Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study

Systemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity. We model SSc disease trajectories in the European Scleroderma Trials and Research (EUSTAR) database, containing 14,000 patients across 67,000 medical visits, and identify clinically meaningful subtypes to enhance patient stratification and prognosis. We systematically evaluate the model's predictive accuracy, robustness to missing data, and clinical interpretability. We identified five patient clusters, separating patients based on the degree of organ involvement. Notably, a subset with limited skin involvement still showed high risks of lung and heart complications, underscoring the importance of data-driven methods and multi-organ models to complement established insights from clinical practice.

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Publication Details

Journal
npj Digital Medicine
Published
2025-09-01
DOI
https://doi.org/10.1038/s41746-025-01962-y
Citations
1
Primary Topic
Systemic Sclerosis and Related Diseases
Type
article
Field-Weighted Citation Impact
1.47

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article

Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study

Marzena Olesińska, N. Manukyan, Anna‐Maria Hoffmann‐Vold, S. Blaise et al.
1 citations
npj Digital Medicine
Systemic Sclerosis and Related Diseases
1.47
article

Deep hierarchical subtyping of multi-organ systemic sclerosis trajectories - a EUSTAR study

Marzena Olesińska, N. Manukyan, Anna‐Maria Hoffmann‐Vold, S. Blaise, Irene Carrión-Barberà, Gonçalo Boleto, Luc Mouthon, Petros Paul Sfikakis, Edoardo Rosato, Svetlana Agachi, Ulrich A. Walker, Ivan Castellvi, Fabiola Atzeni, Rosario Foti, Srđan Novak, Marie Vanthuyne, Jörg Henes, Marta Mosca, G. Szücs, David Launay, Joško Mitrović, Florenzo Iannone, Ahmed E. Allam, Alexandra Balbir‐Gurman, Christina Bergmann, Gabriela Riemekasten, Patricia Senet, Cécile Trottet, N Hunzelmann, K. Ginosyan, Francesco Paolo Cantatore, Claudia Ickinger, Ulrich Gerth, Fatma Alıbaz-Öner, Amato de Paulis, Carlomaurizio Montecucco, Ivan Foeldvari, Ira Litinsky, Lèlita Santos, Maria Sole Chimenti, Antonella Marcoccia, Eiman Soliman, Enrico Selvi, L. Petelytska, Michael Krauthammer, Marta Dzhus, Maurizio Cutolo, Francesco Benvenuti, Gianluca Moroncini, Oscar Massimiliano Epis, Elena Rezuş, Samah A. El-Bakry, Ana-Maria Ramazan, Alberto Cauli, Andra Rodica Balanescu, Kamal Solanki, Przemysław Kotyla, Mehmet Tuncay Duruöz, Bojana Stamenković, Katja Perdan Pirkmajer, Paolo Airó, Qingran Yan, Rong Mu, Marie‐Elise Truchetet, Duygu Temiz Karadağ, Bogdan Batko, Anastas Batalov, Jeska de Vries‐Bouwstra, Carolina de Souza Müller, Jelena Čolić, Marek Brzosko, Simona Rednic, Madelon C Vonk, Yannick Allanore, Juan José Alegre Sancho, Monique Hinchcliff, Roberto Giacomelli, Chris T. Derk, Massimiliano Limonta, Silvia Bellando-Randone, Ana Maria Gheorghiu, Luca Idolazzi, Valeria Riccieri, Oliver Distler, Esther Vicente Rabaneda, Cristina Maglio, Mette Mogensen, Francesco Del Galdo, Patricia Esmeralda Carreira, Rossella De Angelis, Jasminka Milas-Ahic, Radim Bečvář, Helbert Natan da Silva Carneiro, Julia Spierings, Manuel Schürch, Nicoletta Del Papa, Maria De Santis, Masataka Kuwana, Klaus Søndergaard, Vanessa Smith, Britta Maurer, Andrea‐Hermina Györfi, Mickaël Martin, Yasser El Miedany, Tânia Santiago, Emmanuel Chatelus, Miriam Retuerto, Mislav Radić, Alejandro Brigante, Eduardo Kerzberg, Daniel Brito de Araújo, Gabór Kumánovics, Anna Wojteczek, Anna Lewandowska‐Polak, A. Mékinian, Giovanna Cuomo, Alain Lescoat, Carmen Pilar Simeón‐Aznar, Gianluigi Bajocchi, Elisabetta Zanatta, Thierry Martin, Brigitte Granel, Mohammad Naffaa, Christopher Paul Denton, Lidia P Ananieva, Marco Matucci Cerinic, Seda Çolak, Yair Levy, L. Núñez, Futoshi Iwata, Alexandra Daniel, Magda Pârvu, Lijun Zhang, Ivette Casafont Sole, Janeth Villegas Guzmán, Claudia Mora-Trujillo, Nihal Awad
article en
1 citations

Abstract

Systemic sclerosis (SSc) is a chronic autoimmune disease with multi-organ involvement. Historically, SSc classification has focused on the type of skin involvement (limited versus diffuse); however, a growing evidence of organ-specific variability suggests the presence of more than two distinct subtypes. We propose a semi-supervised generative deep learning framework leveraging expert-driven definitions of organ-specific involvement and severity. We model SSc disease trajectories in the European Scleroderma Trials and Research (EUSTAR) database, containing 14,000 patients across 67,000 medical visits, and identify clinically meaningful subtypes to enhance patient stratification and prognosis. We systematically evaluate the model's predictive accuracy, robustness to missing data, and clinical interpretability. We identified five patient clusters, separating patients based on the degree of organ involvement. Notably, a subset with limited skin involvement still showed high risks of lung and heart complications, underscoring the importance of data-driven methods and multi-organ models to complement established insights from clinical practice.

npj Digital MedicineVol. 8(1)
University of Foggia (IT), Ain Shams University (EG), University of Messina (IT), University of Verona (IT), Marche Polytechnic University (IT), Oslo University Hospital (NO), Cliniques Universitaires Saint-Luc (BE), University of Debrecen (HU), Harvard University (US), University of Padua (IT), Radboud University Nijmegen (NL), University of Nis (RS), University of Rijeka (HR), Vita-Salute San Raffaele University (IT), Carol Davila University of Medicine and Pharmacy (RO), Medical University of Silesia (PL), Universidade Federal de Pelotas (BR), Instituto Politécnico de Leiria (PT), University of Cagliari (IT), Peking University (CN), University of Zurich (CH), Université Paris Cité (FR), Iuliu Hațieganu University of Medicine and Pharmacy (RO), Charles University (CZ), University of Pavia (IT), Tel Aviv Sourasky Medical Center (IL), Western Galilee Hospital (IL), Leiden University Medical Center (NL), Chris Hani Baragwanath Hospital (ZA), Policlinico Umberto I (IT), Centre Hospitalier Universitaire de Grenoble (FR), Renji Hospital (CN), University Hospital Dubrava (HR), Sahlgrenska University Hospital (SE), Medical University Plovdiv (BG), The Royal Free Hospital (GB), Rambam Health Care Campus (IL), Ljubljana University Medical Centre (SI), Regione Campania (IT), Waikato Hospital (NZ), Hospital de Sant Pau (ES), Meir Medical Center (IL), Bispebjerg Hospital (DK), Hospitais da Universidade de Coimbra (PT), Aarhus University Hospital (DK), University Hospital of Basel (CH), Radboud University Medical Center (NL), Centre Hospitalier Universitaire de Bordeaux (FR), University Medical Center Utrecht (NL), Centre Hospitalier Universitaire de Lille (FR), Grigore T. Popa University of Medicine and Pharmacy (RO), Ghent University (BE), Université de Poitiers (FR), ETH Zurich (CH), University of Catania (IT), Sorbonne Université (FR), St. Luke's International Hospital (JP), Hospital Son Llatzer (ES), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), Gülhane Askerî Tıp Akademisi (TR), Universitätsklinik für Neurologie (AT), Sorbonne Paris Cité (FR), Institute of Rheumatology (CZ), Cracow University of Technology (PL), Hôpital Cochin (FR), Hospital Nacional Cayetano Heredia (PE), Universitätsklinikum Tübingen (DE), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Mikaelyan Institute of Surgery (AM), Universitäres Kinderwunschzentrum Lübeck (DE), University Hospital of Zurich (CH), Hospital Universitario 12 De Octubre (ES), Hôpital Saint-Antoine (FR), Hospital Ramos Mejía (AR), Ospedale Papa Giovanni XXIII (IT), Radboud Institute for Molecular Life Sciences (NL), Institutul Cantacuzino (RO), Zurich University of Teacher Education (CH), Laboratoire National de Référence (MA), University Hospital Schleswig-Holstein (DE), Hautklinik Heidelberg (DE), Istituto Ortopedico Gaetano Pini (IT), NIHR Leeds Musculoskeletal Biomedical Research Unit (GB), Hôpital Nord (FR), Azienda Ospedaliero-Universitaria Careggi (IT), Dana-Farber Cancer Institute (US), Association of Rheumatologists of Russia (RU), Medical University of Lodz (PL), Azienda Ospedaliera S.Maria (IT), Assiut University Hospitals (EG), Instituto Português de Malacologia (PT), Nicolae Testemițanu State University of Medicine and Pharmacy (MD), Hospital Nacional Dos de Mayo (PE), Hospital Universitario Doctor Peset (ES), Vall d'Hebron Hospital Universitari (ES), Centro di Riferimento Oncologico (IT), Hospital Universitario de La Princesa (ES), Hospital Del Mar (ES), Klinički bolnički centar Osijek (HR), Hospital de Clínicas Universidade Federal do Paraná (BR), Azienda Ospedaliera Universitaria Senese (IT), National Institute of Geriatrics, Rheumatology and Rehabilitation (PL), Società Italiana di Reumatologia (IT), Policlinico Tor Vergata (IT), Scleroderma Foundation (US), University of Hong Kong - Shenzhen Hospital (CN), Peking University Third Hospital (CN), Institut Cochin (FR), Campus Bio Medico University Hospital (IT), Ospedale Policlinico San Martino (IT), Centrum für Integrierte Onkologie (DE), Hospital de Santa Maria (PT), Policlinico San Matteo Fondazione (IT), Ospedale San Bortolo (IT), Hospital Universitari Germans Trias i Pujol (ES), Reha Rheinfelden (CH), Spitalul Clinic Colentina (RO), Nippon Medical School Hospital (JP), Hôpital Claude Huriez (FR), Hôpital d'Hautepierre (FR), IRCCS Humanitas Research Hospital (IT), Spitalul Clinic Judetean de Urgenta Sibiu (RO), Hôpital Civil, Strasbourg (FR), Complejo Asistencial Universitario de Palencia (ES), Azienda Ospedaliera Universitaria Pisana (IT), Egyptian Society of Laboratory Medicine (EG), Hôpital Tenon (FR), Instituto Português de Reumatologia, Heinrich Heine University Düsseldorf (DE), University College London (GB), Kocaeli Üniversitesi (TR), University of Bari Aldo Moro (IT), Yerevan State Medical University (AM), University of Naples Federico II (IT), Athens State University (US), Marmara University (TR), Gdańsk Medical University (PL), University of Pennsylvania (US), University of Pecs (HU), Pomeranian Medical University (PL), University of Brescia (IT), Bogomolets National Medical University (UA), Alexandria University (EG), Sapienza University of Rome (IT), University of Hong Kong (HK), Université Grenoble Alpes (FR), Assiut University (EG), University of Split (HR), University of Lübeck (DE), UCLouvain (BE)
National Science Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Openalex Percentile: Top 16%
Systemic Sclerosis and Related Diseases
1.47
DOIOpen Access PDFOpenAlex
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