Association of Silica Exposure with Anti-neutrophil Cytoplasmic Autoantibody Small-vessel Vasculitis: a Population-based, Case-control Study

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P = 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P = 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV.