Tobacco smoking and autoimmune rheumatic diseases

Abstract

Autoimmune rheumatic diseases are considered to be influenced by both genetic and environmental factors. Tobacco smoking has been linked to the development of rheumatic diseases, namely systemic lupus erythematosus and rheumatoid arthritis, and has been shown to interact with genetic factors to create a significant combined risk of disease. Smoking also affects both the course and the outcome of rheumatic diseases. Smoking increases the risk of dermatologic features and nephritis in systemic lupus erythematosus, rheumatoid nodules and multiple joint involvement in rheumatoid arthritis and digital ischemia in systemic sclerosis, as well as further increasing the risk of accelerated atherosclerosis in these diseases. Smoking is known to modulate the immune system through many mechanisms, including the induction of the inflammatory response, immune suppression, alteration of cytokine balance, induction of apoptosis, and DNA damage that results in the formation of anti-DNA antibodies. No sole mechanism, however, has been linked to any of the autoimmune illnesses, which therefore complicates full comprehension of the 'smoking effect'. Further studies, perhaps using animal models, are needed to analyze the exact effect of smoking on each disease separately.

Key Points

  • Smoking is associated with an increased risk of systemic lupus erythematosus and the formation of anti-dsDNA antibodies

  • Smoking is associated with an increased risk of cutaneous lupus manifestations

  • There is an increased risk of developing rheumatoid arthritis (RA), especially seropositive RA, associated with smoking; this risk is more profound in men than in women

  • Smoking synergizes with genetic factors such as shared HLA epitopes to create a profoundly increased risk of RA

  • Induction of apoptosis, alteration of cytokine and hormonal balance, immunogenesis of self-antigens, and an influence on lymphocyte function are all mechanisms through which smoking can induce autoimmunity

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Figure 1: Mechanisms by which smoking contributes to autoimmunity.

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Correspondence to Yehuda Shoenfeld.

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Harel-Meir, M., Sherer, Y. & Shoenfeld, Y. Tobacco smoking and autoimmune rheumatic diseases. Nat Rev Rheumatol 3, 707–715 (2007). https://doi.org/10.1038/ncprheum0655

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