From the Research
In scleroderma, fibrosis is deposited in multiple tissues and organs throughout the body, primarily affecting the skin, blood vessels, and internal organs, as evident from the most recent study 1. The most characteristic fibrotic changes occur in the skin, where excessive collagen deposition leads to thickening and hardening. Beyond the skin, fibrosis commonly affects the:
- Gastrointestinal tract (especially the esophagus)
- Lungs (causing interstitial lung disease)
- Heart (myocardium and pericardium)
- Kidneys
- Musculoskeletal system This widespread fibrosis results from dysregulated immune responses and overproduction of extracellular matrix proteins by activated fibroblasts and myofibroblasts, as described in 2. The pathophysiology involves initial vascular damage and inflammation, followed by fibroblast activation and excessive collagen production. This process is driven by various cytokines and growth factors, particularly transforming growth factor-beta (TGF-β), which stimulates fibroblasts to produce excessive amounts of collagen and other extracellular matrix components, as mentioned in 3. The pattern and extent of fibrosis deposition vary between limited and diffuse forms of scleroderma, with the diffuse form typically involving more extensive internal organ fibrosis, as noted in 4 and 5.