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Background and Objectives Myasthenia gravis (MG), an autoimmune disease characterized by fluctuating muscle weakness, is believed to result from complex gene-environment interactions, yet few risk factors have been identified. The objective of this study was to determine the effect of nicotine and alcohol on MG disease risk.

Methods The Genes and Environment in Myasthenia Gravis study is a Swedish, nationwide cross-sectional case-control study where prevalent patients with MG were invited to submit an extensive questionnaire on lifestyle and environment. Data collection took place between November 2018 and August 2019, and cases were matched by sex and year of birth to population controls. Year of disease onset was used as index year. Associations between use of alcohol, tobacco smoke, Swedish snuff, and MG risk were investigated using multivariable logistic regression.

Results A total of 1,067 patients with MG (mean age at onset 48 (SD 21) years, 53% female) were matched to 2,087 controls. Any alcohol consumption was associated with a lower MG risk compared with not drinking at all (odds ratio [OR] 0.48, 95% CI 0.39-0.59, p < 0.001, exposed cases n = 616). Effects were observed in a similar direction across disease subtypes, with the strongest association in the late-onset MG group (onset ≥50 years). Although neither cigarette smoke nor use of Swedish snuff affected the disease risk of the whole group, subset specific effects were observed. Smoking at onset was associated with an increased risk of early-onset MG (EOMG, onset 18-49 years; OR 1.60, 95% CI 1.17-2.20, p = 0.003, n = 133), which was accentuated in acetylcholine receptor antibody-positive EOMG (OR 2.08, 95% CI 1.34-3.25, p = 0.001, n = 74). Use of Swedish snuff, which contains high levels of nicotine, at disease onset was also associated with an increased risk of EOMG (OR 1.61, 95% CI 1.02-2.54, p = 0.039, n = 43).

Discussion We observed an inve rse correlation of MG risk and alcohol consumption. Furthermore, smoking and the use of Swedish snuff at disease onset were positively associated with EOMG. We recognize limitations related to retrospective data and limited number of available controls. However, multiple sensitivity analyses were performed supporting the robustness of our results.