Discussion
We reported a clinical observation of a selective immediate
hypersensitivity to omeprazole confirmed by skin and provocation tests.
A clear temporal relationship was observed between omeprazole
administration and the onset of symptoms; and the skin test to this drug
was positive. Based on the Naranjo algorithm (4), it is probable that
the urticaria was induced by omeprazole (Naranjo’s score - 5).
IgE-mediated reactions are the most frequently reported hypersensitivity
reactions to PPIs (5). Urticaria was the most common clinical
presentation in patients with immediate hypersensitivity reactions to
PPIs after anaphylaxis (6). In our case, urticaria occurred four hours
after omeprazole intake which is in line with literature. Indeed,
immediate hypersensitivity reactions generally occur within a few hours
after a dose, even though some case reports of delayed anaphylaxis to
PPIs that occur between 2 and 24 hours after the intake of the latter
drugs have been described (5,7). The incidence of hypersensitivity to
omeprazole, the culprit PPI in our patient, is variable. For example,
Kepil Özdemir et al. have reported a large series of 60 patients with
PPIs-induced hypersensitivity reactions, and found that omeprazole was
incriminated in only one patient (1.7%) after lansoprazole (68.3%),
pantoprazole (20%), esomeprazole (10.%) and rabeprazole (6.7%) (7).
In contrast, Tourillon et al. have found in 38 patients that omeprazole
was the first culprit drug of immediate hypersensitivity reactions (33%
vs. 23.8%, 23.8%, 11.9%, 7.2% for esomeprazole, pantoprazole,
lansoprazole and rabeprazole, respectively) (8). Overall, 12 studies
evaluating 395 patients with 416 immediate-type hypersensitivity
reactions to PPIs were identified. The main PPI elicitor of these
reactions to PPIs was lansoprazole (40.6%) followed by omeprazole
(26.2%), pantoprazole (15.6%), esomeprazole (14.4%), and rabeprazole
(3.1%) (6).
The first case of hypersensitivity to omeprazole was described in 1994
by Bowlby and Dickens and the reaction was An anaphylactic shock (9).
According to some studies, omeprazole was found to induce rarely
anaphylaxis (10). in our patient, the diagnosis of omeprazole-induced
urticaria was made possible by a positive skin test. This finding
suggests that skin tests to this PPI are safe, as no systemic reaction
was observed after the test. In case of PPI-induced IgE-mediated
hypersensitivity reactions, many studies demonstrated that skin tests
are a useful tool for the diagnosis (2). Kepil Özdemir et al. have
analyzed the diagnostic value of skin tests in a group of 38 patients
with PPI-induced immediate-type hypersensitivity reactions and in 30
healthy controls and found that specificity and positive predictive
value of these tests were both 100%, and the sensitivity and negative
predictive value were 58.8 and 70.8%, respectively (11,12) . Hence, we
can confirm that the urticaria manifested by our patient was due to
omeprazole as the concentration used in the test (0.2 and 2 mg/mL) was
in accordance with the literature (13). Interestingly, in our case skin
tests and oral provocation tests were all negative to esomepraole,
lanzopraole and pantoprazole, suggesting a selective hypersensitivity to
omeprazole. PPI have a common chemical structure composed by a
benzimidazole and a pyridine ring but vary in the specific side-ring
substitution (14). Accordingly, four general patterns of
cross-reactivity have been identified: whole-group hypersensitivity,
omeprazole -esomeprazole-pantoprazole hypersensitivity,
lansoprazole-rabeprazole hypersensitivity, and selective sensitization
to a single PPI (11). However, some studies have reported other patterns
of cross-reactivity between PPIs such as lanzopraole-pantoprazole (7)
and omeprazole-lanzoprazole(15–17). As the skin and provocation tests
to lanzoprazole, pantoprazole and esomeprazole were negative in our
patient, it could be argued that he has a selective hypersensitivity to
omeprazole. Rabeprazole was not tested in our patient as not available
in our country. To our knowledge we are the first describe a clinical
observation of a type I hypersensitivity reaction to omeprazole without
a cross reactivity to esomeprazole, pantoprazole and lansoprazole,
confirmed by skin and drug provocation tests.
In conclusion we add to the medical literature a case report of
omeprazole-induced urticaria and point out the usefulness and safety of
skin and provocation testing in diagnosing this drug reaction and in the
assessment of cross-reactivity between PPIs. Furthermore, we demonstrate
the lack of cross-reactivity between omeprazole and esomeprazole,
pantoprazole and lansoprazole. These PPIs could be safe alternatives in
case of hypersensitivity to omeprazole.