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.