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 2–10% of all SSc patients have onset in childhood.
  • Mean age of onset: 8 to 10.8 years
  • Sex ratio: female > male (4:1)
  • In adult population: annual incidence 0.45 to 1.9 cases per 100,000, prevalence 24 in 100,000
• dcSSc: Majority of children with SSc have dcSSc.
• lcSSc: earlier age of onset than dcSSc

RISK FACTORS

PATHOPHYSIOLOGY

• Three-part process of dysfunction: endothelial cells, immune system, and extracellular matrix
• Endothelial injury and dysfunction can cause 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