Guideline sources The following summarized guidelines for the evaluation and management of eosinophilic esophagitis (EoE) are prepared by our editorial team based on guidelines from the British Society of Gastroenterology (BSG/BSPGHAN 2022), the American Gastroenterological Association (AGA 2022; 2020), the European Society of Gastrointestinal Endoscopy (ESGE 2021), the European Society of Eosinophilic Oesophagitis (EUREOS/EAACI/UEG/ESPGHAN 2017), the European Academy of Allergy and Clinical Immunology (EAACI 2014), the American Society for Gastrointestinal Endoscopy (ASGE 2014), and the American College of Gastroenterology (ACG 2013). 1 2 3 4 5 6 7 8 9 9 9 9 10 Definition EoE is chronic, immune/antigen-mediated esophageal disease characterized by eosinophilic infiltration of the esophageal epithelium. 9 Epidemiology In patients with EoE, environmental exposures to food antigens and aeroallergens lead to recruitment of eosinophils to the esophagus. Genetic pleomorphisms (encoding thymic stromal https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 1/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway lymphopoietin, eotaxin-3, and calpain-14 genes) are associated with an increased risk. 9 Pathophysiology The incidence of EoE is estimated at 0.35-12.8 cases per 100,000 person-years, while its prevalence is estimated at 7.3-90.7 persons per 100,000 population. 10 Disease course Eosinophil-mediated inflammation and fibrosis lead to esophageal dysmotility and formation of esophageal strictures that causes clinical manifestations of dysphagia, and food impaction. 9 Prognosis and risk of recurrence In some patients, symptomatic remission occurs spontaneously or following esophageal dilation, without the need for further dietary modification or medical therapy; however, in most patients, the symptoms recur after discontinuation of treatment. 9 Guidelines 1. Screening and diagnosis Clinical presentation: As per BSG 2022 guidelines, recognize that eoE is characterized by symptoms of dysphagia and/or food impaction in adult patients with esophageal histology showing a peak eosinophil count of 15 eosinophils/hpf, or 15 eosinophils/0.3 mm or > 60 eosinophils/mm in the absence of other causes of esophageal eosinophilia A eoE responding clinically and histologically to a PPI is the same disease as EoE not responding to a PPI B eoE and GERD are not mutually exclusive and can coexist in the same patient A eoE is increasing in prevalence in both adults and children A eoE is more common in males than females and in people of white ethnic origin compared with other ethnic groups B having an affected first-degree relative increases the risk of EoE B the incidence rises during adolescence and peaks in early adulthood A there is seasonal variation in the symptoms of EoE in many patients, which seems to be associated with higher pollen counts B food bolus obstruction and dysphagia are strongly associated with a diagnosis of EoE in adult patients B eosinophilic oesophagitis is the most common cause of spontaneous perforation of the esophagus and this can occur at any age. A As per UEG 2017 guidelines, recognize that: eoE is a chronic, local immune-mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation; do not interpret clinical manifestations or pathologic data in isolation https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 2/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway solid food dysphagia, food impaction, and non-swallowing associated chest pain are the most commonly reported symptoms in adult patients with EoE A untreated EoE is usually associated with persistent symptoms and inflammation, leading to esophageal remodeling resulting in stricture formation and functional abnormalities B eoE significantly impacts the health-related quality of life impairing the social and psychological functioning B there is no evidence that EoE is a premalignant condition B eoE appears to have no causal or temporal relationship with hypereosinophilic syndromes, IBD, esophageal atresia, and connective tissue disorders B eoE is a distinct form of food allergy and IgE-mediated food allergies are common in patients with EoE A rhinitis, asthma, and eczema are significantly more common in patients with EoE compared to the general population, however, insufficient evidence to support that atopy predisposes to EoE B eoE and GERD are different entities and may coexist, either unrelated or interacting bidirectionally. B Diagnostic criteria: As per UEG 2017 guidelines, set a 15 eosinophils/hpf (standard size of ~ 0.3 mm ) in esophageal mucosa, taken as the peak concentration in the specimens examined, as the threshold for eosinophil density for the diagnosis of EoE. B Show 3 more As per ACG 2013 guidelines, diagnose esophageal eosinophilia in patients in whom eosinophils are identified in the squamous epithelium of the esophagus, and assess for an underlying cause. A Show 2 more Differential diagnosis: As per UEG 2017 guidelines, exclude other systemic and local causes of esophageal eosinophilia. As per ACG 2013 guidelines, diagnose PPI-responsive esophageal eosinophilia when patients have esophageal symptoms and histologic findings of esophageal eosinophilia, but demonstrate symptomatic and histologic response to proton-pump inhibition. B 2. Diagnostic investigations Allergy tests: As per BSG 2022 guidelines, do not obtain allergy testing to foods (such as skin prick test, specific IgE, or patch testing) for choosing the type of dietary restriction therapy for EoE. D As per UEG 2017 guidelines, insufficient evidence to recommend obtaining allergy tests to identify food triggers of EoE. I As per EAACI 2014 guidelines, insufficient evidence to recommend obtaining serum food allergen-specific IgE or a skin prick test to generate a successful elimination diet. I https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 3/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway Esophageal physiologic testing: consider obtaining esophageal physiological testing in patients with EoE with ongoing dysphagia, despite histological remission and the absence of fibrostenotic disease at endoscopy. B 3. Diagnostic procedures Esophageal biopsy: As per BSG 2022 guidelines, perform esophageal biopsies in all adult patients undergoing endoscopy in the presence of endoscopic signs associated with EoE, or symptoms of dysphagia or food bolus obstruction, with a normal-looking esophagus. A Show 9 more As per ESGE 2021 guidelines, take at least 6 biopsies, 2-4 biopsies from the distal esophagus and 2-4 biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities in patients with suspected EoE. Place distal and proximal biopsies in separate containers. B Show 2 more As per UEG 2017 guidelines: Take at least 6 biopsies from different locations, focusing on areas with endoscopic mucosal abnormalities. B Do not rely on endoscopic findings only to establish a diagnosis of EoE. D As per EAACI 2014 guidelines, perform upper endoscopy with 2-4 biopsies from both the proximal and distal esophagus for the diagnosis of EoE. Perform biopsy after double-dose PPI therapy of at least 6 weeks to rule out esophageal eosinophilia caused by GERD and to exclude PPI-responsive esophageal eosinophilia. B As per ACG 2013 guidelines, obtain esophageal biopsies to diagnose EoE; 2-4 biopsies should be obtained from both the proximal and distal esophagus to maximize the likelihood of detecting esophageal eosinophilia. B 4. Medical management General principles: As per BSG 2022 guidelines, attempt early diagnosis and treatment of EoE effectively to prevent long-term complications of fibrosis and strictures requiring subsequent endoscopic intervention. B As per UEG 2017 guidelines, decide on the choice of initial therapy (PPIs, diet, or topical corticosteroids) individually discussed with the patient and might be potentially interchangeable over time. B Swallowed corticosteroids: As per BSG 2022 guidelines: Administer topical corticosteroids to induce clinical and histological remission A and to reduce the development of strictures in patients with EoE. B https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 4/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway Recognize that systemic side effects of topical corticosteroids have not been documented during the long-term treatment of patients with eosinophilic oesophagitis. A As per AGA 2020 guidelines: Administer topical corticosteroids in patients with EoE. B Consider topical rather than oral corticosteroids in patients with EoE. C As per UEG 2017 guidelines, administer topical corticosteroids for induction of histological remission in patients with EoE. A As per ACG 2013 guidelines: Administer topical corticosteroids (fluticasone or budesonide, swallowed rather than inhaled) for an initial duration of 8 weeks as first-line pharmacotherapy in patients with EoE. A Consider offering a longer course or a higher dose of topical corticosteroids in patients without symptomatic and histologic improvement after an initial course of topical corticosteroids. C Systemic corticosteroids: As per BSG 2022 guidelines, do not use systemic corticosteroids in patients with EoE. D As per UEG 2017 guidelines, do not use systemic cortiocosteroids in patients with EoE. D As per ACG 2013 guidelines: Consider initiating prednisone for the treatment of EoE if topical corticosteroids are not effective or in patients requiring rapid improvement in symptoms. C Consider initiating systemic corticosteroids in patients without symptomatic and histologic improvement after an initial course of topical corticosteroids. C Proton pump inhibitors: As per BSG 2022 guidelines: Initiate PPI therapy to induce clinical and histological remission in patients with eosinophilic oesophagitis. B Continue PPIs BID for at least 8-12 weeks before assessment of histological response. B Consider switching to alternative treatments, such as diet or topical corticosteroids, if PPI therapy causes unwanted side effects (diarrhea, gastrointestinal infections, or magnesium deficiency). B As per AGA 2020 guidelines, consider PPIs in patients with symptomatic EoE. C As per UEG 2017 guidelines, initiate PPI therapy to induce clinical and histological remission in patients with EoE. B Anti-immunoglobulin E therapy: do not offer anti-IgE therapy for the treatment of patients with EoE. D Other pharmacologic therapies: As per BSG 2022 guidelines: Do not use sodium cromoglycate, montelukast, and anti-histamines for the treatment of EoE, but consider offering for concomitant atopic disease. D Do not use immunomodulators (such as azathioprine and 6-mercaptopurine) and monoclonal antibody therapies (such as anti-TNF and anti-integrin therapies) in patients https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 5/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway with EoE. D As per AGA 2020 guidelines, consider the following treatment options in patients with EoE only in the context of a clinical trial: anti-IL-5 therapy anti-IL-13 therapy anti-interleukin-4 receptor-alpha therapy anti-TNF therapy immunomodulators montelukast cromolyn sodium. C As per ACG 2013 guidelines, insufficient evidence to support the use of mast cell stabilizers or leukotriene inhibitors, and biological therapies in patients with EoE. I Management of anxiety/depression: offer effective therapy to alleviate anxiety and depression in patients with EoE as it affects patients due to persistent symptoms and social restrictions. B Maintenance therapy (indications): aim maintenance therapy at minimizing symptoms and preventing complications of EoE, while preserving quality of life and minimizing long-term adverse effects of treatments. B Maintenance therapy, corticosteroids: As per BSPGHAN/BSG 2022 guidelines, offer maintenance therapy with topical corticosteroids to reduce the risk of recurrent food bolus obstruction. B As per BSPGHAN/BSG 2022 guidelines, initiate maintenance treatment following clinical review as clinical and histological relapse is high after withdrawal of topical corticosteroid treatment. B As per EUREOS/EAACI/ESPGHAN/UEG 2017 guidelines, offer long-term topical corticosteroids for maintaining remission in corticosteroid-responsive patients. B As per ACG 2013 guidelines, consider offering maintenance therapy with topical corticosteroids and/or dietary restriction in all patients, particularly in patients with severe dysphagia or food impaction, high-grade esophageal stricture, and rapid symptomatic/histologic relapse following initial therapy. C Maintenance therapy, proton pump inhibitors: As per AGA 2022 guidelines, avoid offering a trial of deprescribing PPI therapy in patients with EoE. D As per BSPGHAN/BSG 2022 guidelines, continue PPIs to maintain remission in patients achieved histological response. B As per EUREOS/EAACI/ESPGHAN/UEG 2017 guidelines, offer long-term PPI therapy for maintaining remission in PPI-responsive patients. B 5. Nonpharmacologic interventions Dietary modifications: https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 6/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway As per BSG 2022 guidelines, offer elimination diets to achieve clinical and histological remission in adult patients with EoE. B Show 5 more As per AGA 2020 guidelines, consider advising the following dietary interventions in patients with EoE: elemental diet C empirical six-food elimination diet C allergy testing-based elimination diet. C As per UEG 2017 guidelines, consider offering an elemental diet only after the failure of proper medical treatment and/or elimination diet. C As per ACG 2013 guidelines: Advise dietary elimination as initial therapy in the treatment of eosinophilic eosinophilia in both pediatric and adult patients with EoE. B Consider offering an elimination diet in patients without symptomatic and histologic improvement after an initial course of topical corticosteroids. C 6. Therapeutic procedures Esophageal dilation: As per BSG 2022 guidelines, perform endoscopic dilatation to improve symptoms in patients with fibrostenotic disease due to eosinophilic oesophagitis. B Show 2 more As per AGA 2020 guidelines, consider performing endoscopic dilation in adult patients with dysphagia from a stricture associated with EoE. C As per UEG 2017 guidelines, consider performing endoscopic dilation in patients with dysphagia/food impaction unresponsive to anti-inflammatory treatment. B As per ASGE 2014 guidelines, reserve esophageal dilation for adult patients with a dominant esophageal stricture or ring and if remaining symptomatic despite medical therapy. B As per ACG 2013 guidelines, consider performing esophageal dilation, approached conservatively, as an effective therapy in symptomatic patients with strictures that persist in spite of medical or dietary therapy. C 7. Specific circumstances Pediatric patients, diagnosis: As per BSPGHAN/BSG 2022 guidelines, recognize that symptoms of EoE in pediatric patients may be nonspecific and vary with the age of the patient. B Show 2 more As per EUREOS/EAACI/ESPGHAN/UEG 2017 guidelines: Recognize that the most common symptoms in younger pediatric and infant patients with EoE are reflux-like symptoms, vomiting, abdominal pain, food refusal, and failure to thrive. A https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 7/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway Recognize that solid food dysphagia, food impaction, and non-swallowing associated chest pain are the most commonly reported symptoms in older pediatric patients with EoE. A Pediatric patients (management): Offer elimination diets to achieve clinical and histological remission in pediatric patients with EoE. B Consider ensuring a formal transition of care from pediatric to adult services to improve symptom control, concordance with therapy, and reduce emergency presentations in EoE. C Patients with esophageal perforation: Obtain contrast-enhanced CT to assess the degree of extravasation in patients with EoE perforation. B Offer conservative management with multidisciplinary input from gastroenterology, surgery, and radiology specialists in patients with EoE perforation if there is limited extravasation. B Patients with Candida infection: administer topical antifungals while continuing topical corticosteroids in patients with Candida infection secondary to topical corticosteroid treatment. B 8. Patient education General counseling: counsel patients about the chronic nature of the disease and the high likelihood of symptom recurrence after discontinuation of treatment. B 9. Follow-up and surveillance Indications for referral: As per BSG 2022 guidelines, manage patients with EoE refractory to treatment and/or with significant concomitant atopic disease jointly by a gastroenterologist and specialist allergist to optimize treatment. B As per EAACI 2014 guidelines, refer patients with EoE to an allergist/immunologist for diagnostic evaluation. B As per ACG 2013 guidelines, consider consultation with an allergist to identify and treat extraesophageal atopic conditions, assist with treatment of EoE, and help guide elemental and elimination diets. C Assessment of treatment response: As per BSG 2022 guidelines, perform endoscopy with biopsy while on treatment (dietary or pharmacological treatment) to assess response to treatment as symptoms may not always correlate with histological activity. B Show 2 more As per UEG 2017 guidelines, assess the efficacy of any therapy by a follow-up endoscopy after a 6- to 12-week initial course. B Perform a follow-up histological examination to monitor the disease because symptoms do not correlate accurately with histologic disease activity. B https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 8/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway As per ACG 2013 guidelines, aim treatment at complete resolution of symptoms and pathology in patients with EoE, acknowledging that a range of reductions in symptoms and histology is a more realistic and practical goal in clinical practice. B Clinical findings Symptoms Past medical history Abdominal pain Allergic reactions Chest discomfort Allergic rhinitis Chest pain Asthma Dysphagia Atopic dermatitis Food impaction Atopy Food regurgitation Ehlers-danlos syndrome Heartburn GERD Loss of appetite Loeys-dietz syndrome Nausea Marfan syndrome Vomiting Hematological findings Weight loss blood eosinophils Anthropomorphic exam Malnutrition Histological findings Tissue eosinophilia References 1. Anjan Dhar, Hasan N Haboubi, Stephen E Attwood et al. British Society of Gastroenterology BSG and British Society of Paediatric Gastroenterology, Hepatology and Nutrition BSPGHAN joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut. 2022 May 23;gutjnl-2022 327326. Open 2. Ikuo Hirano, Edmond S Chan, Matthew A Rank et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Ann Allergy Asthma Immunol. 2020 May;124 5 416 423. Open 3. Roos E Pouw, Maximilien Barret, Katharina Biermann et al. Endoscopic tissue sampling Part 1 Upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy ESGE Guideline. Endoscopy. 2021 Nov;53 11 1174 1188. Open 4. Lucendo AJ, Molina-Infante J, Arias et al. Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults. United European Gastroenterol J. 2017 Apr;5 3 335 358. Open 5. 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. Open https://web.pathway.md/diseases/rec3GVLRFQcwb3MLy 9/10 6/29/23, 4:18 AM Eosinophilic esophagitis Pathway 6. Muraro A, Werfel T, Hoffmann-Sommergruber K et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014 Aug;69 8 1008 25. Open 7. Pasha SF, Acosta RD, Chandrasekhara V et al. The role of endoscopy in the evaluation and management of dysphagia. Gastrointest Endosc. 2014 Feb;79 2 191 201. Open 8. Laura E Targownik, Deborah A Fisher, Sameer D Saini. AGA Clinical Practice Update on De- Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022 Feb 16;S0016 5085 21 04083 X. Open 9. Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015 Oct 22;373 17 1640 8. Open 10. Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018 Jan;154 2 319 332.e3. Open 11. Jean-Marc Dumonceau, Pierre H Deprez, Christian Jenssen et al. Indications, results, and clinical impact of endoscopic ultrasound EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy ESGE Clinical Guideline Updated January 2017. 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