A 28-year-old man presents to the emergency department with acute dysphagia and retrosternal discomfort after eating a meat sandwich. Endoscopy reveals the appearance marked **A** in the diagram — concentric fixed rings with linear furrows and white exudates on the esophageal mucosa. Biopsies from both proximal and distal esophagus show ≥15 eosinophils per high-power field. The patient reports a 2-year history of progressive solid-food dysphagia with adaptive eating behaviors (slow chewing, avoiding bread and meat). He has a past medical history of asthma and allergic rhinitis. Which of the following best describes the PRIMARY PATHOGENIC MECHANISM underlying the endoscopic findings marked **A**?

Explanation

## Why "TH2-mediated immune response to food and aeroallergens with IL-5 and IL-13-driven eosinophilic infiltration and epithelial barrier dysfunction" is right Eosinophilic esophagitis (EoE) is fundamentally a chronic, immune/antigen-mediated disease driven by a TH2-skewed inflammatory response in genetically predisposed individuals. The concentric rings, linear furrows, and white exudates marked **A** are the direct endoscopic manifestations of dense eosinophilic infiltration (>15 eosinophils per high-power field). IL-5 mediates eosinophil recruitment and survival, while IL-13 causes epithelial barrier dysfunction and induces eotaxin-3, perpetuating the inflammatory cascade. The patient's atopic background (asthma, allergic rhinitis) and progressive dysphagia with food avoidance are classic presentations. This TH2-mediated pathogenesis is the defining feature of EoE and distinguishes it from other esophageal conditions (Sleisenger & Fordtran 11e Ch 45; AGA Clinical Practice Update 2020). ## Why each distractor is wrong - **Acid-induced mucosal injury with secondary eosinophilic recruitment**: This describes reflux esophagitis (structure **B**), which presents with confluent erosions and is driven by gastric acid, not immune-mediated TH2 inflammation. GERD may coexist with EoE but is not the primary mechanism of EoE. - **Candidal colonization triggering a Th1-mediated response with neutrophil predominance**: This describes candidal esophagitis (structure **C**), which occurs in immunocompromised patients and presents with discrete white plaques on erythematous mucosa. EoE is not infectious and is characterized by eosinophils, not neutrophils. - **Achalasia-related stasis leading to bacterial overgrowth and mechanical obstruction**: This describes achalasia (structure **D**), a primary motility disorder with a dilated esophagus and "bird beak" LES appearance. Achalasia is not immune-mediated and does not produce the characteristic rings and furrows of EoE. **High-Yield:** EoE = TH2-mediated (IL-5, IL-13) eosinophilic inflammation in atopic individuals; rings + furrows + white exudates on endoscopy; ≥15 eos/HPF on biopsy from 2 levels = diagnostic. [cite: Sleisenger & Fordtran 11e Ch 45; AGA Clinical Practice Update on EoE Gastroenterology 2020]