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Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database
  1. Anthony J Tyndall1,
  2. Bettina Bannert1,
  3. Madelon Vonk2,
  4. Paolo Airò3,
  5. Franco Cozzi4,
  6. Patricia E Carreira5,
  7. Dominique Farge Bancel6,
  8. Yannick Allanore7,
  9. Ulf Müller-Ladner8,
  10. Oliver Distler9,
  11. Florenzo Iannone10,
  12. Raffaele Pellerito11,
  13. Margarita Pileckyte12,
  14. Irene Miniati13,
  15. Lidia Ananieva14,
  16. Alexandra Balbir Gurman15,
  17. Nemanja Damjanov16,
  18. Adelheid Mueller17,
  19. Gabriele Valentini18,
  20. Gabriela Riemekasten19,
  21. Mohammed Tikly20,
  22. Laura Hummers21,
  23. Maria JS Henriques22,
  24. Paola Caramaschi23,
  25. Agneta Scheja24,
  26. Blaz Rozman25,
  27. Evelien Ton26,
  28. Gábor Kumánovics27,
  29. Bernard Coleiro28,
  30. Eva Feierl29,
  31. Gabriella Szucs30,
  32. Carlos Alberto Von Mühlen31,
  33. Valeria Riccieri32,
  34. Srdan Novak33,
  35. Carlo Chizzolini34,
  36. Anna Kotulska35,
  37. Christopher Denton36,
  38. Paulo C Coelho37,
  39. Ina Kötter38,
  40. Ismail Simsek39,
  41. Paloma García de la Pena Lefebvre40,
  42. Eric Hachulla41,
  43. James R Seibold42,
  44. Simona Rednic43,
  45. Jiří Štork44,
  46. Jadranka Morovic-Vergles45,
  47. Ulrich A Walker1
  1. 1Department of Rheumatology, University of Basel, Basel, Switzerland
  2. 2Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
  3. 3Servizio di Reumatologia Allergologia e Immunologia Clinica, Brescia, Italy
  4. 4Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
  5. 5Servicio de Reumatología, Hospital Universitario 12 de Octubre, Madrid, Spain
  6. 6Department of Internal Medicine, Hopital Saint-Louis, Paris, France
  7. 7Department of Rheumatology, Hopital Cochin, Paris, France
  8. 8Abteilung für Rheumatologie und Klinische Immunologie, Kerckhoff-Klinik, Bad Nauheim, Germany
  9. 9Department of Rheumatology, University Hospital Zürich, Zurich, Switzerland
  10. 10UO Reumatologia Università degli Studi di Bari, Bari, Italy
  11. 11Ospedale Mauriziano, Centro di Reumatologia, Torino, Italy
  12. 12Department of Rheumatology, Kaunas University of Medicine Hospital, Kaunas, Lithuania
  13. 13Department of BioMedicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy
  14. 14Institute of Rheumatology, Russian Academy of Medical Science, Moscow, Russia
  15. 15B Shine Department of Rheumatology, Rambam Health Care Campus, Haifa, Israel
  16. 16Institute of Rheumatology, Belgrade, Serbia
  17. 17Department of Internal Medicine I, University of Regensburg, Regensburg, Germany
  18. 18Dipartimento Medicina Clinica e Sperimentale ‘F-Magrassi’ Il Policlinico UO Reumatologia, Napoli, Italy
  19. 19Department of Rheumatology, Charitè University Hospital, Berlin, Germany
  20. 20Rheumatology Unit, Department of Medicine Chris Hani Baragwanath, Hospital and University of the Witwatersrand, Johannesburg, South Africa
  21. 21Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA
  22. 22Reumatologia, Hospitais da Universidade Coimbra, Coimbra, Portugal
  23. 23Dipartimento di Medicina Clinica e Sperimentale, Reumatologia-Medicina Interna B, Università degli Studi di Verona, Verona, Italy
  24. 24Department of Rheumatology, Lund University Hospital, Lund, Sweden
  25. 25Department of Rheumatology, University Medical Center, Ljublijana, Slovenia
  26. 26University Medical Centre, Utrecht, The Netherlands
  27. 27Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary
  28. 28'Stella Maris' Balzan, Balzan, Malta
  29. 29Division of Rheumatology, Medical University of Vienna, Vienna, Austria
  30. 30Institute of Internal Medicine, Department of Rheumatology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary
  31. 31Rheuma Clinic, Porto Alegre, Brazil
  32. 32Divisione di Reumatologia, Università di Roma La Sapienza, Rome, Italy
  33. 33Department of Rheumatology and Clinical Immunology, KBC Rijeka, Rijeka, Croatia
  34. 34Department of Immunology and Allergy, University Hospital, Geneva, Switzerland
  35. 35Department of Internal Medicine and Rheumatology, Medical University of Silesia, Katowice, Poland
  36. 36Centre for Rheumatology, Royal Free and University College London Medical School, London, UK
  37. 37Instituto Portugues de Reumatologia, Lisboa, Portugal
  38. 38Internal Medicine/Rheumatology/Haematology/Oncology, Universitätsklinikum Tübingen, Tübingen, Germany
  39. 39Division of Rheumatology, Gulhane Military Medical Academy, Etlik-Ankara, Ankara, Turkey
  40. 40Servicio de Reumatología, Hospital Ramon y Cajal, Madrid, Spain
  41. 41Department of Internal Medicine Hôpital Claude Huriez, Lille, France
  42. 42University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA
  43. 43Clinica Reumatologie, University of Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj-Napoca, Romania
  44. 44Department of Dermatology, Charles University, Prague, Czech Republic
  45. 45Division of Clinical Immunology and Rheumatology, Dubrava University Hospital, Zagreb, Croatia
  1. Correspondence to Ulrich A Walker, Department of Rheumatology, University of Basel, Felix Platter Spital, Burgfelderstrasse 101, 4012 Basel, Switzerland; ulrich.walker{at}


Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc).

Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan–Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality.

Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points).

Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.

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  • Competing interests None.

  • Funding EUSTAR is supported by research grant from EULAR and is under the auspices of the Standing Committee for Clinical Affairs (ESCCA).

  • Patient consent Obtained.

  • Ethics approval All participating EUSTAR MEDS database centres have ethics committee approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.