1364: Diffuse Juvenile Systemic Sclerosis Patients Show Distinct Organ Involvement and Have More Severe Disease in the Largest jSSc Cohort of the World. Results from the the Juvenile Scleroderma Inception Cohort

Ivan Foeldvari¹, Jens Klotsche², Ozgur Kasapcopur³, Amra Adrovic⁴, Kathryn Torok⁵, Maria Teresa Terreri⁶, Ana Paula Sakamoto⁷, Brian Feldman⁸, FLAVIO SZTAJNBOK⁹, Valda Stanevica¹⁰, Jordi Anton¹¹, Sindu Johnson¹², Raju Khubchandani¹³, Ekaterina Alexeeva¹⁴, Maria Katsicas¹⁵, Sujata Sawhney¹⁶, Vanessa Smith¹⁷, Simone Appenzeller¹⁸, Tadey Avcin¹⁹, Mikhail Kostik²⁰, Thomas Lehman²¹, Hana Malcova²², Edoardo Marrani²³, Clare Pain²⁴, Dieneke Schonenberg-Meinema²⁵, Walter Alberto Sifuentes-Giraldo²⁶, Natalia Vasquez-Canizares²⁷, Patricia Costa Reis²⁸, Mahesh Janarthanan²⁹, Dana Nemcova³⁰, Anjali Patwardhan³¹, Maria José Santos³², Sima Abu Alsaoud³³, Cristina Battagliotti³⁴, Lillemor Berntson³⁵, Blanca Bica³⁶, Jürgen Brunner³⁶, Rolando Cimaz³⁷, Despina Eleftheriou³⁸, Liora Harel³⁹, Gerd Horneff⁴⁰, Daniela Kaiser⁴¹, Tilmann Kallinich⁴², Dragana Lazarevic⁴³, Farzana Nuruzzaman⁴⁴ and Nicola Helmus⁴⁵, ¹Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany, ²German Rheumatism Research Center, Berlin, Germany, ³Istanbul University-Cerrahpaşa, Cerrahpaşa Medical School, Istanbul, Turkey, ⁴Cerrahpaşa Medical School, Istanbul University, Istanbul, Turkey, ⁵Pediatric Rheumatology, Children's Hospital of UPMC, Pittsburgh, PA, ⁶Universidad Federal São Paulo, São Paulo, Brazil, ⁷Federal University of Sao Paulo (UNIFESP), São Paulo, Brazil, ⁸Division of Rheumatology, The Hospital for Sick Children; Child Health Evaluative Services, SickKids Research Institute; Department of Paediatrics, University of Toronto, Toronto, ON, Canada, ⁹UFRJ/UERJ, São Paulo, Brazil, ¹⁰Children's Clinical University Hospital, Zemgales priekšpilseta, Riga, Latvia, ¹¹Pediatric Rheumatology, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain, ¹²University of Toronto, Toronto, ON, Canada, ¹³SRCC Children's Hospital, Mumbai, India, ¹⁴National Medical Research Center of Children's Health, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation,, Moscow, Russia, ¹⁵Hospital Garrahan, Buenos Aires, Argentina, ¹⁶Sir Ganga Ram Hospital, Sector 37 noida, Uttar Pradesh, India, ¹⁷Department of Rheumatology, Ghent University Hospital – Department of Internal Medicine, Ghent University, Belgium – Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Gent, Belgium, ¹⁸Unicamp, Campinas, São Paulo, Brazil, ¹⁹University Children's Hospital University Medical Center Ljubljana, Ljubljana, Slovenia, ²⁰Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russia, ²¹Hospital for Special Surgery, New York, NY, ²²Motol University Hospital, Prague, Czech Republic, ²³University of Florence, Firenze, Italy, ²⁴Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom, ²⁵Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands, ²⁶Hospital Universitario Ramon y Cajal, Madrid, Spain, ²⁷Children’s Hospital at Montefiore, Bronx, NY, ²⁸Hospital de Santa Maria, Lisbon, Portugal, ²⁹SRI RAMACHANDRA INSTITUTE OF HIGHER EDUCATION AND RESEARCH, Chennai, India, ³⁰Charles University, Prague, Czech Republic, ³¹University of Missouri, Columbia, MO, ³²Hospital Garcia de Orta, Almada, Charneca da Caparica, Portugal, ³³Makassed, Jerusalem, Israel, ³⁴Hospital de Niños Dr Orlando Alassia, Santa Fe, Argentina, ³⁵Dept. of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden, ³⁶UNIVERSIDADE FEDERAL DO RIO DE JANEIRO, Rio de Janeiro, Brazil, ³⁷University of Milano, Milano, Italy, ³⁸Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom, ³⁹Schneider Children's Medical center, Tel Aviv University, Nettnja, Israel, ⁴⁰Pediatrics, Asklepios Klinik Sankt Augustin GmbH, Sankt Augustin, Germany, ⁴¹Children's Hospital Lucerne, Lucerne, Switzerland, ⁴²Charité - Universitätsmedizin Berlin, Nuremberg, Germany, ⁴³Faculty of Medicine, University of Niš, Nis, Serbia, ⁴⁴Stony Brook Children's Hospital, East Setauket, NY, ⁴⁵Hamburg Centre for Pediatric and Adolescence Rheumatology, Hamburg, Germany

Background/Purpose: Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. In adult patients there are significant differences between the clinical presentation of diffuse and limited subtypes. We reviewed clinical differences in presentation of subtypes in patients in the juvenile systemic scleroderma inception cohort up to 2021.

Methods: We reviewed the clinical baseline characteristics of the patients, who were recruited to the juvenile scleroderma inception cohort (jSScC) till 1^st 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.

Results: 210 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< 0.001). Antibody profile was quite similar, with the exception of a significantly higher number of anticentromere positive patients in the ljSSc (12% versus 2%, p=0.013). Decreased FVC < 80% was found in approximately 30% and decreased DLCO < 80% was found in around 40% in both subtypes. Pulmonary hypertension assessed by ultrasound was identified in 5% in both groups. Patients with diffuse subtype had significantly higher modified Rodnan Skin Score (mRSS) (16 versus 4.5, p< 0.001), sclerodactyly (84% versus 60%, p< 0.001), history of digital ulceration (62% versus 31%, p< 0.001), decreased Body Mass Index (BMI) ≤ -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, p< 0.001) and physician reported global disease damage (VAS 0 – 100) (30 versus 15, p=0.014) was significantly higher in djSSc.

Conclusion: In 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.

This project was supported by an unrestricted grant from "Joachim Herz Stiftung"

Disclosures: I. Foeldvari, None; J. Klotsche, None; O. Kasapcopur, None; A. Adrovic, None; K. Torok, None; M. Terreri, Roche, Pfizer, UCB, Janssen, Bristol-Myers Squibb(BMS), Eli Lilly, AbbVie/Abbott; A. Sakamoto, None; B. Feldman, Pfizer, AB2-Bio, Janssen; F. SZTAJNBOK, None; V. Stanevica, None; J. Anton, for Sobi, Novimmune, Novartis, Abbvie, Pfizer, GSK, Roche, Amgen, Lilly, BMS, Sanofi, Sobi, Novimmune, Novartis, Pfizer, GSK, Sobi, Novimmune, Novartis, GSK, Pfizer.; S. Johnson, None; R. Khubchandani, None; E. Alexeeva, None; M. Katsicas, None; S. Sawhney, None; V. Smith, Boehringer-Ingelheim, Janssen; S. Appenzeller, None; T. Avcin, None; M. Kostik, None; T. Lehman, None; H. Malcova, None; E. Marrani, None; C. Pain, None; D. Schonenberg-Meinema, None; W. Sifuentes-Giraldo, None; N. Vasquez-Canizares, None; P. Costa Reis, None; M. Janarthanan, None; D. Nemcova, None; A. Patwardhan, None; M. Santos, AbbVie/Abbott, AstraZeneca, pfizer, Novartis, Eli Lilly; S. Abu Alsaoud, None; C. Battagliotti, None; L. Berntson, Pfizer; B. Bica, None; J. Brunner, None; R. Cimaz, None; D. Eleftheriou, None; L. Harel, None; G. Horneff, Roche, Pfizer, Novartis, Merck/MSD, Eli Lilly, AbbVie/Abbott; D. Kaiser, None; T. Kallinich, Roche; D. Lazarevic, None; F. Nuruzzaman, None; N. Helmus, None.