Case Report: First report of vonoprazan-associated severe Gly m 4-mediated PFAS anaphylaxis in the era of potent acid suppression.

BACKGROUND: Pollen-food allergy syndrome (PFAS) usually causes localized oral symptoms through cross-reactivity between pollen allergens and plant-derived foods. However, the soybean PR-10 allergen Gly m 4 can provoke systemic reactions, including anaphylaxis. Proton pump inhibitors (PPIs) are recognized in PFAS consensus statements as potential cofactors, although acid suppression is not established as a major cofactor for food-induced anaphylaxis overall. Increasingly prescribed potassium-competitive acid blockers (P-CABs), including vonoprazan, provide potent and sustained acid suppression beyond conventional PPIs. To our knowledge, severe PR-10-related PFAS temporally associated with P-CAB therapy has not been previously reported. CASE PRESENTATION: A 59-year-old woman had experienced mild oral allergy syndrome-like symptoms, including lip swelling, after soy milk ingestion, while tolerating other soybean products. Two weeks after starting vonoprazan 20 mg for gastroesophageal reflux disease, she developed generalized urticaria, throat discomfort, and dyspnea after dinner containing inadequately cooked soybean sprouts, requiring epinephrine. Three months later, within 15 min after eating ramen containing inadequately cooked soybean sprouts, she developed generalized urticaria and dyspnea, requiring hospitalization and epinephrine. Component-resolved testing showed positive specific IgE to Gly m 4, whereas crude soybean extract, ω-5 gliadin, and other food-related allergens were negative. These findings supported Gly m 4-mediated PR-10-related PFAS. Because vonoprazan was the only new factor common to both episodes, it was considered a possible cofactor. Vonoprazan was discontinued, and the patient was advised to avoid soy milk and undercooked soybean sprouts and to be cautious regarding recognized cofactors. Over 6 months of follow-up, no further anaphylaxis occurred, and soybean sprouts were tolerated. CONCLUSION: To our knowledge, this is the first report of severe Gly m 4-mediated PFAS anaphylaxis temporally associated with vonoprazan use. Potent P-CAB-mediated acid suppression may theoretically reduce gastric degradation of labile PR-10 allergens and increase systemic exposure to immunologically active Gly m 4, although causality was not proven because oral food challenge with and without vonoprazan was not performed. These findings suggest that, in PR-10-related PFAS, medication review and anticipatory counseling regarding potent acid suppression, particularly P-CAB therapy, may be important in patients with PFAS, even when previous symptoms have been limited to mild oral reactions.