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