CD31 Not so innocent after all: H1-antihistamine-induced fixed drug eruption confirmed by lesional patch testing

Abstract

Fixed drug eruption (FDE) is a delayed, T-cell-mediated adverse drug reaction in which sharply demarcated erythematous or violaceous plaques recur at identical sites after re-exposure. Although H1-antihistamines are widely regarded as low risk, they have occasionally been reported to cause paradoxical cutaneous reactions. H1-antihistamines can be grouped by chemical structure into alkylamines (chlorphenamine), piperazines (hydroxyzine and cetirizine) and piperidines (loratadine and fexofenadine). Crossreactivity has been described within structurally related agents, particularly among piperazine derivatives. Lesional (in situ) patch testing is a practical, safe adjunct to support diagnosis and explore crossreactivity, although sensitivity is variable and influenced by drug concentration, vehicle and site selection. A 32-year-old previously well police officer developed a solitary, well-circumscribed erythematous plaque on the dorsum of the left hand 1 day after taking cetirizine 10 mg for rhinitis symptoms. Continued dosing was followed by a petechial rash on the dorsa of the feet. The lesions resolved fully after discontinuation. Twelve months later, he developed an acute urticaria, for which he took chlorphenamine and fexofenadine. The following day, he developed a similar rash on the dorsum of his left hand and a petechial eruption on his feet. Symptoms persisted despite oral prednisolone but improved rapidly after stopping antihistamines. In situ patch testing to oral antihistamines prepared at 10% in petrolatum in Finn chambers applied for 48 h demonstrated persistent erythema at 96 h to cetirizine and minimal erythema to loratadine. There was no reaction to fexofenadine, although the involved area was small, so patch placement outside the affected skin may have caused a false negative result. Repeat patch testing with fexofenadine and diphenhydramine is planned to assess cross-sensitivity. This case describes a rare antihistamine-associated fixed drug eruption with postulated class-related crossreactivity in a presumed safe drug class and highlights in situ patch testing as a safe diagnostic tool.