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The major apple allergen Mal d 1 cross-reacts with the homologous birch pollen allergen Bet v 1 and causes immunoglobulin E (IgE)-mediated immediate-type allergic reactions. In some patients, delayed-type hypersensitivity to apples may develop within 72 hours without evidence of specific IgE or a positive skin prick test (SPT). The aim of the study was to evaluate the concomitance of delayed-type hypersensitivity reactions and immediate IgE-mediated reactions against high- and low-allergenic apple cultivars in patients with birch pollen allergy. Data were obtained from 45 adults with clinical symptoms of birch pollen allergy. Patients were exposed to apple pulp via atopy patch tests (APTs) and SPTs. Levels of IgE specific to Bet v 1 and Mal d 1 were measured with a radioallergosorbent test. Patients allergic to birch pollen showed the highest rate of positive SPT responses to Golden Delicious apples and the lowest rate to low-allergenic cultivar Grey French Reinette. Among these patients, 9% developed delayed hypersensitivity reactions to either Golden Delicious or Grey French Reinette apples; these reactions manifested clinically as erythema with papules (class ++). Fifty percent of APT-positive patients were concomitantly SPT-negative. Here, we show for the first time the clinical relevance of T cell-driven allergic reactions to apples. APTs may reveal type IV sensitization in patients who are negative for the corresponding type I sensitization tests. Thus, utilization of the APT procedure with fresh apple appears to be a valuable tool for the diagnosis of apple allergy and may improve the accuracy of food allergy diagnoses.

The Incidence of Delayed-Type Hypersensitivity Reactions to Apples Among Patients Allergic to Birch Pollen