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
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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)