Are proton pump inhibitors (PPIs) known to cause hypereosinophila and urticaria?

Fråga: Are proton pump inhibitors (PPIs) known to cause hypereosinophila and urticaria?

Sammanfattning: Both urticaria and hypereosinophilia are known adverse reactions to PPIs. Whether or not this holds true after 13 years treatment is unknown. Discontinuation of lansoprazole should be considered. We recommend that the patient is referred to an allergy clinic.

Svar: According to the summary of product characteristics for Lanzo, urticaria is a common adverse reaction affecting > 1/100, < 1/10 (1). Eosinophilia is also listed, but as a less common adverse reaction (>1/1000, <1/100). It is not stated how often the combination may occur. There is also no information regarding the time frame from start of treatment.

In the Swedish adverse drug reactions register, SWEDIS, there are currently 1367 reports where PPIs are likely to have caused the adverse reaction (2). Out of these, there are 73 cases of urticaria and one case of eosinophilia. Of the 73 reported cases of urticaria, the majority (62) regarded omeprazole, six esomeprazole and five lansoprazole.

We have not found any published articles on eosinophilia as an adverse reaction to PPIs.

A review article describes nine patients who reacted with urticaria (n=7) or anaphylaxis (n=2) to omeprazole (3). Eight out of nine had a positive prick test to omeprazole, which implies an IgE-mediated reaction. Skin tests (skin prick test och intradermal test) are recommended for the diagnosis of such reactions. Skin reactions to PPIs are most commonly mild, but one case of DRESS syndrome, with a toxic skin reaction, hypereosinophilia and liver failure, has been reported (4).

In one study, 53 patients who had reacted with immediate allergic reactions to PPI (grade I-III, ranging from pruritus and urticaria to laryngeal edema and chock) were tested with skin tests (skin prick- or intradermal tests) (5). Skintests were positive only in 12 out of the 53 patients, and mostly so in those patients who had experienced a grade III reaction. Those patients who tested positive for lansoprazole, had a negative skin test for omeprazole, esomeprazole and pantoprazole. Although the number of patients is too small to make any general conclusions, it may imply that a patient who is allergic to lansoprazole can benefit from a change in PPI choice. This finding is congruent with another case report, where a woman developed urticaria and angioedema from lansoprazole. Prick test for lansoprazole was positive, but not for the other PPIs (6).

The current patient was treated with PPIs for many years before developing symptoms. We have not found any published literature as to whether urticaria can appear after long-term treatment. As both urticaria and eosinophilia are reported adverse reactions to PPI, it is difficult to completely rule out that lansoprazole is causing the symptoms and we recommend a report to SWEDIS.

As stated in the question, this patient has had pronounced urticaria and eosinophilia for two years. The case was discussed with clinical pharmacologist Dr Wikstrom Jonsson, who also has vast experience from working in an allergy clinic. We recommend that the patient is referred to an allergy clinic for closer evaluation.

The indication for lansoprazole treatment in this patient is not known. It may be advantageous for this patient to discontinue lansoprazole. Other treatment options such as other PPIs or ranitidine, which is sometimes used as a complement to antihistamines in patients with urticaria, should be considered.