Systemic Sclerosis

Systemic Sclerosis

Multisystem disorder
Unknown etiology
Thickening of skin caused by accumulation of connective tissue (collagen types I and III)
Involvement of visceral organs

Epidemiology

Peak age range: 35-64
Younger age in women and with diffuse disease.
Female:Male = 3:1
Incidence: 20/million per year in US
Prevalence: 240/million in US.

Etiology

Unknown
Environmental Exposures
Silica exposure in men conferred increased risk
Silicone breast implants: no definite risk identified
Aniline laced Contaminated rapseed oil in Spain
Vinyl chloride exposure increased risk of SSc like disorder: Eosinophilic Fasciitis
Bleomycin therapy
L-tryptophan: Eosinophilia Myalgia syndrome

Genetic Factors
Familial Clustering: 1.5-2.5% of those with 1st degree relative
HLA-haplotypes: there are higher risk haplotypes in certain populations


Pathogenesis: general principles

Endogenous or exogenous pathogen stimulates antigen presenting cells.
Antigen presenting cells stimulate CD4+ T cells
Cytokines are produced by both of these cells.
Cytokines stimulate growth factors to stimulate fibroblasts to produce collagen
Vascular damage occurs with thickened intima and narrowing of the lumen.
Narrowing of the lumen leads to ischemia.
Ischemia leads to prostacyclin production which is a platelet aggregant and platelets bind to endothelium and release PDGF which is chemotactic and mitogenic for fibroblasts.