Contact allergy to a reaction product in Hirudoid® cream: an example of compound allergy

SUMMARY We have investigated patients with a contact allergy to Hirudoid® cream. The hypersensitivity reactions appeared to be due to an allergy to the cream base, but the separate ingredients did not give rise to positive patch test reactions. The hypersensitivity proved to be due to an allergy to a reaction product, and the simultaneous presence of the preservatives 1, 3, 5-trihydroxyethylhexa-hydrotriazine and thymol was found to be necessary for the occurrence of a positive patch test reaction. A new allergen was found to be formed by the reaction between thymol and the degradation products of the triazine derivative. This allergen was identified by nuclear magnetic resonance spectroscopy and infrared spectroscopy as 3-(hydroxyethyl)-5-methyl-8-(2-methyl-ethyl)-3,4-dihydro-2H-1,3-benzoxazine.