Proton Pump Inhibitor Allergy

Proton Pump Inhibitors (PPIs) are commonly used medications for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, as well as for the treatment of infections. PPIs act to block acid pumps in the stomach, thereby decreasing acid production, and are very effective at treating a wide variety of acid-related gastrointestinal diseases. There are a number of proton pump inhibitors available on the market, including omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), rabeprazole (Aciphex) and lansoprazole (Prevacid). Generally, PPIs are very safe medications with few side effects. This is likely the reason that omeprazole and lansoprazole are available over-the-counter/without a prescription (as of the date of this article being written, esomeprazole, pantoprazole, and rabeprazole are available only by prescription).

Woman looking at medication
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Allergic reactions to proton pump inhibitors are not particularly common but do occur. Many of these reactions include urticaria, asthma, and even anaphylaxis. It is often difficult to identify a PPI as the cause of an allergic reaction since other medications, including NSAIDs and antibiotics such as penicillins, are often given along with PPIs to help prevent stomach ulcers or to treat Helicobacter pylori infections.

A number of different studies have been performed on people who have experienced allergic reactions as a result of taking proton pump inhibitors. Skin testing, including both prick and intradermal methods, has been performed using PPIs (and other medications that the person was taking) that could have possibly caused the allergic reaction. These skin tests appeared to be helpful in identifying the cause of the allergic reaction, especially when the PPI was the cause. Oral challenges using the culprit PPI resulted in symptoms of an allergic reaction when the skin test was positive. However, people who had ​negative skin tests were not always able to tolerate the PPI in question during an oral challenge.

Cross-Reactivity Between Proton Pump Inhibitors

The five different proton pump inhibitors don’t share the same chemical structure, which suggests that if a person were allergic to one PPI, one or more of the other PPIs might be tolerated. Studies performed on the cross-reactivity of proton pump inhibitors have found that people allergic to omeprazole are frequently allergic to pantoprazole (and vice versa), and people allergic to lansoprazole are often allergic to rabeprazole (and vice versa). This cross-reactivity is due to the similar structures between certain PPIs; the lack of cross-reactivity between other PPIs may allow a person with an allergy to a certain PPI to tolerate another PPI. For example, people allergic to omeprazole or pantoprazole are often able to take lansoprazole or rabeprazole, and those allergic to lansoprazole or rabeprazole are often able to take omeprazole or pantoprazole.

For people who have experienced an allergic reaction as a result of taking a particular proton pump inhibitor, skin testing might be helpful in confirming the diagnosis. If skin testing for the culprit PPI is positive, then skin testing to a non-cross-reacting PPI may be performed in an attempt to find a PPI that the person can tolerate. However, an oral challenge, performed under medical supervision, should be performed with a non-cross-reacting PPI (with a negative skin test) to ensure that it is safely tolerated.

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Additional Reading
  • Chang YS. Hypersensitivity Reactions to Proton Pump Inhibitors. Curr Opin Allergy Clin Immunol. 2012;12:348-53.

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