Title: Elucidating Mechanisms of Allergic Inflammation in Eosinophilic Esophagitis
Abstract: To study the potential role of IgE in eosinophilic esophagitis (EoE) using anti-IgE (Omalizumab) therapy. We recruited 17 pediatric and adult subjects (ages between 12-75) with EoE (who failed diet or steroid therapy) to receive omalizumab for 3 months. Improvement was measured both histologically (reduction of esophagus eosinophil count to <5 eosinophils per high-power-field at study completion) and clinically (resolution of vomiting, heartburn, dysphagia, nausea, and abdominal pain). Four subjects showed 50% improvement in self-reported symptom survey results, one with partial histologic improvement and three with complete histological remission. One subject had complete histological and clinical improvement. Another five participants had resolution of their most severe symptom, but did not demonstrate histological remission. Clinical and histological response to omalizumab did not correlate with the level of serum IgE and blood or tissue eosinophil counts. Esophageal mast cell numbers per high power field showed a significantly decrease (p = 0.0016) after omalizumab therapy independent of clinical or histological improvement. Assessment of response to therapy in rare disorders such as EoE is complex, requiring careful defining of meaningful clinical endpoints. Favorable clinical response to omalizumab in a subset of patients with EoE suggests a pivotal role of IgE, but also indicates non-IgE mediated pathways playing role in others. Decrease in esophagus tissue mast cells, however, suggests these cells may not be critical in the pathophysiology of EoE, but perhaps play an important role in the mechanism of action of omalizumab.