• Clinical science

Systemic sclerosis (Scleroderma)


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.


  • > (∼ 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.


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


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




Differential diagnoses

Mixed connective tissue disease (MCTD, Sharp syndrome)


The differential diagnoses listed here are not exhaustive.


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

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  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
last updated 11/19/2020
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