Clinical & Experimental Allergy

Suppression of gastric acid increases the risk of developing Immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model


Erika Jensen-Jarolim, Department of Pathophysiology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.


Background Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins.

Objective Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm.

Methods We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays.

Results Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo.

Conclusion Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.

Cite this as: A. B. Riemer, S. Gruber, I. Pali-Schöll, T. Kinaciyan, E. Untersmayr and E. Jensen-Jarolim, Clinical & Experimental Allergy, 2010 (40) 486–493.