Local immune responses in eosinophilic esophagitis: Implications for disease pathophysiology and dietary management

Abstract

Once considered a rare condition, eosinophilic esophagitis (EoE) – a chronic, allergen-driven disorder of the esophagus – is now one of the most common conditions diagnosed during the evaluation of food impaction in adults. Since the first case description back in 1978, current prevalence has been estimated at 34.2 cases per 100,000 inhabitants in the USA and Europe. EoE substantially impacts patient’s quality of life because of symptoms, dietary restrictions, and the social and psychological implications of living with food-related illness. Current treatment options can be effective but may not provide long-term disease control for all patients due to differences in disease endotype. It is therefore crucial that we continue to unravel the complex etiology and pathophysiology of EoE to enable future therapies to be more effective.

Major advances in the understanding of EoE disease course and pathophysiology have been made over the past 25-30 years. Nonetheless, many unmet needs associated with the prevention, phenotyping, diagnosis, and management of the disease remain. It is evident that there is a demand to better understand the (food-induced) local immune responses that lead to eosinophilic inflammation of the esophagus to enable future therapies to be more effective. Therefore, this thesis aims to investigate these local immune mechanisms that underly EoE. Furthermore, due to the need for novel (dietary) treatment protocols, we studied the potential of local esophageal food challenge to identify causative foods and make a personalized diet possible, and assessed the therapeutic potential of short-chain fatty acids on the esophageal epithelial barrier.