Our objective was to prospectively evaluate the relation between smoking and incidence of psoriasis in a large cohort of women. We found that both past and current smokers were at increased risk for developing psoriasis, and the risk was greater for current smokers. The risk was graded and increased with the duration, intensity and pack-years of smoking. Furthermore, the risk of incident psoriasis decreased with increasing years of smoking cessation reaching nearly that of never smokers 20 years after cessation. These associations were independent of other purported risk factors. The current study provides the first prospective evidence that smoking is a strong risk factor for incident psoriasis.
The impact of smoking on psoriasis has been evaluated in a cross-sectional study that compared 557 psoriatic patients attending the University of Utah Dermatology Clinics, with external population databases.9
The prevalence of smoking in the psoriatic patients was higher than in the general Utah population (37% vs 13%; P <0.001) and higher than in the non-psoriatic patients attending the same dermatology clinics (37% vs 25%; P <0.001). A previous case-control study of 108 psoriasis cases from the dermatology department of South Glamorgan (UK), and 108 control patients from family practices of the same region, reported a similarly strong association between prior smoking and the risk of psoriasis (OR = 3.75; 95 % CI, 1.68–9.47).15
A recent Italian, multi-center, case-control study involving 318 men and 242 women with newly diagnosed psoriasis and 690 controls also reported that there was a significant association (multivariate OR = 1.9 [95 % CI, 1.3–2.7] for past smokers and 1.7 [95 % CI, 1.1–3.0] for current smokers). The same study reported that the risk of psoriasis was significantly higher in female current smokers, whereas the risk was not significant in female past smokers (OR, 1.2; 95% CI, 0.6–2.2).16
Furthermore, no graded response was observed across smoking intensity and duration, unlike our findings. Our prospectively obtained smoking history data, coupled with a larger sample size may explain the differences. While previous cross-sectional studies left uncertainty regarding the temporal relationship between smoking and psoriasis,9, 17
our prospective longitudinal data indicate that increased smoking precedes the occurrence of new cases of psoriasis. Furthermore, potentially biased recall of various facets of smoking history was avoided in this study because smoking data were collected prior to the data on incident psoriasis.
Psoriasis is a T cell immune-mediated disease that involves over-expression of proinflammatory cytokines and chemokines such as TNF-α, IL-2, IL-6, IL-8, and γ-interferon. There are several speculated mechanisms by which cigarette smoke could augment the risk of psoriasis. Cigarette smoke contains many potentially toxic materials such as nicotine, reactive oxygen species, nitric oxide, peroxynitrite, and free radicals of organic compounds, and may affect the immunopathogenesis of psoriasis.10
Abnormalities in T-cell function,18, 19
reduction in natural killer cells,20
impairment of humoral immunity,20–22
and elevated levels of inflammatory markers such as interleukin-6 and C-reactive protein 23–25
have been observed in smokers. Specifically, nicotine may stimulate the functional capacity of antigen presenting cells leading to T-cell proliferation and release of proinflammatory cytokines,16, 26
which are thought to be involved in the pathogenesis of psoriasis. Some studies 27–30
have also shown that cigarette smoking induces an overproduction of interleukin IL-1β, and increases the production of TNF-α and transforming growth factor-β, which have been associated with psoriasis severity.
The constituents of cigarette smoke, including mutagenic, neurotoxic and fetotoxic agents can pass through the placenta and are detectable in the urine of newborns.31, 32
Maternal smoking is known to increase a woman’s risk of spontaneous abortion, preterm delivery, and lower birth weight.31, 33
A previous study that evaluated the role of passive smoking in psoriasis did not find it to be a risk factor.16
However, the study did not evaluate separately for prenatal, childhood and adult exposure. Our study found passive exposure to serve as a risk factor in the first two groups. It is conceivable that for psoriasis, passive exposure to smoke has greater negative consequences earlier rather than later in life.
Conversely, smoking cessation may be an important target for prevention and management of psoriasis.34, 35
Smoking cessation may decrease the degree of smoke-induced inflammation by lowering the level of circulating inflammatory cytokines or restoration of T-cell impairments. Indeed, our study found that the risk for psoriasis in past smokers was consistently lower than it was for current smokers. The risk progressively decreased with increasing years of smoking cessation and became insignificant, 20 years after cessation. Furthermore, among patients with existing psoriasis, higher intensity and duration of smoking was associated with increased clinical severity of psoriasis.11
These findings, along with well-established hazardous health effects of smoking, provide clear incentives for smoking cessation in those at risk for and suffering from psoriasis. Beyond the potential effect on psoriasis, smoking cessation would lead to a better overall clinical outcome in psoriasis patients, who often suffer co-morbidities related to smoking.34, 36
There are several strengths and limitations of our study. It is the largest, prospective assessment of multiple markers of smoking status, duration and intensity in relation to the risk of psoriasis. Similar to other population-based epidemiologic studies of psoriasis,3, 37, 38
we did not confirm the nurses’ self-reported physician-diagnosis of psoriasis clinically with an examination by a dermatologist. A recent French study of a non-health professional population reported that the agreement between self-reported and dermatologists’ diagnoses of psoriasis was moderate, although it was the second best among five common skin disorders.39
While we expect the overall accuracy of self-reported physician-diagnosis of psoriasis to be higher among registered nurses, as was the case with other health data in our cohort, the corresponding accuracy against a dermatologist’s examination is not available. However, when we additionally adjusted for self-reported physician-diagnosed co-morbidities associated with increased smoking such as asthma, chronic obstructive lung disease, cardiovascular disease, and hypertension, our results did not change materially. These data suggest that these co-morbidities associated with smoking did not contribute to an increased ascertainment of psoriasis among women smokers in our cohort. Furthermore, any non-differential misclassification of psoriasis would have biased the study results toward the null and would not explain the strong associations observed in this study. Nonetheless, confirmation of these results using more specific case definitions of psoriasis as well as evaluation of psoriasis subtypes would be valuable.
The restriction to registered nurses in our cohort is both a strength and a limitation. The cohort of well-educated women minimizes potential for confounding associated with socioeconomic status, and we were able to obtain high quality data with minimal loss to follow-up. Although the absolute rates of psoriasis and frequency of smoking may not be representative of a random sample of US women, the biological effects of smoking should be similar. Our findings would be most directly generalizable to Caucasian women with no history of psoriasis. Furthermore, between the reported bimodal peaks of psoriasis onset time (23 and 55 years),40
the age range of our cohort during the follow-up tended to overlap more with the second peak of incidence. Thus, our results may be more applicable to the later-onset cases of psoriasis.
In conclusion, this prospective study suggests that the risk of incident psoriasis in women is increased in past and current smokers, and with increasing duration and intensity of smoking. The risk of incident psoriasis among former smokers decreases nearly to that of never smokers, 20 years after cessation. Smoking cessation may be a potentially important target for the prevention and management of psoriasis.