Genetic and environmental factors in systemic sclerosis

The occurrence of autoantibodies in patients with systemic sclerosis has suggested a role for immune dysregulation in this disease. Recent genetic studies have concentrated on the major histocompatibility complex-encoded antigens and found an association of particular HLA-DQ alleles with anticentromere antibodies. Although the role of major histocompatibility complex antigens and autoantibodies in the pathogenesis of systemic sclerosis remains unclear, determination of major histocompatibility complex alleles may have clinical value in identifying patients who are at increased risk for development of pulmonary fibrosis or rapidly advancing skin disease. A variety of environmental factors have been associated with systemic sclerosis-like skin diseases, including silica, vinyl chloride, paraffin, adulterated L-tryptophan, and "toxic" rapeseed oil. It has been suggested that silicone used during breast augmentation may be a risk factor for development of systemic sclerosis, but ascertainment bias in case reporting makes interpretation of these studies difficult. The heterogeneity of clinical features, major histocompatibility complex status, and autoantibody profiles in systemic sclerosis suggest that this disorder may actually be a group of distinct disorders, each of which has its own characteristic genetic and environmental predisposing risk factors.