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.