Scleroderma

Definition

Scleroderma, or systemic sclerosis (SSc), is a chronic autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, vascular abnormalities, and immune system dysregulation.

Epidemiology

• Rare disease with prevalence approximately 50–300 per million
• Female-to-male ratio approximately 4:1
• Peak onset between ages 30–50 years
• More common in African Americans and certain Native American populations
• Limited cutaneous form more common than diffuse cutaneous form
• Associated with significant morbidity and mortality due to organ involvement
• Incidence varies geographically

Etiology

• Exact cause unknown; multifactorial origin
• Genetic predisposition: HLA class II alleles (HLA-DR, HLA-DQ)
• Autoimmune dysregulation with autoantibody production (anti-centromere, anti-Scl-70, anti-RNA polymerase III)
• Vascular injury and endothelial dysfunction leading to fibrosis
• Environmental triggers: silica dust, solvents, viral infections proposed
• Oxidative stress and abnormal fibroblast activation contribute to excessive collagen deposition
• Combination of genetic susceptibility and environmental triggers

Pathophysiology

• Immune-mediated vascular injury leading to endothelial dysfunction
• Fibroblast activation causing excessive collagen and extracellular matrix deposition
• Microvascular abnormalities and tissue ischemia
• Progressive fibrosis of skin and internal organs (lungs, heart, kidneys, GI tract)
• Autoantibody production contributes to immune-mediated tissue damage
• Inflammation precedes fibrosis in early disease
• Leads to tissue stiffness, organ dysfunction, and systemic complications