1-INTRODUCTION
Proton pump inhibitors (PPIs) belong to a group of chemically related compounds whose primary function is the inhibition of acid production by blocking the hydrogen potassium adenosine triphosphatase enzyme system (H+/K+-ATPase).1,2 In adults and pediatric population, these drugs are widely used for the treatment of peptic conditions, such as gastric ulcers, gastroesophageal reflux disease, Helicobacter pylori infections, eosinophilic esophagitis, as well as used to prevent gastric damages due to prolonged use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 They are usually well-tolerated leading to over-prescription and consumption, with a risk of side effects of approximately 1–3%.5 Given the population-based PPI consumption ranging from 8% or 11% in the 20-24 aged males or females, to 34 – 41% in the 65 – 69 aged males or females,6 , the risk for allergic side effects is substantial. Observational studies have suggested an association between PPI intake and risk of pneumonia, osteoporosis, enteric infection,Clostridium difficile –associated diarrhoea, cerebrovascular events, chronic renal failure, dementia, and all-cause mortality, especially in long-term usage.7,8 Their long term intake has been facilitated by over-the-counter sales in most countries and connects them with de novo induction of Th2 responses to food and environmental allergens, in experimental, clinical and population based epidemiologic studies. Their mechanisms of promoting Th2 immunity and dysbiosis have been revealed in detail.6 Still,in addition to their well-known risk profile, PPIs can induce immediate and delayed hypersensitivity reactions (HSRs).9 The optimal management of patients with HSRs to PPIs is still a matter of discussion. This Position Paper, aims to provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs along with unmet needs in this area.