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eosinophilic esophagitis

Etiology: - associated with atopy [4] a) asthma, dermatitis, food allergies, allergic rhinitis b) other allergies - food allergy [6] - dairy (44%), eggs (44%), wheat (22%) - shellfish, legumes, nuts Epidemiology: - male predominance - most common in 3rd decade of life - prevalence in adults ranges from a) 4 in 1000 in Scandinavia, to b) 1 in 70,000 in Australia Pathology: - exposure to food antigens - antigen-driven eosinophil accumulation in the esophagus - esophageal biopsy with microscopy: >= 15 eosinophils/HPF - adaptive T-cell immunity that involves IL-5 & IL-13- induced esophageal epithelial cell responses - chronic esophatitis - esophageal stricture - esophageal smooth-muscle dysfunction - eosinophilic degranulation can increase smooth-muscle reactivity by disruption of vagal muscarinic receptors - release of fibroblast growth factor & stimulation of epithelial proliferation - symptoms & pathology are largely reversible [3] Genetics: - polymorphism in eosinophil chemoattractant eotaxin-3 associated with 14% of cases [3] History: - history of allergy Clinical manifestations: - food impaction. odynophagia & dysphagia in adults - classic presentation is a young man with dysphagia for solid foods requiring endoscopy for removal [4] - feeding intolerance & GERD symptoms in children - poor response to medical (trial of proton pump inhibitor) &/or surgical GERD management [4] Special laboratory: - upper GI endoscopy with biopsy, microscopy: >= 15 eosinophils/HPF - all adults with dysphagia or food bolus obstruction [12] - food impactation may require removal during endoscopy [4] - esophageal stricture may require esophageal dilation [4] (see Complications) - endoscopic findings may include: - mucosal furrowing, stacked or fixed esophageal rings or "trachealization" of the esophagus [8], white specks, mucosal friability - ambulatory pH monitoring to exclude GERD [4] - food allergy testing not helpful [4] - ref [6] less confident food allergy testing not helpful * images [8] * withdrawal of proton pump inhibitor >= 3 weeks prior to endoscopy [12] Differential diagnosis: - difficult to distinguish from GERD [4] - seems that an esophageal biopsy distinguishes Complications: - esophageal stricture [4] - patients with eosinophilic esophagitis are prone to mucosal tears with esophageal dilation [4] Management: - proton-pump inhibitors are generally recommended, even if pathologic reflux is not evident - high-dose proton-pump inhibitor is 1st line treatment [4] - BID treatment for >= 8-12 weeks [12] - dietary approaches based upon eliminating exposure to food allergens [6] - 71% response rate [6] - food elimination diet: - 69% with only 1 food trigger (milk or wheat most common, followed by soy & egg) [13] - 6-food elimination diet no better than avoiding milk - topical glucocorticoids (swallowed inhaled glucocorticoids) - viscous budesonide or swallowed fluticasone provided by pulmonary inhalers - budesonide may be preferred due to inadvertent inhalation of excess fluticasone dose despite careful patient education [9] - budesonide oral suspension (Eohilia) FDA-approved Feb 2024 - systemic glucocorticoids may be needed [4]; not supported [10] - chronic treatment is necessary to prevent relapse [3,4] - long-term maintenance therapy in asymptomatic patients not supported [10] - dupilumab (Dupixent) FDA-approved for adults &children >= 12 years, 40 Kg (88 lbs) [11] - weekly dupilumab improves histologic outcomes & alleviates symptoms in adults & adolescents [14]

General

esophagitis

References

  1. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME; First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007 Oct;133(4):1342-63. Epub 2007 Aug 8. Review. PMID: 17919504
  2. Prasad GA et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol 2009 Oct; 7:1055. PMID: 19577011
  3. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gastroenterology 2009 Oct; 137:1238. PMID: 19596009
  4. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Prasad GA, Talley NJ. Eosinophilic esophagitis in adults. Gastroenterol Clin North Am. 2008 Jun;37(2):349-68, PMID: 18499024
  6. Sampson HA et al. Food allergy: A practice parameter update - 2014. J Allergy Clin Immunol 2014 Nov; 134:1016. PMID: 25174862 http://www.jacionline.org/article/S0091-6749%2814%2900672-1/abstract - Wolf WA et al. Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2014 Aug; 12:1272 PMID: 24440337
  7. Dellon ES, Gonsalves N, Hirano I et al ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013 May;108(5):679-92 PMID: 23567357
  8. Nandy N, Rustagi T. "Trachealization" of the Esophagus. N Engl J Med 2019; 380:177. Jan 10. PMID: 30625054 https://www.nejm.org/doi/full/10.1056/NEJMicm1807124
  9. Dellon ES, Woosley JT, Arrington A et al. Efficacy of budesonide vs fluticasone for initial treatment of eosinophilic esophagitis in a randomized controlled trial. Gastroenterology 2019 Mar 11; PMID: 30872104 https://www.gastrojournal.org/article/S0016-5085(19)33555-3/pdf - Lucendo AJ, Miehlke S, Schlag C et al. Efficacy of budesonide orodispersible tablets as induction therapy for eosinophilic esophagitis in a randomized placebo-controlled trial. Gastroenterology 2019 Mar 25; PMID: 30922997 Free Article https://www.gastrojournal.org/article/S0016-5085(19)33580-2/pdf
  10. Hirano I et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters clinical guidelines for the management of eosinophilic esophagitis. Gastroenterology 2020 May; 158:1776. PMID: 32359562 https://www.gastrojournal.org/article/S0016-5085(20)30265-1/pdf
  11. George J First Treatment Approved for Eosinophilic Esophagitis. FDA expands dupilumab's label to treat inflammatory condition. MedPage Today May 20, 2022 https://www.medpagetoday.com/gastroenterology/generalgastroenterology/98858 - FDA News Release. May 20, 2022 FDA Approves First Treatment for Eosinophilic Esophagitis, a Chronic Immune Disorder. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-eosinophilic-esophagitis-chronic-immune-disorder
  12. British Society of Gastroenterology, British Society of Paediatric Gastroenterology, Hepatology and Nutrition Eosinophilic Esophagitis Clinical Practice Guidelines (BSG/BSPGHAN, 2022) Medscape. September 29, 2022 https://reference.medscape.com/viewarticle/981522
  13. Zalewski A et al. Long-term outcomes of the six-food elimination diet and food reintroduction in a large cohort of adults with eosinophilic esophagitis. Am J Gastroenterol 2022 Dec; 117:1963. PMID: 35971213 https://journals.lww.com/ajg/Abstract/2022/12000/Long_Term_Outcomes_of_the_Six_Food_Elimination.19.aspx
  14. Dellon ES et al. Dupilumab in adults and adolescents with eosinophilic esophagitis. N Engl J Med 2022 Dec 22; 387:2317. PMID: 36546624 https://www.nejm.org/doi/10.1056/NEJMoa2205982
  15. Kliewer KL et al. One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: A multicentre, randomised, open-label trial. Lancet Gastroenterol Hepatol 2023 May; 8:408. PMID: 36863390 PMCID: PMC10102869 (available on 2024-05-01) https://www.thelancet.com/journals/langas/article/PIIS2468-1253(23)00012-2/fulltext - Attwood SE. Bringing dietary therapy for eosinophilic oesophagitis under scientific scrutiny. Lancet Gastroenterol Hepatol 2023 May; 8:392. PMID: 36863389 https://www.thelancet.com/journals/langas/article/PIIS2468-1253(23)00041-9/fulltext
  16. Brooks M FDA OKs First Oral Agent for Eosinophilic Esophagitis. Medscape. Feb 12, 2024 https://www.medscape.com/viewarticle/fda-oks-first-oral-agent-eosinophilic-esophagitis-2024a100031d