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BackgroundJuvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children (1). In adult patients there are significant differences between the clinical presentation of diffuse and limited subtypes (2). We reviewed clinical differences in presentation of subtypes in patients in the juvenile systemic scleroderma inception cohort up to 2021.ObjectivesTo study the clinical presentation of jSSc patients with diffuse (djSSc) and limited (ljSSc) subtypes.MethodsWe reviewed the clinical baseline characteristics of the patients, who were recruited to the juvenile scleroderma inception cohort (jSScC) (3, 4) till 1st of December 2021. jSScC is a prospective cohort of jSSc patients, who developed the first non-Raynaud´s symptom before the age of 16 years and are under the age of 18 years at the time of inclusion.Results210 patients with jSSc were included in the cohort, 71% (n=162) had diffuse subtype. The median age at onset of Raynaud phenomenon was 10.4 years (7.3 – 12.9) and the median age at the first non-Raynaud symptom was 10.9 years (7.4 – 13.2). Median disease duration was 2.5 years (1 – 4.4) at the time of inclusion. The female/male ratio was significantly lower in the djSSc subtype (3.7:1 versus 5:1, p< -2 z score (20% versus 4%, p=0.003) and decreased joint range of motion (64% versus 46%, p=0.019). Patients with ljSSc had significantly higher rate of cardiac involvement (13% versus 2%, p=0.001).Regarding patient related outcomes djSSc patients had more severe disease, looking at patient reported global disease activity (VAS 0 – 100) (40 versus 25, p=0.039), patient reported global disease damage (VAS 0 – 100) (40 versus 25, p=0.021) and patient reported assessment of ulceration activity (10 versus 0, p=0.044). Regarding physician related outcomes the physician reported global disease activity (VAS 0 – 100) (32 versus 20, pConclusionIn this jSSc cohort, the largest in the world, djSSc patients have a significantly more severe disease than ljSSc patients. Interestingly, we found no differences regarding interstitial lung disease and pulmonary hypertension.References[1]Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States. Journal of Scleroderma and Related Disorders. 2018;3(2):189-90.[2]Dougherty DH, Kwakkenbos L, Carrier ME, Salazar G, Assassi S, Baron M, et al. The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts. Rheumatology (Oxford). 2018;57(9):1623-31.[3]Foeldvari I, Klotsche J, Kasapcopur O, Adrovic A, Terreri MT, Sakamoto AP, et al. Differences sustained between diffuse and limited forms of juvenile systemic sclerosis in expanded international cohort. www.juvenile-scleroderma.com. Arthritis Care Res (Hoboken). 2021.[4]Foeldvari I, Klotsche J, Torok KS, Kasapcopur O, Adrovic A, Stanevica V, et al. CHARACTERISTICS OF THE FIRST 80 PATIENTS AT TIMEPOINT OF FIRST ASSESSMENT INCLUDED IN THE JUVENILE SYSTEMIC SCLEROSIS INCEPTION COHORT. WWW.JUVENILESCLERODERMA.COM. Journal of Scleroderma and Related Disorders. 2018;4(1-13).Disclosure of InterestsNone declared

BackgroundRheumatic diseases are associated with reduced bone mineral density (BMD) as measured by Dual Energy x-ray absorptiometry (DXA). Mixed connective tissue disease (MCTD) is a rare connective tissue disease, and about 25% of all cases have a pediatric presentation. One study implies that osteoporosis is common in postmenopausal women with MCTD (1), but data regarding BMD and osteopenia are lacking in younger patients with the disease.ObjectivesTo assess the BMD in a cohort of juvenile mixed connective tissue disease (JMCTD) patients compared to a matched control group.MethodsBMD was measured in a cohort of 52 JMCTD patients with mean age 28.2 years (SD 10.3) and mean disease duration 16.2 years (SD 10.3), and 52 controls matched for age and gender. Inclusion criteria were fulfilment of the Kasukawa- or the Alarcon-Segovia criteria and symptom debut before the age of 18 years.ResultsPatients and controls did not differ in age, body mass index, smoking habits, level of physical activity or vitamin D status (Table 1). Forty-four (85%) were female. Patients were shorter and had lower body weight compared to controls. None had had osteoporotic fractures. Patients over 20 years of age at examination had significantly lower BMD in the spine, femoral neck, proximal- and distal radius. Patients also had lower T-score compared to matched controls.Table 1.VariableJMCTD patients (n=52)Controls (n=52)P valueBMI, kg/m222.7 (3.5)23.4 (3.0)0.239Height, cm166.0 (7.5)170.1 (8.5)0.016Weight, kg63.0 (12.1)68.1 (12.1)0.033Never smokers, n (%)35 (67)34 (65)0.83Moderate physical activity (hours/week), median (range)2.0 (0-28)1.2 (0-30.0)0.278Vitamin D*, nmol/l, median (range)50.0 (27-106)51.5 (23-115)0.829BMD, gm/cm2Spine L2-L41.19 (0.13)1.25 (0.10)0.110< 20 years (n = 14, 27%)1.14 (0.21)1.17 (0.11)0.496>20 years (n = 38, 73%)1.19 (0.12)1.26 (0.10)0.018Femoral neck0.97 (0.12)1.04 (0.09)0.006>20 years0.97 (0.12)1.04 (0.09)0.002Proximal radius0.79 (0.12)0.86 (0.09)0.007>20 years0.79 (0.12)0.86 (0.09)0.013Distal radius0.40 (0.07)0.50 (0.10)>20 years0.41 (0.07)0.51 (0.10)T-score >20 yearsSpine L2-L4, median (range)-0.40 (-2.3 to 2.0)0.29 (-1.4 to 1.8)0.006Femoral neck, median (range)-0.50 (-2.2 to 2.1)0.40 (-1.7 to 1.6)0.007Proximal radius, median (range)-0.90 (-0.2 to 1.6)-0.30 (-0.2 to 1.3)0.044Distal radius, median (range)-1.0 (-3.0 to 1.3)0.20 (-2.6 to 3.8)All values are mean (SD) unless otherwise statedConclusionBone mineral density was impaired in JMCTD patients after 16 years disease duration compared to matched controls.References[1]Bodolay E et. Al, Osteoporosis in mixed connective tissue disease, Clin Rheumatol. 2003Disclosure of InterestsNone declared

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan autoimmune disease with a prevalence of 3 in 1 000 000 children. Information on long-term development of organ involvement and clinical characteristics of jSSc patients in adulthood are lacking. It was believed that patients in adult cohorts may represent a survival biased population.ObjectivesTo assess differences in clinical characteristics of jSSc-onset patients from the pediatric age group, with a mean disease duration of 3 years, compared to the adult age jSSc-onset group, with a mean disease duration of 18.5 years.MethodsWe extracted clinical data at time of inclusion into the cohorts from the Juvenile Scleroderma Inception Cohort (jSScC) and data from juvenile-onset adult SSc patients from the European Trials and Research Group (EUSTAR) cohort. We compared the clinical characteristics of the patients by descriptive statistics.ResultsWe extracted data of 187 jSSc patients from the jSScC and 236 patients from EUSTAR. The mean age at time of assessment was 13.4 years old in the jSScC and 32.4 years old in EUSTAR. The mean disease duration since first non-Raynaud was 3.0 years in jSScC and 18.5 years in the EUSTAR (Table 1).We found significant differences between the cohorts. There were more female patients in EUSTAR (87.7% versus 80.2%, p=0.04). More patients had diffuse subtype in jSScC (72.2% versus 40%, pTable 1.Clinical characteristics of juvenile onset SSc patients at time point of the inclusion into the juvenile scleroderma inception (jSScC) cohort and in the adult EUSTAR- cohortjSScCEUSTAR CohortP valueNumber of patients1872360.04Age in years, mean (SD)13.4 (3.6)32.4 (15.4)Female patients, n (%)150 (80.2%)207 (87.7%)jSSC Subtype, n (%)diffuse135 (72.2%)87 (38.1%)limited52 (27.8%)121 (53.3%)Age at Raynaud onset in years, mean (SD)10.0 (3.9)13.7 (9.1)Age at non-Raynaud onset in years, mean (SD)10.3 (3.9)11.7 (3.7)Duration since first Raynaud symptoms in years, mean (SD)3.4 (2.7)20.6 (15.9)Duration since first non-Raynaud symptoms in years, mean (SD)3.0 (2.7)18.5 (15.6)Raynaud´s, n (%)170 (90.9%)222 (94.9%)ANA positive, n (%)166 (91.7%)210 (92.9%)0.99Anti-Scl 70 positive, n (%)62 (34.4%)73 (33.3%)0.68Modified Rodnan Skin Score, mean (SD)5%Data missingModified Rodnan Skin Score, mean (SD)14.2 (11.7)12.1 (14.5)0.02Digital ulceration, n (%)At the time of inclusion33 (17.8)21 (26.6%)0.01In the past history100 (54.1%)34 (43%)Telangiectasia62 (37.4%)42 (53.2%)0.04FVC, mean (SD)84.1 (18.6)84 (22.4)0.96DLCO, mean (SD)75.4 (19.2)86.3 (19.9)Arterial hypertension, n (%)10 (5.4%)20 (8.5%)0.26Renal crisis, n (%)03 (1.3%)0.26Esophageal involvement, n (%)63 (33.7%)149 (63.7%)Intestinal involvement, n (%)62 (33.2%)56 (23.8%)0.04Articular involvement, n (%)34 (18.3%)27 (11.6%)0.06Muscular involvement, n (%)31 (19.3%)46 (19.8%)0.45ConclusionPatients with jSSc-onset who are currently adult age (defined as >18 years of age) are less frequently male and from the diffuse subset, have lower mRSS, less digital ulcers and intestinal involvement. This might represent a combination of both survival bias and/or be explained by the longer observation time with less active disease (i.e. natural progression decreased mRSS over time). Further long-term observational studies with jSSc patients are required to address this issue.Disclosure of InterestsNone 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.