100261 - Cross-reactivity among different proton pump inhibitors in a patient with recurrent anaphylaxis to pantoprazole and esomeprazole

Background: Hypersensitivity reactions (HSRs) to proton pump inhibitors (PPIs) are an increasingly recognized clinical issue, particularly given the widespread use of these drugs for gastroesophageal reflux disease (GERD). Although HSRs to PPIs are uncommon, they can lead to severe, life-threatening conditions such as anaphylaxis, often occurring hours after drug administration. The delayed onset of these reactions presents diagnostic challenges, requiring comprehensive testing to confirm the allergenic mechanisms. We present the case of a 42-year-old woman with severe GERD who visited the emergency room twice with symptoms of dyspnea, facial angioedema, flushing, dizziness and fatigue occurring one hour after taking pantoprazole and esomeprazole. This case aims to explore the clinical presentation and potential cross-reactivity of PPIs.

Results: Skin prick tests (SPTs) were strongly positive for omeprazole and rabeprazole, while SPTs for pantoprazole, esomeprazole, dexlansoprazole, and lansoprazole were negative. Further intradermal testing confirmed type I sensitization to esomeprazole and pantoprazole, though testing for dexlansoprazole and lansoprazole was not performed due to the lack of an injectable solution. A basophil activation test (BAT) was positive for omeprazole, esomeprazole, pantoprazole, and rabeprazole. Lansoprazole was only positive at the highest concentration tested, while dexlansoprazole was negative. Given that dexlansoprazole is the R–enantiomer of lansoprazole, a high degree of cross-reactivity would be expected (despite a negative BAT). We have therefore planned a DPT with dexlansoprazole as the next step in the diagnostic process.

Conclusion: This case underscores the diagnostic challenges of PPI-induced HSRs and the difficulty in identifying a tolerable PPI for the patient. All PPIs share structural components, such as the benzimidazole and pyridine rings, which are crucial for their pharmacological activity. Notably, lansoprazole and dexlansoprazole contain a trifluoroethoxy group, while pantoprazole and esomeprazole contain a methoxy group. This structural variation may explain the differing sensitization pattern observed in our patient, although up to 10% of patients may be allergic to all PPIs. Despite the lack of documented systemic anaphylactic reactions to dexlansoprazole in the literature, as well as a negative skin prick test and a negative BAT, a DPT is planned to assess its tolerance. Currently, the GERD is being managed with famotidine (an H₂ receptor antagonist).