D3.315 - Management of Drug Hypersensitivity Reactions in an Oncology Patient: An Atypical Case of Omeprazole Allergy with Pantoprazole Tolerance

Immediate hypersensitivity reactions to proton pump inhibitors (PPIs) are increasingly reported and represent a significant clinical challenge, particularly in oncology patients undergoing polytherapy. Although pantoprazole is frequently cited as the molecule with the highest rate of sensitization and cross-reactivity among PPIs, individual reactivity patterns can vary significantly. This requires an accurate diagnostic workup to ensure the continuity of life-saving oncological treatments.

A 65-year-old female patient with cancer, undergoing treatment with carboprost, pemetrexed, and pembrolizumab (all well-tolerated), experienced four episodes of systemic reactions (Grade I-III) within 30 minutes of receiving chemotherapy premedication. Symptoms ranged from palmar-plantar pruritus and erythema to hypotension and dyspnea. To identify the causative agent among aprepitant, dexamethasone, omeprazole, ondansetron, and chlorhexidine, we performed skin prick tests (SPT), intradermal tests (IDT) and drug provocation tests (DPT) for drugs that emerged negative at the skin test results.

Allergological investigations revealed a positive SPT for omeprazole (40 mg/ml). Skin tests were also positive for esomeprazole (4 mg/ml, spt), suggesting cross-reactivity within the benzimidazole derivative subgroup. Conversely, skin tests were negative for pantoprazole, lansoprazolo, and rabeprazole. Tests for ondansetron, chlorhexidine, and dexamethasone were also negative. The diagnosis was confirmed by documented clinical tolerance during DPTs with pantoprazole, ondansetron, and dexamethasone, all of which were completed without adverse reactions. Basal serum tryptase levels were within the normal range (6.2 mcg/l), ruling out underlying mastocytosis. Despite the clear positivity of the skin tests, the Basophil Activation Test (BAT) for omeprazole, esomeprazole, pantoprazole, and lansoprazole yielded negative results, highlighting a potential discrepancy between in vitro and in vivo diagnostics in this specific case.

This case is noteworthy as the patient demonstrated selective sensitization to omeprazole and esomeprazole while maintaining tolerance to pantoprazole, a molecule typically considered the most frequent culprit in PPI cross-reactivity. The diagnostic process allowed us to rule out allergy to essential antiemetics and corticosteroids, highlighting the crucial role of skin and provocation tests in preventing unnecessary and potentially harmful pharmacological restrictions in complex patients.  The negativity of the BAT, contrasted with the positive skin prick test for omeprazole, emphasizes that skin testing remains the gold standard for PPI allergy diagnosis. Furthermore, the normal basal tryptase levels suggest a specific IgE-mediated mechanism rather than a systemic predisposition to mast cell degranulation.