Description

• Systemic sclerosis (SSc) is an autoimmune vasculopathic disease causing fibrosis of skin and internal organs.
  • SSc is a type of scleroderma (meaning “hard skin”) but should not be confused with localized scleroderma, otherwise known as morphea, which involves only the skin, is more common, and has a much better overall prognosis.
• Characterized by Raynaud phenomenon (RP), skin thickening proximal to the metacarpophalangeal (MCP) joints, and internal organ involvement
• There are two main subtypes of SSc:
  • Diffuse cutaneous SSc (dcSSc):
    • Widespread fibrosis of skin, gastrointestinal (GI), pulmonary, cardiovascular, and renal systems
    • Skin thickening proximal to the elbows or knees, face, chest, abdomen, flanks, legs, feet
    • More rapid progression of skin thickening versus limited cutaneous SSc (lcSSc), associated with joint contractures, myopathy, interstitial lung disease, myocardial and GI involvement, and renal crisis
    • Skin thickening reaches maximal point by 5 years and then softens while internal organ involvement can continue to accrue.
    • Autoantibodies to Scl-70 or other rare autoantibodies
  • lcSSc:
    • Distal skin fibrosis and internal organ involvement
    • Previously known as CREST: calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
    • Skin thickening restricted to fingers, hands, forearms, lower legs, and feet; can include face
    • Slower progression of skin thickening over years associated with esophageal disease, pulmonary hypertension, and malabsorption
    • Better long-term survival prognosis than dcSSc
    • Can be associated with centromere antibodies

Epidemiology

• SSc—all types
  • Estimated ~3% of all SSc patients have onset in childhood.
  • Mean age of onset 8 to 12.4 years
• dcSSc
  • Adult age of onset generally 30 to 50 years
  • In general population: annual incidence 0.45 to 1.9 cases per 100,000, prevalence 24 in 100,000
  • Sex ratio
    • <8 years, male = female
    • ≥8 years, female > male (3:1)
  • 90% of pediatric patients with SSc have dcSSc.
• lcSSc
  • Earlier age of onset than dcSSc
  • Female > male

Risk Factors

Pathophysiology

• Three-part process of dysfunction: endothelial cells, immune system, and extracellular matrix
• Primary insult is endothelial injury and dysfunction causing vasculopathy in skin and organs.
  • Chemical, microbial, autoantibody, and sheer stress injury to endothelial cells
  • Vascular injury activates immune system and contributes to tissue fibrosis.
  • Progressive vascular damage causes obliteration of small vessels in various organs.
• Immune dysfunction
  • Within innate immune system: dendritic cells, toll-like receptors, interferons
  • Within adaptive immune system: autoantibody production, T- and B-cell dysfunction
  • Elevated proinflammatory cytokines in serum, skin
• Extracellular matrix
  • Overactive connective tissue remodeling: fibrotic changes in extracellular matrix
  • Transforming growth factor-β causes fibroblast activation.
  • Collagen accumulation, extracellular matrix deposition, matrix remodeling, and contraction