Report
Contact sensitization pattern in 172 atopic subjects
Lilla Landeck1, MD, Peter Schalock1, MD, Lynn Baden2, MD, MPH, and
Ernesto González1, MD
1
Department of Dermatology, Harvard
Medical School, Massachusetts General
Hospital, Boston, MA, USA, and
2
Centre for Dermatology and Aesthetic
Medicine, Newton, MA, USA
Correspondence
Ernesto González, MD
Department of Dermatology/BAR610
Massachusetts General Hospital
55 Fruit Street
Boston
MA 02114
USA
E-mail: egonzalez1@partners.org
Funding: None.
Conflicts of interest: None.
Abstract
Background Some authors have claimed a decreased cell-mediated immunity among
atopic individuals, which would lead to observations of decreased rates of allergic contact
dermatitis (ACD).
Objectives The purpose of our study was to investigate contact sensitization patterns in
atopic subjects compared with non-atopic subjects.
Methods Patch test data for 1247 patients undergoing patch testing at Massachusetts
General Hospital between 1990 and 2006 were reviewed. Using accepted criteria, 172
subjects were classified as atopic individuals (AIs), and 1075 were classified as non-atopic
individuals (NAIs). Sensitization rates were compared between these two groups.
Results Sensitization rates (65.0% and 57.4% in the AI and NAI groups, respectively)
and average numbers of positive responses (1.5 and 1.2 in the AI and NAI groups,
respectively) were higher in AIs. Leading allergens observed were similar for both groups.
Sensitization to potassium dichromate and phenylmercuric acetate was significantly greater
in the AI group. The most frequent diagnosis in both groups was ACD (41.9% and 45.5%
in the AI and NAI groups, respectively). In addition, more NAIs who were employed in
occupations with exposure to wet and/or irritant conditions had hand eczema (P < 0.005).
Conclusions Atopic individuals were shown to be at least as likely to have ACD as NAIs.
The most common sensitizers were similar in both groups, suggesting common sources of
sensitization.
Introduction
Dermatitis Clinic, MGH, between 1990 and 2006. Test
procedures and readings were conducted using a standardized
The term ‘‘atopy’’ describes a polygenic inherited disposition to develop one or more of the following disorders:
atopic dermatitis (AD), allergic rhinoconjunctivitis (AR),
and allergic asthma (AA). Although consensus exists that
atopic individuals have a heightened tendency to develop
immunoglobulin E (IgE) type I antibodies to environmental factors, some authors have claimed a decreased
cell-mediated immunity,1 which would lead to the observation of decreased rates of allergic contact dermatitis
(ACD). The purpose of our study was to investigate contact sensitization patterns in atopic patients compared
with those without atopy.
technique in accordance with international recommendations by
applying Finn chambers (Epitest Oy, Tuusula, Finland) affixed
with Scanpor tape (Norgesplaster A/S, Vennesla, Norway) to the
upper back.2 Allergens were purchased from Almirall-Hermal
(Reinbek, Germany). Tests remained in place for two days, and
sites were initially evaluated at 48 hours and again at 72 hours.
In selected rare cases, a 120-hour and/or 168-hour reading was
performed. In this analysis only 48- and 72-hour readings were
incorporated. All interviews and interpretations of patch test
reactions over the 17-year study period were performed by a
single observer (EG). Patch test readings were classified
according to the International Contact Dermatitis Research
Group (ICDRG) recommendations as allergic (+, ++, +++),
806
Materials and methods
questionable, irritant, or negative.2
To reduce the potential for false positive reactions, positive
Study approval was obtained from the Institutional Review
allergic results were rated based on a minimum of
Board of Massachusetts General Hospital (MGH). Data were
erythematous infiltration, vesiculation or both. Questionable,
then collected from chart review for 1247 patients who underwent
irritant and negative reactions were considered negative.
patch testing to the standard and, depending on the individual’s
history and clinical picture, to the supplemental series (e.g.
individuals (AIs) according to a current history of at least one of
preservatives, cosmetic tray, etc.) available at the Contact
AD, AR, or AA.3 The remaining 1075 subjects were categorized
International Journal of Dermatology 2011, 50, 806–810
Using accepted criteria, 172 patients were classified as atopic
ª 2011 The International Society of Dermatology
Landeck et al.
Contact sensitization in atopic subjects
Table 1 General epidemiologic data on tested atopic and
non-atopic individuals following the MO(A)HLFAa index
Male, n (%)
Occupational, n (%)
Hand, n (%)
Leg, n (%)
Face, n (%)
Age, years,
mean ± SD
AIs
(n = 172)
NAIs
(n = 1075)
P-value, AIs
vs. NAIs
51 (29.7%)
5 (3%)
42 (24.4%)
21 (12.2%)
48 (27.9%)
46.7 ± 15.21
322 (30%)
109 (10%)
371 (34.5%)
168 (15.6%)
261 (24.3%)
46.2 ± 15.19
0.936
0.020
0.009
0.246
0.306
0.702
a
Atopy was deleted and is not tabulated.
MOAHLFA index: male, occupational, atopic, hand, leg or
face dermatitis, age > 40 years.
AIs, atopic individuals; NAIs, non-atopic individuals; SD,
standard deviation.
as non-atopic individuals (NAIs). In cases of AD, patients were
only tested during periods of quiescent inflammatory disease.
For a descriptive characterization of the patient population, the
MOAHLFA index (male, occupational, atopic, hand, leg, or face
dermatitis, age >40 years) was used as shown in Table 1.4 The
relevance of positive results was determined by assessing the
subject’s past history of contact with the allergen and whether
the symptoms expressed were consistent with the clinical
picture and history. Probable and definite relevance were
pooled under ‘‘relevant’’, whereas possible, past and unknown
relevance were designated ‘‘non-relevant’’.
Statistical evaluation
Data were recorded, retrieved, and evaluated using a
computerized database (Microsoft Access 2000), Microsoft
Cooperation, Redmont, WA, USA. Statistical analysis was
performed using SPSS Version 15.0 (SPSS Inc., Chicago, IL,
USA). Frequencies were compared using the Chi-squared test
and Fisher’s exact test where appropriate. Statistical analysis
was performed on the 23 allergens occurring most frequently
among the 172 atopic patients. The multiple level of
significance was a = 0.05. To adapt for multiple testing, the
level of significance for allergens tested was adjusted to
a = 0.002 (Bonferroni correction of factor 23).
Results
Sensitization rates (65.0% and 57.4% in the AI and NAI
groups, respectively) and average numbers of positive
responses (1.5 and 1.2 in the AI and NAI groups, respectively) were significantly higher in the AI group
(P < 0.05). No significant difference between the AI and
NAI groups was observed with regard to patient age and
gender distribution (Table 1). Leading allergens observed
for both groups were nickel and fragrance mix (Table 2).
ª 2011 The International Society of Dermatology
Report
Although there was a trend among AIs towards higher
sensitization to triclosan and wool alcohols, this finding
was significant only for potassium dichromate and phenylmercuric acetate.
A subgroup analysis (data not shown) was conducted
to investigate possible differences between patients
affected by cutaneous (AD) and mucous membrane (AR
and AA) involvement. No statistical differences between
the groups emerged for any of the allergens listed in
Table 2.
Allergic contact dermatitis was the most frequent diagnosis in both the AI and NAI groups (41.9% and 45.5%
in the AI and NAI groups, respectively). As demonstrated
in Table 3, more NAIs were employed in occupations with
exposure to wet and/or irritant conditions (P < 0.005),
and a final diagnosis of irritant contact dermatitis was seen
more commonly in this group (NAI: 3.8%; AI: 2.3%).
Discussion
Early studies suggested that AIs are less prone than NAIs
to developing type IV sensitizations. This assumption
derived from investigations in which patients with severe
AD were not readily sensitized by repeated application of
dinitrochlorobenzene (DNCB) in an experimental setting.
However, once the AD improved or in periods of remission, the DNCB challenges turned positive.1,5 There are
several possible reasons why AIs might have an increased
incidence of allergic contact sensitization and, more specifically, to allergens from topical medications: AIs are
known to use an increased amount of topical medications
and moisturizers because of their disease, and the disruption of their skin barrier permits the increased penetration
of allergens. Recent findings from patch test studies investigating the sensitization profile of AIs suggest rates and
patterns of allergic contact sensitization comparable with
those of NAIs.6
A comparison of the general epidemiologic data from
our study, as presented in Table 1, shows no significant
differences between the AI and NAI groups. By contrast,
and as an unexpected finding, statistically significantly
more NAIs than AIs were evaluated for occupational dermatitis and hand eczema. Furthermore, the NAIs had a
higher prevalence of irritant contact dermatitis derived
from wet and irritant occupational exposure. Although
the low numbers of AIs in these categories are too small
for valid comparison, they may reflect avoidance by AIs
of occupations with inherently high risk for contact irritation. Conversely, early detection and avoidance may preclude the referral of AIs to specialized clinics for patch
testing. Heine et al.,6 in their comparative patch test
study of AIs and NAIs, reported a higher prevalence
of face and hand involvement among atopic patients.
International Journal of Dermatology 2011, 50, 806–810
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808
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Contact sensitization in atopic subjects
Landeck et al.
Table 2 Most frequent allergens with rate of sensitization and relevancies in atopic individuals (AIs) compared with non-atopic
individuals (NAIs)
AIs (n = 172)
NAIs (n = 1075)
Allergen
n
%
Relevant
reactions, %
Nickel sulfate
Fragrance mix
Balsam of Peru
N-isopropyl-N-phenyl-p-phenylenediamine (IPPD)
Wool alcohols
Cobalt chloride
Potassium dichromate
Thimerosal
Phenylmercuric acetate
Quaternium 15
Methylchloroisothiazolinone/methylisothiazolinone
(3:1 in water)
Formaldehyde
Neomycin sulfate
Thiuram mix
Sodium metabisulfite
Benzalkonium chloride
Colophony
Glutaraldehyde
Epoxy resin
Triclosan
Carba mix
Mercapto mix
Mercaptobenzothiazole
29
25
19
16
15
15
14
14
10
10
9
16.9
14.5
11.0
9.3
8.7
8.7
8.1
8.1
5.8
5.8
5.2
12.1
5.3
5.8
4.7
4.4
2.0
1.9
3.7
2.9
2.9
1.7
153
170
125
30
43
78
31
23
20
71
12
14.2
15.8
11.6
2.8
4.0
7.3
2.9
2.1
1.9
6.6
1.1
0.380
0.651
0.801
0.660
0.007
0.503
0.001
0.685
0
0.684
0.097
8
7
6
6
5
5
5
4
4
4
3
3
4.7
4.1
3.5
3.5
2.9
2.9
2.9
2.3
2.3
2.3
1.7
1.7
4.7
1.4
1.2
1.8
0.7
2.3
0
1.5
0
0
1.1
0
66
52
56
8
6
46
5
30
0
30
14
0
6.1
4.8
5.2
0.7
0.6
4.3
0.5
2.8
0
2.8
1.3
0
0.436
0.605
0.329
0.538
0.907
0.393
0.572
0.722
0.006
0.677
0.648
0.030
Table 3 Occupational backgrounds of tested atopic individu-
als (AIs) and non-atopic individuals (NAIs)
AIs
(n = 172)
Office
Home/retired
Medical
Teaching
Wet/irritant work
Sales
Construction
Industrial
Food
Other and unknown
NAIs
(n = 1075)
n
%
n
%
P-value,
AI vs. NAI
51
35
25
12
5
5
5
4
4
16
29.7
20.3
14.5
7.0
2.9
2.9
2.9
2.3
2.3
15.5
274
145
147
91
100
24
18
37
26
164
25.5
13.5
13.7
8.5
9.3
2.2
1.7
3.4
2.4
19.8
0.248
0.017
0.761
0.51
0.005
0.586
0.268
0.446
0.941
0.039
The study did not find any statistical differences between
the two groups when their occupational backgrounds
were assessed.6
With regard to whether AIs tend to develop allergic
contact sensitization as frequently as NAIs, our study
demonstrated that atopic subjects had statistically significantly more positive patch tests than NAIs (1.52 and
1.26 in the AI and NAI groups, respectively; P = 0.006).
International Journal of Dermatology 2011, 50, 806–810
n
%
P-value, AIs
vs. NAIs
Other studies have made similar findings, showing that
AIs are at least as likely to have ACD as NAIs.6–8
Considerable differences between AIs and NAIs were
observed in regard to some of the most frequent sensitizers, such as potassium dichromate, phenylmercuric
acetate, triclosan, and wool alcohol. This finding was statistically significant for potassium dichromate and phenyl
mercuric acetate.
Wool alcohol is a non-drying organic compound
produced from lanolin, found in sheep’s wool, which has
been reacted with acetic acid. For decades, vehicles for
prescription creams and skin care products have contained lanolin. Frequent contact sensitization to wool
alcohol is associated with stasis dermatitis and leg ulcers.9
However, because AIs exhibit dry and inflamed skin, their
use of topical agents containing lanolin may be higher
than among NAIs. Previous patch test studies have demonstrated similarly increased lanolin sensitization among
AIs, with sensitization rates of around 4%.6,10 Other
reports have shown no significant difference between the
groups for atopic eczema status and wool alcohol
allergy.9
Triclosan, a common antibacterial chemical, is another
substance to which AIs show higher sensitization rates. In
the USA, triclosan is frequently used as an ingredient in
ª 2011 The International Society of Dermatology
Landeck et al.
both medical and consumer products, such as deodorants
and toothpastes. Its common presence results in a generally high exposure rate, which may account for increased
rates of contact sensitization.11 Our results appear to conflict with European reports showing that triclosan is well
tolerated in AIs with low sensitizing potential and citing
sensitization rates of <1%, even in high-risk patients
affected by eczema.12
Phenylmercuric acetate, found in preservatives, is a
potent sensitizer described as causing frequent type IV
sensitization in AIs.13 Dastychová et al.13 reported a
7.8% prevalence of sensitization in a study population of
194 AIs. Sensitization to phenylmercuric acetate can be
linked to the frequent use of moisturizers and topical
medications that contain this preservative.
The finding of a higher rate of sensitization to potassium dichromate in the AI group was unexpected,
although other studies have also reported this allergen as
a frequent sensitizer among AIs, with sensitization rates
as high as 7.9%.6,12,14,15 Another investigation showed
that this antigen sensitized 2.6% of subjects among a
pediatric population of 137 atopic children.10 Because
exposure to dichromates, such as are found in cement
and leather, is uncommon in childhood, it is conceivable
that this study’s results10 may have included subjects with
irritant contact dermatitis, rather than a true contact
allergy. A German group investigated concurrent patch
test reactions to nickel, cobalt, and chromate and found
that positive reactions to chromate were consistently associated with atopic eczema.16 The authors concluded that
some false positive reactions may have occurred as a
result of the marginally irritating properties of the chromate patch test preparation and the high susceptibility of
atopic patients to developing irritant reactions.16
Conclusions
Atopic individuals were shown to be at least as likely
as NAIs to have ACD. The most frequent sensitizers
were similar in the two groups, which suggests that the
important sources of sensitization do not vary. Nonetheless, a statistically significant higher number of positive results were observed for potassium dichromate
and phenylmercuric acetate. Statistically significantly
more NAIs were affected by hand eczema and were
employed in occupations involving wet or irritant exposure, although the numbers of AIs in our study group
were too small to make a statistically valid comparison.
The reduced numbers of atopic employees in professions with wet/irritant exposure may reflect the avoidance of these occupations by a population aware of
their skin vulnerability. Patch testing is an important
tool with which to diagnose eczemas of uncertain
ª 2011 The International Society of Dermatology
Contact sensitization in atopic subjects
Report
etiologies and is of substantial use in the development
of a better therapeutic approach to the management of
atopic patients.
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ª 2011 The International Society of Dermatology