Silica autoimmune diseases

Occupational exposure to silica dust has been identified as a risk factor for several systemic autoimmune diseases. This literature dates back almost 100 years, to the description by Bramwell of diffuse scleroderma in stone masons.26 Rheumatoid arthritis and scleroderma in miners were described in the 1950s, and more formal cohort studies of miners and of granite workers were conducted in the 1980s. Other studies focusing on silicosis patients, and several case-control studies of these diseases and of Wegner... 

Recent (1990-2005) Epidemiologic Studies of Occupational Silica Exposure and Risk of Autoimmune Diseases... 

Issues regarding the influence of duration or intensity of exposure in relation to effect on autoimmune disease processes are questions that have not been established, with some inconsistencies seen in the epidemiologic studies (Table 25.2). Dose or intensity of silica exposure affects the clearance from the lung and silica-containing macrophages can be translocated to pulmonary lymph nodes. Increased production of immunoglobulins and of lymphocyte-derived interferon-gamma is seen at these sites.49... 

Parks, C.G., Conrad, K., and Cooper G.S., Occupational Exposure to Crystalline Silica and Autoimmune Disease, Environ. Health Perspect. 107, 793, 1999. 

Crystalline silica or silicon dioxide (Si02), the most abundant mineral in the earth s crust, is found in rock, sand, and soil. Most studies of silica and autoimmune disease have focused on occupational exposures within the traditional dusty trades , which... 

Occupational silica exposure and systemic autoimmune diseases... 

Table 10. Recent (1985-2005) epidemiological studies of occupational silica exposure and risk of autoimmune diseases...

Brown JM, Archer AJ, Pfau JC, Holian A (2003) Silica accelerated systemic autoimmune disease in lupus-prone New Zealand mixed mice. Clin Exp Immunol, 131(3) 415-421. 

Parks CG, Conrad K, Cooper GS (1999) Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect, 107(Suppl 5) 793-802. 

Table 6. Autoimmune diseases in association with silica exposure (according to Sanchez-Roman et al. 1993 and Wichmann et al. 1996)...

As silica cannot be removed from the body once it is incorporated, its deleterious precipitating effect is unavoidable. This indicates that the clinical course of silica-induced disorders is quite similar to classical autoimmune diseases or SSc, characterized by progressions and remissions. The subsequent therapy should take these findings into account and has to be adjusted according to the criteria for the extent, organ involvement, and clinical activity of the disease. The best way to prevent this type of SSc is to minimize the exposure to silica. 

Silica-induced LE is a chronic multiorgan system autoimmune disease with frequent exacerbations and remissions similar to the natural course of mixed connective tissue disease. The pathomechanism of LE is not yet completely understood. Based on a genetic background, a major role seems to be played by disturbances of immune regulation, such as T-cell abnormalities, including T-cell cytokine network. 

SLE is a chronic autoimmune connective tissue disease characterized by inflammation and injury to the joints, tendons, and other connective tissues. Organs affected include the lungs, heart, blood vessels, brain, kidneys, and skin. SLE onset is associated with exposure to silica. Though earlier studies have suggested that organic solvent exposure can also be causative for SLE, more recent studies have refuted thisJ2,3,9 No literature references were found associating SLE onset with exposures to chemical mixtures. 

Increased cytokine production may also play a role in silica-induced autoimmune vascular disease. Adhesion molecule expression is elevated on vascular endothelial cells in response to TNF-a and IL-1. Adhesion molecules such as endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) recruit inflammatory cells to specific sites on the vascular endothelium, and it has been hypothesized that vascular pathology following silica exposure may be the result of this interaction (Nowack et al., 1998). IFN-y is expressed at elevated levels by lymphocytes in silicotic thoracic lymph nodes and may be responsible for the long-lasting inducible nitric oxide synthase (iNOS) expression in these tissues (Friedetzky et al., 2002). The increase in IFN-y may also cause a shift towards a dominant Thl response, contributing to the maintenance of a chronic inflammatory state in silica-containing lymph nodes (Gam et al., 2000). 

By summarizing various studies and case reports, Gregorini (working in Brescia) showed that extrapul-monary silicotic lesions and/or autoimmune processes may play a role in kidney diseases after silica exposure, more specifically MPO-ANCA-positive microscopic polyangiitis and its renal-limited form of idiopathic , rapidly progressive glomerulonephritis (Conrad et al. 

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