Evaluation of diagnostic tests for suspected hypersensitivity reactions to proton pump inhibitors in children

<b>Background:</b> Proton-pump inhibitors (PPI) are widely used in pediatric populations, although hypersensitivity reactions (HSR) to these agents are rare and not well characterized in children. <b>Objective:</b> This study aimed to evaluate the clinical characteristics and diagnostic findings of pediatric patients with suspected HSRs to PPIs. <b>Methods:</b> Pediatric patients referred to our allergy clinic with suspected PPI-related HSRs between January 2012 and October 2023 were retrospectively analyzed. Data on demographics, reaction characteristics, comorbidities, and diagnostic test outcomes (skin-prick test, intradermal test, and drug provocation test) were collected. <b>Results:</b> Twenty-two patients (median age, 12 years; 81% girls) were included. Lansoprazole was the most commonly implicated PPI (64%). Clinical manifestations included urticaria (41%), anaphylaxis (36%), maculopapular eruption (14%), angioedema (4.5%), and toxic epidermal necrolysis (4.5%). Most reactions (77%) occurred within 6 hours of drug intake. Among 18 patients undergoing diagnostic evaluation, 11 were tested with the suspected PPI and 7 were tested with an alternative PPI. One patient had a positive intradermal test result to omeprazole but tolerated lansoprazole. In total, 10 patients had their PPI allergy label removed after a negative diagnostic workup; 9 tolerated an alternative PPI. <b>Conclusion:</b> Urticaria and anaphylaxis were the most common presentations of PPI hypersensitivity. Lansoprazole was the most frequently suspected drug. Skin testing, followed by a drug provocation test with a tolerated alternative, remains essential for diagnostic clarification. Clinicians should be aware of possible cross-reactivity among PPIs. Further pediatric studies are needed to optimize diagnostic and management strategies for PPI-induced HSRs.