4.05 Scleroderma

Rheumatology review for the USMLE Step 1 exam

• Scleroderma is a chronic autoimmune connective tissue disease that causes thickening and hardening of the skin, as well as fibrosis (excess deposition of collagen and other ECM proteins) throughout the body.
• Autoreactive immune cells activate endothelial cells, which produce large amounts of endothelin 1, leading to overactivation of fibroblasts that overexpress collagen.
• It typically affects younger women (35-50 years old) with a F:M ratio of 5:1.
• There are two distinct forms of scleroderma: diffuse (systemic) and limited, each associated with unique antibodies and clinical presentations.
• Diffuse scleroderma involves the skin and internal organs and is rapidly progressive. Skin tightens especially in the fingers, and internal organs including the lungs, kidneys, GI system, and heart can be affected. It is associated with anti-Scl-70 antibody and anti-RNA III polymerase.
• Limited scleroderma tends to only affect the skin, characterized by the mnemonic CREST: Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. It is associated with anti-Centromere antibody.
• Treatment involves NSAIDs and DMARDs for musculoskeletal pain, H2 blockers or PPIs for esophageal reflux, and Ace inhibitors for scleroderma renal crisis. There is no cure for the disease.