Epidemiology and natural history of systemic sclerosis

Systemic sclerosis is an acquired generalized disorder of connective tissue characterized epidemiologically by several distinctive features. From a demographic viewpoint, the disease spares children and its incidence increases steadily with age among adults; is much more frequent in women, especially during the childbearing years; occurs most frequently and severely in young black women, but overall has no prominent racial predilection. If any conclusions can be drawn here, the strongest influences may be age-related hormonal factor and degenerative vascular processes. Family and genetic studies suggest a weak genetic predisposition. There are many environmental agents which may be implicated in pathogenesis. The result of host factors and environmental "triggers" is a multi-system disease which has as prominent features microvascular injury, immunologic dysregulation, and fibroblast activation. The resulting widespread pathologic process leads to vascular insufficiency and fibrosis, which diminishes the reserve function of many organ systems. The result, a significant reduction in lifespan, with a 10-year survival from diagnosis of under 50 per cent. Further epidemiologic studies should take full advantage of established and newly proposed subsets of patients with homogeneous clinical, laboratory, serologic, and natural history features. The environment-host interactions noted above must be fully explored, especially in early untreated disease, where primary rather than secondary mechanisms are most likely to be operative.