Systemic sclerosis

Last updated: January 5, 2023

Summarytoggle arrow icon

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy and fibrosis of the skin and other organs. Based on the extent of cutaneous involvement, SSc is categorized as limited or diffuse. Limited SSc, which is more common, begins with cutaneous sclerosis of the fingers, hands, and face, which then progresses proximally toward the center of the body. Cutaneous involvement may be followed by internal organ involvement 10–20 years after disease onset. Diffuse SSc, which is less common, may be life-threatening in individuals with early involvement of the heart, lungs, or kidneys. The term CREST syndrome (calcinosis cutis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) has historically been used to describe a group of symptoms that are typically present in patients with limited SSc; however, these symptoms may also be seen in patients with diffuse SSc. Treatment is symptomatic and based on the extent of skin and internal organ involvement. A multidisciplinary approach is recommended to address the complex and heterogeneous manifestations of SSc. Scleroderma renal crisis (SRC) is a life-threatening complication of SSc characterized by the abrupt onset of hypertension and oliguric AKI. Management of SRC includes initiation or uptitration of ACE inhibitors and nephrology consultation. Cardiopulmonary complications of SSc are common and require management of the specific condition as well as possible additional immunosuppressive therapy. The prognosis varies depending on organ involvement; pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and cardiac disease significantly increase the mortality rate.

Epidemiologytoggle arrow icon

Epidemiological data refers to the US, unless otherwise specified.

Pathophysiologytoggle arrow icon

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


Clinical featurestoggle arrow icon

Overview [5][6]

SSc is most commonly described as limited or diffuse based on the cutaneous manifestations and symptom progression. [7]

Common SSc subtypes
Limited SSc Diffuse SSc
Cutaneous distribution
  • Neck, face, and distal limbs
  • Sparing of the trunk
  • Trunk, face, and extremities
Extracutaneous manifestations [8]
Onset of systemic symptoms [5]

CREST syndrome

CREST syndrome refers to a constellation of symptoms traditionally associated with limited SSc (can also be seen in diffuse SSc).

Cutaneous [5]

  • Thickening and hardening of the skin, which appears smooth, shiny, and puffy
  • Sclerodactyly: fibrotic thickening and tightening of the skin on the fingers and hands
  • Multiple, painful ischemic digital ulcers with atrophy and necrotic spots
  • Digital pitting: hyperkeratotic scarring that most commonly affects the fingertips
  • Lesions on the proximal nail fold
  • Depigmentation with sparing of perifollicular pigmentation (salt-and-pepper appearance)
  • Face changes
    • Loss of expression (mask-like facies)
    • Smoothing of deep wrinkles
    • Microstomia (a disproportionately small mouth) accompanied by characteristic perioral wrinkles
    • Shortened frenulum


Cardiopulmonary [8][9][10][11]

The heart and lungs are commonly affected by SSc, but usually remain asymptomatic in the early stages of the disease. Overt cardiopulmonary symptoms are associated with poor outcomes. [12][13]

Other extracutaneous [5]

Diagnosticstoggle arrow icon

Approach [6][8]

Consult rheumatology for all patients.

  • SSc is a clinical diagnosis.
    • Skin thickening on both hands that extends proximal to the MCP joints is diagnostic.
    • Multiple organ system involvement is a hallmark.
  • Perform a comprehensive evaluation to determine disease severity.
    • Obtain routine laboratory studies and SSc-specific evaluations.
    • Assess for cardiopulmonary complications (even if asymptomatic).
    • Consider additional studies to monitor for organ involvement.
  • Classification criteria for SSc can help identify SSc . [15]

Organ involvement typically occurs early in the course of SSc. [8]

Scleroderma renal crisis is a medical emergency with a high mortality rate. Promptly evaluate serum creatinine and urine protein in individuals with SSc who present with an acute rise in blood pressure and start management of SRC. [14]

Routine evaluations [6][8][14]

Obtain the following studies in all patients with suspected SSc.

Consider early diagnostic testing to uncover silent disease.

Additional studies [6][8]

Depending on the patient's clinical features and risk factors, consider the following studies:

Upper gastrointestinal tract involvement is observed in almost all patients who have had SSc for > 10 years.

Differential diagnosestoggle arrow icon

Mixed connective tissue disease (MCTD, Sharp syndrome)


The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

General principles [8][14][19]

  • Refer to a specialist early.
  • Treatment focuses on organ-specific, symptomatic therapy.
  • In diffuse cutaneous disease or severe organ involvement, systemic immunomodulatory medication is indicated.
  • Monitor for organ involvement and complications frequently to reduce mortality. [8]

Cutaneous disease [8][19]

Supportive care [6][20]

Avoid beta blockers, which can cause vasospasm and may worsen Raynaud phenomenon and digital ischemia in patients with SSc. [14]

Renal disease

Cardiopulmonary disease

Manage specific cardiac and/or pulmonary conditions depending on manifestations (see “Clinical features”).

Screen all patients for signs of respiratory distress as this can signify cardiopulmonary disease.

Systemic sclerosis is a cause of group 1 pulmonary hypertension, so affected individuals are likely to benefit from pulmonary vasodilators. [19]

Gastrointestinal disease [6][8][19]

Scleroderma renal crisistoggle arrow icon

Scleroderma renal crisis (SRC) is a life-threatening complication of SSc characterized by the abrupt onset of hypertension and oliguric AKI. [21][22]

Management of SRC [21]

Consider ICU admission for patients with features of end-organ damage, e.g., hypertensive encephalopathy, pulmonary edema, tachyarrhythmia, MAHA, or severe AKI requiring hemodialysis.

Normotensive blood pressure does not rule out SRC.

Secondary prevention [21]

Individuals with diffuse SSc, those receiving glucocorticoids, and/or with anti-RNA polymerase III antibodies are at higher risk for SRC and should be closely monitored (e.g., blood pressure measurement three times a week and urinalysis at regular intervals). [8][19]

Referencestoggle arrow icon

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