The present article reviews the literature (up to 1994) on contact sensitivity to imidazoles and presents the results obtained from 15 patients observed at the Contact Allergy Unit in Leuven. The frequency as well as the cross-reaction patterns described are analyzed. Although allergic contact reactions may have been missed in the past (mainly because of problems with the correct choice of vehicle for patch testing), they seem to be relatively infrequent in view of their widespread use. The imidazole derivatives most frequently reported to be allergens are miconazole, econazole, tioconazole, and isoconazole. As far as cross-reactivity is concerned, statistically significant associations were found in the patient data between miconazole, econazole, and isoconazole; between sulconazole, miconazole, and econazole; and also between isoconazole and tioconazole. Patients sensitive to phenylethyl imidazoles (except ketoconazole) needing antimycotic therapy should be advised to use ketoconazole, clotrimazole, bifonazole, or, perhaps, the new flutrimazole. Clearly, non-imidazole antifungals can also be used.Key words: allergic contact dermatitis; antimycotic agents; imidazoles; cross-sensitivity; medicaments; ketoconazole; clotrimazole; bifonazole; miconazole; tioconazole; croconazole. © Munksgaard, 1995.
Accepted for publication 23 November 1994Since they were first introduced in 1969, imidazoles have probably become the most widely used of all antifungals in human and veterinary medicine. Moreover, imidazole derivatives such as enilconazole are also used for antifungal protection of citrus fruit, vegetables, and other plants (1).Considering the tremendous amounts of imidazole derivatives used and the possibility of them being stored in the skin (2), the paucity of published reports on their contact sensitization capacity would indicate that they are very weak allergens. However, a growing number' of case reports and real or quasi-cross-reaction studies have made it possible to evaluate which are the "stronger" and which the "weaker" allergens, as well as potential cross-reaction patterns.To evaluate studies concerning frequency as well as cross-reaction patterns described, we surveyed the available literature up to 1994 on contact sensitivity to imidazoles and included the results of 15 of our own patients with imidazole contact allergy, with a view to a better understanding of the chemical structure required for sensitization and crosssensitization, and also to proposals for an imidazole series for testing and for therapeutic alternatives for patients sensitive to particular imidazole derivatives.