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.