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Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database
  1. Elina G Wirz1,2,
  2. Veronika K Jaeger1,
  3. Yannick Allanore3,
  4. Gabriela Riemekasten4,5,
  5. Eric Hachulla6,
  6. Oliver Distler7,
  7. Paolo Airò8,
  8. Patricia E Carreira9,
  9. Mohammed Tikly10,
  10. Serena Vettori11,
  11. Alexandra Balbir Gurman12,
  12. Nemanja Damjanov13,
  13. Ulf Müller-Ladner14,
  14. Jörg Distler15,
  15. Mangtao Li16,
  16. Peter Häusermann2,
  17. Ulrich A Walker1
  18. EUSTAR coauthors
    1. 1Department of Rheumatology, University Hospital Basel, Basel, Switzerland
    2. 2Department of Dermatology, University Hospital Basel, Basel, Switzerland
    3. 3Department of Rheumatology A, Paris Descartes University, Cochin Hospital, Paris, France
    4. 4Department of Rheumatology, Charité University Hospital, Berlin, Germany
    5. 5German Rheumatism Research Centre (DRFZ), Leibniz Institute, Berlin, Germany
    6. 6Department of Internal Medicine, Hôpital Claude Huriez, University Lille, Lille Cedex, France
    7. 7Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
    8. 8Rheumatology and Clinical Immunology Service, Spedali Civili di Brescia, Brescia, Italy
    9. 9Servicio de Reumatologia, Hospital Universitario 12 de Octubre, Madrid, Spain
    10. 10Division of Rheumatology, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
    11. 11Rheumatology Department, Second University of Naples, Naples, Italy
    12. 12B. Shine Rheumatology Unit, Rappaport Faculty of Medicine, Rambam Health Care Campus, Technion-Institute of Technology, Haifa, Israel
    13. 13Institute of Rheumatology, University of Belgrade Medical School, Belgrade, Serbia
    14. 14Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff Clinic, Bad Nauheim, Germany
    15. 15Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany
    16. 16Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
    1. Correspondence to Dr Ulrich A Walker, Department of Rheumatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; ulrich.walker{at}


    Objectives To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort.

    Methods 695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan–Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors.

    Results The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies.

    Conclusion Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.

    • Systemic Sclerosis
    • Epidemiology
    • Autoantibodies

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