Blue-collar work is a risk factor for developing IgG4-related disease of the biliary tract and pancreas

Lowiek M Hubers,Alex R Schuurman,Jorie Buijs,Nahid Mostafavi,Marco J Bruno,Roel C.H Vermeulen,Anke Huss,Henk R Van Buuren,Ulrich Beuers

doi:10.1016/j.jhepr.2021.100385

Abstract

Background & AimsImmunoglobulin G4-related disease (IgG4-RD) of the biliary tract and pancreas is a fibroinflammatory disease of unknown origin with striking male predominance. We aimed to investigate whether blue-collar work and occupational contaminant exposure are risk factors for IgG4-RD of the biliary tract and pancreas.MethodWe performed an age-/sex-matched case-control study in the largest academic medical centers of the Netherlands. Occupational history was surveyed by questionnaires. The International Standard Classification of Occupations (ISCO88) was used to classify jobs. Job exposure matrices ALOHA and DOM were utilized to assess the years individuals were exposed to compounds. The disease control cohort consisted of patients from 6 equally sized groups. Conditional logistic regression was used to assess effects of blue-collar work and exposure to occupational contaminants on developing IgG4-RD of the biliary tract and pancreas.ResultsOverall, 101 patients with IgG4-RD of the biliary tract and pancreas were matched 1:3 to 303 controls. Patients with IgG4-RD had a lower level of education (p = 0.001). Individuals who at least once performed blue-collar work (>1 year), had higher odds of developing IgG4-RD than individuals that only performed white-collar work (odds ratio [OR] 3.66; CI 2.18–6.13; p <0.0001). Being ever exposed (>1 year) to industrial ALOHA (e.g. mineral dust; vapors-dust-gases-fumes) and DOM compounds (e.g. asbestos) resulted in higher odds of IgG4-RD (OR 2.14; 95% CI 1.26–3.16; p <0.001 and OR 2.95; 95% CI 1.78-4.90; p <0.001, respectively).ConclusionBlue-collar work is a risk factor for developing IgG4-RD of the biliary tract and pancreas putatively driven by exposure to selected industrial compounds; this may explain the striking male predominance among patients.Lay summaryImmunoglobulin G4-related disease (IgG4-RD) causes tumor-like lesions and typically affects middle-aged to elderly men. The background and cause of this disease remain relatively unknown. In this study, we identified blue-collar work as a risk factor for developing IgG4-RD of the biliary tract and pancreas, which may explain the striking male predominance among patients. Furthermore, these results suggest that toxic exposure to occupational contaminants may drive autoimmunity in IgG4-RD of the biliary tract and pancreas.

Highlights

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized multi-organ fibroinflammatory condition.[1]
We investigated in a cohort of 404 patients whether blue-collar work and exposure to occupational contaminants are risk factors for developing IgG4-RD of the biliary tract and pancreas when compared to disease control patients
Controls were selected from the outpatient clinics of the Departments of Gastroenterology & Hepatology in the same medical centers and consisted of patients from six -sized groups with digestive diseases not known to be provoked by occupational risk factors and not associated with IgG4-RD, including primary sclerosing cholangitis, inflammatory bowel disease, non-alcoholic chronic pancreatitis, malignant and premalignant pancreatobiliary tumors, benign gastrointestinal polyps, and gastrointestinal malignancies

Summary

Introduction

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized multi-organ fibroinflammatory condition.[1] The various organ manifestations share distinct histological changes, including lymphoplasmacytic infiltrates with large quantities of IgG4-producing plasma cells, a typical storiform pattern of fibrosis and obliterative phlebitis.[2] The biliary tract and pancreas belong to the organs most frequently affected.[3,4] Mass-forming lesions and strictures of IgG4-RD are often difficult to differentiate from pancreatobiliary malignancies. This diagnostic dilemma leads to major unnecessary surgical and medical interventions for presumed malignancy.[5] if early recognized, lesions may completely disappear upon start of first-line treatment with predniso(lo)ne.[6]

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