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To study the demographic and clinical profile of children with suspected physical or sexual abuse.Retrospective records of children who were admitted to hospital between January, 2015 to December, 2020 with suspected physical or sexual abuse were evaluated.The records of 52 children [mean (SD) age 12.24 (5.32) y, 39 boys] were retrieved. Contusions were the most common injury in 53.8% of boys and 69.2% of girls. The majority (70%) of 8-18 year-old-children were abused by peers, and parents/caregivers were the main perpetrators in 72.7% of younger children.Child abuse is often underreported, and requires a high index of suspicion and multidisciplinary approach of management.

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

Oxidative stress is believed to be of great importance for both the etiology and the persistence of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the association of -262C/T polymorphism of the catalase (CAT) gene with JIA, as well as to evaluate whether this polymorphism can influence plasma CAT activity and outcome in JIA patients treated with etanercept. A total of 154 subjects (60 JIA patients and 94 healthy volunteers) were screened for CAT-262C/T gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma CAT activity was determined using the spectrophotometric method according to Goth, prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA ACR (American College of Rheumatology) response criteria. The genotype and allele frequency distributions of CAT-262C/T polymorphism in the patients were significantly different from those of the controls (p = 0.014, p = 0.006). The TT genotype (polymorphic homozygous) was associated with a 4.36-fold higher likelihood of having JIA (95% CI 1.545-12.323, p = 0.005) as compared to the CC genotype (wild-type). At month 12 of treatment, JIA patients, carriers of the CC genotype, showed significantly higher plasma CAT activity (p = 0.004) and achieved the JIA ACR 70 response more often (p = 0.003) than the patients, carriers of the CT/TT genotype. This is the first study implying the possible association of CAT-262C/T polymorphism with JIA. The results suggest the potential protective effect of the CC genotype, with regard to CAT activity and treatment outcome.

Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.

Linear IgA dermatosis (LAD) is a rare autoimmune disorder in children. A 9-year-old boy was presented with blisters on the intact skin (face, body, arms, hands, soles, perigenital and perianal area) after amoxicillin treatment. Systemic corticosteroids and dapsone treatment for 6 weeks was successful. Clinical and immunofluorescence examinations are most important for differentiation of LAD and other drug-induced bullous dermatoses. They enable an early introduction of proper therapy.

Vitamin D receptor (VDR) gene FokI (rs2228570) polymorphism was postulated to influence outcome of several inflammatory diseases. The aim of this study was to evaluate the influence of rs2228570 polymorphism on lipid profile and on outcome in patients with juvenile idiopathic arthritis (JIA) treated with etanercept. A total of 153 subjects (62 JIA patients and 91 controls) were screened for the rs2228570 using the PCR-RFLP method. Lipid profile (cholesterol, triacylglycerol, HDL-C, and LDL-C) was determined using standard biochemical analysis in controls, while in JIA patients, it was determined prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA-American College of Rheumatology (ACR) response criteria. There were significant differences in the distribution of genotypes (p = 0.024) and alleles (p = 0.006; OR = 2.222, 95% CI 1.136-4.348) of the rs2228570 between patients and controls. Etanercept treatment significantly increased HDL-C levels (p = 0.006) in JIA patients with FF genotype in comparison to baseline values. No significant differences were seen in JIA-ACR 30/50/70 responses at month 12 between FF and Ff/ff genotype carriers. This is the first study to demonstrate the protective effect of the VDR FokI FF genotype on lipid profile in JIA patients treated with etanercept. However, this has to be confirmed in a larger cohort of patients.

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 Serbian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 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). A total of 248 JIA patients (5.2% systemic, 44.3% oligoarticular, 23.8% RF-negative polyarthritis, 26.7% other categories) and 100 healthy children were enrolled in three centres. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Serbian 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 clinical research.

Background:Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 per 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is the largest multinational registry that prospectively collects information about jSSc patients.Objectives:Evaluation of the jSSc patients at the time of inclusion in the JSSIC.Methods:Patients were included in the JSSIC if they fulfilled the adult ACR/EULAR classification criteria for systemic scleroderma, if they presented the first non-Raynaud symptom before 16 years of age and if they were younger than 18 years of age at time of inclusion. Patients’ characteristics at time of inclusion were evaluated.Results:Until 15thof December 2019 hundred fifty patients were included, 83% of them being Caucasian and 80% female. The majority had the diffuse subtype (72%) and 17% of all jSSc had overlap features. The mean age of first presentation of Raynaud´s phenomenon was 9.8 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc) (p=.197). The mean age at first non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.2 years in the ljSSc (p=0.247). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group.Significant differences were found between the groups regarding mean modified Rodnan skin score, 18.2 in the djSSc vs 6.2 in the ljSSc (p=0.02); presence of Gottron´s papulae (djSSc 30% vs ljSSc 13%, p=0.43);presence of teleangiectasia (djSSc 42% vs 18% ljSS, p=0.01); history of ulceration (djSSc 42% vs 18% ljSSc,p=0.008); 6 Minute walk test below the 10thpercentile (djSSc 85% vs ljSSc 54%, p=0.044), total pulmonary involvement (djSSc 49% vs ljSSc 31%, p=0.045), cardiac involvement (ljSSc 17% vs djSSc 3%, p=0.002). djSSc patients had significantly worse scores for Physician Global Assessment of disease activity compared to ljSSc patients (VAS 0-100) (40 vs 15) (p=0.001) and for Physician Global Assessment of disease damage (VAS 0-100) (36 vs 17) (p=0.001).There were no statistically significant differences in the other presentations. Pulmonary hypertension occurred in approximately 6% in both groups. No systemic hypertension or renal crisis was reported. ANA positivity was 90% in both groups. Anti-Scl70 was positive in 35% in djSSc and 36% in the ljSSc group. Anticentromere positivity occurred in 3% in the djSSc and 7% in the ljSSc group.Conclusion:In this unique large cohort of jSSc patients there were significant differences between djSSc and ljSSc patients at time of inclusion into the cohort regarding skin, vascular, pulmonary and cardiac involvement. According to the physician global scores the djSSc patients had a significantly more severe disease. Interestingly the antibody profile was similar in both scleroderma phenotypes.Supported by the “Joachim Herz Stiftung”Disclosure of Interests: :Ivan Foeldvari Consultant of: Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Brian Feldman Consultant of: DSMB for Pfizer, OPTUM and AB2-Bio, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Maria Katsikas: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, edoardo marrani: None declared, Mikhail Kostik: None declared, Natalia Vasquez-Canizares: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Anjali Patwardhan: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Sujata Sawhney: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Blanca Bica: None declared, Juergen Brunner Grant/research support from: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Abbvie, Roche, BMS, Speakers bureau: Pfizer, Novartis, Abbvie, Roche, BMS, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Daniela Kaiser: None declared, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

OBJECTIVE: To develop a composite DAS for JDM and provide preliminary evidence of its validity. METHODS: The Juvenile DermatoMyositis Activity Index (JDMAI) is composed of four items: physician's global assessment of overall disease activity ; parent's/child's global assessment of child's wellbeing ; measurement of muscle strength ; and assessment of skin disease activity. The score of the JDMAI is the arithmetic sum of the scores of each individual component. Six versions of the JDMAI were tested, which differed in the tools used to assess the third and fourth items. Validation procedures were conducted using three large multinational patient samples including a total of 627 patients. RESULTS: The JDMAI was found to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha = 0.58- 0.89), fair responsiveness to clinically important change (standardized response mean = 0.82-3.12 among patients improved) and strong capacity to discriminate patients judged as being in the state of inactive disease or low, moderate or high disease activity by the physician (P < 0.001) or whose parents were satisfied or not satisfied with the course of their child's illness (P < 0.001). Overall, the six versions of the JDMAI showed similar metrological performances in validation analyses. CONCLUSION: The JDMAI was found to possess good measurement properties in a large population of patients with a wide range of disease activity, and is, therefore, suitable for use in both clinical and research settings. The final version of the JDMAI will be selected after its prospective validation

Background Assessment of muscle strength is a fundamental component of the clinical evaluation of children with juvenile dermatomyositis (JDM). Regular measurement of muscle strength in daily care requires the availability of simple and quick muscle assessment tools. Objectives To investigate whether reduced versions of the MMT8 and CMAS are equally reliable as the original tools. Methods The following 4 reduced instruments were devised: 1) MMT4 (score 0-40), including 4 items of MMT8 (neck flexors, deltoid middle, gluteus maximus, and gluteus medius); 2) MMT6 (score 0-60), composed of the same items of MMT4 plus biceps brachii and quadriceps; 3) head lift time of CMAS (0-120 seconds or 0-5 points); 4) sum of CMAS head lift time in points and the 6 sit-ups maneuvers of CMAS (score 0-11). Validation was conducted according to OMERACT filter on 213 patients followed in standard clinical care at 13 international pediatric rheumatology centers and evaluated at baseline and after a median of 5.9 months. Results All reduced instruments revealed strong correlations (r > 0.7) with muscle activity VAS and total DAS, moderate correlations (r = 0.4-0.7) with physician’s global VAS, muscle DAS, skin activity VAS, pain VAS, parent’s overall wellbeing VAS, and CK. Correlations with skin DAS and fatigue VAS were low (r Conclusion We found that reduced versions of the MMT8 and CMAS have good metrologic properties and perform similarly to the original tools in a population of patients followed in standard clinical care. Our results suggest that these simplified and shortened instruments could serve as surrogate for the complete measures in routine practice, particularly in a busy clinical setting. References [1] Measures of adult and juvenile dermatomyositis, polimyositis, and inclusion body myositis. Rider LG, Werth VP, Huber AM, Alexanderson H, Rao AP, et al. Arthritis Care Res (Hoboken)2011;63:S118-57. [2] Clinical assessment in juvenile dermatomyositis. Ravelli A, Ruperto N, Trail L, Felici E, Sala E, et al. Autoimmunity2006;39:197-203. Disclosure of Interests Silvia Rosina: None declared, Giulia Camilla Varnier: None declared, Angela Pistorio: None declared, Alessandro Consolaro Grant/research support from: AbbVie, Pfizer, Clarissa Pilkington: None declared, Susan Maillard: None declared, Adele Civino: None declared, Elena Tsitsami: None declared, Jaime de Inocencio: None declared, Marija Jelusic: None declared, Jelena Vojinovic: None declared, Graciela Espada: None declared, Balahan Makay Speakers bureau: Enzyvant, Novartis, Roche, Abbvie, Maria Katsikas: None declared, Polixeni Pratsidou-Gertsi: None declared, Dragana Lazarevic: None declared, Anand Prahalad Rao: None declared, Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is a multinational registry that prospectively collects information regarding patients with this disease in a standardized manner. Objectives Evaluation of the jSSc patients at the time of inclusion in the JSSIC. Methods Patients were included in the JSSIC if they fulfilled the adult classification criteria, if they presented the first non Raynaud symptom before 16 years old and if they were younger than 18 years of age at the time of inclusion. Patients’ characteristics at time of inclusion were evaluated. Results Currently, the cohort includes 120 patients, being 89% Caucasian and 80% female. The majority had diffuse subtype (74%) and 18% had overlap features. The mean age of onset of Raynaud phenomenon was 9.7 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc). The mean age of non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.4 years in the ljSSc (p=0.041). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group. Mean Modified Rodnan skin score was 17.5 in the djSSc and 7.3 in the ljSSc (p=0.002). Gottron papulae were significantly more common in the djSSc compared to ljSSc group (29% vs 6%, respectively) (p=0.011). History of ulceration was significantly more common in the djSSc than in the ljSSc group (57% vs 30%, respectively) (p=0.004). FVC Conclusion In this large cohort of jSSc patients there were surprisingly not many significant differences between djSSc and ljSSc. According to the physician global scores the djSSc patients have a significantly more severe disease. Disclosure of Interests Ivan Foeldvari Consultant for: Chugai, Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Valda Stanevicha: None declared, Flavio R. Sztajnbok: None declared, Maria T. Tererri: None declared, Ekaterina Alexeeva: None declared, Jordi Anton Grant/research support from: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Consultant for: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Speakers bureau: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Maria Katsikas: None declared, Vanessa Smith: None declared, Tadej Avcin: None declared, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Thomas Lehman: None declared, Walter Alberto Sifuentes-Giraldo: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Maria Jose Santos: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson: None declared, Blanca Bica: None declared, Juergen Brunner: None declared, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff: None declared, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Dragana Lazarevic: None declared, Kirsten Minden Consultant for: AbbVie, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Anjali Patwardhan: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

Background Autoinflammatory syndromes represent the wide spectrum of rare diseases (associated with genetic disturbances) characterized by the presence of chronic or recurrent systemic inflammation with diverse clinical presentation. Objectives We report a case report of child with confirmed two heterozygous mutations in the MVK gene with clinical features associated hyperimmunoglobulin D syndrome. Results We present girl with clinical symptoms starting just after birth when in the first days of life she was examined at gastroenterology department in Belgrade due to elevated parameters of inflammation, anemia, direct hyperbilirubinaemia, abdominal bloating and hepatosplenomegalia. Breastfeeding was discontinued due to galactosuria and lactose free diet was advised. Due to the maintenance of hepatomegaly, a detailed hematological, virusological and gastroenterological diagnostic testing was performed. Since liver biopsy has showed portal and lobular hepatitis with cholestasis without fibrosis she was on ursofalk treatment with partial response. At five months of age she started to have recurrent episodes of fever every month for few days with no associated infection, but always followed with digestive symptomatology (abdominal pain and abdominal flatulence) and elevation of inflammatory parameters. Despite antibiotics, episodes of fever continued to repeat twice monthly with accompanying occurrence of hypersalivation, small ulcers in the mouth, skin rash, cervical lymphadenopathy, hepatosplenomegaly, abdominal pain and abdominal bloating with elevated inflammatory markers. One year later she was admitted for the first time at our department and detailed differential diagnostic testing was performed. Clinical spectrum of presenting symptoms with specific phenotypic aspect (hypertelorismus and frontal bossing) were enough to suspect on autoinflammatory disease background (hyper IgD syndrome), but without IgG increase. Genetic testing have revealed presence of two heterozygous mutations ( heterozygous variant c.790del p.(Leu264Serfs*2) and heterozygous variant c.1129G>A p.(Val377Ile) in the mevalonate kinase deficiency gene (MVK gene) confirming hyperimmunoglobulin D syndrome. Introduction of nonsteroidal antiinflammatory drug and corticosteroids have led to complete or partial remission during a fever episodes. As fever episodes continued on every two weeks we are about to start with donated fully-humanized protein (canakinumab), highly efficacious in fever episodes resolution by blocking interleukin-1 beta cytokine. Conclusion Diverse clinical manifestations of some patients with autoinflammatory diseases can provoke differential diagnostic and treatment dilemmas. Genetic testing is of great importance for establishing the final diagnosis and starting accurate treatment in order to prevent potential serious complications seen in these patients. Disclosure of Interests None declared

Background:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of around 3 in 1, 000,000 children. It is known that in pediatric jSSc cohorts, there are a significant number of patients with overlap features, such as arthritis and myositis. However, the disease burden between those with and without overlap features in jSSc has not been defined.Objectives:Compare the clinical phenotype between children with and without overlap features in the juvenile systemic scleroderma inception cohort (jSScC).Methods:A cross-sectional study was performed using baseline visit data. Demographic, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were extracted from jSScC. Comparison between patients with and without overlap features was performed using chi-square test and Mann Whitney U-test.Results:At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s onset was 10 years (±3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Overlap features occurred 17% (n=30) of the cohort, 12.5% in the diffuse cutaneous (dc) jSSc and in 30% in the limited cutaneous (lc) jSSc. Significant differences in clinical characteristics were found between those patients with compared to without overlap characteristics. Patients with overlap features presented more frequently with Gottron papules (p=0.007), swollen joints (p=0.019), muscle weakness (p=0.003), and lung involvement documented by decreased DLCO < 80% (p=0.06) and/or abnormal high resolution computed tomography (p=0.049). Anti-PM/Scl autoantibodies were also more common in this group (p=0.001). Significantly more patients without overlap features had Raynaud´s (p=0.006). Physician Global Assessment of disease activity was significantly higher in patients with overlap features (41 vs 34; p=0.041). (Table 1.)Table 1.Demographic and clinical characteristics of jSSc patients with and without overlap features.Whole CohortN=175Patients without overlapN=145Patients with overlapN=30P valueFemale to Male Ratio 4.3:1(142/33)4:1(116/29)6.5:1(26/4)0.395Cutaneous subtypeDiffuse subtype (N)73% (128)11216Limited subtype (N)27% (47)3317Mean disease duration (years)3.1 (± 2.7)3.2 (± 2.8)3.1 (± 2.2)0.291Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud10.0 (± 3.8)10 non-Raynaud10.0 (± 3.7)7 non-Raynaud0.931Mean age of onset of non-Raynaud´s (years)10.2 (± 3.8)10.2 (± 3.9)9.8 (± 3.7)Disease modifying drugs (N)88% (154) 89% (129)83% (25)0.388Raynaud´s phenomenon90% (158)93% (135)77% (23)0.006Anti-PMScl18% (12/68)9% (5/53)47% (7/15)0.001Gottron Papules (N)27% (46/171)23% (33/144)48% (13/27)0.007DLCO 44% (39/88)39% (28/71)65% (11/17)0.06Abnormal findings in HRCT (N)44% (59/133)40% (43/107)62% (16/26)0.049Proportion of patients with swollen joints 18% (32) 14% (21) 37% (11)0.019Muscle Weakness (N) 21% (31/149)16% (20/123) 42% (11/26)0.003Physician global disease activity(0-100) min -max35 (0-90) n=14134 (0-90) n=11441 (0-80) n=270.041Conclusion:Results from this large international cohort of jSSc patients demonstrate significant differences between patients with and without overlap features. Patients with overlap have significantly more interstitial lung disease and more physician rated disease activity and should not be considered to have more “mild disease”.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:None declared

Background:Juvenile systemic sclerosis (jSSc) is a rare disease with a prevalence of around 3 in 1,000,000 children. To better capture the clinical manifestations of jSSc the juvenile systemic sclerosis inception cohort (jSScC) has been prospectively enrolling patients with predetermined clinical variables over the past 12 years. One of the goals is to study the demographic, clinical features, and physician and patient reported outcome differences between those with juvenile limited cutaneous (lc) compared to diffuse cutaneous (dc) disease subtypes, to determine if characteristics are similar or different between dc and lc jSSc.Objectives:Evaluation of the baseline clinical characteristics of jSSc patients in the jSScC. Compare clinical phenotype between diffuse (dcjSSc) and limited cutaneous (lcjSSc) subtypes.Methods:Demographic, physical examination, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were evaluated from the jSSc Inception cohort and summary statistics applied using chi-square test and Mann Whitney U-test comparing lcjSSc and dcjSSc subtypes.Results:At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Diffuse cutaneous jSSc subtype predominated (73%). Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s was 10 years (+3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Significant differences were found between dcjSSc versus lcjSSc, regarding several clinical characteristics. Patients with diffuse cutaneous subtype had significantly higher modified Rodnan skin score (p=0.001), presence of sclerodactyly (p=0.02), presence of Gottron’s papules (p=0.003), presence of telangiectasia (p=0.001), history of digital tip ulceration (p=0.01), and frequency of elevated CK value (p=0.04). Cardiac involvement was significantly higher in limited cutaneous jSSc subtype (p=0.02). Diffuse cutaneous jSSc patients had significantly worse scores for Physician Global Assessment of disease activity (38 vs 25; p=0.002) and disease damage (34 vs 19; p=0.008).Table 1.Comparison of demographic data and significant differences between dcjSSc and lcjSSc at time of inclusionWhole CohortN=175Diffuse SubtypeN=128Limited SubtypeN=47P valueFemale to Male Ratio4.3:1 (142/33)4.1:1 (103/25)4.8:1 (39/8)0.829Cutaneous subtypeDiffuse subtype73% (128)1280Limited subtype27% (47)047Mean Disease duration (years)3.1 (± 2.7)3.3 (± 2.9)2.6 (± 2.2)0.135Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud9.8 (± 3.6)10 non-Raynaud10.6 (± 4.3)7 non-Raynaud0.219Mean age of onset of non-Raynaud´s (years)10.2 (± 3.9)10.0 (± 3.7)10.9 (± 4.3)0.173Disease modifying drugs88% (154)89% (114)85% (40)0.446CutaneousMean modified Rodnan skin score14.3 (0-51)17.4 (0-51)6.1 (0-24)0.001Gottron Papules27% (46/171)33% (41/124)11% (5)0.003Sclerodactyly78% (126/162)82% (98/119)65% (28/43)0.020Laboratory valuesElevated CK25% (30/122)30% (26/88)12% (4/34)0.041VascularTelangiectasia36% (56/154)44% (49/111)16% (7/43)0.001History of ulceration53% (91/173)61% (77/127)30% (14/46)0.001CardiacCardiac Involvement6% (10)2% (3)15% (7)0.002Patient Related OutcomesPhysician global disease activity(0-100) min -max35(0-90) n=14138(0-90) n=10825(0-80) n=330.002Physician global disease damage(0-100) min -max31(0-85) n=14034(0-85) n=10819(0-60) n=320.008Conclusion:Results from this large international cohort of jSSc patients demonstrate significant differences between dcjSSc and lcjSSc patients. According to the general organ involvement and physician global scores, the dcjSSc patients had significantly more severe disease. These observations strengthen our previous findings of the unique organ pattern of pediatric patients.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:None declared.

Background:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence in around 3 in a million children. Pulmonary involvement in jSSc occurs in approximately 40 % in the inception cohort. Traditionally in jSSc, pulmonary function testing (PFT) with FVC and DLCO are used for screening and computed tomography (HRCT) was more reserved for those with abnormal PFTs. More recently, it has become apparent that PFTs might not be sensitive enough for detecting ILD in children.Objectives:Utilizing a prospective international juvenile systemic scleroderma cohort (JSScC) [2], to determine if pulmonary screening with FVC and DLCO is sufficient enough to assess the presence of interstitial lung disease in comparison to CT evaluation.Methods:The international juvenile systemic scleroderma cohort database was queried for available patients with recorded PFT parameters and HRCT performed to determine sensitivity of PFTs detecting disease process.Results:Of 129 patients in the jSScC, 67 patients had both CT imaging and an FVC reading from PFTs for direct comparison. DLCO readings were also captured but not in as many patients with tandem HRCT (n =55 DCLO and HRCT scan). Therefore, initial analyses focused on the sensitivity, specificity and accuracy of the FVC value from the PFTs to capture the diagnosis of interstitial lung disease as determined by HRCT.Overall, 49% of the patients had ILD determined by HRCT, with 60% of patients having normal FVC (>80%) with positive HRCT findings, and 24% of patients having normal DLCO (> 80%) with positive HRCT findings. Fourteen percent (n = 3/21) of patients with both FVC and DLCO values within the normal range had a positive HRCT finding.Conclusion:The sensitivity of the FVC in the JSScC cohort in detecting ILD was only 39%. Relying on PFTs alone for screening for ILD in juvenile systemic sclerosis would have missed the detection of ILD in almost 2/3 of the sample cohort, supporting the use of HRCT for detection of ILD in children with SSc. In addition, the cut off utilized, of less than 80% of predicted FVC or DLCO could be too low for pediatric patients to exclude beginning ILD. This pilot data needs confirmation in a larger patient population.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:Ivan Foeldvari Consultant of: Novartis, Bernd Hinrichs: None declared, Kathryn Torok: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Maria Katsikas: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Blanca Bica: None declared, Juergen Brunner Grant/research support from: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Abbvie, Roche, BMS, Speakers bureau: Pfizer, Novartis, Abbvie, Roche, BMS, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Anjali Patwardhan: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

Objective To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing 8 (MMT8) and the Childhood Myositis Assessment Scale (CMAS), but is more comprehensive than the former and more feasible than the latter. Methods The hybrid MMT/CMAS (hMC) is composed of all 8 items of the MMT8 and 3 items of the CMAS: 1) time of head lift; 2) assessment of abdominal muscles; 3) floor rise. The score ranges from 0 to 100, with 100 indicating normal muscle strength. Validation procedures were conducted using three large multinational patient samples including a total of 810 JDM patients. Results The hMC revealed face and content validity, good construct validity, excellent test-retest reliability (intraclass correlation coefficient = 0.99) and internal consistency (Chronbach's alpha = 0.94), strong responsiveness to clinical change over time (standardized response mean = 0.8 among patients judged as improved by the caring physician), and satisfactory capacity to discriminate patients judged as being in the states of inactive disease or low, moderate, or high disease activity by the physician (p < 0.001) or patients whose parents were satisfied or not satisfied with illness course (p < 0.001). Conclusion The hMC was found to possess good measurement properties in a large population of patients with a wide range of disease activity and severity. The new tool, which is primarily intended for use in routine clinical care, should be further tested in other populations of patients evaluated prospectively. This article is protected by copyright. All rights reserved.

Background The Mediterranean fever (MEFV) gene codes for protein pyrin, one of the regulators of inflammasome activity in innate immune cells. Mutations in this gene are considered the primary cause of Familial Mediterranean fever, but are also found in other monogenic and multifactorial autoinflammatory diseases. The aim of the study was to determine if healthy carriers of MEFV gene mutations and R202Q polymorphism have clinical manifestations of inflammation and impaired oxidative stress parameters. Methods One hundred DNA samples from healthy volunteers (13.3 ± 8.87 years of age (mean ± SD); range 2–35) were sequenced by ABI PRISM 310 automated sequencer (PE Applied Biosystems, Norwalk, USA). The Eurofever questionnaire was used to collect retrospectively medical history data. Oxidative stress was determined by measuring spectrophotometrically thiobarbituric acid reactive substances (TBARS) in plasma and erythrocytes, as well as advanced oxidation protein products in plasma. Superoxide dismutase (SOD) activity was determined by McCord and Fridovich method in plasma and erythrocytes, while the catalase erythrocyte activity was assessed using a catalase ELISA kit. Results We found heterozygous carriers of K695R/N mutations in 5 %, E148Q/N mutations in 6 %, R202Q homozygous polymorphism in 10 % and heterozygous R202Q alterations in 45 % of healthy volunteers. The MEFV mutation carriers and R202Q polymorphism homozygotes reported significantly more often recurrent febrile episodes (p = 0.009), diffuse abdominal pain (p = 0.025), and malaise (p = 0.012) compared to non-carriers. Erythrocyte TBARS levels and plasma SOD activity were higher in persons with MEFV mutations and R202Q/R202Q (p = 0.03 and p = 0.049, respectively). Conclusions Healthy individuals may bear E148Q and K695R MEFV gene mutations, as well as R202Q polymorphism in homozygous state. The determined gene alterations contribute to a subtle oxidative stress and may be associated with more frequent episodes of fever and unspecific inflammatory manifestations. An incomplete penetrance or variable expressivity of R202Q in populations of different ethnicity could influence the expression of autoinflammatory diseases phenotype.

Objectives To develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM). Methods The Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated prospectively up to 24 months. Thirty-eight patients off therapy at 24 months were defined as clinically inactive and included in the reference group. These were compared with a random sample of 76 patients who had active disease at study baseline. Individual measures of muscle strength/endurance, muscle enzymes, physician9s and parent9s global disease activity/damage evaluations, inactive disease criteria derived from the literature and other ad hoc criteria were evaluated for sensitivity, specificity and Cohen9s κ agreement. Results The individual measures that best characterised inactive disease (sensitivity and specificity >0.8 and Cohen9s κ >0.8) were manual muscle testing (MMT) ≥78, physician global assessment of muscle activity=0, physician global assessment of overall disease activity (PhyGloVAS) ≤0.2, Childhood Myositis Assessment Scale (CMAS) ≥48, Disease Activity Score ≤3 and Myositis Disease Activity Assessment Visual Analogue Scale ≤0.2. The best combination of variables to classify a patient as being in a state of inactive disease on or off therapy is at least three of four of the following criteria: creatine kinase ≤150, CMAS ≥48, MMT ≥78 and PhyGloVAS ≤0.2. After 24 months, 30/31 patients (96.8%) were inactive off therapy and 69/145 (47.6%) were inactive on therapy. Conclusion PRINTO established data-driven criteria with clearly evidence-based cut-off values to identify JDM patients with clinically inactive disease. These criteria can be used in clinical trials, in research and in clinical practice.

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

There are no official published recommendations how and when to stop treatment with biologics when remission achieved.

Fever of unknown origin (FOU) i.e.: (1) a temperature greater than 38.3°C on several occasions, (2) more than 3 weeks' duration of illness, and (3) failure to reach a diagnosis despite 1 week of inpatient investigation are commonly seen in pediatric practice. The conditions could be caused by mutations of genes coding inflammasome sequences. In these instances activated neutrophils and monocytes intensively generate reactive oxidative species.

Background Physical function in children with juvenile dermatomyositis (JDM) is traditionally assessed through the Childhood Health Assessment Questionnaire (CHAQ), which has been originally devised for juvenile idiopathic arthritis, but has been validated for use in JDM. Recently, the first physical functional questionnaire specific for JDM, named MyoFun, has been developed. The MyoFun is a 15-item questionnaire in which the ability of the child to perform each task is scored as follows: 0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; 3 = unable to do. Questionnaire completers are asked to note only those difficulties that are caused by myositis. The total score ranges from 0 to 45. Objectives To compare the construct validity of the CHAQ and MyoFun in children with JDM. Methods Construct validity of the CHAQ and Myofun was assessed by evaluating their Spearman’s correlation with the other traditional JDM outcome measures. Construct validity of the CHAQ and MyoFun was assessed in 3 different cross-sectional patient samples. The first and second samples, in which physical function was assessed with the CHAQ, included 327 patients enrolled in a long-term outcome study (Arthritis Care Res 2010;62:63-72) and 294 patients evaluated at disease onset or at the time of a disease flare (Arthritis Rheum 2008;59:4-13), respectively. The third sample, in which physical function was assessed with the MyoFun, was composed by 37 patients seen at study centers in the context of standard clinical care. Results Table shows Spearman’s correlations yielded by the CHAQ and MyoFun. Conclusions The construct validity of the MyoFun was overall superior to that of the CHAQ, which suggests that this tool is suitable for the assessment of physical function in children with JDM in both clinical practice and research. Disclosure of Interest None Declared

Methods The study was performed in 25 JIA patients who donated paired serum samples prior and one year after continous etanercept therapy. Basic clinical data (six core set variables defined in ACR PEDI outcome score) were recorded along with alkalyne DNase I serum levels using the method where acid soluble nucleotides are determined spectrophotometrically at 260 nm. Treatment schedule of etanercept was 0,4mg/kg body weight subcutaneously twice weekly.

Methods 275 patients in active phase of JDM

Results Average duration of etanercept therapy was 34.61±12.11 months. Disease subtype distribution was 6.78% systemic, 54.24% poly RFand extended-oligo, 18.64% poly RF+, 16.95% ERA and 3.38 PsA. The distribution of TNFὰ308 and T676G genotypes was not significantly different among JIA subtypes. TNFὰ308 genotypes distribution was 6.78% AA, 30.51% GG and 62.71% GA while T676G genotypes were 59.3% TT, 8.3% GG and 26.4% TG. T676G genotype polymorphism did not significantly influenced outcome. ACR Pedi 30,50,70 and 100 improvement was significantly faster and sustained in TNFὰ308 GG-genotype patients compared to GA genotype (results shown in table:*significant compared to 1 year; a-significant compared to GG). Treatment induced remission in 35.14%, had to be reintroduced due to disease worsening in 16.22%, disease was in remission under medication in 21.62% or still active in 24.32% GA patients and in 38.9%, 16.7%, 27.8% and 11.1% in GG patients, respectively. Patients with systemic or RF+ disease course were mostly treatment resistant in both genotypes. (Table 1)

Methods The MyoFun assesses the ability of the child to perform 15 activities that require the use of all skeletal muscles and muscle groups. Each item is scored from 0 to 3 (0=with no difficulty; 1=with some difficulty; 2=with much difficulty; 3=unable to do). The total score ranges from 0 (normal physical function) to 45 (worst physical function). A parent of 27 children with JDM was asked to complete the MyoFun and the Childhood Health Assessment Questionnaire (C-HAQ) and to rate the child’s overall well-being and pain intensity on a 21numbered circle visual analog scale (VAS). The attending physician assessed the child’s muscle strength/function with the Kendall’s Manual Muscle Testing (MMT) and the Childhood Myositis Assessment Scale (CMAS). Laboratory tests included creatine phosphokinase (CK) and lactic dehydrogenase (LDH). Construct validity of the MyoFun was examined by calculating its Spearman’s correlations with the other JDM outcome measures on both cross-sectional data and change between 2 consecutive visits. Correlations were considered high, moderate or low when >0.7, 0.4-0.7, or