Early Life Risk Factors in Pediatric EoE: Could We Prevent This Modern Disease?

Abstract

Eosinophilic esophagitis (EoE) is a chronic antigen-mediated inflammatory disease that affects the esophagus. In the last 20 years, a large number of epidemiological studies showed a significant increase in the incidence and prevalence of EoE, especially in developed countries. This phenomenon might correlate to the overall increase in pediatric allergic diseases or might be a result of improved medical awareness and knowledge through modern diagnostic instruments. Since 1993, when EoE was first recognized as a distinct clinical entity, several signs of progress in the pathophysiology of EoE were achieved. However, a few studies reported data on early risk factors for pediatric EoE and how these factors may interfere with genes. Currently, the most defined risk factors for EoE are male sex, Caucasian race, and atopic comorbidities. Other putative risk factors may include alterations in epithelial barrier function and fibrous remodeling, esophageal dysbiosis, variation in the nature and timing of oral antigen exposure, and early prescription of proton pump inhibitors and antibiotics. Notably, the timing and nature of food antigen exposure may be fundamental in inducing or reversing immune tolerance, but no studies are reported. This review summarized the current evidence on the risk factors that might contribute to the increasing development of EoE, focusing on the possible preventive role of early interventions.

Malnutrition in Eosinophilic Gastrointestinal Disorders

“…Putative explanations could probably be found in environmental and genetic risk factors and EGID-related comorbidities. The overall prevalence of EGIDs seems to higher in developed Western countries, where childhood obesity and atopic diseases were significantly increased through time [ 7 , 28 ]. Indeed, obesity and the Western lifestyle, mainly characterized by high calorie/fat consumption and reduced physical activity, might be directly related to the increased risk of developing allergic diseases, such as EGIDs [ 13 ].…”

“…Another possible pathogenetic mechanism might be the relationship between EoE and GERD. Diagnosis of GERD has also increased, especially in developed countries [ 7 ]. In half of the infants with refractory vomiting and regurgitation, GERD was also expressed in the underlying cow’s milk allergy, and improved with a hydrolyzed formula [ 30 ].…”

“…Indeed, EoE and GERD are not mutually exclusive and might coexist [ 4 ]. Although there are no exact data, four mechanisms have been proposed to explain this association: (1) GERD only causes esophageal eosinophilia; (2) GERD and EoE coexist but are independent phenomena; (3) EoE induces GERD; (4) GERD contributes to or induces EoE [ 7 , 31 ]. Acid reflux alters the esophageal epithelial barrier, leading to high intestinal permeability, with a subsequent passage of food allergens and release of inflammatory and eosinophil chemoattractant molecules might trigger EoE in susceptible subjects [ 32 ].…”

“…On the other hand, the esophageal eosinophilic inflammation is also associated with the production of different proinflammatory cytokines that might impair peristalsis and the esophageal acid clearance [ 7 , 33 ]. The subepithelial fibrosis, a delayed complication of EoE, might also promote esophageal dysmotility and GERD-related symptoms [ 31 ].…”

“…EoE pathogenesis has been more extensively studied, and advances concerning the genetic and environmental contributors and cellular and molecular etiology have been achieved [ 6 ]. EGIDs seem to be multifactorial diseases resulting from genetic predisposition, environmental risk factors, and intestinal dysbiosis, leading to the activation of T-helper type 2 (Th2) inflammation and impaired epithelial barrier [ 1 , 7 ]. To date, no studies have extensively assessed malnutrition in patients with EGIDs.…”