• Clinical science

Systemic sclerosis (Scleroderma)

Summary

Systemic sclerosis (SSc) is a chronic disease caused by abnormal growth of connective tissue, which leads to diffuse thickening and hardening of the skin and often the inner organs. SSc is categorized into limited SSc and diffuse SSc. The more common, limited form of SSc begins with sclerosis of the fingers, hands, and face, which then progresses to the center of the body. Limited SSc is often associated with symptoms of CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) and may be followed by internal organ involvement as the disease progresses. Diffuse SSc is less common but more aggressive, with early organ system involvement that may be life-threatening if damage to the heart, lungs, or kidneys occurs. Treatment is symptomatic and based on the extent of skin and organ system involvement. In the case of diffuse inflammation of the skin and/or organs, immunosuppressive drugs (e.g., methotrexate) should be administered. The prognosis varies depending on which organs are involved, with pulmonary arterial hypertension, interstitial lung disease, and cardiac disease significantly increasing the mortality rate.

Epidemiology

  • > (∼ 5:1) [1][2]
  • Higher incidence in African Americans [1]
  • Peak incidence: 30–50 years [3]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

The pathophysiology of SSc is not completely understood, but several factors play role in the development of the disease.

References:[4]

Clinical features

Common symptoms

  • Cutaneous findings
    • Thickening and hardening of the skin: Skin appears smooth, shiny, and puffy.
    • Sclerodactyly: fibrotic thickening and tightening of the skin of the fingers and hands
      • Initially edema, followed by fibrosis with waxy appearance of the skin
      • Red-blue discoloration of the fingers
      • Limited range of motion and possibly flexure contractures and clawing of the digits
    • Multiple, painful ischemic digital ulcers with atrophy and necrotic spots
    • Digital pitting: hyperkeratotic scarring, most commonly affecting the fingertips
    • Lesions on the proximal nail fold
    • Depigmentation of the skin with sparing of perifollicular pigmentation (salt-and-pepper appearance)
    • Face
      • Loss of expression (mask-like facies)
      • No wrinkles
      • Shortened frenulum
      • Microstomia accompanied with characteristic perioral wrinkles
  • Vascular disease
  • Other

Limited cutaneous systemic sclerosis

Diffuse cutaneous systemic sclerosis

References:[6][7][8][9][10][11][12][13]

Diagnostics

References:[14][15]

Differential diagnoses

Mixed connective tissue disease (MCTD, Sharp syndrome)

References:[16]

The differential diagnoses listed here are not exhaustive.

Treatment

Treatment focuses on organ-specific, symptomatic therapy. In the case of diffuse cutaneous disease or severe organ involvement, immunosuppressive therapy is indicated.

  • 1. Barnes J, Mayes MD. Epidemiology of systemic sclerosis. Curr Opin Rheumatol. 2012; 24(2): pp. 165–170. doi: 10.1097/bor.0b013e32834ff2e8.
  • 2. Bergamasco A, Hartmann N, Wallace L, Verpillat P. Epidemiology of systemic sclerosis and systemic sclerosis-associated interstitial lung disease. Clinical Epidemiology. 2019; Volume 11: pp. 257–273. doi: 10.2147/clep.s191418.
  • 3. Alba MA, Velasco C, Simeón CP, et al. Early- versus Late-Onset Systemic Sclerosis. Medicine. 2014; 93(2): pp. 73–81. doi: 10.1097/md.0000000000000018.
  • 4. Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of systemic sclerosis. Front Immunol. 2015; 6: p. 272. doi: 10.3389/fimmu.2015.00272.
  • 5. Zanatta E, Polito P, Favaro M, et al. Therapy of scleroderma renal crisis: State of the art. Autoimmun Rev. 2018; 17(9): pp. 882–889. doi: 10.1016/j.autrev.2018.03.012.
  • 6. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
  • 7. Sunderkötter C, Riemekasten G. Pathophysiology and clinical consequences of Raynaud's phenomenon related to systemic sclerosis. http://dx.doi.org/10.1093/rheumatology/kel280. Updated October 1, 2006. Accessed April 4, 2017.
  • 8. Varga J. Overview of the Clinical Manifestations of Systemic Sclerosis (Scleroderma) in Adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-systemic-sclerosis-scleroderma-in-adults. Last updated January 6, 2017. Accessed April 13, 2017.
  • 9. Hughes M, Herrick AL. Digital ulcers in systemic sclerosis. Rheumatology. 2016; 56(1): pp. 14–25. doi: 10.1093/rheumatology/kew047.
  • 10. Ficalora RD. Mayo Clinic Internal Medicine Board Review. Oxford University Press; 2013.
  • 11. Oakley A. Telangiectasia. https://www.dermnetnz.org/topics/telangiectasia. Updated January 1, 2014. Accessed December 23, 2017.
  • 12. Singh A, Ambujam S, Varghese A, Vishranth SP, Sadanandan N. Salt-and-pepper appearance: A cutaneous clue for the diagnosis of systemic sclerosis. Indian J Dermatol. 2012; 57(5): pp. 412–3. doi: 10.4103/0019-5154.100512.
  • 13. Giberson M, Brassard A. Salt-and-pepper skin changes. N Engl J Med. 2017; 377(2): pp. 173–173. doi: 10.1056/nejmicm1610737.
  • 14. Saracino A, Denton C. Systemic Sclerosis. https://www.dermnetnz.org/topics/systemic-sclerosis/. Updated January 1, 2018. Accessed April 2, 2018.
  • 15. Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003; 5(2): pp. 80–93. pmid: 12718748.
  • 16. Bennett RM. Clinical Manifestations of Mixed Connective Tissue Disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/clinical-manifestations-of-mixed-connective-tissue-disease. Last updated December 21, 2016. Accessed April 13, 2017.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 11/19/2020
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