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Eosinophilic esophagitis

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Last updated: 29th Nov 2021
Published:29th Nov 2021

What is eosinophilic esophagitis?

Eosinophilic esophagitis (EoE) is a chronic, antigen-driven disease caused by a T helper type 2 (Th2) inflammatory response to food allergens or aeroallergens in contact with the esophagus1. It is characterised clinically by esophageal dysfunction and histologically by eosinophilic infiltration in the esophagus2. EoE was recognised as a distinct disease entity in the early 1990s and is increasing in incidence and prevalence worldwide3. EoE affects people of all ethnicities and age groups but is more prevalent in males than females3. EoE can cause irreversible damage to the esophagus if left untreated or if diagnosis is delayed4.

Unmet needs of eosinophilic esophagitis

Early diagnosis and treatment of EoE are essential for preventing the development of chronic inflammation, which can lead to irreversible structural damage to the esophagus. However, diagnosis of EoE can often be missed or delayed for several years as young children usually present with non-specific symptoms, while older children and adults develop coping mechanisms that mask EoE symptoms2,5. At present, EoE diagnosis relies on upper endoscopy and biopsy6; minimally invasive, office-based tests are in development but have not as yet been adequately validated1,7. There is no cure for EoE and patients with EoE require lifelong dietary and pharmacological intervention to manage symptoms and prevent EoE disease progression. Patients with severe esophageal narrowing may require invasive endoscopic dilation to relieve EoE symptoms. Pharmacological treatment options for EoE are limited and most are only available off-label. Further, currently available EoE treatment options are non-specific anti-inflammatory steroids or, in some cases, proton pump inhibitors (PPIs).

New developments for treatment of eosinophilic esophagitis

A better understanding of the pathophysiology of EoE has led to identification of several potential treatment targets for EoE, including interleukin (IL)-4, IL-5 and IL-13. These agents have a key role in type 2 inflammation and subsequent development of EoE8. Biologic agents that inhibit specific cytokines in the inflammatory pathway are currently in development and are being evaluated in phase 2 or 3 clinical trials for EoE9. These investigational drugs include the monoclonal antibodies mepolizumab and benralizumab, which block IL-5 and the IL-5Rα receptor, respectively, and dupilumab, which blocks IL-4Rα, the receptor for IL-4 and IL-13. Lirentelimab, a monoclonal antibody that prevents activation of mast cells and eosinophils by blocking the receptor Siglec-8, is also an investigational drug in development for treatment of EoE. A new orodispersible tablet formulation of the corticosteroid budesonide, approved recently for the treatment of EoE, provides more localised delivery to the esophagus10,11.

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References

  1. Straumann A, Katzka DA. Diagnosis and Treatment of Eosinophilic Esophagitis. Gastroenterology. 2018;154(2):346–359.
  2. Reed CC, Dellon ES. Eosinophilic Esophagitis. Med Clin North Am. 2019;103(1):29–42.
  3. Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. doi:10.1053/j.gastro.2017.06.067.
  4. Biedermann L, Straumann A, Greuter T, Schreiner P. Eosinophilic esophagitis—established facts and new horizons. Semin Immunopathol. 2021;43(3):319–335.
  5. Pokrzywinski RM, Harding G, Brooks A, Goodwin B, Williams J. Documenting the Journey of Patients with Eosinophilic Esophagitis and the Impact of the Disease on Patients and their Caregivers: A Cross-sectional, Qualitative Research Study. Adv Ther. 2020;37(10):4458–4478.
  6. Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018;155(4):1022-1033.e10.
  7. Kumar S, Choi SS, Gupta SK. Eosinophilic esophagitis: current status and future directions. Pediatr Res. 2020;88(3):345–347.
  8. Davis BP, Rothenberg ME. Mechanisms of Disease of Eosinophilic Esophagitis. Annu Rev Pathol Mech Dis. 2016;11:365–393.
  9. Beveridge C, Falk GW. Novel Therapeutic Approaches to Eosinophilic Esophagitis. Gastroenterol Hepatol. 2020;16(6):294–301.
  10. Miehlke S, Lucendo AJ, Straumann A, Jan Bredenoord A, Attwood S. Orodispersible budesonide tablets for the treatment of eosinophilic esophagitis: a review of the latest evidence. Therap Adv Gastroenterol. 2020;13. doi:10.1177/1756284820927282.
  11. Straumann A, Lucendo AJ, Miehlke S, Vieth M, Schlag C, Biedermann L, et al. Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis. Gastroenterology. 2020;159(5):1672-1685.e5.