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Objective The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry. Methods The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% CI: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections [IR 1.48 (95% CI: 0.88, 2.34)]. As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improvement over 5 years across JIA categories. Conclusion Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission. Trial registration Clinicaltrials.gov, NCT01357668. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Familial Mediterranean Fever (FMF) is a genetic disorder of the innate immunity characterized by chronic inflammatory state. The diagnosis is mainly based on clinical criteria and supported by genotyping, especially in atypical phenotypes. The primary objective was to depict the Familial Mediterranean Fever (FMF) genotype of Greek patients and investigate the contribution of Next Generation Sequencing (NGS) beyond the contemporary techniques [(Polymerase Chain Reaction (PCR)/hybridization and Non-Isotopic RNase Cleavage Assay (NIRCA). The secondary objective was to unravel any associations between the mutated genes with the disease course and response to treatment. Methods: In this single center, retrospective study 31 patients with clinical diagnosis with FMF, but non-conclusive genetic analysis with PCR/hybridization and NIRCA, underwent NGS genotyping. Results: PCR/NIRCA detected ≥ 1 mutation in 25/31 patients, most frequently M694V (29%), while NGS in 26/31 (83.9%), most frequently R202Q (61.3%). NGS genetically confirmed the clinical diagnosis (heterozygosity to compound or complex genotype) in 19 (61.3%) patients of our cohort. R202Q was significantly more prevalent by NGS than by contemporary techniques (61.3 vs 12.9%, p = 0.0002) and was associated with FMF. Rare mutations were detected by NGS in 19.2% patients. Conclusion: NGS clarifies the genetic profile of patients with atypical phenotypes and supports therapeutic management decisions. NGS unveiled the frequent involvement of R202Q in the pathogenesis of our FMF patients. [ABSTRACT FROM AUTHOR]

Objectives: This study on juvenile SLE patients aimed to evaluate retrospectively the impact of a tertiary center's management policy of the disease severity on its long-term progression and cumulative damage development as well as provision of quality-driven medical care (QmC). Methods: Disease activity was assessed by the Physician Global Assessment and SLEDAI-2K, flares by SELENA/SLEDAI, and damage by the pediatric SLICC/DI at diagnosis, 6 months post-diagnosis, and annually thereafter. At the same time, QmC was evaluated by relevant indices and quality of life was captured by the Greek version of the General Health Questionnaire only at the last visit. Results: A total of 35 patients (25/35 females) aged at diagnosis 5.5–15.16 years (median 11.83) with a median lag time to diagnosis 1.8 months had a follow-up of 5 (35/35) and 10 years (13/35), respectively. The predominant baseline manifestations were consistent with those previously reported. Out of 35 patients, 24 (68.5%) were clinically inactive at year 5, and 5/13 (38%) at year 10. All patients received immunosuppressives and 7/35 biologics in addition. At the end of their follow-up, damage was found in 9/35 patients, but none of them had a neuropsychiatric disorder. Over the study, 28/35 patients were compliant with the QmC recommendations. Conclusions: An early diagnosis combined with a longitudinal quantitative assessment of the disease activity and severity contributes to the continuous evaluation of the disease state. They are the key determinants for the selection of an early, targeted, and personalized management; they restrict the cumulative damage development and contribute to an optimal outcome. Key Points • Juvenile SLE has a heavier introductory profile than in adults and an unpredictable trajectory. • The application of contemporary metric tools for assessing the disease state leads to an objective assessment and regimen selection. • An early diagnosis combined with longitudinal quantitative assessment is a key determinant for an optimal management and a minimal damage development. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long‐term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation. Methods: At enrollment, patients with active systemic JIA (ages 2 to <20 years) started open‐label canakinumab (4 mg/kg every 4 weeks subcutaneously). Efficacy measures included the adapted American College of Rheumatology (ACR) Pediatric 50/70/90 criteria, the Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease and clinical remission on medication, evaluated by either the JADAS or ACR criteria. Results: Of the 123 patients (70 with fever and 52 without fever [fever status was not reported for 1 patient]), 84 (68.3%) completed the study (median duration 1.8 years). Comparable efficacy (adapted ACR Pediatric 50/70/90/100) was observed by day 15 in both subgroups (60.0%/48.6%/37.1%/24.3% in those with fever and 67.3%/48.1%/34.6%/19.2% in those without fever), and further increased thereafter. By month 6, clinical remission according to the JADAS or the ACR criteria was achieved in 17 (24.3%) and 26 (37.1%), respectively, of patients with fever and 9 (17.3%) and 12 (23.1%), respectively, of patients without fever. Median time to onset of clinical remission according to the JADAS or ACR criteria was 57 and 30 days, respectively, in those with fever, and 58 and 142 days, respectively, in those without fever. An adapted ACR Pediatric 50 response by day 15 was the strongest predictor of achieving clinical remission according to the JADAS (odds ratio [OR] 13 [95% confidence interval (95% CI) 4, 42]; P < 0.0001) or glucocorticoid discontinuation (OR 19 [95% CI 3, 114]; P = 0.002). Of the 71 of 123 patients (57.7%) who received glucocorticoids at study entry, 27 (38.0%) discontinued glucocorticoids and 21 (29.6%) reached a dose of <0.2 mg/kg/day, with no difference between those with and those without fever; 13 patients (10.6%) tolerated a sustained canakinumab dose reduction to 2 mg/kg every 4 weeks. No new safety findings were observed. Conclusion: Canakinumab provided rapid and sustained improvement of active systemic JIA irrespective of the presence of fever at treatment initiation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate safety and effectiveness of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (JIA) in the STRIVE registry.Methods: STRIVE enrolled patients with polyarticular-course JIA into 2 arms based on treatment with methotrexate (MTX) alone or ADA with/without MTX (ADA ± MTX). Adverse events (AEs) per 100 patient-years of observation time were analyzed by registry arm. Patients who entered the registry within 4 weeks of starting MTX or ADA ± MTX, defined as new users, were evaluated for change in disease activity assessed by the 27-joint Juvenile Arthritis Disease Activity Score with the C-reactive protein level (JADAS-27CRP ).Results: At the 7-year cutoff date (June 1, 2016), data from 838 patients were available (MTX arm n = 301, ADA ± MTX arm n = 537). The most common AEs were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%) in the MTX arm and arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (3.0% each) in the ADA ± MTX arm. Rates of serious infection were 1.5 events/100 patient-years in the MTX arm and 2.0 events/100 patient-years in the ADA ± MTX arm. AE and serious AE rates were similar in patients receiving ADA with versus without MTX. No deaths or malignancies were reported. New users in the ADA ± MTX arm showed a trend toward lower mean JADAS-27CRP compared with new users in the MTX arm in the first year of STRIVE.Conclusion: The STRIVE registry 7-year interim results support the idea that ADA ± MTX is well tolerated by most children. Registry median ADA exposure was 2.47 (interquartile range 1.0-3.6) years, with 42% of patients continuing ADA at the 7-year cutoff date. [ABSTRACT FROM AUTHOR]

To describe the profile of Enthesitis Related Arthritis' (ERA) patients, in the era of biologic DMARDs (bDMARDs). This retrospective cohort study included patients with ERA monitored on a 3-month schedule for at least 1 year. Their metric assessment included the disease status and damage by applying the contemporary tools clinical-Juvenile Arthritis Disease Activity Score (c-JADAS), Juvenile Spondyloarthritis Disease Activity Index (JSpADA), clinical remission (CR) on/off medication and Juvenile Arthritis Damage Index (JADI). 43 patients (males 26) were enrolled, with a mean disease onset of 10.75 years. Median lag time from diagnosis to bDMARDs was 8.5 months. Patients with sacroiliitis received earlier bDMARDs (hazard ratio, HR 3.26). 36/43 patients achieved CR on medication (median time 11 months), which was correlated with compliance (HR: 3.62). The percentage of CR in patients with or without sacroiliitis was 35% and 63% respectively (p = 0.02). Twenty patients (47%) experienced a flare following CR (75%). The median flare-free survival following CR on/off medication was 42 and 34 months, respectively. At the last evaluation, both median baseline cJADAS and JSpADA dropped to 0, 13/43 patients had a persistent disease activity, while 17/43 and 13/43 patients were in CR on/off medication, respectively. The median patient percentage of CR was 54% and no patient had a JADI > 0. Increased lag time to bDMARDs was associated with increased CR (Odds ratio: 1.48). Early administration of bDMARDs and compliance improved long-term outcome of ERA. Sacroiliitis was a negative prognostic factor with an increased need for bDMARDs and diminished rates of CR. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Familial Mediterranean Fever is the most common autoinflammatory disease. As chronic inflammation may result in increased arterial stiffness, we aimed to investigate indices of arterial stiffness in patients with Familial Mediterranean Fever and their associations with disease-related factors and colchicine treatment. Method: The study was conducted with 43 patients with Familial Mediterranean Fever, including 30 children, in attack free period and 42 healthy controls. Arterial stiffness was assessed by carotid-femoral pulse wave velocity and augmentation index. Results: Patients with Familial Mediterranean Fever presented similar carotid-femoral pulse wave velocity values to controls, but significantly higher augmentation index values (patients versus controls, 19.76% and 9.96%, P < 0.05). Augmentation index, adjusted for age and sex, was associated with complete response compared with partial response to treatment (B = − 17.78, 95% CI − 31.17 to − 4.40, P < 0.05) and the presence of M694V.M680I genotype (B = − 16.75, 95% CI − 33.81 to 0.30, P = 0.05). Carotid-femoral pulse wave velocity presented an inverse relationship with colchicine treatment duration (B = − 0.003, 95% CI − 0.006 to − 0.00, P < 0.05). Pulse wave velocity values adjusted for age and systolic blood pressure were associated with attack frequency (B = 0.48, 95% CI 0.01 to 0.96, P < 0.05). Addition of colchicine treatment duration to the model attenuated the association between carotid-femoral pulse wave velocity and attack frequency supporting the protective role of colchicine. Conclusions: The normal values of carotid-femoral pulse wave velocity in Familial Mediterranean Fever patients may reflect the compliance to colchicine treatment, which seems to have a protective role against arterial stiffness. However, the increased values of augmentation index need further investigation. Key points: • FMF patients are prone to present increased cardiovascular risk possibly due to inflammation. • Colchicine treatment may have protective role against arterial stiffness in FMF. • The normal values of cf-PWV in FMF patients may reflect the compliance to colchicine. [ABSTRACT FROM AUTHOR]

Objectives: Systemic lupus erythematosus (SLE) diagnosis and treatment remain empirical and the molecular basis for its heterogeneity elusive. We explored the genomic basis for disease susceptibility and severity.Methods: mRNA sequencing and genotyping in blood from 142 patients with SLE and 58 healthy volunteers. Abundances of cell types were assessed by CIBERSORT and cell-specific effects by interaction terms in linear models. Differentially expressed genes (DEGs) were used to train classifiers (linear discriminant analysis) of SLE versus healthy individuals in 80% of the dataset and were validated in the remaining 20% running 1000 iterations. Transcriptome/genotypes were integrated by expression-quantitative trail loci (eQTL) analysis; tissue-specific genetic causality was assessed by regulatory trait concordance (RTC).Results: SLE has a 'susceptibility signature' present in patients in clinical remission, an 'activity signature' linked to genes that regulate immune cell metabolism, protein synthesis and proliferation, and a 'severity signature' best illustrated in active nephritis, enriched in druggable granulocyte and plasmablast/plasma-cell pathways. Patients with SLE have also perturbed mRNA splicing enriched in immune system and interferon signalling genes. A novel transcriptome index distinguished active versus inactive disease-but not low disease activity-and correlated with disease severity. DEGs discriminate SLE versus healthy individuals with median sensitivity 86% and specificity 92% suggesting a potential use in diagnostics. Combined eQTL analysis from the Genotype Tissue Expression (GTEx) project and SLE-associated genetic polymorphisms demonstrates that susceptibility variants may regulate gene expression in the blood but also in other tissues.Conclusion: Specific gene networks confer susceptibility to SLE, activity and severity, and may facilitate personalised care. [ABSTRACT FROM AUTHOR]

To assess longitudinally the course and outcome of juvenile idiopathic arthritis (JIA) in patients diagnosed and followed-up exclusively in the biologic era; also, to define possible predictors of the disease progression and need for early implementation of biologicals. Prospective and retrospective, monocentric cohort study of 120 JIA patients, diagnosed between 2001 and 2010, and followed-up for ≥ 4 years (median 8.04). Disease activity, cumulative articular/extra-articular damage and quality of life were evaluated by the assessment tools Juvenile Arthritis Disease Activity Score (JADAS71), Juvenile Arthritis Damage Index (JADI) and Childhood Health Assessment Questionnaire (CHAQ), respectively. Moreover, potential predictors of the disease progression and their relation to biologic therapy were investigated. High JADAS71 score (> 9) at diagnosis was indicative of progression to polyarticular course and the need for early introduction of biologic treatment. Other independent predictors of progression to polyarthritis, were: involvement of upper limb, hip and ankle within 6 months following JIA diagnosis and percentage of cumulative time with active disease > 35% within the first year. At the end of the study, both the median JADAS71 score and the Disability Index were significantly lower than the initial (p < 0.001) and remission off medication was achieved in 25% of the patients. Articular and extra-articular (only ocular) cumulative damage was demonstrated only in 5 and 7.5% of patients, respectively. Physical functional ability was found normal/mildly restricted in 93.3% and moderately restricted in 6.7% of the patients. We believe that these findings, fit in with a picture of JIA course and outcome under current conditions of objective “disease status” evaluation and of tightly controlled follow-up. Predictors emerged from our study could contribute to the identification of patients who will need early implementation of biologic treatment. [ABSTRACT FROM AUTHOR]

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Greek language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographics, clinical data, and the JAMAR from 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). The Greek JAMAR was fully cross-culturally adapted with two forward and three backward translations. A total of 272 JIA patients (5.9% systemic, 57.7% oligoarticular, 21.3% RF negative poly-arthritis, 15.1% other categories), and 100 healthy children were enrolled in all centres. The JAMAR components discriminated well-healthy subjects from JIA patients; notably, there was no significant difference between healthy subjects and their affected peers in psychosocial quality of life and school-related items. All JAMAR components revealed good psychometric performances. In conclusion, the Greek version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs), namely PTPRC (rs10919563), TYK2 (rs34536443) and PRKCQ (rs4750316), which were found to be associated with JIA in previous studies. We also investigated whether the intron-4 located 27-bp VNTR of endothelial nitric oxide synthase (eNOS), is associated with risk for JIA in Greece. In total, 125 JIA patients and 221 healthy controls from northern Greece were included in the study as a sample set. Samples were then analyzed, and genotyped for the three SNPs with TaqMan primer-probe sets, using a Real-Time PCR platform (ViiA™ 7 Real-Time PCR system), while eNOS VNTR polymorphism was genotyped by PCR. Statistical analysis was performed using a GraphPad Prism statistical program. The χ² test was used to examine differences of genotype and allele frequencies between patients and controls. Statistical significance was defined by using the two-tailed P<0.05 test. Bioinformatics analysis was conducted by using BlastP, Pymol, Maestro and Desmond. In the case-control association study performed, eNOS only was found to be associated with JIA. Genotype a/a and allele 'a' were found in a higher frequency in JIA patients than in controls [p<0.0001, odds ratio (OR)=0.15, 95% confidence intervals (CI): 0.065-0.37; and p<0.0001, OR=0.34, 95% CI: 0.23-0.49, respectively]. No associations with JIA were detected for TYK2, PTPRC or PRKCQ. Aiming to investigate the structural consequences and the structure/function relationships accompanying the Pro1104 to Ala (rs34536443) mutation on TYK2 protein, bioinformatics analysis was performed. Combining three-dimensional (3D)-modeling and molecular dynamics simulations we identified changes in structural flexibility, affecting the functionality of the kinase domain of TYK2. To the best of our knowledge, this is the first time that eNOS VNTR polymorphism is associated with susceptibility to JIA, suggesting a differential role of allele 'a' in various complex diseases. The current data emphasize the importance of comparative studies in populations of a different ancestral background towards the clarification of the role of specific alleles in the development of JIA. [ABSTRACT FROM AUTHOR]

Objectives. To describe the disease characteristics, continuous course and long-term outcome and to evaluate predictors of outcome in JIA in Greece. Methods. We performed a retrospective cohort analysis of 17 years' prospective data on JIA. Outcome assessment included radiographic (modified Sharp-van der Heidje score), articular and extra-articular damage (Juvenile Arthritis Damage Index), functional ability (HAQ Disability Index), and the cumulative percentage time spent in a state of active disease and also in clinical remission off medication (CR) (according to Wallace's criteria). Results. One hundred and two (72 females) patients under regular follow-up were enrolled. The disease age of onset [mean (SD)] was 7.7 (4) years, the interval from onset to last visit was 17.2 (6.7) years and the patients' current age was 25 (5.9) years. At the last follow-up visit, 53 patients (52%) had disease activity, while 23.5% were in CR. The cumulative percentage time spent in a state of active disease and CR over the disease course was 52.6 and 17.8%, respectively. Polyarticular subtype of onset and longer disease activity during the first 5 years were independent predictors of worse outcome. Additional telephonebased interviews of 205 former JIA patients who had been lost to follow-up as adults were performed to extend the interpretation of our findings to a broader JIA population. Almost half (47.6%) of the total cohort of 307 patients were found to be in CR at the final evaluation and 69.7% had no disability. Conclusion. The available data indicate that JIA as a whole is a heterogeneous disease with significant variability in course and long-term outcome. [ABSTRACT FROM AUTHOR]

Background: Hereditary recurrent fevers (HRF) are a group of rare monogenic diseases leading to recurrent inflammatory flares. A large number of variants has been described for the four genes associated with the best known HRF, namely MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database ( http://fmf.igh.cnrs.fr/ISSAID/infevers ) is a large international registry collecting variants reported in these genes. However, no genotype-phenotype associations are provided, but only the clinical phenotype of the first patient(s) described for each mutation. The aim of this study is to develop a registry of genotype-phenotype associations observed in patients with HRF, enrolled and validated in the Eurofever registry.Results: Genotype-phenotype associations observed in all the patients with HRF enrolled in the Eurofever registry were retrospectively analyzed. For autosomal dominant diseases (CAPS and TRAPS), all mutations were individually analyzed. For autosomal recessive diseases (FMF and MKD), homozygous and heterozygous combinations were described. Mean age of onset, disease course (recurrent or chronic), mean duration of fever episodes, clinical manifestations associated with fever episodes, atypical manifestations, complications and response to treatment were also studied. Data observed in 751 patients (346 FMF, 133 CAPS, 114 MKD, 158 TRAPS) included in the Eurofever registry and validated by experts were summarized in Tables. A total of 149 variants were described: 46 TNFRSF1A and 27 NLRP3 variants, as well as various combinations of 48 MVK and 28 MEFV variants were available.Conclusions: We provide a potentially useful tool for physicians dealing with HRF, namely a registry of genotype-phenotype associations for patients enrolled in the Eurofever registry. This tool is complementary to the Infevers database and will be available at the Eurofever and Infevers websites. [ABSTRACT FROM AUTHOR]

Background: To evaluate the performance of the Quantiferon-TB Gold In-Tube (QFT-IT) interferon (IFN)- γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece. Methods: A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)- α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF- α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated. Results: Agreement between TST and QFT-IT results was moderate ( k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN- γ assay was increased by a factor of 27.6 ( P=0.002), whereas there was no positive TST. There was a significant difference in the mitogen-induced IFN- γ secretion among various treatments ( P=0.038). TNF- α inhibitors were associated with increased mitogen-induced IFN- γ secretion compared to monotherapy with conventional DMARDs ( P=0.008). All children screened prior to anti-TNF- α treatment exhibited a negative QFT-IT and no active TB disease was detected during a 2-year follow-up. Conclusions: QFT-IT may be a more reliable test than TST for detection of LTBI in children with rheumatic diseases receiving anti-rheumatic treatment. Drug regimen might influence the mitogen-induced IFN- γ secretion and the effect of TNF- α inhibitors might vary according to the specific agent administered. [ABSTRACT FROM AUTHOR]

The improved survival of childhood-onset systemic lupus erythematosus (cSLE) has resulted in longer patients' exposure to disease inflammation, medications and/or comorbid diseases, which can all contribute to the development of organ damage. The aim of this study was to assess the evolution of damage accrual in cSLE patients overtime and investigate for predisposing factors. Disease characteristics and treatment in 47 Northern Greek Caucasian cSLE patients were retrospectively reviewed. The Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) was used for damage assessment and the European Consensus Lupus Activity Measurement (ECLAM) to monitor cSLE activity. After a median disease duration of 7.4 years, 17/47 patients (36 %) had developed damage (SDI > 0). The most frequent domains damaged were the ocular (41 %), neuropsychiatric (35 %) and peripheral vascular (35 %) one. Peripheral vascular and neuropsychiatric damage was seen more frequently during the first 5 years of the disease. Longer exposure to azathioprine was associated with higher SDI at the end of follow-up ( β = 0.008 for every additional month of use, p = 0.041). The mean annual flare frequency was associated with a shorter time interval until the development of the first damage (hazard's ratio, HR 2.38 for each unit of increase, p = 0.018), while hydroxychloroquine use was associated with longer time interval (HR 0.19, p = 0.007). The lower rates of damage accrual in this study compared to other cohorts might be due to milder disease phenotype in Greek Caucasian cSLE patients, prompt diagnosis and effective disease control. Damage was noticed early in the disease course, and one-third of patients had an SDI > 0 at study completion. Disease flares and a severe disease course leading to prolonged use of immunosuppressives were significant risk factors, while hydroxychloroquine use was protective against cSLE damage accrual. [ABSTRACT FROM AUTHOR]

Background Rheumatic diseases in children are associated with significant morbidity and poor healthrelated quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases. Findings We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY©) to Simple Measure of Impact of Illness in Youngsters (SMILY©-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY©-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Nineteen children (79% female, n=15) and 17 parents participated. The mean age was 12±4 years, with median disease duration of 21 months (1-172 months). We translated SMILY©- Illness into the following 28 languages: Danish, Dutch, French (France), English (UK), German (Germany), German (Austria), German (Switzerland), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), Spanish (Venezuela), Turkish, Afrikaans, Arabic (Saudi Arabia), Arabic (Egypt), Czech, Greek, Hindi, Hungarian, Japanese, Romanian, Serbian and Xhosa. Conclusion SMILY©-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY©-Illness with its available translations may be used as useful adjuncts to clinical practice and research. [ABSTRACT FROM AUTHOR]

The objective of this retrospective study was to record the achievement of clinical remission (CR) in juvenile idiopathic arthritis patients under a 2-10 years' administration of Etanercept (ETN) and to detect any variables associated with CR. Patients previously resistant to conventional regimens were enrolled. The annual impact of ETN was assessed by: (a) the American College of Rheumatology pediatric criteria (ACRpedi), (b) the pre- and posttreatment disease activity score (juvenile arthritis disease activity score [JADAS71]), and (c) Wallace's criteria for CR. A total of 41 patients (F: 31) were registered. The median age and disease duration at baseline were 10.6 and 4.17 years, respectively, and their disease course was mainly polyarthritis (32/41). In respect to baseline, there was an impressive JADAS71 reduction posttreatment, most prominent after the first year. From year 1 to 5, more than 50 % of the patients achieved and retained CR and 66 % reached an ACRpedi 70, whereas after the 5th year, no patient was withdrawn due to an ACRpedi <30. JADAS71 at baseline was not associated with the subsequent CR achievement. However, JADAS71 1-year posttreatment had a significant association with the CR of the second posttreatment year, ( p = 0.028, OR 0.79; 95 % CI 0.63-0.98) and a similar trend was observed for the following years. These findings emphasize the sustained impact of ETN in the achievement of CR. A low JADAS71 score 1-year posttreatment, may be associated with the maintenance of CR over the next treatment year. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is the major determinant of outcome in pediatric systemic lupus erythematosus (pSLE), and its treatment remains a challenge. The aim of this study was to report the experience of our center in treating with rituximab (RTX) SLE patients with severe LN. Four pSLE patients with biopsy-proven LN, who are refractory to conventional immunosuppressive treatment, received four doses of 375-500 mg/m RTX, 2-3 weeks apart. All patients were concurrently receiving corticosteroids (CSs) and mycophenolate mofetil. Patients' clinical and laboratory findings were recorded at RTX initiation, after each infusion and at 3.4 ± 2.1 month intervals thereafter. pSLE activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM), while LN activity using 24-hour urine protein excretion and serum cystatin C. Patients were followed up for 6-21 months (median: 16 months). Full Β-cell depletion was noticed 2-4 weeks after RTX initiation and lasted 4-7 months. All patients achieved complete LN remission 3.5 months (range: 2-4) after RTX initiation, which was retained in 3 patients through the follow-up period. One patient relapsed 15 months after RTX initiation and received one additional RTX dose. ECLAM scores and CSs doses were markedly reduced in all patients, while complement levels were increased. No side effects or infections were observed. In conclusion, RTX is an alternative, safe and efficient treatment for refractory LN. [ABSTRACT FROM AUTHOR]

In order to investigate HLA-DRB1 and HLA-DQB1 gene polymorphisms in Northern Greek pediatric population with Hashimoto's thyroiditis (HT), we analyzed the distribution of these alleles in 17 patients and in 181 healthy subjects using polymerase chain reaction. No significant association was detected between HT and alleles analyzed. However, HLA-DQB1*05 was significantly increased in patients with age of diagnosis >10 years (87.5%) compared to those with age of diagnosis ≤10 years (33.3%) (P=0.05). These results question the role of sexual maturity in combination with HLA-DQB1*05 as predisposing factor for the onset of HT in Northern Greek children and adolescents. [ABSTRACT FROM AUTHOR]

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Pityriasis lichenoides et varioliformis acuta (PLEVA) represents the acute clinical subtype of pityriasis lichenoides (PL) and its occurrence is relatively common during childhood. Diagnosis and treatment may sometimes pose certain difficulties. We present the recalcitrant case of a 3-year-old boy with an asymptomatic polymorphic eruption consisting of multiple, scattered, 0.5 cm, round to ovoid, erythematous papules covered in places with a fine scale, vesicles and superficial erosions with thick hemorrhagic crusts. The correlation of the clinical features with the lesional histopathology favored the diagnosis of PLEVA. No first-line treatment scheme succeeded in controlling the eruption of new lesions. The only therapeutic approach that eventually managed to cease the disease evolution was the combination of prednisolone and methotrexate. [ABSTRACT FROM AUTHOR]

Purpose: Physiotherapy is an integral part of the treatment of Juvenile Idiopathic Arthritis (JIA) patients, contributing to the rehabilitation of the affected joints, either by sessions of a specialized and individualized program of exercises in the physiotherapy clinic, or by the implementation of this program at home, following education of the child and his parent / guardian. The disease chronicity combined with the psychosocial impact of the whole therapeutic process on children and parents lives,often leads to non-compliance and significant financial burden. These parameters, in the era of the economic crisis, are often difficult to manage by the families and the treatment group,but they are a stimulus to seek new physiotherapy approaches. The purpose of this study was to investigate the applicability and efficacy of a tele-rehabilitation program in JIA patients, in order to alleviate the JIA patients and their family. Methods: Five JIA patients, 8-16 years old, participated in a tele-rehabilitation program (using personal computers,at home), as part of their physiotherapy sessions. During the sessions they performed their exercises under the supervision and guidance of a specialized pediatric physiotherapist, twice a week, for 12 weeks. Before and after the program, parents and children completed two specific questionnaires, one on quality of life (JAMAR) and the other on the applicability and effectiveness of the program. Results: Everyone was satisfied with the program's implementation and effectiveness and wished to continue. Conclusions: The first findings on the feasibility and effectiveness of a tele-rehabilitation program in children with JIAare satisfactory and allow the extension of this application to a larger number of patients. [ABSTRACT FROM AUTHOR]