6.3.a. Cross-reactivity
All current PPIs consist of a benzimidazole and a pyridine ring.33 PPIs are pro-drugs, they are highly bound to proteins and they undergo acid-catalyzed cleavage of a chiral sulfoxide bond (except esomeprazole and dexlansoprazole which are non-chiral) into active sulfenic acid and or sulfonamide.9Cross-reactivity within the PPI family is likely related to their similar chemical structure.29 Reports on cross-reactivity and/or tolerance in immediate HSRs to PPIs confirmed by skin tests and/or DPT are summarized in Table 4. Among patients with an immediate PPI HSR that has been confirmed with skin tests and/or DPTs, available studies,3,17-20,22-24,37-45,53-58,60-61,63-69suggest that 61.6% will show cross-reactivity to another PPI and 8.9% will show cross-reactivity to all available PPIs. However, these results may be underestimated, as most studies have investigated cross-reactivity only towards some preparations and not towards all available PPIs. The highest rates of cross-reactivity are shown in patients who are allergic to omeprazole, esomeprazole or pantoprazole. This is probably related to the fact that such drugs are structurally similar, in fact their benzimidazole rings have a methoxy and a difluoromethoxy chain in common59. Consistent with this, cross-reactivity rates are lower in patients allergic to lansoprazole or rabeprazole, see table 5. Therefore, patients monosensitized to lansoprazole or rabeprazole would more likely tolerate other PPIs.3
Cross-reactivity rates between PPIs in immediate HSRs, according to the available studies, are shown in Table 6. Many different patterns of cross-reactivity were detected among PPIs. Additionally, not all these patterns (e.g. lansoprazole and pantoprazole cross-reactivity; omeprazole and lansoprazole cross-reactivity) can be explained simply with the abovementioned structural similarity. The different patterns of cross-reactivity may be associated with the chemical characteristics (e.g. substitutions, metabolites) and metabolism of the drugs, and, probably, the influence of some potential cofactors.