Silica exposure and autoimmune disease
Silica
Although the most common health effect of silica exposure are the lung diseases occupational exposure to respirable crystalline silica is also associated with a number of other diseases, including systemic autoimmune diseases, such as rheumatoid arthritis, scleroderma, systemic lupus erythematosus (SLE), and some of the small vessel vasculitides and with renal diseases i.e. rapid progressive glomerulonephritis, nephrotic syndrome, and end stage renal disease.
Silica exposure and autoimmune disease
Respiratory complications from crystalline silica exposures have been known for centuries, but the link of silica exposure and autoimmune disease has been more recent. In the 1950s, Caplan first described unusual radiologic changes in the lungs of Welsh coal miners who had pneumoconiosis. In a subsequent study of these miners, Miall et al. (1953) found that the rheumatoid lesions in the lung were predictive for rheumatoid arthritis (subsequently called Caplan's syndrome). Since that time many studies have examined the link between crystalline silica exposure and development of autoimmune diseases. Among the systemic autoimmune diseases, occupational exposure to crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and some of the small vessel vasculitides.
Respiratory complications from crystalline silica exposures have been known for centuries, but the link of silica exposure and autoimmune disease has been more recent. In the 1950s, Caplan first described unusual radiologic changes in the lungs of Welsh coal miners who had pneumoconiosis. In a subsequent study of these miners, Miall et al. (1953) found that the rheumatoid lesions in the lung were predictive for rheumatoid arthritis (subsequently called Caplan's syndrome). Since that time many studies have examined the link between crystalline silica exposure and development of autoimmune diseases. Among the systemic autoimmune diseases, occupational exposure to crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and some of the small vessel vasculitides.
Silica exposure and autoimmune disease
Crystalline silica particles are ingested by alveolar macrophages and result in inflammation and activation of fibroblasts. The digested crystalline silica destroys the macrophages, and the crystalline silica is again digested by new macrophages. This repeated process leads to chronic immune activity and fibrosis. Studies have shown that crystalline silica can be mobilized from the lungs to other organs, including lymph nodes, spleen, and kidney. Silicosis and mineral dust pneumoconiosis have been linked to an increase in autoantibodies, immune complexes, and excess production of immunoglobulins, even in the absence of a specific autoimmune disease. Many of the cases of autoimmune disease were first discovered during screening of silica-exposed workers or workers who were being treated for silicosis. It was not clear in these cases whether the silicosis was a pathologic process that may predispose some individuals to develop autoimmune disease or whether the opposite was true, that the autoimmune disease may predispose some individuals to develop silicosis in the lung.
Crystalline silica particles are ingested by alveolar macrophages and result in inflammation and activation of fibroblasts. The digested crystalline silica destroys the macrophages, and the crystalline silica is again digested by new macrophages. This repeated process leads to chronic immune activity and fibrosis. Studies have shown that crystalline silica can be mobilized from the lungs to other organs, including lymph nodes, spleen, and kidney. Silicosis and mineral dust pneumoconiosis have been linked to an increase in autoantibodies, immune complexes, and excess production of immunoglobulins, even in the absence of a specific autoimmune disease. Many of the cases of autoimmune disease were first discovered during screening of silica-exposed workers or workers who were being treated for silicosis. It was not clear in these cases whether the silicosis was a pathologic process that may predispose some individuals to develop autoimmune disease or whether the opposite was true, that the autoimmune disease may predispose some individuals to develop silicosis in the lung.
Long latency periods (15-25 years) have been reported between first silica exposure and the development of autoimmune diseases. However, in a 1987 study of granite workers, Klockars et al. (1987) documented individuals who developed autoimmune disease in a shorter period of time. The authors published results of a follow up of 35 workers exposed to silica who had developed rheumatoid arthritis. Of the workers, 13 had 5 years of exposure before the onset of rheumatoid arthritis. For 7 of the workers, latency ranged from 1 to 12 years. This study was also interesting in that 20 of the 35 miners had normal chest x-rays at the time of the onset of rheumatoid arthritis.
Silica exposure and autoimmune disease
The mechanism of crystalline silica in the development of autoimmune diseases may be a result of the adjuvant effect on antibody production (An adjuvant is a substance that enhances an immune response to an antigen). The development of silicosis is dose dependent, but no studies have determined a dose-response or threshold effect of crystalline silica as an adjuvant. Genetic differences and susceptibility to autoimmune diseases may vary the characteristics and extent of the inflammation caused by silica exposure. Crystalline silica can also cause cell death by necrosis and apoptosis (an active process involving gene regulation).
The mechanism of crystalline silica in the development of autoimmune diseases may be a result of the adjuvant effect on antibody production (An adjuvant is a substance that enhances an immune response to an antigen). The development of silicosis is dose dependent, but no studies have determined a dose-response or threshold effect of crystalline silica as an adjuvant. Genetic differences and susceptibility to autoimmune diseases may vary the characteristics and extent of the inflammation caused by silica exposure. Crystalline silica can also cause cell death by necrosis and apoptosis (an active process involving gene regulation).
Apoptosis is enhanced by silica and at levels where an acute toxicity is not detected. The sFas ligand, a type II membrane protein that induces apoptosis, is elevated in silicosis patients. The elevation of sFas levels have been reported in silicosis patients who have slight shortness of breath, normal partial pressure of carbon dioxide, or normal partial pressure of oxygen and have been classified with slight respiratory disorders. Tomokuni et al. (1997) speculated that the severity of respiratory involvement may not occur to the same degree as the abnormalities and elevation of apoptosis-related molecules in silicosis patients.
Tomokuni et al. (1999) found no significant correlation of duration of exposure to crystalline silica dust and the serum levels of sFas. Host susceptibility may explain why all workers exposed to silica do not develop autoimmune disorders.
Silica exposure and renal disease
A statistically significant association between crystalline silica exposure and several renal diseases has been reported in epidemiologic studies. Steenland et al. (2001) reported an increasing standardized rate ratio for acute and chronic renal disease with increasing cumulative crystalline silica exposure and an excess of end-stage renal disease incidence (highest for glomerulonephritis). The reported cases of glomerulonephritis in patients with crystalline silica exposure show rapid progression and are associated with positive antineutrophil cytoplasmic antibodies (ANCA) with or without systemic vasculitis, such as Wegener granulomatosis or microscopic polyangiitis. pANCA is strongly associated with microscopic polyangiitis and rapidly progressive glomerulonephritis (RPGN). In a recent study (Gregorini et al. 1997), crystalline silica-exposed patients with positive ANCA showed mainly a pANCA pattern. Not all silica-exposed patients with pANCA-positive RPGN reported by Gregorini et al. (1993) had pulmonary silicosis. Gregorini et al. (1997) reported immune abnormalities in patients with silicosis and in silica-exposed patients with no evidence of lung disease.
A statistically significant association between crystalline silica exposure and several renal diseases has been reported in epidemiologic studies. Steenland et al. (2001) reported an increasing standardized rate ratio for acute and chronic renal disease with increasing cumulative crystalline silica exposure and an excess of end-stage renal disease incidence (highest for glomerulonephritis). The reported cases of glomerulonephritis in patients with crystalline silica exposure show rapid progression and are associated with positive antineutrophil cytoplasmic antibodies (ANCA) with or without systemic vasculitis, such as Wegener granulomatosis or microscopic polyangiitis. pANCA is strongly associated with microscopic polyangiitis and rapidly progressive glomerulonephritis (RPGN). In a recent study (Gregorini et al. 1997), crystalline silica-exposed patients with positive ANCA showed mainly a pANCA pattern. Not all silica-exposed patients with pANCA-positive RPGN reported by Gregorini et al. (1993) had pulmonary silicosis. Gregorini et al. (1997) reported immune abnormalities in patients with silicosis and in silica-exposed patients with no evidence of lung disease.
Silica exposure and renal disease
The intensity of exposure to silica dust may be more important than cumulative exposure or duration in the development of autoimmune diseases. In a study of silica-exposed gold miners, Calvert et al. (1997) investigated end-stage renal disease (ESRD) and exposures. They suggested that crystalline silica exposure was most strongly associated with ESRD (especially ESRD caused by glomerulonephritis) and that the median exposure of the cohort was below the OSHA permissible exposures levels (indicating a lower level of exposure needed to start the disease process).
The intensity of exposure to silica dust may be more important than cumulative exposure or duration in the development of autoimmune diseases. In a study of silica-exposed gold miners, Calvert et al. (1997) investigated end-stage renal disease (ESRD) and exposures. They suggested that crystalline silica exposure was most strongly associated with ESRD (especially ESRD caused by glomerulonephritis) and that the median exposure of the cohort was below the OSHA permissible exposures levels (indicating a lower level of exposure needed to start the disease process).
Silica exposure and renal disease
Effects of silica are thought to be either immune-complex mediated or a result of direct toxic effects of the silica on the glomeruli.
Effects of silica are thought to be either immune-complex mediated or a result of direct toxic effects of the silica on the glomeruli.
Studies have shown that crystalline silica can be mobilized from the lungs to other organs, including the kidney, lymph nodes, and spleen.
