How does systemic sclerosis cause hardening of the skin?

Systemic sclerosis, also known as scleroderma, causes the skin to harden and thicken primarily through the excessive deposition of collagen, the principal structural protein of connective tissue.12

In healthy skin, collagen provides tensile strength and elasticity. In patients with systemic sclerosis, the disease process involves the following mechanisms:

• Collagen Overproduction: The skin's fibroblasts produce significantly more collagen than those in healthy individuals, leading to an accumulation of fibrous tissue in the dermis.12
• Inflammation and Scarring: The targeted tissue becomes inflamed and irritated, eventually losing its elasticity as it becomes scarred.1
• Tethering: The hardened dermal connective tissue becomes markedly tethered to the underlying subcutaneous tissues, which contributes to the characteristic tightening and loss of pliability.2
• Autoimmune Response: This process is believed to be driven by an autoimmune reaction, where the immune system mistakenly attacks the body's own components, though the exact stimulus remains unknown.12

Additionally, some evidence suggests that vascular abnormalities may contribute to these connective tissue changes.2