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Systemic juvenile idiopathic arthritis (SJIA) is regarded as an autoinflammatory disease (AID) of unknown etiology related to abnormalities of the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines as interleukin (IL)-6 and IL-1.

Background Methotrexate (MTX) is the mainstay treatment in the therapy of children with juvenile idiopathic arthritis (JIA) and can lead to prolonged remission and improved quality of life. However JIA patients frequently develop intolerance to MTX, with anticipatory and associative gastrointestinal adverse effects before drug intake, arising as a conditioned response. Parents frequently try to alleviate these symptoms with a variety of countermeasures against nausea. Objectives The objective of this study was to investigate the course of MTX intolerance in pediatric patients over a period of 6 months, as well as the effect of countermeasures by parents on the severity of MTX intolerance. Methods Consecutive patients admitted to the German Center for Pediatric and Adolescent Rheumatology from October 2012 until April 2014 were included in this study. MTX intolerance was measured using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. Inclusion criteria were 1) diagnosis of JIA, 2) treatment with MTX for at least 3 months prior to inclusion, and 3) confirmation of MTX intolerance by a MISS value of ≥6. Exclusion criteria were other diseases leading to nausea and/or abdominal complaints, and concomitant medications possibly inducing nausea (excepting biologics and non-steroidal anti-inflammatory drugs). Methotrexate dose, MISS and countermeasures instituted by the parents were determined at 4 time points (at inclusion, at 6 weeks, 3 months and 6 months). Countermeasures were classified into 4 criteria: antiemetic drugs, covert dosing, taste masking and complementary medicine. Results were analyzed using descriptive statistics and non-parametric testing (Wilcoxon signed rank test). Results 38 patients were included (63% female, median age at inclusion 11.7 years, median disease duration 7.1 years). Average MISS at inclusion was 10.8±4.1, and after 6 months 12.2±7.2 (p=0.316). In 6/38 patients (16%), MTX was reduced or discontinued during the study. In 89 time intervals between study visits, 40 countermeasures were introduced by the parents. Conclusions If MTX intolerance is present, symptoms will not decrease over the course of 6 months. Various modalities used by the parents as countermeasures against nausea by the parents show no discernible effect. Acknowledgements This study was supported by the “Stiftung Hilfe fur das rheumakranke Kind e.V.” Disclosure of Interest None declared

Background Juvenile idiopathic arthritis (JIA) is the most common arthritic disease of childhood and is caused by a combination of genes and environment. In the last few years great advances have been made in dissecting the genetic basis of JIA with now 17 confirmed susceptibility loci identified. One of these loci, the MHC region, has been established for many years but the complexity and the broad linkage disequilibrium across the region has rendered fine-mapping associations challenging. Novel imputation strategies can now be utilized to impute HLA classical alleles and amino acids across the region. Objectives The aim of this work was to gain a greater understanding of the associations across the HLA region in all JIA subtypes. Methods Using the dense genotype data obtained from the analysis of the Illumina ImmunoChip in 4574 JIA cases (not including the systemic-onset cases) and 14412 controls, we imputed HLA classical alleles (2-digit and 4-digit resolution) and amino acids across the MHC region (Chr6:29-34Mb) using the SNP2HLA algorithm and a large reference panel. We performed univariate analysis for all markers across the region and tested all amino acids in HLA-DRB1 by performing an omnibus test of amino acid residues for each position. Conditional analysis, including the most significant marker as a covariate, was performed to identify independent effects. Analysis was repeated in the individual subtypes (persistent oligoarthritis (pO) n=1751, extended oligoarthritis (eO) n=658, RF negative polyarthritis (RF-P) n=1525, RF positive polyarthritis (RF+P) n=337, enthesitis related arthritis (ERA) n=183, psoriatic arthritis (jPsA) n=112). Results The omnibus test for all amino acids across HLA-DRB1 showed most significant association at HLA-DRB1 amino acid (AA) 67 and conditioning on all residues at AA 67 found significant association remaining at HLA-DRB1 AA 13 (the glycine residue most associated), suggesting two independent effects in HLA-DRB1. There was evidence for further effects in HLA-DRB1. Conditioning on all alleles of HLA-DRB1 found additional independent effects at HLA-DPB1-0201 and HLA-A AA 95. These associations hold across RF-P and both pO and eO subtypes, HLA-DRB1 AA 13 is most strongly associated in RF+P with the histidine residue driving the association. In the ERA subtype HLA-B27 showed the strongest association. For jPsA no HLA markers reached genome-wide significance. Conclusions Analysis of the MHC region in the largest cohort of JIA cases and controls studied to date has found the strongest association with the HLA-DRB1 region, with additional multiple independent effects. Acknowledgements Juvenile Arthritis Consortium for Immunochip (JACI) Disclosure of Interest None declared

Background Methotrexate (MTX) is the drug used most frequently in the therapy of juvenile idiopathic arthritis (JIA). However, long-term treatment in children frequently leads to intolerance, with marked revulsion and refusal of treatment. Mutations in the gene for methylenetetrahydrofolate reductase (MTHFR) can lead to increased toxicity of MTX and could possibly represent an initial stimulus for this conditioned response. Objectives The objective of this study was to investigate the relation of common mutations in the MTHFR gene and occurrence of MTX intolerance in pediatric patients with juvenile idiopathic arthritis treated with MTX. Methods Consecutive patients admitted to the German Center for Pediatric and Adolescent Rheumatology from October 2012 until April 2014 included in this study. Inclusion criteria were 1) diagnosis of JIA and 2) treatment with MTX for at least 3 months prior to inclusion. Exclusion criteria were other diseases leading to nausea and/or abdominal complaints, and concomitant medications possibly inducing nausea (excepting biologics and non-steroidal anti-inflammatory drugs). Intolerance to MTX was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire; presence of MTX intolerance was assumed for MISS values of ≥6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a polymerase chain reaction assay, as described previously. Results were analyzed using descriptive statistics and chi square testing. Results 114 patients were included (71% female, age at inclusion (median) 12.6 years, disease duration (median) 4.1 years). Of those, 49 (43%) showed MTX intolerance. 42% of patients were heterozygous, and 7% homozygous for the C677T mutation of the MTHFR gene, 45% of patients were heterozygous, and 12% homozygous for the A1298C mutation; both are comparable to published allele frequencies. Compared to the homozygous wild type, MTX intolerance was not found significantly more frequent in patients with hetero- and homozygous (p=1.000) or homozygous (p=0.125) C677T mutations, nor in patients with hetero- and homozygous (p=0.775) or homozygous (p=0.444) A1298C mutations. Compound heterozygous mutations for C677T and A1298C were also not found significantly more frequently in patients with MTX intolerance (p=0.809). Conclusions Mutations in the MTHFR gene are not found significantly more frequently in JIA patients with intolerance to MTX. Toxicity associated with the MTHFR gene does not seem to be causally related to the development of MTX intolerance. Acknowledgements This study was supported by the “Stiftung Hilfe fur das rheumakranke Kind e.V.” Disclosure of Interest None declared

Background Uveitis is one of the most threatening complications in juvenile idiopathic arthritis (JIA). It occurs in approximately 10% of all JIA patients. Whether the frequency of uveitis in JIA has decreased over time as a result of the widespread use of immunosuppressive substances, is still an open question. Few data on the occurrence of JIA-associated uveitis and related secondary complications are available from population-based studies. Objectives To determine the change in uveitis prevalence and related secondary complications in patients with JIA between 2002 and 2013. Methods Data source for this study was the National Paediatric Rheumatological Database (NPRD). Uveitis onset, disease characteristics and details on treatment were provided by rheumatologists once a year. Ophthalmologists reported about uveitis characteristics such as eye involvement, uveitis activity and eye complications in detail in a specific uveitis add-on module. Data from the years 2002 to 2013 were used to determine the annual prevalence of uveitis and frequency of secondary complications. Two-level random effect models were used for investigating the change between 2002 and 2013. Results A total of 60 centers included 18,555 JIA patients, which were recorded in the NPRD between 2002 and 2013. The mean age of the patients was 11.4±4.6 years, their mean disease duration 4.4±3.7 years. 66.9% were female and 51.7% ANA positive. Patients9 mean age at arthritis onset was 6.9±4.5 years. In a multivariable regression analysis, the following risk factors for uveitis were identified: oligoarthritis (OR=4.21, p Conclusions Uveitis prevalence and the frequency of secondary complications significantly decreased between 2002 and 2013. Both were correlated with a more frequent use of DMARDs. Acknowledgements The study was supported by a grant from Pfizer Pharma GmbH Germany (Forschungsforderung Rheumatologie). The national pediatric database is financially supported by the Children9s Arthritis Foundation (Kinder-Rheumastiftung). Disclosure of Interest J. Klotsche: None declared, K. Minden: None declared, S. Schenck: None declared, M. Niewerth: None declared, T. Hospach Speakers bureau: Pfizer, Abbvie, J.-P. Haas: None declared, R. Berendes: None declared, G. Ganser Grant/research support from: Abbott, Actelion, Pfizer, A. Heiligenhaus Grant/research support from: AbbVie, Pfizer, Novartis, and Deutsche Forschungsgemeinschaft, and has received study fees from AbbVie, Alimera Sciences, Allergan, Santen, and XOMA., C. Tappeiner Grant/research support from: Swiss Foundation for Grants in Biology and Medicine (SFGBM), Swiss National Science Foundation (SNSF) and Novartis.

Background Rituximab (RTX) is used in refractory paediatric rheumatic diseases (PRD). Data regarding the effects of RTX on the immune system in children and safety in PRD is scarce. Objectives To prospectively evaluate indicators of humoral immunity before and until 2 yrs after RTX administration. Methods 20 patients (pts) with PRD (4 SLE, 3 MCTD, 3 JIA, 2 eosinophilic fasciitis, 2 juvenile dermatomyositis, 2 Sjogren-syndrome, 2 GPA (Wegener), 1 MPA, 1 PM/Scl-overlap) after exclusion of common variable immunodeficiency (CVID) received at least 1 standard dose RTX cycle (some pts up to 3 cycles). Additional treatment consisted of prednisolone (10), hydroxychloroquin (10), mycophenolate mofetil (9), methotrexate (6), leflunomide (4), abatacept (2), everolimus (2), cyclosporin (1) and antiinflammatory doses of intravenous immunoglobulin (IVIG) (3). Lymphocyte subpopulations, IgA, IgG, IgM and IgE levels, IgG subclasses, isoagglutinin titers, IgG levels to tetanus toxin, H. influenzae type B (Hib), pneumococcus and measles, spleen size, presence of Howell-Jolly bodies and throat culture were obtained 6, 12 and 24 months (mos) after RTX. IgG levels and vaccine titers in pts receiving IVIG were not included. The continuous variables at time points 6, 12 and 24 mos were compared by paired T test to time point 0 mo (prior to RTX). Results All pts achieved complete B cell depletion. B cells repopulated in all pts with a median of 8.5 mos. IgG and IgM levels were as follows (median [interquartile] mg/dl at 0, 6, 12, 24 mos): IgG 1302 [898;1993], 1172 [839;1409], 902 [732;1248], 1165 [805;1580]; IgM 100 [73;174], 55 [39;85], 33 [28;59], 44 [35;51]. Significant reductions were observed for IgG (6/12 mos), IgM (6/12/24 mos), IgA (6/12/24 mos) and IgE (24 mos). Overall, 7/17 (41%) of patients received IVIG substitution based on predefined threshold levels (3/4 after 3rd cycle of RTX). 1 pt developed low IgG2/3, IgA and IgM levels at 24 mos after one cycle of RTX. 2 pts developed low IgG4 levels. Tetanus toxin IgG decreased significantly at 12 mos but not below a protective threshold. There was a non-significant decrease in pneumococcal antibodies at 12 and 24 mos. Measles IgG levels decreased significantly at 12 and 24 mos but not below a protective threshold. Isoagglutinin titers were present in all pts throughout 24 mos ruling out CVID. There was a remittent non-significant decrease in spleen size. However transient Howell-Jolly bodies indicating temporary hyposplenism were observed in 8 pts. Throat culture following RTX demonstrated colonization with C. albicans in 12, S. aureus in 3, Hib in 2, both P. aeruginosa and S. marcescens in 1, E. coli in 1 and Enterobacter in 1 pts. There were no pneumonias requiring hospitalization. Conclusions Transient IgG-/IgM-deficiency occasionally occurs after RTX treatment of PRDs, especially after repeated treatment cycles, whereas protracted humoral immunodeficiency is very rare. Preventive strategies, including IVIG substitution and/or antibiotic prophylaxis informed by immunologic studies are effective in preventing serious invasive infections. Therefore, we suggest at least 2 yrs of surveillance for acquired humoral immunodeficiency and one-time immunization titers after RTX treatment in PRD. Acknowledgements Supported by a grant from “Verein Hilfe fur das rheumakranke Kind”. Disclosure of Interest None declared

Background Juvenile Idiopathic Arthritis (JIA) patients have arthritis onset of unknown cause that lasts >6 weeks in the inflamed joints of children younger than 16 years. JIA is a complex genetic trait with established increased familial risk and robustly replicated genetic associations (e.g. HLA, PTPN2 ). Multiple single nucleotide polymorphisms (SNPs) in the 22q13.1 locus have reached genome-wide significance in recent genetic association studies using the Immunochip. The 22q13.1 locus contains both IL2RB and RAC2 which are attractive candidates to influence JIA pathology and have respective roles in IL-2 signaling and cell migration. Objectives To identify the statistically, bioinformatically and experimentally most plausible causal SNPs associated with risk of JIA in the 22q13 region. Methods We fine mapped the 22q13.1 locus using data from large scale genotyping projects of a European ancestry cohort of subjects with (3,905) and without JIA (14,388) to predict variants most likely causal at the 22q13.1 locus. Logistic regression conditional analysis was used to define regions of association followed by Bayesian analysis to define variants with large posterior probabilities. Transcription factor binding predictions were used to identify variants for experimental testing by electrophoretic mobility shift assay (EMSA). We limited our investigation to polyarticular RF - and oligoarticular JIA cases to reduce phenotypic heterogeneity. Results Conditional analyses showed independent associations to JIA in both the IL2RB and RAC2 loci. We identified two SNPs that can account for all of the JIA genetic association in this region. Using a Bayesian analysis we identified the SNPs that explained 95% of the posterior probability in the region and are the most likely to be causal. Altered nuclear extract binding was observed with risk and non-risk alleles in the IL2RB locus but not RAC2. These experimental data are consistent with the predicted alteration in transcription factor binding. Conclusions Polymorphic variants in the RAC2 and the nearby IL2RB locus are independent JIA risk loci. Use of the statistical and bioinformatics approach to produce candidates for laboratory validation is an important strategy in defining the function of risk variants in JIA. Disclosure of Interest None declared

Background Varicella zoster virus (VZV) infection is a serious preventable infection in patients receiving immunosuppression. The safety of varicella vacination (VV) in patients with paediatric rheumatic disease (PRD) while receiving immunosuppression (IS) has been debated. Objectives To evaluate the safety of 1st and/or 2nd dose varicella vaccine (VV) in patients (pts) with PRDs receiving IS after passing a pre-vaccination check list of immunologic criteria. Methods In this single centre study, 21 VZV-susceptible pts with clinically inactive PRDs, including different categories of juvenile idiopathic arthritis and connective tissue diseases between the ages of 2–18 years on low-intensity IS (LIIS) (methotrexate [MTX] ≤15mg/m 2 /week and/or prednisolone 15mg/m 2 /week, leflunomide, mycophenolate mofetil [MMF], etanercept, tocilizumab, anakinra, abatacept, or a combination thereof) were included in this study. Prior to vaccination, pts were screened according to an immunologic checklist with predefined cut-offs (for pts on LIIS: WBC>3000/μl, ALC>1200/μl, IgG>500mg/dl, IgM>0, Tetanus toxin-IgG >0,10IU/ml; in addition, for pts on HIIS: CD4 >200/μl [if>5 yrs] or CD4 >500/μl [if 1-5 yrs] and positive T cell reactivity to mitogen or antigen, e.g. via TB-EliSpot positive control. Pts meeting these safety criteria received either a 1st and/or 2nd dose of VV without suspension of IS. VZV-IgG levels were measured before applying VV and after each dose. VZV cellular mediated immunity (CMI) was measured after VV. Potential side effects and PRD flares were monitored. Results Out of 9 pts receiving LIIS and 12 pts receiving HIIS none failed the immunologic checklist. 8 pts (2 LIIS, 6 HIIS) had already received their 1 dose of VV prior to this study and received a 2nd/booster dose of VV only. 13 pts (7 LIIS, 6 HIIS) received their 1st dose of VV within the study and 7 of these 13 pts received a 2nd dose of VV. 11/13 pts demonstrated VZV-IgG levels of >150 IU/ml after the 1st dose of VV, and 5/7 pts of those receiving a 2nd dose of VV achieved levels of >500 IU/ml. 1 pt (on MMF) did not achieve protective VZV-IgG levels and 1 pt (on leflunomide and abatacept) did just achieve a VZV-IgG level of exactly 150 IU/ml, despite 2 doses of VV and adequate humoral and cellular immunity. Of those 8 pts receiving a booster dose only, all exceeded VZV-IgG levels of >500 IU/ml by far. There was no difference in either the mean absolute or relative increase (Δ) in VZV-IgG between pts on LIIS vs. HIIS (after 1st dose of VZV Δ341 IU/ml vs. Δ378 IU/ml and 4.7-fold vs. 4.2-fold, respectively; after 2nd dose Δ745 IU/ml vs. Δ1001 IU/ml and 6.9-fold vs. 6.4-fold, respectively). Data on VZV-CMI were pending at the time of abstract submission. There was no evidence of VV-induced varicella or other VV-associated complications. None of the pts developed a PRD flare and no change in the IS regimen was required in any pt during a minimum follow-up of 4 wks. 7 pts had transient arthralgias of unclear association with VV administration. Conclusions After meeting easy-to-obtain immunologic criteria, the VV could safely be applied to a diverse cohort of pts with clinically inactive PID on IS with excellent response in the majority of pts. Acknowledgements Supported by a grant from “Verein Hilfe fur das rheumakranke Kind”. Disclosure of Interest None declared

Background Patients with polyarticular Juvenile Idiopathic Arthritis (JIA) suffer from functional impairments caused by inflammation [1]. While medical treatment leads to an improvement of disease activity in JIA [2], little is known about the effects on conditional or on coordinative abilities. Both are very important in daily living. Objectives The aim of this work is to verify the balance control of JIA patients before and after 9.8 (Q25: 8.5/Q75: 11.3) months with initial adjustment to an anti-TNF-α therapy combined with functional treatment (e.g. physiotherapy) in comparison to healthy peers. Methods Longitudinal effects on balance control of twenty-six patients with polyarticular JIA were analysed before (T0) and after ten months (T1) with an anti-TNF-α therapy combined with functional treatment (median for duration of disease: T0 6.8yr). In addition, a healthy age matched control group (CG; n=26) was included in the study. The balance control was measured with the S3-Check (TST, Groshoeflein). This is a validated measurement system for functional evaluation of stability and sensorimotor ability of the body [3]. The board has one axis of rotation, which enables an alternation up to an overturning of 12° from left to right. The subjects stand barefoot on the S3-Check with an arbitrary arm position. They had the announcement to keep the board for 30 seconds as horizontal as possible. The best results of the stability and sensory indices after three trials were compared with the Wilcoxon signed-rank and Mann-Whitney-U test (p Results JIA patients had significantly lower stability and sensory indices compared to the healthy peers. The balance indices of the patients did not differ between T0 and T1. In anthropometric characteristics no significant differences could be found between the patients and controls. All results are presented in table 1. Conclusions Lower balance indices of the S3-Check demonstrate that the JIA patients had a significantly better stability and motor control than controls. The patients are able to react better to variable positions of the balance board. As all JIA patients included suffered from bad controlled polyarticular JIA, daily compensatory movements in consequence of polyarticular joint pain might have a positive effect on balance control. Additionally an increased body-awareness of patients by long-term functional physiotherapy could further amplify this effect. An anti-TNF-α therapy of ten months did not further improve coordinative ability. The positive results emphasize the significance of functional treatment in polyarticular JIA patients. References Hartmann M et al. (2010). Int J Pediatrics Vol 2010. Minden K et al. (2013). Z Rheumatol 72(4): 339-46. Raschner C et al. (2008). Sportverl Sportschad 22:100-5. Acknowledgements The authors want to thank Pfizer Inc., the “Deutsche Kinderrheuma-Stiftung” and “Ironman-Hilfe Kinderrheuma” for supporting this study. Disclosure of Interest None declared

Background Comorbidities can have a significant influence on presentation, course and prognosis of JIA. Objectives The aim of this study is to analyse the occurrence of comorbidities in a large JIA cohort. Methods JIA patients starting treatment with biologics or methotrexate were followed by the BIKER registry. This database was screened for comorbid conditions reported at baseline. Differences were analyzed by χ 2 test. Results 3427 pts (67.6% female) were admitted. The median [IQR] age at onset was 7.1 y. [3.1; 11.3], at inclusion was 11.8 y. [7.3-14.9] and the median disease duration was 2.1 y. [0,7-5.2]. 1517 (44.3%) pts started MTX. 1916 (55.7%) pts started a biologic. A total of 1327 comorbidities were reported in 959 pts (up to 4 per pts). Uveitis (327) was the most common followed by asthma (53), short stature (47), atopic dermatitis (44), Hashimoto thyreoiditis (29), obesity (28), heart defects (20), arterial hypertension (20), Psoriasis (25), pain amplification syndrome (19), attention-deficit hyperactivity disorder (19), diabetes mellitus type 1 (18), epilepsies (14) and cushingoid syndrome (14). Thus with the exception of uveitis, comorbidities are rarely reported. On interest, the rate of obesity reported is the same as the rate calculated (BMI SDS>3 according to WHO), the rate of short stature reported is much lower than calculated (n=234, length SDS Conclusions Apart from uveitis comorbidities are rare, but there were marked gender related differences. Gender specific aspects should be taken into account considering the diagnostics and treatment of JIA. The limitation of these analyses is the voluntary reporting of comorbidities in BIKER. Disclosure of Interest None declared

Background Methotrexate (MTX) is the most widely used DMARD in JIA. MTX is regarded to be a safe drug, effective in around 70% of JIA cases. Due to the frequent reoccurrence of disease after discontinuing drug therapy, MTX is often prescribed to patients over an extended period of time. However, little is known about its tolerability in long-term use in JIA. Objectives To determine the frequency of adverse events in JIA patients on MTX and the frequency of drug discontinuation due to MTX intolerance. Methods Patients treated with MTX and prospectively followed in the JIA biologic registers BiKeR and JuMBO were considered for this analysis. Adverse events (AEs) were categorized on the basis of MedDRA. Exposure-adjusted rates for AEs were calculated. MTX intolerance comprised defined preferred terms, representing well-known MTX-induced symptoms, such as nausea, vomiting, and abdominal pain, and direct reports of adverse drug reactions or refusal of MTX. Only events reported by physicians to have at least a possible causal relationship were considered as MTX-related. Results Out of 848 JIA patients followed into adulthood, 725 patients were treated with MTX during the mean observation period of 7.3 years (6,188 patient-years of observation). During this period, patients had been exposed to MTX for a total of 2,762 years (exposure-years [EY]). At enrollment into the register, 687 patients were on MTX (61% of these in combination with a biologic), while at the last follow-up at which patients had a mean age of 21.7 years, only 296 patients were still on MTX (62% in combination with a biologic DMARD). Reasons for MTX discontinuation were provided for 323 cases. MTX was discontinued most frequently because of an AE (39%). Remission was the second most common reason (37%), followed by request from the patient in 22%, inefficacy was the least common reason in 9%. One in three patients received more than one course of MTX, with the first course being the longest with a median treatment duration of 2.6 years (second and third course 1.2 and 1.1 years, respectively). During MTX exposure, 435 AEs (17.7/100 EY) and 50 serious AEs (1.8/100 EY) were considered by the physicians as causally related to MTX. Among these, intolerance dominated with 204 events (7.39/100 EY), followed by infections (n=68, 2.46/100 EY) and hepatotoxicity (n=29, 1.05/100 EY). The frequency of intolerance did not decrease, if patients received further courses of MTX; the exposure-adjusted intolerance rate was 4.3/100 EY during the first MTX course, 11.2, 5.6 and 14.3 during the second, third and fourth course of MTX, respectively. Conclusions These results reflect the major problem of MTX intolerance in the long-term care of JIA patients. Intolerance is the leading cause of MTX discontinuation. Assuming that the request from the patient to stop MTX is related to symptoms experienced during drug exposure, about half of the cases discontinue MTX after almost 3 years due to intolerance. Re-exposure to the drug seems to further increase the intolerance rate of MTX. Acknowledgements BiKeR and JuMBO are funded by unconditional grants from Abbvie, Pfizer, Roche. Disclosure of Interest K. Minden Grant/research support from: Pfizer, Abbvie, Consultant for: Pfizer, Chugai, J. Klotsche: None declared, M. Niewerth: None declared, A. Zink Grant/research support from: AbbVie, BMS, GKS, Medac, MSD, Mundipharma, Roche, Sanofi, Pfizer, UCB, E. Seipelt: None declared, J.-P. Haas Grant/research support from: Pfizer, Novartis, G. Ganser: None declared, G. Horneff Grant/research support from: Pfizer, Abbvie, Roche/Chugai, Consultant for: Pfizer, Chugai

Background In Juvenile idiopathic arthritis (JIA) accompanying pain leads to mal-positioning or compensatory movements [1], increasing the risk for osteoarthritis in long-lasting disease courses. In Germany about 1/3 of JIA patients (JIA-P) with polyarticular affection are treated with biologics [2]. This has led to substantial improvement according to disease activity [3]. Still there are hardly any objective analyses on the longitudinal development of functional effects of JIA on joint limitations, especially under treatment with biologics. Objectives The aim of this work is to analyse the longitudinal effects of a combined treatment of JIA including anti-TNF-α therapy and functional therapies (e.g. physiotherapy) on walking abilities of JIA-P. Methods In a prospective longitudinal study 37 polyarticular JIA-P were included and treated with an anti-TNF-α therapy plus regular physiotherapy. JIA-P performed a 3D- gait analysis (8 infrared cameras (Vicon), 2 ground reaction force (GRF) plates (AMTI)) including the Plug in Gait body model. The cohort diminished the size of participants because of lost to follow up (n=15), drop-out (n=1) and investigator-caused discontinuation (n=1). Finally 15 JIA-P (♀: 8; ♂: 7) were analysed according therapeutic effects at all three time-points: (i) before initial anti-TNF-α therapy (T0: 13.7±3.2yr; 1.58±0.17m; 49.8±18.6kg), (ii) after 3.7±0.7 months (T1) and (iii) after 9.9±2.9 months (T2). The results were compared to matched healthy controls (CG) (n=15, ♀=11; ♂=4; 13.5±4.1yr, 1.55±0.12m, 46.5±12.9kg). Because of multilevel affection in JIA-P, both legs of each participant were included. Additionally the Ped-ACR70 score was determined for 13 JIA-P. For statistics the one-way ANOVA with Dunnett Post-hoc test was used (p Results The results demonstrate that the gait function was significantly limited in the JIA-P at T0. JIA-P showed a reduced walking velocity, a not significant decreased hip range of motion (ROM), less power in the ankle at push-off and a reduced load in the vertical GRF (Fz) in single support phase (Table 1). While the ankle power reached a normal size already in T1, the other parameters: walking velocity, hip ROM and Fz load reduction recovered much more slower, reaching values compatible to CG at T2. ACR70/remission were achieved by 62/62% at T1 and by 46/54% at T2. Limitation: 2 JIA-Ps had a relapse between T1 and T2. Conclusions The results of the 3D gait analysis show that functional limitations in JIA-P with polyarticular affection are not completed even when patients under treatment already show good results according to remission criteria. These findings demonstrate the importance of functional therapies, as physiotherapy which should be continued after the regain of clinical inactivity precisely. References Hartmann, M., et al. Int J Pediatr, 2010. Minden, K., et al. Z Rheumatol, 2013. 72(4): p. 339-46. Hashkes, P.J., et al. Nat Rev Rheumatol, 2010. 6(10): p. 561-71. Acknowledgements The authors want to thank Pfizer Inc., the “Deutsche Kinderrheuma-Stiftung” and “Ironman-Hilfe Kinderrheuma” for supporting this study. Disclosure of Interest None declared

Background Children with trisomy 21 have an increased risk of developing polyarticular arthritis. Traditionally, these patients receive a diagnosis of juvenile idiopathic arthritis (JIA) and are treated accordingly. However, very little data exists regarding presentation and treatment response in these patients. Objectives To determine joint activity and distribution pattern in patients with trisomy 21 and JIA and their response to methotrexate compared to patients with seronegative polyarticular JIA. Methods Retrospective case-control study from database of the German Center for Pediatric and Adolescent Rheumatology. Patients with trisomy 21 (T21, confirmed by karyotyping) and JIA were searched including patients with visits within the last 5 years. As a control group two randomly selected patients with rheumatoid-factor negative polyarticular JIA (SNP-JIA) matching with age and gender were extracted for each T21-patient. A retrospective chart survey was used to extract the following data: affected joints at any time and first visit, extraarticular manifestations, and for patients with polyarticular disease: total joint count. As these data result from a historical database only erythrocyte sedimentation rate, adverse events and total active joint count (TJC) at initiation and 1 year after start of Methotrexate were used to determine the response to MTX. Analyses were performed using descriptive statistics, Spearman9s correlation to compare response to methotrexate. Results 11 T21 patients were included in the study (6 female/5 male), with a median age at diagnosis of 6 years (range 1-13 years). Median follow-up was 6 years (range 1-17 years). 9/11 (82%) showed a polyarticular course of arthritis, and all of these were treated with methotrexate. There was no different prevalence of adverse events under MTX in both groups. T21 patients with SNP-JIA showed a significantly higher total joint count of active and painful arthritis at time of diagnosis (mean, n=27) compared with SNP-JIA patients (mean, n=15,5). Initially 8 of 11 (73%) T21-JIA patients presented with SNP-JIA, which is a not expected distribution in ILAR subgroups (expected percentage: SNP 13 -15%). One T21 patient had S-JIA and two an extended Oligo-JIA. Follow up shows a decreased range of motion in at least one joint in more than 81% of T21-JIA patients. We found a significantly higher rate of hypothyreosis in T21 JIA patients (73%) than in Down–syndrome overall (35%). Notably there was no T21-JIA patient with JIA associated uveitis. Conclusions There is a difference in distribution of subtypes of JIA in trisomy-21 patients with a predominant polyarticular pattern. T21-JIA patients show a significantly higher joint count of active arthritis at time of diagnosis and a decreased range of motion in course of the disease, but no difference in MTX tolerance as compared to SNP-JIA patients. Therefore we propose the early initiation of MTX as efficacious and safe therapy, in patients with Trisomy 21 and Juvenile Idiopathic Arthritis. Disclosure of Interest None declared

Background Reduced immunogenicity and efficacy of vaccinations and waning of vaccine-antigen-specific immunity were reported for patients with rheumatic diseases with immunosuppressive therapy or biologics. So far, the persistence of the humoral and cellular immune response against tick-born-encephalitis-virus (TBEV) vaccine was not analyzed in immunocompromised patients with Juvenile Idiopathic Arthritis (JIA). Objectives Thus, the TBEV-specific humoral and cellular immunity was investigated in 64 patients with JIA and 38 age-matched healthy controls who had received at least three dosages of TBEV-vaccine in the past. Methods Antibody concentrations and avidities were measured by adapted ELISAs, TBEV-specific cellular reactivity by ELISPOT assays in spot forming units (SFUs) per 100.000 cells. Results Positive IgG-anti-TBEV antibody concentrations (>165 VIEU/ml) were found in 59 JIA patients (92.2%) compared to 100% of healthy controls. Forty-one JIA patients (64.1%) had high antibody concentrations >1000 VIEU/ml compared to 34 HC (89.5%). Relative avidity index (RAI) was high in JIA patients (82.9%). Significantly higher SFUs were seen in HC (mean 780 SFU) than in JIA (500 SFU). So far, no correlations between TBEV-specific antibody concentrations, avidities or SFU were found. Conclusions Although lower TBEV-specific antibody concentrations and SFU were demonstrated by JIA patients, a sufficient TBEV-specific humoral and cellular immune response was presented even several years after primary TBEV-vaccination in those patients. Whether TBEV-specific immunity may be influenced by age, therapeutic regimens and disease activity and will wane faster in JIA patients with need for earlier booster doses requires proof by longitudinal studies. Disclosure of Interest None declared

To correlate findings of hip ultrasound on day 4-10 of life with sex, intrauterine position and a positive family history for congenital hip anomalies.The SNiP-study ( Survey of Neonates In Pommerania) registered 2256 neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound results of 1043 term and since October 2003 33 preterm neonates were analysed. Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when reaching their corrected term gestational age. Ultrasound was applied with a 7.5 MHz linear scanner and results were classified according to Graf. Chi-square and Fishers exact test were used for statistical analysis.4.9 % of the screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 % bilateral. Incidence was significantly higher (p0.023) in females (6.6 %) than in males (3.2 %). There was no significant difference in intrauterine position or positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of fathers and 2.4 % of siblings positive. There was a higher incidence for congenital hip dysplasia in preterms with 6.1 %, which is not significant due to the limited number.Current screening methods miss up to 18 % of newborns with severe hip dysplasia. We were able to demonstrate that screening for congenital hip dysplasia with ultrasound is a diagnostic tool even during the first days of life. There is a significantly higher incidence of congenital hip dysplasia in females, but in contrast to other studies we found no significant difference in intrauterine position or familial history. Earlier diagnosis and therapy on the base of relevant risk factors might correspond with an improved prognosis and outcome. Further studies are warranted to evaluate the significance in preterm neonates.

Severe pancytopenia due to azathioprine (AZA) toxicity in patients with autoimmune diseases is not uncommon. We describe a 14-year-old girl with HLA-B27+ spondylarthritis who was treated with AZA 3 mg/kg/day and who suddenly developed severe pancytopenia in the seventh week of treatment. Analysis of the catabolic pathway of AZA revealed a homozygous deficiency of thiopurine methyltransferase (TPMT) on the basis of a combined 2-point mutation at nucleotide positions 460 and 719 in the gene for TPMT, causing a toxic level of the metabolic active 6-thioguanine nucleotides (6-TGN) (2,394 pmoles/8 x 10(8) red blood cells). The patient was transfusion dependent and finally recovered 8 weeks after the development of the pancytopenia. At that time, 6-TGN had already returned to normal therapeutic levels. Family studies revealed another homozygous deficiency in the mother, while the other family members were heterozygous.

The tragic death of a 26-year old hobby soccer player is described, who had a collision with the opposing goalie and suffered from a fracture of the left lateral process of the atlas, an extensive subarachnoid haemorrhage, tamponade of the third and fourth cerebral ventricles, bleeding into both lateral cerebral ventricles, infratentorial and supratentorial cerebral oedema. Furthermore, a survey of the literature concerning acute death in soccer is presented. Language: de

Polymorphism in the upstream regulatory region (URR) of the MHC class II DQA1 gene defines 10 different alleles named QAP (DQA1 promoter). In vitro studies have suggested that allelic polymorphism in the HLA-DQA promoter region may result in differences in HLA-DQA1 gene expression. In the present study, we used real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify differences in HLA-DQA1 gene expression. After the isolation of total mRNA, reverse transcription into cDNA was carried out using random hexamer priming and moloney murine leukaemia virus (MMLV) reverse transcriptase. Quantification of DQA1 mRNA species using a set of six group-specific primer pairs for the detection of HLA-DQA1*01, *02, *03, *04, *05 and *06 was carried out on an ABI PRISM GeneAmp 7700 Sequence Detection System (Perkin Elmer, Foster City, CA) with real-time detection and quantification taking advantage of the fluorescence TaqMan technology (Perkin Elmer, Foster City, CA). Normalization of cDNA templates was achieved by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) quantification. In addition, the total amount of mRNA produced by HLA-DQA1 and HLA-DRA1 expression was quantified for comparison. Subsequently, this approach was validated using Raji and HUT-78 cell lines and tested with peripheral mononuclear cells (PBMC) of 45 samples taken from healthy volunteers. The sensitivity was determined withor = 10(2) copies. Comparison of the allele-specific DQA1 expression with the total expression of DQA1 and DRA1 mRNA indicated that DQA1*04 expression was increased compared with the expression of other alleles of the DQA1 gene. Thus, allele-specific quantification of DQA1 gene products could be achieved by real-time RT-PCR suitable for the analysis of differential expression of DQA1 mRNAs in homozygote and heterozygote combinations.

Silicon array readouts for microchannel plate intensifiers offer several attractive features. In this class of detector, the electron cloud output of the MCP intensifier is converted to visible light by a phosphor; that light is then fiber-optically coupled to the silicon array. In photon-counting mode, the resulting light splashes on the silicon array are recognized and centroided to fractional pixel accuracy by off-chip electronics. This process can result in very high (MCP-limited) spatial resolution while operating at a modest MCP gain (desirable for dynamic range and long term stability). The principal limitation of intensified CCD systems of this type is their severely limited local dynamic range, as accurate photon counting is achieved only if there are not overlapping event splashes within the frame time of the device. This problem can be ameliorated somewhat by processing events only in pre-selected windows of interest of by using an addressable charge injection device (CID) for the readout array. We are currently pursuing the development of an intriguing alternative readout concept based on using an event-driven CMOS Active Pixel Sensor. APS technology permits the incorporation of discriminator circuitry within each pixel. When coupled with suitable CMOS logic outside the array area, the discriminator circuitry can be used to trigger the readout of small sub-array windows only when and where an event splash has been detected, completely eliminating the local dynamic range problem, while achieving a high global count rate capability and maintaining high spatial resolution. We elaborate on this concept and present our progress toward implementing an event-driven APS readout.

Speiserohrenverletzungen konnen durch mechanische, chemische oder elektro-thermische Einwirkungen verursacht werden. Wahrend die Behandlung von Saure- oder Laugenverletzungen in der Regel nicht operativ erfolgt, kann bei mechanischen und elektrothermischen Lasionen sowie bei Sekundarveranderungen eine operative Therapie notwendig werden.

Unless treated with haematopoetic stem cell transplantation, Omenn’s syndrome, a rare variant of severe combined immunodeficiency, is associated with a fatal outcome. We describe a male infant showing all the typical features of Omenn’s syndrome, who was successfully treated with cyclosporin A to improve clinical condition prior to haematopoetic stem cell transplantation.

We report a female who was diagnosed with Wegener's granulomatosis at 4 years of age with life-threatening intracranial bleeding. The patient's serum was positive for c-antineutrophilic cytoplasmic antibodies, and histologic analysis of the lung biopsy revealed evidence of granulomatous vasculitis. Initial treatment with steroids and cyclophosphamide was successfully converted to a long-term medication regimen consisting of azathioprine, trimethoprim, and sulfamethoxazole. Thereafter the patient showed no signs of disease activity for more than 3 years and manifested only a low-grade neurologic handicap. In February 2001, 5 years after the initial diagnosis, she presented with altered consciousness and myoclonic multifocal seizures. Subsequent diagnostic studies confirmed the diagnosis of disseminated cerebral vasculitis unresponsive to steroid treatment. Acute neurologic symptoms relented immediately after cyclophosphamide pulse therapy. Magnetic resonance imaging of the brain demonstrated complete remission within 8 weeks. Her current treatment includes steroids and monthly pulses of cyclophosphamide.

Background JIA is the most common chronic inflammatory rheumatic disease in childhood. It carries a high risk for life-long morbidity and disability. Longitudinal cost-of-illness studies are crucial, given the availability of new drugs, which may alter the course of disease. Objectives To analyze the societal economic burden of JIA, the share of cost components, the shift of costs over time, as well as the influence of disease-associated and sociodemographic parameters on the costs in newly diagnosed JIA patients in paediatric rheumatology care. Methods All data were collected within the ongoing German JIA inception cohort ICON, in which patients with early JIA (diagnosis Results Analyses were based on patients (N=333) with baseline (2.7 month [Median] after diagnosis) and one-year follow-up data. Half of the population (2/3 female, median age 7 years) had oligoarthritis (49%), followed by polyarthritis (29%) and enthesitis-related arthritis (10%). In the year before enrollment, the mean total costs accumulated to 6,186 euros (SD: 7,149.75; Median: 3,818; IQR: 5,902.05) per patient and year. Almost half of the total costs were due to hospitalization, 23% to outpatient care except medication, and 20% to indirect costs. Medication only accounted for 3% of the total costs. Within the first year of routine paediatric rheumatology care, the mean total costs accumulated to 9,754 euros (SD: 21,011.92; Median 3,540; IQR: 10,879.73) per patient and year. Now medication, mostly due to biologics (in 19% of the patients), was the main cost driver and responsible for 43% of the total costs. Inpatient care, outpatient care, and indirect costs due to parents9absenteeism from work accounted for 28%, 15%, and 10% of the total costs, respectively. Costs were significantly associated with the JIA subgroup, patient9s disease activity (JADAS), functional status (CHAQ), quality of life (PedsQL), and other disease-related and sociodemographic parameters. The mean costs borne by the families amounted to 539 euros (Median: 260) in the year before study enrollment, and 836 euros (Median: 228) in the first year of follow-up, which corresponded to 1.5% and 2.3% of the families9 net income. Conclusions In addition to the huge burden on the individual, JIA imposes a relevant economic burden to society. All costs incurred within the early JIA disease must be considered in the light of the patients9 long-term outcomes. Disclosure of Interest M. Storms: None declared, J. Klotsche: None declared, I. Liedmann: None declared, M. Niewerth: None declared, A. Thon: None declared, G. Ganser: None declared, J.-P. Haas: None declared, A. Hospach: None declared, K. Minden Grant/research support: Pfizer, Abbvie. ICON is funded by the Federal Ministry of Research (FKZ: 01ER0812)., Consultant for: Pfizer, Abbvie, Roche/Chugai, Novartis DOI 10.1136/annrheumdis-2014-eular.5056

Background Remission and minimal disease activity have been proposed as treatment goal as both can be achieved. For both JADAS based definitions have been proposed. Methods This retrospective analysis used data of the German BIKER-registry the course of JADAS10 (Physician global assessment VAS 0–10-cm, Parent/patient global assessment VAS 0–10-cm, Active joint count 0-71, truncated at 10, normalized ESR [ESR-20/10], range 0-40) upon first biologic regimen. A JADAS Results 2111 JIA pts starting a first biologic were identified. 1830 received Etanercept (ETA), 209 Adalimumab (ADA) and 33 Tocilizumab (TCZ). Biologics not approved for first line therapy (Abatacept, Anakinra, Infliximab, Golimumab) were used in of 39 pts only. Therefore analysis of the latter patient cohorts seemed not reasonable. Baseline parameters differed for the chosen drugs group. Patients receiving ADA first more often have had chronic uveitis and were more often ANA positive. Age at onset, disease duration, distribution of JIA categories and pretreatments were comparable between ETA and ADA, while TCZ was used more frequently in systemic JIA (table 1). Disease activity indicators at baseline were highest in the ETA group followed by TCZ and lowest with ADA. ESR& CRP were highest in TCZ starters. Upon treatment, the median JADAS decreased in all JIA categories. After 12 months on treatment with ETA, depending of the JIA categories, 28% to 42% of pts had a JADAS Conclusions ETA is by far the most frequently used biologic in JIA pts. ADA is preferred in pts with a history of uveitis, while TCZ is preferred in systemic JIA. Minimal disease activity is reached by the majority of pts but remission only by a part. In summary, a treat to target approach seems reasonable in JIA patients. New therapeutic options are needed for JIA patients with refractory disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2336

T cell activation was analysed in peripheral CD4/ T cells from both systemic lupus erythematosus (SLE) patients with active and inactive disease as well as in normal healthy donors (NHD) to investigate the involvement of CD4/ T cells in the etiopathogenesis of SLE. CD4/ T cell receptor (TCR) b-chain transcripts, containing the complementarity determining region 3 (CDR3), were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analysed by highresolution polyacrylamide gel electrophoresis. In addition the CDR3 of both clonally activated as well as heterogeneous Vb families from SLE patients were analysed at the molecular level. We observed a restricted CDR3 length polymorphism in peripheral CD4/ T cells from SLE patients compared with NHD, more pronounced in patients with high disease activity. Furthermore, in some Vb families single peaks in the histogram indicated nearly monoclonal T cell expansion. Sequencing of selected TCR b-chains revealed a increased content of acidic amino acids in the CDR3 encoded by either proximal Jb elements or N nucleotides. We conclude that CD4/ T cells from peripheral blood of SLE patients display features of a secondary antigen driven immune response. The bias of the CDR3 towards acidic amino acids suggests the involvement of positively charged antigens.

Dominant T cells in idiopathic nephrotic syndrome of childhood. Background Because of several studies, idiopathic nephrotic syndrome (INS) of childhood is suspected to have an immunologic pathogenesis with T cells playing a major role. To investigate this hypothesis further, we studied the diversity of the CDR3 region of the T-cell receptor (TCR) β;-chain from peripheral T cells isolated from patients with INS. Methods The study was performed over a three-year period to obtain longitudinal data on the repertoire of peripheral T cells. mRNA from peripheral mononuclear cells (PBMCs) of seven INS patients and two healthy controls (NHD) was prepared and analyzed for CDR3 length polymorphism of TCR β;-chain by spectratyping. Results All INS patients presented individually skewed spectratype histograms in at least one Vβ;-family. Patients suffering from a frequent relapsing course of INS or a focal global sclerosis showed some alterations to persist in all samples isolated in the observation period (up to 3 years). In addition, sequence analyses of the β;-chain of the TCR CDR3 region confirmed clonal expansion of peripheral T cells in those patients who had displayed spectratype alterations. Conclusions The data give strong evidence for an direct involvement of CD8+ T cells in the complicated course of INS.

The expression of m-fas/apo1 (CD95) and its soluble form (s-fas) was studied in patients with early onset pauciarticular (n = 23) and systemic juvenile chronic arthritis (n = 7). RNA was prepared from peripheral blood of patients and 22 healthy controls and from 23 samples derived from the synovial fluid of JCA patients. The ratio of m-fas/s-fas transcripts was calculated by densitometry of fas-specific RT-PCR products. An inverted ratio of m-fas/s-fas transcripts was found in PBMC and mononuclear cells from the joints of early onset pauciarticular JCA patients. The m-fas/s-fas ratios were similar in PBMC and mononuclear cells from synovial fluid. PBMC from patients with a systemic JCA showed the same m-fas/s-fas ratio as healthy controls, with an inverted ratio of both transcripts in cells from the synovial fluid. The data indicate a role of Fas/Apo1 regulated apoptosis in EOPA-JCA which is not limited to the affected joints.

At NASA GSFC we are developing a high resolution solar-blind photon counting detector system for UV space based astronomy. The detector comprises a high gain MCP intensifier fiber- optically coupled to a charge injection device (CID). The detector system utilizes an FPGA based centroiding system to locate the center of photon events from the intensifier to high accuracy. The photon event addresses are passed via a PCI interface with a GPS derived time stamp inserted per frame to an integrating memory. Here we present imaging performance data which show resolution of MCP tube pore structure at an MCP pore diameter of 8 micrometer. This data validates the ICID concept for intensified photon counting readout. We also discuss correction techniques used in the removal of fixed pattern noise effects inherent in the centroiding algorithms used and present data which shows the local dynamic range of the device. Progress towards development of a true random access CID (RACID 810) is also discussed and astronomical data taken with the ICID detector system demonstrating the photon event time-tagging mode of the system is also presented.

Juvenile chronic arthritis (JCA) is a group of diseases characterized by an arthritis with a pauciarticular (up to 5 joints involved) or a polyarticular type of onset, lasting for more than 6 weeks and an age of onset within the first 16 years of life [Wood P.N. 1977]. According to the clinical course, as well as to certain laboratory findings, different subgroups of JCA are defined. JCA is supposed to be an autoimmune disease of childhood and adolescence. The pathogenesis of the disease still remains unclear although numerous findings point to a disturbance in antigen-presentation between MHC (major histocompatibility complex) molecules and T-cells [Haas J.P. et al. 1991, Fink C.W. 1983]. The most dramatic clinical course of JCA is found in systemic JCA (S-JCA) characterized by pauci- or polyarticular course of arthritis accompanied by symptoms of severe general inflammation. High fever, exanthema and a general lymphadenopathy which are typical symptoms of S-JCA indicate that this disease is the simultaneous appearance of JCA and systemic vasculitis in childhood [Jakobs J.C. 1993].

It is often discussed whether patients with juvenile idiopathic arthritis (JIA) should wear orthopedic insoles or not. The functions of insoles are to minimize pain or to assist foot deformities. JIA often goes along with foot impairments [1,2] describe different deviation and deformities which can develop of various pattern of foot joint involvements, like pes valgoplanus or hallux rigidus.