ARTICLE
Auteur(s) : Zbigniew Samochocki, Witold
Owczarek, Stanislaw Zabielski
Department of Dermatology, Central Clinical Hospital of Military
Institute of Medicine, ul. Szaserow 128, 00-909 Warsaw, Poland
accepté le 23 Decembre 2005
In 1977 Hanifin and Lobitz [1] published their diagnostic criteria
for atopic dermatitis (AD), which were subsequently modified by
Hanifin and Rajka in 1980 [2]. These criteria still serve as the
basic tool in the diagnosis of AD. Among so-called minor criteria
in this classification are positive skin-prick test (SPT) results
for food and/or air-borne allergens (aeroallergens), which are seen
in 66-88% of patients [2, 3]. In adults these tests mainly detect
hypersensitivity to aeroallergens [3]. Laboratory studies have also
revealed elevated specific anti-aeroallergen IgE (sIgE) levels in
73% of adult patients with AD [4]. Together with clinically evident
flare-ups of AD following aeroallergen challenge, these findings
have confirmed a significant role of type I hypersensitivity
response in the aetiopathogenesis of AD. However, this mechanism
cannot account for all findings associated with aeroallergen
intolerance [5-7]. It has also been demonstrated that
hypersensitivity to aeroallergens in patients may be associated
with a type IV response or be of mixed (I/IV) origin [8]. Patch
tests are an accepted method of detecting contact hypersensitivity,
where tested combinations of non-protein origin (haptens) cause a
topical eczema reaction via IV allergic mechanisms associated with
Langerhans cells and Th1 lymphocytes [9]. However, atopic patch
tests are epidermal contact tests made with protein allergens
evoking standard IgE-dependent reactions [10]. The topical
reaction, defined with IgE-dependent contact eczema, does not
differ clinically from conventional contact eczema. It is caused
via presenting protein allergens to Th2 lymphocytes by Langerhans
cells covered with specific IgE [11]. These findings seemed to
provide a rationale for performing patch tests for aeroallergens in
order to detect factors that provoke or exacerbate AD through a
contact hypersensitivity mechanism [12].The aim of our study was to
assess the utility of atopy patch tests for aeroallergens in the
diagnostic work-up for atopic dermatitis.
Material and methods
Patients and control subjects
The study comprised 115 AD patients (63 females and 52 males), aged
18 to 45 years (mean 25.5). The diagnosis was made when at least
three major and three minor features of Hanifin and Rajka criteria
were met [2]. Forty seven out of 115 (40.9%) AD patients examined
also showed allergic rhinitis, 35/115 (30.4%) showed allergic
conjunctivitis, and 19/115 (16.5%) atopic asthma. Patients were
diagnosed and treated in the Department of Dermatology, Central
Clinical Hospital of Military Institute of Medicine in Warsaw
during the years 2002 – 2004. The study was conducted during the
period of complete remission of skin changes. The patients were not
on drugs of a type, or during an administration time, which could
exert any impact on the results of the examinations performed.
A control group was composed of 98 gender- and age-matched
healthy volunteers with negative family and individual history of
atopy.
The patients examined were informed about the aim of the study
and gave informed assent. The agreement of the Local Ethics
Committee was also obtained.
Allergens
Allergenic material consisted of extracts of individual allergens
or allergen mixtures: 1. a mixture of the house dust mite species
Dermatophagoides pteronyssinus and Dermatophagoides farinae, 2.
common birch (Betula alba) pollen, 3. A mixture of five species of
grass: orchard grass Dactylis glomerata, smooth-meadow grass Poa
pratensis, perennial ryegrass Lolium perenne, sweet vernal grass
Anthoxanthum odoratum and timothy Phleum pratense, 4. cat dander.
Atopy patch test
Atopy patch tests (APT) were performed on clinically uninvolved
skin of the back using commercially available reagents of
Stallergenes Company (France). Squares of blotting paper of 1 ×
1 cm, soaked in the solutions of the allergens being examined,
as well as the control test which was composed of the vehicle
(ointment base) i.e. white Vaseline, were applied on the skin.
Subsequently, the blotting paper was covered with plastic foil (1.5
× 1.5 cm) for occlusion. Then hypoallergic adhesive tape was
applied to fix the test dressings. Reagents composed of allergens
in a concentration of 200 IR were used in the study [13, 14]. The
patches were removed after 48 hours and the findings were assessed
at 72 hours after the test application. Tests were classified as
positive if the reaction on the skin was estimated at least as one
plus (+). The following scale was employed: (–) lack of any signs,
(+/–) doubtful reaction, (+) erythema, infiltration, (++) erythema,
a few papules (up to 3), (+++) erythema, papules (4 and more),
(++++) erythema, numerous, disseminated papules, (+++++) erythema,
vesicles, exudates [13].
Statistical analyses
The statistical analyses involved the chi-squared test with Yates’s
correction for small groups, at a confidence level of p < 0.05.
In order to compare the strength of variable results, the
sensitivity (SE) and specificity (SP) of APT was calculated,
formulating the result in percentage according to the following
formula:where WD defines the positive history of exacerbations of
skin lesions following exposure to the aeroallergen and a positive
APT to this allergen, FN – positive history of exacerbations,
negative APT, WN – negative history of exacerbations, negative APT,
FD – negative history of exacerbations, positive APT [15]. In the
case of plant pollen allergens, the exacerbation of skin changes
reported in history, referred to the period of exposure to pollen,
which in Poland is the second half of April and the first week of
May for birch pollen, and June and the first half of July for grass
pollens.
Results
Sixty three patients, out of 115 (54.8%) reported the development
of pruritus and/or exacerbation of the eczematous lesions following
exposure to dust. The respective percentages associated with
intolerance of birch pollen, grass pollen and cat dander were 46.1
(53/115), 46.1 (53/115) and 33.0 (38/115).
Hypersensitivity to the mixture of house dust mites was seen in
52/115 (45.2%) patients, to birch pollen in 37/115 (32.2%)
patients, to the mixture of grass pollen in 26/115 (22.6%), and to
cat dander in 18/115 (15.7%) patients ( (figure 1) ). In the
control group, 6/98 (6.2%) patients were hypersensitive to the
mixture of house dust mites on patch testing.
A total of 62 (53.9%) of the 115 patients in the study group
were found to be hypersensitive to at least one of the study
aeroallergens or their mixtures on patch testing. In the control
group, the corresponding percentage of ATP-positive patients was
6.2% (6/98) and the difference between these values was
statistically significant at p < 0.001.
Hypersensitivity to one group of study allergens was seen in
27/62 (43.5%) of APT-positive patients, while 13/62 (21.0%)
patients were hypersensitive to two groups of aeroallergens, 8/62
(12.9%) were hypersensitive to three groups of aeroallergens and
14/62 (22.6%) were hypersensitive to all four groups of
aeroallergens ( (figure
2) ).
The correlation between positive APT and positive history of
exacerbation in the case of exposure was from 18.5% for cat dander
to 66.6% for the mixture of house dust mites. The specificity of
the atopy patch test ranged from 75.9% for birch pollen to 85.7%
for cat dander (table 1)( Table 1 ).
Table 1 Sensitivity and specificity of atopy patch
tests for aeroallergens in patients with atopic dermatitis (N =
115)
|
Allergen
|
WD
|
FN
|
WN
|
FD
|
Sensitivity
|
Specificity
|
|
Number
|
%
|
Number
|
%
|
Number
|
%
|
Number
|
%
|
%
|
%
|
|
D.pter./D.far.
|
42
|
36.5
|
21
|
18.3
|
42
|
36.5
|
10
|
8.7
|
66.6
|
80.7
|
|
Birch pollen
|
22
|
19.2
|
31
|
26.9
|
47
|
40.9
|
15
|
13.0
|
41.6
|
75.9
|
|
Grass pollen
|
16
|
13.9
|
37
|
32.2
|
52
|
45.2
|
10
|
8.7
|
30.1
|
83.8
|
|
Cat dander
|
7
|
6.1
|
31
|
26.9
|
66
|
57.4
|
11
|
9.6
|
18.5
|
85.7
|
Discussion
Skin lesions associated with AD are non-specific since they also
occur in the course of other dermatoses. There are no diagnostic
criteria based on histopathological findings and the laboratory
findings may vary from patient to patient. Even though the criteria
developed by Hanifin and Rajka [2] embrace a variety of the
features of this condition, AD may be difficult to diagnose in
atypical cases.
Recent literature data point to the possibility of using APT in
diagnostic work-up for AD [11, 16-18]. However, there is no uniform
set of criteria regarding the testing techniques, and the results
of such tests are not unequivocal [19, 20]. In order to increase
allergen penetration, some authors have advocated removing
superficial layers of epidermis by mechanical abrasion or adding
contact irritants to test kits [21]. The resulting damage to the
skin was supposed to facilitate penetration of the antigen into the
skin, creating similar conditions to those resulting from e.g.
scratching. This procedure increases the incidence of non-specific
responses. This has led most authors to recommend performing APT on
intact skin, which is considered to best emulate the conditions
found in the environment of the patient [17, 19, 20]. Based on
these recommendations, the technique employed in our study involved
placing a solution of the allergen under occlusion on lesion-free
intact skin.
Literature data differ also with respect to the form and
concentration of allergens. Concentrations used vary from 1,000 to
10,000 PNU/g (protein nitrogen units) or 200 IR (biological units)
[12-14, 22, 23]. It has also been established that white Vaseline
is the most useful vehicle [24, 25]. Our study used kits supplied
by Stallergenes (France) with allergens suspended in white Vaseline
at a concentration of 200 IR. An exposure time of 48 hours is
commonly accepted [12, 24, 26].
Another significant factor of APT finding evaluation is the time
of its read-out, which is done after 48 and 72 hours. This results
from the fact that the reaction shows a tendency to expire
progressively with time [24], unlike reactions with non-protein
allergens, which tend to accumulate progressively or have late
reactions [9].
Intensification of APT reactions was evaluated according to the
scale proposed by the European Task Force on Atopic Dermatitis
(ETFAD) Consensus [13]. When compared with the evaluation of the
usual patch test [9], the scale mentioned above had been expanded
within the positive reaction intensification formulated by the
number of papules within the reaction.
An analysis of the percentage of positive APT for aeroallergens
in this study showed that the percentage of positive test results
was 53.9% among AD patients and 6.2% among healthy volunteers, the
difference being statistically significant at P < 0.001. Other
authors report similar results, with contact hypersensitivity to
aeroallergens detected in approximately 50% of AD patients [8, 18,
27]. In this study, hypersensitivity in the control group was
limited to infrequent allergy to house dust mites. Other reports
estimate the incidence of contact hypersensitivity to house dust
mite allergens in a control group at 0-15% [12, 23, 25, 28].
Seidenari et al. [29] indicate that a positive result in a healthy
volunteer can be of prognostic value, indicating a tendency to
develop eczema in the future and/or suggesting a so-called “atopic
diathesis”.
The most common type of hypersensitivity in the study group was
an allergy to the mixture of house dust mites (45.2%), which
confirms the observations of others (39-45%) [12, 23]. There was a
similar correspondence between our and literature data for APT
testing for grass pollen and cat dander allergen, while the
frequency of contact hypersensitivity to birch pollen in our study
(32.2%) was twice as high as that reported by Darsow et al. (15.8%)
[12]. This difference may be due to the abundance of this tree in
the patients’ environment. Since the same can be said about other
aeroallergens, this emphasises the need to use different
aeroallergen test kits in different regions of the world [30].
Our results show that 52.5% of patients who tested positive on
APT had polyvalent hypersensitivity, usually to 2 or 4 allergen
groups. In their study using house dust mites, cat dander and a
mixture of grass pollen, Darsow et al. [24] found polyvalent
hypersensitivity in a similar percentage of patients, with most
subjects demonstrating hypersensitivity to 2 allergens.
The diagnostic utility of allergy tests depends on their
sensitivity and specificity. On the basis of history data
suggesting AD flare-ups following exposure to the study
aeroallergens, the sensitivity of APT was established at 18.5-66.6%
and specificity at 75.9-85.7% for various allergens. Our results
corroborate the findings of other authors, who revealed a higher
specificity and a lower sensitivity of atopy patch tests for
aeroallergens [12, 13]. As in the case of patch tests, there is a
possibility of false-positive reactions caused by irritant
reactions, which do not differ clinically from allergic reactions
[9]. This proves APT results should be considered together with the
findings of other allergological tests, including history.
A comparison of our data on the frequency of positive APT for
aeroallergens and the test’s sensitivity and specificity in this
study with literature data on SPT and elevated levels of sIgE
specific to these allergens reveals some similarities as well as
differences. Positive SPT and/or elevated sIgE levels are seen in
AD patients 30% more frequently than positive APT results [3, 4].
This higher incidence of positive SPT and/or elevated sIgE levels
can be explained by the frequent finding of concomitant allergic
rhinitis and/or atopic asthma in these patients [31], since no
correlation has been found between positive APT testing for
aeroallergens and atopic respiratory conditions [19, 32].
Literature data stress the polyvalent nature of aeroallergen
hypersensitivity determined by SPT and/or sIgE levels [3, 4] and
our study of the APT method has led to the same conclusion. It has
also been proved that SPT findings in AD patients and sIgE levels
directed against aeroallergens are characterized by a higher
sensitivity and a lower specificity [12, 13].
In conclusion, our study revealed that:
- 1. atopy patch tests, which are characterised by
considerable specificity, confirm the role of polyvalent contact
hypersensitivity to aeroallergens in the development of atopic
dermatitis ;
- 2. positive aeroallergen ATP results are observed in the
majority of patients and can thus be regarded as an additional
diagnostic criterion in atopic dermatitis.
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