-I and type-II IFN regulation pathways. Thus, affected individuals exhibit higher IFNα and lower IFNγ responses in comparison with healthy donors. This condition upholds the growing evidence supporting the existence of a "continuum" between autoimmune/autoinflammatory diseases and immunodeficiency conditions. IL-6 blockade has been effective in this single patient, being to our knowledge the only ISG15 deficiency case who has been reported as respondent to tocilizumab. This patient's parents have given their consent for presenting the case to this congress and for further publication. Introduction: Childhood onset gouty tophus is a very rare phenomenon. The conventional pharmacotherapy using for adequate hyperuricemia control and acute gouty arthritis treatment are limited in cases of severe tubulointersitial nephritis. Our experience of single injection of Canakinumab in adolescent patient seems to be very successful. Such experience has not been described earlier in available literature.

Objectives: Presentation of our experience with Canakinumab therapy in an adolescent patient with an early onset severe tophaceous gout and severe chronic kidney disease. Methods: Case report. Conclusion: Canakinumab injection provided rapid reverse of gouty arthritis acute attack, and subsequent achievement of target serum uric acid levels after administration of febuxostat in an adolescent patient with severe tophaceous gout and chronic urate tubulointerstitial nephritis, which limited the allopurinol, NSAIDs and colchicine using. Informed consent to publish had been obtained from the parent. Introduction: TRNT1 is a nuclear gene encoding a ubiquitous enzyme (CCA-adding tRNA nucleotidyl transferase enzyme) necessary for aminoacylation of both mitochondrial and cytosolic tRNA. TRNT1 mutations are associated to heterogeneous phenotypes and multisystem involvement of variable severity and progression. Objectives: to characterize clinical features, laboratory assessment and treatment strategies in 2 patients affected by TRNT1 mutations referred to our pediatric rheumatology unit. Methods: The patient 1 (P1) is a twenty years old female. From the first month of life she experienced recurrent fever associated to painful cutaneous lesions, edema of the hands, raised inflammatory markers and anemia. The symptoms were moderately controlled by corticosteroid therapy. One of these episodes was characterized by severe anemia (Hb 6.6 g/dl), requiring blood transfusion. At the age of 8 months she was found to have mild hypogammaglobulinemia, but no other alterations were found on immunological investigations. She showed normalization of the immunoglobulin levels at the age of 22 months. The physical examination found facial dysmorphisms, brittle hair, developmental delay and microcephaly. Splenomegaly was reported by abdomen ultrasound. Isolated Growth Hormone Deficiency (GHD) was diagnosticated at the age of 3 years and it was treated with recombinant human GH (rhGH) for the next 4 years, without improvement. At the age of 8 years she was diagnosed with bilateral sensorineural hearing loss. At the age of 10 she was diagnosticated with posterior subcapsular cataract, probably related to chronic steroid treatment. The patient 2 (P2) is a ten years old female. From four months of age she suffered from recurrent fever, associated from the age of 11 months to painful cutaneous lesions. Laboratory assessment showed elevated serum inflammatory markers, mild anaemia, hypogammaglobulinemia and reduced levels of B-cells. Growing up, she showed failure to thrive, developmental delay, facial dysmorphisms, brittle, microcephaly, hepato-splenomegaly and swelling of the right ankle. At the age of two she was diagnosticated with sensorineural hearing loss and bilateral cataract. At the age of 5 she started therapy with rhGH for GHD. Results: Suspecting Chronic Infantile Neurologic Cutaneous and articular (CINCA) syndrome,even though negativity of molecular analysis of CIAS1, they started treatment with anti-IL1 (Anakinra) at the age of 9 (P1) and 2 (P2). Due to the partial response, P1 shifted to anti-TNFa therapy (Etanercept) at the age of 11 with significant improvement. P2 showed nonresponse to Anakinra so she shifted to Etanercept after four months. A 13-year-old boy was admitted to our clinic with swelling on jaw and gait disturbance. Past medical history revealed that he was diagnosed with juvenile idiopathic arthritis at two years old in another rheumatology clinic and treated with some anti-inflammatory drugs such as steroid and naproxen. However he could not visit regularly. On physical examination at first presentation he suffered from limitation of mandibular movement and pain of right leg. There was no arthritis. Acute phase markers were higher (C reactive protein: 6.6 mg/dl and erythrocyte sedimentation rate: 74 mm/hour). MR imaging revealed contrast enhancement in the right mandibular and ramus bones, right ramus erosion. It was diagnosed as chronic osteomyelitis in his pathology and tissue culture was negative. Firstly the symptoms were controlled with short-term steroid therapy, then the steroid was gradually reduced and ceased. Meanwhile, methotrexate 15 mg / m2 /week was started. Since there was no response, etanercept 50 mg / week was commenced at third month. Although etanercept was administered for 6 months and no response was obtained, biologic treatment was switched to adalimumab (40 mg every two weeks). Significant clinical improvement was seen after a months of the adalimumab treatment and high acute phase markers decreased within six months (C reactive protein:0.22 mg/dl and erythrocyte sedimentation rate:38 mm/hour). He has no complaints for 10 months. Case 2:

A 18-year-old boy presented with a swollen and painful right posterior leg following a minor trauma. Ten years ago he was admitted to another center with this the same complaint and biopsy was performed since it was presumed osteosarcoma. The pathology was found to be compatible with chronic osteomyelitis and also tissue culture was negative. He did not visit regularly the polyclinic like his brother, and he had complaints as irregular consume of steroid and sulfasalazine drug treatment for a long time. On physical examination, right femur and tibia sensitivities were observed. Acute phase reactants were high (C reactive protein: 4.1 mg/dl and erythrocyte sedimentation rate: 80 mm/hour). The whole body MR detected chronic multifocal osteomyelitis in the region extending from the right femur and proximal tibia shafts to the distal metaphyseal region. Methotrexate 15 mg / m2 / week and adalimumab 40 mg / 2 weeks was commenced. The clinical response was complete at 3 months of treatment and acute phase reactants decreased within 9 months of treatment (C reactive protein:0.02 mg/dl and erythrocyte sedimentation rate:27 mm/hour). The genetic screening of patients was planned. Informed consent to publish had been obtained from the patient. Conclusion: CRMO treatment should be individualized. Therapy choice can be variable such as only nonsteroidal anti-inflammatory drugs or steroid or anti-TNF therapy. These CRMO brothers thought to us that there is a strongly probable genetic basis in the etiology of the disease. Introduction: Although familial Mediterranean fever (FMF) is the most common autoinflammatory disease in the world, many problems of FMF management are not standardised for optimal disease control and follow-up. A standardised assessment of disease severity is required for therapeutic decisions in managing patients with FMF. There are several severity scoring systems for FMF. Because there is no consensus on any of them and they were not consistent with each other, an international group of FMF experts developed and initially validated a new severity scoring system for FMF, which was called "international severity scoring system for FMF" (ISSF). It is an easily applicable and widely acceptable scoring system for research and clinical practice. Objectives: To evaluate the disease severity scores of our patients by using ISSF and compare them with literature data. Methods: The patients who were diagnosed as FMF according to the Tel-Hashomer criteria and being followed at Department of Rheumatology in Behçet Uz Children's Hospital for at least 6 months were consecutively enrolled in this cross-sectional study. Demographic data, FMF symptoms, MEFV mutation, disease duration, time to delay for diagnosis, duration of follow-up, duration of attacks, and disease severity score were recorded for each patient. Patients were classified as mild, moderate and severe according to ISSF. The study protocol was approved by the local ethical committee. Results: A total of 160 patients (88 females and 72 males) were enrolled. The mean age of the patients was 12 ± 4.3 years. Thirty four (%21.3) patients have mild, 113 (%70.5) patients moderate, 13(% 8.2) patients have severe score according to ISSF. The most frequently identified mutations in our study population were M694V (%54.3) and E148Q (%18). Homozygous patients (M694V, M694I, M680I, and V726A) had more severe disease. The disease severity score was positively correlated with the duration and dose of colchicine. There was not a significant correlation between age at disease onset and ISSF scores. When the patients were evaluated according to the age groups, the duration of the attack was shorter in older patients (p< 0.05). Besides, different organ involvement during attacks was higher in patients older than 7 years. Conclusion: The compatibility of the data obtained from our study with the literature in general indicates that ISSF is a suitable tool for assessing disease severity. Furthermore, the results of this study suggests that addition of "existence of some pathological MEFV mutations" as a criterion of ISSF may be useful. Introduction: In a recent series of 486 cases of Chronic Nonbacterial Osteomyelitis (CNO) from the Eurofever international registry, association between psoriasis and CNO was observed in 4% of the patients. The tumor necrosis factor-alpha (TNF-α) inhibitors drugs are increasingly used in treating psoriasis. In the Consensus Treatment Plans for Chronic Non-bacterial Osteomyelitis anti-TNF-αare also a therapeutic option for patients with refractory CNO. Based on these considerations we decided to treat 3 patients with CNO and psoriasis with etanercept but we observed a worsening of skin involvement. Objectives: To report the worsening of psoriasis in patients with CNO in relation to use of etanercept. Methods: Children with diagnosis of CNO associated with psoriasis and treated with etanercept were included. Subsequent response to this therapy was recorded. Results: Pt1: caucasian female with diagnosis, at age of 10 years, of CNO (long bones and vertebral lesions) and psoriasis (scalp and left plantar). Due to clinical and radiological worsening of bone involvement after non-steroidal anti-inflammatory drugs (NSAIDs) and 2 cycles of pamidronate (1 mg/kg/day for 3 consecutive days every 3 months), we decided to start etanercept. After 3 months of therapy psoriasis got significantly worse. We discontinued etanercept with initial improvement of skin lesions. Pt2: 17 year-old caucasian female with CNO (long bones, vertebral and pelvic lesions) and psoriasis (scalp and plaque psoriasis on the legs) treated at the onset of the disease with IV cycles of pamidronate and sulfasalazine. Despite an initial and persistent good response, after 2 years of treatment with sulfasalazine the patient showed clear evidence of lack response. We started etanercept and we observed, after 3 months of therapy, an improvement of clinical and radiological bones involvement but a worsening of psoriasis. The patient refused to discontinue etanercept. After 6 months of therapy she had persistent remission of CNO and stable skin lesions. Pt3: caucasian female with diagnosis, at age of 8 years, of CNO (vertebral, pelvic and long bones lesions) and psoriasis (scalp and periauricular lesions). Due to D6 and D9 vertebral wedge deformities patient was treated with glucocorticoids and pamidronate. After 3 months she had a persistent polyarthralgia associated with radiological increase in the number of bone lesions. We started etanercept and we complete pamidronate cycles (a total of 4 cycles). She had good clinical response without pain or functional impairment and with decrease of bone lesions. After starting etanercept we observed a severe exacerbation of psoriasis with increase in the number of skin lesions (scalp, plaque on the legs and nails). After 6 months of therapy we decided to discontinue etanercept. At the last follow up visit, 2 months later, skin and bone lesions were stable. Conclusion: We report three cases of CNO and psoriasis treated with etanercept with worsening of skin lesions. It is unclear the mechanism that leads to exacerbation of previous psoriasis during the course of treatment with etanercept. Further studies with a larger number of patients are needed to clarify this mechanism and the management of the patients. Should be discontinued etanercept, switched to another anti-TNF-α or combined with another systemic treatment such as methotrexate or cyclosporine? Informed consent to publish had been obtained from the parents. Objectives: We describe our brief experience with the second family with a child afflicted with Majeed syndrome from India. Methods: A 3 year old male child born of a consanguineous marriage, presented with recurrent irregular episodes of fever with irritability and failure to thrive since 5 months of age . At 9 months of age parents noticed, small skin 'boils' over the trunk and limbs, which recurred every 15-20 days along with the fever and stayed for 4-5 days. At 18 months, parents noticed that he refused to bear weight and walk and would cry on handling. Gradually the episodes of painful small skin boils, limb pains which the parents could not localize and fever increased in frequency and after multiple pediatric, orthopaedic consults he was referred to us by a pediatric neurologist who had been referred the case to rule out Fabry disease. The pediatric neurologist had asked for whole exome sequencing and referred the case to us for clinical evaluation sensing a musculoskeletal rather than neurological disease. Results: On examination the weight (10 kg) and height (83 cm) were below 3 rd centile. He had pallor, painful swelling over the left tibia, motor delay with hamstring tightness and mild bilateral knee contractures. Language and social milestones were normal. There were no skin lesions at the time of evaluation and systemic examination was normal. Review of his past investigations revealed a persistent, microcytic hypochromic anemia (Hemoglobin 8.3-10.6 gm/dl) with raised erythrocyte sedimentation rate (54-105 mm/hr), C-reactive protein (37-98 mg/l) and platelets (4.3-8.9 x10 3 cu mm). His genetic mutation for LPIN 2 returned positive with homozygous missense variation in exon 17 of the LPIN2 gene resulting in amino acid substitution of cysteine to arginine at codon 736 (p.Arg736Cys;ENST00000261596). Meanwhile a bone scintigraphy done, showed increased vascularity and osseous activity in proximal shaft of left tibia with mild osseous activity at D9 and D10 vertebrae. A bone marrow examination was not performed as a conclusive mutation diagnosis was obtained. He showed a dramatic response to Ibuprofen with abatement of fever, no skin boils and improvement of general mood and playfulness. With a view to attempt to omit NSAIDs intravenous Pamidronate was commenced. After the first course at 10 weeks follow up, he has gained weight (11kg), is afebrile, walks with support with no new skin lesions. Conclusion: Paucity of awareness amongst the medical community about these rare illnesses are responsible for diagnostic delays and complex referral pathways. With the high rates of consanguinity in several parts of our country we believe that we are seeing just the tip of the iceberg of monogenic autoinflammatory diseases. Due to non availability of Interleukin-1 inhibitors in India, which are highly effective at controlling osseous and systemic inflammation in Majeed syndrome, we have limited treatment options to offer to our patient. We have offered educational resource and genetic counselling to the family. Written informed consent was obtained from the patients for publication.

Introduction: PFAPA is an autoinflammatory disease characterized by recurrent febrile episodes with associated symptoms from the mouth and throat, with a typical onset before 5 years of age. Tonsillectomy has been shown to be curative in a majority of patients, but remains debated as PFAPA is self-limiting and usually resolves spontaneously before adulthood. However, the consequences of the recurring fevers in terms of health-related quality of life and family impact have not been previously studied. Objectives: The aim of this pilot study was to investigate healthrelated quality of life in children with PFAPA and the impact of the disease on their families before and after tonsillectomy. Methods: Children with typical PFAPA referred for tonsillectomy in our clinics were enrolled consecutively. Parents to these patients answered PedsQL™ 4.0 GCS to measure health-related quality of life during fever episodes, between episodes and six months after tonsillectomy. Family impact of PFAPA was measured by PedsQL™ FIM filled in by the parents before and six months after tonsillectomy. Parents were also asked to keep a diary of fever episodes during the study period. The PedsQL™ scales were scored according to The PedsQL™ Scoring Algorithm, were items are reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicate better outcome. The total scale score for each patient was obtained by computing the mean of all items on the scale. Results: In this pilot, six patients and their parents have completed the study. The patients had a median of 7,5 episodes (range 5-9) during the six months prior to tonsillectomy. After tonsillectomy, all patients were free of symptoms during the six months of follow-up. Total scale scores on PedsQL™ 4.0 GCS were low during fever episodes with a median of 51,1 (range 43,5-55,4) and improved markedly between episodes to a median of 88,1 (range 67,4-96,6) and after tonsillectomy to a median of 93,9 (range 82,6-99). This also showed a tendency to lower scores between fever episodes before tonsillectomy compared to after tonsillectomy, although no further statistical analysis was made due to the low number of patients. Total scale scores on PedsQL™ FIM had a median of 61,5 (range 42,4-74,3) before tonsillectomy and improved to a median of 93,8 (range 52,1-100) after tonsillectomy. One family stood out with a low and unchanged score on the family impact module after tonsillectomy. In this family, a younger sibling of the patient was diagnosed with PFAPA during the study period. Conclusion: Even though PFAPA syndrome is a benign disease with a good long-term prognosis, this small pilot study indicates that it has considerable negative impact on the child affected by the disease and the entire family. Tonsillectomy may be beneficial as ceasing of the fever episodes improves the wellbeing of the child and the family. There is a plan to continue this study with inclusion of a greater number of patients.

Introduction: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease characterized by sterile bone inflammation. It is an orphan disease with many unclear aspects in diagnosis, treatment and follow-up. Objectives: The aim of this study is to report our experiences of pediatric CRMO patients, as a tertiary pediatric rheumatology center, regarding clinical and laboratory findings, treatments, disease activity and treatment responses. Methods: Children who were diagnosed with chronic recurrent multifocal osteomyelitis (CRMO), and were followed-up in the Pediatric Rheumatology Unit of Hacettepe University between January 2008 and January 2017, were included in this study. Clinical characteristics and laboratory findings (including radiological and pathological evaluation) were reviewed from medical charts and electronic files of the patients. In addition, treatments, treatment responses and disease activity were documented retrospectively. Results: There were 15 CRMO patients (8M/7F) with a median age at diagnosis of 10.5 yrs. Bone pain was the most common presenting symptom. All of the patients had multifocal bone lesions. Vertebra (66%) and femur (66%) were the most commonly affected bones. 8 of the patients also had sacroiliitis however only one of them was HLA-B27 positive. Whole-body MRI used as a diagnostic tool in 13 patients revealing bone marrow edema (84.6%), osteitis (69.2%) and periosteal reaction (61.5%). Bone biopsy was performed in 6 patients showing sterile osteomyelitis with mixed inflammatory infiltration and sclerosis. All patients were initially treated with NSAIDs, however DMARDs, anti-TNF agents or pamidronate were added to therapy due to inadequate treatment response. Clinical remission was achieved in 12 patients (1 with NSAID, 3 with methotrexate, 1 with pamidronate and 7 with an anti-TNF agent). During the follow-up period, relapses were observed in four patients presented with pain and/or a newly formed bone lesion on MRI. However, finally all of these patients also reached remission. Three patients continued to have clinical and radiologic active disease despite anti-TNF treatment in two patients and pamidronate in one patient. Conclusion: CRMO is a chronic disease which may have a progressive or relapsing-remitting course. NSAIDs and anti-TNF drugs are the most efficacious treatment, however pamidronate may also be used for refractory cases. Although there is no consensus on follow-up parameters, WB-MRI is a very useful tool to show active disease even the patient is in clinical remission. Improvement of the knowledge about this rare disease may help to enlighten the unknowns of the disease. The study included 25 patients with CAPS (17 children, 8 adults), there were 11 males and 14 females. A total of 22 pts were diagnosed with MWS and 3 pts had CINCA/NOMID. The aged of pts were from 6 months up to 57 years, the duration of the disease was from 1 month up to 44 years. Fever was noted in all patients, skin rashes in 92%, eye symptoms in 52%, sensorineural hearing loss in one third of patients, arthralgia/arthritis in 60%, neurological disorders in 40%. All patients except one (with CINCA/NOMID) showed mutations in the gene NLRP3, all in heterozygous state. The mutations were p.T348M in 7 pts, Q703K in 13, V198M in 4, other mutations in 6. 11 out of 25 pts received canakinumab (Il-1 inhibitor) for 1 -5 years. The complete response to therapy was received in 9, partial response-in 2 pts previously treated by anakinra. There were no major adverse events (AE) or serious AE (SAE). Conclusion: Despite the rarity, the patients with CAPS are found in the practice of pediatric rheumatologist. Canakinumab is very effective and save treatment for CAPS pts. But the final diagnosis and appointment of therapy should be carried out with the participation of experts in the field of AID. Introduction: Sweet Syndrome (Acute Febrile Neutrophilic Dermatosis) is an uncommon disease, extremely rare in children, where it accounts 5% -8% of all cases. The clinical suspicion is usually confirmed by the presence of a diffuse infiltrate of mature neutrophils in the upper dermis at biopsy. On the bases of recent researches that suggest an aberrant hyperproduction of interleukin-1 in the pathogenesis of this dermatosis, Anakinra, human interleukin 1 receptor antagonist protein, has been used with success in some adults. Objectives: We report our experience with Canakinumab (human anti-IL-1β monoclonal antibody) in a paediatric case of Sweet Syndrome. Methods: A five-years old male was admitted to our hospital for an abrupt onset of fever, multiple, indurated painful red papules, and plaques, associated with increased values of CRP, and ESR and neutrophilia. On histopathological examination, neutrophilic and lymphohistiocytic infiltrate and edema were observed. Results: On the basis of anamnestic, clinical, hystophtologic data and laboratory tests the diagnosis of Sweet's Syndrome was made and prednisone was started. Despite a clear cutanous improvement, lesions apperared to flear at each attempted steroid withdrawal. Anakinra was than introduced with a gradual good response. Because of the scarce compliance due to the inconvenience of daily injections, three months later, Anakinra was switched to Canakinumab (1 injection every 28 days). At a 4-months follow-up visit the patient's cutaneous lesions were nearly resolved with minimal intervention. Conclusion: To our knowledge, this is the first report of anti-IL-1β monoclonal antibody treatment in Sweet syndrome. In our experience Canakinumab proved to be safe and effective. Informed consent had been obtained from the parent. Introduction: Recurrent pericarditis (RP) is a common complication of acute pericarditis (15-30%). Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) with colchicine with the addition of corticosteroids in resistant or intolerant cases. Anakinra is a therapeutic option as steroid-sparing agent. Anakinra neutralises the biologic activity of interleukin-1α (IL-1α) and interleukin-1β (IL-1β) by inhibiting their binding to IL-1 type I receptor, while Canakinumab is a monoclonal antibody against IL-1β only. Objectives: To describe two cases of refractory recurrent pericarditis with a divergent response to two different IL-1 blockers. Methods: The first patient is a 8-years old girl with recurrent pericarditis started in April 2015 (6 years old), after surgical correction of an atrial septal defect. NSAIDs and oral steroids were started and then gradually tapered, with prompt relapse after the steroid suspension requiring a pericardiocentesis. The child showed a steroid-dependent recurrent pericarditis, with several relapses if tapering was attempted and no benefit from colchicine and NSAIDs. After five relapses Anakinra was started with a fast and complete clinical response, but discontinued after 2 weeks for severe local injection reactions. She was firstly evaluated in our Centre in April 2016 and in July 2016 therapy with canakinumab 150 mg (approximately 4 mg/kg) every 4 weeks was started, together with steroids (then gradually tapered) and NSAIDs. The second patient is a 10-years-old girl with a history of idiopathic recurrent pericarditis, started in April 2017 with typical clinical picture, need of an urgent pericardiocentesis at onset and initial benefit from NSAIDs and colchicine. However, ten days after the first episode a relapse occurred and therapy with anakinra was established with dramatic and complete clinical response. Two months later, while being in complete remission, anakinra was replaced with canakinumab (2.5 mg/kg/dose) due to patient's poor compliance to daily injections. Results: Patient 1: She experienced four relapses during Canakinumab therapy (July 2016 -December 2017), despite the modification of the schedule (4 mg/kg every three weeks) associated with the reintroduction of colchicine since April 2017 and continuous steroid treatment with repeated flares at every attempt of tapering. In January 2018 a procedure of desensitization from anakinra was performed, with success. Anakinra therapy is currently ongoing (12 weeks follow up), in association with low-dose colchicine. An almost complete withdrawn of steroid is currently undergoing with no signs of flare. Patients 2:Ten days after the first Canakinumab injection she experienced a relapse requiring oral steroids. Anakinra (2 mg/kg/day) was subsequently re-started allowing steroid tapering in few days. The patient showed complete remission in anakinra as monotherapy with a good tolerance. After further 6 months follow-up under anakinra, the patient did not show any clinical, laboratory or echocardiographic signs of relapse. Conclusion: We describe two cases of substantial failure of the treatment with anti-IL-1b monoclonal antibodies treatment in steroiddependent idiopathic RP. In both case a good response to the treatment with recombinant IL-1 receptor antagonist was achieved. These anecdotal and preliminary observations suggest a different efficacy of the two IL-1 blockers in the management of recurrent pericarditis and support a possible pivotal role of IL-1α in the pathogenesis of this condition. Informed consent to publish had been obtained from the parents. Introduction: PAPA syndrome (Pyogenic arthritis, Acne and Pyoderma gangrenosum) is a rare autosomal dominant autoinflammatory disorder. To our knowledge it has not been described in Bulgarian patients before.

Objectives: To describe the phenotype of five family members with PAPA syndrome from Bulgaria; to report one novel mutation of exon 11 of the PSTPIP1 gene, and a second one not previously associated with PAPA syndrome, and to share our experience with different treatments. Methods: We present five family members from three generations. The children have recurrent pyogenic arthritis, one with Pyoderma gangrenosum as well. Their father and paternal grandmother have suffered similar, although less frequent, episodes as children, developed severe acne as adolescents and started suffering from Pyoderma gangrenosum as adults. Genetic tests confirmed mutations in exon 11 of the PSTPIP1 gene. One (c.766C>A) had been previously described in patients with hyperzincemia and hypercalprotectinaemia, but not in PAPA syndrome, the second was a novel mutation, c.766C>A. Results: We established earlier onset of arthritis in subsequent generations (the youngest of our patients had his first episode at 7 months of age). Pyoderma gangrenosum which usually appears in adulthood started at the age of 4 years in the same patient. Intraarticular steroids provided mixed results. Treatment with Salazopirine in one patient with active arthritis, and with Resochin in another was unsuccessful. Oral steroid therapy for Pyoderma gangrenosum had variable, but mostly unsatisfactory results. Conclusion: We report 2 mutations in the PSTPIP1 geneone novel and one not previously associated with PAPA syndrome. Treatment with some of the standard DMARDs, used in JIA, does not seem to be effective. Informed consent to publish had been obtained from the parents and patients. Introduction: Diffuse sclerosing osteomyelitis of the manidble (DSMO) is a unifocal form of chronic non-bacterial osteitis (CNO) and predominantly affects patients < 18 years. Intravenous pamidronate (IV-PAM) has been reported to be effective in multifocal CNO in short term.

Objectives: To describe a long-term clinical and radiologic outcome of a DSMO patient following treatment with IV-PAM. Methods: A 4-year old Caucasian female was diagnosed with DSMO and prospectively followed from 2007-2017. She presented with a 20-month history of facial asymmetry and painful bony expansion of the left hemimandible. Imaging (radiographs, CT) showed an expansile lesion with radiolucency, some ground-glass appearance, periosteal reaction and soft-tissue swelling. Infectious osteomyelitis was ruled out, due to negative blood cultures and inefficacy of IV and oral antibiotics. Fibrous dysplasia was then considered. She remained symptomatic despite ibuprofen (10 mg/kg/dose 4 times daily) and a jaw replacement surgery was planned due to progressive symptoms. Bone biopsy was performed and histopathology demonstrated paucity of the spindle cells characteristic to fibrous dysplasia, and revealed multiple osteoblasts and inflammatory plasma cells. Whole-body MRI confirmed an isolated lesion in the left hemimandible with soft tissue edema and the diagnosis of DSOM was made at age 4 years. She was referred to rheumatology after failing NSAIDs and analgesics. Examination revealed marked swelling to the left mandibular area. Laboratory investigations showed elevated erythrocyte sedimentation rate [28mm/hr (normal <10 mm/hr)] and platelet count [606 10 9 /L (normal 150-400 10 9 /L)]. C-reactive protein was normal. She was started on monthly 1-day IV-PAM infusions (1st dose 0.5mg/kg; each subsequent dose: 1mg/ kg). The response to treatment was assessed according to visual analogue score for pain (VAS, 0=no pain; 10=maximum pain), sequential MRIs and clinical photos. Results: She received 8 monthly IV-PAM infusions. The base-line VAS was "10", which decreased to "0" after the first infusion and VAS remained "0" throughout the remainder of treatment. MRI documented resolution of abnormal signal at 5 months with gradual mandibular remodeling and sustained improvement at 12 months. Clinical photographs documented the gradual improvement of facial symmetry and improved affect, which was sustained during follow-up. She had no side effects to IV-PAM apart from nausea following the first infusion. She had three MRI confirmed flares at 22, 67 and at 120 months at the identical site with pain and decreased mouth opening. Her pain VAS ranged from 4-6/10 during flares. Each flare responded to Naproxen monotherapy both clinically and by MRI and she required no further IV-PAM. She required dental braces at age 10-years. She remains asymptomatic at 120 month follow-up with excellent functional and cosmetic outcome. Conclusion: DSMO is challenging to diagnose and treat due to its rareness and lack of uniformly effective treatment. IV-PAM was effective in this young refractory patient in resolution of pain, mandibular remodeling and cosmetic improvement that was sustained during longtermfollow-up. We recommend a bone biopsy of mandibular CNO/ DSMO to help confirm the diagnosis to differentiate it from fibrous dysplasia of the jaw. Informed consent to publish had been obtained. Introduction: A type I interferonopathy due to DNase II deficiency has ben recently described in three cases with multi-organ diseases. Objectives: To describe the case of an italian 14-year-old girl with a complex clinical phenotype in which an autoinflammatory disease was suspected and a new deleterious heterozygous DNase II mutation was found. Methods: The most meaningful clinical aspects of our patient are: severe hemolytic anemia detected at six weeks of age, requiring red blood cell transfusions and finally resolved at three years of age cholestatic hepatitis beginning at age 8 months; markers of cholestasis normalized at age 2 years but she developed an inactive liver cirrhosis with stable hepatosplenomegaly and mild thrombocytopenia failure to thrive and recurrent hypoglycemia with need of enteral feeding till age of 6 years antibody-negative insulin dependent diabetes mellitus with onset at 10 years of age normal early psychomotor development with subsequent learning difficulties at school. Brain MRI at age 11 showed multiple alterations of signal intensity in the subcortical and periventricular white matter recurrent episodes of enteritis and keratitis normal erythrocyte sedimentation rate and C-reactive protein with fluctuating hypergammaglobulinemia and antinuclear antibodies Results: The major classes of inborn errors of metabolism, cirrhosis and autoimmune diseases were investigated and ruled out. The peculiar clinical picture put together signs that taken overall can be reminiscent of a rare DNAse II deficiency. In particular, early onset and self-healing anemia and cholestatic hepatopathy, subcortical white matter dystrophy, non-autoimmune insulin dependent diabetes and hypergammaglobulinemia are all described in the recent report about DNAse II deficiency. Moreover, we describe an increased interferon signature and thus decided to sequence DNAse II gene. The analysis revealed a heterozygous mutation (c.621delC deletion on the exon five) predicted to be deleterious. However, the same deletion was found in patient's father, prompting us to perform whole-exome sequencing in the search for other genetic anomalies. So far, the analysis didn't held any definite explanation for the disease. Conclusion: Several evidence support a role for the mutation in DNAse II in the disease of the patient but other yet unknown genetic and environmental factors have to be investigated. Informed consent to publish had been obtained. bone lytic lesions. Symptoms include pain, local swelling and warmth. CNO mainly affects the metaphyses of the long bones, the pelvis, shoulder girdle and, less commonly, the spine and the mandible. Only four cases of CNO involving the cranium have been reported so far [1] Objectives: To describe the prevalence and the clinical manifestations of CNO patients with neurocranium involvement among an Italian cohort of CNO patients. Methods: This is a retrospective study. Charts of patients with CNO admitted to eight Pediatric Rheumatology centres were reviewed. Data collection included patient and family history, age at diagnosis, sex, number and location of bone lesions at onset, diagnostic imaging, laboratory data at presentation and at last visit, histological findings, comorbidity and response to treatments. Results: Eighty-six patients were enrolled in the study. 31 were males and 55 were females. The mean age at diagnosis was 9.4 years (SD ± 3.3). Only 11 patients presented a monofocal involvement while 75 patients presented a multifocal disease at onset. 3 out of 86 patients (3.5%) presented a cranial involvement at onset. These three patients were females; the age of presentation was 2 years old for one patient and 12 for the last two. All of them presented multifocal lesions at onset (12, 20 and 13 lesions respectively) but none of them complained clinical symptoms attributable to skull involvement (headache, vomiting, visual impairment, focal neurological involvement, etc). Cranial involvement were detected only with bone scintigraphy and then confirmed by magnetic resonance imaging and/or computed tomography. 2 patients presented fever and two skin manifestations. Laboratory inflammatory indeces were increased in two patients. All underwent bone biopsy in another bone site confirming the diagnosis. All patients received NSAIDs, without response. Two patients received corticosteroid and then methotrexate reaching clinical remission. One patient received pamidronate without benefit and she still presents an active disease at the end of follow-up. Conclusion: This is the first report of cranial involvement in a cohort of patients affected by CNO. Cranial involvement confirms to be a rare localisation and it seems to be associated with multifocal involvement. In our cohort, in contrast with the 4 patients reported in literature, all patients were asymptomatic. In case of cranial involvement radiological control may be needed during follow-up. Introduction: Blau syndrome is a rare granulomatous autoinflammatory disorder. Optimal response to anti-TNFa treatment has been reported, however therapeutic outcomes are diverse probably due to functional differences in NOD2 mutations.

Objectives: To report the clinical picture of Blau syndrome in a patient carrying 2 NOD2 variants and the response to anti-TNFa treatment with adalimumab. Methods: Case Report.

Results: A 19 month old girl was referred to the pediatric rheumatology department from the dermatology department for an 8-month history of generalized ichthyasiform skin eruption. The rash appeared on the age of 11 months on the shoulders and then spread to the knees trunk and face. Multiple coalescing generalized slightly scaly red to violaceous flat- 16-15 ) years and was statistically higher than the control group (p<0.05). There were no statistically significant differences in age at diagnosis, delay at diagnosis and family history between two groups. The mean platelet volume (MPV) and neutrophil / lymphocyte ratio (NLR) values reflecting subclinical inflammation in attack-free period also did not differ statistically between the two groups. The groups did not differ in having either M694V or exon 10 mutations. Patients with only arthritis did not have proteinuria, colchicine unresponsiveness and indication for biologics. (Table 1) . Of these, 45 (63%) started a biosimilar as their first biologic therapy. Seven (10%) patients switched from their originator. The median (IQR) time on originator before switch was 1.6 (0.7-4.1) years. Nineteen (27%) switched to an infliximab biosimilar from a non-originator biologic with 12 switching for efficacy reasons and 7 for safety reasons. The majority (n=14) switched from adalimumab. Active uveitis was present in 10 patients at the point of starting a biosimilar. Follow-up data out to 2 years were available in 26 patients. Seven patients switched to another biologic in this period: four infliximab biosimilar patients switched to tocilizumab and 2 infliximab biosimilar patients switched to adalimumab. One patient switched back from etanercept biosimilar to originator due to increased pain. Infliximab biosimilars were interchanged in 6 patients due to changes in hospital procurement. No serious adverse events were reported. Two cases of recurrent uveitis in patients on an infliximab biosimilar switching from a non-originator biologic were noted. Conclusion: Biosimilars in children and young people with JIA are being used as both first-line and subsequent-line biologic therapy. Currently few UK children have been switched directly from an originator product. Whether a move towards switching all children receiving originator products to biosimilar products, as has been seen in rheumatoid arthritis, will occur is currently unknown but it is imperative that the safety of these treatment decisions are captured in patient registers. 2)), macrophage activation syndrome )12 (0.2)), malignancies (8(0.1)) and pregnancies (8(0.1)). There were marked differences in the rate of AESI in the cohorts with different biologics. Uveitis reports were most common in TNF-antibody treated cohorts, infections upon GOL, TOC and ANA, cytopenias upon TOC and CAN, hepatic events upon TOC, anaphylaxis upon INF and TOC, CED upon ETA and INF (Table 1) . One case of latent TB but no further opportunistic infections were reported. There was a single death upon treatment due to sepsis in a ETA patient.

Conclusion: Surveillance of pharmacotherapy as provided by BIKER is an import approach especially in the case of long term treatment of children. These data provide support for the long- 

Active uveitis at start of therapy 0 (0%) 10 (56%) 1 (17%)

term and comparative safety of biologics in JIA pts. Overall, tolerance is acceptable. Differences between several biologics were noted and should be considered in daily patient care. Introduction: "Tutti alla pari" is a project made by Apmar Onlus. From the analysis of family and kids needs, it comes out that it's difficult for a kid to feel himself involved in the society system. It is not rare that the kid with a rheumatic disease is socially excluded and sometimes bullied. Involve kids with disabilities is a challenge that can be won focusing on competence and collaboration. Differences must be accepted at school first by the activation of inclusive paths. Objectives: Developing an empowerment path, starting from young people, to build up a most respectful and inclusive society; defining a common strategy to fight social exclusion of people with chronic diseases, especially children.

Methods: Create a participative process and an active involvement of social and institutional actors that take care of border risking minors. It involved pediatricians, parents, formers and journalists, through punctual, sensitizing and informative actions. 15 communication experts, 20 pediatricians, 18 formers and 25 parents took part in 3 participative labs. After those workshops a handbook that collects the "best practices for social inclusion" was realized and It was spread in 20 school and in 25 regional associations of patients with chronic and rare pathologies. The identified method aims to create a participative process and an active involvement of all social and institutional actors, that take care of border risking minors. It' s been involved paediatricians, parents, formers and journalists, through punctual, sensitizing and informative actions. 15 communication experts, 20 paediatricians, 18 formers and 25 parents have been involved in 3 participative labs. Their participation gave birth to the realization of a handbook that collects the "best practices for social inclusion", that was spreaded in 20 school and in 25 regional associations of patients with chronic an Results: Involving the youngest: experience labs organized in 16 schools through which kids could put themselves in a peer with rheumatoid arthritis' shoes. By wearing gloves and special suits they experienced all the functional limitations of the disease. The action had important feedbacks, collected in written witnesses and videos elaborated by kids. Introduction: Through their lifetime, young people with chronic conditions will experience a transition from pediatric care to adult care facilities; this is an important period for the patients since now they will have to take care of themselves.

The main goal of transition is to maximize lifelong functioning through the provision of high-quality, developmentally appropriate healthcare services that continue uninterrupted as the individual moves from adolescence to adulthood. In pediatric clinics, care is provided to patients accompanied by their tutors; therefore, the sense of preparation for independence varies between one part and the other. To our knowledge, there are no reports that identified differences in self-care skills between patients and caregivers, and no information on variables that could influence on that perception has been To compare the perception of self-care skills for transition between adolescents and their caregivers and analyze clinical, familiar and socioeconomic factors that could influence on that perception. Methods: Between January and April 2018 we included patients with rheumatic diseases that were diagnosed during childhood (under 16 years old) and at the time of their participation were between 12 and 22 years old. We excluded patients with more than one condition, neurological disabilities, or refuse to participate (patient or tutor Most of them were female (70%), median age 17 (12 -21) years, and juvenile idiopathic arthritis (JIA) as the most prevalent disease (48%). A high part of our patients was classified as low and median low income families and a few proportion of the parents have superior education. Among transitions questionaires, "Need to change to adult centered care" was answered with a median of 9 (5 -10) by caregivers, that was similar to answer by patient (9, 1 -10, P = 0.42). On "Perception of capability of adult-centered health care", the answers were also similar (9 vs 8). Despite this, other specific areas of "disease knowledge" and "use of health-care services knowledge" were overestimated by caregivers when compared with patients. No differences were seen when results by disease were analyzed. Conclusion: Both patients and tutors are aware of the importance of a adequate transition preparation, also both have the same perception of preparedness of the patient. Both sides think they aren't prepared enough for self care in emergency situations and the use of medications by themselves. Based on the results of this questionnaire we should focus our efforts in educating patients on how to react on an emergency situations as well as the self administration of the medications they use on their daily life. Good relationship fostered by the secondary hospital paediatricians was identified as the biggest driver. Other drivers were, electronic platform for note keeping, communication via certain social media applications and gained knowledge of system and disease by an intern first working in a secondary hospital prior working in a peripheral hospital. Barriers were the healthcare providers own perceived limitation and exposure/knowledge to MSK diseases, poor history given by the person accompanying the patient, limitations in after hour investigations, unpredictable availability of ambulance services and socioeconomic factors of the patient population. Conclusion: The focus groups identified barriers and drivers that play a role in whether children and adolescents presenting with MSK symptoms receive the "right care, delivered at the right time, by the right team, in the right place, with the right resources" these insights will direct further investigation into the drivers and barriers in the other districts of South Africa and other LMICs. The results could give direction in developing policies and Models of Care to improve MSK care outcomes for children and adolescents. Introduction: Chronic pain disorder is a common and underrecognized problem who is increasing in the pediatric population.Osteoarticular pain is one of the most common symptoms.This is a significant problem leading to a decrease in quality of life,school absenteeism and social withdrawal.A multidisciplinary approach is essential to evaluate and manage those patients whom have an unsatisfactory evolution despite primary medical care.Starting In 2014,a group of 4 medical specialists(pediatric rheumatologist, pediatric orthopedist, child psychiatrist and pediatrician specialist in adolescent)and one physiotherapist started a joint outpatient clinic assessing such children.

Objectives: The aim of this study was to describe and outline some characteristics of all patients seen at this platform up to now.

Methods: A retrospective descriptive study was performed based on medical records of patients seen at our center in Lausanne between November 2014 and January 2018.Epidemiological,clinical and therapeutic data was collected and analyzed accordingly.

Results: A total of 35 patients were reviewed.The patients were in most cases(82%)referred by the pediatric rheumatologic or orthopedic surgeon.The sex ratio F/H was 3.3 (27 girls for 8 boys).The average age at the time of consultation was 12.8 years(9 to 18 years).A triggering event was found in 48% of our patients with the notion of trauma in 35% of these cases.The average duration of symptoms was 3.6 years prior to referral to the platform (1-11 years).Chronic pain affected more than 5 joints in 75% of the cases.School absenteeism was noted in 22% of the children with 2 cases of withdrawal.The platform revealed in 52% a primary paindisorder,in 28% an associated orthopedic problem,in 25% a difficult psychosocial situation and in 5% a rheumatologic problem.Therapeutic proposals were mainly personalized physiotherapy or mind body approaches such as hypnoses and depending on the findings,follow-up in orthopedics,rheumatology,child psychiatry or adolescent specialist consultation. Conclusion: A long delay before children with chronic pain reach the platform was noticed.This could explain the severity of the presentation and the significant impact on school attendance and social life.-The integrative clinical approach highlighted the multifactorial aspects of chronic pain and led to the development of an adapted multidimensional treatment to improve the prognosis and reduce the negative impact of chronic pain.We encourage pediatricians to detect and refer such patients early. To inform and prepare them for the transition from the children's hospital to adult medicine. Here they will be expected to take a more independent and active part in their treatment. Methods: 1) More focus was given in the pediatric consultations about living with JIA and going to consultations as an adult. This was begun well in advance before the actual transition.

2) The patients were guided to the location of the adult department of Rheumatology and welcomed by a nurse there at the end of their last pediatric consultation. This was only an option if the patient chose to receive further treatment at the same hospital. Others chose hospitals closer to their home.

3) Development of an application for smartphones that contains information regarding the disease; medication and the organization of the outpatient clinic at both departments with an option to write directly to the nurses. Results: These different methods were well received by both patients and parents, although there was still in most instances a parentguided tendency in the consultations. It was evident that there were still hurdles for the patients to climb in regards to making direct contact and starting to take ownership of their own disease and treatment. Several patients got the application on their phone; none has used it to write directly in to the nurses, instead their parents called the nurses as usual.

Conclusion: The feedback from the department of Rheumatology is positive as they are encountering more prepared patients that have a better understanding of the way the consultations and treatments will be handled. Further efforts are needed in supporting the young patients to take a more active role in their treatment and in the understanding of their disease. Many, especially among the ones that have been diagnosed at an early age, have very little insight into their own disease and Introduction: Published treatment recommendations state to change biologic medications when the goal of inactive disease status is not attained, but the switching of biologic agents has not been well-studied.

Objectives: To examine the frequency of switching of biologic agents in the treatment of JIA in clinical practice in North America. Methods: Using retrospective and prospective data from the Childhood Arthritis & Rheumatology Research Alliance(CARRA) Registry, we identified patients with JIA categories other than systemic arthritis who newly started a biologic agent after 1 January 2008 and had at least 12 months of observable time following medication start. "Switchers" were defined by stopping the first biologic agent and starting a different biologic agent within 6 months of the discontinuation. "Delayed switchers" were defined by stopping the first biologic agent and starting a different biologic agent more than 6 months after the discontinuation. "Non-switchers" were defined by no use of any other biologic agent. Chi-square and Wilcoxon rank sum were used to compare patient characteristics among the different switching patterns.

Results: 708 children with JIA newly started a biologic agent during the study period and had sufficient data available for analysis. 146 (21%) were switchers, 45 (6%) were delayed switchers, and 517 (73%) were non-switchers. Among switchers, the median time between starting the first biologic agent and switching biologic agents was 309 days (interquartile range (IQR) 151 -630) and the median time between the first and second biologic medications was 0 days (IQR 0 -31). Among delayed switchers, the median time between starting the first biologic agent was 1184 days (IQR 669-1442) and the median time between the first and second biologic medications was 587 days (IQR 335-858). Etanercept was the most commonly initiated first biologic agent (N=476,67%). The proportion of patients who used etanercept as the first biologic agent was greater among all switchers (73%) compared to nonswitchers (65%; p=0.04). The proportion of patients who took concurrent methotrexate was greater among all switchers (84%) compared to non-switchers (76%; p=0.03). The prevalence of chronic uveitis and inflammatory bowel disease was similar between switchers and non-switchers. Medication ineffectiveness (N=77, 52%), flare of disease (N=19, 13%), and medication intolerance (N=16, 11%) were the most commonly reported reasons for discontinuing the first biologic agent among all switchers.

Conclusion: Following first initiation of biologic agent use for JIA, nearly 30% of children switched to a second biologic medication after a median of 14 months. All switchers were more likely to have initiated etanercept and more likely to have taken concurrent methotrexate compared to non-switchers. Future studies are needed to examine the short-and medium-term clinical outcomes following biologic switching to help identify the optimal timing of switching and the most effective second-line biologic agent. many clinicians have realized the change of the time from "CARE" to "CURE" Objectives: For the development, approval and early introduction into clinical practice of biologics in pediatric field, we need to grasp the pesent situation of the development to approval of biologics as anti-rheumatic agents for children in Japan, and visualize the pesent problems and give a proposal for the future. Methods: We reviewed the time lag from the development to approval between inside and outside of Japan and between adult use and pediatric use using each Application document.

Results: As results of analysis in various directions, it is apparent that the duration of a review period required for the preparation of clinical trials and the approval in PMDA clearly reduced compared with the past. Thus, it was speculated that a rate limiting step in the process from development to approval was the duration of clinical trials between its start to end. Therefore, it is necessary to consider about the following 3 keywords to promote the development of biologics and their early practical use: they were "Registry", "Centralization" and "Global cooperation", all of which are related to the reduction of duration of a clinical trial. Conclusion: To reduce the duration of clinical trial, it is essential to complete "a world-scale registry system" by developing the registry system established by Pediatric Rheumatology Association of Japan. Then, it is important to carefully plan to participate into the international network using "the world-scale registry system", and aim at global cooperative trials in which we can ensure the sufficient number of entries from Japan. Introduction: With the advent of targeted therapy as biologics for the treatment of juvenile idiopathic arthritis (JIA) and other pediatric rheumatic diseases outcome has improved considerably. However, a major concern in patients treated with these immune-modulators has been the increased risk of opportunistic infections. 1-max 4) . The scheme of RTX frequently used was 1000 mg two weeks apart, except for the PN and 2 JDM that used 375 mg/m 2 four weeks and 575 mg/m 2 in two weeks apart, respectively. The average time between cycles was 12 (min 6-max 26) months. In all but one patient, disease activity improved when comparing the period before and after RTX. The SLEDAI score for JSLE, decreased from a Introduction: Intra-articular knee injection is a common procedure in paediatric rheumatology. However unlike adults, in children it is mostly carried out under general anaesthesia which has its own risks. Thus the effect of the intra-articular injection has to be optimal and long lasting. We undertook this study to find out whether ultrasound (US)assessment and guided intraarticular knee injections leads to a better outcome Kaplan Meier survival analysis, demonstrated that overall, 64% of joints remained clinically quiet at 2 years. There were 58 flares in 158 knees by 2 years. The number of flares according to type of JIA and at end of 3, 6, 12, 18 and 24 months is given in Table 1 . Those with minimal SH pre injection had significantly better outcome at 2 yrs. ( 72% remission) compared to those with marked SH, where just 51% were in remission.

There was no significant difference in flare rates between oligoarticular and polyarticular subtypes. Concomitant steroid or methotrexate did not alter the rates of flares. Longer duration of current episode, higher ESR and CRP and lower total steroid dose were found to predict flares. Conclusion: This is the first study in paediatric rheumatology to use ultrasound guidance in all intra-articular injections. Our outcomes are significantly better than those previously published 1 where 69% were in remission at 6 months compared to our 88%. Whilst another retrospective study 2 observed 49% were still in remission after approximately 2 years compared to our 64%. IACI performed under US control appears to improve the outcome in JIA and MSUS informs the clinician regarding the long term outcome

Introduction: Patient's perspective of disease status is a critical, yet difficult to capture component of outcome in Juvenile Idiopathic Arthritis (JIA). Some patients exhibit high perceived disease activity, pain levels and impaired health-related quality of life despite current inactive disease. Objectives: 1) To examine the relation between pain, physical functioning, quality of life, damage measures and perception of activity in different disease states.

2) To identify determinants of disease activity perception in patients classified in remission.

Methods: Patients enrolled in The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) study were included in this analysis. Data from an unselected of 2102 patients with oligoarticular (n=352) and polyarticular (n=1750) were considered. Evaluated variables included the quantitative items of the Juvenile Arthritis Multidimensional Assessment Report -VAS Pain, VAS Disease Activity, VAS Well Being, Juvenile Arthritis Functional Score (JAFS), physical health (JQLPsH) and psychosocial health (JQLPhH) Quality of Life Scale -and the Juvenile Arthritis Damage Index. Interactions among patientreported physical disability, physical and psychosocial life quality, damage, global well-being and activity perception were explored using network analysis; clustering and centrality indexes were estimated as measures of the strength of connections and relevance of specific items, then compared across patients in activity and remission states. In addition, Pearson's correlation and recursive partitioning were used to identify determinants of patient 'activity perception and global well-being VAS scores in the remission group (n=546).

Results: Network analysis revealed a highly clustered structure, with specific physical function and participation-related items connected to psychological components through pain score. Clusters appeared stable across activity and remission groups; walking and items related to cervical limitations revealed higher centrality in active patients, while impaired hand function was more central in patients in remission. In patients with active disease, pain, difficulties in energy-consuming activities, walking and impaired hand function showed the highest closeness centrality, indicating a high ability to predict other items. After adjusting for disease activity (JADAS10), pain, sadness, anxiety, difficulties in energy-consuming and social activities remained tightly interconnected, exhibiting the highest degree centrality; no substantial differences in the structure were found between polyarticular and oligoarticular patients. In the remission group, patient-perceived disease activity correlated well with well-being (r= 0.81, p<0,001) and pain (r= 0.73, p<0,001) scales. Recursive partitioning identified pain VAS > 4 (p<0.001), JQLPhH score > 6 (p=0.001), pain VAS < 1 (p<0.001) and difficulty in energy-consuming activities (p<0.001) as predictors defining 5 subgroups with different levels of VAS disease activity in patients in remission.

Conclusion: Network analysis revealed the connection between pain and specific psycho-functional domains and their impact on patientperceived disease activity. These findings may inform the development of patient-centered disease assessment tools and the therapeutic targeting of symptoms that are likely to have the greatest impact on patient's perception of treatment effectiveness and global health status. Introduction: "Children with arthritis at school" is a brief text accompanied by illustration spread by APMAR Onlus to give psychological support to children that suffer from juvenile idiopathic arthritis and to their families and teachers.

Objectives: The main goal of the book is spotlighting necessities of children who are forced to live with juvenile idiopathic arthritis and raise awareness of these diseases in teachers and school staff in general. The aim is helping teachers and families to give a proper psychological support to children with arthritis. Furthermore, the publication tries to show how to take care of kids according to their needs. Methods: The book -realized with the contribution of Adele Civino, a pediatrician at the "Cardinal Panico" Hospital of Tricase (LE), Gilda Panzera primary school teacher, the psychologist Silvia Taccone and the illustrator Salvatore Santucciowas diffused by APMAR in schools and pediatrician's offices. Results: With the book "Children with arthritis at school" APMAR Onlus reached the purpose of focusing people's attention on rheumatic diseases. In particular, the association spread information about juvenile idiopathic arthritis (Juvenile" in this context refers to an onset before age 16 and "idiopathic" refers to a condition with no defined cause) and gave guidelines that allow teachers and families to make easier for the youngsters to attend school and make the best of it. "Children with arthritis at school" provide information about drugs and teach how to recognize symptoms. It also promotes the importance of communication: primarily between teachers and the family, but also between the school staff and the pediatrician that attends the child. Create a dialogue is fundamental to help kids enjoying their school career, improve their quality of life and avoid them to feel different or sink into depression. Children well-being pass through the acceptance of the pathology. To manage this achievement, they need the psychological support of their families, their classmates and their teachers. The book gives some practical advice addressed to adults. In the book teachers will find very practical recommendations. For example, tables useful for learning how to intervene in a proper way depending on the situation and on the needs or pains showed by the kid. "Children with arthritis at school" also provide a chart that helps physical education teachers to know which activities can be easily done by the children and which not. Together with "Children with arthritis at school" APMAR created a comic that illustrates how to deal with these diseases and how to recognize the most common symptoms. A comic allows to communicate with children in a language that they know and that is adequate for their age. The project also leads to a Youtube version of the comic called "A new challenge to live together. Rheumatic diseases explained to children". The video is in Italian subtitled in English and is visible at this link: https://youtu.be/o12g3Zz3N-g. Furthermore, as part of the same communication campaign, APMAR realized a video with the popular Italian singer Alessandra Amoroso (https://www.youtube.com/watch?v=8mZSirhXo8U) focused on the disease awareness.

Conclusion: The diffusion of the short text "Children with arthritis at school" was welcomed with approval by families and teachers. School fulfils the essential role of educate but also it allows kids to grow both at a psychological and social level. This is the reason why running an informative campaign among teachers is very important. The book raise awareness and allow many children who suffer from juvenile idiopathic arthritis to feel more comfortable at school. It also turns on the debate about these diseases and spread the knowledge of their symptoms matching the APMAR mission of sensitise public opinion towards rheumatic pathologies.

malignancies (11 lymphomas) among the JIA patients and 132 (15 lymphomas) among the non-JIA individuals. Conclusion: JIA patients are at increased risk to develop cancer and especially malignant lymphoma compared to the general population. There is no signal that the risk of cancer in JIA patients has been increasing over the last years. The low numbers of cancer cases in JIA patients underscores that the absolute risk is low. Introduction: Poor sleep quality is common in children with juvenile idiopathic arthritis (JIA). Sleep quality is affected by the child's activity in disease and experience of pain. Psychological variables seem to have an impact on the sleep quality as well.

Objectives: The aim of this study was to examine how pain, disease activity, and psychological wellbeing differs in children with JIA with poor or normal sleep quality, and the likelihood of these variables on having poor sleep quality. Methods: In the outpatient clinic patients diagnosed with JIA age 6-16 were included. Child and a parent completed questionnaires regarding the child's sleep quality in The Children's Sleep Habits Questionnaire (CSHQ), anxiety symptoms in Spence Children's Anxiety Scale (SCAS), wellbeing in WHO-5 Wellbeing Index (WHO-5)), positive and negative mood in The Positive and Negative Affect Schedule (PANAS). Pain intensity was measured using the VAS 1-10 scale from the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). Disease activity was calculated as JADAS-27. Exclusion criteria were JIA in remission off medication, co-morbidity, non-Danish speaking patients.

Results: In total 62 patients were included. Results indicated that 55% of the children reported poor sleep quality (CSHQ>41). Children with poor sleep quality reported significant lower level of wellbeing and higher levels of anxiety, negative mood, and pain intensity, and showed higher level of disease activity (p =.02-.001). A logistic regression was performed to ascertain the effect of pain, disease activity, wellbeing, anxiety, and negative mood on the likelihood, that the children had poor sleep quality. The model was statistically significant (chi 2 (4) = 16.50, p=.006) and explained 36.4% of the variance in poor sleep quality and correctly classified 75.5% of cases. Increasing level of anxiety symptoms was significantly associated with an increased likelihood of poor sleep quality (p=.01). None of the other predictor variables made a unique, significant contribution. Conclusion: Disease activity, pain, and psychological wellbeing were negatively affected in children with poor sleep quality. Especially the level of anxiety symptoms were a significant predictor of having poor sleep quality, which highlights the importance of focusing on the impact of anxiety and worry on children's sleep quality. Introduction: The Transition Readiness Assessment Questionnaire (TRAQ) was developed to evaluate the transition process of were female, with a mean age of 17.9 ± 1.2 years, 23 were in school (85.2%), with an average schooling of 11.1 years. In the population studied, 41% were able to perform their therapy without help and, in this group, about half were using non-biological or biological disease-modifying antirheumatic drugs. In the overall evaluation of each topic of the questionnaire, the one with the highest score refers to Communication with Health Technicians with an average score of 4.81, with the lowest score corresponding to Consultation Management (3, 30) . In this topic, the points related to Money Management and Health Insurance are the areas with a greater lack of knowledge. For the remaining topics in ascending order we found: Monitoring of health problems (3.44), Medication Management (4.12) and Daily Activities Management (4.31). Conclusion: The transition to adult care is a crucial process of emerging adolescents / adults with chronic diseases. The application of this questionnaire proves to be fundamental in the preparation for the transition, namely in the orientation of the educational interventions provided by the health professionals. Therefore, the scores of each topic are useful in identifying the areas that require a higher level of intervention and thus contribute to better prepare the adolescents with chronic diseases to enter the adult system. In our Paediatric unit we conclude that the Consultation Management is the area where the results are lower and thus a greater degree of investment in this area is needed. [1, 2] . Objectives: To understand the experiences of education and employment of educational and vocational outcomes for young people with arthritis, from the perspective of young people themselves.

We used secondary analysis of narrative and semistructured interviews (n=49) which had been video or audio recorded from a primary qualitative study on the experiences and information and support needs of young people with arthritis [3] . A purposive, maximum variation sampling strategy had been employed. The dataset consisted of 40 young people. The dataset consisted of 39 young people (median age at interview 20, range 10 to 28 years; median age at diagnosis 11, range 2 months to 22 years) and 10 carers of young people who had been diagnosed with arthritis in childhood, adolescence or young adulthood. Data analysis for the primary study combined a thematic approach with the grounded theory technique of constant comparison. NVivo software was used to assist data management and coding. The secondary analysis process aligned with Heaton's categories of supra and supplementary analysis [4] . All 49 original transcripts were re-coded with the overarching aim to identify all material relevant to vocational experiences. We also undertook a series of workshop meetings in which the re-coded data were discussed and reviewed jointly by the authorship group to add a further layer of scrutiny, and debate and refine the emerging findings.

Results: Three key themes were identified: (i) The impact of the unpredictability of arthritis symptoms on education and vocation; (ii) the negotiation of disclosure, understanding, support and flexibility in the workplace or educational setting; and (iii) the appraisal and reappraisal of life's goals in the context of an uncertain prognosis. Findings illustrated how young people with arthritis are faced with a range of challenges and disruptions in their everyday life at a time when key developmental tasks occur, including the educational and vocational aspects of their development. Appropriate support and flexibility in the workplace or educational setting were identified as enablers to successful educational and vocational outcomes. However, negotiating disclosure was not a straightforward process for such young people, with a range of concerns and expectations acting as barriers to disclosure. Furthermore, participants' accounts revealed how disclosure is a necessary but not always sufficient step towards achieving an understanding and supportive environment in school or the workplace. Conclusion: There is a need to strengthen the health-school/work interface to improve the educational and vocational outcomes for young people with arthritis. Addressing disclosure with the young person and employing effective interventions to improve communication, understanding and awareness beyond the clinical domain and across workplace/educational settings are key challenges for health professionals and important areas for further research. [ Introduction: Delayed puberty and reduced adult height have been reported in JIA before the era of biologicals. Long-term consequences of delayed puberty are among others growth disturbances, low bone mineral mass and decreased fertility. Treatment with anti-TNF restores growth, but data on puberty are unknown Objectives: We evaluated onset and course of puberty and growth, in JIA-patients who are treated intensively, including the possibility of biologicals, and identified variables related with puberty and growth Methods: In a longitudinal JIA-cohort, all consecutive patients (10 -21yrs) were followed for three years. Annual examinations were performed regarding demographic and disease-related items as well as Tanner pubertal stages and anthropometric measurements. Median ages at reaching each stage were estimated by Kaplan-Meier curves. Parametric tests were used to determine differences between patients and healthy controls, non-parametric tests between patientgroups. Univariate analyses and mixed models were used to identify associated variables Results: 138 patients were included (66% girls). Median diseaseduration was 7,8 years (IQR 3.7-10.5), median JADAS-27 3,7 (IQR 1,3-8,0), DAS-28 2,16 (1, 8) . Puberty onset was 1,2yrs delayed in girls (p<0,01), in boys 0,6 yrs (ns). The progression was also delayed: endstage (Tanner-5) in girls was 3,3yrs delayed (p<0,01), in boys 1,7 yrs (p<0,01). A positive association was found for longer diseaseduration and a lower BMI. Biological-use was not associated. Both for girls and boys, standardized height was not different at the onset and at the end of puberty Conclusion: In contrast to normalized longitudinal growth, we found in JIA-patients in disease remission or with low disease activity a delayed onset and progression of puberty despite intensive treatment including biologicals. Eventually, puberty was completed and normal adult height was reached. The effects on bone mass and fertility will have to be evaluated in cohort studies

Introduction: Transitional care is a purposeful, planed movement of adolescence and young adults with chronic condition from childhood-to adult-oriented health care systems. Well-organized, systematic transitional health care is of high importance for providing the continuous medical treatment and for reaching optimal outcomes. Up to date, there is no unique, consensus-based model for patients' transition from childhood-to adult oriented health care centers in Turkey. were not sufficient for SLE diagnosis. An ultrasound of lymph node was performed and showed an inhomogeneous and hypoechoic structure, richly vascularized. Total body PET was performed, showing hyperaccumulation of lymph node sites above the diaphragm. Lymph node biopsy led to the diagnosis of Hodgkin's Lymphoma (nodular sclerosis subtype). Chemotherapy and radiotherapy were performed and 3 months later, the total body PET was completely negative. The second case report is about a previously well 8-year-old boy, with 1-month history of multiple subcutaneous plaques and nodules, involving the extremities, trunk and face, onset after a trauma. Panniculitis was diagnosed based on skin biopsy and the child was treated with low doses of steroids. After 6 months, he was admitted to our Unit with high fever, malaise, myalgia and extended cutaneous lesions. Clinical examination revealed liver and spleen enlargement; laboratory data showed anemia, leukopenia and elevated levels of ERS, CRP, AST, ALT, LDH, ferritin and low level of albumin. He was negative to screening of EBV and tuberculosis infection. By the review of the first skin biopsy, Subcutaneous Panniculitis T-cell lymphoma (SPTCL), an unusual type of peripheral T-cell lymphoma, was suspected. Another surgical skin biopsy was performed. The histopathological picture showed a pleomorphic cellular infiltrate and cell surface markers consistent with the diagnosis of SPTLC. Liver biopsy revealed systemic hemophagocitic syndrome, while bone marrow examination and bone biopsy were normal; after a week the boy experienced disseminated intravascular coagulation. He was admitted to the Pediatric Hematology and Oncology Unit and initially treated with chemotherapy and local radiotherapy, then autologous bone marrow transplantation was performed and now he is completely recovered.

Conclusion: The isolated finding of positive autoimmune laboratory data, without suggestive clinical features, should not immediately lead to the diagnosis of rheumatologic disorders, but requires more investigations to exclude oncohematological disease. Likewise, suggestive clinical signs should in any case, lead to differential diagnosis, if the clinical course is atypical or if the response to therapy is inadequate. Informed consents for the publication were obteined from the parents.

Introduction: The association of two or more autoimmune diseases (AIDs) in a single patient may be explained due the fact that those diseases share pathogenic mechanisms, many clinical manifestations are common and the profile of autoantibodies is unspecific for several AIDs and those associations may cause significant morbidity .

There are limited information about polyautoimmunity on juvenile patients. Three years ago was started a registry of patients with polyautoimmunity documented during the follow up at a pediatric rheumatology clinics ( 17 centers on 5 Colombian cities). A preliminary report was presented a PRES meeting 2016. We continue this registry, including new patients and updating the information.

Objectives: Identify the clusters of polyautoimmunity observed on those patients and describe the clinical, laboratory, histopathological features and treatment in juvenile patients with polyautoimmunity (2 AIDs) and multiple autoimmune syndrome (≥3 AIDS) and analyze the clusters of AIDs observed. Methods: Multi-center, retrospective and prospective study. Medical records were reviewed and the information was recollected using a data collection format. Statistical analysis performed using SPSS 20.

Results: N = 313 Sex ratio F22: M1, mean age was 11,3 years (1-16). The first AIDs documented was named as "chaperone" disease followed by the additional AIDs at a variable of time needed to confirm the diagnosis and classified as simultaneous when the interval was less than 6 months or sequential if that interval was longer. Those intervals varied widely between associations. 28 AIDs were identified. The shorter interval was for AIDs associated to SLE and the longer was for Sjogren Syndrome ( confirmed by minor salivary gland biopsy). Some were re classified because developed additional AIDs since their entrance to the registry to the last cut point. 40 patient developed multiple autoimmune syndrome Thyroid was the most common organ-specific AID and SLE was the most frequent systemic AID with polyautoimmunity. SLE preceded, diagnosed simultaneously or followed by other 7 AIDs correspond to the biggest cluster followed by Hashimoto, JIA and Sjogren in association to another AIDs. Other 16 types of associations were documented.

Conclusion: What we have learn?? First: Polyautoimmunity is not an uncommon event on juvenile patients and patients with a AID are at risk of additional AIDs as it has been confirmed on adult patients but the type of associations may vary between populations (ethnicity). Second: Some associations must be searched at the time of diagnosis and during the follow up because may determine severe complications and immunomodulation, hormone supplementation and additional prophylatic and therapeutic measures may benefit the prognosis of the patients. Third: If an atypical clinical course or changes of the symptoms and clinical signs on a patient with AIDs are observed, to check the functional tests of the potential target organs and autoantibody profile is indicated in order to rule out polyautoimmunity. Introduction: Osteoarticular pain can not only be the sign of arthritis and musculoskeletal syndromes, but also of benign or malignant tumors.

Objectives: We describe four paradigmatic cases of acute lymphoblastic leukemia (ALL), osteoid osteomas (OO), Ewing Sarcoma (ES), pigmented villonodular synovitis (PVS). Methods: Diagnostic hypotheses were based on the medical history, physical examination, blood and imaging tests. Results: Case report 1. Since about a month, a six-year-old male child complained of nocturnal pain in the lower limbs with awakening, intermittent fever, asthenia, loss of appetite, headache, weight loss and reported upper airway infection in the last two months. Physical examination showed cutaneous pallor, apathy but absence of hepatosplenomegaly, lymphadenopathy, petechiae, ecchymoses, scrotal swelling and signs of arthritis. Ocular fundus examination was normal. Blood tests showed mild anemia, neutrophilic leukocytosis, thrombocytopenia, increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), increased lactic dehydrogenase and urate. Search for homovanillic and vanillylmandelic acid in the urine was negative. Microscopic observation of peripheral blood highlighted the presence of blasts. Bone marrow needle aspiration and biopsy confirmed the suspicion of ALL. Case report 2. Since about two months, a 14-year-old teenage boy reported pain in the right lower limb, more intense at night, not associated with fever and increased in intensity despite oral administration of ibuprofen. Clinical examination showed lameness and functional limitation of the right coxo-femoral joint. Blood tests were all normal, while radiograph at the proximal femur showed an oval radiolucent lesion of about one centimeter in diameter, surrounded by a sclerotic ring. Computerized tomography (CT) was performed and scintigraphy showed an increased uptake with technetium 99m. Diagnostic suspicion of OO was confirmed following the removal of the lesion. Case report 3. A 15-year-old teenage boy since about a month complained of pain referred to the anterior surface of the left thigh, associated with fever and which resulted in nighttime awakening. At physical examination the patient was limping; laboratory tests showed increased ESR and CRP. Radiological examinations revealed an elongated lytic bone lesion, disrupting the cortex and surrounded by onion-skin periosteal reaction. Bone biopsy confirmed the diagnosis of ES. Case report 4. A 16-year-old teenage girl came to our observation for joint pain in her right knee since more than six months. Physical examination showed swelling, pain and functional limitation of the knee joint. Blood tests turned out to be normal, ultrasonography showed signs of synovial hypertrophy and intra-articular effusion; joint aspiration highlighted dark-brown synovial fluid. Magnetic resonance imaging (MRI) revealed a hypertrophic synovial membrane with a villonodular appearance. Diagnosis of PVS was confirmed following surgical excision. Introduction: Often forgotten in the developed world, vitamin C deficiency occasionally presents to rheumatology. With non-specific multisystem presentation, children can pose a diagnostic challenge and often have extensive investigations to rule out malignancies, neuromuscular disorders or arthritis.

Objectives: To describe cases referred to rheumatology with musculoskeletal symptoms explained by vitamin C deficiency over previous 6 years, with serum vitamin C level <15umol/L. Methods: Retrospective case review Results: We present a series of 4 autistic children whose wide variety of phenotypes were explained by vitamin C deficiency and responded to supplementation. Case 1: 12 year old boy, background Fragile X and autism, with 5 weeks nocturnal hand pain and reduced function, unresponsive to simple analgesia. Joint examination revealed hypermobile fingers only. Subsequent review identified limited diet and bleeding gums. Vitamin C level was 12umol/L and symptoms completely resolved with vitamin C treatment. Case 2: 3 year old autistic girl, with 4 months intermittent limp, finger swelling with morning stiffness; diagnosis of juvenile idiopathic arthritis(JIA) had been considered. Diet was very restricted. No evidence of synovitis on rheumatology review. Ankle X-ray showed osteopenic bones. Vitamin C level was 4umol/L and she was treated with vitamin C. Case 3: 13 year old autistic boy, previously diagnosed with Henoch-Schonlein Purpura, with 1 month limp, painful legs, right knee and ankle swelling and vasculitic rash. Diet was poor with no fruit or vegetables. Rheumatology review identified he was non-weight bearing, thickened left ankle, with pain on hip movement. Dermatology review elicited follicular hyperkeratosis, with coiled follicular hairs. Vitamin C level was <1umol/L and he was successfully treated with vitamin C, with rapid resolution of symptoms, with only some mild residual joint contractures. Case 4: 6 year old autistic boy, thought to have JIA, with 4 months painful legs, lower limb rash and then progressive stiffness and pain. He had a limited diet but reported to take daily multivitamins. On examination, non-blanching follicular rash on lower limbs, painful hips on internal rotation and warm, full ankles. He had brisk reflexes, truncal and proximal weakness. He was investigated thoroughly by Neurology, including lumbar puncture and MRI brain and spine which was essentially normal. After 10 day admission on hospital diet, symptoms improved. Vitamin C level subsequently returned at <1umol/L and he responded well to treatment. Conclusion: We present a series of 4 autistic children with restricted diets, 3 of whom had been given other diagnoses, and several had extensive investigations. Increased awareness following the herald case facilitated earlier diagnosis in the subsequent patients and recognition of other patient groups at potential risk, including those with inflammatory bowel disease. As well as classical perifollicular petechiae, hyperkeratosis, gingival bleeding, bony manifestations may precede in the paediatric population. Pathophysiology includes defective bone structure; degradation of bone trabeculae, haemorrhages within the subperiosteal layer and osteoporosis. Musculoskeletal phenotypic and radiographic variability amongst vitamin C deficient paediatric patients should not dissuade clinicians from the diagnosis. Awareness of this seldom recognised condition, in any child, but especially autistic children, along with the phenotypic variability is necessary to prevent consequent morbidity and unnecessary investigations and treatment. Informed consent to publish had been obtained. This 17 year old girl, presented aged 20 months with bilaterally swollen knees and elbow stiffness. She had a background of global developmental delay (speech and motor), with significant behavioural issues and learning difficulties. Examination elicited bilateral knee flexion contractures and left wrist pain. Initial management included non-steroidal anti-inflammatories, physiotherapy and splints. Over the subsequent few years she developed wrist and 3 rd proximal interphalangeal (PIP) joint restriction. She was noted to have relative short stature (9-25 th centile) and some dysmorphic features, with a prominent forehead, hypertelorism, brachydactyly and 5 th finger clinodactyly and single palmar crease on right hand. Paediatric psychiatry assessment was requested aged 4, due to her unusual behaviour and social interaction, and she was diagnosed with an atypical autistic disorder. By age 6, when she was first seen in paediatric rheumatology, her joint symptoms had progressed. Clinical examination confirmed inflammatory polyarthritis especially of her wrists, knees, ankles and PIP joints. She had short-lived benefit from multiple intra-articular joint injections. She had a partial response to methotrexate but stopped this due to poor tolerance. She had various biological therapies all with limited response; etanercept for 6 months aged 10, infliximab aged 12 stopped after 8 months due to an infusion reaction, tocilizumab for 18 months from age 13 which was stopped as it was ineffective. She has now been on abatacept for 4 years with reasonable control of her arthritis. She developed increasing back pain and stiffness with unusual radiographic appearances: elongated vertebral bodies on x-ray and MRI with endplate changes and loss of anterior vertebral body height. She subsequently developed dystrophic toe nails. Aged 14 years she developed seizures. She had an extensive genetic and metabolic diagnostic work-up with normal karyotype, normal organic and amino acids. Possible diagnoses including Rett's syndrome, Smith Magenic syndrome and mucopolysaccharidoses were excluded. Chronic infantile neurological cutaneous and articular syndrome (CINCA), was considered but clinical picture and investigations were not thought to be consistent and no mutation in NLRP3 was identified. At the age of 14, a genetic mutation in ANKRD11 gene, diagnostic of KBG syndrome was identified. KBG is an autosomal dominant condition cause by mutations in ANKRD11, which has an essential role in controlling acetylation and expression of genes during development of Introduction: Immune-mediated necrotising myopathy (IMNM) is a rare and severe subtype of Idiopathic inflammatory myopathy (IIM). It results from an immune reaction that promotes muscle destruction with consequent necrosis and regeneration, causing proximal muscle weakness. IMNM can be idiopathic, secondary to viral infections, malignancy and connective tissue diseases or be associated with statin administration.

Objectives: To present a clinical case of rare association of IMNM and Autoimmune liver disease.

Methods: Description of a case report.

Results: A 15-years-old healthy boy was admitted to the Liver Unit in April 2017 due to epistaxis and increased liver enzymes levels. A type 1 Autoimmune Hepatitis (AIH) was diagnosed (hypergammaglobulinemia, positive antinuclear and anti-smooth muscle antibodies and histological interface hepatitis) and he started immunosuppressive protocol with steroids and azathioprine. In June 2017 he begun generalized lower limbs myalgia. During the following months the patient had a fluctuating pattern of muscle pain without weakness or cutaneous abnormalities. In parallel, he maintained an oscillating increased liver enzymes and creatine kinase (CK) levels (range: 100-4 610 U/L). The immunosuppressive schedule was modified (steroid, mycophenolate and cyclosporine) but was unsuccessful in inducing remission. In January 2018, after clinical worsening with a limitative mechanical back pain, he was admitted for further investigation and a clinical evaluation by paediatric rheumatologist was performed. The patient presented an extensive 12 cm right lumbar pain that got worsen with muscle masses palpation, without trigger points to myofascial syndrome, and with a normal osteoarticular examination including sacroiliac manoeuvres. A muscle limb ultrasound was performed disclosing muscle oedema. The anti-actine and anti-centromere antibodies were positive, the myositis specific antibodies panel was negative. Muscle histology was compatible with IMNM as well as the electromyography. At present, the patient is under steroids and high doses of mycophenolate and there were notice some improvement in muscle complaints as well as decreased of liver enzymes' and CK levels.

Conclusion: There are only few reported adult cases about the association of autoimmune liver diseases with IIM. In contrast to the present case report, IMNM typically presents with a pronounced acute/subacute symmetrical muscle weakness associated to an increased CK levels, and myalgia may or may not be present. The finding of predominant necrosis with scarce inflammation in the muscle histology is a critical tool in the diagnosis. These patients often require intensive immunomodulation and are prone to relapse. Results: We found a cohort of 7 patients with a mean age at diagnosis of 13 ± 1.2 years old, six (85.7%) patients were female. The range in the diagnosis delay was 2 to 60 months. The most common clinical manifestations were arthritis (100%), Raynaud (85.7%), hand edema (71%), sclerodactyly (71%), Pulmonary Arterial hypertension (42.9%), lung restriction (28.6%), gastroesophageal reflux (28%), delay in voiding (14%), neurological alteration (28.6%), muscle weakness (28%) and vasculitis (85.7%). Respect the immunological features we found that hiper IgG (100%), antinuclear antibodies (100%) and anti RNP/Sm (100%) were present in all the patients while double-stranded anti-DNA antibodies were positive in 57% patients. During follow-up, the management consisted of systemic steroids in 100%, methotrexate in 66%, nifedipine in 57%, and ciclophosphamide in 57%. During the evolution of the patients we identified that a patient died secondary to an infectious process related to immunosuppressive therapy, a patient is on induction therapy with monthly cyclophosphamide for pulmonary arterial hypertension and the rest of the patients are without clinical activity with therapy maintenance. Conclusion: The EMTC is a very uncommon disease in pediatrics, with a very variable clinical presentation, uncertain and potentially fatal prognosis. This study suggests that, in mexican children, the expression pattern of the observed disease is similar to what has been described in patients with pMCTD from other series. Introduction: Kimura's disease, syn : eosinophilic lymphogranuloma is a chronic inflammatory disorder of unknown aetiology with angiolymphatic proliferation. It is a disease of middle aged Asian males and is seen less frequently in children.

Objectives: We describe a seven year old with steroid-dependent Kimura disease, who responded dramatically to cetirizine (histamine H1 receptor-blocker) and montelukast (leukotriene receptor antagonist).

A seven year old boy , weight 17 kg and height 111 cm, presented with complaints of multiple axillary and inguinal lymph node swellings and fever since 2 years of age, for which he was evaluated elsewhere and diagnosed as a case of Kimura disease. He was initially started on oral steroids to which he responded well but lymph node swelling and fever would recur as soon as steroids were tapered to 10mg (0.6 mg/kg/day). He was thus constantly on steroids for about five years and showed significant growth retardation. Azathioprine was attempted as a steroid-sparer, but was discontinued since he developed transaminitis. He was then referred to us for further management.

Results: The clinical details were reviewed and diagnosis reconfirmed by a review of the earlier biopsy. The child was started on cetirizine and montelukast (available as a combination) after a literature search showed scattered reports favouring these agents as steroid-sparers in this condition. Steroid taper was initiated. On first follow up after 6 weeks, he was afebrile and there was no adenopathy on examination. Parent VAS was 10/10. He was continued on cetirizine and montelukast, steroids progressively tapered and stopped in three months. He started gaining weight (18 kg) and height (112.5 cm). Two months have elapsed since cessation of steroids and he continues to remain asymptomatic as per a recent telephonic interview with parents. We propose to discontinue montelukast and observe him in the coming weeks.

Conclusion: Cetirizine and Montelukast should be considered as initial steroid-sparing options in Kimura disease, especially in the pediatric age group where they have a much safer adverse effect profile compared to other immunosuppressives. Response to these drugs whose mechanism of action is known should help to provide a clue to the pathogenesis of this mysterious illness. Informed consent for publication had been obtained

Introduction: Mutations in the ASAH1 gene cause acid ceramidase deficiency (Farber disease), accumulation of the pro-inflammatory and proapoptotic lipid ceramide, and a distinct set of clinical features, which can vary greatly in severity. Typically, Farber disease presents in childhood with polyarticular arthritis or joint contractures, subcutaneous nodules and a hoarse or weak voice due laryngeal nodules. The prevalence of Farber disease is currently unknown, but it is likely underdiagnosed due to lack of awareness of the clinical presentation and of the availability of diagnostic testing. Acid ceramidase enzyme replacement therapy is currently under development.

Objectives: The primary purpose of the study is to establish the natural history of Farber disease, through analysis of retrospective and prospective data on patients, including living patients who have and have not undergone hematopoietic stem cell transplantation (HSCT) and deceased patients. Additionally, the goal is to establish a set of clinical, laboratory (biomarkers), and functional data characterizing distinct groups within this population.

The "Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease" was initiated in November 2017. 19 patients have been enrolled in the study to date (9 living, 10 deceased), from 11 sites in 7 countries. Demographic and epidemiologic data is available in these patients, as is information about the onset of symptoms and time to diagnosis in most cases.

Results: The ratio of females to males is 8:11. 68% (13/19) of the patients enrolled were born in 2008 or later. The ages of the living patients, who may be able to participate in the prospective portion of the study, range from 2-28 years (mean: 12.2 years), with 5/9 (55.5%) living patients currently under the age of 12 years. All patients enrolled to date developed joint disease (arthritis and/or contractures) and subcutaneous nodules at some point over the course of their disease. In the patients for whom this data is available, subcutaneous nodule size ranges from 1-50mm in diameter, and the current number of nodules per patient ranges from 1-68.

Conclusion: This is the first study to systematically collect both retrospective and prospective data in both transplanted and nontransplanted patients with Farber disease. Further patients are expected to be enrolled from additional countries and centers in 2018. The data currently available supports clinical evidence indicating that Farber disease has a broad clinical spectrum, with symptoms and age at onset overlapping with polyarticular JIA. It may take years for typical symptoms to appear together, indicating that additional awareness of Farber disease symptoms and phenotypes among pediatric rheumatologists may allow earlier and more efficient diagnosis. Trial registration identifying number: NCT03233841 and tachycardia. The pleural fluid was exudative, she had fibrinous pericarditis. The bacterial cultures including tuberculosis were negative. She continued to have severe respiratory distress despite pericardiotomy, and pericardiectomy was performed. Fibrinous pericarditis was confirmed by histochemical study of pericardiectomy material and neither malignancy nor tuberculosis were detected. Histopathological examination of pleura consisted of mainly neutrophils. In laboratory, hemoglobin was 9.4 g/dl, leukocytes were 12300/mm 3 , (76% neutrophil, 14% lymphocyte), thrombocytes were 427000/mm 3 , C-reactive protein was 126 mg/L, erythrocyte sedimentation rate was 89 mm/h, procalcitonin was 0.28 ng/ml, troponin was <0,01 ng/ml, and liver and renal function tests, immunoglobulin levels were normal. Anti-nuclear antibodies and anti-neutrophilic cytoplasmic antibodies were found as negative and C3, C4 levels were normal. No malignancy was detected in the bone marrow. High dose IV prednisolone successfully controlled the disease. Colchicine was added due to pericarditis protocol. Detailed history revealed recurrent chest pain and fever attacks. TRAPS was suspected, and p.arg121Gln mutation in TNFRSF1A gene was detected which was recorded as pathological. She was discharged with colchicine, but had another similar attack, which was controlled by anti IL-1 treatment. Conclusion: TRAPS, also known as Hibernian fever, is an autosomal dominant inherited autoinflammatory disease, which is localized in 12p13 chromosome. TRAPS presents with recurrent attacks of fever lasting up to 1-4 weeks, myalgia, periorbital edema, and serosal inflammation (peritonitis, pleuritis). Rarely, pericarditis is reported during the attacks 1 . A study indicates that TRAPS constituted 6% of the idiopathic recurrent pericarditis 2 . TRAPS and other rare autoinflammatory diseases should be kept in mind in the differential diagnosis of recurrent pericarditis. Informed consent for publication had been obtained from the parents. Introduction: Hyperimmunoglobulin D syndrome (HIDS) is an autosomal recessive periodic fever syndrome presenting with fever, vomiting, diarrhea, abdominal pain, rash, arthralgia, and arthritis.

Objectives: Herein, we describe 4 HIDS cases in the same family. Methods: Case 1: A 6 year old boy who applied with recurrent fever, abdominal pain, vomiting, joint swelling and rash every month for 4 years. There was no mutation in the MEFV gene, and colchicine treatment did not prevent his attacks. G18R heterozygote mutation was detected on the MVK genome. The patient is followed without attack by treatment with anti-IL-1 (canakinumab). Case 2: A 3 year old girl, with complaints of fever, vomiting, leg pain for 2 to 3 days every 2-3 months was using colchicine with FMF diagnosis but no improvement in her attacks. Genetic analysis revealed a G18R heterozygote mutation in the MVK gene. After the anti-IL-1 therapy attacks resolved. Case 3: A 2 year old girl, was admitted with episodes of fever, diarrhea and vomiting that lasted 3-4 days, which was observed 4 times in the last 2 months. Genetic analysis revealed a G18R heterozygote mutation in the MVK gene. The patient is followed without attack by treatment with anti-IL-1. Case 4: A 8 year old girl was admitted with complaints of recurrent fever, abdominal pain and headache. Genetic analysis revealed a G18R heterozygote mutation in the MVK gene. Following the initiation of anti-IL-1 therapy, the complaints were resolved. Results: With anti-IL1 therapy, 4 siblings are followed without attacks. Conclusion: Symptoms may be different in patients with HIDS even if they are the members of the same family or carrying the same mutation. HIDS should be considered when recurrent fever episodes are accompanied by rash, arthritis, vomiting and diarrhea. Anti-IL1 treatment is very effective in reducing symptoms and prevention of amyloidosis. Informed consent to publish had been obtained. Introduction: Cryopyrin-associated periodic syndromes (CAPS) are a group of rare congenital auto-inflammatory diseases with onset in the first year of life with the advent of fever, urticarial rash and various options for joint removal -from arthralgia to recurrent and persistent arthritis in severe cases, as well as damage to the nervous system. Objectives: Consider the clinical case of the child with cryopirinassociated periodic syndrome. Methods: The laboratory -instrumental examination was conducted of 1 year and 8 months old boy, who entered the rheumatological department of the National Medical Research Center of Children's Health with the systemic juvenile idiopathic arthritis. Results: The patient A. entered the rheumatological department with diagnosis systemic JIA. Complaints: fever up to 39.0°C, a rash, pain and limitation of movements in the joints. On examination: urticarial rash all over the body, hepatosplenomegaly, lymphadenopathy, polyarthritis with involvement of interphalangeal joints of hands and feet, wrists, elbows, hips, knees, ankles, temporomandibular joints and the cervical spine. Blood tests: hypochromic anemia (Hb 82 g/l), thrombocytosis (platelets 650 x 10 9 /l), ESR -45 mm/h, CRP level -96.88 mg/l, ferritin -2334.86 ng/ml (norm of 15 -80 ng/ml). The child was consulted by the audiologist and ophthalmologist -the pathology of hearing and vision was not presented. The child is suspected of an auto-inflammatory syndrome, because of the severe condition, debuting in first year and the resistance to the standard antirheumatic therapy (prednisolone 13 mg/day, tocilizumab 12 mg/kg once every 14 days within one month). Exon 04 of the NLRP3 gene with adjacent intron regions were examined by the method of direct automatic sequencing. A mutation c.943A> G in the heterozygous state, resulting in the amino acid substitution p.I315V, was detected. A previously prescribed topic was described in patients with cryopyrin-associated periodic syndrome. The "Cryopyrin -associated periodic syndrome" diagnosis was confirmed by the previous research study results, pathogenetic therapy was prescribed by giving the genetically engineered biological agent -canakinumab (interleukin 1 inhibitor) for subcutaneous injection at a dose of 4 mg/kg (52 mg) once every 4 weeks. After the first injection of canakinumab, the rash disappeared, but fever, hepatosplenomegaly, lymphadenopathy persisted, macrophage activation syndrome developed (ferritin -3318.01 ng/ml, white blood cells 6.71 x 10 9 /l). The child was given glucocorticoids for oral administration (prednisolone at a dose of 2 mg/kg, 25 mg per day) and for injection (dexamethasone 20 mg /m 2 / day in 2 divided doses). The therapy was effective, patient`s condition improved significantly -fever, rash, hepatosplenomegaly, lymphadenopathy, arthritis resolved (Hb 111 g/l, ESR -3 mm/h, CRP level -1.48 mg/l, ferritin -25.55 ng/ml). The second and third injection of canakinumab gave no reaction. Intravenous glucocorticoids were withdrawn the dose of oral GK was reduce to 18.75 mg/day. At the moment, the patient is on therapy (canakinumab 52 mg once every 4 weeks, prednisolone 5 mg per day) for more than six months without signs of systemic inflammation. Conclusion: Cryopyrin -associated periodic syndrome, with onset at an early age, characterised by an aggressive course and inefficiency of glucocorticoid therapy. To verify the diagnosis and to provide targeted therapy to children with a clinical picture of systemic juvenile arthritis, a molecular genetic study should be performed to exclude or confirm a monogenic autoimmune syndrome. Informed consent to publish had been obtained from the parent. Results: The patient (female, six years old) was referred to our Unit at the age of 2 years. The family history revealed a mother with rheumatoid arthritis and visual loss due to panuveitis. The clinical history disclosed that at the age of 12 and 15 months the patient had two episodes of diffused rash spontaneously resolved in two weeks. From the age of 18 months recurrent hip pain, defined as transient synovitis of the hip, was reported. It was treated successfully with non-steroideal antinflammatory drugs (NSAID) but pain would reappear once stopped the treatment. Clinical evaluation showed polyarticular symmetrical arthritis of wrists, elbows, knees, proximal interphalangeal (PIP) joints. Polyarticular Juvenile Idiopathic Arthritis (JIA) diagnosis was made and treatment with NSAID and Methotrexate was started without significant improvement, therefore Etanercept was added and NSAID stopped. Screening of uveitis was performed every six months. Persisting arthritis of right wrist after 7 months of therapy, ultrasound was performed showing tenosynovitis. Therefore, she underwent intra-articular injection of glucocorticoids with partial response. At the age of 4 years, she presented papuloerythematous rash, mainly on the trunk, infiltrated and confluent in plaques, so skin biopsy was performed resulting consistent with sarcoid-like granulomatous disease . Suspecting BS molecular analysis was done. At the age of 5 years, she presented scotoma and visual loss; the ocular assessment found bilateral anterior uveitis and posterior bilateral synechiae. She started systemic glucocorticoid therapy and shifted from Etanercept to Adalimumab with improvement of both ocular and articular disease. The molecular analysis of NOD2 showed missense mutation R334W consistent with BS. The ocular disease evolved into iridolenticular synechiae and band keratopathy. She started topical treatment with improvement. Currently, the articular and cutaneous manifestations are controlled by the combined therapy with Adalimumab and Methotrexate. The ocular disease is steady. Conclusion: The patient presents typical clinical manifestations of pediatric sarcoidosis, confirmed by skin biopsy. R334W is one of the most common mutations reported in the international Blau registry. The presence of typical clinical manifestations, NOD2 mutation and family history led to the diagnosis of Blau Syndrome. The molecular analysis of NOD2 gene in the mother is ongoing. Informed consent for the publication was obteined from the parents. Introduction: Sacroiliitis has rarely been reported in patients with familial Mediterranean fever (FMF), especially in the pediatric population.

Objectives: In this report we present patients with FMF related sacroiliitis who had very early disease onset. Methods: Two cases with documented sacroiliitis at 3 and 4.5 years of age were presented.

Results: A 5-year-old male patient had the complaints of intermittent hip pain and limping attacks with duration of 15 days, started at 2 years of age. He had also recurrent fever attacks and his father has FMF. At 3 years of age sacroiliac joint magnetic resonance imaging (MRI) showed left sided sacroiliitis and MEFV gene analysis was compatible with homozygous p.M694V mutation. HLA-B27 was negative. Colchicine was commenced and his complaints improved. Seven months later hip pain and limping attacks started again and described partial improvement with ibuprofen. At the age of 5 years, control MRI revealed bilateral sacroiliitis. Salazopyrin was added to his treatment. The second patient is a 7 year old boy who had the diagnosis of ulcerative colitis at the age of 14 months. He was referred to rheumatology clinic due to hip pain, low back pain and gait disturbance at 3 years of age. He had family history of FMF and ongoing elevated acute phase reactants but no typical FMF attacks. HLA-B27 was negative. Mutation analysis revealed p.M694V/p.M680I, sacroiliac joint MRI showed pelvic enthesitis and colchicine was started. His complaints improved. At the age age of 4.5 years, due to intermittent complaints and elevated acute phase reactants, control MRI was performed and showed bilateral sacroiliitis. Adalimumab was commenced. He had no complaints thereafter. Conclusion: Familial Mediterranean fever related sacroiliitis can be seen in very small children. Furthermore, in patients with early onset sacroiliitis FMF should be investigated in the differential diagnosis. Written consent for publication was obtained from the parents Introduction: Although there are previous studies demonstrating regression of proteinuria due to amyloidosis secondary to familial Mediterranean fever (FMF) by colchicine and/or anti-interleukin 1 treatment, there is no study about response to therapy at tissue level of amyloidosis secondary to FMF (1, 2) . Objectives: We aimed to evaluate the influence of colchicine and anti-interleukin 1 treatment at tissue level in a case of FMF with amyloidosis.

Methods: A 10-year-old boy presented with nephrotic range proteinuria (83.5 mg/m2/hour, 2 g/day) and high level acute phase reactants in May 2011. First kidney biopsy revealed renal amyloidosis. Mediterranean fever mutation test showed homozygous for M694V, R202Q and E148Q mutations. Colchicine (1.5 mg/day) and enalapril (7.5 mg/day) was commenced. Although the proteinuria was reduced to 10 mg/m2/hour within 2 years by this treatment, acute phase reactants did not return to normal values. Therefore, second kidney biopsy was performed in July 2013, since ongoing amyloidosis and subclinical inflammation, anti-interleukin 1 (anakinra 2mg/kg/day) was commenced as an additional treatment to colchicine and enalapril. Two months later, proteinuria (<4mg/m2/ hour) and acute phase reactants were normal. In Semptember 2015 anakinra was switched to canakinumab (2mg/kg/month). Remission was successfully maintained, he didn't experience attacks, after switching to canakinumab. After obtaining from parental and the patient consents, third kidney biopsy was performed in April 2017. Creatinine clearance never deteriorated during followup period. Three renal biopsies were re-evaluated and compared according to the hystopathological classification, scoring and grading system established by Sen et al. (4) .

Although the renal amyloid grade remained stable, RAPS progressed slowly.

Conclusion: We concluded that anti-interleukin 1 treatment in patient with amyloidosis secondary to FMF could not stop progression at tissue level, but it could lead to clinical improvement. We need to new treatment strategies that not only to remove the inflammation, but also to dissolve amyloid deposits. Informed consent for publication had been obtained.

Introduction: The modern period of studying different pathogenetic links of the course of JIA is characterized by a special attention to the formation of changes in bone tissue. Violations of the bone tissue due to a decline in mineral bone density can be registered as the first signs of arthritis and in later stages of the disease. Objectives: To evaluate the possibility of non-drug correction of vitamin d deficiency for the prevention of bone metabolism disorders in children with articular form of JIA. Methods: The study included 32 patients with articular JIA and 28 children with other arthritis, which were divided into three equal and comparable groups. In each of the groups applied different methods of correction of vitamin D deficiency, namely: subgroup Achildren receive a balanced diet and a specialized product for enteral of food containing 52 IU of vitamin D 3 100 ml (non-medicament correction of deficiency/insufficiency of vitamin D); subgroup Bchildren only received nutrition, subgroup С -children were on medical correction of deficiency/insufficiency of vitamin D officinal drugs. Results: In subgroup "А" all children before correction were in deficit (75 %) or deficiency (25%) of vitamin D. After correction, the proportion of children with a level of 25(OH)D below 30 ng/ml did not exceed 30%. Before the beginning of the correction in all children with oligoarticular variants (OAV) of JIA from subgroup "A" vitamin D deficiency was registered (below 20 ng/ml), after correction more than 62% of the examined children reached the level of 25(OH)D more than 30ng/ml in serum. With polyarticular variant (PAV) JIA succeeded in all children with vitamin D insufficiency increase its level in blood serum above 30 ng/ml, while 50% of children with a deficiency to increase the level of vitamin D in the blood serum before 21-29 ng/ml. The use of nonpharmacological correction of vitamin D deficiency in children with other arthritis in history has allowed more than 80 % of patients to achieve normal values of 25(Oh)D in serum (more than 30 ng/ml). In subgroup "B" 95% of children at the beginning of the study had a level of 25(OH)D in serum below 30 ng/ml. After 4 weeks of observation, there was a slight improvement in the indicators 25(OH)D in serum, and the proportion of children who have overcome the threshold of 30 ng/ml, increased to 10%. Among children with other arthritis in the anamnesis it was possible to achieve a twofold increase in the proportion of patients with a level of 25(OH)D in serum more than 30 ng/ml. In subgroup "C" 90% of children at the time of the study had vitamin D deficiency (serum 25(OH)D level below 20 ng/ml), only 2 patients had vitamin D level in the zone of insufficiency (21-29 ng/ml). After 4 weeks of medical correction in patients of this subgroup, the proportion of children who overcame the threshold of 30 ng/ml was 85%. In the subgroup "C" after 4 weeks of medical correction in all patients with polyarthritis, in 90% of children with oligoarthritis and in 87,5% of cases in children with other arthritis in the history noted a positive result-the concentration of 25 (OH)D in serum levels above 30 ng/ml. Conclusion: The increase in the subgroups "A" and "C" after the 4week course as a non-pharmacological and pharmacological correction of deficit of 25(Oh)D in serum in the proportion of children with a normal supply of vitamin D is from 0 to 75%, and 90% of cases, respectively, demonstrates the effectiveness of the applied methods, and the lack of significant differences in the achieved level of 25(Oh)D in the serum of patients in these subgroups confirms the possibility of using non-pharmacological correction of vitamin D deficiency for the prevention of osteopenia, based on the use of specialized products for enteral nutrition. Introduction: Important advances in management of JIA have been made over the last few decades. However, there are still differences with regard to outcomes across European countries.

Objectives: To assess disease activity, functional status and damage in JIA patients of all subtypes followed in a southeastern Pediatric Rheumatology tertiary center (Greece). Methods: JIA patients consecutively seen in a Pediatric Rheumatology reference center between January and April 2018 were enrolled in this observational cross-sectional study. Outcome measures included numbers of active and limited joints, physician's VAS of overall disease activity, parent's VAS of global wellbeing and pain, CHAQ, articular and extra-articular damage. Criteria for inactive, low, moderate and high disease activity were applied [1; 2] ; for patients with enthesitis-related arthritis, (ERA) the absence of enthesitis was an additional criterion. CHAQ score, overall wellbeing and pain scores were divided into 4 categories: 0 (no disability), >0 and ≤0.5 (mild disability), >0.5 and ≤1.5 (moderate disability), and >1.5 (severe disability), as previously described [3] . For statistical analysis, non-parametrical tests were used. Results: A total of 24 JIA patients were included. Our cohort comprised 67% oligoarticular JIA, 12% polyarticular RF-negative JIA and 21% ERA patients with median disease duration of 1 year (range 1 month -15 years). Treatment comprised NSAIDs (54%), MTX (71%), intra-articular corticosteroids (50%), systemic corticosteroids (25%) and biotherapy (38%). Criteria for inactive disease and low, moderate and high disease activity were met by 13% and 8%, 50%, 29% of patients, respectively. Uveitis developed in 13% of patients, all with oligoarticular JIA. The median value of CHAQ score was 0 (range 0-1.875). The majority of patients had no or mild functional disability (88%) and pain (63%); however moderate or severe overall well being impairment was present in more then half of the patients (58%). Within JIA subgroups, ERA patients had significantly worse scores for CHAQ, VAS wellbeing and pain. CHAQ significantly correlated with disease activity (p<0.0001), physician's global VAS (p<0.0001) and with VAS scores for overall wellbeing (p=0.0009) in altogether JIA patients. Articular and extra-articular damage were found in 8% and 13% of patients, respectively. Conclusion: Conclusion. In the present cohort, the majority of patients had moderate disease activity but good functional scores, probably related to the short disease duration. ERA patients still represent a management challenge. A good control of disease is essential in order to preserve the functional abilities and the overall wellbeing of JIA patients. Introduction: Acute rheumatic fever (ARF) is an autoimmune disease following group A streptococcal (GAS) infection. Despite being rare, in Latvia new cases still occur. RF remains a clinical syndrome which has variable manifestations according to genetic predisposition, prevalence of GAS strains, and socio economical conditions. There are data that genetic susceptibility to RF is linked to HLA class II alleles. However, studies in different populations have given conflicting results of susceptibility and/or protective alleles [1] . In Latvian patients diagnosed with RF between 1995 and 2001, DRB1*07 allele was associated with the disease [2] . Since 2001, 27 newly diagnosed RF cases have been reported in Latvia. Therefore, a thorough understanding of immunological mechanisms involved in the development of RF is required. Objectives: To describe the clinical characteristics of ARF in children in Latvia between 1995 and 2016 and to investigate immunogenetic markers of HLA-DRB1; -DQB1; -DQA1 in patients diagnosed with RF since 2001. Methods: Part A: A retrospective study included 96 children diagnosed with RF between 1995 and 2016 at Children's Clinical University Hospital (CCUH). We analysed medical case reports, evaluating clinical and laboratory data and compliance with the Jones criteria. Statistical analysis was performed using SPSS Statistics. Part B: A prospective study included 21 out of 27 patients diagnosed with RF between 2001 and 2016, and 100 healthy controls. Patients were genotyped for HLA-DRB1; -DQB1; -DQA1 using RT-PCR with sequencespecific primers. Statistical analysis was performed using DOS StatCalc program, Cochran-Mantel-Haenszel test and Fisher's exact correction. Results: Part A: Among 96 RF patients 64.6% (n=62) were boys. The age of patents at time of diagnosis varied between 4 and 17 years, the median age was 10 years (IQR 5-15). Carditis (85.4%) and polyarthritis (42.7%) were the most frequent Jones criteria. Most commonly (in 41.5% of cases) patients had either mitral valve or multivalvular (MV+AV) lesions. Sydenham's chorea occurred in significantly fewer patients (16.7%). Erythema marginatum and subcutaneous nodules were rarely observed (10.4%, 1% respectively). Of the minor Jones criteria the most common were arthralgia (81.3%), elevated inflammatory markers (79.2%) and fever (61.5%). Part B: Significant associations were found between the RF and control groups. Alleles DRB1*04:01 (OR=1.28, p=0.027), *07:01 (OR=9.8, p=0.001) and *11:01 (OR=1.38, p=0.029) were more often observed in the group with RF and described as risk alleles. The risk variants were also DQB1*03:01 (OR=1.13, p=0.01), *03:02 (OR=2.12, p=0.017), *04:01-2 (OR=1.6, p=0.01) and DQA1*02:01 (OR=1.90, p=0.015), *03:01 (OR=1.75, p=0.018) alleles. The frequencies of DQB1*06:02-8 (OR=0.46, p=0.019) and DQA1*05:01 (OR=0.99, p=0.001), *06:01 (OR=0.67, p=0.01) alleles were decreased and described as protective for RF. Conclusion: ARF most commonly occured in school-aged children, and boys were more affected by the disease. Clinical presentation was typical with cardiac (85.4%), polyarticular (42.7%) and neurological involvement (16.7%). Our study confirms that certain HLA class II alleles are associated with risk or protection from RF.

Introduction: Juvenile Idiopatic Arthritis (JIA) is one of the most common chronic, rheumatic diseases in children. The prevalence of disease in a systematic study is reported to be 1,6-23/100,000 in Europe. In Turkey, this ratio has been reported as 6.4/100.00. Objectives: The aim of this study is to compare the characteristics of children with JIA in the Turkish and British communities. Methods: The study included children of the same age and sex, diagnosed with JIA who were followed in the Pediatric Rheumatology Department of the Hacettepe University İhsan Doğramacı Children's Hospital and the Great Ormond Street Hospital for Children. The Child Health Assessment Questionnaire (CHAQ) was used to assess the general health status of children, the visual analogue scale of the clinician and the family was used to assess the general condition of the child. Demographic data and active and limited joint numbers were recorded. Results: A total of 26 children participated in the study (n=13 for British, n?13 for Turkish). There was no difference in age, diagnosis, sex, CHAQ, and number of active joints in the two groups (p>0,05). However, there was a difference between limited joints and general health assessments from family and clinician (p<0,05).

Conclusion: As a result of this pilot study, there was no difference in the CHAQ scores of children with JIA when age and gender matched, but there were differences in the general situation assessment between the family and the clinician. This study will be continued by increasing the number. Introduction: Juvenile Idiopathic Arthritis (JIA) is a group of diseases of unknown origin, lasting more than 6 weeks, beginning before the age of 16 years. It is the most frequent rheumatic disease in childhood, affecting predominantly girls, especially in the oligoarticular subtype (the most frequent, corresponding to 50% of cases). Treatment is based on a pharmacological combination, rehabilitation and psychosocial support. The manifestation of the disease is demonstrated by the inflammatory activity. The implication of the inflammatory activity in the daily life activities is a focal point of the evaluation.

Objectives: The aim of this study is to characterize patients with JIA followed at the Multidisciplinary Clinic of Pediatric Rheumatology of the University Hospital Center of the Algarve (CHUA).

Methods: Descriptive observational study based on the clinical record and the national registry of rheumatic patients (Reuma.pt) of all patients with JIA, followed during 2017, at the Multidisciplinary Clinic of Pediatric Rheumatic Diseases of CHUA. Sociodemographic, clinical, analytical and therapeutic data were analysed. We have included the reference to Physical Medicine and Rehabilitation (MFR). Statistical analysis was performed using Microsoft Excel 2010. Results: Sample of 10 patients (total of 32), 6 boys and 4 girls. The average age of onset was 6.6 years (1-15); age at diagnosis 6.8 years and duration of illness 4.2 years (1-10). The distribution of the ILAR classification was: persistent oligoarticular 60%, arthritis / entesitis 30% and systemic 10%. Analytically we noted ANA and HLA B27 positive in 30% of the cases; the RF and anti-CCP were always negative. 60% of the patients had active disease and 40% were in remission; in relation to CHAQ / HAQ, we obtained a mean score of 0.28 points, with only 2 patients presenting values different from zero; on the JADI A and E scale we obtained an average score of 0.1 and 0.2 points, respectively. 50% of patients had already been exposed to corticosteroids (CE), 60% to synthetic DMARDs and 10% to biological DMARDs; currently only 10% are under CE, remaining 60% with synthetic DMARDs (Methotrexate) and 10% with biological DMARDs (Etanercept). The cumulative exposure to therapy was 0.76 years for CE, 3.11 years for synthetic DMARDs and 0.1 years for biological DMARDs. 20% of patients already had (at some point during the course of the disease) been referred to the MFR consultation, both for elbow flexion deformity. Conclusion: The high frequency of JIA justifies the 31% of patients found; there was no predominance of expected gender, despite the dominance of the oligoarticular category. This category occurs preferentially in girls and before the age of 6; in our sample we found 4 (in this category), with onset of the disease before 6 years old. Two of the 3 patients with HLA B27 positive belonged to the arthritis / enthesitis category, as expected. This category occurs predominantly in boys, after 7-8 years; the 3 cases obtained fit these characteristics. Positive evolution is expected, given negativity for RF and anti-CCP, as well as absence of polyarticular and systemic variants. Although 60% of the patients still have active disease, in 50% of them the duration of the disease and the follow-up is less than 2 years, which may explain this percentage. The main purposes of the treatment are pain control, preservation of joint amplitudes, management and prevention of complications and facilitation of adequate psychomotor development. Thereby, MFR will play a predominant role in the multidisciplinary team responsible for the support provided to these patients, as seen by the 20% of patients referred to this clinic. A five-month-old girl was hospitalized following her consultation to the emergency department with discomfort and vomiting. She had dehydration with abdominal distention with no bowel sounds. Computerized tomography revealed generalize fluid in the abdominal cavity. Exploratory laparotomy demonstrated intense lipoid deposits in the mesenteric of the small and large intestines and the appendix. Histopathological examination showed necrotic foci, suppurative inflammation and fibrinous exudate of the omentum, compatible with mesenteric panniculitis. Case 2: A ten-year-old boy was consulted to emergency department with abdominal pain and nausea for two weeks. There was rebound tenderness in the right lower quadrant. The abdominal ultrasonography revealed appendicitis and the patient was operated. The omentum tissue was compatible with mesenteric panniculitis, and lymphoid hyperplasia with fibrolipomatous appearance was detected in the histopathologic investigation. The patient recovered following the operation. Consent had been obtained from the parents. Case 3: A fifteen-year-old girl with RF negative polyarticular JIA was in remission for three years. She had a progressive worsening of general condition with vomiting. Bilateral hydronephrosis was detected in abdominal ultrasonography, and a further MRI revealed retroperitoneal fibrosis surrounding perirenal tissue and ureters. Histopathologic examination, adipose tissue necrosis and septal fibrosis, but there was no amyloid deposition. IgG4 related disease was excluded. She was diagnosed as mesenteric panniculitis. Initial therapy with high dose steroids was successful. The maintenance therapy was provided with methotrexate and azathioprine. Tocilizumab therapy was started due to recurrence. She is still under remission for the last year. Conclusion: Mesenteric panniculitis is characterized by chronic nonspecific inflammation of the mesenteric adipose tissue of the small intestine and colon. It is reported as a very rare condition in children. Also, mesenteric panniculitis was characterized with different findings in these three cases and came up in an early age as 5-month old. It should be in the differential diagnosis of children with acute abdomen. Consent had been obtained from the parents. Introduction: Autoimmune blistering diseases (AIBDs) are a group of disorders mostly affecting the skin and mucous membranes. Occasionally, other organ systems may be involved, such as eye.

Objectives: We present two cases of severe childhood AIBDs referred to our Department with diagnosis of Rheumatic diseases. Methods: Case report Results: A 9-year-old girl with three years history of conjunctivitis with conjunctival scarring evolved in ocular sicca syndrome, was referred to our Department with diagnosis of Sjögren's syndrome, treated with high doses of steroids. Clinical history revealed also mucocutaneous involvement, with oral and anovulvar ulceration. Laboratory data showed anemia, elevated serum levels of ERS and CPR, normal serum levels of autoantibodies (ANA, anti-dsDNA, ENA). Biopsies of buccal mucosa, vulval skin, parotid and colon were performed. The histopathological study showed an infiltrate of lymphocytes, plasma cells and eosinophils; the direct immunofluorescence (DIF) showed linear deposition of IgG and C3 at the mucosal/submucosal junction. These findings were considered consistent with Sjögren's syndrome, and inflammatory bowel disease. Six months later the girl was admitted to our Department: the clinical examination revealed bilateral fornix foreshortening, symblepharon, entropion, corneal scarring, blisters around the nails, oral ulcerations; the vulval mucosa was completely denuded and adhesions were developing between the anterior aspects of the labia majora. The airway examination showed bilateral choanal atresia and laryngeal stenosis due to scarring. She started corticosteroid and she underwent surgery to remove cicatricial lesions of eyes, vulval area and choanae. Immunofluorescence findings of the surgical biopsies reveals the presence of linear homogeneous deposits of IgG and C3 along the epithelial basement membrane zone, therefore diagnosis of cicatricial pemphigoid (CP) was made. Ciclosporine was introduced without improvement, therefore after one month on the therapy was shifted to tacrolimus with initial response but worsening of ocular disease after two months. Many therapeutic trials were performed (thalidomide, cyclophosphamide and etanercept) without improvement. The patient was admitted to Intensive Care Unit, she underwent tracheostomy and died after 4 months. The second case is a 15-year-old girl with recent onset of oral e genital ulcers, referred to our Unit with suspect of Behçet's disease. She was on prednisone and cyclosporine. Laboratory data showed raised inflammatory markers and ANA positivity. At the admission the clinical examination revealed facies cushingoide, strie rubrae, multiple eruptions and blisters was found in her face, trunk, genital area and proximal limbs. Skin biopsy showed intraepidermal suprabasal acantholysis with infiltrate of lymphocytes and eosinophilis. Direct immunofluerescence showed IgG deposits at the surface of epidermal keratinocytes and confirmed the diagnosis of pemphigus vulgaris (PV). Oral prednisone combined with mycophenolate mofetil (MMF) resulted in complete clinical remission off therapy.

Introduction: Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by inflammation of the lacrimal and salivary glands, secondary to infiltration of lymphocytes and in the presence of auto antibodies (Anti-Ro and Anti-La). Primary SS occurs without association of other systemic autoimmune diseases, and is more often in women of medium to advanced age, being rare in childhood. It presents as dry mucosa surfaces of the mouth and eyes. In addition, 40% of the patients have extraglandular involvement, such as skin manifestations, musculoskeletal and neurological disorders. Systemic vasculitis manifestations of SS occur in approximately 5 to 10% of adult patients, however, the incidence decreases with age. Half of the individuals that develop vasculitis presents with a single episode, and histologically findings of leukocytoclastic vasculitis or necrotizing arteritis. These patients develop a more serious illness and have a worse prognosis. Objectives: We describe a pediatric patient with leukocytoclastic vasculitis as the initial clinical manifestation of Sjögren's Syndrome. Methods: Descriptive. Clinical case presentation. Results: A 13 year old female, referred to the Pediatric Rheumatology Department, with a year of palpable purpuric lesions, in both lower extremities, limited to the knees, and associated with painful edema of the ankles. The manifestations became recurrent, being treated with low dose oral steroid for two months without remission. Subsequently the patient developed dry eye, with recurrent episodes of conjunctivitis and arthralgia in both ankles and knees. Laboratory finding include elevated ESR 43mm/hr, and FR, 37.1 Ul/ml, anti-SS-A (Ro) 198.74 RU/ml and anti-SS-B (La) 200 RU/ml, IgA 411 mg/dl and IgG 2410 mg/dl, IgG1 11600 mg/dl, ANA fine speckled 1:640. The rest of immunological and serology profile was negative. Minor salivary gland biopsy reported chronic sialodenitis with inflammatory lymphoplasmocytic infiltrate and intralobular infiltrate around the ducts and the rest of the lobules, compatible with SS. Skin biopsy reported leukocytoclastic vasculitis. With this finding we integrated primary SS and we started high dose steroid for ten days and immunomodulation with hydroxychloroquine, in addition to sunscreen and eye lubricant. The patient responded to this treatment, with remission of cutaneous manifestations and improvement of ocular symptomatology. Introduction: Fever is the most common reason for pediatric counseling and when it becomes persistent, even the most rare causes need to be considered. Objectives: We present the diagnostic approach to persistent fevers in pediatric patients by describing 5 exemplary case reports. Methods: Diagnostic hypotheses were formulated according to the medical history, detection of pathological signs at the physical examination and the results of laboratory and imaging tests.

Results: Case report 1. 3-year-old girl with high fever recurrent every month since a year, lasting about 5 days and associated with pharyngitis, aphthous stomatitis, cervical lymphadenitis with neutrophilic leukocytosis and increased erythrocyte sedimentation rate (ESR) and Creactive protein (CRP). Between episodes, the patient was asymptomatic and laboratory tests were normal. With the passing of the years, these episodes were reduced in intensity and frequency until they disappeared completely 6 years later. The patient, nowaday adult, has grown up normally thus confirming PFAPA syndrome diagnosis. Case report 2. In the last 6 months, 8-year-old male child reported 5 episodes of periodic fever, lasting about 3 days and associated with abdominal and thoracic pain, arthralgia and myalgia particularly in the lower limbs. Laboratory tests showed neutrophilic leukocytosis and increased ESR and CRP, while diagnostic imaging tests were negative. Suspected diagnosis of FMF was confirmed by genetic analysis and satisfactory response to colchicine therapy. Case report 3. 14-year-old girl with intermittent fever (37,5°C-37,8°C) since 2 month, associated with asthenia and pains in the lower limbs. Physical examination showed arthritis of the knees. Diagnostic tests showed anemia, increased ESR and CRP, presence of antinuclear antibodies (ANA), anti-native DNA and anti-Sm antibodies confirming the diagnosis of SLE. Case report 4. 10-year-old girl reported muscle weakness associated with low-grade fever since about a month. Physical examination showed muscular hypostenia in the upper and lower limbs and in the neck muscles, Gottron papules in the metacarpophalangeal joints and eyelid rash. Blood tests showed an increase in ESR, CRP, muscle enzymes (LDH, aldolase, CK and transaminases) and presence of ANA. Electromyography revealed reduction in amplitude and duration of action potentials; magnetic resonance imaging revealed signs of muscular inflammation confirmed at biopsy, thus supporting JDM diagnosis. Case report 5. 13-year-old girl reported several episodes of persistent fever lasting 3 -4 consecutive days since at least 1 year. Physical examination revealed maculo-erythematosus rash, splenomegaly and asymmetric polyarthritis of the knee, hip, ankle, wrist and hip, while blood tests showed anemia, increased ESR and CRP, leukocytosis and thrombocytosis. Blood culture, bone marrow needle aspiration, the research of vanilmandelic and homovanillic acid in the urine all turned out to be normal. Radiological examinations of the joints affected by signs of arthritis highlighted just joint space narrowing and erosions, thus finally confirming s-JIA diagnosis. Conclusion: Persistent fevers in pediatric patients may have not only an infectious, vasculitic or oncologic etiology, but also autoimmune or autoinflammatory causes. Informed consent to publish had been obtained.

1,2%; 22. Others ophthalmologic conditions 1,1%, 23. Normal variants 1,0%; 24. Vascular malformations 1,0% (primary and secondary lymphedema 0,6%); 25. Miscellaneous conditions 9,9%. Globally, "Rheumatic Diseases" represent 45,4% (Groups 1, 4, 7, 8, 9, 14, 17) and "Non Rheumatic Diseases" 54,6%. Conclusion: The many differential diagnosis of the rheumatic diseases justifies the reason for the many different pathologies observed in pediatric rheumatology units. It also justify that less than half of the patienets observed in our unit had the classic "Reumatic Diseases". The sum of Nonspecific musculoskeletal pain, Amplified pain syndromes and excess Laboratory diagnostic investigation represents 30% of patients observed, also justifying the need of training in basic issues of pediatric rheumatology. Conclusion: SSc is very rare in children. The incidence of juvenile SSc is around 0.05 per 100,000 children. In our study the ratio of SSc to LS was 1/23. Juvenile LS (JLS) is more common in girls (female to male ratio 2.4: 1) with mean age-at onset of 7.3 years. According to our results, female-to-male ratio of LS was 3.8/1 and the mean ageat-onset of LS was similar to literature as 9.13±4.13 years. Laboratory results are suggestive, but not specific enough for diagnosis of scleroderma. There is no single therapy for JS. MTX had been successfully used both in adults and in children with localized scleroderma. MTX and/or corticosteroids (oral or intravenous) are accepted as first line treatment.

In conclusion, juvenile scleroderma is very rare in children, and characterized by the thickening and hardening of the skin. Most presented as a localized form of the disease. Close monitoring of the disease status and treatment response is important for clinical evaluation and early clarification of disease complication. The prognosis of LS in children is better than in adults. If disease showed progressing clinically, it should be treated aggressively even when the skin lesion are localized initially. There is a need for new studies for better understanding of the prognosis, evaluation of the disease and new treatment modalities. Introduction: SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) belongs to autoinflammatory diseases without genetic correlation. The incidence of the disease is very low, and the disease is classified as an orphan disease. In addition to skin manifestation, clinical manifestation includes musculoskeletal symptoms, with a dominant affection of the axial skeleton, therefore the SAPHO syndrome is currently classified as juvenile spondylartropathy. A frequent location of aseptic inflammation, in addition to axial involvement, is the area of the anterior wall of the cheststernoclavicular and sternocostal joints. The syndrome may not be fully expressedskin manifestations often occur independently, and only after several months, synovitis and osteitis develop, or vice versa. In the active stage of the disease, increased inflammatory parameters (erythrocyte sedimentation, CRP) can be observed. Imaging examinations (magnetic resonance imaging and scintigraphy) have an irreplaceable role in diagnosis. Differential diagnosis is necessary to exclude particularly an infectious process and neoplasia, therefore biopsy examination is a "gold standard". Current treatment options include the use of disease-modifying antiinflammatory drugs (NSAIDs, antibiotics, corticosteroids, sulfasalazine, methotrexate). For relapsing and high-activity forms of the disease, there is sufficient data on the use of biological treatment (adalimumab, infliximab). The response to the treatment determines the prognosis of the patients; with the good response to DMARDs, the prognosis is optimal. Objectives: We present the case of a 17-year-old patient initially admitted with back pain in the lumbosacral region. In the course of two weeks, the condition progressed into a spastic triparesis with the impossibility of independent walking. The patient had a history of a total and local acne conglobata treatment lasting for several months. Laboratory parameters showed high inflammatory activity with insufficient response to broad-spectrum antibiotic therapy. Cerebrospinal fluid analysis and imaging examination of brain, C, Th, LS spinal cord without pathology. Due to oedema and tenderness of the sternocostal joint to the left, the MR examination was carried out with the finding of an inflammatory processosteitis; the SAPHO syndrome is considered for the first time. Scintigraphy with a picture of high rearrangement and increased perfusion in the clavicle, in the sternoclavicular joints, sacroiliac articulations, in both ischial bones. Biopsy of the sternoclavicular joint confirmed chronic non-specific synovitis. Based on both clinical and laboratory findings, the patient met the SAPHO syndrome criteria. Methods: Case report. Results: The purpose of the case report was to point to differential diagnostic pitfalls, which led to a definitive diagnosis of autoinflammatory disease. At the same time, we provide an overview of the current therapeutic options for this rare disease , especially the effectiveness of biologic drugs in our case. Conclusion: The purpose of the case report was to point to differential diagnostic pitfalls, which led to a definitive diagnosis of autoinflammatory disease. At the same time, we provide an overview of the current therapeutic options for this rare disease , especially the effectiveness of biologic drugs in our case. Informed consent to publish has been obtained from the patient. Introduction: Systemic juvenile idiopathic arthritis (sJIA) has a special place among childhood arthritis with a broad spectrum of mild to severe joint problems and significant extraarticular features. Objectives: It is aimed to present the characteristics of sJIA patients who are followed in Izmir Dr. Behcet Uz Children's Hospital. Methods: The medical files of 12 sJIA patients who are followed in Izmir Dr. Behcet Uz Children's Hospital were investigated retrospectively. Results: Six girls and six boys with sJIA were included in the study. The median age was 115.5 months (min-max: 15-195 months), median diagnosis age was 74,5 months (min-max: 10-122 months), and median follow-up time was 20 months (min-max: 1-84 months). The median delay for the diagnosis was 12 days (min-max: 7-30 days). All the cases had intermittent fever. The half of the patients showed rashes and/or joint involvement. Serositis was present in only one patient (8.3%). The complications were as follows: macrophage activation syndrome (MAS) in 4 patients, and severe growth retardation due to long-term corticosteroid use in 1 patient. Lymphadenopathy, HSM, and uveitis were not present in any cases. The cases were using the following medications: NSAID (8.3%), steroid (41.7%), methotrexate (66.7%), anakinra (8.3%), canakinumab (25%), tocilizumab (33.3%). While no remission was achieved in 1 case, 9 cases achieved remission under medical treatment. Two patients (16.7%) have achieved remission without need of medications. The laboratory findings regressed to the normal levels following the treatment (p<0.05). Conclusion: sJIA is a differential diagnosis and it might take a while to diagnose a patient with sJIA. This delay might lead unwanted situations as MAS. sJIA might be controlled with proper treatment plans. Introduction: In children with lupus nephritis, 24 hour estimation of urinary protein measurement is considered as gold standard. But it is fraught with difficulties of collection.This study was undertaken to find out if a random urine spot protein/creatinine is reliable and can be interchanged with a 24 hour urine protein estimation Objectives:

1. To find out the correlation of spot protein/creatinine estimation and 24 hour urine protein estimation 2. To find the value of spot protein/creatinine ratio that best correlates with the 24 hour protein value

Methods: 209 paired samples of spot protein/creatinine ratio and 24 hour urine protein were retrospectively recorded from charts of 64 children with lupus nephritis. Statistical analysis was done using SPSS version 16.1. Results: Spot protein creatinine ratio showed a good correlation with 24 hour urine protein values with p value <0.01.The correlation was poor for spot protein/creatinine ratio <0.5(p value=0.5).

Using ROC, the cut off value of spot protein creatinine ratio to predict nephrotic range proteinuria (>1gram) was 1.81 with area under curve 95%(0.875). 95% confidence interval(0.817-0.932). Sensitivity 73.1%, specificity 90.8%. Positive predictive value is 0.79, negative predictive value 0.87. Conclusion: The spot protein/creatinine ratio in ranges>0.5 correlate well with 24 hour protein values and can be reliably used in routine clinical practice.The urine spot protein/creatinine ratio can thus be utilised fairly accurately as a guideline to determine whether child has nephrotic range proteinuria or not.It however cannot be used interchangeably in higher values of spot protein/creatinine ratio. 

Outcome and Complications in Children with Systemic Onset Juvenile Idiopathic Arthritis

Systemic-onset juvenile idiopathic arthritis. Autoimmunity reviews

Juvenile Idiopathic Arthritis. Balkan medical journal

Poststreptococcal reactive myalgia: a novel syndrome secondary to infection with group A or G streptococci

A rare case of recurrent poststreptococcal myalgia

Post Streptococcal Myalgia: An Underrecognized Clinical Syndrome

Juvenile idiopathic arthritis. Lancet

Network analysis and juvenile idiopathic arthritis (JIA): a new horizon for the understanding of disease pathogenesis and therapeutic target identification

Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis

American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Initiation and Safety Monitoring of Therapeutic Agents for the Treatment of Arthritis and Systemic Features

American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis

A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein

Measurement of health status in children with juvenile rheumatoid arthritis

Pediatric ocular rosacea, a misdiagnosed disease with high morbidity: Proposed diagnostic criteria

Blepharokeratoconjunctivitis in children

Clinical spectrum of pediatric blepharokeratoconjunctivitis

Ocular rosacea: Common and commonly missed

Pediatric Ocular Rosacea: 2 Cases

Wimalasundera Employee of: Roche, I. Calvo Penades: None Declared, R. Cuttica Consultant for

Opoka-Winiarska V. Vaccination in paediatric and adult patients with rheumatic diseases

Factors associated with the use of complementary and alternative medicine in juvenile idiopathic arthritis

Complementary and alternative medicine use among youth with juvenile arthritis: are youth using CAM, but not talking about it?

Longitudinal analysis of complementary and alternative health care use in children with juvenile idiopathic arthritis

Unconventional remedies used for patients with juvenile arthritis

Adverse events associated with the use of complementary and alternative medicine in children

Diphtheria & Tetanus Antibodies, IgG

World Health Organization, Tetanus position paper

World Health Organization, Diphtheria position paper

Pharm-Allergan (honoraria for lectures), J. Breedt: None Declared, X. Li Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, R. Wong Shareholder of: Bristol-Myers Squibb, Employee of

Congress 2016: poster P215. Disclosure of Interest T. Simon Shareholder of: Bristol-Myers Squibb

Employee of: Bristol-Myers Squibb, N. Ray Consultant for: Bristol-Myers Squibb, S. Singhal Consultant for: Bristol-Myers Squibb, H. Kawabata Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb (retired), D. Lovell Grant / Research Support from: AbbVie

Are RASopathies new monogenic predisposing conditions to the development of systemic lupus erythematosus? Case report and systematic review of the literature

JMML and RALD (Ras-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities

Authors thank FAPESP (grant 2012/22997

Authors thank São Paulo Research Foundation (FAPESP grants 2008/58238-4 and 2012/22997-4) and Fundação para a Ciência e a Tecnologia, Portugal (Postdoctoral fellowship SFRH / BPD / 111454 / 2015) for their financial support

Walker Consultant for: Novartis Pharmaceutical Corporation, H. Tilson Consultant for: Novartis Pharmaceutical Corporation, P. Hawkins: None Declared, T. Van der Poll: None Declared, K. Franke Consultant for: Novartis Pharmaceutical Corporation, A. Speziale Employee of: Novartis Pharma AG, E. Vritzali Employee of

Tamer Rezk 2

University College London; 3 Department of Infection, Inflammation and Rheumatology, UCL Great Ormond Street Institute of Child Health; 4 National Amyloidosis Centre, Division of Medicine

Activated STING in a vascular and pulmonary syndrome

References 1. Recessive coding and regulatory mutations in FBLIM1 underlie the pathogenesis of chronic recurrent multifocal osteomyelitis (CRMO)

Trial registration identifying number: Our data seem to confirm a possible role of FBLIM1 in the pathogenesis of CNO suggesting that CNO is a disorder of chronic inflammation and imbalanced bone remodeling

Recessive coding and regulatory mutations in FBLIM1 underlie the pathogenesis of chronic recurrent multifocal osteomyelitis (CRMO)

Pediatric Rheumatology, Hospital Niño Jesus; 4 Pediatric Rheumatology, Hospital Ramon y Cajal, Madrid; 5 Pediatric Rheumatology, Hospital Virgen del Rocío, Sevilla; 6 Pediatric Rheumatology, Hospital Doce de Octubre, Madrid; 7 Pediatric Rheumatology

Pediatric Rheumatology, Hospital Marques de Valdecilla

Hospital Virgen de Arrixaca, Murcia; 10 Pediatric Rheumatology, Hospital Infanta Cristina, Badajoz; 11 Pediatric Rheumatology, Hospital de Getafe, Madrid; 12 Pediatric Rheumatology

Introduction: Biologics are the most effective drugs for treatment of juvenile idiopathic arthritis (JIA) in the cases of methotrexate (MTX) inefficacy or intolerance. The question about superiority of combination therapy (biologics+MTX) above monotherapy is still open. In some studies were shown that combination therapy is more effective, but others did not show any differences. The problem of MTX intolerance has been still actually, especially in adolescent patients. Several studies confirm that MTX can prevent development anti-drug antibodies avoiding to loss their efficacy. In patients with remission the MTX discontinuation leads to flare of JIA in 10-15%. Objectives: to evaluate the role of MTX discontinuation in flare risk and survival of first biologic medication in non-systemic JIA. Methods: in the study were included 692 non-systemic JIA patients, whom biologic therapy was prescribed. Inclusion criteria: patient whom first biologic was administrated with or without MTX or MTX was discontinued after start of biologics due to different reasons (remission, intolerance, adverse events)

There were no differences in flare probability (p=0.4) and probability of switching biologics (p=0.46) between subgroup of TNFa inhibitors: etanercept mono; etanercept +MTX, adalimumab mono, adalimumab+MTX. Conclusion: we suppose that discontinuation of MTX due to remission or intolerance does not increase the flare rate and probability of flare, switching the first biologics and probability to switch in non-systemic JIA patients with first administered biologics. Further trials are required

Introduction: Methotrexate (MTX) is the "gold standard" treatment of juvenile idiopathic arthritis (JIA); however, this therapy is not always effective and predictable, most often in connection with toxicity.The aim of our study was to identify the relationship between inefficient assignment of MTX and the presence of folate exchange genes polymorphism. Objectives: In the period between 2016 and 2017 in the Department of Pediatrics of the hospital "OKHMATDYT" 79 children between the ages of 5 and 18 (mediane 12.8 years old) were diagnosed with JIA. All children were initially treated with MTX. 15 children were also given biological therapy during the first year of treatment. Methods: Due to the ineffectiveness of basic therapy and toxic effects of MTX(nausea, vomiting, toxic hepatitis), 11 children were further studied for the molecular genetic study of folate exchange genes polymorphism (MTHFR C677T, rs1801133 and A1298C, rs1801131; MTR1 A2756G; rs1805087; MTRR A66G; rs1801394; RFC1 G80A; rs1051266), homocysteine levels, folic acid and vitamin B12 in the serum. Of the 11 children examined, 4 had a systemic variant of JIA with the active arthritis

children had showed an increase in homocysteine levels: 5.9-8.6 μmol/l(norm-5 μmol / L), 2-increasing the level of vitamin В 12: 980-1530 pg/ml (norm-174-878 pg/ml), the level of folic acid in serum was within regulatory limits

None Declared, T. Simon Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Martini Grant / Research Support from: Istituto Giannina Gaslini has received contributions from: Bristol-Myers Squibb

Disclosure of Interest None Declared P395 DETERMINANTS OF PATIENT 'PERCEPTION OF DISEASE ACTIVITY IN A MULTINATIONAL COHORT OF OLIGOARTYCULAR AND POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS

Miroslav Harjacek 3 , Miroslav Harjacek 3

Istituto Giannina Gaslini

Methods: Clinical charts of patients with JIA recruited at one of the 16 centres in the ReACCh-Out cohort (diagnosed 2005-2010) were assessed at the last available follow-up visit for disease activity, clinical remission on or off medications (Wallace criteria), and articular and extra articular damage Results: From the identified eligible cohort 236 subjects (97.5%) had follow-up information until discharged or transferred to adult care; 135(57.2%) were females and the median age was 17.2y (IQR 13, 18)

at least one erosion or joint space narrowing, 2 (1%) had avascular necrosis and 5 (2%) required joint surgery. Table 1 depicts outcomes at last visit for each JIA category. Patients with systemic JIA had the highest frequency of remission off medications (68%)

Istituto Giannina Gaslini , Genoa; 6 IRCCS Ospedale Pediatrico Bambino Gesù

Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany; 9 ASST Mantova

Objectives: EULAR/PReS task force objective was to develop EULAR/ PReS Standardized Procedures for Ultrasound Imaging in Pediatric Rheumatology through a consensus process among rheumatologists, paediatric rheumatologists, and radiologists highly experienced in the performance, teaching and research in paediatric MSUS in rheumatologic diseases. Methods: In the first phase we performed a systematic literature review (SLR) on guidelines for MSUS for children published by international societies and articles on how to perform MSUS scanning in children. Based on the SLR results, project conveners (JV and PC) formulated a Delphi survey by selecting the items to be included (i.e. musculoskeletal anatomic structures evaluable by ultrasound, scanning technique, and their lesions/abnormalities detectable by ultrasound at the principal joint areas). The Delphi survey was distributed among a broad panel of experts in MSUS (i.e. rheumatologists, paediatric rheumatologists, radiologists), selected by their high experience in the performance, teaching and research in MSUS in children. Based on the Delphi results main anatomical structures (for definitions, photo and video recordings) were selected to be used in the final phase organized as an exercise (lasting 4 days) on live healthy children models. The meeting involved: 16 project participants (13 pediatric US experts, fellow, as well as, AHP and PARE representative), 16 healthy children models (representing four different age groups) accompanied by their parents (who has signed informed consent to participate), 4 photo/imaging technicians, 2 expert US machine technicians. Results: Structures from nine musculoskeletal areas (i.e. shoulder, elbow, wrist and hand, hip, knee, ankle and foot) in four age groups of children were selected. Detailed scanning procedures (i.e. patient position, probe placement, scanning method and bony/other landmarks) were used to produce the photo and video records of the scanning procedures. As a result, we obtained photo and video image library with a detailed description of the standardized procedures

Sezgin Sahin 1 , Kenan Barut 1 , Oya Koker 1 , Serdal Ugurlu 2 , Huri Ozdogan 2 , Ozgur Kasapcopur 1 1 Department of Pediatric Rheumatology; 2 Department of Internal Medicine

There was no statistically significant difference between different patients groups regarding the age of transition. The education levels of patients were as following: university 60 (61.9%), high-school 21 (21.6%), middle-school 13 (13.4%), primary school 3 (3.1%). Majority of patients was single at the time of study (79 (81.4%) patients) while only 18 (18.6%) patients were married; half of them being child owner. At the time of study, 44 (30%) patients were employed and mean age at employment was 19.06±3.1 years. Most of patients had health insurance at the time of study (94 (96.9%)). Seventy-one (73.2%) patients continued their regular follow up at adult department while 26 (25.8%) patients discontinued medical treatment. The most common reasons for cessation of follow up were the work/ school absence (20 (76.9%)), followed by patients' personal reasons (2(7.6%)) and dissatisfaction with adult clinic services (4(15.5%))

Most studies (82%) were conducted in either North America or Europe. The most commonly studied diseases were SLE (in 61% of studies), IIM (18%), and systemic sclerosis (11%). The most commonly reported primary outcomes were organ damage (29%), cardiovascular outcomes (14%), and mortality (14%). The mean ages at outcome assessment were 19.5 -46.8 years for adult-only studies and 19.3 -35 years for mixed studies. Moderate to high risk-of-bias was found in 100% of studies for study participation, 90% for study attrition, 61% for prognostic factor measurement, 36% for outcome measurement, 89% for confounding, and 54% for statistical analysis. Conclusion: There is clear need for more information about adulthood outcomes of ChildSARDs. Longitudinal data collection and analyses were especially lacking. We recommend that future studies on Child-SARD outcomes be undertaken in the framework of a longitudinal cohort, have adulthood outcomes separately reported from outcomes in childhood, and have study populations clearly defined to allow for accurate MESH coding so as to facilitate easy searching for such information and for knowledge dissemination. Careful attention should be paid especially during study design to reduce bias in choice of study populations, accounting for attrition and confounding

Pediatric Rheumatology, Posgraduate of pediatrics

Universidad El Bosque, Bogota; 4 Pediatric Rheumatology. Posgraduate of pediatrics

Universidad de Cartagena, Cartagena; 6 Pediatric Rheumatology. Posgraduate of Pediatrics

Disclosure of Interest None Declared Reference Jean-Baptiste G, De Ceulaer K.Osteoarticular disorders of haematological origin

Paediatric Neurology; 4 Paediatric Biochemistry, Royal Hospital for Children, Glasgow; 5 Paediatrics, Raigmore Hospital, Inverness; 6 Paediatrics, Royal Alexandra Hospital

Idiopathic inflammatory myopathies -a guide to subtypes, diagnostic approach and treatment

Immune-Mediated Necrotizing Myopathy: Update on Diagnosis and Management

Autoimmune hepatitis as a presenting manifestation of mixed connective tissue disease in a child Case report and review of the literature

Simultaneously developed polymyositis and autoimmune hepatitis

Alcobendas 1 , Agustin Remesal 1

The mean age at onset was 25.5 ± 10 months, all of them younger than 4 years. The mean delay time until diagnosis was 15.6 ± 8 days (3-32). Eleven patients (44%) presented fever at some point in the evolution, being other reasons for consultation: rejection of sitting (44%), limp (36%), pain (28%), immobility (24%), irritability (20%) and abdominalgia or hyperlordosis (both 8%). In addition, 9 patients (36%) associated previous or concomitant upper respiratory infection. Blood test was performed in all patients, obtaining erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) in 22 and 23 cases, respectively

All the children had a good response to the treatment and did not present follow-up sequelae. Conclusion: Osteoarticular infections affecting the axial axis were infrequent in our hospital. Moreover, the symptoms at onset was nonspecific and without accompanying fever in more than half cases. For those reasons, high index of suspicion is needed. The rejection of sitting or irritability were complains that should put us on alert

FARBER DISEASE: INITIAL RESULTS FROM AN ONGOING GLOBAL NATURAL HISTORY STUDY COLLECTING RETROSPECTIVE AND PROSPECTIVE CLINICAL DATA IN ACID CERAMIDASE DEFICIENCY, WHICH IS OFTEN MISDIAGNOSED AS JIA

UCSF Children's Hospital Oakland, Oakland; 3 Children's National Medical Center

Children's Hospital of Cordoba

Magnusson: None Declared P421 CHALLENGES IN ACHIEVING CONSENSUS FOR VACCINATION WITH LIVE ATTENUATED VACCINES IN CHILDREN WITH RHEUMATOLOGICAL DISEASE -THE VARIABILITY OF VACCINATION PRACTICES ACROSS THE GLOBE Natasa Toplak 1 , Yosef Uziel 2

Bratislava, Slovakia; 11 General Univ. Hosp.,1st Faculty of Med

The Netherlands and Norway where vaccinations are optional, the vaccination rate is high, at around 95%. However, coverage for MMR fell below 95% in Croatia, Czech Republic, Serbia and Slovenia, where vaccination is mandatory. Vaccinations were optional in France and Italy; however, due to low coverage, they are now mandatory. Conclusion: There are considerable differences amongst countries in vaccination programmes, coverage, and in parental obligation to vaccinate their child. A powerful anti-vaccine campaign has gained momentum in many countries and has resulted in a significant drop in vaccination coverage to a level that is no longer sufficient for herd immunity. This is especially dangerous for children with rheumatic diseases on immunosuppressive therapy. Our future goals are to prospectively examine the outcomes of live vaccination in children with rheumatic diseases who are treated with immunosuppressive drugs and hopefully to demonstrate

B01 Introduction: Pericarditis is the inflammation of pericard and may occur following infections, malignancy, autoimmune and autoinflammatory diseases. It might be acute, chronic and recurrent. It might be life threatening by altering the hemodynamics of the heart and causing constructive pericarditis. Objectives: The patient with TRAPS was reported. Methods: The patient's file rewieved retrospectively. Phsical examination, laboratory test, imaging and genetic analyses results evaluated. Results: CASE: A fifteen-year-old girl was consulted to the emergency department with high fever and chest pain

Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever patients complicated with amyloidosis

Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis

A proposed histopathologic classification, scoring, and grading system for renal amyloidosis: standardization of renal amyloid biopsy report

Chernenkov Department of Hospitality Pediatrics

Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis

Development and validation of a composite disease activity score for juvenile idiopathic arthritis

Muresan Shareholder of: none, Grant / Research Support from: none, Consultant for: none, Employee of: none, Paid Instructor for: none

Methods: She was otherwise well and there was no family history of note. Blood tests including full blood count, inflammatory markers, thyroid function, renal and bone profile were normal. On examination, she was noted to have painless multiple soft tissue swellings, varying in size from 0.5cm to 4cm across her phalanxes and the dorsum of her feet. These were raised with no overlying skin changes. An xray of her foot showed no evidence of bone or joint space abnormality. She went on to have an ultrasound of her right foot, where multiple well defined simple fluid structures consistent with ganglion cysts were evident. This was confirmed with a MRI of her right foot, which showed multiple simple cysts adjacent to and communicating with the joints of the foot, predominantly the tarus. Results: A diagnosis of cystic ganglionosis was made and she has been referred to the National Centre of Rheumatology for further review

A rare case of cystic ganglionosis in a child with associated imaging findings

Multiple ganglion cyst ('cystic ganglionosis'): an unusual presentation in a child

Pleural and Pericardial Associations After Minimal Pectus Repair

Etiology of Pericarditis Cohort of 1162 Cases

Postpericardiotomy syndrome after thymothymectomy: report of two cases

Some of the people, some of the time: susceptibility to acute rheumatic fever

HLA class II DR and DQ genotypes and haplotypes associated with rheumatic fever among a clinically homogeneous patient population of Latvian children

Gamze Arın 1 , Lauren Trotman 2 , Susan Maillard 2

Great Ormond Street Hospital for Children

Harlequin Ichthyosis and Inflammatory Arthritis: Case Reports of a very Rare Combination

Harlequin ichthyosis and juvenile idiopathic arthritis: a rare combination

Harlequin Ichthyosis in Association with Hypothyroidism and Juvenile Rheumatoid Arthritis

JIA) and it is associated with enthesitis related arthritis 1 , .spondyloarthropathies and reactive arthritis. 2 Objectives: Our objective is to investigate associations of HLA-B27 and the joint involvement in JIA patients and to determine which of the JIA subtypes most frequently has positive HLA-B27. Methods: The retrospective analysis included 21 HLA-B27 positive JIA patient hospitalized in a referral rheumatology centre in the period of two years Patients were followed for sixth months. The diagnosis of JIA was based on criteria by the International League of Association for Rheumatology (ILAR). 3 Detection of HLA -B27 was done by using a DNA-based PCR-SSP test. Results: In our group of 21 HLA B27 positive JIA patients, there were diagnosed JIA subtype was enthesitis related arthritis (ERA) in 8 patients (38.1%), followed by an oligoarticular JIA in 7 patients (33%) and polyarticular JIA in 5 children (23.8%). One patient could not fit any JIA category so he was diagnosed as having undifferentiated JIA

B18 Introduction: There are multifactorial causes of decrease in bone mass in JIA patients which correlate with the duration of active disease.By measuring the vitamin D level we can assess the deficiency or insufficiency earlier and can predict the risk of osteoporotic bone fracture and give appropriate supplementation of vitamin D and calcium. Objectives: This study was done to determine the status of serum 25(OH)D

Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborat

How to Treat Involvement of the Central Nervous System in Hemophagocytic Lymphohistiocytosis?

Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome

Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study

Only one patient had a diagnosis of SoJIA, which was recognized several days before the diagnosis of MAS. The mean duration of their symptoms prior to diagnosis was 20 days (range: 9-44 days), while the mean duration of hospitalization prior to diagnosis was 8 days (range: 1-24 days). All patients presented with fever, 7 presented with rash and joint paint and 2 with arthritis. Regarding the laboratory investigation which correlates with the MAS criteria, mean ferritin was 16.714 ng/ml (range 150-44.000), mean platelet count was 170 x 10 9 / liter (range 48-459 x 10 9 /liter), aspartate aminotransferase was 172 U/l (range 24-621), mean triglycerides 260 mg/dl (range 79-700) and mean fibrinogen 309 mg/dl (range 70-577). 7 patients revealed macrophage hemophagocytosis in bone marrow biopsy. 4 patients were admitted to the Intensive care Unit. Furthermore, 6 patients B35 LEUKOCYTOCLASTIC VASCULITIS AS THE INITIAL CLINICAL MANIFESTATION OF PRIMARY SJÖGREN'S SYNDROME IN A 13-YEAR-OLD FEMALE PATIENT

Methods: A total of 3.451consecutive referrals to Coimbra's Pediatric Rheumatology Department during the period 1987-2017 (31 years) were analyzed. The main diagnosis, 1 to 4 per patient, were prospectively analyzed. The diagnostic criteria of each disease or syndrome were those used in recent textbooks of Pediatric Rheumatology 1,2 . Patients were classified in 25 large groups. The non-classifiable conditions were grouped into symptomatic groups. The main diagnosis (no more than four per patient) were recorded.The diagnostic criteria of each disease were those used in recent textbooks of Pediatric Rheumatology 1,2 . Patients were classified in 25 large groups. The non-classifiable conditions were grouped into symptomatic groups. Results: Among the 3.451 patients we established 4.147 different diagnosis: average 1,2 diagnosis/child, justifying 120% of diagnosis comparatively to the number of patients. The distribution of the 25 groups was: 1

Textbook of Pediatric Rheumatology

Longitudinal Analysis of a Pediatric Clinic Population

Disclosure of Interest None Declared B42 ASSOCIATION OF RAGHIB SYNDROME WITH AUTOIMMUNE PANCREATITIS (EXTREMELY RARE ASSOCIATION Shima Salehi 1

Iran University of Medical Siences; 2 Pediatric Cardiology; 3 Pediatric gastroenterology, Hazrate Rasool General Hospital

Urine protein-to-creatinine ratio is a reliable measure of proteinuria in lupus

Can spot urine protein/ creatinine ratio replace 24 h urine protein in usual clinical nephrology?

Sixty patients (52.17%) were treated with only one BA. In this patients, etanercept in 26 patients, adalimumab in 28 patients, infliximab in 3 patients, tocilizumab in 3 patients were given as the first BA. Thirty-one patients with inactive disease, 19 patients with active disease were still treated with first BA. Biological agents were stopped in 9 patients treated with one BA (clinical remission: 6, adverse event: 2, lack of effectiveness: 1). Twenty-nine patients had once, 7 patients had twice, 2 patients had three times, 1 patients had five times, 1 patient seven times switches. For all BA switches

Ten local reactions, 4 allergic reactions, 3 anaphylaxes were documented. Conclusion: In JIA, biological agents are switched for many reasons such as lack of effectiveness, disease activation, adverse event and noncompliance to treatment. In our study, most common reason of switch was the lack of effectiveness. Also

This work was supported by an institutionnal grant from NORDIC Pharma to ANDAR. All medical experts and patients volunteered. Gaslini Hospital, which is the public Hospital where NR works as full time public employee, has received contributions from the following industries for the coordination activity of the PRINTO network: BMS, GlaxoSmithKline (GSK), Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Abbott, Francesco Angelini S.P.A., Sobi, Merck Serono. This money has been reinvested for the research activities of the hospital in fully independent manners without any commitment with third parties, Speaker Bureau of: NR has received speaker's bureaus and consulting fees from the following pharmaceutical companies: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH., A. Ravelli: None Declared, A. Consolaro: None Declared

Introduction: Juvenile idiopathic arthritis (JIA) is the most prevalent pediatric rheumatic disease [1] . Long term complications include physical disability and a decreased quality of life [2] . Since the introduction of anti-TNF drugs for JIA, its prognosis has improved significantly [1, 3] . Personalized medicine is the next step to improve treatment in JIA. Anti-TNF trough levels and demonstration of the presence of anti-drug antibodies (ADA) could help individualize treatment decisions in JIA patients, but evidence supporting this is missing. Objectives: To describe cross-sectional data of anti-TNF trough levels and ADA, combined with decision effects, in children with JIA. Methods: Patients' records in children with JIA using etanercept, adalimumab or infliximab were retrospectively checked for measurements of anti-TNF trough levels and ADA. Anti-TNF trough concentrations and ADA were measured using an enzyme-linked immunosorbent assay (ELISA) and antigen-binding test. Data on age, sex, JIA subtype, reason for testing and the decision effect of trough level or presence of ADA on the current therapy were collected. Results: Eighty-one anti-TNF trough levels were measured in 45 children with JIA. A wide variety of anti-TNF trough levels was found. Therapeutic drug concentrations, according to adult ranges in RA and IBD [4, 5, 6] , were found in 11 (58%) patients on etanercept (n=19), 2 (14%) on adalimumab (n=14) and 8 (17%) on infliximab (n=48). Four patients on adalimumab and one patient on infliximab showed ADA. All of these five patients had non-detectable drug trough levels. Reasons for testing trough level and/or presence of ADA were loss of response (20%), partial or no response (40%), measurement after dosage increase (2%), remission (17%), uveitis flare (9%) and allergic reaction (11%). Treatment decisions were influenced by trough levels in 70/81 (86.4%) of measurements and in 5/5 (100%) of patients with ADA. Conclusion: Measuring anti-TNF trough levels and ADA was a valuable tool in making personalized treatment decisions in JIA. Treatment changes included dose/frequency increase, or stopping and switching treatment in the presence of ADA combined with undetectable drug levels. Variation in anti-TNF trough levels seems even greater in children than in adults. More data are needed to access optimal therapeutic drug levels in anti-TNF treatment in JIA and to implement this strategy more widely. Introduction: Poor submaximal capacity is previously reported in juvenile idiopathic arthritis (JIA) patients, and is often assessed by the 6 minute walking test. However, due to improved management of JIA, there is a need for a more physically challenging submaximal test to measure submaximal capacity in JIA patients, and also to estimate peak oxygen uptake (VO 2 peak ). Objectives: To estimate VO 2peak and measure submaximal parameters using an eight-minute submaximal treadmill test 1 in oligo-and polyarticular JIA patients and controls. Further, to study associations between disease variables and estimated VO 2peak and walking distance in patients. The submaximal treadmill test has shown good validity at group level in JIA patients. Methods: Patients with persistent arthritis or polyarticular disease were recruited consecutively at Oslo University Hospital. Age-and sex-matched controls were selected randomly from the National Registry. In all participants, VO 2peak was estimated using the eightminute submaximal treadmill test. Submaximal parameters included heart rate and rating of perceived exertion (Borg 6-20 ) at 3 and 8 minutes, speed and walking distance. Current pain, and pain and fatigue during the previous week were assessed by a Numeric Rating Scale. Disease activity, functional ability, disease duration and current medication were registered in patients. Differences between groups were tested with t-tests and correlations with Spearman's rho correlation coefficients. Results: Sixty JIA patients (50 girls), 30 with persistent oligoarthritis and 30 with polyarticular disease (extended oligoarthritis and polyarticular RF +/-) aged 10-16 years and 60 controls were included. Biologic drugs were used by 25 (42 %) patients. No significant differences were found in estimated VO 2peak (ml/kg/min) in patients vs controls or in patients with persistent oligoarthritis vs polyarthritis (Table 1) . Submaximal parameters did not differ significantly between patients and controls or between JIA subsets. In patients, there were no correlations between any disease variables and estimated VO 2peak or walking distance (all r's<-0.3, p=NS). Conclusion: Estimated VO 2peak and submaximal responses from a submaximal treadmill test are comparable between JIA patients and controls, and also comparable between patients with persistent oligo arthritis and polyarticular disease. The encouraging results may possibly be explained by advances in the multidisciplinary management of JIA, including biologic therapy and individualized tailored patient education about physical activity. Methods: This is a year (yr) 8 interim analysis of an ongoing, multicenter, observational registry of patients (pts) with pJIA with up to 10 yr safety follow-up. Pts included in the registry were treated with ADA, alone or in combination with methotrexate (ADA±MTX), or MTX alone as a comparison arm, according to routine clinical care in PRINTO/PRCSG centres in the US, Australia, and Europe. This analysis included only ADA±MTXtreated pts who were sub-grouped according to enrolling site into two groups: F-D (10 -<15 kg, 10 mg every other week [eow] ; 15 -<30 kg, 20 mg eow; ≥30 kg, 40 mg eow) or BSA-D (24 mg/m 2 [maximum of 40 mg] eow). MedDRA observational adverse events (AEs) were recorded from registry entry through last contact, irrespective of duration of registry treatment with ADA±MTX. Results: Of the 537 pts enrolled in the ADA±MTX arm, 272 and 263 received F-D and BSA-D, respectively. At registry entry, F-D and BSA-D groups were similar for mean JIA duration (3.5 yrs vs. 3.9 yrs), JADAS27(CRP) (10.8 vs. 12.2), and CHAQ-DI (0.6 for both). Registry follow-up in the F-D and BSA-D groups were comparable [mean (range) in yrs: 3.96 (0.00-8.92) vs. 3 .58 (0.00-7.01)]. Overall, 166 pts (61%) in the F-D and 128 (49%) in the BSA-D group discontinued registry drug. Frequencies and rates of observational AEs per 100 pt years of observation time (from registry entry up to last contact, irrespective of drug treatment duration) were comparable between groups (Table 1) , including rates of serious infection. Two pts from the BSA-D group reported latent TB, although there were no cases of active TB across enrolling sites. One pt (0.2%) from the BSA-D group reported an event of opportunistic infection (fungal oesophagitis). There were no reports of death, malignancy, oral candidiasis, demyelination, or congestive heart failure. Conclusion: Overall, ADA±MTX was well-tolerated in pts with pJIA where administration has been with a fixed dose, per weight category, or based on BSA, respectively.interventions ranging from one-to-one therapy to intensive inpatient rehabilitation programmes. It was identified that further ongoing community based support would be beneficial for the maintenance of physical fitness and wellbeing once the input of the specialist teams was no longer indicated. Objectives: An opportunity to develop an innovative approach to community based self-management group aquatic therapy was identified by bringing together the expertese of Fluid Motion, a social enterprise group with establised success in delivering community group aquatic therapy for adults using artificial intelligence technology, the clinical teams from the paediatric rheumatology and peadiatric chronic pain services in Oxford, and the research experience of the musculoskeletal team at Oxford Brookes University. We aimed to develop a self-management aquatic therapy programme for adolescents with musculoskeletal pain and disability using individualised digital progragrammes, enhanced with AI technology. Methods: The specialist physiotherapists identified patients that were actively under their care between the ages of 12-18 year. The group had a range of diagnoses but all had the common finding of ongoing musculoskeletal pain and disability. It was recognised that a higher proportion would have a chronic pain condition. The level of function required to take part was agreed as, independently mobile, able to get in and out of pool without assistance, independent dressing (parents will not be permitted to stay at pool side). It was acknowledged that some patients may be inappropriate for group work including those with specific behavioural difficulties. Results: Outline of the programme: Patients were invited to attend a 7 week aquatic self management group under the supervision of our physiotherapists. The patients had all been assessed by the specialist physiotherapists and identified as being appropriate for the programme. The physiotherapists selected exercises from the digital rehabilitation package in order to create an individualised programme for each participant. The paediatric rheumatology hydrotherapy pool was used. This was identified as an appropriate place to assess the initial intervention with a view to hosting future programmes in community pools. 5-6 patients were in each group. The physiotherapist was in the pool for each session to provide support with the physiotherapy assistant on poolside. Patients were introduced to their programme on the tablet before entering the pool. The the patients used the tablets during each session and provided real time feedback on their experiences to inform development of their programme using AI technology. Reassessment was carried out in the final session. All patients had to commit to 6 out of 7 sessions including the final session. Assessing the intervention: Rheumatology patients completed CHAQ assessments before and after the programme. Chronic pain patients completed the Oxford pain questionnaire including a pain map before and after the programme. Physical tests, were completed in clinic before the intervention and in the 7th session of the programme Conclusion: We identified a need to provide ongoing support for young people with musculoskeletal pain and disability once the input of highly specialised services was no longer indicated and recognised the potential for supervised self management group aquatic therapy. We present our experience of designing a programme using digital technology that can be easily utilised by young people during their therapy sessions and provide real time feedback to progress their therapy using AI technology. Introduction: Physiotherapy (PT) and occupational therapy (OT) are widely accepted as mainstay treatments for Paediatric rheumatological conditions. Historically in Qatar children with rheumatological illness were referred to a paediatric rheumatologist, then to general outpatient therapy services hosted in separate sites. There were no formal feedback mechanisms between therapy services and the pediatric rheumatologist.

Objectives: This study reviews the patterns of referral to PT and OT services since opening the Pediatric Rheumatology clinic at Sidra Medicine. The study also presents specific outcomes; range of movement and goal attainment. Methods: Patients referred for OT or PT were identified through Sidra Medicine's electronic medical records system. All patients referred for OT or PT were identified between June 2017 and March 2018. A retrospective review of the EMR was conducted by the therapists. Passive range of movement measurements and goal ratings were compared at baseline and at the final assessment within the designated timeframe of the review. Results: A total of 88 patients were referred to the rheumatology service. Of these 15(18%) were referred for therapy. Seven (39%) of these were seen jointly by OT and PT while 7(39%) were seen by PT alone. One patient was seen for OT assessment and intervention only. There were 4 Qatari nationals and 11 non-nationals. Juvenile Idiopathic Arthritis (JIA) was the most frequent diagnosis with 9 patients. There were 3 patients with scleroderma and 2 patients with Juvenile Dermatomyositis (JDM). Five patients with restricted range of movement and functional limitations were seen for therapy. The remaining 10 patients were seen for strengthening only. Range of movement measurements were taken at commencement of therapy and at the end of the period included in the data. All patients set goals for therapy in conjunction with their treating therapist and these were reviewed at every session to assess progress. The results of the initial and final range of motion measurements and goal attainment are summarized below in Table 1 .2. All patients demonstrated an improvement in passive range of movement in the joints assessed. Two of the patients continued to experience an uncontrolled disease flare (patient 3 and patient 5) however despite this demonstrated improvements in passive range of movement following therapy intervention. At Sidra Medicine goals are set with the patient and family and reflect the functional goals that the patient and/or their family are hoping to achieve by attending therapy. Four of the 8 patients met all of their established goals. Two patients met 66% of their goals and are continuing with therapy to meet these remaining goals. A final two patients did not meet their goals however both continued to have active disease. These are the same two patients who experienced the smallest improvements in passive range of motion of their joints. Conclusion: Although only a small number of patients have been seen for specialist OT and PT treatment at Sidra the review suggests that outcomes for these patients in terms of improved range of motion and attainment of treatment goals is positive. The pediatric rheumatologists report that the increase in communication with treating therapists has positively affected their ability to manage disease flares ensuring improved care.

Introduction: Summer camps for children with chronic conditions like Juvenile Idiopathic Arthritis (JIA) seem to have a positive impact on physical, psychological, emotional and social aspects. The first Portuguese Summer Camp for Children with JIA was an initiative of the Pediatric Rheumatology Unit of Hospital de Santa Maria, in Lisbon. There have been 2 editions (Ed): the 1 st in 2016 and the 2 nd in 2017, with one-week duration and 19 participants each. Objectives: The goal of this prospective pre-post study was to evaluate the impact of the Summer Camp for children with JIA. Methods: Inclusion criteria were all children who participated in the 1 st or 2 nd Ed of the JIA Summer Camp and completed the 4 questionnaires: the Childhood Health Assessment Questionnaire (CHAQ), the Functional Assessment of Chronic Illness Therapy (FACIT), the KIDSCREEN-52 and the "Emotional and Social Competence Evaluation Scale" (EACSE) questionnaires. These were done at 2 separate time periods: "pre-camp", in the 3 months that preceded the camp; and "post-camp", within 3 months after camp. Informed consent was obtained from parents. Questionnaires with missing answers were excluded, as were children that only responded pre or post camp. Results: A total of 33 questionnaires were completed by 20 children who participated in one or both editions. Table 1 shows the demographic characteristics. The median CHAQ result was 0.125 (IQ 0-0.312) pre-camp and 0 (IQ 0-0.25) post-camp. There was a negative variation in pre and post camp CHAQ with statistical significance difference (SSD) (p-value 0.035). The median FACIT result pre-camp was 46 (IQ 43-50) and post-camp was 45 (IQ 42.5-49), with no SSD. In the KIDSCREEN questionnaire, the domain of Parent Relations and Home Life and the domain of Social Support and Peers had a positive SSD of 0. 33 Introduction: Children with juvenile idiopathic arthritis (JIA) appear to have an increased rate of incident malignancy compared to children without JIA, although data are inconsistent. 1, 4 The relationship between JIA and malignancy is uncertain. High incidence risk of new autoimmune disease in patients affected with JIA was established. 2 Childhood cancer survivors are at increased risk for certain types of autoimmune diseases (AID) 3 and there is lack of data of JIA in those patients. Objectives: To evaluate the frequency of malignant disease in a cohort of patients included in JIA Registry in single tertiary center, to assess the time of manifestation onset with respect to the time of diagnosis of JIA and to assess presence of another autoimmune disease in the same patient. Methods: medical records of registered patients were reviewed. Data on JIA diagnosis, malignant and autoimmune disease were analyzed. The time of each manifestation onset was determined and compared with the time of JIA diagnosis. Results: as of the May 2018, 176 patients were registered in er JIA Registry in single tertiary cent (females 118 (67%), males 58 (33%)). Three patients (1,7%) were identified with malignancy in biological naive patients. Patient 1, boy, with unremarkable personal and family history regarding autoimmune and malignant disease, was diagnosed as systemic onset JIA and synovial sarcoma at the same time. Treated accordingly for SoJIA and malignancy (surgery, followed with hemotherapy (CWS 2012 Protocol: iphosphamide, vincristin, actinomicin) and radiotherapy. On month 10th of therapy (while receiving radiotherapy) developed macrophage activation sy as well as diagnosed as autoimmune thyroiditis (AIT). Patient 2, girl 15,5y, developed hard to treat enthesitis-related arthritis while on maintenance therapy (MTX 50 mg/weekly) for T-cell Non -Hodgkin lymphoma (ALL BFM 2009 Protocol) previously diagnosed also as AIT. Patient 3, boy 15y, diagnosed as juvenile spondiloarthropaty, with history of allogeneic bone marrow transplantation (BMT) at age 6y for acute myeloid leukemia, AIT and hyperinsulinemia. Patients were not receiving biologics. Conclusion: In JIA, cancer is a relatively rare event, which is reassuring for patients and physicians. Registry data revealed 3 patients with JIA, malignancy and hypothyreosis at the same time. Synovial sarcoma and systemic onset JIA is quite rare comorbidity. Two other patients developed JIA during of after treatment for hematological malignancywe don't know if it could be atribute to genetic instability or something else. Persistent immune abnormalities after treatment with chemotherapy predispose to the development of autoantibodies, which are central to the pathogenesis of many autoimmune diseases, probably including JIA . Long-term follow up and large sample in JIA registry are warranted. Objectives: Primary: To study the vaccination coverage of children and adolescents with PRD due to the lack of relative Greek studies. Secondary: To investigate the reasons of incomplete vaccinations. Methods: In this case-control prospective study, all patients of the Referral Center with PRD were enrolled, following a patient/parent consent over a 6-mo period (1/2017 -7/2017). Demographics and disease characteristics were recorded in a pre-formatted registry along with their vaccination status according to their personal Child Health Booklet. Additionally, the vaccinations of age-matched healthy students (HS) were collected. The vaccination coverage was estimated according to the National Immunization Program for the relevant age group. Results: The vaccination status of 101 children/adolescents (Male: Female 32:69) with PRD and a mean age of 11 years was recorded. The control group was a population of 66 HS (Male: Female 25:41), with a mean age of 9.76 years. 45.5% of patients with PRD and 42.40% of HS were found with missing immunizations, mainly due to their physician's recommendation (p=0.81). In respect to the type of vaccination administered, complete vaccination for DTP-Hib was recorded in 60% of the PRD patients and 68.2% of the HS (p=0.32); for pneumococcus the relevant percentages of the studied groups were 90% and 92. 4%, respectively (p=0.65). One dose for measles's protection with MMR had 97% of the PRD and 100% of HS (p=0.26) and for HPV 18.18% and 0%, respectively (p=0.21). As for the influenza vaccination, at least one dose was recorded in 40% of the PRD and 15.15% of the HS (p=0.001). Conclusion: Vaccination coverage of Greek pediatric patients with PRD is not inferior to the relevant of HS, indicating the acceptance and compliance to the recommended National Immunization Program, especially for pathogens leading to invasive infections. About half of the PRD patients comply with the EULAR influenza vaccination recommendation. In HS, the absence of regarding HPV and lower level of influenza immunization is in alliance to the National Immunization Program regarding age and disease indications. Introduction: Nowadays a lot of patients, who are suffering from juvenile idiopathic arthritis (JIA), are treated with anti-TNF therapy. The issues of duration of anti-TNF therapy in children with JIA, receiving anti-TNF therapy and reached remission on it, are relevant and debatable. Objectives: To evaluate the efficiency of anti-TNF therapy after 3 years of treatment with TNF-alpha inhibitors in children suffering from JIA and having a remission of at least one year, which was achieved on anti-TNF therapy, in 2 compared groups on different treatment regimens. Methods: This prospective study included 40 children (mean age 12.7±2.4) suffering from JIA (mean disease duration 5.2±1.4), receiving anti-TNF-therapy for 3 consecutive years (20(50%) children were treated with adalimumab(ADA), 20(50%)with etanercept(ETA)). All children also received methotrexate(MTX) (mean duration of MTX therapy was 4.6±0.5) and had a remission (mean duration of remission was 1.4±0.3). The first group included patients who after 3 years of anti-TNF therapy continued anti-TNF therapy for another 6 months in standard dose and in standard scheme (this group included 10(25%) children who were treated with ADA and 10(25%) children who were treated with ETA). The second group included children who after 3 years of anti-TNF therapy continued anti-TNF therapy for the next 6 months in standard dose, but the intervals between injections of TNF-alpha inhibitors were doubled (this group also included 10(25%) children who were treated with ADA and 10(25%) children who were treated with ETA). Both groups were comparable in age, disease duration, and duration of treatment with both MTX and TNF-alfa inhibitors. Efficacy was determined using the American College of Rheumatology (ACR) Pediatric (Pedi) response criteria at the time of inclusion in this study and after 12 and 24 weeks. Results: At the time of inclusion in our study 90% improvement according to ACR pedi criteria were registered in both groups. After 12 weeks of treatment all children in the first group maintained 90% improvement according to ACR pedi criteria, in the comparison group in 100% of children were registered 70% improvement according to ACR pedi criteria, and 18(90%) children had 90% improvement according to ACR pedi criteria. After 24 weeks of treatment in all children (100%) in the first group remained 90% improvement according to ACR pedi criteria, in the comparison group 4(20%) children didn't achieve 30% improvement according to ACR pedi criteria (2 children were treated with ADA, 2with ETA), 16(80%) patients had 70% improvement according to ACR pedi criteria, and 15 (75%) children -90% improvement according to ACR pedi criteria. Conclusion: According to the obtained data, we can conclude that after 3 years of therapy with TNF-alpha inhibitors (ADA or ETA) in the standard dose, standard scheme and with the presence of remission for at least one year, it is possible to correct anti-TNF therapy by increasing the intervals between the injections of ADA or ETA. Objectives: To evaluate rates of LTBI in patients with juvenile idiopathic arthritis preceding anti-TNF therapy for more than 2 years. Methods: This was a retrospective study that included JIA patients treated with anti-TNF therapy for more than 2 years. 43 JIA patients with current age of 10.1±3.4 years, mean disease duration of 3.8±1.9 years were included. All patients received a single anti-TNF: 24(55.8%) patients were treated with etanercept, another 19(44.2%) patients were treated with adalimumab. All patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest computer tomography (CT) and history of exposure to tuberculosis. Patients were regularly followed at 6-month intervals. Before patients started receive anti-TNF therapy, LTBI screening (solely TST-positive) was positive in 7(16.2%) patients: 4(9.3%) patients in group of etanercept and 3(6.9%) -in group of adalimumab, no one had active tuberculosis (TB) or history of TB exposure. All this patients were treated with standard course of anti-TB therapy before the beginning of anti-TNF therapy. Results: Through more than 2 years duration anti-TNF therapy in patients with JIA, LTBI screening was positive in 11(25.5%) patients: 2(4.6%) had TST-positive (1(2.3%) patient was treated with adalimumab and 1(2.3%) with etanercept) and history of TB exposure, Numbers are median and IQR, unless otherwise indicated Conclusion: This long-term follow-up of an inception cohort diagnosed early in the biologic era suggests a reduction in permanent damage, good prognosis for systemic JIA and a much lower progression to an oligoarthritis extended category than previously reported. Considerable disease activity persists in a quarter of the patients. Extension of this study to the entire cohort will help confirm findings and identify predictors of longterm outcome. Introduction: The risk of malignancies, in particular malignant lymphomas, in Juvenile Idiopathic Arthritis (JIA) patients is low but has been reported to be elevated compared to the general population. Objectives: To assess the risk of cancer in patients with JIA in comparison to non-JIA individuals both in the pediatric age range and in adulthood. Methods: Register-based cohort study of patients with a first JIA diagnosis recorded from 1987 to 2016, based on data retrieved from the Swedish Patient Register (with information on hospitalizations (1987 and onwards) and outpatients visits (2001 and onwards)), and the Swedish Cancer Register. JIA patients were matched (on sex and age) to five non-JIA individuals sampled from the Swedish child population. All participants were followed up from six months after date of 2nd visit with a JIA diagnosis (for JIA patients) or the corresponding date (for non-JIA individuals) until the first date of the following events: cancer diagnosis, migration, death, 18 years of age, or 31 Dec. 2016. The occurrence of malignancies was compared through standardized incidence rates (SIR). The same analysis was rerun allowing participants to be followed up through adult ages (age at 31 Dec. 2016). Results: 7988 JIA patients and 39714 non-JIA individuals were identified and followed up, with a median follow-up time until 18 years old of 4,7 years and a median follow-up time into adulthood of 9.5 years. Fourteen malignancies (among which 6 lymphomas) until the age of 18, were recorded among the JIA patients and 37 (4 lymphomas) among the non-JIA individuals. Allowing the follow-up to cover ages above 18, identified 37 SHC registers a 12-channel ECG with a multi-level analysis of the signal-averaged complex. It studies alternate parameters (standard deviation, level of the overall adaptive potential, rapid rate of heart rate, sympathetic and parasympathetic regulation, generalized signs of heart failure, symmetry of the T wave), it takes into account the variability of complexes, allows control of regulation and functional state of the myocardium (by the form of ST, amplitude and waves square indexes, angles of deviations), detects a violation of the rhythm, indirectly assesses the psycho-emotional state. The monitor demonstrates the graphical form of the 4-level estimate of ECG analysis and the integral index of the functional state of the cardiovascular system. Results: Analysis of the data showed that only in 14.2% of cases for HSC there were no violations of the heart rate. The comprehensive assessment of regulation showed a significant decrease in patients with RD (65.82±1.97 at a rate of 76-100), mostly due to vegetative imbalance. The triangular index grew to 25525.2±27.6 (norm 9-100), the voltage index up to 164.59±33.46 (0-120). Operational control of the myocardium was also decreased to 55.5±2.41 (75-100). The decrease in the amplitude of the wave T in the leads I and AVL and its increase in the leads of the III AVF with its asymmetry indicated the presence of cardiometabolic changes. The integral indices of the ST-T form were changed in all leads, the highest of I 60.36±3.74 (75-100), the ratio of the amplitudes of the waves T and R increased 0.83±0.21 (0.14-0. 33 Introduction: The lesions of the respiratory system, namely the pulmonary tissue, are not specific for the development of poly-and oligoarticular juvenile arthritis. However, sclerotic damage to the mesenchymal tissue is one of the complications of long-term therapy with methotrexate and one of the factors determining the long-term prognosis of these patients of adult age. Rheumatic diseases are characterized by frequent involvement of respiratory organs. In children, pulmonary function disorders often occur latently, with minimal clinical manifestations, which is due to the high compensatory abilities of the child's organism.

Objectives: For the timely diagnosis and prevention of pulmonary complications the ventilatory lung function in children with rheumatic diseases was assessed.Methods: Spirometry was performed in 129 children from 5 to 18 years with rheumatic diseases, among them 35 boys and 94 girls. In the structure of diagnoses were patients with JIA -89 people (69%), with SLE -18 people (13.95%), with scleroderma 12.40% (16 people), dermatomyositis -4 people (3.1%), nodular polyarteritis -2 people (1.55%).Results: 29 children showed a violation of the ventilation function of the lungs (which amounted to 22.8% of the total number of patients). In all cases, the violations were as a restrictive type. Among them lung lesions were noted more often in patients with SLE (up to 44%), in patients with JIA to 21%, with systemic scleroderma -12%. Among children with dermatomyositis and nodular polyarteritis, there were no abnormalities, which is probably due to the small number in the structure of the subjects. An analysis based on gender were carried out , it showed that girls made up 84% with JIA, and with SLE -75%, with systemic scleroderma, violations were detected only in girls. In most patients, external respiratory function impairments were mild or moderate severity, and severe respiratory ventilation dysfunction was detected only in patients with JIA. A correlation analysis was made of the relationship between the spirogram score and individual patient parameters, such as gender, age, physical development by BMI. There were not reveal a reliable relationship between these parameters. An additional analysis of the correlation was made with the duration of the disease in patients with JIA. As a result, a weak positive relationship was found with the duration of the disease (r = 0.36, p <0.05).Conclusion: In children with juvenile idiopathic arthritis before the age of 18 we found signs of a violation of the respiratory function of a restrictive type, which is indicate of a lesion of the pulmonary parenchyma. The revealed changes depend on the duration of the disease and do not depend on the clinical parameters of the patients. Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a chronic systemic inflammatory condition with an unclear pathophysiology and IgG4-positive plasma cells infiltration of various organs and parts of the body. Objectives: If untreated, the disease can lead to fibrosis and irreversible organ damage. IgG4-RD mostly has been described in adults, hence it is generally unknown among pediatricians. Methods: We conducted a retrospective analysis of clinical features and response to therapy of five patients (one female, four males, median age 13,6 years) with IgG4-related disease, treated in our Center. The diagnosis was confirmed by detection of lymphoplasmacytoid infilatration with >30% of cells expressing IgG4 in all, and elevated IgG4 serum concentration in 4 cases. Results: Three patients had localized lesions (orbit, hip muscle, perirancreatic tissue, respectively), twomultiorgan disease with polylymphadenopathy, pulmonary, renal and hepatic foci, dacryoadenitis with edema of the eyelids. Autoimmune thrombocytopenia (70 х10 9 /l), neutropenia (0,79 х10 9 /l) were present in one patient. Rituximab therapy was successful in 2 cases (one patient received monotherapy with rituximab, another one -Rituximab and Sirolimus). Two other patients received JAK inhibitor therapy (ruxolitinib) with good effect. No side effects were noted. One patient underwent surgery -the infiltration in the abdominal cavity was removed with positive effect without specific therapy.Conclusion: IgG4-RD symptoms can be diverse and sometimes atypical, so dealing with this pathology requires physician's awareness. Rituximab was effective in patients with multi-organ manifestations, and JAK inhibitor (Ruxolitinib) was effective in patients with mono-focal disease. Steroids are routinely used in IgG4-RD as a first line of treatment with significant side effects. We propose that alternative drugs could be used in IgG4-RD, especially in pediatric patients to achieve fast remission with significan morbidity Objectives: We describe in sequence three paradigmatic case reports on sickle cell anemia, beta thalassemia minor and hemophilia A manifested at onset with osteoarticular symptomatology. Methods: Diagnosis were formulated in consideration of reported clinical history, signs highlighted at the physical examination and results of laboratory tests. Results: Case report 1. Two year old black male child, whose parents were both african, presented inconsolable afebrile crying, macroscopic haematuria and acute swelling of the fingers of both hands and feets. Physical examination showed dactylitis of hands and feet, scleral jaundice, splenomegaly and absence of focal neurological signs. Blood tests showed moderate anemia, hyperbilirubinemia, reticulocytosis and increased lactic dehydrogenase, while chest radiography and abdomen ultrasound were normal. Microscopic observation of the peripheral blood smear showed sickle-shaped red cells; the suspected diagnosis of sickle cell anemia was confirmed by high-performance liquid chromatography, sickle cell test and search for genetic mutation. Case report 2. Seven year old girl came for widespread joint pains without fever since several months. Physical examination revealed mild scleral jaundice, hepatosplenomegaly and pain in the mobilization of hips, ankles, wrists, knees and elbows without signs of joint limitation. Blood tests showed mild hyperbilirubinemia and moderate microcytic and hypochromic anemia with sideremia, transferrin, ferritin and inflammatory indices in the norm. Radiological examinations were normal, while the hemoglobin electrophoresis showed a percentage increase in hemoglobin A2, confirming in association with DNA analysis the suspicion of beta thalassemia minor. Case report 3. Sixteen months old male child, came to our observation for the swelling of both ankles and knees in the absence of fever. Physical examination revealed several hematomas on the skin surface and considerable swelling of ankles and knees with reduced joint mobility. Blood tests showed a lengthening of the activated partial thromboplastin time (APTT). In the suspicion of hemophilia A, the factor VIII dosage was performed, which was reduced thus confirming the diagnostic hypothesis. Conclusion: Sickle cell anemia occurs almost exclusively in black children and the joint symptomatology of hands and feet is usually symmetrical. Thalassemias are a heterogeneous group of syndromes in which bone pain is often reported. Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in patients with haemophilia; joint aspiration has a limited therapeutic role, but should be preceded by the administration of factor VIII. Finally, research of the etiology of osteoarticular clinical signs must include these haematological diseases if there are suggestive clues that justify the request for targeted diagnostic tests. Informed consent to publish had been obtained. Introduction: Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disease characterized by elevated serum immunoglobulin E levels, recurrent skin and lung infections, chronic dermatitis and various connective tissue and skeletal abnormalities.

Objectives: To investigate the effectiveness of orthosis and cilinical pilates exercises for eliminating knee joint deficits in the presence of HIES. Methods: 12,5 years old boy with HIES, applied to the rheumatology department with complaints of the weakness and stiffness of the gastrocnemius muscles and effusion on the knees for the last 2 months. It was reported that the complaints were relieved by removal of fluid from the patient's knees, but there was an abnormality in the direction of the genu valgus in the knee and the development of walking difficulty due to it. The patient was directed to physiotherapy at this stage. A goniometric measurement was made for knee joint positional sensation while lying on the back of the patient and antropometric measurement was made for the edema. For functional evaluation, observational walking analysis, 10 m walking test, time up and go test (TUG) were performed. The Childhood Health Assessment Questionnaire (CHAQ) was administered for activities of daily living and pain. Exercise training was given once a week for 8 weeks.The home exercise program was given for other days. Clinical Pilates exercises were given for the proprioception and muscle strength. It was decided to support the knee with a double articulated orthosis covering the knee and ankle to increase medial-lateral control. The skin was followed up frequently and edema-related orthosis adaptations were made. Results: After 8 weeks of training, improvement in knee position sensation, TUG, CHAQ scores was observed (Table 1) . However, the improvement observed until the sixth week was delayed due to the effusion on the knees in the seventh week. This decline was reflected in the results of anthropometric measurements and changes in pain scores at week 8.Conclusion: In the case of HIES, selected clinical pilates exercises for ankle and knee joints and orthosis practice was found to be beneficial for the patient's walking. Considering the attacks of the disease, it was concluded that the patient should be evaluated at frequent intervals. Informed consent to publish had been obtained.

Immunoregulation and basic science Results: A 6 year-old male with HI was referred to our rheumatology centre because of chronic polyarthritis. The child was born at term with classical features of HI. During his first years of life he was hospitalised several times due to severe infections. At 4 years of age he developed chronic arthritis with symmetrical involvement of knees; suspecting a septic arthritis associated with HI, he was unsuccessfully treated with antibiotics. Two years later he presented to our centre with erythrodermic skin, joint contractures, severe ectropion. Swelling, pain and severe limitation of motion of hips, knees, ankles, midfeet, wrists, elbows and left shoulder was detected. The patient was unable to walk since 2 years. Laboratory examinations showed microcytic anemia, mild leukocytosis, thrombocytosis and mild elevation of C-reactive protein (0.79 mg/dl). Antibodies to nuclear antigens, extractable nuclear antigens, cyclic citrullinated peptide and rheumatoid factor were negative. Uveitis screening was negative. He was treated with multiple intra-articular corticosteroid injections (IACI) in both knees, wrists, elbows, and ankles and he was started on methotrexate; due to his severe dermatological involvement oral route was preferred. One month later a dramatic response to treatment was observed and the child started walking again. A limitation of motion at the mid-feet and ankles persisted. Considering the brilliant response to injective treatment, a multiple ultrasound-guided IACI in the mid-feet (previously not injected) is going to be performed at this time. We did not observe any adverse events or infections related to the treatment so far (almost two months follow up). Conclusion: To the best of our knowledge this is the youngest HI patient with polyarthritis described so far, [2, 3] and the first one treated with IACI. The increased susceptibility to infection and the growth retardation reported in children with HI make systemic glucocorticoid therapy and global immunosuppression undesirable. IACI allows to avoid most of the systemic side effects of glucocorticoid treatment and results in a more effective and rapid improvement of articular function. In our patient, combined treatment with IACI and methotrexate, successfully controlled articular symptoms and improved his quality of life. Informed consent to publish had been obtianed. Introduction: It is known that chronic non-specific inflammation in rheumatoid arthritis (RA) acts as an inducer of activation of the coagulation link of hemostasis, contributes to the deficiency of physiological anticoagulants, as well as to the decrease of fibrinolytic activity, which creates pathogenic preconditions for the occurrence of hemocoagulation disorders.Objectives: It was considered necessary to determine the features of the hemostasis system in children with juvenile idiopathic arthritis (UIA) with comorbid pathology. Methods: 97 children (5-18 years) of patients with UIA with oligo and polyarticular variants of the disease were examined. Patients were divided into two groups. The first group consisted of 38 children (39.2%) without symptoms of comorbidity, and the second group, with signs of comorbidity, included 59 children (60.8%). In the group with the presence of comorbidity, the signs of high activity of the rheumatoid process, such as C-reactive protein and circulating immune complexes, were significantly more often recorded. The components of the blood coagulation system were determined from the data of the coagulogram, which included determination of the level of fibrinogen (FG, g / l), prothrombin index (PTI,%), thrombin time (PM, c), activated partial thromboplastic time (AFTV, c), international normalized the ratio (MNF, U.S.), D-dimer, y. at. Statistical processing was performed using the Statgrafics 16.0 application package. Results: In the group of children with signs of comorbidity, an increase in the prothrombin index (p <0,05) was found, as well as a probable prolongation of thrombin time (p <0,03) indicating the probability of thrombotic formation. The parameters of the study of the coagulation system were also studied in a group of patients with signs of kidney damage. There is a probable increase in the prothrombin index (p <0.05), which may indicate a possible development of thrombosis. As for atherosclerosis and thrombosis, inflammation is the main binding factor; we analyzed parameters of hemostasis in a group of children with UIA with signs of atherogenic orientation changes in the lipid spectrum.Signs of the development of thrombocytopenia development were revealed by parameters of PTI (p <0,05). Only in this group of patients a probable increase in the level of D-dimer, the main marker of thrombotic readiness (p <0,05), was established. Conclusion: Thus, in children with UIA, with signs of comorbid pathology, signs of thrombophilic formation have been identified, as evidenced by an increase in both the prothrombin index and the main marker of thrombotic readiness -the D-dimer. Thus, precisely inflammation is the most important factor that supports the threat of development of atherosclerosis, atherothrombosis and venous thrombosis in children with SLE, and it is dangerous not only the process of inflammation in the vascular wall itself, but also the pathological influence on the endothelium of the cells of the immune system and products of the systemic inflammatory responses -acute phase proteins and circulating immune complexes.Introduction: In the differential diagnostics of juvenile idiopathic arthritis (JIA), different rare diseases that mimic chronic arthritis, should be considered. Our article describes the case, where the rare disease -Synovial chondromatosis had to be excluded in spite of findings by imaging methods.Objectives: A 4 year old female patient presents with complaints of walking difficulties, morning stiffness, swelling of right knee, and limitation of movement. Blood results did not show increased inflammatory activity. The patient was RF and ANA negative. Slit-lamp examination excluded uveitis. Based on signs and symptoms, the diagnosis of Juvenile idiopathic arthritis was considered. Plain radiograph of the knee showed soft tissue swelling. Findings of MRI examination revealed the diagnosis of primary synovial chondromatosis (Reichel´s syndrome). However, the musculoskeletal sonography showed a typical image of proliferative synovitis with high power doppler signal and small amount of anechoic fluid. Inflammatory etiology was confirmed by analysis of the synovial fluid. The diagnosis of JIA was confirmed and the patient was treated by intra-articular application of triamcinolone hexacetonide. Synovial chondromatosis (Reichel´s syndrome or Reichel-Jones-Henderson syndrome) is a benign cartilaginous metaplasia of the synovium, which may affect any synovial joint. Typically, free fragments of cartilage originating from the synovium of the joint are seen in the joint cavities. The disease is usually monoarticular, it affects most commonly the knee, hip, or elbow and less commonly the wrist, ankle, and shoulder. It involves rarely the TMJ. The joint most commonly involved is the knee joint. The condition is connected with pain, swelling and limitation of movement. It typically affects adults between 30 to 50 years old, and occurs extremely rarely in children. Synovial chondromatosis exists as primary and secondary. In primary form the cause is unknown, frequently without known prior trauma or inflammation. Diagnosis is made by radiographs, computed tomography (CT), magnetic resonance imaging (MRI) , by surgery and histology. The prognosis of this disease is good. Asymptomatic patients do not require therapy. Symptomatic patients should undergo arthroscopic or surgical removal of intraarticular bodies. There have been documented very rare cases of malignant transformation. Written consent of the legal guardian has been obtanied to publish this case study. Methods: Case report.Results: Six months after administration of triamcinolone hexacetonide to the right knee, the patient is asymptomatic with complete clinical and ultrasound remission. Conclusion: Although MRI confirmed the diagnosis of Reicheľs syndrome, due to the age of the patient and clinical and ultrasound findings we decided to treat the patient according to the guidelines for JIA. Treatment of the patient was successful without surgical intervention. Imaging methods can be helpful in differential diagnosis of JIA, however, findings might sometimes be confusing or misleading. Objectives: In this article, we report a case of a boy who is newly diagnosed with oligoarticular JIA with unexpected joint involvement.

Results: A formerly healthy 11-year-old boy with a month history of left ankle swelling and pain with morning stiffness was admitted to our clinic with SCJ pain and swelling for one week. He reported no hospitalization and regular use of medication in his previous medical history. Family history was not remarkable for rheumatological disease. At presentation, the child had pain and limitation of movement of the left ankle. The SCJ was warm, effused and painful when pressure was applied. There was no enthesitis or complaints in other peripheral joints. The other organ systems were healthy upon physical examination. Laboratory evaluation revealed significantly elevated erythrocyte sedimentation rate and C-reactive protein levels, and an ANA test was positive. According to the physical, laboratory and imaging evaluations, and bone marrow aspiration, there was no evidence for malignancy and infectious disorders.After the evaluation of clinical and radiological findings, the child was diagnosed with oligoarticular JIA without uveitis and was started on 10 mg of weekly subcutaneous methotrexate in addition to oral prednisolone 2 mg/kg daily. Prednisolone was tapered and ceased within 4 weeks. Two weeks after stopping steroids, despide efficient methotrexate treatment the patient presented at our department with reexacerbation of pain and swelling in the SCJ. Acute phase reactants were risen again and the MRI of the left SCJ was consistent with marked bone marrow edema, joint effusion, synovial thickening and bone erosion. Meanwhile etanercept (0.8 mg/kg/week subcutaneous) was added. The responses to treatment in the third and sixth month were optimal according to the American College of Rheumatology (ACR) Paediatric 30/70. It was observed that the patient had significant healing after a year without any adverse reaction to treatment. We report a case study of a boy with oligoarticular JIA who presented with arthritis of unexpected joint involvement. Oligoarticular JIA is the most prevalent chronic inflammatory arthritis of childhood. SCJ involvement in JIA has not been reported yet. However, symptomatic SCJ involvements in adult RA were reported at varying rates. Recently, Rodríguez-Henríquez et al. reported that 15% of RA patients had synovitis in the SCJ according to ultrasound. If the patient has no complaint, SCJ involvement might be missed upon routine rheumatological examination. Conclusion: We concluded that SCJ involvement in JIA is very rare, but it may actively participate in the inflammatory process, as do other peripheral synovial joints. Careful clinical examination of the musculoskeletal system is essential for early diagnosis, and advanced radiological tools simplify the evaluation of joints in early phases effectively. In addition, biologic agents particularly seem to be more useful in early phase. Informed consent for publication had been obtained from the parent. Objectives: -Methods: The infant presented with cerebral irritability, pain, takypnea and vomiting during 10 days. He had no history of fever or rash. Ad admittance mild pleiocytosis (37 x 10E6/L) in the cerebrospinal fluid (CSF) was found. Antibiotic treatment was initiated without any clinical response. No bacteria or viral DNA was detected in CSF, blood, urine, or airways. Pericardial effusion was seen on echocardiogram in addition to severe dilatation of coronary arteries (LAD: 4.2 mm Z-score 12,68; RCA: 4,2 mm Z-score 9,3). Treatment with intravenous Immunoglobulin (IVIG) and aspirin was initiated for KD without any response. Addition of infliximab reduced the pericardial effusion but otherwise the condition was unchanged. High dose methylprednisolone was initiated followed by prednisolone but 5 days later criteria for MAS were fulfilled. High dose Anakinra was started resulting in dramatically improvement in his clinical condition. Introduction: We report a clinical case of a 9-year old girl diagnosed with juvenile dermatomyositis, complicated with macrophage activation syndrome , probably triggered by Herpes simplex infection. Objectives: Our objective is to describe the presentation of macrophage activation syndrome in a child with newly diagnosed juvenile dermatomyositis Methods: Our patient is 9-year old girl who presented to a Pediatric Department with a 6-month history of abnormal gait and lower limbs pain, which appeared mainly in the evening and after physical activities. On admission she had polyarthritis, maculopapular rash over the cheeks and erythema over the nasal tip. The lab studies revealed leucopenia with lymphopenia, mild anemia, slightly elevated ESR, positive ANA titer and negative anti-dsDNA. Treatment with NSAIDs and Methotrexate was prescribed, but the parents decided to try alternative therapy -homeopathy, and refused the treatment.

In the following months the child deteriorated with progressive muscle weakness, difficulty walking, skin rash, alopecia, persistent fever, progressive weight loss and abdominal pain. On examination there was marked symmetrical proximal muscle weakness and the girl was unable to perform the usual daily activities on her own. Characteristic cutaneous changes were observed -heliotrope discoloration of the eyelids with periorbital edema and a malar rash.She had also hyperpigmented lesions around the elbows, knees and ankles, Gottron's papules and aphtous stomatitis. Due to the clinical signs a diagnosis of JDM was suspected,but was inconclusive due to the normal lab studies with normal creatine phosphokinase levels, normal inflammatory and immunology markers and the technical inability to perform electromyography.Finally the diagnosis was supported by magnetic resonance imaging of the thigh muscles revealing the characteristic pattern of muscle involvement in JDM. What made the case more perplexing were the additional overlap clinical signs of subtle arthritis with flexion contractures at the elbows and knees, alopecia, butterfly-like rash and aphtous stomatitis. For the latter, a positive result for HSV infection was received . In addition we observed jaundice with enlarged liver and spleen, lab studies revealed hepatitis and cholestasis, so an exclusion of underlying reasons for the development of hepatitis (viruses, autoimmune hepatitis, drug induced, metabolic diseases) was required.Overall, a diagnosis of JDM complicated with MAS (the lab studies revealed pancytopenia, normal ESR, elevated liver enzymes, increased bilirubin levels, elevated LDH levels, decreased levels of albumin and total protein, hypertryglyceridemia, hyperferritinemia) was established.Results: Pulse therapy with high-dose intravenous methylprednisolone and intravenous immunoglobulin was initiated. After almost two months of hospital stay, the girl was discharged with great improvement in the range of motions and normal laboratory markers Conclusion: MAS is a rare and life-threatening complication of JDM, most commonly triggered by infections.In our case the triggering factor might be the HSV infection .JDM can present with inconclusive lab studies and our challenge was also associated with the differential diagnosis of liver involvement in MAS. Informed consent to publish had been obtained from the parent.

Conclusion: Cicatricial pemphigoid and pemphigus vulgaris are autoimmune disorders, rare in pediatric age. Both could involve skin and eyes. Immunohistopathologic evaluation with direct immunofluorescence are essential for diagnosis and repeat biopsies may be useful in patients with atypical disease courses. Corticosteroids and immunosuppressants were the mainstay of treatment. The inclusion of these disorders in differential diagnosis of rheumathologic diseases with dermatologic and ocular manifestations is important to start an appropriate and early treatment. Informed consent to publish had been obtained. Introduction: The Fabry's disease (FD) is a lysosomal storage disease, X linked, that may affect both men and women. Mutations in alpha Gal A gene carry a partial or total deficiency of the Galactosidase A alpha enzyme with secondary globotriaosylceramide (Gb3) accumulation in the skin, eyes, kidney, heart, brain and peripheral nervous system. It generates clinical heterogeneous profiles with some specific features according to the age groups.

Objectives: To describe a Fabry's disease pediatric clinical case confirmed whose clinical manifestation was the neuropathic pain.Methods: A report about a Fabry's disease case in a pediatric patient is submitted Results: 12-year old male patient, with no pathological personal antecedents. Two-year evolution clinical profile showing fever episodes each 4 months without associated infectious symptoms with a duration of 3 to 5 days and spontaneous improvement. He has been admitted in hospital, infectious processes discarded. In addition, he presents burning pain episodes, described as "burning sensation" in soles and palms with an approximate 10-minute duration, which spontaneously or when dipping his hands in cold water get better, followed by a hand redness and then paleness, without cyanosis. These episodes occur each 2 to 3 months and are not related to fever. During the last 6 months, said episodes have been more frequent. Conclusion: FD is the second more frequent lysosomal storage disease because among its pathophysiological aspects, the abnormal Gb3 storage in multiple tissues endothelium, triggers structural alterations which alter the normal function thereof resulting in a large set of clinical manifestations. The neurological compromise, typical of an early damage of both the little somatic peripheral nervous fibers and the autonomic ones is one of the earliest observed symptoms predominantly in males. The neuropathic pain of the case presented was the only clinical manifestation, and it teaches us to highly suspect of the large variety of symptoms, which must be timely recognized by the clinician in order to make an early diagnosis and thus to initiate the enzymatic supply therapy to improve both the prognosis and the patient' life quality. Informed consent to publish had been obtained from the parent. Introduction: IgG4-related disease (IgG4-RD) is a wide spectrum of fibro-inflammatory diseases that affect many organ systems and characterized by storiform fibrosis, mild to moderate tumor-like eosinophile and significant IgG4-producing plasma cell infiltration in histopathology, and the high level of serum IgG4 concentration. Its pathophysiological mechanism is unclear; however, when untreated may lead to fibrosis and irreversible organ damage. This rare disease mostly has been described in middle-aged adults and more rarely in children. Enlargment of lacrimal and salivary glands, cervical lymphadenopathy, retro-orbital and other organ pseudotumors, pancreatitis, sclerosing cholangitis and mesenteritis,retroperitoneal fibrosis, pulmonary and aortic inflammatory disease, thyroiditis, and joint disease are some aspects of the disease.

Objectives: To report a boy with orbital mass with final diagnosis of IgG4-related disease Methods: -Results: Case report: Herein, a 12-year-old boy is reported which presented with orbital mass. He had high IgG4 serum level (175 mg/dl) and histopathologic manifestation of pseudotumor compatible with IgG4-RD. Investigation for other organ involvements as part of the IgG4-RD spectrum was normal. After resection of tumor and treatment with an oral corticosteroid, 9 months follow-up has not been shown flare. Conclusion: Recognition of IgG4-RD spectrum condition leads to early diagnosis and treatment of the disease and so is important because it is usually responsive and prevent fibrosis and organ damages. Informed consent to publish had been obtained from the parent.

Introduction: Herein we describe an unusual finding of raghib syndrome(an unroofed left superior vena cava) in a case of autoimmune pancreatitis with IgG4 related disease(AIP/IgG4RD) . Objectives: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis with characteristic clinical, histologic, and morphologic findings rarely reported in children which clinically present with abdominal pain, weight loss, and jaundice also introduced by Kamisawa as a syndrome characterized by elevated serum IgG4 levels, prominent lymphoplasmacytic infiltrates with increased IgG4 + plasma cells, and dense sclerosis.time is still needed till its cardiac complications and assosiation be declared. Methods: after thorough history taking and physical examination a standard transthoracic echocardiography performed by expert pediatric cardiologist. Results: after visualization of a dilated coronary sinus,contrast echocardiography by injecting agitated salin via left antecubital vein performed at first, which revealed entrance of bubbles into left atrium that is charactristic of unroofed LSVC.then it was confirmed with a more accurate procedure of transesophageal echocardiography. Conclusion: Raghib syndrome is an extremely rare congenital heart defect characterized by persistent left superior vena cava (LSVC) draining into the left atrium and absence of the coronary sinus.An unroofed left superior vena cava (LSVC) is usually asymptomatic and diagnosed incidentally although it gives rise to increased risk of paradoxical embolism. The standard technique for the diagnosis is echocardiography, either transthoracic or transoesophageal.Up to now some cardiac complications like lymphoplasmacytic aortitis is described in association with AIP but best of our knowledge occurrence of raghib syndrome or unroofed LSVC in a case of AIP hasnt been reported yet Introduction: The Autoimmune Lymphoproliferative Syndrome (ALPS) is a disease associated to alterations in apoptosis due to a genetic defect (mutations of the FAS, FASLG and CASP10 genes), characterized by a nonneoplasic lymphoproliferative state and fever for more than 6 months. Objectives: Describe clinical presentation, treatment and outcomes of ALPS patients followed at a Pediatric Hospital Center in Colombia.Methods: A retrospective observational study was conducted, 2300 clinical records of children attended at Fundación HOMI between 2010 and 2016 . Based CIE-10 codes 31 cases met clinical criteria of NIH for ALPSDemographic characteristics, clinical presentation and laboratories were recollected in a Microsoft Excel® sheet. Stata 8® software was used to statistical analysis Results: Of the 31 patients , 67.7% were male, Average age at diagnosis was 6 years old (6 months to 15 years old). Among the reasons for consultation we found that fever and lymphadenopathy was the most frequent symptom (96.7%), followed by hepatomegaly (58%), splenomegaly (54%), exanthema (25.8%) and arthritis 2(2.6%). Doubly negative lymphocytes high count was founded in in all cases (values between 1.5% and 16.2%). B12 vitamin average was 987.5 ng/L (range 237-2000ng/L) and total immunoglobulin G levels was found 240 -5104 mg/dl. Molecular studies for mutations in the FAS, FASLG y CASP10 genes were negatives in 9 cases, in 7 patients was pending at moment of this revision, and was not possible to do in 15 due to administrative limitations from insurances. Table 1 summarizes the characteristics of the patients. About treatment in acute phase, 20 patients received oral corticosteroids, 7 patients with thrombocytopenia received intravenous immunoglobulin (IVIg) , and 8 children with hemolytic anemia received methylprednisolone. Maintenance medications include: Cyclosporine A in 6 patients, methotrexate in 5 cases with joint manifestations, mycophenolate mofetil in 3 children, sirolimus in 2 cases with refractory thrombocytopenia and rituximab in 1 patient. Conclusion: All patients this study configure probable diagnosis of ALPS since none has positive genetic test for apoptosis mutations, although 40% of the cases do not have any mutation according to the literature. The ALPS is confused with other hematology, oncology and autoimmune diseases for its presentation. The ALPS is a non-prevalent genetic disease that should be considered in patients with signs of chronic lymphoproliferation without neoplasic pathology. 4) . IAS has been proven a safe and efficacious treatment for active arthritis either as single treatment or in combination with medicine therapy. IAS have been shown to drastically relieve pain, swelling and to increase mobility in the injected joint (1-4). At our clinic the patients who receive IAS are to be offered a follow up at the physiotherapy department or occupational therapy department (depending on the joint injected) within two to four weeks following the injection, according to the care program. As to this date there has been no survey at our clinic to show how many patients are followed up as agreed.

Objectives: 1) How many of the patients are offered follow up at the physiotherapy clinic within two to four weeks after IAS? 2) What is the time between the injection and the actual follow up? 3) What was the effect of the IAS? Methods: A retrospective review of the patient registry and charts at the rheumatology clinic at Queen Silvia Children's Hospital, during January 1st -December 31st 2017.Results: The total number of individual patients who received IAS during 2017 at the rheumatology clinic was 63. The number of appointments for IAS was 93 and the number of injections given was 174. The department of physiotherapy followed up a total of 92% the patients relevant for physiotherapy. Out of these, 53% were followed up within 28 days. Of the patients followed up 46% experienced good effect of the injection, though the effect was not always well documented in the charts. See Table 1 for details. Conclusion: All patients were offered follow up, however not always in time. Of patients 92% were followed up and 46% received good effect from the injection. This retrospective study has lead to a further development of the post-injection assessment of the patients with a more structured guide how to evaluate the effect of injections. A further question to evaluate is the actual care programme, if it functions as intended, with an efficient communication within the team, and as to what happens in case of no effect of the injection, are the patients offered a doctor's appointment earlier or even another injection? Another important matter is if the care programme is relevant for the patient. Introduction: Rheumatic diseases in children are a multisystemic, heterogeneous group of diseases involving mainly the muscoloskeletal system resulting in disability. The multidisciplinary approach is essential in the management of rheumatic diseases in children.Objectives: Aim of this study is to evaluate the rehabilitation aspect of the child with chronic rheumatic disease in a more holistic view of his care and his recovery. Rehabilitation must be based not only on diagnostic and prognostic evaluation of the damage but also the awareness of the repercussions of the motor impairment on the psychomotor, intellectual, and emotional development. Equestrian rehabilitation (ER) is not a method but a rehabilitative practice using the horse as a mean of rehabilitation, the horse facilitates postural, motorial, perceptive and relational-motivational reeducation; ER is therefore a therapeutic intervention methodology that is an individual rehabilitation project. Methods: Besides clinical assessment of different types of arthritis, the specific rehabilitative aspects (joint evaluation, muscular strength, CHAQ, VAS dolor) must be evalueted, around which must organizing the intervention and the objectives. ER consists of 3 levels of intervention:1.horse therapy (hippotherapy), uses bodily features of the horse to the gait where the horse transmits to the child over three levels (longitudinal, transverse and sagittal plane) the correct human gait, playing a physiological pattern movement. At this level you are working on fine motor movements, balance, laterality, body image and cognitive aspects of attention-perception; 2.re-education trought horse riding, aims to achieve autonomy in the conduct of the horse; at this level you are working on the body pattern, lateralization movements with the use of the reins in the conduct of the horse, the balance on the saddle with stirrups, on fine motor coordination, on taking the reins, and space-time continuity, both sensory and motor; at this level we can introduce the trotting gait stimulating the adaptive, coordinative capacities in the relationship with the horse. The motivational aspect are so stimulated that leads to the pattern of movement; 3.equestrian rehabilitation therapeutic group (disability group).Results: In horse-assisted therapy observations are made on the effects on the neuromuscular system of the patient caused by the mechanical influence of the horse walk. Specific to the horse therapy is that the patient continuously receives impulses from the horse walk, which lead to a relaxed perception of the body, equilibrium, and coordination of movement. Conclusion: In horse-assisted therapy observations are made on the effects on the neuromuscular system of the patient caused by the mechanical influence of the horse walk. Specific to the horse therapy is that the patient continuously receives impulses from the horse walk, which lead to a relaxed perception of the body, equilibrium, and coordination of movement. Trial registration identifying number: Rehabilitative therapy during childhood and adolescence is aimed primarily to prevent primary damage effects produced by sensory-motor development. The child with a disability due to chronic rheumatologic disease must follow a rehabilitation program aimed to the functional motor recovery and also psycho-affective recovery in which the horse is the rehabilitation mean. Arthritis was the most frequent rheumatic disease (55.7%), the disease was considered active in 71.4%, with only 2 patients were without medication and the most frequently received treatment was sulfasalazine. The neurological assessment showed alteration in 88.8%, with predominance in muscle tone as spontaneous motor activity (n=7), the 57% showed hypertonia in neck flexors. When directed, there were alterations in the way of loading the child, which was modified predominantly by pain in the upper extremities, position which would explain the alterations in the tone found in the patients evaluated.

Conclusion: This study showed an important relation between the mother diagnoses, its activity degree, and neurological maturity abnormalities in their children. The musculoskeletal affection in rheumatic diseases especially the upper extremities apparently affects the maturity of the children due to the erroneous racing way. We propose the realization of prospective studies that evaluate the response to interventions and the modification in neuronal maturation in these patients. In addition to reporting evidence of alterations in the neurodevelopment of children of mothers with musculoskeletal involvement, secondary probably to changes in the way of parenting. basin of the right posterior cerebral artery. In order to clarify the nature of the inflammation, a skin biopsy was performed: lymphocytic infiltration around the vascular bundles, vascular walls with microvessel thickening, fibrinoid swelling, endothelium with manifestations of dystrophy. A part of vessels are with obliteration of lumens, vacuolic dystrophy of the epidermis, focal fibrinoid swelling. These changes allowed to completely eliminate sarcoidosis and treat the disease as SLE. Due to the impossibility of conducting genetic studies, clinical differential diagnosis was performed between the forms of the congenital lupus. The presence with an early onset, infectious syndrome, lung injury, CNS, hematologic and lymphoproliferative syndrome, cold changes, absence of antibodies to DNA, ANCA, normal level of complement and IgM, indicated the possibility of interferonopathy. Correction of therapy has been performed: the dose of GС was increased to 1.5 mg/kg/d, DMARD has been changed to cyclophosphamide, anticonvulsant and antihypertensive drugs have been added. Conclusion: Possibility of development of identic symptoms in rheumatic diseases can lead to the appointment of therapy before establishing the final diagnosis. Improving the possibilities of in-depth examination of the child will promote the appointment of effective therapy. Informed consent to publish has been obtained. Headache was present in all patients, while a patient reported blurring of vision, a patient reported orbital pain and other two patients reported nausea and vomiting. The prediagnosis was pseudotumor cerebri in two patients, thrombophilia in one patient and multiple sclerosis in one patient. Behçet family history and recurrent aphthous lesions in the family were present in one patient. All patients had oral aphthous lesions and one patient had genital aphthous lesions. Three patients presented with papilla edema. Pathergy test was negative in all patients. Lumbar puncture was performed in three patients for diagnostic and therapeutic purposes. HLA B51 was screened in two patients and both were positive. MRI revealed venous sinus thrombosis in three patients, optic nerve thickening was observed in two patients and demyelination plaques were found in one patient without thrombosis. ANA and ANCA tests were found as negative, and thrombosis tests were normal in all patients. All patients were receiving azathioprine, there patients were using steroids and low molecular weight heparin additionally. A patient with severe apthous lesion was using colchicine, another patient was using methotrexate and sulfasalazine due to sacoiliitis Adalimumab was started to patient with unresponsive optic nerve compression and sinus venous thrombosis. While three patients who had thrombosis were followed in the remission clinically and radiologically, but the patient with the parenchymal lesion did not reach to remission. Remission was achieved following 8.6 months in average. Conclusion: Neurological involvement of Behçet disease is rare in the childhood. Neurological involvement is classified in two groups as parenchymal involvement due to inflammatory meningo-encephalitis process and non-parenchymal involvement due to vascular process. While meningo-encephalitis is more common in adult patients, children have cerebral venous thrombosis more commonly. In a study which covers both adult and pediatric cases, thrombosis was reported 88.5% of the pediatric cases, only three cases had parenchymal involvement. Three of the four cases in our study also presented vascular involvement. Results: We report the case of a 13-year-old caucasian girl who presented with stridor and respiratory distress at the age of 11. The naso-pharyngo-laryngoscopy showed an isolated subglottic swelling. Infectious researches were negative; no evidence for granulomatosis with polyangiitis nor sarcoidosis was found. She was treated with a one-month course of oral prednisone leading to complete resolution and then a quick tapering of the steroid therapy, with no relapse ever since. After one uneventful year, she complained of low-grade intermittent fever and transient erythematous rash, with no other symptom. Clinical examination was normal. Blood tests showed a moderate inflammation with elevated CRP, ESR and IgG as well as a slight inflammatory anemia; otherwise complete blood count, blood smear, liver and renal functions and urinalysis were normal; auto-antibodies were negative. Thoracic x-ray, pulmonary fonction, cardiac and abdominal US and large infectious researches were negative. After 10 months of unchanged symptoms, she presented with arterial hypertension and a pathologic Doppler on renal arteries. A thoracoabdominal CT-scan was performed showing wall thickening, stenosis and enlargement of the descending thoracic and abdominal aorta, renal and mesenteric arteries, the coeliac trunk and lobar and segmental pulmonary arteries. The total body angio-MRI showed similar findings, without involvement of cerebral and cervical arteries. The diagnosis of TA was confirmed and a therapy with steroids, infliximab and methotrexate was started on March 2018. Conclusion: The diagnosis of TA can be very challenging in the absence of specific symptoms, as in our patient. As an early diagnosis can possibly reduce the risk of permanent vascular complications, TA should be considered in the presence of persistent and unexplained biologic inflammation, particularly in adolescent girls.

Regarding the subglottic swelling, its origin is not completely understood, but a non-infectious chondritis seems to be the most reasonable explanation. Even if our patient did not meet the criteria for the RP, a possible association between the chondritis and TA should be considered, as they could both be the consequence of a unique dysimmune process. Written informed consent obtained from the parents. Introduction: Kawasaki disease is one of the most frequent vasculitis and the main cause of acquired heart disease in childhood; the cause is still unknown and affects mainly children under 5 years old. Timely treatment with intravenous immunoglobulin (IVIG) has succeeded in decreasing the incidence of coronary aneurysms from 25% to approximately 4%, with the risk of developing future thrombosis, stenosis, myocardial ischemia or involution of aneurysms.Objectives: Presentation of the case and treatment initiated in the presence of giant coronary aneurysms as well as systemic aneurysms in a 3-month-old girl. Methods: Description of the clinical case of a patient outside the age range for Kawasaki disease with formation of giant aneurysms of the coronary arteries, iliac arteries and abdominal artery. Results: We present the case of a female patient of 3 months of age, with no relevant history, who comes to our institution for 16 days with fever as well as irritability, treated with antipyretic and multiple antibiotic schemes without clinical response. At hospital admission, an approach was made to rule out an infectious process, requesting an echocardiogram, which reported: right coronary artery with a 6 x 11mm aneurysm (z 11.7) before the bifurcation and right coronary artery with a 4 x 6mm saccular aneurysm (z 10.2). Physical examination with fever, conjunctival nonexudative erythema, cleft lip, generalized maculopapular rash and BCGitis, which integrates the definitive diagnosis. Subsequently, management was started with intravenous immunoglobulin 2 g/kg, methylprednisolone bolus 30 mg/kg, acetyl salicylic acid 80 mg/kg and enoxaparin 1 mg/kg/ per dose. The control echocardiogram reported a decrease in the right coronary aneurysm, which was now medium but an increase in the giant aneurysm of the left coronary artery, added to the increase of inflammatory markers, we decided a second dose of IVIG followed by 7 days with full dose of prednisone (2 mg/kg). Angiotomography was performed three days later reporting fusiform aneurysms in the abdominal artery and common iliac arteries but without fever and normalization of C-reactive protein (CRP), so decided decrease of acetyl salicylic acid to 4 mg/kg, continue with anticoagulation and hospital discharge.Conclusion: The incidence of systemic aneurysms is not well described with series that report between 0.6 to 2.5%, developing giant aneurysms up to 10%, and an age range of 1 to 20 months with an average of 6 months as the case of our patient. The sites mainly affected are brachial artery, common iliac artery, internal iliac artery, subclavian artery, axillary artery, lateral thoracic artery, femoral artery, and renal artery. Informed consent to publish had been obtained from the parent. Objectives: Patient is an 11-year-old boy complaining of fever, pain and swelling of the ankles and ecchymotic skin lesions on the legs and buttock, and purpuric lesions resembling erythema multiform on the elbows and dorsal side of forearms.One day after admission, petechiae presented on the surface of his mouth and patient had hemoptysis for several times. Microscopic hematuria was detected in urine analysis. The next day due to massive hemoptysis, evidence of pulmonary hemorrhage in CT scan of the lungs and patient's respiratory distress, he was candidate to be admitted in the ICU. According to the presentation and physical examination of the patient and C-ANCA titer which has been reported more than 300, the diagnosis of AAV (Wegener) was made with Printo's criteria. Methods: case report Results: case report Conclusion: This case was an 11-year-old boy presenting with purpuric rashes on the limbs and arthritis who has been diagnosed with WG by the result of C-ANCA titer and ruling other diagnosis out such as infectious diseases, immune disorders, neoplastic disorders, Anti GBM disease, ANCA positive ulcerative colitis and other autoimmune diseases. Patient has been treated with methylprednisolone pulse for three days with 30mg/Kg/day dosage and after that cyclophosphamide pulse and 2mg/Kg/day of prednisolone as maintenance therapy. Informed consent for publication had been obtained. Introduction: We present a 4 years old girl with prolonged fever who was diagnosed as perforated appendicitis at the same time with coronary artery dilation as a complication of Kawasaki disorder Objectives: Atypical presentations of the kawasaki disease can pose a diagnostic dilemma. The prevalence of incomplete or atypical disease that do not meet the classical presentation of the disease is relatively high(13.8 percent in Japan). It is important to know other significant, though not diagnostic, findings that raise a suspicion of the disease in absence of the classical criteria. Methods: Our patient is a 4 years old girl with no prior positive medical history who presented to our emergency department with prolonged fever and a febrile seizure on the first day of her feve.Three days after the fever began she started having generalized colicky abdominal pain .Her initial lab results showed a WBC count of 19500 per mm3 with 73% Neutrophils, a hemoglobin of 9.2 with normal MCV and MCHC, normal platelet count and an elevated ESR and CRP at 81 and 116 respectively. Serum Albumin and liver function tests were normal. Results: To diagnose the source of her prolonged fever an echocardiogram and abdominal ultrasound was ordered.Abdominal ultrasound showed a collection in the right lower quadrant compatible with a diagnosis of perforated appendicitis. Echocardiogram showed dilation of LAD with a Z score of 4(small aneurysm).CT Angiography of abdominal aorta and femoral arteries revealed no dilation or narrowing. Conclusion: upto now just two cases similar to ours has been previously described. Our case provides the third example of this extremely rare presentation of the disease.In every person with prolonged fever and abdominal pain vasculitides like kawasaki disease must be ruled out. Informed consent to publish had been obtained. There was no significant difference in clinical manifestations, laboratory results, therapeutic approach and outcome in children with Kawasaki disease compared to other studies.

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