musculoskeletal and connective tissue disorders
Systemic Sclerosis
Pathophysiology of Systemic Sclerosis
Pathophysiology involves vascular damage and activation of fibroblasts; collagen and other extracellular proteins in various tissues are overproduced. In systemic sclerosis, the skin develops more compact collagen fibers in the reticular dermis, epidermal thinning, loss of rete pegs (epithelial extensions that project into the underlying connective tissue), and atrophy of dermal appendages. T cells may accumulate, and extensive fibrosis in the dermal and subcutaneous layers develops. In the nail folds, capillary loops dilate and some microvascular loops are lost. In the extremities, chronic inflammation and fibrosis of the synovial membrane and surfaces and periarticular soft tissues occur. Esophageal motility becomes impaired, and the lower esophageal sphincter becomes incompetent; gastroesophageal reflux and secondary strictures can develop. The intestinal muscularis mucosa degenerates, leading to pseudodiverticula in the colon and ileum. Interstitial and peribronchial fibrosis or intimal hyperplasia of small pulmonary arteries can develop; if long-standing, pulmonary hypertension can result. Diffuse myocardial fibrosis or cardiac conduction abnormalities occur. Intimal hyperplasia of interlobular and arcuate arteries can develop within the kidneys, causing renal ischemia and hypertension. Systemic sclerosis varies in severity and progression, ranging from generalized skin thickening with rapidly progressive and often fatal visceral involvement (diffuse systemic sclerosis) to isolated skin involvement (often just the fingers and face) and slow progression (often several decades) before visceral disease develops. The latter form is termed limited cutaneous scleroderma or CREST syndrome. In addition, systemic sclerosis can overlap with other autoimmune rheumatic disorders—eg, sclerodermatomyositis (tight skin and muscle weakness indistinguishable from autoimmune myositis) and Mixed Connective Tissue Disease (MCTD) . 