Recurrent idiopathic anaphylaxis linked to pantoprazole

Abstract

Rationale We investigated a case of idiopathic anaphylaxis for the potential role of pantoprazole hypersensitivity and its relationship to cytochrome P450 polymorphisms. Methods and results A 47-year-old Hispanic male was referred for evaluation of recurrent idiopathic anaphylaxis (urticaria, angioedema, substernal chest discomfort, orthostasis and impaired consciousness) of 8 months duration. He was otherwise well with the exception of gastroesophageal reflux treated with intermittent pantoprazole. Serum IgE to aeroallergens and foods were positive for cockroach. He was prescribed an antihistamine, equipped with an EpiPen, and advised to report additional episodes. One month later, he experienced severe anaphylaxis with an associated tryptase level of 31μg/L (nl<15.8), 3 hours following 40mg pantoprazole. Previous anaphylactic events occurred sequentially 24, 10 and 4 hours after pantoprazole, each following several days of uneventful use. Intradermal skin test with pantoprazole was positive. Pantoprazole was discontinued with a benign 10 month course of follow-up. We investigated whether reported polymorphisms in the cytochrome P450 CYP2C19 gene (associated with a poor metabolizer phenotype) were related to anaphylactic timing. Genomic DNA was analyzed for polymorphic alleles ( CYP2C19 m1 and CYP2C19 m2 ) by polymerase chain reaction followed by restriction enzyme digestion. The patient was homozygous for the wild-type allele. Conclusion Pantoprazole should be considered in the differential diagnosis of idiopathic anaphylaxis. Although CYP2C19 m1, m2 alleles were not identified, the timing of anaphylactic events invokes the possible involvement of modifying pharmacogenetic factors. In our patient, the positive skin test and elevated tryptase level are consistent with prior case reports of proton pump inhibitor anaphylaxis and suggest an immediate hypersensitivity mechanism.