Contact sensitization to corticosteroids: increased risk in long term dermatoses

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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