Pathology-Systemic Sclerosis (Scleroderma)

I. Definition & Epidemiology:

• Definition: Systemic sclerosis (SSc) is a rare, multisystem autoimmune disease characterized by excessive fibrous tissue accumulation in various organs. Crucially, this fibrosis leads to organ dysfunction.
• Epidemiology:
  • Annual incidence: 2-10 per million.
  • Predominantly affects women (30-40 years old).

II. Aetiology & Pathogenesis:

• Aetiology: The underlying cause of SSc remains unknown.
• Pathogenesis: An aberrant immune response to an unidentified trigger leads to cytokine production (e.g., IL-4, TGF-β). These cytokines stimulate fibroblasts, resulting in excessive collagen deposition and fibrosis. This fibrosis affects multiple organ systems.

III. Clinical Presentation:

Two main subtypes exist, differing significantly in presentation and prognosis:

• A. Limited Systemic Sclerosis (lSSc):
  • Onset: Typically begins with Raynaud's phenomenon (cold-induced vasospasm in fingers and toes).
  • Progression: Gradual thickening and tightening of skin (fingers, face, neck).
  • Late Complications (after 10-15 years): Calcium deposits (calcinosis) in finger pads, small bowel involvement, and pulmonary hypertension.
• B. Diffuse Systemic Sclerosis (dSSc):
  • Onset: More rapid onset with widespread skin thickening, contractures, and ulcers.
  • Visceral Involvement: Early involvement of internal organs including pulmonary fibrosis (lung scarring).
  • Major Complications: Severe hypertension leading to acute renal failure ("scleroderma renal crisis") is a life-threatening complication.

IV. Immunology:

• Autoantibodies are frequently present, aiding in diagnosis and subtype classification:
  • Anti-nuclear antibodies (ANA): Present in ~65% of patients. Note: ANA is not specific to SSc.
  • Anti-centromere antibodies: Found in 70-80% of lSSc patients. Suggestive of limited disease.
  • Anti-topoisomerase I (Scl-70) antibodies: Present in ~40% of dSSc patients. Associated with diffuse disease and worse prognosis.

V. Prognosis & Treatment:

• Prognosis: Currently incurable.
• Treatment: Immunosuppressive therapies are used to manage organ involvement and progressive skin disease.
• Causes of Death: Primarily due to renal and lung complications (renal failure and pulmonary fibrosis).

VI. Key Differences between lSSc and dSSc: