Psoriasis is a common chronic systemic skin disease induced by a combination of environmental and genetic factors (1, 2). Globally, the prevalence of psoriasis in adults ranges from 0.51 to 11.43% (3). A recent epidemiological investigation reveals that psoriasis affects ~125 million population worldwide and the prevalence of psoriasis is increasing gradually (4). Previous studies have indicated that the Chinese population has relatively lower psoriasis prevalence, but in recent years, the prevalence of psoriasis in China has increased from 0.16% in 1982 to 0.47% in 2012. It can be speculated that there are about 6 million patients with psoriasis in the 1.4 billion Chinese population (5, 6). Clinically, psoriasis is characterized as erythematous plaques, silvery scales on the skin lesion, accompanied by joint damage and multiple organs' dysfunctions (7, 8). Psoriasis adversely affects the quality of life and work efficiency of patients, leads to severe economic burden as well (9–11), and is considered to be a serious global problem.

In recent years, a growing number of studies have indicated that environmental factors are vital triggers for the initiation of psoriasis, and tobacco smoking is one of the key environmental pathogenic factors which affects the onset of psoriasis (12, 13). Bertesi et al. reported that the onset of psoriasis is associated with the role of keratinocytes, fibroblasts, immune cells, and inflammatory factors (14), and the psoriasis severity is closely related to the inflammation. In addition, tobacco smoking can induce oxidative stress, free radical damage, increase vascular endothelial dysfunction, and immune cell activation, and can interact with the key signaling pathways in psoriasis pathogenesis. Multiple studies have been implemented previously to investigate the association between psoriasis and tobacco smoking, and tobacco smoking is proved as an independent risk factor that accounts for the increased prevalence of psoriasis (15, 16). Therefore, advocating tobacco smoking cessation is crucial to curb the elevated prevalence and the severe influence of psoriasis in the world.

Tobacco smoking is the single most avoidable cause of death and disability globally, and it is estimated that there are 1.2 billion tobacco smokers in the world. In recent years, tobacco smoking in low- and middle-income countries is increasing rapidly, and the prevalence of tobacco smoking among men in Asian countries is now far higher than in Western countries, with 45% in India, 53% in Japan, 63% in China, 69% in Indonesia, and 73% in Vietnam (17). As the largest tobacco producer and consumer in the world, China is facing a public crisis with an estimation of 320 million tobacco smokers with current smoking prevalence (18). The Global Adult Tobacco Survey (GATS) conducted in 2010 indicates that nearly 1 million smokers died from tobacco-related diseases, and about 52% of non-smokers are exposed to second-hand tobacco smoke in China (19). Due to the tobacco-induced heavy disease burden, and its association with psoriasis, it is critical to understand the prevalence of tobacco smoking among patients with psoriasis for future tobacco control in this targeted population. However, evidence on the prevalence of tobacco smoking and, especially, its association with psoriasis severity is still limited in China (20–22).

In this study, we implemented a cross-sectional investigation that covered 200 hospitals in China. We aimed to understand the prevalence of tobacco smoking among patients with psoriasis and to explore the association between tobacco smoking and psoriasis severity. Accurate assessment of potentially modifiable factors is critical for psoriasis management, and confirmation of the relationship between tobacco smoking and psoriasis severity indicates the need for behavior modification among patients with psoriasis in the future.

In this study, we finally included 4,529 patients with psoriasis and classified them into non-smokers (3,134, 69.2%), former smokers (281, 6.2%), and current smokers (1,114, 24.6%). The average age of the 4,529 patients with psoriasis was 38.6 years (SD: 15.5); 64.1% of them were men and 70.4% of them were married. Notably, 33.0% of 4,529 patients with psoriasis had college and above education, nearly half of them were overweight or obese, and ~97% of them had medical insurance. Data in Table 1 indicate that non-smokers were younger than tobacco smokers, the proportion of male and married patients with psoriasis both in former smokers and current smokers was higher than that in non-smokers, respectively, and the differences were all statistically significant (p < 0.05). Psoriasis patients without tobacco smoking (non-smokers) had a higher percentage of college and above education, and a lower percentage of overweight and obesity, in comparison with both former smokers and current smokers; the differences were statistically significant (p < 0.05).

This is the first large population size study in China that enrolled 4,529 patients with psoriasis to explore the association between tobacco smoking and disease severity of psoriasis. This study indicated that the prevalence of tobacco smoking among patients with psoriasis was 30.8%, with 24.6% for current tobacco smoking and 6.2% for former tobacco smoking, which was in line with the findings in previous studies (23, 24). In this study, the average PASI score among the patients with psoriasis was 9.4 (SD: 8.4), and male patients had a higher PASI score than female patients. Logistic regression analysis indicated that both the former smokers and current smokers had at least 1.2 times higher PASI scores than non-smokers, and PASI score was positively correlated with tobacco smoking years as well as number of daily consumed cigarettes. Therefore, we concluded that tobacco smoking was positively associated with the disease severity of psoriasis, and both the tobacco smoking duration and smoking intensity were positively correlated with the psoriasis severity among patients with tobacco smoking. These findings have important implications concerning the management and treatment of psoriasis patients, meanwhile, providing direct evidence to support advocating smoking cessation among patients with psoriasis. Therefore, doctors should promote tobacco control measures, such as pharmacotherapy, smoking cessation advice, and behavioral support, and provide assistance for smoking cessation among patients with psoriasis. Moreover, the effect of doctors' advice and assistance for tobacco smoking cessation should be evaluated among patients with psoriasis in the future, both for the direct effect of decreased smoking prevalence, and the recurrence and severity of psoriasis.

Growing evidence demonstrates the association between tobacco smoking and the onset and development of psoriasis. Therefore, it is important to understand the tobacco smoking status in patients with psoriasis. Previous evidence has indicated that the prevalence of tobacco smoking varies substantially in different studies. Kridin et al. (25) implemented an investigation that enrolled 121,801 patients with psoriasis, of whom 38.9% were tobacco smokers. A cross-sectional study in Korea with 1,260 patients with psoriasis showed a 51.2% of tobacco smoking prevalence (26); meanwhile, a meta-analysis with pooled data indicated a 30.04% of tobacco smoking prevalence among patients with psoriasis (20). In this study, the prevalence of tobacco smoking was 30.8%, which was consistent with the finding (33.4% of tobacco smoking prevalence) of a recent multicenter study in China (27). The low tobacco smoking prevalence in the Chinese psoriasis population might partially attribute to a lower prevalence of tobacco smoking among female patients with psoriasis. In this study, the prevalence of tobacco smoking was 5.0% among female patients, which was extremely lower than that of Fortes' survey (50% of female patients with psoriasis were smokers) (28). Meanwhile, a growing number of population in China have noticed the physical harmfulness of tobacco use in recent years and stopped smoking successfully, which might also contribute to the lower prevalence of tobacco smoking in this study (29). In contrast, we should notice the high prevalence of tobacco smoking in men, especially with senior high education; we suggest that tobacco control measures should be focused on this specific population in the future.

In clinical practice, psoriasis severity is often categorized as mild, moderate, and severe. Although there were numerous and reliable tools to assess the psoriasis severity, PASI was the primary tool for disease severity evaluation to reflect the treatment response in patients with psoriasis by a dermatologist. Meanwhile, we also emphasized that evaluators should consider the type and location of lesions among patients with psoriasis in order to assess the severity of skin lesions more accurately. In this study, the average PASI score among the patients with psoriasis was 9.4 that indicated mild to moderate psoriasis severity, and male patients with psoriasis had a higher PASI score than female patients; this might be partially due to the higher tobacco smoking prevalence among male patients. In this study, we also noticed that over 93% of patients suffered from psoriasis vulgaris, and psoriasis lesion severity scores were higher for lower limbs among patients, which was in line with the findings of the nationwide survey in China during 2009 and 2010 (23). In contrast, investigation in Western countries indicated that the most frequently seriously affected areas are knees, scalp, body trunk, and hands (30, 31). These inconsistent findings indicated the multifacet variation of psoriasis phenotype, so a better understanding of the distribution and impact of different body areas for psoriasis is crucial for disease management.

Tobacco smoking is one of the well-established environmental risk factors for psoriasis, but its association with psoriasis severity is still limited. A meta-analysis shows that both current smokers [1.63 (95% CI: 1.48–1.80)] and former smokers [1.36 (95% CI: 1.13–1.64)] have a higher risk of developing psoriasis than nonsmokers (32). Other studies indicated that 15–20% of psoriasis onset could attribute to the former or current tobacco smoking, suggesting that tobacco smoking increased the risk of psoriasis both in women and men (33). This study showed that tobacco smoking impacts the severity of psoriasis in a dose-dependent fashion, and tobacco smoking intensity and smoking duration were positively associated with the severity of psoriasis, which were in line with the findings in the previous studies (34). Meanwhile, tobacco smoking might also directly impact the treatment response and lower the adherence to therapy among patients with psoriasis, leading to the aggravation of psoriasis severity in patients. In comparison with non-smokers, former smokers were less likely to achieve disease improvement with biologic agent treatment. Interestingly, in a series of 110 psoriasis patients treated with anti-TNF therapy, the majority of non-responders were smokers, especially those with overweight/obesity or higher baseline PASI scores (35). In this study, both the former smokers and current smokers had higher PASI scores, which predicted the lower response rate of treatment in these patients with tobacco smoking, so implementing tobacco control measures among patients with psoriasis is crucial for the improvement of treatment response in the future.

Tobacco smoking as a complex risk factor might influence the onset and development of psoriasis in many ways, but the underlying mechanism is still not clear. The pathophysiological mechanisms for the direct association between psoriasis and tobacco smoking include oxidative stress, free radical damage, increasing vascular endothelial dysfunction, immune cell activation, genetic mechanisms and interaction with key signaling pathways in psoriasis [nuclear factor kappa B (NF-κB), Janus kinase/signal transducers and activators of transcription (JAK-STAT)], and mitogen-activated protein kinase (MAPK) (36–38). The consequences of oxidative stress and free radical damage had been shown to transform the morphology and function of psoriatic polymorphonuclear cells, which comprised the dominant inflammatory infiltrate in psoriasis (28). In addition, it was also suggested that tobacco smoke could increase vascular endothelial dysfunction, which is an important factor for angiogenesis of psoriasis (39). Nicotine in tobacco smoke was the major alkaloid of cigarettes that activated the interleukin-1β (IL-1β), IL-2, IL-12, and tumor necrosis factor (TNF), which played a central role in psoriasis pathogenesis (40, 41). Presumably, nicotine might facilitate keratinocyte adhesion and upward migration in the epidermis and eventually impacted keratinocyte proliferation and skin inflammation (42). Nicotine also stimulated innate immune cells, including keratinocytes, macrophages, and dendritic cells (32). These cells release cytokines that trigger T-lymphocytes and perpetuate the cycle of chronic inflammation, leading to the onset and development of psoriasis.

A key strength of this study is the large population size of the patient with psoriasis. We sampled 4,529 patients from 200 hospitals, which accounted for ~2% of all 12,436 tertiary hospitals and secondary hospitals in China, so the findings could be generalized to patients with psoriasis in China. Meanwhile, the data collection was conducted by an electronic software that was convenient to the paperless data input, the full-time audio record benefit the subsequent inspection, and the clinical data of psoriasis patients were extracted from the health information system (HIS) directly without recall bias, which ensures the high quality of data is another strength of this study.

There are some limitations in this study. First, tobacco smoking status among patients is self-reported which might lead to recall bias, and the missing information of second-hand smoke exposure might underestimate the influence of tobacco smoking on psoriasis severity to some degree. Second, indicators for life quality assessment are not included in this study, so we missed the chance to evaluate the influence of psoriasis severity for life quality of patients with and without tobacco smoking; the incorporation of Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Professional Quality of Life Scale (PRQoL) and Visual Analog Scale (VAS) should be considered in future study. Third, the nature of cross-sectional study design only allows the calculation of tobacco smoking prevalence and estimation of the correlation between tobacco smoking and psoriasis severity, but not the causal relationship. All of these aforementioned limitations would restrict the interpretations of clinical findings to some degree. Therefore, a better designed cohort or case–control study to explore the potential mechanism of smoking behavior on diseases severity among patients with psoriasis may be particularly useful for the development of future research directions and intervention strategies.

The prevalence of tobacco smoking among patients with psoriasis was high, especially among male patients and those with senior high education. Tobacco smoking was positively associated with psoriasis severity; moreover, both smoking intensity and smoking duration were positively correlated with the severity of psoriasis in a dose-dependent fashion.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Institutional Review Board of Peking University First Hospital and Shanghai Skin Diseases Hospital. The patients/participants provided their written informed consent to participate in this study.

RW and BL proposed and designed the study. LW, SC, ZZ, LK, and RZ collected the data. NY and RW performed the statistical analyses. WL and SC drafted the manuscript. ZZ, YS, and BL supervised the study. RW revised the manuscript. All authors contributed to the article and approved the submitted version.

This study was supported by the National Key Research and Development Program of China (No. 2018YFC1705301), and the NSFC of China (Nos. 81973860, 81874470, 82074427, and 81904214), and Intelligence Funds of Shanghai Skin Disease Hospital (2021KYQD01), the Shanghai Talent Development Fund (2021073), the Shanghai Shenkang Hospital Development Center Management Research Program (2020SKMR-32), the Shanghai Sailing Program (No. 21YF1448100), the Xinglin Youth Scholar of Shanghai University of Traditional Chinese Medicine (No. RY411.33.10), and the Shanghai Development Office of TCM (No. ZY(2018-2020)-FWTX-1008 and ZY(2018-2020)-FWTX-4010), the Shanghai Municipal Key Clinical Specialty (No. shslczdzk05001), and the Shanghai Pujiang Talent Program (No. 2020PJD067). These funders had no role in study design, data collection and analysis, decision for publication, or preparation of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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