ABSTRACT
Systemic sclerosis, or scleroderma (SSc), is an autoimmune disease, which manifests clinically by progressive cutaneous and visceral fibrosis. SSc is a complex, heterogeneous disease with clinical forms ranging from limited skin involvement (lcSSc) to diffuse disease (dcSSc) causing extensive cutaneous sclerosis and severe internal organ alterations. Age, race and genetic factors have all been found to influence the development and course of SSc, 1 but the strongest genetic factor is gender. The incidence of SSc in females is in great excess compared to its incidence in males, ranging from 3:1 to 8:1. 1 , 2 The etiology of SSc remains unknown but its occurrence has been associated with numerous risk factors including various environmental agents, genetic influences, viruses and more recently with microchimerism. 3 , 4 Environmental agents associated with SSc or closely related syndromes include organic solvents such as vinyl chloride and trichloroethylene, adulterated rapeseed oil, certain tryptophan products, bleomycin and silica. 5 , 6 Genetic factors have also been associated with the onset of SSc. 5 Vinyl chloride-induced disease has an HLA-DR5 association in those individuals who progress to SSc 7 and specific HLA alleles have been associated with autoantibody subgroups expressed in SSc patients. 8 Viruses have also been implicated in the pathogenesis of SSc, and recent interest has been focused on retroviruses and cytomegalovirus. 10 , 11 Sequence homologies have been identified between several retroviruses and topoisomerase I, the target antigen of the SSc-specific scleroderma-70 (Scl-70) autoantibody 12 and sera from SSc patients containing anti- Scl-70 autoantibodies were able to recognize the retrovirus responsible for equine infectious anemia. 13 In spite of the initiating exposure in SSc, cellular and humoral immunological changes are early events and precede vasculopathy and fibrosis. Although aggressive treatments may suppress SSc disease activity in some cases, there are few, if any, complete cures. Since these conditions arise as a direct result of dysregulation of the immune system, modification of immune stem cells may be important in the control of SSc.
