Eosinophilic Esophagitis and Cow's Milk: Mechanisms, Challenges, and Treatment Perspectives

Abstract

Eosinophilic esophagitis is a chronic, antigen-driven, immune-mediated disease characterized by esophageal dysfunction and significant eosinophilic infiltration. Its rising incidence and prevalence over recent decades reflect both increased clinical awareness and the influence of environmental factors such as dietary patterns and allergen exposure. Among food allergens, cow's milk proteins are the most commonly implicated triggers, contributing to esophageal inflammation through complex immunological pathways involving both IgE-mediated and non-IgE-mediated mechanisms. Dietary elimination of cow's milk has been shown to induce histologic remission in over 60% of pediatric patients, underscoring its pivotal role in eosinophilic esophagitis management. Despite these promising results, challenges persist, including variability in individual responses, the burden of adherence to restrictive diets, and gaps in understanding the molecular mechanisms driving cow's milk-induced esophageal inflammation. This review examines the complex relationship between eosinophilic esophagitis and cow's milk, focusing on its role in disease pathogenesis and management, offering insights into its therapeutic implications. Understanding the interplay between eosinophilic esophagitis and dietary allergens, particularly cow's milk, may inform the development of targeted interventions and improve clinical outcomes for affected patients.

Keywords: Th2 immune response; cow’s milk proteins; dietary therapy; elimination diet; eosinophilic esophagitis; esophageal inflammation; food hypersensitivity; histologic remission; milk allergy.

Figure 1

Environmental, genetic, and epithelial barrier impairment factors contribute to the pathogenesis of EoE [24,25,26,27,28,29,30,31,32]. Cow’s milk processing, such as UHT homogenization, alters the structure of milk proteins and lipids, leading to the formation of lipid-protein nanoparticles [14]. These nanoparticles can penetrate the esophageal mucosa, act as immune adjuvants, and drive a Th2 immune response characterized by the production of cytokines (IL-4, IL-5, IL-13), eosinophil recruitment, and subsequent tissue remodeling [13,14,15]. Additionally, these nanoparticles can stimulate an IgG4-mediated immune response. Although the precise role of IgG4 in EoE remains unclear, it may further amplify local inflammation, contributing to chronic antigen stimulation and inflammatory cell recruitment. This cascade creates a self-sustaining inflammatory loop characterized by persistent eosinophilic infiltration, epithelial damage, and the activation of fibroblasts and myofibroblasts. Ultimately, this process results in tissue remodeling, including subepithelial fibrosis and basal cell hyperplasia, leading to esophageal dysfunction.

Figure 2

Algorithm for the management of EoE. Following a confirmed diagnosis, treatment options include medical therapy—proton pump inhibitors, swallowed steroids, and dupilumab—and dietary therapy, ranging from milk exclusion to empirical elimination diets (TFED, FFED, SFED) and elemental diets. The approach is guided by patient response, assessed after 8–12 weeks via repeat endoscopy and histological evaluation [35,36]. TFED: two-food elimination diet; FFED: four-food elimination diet; SFED: six-food elimination diet; eos: eosinophils; HPF: high-power field.

Figure 3

Comparison of dietary strategies for the management of eosinophilic esophagitis (EoE), highlighting efficacy and limitations [12].