Contact Dermatitis • Original Article COD

Contact Dermatitis

Nickel allergy in relation to piercing and orthodontic appliances – a

population study
Ronny Fors1 , Berndt Stenberg2 , Hans Stenlund3 and Maurits Persson1
1 Department of Odontology, Orthodontics, Umeå University, SE-901 87 Umeå, Sweden, 2 Department of Public Health and Clinical Medicine, Dermatology &
Venereology and Epidemiology & Global Health, Umeå University, SE-901 87 Umeå, Sweden, and 3 Department of Public Health and Clinical Medicine,
Epidemiology, Umeå University, SE-901 87 Umeå, Sweden

doi:10.1111/j.1600-0536.2012.02097.x

Summary Background. Studies have shown conflicting results on the association between nickel
exposure from orthodontic appliances and nickel sensitization.
Objectives & Method. In a cross-sectional study, we investigated the association
between nickel sensitization and exposure to orthodontic appliances and piercings. 4376
adolescents were patch tested following a questionnaire asking for earlier piercing and
orthodontic treatment. Exposure to orthodontic appliances was verified in dental records.
Results. Questionnaire data demonstrated a reduced risk of nickel sensitization when
orthodontic treatment preceded piercing (OR 0.46; CI 0.27–0.78). Data from dental
records demonstrated similar results (OR 0.61, CI 0.36–1.02), but statistical significance
was lost when adjusting for background factors. Exposure to full, fixed appliances
with NiTi-containing alloys (OR 0.31, CI 0.10–0.98) as well as a pooled ‘high nickel-
releasing’ appliance group (OR 0.56, CI 0.32–0.97) prior to piercing was associated with
a significantly reduced risk of nickel sensitization.
Conclusion. High nickel-containing orthodontic appliances preceding piercing
reduces the risk of nickel sensitization by a factor 1.5–2. The risk reduction is associated
with estimated nickel release of the appliance and length of treatment. Sex, age at piercing
and number of piercings are also important risk indicators. Research on the role of dental
materials in the development of immunological tolerance is needed.

Key words: cross-sectional; dental braces; patch test; questionnaire; tolerance.

Nickel is the most common contact allergen in Europe and earlier study, we found orthodontic appliances in 45% of
the United States (1, 2). Many children and adolescents adolescents (4).
are exposed to nickel intra-orally from orthodontic The level of in vitro release of nickel from orthodontic
appliances (dental braces) with alloys containing up to appliances has been reported to be 22–40 µg of nickel
50% nickel (3). There is public concern about the release per day, which is low in comparison with the estimated
of nickel and sensitization from such appliances. In an dietary intake of 100–800 µg per day (5–9). The release
of nickel varies with the composition and manufacture of
the appliance components, and between archwire alloys
Correspondence: Ronny Fors, Department of Odontology, Orthodontics, and mechanical straining, but not with actual nickel
Umeå University, SE-901 87 Umeå, Sweden. Tel: +46 (0)90 785 61 94; Fax: content (6–8).
+46 (0)90 13 25 78. E-mail: [email protected] The results from studies in vivo on nickel content in
Conflicts of interest: The authors have declared no conflicts. Funding: saliva and other body fluids as a result of insertion of
The Vårdal Foundation, the Asthma and Allergy Research Foundation, the orthodontic components are inconsistent (10–13). No
Swedish Dental Association, and the County Council of Västerbotten.
differences have been demonstrated between individuals
Accepted for publication 3 March 2012 with or without orthodontic appliances, or between saliva

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342 Contact Dermatitis, 67, 342–350
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collected before and after appliance insertion (14–17). Sampling and calculation of sample size
We have recently found significantly higher nickel con- Of 7543 adolescents (4409 girls and 3134 boys) in
tents in dental plaque in patients with orthodontic the visited school classes, 6095 (81%) answered a
appliances than in non-orthodontic patients (17). questionnaire following a briefing session. The median age
The diverse findings regarding nickel release between of respondents was 17.1 years (range 14.0–23.4 years).
in vitro and in vivo studies are probably attributable to the Among pupils present at the briefing sessions (6364),
lack of comparable micro-environmental conditions in nearly 96% answered the questionnaire, and 70% (4439)
relation to pH, temperature, stress simulation, presence of of those consented to patch testing. Sixty-three patch tests
microbes, and properties of the saliva. The methodological fell off and could not be evaluated. Of the 4376 adolescents
reliability and the clinical relevance of the in vitro models who answered the questionnaire and performed the patch
used have been questioned, as they differ from the test, 2976 (68%) were girls and 1400 (32%) boys (Fig. 1).
conditions in the oral cavity (3). The population and study design, as well as the statistical
Clinical studies indicate an insignificant risk of sensiti- management of dropout/non-participation, have been
zation to nickel from orthodontic appliances or elicitation described previously (33).
of reactions in sensitized persons (18–27). Rather, a
The sample size was chosen to achieve a sufficient num-
reduced risk of nickel allergy, owing to oral tolerance,
ber of adolescents for a case–referent analysis on exposure
has been suggested in some clinical and experimental
to nickel and nickel allergy by investigating orthodontic
studies (23, 28–31).
appliance treatment preceding (non-exposed/reference
Piercing, in particular, seems to trigger nickel sensiti-
exposure) and following (exposed/risk exposure) pierc-
zation (32). Intra-oral release of nickel from orthodontic
ing. Thirty per cent of the adolescents were estimated to
appliances may act synergistically or antagonistically in
have received orthodontic appliance treatment, 90% of
the development of nickel allergy (23).
the schoolgirls were estimated to have pierced their ears
The purpose of this study was to investigate the
at 15 years of age, and the prevalence of nickel allergy
association between nickel allergy, exposure to intra-oral
was estimated to be 12–15%. The power was set to 80%,
orthodontic appliances, and piercings. We aimed to secure
the significance level to 0.05, the smallest detectable odds
high quality exposure data on orthodontic appliance
ratio (OR) to 2.0, and the case–referent ratio to 1:4. A
treatment by analysing dental records and obtaining
minimum of 184 ‘cases’ (with nickel allergy and exposed
valid health data from test-verified cases of nickel allergy.
to both orthodontic appliances and piercing in varying
order) were needed. On the basis of these assumptions,
Hypothesis it was determined that the analysis would require 3700
We hypothesize that oral exposure to nickel in orthodontic girls, and the total sample size would need to be 7400
appliances prior to a piercing event may have a protective male and female students. After testing 4376 pupils, we
effect against nickel sensitization. Age at piercing, atopy had retrieved 197 ‘cases’, and the data collection was
and sex were considered to be potential confounding stopped (Fig. 1).
factors.
Questionnaire
Subjects and Methods A questionnaire was administered during visits to classes,
at which point the patch test was also offered. The
Study design pupils were asked whether they had received orthodontic
The study was a cross-sectional survey on nickel allergy appliance treatment, and, when there were affirmative
in upper secondary schools in the cities of Umeå and answers, their age when the appliance was placed and
Örebro, Sweden. The study period extended from Septem- a description of their first appliance were recorded. In
ber 2000 to May 2004. Nickel allergy was verified by addition, the questionnaire included questions on age at
a positive patch test reaction. Exposure to piercing was (ear) piercing, number of piercings, eczema caused by
reported by questionnaire [age at piercing, and number metal contact, tattooing, diet, smoking habits, atopy, and
and localization of piercing(s)]. Exposure to intra-oral hand eczema (33).
orthodontic appliances was recorded with a question-
naire (age at start of orthodontic appliance treatment)
and verified from dental records. For all participants who Patch test method
reported having received orthodontic treatment, dental We used ready-to-use TRUE Test® panels 1 and 2 (Mekos
records were examined. Laboratories A/S, Hillerød, Denmark) containing 24 of the

© 2012 John Wiley & Sons A/S

Contact Dermatitis, 67, 342–350 343
NICKEL ALLERGY AND ORTHODONTIC APPLIANCES • FORS ET AL.

4376 patch-tested in Umeå and Örebro

2976 (68%) girls
1400 (32%) boys

Orthodontic appliance and piercing (questionnaire)

1379 for case–referent analysis
1285 girls
94 boys

14 no reported age at piercing

24 no permission to search dental

records

Eligible orthodontic appliance verified by dental records

1341 for case–referent analysis
1251 girls
90 boys

9 dental records or data on treatment

totally missing

17 records added to the study from

Data obtained for extended exposure analyses the validity check
1332 + 17 = 1349
1254
12 4 girls
il
95 boys

197/1349 (15%) nickel-positive patch test = cases

1152/1349 (85%) nickel-negative patch test = referents

Fig. 1. Retrieval of cases and referents for statistical analyses in the cross-sectional study.

most common allergens. No patch tests were performed The following data were collected from dental records:
during the summer months (June–August) (33). Nickel (i) date(s) at placement of appliance(s); (ii) type of
allergy was defined as a positive test (+, ++, or +++) at appliance; and (iii) duration of appliance treatment. The
day 4 and read according to international guidelines (34). orthodontic appliances were categorized into groups,
on the basis of an estimated rate of exposure to nickel
(Table 1) (5–6, 8, 35–39).
Verification of intra-oral exposure to orthodontic
appliances from dental records
Of 4376 (2976 girls and 1400 boys; Fig. 1) successfully Data handling and statistical analysis
patch-tested students, 4161 (95.1%) [2871 (96.5%) girls The χ 2 -test was used for comparison of proportions. Sta-
and 1290 (92.1%) boys] gave permission for data to be tistical significance was defined as p < 0.05. Associations
collected on exposure to orthodontic treatment from their between the dependent variable (positive nickel patch test
dental records. Among the 1379 students with reported reaction) and independent variables were analysed as
exposure to both orthodontic treatment and piercing, we ORs with 95% confidence intervals (CIs) with logistic
traced all dental records from general and specialist dental regression.
clinics for 1341 (97.5%) individuals. Data were obtained Age at piercing was converted into a piercing date by
from 1332 dental records. In addition, 17 records from a adding 6 months to individual dates of birth (mid-year
validity test among a random sample (n = 330) of students method). The estimated difference in exposure to nickel
reporting non-exposure to orthodontic appliances were from intra-oral orthodontic appliances was expressed by
added to the dataset. the following variables: (i) total time spent undergoing

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344 Contact Dermatitis, 67, 342–350
 NICKEL ALLERGY AND ORTHODONTIC APPLIANCES • FORS ET AL.

Table 1. Classification of recorded types of appliance based on their estimated intra-oral nickel release

Estimated intra-oral nickel

Group Type of appliance Metal exposure release

1 Appliances with no metal components; None None

acrylic or resilient splints without clasps
2 Plates, activators with and without extra-oral Few stainless steel components, no solders i.o. Probably lowa
traction, bonded buttons
3 One or two molar bands, lingual arches, Stainless steel components, solders (intra-oral or Moderateb
extra-oral traction, sectional fixed extra-oral)
appliance in one jaw
4 Full fixed appliance unimaxillary or Stainless steel components; extensive exposure Probably highc
bimaxillary, rapid maxillary
expansion-appliances or similar
5 Same as group 4, but with NiTi-containing Stainless steel components; high Ni content Highd
alloys verified
6 All types of retention appliance, etched or Mainly stainless steel; long-term; unknown Unknown; probably low
enamel retained bridges, brass ligatures
7 Ag-/Au-chains applied to surgically Alloys contacting open wounds Unknown
uncovered teeth
a Toms (35), Jones et al. (36).
b Grimsdottir et al. (6), Gjerdet & Hero (37).
c
Park & Shearer (5), Maijer & Smith (38).
d
Jia et al. (8), von Fraunhofer (39).

appliance treatment (in days); and (ii) different types The median age, according to the questionnaire, when
of appliance groups, including a (‘pooled’) variable orthodontic appliances were first placed was ∼1 year
expressing appliances with estimated low or high nickel higher than the median age verified from dental records
release. In case–referent analyses, exposure to appliances (11.4 years for girls and 11.7 years for boys).
placed before piercing (reference category) was compared
with exposure to appliances following piercing (risk Self-reported prevalence of orthodontic treatment and piercing.
category). Among the 4376 patch tested students, orthodontic
The statistical software package SPSS™ (version 12.0.1) appliance treatment was reported in 51.7% of females
was used. and in 38.5% of males (Table 2). From the questionnaire
data, the median age when orthodontic appliances were
first placed was 12 years (range 5–20 years; girls 12 years
Ethical considerations
and boys 13 years). Piercing was reported for 83.8% of
The study was approved by the Ethics Committee of the the girls and 19.5% of the boys. The self-reported median
Faculty of Medicine and Odontology, Umeå University age at piercing was 10 years (range 1–19 years; girls
(§491/98, dnr 98-390). Participation in the study was 10 years and boys 11 years).
based on written consent from the pupils following
parental approval. Distribution of nickel allergy (patch test-positive) for self-reported
orthodontic appliance treatment and piercing (Table 3). The
overall prevalence of nickel allergy among 4376 patch-
Results tested students was 9.9% (girls 13.3% and boys 2.5%).
For girls reporting exposure to piercing with or without
General characteristics orthodontic treatment, higher prevalences of nickel
Reliability of self-reported data. Among 330 randomly allergy (up to 18.7%) were found. A low prevalence
selected students reporting no orthodontic appliance of nickel allergy was found for students who had not had
treatment, dental records from 30 (9.1%) verified expo- orthodontic appliance treatment or piercing, as well as
sure to some type of intra-oral appliance. After exami- for those exposed exclusively to orthodontic appliances,
nation of 1341 dental records for those adolescents who with similar occurrence in boys and girls. A lower
reported exposure to orthodontic appliances, 5 (0.4%) prevalence of nickel allergy was observed in total and
were identified as having received no treatment with among girls (p < 0.0001) when orthodontic treatment
orthodontic appliances. preceded piercing.

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Table 2. Characteristics of patch tested students (from questionnaire)

Females, n = 2976 Males, n = 1400 Total, n = 4376

Variable n % n % n %

Orthodontic appliance 1531 51.7 540 38.5 2071 47.4

Orthodontic appliance and piercing 1285 43.2 94 6.7 1379 31.5
Piercing 2494 83.8 272 19.5 2766 63.3
Piercinga
Single 1824 73.1 235 86.4 2059 74.4
Multiple, ≥2 670 26.9 37 13.6 707 25.6
Age at piercingb
1–8 years 908 36.8 49 18.8 957 35.0
9–11 years 850 34.4 95 36.4 945 34.6
12–19 years 713 28.8 117 44.8 830 30.4
Atopy 1532 52.4 565 40.9 2097 48.7
a Refers to percentage among pierced subjects.
b No age reported (n = 23).

Table 3. Nickel allergy in relation to reported use and sequence of orthodontic appliances and piercing

Nickel patch test-positive (%) Nickel patch test-positive (%)

Orthodontic appliance Piercing Total (n = 4376) (%) Girls (n = 2976) Boys (n = 1400)

No No 24/912 (2.6) 6/235 (2.6) 18/677 (2.7)

Yes No 17/692 (2.5) 8/246 (3.3) 9/446 (2.0)
Yes, first Yes 28/353 (7.9) 28/324 (8.6) 0/29 (0.0)
No Yes 185/1382 (13.4) 180/1198 (15.0) 5/184 (2.7)
Yesa Yesa 204/1379 (14.8) 201/1285 (15.6) 3/94 (3.2)
Yes Yes, first 156/875 (17.8) 153/819 (18.7)) 3/56 (5.4)
a Without the sequence of orthodontic appliance and piercing being taken into account.

Case–referent analysis based on reported exposure to Case–referent analysis based on exposure to

orthodontic appliances orthodontic appliances verified by dental records
(Table 4)
No difference in the prevalence of nickel sensitivity
was observed between adolescents reporting exposure Association between nickel sensitivity and sequence of orthodontic
(10.7%) and those reporting non-exposure (9.1%) to appliance treatment and piercing. As with the case–referent
orthodontic appliances. analysis based on questionnaire data, a comparable
The association between nickel sensitivity and expo- variable based on the sequence of orthodontic appliance
sure to orthodontic appliances preceding and following treatment and piercing was created, and included three
piercing was evaluated with multivariate logistic regres- categories: (i) placement of an orthodontic appliance
sion analysis. In the final multivariate model, adjustments 1 year or more before the reported age at first piercing; (ii)
were made for other significant variables (sex, piercing orthodontic appliance treatment placement and piercing
age, and number of piercings). Atopy was not found to within the same year; and (iii) first piercing performed
be a significant risk indicator. There was a significant 1 year or more before placement of an orthodontic
association between nickel sensitivity and sequence of appliance. The results were similar to those from the
orthodontic appliance treatment and piercing, with a questionnaire data when this variable was incorporated
reduced risk of having a positive patch test reaction if into the multivariate model (Table 4). Although statistical
orthodontic treatment preceded piercing (n = 1334, OR significance was lost, the same trend of a reduced risk of
0.46, 95% CI 0.27–0.78). There was also a significant nickel sensitivity (OR 0.61) was seen in the multivariate
association between nickel sensitivity and sex, suggesting analysis adjusting for sex, piercing age and number of
a five-fold increased risk of nickel allergy among girls piercings when an appliance was placed 1 year or more
as compared with boys (OR 5.10, 95% CI 1.59–16.40). before piercing (Table 4).
Multiple piercing increased the risk of a positive patch test
reaction to nickel by almost 50% as compared with single Nickel sensitivity in relation to type of orthodontic appliance. Of
piercing (OR 1.48, 95% CI 1.06–2.06). the orthodontically treated students, 62% had worn two

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346 Contact Dermatitis, 67, 342–350
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Table 4. Risk [odds ratios (ORs) with 95% confidence intervals (CIs)] of nickel sensitivity based on dental records in a multivariate logistic
regression model with the dependent variable ‘positive patch test reaction to nickel’ and independent variables (sex, timing of orthodontic
treatment, and piercing, age at time of piercing, and number of piercings); ref., reference category

Variable No of students OR Multivariate analysis 95% CI p-value

Orthodontic appliance
Before piercing 406 0.61 0.36–1.02 0.06
Within the same year 267 0.85 0.55–1.31 0.47
After piercing (ref.) 676 1.00
Sex
Female 1254 5.00 1.56–16.05 <0.01
Male (ref.) 95 1.00
Age at time of piercing
1–8 years 472 1.32 0.76–2.29 0.32
9–11 years 459 1.64 1.02–2.62 0.04
12–19 years (ref.) 418 1.00
Piercing
Multiple 360 1.54 1.11–2.15 0.01
Single (ref.) 989 1.00

Table 5. Risk [odds ratios (ORs) with 95% confidence intervals (CIs)] of nickel sensitivity in students exposed to orthodontic appliances before
piercing. Univariate and multivariate logistic regression analyses are based on data verified from dental records. Exposure to nickel from
appliances is given for (a) each group of appliance(s) before versus after piercing, and similarly, for (b) pooled groups with nickel-releasing
appliances (low/high exposure to nickel) before versus after piercing. The reference category is appliances or groups of appliances placed after
piercing

Univariate analysis Multivariate analysisa

Number (n) in analysis OR 95% CI p-value OR 95% CI p-value

(a) Group of appliance(s)

Group 1b 61 0.79 0.18–3.42 0.75 0.63 0.12–3.33 0.59
Group 2b 662 0.58 0.37–0.92 0.02 1.30 0.67–2.50 0.44
Group 3b 318 0.60 0.30–1.20 0.15 0.93 0.36–2.39 0.88
Group 4b 275 0.52 0.23–1.17 0.11 0.54 0.20–1.48 0.23
Group 5b 324 0.40 0.18–0.92 0.03 0.31 0.10–0.98 0.04
Group 6b 445 0.46 0.20–1.05 0.06 0.80 0.26–2.50 0.70
Group 7b 34 0.32 0.03–3.06 0.32 c c c

(b) Pooled groups with Ni-releasing appliances

Low exposure (groups 1 + 2) 418 0.43 0.24–0.79 <0.01 1.23 0.66–2.29 0.52
Low exposure (groups 1 + 2 + 3) 564 0.52 0.32–0.84 <0.01 1.32 0.66–2.61 0.19
High exposure (groups 4 + 5) 785 0.57 0.36–0.89 0.01 0.56 0.32–0.97 0.04
High exposure (groups 3 + 4 + 5) 931 0.61 0.41–0.91 0.02 0.66 0.40–1.08 0.10
a
Adjusted for sex, age at time of piercing, and number of piercings.
b
Appliance group as a singular variable or combined with other appliance groups regardless of grading.
c
No data available, owing to an insufficient number of cases.

or more orthodontic devices. Multivariate analyses of preceded piercing (OR 0.56, 95% CI 0.32–0.97). All other
exposure to each appliance group (1–7), exclusively or in groups did not differ significantly from the corresponding
combination with other groups of appliances, before and reference categories in multivariate analysis.
after piercing, are shown in Table 5. Exposure to group 5 Non-pierced students exposed to orthodontic appli-
in combination with other appliances showed a reduced ances showed no enhanced risk of nickel allergy (OR
risk of nickel allergy when it preceded piercing (OR 0.31, 0.85, 95% CI 0.43–1.70) as compared with the reference
95% CI 0.10–0.98) as compared with exposure to the category without any exposure.
same types of appliance after piercing. Similarly, the ‘high
Ni-release’ group (groups 4 and 5) showed a reduced Nickel sensitivity in relation to length of exposure to an orthodontic
risk of nickel allergy when exposure to the appliance appliance. The risk of nickel allergy decreased with

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duration of orthodontic treatment. Exposure to an Association between nickel allergy and type
orthodontic appliance (before piercing) for a period of of orthodontic appliance
>6 months indicated a reduced risk of nickel allergy (OR The majority of students reporting appliance treatment
0.62, 95% CI 0.38–1.02). Extending the treatment to had been exposed to multiple orthodontic devices, each of
1–2.5 years lowered the risk even further (OR 0.53, 95% which is likely to vary in its release of nickel, owing
CI 0.27–1.00). to composition, corrosion resistance, and mechanical
straining (6–8, 44). We introduced a detailed and graded
classification based on estimated nickel release in our anal-
Discussion
yses (Table 1). There is, however, uncertainty regarding
the factors influencing this release (3, 44, 45). There is a
Reliability of data
lack of studies on the role of galvanic coupling between
The strengths of our study are the use of test-verified nickel dissimilar metal components of the appliances, which
allergy, the collection of data on exposure to orthodontic may promote corrosion and subsequent ionic release
appliances from dental records, a large sample size, and from the alloys. Various combinations of appliances were
the use of multivariate logistic regression models. therefore analysed. The multivariate analyses showed a
The risk of recall bias in data from our questionnaire reduced risk among students exposed to full fixed appli-
was partly confirmed by a tendency to report the onset ances with NiTi-containing alloys (before piercing). Fixed
of orthodontic treatment as being approximately 1 year appliances, used before the piercing event, were also
later than was noted in dental records. The time of first shown by Kerosuo et al. (23) to significantly lower the
piercing, which we could not verify, may be biased in a risk of nickel sensitivity.
similar way. However, it has been suggested that piercing, Extra-oral traction devices would theoretically increase
as a singular event, is easier to recall than extended periods the risk of nickel sensitization, owing to skin exposure.
of orthodontic treatment (23). We did not see such an effect. This may be explained by
Selection bias was minimized as dental records for an increased awareness of the risk of nickel sensitization,
almost 96% of those included in the case-referent study which has led to measures aimed at minimizing skin
were traced. In the questionnaire-based data there was exposure (46).
a small proportion of misclassification regarding earlier
orthodontic treatment. This did not induce any bias other
Association between nickel allergy and duration
than dilution of the risk estimates as these adolescents did
of appliance treatment
not differ from others with respect to nickel allergy.
A trend towards more allergic response with time was
found by Feasby et al. (47). In contrast to this, our
Risk of nickel allergy in relation to orthodontic
results indicate a reduced risk when the duration of
treatment and piercing
appliance treatment (before piercing) is increased to up to
In line with observations by Kerosuo et al. (23), the 2.5 years, which corresponds with the treatment periods
present study did not find any increased risk of nickel that are common in orthodontics. Our data support the
sensitization following orthodontic appliance treatment. hypothesis that oral nickel exposure from appliances,
Recently, Johansson et al. (21) drew similar conclusions, when exceeding a threshold level, induces a state of
although their study was not designed to answer the tolerance rather than sensitization (23).
present research question. The five-fold increase in risk of
nickel allergy in girls as compared with boys, which was
Possible nickel-specific immunological tolerance
also apparent in the multivariate analyses where piercing
induction
was adjusted for, is likely to reflect a difference in nickel
exposure between the sexes, which can be hypothetically The term ‘oral tolerance’ is used to describe a state of
explained by boys being pierced at an older age and using immunological unresponsiveness to an antigen presented
less nickel-containing jewellery than girls (40). via the oral route. Our results indicate such a supportive
effect of nickel exposure from orthodontic appliances prior
to piercing, as suggested by the results of other exper-
Sequence of piercing and orthodontic treatment imental and epidemiological studies (23, 24, 28–31,
The risk of nickel sensitivity almost halved (OR 0.46) 42, 43, 48–51). Furthermore, our observations show
when orthodontic appliance treatment preceded exposure a time-dependent and dose-dependent immune response.
to piercing. This supports conclusions drawn in other Such an immunological response is also supported by
studies (23, 28, 29, 41–43). recent studies that have demonstrated the pivotal role

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in immunosuppression played by the oral mucosa and When orthodontic appliance use preceded exposure to
regional lymph nodes (52–54). The critical Langerhans piercing, there was a reduced risk of nickel sensitivity.
cells have been found in larger numbers in early gingivi- Furthermore, there was a reduced risk with the use of
tis, which is frequently observed in orthodontic patients, full fixed appliances with an assumed high release of
and nickel has been found in the dental plaque as well as nickel as compared with appliances including alloys with
in the oral mucosa of orthodontic patients (17, 55, 56). a lower nickel release. The risk reduction was most promi-
Specifically in relation to nickel-specific oral tolerance in nent when the duration of orthodontic treatment (before
orthodontic patients, Rustemeyer et al. (51) found that piercing) was 1–2.5 years.
‘successfully tolerized’ individuals may be immunologi- These results should thus reduce parental and patient
cally characterized by nickel-specific T cell release of a concerns about sensitization from orthodontic appliances.
downregulatory cytokine, interleukin-10, and thus sug- The results support the concept of induction of immuno-
gest that long-lasting oral exposure to nickel may induce logical tolerance via oral administration of nickel.
an active immunological tolerance mediated by regula-
tory T cells, preventing subsequent sensitization.
Acknowledgements
Conclusions
We acknowledge the skilful assistance of Dr Birgitta
The following conclusions may be drawn from our study. Stymne and school nurses Ingrid Nilsson, Margarethe
There was no increase in the risk of sensitizing adoles- Bäckman and Monica Nyrén in the patch testing and
cents to nickel by the use of oral orthodontic appliances. questionnaire procedures.

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