3-EPIDEMIOLOGY and PPI USE AS A RISK FACTOR FOR ALLERGIC DISEASES
It has been reported that gastric acid suppression promotes allergy in animal and observational human studies.12,13 In line with these trials, a current population-based study provided evidence for an epidemiological association between gastric acid suppression and the development of allergic symptoms. In the study, ratios of using anti-allergic medications, increased from 1.47 (95%CI:1.45–1.49) in subjects <20 years, to 5.20 (95%CI:5.15–5.25) in > 60 years old after gastric acid-inhibiting drug prescriptions were found. This finding was specific to all gastric acid-inhibiting drugs and was more prominent in females.6
There is also evidence that PPI use may be associated with de novo type I allergic sensitizations to dietary compounds and to oral drugs.6,13 The risk for food allergy associated with PPI treatment showed a dose-dependent effect related to days of treatment. Children who had been prescribed for more than 60 days of PPIs had a 52% greater risk of being diagnosed with food allergy during childhood than those prescribed for 1 to 60 days of PPIs.14 A low gastric pH (1 - 3.5) is necessary to activate gastric pepsin and only acidic chymus stimulates duodenal secretions and the release of pancreatic enzymes at the next level of digestion hierarchy. When anti-acid drugs inhibit acid gastric secretion, therefore, food-related allergens may remain intact and absorbed, facilitating an allergic sensitization.2
In a nested case-control \soutin a retrospective cohort study \soutin on hospitalized patients, the use of PPIs was associated with a significant increased risk of drug HSRs (OR: 4.35; 95% CI: 2–9.45) along with a personal history of drug allergies and a long hospitalization time.15 PPI therapy is also considered a possible cofactor, along with exercise, anti-inflammatory medications and alcohol, in decreasing the allergens eliciting threshold dose for anaphylaxis.2
Additionally, PPIs may act as a cofactor in patients undergoing oral immunotherapy (OIT), triggering adverse reactions, irrespective of the PPI used or the dosage. Since OIT is a new form of treatment, long-term adverse events arising from PPI treatment and other possible triggers are still uncertain and needs long term follow-up.16
The PPIs involved in the HSRs vary among countries: lansoprazole in studies from Turkey,17,18 esomeprazole and lansoprazole in Italy3 and omeprazole in Spain19-24, probably reflecting the consumption/prescription rate. To date, there are no reported cases of HSRs to dexlansoprazole or tenatoprazole.
The incidence of anaphylaxis due to PPIs is expected to grow in the next few years due to the increasing consumption, the over-the-counter availability and greater awareness of clinicians.19-20,25,26 Nevertheless, epidemiological studies reporting true incidence and prevalence are still lacking.