Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Several publications in adults looked at the differences between limited and diffuse subtypes. There is rarity of data regarding this topic in pediatric jSSc. The juvenile scleroderma inception cohort (www.juvenilescleroderma.com) is a prospective standardized register for patients with jSSc. Objectives Comparison of features of patients with limited jSSc (ljSSc) and diffuse jSSc (djSSc) subtypes at the time of inclusion in the registry Methods Patients with jSSc were included worldwide into the juvenile scleroderma inception cohort. We compared the demographics and clinical features of the ljSSc and djSSc. Results Up till now 39 patients were enrolled, 29 with djSSc and 10 with ljSSc. 5 in the diffuse (17%) and 3 in the limited subtype (30%) had an overlap feature. The mean follow up of the patients in the cohort was 6.4 years in the djSSc and 5.3 years in ljSSc. 76% in the djSSc and 80% in the ljSSc group were female. The mean age at the onset of Raynaud's Phenomenon was 8.7 years in the jdSSc and 12.9 years in ljSSc group while the mean age at the onset of the first non-Raynaud presentation was 9.1years in djSSc and 13.8 years ljSSc. At the time of the inclusion the mean modified Rodnan Skin Score was 19.6 in the djSSc and 7.5 in ljSSc. 70% of patients in both groups had already capillary changes, but 67% in djSSc and only 33% in ljSSc had already history of ulcerations and 32.1% presented with active ulceration in the djSSc and none in the ljSSc. 72% of djSSc and 50% of ljSSc had cardiopulmonary involvement. The two patients with pulmonary hypertension had djSSc. 27.5% in djSSc and 30% in ljSSc group showed signs of interstitial lung disease on imaging. All 3 patients with renal involvement had djSSc. In both groups 30% had gastrointestinal involvement. Around 80% had musculoskeletal involvement in both subtypes. Anti-Scl 70 positivity was found in 40% of djSSc and 37.5% in ljSSc. Only 1 patient in the djSSc group had anticentromere antibody. Conclusions We present the data on the first 39 patients with jSSc included in our cohort. Patients with djSSc and ljSSc differ in several characteristics. Patients with djSSc were younger at onset, had more often capillary changes and active ulcerations, pulmonary hypertension and renal involvement. The characteristics of the pediatric subtypes differs from adults with SSc. Disclosure of Interest None declared

Background Primary immunodeficiency (PID) can present as rheumatic disease due to improper immune regulation. Objectives Study objective was to evaluate prevalence of rheumatic diseases in Slovene patients with PID. Methods Medical records of patients entered in Slovene PID registry were reviewed. Data on rheumatic disease and PID were collected and analysed. Results 240 patients with 49 different PIDs are registered in Slovene PID registry. At least one rheumatic disease is diagnosed in 12 (5%) patients in Slovene PID registry. Five different rheumatic diseases were diagnosed: juvenile idiopathic arthritis (6 patients), rheumatoid arthritis (2 patients), skin vasculitis (2 patients), systemic lupus erythematosus (1 patient) and Kawasaki disease (1 patient). Rheumatic disease was the presenting manifestation of PID in 8 patients. Four patients developed rheumatic disease after PID has been diagnosed. Rheumatic disease was present in 5 out of 19 patients with IgA deficiency, 3 patients with yet undefined PID, 2 out of 12 patients with CVID, 1 out of 3 patients with autoimmune lymphoproliferative syndrome and 1 out of 13 patients with DiGeorge syndrome. Conclusions Patients with PID do suffer from different rheumatic diseases. Therefore patients with rheumatic disease should be evaluated for possible underlying PID. Rheumatic diseases are most common in Slovene patients with predominantly antibody deficiencies which form the largest group of inherited disorders of immune system. Patients with PID should be screened for signs of autoimmunity when diagnosis of PID is made and during follow up. Disclosure of Interest None declared

Background Tumor necrosis factor α (TNF α) inhibitors are efficient drugs in treating patients with juvenile idiopathic arthritis (JIA), refractory to treatment with methotrexate. Nevertheless, a proportion of patients does not reach and sustain remission. Single nucleotide polymorphisms (SNP) in the promotor of TNF α and in the gene of TNF receptor-associated factor 1 (TRAF1) have been previously reported to be associated with response to treatment with biologics in adults patients with rheumatoid arthritis. Objectives To investigate the effect of single nucleotide polymorphisms in the promotor gene for TNF α and in the genes for TRAF on response to therapy with TNF α inhibitors in JIA. Methods The data of 61 consecutive patients with JIA treated with TNF α inhibitors at the University Children's Hospital Ljubljana from June 2011 to January 2015 were retrospectively reviewed. The disease activity was measured by JADAS 71 score 6 months after the beginning of treatment with TNF α blocker. Genotyping of SNPs in the genes for TNF α was performed using real time PCR methods. The following SNPs were analyzed: TNF A308G, TRAF 1b rs 3761847, TRAF 1a rs 10818488. Fisher exact test was used for statistical analysis. Results The study group included 43 (70%) girls and 18 (30%) boys with JIA. Mean age at disease onset was 8.7 years. Seven (11%) patients had systemic arthritis, 19 (31%) polyarthritis (2 out of these were RF positive), 10 (15%) persistent oligoarthritis, 14 (22%) extended oligoarthritis, 7 (11%) juvenile psoriatic arthritis and 4 (7%) patients suffered from enthesitis related arthritis. Median disease duration until TNF α blockers were introduced was 18 months. Patients received 3 different TNF α blockers, 24 (39%) patients received infliximab, 22 (36%) etanercept and 15 (25%) adalimumab, respectively. Mean follow up time was 80 months. Six months after treatment was introduced 33 (54%) patients had inactive disease. Mean time to inactive disease was 6.9 months. Eight (13%) patients received two and 3 (5%) patients received three different TNF α blockers in the follow up period. Fifty one (84%) patients had at least one polymorphic allele in TRAF 1a rs 10818488 and 42 (69%) had at least one polymorphic allele in TRAF 1b rs 3761847. Using Fisher exact test no statistically significant relationship was found between the analyzed SNPs and inactive disease after 6 months of treatment. Conclusions The analyzed SNPs in the promotor gene for TNF α and in the TRAF genes do not seem to significantly affect response to TNF α inhibitors in JIA. TRAF 1a rs 10818488 and TRAF 1b rs 3761847 might be associated with increased disease susceptibility as the incidence of polymorphic alleles was high in the population studied. Disclosure of Interest None declared

Management of a child with juvenile idiopathic arthritis (JIA) is directed toward treating the underlying inflammation, preventing complications (e.g. joint damage, loss of function) and decreasing pain. Treatment is aimed at inducing and maintaining remission with the least toxic medications. The mainstays of JIA therapy represent drugs that suppress the inflammatory and immune responses, and include non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and biologic agents. Systemic corticosteroids are the most potent anti-inflammatory agents and still have an important role especially as an initial treatment in certain JIA subtypes such as systemic JIA, severe forms of polyarthritis with functional impairment and for chronic uveitis unresponsive to topical therapy. Indications for corticosteroids use in systemic JIA include uncontrolled fever, symptomatic serositis, severe anemia and macrophage activation syndrome, while in patients with polyarthritis corticosteroids are usually used as a low-dose and short term bridging therapy before the full therapeutic efficacy of DMARD. Injections of long-acting corticosteroid directly into inflamed joints is a standard therapy in children with oligoarthritis and are sometimes given also in patients with polyarticular disease while awaiting response to DMARD. The goal of treatment with DMARDs is to achieve and maintain inactive disease and then stop other treatments such as NSAIDs and corticosteroids. Methotrexate is safe and effective drug for treatment of JIA and is the most frequently prescribed DMARD. It has the greatest efficacy in patients with extended oligoarthritis and polyarthritis, and may also have a disease-modifying effect to slow down the radiologic progression of the disease. The disease flare will occur in as many as 60% of the patients after stopping methotrexate and it is not firmly established when a patient can stop taking the drug. Tumor necrosis factor (TNF)-α antagonists are the most often used biologic therapy in patients with JIA. In general, biologics are indicated in JIA patients who have had an inadequate response to 3 months of methotrexate at the maximum tolerated typical dose or who have not tolerated methotrexate. Since biologic agents have a more rapid onset of action and appear to be more efficacious than methotrexate, treatment with biologics may also be considered before or concurrent with methotrexate, particularly in patients with severe polyarthritis or cervical spine involvement. At present, there is no clear evidence for how long JIA patients should be treated and when to discontinue treatment with biologics. In general, it is advised that the biologic treatment should be slowly tapered and it is not recommended to completely discontinue all therapy (e.g. patients should stay at least on methotrexate). Current evidence suggests that up to 70% of children with JIA that achieved clinical remission on medication will have a disease flare within three years off their medication. Disclosure of Interest None declared

Background Mutations of MEFV gene are considered as the primary cause of Familial Mediterranean Fever but are also found in other multifactorial autoinflammatory and/or autoimmune diseases. Objectives The aim of our study was to determine the incidence of recurrent fevers and other clinical signs of inflammation in healthy subjects with present mutations and/or R202Q polymorphism of MEFV gene and to compare incidence of this events and oxidative stress parameters with subjects without MEFV changes. Methods Study was performed as addition to recently published study by Debeljak M et al (Clin Exp Rheum 2015) intended to evaluate distribution of MEFV gene mutations in healthy population of South East Europe. 100 healthy subjects donated blood samples for genetics and oxidative stress parameters analysis. Data about inflammatory clinical manifestations were obtained retrospectively using Eurofever project questionnaire. DNA was extracted from peripheral blood and sequencing was performed using automated sequencer. Oxidative stress was determined by measuring thiobarbituratic acid reactive substances (TBARS) and advanced oxidation protein products spectrophotometrically. Superoxide dismutase (SOD) activity was determined by McCord and Fridovich method and catalase activity using ELISA kit. According the genetic findings patients were stratified into 3 groups:A-with MEFV gene mutations associated with R202Q homozygotes; B-only with MEFV gene mutations and C-only R202Q homozygotes. Results Out of 100 examined subjects 11% had MEFV gene mutation:6% heterozygous E148Q/N and 5% K695R/N; 10% homozygotes and 45% heterozygotes of R202Q polymorphism.The established carrier frequency of mutations and R202Q polymorphism was unexpectedly high for a healthy population. Group A and B reported more frequently febrile episodes of unknown cause (pA=0.027, pB=0.048), diffuse abdominal pain (pA=0.015, pB=0.017), peritonitis (pA=0.019, pB=0.008) and fatigue (pA=0.012, pB=0.032) in comparison with subjects without these gene changes. Group C had significantly more often repeated episodes of fever (p=0.022), diffuse abdominal pain (p=0.009) and lymphadenopathy (p=0.035). Group A had significantly higher concentration of TBARS compared with persons without gene changes (p=0.03) suggesting the existence of increased oxidative damage. SOD activity was significantly higher in A (p=0.049) and C group (p=0.001), probably due to increased induction of extracellular SOD. Changes in oxidative stress parameters in the MEFV carriers significantly were associated with inflammation parameters: leukocytes count with TBARS (p=0.009) and ESR and SOD levels (p=0.031). Conclusions Healthy individuals may bear E148Q and K695R MEFV gene mutations and R202Q polymorphism in homozygous state. These gene alterations contribute to a subtile oxidative stress and may be associated with more frequent episodes of fever and unspecific inflammatory manifestations, as a predisposing factor for inflammation. Disclosure of Interest None declared

PFAPA syndrome is the most common autoinflammatory disorder in childhood with unknown etiology. The aim of our study was clinical evaluation of PFAPA patients from a single tertiary care center and to determine whether variations of AIM2, MEFV, NLRP3, and MVK genes are involved in PFAPA pathogenesis. Clinical and laboratory data of consecutive patients with PFAPA syndrome followed up at the University Children's Hospital, Ljubljana, were collected from 2008 to 2014. All four genes were PCR amplified and directly sequenced. Eighty-one patients fulfilled criteria for PFAPA syndrome, 50 (63%) boys and 31 (37%) girls, with mean age at disease onset of 2.1 ± 1.5 years. Adenitis, pharyngitis, and aphthae were present in 94%, 98%, and 56%, respectively. Family history of recurrent fevers in childhood was positive in 78%. Nineteen variants were found in 17/62 (27%) patients, 4 different variants in NLRP3 gene in 13 patients, and 6 different variants in MEFV gene in 5 patients, and 2 patients had 2 different variants. No variants of clinical significance were found in MVK and AIM2 genes. Our data suggest that PFAPA could be the result of multiple low-penetrant variants in different genes in combination with epigenetic and environmental factors leading to uniform clinical picture.

To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA).