Evaluation and management of hypersensitivity to proton pump inhibitors

Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. PPIs are well tolerated, but they can cause hypersensitivity reactions (HSRs). Although simply avoiding a PPI after an HSR is appropriate for most patients, there are clinical scenarios that require treatment with a PPI.

A comprehensive literature review was performed to propose an evidence-based approach to the evaluation and management of HSRs to PPIs.

Articles from June 1986 through September 2012 on PPI hypersensitivity were reviewed. Thirty-nine studies that met the search criteria were included in the review. HSRs to PPIs and skin testing protocols used to evaluate HSRs were analyzed from the 39 identified publications. For each case, the culprit drug and dose, the age and sex of the patient, and the symptoms and timing of the HSR were recorded. HSRs were classified into immune- or nonimmune-mediated categories.

A total of 118 cases of immune-mediated HSRs to 5 PPIs were identified, most of which were suspected IgE-mediated HSRs. Omeprazole was the culprit PPI most frequently associated with HSRs. The most common clinical manifestations of PPI HSRs were cutaneous reactions. Nonirritating concentrations for skin prick and intradermal testing were identified. Skin testing showed variable cross-reactivity patterns among the different PPIs.

The HSRs to PPIs should be formally investigated, especially when reasonable alternative therapies do not exist. The reviewers propose an evidence-based algorithm for evaluating and managing patients with an HSR to a PPI.