Studies of lupus-prone mice provide strong evidence of an accelerated autoimmune response from dosing with trichloroethylene, including accelerated autoantibody expression, T-cell activation, and secretion of inflammatory cytokines (as reviewed by Cooper 2009) (7). hydrocarbons (i.e., mineral oils) is usually warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g., antinuclear antibodies), clinical features (e.g., nephritis) and outcomes. strong class=”kwd-title” Keywords: Systemic Lupus Erythematosus, environmental risk factors, occupational exposures, silica, pesticides, epidemiology Systemic lupus erythematosus (SLE) is usually a complex disease caused by interactions of intrinsic susceptibility with environmental risk factors. Growing evidence supports the idea that risk of developing SLE may be increased by exposure to chemicals and industrial pollutants. Here we review research on the risk of SLE associated with occupational and environmental exposures, primarily drawing on studies in human populations, along with supportive findings from experimental studies and relevant research on related systemic autoimmune diseases. We review the evidence on (1) silica and silicates, (2) agricultural and residential pesticides, (3) solvents and other hydrocarbons, and other occupational exposures and summarize relevant findings from several studies published in the past decade (Table 1) (1C6). The biologic mechanisms leading to development of autoimmunity and progression to clinical SLE are not fully understood, but it seems plausible that exposures may have effects at different points in these processes (7). Thus, we also consider findings on exposure-associated autoantibodies. Table 1 Studies of occupational, industrial, and other chemical risk factors for SLE thead th align=”left” valign=”top” rowspan=”1″ colspan=”1″ Publications /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ Population/sample/design /th th align=”left” valign=”top” rowspan=”1″ colspan=”1″ Exposure assessment/ br / Analyses /th th align=”left” rowspan=”1″ colspan=”1″ Findings br / Odds Ratio or other effect measure br / (95% Confidence Interval) /th /thead Cooper et al., 2004(2); br / Parks et al., 2008(1)US, North and South Carolina; Case-control br / br / 265 cases Tyrosine kinase inhibitor from rheumatology clinics and primary care br / br / 355 controls from drivers license registries, matched by age, sex, stateIn person interview br / br / Questionnaire included lifetime job history of all jobs 1 year or longer, specific questions on jobs, tasks and materials, including silica, solvents; lifetime farm history (including pesticide mixing or application), crop/task-specific questions for dust, soil type mapping for silica br / br / Expert assessment occupational exposures: solvents br / br / Adjusted for matching factors, race, educationPesticides (agricultural) C br / Mixing: OR=7.4 (1.4, 40) br / Applying: OR=0.77 (0.34, 1.8) br / br / Mercury C br / Exposure at work: OR=3.6 (1.3, 10) br / Dental worker: OR=7.1 (2.2, 23.4) br / br / Non-significant elevations1: br / Hog or poultry processing (OR=1.6) br / Furniture or paper manufacture (OR=1.9) br / Beauticians (OR=1.6) br / br / No associations: occupational solvents br / Prior associations: silica (10)Finckh et al., 2006(3)US, Boston; Case-control br / br / 95 cases from community screening, hospital-databases br / br / 191 controls from community volunteers, matched by age and raceIn person interview br / br / Questionnaire included lifetime job history of all jobs 1 year or longer, specific questions on jobs, tasks and materials, including silica, solvents br / br / Expert assessment: silica and solvents, using same protocol as Carolina Lupus Study (refs) br / br / Adjusted for parity, smoking, educationSilica C br / 1 year exposure: OR=4.3 (1.7, 11.2) br / No effect modification by smoking br GRS / br / No association: occupational solventsGold et al., 2007(5)US, 26 says; Case-control br / br / 7241 cases identified with ICD9 code for SLE on death certificate br / br / 264,569 controls who died without systemic autoimmune diseasesUsual occupation listed on the death certificate br / br / Job-exposure matrix (JEM) to assign exposures based on usual occupation br / br / Adjusted for age, sex, race, death year, US region, and socioeconomic statusSelected jobs with increased risk of SLE C br / Artists, performers, related: OR=2.90 (1.37, 6.15) br / Dental hygienists: OR=2.98 (22.214.171.124) br / Farmers: OR=1.18 (0.95, 1.46) br / Tyrosine kinase inhibitor Mining machine operators: OR=1.77 (1.15. 2.73) br / Miscellaneous textile machine operators: OR=1.50 (1.05, 2.14) br / Hand painting, coating, decorating: OR=3.73 (1.31, 10.6) br / Garage/service station related: OR=2.26 (0.91, 5.63) br / br / Borderline association with JEM exposures C br / Solvents: OR=1.06 (0.99, 1.13) br / Pesticides (high vs. none): OR=1.07 (0.93,1.22) br / br / No association with JEM exposures: asbestos, benzene, silica, inorganic Tyrosine kinase inhibitor dust, lead, metal dust, polycyclic aromatic hydrocarbons, wood dustCooper et al., 2010 (4)Canada; Case-control br / br / 258 cases from rheumatology clinics, with at least 4 ACR criteria and 2 live parents (for DNA study); 90% female, 82% Caucasian br / br / 263 controls from random digit dialing, matched by age, sex, and areaTelephone interview br / br Tyrosine kinase inhibitor / Questionnaire on occupational exposures, based on job and task-specific questions: silica, gasoline, solvents, stains/varnishes, mercury, pesticides, hair dyes, permanents, relaxers, nail polish and application br / br / Adjusted for matching factorsJobs/exposures C br / Artist (paints, dyes, film): OR=3.9 (1.3, 12.3) br / Nail polish or application: OR=10.2 (1.3, 81.5) br / Pottery/ceramics hobby: OR=3.9 (1.3, 12.3) br / br / Increasing risk across multiple sources of silica exposure (OR=1.00, 1.3, 2.1.
Studies of lupus-prone mice provide strong evidence of an accelerated autoimmune response from dosing with trichloroethylene, including accelerated autoantibody expression, T-cell activation, and secretion of inflammatory cytokines (as reviewed by Cooper 2009) (7)
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