Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?

Eosinophilic esophagitis (EoE) is an immune-mediated, chronic esophageal disease characterized by esophageal symptoms and esophageal eosinophilia. It is triggered by foods and possibly by environmental allergens. Currently, there are no FDA-approved therapies for EoE. Commonly used treatments include dietary restrictions and topical corticosteroids. Many of these therapies are suboptimal in their efficacy, have side effects, or diminish patients' quality of life. Biologic therapies for EoE have therefore been sought as an alternative. The mechanism by which food allergens trigger EoE is thought to be a T helper type 2 (Th2) reaction, resulting in secretion of the cytokines IL-4, IL-5, and IL-13. IL-5 induces eosinophil production and trafficking to the esophagus, and IL-13 induces esophageal epithelial cells to secrete eotaxin-3, which drives eosinophil chemotaxis and activation. Mepolizumab and reslizumab, two anti-IL-5 antibodies, were studied in children and adults with EoE and resulted in reduction of esophageal tissue and blood eosinophils, but no significant reduction in symptoms. QAX576, an anti-IL-13 antibody, was studied in adults with EoE and showed a decrease in the esophageal eosinophil load and a trend towards clinical improvement. Since in situ IgE production was demonstrated in the EoE esophagus, omalizumab, an anti-IgE antibody, was studied in patients with EoE and not found to be overall beneficial. Furthermore, given the increased esophageal epithelial cell TNF-α expression in EoE, infliximab, an anti-TNF-α antibody, was studied in patients with EoE, with lack of success both clinically and histologically. In summary, although none of the biologicals studied so far in EoE have been highly effective, many demonstrated some histological benefit, especially those that targeted the Th2 axis. Therefore, the future for biologicals is promising as the pathophysiology of EoE is better understood, clinical assessment tools are validated, identification of patient subsets that respond best to biologicals is made, and dosages of biologicals are optimized.

Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report of the American Academy of Allergy, Asthma, and Immunology.

Eosinophilic esophagitis (EoE) is a chronic/immune-antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Dietary elimination therapy has been shown to be an effective, drug-free prescription for the treatment of EoE. A range of different dietary elimination therapies have been used. Regardless of the elimination diet chosen, dietary therapy requires in-depth nutrition assessment and management. Elimination diets are not without risk and may impact nutritional status, eating pleasure, and overall quality of life. With adequate guidance, dietary therapy can be effective and nutritionally balanced, and the adverse impact on lifestyle can be minimized. This work group report addresses the potential challenges of implementing an elimination diet for the management of EoE and provides instructions and tools for physicians, dietitians, and other allied health professionals to help guide them in planning elimination diets for both children and adults.

The Flavonoid 7,4'-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts.

Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4'-dihydroxyflavone (7,4'-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4'-DHF compared with other compounds from G. uralensis, to compare 7,4'-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4'-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4'-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4'-DHF co-culture. 7,4'-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4'-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production. Copyright © 2017 John Wiley & Sons, Ltd.

IgE and non-IgE-mediated food allergy: treatment in 2007.

PURPOSE OF REVIEW: Our understanding of the mechanism of food allergy has substantially increased over the past decade. Food allergies can be classified into those that are IgE mediated and those that are non-IgE mediated. RECENT FINDINGS: Various advances have been made in treating IgE-mediated food allergies. A phase II clinical trial of a second anti-IgE antibody, omalizumab, was recently initiated in subjects with peanut allergy, but was stopped as a result of safety concerns after severe reactions occurred during initial oral challenges. Oral immunotherapy is showing promise in various studies on patients with IgE-mediated food allergies. Gastrointestinal food allergic disorders involving non-IgE-mediated food allergies have recently received attention, particularly eosinophilic esophagitis. Although amino acid-based formula therapy remains the most successful in controlling inflammation and symptoms in these disorders, other therapeutic options including various dietary elimination protocols and swallowed fluticasone are showing success. Anti-IL-5 therapy may prove to be a promising future therapeutic option for refractory patients. SUMMARY: Although there are no specific therapeutic recommendations for many IgE-mediated and non-IgE-mediated food allergic disorders besides allergen avoidance, various novel approaches are currently being investigated and may influence treatment approaches in the future.