Tobacco Smoking and Lupus

Table of Contents

1. Smoking and the Risk of Developing Lupus
2. Smoking and Anti-DNA Antibodies
3. Skin Disease Activity in Smokers
4. Response to Hydroxychloroquine and Chloroquine
5. Response to Belimumab
6. Heart, Blood Vessel and Clot Risk
7. Organ Damage Over the Years
8. Possible Mechanisms Are Still Hypotheses
9. What Studies Report About Former Smokers
10. What Is Not Known
11. Key Research Papers
12. Connections
13. Featured Videos

Smoking and the Risk of Developing Lupus

Single studies on smoking and the risk of systemic lupus disagreed with each other for years, so researchers pooled them. Four separate pooled analyses (meta-analyses) have now been published, and they point the same way for current smokers.

• 2004, nine studies. A Harvard-led meta-analysis reviewed 52 studies and pooled the 9 that fit (7 case-control and 2 cohort studies). Current smokers had an odds ratio of 1.50 for developing systemic lupus compared with non-smokers, meaning about one and a half times the odds. Former smokers had an odds ratio of 0.98, which is no increase at all.
• 2015, thirteen studies. An updated analysis of 13 studies found a pooled odds ratio of 1.56 for current smokers. For ex-smokers the figure was 1.23, and that result was not statistically significant.
• 2019, nine case-control studies. A review by French and Belgian researchers, called TABALUP, pooled 9 case-control studies and found an odds ratio of 1.49 for current smokers compared with never-smokers, while former smokers were not at increased risk.
• 2020, twelve studies. A Bayesian meta-analysis of 12 studies, covering 3,234 people who developed lupus and 288,336 comparison subjects, found an odds ratio of 1.54 for current smokers. For former smokers there was only a non-significant trend (odds ratio 1.39). The year of publication, sex and age did not explain the differences between studies.

The largest single follow-up study comes from the two Nurses' Health Study cohorts in the United States, which enrolled 121,701 nurses in 1976 and 116,430 in 1989 and followed them with questionnaires every two years. Among 286 women who developed lupus, smoking was not linked to lupus overall. It was linked to one kind: lupus with anti-double-stranded DNA antibodies at diagnosis. Current smokers had a hazard ratio of 1.86 for that kind, and women with more than 10 pack-years of smoking (one pack-year is one pack a day for a year) had a hazard ratio of 1.60. Past smokers did not have a significant increase (hazard ratio 1.31). The authors read this as a sign that smoking is involved specifically in the antibody-positive form of the disease.

A 2014 review by members of the same research group summarised the evidence as pointing to a short-term increase in lupus risk from cigarette smoking in people who are already genetically susceptible.

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Smoking and Anti-DNA Antibodies

Anti-double-stranded DNA antibodies are one of the blood markers most specific to lupus (the autoantibodies page explains the test). Several studies have asked whether smoking is tied to these antibodies, and the answer differs by study design.

• A 2006 study from San Francisco, among people who already had systemic lupus, found that current smokers had an odds ratio of 4.0 for testing positive for anti-double-stranded DNA antibodies compared with never smokers, and an odds ratio of 3.0 compared with former smokers. The link held after the researchers allowed for sex, age at diagnosis, amount smoked, the age smoking began and how long former smokers had been off cigarettes.
• The Nurses' Health Study, described above, found the link between current smoking and new lupus only in the antibody-positive form.
• A 2025 Italian study of 119 people with systemic lupus found that smoking was significantly associated with higher anti-double-stranded DNA antibody levels, and that more pack-years predicted high levels.
• The 2019 TABALUP review, however, did not find a higher rate of anti-double-stranded DNA, anti-Sm or anti-SSA antibodies according to smoking status when it pooled the studies available.

So the antibody link is supported by several individual studies and not by the pooled review. The studies used different groups of people and different ways of measuring smoking, and the reason for the disagreement has not been settled.

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Skin Disease Activity in Smokers

Skin lupus is where the smoking studies are most consistent. Skin activity is usually scored with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), where a higher number means more active or more damaged skin.

• Philadelphia, 2012. A clinic cohort of 218 people with lupus skin disease, seen between 2007 and 2010, found that current smokers had higher median skin activity scores (9.5) than never smokers (7.0) and past smokers (6.0). Current smokers also scored worse on every part of a skin-related quality-of-life questionnaire.
• Europe, 2014. The European Society of Cutaneous Lupus Erythematosus collected data on 1,002 people with skin lupus in 14 countries, with smoking recorded for 838 of them. Of the 499 who had ever smoked, 87.2% were already smoking when they were first diagnosed. Both the skin activity and the skin damage scores were higher in people who had ever smoked than in non-smokers. People with the intermittent form of cutaneous lupus had ever smoked more often than people with the subacute or chronic forms.
• Canada, 2013. Among 1,346 people with systemic lupus in a multicentre Canadian cohort, 14.0% were current smokers and 27.1% past smokers. Current smoking was linked to an active lupus rash (odds ratio 1.63). Having ever smoked was linked to discoid rash (odds ratio 2.36) and to sun sensitivity (odds ratio 1.47). Past smoking was not linked to active skin disease, and smoking was not linked to skin damage or mouth ulcers.
• Montreal, 2009. In a registry of 276 people with systemic lupus, 17.5% of them current smokers, current smoking was linked to total skin damage (odds ratio 2.73), scarring (odds ratio 4.70) and active lupus rash (odds ratio 6.18). The confidence ranges around these numbers are wide (for scarring, 1.04 to 21.2).

The two Canadian studies disagree on skin damage: the larger 2013 study found no link, the smaller 2009 study found one. Both found that current smokers more often had an active rash.

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Response to Hydroxychloroquine and Chloroquine

The 2015 meta-analysis below describes the antimalarial drugs, hydroxychloroquine and chloroquine, as the mainstay of treatment for skin lupus. The current US label for hydroxychloroquine lists the treatment of systemic lupus erythematosus and of chronic discoid lupus erythematosus in adults. The label text says nothing about smoking. The smoking evidence comes from observational studies.

• The 2015 meta-analysis. French researchers found 240 citations and pooled the 10 studies that reported skin response to antimalarials by smoking status, covering 1,398 people with skin lupus (797 smokers and 601 non-smokers). The pooled odds ratio for responding was 0.53 in smokers. The authors described this as a two-fold decrease in the share of patients whose skin improved. They could not separate the results by lupus subtype, by which antimalarial was used, or by dose, because the original studies did not report those details. The page therefore cannot say whether hydroxychloroquine and chloroquine differ in this respect.
• The 2019 TABALUP review found the same pooled odds ratio of 0.53 for the skin response to hydroxychloroquine in smokers.
• The European registry reported that antimalarial treatment worked in 84.3% of cases overall, and worked significantly more often in non-smokers than in people who had ever smoked.
• The Philadelphia cohort found that current smokers on hydroxychloroquine were more often also given a second antimalarial, quinacrine. Its timeline results were mixed. Two to seven months after enrolment, current smokers taking antimalarials alone improved more than never and past smokers (median skin score change of minus 3, against plus 1 and 0). At eight months or later, current smokers taking antimalarials plus at least one other immune-modifying drug improved less (median change of plus 3.5, against minus 1.5 and 0).
• The Canadian cohort of 1,346 people with systemic lupus saw no interaction between smoking and antimalarials in its analysis of skin findings.

A 2012 review of hydroxychloroquine and smoking in skin lupus concluded that smoking seems to reduce how well antimalarials work but that the reason is unclear. The section on mechanisms below describes what has been tested.

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Response to Belimumab

Belimumab is a biologic drug that blocks a protein called B-lymphocyte stimulator. Its current US label lists active systemic lupus erythematosus and active lupus nephritis in patients 5 years of age and older who are receiving standard therapy. The label text says nothing about smoking.

The smoking findings below come from Swedish clinic cohorts.

• 2017. Fifty-eight patients were followed from the start of belimumab for up to 53 months in three Swedish centres. Current smokers had a hazard ratio of 0.103 for reaching a standard response measure (the SLE Responder Index) compared with non-smokers, meaning a much lower chance of response and a longer wait for it. People who already had organ damage before starting also responded less often (hazard ratio 0.449). The 2019 TABALUP review lists the belimumab effect with the same figure, a hazard ratio of 0.10.
• 2018. In 62 patients treated between 2011 and 2017, current or previous smokers were more likely to have unchanged or worse skin and mouth disease on belimumab than never smokers (odds ratio 6.4), and this held after the researchers allowed for antimalarial use. Smoking had no effect on how joint disease responded to belimumab.

Both studies are small, and the 2018 study grouped current and previous smokers together, so it cannot say whether quitting changes the result.

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Heart, Blood Vessel and Clot Risk

People with systemic lupus already have a higher risk of heart and blood vessel disease than the general population. The studies below ask whether smoking adds to it.

• Cardiovascular disease, 2022 meta-analysis. Ten studies with 6,984 participants were pooled. Smoking was more common among people with lupus who had cardiovascular disease (39.28%) than among those who did not (31.36%). Current smokers had a risk of 1.42 for developing cardiovascular disease compared with never smokers. The authors rated the overall quality of the evidence as moderate to low and noted several negative studies among those included.
• Blood clots, 2009. In a multi-ethnic cohort of 1,930 people with systemic lupus, smoking was a risk factor for a documented blood clot (thrombosis), with an odds ratio of 1.26. Antiphospholipid antibodies carried a much larger risk (odds ratio 3.22). In the same cohort, hydroxychloroquine use was linked to fewer clots (odds ratio 0.62) after the researchers adjusted for disease severity.
• Peripheral artery disease, 2020. A Spanish study of 216 people with systemic lupus found that tobacco use at any time was associated with peripheral arteriopathy, disease of the arteries away from the heart.

The clot study counted any history of thrombosis and did not separate current from former smoking in its summary. The antiphospholipid antibody link is covered on the Antiphospholipid Syndrome page.

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Organ Damage Over the Years

Lupus doctors track permanent harm with a damage index (the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). Several cohorts have compared it by smoking status.

• United States, 2021. In a cohort of newly diagnosed patients seen at one academic centre from 2008 to 2016, the median time until damage increased or the patient died was 4.5 years in current smokers and 3.4 years in former smokers, against 9.0 years in never smokers. After adjustment, current smokers built up damage at about twice the rate of never smokers (hazard ratio 2.18), as did people with more than 10 pack-years (hazard ratio 2.35).
• Argentina, 2025. Among 623 consecutive patients, 16% were current smokers. Current smoking was linked to severe damage, defined as a damage score of 3 or more (odds ratio 1.82), along with older age, longer disease and past cyclophosphamide treatment.
• Brazil, 2016. In 105 patients followed for a mean of 8.98 years, those never exposed to smoke had 0.78 times the risk of moving into any recorded damage compared with those ever exposed, a group that included secondhand smoke.
• Spain, 2020. In the study of 216 patients, 53% had smoked at some point. Any past smoking history remained linked to damage of the retina, the light-sensing layer of the eye, in a multivariate analysis. Only 54.8% of current smokers recalled having been told about the harms of smoking, against 83.3% of never smokers.

The Spanish retina finding is worth reading carefully: the abstract does not say which kind of retinal damage was counted, and retinal damage is also a known risk of long-term hydroxychloroquine (see the antimalarials page). The study does not settle how the two relate.

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Possible Mechanisms Are Still Hypotheses

No study has shown how tobacco smoke worsens lupus. Reviews list several candidate pathways; each is a hypothesis.

• Immune cells and inflammation. A 2018 review of smoking and the development of systemic lupus lists effects on T cells and B cells, inflammatory signalling proteins (cytokines), oxidative stress, and the formation of short-lived DNA adducts, which are chemicals from smoke bound to DNA. The time pattern in the studies, with risk linked mainly to current smoking, is part of what these ideas try to explain.
• The skin. A 2025 review of smoking in cutaneous lupus proposes that cigarette smoke may act through oxidative stress, interferon signalling, recruitment of inflammatory cells, extracellular vesicles (tiny particles cells release), immune regulation, epigenetic changes and heat injury. The authors write that minimal work has examined the molecular drivers of the differences seen in smokers.
• Anti-DNA antibodies. The link between current smoking and anti-double-stranded DNA antibodies, described above, is one reason researchers suspect smoking acts on antibody formation.
• Drug handling. One idea is that smoking changes how the body handles hydroxychloroquine. Two blood-level studies did not support it. A French analysis of 509 patients taking 400 mg a day found no association between smoking and blood hydroxychloroquine levels, and no drug interaction with medicines that speed up or slow down the cytochrome P450 drug-processing enzymes. A Korean study of 189 patients also found no significant association between smoking and hydroxychloroquine levels.
• Immune cells on hydroxychloroquine. A small French study of 58 patients on hydroxychloroquine found that higher drug levels were linked to fewer memory-type helper T cells (CD4+CD45RO+), while smoking was linked to more of them. This pulls in the opposite direction from the drug but does not show that it explains the weaker response.

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What Studies Report About Former Smokers

None of the studies on this page assigned people to quit and then measured what happened. What they offer instead is a comparison of former smokers with current and never smokers.

• Risk of developing lupus. Former smokers did not show a significant increase in any of the four meta-analyses (odds ratios of 0.98, 1.23 and 1.39, and no increase in the TABALUP review) or in the Nurses' Health Study (hazard ratio 1.31). The 2018 review of mechanisms describes the risk as decreasing 5 years after smoking stops.
• Skin activity. In the Philadelphia cohort, past smokers had the lowest median skin activity score (6.0), compared with 9.5 in current smokers. In the Canadian cohort, past smoking was not linked to active skin disease, but having ever smoked was still linked to discoid rash and sun sensitivity.
• Antibodies. Current smokers had three times the odds of former smokers of testing positive for anti-double-stranded DNA antibodies in the 2006 San Francisco study (odds ratio 3.0).
• Organ damage. In the 2021 US cohort, former smokers reached their first damage increase sooner than never smokers (median 3.4 against 9.0 years). Former smokers in that cohort were also older and more often had late-onset lupus (54%, against 33% of never smokers).

The authors of the 2015 antimalarial meta-analysis wrote that stopping smoking deserves attention in people whose skin lupus does not respond to treatment, and the authors of the 2019 TABALUP review called stopping smoking one of the main goals for doctors who treat lupus. Those are the authors' conclusions. Decisions about treatment belong with a clinician. Nicotine itself, studied apart from tobacco smoke, is covered under Nicotine: The Research.

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What Is Not Known

• Cause or association. Every study on this page is observational. Smokers may differ from non-smokers in other ways, such as income, insurance, age or other health habits, that the studies only partly adjust for.
• Secondhand smoke. The 2019 TABALUP review describes the data on passive smoking as scarce and controversial. See Secondhand Smoke for the wider evidence.
• Other nicotine products. The studies here measured cigarette smoking. They did not study electronic cigarettes, heated tobacco, smokeless tobacco or nicotine replacement, so they say nothing about those products in lupus.
• Which antimalarial, what dose. The 2015 meta-analysis could not compare hydroxychloroquine with chloroquine or look at dose, because the original studies did not report it.
• Why the drugs work less well. Blood-level studies did not find that smoking lowers hydroxychloroquine levels, and no other explanation has been proven.
• Other biologics. The smoking evidence on biologics found for this page concerns belimumab from small Swedish cohorts. The studies read for this page did not report on anifrolumab or rituximab.
• Antibodies. Individual studies and the pooled review disagree on whether smoking is tied to anti-double-stranded DNA antibodies.
• Evidence quality. The heart-disease meta-analysis rated its evidence moderate to low, and several of the treatment studies enrolled fewer than 100 people.

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Key Research Papers

1. Parisis D, Bernier C, Chasset F, Arnaud L. Impact of tobacco smoking upon disease risk, activity and therapeutic response in systemic lupus erythematosus: A systematic review and meta-analysis. Autoimmun Rev. 2019;18(11):102393. PubMed PMID: 31520802
2. Chasset F, Francès C, Barete S, Amoura Z, Arnaud L. Influence of smoking on the efficacy of antimalarials in cutaneous lupus: a meta-analysis of the literature. J Am Acad Dermatol. 2015;72(4):634-9. PubMed PMID: 25648824
3. Piette EW, Foering KP, Chang AY, Okawa J, Ten Have TR, Feng R, Werth VP. Impact of smoking in cutaneous lupus erythematosus. Arch Dermatol. 2012;148(3):317-22. PubMed PMID: 22105815
4. Costenbader KH, Kim DJ, Peerzada J, Lockman S, Nobles-Knight D, Petri M, Karlson EW. Cigarette smoking and the risk of systemic lupus erythematosus: a meta-analysis. Arthritis Rheum. 2004;50(3):849-57. PubMed PMID: 15022327
5. Jiang F, Li S, Jia C. Smoking and the risk of systemic lupus erythematosus: an updated systematic review and cumulative meta-analysis. Clin Rheumatol. 2015;34(11):1885-92. PubMed PMID: 26188616
6. Chua MHY, Ng IAT, W L-Cheung M, Mak A. Association Between Cigarette Smoking and Systemic Lupus Erythematosus: An Updated Multivariate Bayesian Metaanalysis. J Rheumatol. 2020;47(10):1514-1521. PubMed PMID: 31787611
7. Barbhaiya M, Tedeschi SK, Lu B, Malspeis S, Kreps D, Sparks JA, Karlson EW, Costenbader KH. Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses' Health Study cohorts. Ann Rheum Dis. 2018;77(2):196-202. PubMed PMID: 28988206
8. Takvorian SU, Merola JF, Costenbader KH. Cigarette smoking, alcohol consumption and risk of systemic lupus erythematosus. Lupus. 2014;23(6):537-44. PubMed PMID: 24763538
9. Freemer MM, King TE Jr, Criswell LA. Association of smoking with dsDNA autoantibody production in systemic lupus erythematosus. Ann Rheum Dis. 2006;65(5):581-4. PubMed PMID: 16150789
10. Borrelli R, Nicola S, Corradi F, Lo Sardo L, Badiu I, Quinternetto A, et al. Impact of Smoking, Steroid Use and Immunosuppression on Anti-dsDNA Antibodies in Systemic Lupus Erythematosus. Int J Mol Sci. 2025;26(17):8705. PubMed PMID: 40943621
11. Kuhn A, Sigges J, Biazar C, Ruland V, Patsinakidis N, Landmann A, Amler S, Bonsmann G. Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database. Br J Dermatol. 2014;171(3):571-9. PubMed PMID: 24673427
12. Bourré-Tessier J, Peschken CA, Bernatsky S, Joseph L, Clarke AE, Fortin PR, et al. Association of smoking with cutaneous manifestations in systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2013;65(8):1275-80. PubMed PMID: 23401335
13. Turchin I, Bernatsky S, Clarke AE, St-Pierre Y, Pineau CA. Cigarette smoking and cutaneous damage in systemic lupus erythematosus. J Rheumatol. 2009;36(12):2691-3. PubMed PMID: 19884279
14. Ezra N, Jorizzo J. Hydroxychloroquine and smoking in patients with cutaneous lupus erythematosus. Clin Exp Dermatol. 2012;37(4):327-34. PubMed PMID: 22582908
15. Parodis I, Sjöwall C, Jönsen A, Ramsköld D, Zickert A, Frodlund M, et al. Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus. Autoimmun Rev. 2017;16(4):343-351. PubMed PMID: 28216072
16. Parodis I, Gomez A, Frodlund M, Jönsen A, Zickert A, Sjöwall C, Bengtsson AA, Gunnarsson I. Smoking reduces the efficacy of belimumab in mucocutaneous lupus. Expert Opin Biol Ther. 2018;18(8):911-920. PubMed PMID: 29958508
17. Zhang WT, Liu Z, Zhu BC, Cui ZY, Huang C, Wang XJ, et al. Effects of tobacco smoking on cardiovascular disease in patients with systemic lupus erythematosus: A systematic review and meta-analysis. Front Immunol. 2022;13:967506. PubMed PMID: 35967334
18. Kaiser R, Cleveland CM, Criswell LA. Risk and protective factors for thrombosis in systemic lupus erythematosus: results from a large, multi-ethnic cohort. Ann Rheum Dis. 2009;68(2):238-41. PubMed PMID: 18782792
19. McKown T, Schletzbaum M, Unnithan R, Wang X, Ezeh N, Bartels CM. The effect of smoking on cumulative damage in systemic lupus erythematosus: An incident cohort study. Lupus. 2021;30(4):620-629. PubMed PMID: 33470148
20. Cosatti MA, Muñoz SA, Tamborenea MT, García M, Curti A, Cappuccio A, et al. Current smoking is related to severe damage in systemic lupus erythematosus patients. Lupus. 2025;34(1):28-33. PubMed PMID: 39556029
21. Montes RA, Mocarzel LO, Lanzieri PG, Lopes LM, Carvalho A, Almeida JR. Smoking and Its Association With Morbidity in Systemic Lupus Erythematosus Evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index: Preliminary Data and Systematic Review. Arthritis Rheumatol. 2016;68(2):441-8. PubMed PMID: 26359794
22. Rúa-Figueroa I, Erausquin C, Rua-Figueroa C, González-Martín J, Naranjo A, Ojeda S, et al. Tobacco smoking is an independent factor associated with retinal damage in systemic lupus erythematosus: a cross-sectional and retrospective study. Rheumatol Int. 2020;40(3):367-374. PubMed PMID: 31773393
23. Speyer CB, Costenbader KH. Cigarette smoking and the pathogenesis of systemic lupus erythematosus. Expert Rev Clin Immunol. 2018;14(6):481-487. PubMed PMID: 29724134
24. Homer RO, Eldaboush A, Kang D, Ahmed NS, Khosravi-Hafshejani T, Liu ML, Werth VP. Ashes to Rashes: An Exploration of the Intersection Between Smoking and Cutaneous Lupus Erythematosus. Biomolecules. 2025;15(9):1250. PubMed PMID: 41008557
25. Jallouli M, Galicier L, Zahr N, Aumaître O, Francès C, Le Guern V, et al. Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol. 2015;67(8):2176-84. PubMed PMID: 25989906
26. Yeon Lee J, Lee J, Ki Kwok S, Hyeon Ju J, Su Park K, Park SH. Factors Related to Blood Hydroxychloroquine Concentration in Patients With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2017;69(4):536-542. PubMed PMID: 27390146
27. Sailler L, Puissant B, Méliani P, Castex JO, Saivin S, Adoue D, et al. Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients. Ann N Y Acad Sci. 2007;1108:41-50. PubMed PMID: 17893969

Drug labels: the current US labels for belimumab and hydroxychloroquine on DailyMed (National Library of Medicine), read for the approved uses described above.

PubMed Topic Searches

1. PubMed: smoking and the risk of systemic lupus
2. PubMed: smoking and antimalarial response in skin lupus
3. PubMed: smoking and belimumab
4. PubMed: smoking, heart disease and clots in lupus
5. PubMed: smoking and organ damage in lupus

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Connections

• Lupus — the main topic page
• Cutaneous Lupus and Photoprotection — skin lupus forms and treatment
• Hydroxychloroquine and Antimalarials — the drugs whose response smoking is linked to
• Biologics for Lupus — belimumab and the newer drugs
• Lupus Autoantibodies — what the anti-DNA test measures
• Anti-dsDNA Test — the lab test itself
• Antiphospholipid Syndrome — the strongest clot risk in lupus
• Secondhand Smoke — passive exposure
• Nicotine: The Research — the drug apart from tobacco smoke

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