ARTICLE
Contact hypersensitivity to topical medicaments may be a cause of induction,
persistance or worsening of skin diseases. In particular, in unresponsive
dermatites, sensitization to topically applied corticosteroids must be
considered, as an important number of reports has evidenced [1-17].
The aim of our study was to evaluate allergic contact reactions to corticosteroids
in chronic cutaneous dermatoses and to compare our data with those referred
in the literature.
Patients and methods
Sixty consecutive subjects, 18 males and 42 females, mean age 44.3 years
(range 20-81), affected by cutaneous diseases they had had for over a
year (mean duration 6 years, range 1.1-26) were selected from the dermatology
clinic. The cases, resistant to conventional therapies, were: hand contact
and dyshidrotic eczema: 30 cases; genital lichen simplex chronicus: 18;
face contact eczema: 6; diffuse contact and atopic dermatitis: 6. All
the patients were patch tested with the GIRDCA series and our corticosteroids
series (Table I); in addition,
according to their clinical history, some of the subjects underwent testing
for further series and for their own products. Patch tests were applied
in Finn Chambers on Scanpor tape for 48 hrs and were read at day 2, 3
and 7; clinical scoring was performed according to the ICDRG recommendations
as follows: + weak positive reaction; ++ strong reaction; +++ extreme
positive reaction. We excluded 1+ positive skin reactions at 48 hrs if
not confirmed at the following readings (D3 and D7); in fact it may be
difficult to distinguish a weak allergic reaction from an irritant reaction.
Results
Of the 60 patients tested, 8 (13.3%) showed positive reactions to corticosteroids:
5 subjects reacted only to 1 corticosteroid, while in 3 patients multiple
sensitizations were found (Table
II). Five of the sensitized subjects were affected by hand eczema
(patients n° 6, 30, 41, 42, 44) and 3 by genital dermatoses. Budesonide
was the commonest allergen (7 positives), followed by hydrocortisone-17-butyrate
(2 positives) and betamethasone-17-valerate (1 positive). Of the 3 patients
with multiple sensitizations, one was allergic to budesonide and betamethasone-17-valerate
and another to budesonide and hydrocortisone-17 butyrate.
A woman who reacted to budesonide also presented a positive reaction
to methylprednisolone aceponate; this allergen, not included in our corticosteroids
series, was obtained from the manufacturers, as the patient had had a
strong positive test to her own cream containing methylprednisolone aceponate.
Four patients, all affected by hand eczema, showed further sensitizations
to GIRDCA allergens, as reported in Table
II.
Discussion
Corticosteroids are the most widely used topical medicaments in dermatological
practice. Although they represent the main anti-allergic drugs, they are
well recognized as common contact allergens. Several studies have not
only confirmed the sensitizing power of corticosteroids but have also
shown the possibility of cross-reactions [1-15].
In 1989, Coopman, by means of a statistical analysis of literature and
personal data, showed that cross-reactions between corticosteroids were
more frequent among structurally-related compounds. This observation induced
the authors to suggest, on the basis of different substitutions on the
D-ring or on the carbon side-chain (C20, C21), a classification of corticosteroids
in 4 classes (A, B, C, D) [1]. Further clinical and conformational studies
have highlighted the possibility that there may be a reaction to steroids
of different classes [9]. However some molecules have been recommended
as contact allergy markers for the different classes: tixocortol pivalate
for corticosteroids of group A, budesonide for group B and D and hydrocortisone-17-butyrate
for group D [2, 3, 12, 15].
Despite the efforts to standardize substances and test procedures, the
prevalence of positive reactions to corticosteroids reported in the literature
varies from 0.2 to 6%, as it is strongly related to test populations and/or
country-specific factors [2-4, 6-8, 10-15].
Regarding the present study, we found a much higher percentage of sensitization
to corticosteroids (13.3%) than those usually described; in our opinion,
this value may be due both to methodological reasons and local prescription
habits. In particular, we believe that the prevalence of our positive
reactions may be partially explained by the selection of patients submitted
to the tests: in fact, only subjects affected by chronic dermatites lasting
for more than 1 year were examined. A further, indirect proof of the influence
of our selection-standards seems to derive from the cutaneous involvement
observed in our positive patients; all our sensitized subjects complained
of dermatites of the hands and genitals, typical sites of allergy to topical
steroids [2-4, 8, 11, 16].
Budesonide was the most common allergen we found. This confirms that
the compound is a strong sensitizer [2, 3], but also that it was one of
the most widely employed corticosteroids in our area in the years just
before the present study [10].
Regarding the relationship between positive
patch test reactions and previous exposure to the same active principle,
it was not possible to demonstrate complete relevance in all our cases;
in fact only 4 positivities, 3 to budesonide and 1 to methylprednisolone
aceponate, were certainly related to the specific drug-exposure. The patients'
history, in fact, was positive for the use of these corticosteroids and
their dermatitis improved when avoiding the drug. The problem of the relevance
to corticosteroids has been underlined by Dooms-Goossens: it has been
suggested that a positive test to a particular corticosteroid may also
be related to the previous use of another cross-reactive corticosteroid
agent [11]. In any case, it is well known that allergic reactions to corticosteroid
markers are more frequent among subjects exposed to a wide number of topical
compounds. This proved to be the case with our patients who referred a
history of chronic dermatites unresponsive to various, unspecified, topical
steroids.
Although we had had the opportunity of submitting our population to
an extensive corticosteroids series, we observed sensitizations only to
2 of the 3 recognized corticosteroid markers (budesonide = class B/D and
hydrocortisone-17-butyrate = class D). No positive reaction was noticed
to tixocortol pivalate (class A). Positive reactions to betamethasone-17-valerate
and methylprednisolone aceponate were found in patients also allergic
to budesonide [17].
Our results seem to demonstrate that the recommended corticosteroid
contact-allergy markers are adequate for the detection of sensitive subjects
and that the inclusion of tixocortol pivalate, budesonide and hydrocortisone-17-butyrate
in the Standard series may be a useful, relatively cheap and fast screening-procedure
to establish the corticosteroid-sensitization rate. However, patients
affected by unresponsive chronic dematoses or strongly suspected for corticosteroid
allergy should be tested with a further, wider panel of compounds corresponding
to individual products and to the corticosteroids prescribed locally.
This approach may identify an increased number of cases of corticosteroid
hypersensitivity and may supply better information about cross-reactions
[4-6, 8], furthermore it becomes mandatory to choose an appropriate corticosteroid
belonging to a different class to obtain adequate treatment [4, 6, 7,
13].
Given the impossibility of testing the whole range of topical steroids,
including recently marketed corticosteroids not present in standardized
steroid series, it may be useful to ascertain sensitization through closed
patch tests and usage tests such as the repeated open application test
(ROAT). We agree with other authors that ROAT represents an additional
method for the detection of corticosteroid sensitizations [4-7, 12, 13].
Article accepted on16/8/00
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