The underlying mechanisms of HSRs to PPIs are not yet fully explained. Most of the PPI HSRs are IgE-mediated and confirmed by skin prick tests (SPT) or intradermal tests (IDT) or basophil activation test (BAT) positivity. An IgE-mediated mechanism has also been reported in reactions occurring after 3-24 hours from PPI intake.3,18,22,30,34 This may be due to the delayed-release formulation of some PPIs (enteric-coated tablets) or polymorphisms in the cytochrome P450 CYP2C19 gene leading to slow drug metabolism. In addition, PPI as a prodrug is activated by acid and then binds covalently not only to the gastric H+, K+-ATPase enzyme,35, but to a wide range of proteins.36 Thereby, the PPI as a hapten may acquire the characteristics of a complete antigen and lead to IgE formation, as previously demonstrated for other drugs.13T cell–mediated delayed reactions to PPIs are less frequent, ranging from maculopapular exanthemas to severe cutaneous adverse reactions (SCARs); positive patch tests support the confirmatory diagnosis. Type II and T cell–mediated HSRs have also been reported.27