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Determinants of mortality in systemic sclerosis: a focused review

  • Dilli Ram Poudel
  • Divya Jayakumar
  • Abhijeet Danve
  • Shiv Tej Sehra
  • Chris T. Derk
Observational Research

Abstract

Scleroderma (systemic sclerosis) is an autoimmune rheumatic disorder that is characterized by fibrosis, vascular dysfunction, and autoantibody production that involves most visceral organs. It is characterized by a high morbidity and mortality rate, mainly due to disease-related complications. Epidemiological data describing mortality and survival in this population have been based on both population and observational studies. Multiple clinical and non-clinical factors have been found to predict higher likelihood of death among thepatients. Here, we do an extensive review of the available literature, utilizing the PubMed database, to describe scleroderma and non-scleroderma related determinants of mortality in this population. We found that even though the mortality among the general population has declined, scleroderma continues to carry a very high morbidity and mortality rate, however we have made some slow progress in improving the mortality among scleroderma patients over the last few decades.

Keywords

Mortality Predictor Systemic sclerosis Scleroderma Review Survival 

Notes

Compliance with ethical standards

Funding

No financial support received.

Conflict of interest

None of the authors have conflict of interest.

References

  1. 1.
    Jimenez SA, Derk CT (2004) Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med 140:37–50CrossRefPubMedGoogle Scholar
  2. 2.
    Varga J (2016) Etiology and pathogenesis of scleroderma. In: Kelley Firestein’s textbook of rheumatology, vol 2, 10th edn. Elsevier/Saunders, PhiladelphiaGoogle Scholar
  3. 3.
    Wigley FM (2016) Clinical features & treatment of scleroderma. In: Kelley Firestein’s textbook of rheumatology, vol 2, 10th edn. Elsevier/Saunders, PhiladelphiaGoogle Scholar
  4. 4.
    Mukerjee D, St G, Coleiro B, Knight C, Denton C, Davar J et al (2003) Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 62:1088–1093. doi: 10.1136/ard.62.11.1088 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Tamaki T, Mori S, Takehara K (1991) Epidemiological study of patients with systemic sclerosis in Tokyo. Arch Dermatol Res 283:366–371CrossRefPubMedGoogle Scholar
  6. 6.
    Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O et al (2007) Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis 66:754–763. doi: 10.1136/ard.2006.062901 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mayes MD, Lacey JV, Beebe-Dimmer J, Gillespie BW, Cooper B, Laing TJ et al (2003) Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum 48:2246–2255. doi: 10.1002/art.11073 CrossRefPubMedGoogle Scholar
  8. 8.
    Altman RD, Medsger TA, Bloch DA, Michel BA (1991) Predictors of survival in systemic sclerosis (scleroderma). Arthritis Rheum 34:403–413. doi: 10.1002/art.1780340405 CrossRefPubMedGoogle Scholar
  9. 9.
    Steen VD, Medsger TA (2007) Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis 66:940–944. doi: 10.1136/ard.2006.066068 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Medsger TA (1971) Survival with systemic sclerosis (scleroderma): a life-table analysis of clinical and demographic factors in 309 patients. Ann Intern Med 75:369. doi: 10.7326/0003-4819-75-3-369 CrossRefPubMedGoogle Scholar
  11. 11.
    Gelber AC, Manno RL, Shah AA, Woods A, Le EN, Boin F et al (2013) Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature. Medicine (Baltimore) 92:191–205. doi: 10.1097/MD.0b013e31829be125 CrossRefGoogle Scholar
  12. 12.
    Bulpitt KJ, Clements PJ, Lachenbruch PA, Paulus HE, Peter JB, Agopian MS et al (1993) Early undifferentiated connective tissue disease: III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis). Ann Intern Med 118:602. doi: 10.7326/0003-4819-118-8-199304150-00005 CrossRefPubMedGoogle Scholar
  13. 13.
    Bryan C, Knight C, Black CM, Silman AJ (1999) Prediction of five-year survival following presentation with scleroderma: development of a simple model using three disease factors at first visit. Arthritis Rheum 42:2660–2665. doi: 10.1002/1529-0131(199912)42:12<2660:AID-ANR23>3.0.CO;2-N CrossRefPubMedGoogle Scholar
  14. 14.
    Walsh SJ, Fenster JR (1997) Geographical clustering of mortality from systemic sclerosis in the Southeastern United States, 1981–90. J Rheumatol 24:2348–2352PubMedGoogle Scholar
  15. 15.
    Ioannidis JPA, Vlachoyiannopoulos PG, Haidich A-B, Medsger TA, Lucas M, Michet CJ et al (2005) Mortality in systemic sclerosis: an international meta-analysis of individual patient data. Am J Med 118:2–10. doi: 10.1016/j.amjmed.2004.04.031 CrossRefPubMedGoogle Scholar
  16. 16.
    Rubio-Rivas M, Royo C, Simeón CP, Corbella X, Fonollosa V (2014) Mortality and survival in systemic sclerosis: systematic review and meta-analysis. Semin Arthritis Rheum 44:208–219. doi: 10.1016/j.semarthrit.2014.05.010 CrossRefPubMedGoogle Scholar
  17. 17.
    Elhai M, Meune C, Avouac J, Kahan A, Allanore Y (2012) Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology 51:1017–1026. doi: 10.1093/rheumatology/ker269 CrossRefPubMedGoogle Scholar
  18. 18.
    Psarras A, Soulaidopoulos S, Garyfallos A, Kitas G, Dimitroulas T (2017) A critical view on cardiovascular risk in systemic sclerosis. Rheumatol Int 37:85–95. doi: 10.1007/s00296-016-3530-3 CrossRefPubMedGoogle Scholar
  19. 19.
    Simeón-Aznar CP, Fonollosa-Plá V, Tolosa-Vilella C, Espinosa-Garriga G, Campillo-Grau M, Ramos-Casals M et al (2015) Registry of the Spanish network for systemic sclerosis: survival, prognostic factors, and causes of death. Medicine (Baltimore) 94:e1728. doi: 10.1097/MD.0000000000001728 CrossRefGoogle Scholar
  20. 20.
    Meier FMP, Frommer KW, Dinser R, Walker UA, Czirjak L, Denton CP et al (2012) Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 71:1355–1360. doi: 10.1136/annrheumdis-2011-200742 CrossRefPubMedGoogle Scholar
  21. 21.
    Steen VD, Medsger TA (2000) Long-term outcomes of scleroderma renal crisis. Ann Intern Med 133:600–603CrossRefPubMedGoogle Scholar
  22. 22.
    Steen VD, Costantino JP, Shapiro AP, Medsger TA (1990) Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. Ann Intern Med 113:352–357CrossRefPubMedGoogle Scholar
  23. 23.
    Boin F, Rosen A (2007) Autoimmunity in systemic sclerosis: current concepts. Curr Rheumatol Rep 9:165–172CrossRefPubMedGoogle Scholar
  24. 24.
    Traub YM, Shapiro AP, Rodnan GP, Medsger TA, McDonald RH, Steen VD et al (1983) Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine (Baltimore) 62:335–352CrossRefGoogle Scholar
  25. 25.
    Steen VD, Syzd A, Johnson JP, Greenberg A, Medsger TA (2005) Kidney disease other than renal crisis in patients with diffuse scleroderma. J Rheumatol 32:649–655PubMedGoogle Scholar
  26. 26.
    Steen VD, Medsger TA, Osial TA, Ziegler GL, Shapiro AP, Rodnan GP (1984) Factors predicting development of renal involvement in progressive systemic sclerosis. Am J Med 76:779–786CrossRefPubMedGoogle Scholar
  27. 27.
    Eason RJ, Tan PL, Gow PJ (1981) Progressive systemic sclerosis in Auckland: a ten year review with emphasis on prognostic features. Aust N Z J Med 11:657–662CrossRefPubMedGoogle Scholar
  28. 28.
    Penn H, Howie AJ, Kingdon EJ, Bunn CC, Stratton RJ, Black CM et al (2007) Scleroderma renal crisis: patient characteristics and long-term outcomes. QJM Mon J Assoc Physicians 100:485–494. doi: 10.1093/qjmed/hcm052 CrossRefGoogle Scholar
  29. 29.
    Teixeira L, Mouthon L, Mahr A, Berezné A, Agard C, Mehrenberger M et al (2008) Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients. Ann Rheum Dis 67:110–116. doi: 10.1136/ard.2006.066985 CrossRefPubMedGoogle Scholar
  30. 30.
    Helfrich DJ, Banner B, Steen VD, Medsger TA (1989) Normotensive renal failure in systemic sclerosis. Arthritis Rheum 32:1128–1134CrossRefPubMedGoogle Scholar
  31. 31.
    DeMarco PJ, Weisman MH, Seibold JR, Furst DE, Wong WK, Hurwitz EL et al (2002) Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose d-penicillamine in early diffuse systemic sclerosis trial. Arthritis Rheum 46:2983–2989. doi: 10.1002/art.10589 CrossRefPubMedGoogle Scholar
  32. 32.
    Kohno K, Katayama T, Majima K, Fujisawa M, Iida S, Fukami K et al (2000) A case of normotensive scleroderma renal crisis after high-dose methylprednisolone treatment. Clin Nephrol 53:479–482PubMedGoogle Scholar
  33. 33.
    Steen VD, Medsger TA (1998) Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum 41:1613–1619. doi: 10.1002/1529-0131(199809)41:9<1613:AID-ART11>3.0.CO;2-O CrossRefPubMedGoogle Scholar
  34. 34.
    Guillevin L, Bérezné A, Seror R, Teixeira L, Pourrat J, Mahr A et al (2012) Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. Rheumatol Oxf Engl 51:460–467. doi: 10.1093/rheumatology/ker271 CrossRefGoogle Scholar
  35. 35.
    Abbott KC, Trespalacios FC, Welch PG, Agodoa LYC (2002) Scleroderma at end stage renal disease in the United States: patient characteristics and survival. J Nephrol 15:236–240PubMedGoogle Scholar
  36. 36.
    Gibney EM, Parikh CR, Jani A, Fischer MJ, Collier D, Wiseman AC (2004) Kidney transplantation for systemic sclerosis improves survival and may modulate disease activity. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 4:2027–2031. doi: 10.1111/j.1600-6143.2004.00605.x CrossRefGoogle Scholar
  37. 37.
    Gliddon AE, Doré CJ, Black CM, McHugh N, Moots R, Denton CP et al (2007) Prevention of vascular damage in scleroderma and autoimmune Raynaud’s phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril. Arthritis Rheum 56:3837–3846. doi: 10.1002/art.22965 CrossRefPubMedGoogle Scholar
  38. 38.
    Becker MO, Riemekasten G (2016) Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course. Expert Rev Clin Immunol 12:115–135. doi: 10.1586/1744666X.2016.1115717 CrossRefPubMedGoogle Scholar
  39. 39.
    Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G et al (2002) Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore) 81:139–153CrossRefGoogle Scholar
  40. 40.
    Tyndall AJ, Bannert B, Vonk M, Airò P, Cozzi F, Carreira PE et al (2010) Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69:1809–1815. doi: 10.1136/ard.2009.114264 CrossRefPubMedGoogle Scholar
  41. 41.
    Janosik DL, Osborn TG, Moore TL, Shah DG, Kenney RG, Zuckner J (1989) Heart disease in systemic sclerosis. Semin Arthritis Rheum 19:191–200CrossRefPubMedGoogle Scholar
  42. 42.
    Allanore Y, Meune C, Vonk MC, Airo P, Hachulla E, Caramaschi P et al (2010) Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis. Ann Rheum Dis 69:218–221. doi: 10.1136/ard.2008.103382 CrossRefPubMedGoogle Scholar
  43. 43.
    Allanore Y, Meune C (2010) Primary myocardial involvement in systemic sclerosis: evidence for a microvascular origin. Clin Exp Rheumatol 28:S48–S53PubMedGoogle Scholar
  44. 44.
    Meune C, Vignaux O, Kahan A, Allanore Y (2010) Heart involvement in systemic sclerosis: evolving concept and diagnostic methodologies. Arch Cardiovasc Dis 103:46–52. doi: 10.1016/j.acvd.2009.06.009 CrossRefPubMedGoogle Scholar
  45. 45.
    Perera A, Fertig N, Lucas M, Rodriguez-Reyna TS, Hu P, Steen VD et al (2007) Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. Arthritis Rheum 56:2740–2746. doi: 10.1002/art.22747 CrossRefPubMedGoogle Scholar
  46. 46.
    Meune C, Avouac J, Wahbi K, Cabanes L, Wipff J, Mouthon L et al (2008) Cardiac involvement in systemic sclerosis assessed by tissue-doppler echocardiography during routine care: a controlled study of 100 consecutive patients. Arthritis Rheum 58:1803–1809. doi: 10.1002/art.23463 CrossRefPubMedGoogle Scholar
  47. 47.
    de Groote P, Gressin V, Hachulla E, Carpentier P, Guillevin L, Kahan A et al (2008) Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann Rheum Dis 67:31–36. doi: 10.1136/ard.2006.057760 CrossRefPubMedGoogle Scholar
  48. 48.
    Kahan A, Allanore Y (2006) Primary myocardial involvement in systemic sclerosis. Rheumatol Oxf Engl 45(Suppl 4):iv14–iv17. doi: 10.1093/rheumatology/kel312 CrossRefGoogle Scholar
  49. 49.
    D’Andrea A, Stisi S, Bellissimo S, Vigorito F, Scotto di Uccio F, Tozzi N et al (2005) Early impairment of myocardial function in systemic sclerosis: non-invasive assessment by Doppler myocardial and strain rate imaging. Eur J Echocardiogr J Work Group Echocardiogr Eur Soc Cardiol 6:407–418. doi: 10.1016/j.euje.2005.01.002 CrossRefGoogle Scholar
  50. 50.
    Steen V, Medsger TA (2003) Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement. Arthritis Rheum 48:516–522. doi: 10.1002/art.10775 CrossRefPubMedGoogle Scholar
  51. 51.
    Chu S-Y, Chen Y-J, Liu C-J, Tseng W-C, Lin M-W, Hwang C-Y et al (2013) Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study. Am J Med 126:982–988. doi: 10.1016/j.amjmed.2013.06.025 CrossRefPubMedGoogle Scholar
  52. 52.
    Nordin A, Jensen-Urstad K, Björnådal L, Pettersson S, Larsson A, Svenungsson E (2013) Ischemic arterial events and atherosclerosis in patients with systemic sclerosis: a population-based case–control study. Arthritis Res Ther 15:R87. doi: 10.1186/ar4267 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kotnur MR, Suresh P, Reddy VSP, Sharma T, Salim NA (2016) Systemic sclerosis with multiple pulmonary manifestations. J Clin Diagn Res JCDR 10:OD16–OD17. doi: 10.7860/JCDR/2016/18781.8032 PubMedGoogle Scholar
  54. 54.
    Kane GC, Varga J, Conant EF, Spirn PW, Jimenez S, Fish JE (1996) Lung involvement in systemic sclerosis (scleroderma): relation to classification based on extent of skin involvement or autoantibody status. Respir Med 90:223–230CrossRefPubMedGoogle Scholar
  55. 55.
    Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M et al (2013) Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 62:D42–D50. doi: 10.1016/j.jacc.2013.10.032 CrossRefPubMedGoogle Scholar
  56. 56.
    Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62:D34–D41. doi: 10.1016/j.jacc.2013.10.029 CrossRefPubMedGoogle Scholar
  57. 57.
    Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas J (2013) Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol 32:1519–1531. doi: 10.1007/s10067-013-2307-2 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Chung L, Domsic RT, Lingala B, Alkassab F, Bolster M, Csuka ME et al (2014) Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry. Arthritis Care Res 66:489–495. doi: 10.1002/acr.22121 CrossRefGoogle Scholar
  59. 59.
    Lefèvre G, Dauchet L, Hachulla E, Montani D, Sobanski V, Lambert M et al (2013) Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Arthritis Rheum 65:2412–2423. doi: 10.1002/art.38029 CrossRefPubMedGoogle Scholar
  60. 60.
    Mathai SC, Hummers LK, Champion HC, Wigley FM, Zaiman A, Hassoun PM et al (2009) Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum 60:569–577. doi: 10.1002/art.24267 CrossRefPubMedGoogle Scholar
  61. 61.
    Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE (2003) Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 123:344–350CrossRefPubMedGoogle Scholar
  62. 62.
    Fisher MR, Mathai SC, Champion HC, Girgis RE, Housten-Harris T, Hummers L et al (2006) Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum 54:3043–3050. doi: 10.1002/art.22069 CrossRefPubMedGoogle Scholar
  63. 63.
    Michelfelder M, Becker M, Riedlinger A, Siegert E, Drömann D, Yu X et al (2017) Interstitial lung disease increases mortality in systemic sclerosis patients with pulmonary arterial hypertension without affecting hemodynamics and exercise capacity. Clin Rheumatol 36:381–390. doi: 10.1007/s10067-016-3504-6 CrossRefPubMedGoogle Scholar
  64. 64.
    Scotton CJ, Chambers RC (2007) Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest 132:1311–1321. doi: 10.1378/chest.06-2568 CrossRefPubMedGoogle Scholar
  65. 65.
    Hunninghake GW, Kalica AR (1995) Approaches to the treatment of pulmonary fibrosis. Am J Respir Crit Care Med 151:915–918. doi: 10.1164/ajrccm/151.3_Pt_1.915 CrossRefPubMedGoogle Scholar
  66. 66.
    Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC et al (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4:708–719. doi: 10.1016/S2213-2600(16)30152-7 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE et al (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–2666. doi: 10.1056/NEJMoa055120 CrossRefPubMedGoogle Scholar
  68. 68.
    Khanna D, Yan X, Tashkin DP, Furst DE, Elashoff R, Roth MD et al (2007) Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study. Arthritis Rheum 56:1676–1684. doi: 10.1002/art.22580 CrossRefPubMedGoogle Scholar
  69. 69.
    Strange C, Bolster MB, Roth MD, Silver RM, Theodore A, Goldin J et al (2008) Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med 177:91–98. doi: 10.1164/rccm.200705-655OC CrossRefPubMedGoogle Scholar
  70. 70.
    Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG et al (2011) Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 365:1079–1087. doi: 10.1056/NEJMoa1103690 CrossRefPubMedGoogle Scholar
  71. 71.
    Gyger G, Baron M (2015) Systemic sclerosis: gastrointestinal disease and its management. Rheum Dis Clin N Am 41:459–473. doi: 10.1016/j.rdc.2015.04.007 CrossRefGoogle Scholar
  72. 72.
    Turner R, Lipshutz W, Miller W, Rittenberg G, Schumacher HR, Cohen S (1973) Esophageal dysfunction in collagen disease. Am J Med Sci 265:191–199CrossRefPubMedGoogle Scholar
  73. 73.
    Akesson A, Wollheim FA (1989) Organ manifestations in 100 patients with progressive systemic sclerosis: a comparison between the CREST syndrome and diffuse scleroderma. Br J Rheumatol 28:281–286CrossRefPubMedGoogle Scholar
  74. 74.
    Krause L, Becker MO, Brueckner CS, Bellinghausen C-J, Becker C, Schneider U et al (2010) Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann Rheum Dis 69:1951–1957. doi: 10.1136/ard.2009.123273 CrossRefPubMedGoogle Scholar
  75. 75.
    Mecoli C, Purohit S, Sandorfi N, Derk CT (2014) Mortality, recurrence, and hospital course of patients with systemic sclerosis-related acute intestinal pseudo-obstruction. J Rheumatol 41:2049–2054. doi: 10.3899/jrheum.131547 CrossRefPubMedGoogle Scholar
  76. 76.
    Derk CT, Rasheed M, Artlett CM, Jimenez SA (2006) A cohort study of cancer incidence in systemic sclerosis. J Rheumatol 33:1113–1116PubMedGoogle Scholar
  77. 77.
    Rosenthal AK, McLaughlin JK, Linet MS, Persson I (1993) Scleroderma and malignancy: an epidemiological study. Ann Rheum Dis 52:531–533CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Olesen AB, Svaerke C, Farkas DK, Sørensen HT (2010) Systemic sclerosis and the risk of cancer: a nationwide population-based cohort study. Br J Dermatol 163:800–806. doi: 10.1111/j.1365-2133.2010.09861.x CrossRefPubMedGoogle Scholar
  79. 79.
    Pontifex EK, Hill CL, Roberts-Thomson P (2007) Risk factors for lung cancer in patients with scleroderma: a nested case-control study. Ann Rheum Dis 66:551–553. doi: 10.1136/ard.2006.056424 CrossRefPubMedGoogle Scholar
  80. 80.
    Domsic RT, Rodriguez-Reyna T, Lucas M, Fertig N, Medsger TA (2011) Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis 70:104–109. doi: 10.1136/ard.2009.127621 CrossRefPubMedGoogle Scholar
  81. 81.
    Strickland G, Pauling J, Cavill C, Shaddick G, McHugh N (2013) Mortality in systemic sclerosis-a single centre study from the UK. Clin Rheumatol 32:1533–1539. doi: 10.1007/s10067-013-2289-0 CrossRefPubMedGoogle Scholar
  82. 82.
    Woodworth TG, Suliman YA, Furst DE, Clements P (2016) Scleroderma renal crisis and renal involvement in systemic sclerosis. Nat Rev Nephrol 12:678–691. doi: 10.1038/nrneph.2016.124 CrossRefPubMedGoogle Scholar
  83. 83.
    Al-Dhaher FF, Pope JE, Ouimet JM (2010) Determinants of morbidity and mortality of systemic sclerosis in Canada. Semin Arthritis Rheum 39:269–277. doi: 10.1016/j.semarthrit.2008.06.002 CrossRefPubMedGoogle Scholar
  84. 84.
    Alba MA, Velasco C, Simeón CP, Fonollosa V, Trapiella L, Egurbide MV et al (2014) Early- versus late-onset systemic sclerosis: differences in clinical presentation and outcome in 1037 patients. Medicine (Baltimore) 93:73–81. doi: 10.1097/MD.0000000000000018 CrossRefGoogle Scholar
  85. 85.
    Fernández-Codina A, Simeón-Aznar CP, Pinal-Fernandez I, Rodríguez-Palomares J, Pizzi MN, Hidalgo CE et al (2017) Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival. Rheumatol Int 37:75–84. doi: 10.1007/s00296-015-3382-2 CrossRefPubMedGoogle Scholar
  86. 86.
    Hao Y, Hudson M, Baron M, Carreira P, Stevens W, Rabusa C et al (2016) Early mortality in a multinational systemic sclerosis inception cohort. Arthritis Rheumatol Hoboken NJ. doi: 10.1002/art.40027 Google Scholar
  87. 87.
    Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG et al (2014) Prediction of pulmonary complications and long-term survival in systemic sclerosis: pulmonary complications and survival in SSc. Arthritis Rheumatol 66:1625–1635. doi: 10.1002/art.38390 CrossRefPubMedGoogle Scholar
  88. 88.
    Domsic RT, Nihtyanova SI, Wisniewski SR, Fine MJ, Lucas M, Kwoh CK et al (2014) Derivation and validation of a prediction rule for two year mortality in early diffuse cutaneous systemic sclerosis. Arthritis Rheumatol Hoboken NJ 66:1616–1624. doi: 10.1002/art.38381 CrossRefGoogle Scholar
  89. 89.
    Hachulla E, Carpentier P, Gressin V, Diot E, Allanore Y, Sibilia J et al (2009) Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinérAIR-Sclérodermie study. Rheumatology 48:304–308. doi: 10.1093/rheumatology/ken488 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Nietert PJ, Silverstein MD, Silver RM (2001) Hospital admissions, length of stay, charges, and in-hospital death among patients with systemic sclerosis. J Rheumatol 28:2031–2037PubMedGoogle Scholar
  91. 91.
    Komócsi A, Vorobcsuk A, Faludi R, Pintér T, Lenkey Z, Költo G et al (2012) The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies. Rheumatol Oxf Engl 51:1027–1036. doi: 10.1093/rheumatology/ker357 CrossRefGoogle Scholar
  92. 92.
    Hinchcliff M, Desai CS, Varga J, Shah SJ (2012) Prevalence, prognosis, and factors associated with left ventricular diastolic dysfunction in systemic sclerosis. Clin Exp Rheumatol 30:S30–S37PubMedPubMedCentralGoogle Scholar
  93. 93.
    Assassi S, del Junco D, Sutter K, McNearney TA, Reveille JD, Karnavas A et al (2009) Clinical and genetic factors predictive of mortality in early systemic sclerosis. Arthritis Care Res 61:1403–1411. doi: 10.1002/art.24734 CrossRefGoogle Scholar
  94. 94.
    Draeger HT, Assassi S, Sharif R, Gonzalez EB, Harper BE, Arnett FC et al (2013) Right bundle branch block: a predictor of mortality in early systemic sclerosis. PLoS One 8:e78808. doi: 10.1371/journal.pone.0078808 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Czirjak L, Kumanovics G, Varju C, Nagy Z, Pakozdi A, Szekanecz Z et al (2008) Survival and causes of death in 366 Hungarian patients with systemic sclerosis. Ann Rheum Dis 67:59–63. doi: 10.1136/ard.2006.066340 CrossRefPubMedGoogle Scholar
  96. 96.
    Sehra ST, Kelly A, Baker JF, Derk CT (2016) Predictors of inpatient mortality in patients with systemic sclerosis: a case control study. Clin Rheumatol 35:1631–1635. doi: 10.1007/s10067-016-3245-6 CrossRefPubMedGoogle Scholar
  97. 97.
    Chung L, Krishnan E, Chakravarty EF (2007) Hospitalizations and mortality in systemic sclerosis: results from the Nationwide Inpatient Sample. Rheumatol Oxf Engl 46:1808–1813. doi: 10.1093/rheumatology/kem273 CrossRefGoogle Scholar
  98. 98.
    Hudson M, Baron M, Tatibouet S, Furst DE, Khanna D (2014) International scleroderma renal crisis study investigators. Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the international scleroderma renal crisis survey. Semin Arthritis Rheum 43:666–672. doi: 10.1016/j.semarthrit.2013.09.008 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Internal MedicineReading Health SystemWest ReadingUSA
  2. 2.Department of Internal MedicineWestchester Medical CenterValhallaUSA
  3. 3.Department of MedicineYale University School of MedicineNew HavenUSA
  4. 4.Division of RheumatologyMt. Auburn HospitalCambridgeUSA
  5. 5.Division of RheumatologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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