Вы находитесь на странице: 1из 11

BJD

British Journal of Dermatology

S Y S TE M A T IC R E V IE W

Psoriasis and smoking: a systematic review and


meta-analysis
A.W. Armstrong,1 C.T. Harskamp,1 J.S. Dhillon1 and E.J. Armstrong2
1

Department of Dermatology, 2Division of Cardiovascular Medicine, University of California, Davis, 3301 C Street Suite 1400, Sacramento, CA 95816,
U.S.A.

Summary
Correspondence
April W. Armstrong.
E-mail: aprilarmstrong@post.harvard.edu

Accepted for publication


3 October 2013

Funding sources
No external funding.

Conflicts of interest
None declared.
DOI 10.1111/bjd.12670

Psoriasis is an inflammatory skin disease associated with increased cardiovascular


comorbidity. Smoking is associated with an increased risk of cardiovascular disease, and prior studies have suggested that patients with psoriasis are more likely
to be active smokers. Smoking may also be a risk factor in the development of
psoriasis. We conducted a systematic review and meta-analysis to assess the prevalence of smoking among patients with psoriasis, and we reviewed the contribution of smoking to the incidence of psoriasis. A total of 25 prevalence and three
incidence studies were identified. The meta-analysis of prevalence studies
included a total of 146 934 patients with psoriasis and 529 111 patients without
psoriasis. Random effects meta-analysis found an association between psoriasis
and current smoking [pooled odds ratio (OR) 178, 95% confidence interval (CI)
152206], as well as between psoriasis and former smoking (pooled OR 162,
95% CI 133199). Meta-regression analysis did not reveal any sources of study
heterogeneity, but a funnel plot suggested possible publication bias. A subset of
studies also examined the association between moderate-to-severe psoriasis and
smoking, with a pooled OR of 172 (95% CI 133222) for prevalent smoking.
The three incidence studies found an association between smoking and incidence
of psoriasis, with a possible dose-effect of smoking intensity and duration on
psoriasis incidence. These findings suggest that smoking is an independent risk
factor for the development of psoriasis, and that patients with established psoriasis continue to smoke more than patients without psoriasis.

Whats already known about this topic?

Psoriasis is associated with a number of cardiovascular risk factors, many of which


are influenced by smoking.

What does this study add?

Patients with psoriasis are more likely to be current or former smokers.


Smoking is also associated with an increased risk of developing psoriasis.
These findings emphasize that patients with psoriasis should be screened for smoking, and that public health efforts to reduce smoking could also decrease the incidence of psoriasis.

Psoriasis is a chronic, immune-mediated skin disease that


affects approximately 24% of the world population.1,2 Psoriasis is associated with a number of cardiovascular risk factors,
including hypertension,3,4 diabetes,5 obesity,6 metabolic syndrome7 and dyslipidemia.8 Smoking is a well-established risk
factor for the development of cardiovascular diseases such as
304

British Journal of Dermatology (2014) 170, pp304314

coronary artery disease, cerebrovascular disease and myocardial infarction.9 Furthermore, smoking is also associated with
certain types of malignancies, gastrointestinal disease and
chronic obstructive pulmonary disease.10 In a 2012 study that
assessed the smoking status among 3 billion individuals from
16 different countries, 661 million (22%) were smokers.11
2013 British Association of Dermatologists

Psoriasis and smoking: meta-analysis, A.W. Armstrong et al. 305

Previous studies have suggested that smoking is associated


with increased severity of psoriasis and diminished treatment
responses among patients with psoriasis.12 In this systematic
review and meta-analysis, we characterize the prevalence of
smoking among patients with psoriasis as well as the contribution of smoking to psoriasis development.

Methods
We performed a systematic review using the MEDLINE, Embase and Cochrane Central Register databases with the following
search
criteria:
[Psoriasis(MeSH)
AND
Smoking(MeSH)]. Our search was limited to English-language, human-subject studies published between 1 January
1980 and 15 June 2013. We also manually searched the references of retrieved articles for any additional studies not identified in the initial searches. To be eligible for study inclusion,
original studies needed to fulfil the following criteria: case
control, cross-sectional, cohort or nested casecontrol design;
evaluation of smoking in conjunction with psoriasis; and
analyses that compared patients with controls. Specifically, the
studies had to evaluate the prevalence or incidence of psoriasis
in patients who smoked as defined by either patient self-report
or medical chart review.
A total of 128 articles were identified from the initial search,
and seven additional studies were found from manual review
(Fig. 1). After reviewing all abstracts, 74 full-text articles were
further evaluated. Ten of these studies were excluded because
they were reviews; five did not include a control group; 15 did
not measure the association between psoriasis and smoking; 11
were commentaries, letters or editorials; three lacked adequate
data for meta-analysis (such as odds ratio calculations); one
study included only palmopustular psoriasis,13 and one study

included only psoriatic arthritis.14 After these exclusions, 28


studies were included in the meta-analysis (25 prevalence studies and three incidence studies).
Two reviewers (C.T.H., A.W.A.) independently extracted the
data and performed the systematic review, and any disagreements were adjudicated by consensus. The Meta-Analysis of
Observational Studies in Epidemiology (MOOSE) guidelines
were used to guide analysis.15 For each study included, we
recorded the study year, country in which the study population
lived, setting in which the study took place, study design, numbers of case and control subjects, age, sex, whether the results
were adjusted for comorbidities, data collection processes (prospective or retrospective), whether the results were a primary or
secondary analysis of the publication, and whether psoriasis disease severity was assessed. To measure study quality, we used a
previously validated 7-point scale, with values of 0 or 1 assigned
to study design, assessment of exposure, assessment of outcome, control for confounding, evidence of bias, and assessment of psoriasis severity. Studies with a score of 03 were
categorized as lower quality, while studies with scores of 46
were categorized as higher quality.16
Most of the studies were of casecontrol design and
reported adjusted odds ratios (ORs). Studies that reported
prevalence (n = 25) were analysed separately from studies that
reported incidence (n = 3). To estimate the pooled OR and
pooled relative risk (RR), we used fixed-effects and randomeffects models of DerSimonian and Laird.17 Multivariate
adjusted ORs were used for meta-analysis when available;
otherwise, the unadjusted ORs were used in studies where
multivariate adjustment had not been performed. All prevalence studies reported current smoking status, while some
differentiated prior smoking from current smoking. A subset
of studies also differentiated mild from moderate-to-severe

Fig 1. Study selection. PPP, palmoplantar


pustulosis; Ps, psoriasis; PsA, psoriatic
arthritis.
2013 British Association of Dermatologists

British Journal of Dermatology (2014) 170, pp304314

306 Psoriasis and smoking: meta-analysis, A.W. Armstrong et al.

psoriasis, and they assessed the association of smoking with


psoriasis severity. Study heterogeneity was assessed using the
I2 statistic. Due to significant between-study heterogeneity,
reported pooled ORs are based on random-effects modelling.
Publication bias was assessed by visual inspection of a funnel
plot of the study size vs. standard error, with formal statistical
testing performed using the Begg adjusted rank correlation
test.18,19 To explore sources of study heterogeneity, we performed a meta-regression using prespecified variables and random-effects meta-analysis. Prespecified sources of heterogeneity
included study country, subject location (ambulatory or inpatient), multivariate adjustment for confounders, prospective vs.
retrospective study design, ascertainment of prevalence vs. incidence, primary vs. secondary analysis, ascertainment of psoriasis
disease severity, measure of outcome, and study quality (03
vs. 46). All analyses were performed using STATA version 11.2
(STATA Corp, College Station, TX, U.S.A.).

Results
A total of 28 studies assessed either the prevalence of smoking
among patients with psoriasis or the incidence of psoriasis
among smokers.3,15,2046 Study population characteristics are
outlined in Table 1 for prevalence studies and in Table 4 for
incidence studies.
Prevalence of smoking among patients with psoriasis
A total of 25 studies assessed the prevalence of smoking
among 146 934 patients with psoriasis and 529 111 patients
without psoriasis (Tables 1 and 2). All but three studies
reported a statistically significant relationship between psoriasis
and an increased prevalence of smoking. Twenty-two of the
studies were conducted among outpatients with psoriasis, and
the studies were conducted in diverse locations including Eur-

Table 1 Psoriasis and prevalence of smoking: study population characteristics


Total n of patients

Mean age (years)

Study

Study setting

Study design

No psoriasis
(controls)

Armesto, 201222
a
Shapiro, 201239
Armstrong, 201151
a
Al-Mutairi, 201021
a
Gerdes, 201026
Takahashi, 201046
a
Driessen, 200925

Spain; outpatient
Israel; inpatient
U.S.A.; outpatient
Kuwait; outpatient
Germany; inpatient
Japan; outpatient
Netherlands;
outpatient
Montenegro;
outpatient
China; outpatient
Sweden; outpatient
France; outpatient

Casecontrol
Casecontrol
Casecontrol
Casecontrol
Casecontrol
Casecontrol
Cross-sectional

661
1079
2418
1835
6942
154
396

661
1079
835
1835
1097 (severe Ps)
151
107 (severe Ps)

474
687
617
527
NR
572
512

474
686
615
523
497
531
485

Casecontrol

200

110

461

455

Casecontrol
Casecontrol
Casecontrol

178
373
1068

178
373
356

254
46
516

262
46
516

China; outpatient

Cross-sectional

1521

3092

436

a
Bo, 200823
Naldi, 200838
Cohen, 200724
a
Neimann, 200636

Norway; outpatient
Italy; outpatient
Israel; outpatient
U.K.; outpatient

Cross-sectional
Casecontrol
Casecontrol
Cross-sectional

1144
560
340
Mild Ps: 127 706
Severe Ps: 3854
Combined: 131 560

NR
NR
470
Mild Ps: 457
Severe Ps: 463

Sommer, 200640
Herron, 200527
a
Naldi, 200533
a
Zheng, 200445
a
Zhang, 200244

Germany; inpatient
U.S.A.; outpatient
Italy; outpatient
China; outpatient
China; outpatient

Cross-sectional
Cross-sectional
Casecontrol
Cross-sectional
Casecontrol

17 603
690
6643
Mild Ps: 465 252
Severe Ps: 14 065
Combined:
479 317
1044
4080
690
333
789

Mild Ps: 436


Severe Ps: 463
NR
NR
477
Mild Ps: 464
Severe Ps: 498

581
557
560
189
789

Italy; outpatient
Finland; outpatient
and inpatient
Wales; outpatient
and inpatient
Italy; outpatient

Casecontrol
Casecontrol

616
108

404
55

585
457
Median age 36
NR
Male: 322
Female: 293
Median age 36
NR

544
498
Median age 38
NR
Male: 354
Female: 312
Median age 35
NR

Casecontrol

106

106

NR

433

267

215

NR

NR

Jankovic, 200929

Jin, 200930
Wolk, 200941
a
Wolkenstein,
200942
Xiao, 200943
a

Naldi, 199935
Poikolainen,
199437
a
Mills, 199220
a

Naldi, 199234

Casecontrol

Psoriasis
(cases)

No psoriasis
(controls)

Psoriasis
(cases)

NR, not reported; PPP, palmoplantar pustulosis; Ps, psoriasis. Smoking was the primary study variable.

British Journal of Dermatology (2014) 170, pp304314

2013 British Association of Dermatologists

Psoriasis and smoking: meta-analysis, A.W. Armstrong et al. 307


Table 2 Psoriasis and prevalence of smoking
Number of patients (%) who smoke
Study

Study period
22

No psoriasis
(controls)

Psoriasis (cases)

Measure of association (95% CI)

190 (287)

232 (351)

Current: 174 (161)

Current: 234 (217)

Current smoker: OR 134


(106170)
Current smoker: OR 144
(116179)
Adjusted OR 138 (110173)
Current smoker: OR 138
(107177)
Adjusted OR 143 (101202)
Former smoker: OR 159
(110158)
Adjusted OR 122 (095155)
Current smoker: OR 219
(186257)
Current smoker: OR 208
(181239)
Adjusted OR 205 (177239)
Current smoker: OR 177
(112278)
Current smoker: OR 173
(108275)
Former smoker: OR 192
(114322)
Smoking (both current and
former): OR 109 (067176)
Current smoking: OR 231
(132380)
Adjusted OR 207 (112382)
Current smoking: Adjusted OR
17 (1126)
Current or former smoker: OR
141 (110179)
Adjusted OR 146 (111194)

Shapiro, 201239

19932006

Questionnaire;
manual chart review
ICD-9

Armstrong,
201151

20042009

Manual chart review

Current: 260 (12)


Former: 745 (36)

Current: 113 (14)


Former: 310 (39)

Al-Mutairi,
201021
a
Gerdes, 201026

20032007

Manual chart review

Current: 371 (325)

Current: 762 (513)

Manual chart review

2295 (322)

509 (450)

Takahashi, 201046

20062008

Manual chart review

NR

NR

Manual chart review

Current: 114 (288)


Former: 233 (588)

Current: 50 (467)
Former: 81 (757)

Current: 72 (360)
Former: 34 (170)
Smoking habit: 31
(174)

Current: 42 (382)
Former: 20 (182)
Smoking habit: 57
(320)

Armesto, 2012

Driessen, 200925

NR

Smoking
ascertainment

NR

NR

2007

Interview

19972001

Interview

20012006

Questionnaire

82 (220)

138 (370)

Questionnaire

Current: 197 (186)


Former: 309 (292)
Current and former
smoker: 506
(478)
241 (158)

Current: 72 (206)
Former: 125 (357)
Current and former
smoker: 197
(563)
Mild Ps: 309 (191)
Severe Ps: 376
(255)

Jankovic, 200929
Jin, 200930

Wolk, 200941

Wolkenstein,
200942

NR

Xiao, 200943

19992007

Medical code
consistent with
smoking

Bo, 200823

20002001

Questionnaire

NR

Current: 4739
Former: 5581

Naldi, 200838

19881997

Questionnaire

Ever smoked: 350


(507)
1648 (248)

Ever smoked: 357


(637)
118 (347)

Cohen, 200724

NR

Reported in database

2013 British Association of Dermatologists

Mild Ps: OR 135 (101180)


Adjusted OR 131 (104165)
Severe Ps: OR 157 (120205)
Adjusted OR 142 (112179)
Men
Current smoker: OR 145
(115184)
Adjusted OR 149 (111200)
Former smoker: OR 163
(131202)
Adjusted OR 167 (129216)
Women
Current smoker: OR 165
(135202)
Adjusted OR 148 (115191)
Former smoker: OR 157
(129191)
Adjusted OR 155 (121199)
Adjusted OR 18 (1327)
OR 16 (1320)

British Journal of Dermatology (2014) 170, pp304314

308 Psoriasis and smoking: meta-analysis, A.W. Armstrong et al.


Table 2 (continued)
Number of patients (%) who smoke
Study period

Smoking
ascertainment

No psoriasis
(controls)

Neimann, 2006

19872002

Medical code

Sommer, 200640
a
Herron, 200527
a
Naldi, 200533

19962002
NR
19881997

Manual chart review


Questionnaire
Interview

Zheng, 200445

19972001

Questionnaire

Zhang, 200244

19972001

Questionnaire

Naldi, 199935

19881997

Questionnaire

Poikolainen,
199437

19891991

Mills, 199220

Naldi, 199234

Study
a

36

NR
19881990

Psoriasis (cases)

Measure of association (95% CI)

Mild Ps: 98 337


(211)
Severe Ps: 3157
(225)
219 (210)
530 (130)
Never smoker: 340
(493)
Current, cigarettes
per day: < 110:
108 (157)
1120: 113 (164)
21: 38 (55)
Former: 91 (132)

Mild Ps: 35 762 (28)


Severe Ps: 1158
(301)

Male: 49 (280)
Female: 2 (13)
Male: 126 (291)
Female: 5 (14)
Never smoker: 318
(516)
Current, cigarettes
per day: 15: 130
(211)
1624: 64 (104)
25: 21 (34)
Former: 83 (135)

Male: 53 (505)
Female: 0 (0)
Male: 215 (489)
Female: 9 (26)
Never smoker: 154
(381)
Current, cigarettes
per day: 15: 95
(235)
1624: 56 (139)
25: 24 (59)
Former: 75 (185)

Mild Ps: OR 140 (138143)


Adjusted OR 131 (129134)
Severe Ps: OR 131 (120144)
Adjusted OR 131 (117147)
OR 296 (227384)
OR 402 (331488)
Current smoker, cigarettes per
day: < 110: Adjusted OR 16
(1222)
1120: Adjusted OR 17
(1125)
21: Adjusted OR 17
(1032)
Former smoker: Adjusted OR
19 (1327)
Male: OR 262 (153449)

Questionnaire

NR

NR

Questionnaire

Current: 25 (236)

Current: 49 (462)

Questionnaire

Never smoker: 133


(498)
Current, cigarettes
per day: < 15 per
day: 66 (247)
15 per day: 30
(112)
Former: 38 (142)

Never smoker: 79
(367)
Current, cigarettes
per day: < 15 per
day: 54 (251)
15 per day: 47
(219)
Former: 33 (153)

264 (454)
205 (370)
Never smoker: 203
(363)
Current, cigarettes
per day: < 110:
99 (177)
1120: 114 (204)
21: 40 (71)
Former: 103 (184)

Male: OR 233 (174311)


Female: OR 186 (056643)
Current smoker, cigarettes per
day: 15: Adjusted OR 14
(1020)
1624: Adjusted OR 17
(1127)
25: Adjusted OR 21
(1139)
Former smoker: OR 18
(1226)
Adjusted OR 15 (1122)
Before onset of psoriasis
(20 cigarettes per day): OR 19
(0847)
Adjusted OR 33 (1479)
After onset of psoriasis
(20 cigarettes per day): OR
20 (0847)
Adjusted OR 26 (1165)
Current smoker: OR 271
(144542)
Current smoker, cigarettes per
day: < 15: OR 14 (0823)
Adjusted OR 11 (0618)
15: OR 26 (1546)
Adjusted OR 21 (1140)
Former smoker: OR 15
(08, 27)
Adjusted OR 11 (0620)

NR, not reported; OR, odds ratio; PASI, Psoriasis Area and Severity Index; Ps, psoriasis. aSmoking was the primary study variable.

ope, Asia and the Middle East. Fourteen of the studies were
deemed high quality (quality score of 46), with the major
quality difference being the level of covariate adjustment
performed within each study. Meta-analysis of these studies
revealed a significant association between psoriasis and current
smoking, with a pooled OR of 178 (95% CI 153206,
Fig. 2). Meta-regression of current smoking among patients
British Journal of Dermatology (2014) 170, pp304314

with psoriasis did not reveal any statistically significant sources


of heterogeneity. However, studies of higher quality and
multivariate adjustment generally reported lower ORs for the
association between psoriasis and smoking, suggesting that
studies without multivariate adjustment retained some residual
confounding (Table 3). Visual inspection of a funnel plot suggested possible publication bias, with an absence of small,
2013 British Association of Dermatologists

Psoriasis and smoking: meta-analysis, A.W. Armstrong et al. 309

Fig 2. Meta-analysis of psoriasis and


prevalence of current smoking. CI, confidence
interval; OR, odds ratio.

negative studies (Fig. 3). Formal assessment of publication


bias with the Begg adjusted rank correlation test confirmed
likely publication bias (P = 0002).
The association between psoriasis severity and the prevalence of smoking was addressed in five studies. Patients with
moderate-to-severe psoriasis had a pooled OR of 172 (95%
CI 133222) for prevalent smoking, which did not differ
significantly from the overall meta-analysis results (Fig. 4).
Seven studies also differentiated former smoking from current
smoking among patients with psoriasis. Meta-analysis of the
association between psoriasis and a history of former smoking
found a pooled odds ratio of 162 (95% CI 133198) for
former smoking (Fig. 5).
Number of cigarettes per day
A total of seven studies quantified the number of cigarettes
smoked per day among patients with psoriasis compared with
control subjects. One study of 178 patients with psoriasis and
178 controls reported a dose-effect relationship: patients with
psoriasis had an OR of 181 (95% CI 084390) for smoking
110 cigarettes per day and an OR of 223 (95% CI 104
475) for smoking > 10 cigarettes per day compared with
controls.30 A self-report questionnaire-based study from Norway found that men who smoked 20 cigarettes per day
were 14 times more likely (95% CI 106185) to report
having psoriasis, compared with those that smoked < 20 cigarettes per day, whereas women who smoked 20 cigarettes
per day were 112 times more likely to report having psoria 2013 British Association of Dermatologists

Table 3 Potential prespecified sources of heterogeneity explored


among the studies reporting an association between psoriasis and
prevalence of smoking

Prespecified
source of
heterogeneity

Number
of
estimates

Study location
U.S.A.
2
Europe
14
Other
9
Source population
Inpatient
3
Outpatient
22
Statistical adjustment
Not adjusted
10
Adjusted
15
Study quality
Lower (03)
11
Higher (46)
14
Outcome ascertainment
Billing data
11
Chart review
14
Analysis of outcome
Primary
18
Secondary
7
Severity of psoriasis
No distinction 20
Mild vs. severe 5

Stratified
random-effects
meta-analysis
OR (95% CI)

Meta-regression
P-value for
heterogeneity

242 (088667)
170 (14420)
173 (143208)

03

202 (139294)
174 (148204)

04

201 (154262)
163 (141188)

01

190 (144251)
168 (143197)

02

167 (14020)
188 (148240)

04

182 (150221)
167 (133210)

06

184 (155218)
157 (123201)

04

CI, confidence interval; OR, odds ratio.

British Journal of Dermatology (2014) 170, pp304314

310 Psoriasis and smoking: meta-analysis, A.W. Armstrong et al.

Because these studies used different cut-off points for the


number of cigarettes per day (e.g. 10, 15 or 20), meta-analysis could not be performed on the association between psoriasis and the number of cigarettes smoked per day. However,
these studies generally support an increased number of cigarettes per day smoked by patients with psoriasis when compared with patients without psoriasis.
Duration and pack-years of smoking

Fig 3. Funnel plot of psoriasis and prevalence of current smoking.


The absence of studies in the lower left corner suggests possible
publication bias, with missing studies of smaller cohort and effect
size. OR, odds ratio.

sis, in comparison with those who smoked less frequently.23


Other studies found similar associations between psoriasis and
number of cigarettes smoked per day20,3335,37 (Table 2).

Four studies reported associations between psoriasis and the


total number of pack-years smoked. In one study, patients with
psoriasis were 142 times more likely to have smoked for 1
10 years, compared with those without psoriasis (95% CI
067301), and nearly three times more likely to have smoked
10 years, compared with patients without psoriasis (adjusted
OR 296, 95% CI 130672).30 Other studies did not find
robust differences in smoking duration between patients with
and without psoriasis3335 (Table 2). In the same study that
examined duration of smoking, patients with psoriasis were
also 173 times more likely to have 15 pack-years and 232
times more likely to have 5 pack-years of smoking history,

Fig 4. Meta-analysis of moderate/severe


psoriasis and prevalence of smoking. CI,
confidence interval; OR, odds ratio.

Fig 5. Meta-analysis of psoriasis and former


smoking. CI, confidence interval; OR, odds
ratio.
British Journal of Dermatology (2014) 170, pp304314

2013 British Association of Dermatologists

Psoriasis and smoking: meta-analysis, A.W. Armstrong et al. 311

cases of psoriasis, while the GPRD population included 3994


cases of incident psoriasis and 10 000 control subjects.
In the pooled analysis of the NHS, NHS II and HPFS, individuals with a history of smoking were 139 times more likely
to develop incident psoriasis, after multivariate adjustment for
confounders (95% CI 127152), and current smokers were
nearly twice as likely to develop psoriasis, compared with
nonsmokers (adjusted OR 194, 95% CI 164228).31 Similar
results were found in the GPRD study, where active smokers
had an increased risk of developing psoriasis (adjusted OR
145, 95% CI 131159).
Pooled analysis of the NHS, NHS II and HPFS also revealed
a positive association between smoking intensity, smoking
duration and risk of incident psoriasis. Those who smoked 1
14 cigarettes per day were 181 times more likely to develop
psoriasis, compared with nonsmokers (95% CI 138236),

compared with patients without psoriasis (95% CI 079383;


95% CI 108500, respectively)30 (Table 2).
Smoking and incident psoriasis
A total of three publications assessed smoking and incident
psoriasis (Tables 4 and 5). One study reported results from
three populations of patients [the Nurses Health Study
(NHS), the Nurses Health Study II (NHS II), and the Health
Professionals Follow-Up Study (HPFS)];31 another publication
was an earlier analysis of the NHS II and therefore included
the same population of patients.32 The third publication
assessed incident psoriasis in the General Practice Research
Database (GPRD), a U.K.-based database of patients from the
general community.28 The pooled data from the NHS, NHS II
and HPFS included 185 836 participants with 2410 incident
Table 4 Smoking and incident psoriasis: study population characteristics

Total number of patients

Mean age

Smokers (cases)

Nonsmokers
(controls)

Smokers
(cases)
Current: 487
Former: 502
NR

Study

Study setting

Study design

Nonsmokers
(controls)

U.S.A.; outpatients

Prospective cohort

NR

NR

492

a,b

U.K.; outpatient

Prospective cohort, nested


casecontrol analysis
Prospective cohort

10 000 nonpsoriasis
controls
51 779

3994 psoriasis
cases
Current: 9023
Former: 17 730

NR

Li, 201231

Huerta,
200728
a
Setty, 200732

U.S.A.; female
outpatients

353

Current: 361
Former: 366

NR, not reported. aSmoking was the primary study variable. bThe odds ratio is an unbiased estimator of the incidence ratio with this study
design.
Table 5 Smoking and incident psoriasis: study outcomes

Smoking
ascertainment

Nonsmokers that
developed psoriasis
(control) (%)

Smokers that
developed
psoriasis (%)

19962008 (NHS);
19912005 (NHS II);
19862006 (HPFS)

Questionnaire

1124

Current: 309
Former: 977

a,b

Huerta,
200728

19961997

OXMIS/Read

Setty, 200732

19912005

Questionnaire

Patients without
psoriasis who
smoke: 2008 (201)
494

Patients with
psoriasis who
smoke: 1013 (254)
Current: 131
Former: 262

Study
a

Study period
31

Li, 2012

Measure of association (95% CI)


Current smoker: Age-adjusted RR
195 (168227)
Multivariate-adjusted RR 194
(164228)
Former smoker: Age-adjusted RR
143 (131156)
Multivariate-adjusted RR 139
(127152)
OR 137 (125150)
Adjusted OR 145 (131159)
Current smoker: Age-adjusted RR
182 (150221)
Multivariate-adjusted RR 178
(146216)
Former smoker: Age-adjusted RR
140 (120162)
Multivariate-adjusted RR 137
(117159)

NR, not reported; OR, odds ratio; PsA, psoriatic arthritis; RR, relative risk. aSmoking was the primary study variable. bThe odds ratio is an
unbiased estimator of the incidence ratio with this study design.

2013 British Association of Dermatologists

British Journal of Dermatology (2014) 170, pp304314

312 Psoriasis and smoking: meta-analysis, A.W. Armstrong et al.

and those who smoked 25 cigarettes per day were over


twice as likely to develop psoriasis, compared with nonsmokers (adjusted OR 229, 95% CI 174301).31 Subjects who
had smoked < 10 years had close to the same risk of developing psoriasis as nonsmokers (adjusted OR 107, 95% CI 083
139), whereas those who had smoked 30 years were nearly
twice as likely to develop psoriasis (adjusted OR 199, 95% CI
175225).31 The overall population-attributable risk of
smoking to incident psoriasis ranged from 15% in the NHS II
to 20% in the NHS, suggesting that up to one in five cases of
psoriasis is attributable to smoking.

Discussion
This systematic review and meta-analysis supports and quantifies the association between psoriasis and smoking. We examined both the prevalence of smoking among patients with
psoriasis and the association between smoking and incident
psoriasis. From the studies included in this systematic review,
both current and former smokers were more likely to develop
incident psoriasis, compared with nonsmokers. Additional factors associated with increased odds of developing psoriasis
included a greater number of cigarettes smoked per day,
longer durations of smoking habits, and greater pack-years of
smoking. Similarly, among prevalence studies, patients with
psoriasis were more likely to be either current or former
smokers compared with those without psoriasis.
A number of pathophysiological mechanisms likely underlie
the associations between smoking and psoriasis.47 Smoking
induces oxidative stress and free radical damage, reduces concentrations of antioxidants in the plasma, increases vascular
endothelial dysfunction, and increases plasma viscosity.48
Cigarette smoke contains approximately 1017 free radicals per
puff.49 This increased free radical exposure has the potential to
trigger a cascade of systemic consequences, including development of psoriasis. A study conducted of patients with plaque
psoriasis, for example, showed significantly higher Psoriasis
Area and Severity Index (PASI) scores in patients with psoriasis
who are smokers (n = 28), compared with nonsmoking
patients with psoriasis (n = 26; P = 0014).50 Oxidants,
including superoxide (O2 ) and hydrogen peroxide (H2O2),
are elevated in both lesional and nonlesional skin of patients
with psoriasis, whereas many antioxidant levels are reduced.51
Nicotine induces an increased secretion of interleukin (IL)-12
from dendritic cells. Numerous other inflammatory cells and
cytokines, including tumour necrosis factor, interferon-c, IL-2
and granulocyte-monocyte colony-stimulating factor, are produced through nicotine-activating pathways.51 Smokers also
show a dysregulated expression of vascular endothelial growth
factor, an important element in angiogenesis. Increased, abnormal angiogenesis induced by nicotine is shown to accelerate
atherosclerotic plaque formation in mice.52 This pathological
blood vessel formation may, in part, explain the relationship
between smoking and both psoriasis and atherosclerosis.51
Environment and behaviour also likely interact with the
genetic loci that predispose for psoriasis. A two-stage case
British Journal of Dermatology (2014) 170, pp304314

control study (n = 7223) investigated the relationship


between smoking behaviour and nine different single nucleotide polymorphisms (SNPs) that are associated with risk of
psoriasis.53 Two SNPs at the CSMD1 gene (a tumour suppressor gene that influences epithelial cell turnover), rs7007032
and rs10088247, were significantly associated with smoking
(P-value of 00023 for both SNPs). However, multiple logistic
regression analysis did not show a significant association
between psoriasis and these two SNPs. CSMD1 may also contribute to psoriasis development by influencing the differentiation of keratinocytes, and to smoking habits by influencing
addictive behaviour at a neuronal level. The interaction
between these genetic loci and smoking behaviour may play a
role in influencing the development of psoriasis but will
require further investigation.
This study has several strengths. Firstly, we performed a systematic review and meta-analysis using multiple data sources.
Secondly, multiple authors reviewed the data independently
and assessed study quality. We also used random effects metaanalysis to arrive at a more conservative estimate of effect size,
due to between-study heterogeneity. We also formally assessed
possible sources of heterogeneity using meta-regression analysis. The findings of this systematic review and meta-analysis
are limited by the quality of the primary data. For example,
some studies did not perform multivariable adjustment,
thereby possibly overestimating the effect size in some cases.
Because most studies were casecontrol and used ORs as a
measure of effect size, it is also possible that the meta-analysis
point estimates provide an overestimate of the effect relative to
studies of incidence. We also found evidence of possible publication bias, with an absence of small, negative studies. The
currently published studies were also limited in their assessment of psoriasis disease severity, making it difficult to draw
any conclusions on any possible association between smoking
and the severity of psoriasis.
In conclusion, this systematic review and meta-analysis supports a strong association between increased prevalence of
smoking among patients with psoriasis and an increased incidence of psoriasis among smokers. Patients who smoke should
be informed of the increased risk of developing psoriasis as
well as the additional adverse effects that any amount of
smoking can have on ones health. Patients with established
psoriasis should also be strongly counselled to quit smoking
in order to minimize the risk of cardiovascular comorbidities
associated with psoriasis.

References
1 Gelfand JM, Weinstein R, Porter SB et al. Prevalence and treatment
of psoriasis in the United Kingdom: a population-based study. Arch
Dermatol 2005; 141:153741.
2 Parisi R, Symmons DP, Griffiths CE et al. Global epidemiology of
psoriasis: a systematic review of incidence and prevalence. J Invest
Dermatol 2013; 133:37785.
3 Armstrong AW, Lin SW, Chambers CJ et al. Psoriasis and hypertension severity: results from a casecontrol study. PLoS ONE 2011; 6:
e18227.
2013 British Association of Dermatologists

Psoriasis and smoking: meta-analysis, A.W. Armstrong et al. 313


4 Armstrong AW, Harskamp CT, Armstrong EJ. The association
between psoriasis and hypertension: a systematic review and
meta-analysis of observational studies. J Hypertens 2012; 31:433
42.
5 Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis and the risk
of diabetes mellitus: a systematic review and meta-analysis. JAMA
Dermatol 2013; 149:8491.
6 Armstrong AW, Harskamp CT, Armstrong EJ. The association
between psoriasis and obesity: a systematic review and metaanalysis of observational studies. Nutr Diabetes 2012; 2:e54.
7 Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis and metabolic syndrome: a systematic review and meta-analysis of observational studies. J Am Acad Dermatol 2013; 68:65462.
8 Ma C, Harskamp CT, Armstrong EJ et al. The association between
psoriasis and dyslipidaemia: a systematic review. Br J Dermatol
2013; 168:48695.
9 Lakier JB. Smoking and cardiovascular disease. Am J Med 1992;
93:8S12S.
10 Fielding JE. Smoking: health effects and control (1). N Engl J Med
1985; 313:4918.
11 Giovino GA, Mirza SA, Samet JM et al. Tobacco use in 3 billion
individuals from 16 countries: an analysis of nationally representative cross-sectional household surveys. Lancet 2012; 380:66879.
12 Fortes C, Mastroeni S, Leffondre K et al. Relationship between
smoking and the clinical severity of psoriasis. Arch Dermatol 2005;
141:15804.
13 Hagforsen E, Michaelsson K, Lundgren E et al. Women with
palmoplantar pustulosis have disturbed calcium homeostasis and a
high prevalence of diabetes mellitus and psychiatric disorders: a
casecontrol study. Acta Derm Venereol 2005; 85:22532.
14 Li W, Han J, Qureshi AA. Smoking and risk of incident psoriatic
arthritis in US women. Ann Rheum Dis 2012; 71:8048.
15 Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Metaanalysis Of Observational Studies in Epidemiology (MOOSE)
group. JAMA 2000; 283:200812.
16 Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and
diabetes mellitus: a systematic review and meta-analysis. Circulation
2010; 121:227183.
17 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin
Trials 1986; 7:17788.
18 Egger M, Davey Smith G, Schneider M et al. Bias in meta-analysis
detected by a simple, graphical test. BMJ 1997; 315:62934.
19 Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50:1088101.
20 Mills CM, Srivastava ED, Harvey IM et al. Smoking habits in psoriasis: a case control study. Br J Dermatol 1992; 127:1821.
21 Al-Mutairi N, Al-Farag S, Al-Mutairi A et al. Comorbidities associated with psoriasis: an experience from the Middle East. J Dermatol
2010; 37:14655.
22 Armesto S, Santos-Juanes J, Galache-Osuna C et al. Psoriasis and
type 2 diabetes risk among psoriatic patients in a Spanish population. Australas J Dermatol 2012; 53:12830.
23 Bo K, Thoresen M, Dalgard F. Smokers report more psoriasis, but
not atopic dermatitis or hand eczema: results from a Norwegian
population survey among adults. Dermatology 2008; 216:405.
24 Cohen AD, Gilutz H, Henkin Y et al. Psoriasis and the metabolic
syndrome. Acta Derm Venereol 2007; 87:5069.
25 Driessen RJ, Boezeman JB, Van De Kerkhof PC, De Jong EM.
Cardiovascular risk factors in high-need psoriasis patients and its
implications for biological therapies. J Dermatolog Treat 2009;
20:427.

2013 British Association of Dermatologists

26 Gerdes S, Zahl VA, Weichenthal M et al. Smoking and alcohol


intake in severely affected patients with psoriasis in Germany. Dermatology 2010; 220:3843.
27 Herron MD, Hinckley M, Hoffman MS et al. Impact of obesity and
smoking on psoriasis presentation and management. Arch Dermatol
2005; 141:152734.
28 Huerta C, Rivero E, Rodriguez LA. Incidence and risk factors for
psoriasis in the general population. Arch Dermatol 2007; 143:1559
65.
29 Jankovic S, Raznatovic M, Marinkovic J et al. Risk factors for psoriasis: a casecontrol study. J Dermatol 2009; 36:32834.
30 Jin Y, Yang S, Zhang F et al. Combined effects of HLA-Cw6
and cigarette smoking in psoriasis vulgaris: a hospital-based
casecontrol study in China. J Eur Acad Dermatol Venereol 2009;
23:1327.
31 Li W, Han J, Choi HK, Qureshi AA. Smoking and risk of incident
psoriasis among women and men in the United States: a combined
analysis. Am J Epidemiol 2012; 175:40213.
32 Setty AR, Curhan G, Choi HK. Smoking and the risk of psoriasis in
women: Nurses Health Study II. Am J Med 2007; 120:9539.
33 Naldi L, Chatenoud L, Linder D et al. Cigarette smoking, body
mass index, and stressful life events as risk factors for psoriasis:
results from an Italian casecontrol study. J Invest Dermatol 2005;
125:617.
34 Naldi L, Parazzini F, Brevi A et al. Family history, smoking habits,
alcohol consumption and risk of psoriasis. Br J Dermatol 1992;
127:21217.
35 Naldi L, Peli L, Parazzini F. Association of early-stage psoriasis
with smoking and male alcohol consumption: evidence from an
Italian casecontrol study. Arch Dermatol 1999; 135:147984.
36 Neimann AL, Shin DB, Wang X et al. Prevalence of cardiovascular
risk factors in patients with psoriasis. J Am Acad Dermatol 2006;
55:82935.
37 Poikolainen K, Reunala T, Karvonen J. Smoking, alcohol and life
events related to psoriasis among women. Br J Dermatol 1994;
130:4737.
38 Naldi L, Chatenoud L, Belloni A et al. Medical history, drug
exposure and the risk of psoriasis. Evidence from an Italian
casecontrol study. Dermatology 2008; 216:12530; discussion
1302.
39 Shapiro J, Cohen AD, Weitzman D et al. Psoriasis and cardiovascular risk factors: a casecontrol study on inpatients comparing psoriasis to dermatitis. J Am Acad Dermatol 2012; 66:2528.
40 Sommer DM, Jenisch S, Suchan M et al. Increased prevalence of the
metabolic syndrome in patients with moderate to severe psoriasis.
Arch Dermatol Res 2006; 298:3218.
41 Wolk K, Mallbris L, Larsson P et al. Excessive body weight and
smoking associates with a high risk of onset of plaque psoriasis.
Acta Derm Venereol 2009; 89:4927.
42 Wolkenstein P, Revuz J, Roujeau JC et al. Psoriasis in France and
associated risk factors: results of a casecontrol study based on a
large community survey. Dermatology 2009; 218:1039.
43 Xiao J, Chen LH, Tu YT et al. Prevalence of myocardial infarction
in patients with psoriasis in central China. J Eur Acad Dermatol Venereol
2009; 23:131115.
44 Zhang X, Wang H, Te-Shao H et al. Frequent use of tobacco and
alcohol in Chinese psoriasis patients. Int J Dermatol 2002; 41:659
62.
45 Zheng GY, Wei SC, Shi TL et al. Association between alcohol,
smoking and HLA-DQA1*0201 genotype in psoriasis. Acta Biochim
Biophys Sin (Shanghai) 2004; 36:597602.
46 Takahashi H, Takahashi I, Honma M et al. Prevalence of metabolic syndrome in Japanese psoriasis patients. J Dermatol Sci 2010; 57:1434.

British Journal of Dermatology (2014) 170, pp304314

314 Psoriasis and smoking: meta-analysis, A.W. Armstrong et al.


47 Zhu KJ, He SM, Sun LD et al. Smoking and psoriasis: a meta-analysis of casecontrol studies. J Dermatol Sci 2011; 63:1268.
48 Yanbaeva DG, Dentener MA, Creutzberg EC et al. Systemic effects
of smoking. Chest 2007; 131:155766.
49 Pryor WA, Stone K. Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann N Y Acad Sci
1993; 686:1227; discussion 278.
50 Emre S, Metin A, Demirseren DD et al. The relationship between
oxidative stress, smoking and the clinical severity of psoriasis. J Eur
Acad Dermatol Venereol 2012; 27:e3705.

British Journal of Dermatology (2014) 170, pp304314

51 Armstrong AW, Armstrong EJ, Fuller EN et al. Smoking and pathogenesis of psoriasis: a review of oxidative, inflammatory and
genetic mechanisms. Br J Dermatol 2011; 165:11628.
52 Heeschen C, Jang JJ, Weis M et al. Nicotine stimulates angiogenesis
and promotes tumor growth and atherosclerosis. Nat Med 2001;
7:8339.
53 Yin XY, Cheng H, Wang WJ et al. TNIP1/ANXA6 and CSMD1 variants interacting with cigarette smoking, alcohol intake affect risk
of psoriasis. J Dermatol Sci 2013; 70:948.

2013 British Association of Dermatologists

Вам также может понравиться