Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Several adult publications looked at the differences between male and female patients with Systemic Sclerosis. 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 patients characteristic at the time of inclusion in the registry who are male or female. Methods Patients with jSSc were included worldwide to the juvenile scleroderma inception cohort. We compered the demographics and clinical characteristics of the male and female patients. Results Up till now 74 patients were enrolled, 54 with djSSc (76%) and 18 with ljSSc (24%). 14 (19%) of the patients were male (M) and 60 female (F) (81%). The mean disease duration at the time of inclusion was 9.3 in M and 9.2 in F patients. 74.4% of the M and 76.7% of the F had diffuse subset. The mean age of the onset of Raynaud symptomatic was 9.3 in M and 9.2 years in the F patients and the non-Raynaud symptomatic with 9.1 in M and 9.9 in F patients. At the time of the inclusion the mean modified Rodnan Skin Score was 20 in M and 15.1 in F patients. Anti-Scl 70 positivity was found in 42.9% in M and 32.1% in F patients. Anticentromere positivity occurred in 16.7% in M and 3.3% in F patients (p=0.027). Capillary changes were present in 50% of the M and 60% of F patients, but 50% in M and F had already history of ulcerations, but 28.6% in M and 15.5% in F had active ulceration. 57.1% of the M and 50% of the F patients had cardiopulmonary involvement. Six patients had pulmonary hypertension, they were all F. 75% of M and 46.7% of F patients had signs of interstitial lung disease on imaging. Renal involvement was around 7% in both sexes. 21.4% in M and 38.3% in F patients had gastrointestinal involvement. 92.9% of M and 55.9% in M patients had musculoskeletal involvement. Conclusions We present the data on the first 74 patients with jSSc included in our cohort. Patients with male sex have a more severe disease similar to adult male patients. Disclosure of Interest None declared

Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Several adult publications looked at the differences between limited (ljSSc) and diffuse subtype (djSSc). There is rarity of data regarding this topic in pediatric jSSc. The juvenile scleroderma inception cohort is a prospective standardized register for patients with jSSc. Objectives comparison of patients characteristic at the time of inclusion with ljSSc and djSSc Methods We compered the demographics and clinical characteristics of the ljSSc and djSSc. Results Up till now 74 patients were enrolled, 54 (76%) with djSSc and 18 with ljSSc (24%). 9% in djSSc and 25% in ljSSc showed overlap features. Disease duration at time of inclusion in the cohort was 3.7 years in the djSSc and 3.3 years in ljSSc. 82% in the djSSc and 78% in the ljSSc group were female. The mean age of the onset of Raynaud symptomatic was 9.0 years in the jdSSc and 9.9 years in ljSSc group and onset of the non-Raynaud symptomatic with 9.4 in djSSc and 10.6 ljSSc. At the time of inclusion the mean modified Rodnan Skin Score was 18.5 in the djSSc and 8,4 in ljSSc (p=0.0001). Anti-Scl 70 positivity was found in 31.5% of djSSc and 30.8% in ljSSc. Only 2 patient in the djSSc group and one in the ljSSc group was anticentromere positive. Capillary changes occurred in 60.7% in the djSSc and 50% in ljSSc, but 58.2% in djSSc and only 23.5% in ljSSc had already history of ulcerations (p=0.013) and 21.8% had active ulceration in the djSSc and 5.9% in the ljSSc. 33.3% of djSSc and 72.7% of ljSSc had cardiac involvement (p=0.027). pulmonary hypertension occurred in 57.1% djSSc and 18.2% in ljSSc. 63% in djSSc and 27.3% in ljSSc group had signs of interstitial lung disease on imaging (p=0.046). Renal involvement occurred in 7.1% djSSc and 5.6% in ljSSc. 39.3% of djSSc and 22.2% of ljSSc had gastrointestinal involvement. 56.4% in djSSc and 83.35 in ljSSc had musculoskeletal involvement (p=0.04). Conclusions Patients with djSSc have younger age at onset, have more often capillary changes and active ulcerations, pulmonary hypertension and less gastorintestinal and joint involvement and more disease damage. The characteristics of the pediatric subtypes differs from adults with SSc, especially the high proportion of patients with diffuse subtype. Disclosure of Interest None declared

Objective. The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). Methods. CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample). Results. There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported. Conclusion. Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.

Neonatal onset multisystem inflammatory disease is a rare autoinflammatory disorder. Clinical features include fever episodes, urticarial rash, arthralgia and arthritis, eyes and central nervous system involvement. It belongs to the group of cryopyrin-associated periodic syndromes which  result from a gain-of-function mutations of the NLRP3 gene on chromosome 1p44 that encodes the cryopyrin protein. Defects lead to overproduction of inflammatory cytokines involved in the innate immune system, especially interleukin 1. This article reports a clinical case of a 6-year-old boy, who presented with  first clinical signs of the disease soon after birth. We present a diagnostic approach in a case of suspected periodic fever syndrome. It is based on exclusion of infections, primary immunodeficiencies, autoimmune and malignant disorders. For confirmation of the disease, genetic analysis is mandatory. The patient was successfuly treated with biological medications which block interleukin 1.

To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA—associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

Data from Slovene national primary immunodeficiency (PID) registry are presented. Besides clinical and genetic data of patients with PID, quality indicators in patient care are included. Data are systematically collected in Department of Allergology, Rheumatology and Clinical Immunology in collaboration with physicians of different specialities. Increasing number and spectrum of PID are recognised in Slovenia. After establishment of Slovene multidisciplinary group in PID care in 2007 thorough immunological and genetic diagnostics, subcutaneous immunoglobulin replacement and treatment of PID with haematopoietic stem cell transplantation were introduced in routine clinical practice in Slovenia. Increased medium age of PID patients reflects improved survival and better recognition of PID in adults. According to the data in comparable registries percentages of patients with predominantly antibody deficiencies and complement deficiencies are low and high, respectively.

Objective To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation.

OBJECTIVES Familial Mediterranean fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Eastern Mediterranean populations have the highest number of carriers, whereas western Mediterranean populations are less frequently affected. The aim of this study was to determine the carrier rate and spectrum of MEFV gene mutations in apparently healthy populations and in suspected FMF patients from central and southeastern European (CSEE) countries. METHODS We screened 507 apparently healthy persons from 5 CSEE countries. Exons 2 and 10 of the MEFV gene were PCR amplified and subsequently sequenced with ABI prism310 genetic analyser. Six most common mutations in the MEFV gene were tested: V726A, K695R, M694V, M694I, M680I in exon 10, and E148Q in exon 2. In suspected FMF patients we screened all MEFV exons in selected cases. RESULTS The overall carrier frequency of all MEFV mutations was higher than expected (9.3%). In the whole cohort we did not find any apparently healthy persons with two mutations. Heterozygous mutations were found in apparently healthy subjects from different CSEE countries as follows: Macedonia 16%, Serbia 11%, Bosnia and Herzegovina 8%, Slovenia 6% and Hungary 5%. The most common mutation in healthy controls was K695R, appearing in 40% of mutated alleles. The most common mutation in suspected FMF patients was M694V, followed by K695R. CONCLUSIONS We found a higher than expected carrier rate of MEFV gene mutations in populations from CSEE countries. It is interesting to note that 40% of detected carriers carry the K695R mutation.

The dynamic process of the development of the immune system can in itself result in age-related immune malfunctions. In this study, we analysed lymphocyte subsets in the peripheral blood of 60 healthy donors, divided into groups of children, adolescents, and adults, focusing on effector (Teff) and regulatory (Treg) T lymphocytes and STAT1/STAT5 signalling response in helper T lymphocytes (Th) in adults, using flow cytometry. Our results demonstrate a decrease in the percentage of total Tregs and an increase in the percentage of total Teffs with age and a consequential immense increase in the Teff/Treg ratio. The increase of Teffs was most apparent in Th1, Th1Th17, and Th17CD161− subsets. Significant Th lymphocyte STAT1 expression differences were observed between children and adolescents, which were associated with the decrease in activated Tregs. Higher expression of STAT1 was found in FoxP3hi than in FoxP3low Th lymphocytes, while significant IL-2 induced STAT5 phosphorylation differences were found among the subsets of Th lymphocytes in adults. Our study demonstrates age-related changes in circulating Teff and Treg, as well as significant differences in STAT5/STAT1 signalling among FoxP3+ Th lymphocytes, providing new advances in the understanding of immunosenescence.