The proton pump inhibitors (PPI) omeprazole and lansoprazole are extensively used in the treatment of peptic ulcer. Both these drugs are benzimidazole derivatives and are structurally and pharmacologically related (1).
A 40-year-old woman was referred to our unit because she had experienced an episode of urticaria and facial edema, 30 minutes after oral intake of omeprazole (40 mg) for dyspepsia one year previously. She had previously taken lansoprazole with good tolerance. The patient had no personal or family history of atopic disease, or other drug sensitivity. At the time of the reactions, she was not taking any concomitant therapy.
ALLERGOLOGIC STUDY
Skin prick tests with common inhalant, food, latex, and Anisakis simple ×were negative. Skin prick tests with omeprazole (4 mg/ml), pantoprazole (4 mg/ml) and lansoprazole (3 mg/ml) diluted in saline serum were positive (wheal 8 ×10 mm and 7 ×6 mm respectively with erythema). The lansoprazole wheal was 3 ×3 mm. Skin prick tests with the previous drugs were negative in 10 healthy controls. Total IgE was 53 UI/ml. No specific IgE antibodies to PPI were detected using an enzyme-linked immunosorbent assay technique.
The patient's written informed consent was obtained and challenge tests with other imidazole derivatives was carried out: cimetidine, metronidazole, and ketoconazole were administered in increasing amounts until therapeutic dose, with good tolerance. Challenge with lansoprazole was carried out and 30 minutes after oral intake of 15 mg the patient developed generalized itching, facial edema, vomiting and hypotension. The clinical picture resolved within 90 minutes after treatment with adrenaline, methylprednisolone, chlorpheniramine and ringer's lactate. Serum tryptase levels were determined 3 hours later and again 15 days after the adverse reaction to lansoprazole by radioimmunoassay (tryptase RIACT Pharmacia) and measured 4 and 0.8 U/l respectively.
DISCUSSION
We present a patient who experienced an episode of urticaria and angioedema after oral intake of omeprazole and an episode of anaphylactic shock to lansoprazole.
The clinical findings, positive skin prick test to PPI and elevated serum tryptase levels suggest that an IgE-mediated mechanism was involved in both reactions. An experimental protocol was used to detect specific IgE antibodies against PPI, which could explain RAST negativity.
To date anaphylaxis to PPI has rarely been described. Galindo et al (2). and Ottenwanger (3) reported patients who developed anaphylaxis to omeprazole. In both patients, skin prick tests with PPI were positive. Natch (4) reported two patients with anaphylactic reactions to omeprazole, lansoprazole and pantoprazole.
The adverse reactions to omeprazole and lansoprazole experienced by our patient, and the positivity of skin prick tests with PPI suggests cross-reactivity between these drugs, as others authors have suggested (4). Skin prick tests may be a useful tool for detecting patients sensitized to PPI.
Cross-reactivity among imidazoles has previously been postulated. Marren and Powell (5) found 34 reports of cross reactions between imidazoles. The nature of cross reactions, especially of contact dermatitis reactions, seems to be unpredictable.
Our patient tolerated other imidazoles (cimetidine, ketoconazole, metronidazole). Thus, in this case, cross-reactivity was restricted to PPI, although further studies are needed to provide more precise information.
PPIs are extensively used and reported experience indicates that they are well tolerated. However, anaphylactic reactions can sometimes be observed, and cross-reactivity between the different molecules exists.
