Farm Exposure as a Differential Risk Factor in ANCA-Associated Vasculitis

PLOS ONE, Dec 2019

Objective To investigate the association of farm exposure and the development of ANCA-associated vasculitis (AAV). Methods One hundred eighty-nine well defined patients with AAV (n = 119 with granulomatosis with polyangiitis [GPA], n = 48 with microscopic polyangiitis [MPA], n = 22 patients with eosinophilic granulomatosis with polyangiitis [EGPA]) and 190 controls (n = 119 patients with rheumatoid arthritis, n = 71 with large vessel vasculitis) were interrogated using a structured questionnaire. Factors investigated were occupation, farm exposure, contact to different livestock, participation in harvesting, residence next to a farm, MRSA status, and contact to domestic pets at disease onset or ever before. The odds ratio (OR) and 95% confidence interval [95%CI] were calculated for each item. Results Univariate analysis revealed a strong association of AAV with regular farm exposure; OR 3.44 [95%CI 1.43–8.27]. AAV was also associated with regular contact to cattle 4.30 (1.43–8.27), pigs 2.75 (1.12–6.75) and MRSA carriage 3.38 (1.11–10.3). This association was stronger in the subgroup of GPA patients. OR in this group for farm exposure was 4.97; [2.02–12.2], for cattle 6.71 [95% CI 2.19–20.7], for pigs 4.34 [1.75–10.9], and MRSA carriage 5.06 [1.62–15.8]). There was no significant association of MPA or EGPA with these parameters. Conclusion A significant association between farm exposure or farm animal exposure and AAV especially in the subgroup of patients with GPA has been identified. This suggests that these entities are distinct and have different triggers for the immune process.

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Farm Exposure as a Differential Risk Factor in ANCA-Associated Vasculitis

September Farm Exposure as a Differential Risk Factor in ANCA-Associated Vasculitis P. Willeke 0 1 B. Schlüter 0 1 C. Sauerland 0 1 H. Becker 0 1 S. Reuter 0 1 A. Jacobi 0 1 H. Schotte 0 1 0 1 Department of Medicine D, Section of Rheumatology and Clinical Immunology, University Hospital Münster , Münster, Germany , 2 Centre for Laboratory Medicine, University Hospital Münster , Münster, Germany , 3 Institute of Biostatistics and Clinical Research, University of Münster , Münster, Germany , 4 Division of Rheumatology and Clinical Immunology, Brandenburg Medical School , Neuruppin , Germany 1 Editor: Joerg Latus, Robert Bosch Hospital , GERMANY - Competing Interests: The authors have declared that no competing interests exist. To investigate the association of farm exposure and the development of ANCA-associated vasculitis (AAV). One hundred eighty-nine well defined patients with AAV (n = 119 with granulomatosis with polyangiitis [GPA], n = 48 with microscopic polyangiitis [MPA], n = 22 patients with eosinophilic granulomatosis with polyangiitis [EGPA]) and 190 controls (n = 119 patients with rheumatoid arthritis, n = 71 with large vessel vasculitis) were interrogated using a structured questionnaire. Factors investigated were occupation, farm exposure, contact to different livestock, participation in harvesting, residence next to a farm, MRSA status, and contact to domestic pets at disease onset or ever before. The odds ratio (OR) and 95% confidence interval [95%CI] were calculated for each item. Univariate analysis revealed a strong association of AAV with regular farm exposure; OR 3.44 [95%CI 1.43–8.27]. AAV was also associated with regular contact to cattle 4.30 (1.43–8.27), pigs 2.75 (1.12–6.75) and MRSA carriage 3.38 (1.11–10.3). This association was stronger in the subgroup of GPA patients. OR in this group for farm exposure was 4.97; [2.02–12.2], for cattle 6.71 [95% CI 2.19–20.7], for pigs 4.34 [1.75–10.9], and MRSA carriage 5.06 [1.62–15.8]). There was no significant association of MPA or EGPA with these parameters. A significant association between farm exposure or farm animal exposure and AAV especially in the subgroup of patients with GPA has been identified. This suggests that these entities are distinct and have different triggers for the immune process. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic necrotising vasculitis predominantly affecting small vessels. AAV comprises granulomatosis with polyangiits (GPA, Wegener’s), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) [1]. The annual incidence of AAV as a group is estimated at about 10–20 patients per million [2]. The causes of AAV are poorly understood and their pathophysiological mechanisms remain uncertain [3]. In a recent genome-wide association study of patients with AAV a genetic contribution to the pathogenesis has been confirmed [4]. Beside the genetic susceptibility microbial pathogens and environmental factors have been implicated in the pathogenesis of AAV [5]. Various potential environmental risk factors have been suggested [4, 6]. Particularly, occupational exposure to different agents has been associated with the development of AAV [7, 8]. Several case-control studies found a positive association between crystalline silica exposure and other inhaled agents with GPA and MPA [6]. Also differences in the geographic distribution have been reported suggesting that environmental factors may play a role in the pathogenesis of the disease [9]. In addition, an association with bacterial infection could be suggested in AAV [10]. Farming has been reported as a risk factor for the development of several autoimmune diseases [7, 11]. An association of farming and AAV has also been reported [12, 13]. However, there are inconsistent data about farming as a risk factor for AAV. In a recent Swedish casecontrol study no significantly association of farming or animal exposure with the development of AAV or GPA respectively could be detected [14]. The information about the disease and the occupation of patients in this study was obtained from registry data of inpatient care and may thus be less precise than data directly acquired using questionnaires. The aim of the present study was to investigate in a large hospital based case-control study whether farming or farm exposure represent risk factors for the development of AAV in the north western part of Germany. Materials and Methods AAV patients and controls The study protocol was approved by the local independent ethics committee (Ethikkommission der Ärztekammer Westfalen-Lippe). All patients and controls provided written informed consent before participating in the study. This study was conducted in compliance with Good Clinical Practices and the Declaration of Helsinki and was approved by the local independent ethics committee. We included patients with different AAV subtypes. GPA was diagnosed acco (...truncated)


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P. Willeke, B. Schlüter, C. Sauerland, H. Becker, S. Reuter, A. Jacobi, H. Schotte. Farm Exposure as a Differential Risk Factor in ANCA-Associated Vasculitis, PLOS ONE, 2015, 9, DOI: 10.1371/journal.pone.0137196