Aetiology
Some drugs and external agents (e.g., silica, bleomycin, and possibly vinyl chloride) may trigger systemic sclerosis, but the precipitators are not fully known.[14] There are some similarities to graft-versus-host disease, and a theory of retained maternal (or fetal) cells has been proposed but is not fully accepted. There may be a genetic predisposition, as a family history of Raynaud's phenomenon and other connective tissue diseases is associated with the syndrome.[2][8][15]
Pathophysiology
Vascular injury, especially of the arterioles, is precedent to clinical manifestations. The endothelial cells are disrupted and mononuclear infiltrates occur. Vascular endothelial growth factors are increased due to hypoxia, causing a proliferation of blood vessels. The presence of anti-centromere auto-antibodies increases the likelihood of systemic organ involvement. There is a polyclonal upregulation of fibrosis starting at the lower dermis and subcutaneous tissue with fibrillin deposition early and type 1 collagen later. Fibroblasts overexpress transforming growth factor beta, which causes more fibrosis. Platelet-derived growth factor receptor is increased and pericytes (which can differentiate into vascular smooth muscle cells, fibroblasts, and myofibroblasts) increase, causing increased vascular wall thickness and loss of endothelial cells.[16][17]
Classification
Clinical classification: scleroderma
Non-systemic
Systemic
Limited cutaneous systemic sclerosis
Diffuse cutaneous systemic sclerosis
Systemic sclerosis sine scleroderma
Indeterminate subset
Overlap syndromes with other connective tissue diseases
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