Epidemiologic studies of environmental agents and systemic autoimmune diseases.

Abstract

Systemic lupus erythematosus and systemic scleroderma are autoimmune diseases thought to have an exogenous trigger. This review summarizes relevant case-control and cohort studies that investigated exogenous sex hormones, silica, silicone, solvents, pesticides, mercuric chloride, and hair dyes as putative risk factors for the development of these diseases. These studies indicate that estrogen replacement therapy in postmenopausal women increases the risk of developing lupus, scleroderma, and Raynaud disease, although the increase in risk is relatively modest. Oral contraceptives may also play a role in disease susceptibility in lupus but not apparently in scleroderma. Environmental endocrine modulators, in the form of pesticides, may represent another opportunity for estrogenlike effects to occur, but there is scant evidence that these agents play a role in human systemic autoimmune disease. Although exposure to silica dust increases the risk of scleroderma in men occupied in the industry, this does not explain most male scleroderma cases. When this exposure was investigated among women, no significant risk was found. Additionally, silicone in implanted devices as well as occupational exposure to silicone-containing compounds did not pose an increased risk among women for scleroderma. The role of solvent exposure has been investigated as a risk factor for scleroderma with mixed findings. One study suggested a potential role in male patients or in those individuals with Scl-70 antibody positivity either male or female. Two other studies were unable to corroborate this finding. Mercuric chloride causes antifibrillarin antibodies and immune complex glomerulonephritis in susceptible mouse strains. Antifibrillarin antibodies, but not glomerulonephritis, occur in a subset of scleroderma patients and preliminary evidence suggests that mercury levels may be higher in this group of individuals. Hair products have been studied as possibly raising the risk of developing lupus, since such products contain an aromatic amine similar to a compound known to cause drug-induced lupus. A 1986 study suggested a positive association, but two subsequent studies did not support this association.

Clinical, immunologic, and genetic features of familial systemic sclerosis

“…Several environmental factors have been studied, and some have been found to be associated with SSc (for review, see ref. 22). In terms of environmental versus genetic factors in the etiology of SSc, only 2 case reports of spouses with SSc have been published (in 1 case silica and in the other solvent exposure was implicated) (23,24), whereas 44 familial SSc cases have been previously reported (refs.…”

Casting the runes

“…Urinary mercury excretion has been reported to be higher in scleroderma patients who are positive for antifibrillarin antibodies. However this level is still in the normal and unexposed ranges, and these patients never develop immune complex glomerulonephritis (Mayes 1999).…”

Immunological effects of mercury (IUPAC Technical Report)

“…Others did not find evidence for such an effect of mercury [89][90][91][92][93], even at higher dosage [94], and found no correlation with acute autoimmune disease such as acute glomerulonephritis or childhood purpura [95]. An epidemiological analysis found a weak association with lupus erythematosus, but this remains to be further investigated [96]. When lymphocytes of patients with autoimmune thyroiditis were incubated in vitro with mercury salts, there was a trend for an increased production of antibodies [97].…”