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Overview of the clinical manifestations of systemic sclerosis (scleroderma) in adults

Author
John Varga, MD
Section Editor
John S Axford, DSc, MD, FRCP, FRCPCH
Deputy Editor
Monica Ramirez Curtis, MD, MPH

INTRODUCTION

The term scleroderma is used to describe the presence of thickened, hardened skin (from the Greek “scleros”) [1]. Scleroderma is the hallmark feature of a heterogeneous group of conditions, the classification of which is discussed in more detail separately. (See "Overview and classification of scleroderma disorders".)

Scleroderma may be a clinical feature of limited anatomic extent affecting only the skin and subjacent tissues, or it may be associated with systemic involvement. When the characteristic skin disorder is associated with internal organ involvement, the disease is termed systemic sclerosis (SSc). SSc is subcategorized further into diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) on the basis of the extent and distribution of skin involvement. lcSSc is commonly associated with the CREST syndrome [2]. (See 'Limited cutaneous SSc' below.)

Other disorders that may either have typical scleroderma skin changes or those that have scleroderma-like cutaneous involvement are considerations in the differential diagnosis of SSc. (See "Diagnosis and differential diagnosis of systemic sclerosis (scleroderma) in adults".)

The systemic manifestations of SSc are diverse. Most prominent are abnormalities of the circulation (most notably Raynaud phenomenon) and involvement of multiple organ systems, including the musculoskeletal, renal, pulmonary, cardiac, and gastrointestinal systems, with fibrotic and/or vascular complications.

The prevalence rates of scleroderma-like conditions range from 4 to 489 cases per million individuals [3,4]. Incidence figures for SSc are 0.6 to 122 per million persons per year; the actual prevalence is probably at the high end of the range noted above [4]. There are regional differences in incidence. For example, higher rates are seen in the United States and Australia than in Japan or Europe, and in blacks than whites [4].

                          

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Literature review current through: Nov 2016. | This topic last updated: Fri Jun 03 00:00:00 GMT+00:00 2016.
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References
Top
  1. Black CM. Scleroderma--clinical aspects. J Intern Med 1993; 234:115.
  2. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988; 15:202.
  3. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41:778.
  4. Chifflot H, Fautrel B, Sordet C, et al. Incidence and prevalence of systemic sclerosis: a systematic literature review. Semin Arthritis Rheum 2008; 37:223.
  5. Sandusky SB, McGuire L, Smith MT, et al. Fatigue: an overlooked determinant of physical function in scleroderma. Rheumatology (Oxford) 2009; 48:165.
  6. Thombs BD, Bassel M, McGuire L, et al. A systematic comparison of fatigue levels in systemic sclerosis with general population, cancer and rheumatic disease samples. Rheumatology (Oxford) 2008; 47:1559.
  7. Scheja A, Akesson A. Comparison of high frequency (20 MHz) ultrasound and palpation for the assessment of skin involvement in systemic sclerosis (scleroderma). Clin Exp Rheumatol 1997; 15:283.
  8. Hesselstrand R, Scheja A, Wildt M, Akesson A. High-frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease. Rheumatology (Oxford) 2008; 47:84.
  9. Avouac J, Guerini H, Wipff J, et al. Radiological hand involvement in systemic sclerosis. Ann Rheum Dis 2006; 65:1088.
  10. Poormoghim H, Lucas M, Fertig N, Medsger TA Jr. Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum 2000; 43:444.
  11. Schoenfeld SR, Choi HK, Sayre EC, Aviña-Zubieta JA. Risk of Pulmonary Embolism and Deep Venous Thrombosis in Systemic Sclerosis: A General Population-Based Study. Arthritis Care Res (Hoboken) 2016; 68:246.
  12. Chung WS, Lin CL, Sung FC, et al. Systemic sclerosis increases the risks of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology (Oxford) 2014; 53:1639.
  13. Turner R, Lipshutz W, Miller W, et al. Esophageal dysfunction in collagen disease. Am J Med Sci 1973; 265:191.
  14. Akesson A, Wollheim FA. Organ manifestations in 100 patients with progressive systemic sclerosis: a comparison between the CREST syndrome and diffuse scleroderma. Br J Rheumatol 1989; 28:281.
  15. Marie I, Dominique S, Levesque H, et al. Esophageal involvement and pulmonary manifestations in systemic sclerosis. Arthritis Rheum 2001; 45:346.
  16. Medsger TA Jr, Masi AT, Rodnan GP, et al. Survival with systemic sclerosis (scleroderma). A life-table analysis of clinical and demographic factors in 309 patients. Ann Intern Med 1971; 75:369.
  17. Medsger TA Jr, Masi AT. Survival with scleroderma. II. A life-table analysis of clinical and demographic factors in 358 male U.S. veteran patients. J Chronic Dis 1973; 26:647.
  18. Livi R, Teghini L, Pignone A, et al. Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement. Ann Rheum Dis 2002; 61:682.
  19. Traub YM, Shapiro AP, Rodnan GP, et al. Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine (Baltimore) 1983; 62:335.
  20. TUFFANELLI DL, WINKELMANN RK. Systemic scleroderma, A clinical study of 727 cases. Arch Dermatol 1961; 84:359.
  21. Nikpour M, Hissaria P, Byron J, et al. Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort. Arthritis Res Ther 2011; 13:R211.
  22. Janosik DL, Osborn TG, Moore TL, et al. Heart disease in systemic sclerosis. Semin Arthritis Rheum 1989; 19:191.
  23. Elhai M, Avouac J, Walker UA, et al. A gender gap in primary and secondary heart dysfunctions in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 2016; 75:163.
  24. Byers RJ, Marshall DA, Freemont AJ. Pericardial involvement in systemic sclerosis. Ann Rheum Dis 1997; 56:393.
  25. Tzelepis GE, Kelekis NL, Plastiras SC, et al. Pattern and distribution of myocardial fibrosis in systemic sclerosis: a delayed enhanced magnetic resonance imaging study. Arthritis Rheum 2007; 56:3827.
  26. de Groote P, Gressin V, Hachulla E, et al. Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann Rheum Dis 2008; 67:31.
  27. Meune C, Avouac J, Wahbi K, et al. Cardiac involvement in systemic sclerosis assessed by tissue-doppler echocardiography during routine care: A controlled study of 100 consecutive patients. Arthritis Rheum 2008; 58:1803.
  28. Chu SY, Chen YJ, Liu CJ, et al. Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study. Am J Med 2013; 126:982.
  29. Nordin A, Jensen-Urstad K, Björnådal L, et al. Ischemic arterial events and atherosclerosis in patients with systemic sclerosis: a population-based case-control study. Arthritis Res Ther 2013; 15:R87.
  30. Morrisroe KB, Nikpour M, Proudman SM. Musculoskeletal Manifestations of Systemic Sclerosis. Rheum Dis Clin North Am 2015; 41:507.
  31. Steen VD, Medsger TA Jr. The palpable tendon friction rub: an important physical examination finding in patients with systemic sclerosis. Arthritis Rheum 1997; 40:1146.
  32. Doré A, Lucas M, Ivanco D, et al. Significance of palpable tendon friction rubs in early diffuse cutaneous systemic sclerosis. Arthritis Care Res (Hoboken) 2013; 65:1385.
  33. Avouac J, Walker UA, Hachulla E, et al. Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 2016; 75:103.
  34. Walker UA, Tyndall A, Ruszat R. Erectile dysfunction in systemic sclerosis. Ann Rheum Dis 2009; 68:1083.
  35. Hong P, Pope JE, Ouimet JM, et al. Erectile dysfunction associated with scleroderma: a case-control study of men with scleroderma and rheumatoid arthritis. J Rheumatol 2004; 31:508.
  36. Bhadauria S, Moser DK, Clements PJ, et al. Genital tract abnormalities and female sexual function impairment in systemic sclerosis. Am J Obstet Gynecol 1995; 172:580.
  37. Rosenthal AK, McLaughlin JK, Gridley G, Nyrén O. Incidence of cancer among patients with systemic sclerosis. Cancer 1995; 76:910.
  38. Kyndt X, Hebbar M, Queyrel V, et al. [Systemic scleroderma and cancer. Search for predictive factors of cancer in 123 patients with scleroderma]. Rev Med Interne 1997; 18:528.
  39. Bielefeld P, Meyer P, Caillot D, et al. [Systemic scleroderma and cancers: 21 cases and review of the literature]. Rev Med Interne 1996; 17:810.
  40. Hill CL, Nguyen AM, Roder D, Roberts-Thomson P. Risk of cancer in patients with scleroderma: a population based cohort study. Ann Rheum Dis 2003; 62:728.
  41. Derk CT, Rasheed M, Spiegel JR, Jimenez SA. Increased incidence of carcinoma of the tongue in patients with systemic sclerosis. J Rheumatol 2005; 32:637.
  42. Chatterjee S, Dombi GW, Severson RK, Mayes MD. Risk of malignancy in scleroderma: a population-based cohort study. Arthritis Rheum 2005; 52:2415.
  43. Olesen AB, Svaerke C, Farkas DK, Sørensen HT. Systemic sclerosis and the risk of cancer: a nationwide population-based cohort study. Br J Dermatol 2010; 163:800.
  44. Derk CT, Rasheed M, Artlett CM, Jimenez SA. A cohort study of cancer incidence in systemic sclerosis. J Rheumatol 2006; 33:1113.
  45. Pontifex EK, Hill CL, Roberts-Thomson P. Risk factors for lung cancer in patients with scleroderma: a nested case-control study. Ann Rheum Dis 2007; 66:551.
  46. Shah AA, Rosen A, Hummers L, et al. Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum 2010; 62:2787.
  47. Moinzadeh P, Fonseca C, Hellmich M, et al. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther 2014; 16:R53.
  48. Joseph CG, Darrah E, Shah AA, et al. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 2014; 343:152.
  49. Rothfield N, Kurtzman S, Vazques-Abad D, et al. Association of anti-topoisomerase I with cancer. Arthritis Rheum 1992; 35:724.
  50. Derk CT, Sakkas LI, Rasheed M, et al. Autoantibodies in patients with systemic sclerosis and cancer: a case-control study. J Rheumatol 2003; 30:1994.