Tobacco smoking and autoimmune rheumatic diseases


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

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Mechanisms by which smoking contributes to autoimmunity.


  1. 1

    Harel M and Shoenfeld Y (2006) Predicting and preventing autoimmunity, myth or reality. Ann N Y Acad Sci 1069: 322–345

    Article  Google Scholar 

  2. 2

    Shepshelovich D and Shoenfeld Y (2006) Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity. Lupus 15: 183–190

    CAS  Article  Google Scholar 

  3. 3

    Sherer Y et al. (2004) Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. Semin Arthritis Rheum 34: 501–537

    CAS  Article  Google Scholar 

  4. 4

    Molina V and Shoenfeld Y (2005) Infection, vaccines and other environmental triggers of autoimmunity. Autoimmunity 38: 235–245

    CAS  Article  Google Scholar 

  5. 5

    Petri M and Robinson C (1997) Oral contraceptives and systemic lupus erythematosus. Arthritis Rheum 40: 797–803

    CAS  Article  Google Scholar 

  6. 6

    Formica MK et al. (2003) Smoking, alcohol consumption, and risk of systemic lupus erythematosus in the Black Women's Health Study. J Rheumatol 30: 1222–1226

    PubMed  Google Scholar 

  7. 7

    Washio M et al. (2006) Smoking, drinking, sleeping habits, and other lifestyle factors and the risk of systemic lupus erythematosus in Japanese females: findings from the KYSS study. Mod Rheumatol 16: 143–150

    Article  Google Scholar 

  8. 8

    Freemer MM et al. (2006) Association of smoking with dsDNA autoantibody production in systemic lupus erythematosus. Ann Rheum Dis 65: 581–584

    CAS  Article  Google Scholar 

  9. 9

    Costenbader KH et al. (2004) Cigarette smoking and the risk of systemic lupus erythematosus: a meta-analysis. Arthritis Rheum 50: 849–857

    Article  Google Scholar 

  10. 10

    Rubin RL et al. (2005) Effect of cigarette smoke on autoimmunity in murine and human systemic lupus erythematosus. Toxicol Sci 87: 86–96

    CAS  Article  Google Scholar 

  11. 11

    Boeckler P et al. (2005) The combination of complement deficiency and cigarette smoking as risk factor for cutaneous lupus erythematosus in men; a focus on combined C2/C4 deficiency. Br J Dermatol 152: 265–270

    CAS  Article  Google Scholar 

  12. 12

    Miot HA et al. (2005) Association between discoid lupus erythematosus and cigarette smoking. Dermatology 211: 118–122

    Article  Google Scholar 

  13. 13

    Rahman P et al. (1998) Smoking interferes with efficacy of antimalarial therapy in cutaneous lupus. J Rheumatol 25: 1716–1719

    CAS  PubMed  Google Scholar 

  14. 14

    Turchin I et al. (2006) Effect of smoking on skin manifestations and damage in systemic lupus erythematosus [abstract]. ACR/ARHP Annual Scientific Meeting 2006

    Google Scholar 

  15. 15

    Ward MM and Studenski S (1992) Clinical prognostic factors in lupus nephritis. The importance of hypertension and smoking. Arch Intern Med 152: 2082–2088

    CAS  Article  Google Scholar 

  16. 16

    Ho KT et al. (2005) Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events. Rheumatology (Oxford) 44: 1303–1307

    CAS  Article  Google Scholar 

  17. 17

    Ghaussy NO et al. (2003) Cigarette smoking and disease activity in systemic lupus erythematosus. J Rheumatol 30: 1215–1221

    PubMed  Google Scholar 

  18. 18

    Gabriel SE et al. (1999) The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955–1985. Arthritis Rheum 42: 415–420

    CAS  Article  Google Scholar 

  19. 19

    Seldin MF et al. (1999) The genetics revolution and the assault on rheumatoid arthritis. Arthritis Rheum 42: 1071–1079

    CAS  Article  Google Scholar 

  20. 20

    Vessey MP et al. (1987) Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception 35: 457–464

    CAS  Article  Google Scholar 

  21. 21

    Heliovaara M et al. (1993) Smoking and risk of rheumatoid arthritis. J Rheumatol 20: 1830–1835

    CAS  PubMed  Google Scholar 

  22. 22

    Hernandez Avila M et al. (1990) Reproductive factors, smoking, and the risk for rheumatoid arthritis. Epidemiology 1: 285–291

    CAS  Article  Google Scholar 

  23. 23

    Uhlig T et al. (1999) Current tobacco smoking, formal education, and the risk of rheumatoid arthritis. J Rheumatol 26: 47–54

    CAS  PubMed  Google Scholar 

  24. 24

    Krishnan E et al. (2003) Smoking–gender interaction and risk for rheumatoid arthritis. Arthritis Res Ther 5: R158–R162

    Article  Google Scholar 

  25. 25

    Stolt P et al. (2003) Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case–control study, using incident cases. Ann Rheum Dis 62: 835–841

    CAS  Article  Google Scholar 

  26. 26

    Karlson EW et al. (1999) A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum 42: 910–917

    CAS  Article  Google Scholar 

  27. 27

    Criswell LA et al. (2002) Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women's Health Study. Am J Med 112: 465–471

    Article  Google Scholar 

  28. 28

    Costenbader KH et al. (2006) Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med 119: 503. e1–9

    Article  Google Scholar 

  29. 29

    Pedersen M et al. (2006) Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther 8: R133

    Article  Google Scholar 

  30. 30

    Padyukov L et al. (2004) A gene–environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum 50: 3085–3092

    CAS  Article  Google Scholar 

  31. 31

    Klareskog L et al. (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54: 38–46

    CAS  Article  Google Scholar 

  32. 32

    Linn-Rasker SP et al. (2006) Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis 65: 366–371

    CAS  Article  Google Scholar 

  33. 33

    Criswell LA et al. (2006) Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women. Ann Rheum Dis 65: 1163–1167

    CAS  Article  Google Scholar 

  34. 34

    Papadopoulos NG et al. (2005) Does cigarette smoking influence disease expression, activity and severity in early rheumatoid arthritis patients?. Clin Exp Rheumatol 23: 861–866

    CAS  PubMed  Google Scholar 

  35. 35

    Nyhäll-Wåhlin BM et al. (2006) Smoking is a strong risk factor for rheumatoid nodules in early rheumatoid arthritis. Ann Rheum Dis 65: 601–606

    Article  Google Scholar 

  36. 36

    Manfredsdottir VF et al. (2006) The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis. Rheumatology (Oxford) 45: 734–740

    CAS  Article  Google Scholar 

  37. 37

    Hyrich KL et al. (2006) Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 45: 1558–1565

    CAS  Article  Google Scholar 

  38. 38

    Glossop JR et al. (2006) Association between cigarette smoking and release of tumour necrosis factor alpha and its soluble receptors by peripheral blood mononuclear cells in patients with rheumatoid arthritis. Rheumatology (Oxford) 45: 1223–1229

    CAS  Article  Google Scholar 

  39. 39

    Gerli R et al. (2005) Early atherosclerosis in rheumatoid arthritis: effects of smoking on thickness of the carotid artery intima media. Ann N Y Acad Sci 1051: 281–290

    Article  Google Scholar 

  40. 40

    Harrison BJ et al. (2002) Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis. Arthritis Rheum 46: 3312–3316

    Article  Google Scholar 

  41. 41

    Erkan D et al. (2002) A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 41: 924–929

    CAS  Article  Google Scholar 

  42. 42

    Costenbader KH and Karlson EW (2006) Cigarette smoking and autoimmune disease: what can we learn from epidemiology. Lupus 15: 737–745

    CAS  Article  Google Scholar 

  43. 43

    Kravitz MS and Shoenfeld Y (2006) Autoimmunity to protective molecules: is it the perpetuum mobile (vicious cycle) of autoimmune rheumatic diseases. Nat Clin Pract Rheumatol 2: 481–490

    CAS  Article  Google Scholar 

  44. 44

    Shoenfeld Y et al. (2005) Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112: 3337–3347

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Yehuda Shoenfeld.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Harel-Meir, M., Sherer, Y. & Shoenfeld, Y. Tobacco smoking and autoimmune rheumatic diseases. Nat Rev Rheumatol 3, 707–715 (2007).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing