Hyperresponsiveness to antihistamines in spontaneous urticaria and heat urticaria

Abstract. Background: H(1) antihistamines are important drugs for the treatment of urticaria and are commonly well tolerated. Cases of hypersensitivity reactions to antihistamines have rarely been reported, the underlying pathomechanism is unknown yet. Case report: We report the case of a 28-year-old female patient suffering from chronic spontaneous urticaria who experienced severe episodes of wheals and flares induced by different H(1) antihistamines. Methods: We performed skin prick tests (SPT) with a diversity of H(1) antihistamines and CAST and FlowCAST analyses. Moreover, a placebo controlled oral challenge test to mizolastin was done. Results: We saw positive SPT reactions to nearly all H(1) antihistamines tested with the exception of mizolastin. We observed neither a release of sulfidoleukotrienes nor an upregulation of basophil activation markers in the CAST and FlowCAST analyses. The oral challenge test with mizolastine resulted in the development of generalized wheals and flares. Conclusion: H(1) antihistamines are effective drugs for the treatment of urticaria, but they may lead to hypersensitivity reactions in rare cases. Because of the negative CAST and FlowCAST results, an IgE-mediated pathomechanism is improbable. We propose that hypersensitivity reactions to H(1) antihistamines may be induced by a paradox H(1) receptor activation.