Effect of Tobacco Smoking and Alcohol Consumption on the Prevalence of Nickel Sensitization and Contact Sensitization

Abstract

There is evidence that stimulants such as alcohol and tobacco have an effect on the immune system, but little is known about how these lifestyle factors affect the prevalence of contact sensitization. This study investigated whether smoking and alcohol consumption were associated with contact sensitization and nickel sensitization. A random sample of adults (n=3460) from the general population of Copenhagen was invited to participate in a general health examination including patch-testing. Alcohol consumption was not associated with nickel sensitization, whereas a significant trend (p<0.05) was identified between smoking status and nickel sensitization in an adjusted model; i.e. nickel sensitization was higher among both previous smokers (odds ratio (OR) = 1.19; confidence interval (CI) = 0.81-1.76), current light smokers (OR=1.50; CI=0.94-2.37) and current heavy smokers (OR=1.56; CI = 0.87-2.80) compared with never smokers. This study confirmed that smoking is associated with nickel sensitization, but rejected an association with alcohol consumption.

Full text

Acta Derm Venereol 90
INVESTIGATIVE REPORT
Acta Derm Venereol 2010; 90: 27–33
© 2010 The Authors. doi: 10.2340/00015555-0772
Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555
There is evidence that stimulants such as alcohol and to-
bacco have an effect on the immune system, but little is
known about how these lifestyle factors affect the pre-
valence of contact sensitization. This study investigated
whether smoking and alcohol consumption were asso-
ciated with contact sensitization and nickel sensitization.
A random sample of adults (n = 3460) from the general
population of Copenhagen was invited to participate in
a general health examination including patch-testing.
Alcohol consumption was not associated with nickel sen-
sitization, whereas a signicant trend (p < 0.05) was iden-
tied between smoking status and nickel sensitization in
an adjusted model; i.e. nickel sensitization was higher
among both previous smokers (odds ratio (OR) = 1.19;
condence interval (CI) = 0.81–1.76), current light smo-
kers (OR = 1.50; CI = 0.94–2.37) and current heavy smo-
kers (OR = 1.56; CI = 0.87–2.80) compared with never
smokers. This study conrmed that smoking is associa-
ted with nickel sensitization, but rejected an association
with alcohol consumption. Key words: alcohol drinking;
contact sensitization; general population; public health;
tobacco smoking.
(Accepted September 24, 2009.)
Acta Derm Venereol 2010; 90: 27–33.
Jacob Pontoppidan Thyssen, National Allergy Research
Centre, Department of Dermato-Allergology, Gentofte
Hospital, University of Copenhagen, Niels Andersens
Vej 65, DK-2900 Hellerup, Denmark. E-mail: jacpth01@
geh.regionh.dk
Contact sensitization affects 10–20% of the general
population (1, 2). It is caused mainly by exposure to
nickel, fragrances, and preservatives, whereas genetic
susceptibility seems to be of limited importance (3, 4).
There is substantial evidence that alcohol and tobacco
have an effect on the immune system (5–9), but little is
known about how these lifestyle factors affect the pre-
valence of contact sensitization. Recently, a prospective
Danish population-based study revealed contradictory
results regarding a possible association between alcohol
consumption and contact sensitization (10). Furthermore,
three general population studies have examined whether
tobacco smoking is associated with contact sensitization
(11–13): among 1056 adult Danes, a signicant dose-
response relationship was identied between smoking
and contact sensitization (11). Furthermore, current
smoking was significantly associated with contact
sensitization among 690 Norwegian adult women (12),
whereas no association was identied among 520 young
Swedish young men doing military service (13). Thus, it
remains to be determined convincingly whether alcohol
consumption and tobacco smoking affect the prevalence
and risk of contact sensitization.
The present study aimed to re-investigate a possible
association between these lifestyle factors and contact
sensitization. A random sample of adults from the ge-
neral population in Copenhagen, Denmark, was invited
to participate in a general health examination including
patch-testing. The study focused on nickel sensitization
as it is by far the most prevalent contact sensitization
in the general population (1). Furthermore, data from
previous cross-sectional studies have suggested that
the association between tobacco smoking and nickel
sensitization was slightly stronger than the association
between smoking and contact sensitization to at least
one allergen (11). The current study is of relevance, as
smoking and drinking is prevalent in many countries,
and as an association may have clinical implications
(e.g. the interpretation of patch-test reactions in smo-
kers).
MATERIALS AND METHODS
Study population
A cross-sectional study was performed in the general popula-
tion in Copenhagen. A random sample of 7931 subjects aged
18–69 years was obtained from the Danish Central Personal
Register. All were Danish adults with Danish citizenship and
born in Denmark. A total of 3471 (43.7%) subjects participated
in a general health examination and 3460 were patch-tested.
The participation rate was higher among older age-groups than
among younger age-groups in both genders (14). The study was
approved by the ethics committee of Copenhagen County (KA-
20060011). Written informed consent form was obtained from
all participants prior to the beginning of the study.
Patch-tests
Patch-testing was performed by using panel 1 and 2 from the
standardized ready to apply TRUE-test® (Mekos Laboratories,
Hillerød, Denmark). Directions to apply the patch-test panels to
Effect of Tobacco Smoking and Alcohol Consumption on the
Prevalence of Nickel Sensitization and Contact Sensitization
Jacob P. THYSSEN1, Jeanne D. JOHANSEN1, Torkil MENNÉ2, Niels H. NIELSEN3 and Allan LINNEBERG4
1 Department of Dermato-Allergology, National Allergy Research Centre, 2Department of Dermato-Allergology, Gentofte University Hospital, 3Dermato-
logy Clinic, Bagsværd, Denmark, and 4Research Centre for Prevention and Health, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark

28 J. P. Thyssen et al.
the upper back 2 days before examination were posted together
with the patch-tests. All testing was performed between June
2006 and May 2008. On the day of examination, they were read
and photographed 1–1.5 h after removal by trained healthcare
personnel (supervised by JPT and AL). The photographs were
reviewed by TM, NHN, AL and JPT to ensure that the Inter-
national Contact Dermatitis Research Group (ICRDG) criteria
were used consistently over time. Contact sensitization was
defined as a positive (at least grade 1+ according to ICRDG
criteria) patch-test to at least one allergen or mixes of haptens.
It has been estimated that approximately 18–29% of posi-
tive patch-test reactions to nickel are missed when patch-test
readings are performed only on day 2 and not on day 4 (15).
If the patch was found to have no skin contact upon patch-test
removal, or if the subject had removed the patch prior to testing
as a result of known contact sensitization, it was regarded as
missing data.
Measurement of immunoglobulin E antibodies
Venous blood was taken on the day of examination and was
left to coagulate for 2 h. The serum was then separated by
centrifugation at 3000 rpm for 10 min and frozen immediately
afterwards. The serum samples were analysed for immunoglo-
bulin E (IgE) specific to birch, grass (timothy), cat, and mite
(Dermatophagoides pteronyssinus) with the ADVIA Centaur
IgE antibody assay system (Bayer Corporation, Leverkusen,
Germany) (16). Analysis for IgE antibodies was judged to be
positive if the measurement was in excess of 0.35 kU/l. Specific
IgE positivity was defined as a positive test to at least one of
the four allergens tested.
Questionnaire
Table I lists the questions used for the present study. Partici-
pants were asked about smoking and drinking habits as well as
about vocational training, social status and ear-piercing status.
Occasional smokers (3.3%) were excluded from the analyses.
The amount of tobacco in grams smoked per day among current
smokers were calculated for cigarettes, cheroots, cigars and
pipe tobacco by equating one cigarette or 1 g of pipe tobacco
to 1 g tobacco, one cheroot to 3 g tobacco and one cigar to 5
g tobacco. The information was used to define smoking status
(as “never smokers”, “previous smokers”, “current light smo-
kers: ≤ 15 g/day”, or “current heavy smokers: > 15 g/day”). It
was assumed that one normal beer, one glass of wine, and one
serving of spirits equalled one drink (each containing 12 g
ethanol/15 ml) whereas one strong beer was assumed to equal
1.5 drinks (each contained 18 g ethanol/15 ml). The total weekly
consumption was then calculated by adding the number of
drinks of beer, wine, and spirits. The total alcohol consumption
was categorized as 0, 1–7, 8–14, ≥ 15 drinks per week for the
Table I. Questions used in the questionnaire
Question category Group questioned Question List of answers
Smoking All participants Do you smoke? Yes, daily
Yes, occasionally (less than 1 cigarette, or 1 cheroot, or 1 pipe
of tobacco per day)
No, but previously
No, never
Daily smokers only Please indicate how much tobacco you
smoke on average per day?
Number of cigarettes
Number of cheroots
Number of cigars
Grams of pipe tobacco
Alcohol consumption All participants Have you consumed any alcoholic drinks
during the past 12 months?
Yes
No
Drinkers within the
past 12 months
How many of the following drinks have
you had on average per week during the
past 12 months?
Number of normal beers
Number of strong beers
Number of glasses of wine (1 bottle of wine equals 6 glasses)
Number of glasses/units of spirits (standard drinks)
Ear-piercing All participants Have you ever had your ears pierced? Yes
No
Vocational training All participants Have you ever had vocational training? Yes
No
All participants What is your educational level? Skilled or unskilled blue-collar workers
Short-cycle higher education (< 3 years, e.g. dental technician
and nursing assistants)
Medium higher education (3–4 years, e.g. nurse, school teacher,
and physiotherapist)
Long-cycle higher education (> 4 years, e.g. medical physician,
psychologist, and engineer
Other education
Social status All participants What is your self-estimated social status
based on education, job, income, etc.
Very high
High
Middle
Below middle
Low
Type of residence All participants What kind of residence do you live in? House
Apartment
Other
Acta Derm Venereol 90

29
Contact allergy and lifestyle factors
prevalence calculations. The questions used for assessment of
alcohol consumption had been validated previously against
increased levels (≥ 80 IU/l) of serum γ-glutamyl transferase
(GGT), a marker of alcohol exposure (17). The results revealed
that self-reported total alcohol intake (total number of drinks/
week) was significantly and positively associated with increased
levels of GGT (18).
Statistical analysis
Characteristics of participants were compared using the χ2
test. A logistic regression model was performed with nickel
sensitization as the dependent variable, and sex, age-group
(“18–35 years”, “36–55 years”, “56–69 years”), and smoking
status (“never smokers”, “previous smokers”, “current light
smokers: ≤ 15 g/day”, “current heavy smokers: > 15 g/day”)
as the independent variables. In this model, a test for inter-
action between sex and smoking status was performed by using
a log-likelihood ratio test. In order to examine the potential
confounding effects of selected variables, we performed several
logistic regression models adding one variable at a time while
observing changes in the risk estimates for the exposure vari-
ables (smoking and alcohol consumption). These analyses were
performed with nickel sensitization as the dependent variable
and with sex, age-group (“18–35 years”,”36–55 years”, “56–69
years”), smoking status (“never smokers”, “previous smokers”,
“current light smokers: ≤ 15 g/day”, “current heavy smokers:
> 15 g/day”), ear-piercing (“yes”, “no”), alcohol consumption
(“0”, “1–7”, “8–14”, “≥ 15”), and educational level (“skilled or
unskilled blue-collar workers”, “short-cycle higher education”,
“medium higher education”, “long-cycle higher education”,
“other education”) as the explanatory variables. In further ana-
lyses, possible confounding by other socio-economic variables,
such as “self-estimated social status”, “vocational training” and
“type of residence”, were investigated and revealed essentially
similar results as adjustment with the variable for educational
level. In fact, an analysis adjusted for “self-estimated social
status” instead of educational level revealed a much stronger
association between tobacco smoking and nickel sensitization.
Also, adjustment for the occurrence of IgE antibodies was
performed, but this did not change the results. Finally, similar
logistic regression analyses were performed with “contact sensi-
tization to at least one allergen” and “contact sensitization to at
least one allergen but not nickel”, respectively, as the dependent
variables and with the explanatory variables listed in Table III.
Associations were expressed as odds ratios (ORs) with 95%
confidence intervals (95% CI). Data analyses were performed
using the Statistical Products and Service Solutions package
(SPSS Inc., Chicago, IL, USA) for Windows (release 15.0).
RESULTS
Characteristics of the study population according to
gender are presented in Table II. The prevalence of
contact sensitization to at least one allergen, nickel
contact sensitization, and ear-piercing was markedly
higher among women than men, whereas men consumed
signicantly more alcohol than women. The prevalence
of never smokers and previous smokers was nearly iden-
tical among women and men, whereas the prevalence
of current light smokers (≤ 15 g/day) was higher among
women than men (16.3% vs. 9.5%) and the prevalence
of current heavy smokers (> 15 g/day) was higher among
men than women (12.6% vs. 7.9%).
Table III shows the baseline characteristics of parti-
cipants stratied by smoking status. The proportion of
current light smokers (≤ 15 g/day) was higher among
subjects who were ear-pierced or were nickel sensitized
Table II. Gender-specic characteristics regarding contact sensitization (to at least one of 24 allergens), nickel contact sensitization,
a history of ear-piercing, specic immunoglobulin (Ig)E status, alcohol consumption, smoking status, and educational level. Data was
based on a general health examination including patch-testing among 3471 18–69-year-old participants from a cross-sectional study
performed in Copenhagen, Denmark between 2006 and 2008
Men
% (n/total)
Women
% (n/total) p-valuea
Contact sensitization to at least one allergen 4.7 (73/1547) 14.2 (272/1913) 0.001
Nickel contact sensitization 1.0 (15/1495) 10.3 (189/1913) 0.001
Ear-piercing 17.0 (261/1538) 82.2 (1564/1902) 0.001
Specic IgEb27.3 (418/1531) 20.0 (378/1889) 0.001
Alcohol consumption (drinks per week within past 12 months)
0 9.0 (138/1532) 19.2 (367/1912) < 0.001
1–7 33.7 (516/1532) 53.0 (1013/1912)
8–14 24.3 (372/1532) 17.7 (338/1912)
≥ 15 33.0 (506/1532) 10.1 (194/1912)
Smoking status
Never smokers 43.3 (640/1478) 43.1 (795/1846) < 0.001
Previous smokers 34.6 (512/1478) 32.7 (604/1846)
Current light smokers ≤ 15 g/day 9.5 (140/1478) 16.3 (301/1846)
Current heavy smokers > 15 g/day 12.6 (186/1478) 7.9 (146/1846)
Educational level
Skilled or unskilled blue-collar workers 44.8 (602/1345) 37.3 (609/1633) < 0.001
Short-cycle higher education 14.1 (189/1345) 20.1 (328/1633)
Medium higher education 17.4 (234/1345) 26.1 (426/1633)
Long-cycle higher education 13.4 (180/1345) 7.5 (122/1633)
Other 10.4 (140/1345) 9.1 (148/1633)
ap-value of χ2 test for the comparison of women and men.
bAnalysis for IgE specic to birch, grass (timothy), cat, and mite (Dermatophagoides pteronyssinus). The analysis was judged to be positive if the
measurement was in excess of 0.35 kU/l.
Acta Derm Venereol 90

30 J. P. Thyssen et al.
in comparison with subject who were not ear-pierced
and who were not nickel sensitized. Alcohol consump-
tion tended to increase with smoking status and the
proportion of current heavy smokers (> 15 g/day) was
higher among subjects with a short education.
Crude data analyses without adjustment for poten-
tial confounders showed that nickel sensitization was
signicantly associated with female sex, ear-piercing,
alcohol consumption (≥ 15 drinks per week), and to-
bacco smoking (Table IV). The relationship between
nickel sensitization and educational level revealed
no clear pattern except a higher prevalence of nickel
sensitization among subjects with a short-cycle higher
education. We evaluated whether it could be assumed
that the effects of smoking were independent of gender.
Thus, a logistic regression model was performed with
nickel sensitization as the dependent variable, and with
sex, age-group (“18–35 years”,”36–55 years”, “56–69
years”), smoking status (“never smokers”, “previous
smokers”, “current light smokers ≤ 15 g/day”, “current
heavy smokers > 15 g/day”), and an interaction term
between sex and smoking status as the independent
variables. No signicant interaction was found between
sex and smoking status (p = 0.97), which means that the
possible effect of smoking status on the prevalence of
nickel sensitization did not differ between men and wo-
men. In order to examine possible confounding, several
logistic regression models were performed in which one
variable was added at a time while observing changes in
the risk estimates for the exposure variables (smoking
and alcohol consumption) (Table IV). The regression
analyses revealed that ear-piercing was an important
confounder, which indicates that nickel sensitization to a
high degree is an environmental disorder. Furthermore,
the analyses showed that alcohol consumption was not
associated with nickel sensitization, whereas a signi-
cant trend (p < 0.05) was identied between smoking sta-
tus and nickel sensitization in the fully adjusted model
(Table IV). Finally, similar logistic regression analyses
were performed with “contact sensitization to at least
one allergen” and “contact sensitization to at least one
allergen but not nickel”, respectively, as the independent
variable and with the explanatory variables listed in
Table IV. These analyses did not show any signicant
associations between contact sensitization on the one
hand and alcohol consumption or smoking status on the
other hand. Thus, the fully adjusted regression analysis,
with contact sensitization to at least one allergen as the
dependent variable, revealed a non-signicant trend test
for smoking status (p < 0.6) (data not shown).
DISCUSSION
The results of this study show that nickel sensitization
is signicantly associated with tobacco smoking. The
association was dose-dependent and independent of
gender. The results are in line with those from another
cross-sectional population-based study performed in
1056 Danish adults (11) and are supported by a Norwe-
gian patch-test study in which a signicant association
was identied in adult women (12).
It is important to evaluate to what extent confounding
by other factors could explain the positive association
Table III. Characteristics of 3471 participants from a cross-sectional study performed in Copenhagen grouped by smoking status
Smoking status
p-valuea
Never smokers
% (n)
Previous smokers
% (n)
Current light smokers
≤15 g/day
% (n)
Current heavy smokers
> 15 g/day
% (n)
Age (years)
18–35 (n = 593) 57.8 (343) 20.4 (121) 14.2 (84) 7.6 (45) 0.001
36–55 (n = 1613) 39.7 (641) 35.0 (565) 13.9 (224) 11.3 (183)
56–69 (n = 1118) 40.3 (451) 38.5 (430) 11.9 (133) 9.3 (104)
Ear-piercing
Yes (n = 1752) 38.7 (678) 34.1 (598) 17.1 (300) 10.0 (176) 0.001
No (n = 1563) 48.0 (751) 33.0 (516) 9.0 (140) 10.0 (156)
Nickel sensitization
Yes (n = 1752) 31.4 (678) 36.6 (598) 21.1 (300) 10.8 (176) 0.001
No (n = 1563) 44.4 (751) 33.2 (516) 12.6 (140) 9.7 (156)
Alcohol consumption (drinks/week within past 12 months)
0 (n = 472) 43.2 (204) 31.8 (150) 12.5 (59) 12.5 (59) 0.001
1–7 (n = 1484) 50.1 (743) 30.1 (447) 12.7 (188) 7.1 (106)
8–14 (n = 673) 39.5 (266) 36.4 (245) 15.5 (104) 8.6 (58)
≥15 (n = 668) 31.0 (207) 40.0 (267) 13.0 (87) 16.0 (107)
Educational level
Skilled or unskilled blue-collar worker (n = 1174) 38.4 (451) 35.2 (413) 14.1 (166) 12.3 (144) 0.001
Short cycle higher education (n = 499) 37.7 (188) 36.5 (182) 14.0 (70) 11.8 (59)
Medium cycle higher education (n = 631) 46.0 (290) 37.1 (234) 11.6 (73) 5.4 (34)
Long cycle higher education (n = 289) 64.7 (187) 24.9 (72) 6.2 (18) 4.2 (12)
Other education (n = 275) 44.4 (122) 35.3 (97) 12.7 (35) 7.6 (21)
ap-value of χ2 test for the comparison of different categories of smoking status.
Acta Derm Venereol 90

31
Contact allergy and lifestyle factors
observed between smoking and nickel sensitization
(Table III). The association remained relatively unchan-
ged after adjustment for confounders by multivariable
regression analyses (Table IV) although it cannot be
ruled out that residual confounding (insufcient adjust-
ment) or confounding by factors not included in this
study could play a role. When the logistic regression
analysis was adjusted for educational level, the asso-
ciation be tween smoking and nickel sensitization was
weakened. Thus, it is possible that we were not able to
sufciently adjust for social status in our analyses as
an association between nickel sensitization and socio-
economic status has been suggested previously (19). In
Malmö, Sweden, the prevalence of nickel sensitization
was signicantly higher among immigrants, unemploy-
ed, and patients on social security than among patients
from higher socio-economic groups (19). Furthermore,
a German study showed that the prevalence of nickel
sensitization was higher among nurses (24.9%) and
receptionist (29.3%) than among physicians (12.1%),
indicating that nickel sensitization may be less prevalent
in high-income groups (20). Despite the suggested asso-
ciation between nickel sensitization and socio-economic
status, no association was identied between educatio-
nal level and nickel sensitization in both an adjusted and
an unadjusted analysis in this study (Table IV). We can-
not exclude that the association between nickel allergy
and tobacco smoking to some degree was explained by
ear-piercing as it was more frequently reported among
current light smokers (Table III).
This study did not identify any signicant associations
between smoking status and “contact sensitization to at
least one allergen but not nickel” and “contact sensitiza-
tion to at least one allergen”, respectively. It should be
emphasized that the prevalence of contact sensitization
to contact allergens other than nickel was low in this
general population (Table II). Also, since patch-test
readings were performed only on day 2 in this study, a
lower prevalence of contact sensitization was expected
(15, 21). The low prevalence estimates will necessarily
lead to reduced statistical power in the regression analy-
ses, which may hide associations. However, a previous
Danish study also showed that nickel sensitization had a
slightly stronger association with smoking than contact
sensitization to at least one allergen (11). The stronger
association observed for nickel sensitization may be
explained by the fact that nickel is found in tobacco
plants as a result of absorption from soil, fertilizing
Table IV. The relationship of different potential risk factors to the prevalence of nickel sensitization
Nickel sensitization
% (n/total)
Crude OR
(95% CI)
Adjusted ORa
(95% CI)
Adjusted ORb
(95% CI)
Adjusted ORc
(95% CI)
Adjusted ORd
(95% CI)
Smoking status
Never smokers 4.4 (61/1397) 1.00 1.00, ep < 0.001 1.00, ep < 0.005 1.00, ep < 0.009 1.00, ep < 0.05
Previous smokers 6.6 (71/1071) 1.56 (1.09–2.21) 1.60 (1.11–2.91) 1.45 (1.00–2.09) 1.41 (0.98–2.05) 1.19 (0.81–1.76)
Current light smokers ≤ 15 g/day 9.7 (41/421) 2.36 (1.57–3.57) 1.91 (1.25–2.31) 1.72 (1.13–2.63) 1.65 (1.08–2.53) 1.50 (0.94–2.37)
Current heavy smokers > 15 g/day 6.7 (21/313) 1.58 (0.94–2.63) 1.97 (1.15–3.35) 1.78 (1.04–3.05) 1.73 (1.01–2.98) 1.56 (0.87–2.80)
Sex
Men 1.0 (15/1495) 1.00 1.00 1.00 1.00 1.00
Women 10.3 (189/1843) 11.27 (6.63–19.16) 11.03 (6.36–19.16) 5.50 (2.95–10.2) 5.83 (3.10–10.97) 5.55 (2.85–10.81)
Age (years)
18–35 7.2 (45/622) 1.00 1.00 1.00 1.00 1.00
36–55 7.9 (128/1625) 1.10 (0.77–1.56) 1.04 (0.71–1.52) 1.09 (0.75–1.60) 1.03 (0.70–1.52) 0.99 (0.65–1.51)
56–69 2.8 (31/1091) 0.38 (0.24–0.60) 0.41 (0.25–0.64) 0.48 (0.29–0.79) 0.45 (0.27–0.74) 0.41 (0.24–0.73)
Ear-piercing
No 1.2 (19/1567) 1 – 1.00 1.00 1.00
Yes 10.6 (184/1741) 9.63 (5.97–15.52) – 3.35 (1.89–5.96) 3.44 (1.93–6.13) 3.01 (1.66–5.46)
Alcohol consumption (drinks/week within past 12 months)
0 7.6 (36/475) 1.00 – – 1.00 1.00
1–7 6.7 (98/1472) 0.87 (0.59–1.29) – – 1.02 (0.67–1.56) 0.96 (0.61–1.52)
8–14 6.4 (44/683) 0.84 (0.53–1.32) – – 1.42 (0.86–2.34) 1.33 (0.77–2.29)
≥ 15 3.8 (26/682) 0.48 (0.29–0.81) – – 1.34 (0.77–2.37) 1.05 (0.56–1.97)
Educational level
Skilled or unskilled blue-collar
worker
5.8 (67/1151) 1.00 – – – 1.00
Short cycle higher education 9.3 (46/495) 1.66 (1.12–2.45) – – – 1.16 (0.76–1.76)
Medium cycle higher education 6.4 (41/638) 1.11 (0.74–1.66) – – – 0.87 (0.57–1.33)
Long cycle higher education 4.0 (12/297) 0.68 (0.36–1.28) – – – 0.71 (0.33–1.49)
Other education 5.3 (15/281) 0.91 (0.51–1.62) – – – 0.99 (0.54–1.84)
aLogistic regression analysis adjusted for sex, age and smoking.
bLogistic regression analysis adjusted for sex, age, smoking, and ear-piercing.
cLogistic regression analysis adjusted for sex, age, smoking, ear-piercing, and alcohol consumption.
dLogistic regression analysis adjusted for sex, age, smoking, alcohol consumption, ear-piercing and educational level.
eTrend test.
OR: odds ratio; CI: condence interval.
Acta Derm Venereol 90

32 J. P. Thyssen et al.
products or pesticides. Furthermore, the nickel content
in cigarettes and tobacco is high regardless of its kind
and origin (22). One study examined the nickel concen-
tration in 123 blood samples and 147 urine samples from
smokers and non-smokers. It revealed a signicantly
higher concentration of nickel in the urine but not in
the blood of smokers in comparison to non-smokers
(22). It is therefore possible that T-cells in smokers are
exposed to nickel in concentrations that may lead to
nickel sensitization. However, nickel exposure from
cigarettes is probably of minor importance in terms of
inducing nickel contact sensitization as the prevalence
of nickel sensitization in men was approximately 1%,
whereas almost 50% of men reported current or pre-
vious smoking. Finally, the ndings in this study (i.e. a
stronger association for nickel sensitization than contact
sensitization) could be coincidental or a result of con-
founding, as nickel sensitization may have a stronger
association with lower social groups than, for example,
fragrance and preservative sensitization.
Contact sensitization and autoimmune conditions
have traditionally been regarded as T-helper 1 (Th1)-
mediated immune responses, whereas sensitization
to aeroallergens, as observed in allergic asthma and
rhinitis, has been regarded as a Th2 mediated condition
(23, 24). The Th1/Th2 dichotomy was for many years the
cornerstone of immunological thinking and dictated that
Th1 cells were down-regulated by cytokines released
from Th2 cells and vice versa. As it was recently
demonstrated that a subgroup of T cells, “T-regulatory”
(Treg), may suppress both Th1- and Th2-mediated
immune responses, the dichotomy may only partially
explain the development of various immune responses
(25, 26). However, tobacco smoking has been causally
linked to the development of autoimmune diseases, such
as systemic lupus erythematosus, multiple sclerosus,
Grave’s hyperthyroidism, rheumatoid arthritis (27),
and contact sensitization (11, 12) whereas prospective
population-based studies have suggested that tobacco
smoking may decrease the risk of IgE-mediated allergic
sensitization to aeroallergens (28, 29). Also, cross-
sectional population based studies have demonstrated a
lower prevalence of sensitization to common aeroaller-
gens among smokers and ex-smokers than among non-
smokers (30, 31). Thus, it seems plausible that tobacco
smoking favours Th1-mediated immune responses and
suppresses Th2-mediated immune responses. These
immunological perspectives support the ndings from
this study, although it should be recognized that humane
immune responses are very complex as demonstrated
by contact sensitization being inversely related to type
I diabetes and inammatory bowel diseases (32, 33).
This study did not identify any association between
alcohol consumption and the prevalence of nickel sen-
sitization (or contact sensitization), although nickel al-
lergy appeared to be lower for individuals who reported
alcohol abstinence in the adjusted analysis (Table IV).
However, as participants were asked only about alcohol
consumption within the past 12 months, it is possible
that we did not accurately assess the cumulated alcohol
exposure. Also, the limitations of day two patch-test
readings reduced statistical power in our analysis, which
may hide an association (15, 21). We are aware of only
one previous study that also addressed the association
between contact sensitization and alcohol consumption
(10). This study did not identify any association between
the prevalence of alcohol consumption and contact
sensitization, whereas it suggested that the 8-year
incidence of contact sensitization was signicantly
higher among non-drinking women (10). In general, a
prospective incidence-based analysis is considered more
reliable than cross-sectional studies when determining
the cause-effect relationship. A follow-up of the present
study population would be of interest to investigate this
issue further. Furthermore, it may be of interest to take
into account genetic variations in alcohol metabolism,
as certain genetic variations may inuence both alcohol
drinking behaviour and susceptibility to the immuno-
logical effects of alcohol (34). Such genetic inuence
would tend to bias associations between alcohol and
immune effects.
In conclusion, this general population study conr-
med our previous nding that smoking is associated
with nickel sensitization. The possible biological
mechanisms underlying this association remain to be
elucidated. We could not conrm the previously repor-
ted negative association between alcohol consumption
and the development of contact sensitization. In future
prospective studies, it could be of interest to investigate
whether tobacco-smoking leads to a poor prognosis of
allergic nickel contact dermatitis in comparison with
non-smokers.
ACKNOWLEDGEMENTS
Funding sources: The Danish Board of Health, The Danish
Environmental Protection Agency, The Copenhagen County
Research Foundation, Aase and Einar Danielsens Foundation,
The Velux Foundation, ALK-Abelló A/S, Denmark and The
Danish Scientific Research Council. Furthermore, MEKOS
Laboratories and ALK-Abelló A/S, Denmark kindly donated
some of the TRUE tests.
The authors declare no conflict of interest.
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