Systemic Sclerosis (Systemic Scleroderma)
- 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
- 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
- Diffuse cutaneous SSc (dcSSc):
- SSc—all types
- Estimated ~3% of all SSc patients have onset in childhood.
- Mean age of onset 8 to 12.4 years
- 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.
- Earlier age of onset than dcSSc
- Female > male
- Associations with histocompatibility antigens (Choctaw Native Americans in Oklahoma)
- Rare reports of familial and twin occurrences
- 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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