• 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's 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

  • > (3:1)
  • Higher incidence in African Americans
  • Peak incidence: 30–50 years

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiology

  • The pathophysiology of SSc is not completely understood

References:[3]

Clinical features

Common symptoms

  • Cutaneous findings
    • Thickening and hardening of the skin (skin appears smooth and shiny)
    • Depigmentation of the skin with sparing of perifollicular pigmentation (salt-and-pepper appearance)
    • Sclerodactyly
      • Red-blue discoloration of the fingers
      • Edema and fibrosis with waxy appearance of the skin and limited range of motion
      • Atrophy and necrotic spots
      • Lesions on the proximal nail fold
    • Multiple, painful ischemic digital ulcers
    • Face
      • Loss of expression (mask-like facies)
      • Shortened frenulum
      • Microstomia accompanied with characteristic perioral wrinkles
  • Vascular disease
  • Fatigue, weakness
  • Joint stiffness/pain

Limited cutaneous systemic sclerosis

  • In 90% of cases, Raynaud's phenomenon precedes the onset of other symptoms.
  • Skin manifestations are usually restricted to the hands, fingers, and face.
  • Extracutaneous organ involvement may occur.
  • Often manifests as CREST syndrome:

Diffuse cutaneous systemic sclerosis

References:[1][4][5][6][7][8][9][10]

Diagnostics

References:[11][12]

Differential diagnoses

Mixed connective tissue disease (MCTD, Sharp's syndrome)

References:[13][14][15]

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.

References:[16]

  • 1. 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.
  • 2. Goldman L, Schafer AI. Goldman-Cecil Medicine, 25th Edition. Philadelphia, PA: Elsevier; 2016.
  • 3. Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of systemic sclerosis. Front Immunol. 2015; 6: p. 272. doi: 10.3389/fimmu.2015.00272.
  • 4. 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.
  • 5. 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.
  • 6. Hughes M, Herrick AL. Digital ulcers in systemic sclerosis. Rheumatology. 2016; 56(1): pp. 14–25. doi: 10.1093/rheumatology/kew047.
  • 7. Ficalora RD. Mayo Clinic Internal Medicine Board Review. Oxford University Press; 2013.
  • 8. Oakley A. Telangiectasia. https://www.dermnetnz.org/topics/telangiectasia. Updated January 1, 2014. Accessed December 23, 2017.
  • 9. 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.
  • 10. Giberson M, Brassard A. Salt-and-pepper skin changes. N Engl J Med. 2017; 377(2): pp. 173–173. doi: 10.1056/nejmicm1610737.
  • 11. Saracino A, Denton C. Systemic Sclerosis. https://www.dermnetnz.org/topics/systemic-sclerosis/. Updated January 1, 2018. Accessed April 2, 2018.
  • 12. Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003; 5(2): pp. 80–93. pmid: 12718748.
  • 13. Greidinger EL. Mixed Connective-Tissue Disease. In: Diamond HS. Mixed Connective-Tissue Disease. New York, NY: WebMD. http://emedicine.medscape.com/article/335815. Updated July 8, 2016. Accessed April 13, 2017.
  • 14. 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.
  • 15. Schwartz RA. Dermatologic Manifestations of Mixed Connective Tissue Disease. In: James WD. Dermatologic Manifestations of Mixed Connective Tissue Disease. New York, NY: WebMD. http://emedicine.medscape.com/article/1066445. Updated June 13, 2016. Accessed April 13, 2017.
  • 16. Schwartz RA. Systemic Sclerosis. In: Elston DM. Systemic Sclerosis. New York, NY: WebMD. http://emedicine.medscape.com/article/1066280. Updated April 4, 2017. Accessed April 13, 2017.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 08/05/2019
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