3.14 Skin

Last updated: June 2021
Suggested citation: Purcell, K, Winnall, WR, Greenhalgh, EM & Winstanley, MH. 3.14 Skin. In Greenhalgh, EM, Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2021. Available from  http://www.tobaccoinaustralia.org.au/3-14-effects-of-smoking-on-the-skin

 

Smoking adversely affects the skin. Delayed wound healing is discussed in Chapter 3, Section 3.15.1.2 and other smoking-associated skin conditions are detailed in this section.

3.14.1 Facial appearance and premature skin ageing

Smoking affects facial appearance in men and women, independent of sun exposure and age. Increased wrinkling1-5 and altered complexion colour1 have been attributed to smoking, as have elastosis (loss of elasticity in the skin resulting from degeneration of connective tissue) and, in men, telangiectasia (dilatation of fine blood vessels in the skin visible as fine red lines).6 Smoking is also associated with looking older than a person’s age.7 One study found that smokers appear up to 4.7 years older than non-smokers.8 Two studies of twins have also confirmed that smokers tend to look older.9, 10

Studies have shown that in the majority of cases smokers and non-smokers could be correctly distinguished as such by examining photographs of the face and temple region.8, 11 A twin study found that participants judged the faces of the non-smokers more attractive compared with smokers.11, 12

Visible wrinkling is most evident in older smokers, but even smokers aged in their 20s and 30s may show evidence of microscopic superficial wrinkling.4 Smoking is associated with an increased severity of wrinkles including forehead, crow's feet, and glabellar lines (vertical lines between the eyebrows); under-eye puffiness and lines around the mouth.13 Combined exposure to both sunlight and tobacco smoke causes a greater degree of damage than exposure to one agent alone,14 possibly through the phototoxic effects of tobacco smoke condensate, which increase the skin’s vulnerability to UV radiation.15 Even non-facial, non-sun-exposed skin may be more wrinkled in smokers than non-smokers.16

A possible mechanism for premature wrinkling is that smoke affects the function of human skin fibroblasts (cells present in connective tissue that produce collagen and elastin), thereby accelerating the appearance of ageing.3, 17, 18 Exposure to tobacco smoking and sunlight can also cause changes to the structure and amount of elastic fibres and fibrillar collagens in the dermal extracellular spaces.19 Heavy smokers (>40 per day for 5 years) have signs of damage to their skin structure and function compared to non-smokers. Heavy smokers had changes to their skin’s elastic fibre network and increased stiffness of the dermis and epidermis layers of their skin.20 A genetic study showed that the skin of smokers had differences in the use of genes that indicated a possible increase in permeability of the skin.21 Studies also suggest a connection between wrinkling in smokers and the development of chronic obstructive pulmonary disease (COPD). Smokers with severe facial wrinkling may have a higher susceptibility to developing COPD; possible mechanisms being damage to collagen and elastin, which are important to both skin and lung function.22

3.14.2 Acne and other sebaceous conditions

A review of smoking-associated skin conditions published in 2010 noted that the evidence linking acne to smoking is conflicting. Only two of the five studies reviewed reported an association.23 Another study, published after the review, found a higher prevalence of comedonal post-adolescent acne in women who were smokers compared with non-smokers.24

The evidence linking some other sebaceous conditions with smoking is stronger. Smokers appear to be more at risk for hidradenitis suppurativa (clusters of chronic abscesses or cysts in areas of sweat or sebaceous glands).23 A large retrospective cohort analysis found that the incidence of hidradenitis suppurativa in smokers is double that of non-smokers (overall incidence of HS was 0·20% among tobacco smokers and 0·11% among non-smokers.25 Current smokers have more severe disease than non-smokers and also have a poorer response to first line treatment such as oral antibiotics, topical antibiotics, intralesional corticosteroids, or antibacterial washes/creams/lotions compared with never smokers.26

A case–control study found smoking was a risk factor for epidermal inclusion cysts in men, but not in women.27

3.14.3 Dermatitis

Multiple studies have concluded that there is relationship between smoking and dermatitis. A 2016 US study of 1,301 participants, aged 20–59 years using the 2003–2004 National Health and Nutrition Examination Survey (NHANES) database found that smoking has a significant association with active hand dermatitis.28 A dose response relationship was observed in this study. Heavy smokers (>15 g tobacco daily) were 5.11 times more likely to have active hand dermatitis compared with non-smokers. Those with serum cotinine >3 ng/ml (a biomarker indicating nicotine exposure) were also more likely to have active hand dermatitis, compared with those with lower serum cotinine.28

A 2016 systematic review and meta-analysis included 86 studies, with 20 studies having valid data to assess the effects of active smoking, 66 for passive exposure to tobacco smoke, and 23 for maternal smoking during pregnancy.29 Atopic dermatitis was associated with both active smoking and exposure to second-hand smoke, but not maternal smoking during pregnancy.29 The association between active smoking and atopic dermatitis was significant in both children and adults.29 A 2017 systematic review found that seven of eight articles described a positive relationship between smoking and allergic or irritant contact dermatitis, while nine of nineteen articles found a positive association between smoking and hand eczema and concluded that smoking may be an important risk factor for both allergic and irritant contact dermatitis as well as hand eczema.30 A secondary analysis of cross sectional data in Korea examined the relationship between smoking, atopic dermatitis and asthma found that atopic dermatitis prevalence in women but not men was associated with current smoking status.31

Cigarettes themselves have been reported to induce allergic contact dermatitis in both occupational and non-occupational settings.23, 32

3.14.4 Psoriasis

Psoriasis is a chronic autoimmune disease, the most common type being plaque psoriasis, characterised by scaly patches on the top layer of the skin.23, 33-35 Smoking is a well-established risk factor for psoriasis. Higher intensity smoking is associated with clinically severe disease,23, 36, 37 and psoriasis is less responsive to treatment in smokers.23, 38 In a meta-analysis from 2015, eight of 11 studies with data on smoking and the severity of psoriasis suggested that severity increases with smoking status, number of cigarettes smoked and pack-years of smoking.34 The risk of developing psoriasis decreases progressively with increased time since smoking cessation.38 A later meta-analysis from 2020 showed that the prevalence of ever smoking was increased 1.84-fold in people with psoriasis compared with the general population.39 People who were ever-smokers (1.60), current smokers (1.63) or former smokers (1.36) were at higher risk of psoriasis than non-smokers in a meta-analysis of 34 studies from 2020.40 Smokers were also less likely to respond to six months of treatment for psoriasis.40

A 2015 twin study found that smoking and childhood exposure to second hand smoke are significantly associated with psoriasis,41 and that the risk for psoriasis increased substantially for smokers with a history of >5 pack-years.41 Another study found that current smoking increased the risk of psoriasis, particularly for smokers who smoked >25 cigarettes per day and for >20 pack-years.42

Multiple mechanisms are thought to explain the association between smoking and psoriasis. Smoking enhances the expression of genes known to confer an increased risk of psoriasis. It increases oxidative damage—the free radicals in cigarette smoke, for example, triggering a cascade of systemic reactions.38 Nicotine also promotes a chronic pro-inflammatory state by activating innate immune cells and T-lymphocytes.38

The form of psoriasis known as palmoplantar pustulosis (which is confined to the hands and soles and is also known as ‘pustular psoriasis of the extremities’) is strongly associated with smoking;23 in one study, the prevalence of ever-smoking was 36 times higher among those with palmoplantar pustulosis than among those with other dermatologic patients.43 High severity palmoplantar pustulosis was more likely to occur in those addicted to smoking and with higher pack number per year smoked, in a study of 51 people with this condition.44

3.14.5 Lupus erythematosus

Lupus erythematosus is a chronic autoimmune condition that has numerous different types. The systemic form is referred to as systemic lupus erythematosus (SLE). Other types of lupus erythematosus often only involve the skin (cutaneous). Skin symptoms are often a rash and sometimes scaly patches or ulcers. Systemic symptoms may include fever, joint and muscle pain, weight loss, fatigue and many others.45

A meta-analysis of seven case–control studies and two cohort studies found smoking to be associated with SLE. Current smokers have about a 50% increased risk of SLE compared with never smokers.46 The risk was not elevated for ex-smokers in this study. Smokers also have increased SLE disease activity,47 and poorer health-related quality of life has been reported.48 The extent of skin manifestations of SLE and skin damage were associated with smoking exposure (in pack-years) in a dose-dependent manner.49 However, there are studies that failed to find similar results. In 2014, the US Surgeon General’s report concluded that there is mixed and therefore inadequate evidence that smoking causes SLE, or affects its severity or treatment.50 The report noted that, at the time, while seven studies had found an association, four had not, and that many of the studies were small and underpowered.50

Since the release of the US Surgeon General’s report in 2014, several meta-analyses have been published. A 2019 meta-analysis of twelve eligible studies comprising 3,234 individuals who developed SLE and 288,336 control subjects revealed a significant association between SLE occurrence and current-smoking status. The association between SLE and former smoking was not significant.51 Another 2019 meta-analysis of nine case-controls studies found an increased risk of SLE in current-smokers compared to never-smokers, while former-smokers were not at increased risk of SLE. Smoking also influences the disease course and reduces the effectiveness of some therapeutic treatments for SLE.52 A 2017 study of 5,018 patients with SLE and 25,090 age- and sex-matched controls also found a significant association between smoking and SLE.53 A large female cohort study in 2017 found that an increased risk of SLE associated with smoking >10 pack-years compared with never smokers.54

Smoking is independent predictor of retinal damage in SLE patients55 and may be associated with more rapid cumulation of end-organ damage.56 Smoking may also be associated with distinct clinical phenotypes of SLE. Heavy smokers with SLE were more likely to have neurological disorder, discoid rash and photosensitivity, and less likely to have haematological disorder, renal disorder and non-erosive arthritis, compared to non-smokers with SLE.57

The 2014 US Surgeon General’s report concluded that smoking is a risk factor for cutaneous lupus, but noted that the evidence is too limited to determine if it is a cause.50 Numerous studies predict that smoking increases the risk of developing some of the cutaneous forms of lupus23, 53, 54, 58, 59 and has been reported to decrease the effectiveness of the antimalarial drugs that are sometimes prescribed for cutaneous lupus.60

3.14.6 Other skin conditions

Smoking is a risk factor for the development of alopecia (hair loss, usually from the scalp) and may increase the likelihood of premature grey hair.23

For information about anal fistula, see Section 3.17.2.


Relevant news and research

For recent news items and research on this topic, click  here. ( Last updated  March 2024)

 

References

1. Model D. Smoker's face: an underrated clinical sign? British Medical Journal (Clinical Research Edition), 1985; 291(6511):1760-2. Available from: https://www.ncbi.nlm.nih.gov/pubmed/3936573

2. Ernster VL, Grady D, Miike R, Black D, Selby J, et al. Facial wrinkling in men and women, by smoking status. American Journal of Public Health, 1995; 85(1):78-82. Available from: https://www.ncbi.nlm.nih.gov/pubmed/7832266

3. Yin L, Morita A, and Tsuji T. Skin ageing induced by ultraviolet exposure and tobacco smoking: evidence from epidemiological and molecular studies. Photodermatology Photoimmunology Photomedicine, 2001; 17:178-83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11499540

4. Koh JS, Kang H, Choi SW, and Kim HO. Cigarette smoking associated with premature facial wrinkling: image analysis of facial skin replicas. International Journal of Dermatology, 2002; 41(1):21-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11895509

5. Leung W and Harvey I. Is skin ageing in the elderly caused by sun exposure or smoking? British Journal of Dermatology, 2002; 147:1187-91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12452869

6. Kennedy C, Bastiaens MT, Bajdik CD, Willemze R, Westendorp RG, et al. Effect of smoking and sun on the aging skin. Journal of Investigative Dermatology, 2003; 120(4):548-54. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12648216

7. Schou AL, Molbak ML, Schnor P, Gronbaek M, and Tolstrup JS. Alcohol consumption, smoking and development of visible age-related signs: a prospective cohort study. Journal of Epidemiology and Community Health, 2017; 71(12):1177-84. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29114032

8. Raitio A, Kontinen J, Rasi M, Bloigu R, Röning J, et al. Comparison of clinical and computerised image analyses in the assessment of skin ageing in smokers and non-smokers. Acta Dermato Venereologica, 2004; 84:422-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15844630

9. Guyuron B, Rowe DJ, Weinfeld AB, Eshraghi Y, Fathi A, et al. Factors contributing to the facial aging of identical twins. Plastic and Reconstructive Surgery, 2009; 123(4):1321-31. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19337100

10. Martires KJ, Fu P, Polster AM, Cooper KD, and Baron ED. Factors that affect skin aging: a cohort-based survey on twins. Archives of Dermatology, 2009; 145(12):1375-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20026845

11. Skinner AL, Woods A, Stone CJ, Penton-Voak I, and Munafo MR. Smoking status and attractiveness among exemplar and prototypical identical twins discordant for smoking. Royal Society Open Science, 2017; 4(12):161076. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29308214

12. Skinner AL, Woods A, Stone CJ, Penton-Voak I, and Munafo MR. Correction to 'Smoking status and attractiveness among exemplar and prototypical identical twins discordant for smoking'. Royal Society Open Science, 2018; 5(2):172231. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29517075

13. Goodman GD, Kaufman J, Day D, Weiss R, Kawata AK, et al. Impact of smoking and alcohol use on facial aging in women: Results of a large multinational, multiracial, cross-sectional survey. The Journal of Clinical and Aesthetic Dermatology, 2019; 12(8):28-39. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31531169

14. Kadunce DP, Burr R, Gress R, Kanner R, Lyon JL, et al. Cigarette smoking: risk factor for premature facial wrinkling. Annals of Internal Medicine, 1991; 114(10):840-4. Available from: https://www.ncbi.nlm.nih.gov/pubmed/2014944

15. Placzek M, Kerkmann U, Bell S, Koepke P, and Przybilla B. Tobacco smoke is phototoxic. British Journal of Dermatology, 2004; 150:991-3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15149514

16. Helfrich Y, Yu L, Ofori A, Hamilton T, Lambert J, et al. Effect of smoking on ageing of photoprotected skin. Archives of Dermatology, 2007; 143:397-402. Available from: http://archderm.ama-assn.org/cgi/content/full/143/3/397

17. Kim JN, Jeong JT, Jeong SH, Kim SA, Lee KG, et al. Cigarette smoke-induced Egr-1 represses T beta R-II expression in human skin dermal fibroblasts. Toxicology, 2010; 275(1-3):29-35. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20621662

18. Ono Y, Torii K, Fritsche E, Shintani Y, Nishida E, et al. Role of the aryl hydrocarbon receptor in tobacco smoke extract-induced matrix metalloproteinase-1 expression. Experimental Dermatology, 2013; 22(5):349-53. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23614742

19. Langton AK, Tsoureli-Nikita E, Griffiths CEM, Katsambas A, Antoniou C, et al. Lysyl oxidase activity in human skin is increased by chronic ultraviolet radiation exposure and smoking. British Journal of Dermatology, 2017; 176(5):1376-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27514484

20. Langton AK, Tsoureli-Nikita E, Merrick H, Zhao X, Antoniou C, et al. The systemic influence of chronic smoking on skin structure and mechanical function. Journal of Pathology, 2020; 251(4):420-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32472631

21. Percoco G, Patatian A, Eudier F, Grisel M, Bader T, et al. Impact of cigarette smoke on physical-chemical and molecular proprieties of human skin in an ex vivo model. Experimental Dermatology, 2020. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32939877

22. Freiman A, Bird G, Metelitsa AI, Barankin B, and Lauzon GJ. Cutaneous effects of smoking. Journal of Cutaneous Medicine and Surgery, 2004; 8(6):415-23. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15988548

23. Metelitsa AI and Lauzon GJ. Tobacco and the skin. Clinics in Dermatology, 2010; 28(4):384-90. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20620754

24. Capitanio B, Sinagra JL, Bordignon V, Cordiali Fei P, Picardo M, et al. Underestimated clinical features of postadolescent acne. Journal of the American Academy of Dermatology, 2010; 63(5):782-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20619486

25. Garg A, Papagermanos V, Midura M, and Strunk A. Incidence of hidradenitis suppurativa among tobacco smokers: a population-based retrospective analysis in the U.S.A. British Journal of Dermatology, 2018; 178(3):709-14. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28960235

26. Denny G and Anadkat MJ. The effect of smoking and age on the response to first-line therapy of hidradenitis suppurativa: An institutional retrospective cohort study. Journal of the American Academy of Dermatology, 2017; 76(1):54-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27692736

27. Lin SH, Yang YC, Chen W, and Wu WM. Facial epidermal inclusion cysts are associated with smoking in men: a hospital-based case-control study. Dermatologic Surgery, 2010; 36(6):894-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20482735

28. Lai YC and Yew YW. Smoking and hand dermatitis in the United States adult population. Annals of Dermatology, 2016; 28(2):164-71. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27081262

29. Kantor R, Kim A, Thyssen JP, and Silverberg JI. Association of atopic dermatitis with smoking: A systematic review and meta-analysis. Journal of the American Academy of Dermatology, 2016; 75(6):1119-25 e1. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27542586

30. Zimmer KA, Armbrecht ES, and Burkemper NM. The association of smoking with contact dermatitis and hand eczema - a review. International Journal of Dermatology, 2018; 57(4):375-87. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28960277

31. Moon HM, Kim Y, Kwak Y, and Kim K. Association between smoking type and prevalence of atopic dermatitis and asthma in men and women. International Journal of Nursing Practice, 2018; 24(6):e12680. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30397983

32. Glick ZR, Saedi N, and Ehrlich A. Allergic contact dermatitis from cigarettes. Dermatitis, 2009; 20(1):6-13. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19321114

33. Wolk K, Mallbris L, Larsson P, Rosenblad A, Vingard E, et al. Excessive body weight and smoking associates with a high risk of onset of plaque psoriasis. Acta Dermato-Venereologica, 2009; 89(5):492-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19734975

34. Richer V, Roubille C, Fleming P, Starnino T, McCourt C, et al. Psoriasis and smoking: A systematic literature review and meta-analysis with qualitative analysis of effect of smoking on psoriasis severity. Journal of Cutaneous Medicine and Surgery, 2016; 20(3):221-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26553732

35. Pezzolo E and Naldi L. The relationship between smoking, psoriasis and psoriatic arthritis. Expert Review of Clinical Immunology, 2019; 15(1):41-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30380949

36. Attwa E and Swelam E. Relationship between smoking-induced oxidative stress and the clinical severity of psoriasis. Journal of the European Academy of Dermatology and Venereology, 2011; 25(7):782-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21039915

37. Gerdes S, Zahl VA, Weichenthal M, and Mrowietz U. Smoking and alcohol intake in severely affected patients with psoriasis in Germany. Dermatology, 2010; 220(1):38-43. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19996578

38. Armstrong AW, Armstrong EJ, Fuller EN, Sockolov ME, and Voyles SV. Smoking and pathogenesis of psoriasis: a review of oxidative, inflammatory and genetic mechanisms. British Journal of Dermatology, 2011; 165(6):1162-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21777217

39. Gazel U, Ayan G, Solmaz D, Akar S, and Aydin SZ. The impact of smoking on prevalence of psoriasis and psoriatic arthritis. Rheumatology, 2020; 59(10):2695-710. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32500136

40. Zhou H, Wu R, Kong Y, Zhao M, and Su Y. Impact of smoking on psoriasis risk and treatment efficacy: a meta-analysis. Journal of International Medical Research, 2020; 48(10):300060520964024. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33121308

41. Lonnberg AS, Skov L, Skytthe A, Kyvik KO, Pedersen OB, et al. Smoking and risk for psoriasis: a population-based twin study. International Journal of Dermatology, 2016; 55(2):e72-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26275356

42. Dai YX, Wang SC, Chou YJ, Chang YT, Chen TJ, et al. Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study. Journal of the American Academy of Dermatology, 2019; 80(3):727-34. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30528570

43. Miot H, Miot L, Lopes P, Haddad G, and Marques S. Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case-control study. Journal of the European Academy of Dermatology and Venereology, 2009; 23(10):1173–7. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1468-3083.2009.03282.x

44. Putra-Szczepaniak M, Reich A, Jankowska-Konsur A, Czarnecka A, Baglaj-Oleszczuk M, et al. Pack-year cigarette smoking affects the course of palmoplantar pustulosis. Advances in Clinical and Experimental Medicine, 2021; 30(2):189-95. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33636060

45. Healthdirect. Lupus. Sydney, Australia: Healthdirect, 2019. Available from: https://www.healthdirect.gov.au/lupus.

46. Costenbader KH, Kim DJ, Peerzada J, Lockman S, Nobles-Knight D, et al. Cigarette smoking and the risk of systemic lupus erythematosus: a meta-analysis. Arthritis and Rheumatism, 2004; 50(3):849-57. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15022327

47. Ghaussy NO, Sibbitt W, Jr., Bankhurst AD, and Qualls CR. Cigarette smoking and disease activity in systemic lupus erythematosus. Journal of Rheumatology, 2003; 30(6):1215-21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12784392

48. Barta Z, Harrison MJ, Wangrangsimakul T, Shelmerdine J, Teh LS, et al. Health-related quality of life, smoking and carotid atherosclerosis in white British women with systemic lupus erythematosus. Lupus, 2010; 19(3):231-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20007814

49. Ezeh N, McKown T, Garg S, and Bartels CM. Smoking exposure in pack-years predicts cutaneous manifestations and damage in systemic lupus erythematosus. Lupus, 2021:961203321995257. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33626970

50. US Department of Health and Human Services. The health consequences of smoking - 50 years of progress. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Available from: https://www.ncbi.nlm.nih.gov/books/NBK179276/pdf/Bookshelf_NBK179276.pdf 

51. Chua MHY, Ng IAT, M WLC, and Mak A. Association between cigarette smoking and systemic lupus erythematosus: An updated multivariate bayesian metaanalysis. Journal of Rheumatology, 2020; 47(10):1514-21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31787611

52. Parisis D, Bernier C, Chasset F, and Arnaud L. Impact of tobacco smoking upon disease risk, activity and therapeutic response in systemic lupus erythematosus: A systematic review and meta-analysis. Autoimmunity Reviews, 2019; 18(11):102393. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31520802

53. Versini M, Tiosano S, Comaneshter D, Shoenfeld Y, Cohen AD, et al. Smoking and obesity in systemic lupus erythematosus: a cross-sectional study. European Journal of Clinical Investigation, 2017; 47(6):422-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28382625

54. Barbhaiya M, Tedeschi SK, Lu B, Malspeis S, Kreps D, et al. Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses' Health Study cohorts. Annals of the Rheumatic Diseases, 2018; 77(2):196-202. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28988206

55. Rua-Figueroa I, Erausquin C, Rua-Figueroa C, Gonzalez-Martin J, Naranjo A, et al. Tobacco smoking is an independent factor associated with retinal damage in systemic lupus erythematosus: a cross-sectional and retrospective study. Rheumatology International, 2020; 40(3):367-74. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31773393

56. McKown T, Schletzbaum M, Unnithan R, Wang X, Ezeh N, et al. The effect of smoking on cumulative damage in systemic lupus erythematosus: An incident cohort study. Lupus, 2021; 30(4):620-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33470148

57. Leffers HCB, Troldborg A, Voss A, Kristensen S, Lindhardsen J, et al. Smoking associates with distinct clinical phenotypes in patients with systemic lupus erythematosus: a nationwide Danish cross-sectional study. Lupus Science & Medicine, 2021; 8(1). Available from: https://www.ncbi.nlm.nih.gov/pubmed/33811110

58. Boeckler P, Cosnes A, Frances C, Hedelin G, and Lipsker D. Association of cigarette smoking but not alcohol consumption with cutaneous lupus erythematosus. Archives of Dermatology, 2009; 145(9):1012-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19770440

59. Kallas R, Li J, and Petri M. Association of African-American ethnicity and smoking status with total and individual damage index in systemic lupus erythematosus. Clinical Rheumatology, 2020; 39(2):365-73. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31705325

60. Rahman P, Gladman DD, and Urowitz MB. Smoking interferes with efficacy of antimalarial therapy in cutaneous lupus. Journal of Rheumatology, 1998; 25(9):1716-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9733451