Environmental Toxins and Scleroderma

By Alan M. Rosenberg, MD, FRCPC (From The Journal of the Canadian Rheumatology Association. Vol. 3, No. 1, March 1994) Reviewed and revised January 1998

Factors involved in the induction and perpetuation of auto-immune diseases remain poorly understood. Clinical and epidemiological observations, however, have promoted an impression that environmental factors in general   and chemical toxins in particular  may induce certain autoantibodies and play a role in the etiopathogenesis of the diseases with which such antibodies are associated. Even though there is emerging evidence to suggest that human exposure to environmental toxins could induce aberrations of the immune system, no comprehensive, multi-disciplinary studies have been reported. Polyvinyl chloride: In factories producing polyvinyl chloride, workers who are exposed to vinyl chloride fumes may develop a systemic scleroderma-like disease characterized by Raynaud's phenomenon, sclerodactyly, arthritis, acro-osteolysis and pulmonary fibrosis. Genetic predisposition to the development of a vinyl chloride-induced disease is suggested by the identification of significant associations with certain histocompatibility antigens.

Silica Dust: Occupational exposure to silica dust has been associated with scleroderma in men. In former East Germany, it was established that the risk of scleroderma developing in men is 110 times greater in a population with silicosis that in the normal population. High-intensity (rather than long-duration) exposure to silica dust, observed in coal and gold miners, has been associated with the development of scleroderma, even in the absence of silicosis. Auto-immune phenomena have also been observed in patients with silicosis and in those with histories of intense exposure even in the absence of silicosis. Increased prevalence of rheumatoid factor and antinuclear antibodies have been found in South African gold miners.

Silicone Breast Implantations: Connective tissue disease has been reported to occur following cosmetic and reconstructive surgery. In particular, silicone breast implantation has been associated with the development of scleroderma and of characteristic antinuclear antibody profiles.

Other Substances: Organic solvents (benzene, toluene and xylene), chlorinated hydrocarbons (trichloroethylene) and aliphatic hydrocarbons have been suggested as scleroderma-inducing agents in individuals having prolonged contact with these agents. Isolated reports have been recorded of scleroderma developing in workers involved in polymerization of epoxy resins and in workers exposed to meta-phenylenediamine following an accidental spill.

Toxic Oil Syndrome: In 1981, the ingestion of tainted rapeseed oil by a population of Spaniards led to more than 700 deaths and to morbidity in thousands (toxic oil syndrome). Although the acute illness was characterized by fever, pneumonitis and eosinophilia, a substantial number of affected individuals who survived the acute phase of the poisoning subsequently developed features including Raynaud's phenomenon, sclerodermatous skin changes, pulmonary hypertension, Sjšgren's syndrome and polymyositis. The contaminant of the adulterated cooking oil was subsequently found to be an anilide of unsaturated fatty acids. Thirty-four percent of sera from affected subjects contained antinuclear antibodies. Bleomycin and vinblastine used in cancer chemotherapy have been associated with the development of Raynaud's phenomenon. Mercuric chloride, when injected into rabbits and certain rat strains, induces glomerulonephritis and antibodies to nucleolar constituents including fibrillarin, an antigenic target thought to be specific for human scleroderma.

The Pediatric Rheumatic Disease Research Laboratory at the University of Saskatchewan has developed an interest in exploring more thoroughly the possible associations between environmentally encountered potential toxins particularly those used in the agricultural industry   and the induction of scleroderma-like disease. The laboratory is seeking to collaborate with rheumatologists with a similar interest. The laboratory is particular interested in learning of individual patients or groups of patients with scleroderma or scleroderma-like diseases in whom exposure to environmental toxins is known to be   or suspected of being   an etiologic factor. The laboratory is also interested in communicating with rheumatologists who may be interested in participating in the development of a protocol to explore more extensively the issue of environmental toxins and induction of scleroderma or other auto-immune disorders. Reviewed and revised Jan. 1998.

For further information concerning this article, please contact: Dr. Alan Rosenberg, Pediatric Rheumatic Disease Research Laboratory, Department of Pediatrics, Royal University Hospital, Saskatoon, Saskatchewan S7N 0W8. Phone (306) 966-8117, or fax: (306)975-3767.