Systemic Sclerosis (Systemic Scleroderma)

Systemic Sclerosis (Systemic Scleroderma) is a topic covered in the 5-Minute Pediatric Consult.

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Basics

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

Genetics

  • Associations with histocompatibility antigens (Choctaw Native Americans in Oklahoma)
  • Rare reports of familial and twin occurrences

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

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