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.

c-Jun N-Terminal Kinase Is Involved in Mercuric Ions-Mediated Interleukin-4 Secretion in Mast Cells

“…Environmental or occupational exposures to metal compounds including mercurials have been linked to dysfunctions of the immune system, such as allergic and autoimmune diseases [1, 2, 3, 4]. Mercuric compounds induce abnormal immune responses including induction of specific and polyclonal IgE [5]and autoimmunity [6, 7]in rats and mice.…”

Seasonal distribution of systemic lupus erythematosus activity and its correlation with climate factors

“…Recent study has found that the incidence of SLE is constantly increasing. In addition to the improvement of diagnosis level, the increasing of environmental risk factors may play an important role in the occurrence and progress of SLE; therefore, further exploration for risk factors for SLE seems to be of great significance [12,13]. As an important part of the environmental factors, climate factors have been confirmed to play an important role in rheumatic diseases (such as SLE and arthritis).…”

“…As an important part of the environmental factors, climate factors have been confirmed to play an important role in rheumatic diseases (such as SLE and arthritis). Climate factors could influence the progress of diseases by influencing inflammatory mediators [13].…”

Case Study for Selected Heavy Elements in Blood and Plasma from Six Female Patients with Systemic Sclerosis (Scleroderma, SSc). The Concentrations of Mercury, Lead, Antimony, Cobalt, Copper, and Zinc

“…Significant toxic compound and heavy element intake by the body is considered a potential co-factor in triggering auto-immune diseases [1][2][3]. To our knowledge, there have been no large systematic investigations on the concentration of heavy elements in the body of patients with auto-immune diseases.…”

“…A preliminary statistical study directed by one of the authors (RM) and conducted during the past ten years at the clinic of Rheumatology, University of Siena, on the rate of SC in patients from the volcanic Amiata mountain area population, showed significantly higher values when compared to a control population. 1 It should be noted that the reference values for most of the trace elements in blood, urine, tissues and organs in humans and other animals is currently a matter of intensive research in several laboratories world-wide [31][32].…”