Published online: January 12, 2018
Proton pump inhibitors (PPI) are drugs commonly used in clinical practice for the treatment of many gastrointestinal diseases. Incidences of hypersensitivity reactions to PPI have risen in recent years, likely due to increased consumption. Most hypersensitivity reactions are immediate, appearing in less than one hour after drug intake. They account for approximately 85% of all immunological reactions to PPI. Diagnosis is difficult due to the low sensitivity reported for skin tests (ST), making it necessary to perform drug provocation testing (DPT), a complex procedure that is not risk-free for the patient, especially for severe reactions. There is a lack of studies investigating the mechanisms of these reactions and the involvement of IgE. Moreover, the potential of in vitro tests, such as the basophil activation test (BAT), for the diagnosis of immediate reactions to PPI is increasingly relevant.
The recent study of Laguna et al. in The Journal of Allergy and Clinical Immunology: In Practice evaluated the utility of BAT to diagnose omeprazole hypersensitivity in a group of well-characterized patients and the potential involvement of specific IgE in the development of the reaction. The study included 42 patients with a clear clinical history of an immediate allergic reaction after administration of omeprazole, confirmed as allergic based on the presence of a positive ST or DPT to this drug. BAT was performed for all patients, as well as in a control group of 22 age- and sex-matched subjects with negative ST and confirmed tolerance to omeprazole by DPT. Skin prick (SPT) was performed with omeprazole using an undiluted commercial preparation (40 mg/mL) and intradermal tests (IDT) were carried out with 0.04 mg/ml, 0.4 mg/ml, 4 mg/ml dilutions. Single-blind placebo-controlled DPT was carried out using omeprazole if ST was negative. Briefly, placebo capsules were given at different times on the first day; on the second day omeprazole was administered at 30-min intervals in escalating doses (5, 5, 10 and 20 mg) until cutaneous and/or respiratory symptoms or alterations in vital signs appeared. BAT was performed with omeprazole at 2, 0.2 and 0.02 mg/mL using CCR3 to select basophils and comparing the expression of two different activation markers, CD63 and CD203c.
Comparisons between CD63 and CD203c, showed a significantly higher expression of CD63 in patients, making it the best activation marker for this study. Using CD63 as the activation marker for BAT, the test was positive in 74% of the patients, without any false positive results within the control group. Moreover, the test was positive in 8 of 14 patients with a negative ST; thus, by combining ST and BAT to omeprazole, the authors could diagnose 86% of patients correctly. Additionally, to prove that the activation observed was IgE mediated, BAT was performed after incubating cells with wortmannin, a potent inhibitor of the IgE signaling pathway. This led to a significant decrease in basophil activation, demonstrating the involvement of IgE in the stimulation of basophils by omeprazole.
Laguna et al. found that BAT with omeprazole represents a promising complementary tool for inclusion in the allergological work-up for possible allergic reactions to omeprazole When combined with skin testing, it can help the clinician to decide whether or not to perform a DPT. This finding is particularly important because PPIs frequently cause severe reactions, yet comparatively little is known about the mechanisms involved, and there is a lack of consensus regarding the best practices for diagnosis.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.