Learning Objectives
Analyze the Systemic Sclerosis (Scleroderma) triad of autoimmunity, vasculopathy, and fibrosis. Differentiate between Diffuse and Limited types using specific autoantibodies (Anti-Scl-70 vs. Anti-Centromere) and clinical patterns of organ involvement.
1. Pathophysiology & Clinical Triad
Systemic Sclerosis is a chronic multi-system disorder. It is defined by three hallmark processes that lead to the characteristic “tight” appearance of the skin and internal organ dysfunction.
- Autoimmunity: Activation of the immune system leads to cytokine production.
- Noninflammatory Vasculopathy: Proliferation of the intima in small vessels, leading to narrowing and ischemia.
- Fibrosis: Excessive collagen deposition in the skin and visceral organs.
2. Major Subtypes of Scleroderma
Scleroderma is categorized by the extent of skin involvement and the presence of specific antibodies. Both types are predominantly seen in females (75%).
| Feature | Diffuse Scleroderma | Limited Scleroderma (CREST) |
|---|---|---|
| Skin Extent | Widespread (trunk and proximal limbs). | Confined to fingers and face. |
| Antibody | Anti-Scl-70 (DNA Topoisomerase I). | Anti-Centromere. |
| Progression | Rapid, early visceral involvement. | Slow; more benign clinical course. |
3. Organ-Specific Manifestations
Beyond the skin, scleroderma can cause severe morbidity through internal organ damage.
- Renal: Scleroderma Renal Crisis (abrupt hypertension). Treatment: ACE Inhibitors (even if creatinine is high).
- GI: Decreased peristalsis and lower esophageal sphincter (LES) tone leading to heartburn and dysphagia.
- Pulmonary: Interstitial fibrosis or Pulmonary HTN (often the leading cause of death).
Activity: The CREST Mnemonic Breakdown
High-Yield Mnemonics:
- CREST: Calcinosis cutis, anti-Centromere, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia.
- Diffuse Antibody: Diffuse involves DNA Topoisomerase I (Scl-70).
- Treatment: “ACE the Renal Crisis” (ACE inhibitors are the gold standard for scleroderma kidney issues).