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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:It has been published that the presence of NXP2 autoantibodies presents a risk for calcinosis in patients with JDM.Objectives:To investigate the incidence of calcinosis and response to the treatment in NXP2 positive JDM patients with calcinosis.Methods:The study design is a retrospective, multinational, multicenter study. Data on gender, race, age at disease onset and age at disease diagnosis, age at inclusion in the study, clinical presentation, muscle function tests, laboratory results, imaging, data on treatment and outcome of disease were collectedResults:we collected 26 patients (19 F, 7 M) with JDM and positive NXP2 antibodies. Fourteen patients were white, eight asian, three black and one Hispanic ethnicity. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5- 27 months). Patients were divided in two groups (A and B) based on the presence of calcinosis.Eleven patients (42%) developed calcinosis (group A) in the course of the disease, 10 females and 1 male. Four patients already had calcinosis at presentation, 1 developed after 4 months, and 6 developed calcinosis later in disease course (median 2 years, range 0,8- 7,8). Four patients developed lipodystrophy in group A (1 in group B). In group A, 3 patients developed skin ulcerations (1 in group B), 2 patients had polyarthritis (1 in group B), 2 patients had gut involvement (1 in group B) and 1 patient had lung involvement (2 in group B).The mean age at disease presentation (5.2 / 7.5 y) and mean CK level (1548.6 / 1811.6 U/L) were lower in group A. The platelet count (306.5 / 258 109/L), and mean values of AST (111.4 / 103.8 U/L), ALT (72.2 / 50.8 U/L), LDH (1048.3 / 808 IU/L), and IgG (11.8 / 9.9 g/L) were higher in group A. However, the differences were not statistically significant. ANA antibodies were positive in 9/11 in group A and 12/15 in group B. One patient in group A was also positive for anti-MDA5 antibody. The data on muscle strength measurement (MMT/CMAS) were available only in a few patients.Treatments used for patients with calcinosis includes, methotrexate and glucocorticosteroids (GCS) (all patients), hydroxychloroquine (9), IVIG (7), cyclosporine (4), bisphosphonate (4), MMF (5), rituximab (4), cyclophosphamide (1), abatacept (1) and TNF alpha blocker (1).Disease outcome (by evaluation of the treating physician) was excellent in 4, good in 2, stable in 2 and poor in 3 patients. None of the patients from group B had a poor disease outcome. Patients with excellent disease outcomes from group A were treated with GCS and methotrexate (4), hydroxychloroquine (3), IVIG (1) and cyclosporine (1). Out of two patients who had good outcomes, one was additionally treated with MMF, bisphosphonates and rituximab and the second was treated with cyclophosphamide and rituximab. One patient with calcinosis at the presentation (age 4 years) was treated also with anti-TNF alpha therapy which not only stopped progression but partially dissolved the calcinosis. However, after 2 years of anti-TNF alpha therapy the calcinosis start to progress and the therapy was changed to MMF and rituximab, which stopped the progression of calcinosis.Conclusion:Our preliminary results showed that calcinosis occurred in 42% of NXP2 positive JDM patients. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and in one case, for limited time of 2 years, anti-TNF alpha agent, were used successfully.References:[1]Chung MP, Richardson C, Kirakossian D, Orandi AB, Saketkoo LA, et al. Calcinosis biomarkers in adult and juvenile dermatomyositis. Autoimmun Rev 2020; 19(6):102533.Disclosure of Interests:Natasa Toplak: None declared, Pallavi Pimpale Chavan: None declared, Silvia Rosina: None declared, Tomas Dallos Consultant of: Abbvie, Novartis, Rotem Semo Oz: None declared, Cassyanne Aguiar: None declared, Raju Khubchandani: None declared, Angelo Ravelli: None declared, Anjali Patwardhan: None declared.

Background Macrophage activation syndrome (MAS) is a potentially life-threatening complication of systemic juvenile idiopathic arthritis (sJIA). It is common view that sJIA-associated MAS bears a close clinical resemblance to the group of hemophagocytic lymphohistiocytosis (HLH) syndromes, including familial HLH (FHL). This has led to suggest the use of the HLH-2004 guidelines to diagnose MAS in sJIA. However, MAS develops in the context an underlying highly inflammatory condition, whereas FHL is a primary disorder with genetic basis. It is, thus, conceivable that some differences exist in the clinical expression and severity of the two conditions. However, their clinical picture has previously been compared only in a small study 1 Objectives To compare the demographic, clinical, laboratory and histopathologic features of sJIA-associated MAS and FHL Methods Data on sJIA-associated MAS were collected by pediatric rheumatologists and pediatric hemato-oncologists in a large multinational collaborative effort 2 . Data on FHL patients were gathered from the HLH-94 and HLH-2004 trials 2 . Clinical and laboratory features at disease onset were compared between by means of Mann-Whitney U test or chi-square/Fisher exact test, as appropriate Results A total of 620 patients were enrolled: 362 (58.4%) with sJIA-associated MAS and 258 (41.6%) with FHL. The main differences in demographic, clinical, laboratory and histopathologic features between the two patient groups are presented in Table 1 Conclusions Although MAS and FHL showed similar clinical features and laboratory abnormalities, the frequency of most clinical manifestations and the severity and trend of laboratory changes were different. FHL patients had greater frequency of hepatosplenomegaly and more profound cytopenia, hypofibrinogenemia and hypertransaminasemia, whereas MAS patients had higher levels of ferritin and LDH. The prevalence of CNS disease was comparable between the two groups. Hemophagocytosis was detected more commonly in FHL. The observed differences suggest the use of different diagnostic criteria for the two conditions References Lehmberg et al. Differentiating macrophage activation syndrome in systemic juvenile idiopathic arthritis from other forms of hemophagocytic lymphohistiocytosis. J Pediatr 2013;162:1245-51. Minoia et al. Clinical features, treatment and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. A multinational, multicentre study of 362 patients. Arthritis Rheumatol 2014;66:3160-9. Henter et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31 Disclosure of Interest None declared

Background Polyarteritis nodosa (PAN) is a predominantly medium size vasculitis characterized by non granulomatous necrotizing vasculitis. In children (c-) the disease may be confined to the skin only (cutaneous involvement-PAN) or may present with systemic involvement (systemic c-PAN) as in adult polyarteritis nodosa. Objectives We aimed to evaluate clinical, laboratory and imaging features of cutaneous c-PAN and the systemic c-PAN form in a large international pediatric vasculitis registry available on the PRINTO database. Methods We extracted from the PRINTO database all the patients who fulfilled the Ankara 2008-EULAR/PRES/PRINTO criteria for systemic c-PAN. The cutaneous c-PAN patients as per the treating physician diagnosis were also extracted. To define clinical and laboratory characteristics who could help to differentiate cutaneous PAN from cPAN and univariate logistic regression analysis was performed. Results There were 109 and 45 patients classified as systemic c-PAN, and cutaneous c-PAN respectively with a mean age at diagnosis of 9.47±3.59 years; and 9.12±3.83 years; respectively. The female/male ratio and ethnicity did not differ in the 2 subtypes. The cutaneous group had significantly less constitutional features and less acute phase reactant levels, as expected. The median values (IQR 25-75%) for the ESR and CRP for cPAN were 78 (48-108) mm/h and 7.36 (2.76-15.03) mg/dL. Musculoskeletal features such as myalgia was present in 82 (75.2%) patients with c-PAN and 18 (40.9%) patients with cutaneous PAN (p