EoE ToT Module 4 References-O'Shea et al Gastroenterology 2018 Pathophysiology of Eosinophilic Esophagitis

O'Shea et al Gastroenterology 2018 Pathophysiology of Eosinophilic Esophagitis

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Eosinophilic Esophagitis (EoE) is a chronic allergic inflammatory disease characterized by elevated eosinophil counts in the esophagus. Its pathogenesis involves T helper type 2 (Th2) cytokines and the interplay between genetic susceptibility and environmental factors, particularly allergens. EoE is distinguished from GERD (gastroesophageal reflux disease) by distinct genetic markers and is closely associated with allergic conditions such as asthma and atopic dermatitis.<br /><br />Prominent genetic contributions include susceptibility loci like TSLP (5q22) and CAPN14 (2p23), both pivotal in allergic responses and epithelial barrier integrity. Genetic studies and rare syndromes have pointed to the importance of barrier function disruption, with proteins like desmoglein 1 playing a central role.<br /><br />Pathophysiologically, EoE is driven by allergic sensitization to food and environmental allergens, with the cytokines IL-5 and IL-13 being crucial. These cytokines mediate eosinophilic infiltration, tissue remodeling, and barrier dysfunction. Th2 cytokines are produced by various cells, including pathogenic effector Th2 cells (peTH2), group 2 innate lymphoid cells, and invariant natural killer T cells, which are abundant in EoE patients.<br /><br />Therapeutically, EoE is managed using corticosteroids and dietary elimination. Emerging treatments target specific cytokines (e.g., anti-IL-13 antibodies, CRTH2 inhibitors) and aim to modulate the allergic inflammatory response. Epigenetic and microbial factors are also implicated, highlighting the complex interactions between host genetics, environmental exposures, and microbial populations.<br /><br />EoE can lead to esophageal remodeling, fibrosis, and strictures, complicating the disease management, especially in long-term untreated patients. Understanding the molecular and genetic underpinnings is crucial for developing targeted therapies and improving patient outcomes.<br /><br />Research supported by organizations like the NIH, and initiatives such as the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), are advancing the understanding and treatment options for EoE, providing insights into allergy-mediated tissue inflammation and paving the way for improved clinical practices.

Keywords

Eosinophilic Esophagitis

Th2 cytokines

genetic susceptibility

environmental allergens

TSLP

CAPN14

IL-5

IL-13

corticosteroids

dietary elimination