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Updates: Revised diagnostic criteria for eosinophilic esophagitis

Revised criteria for eosinophilic esophagitis (EoE) no longer require a two-month trial of a proton pump inhibitor with persistence of esophageal eosinophilia on mucosal biopsy to establish the diagnosis of EoE in patients with symptoms of esophageal dysfunction in whom other causes of symptoms have been excluded.

The 2018 Appraisal of Guidelines for Research and Evaluation (AGREE) conference has published new consensus criteria for the diagnosis of eosinophilic esophagitis [5]. The diagnosis of eosinophilic esophagitis requires symptoms of esophageal dysfunction, at least 15 eosinophils per high-power field on esophageal biopsy, and exclusion of other causes that may be responsible for or contributing to symptoms and esophageal eosinophilia. In contrast to prior guidelines, persistence of mucosal eosinophilia in the esophagus after two months of treatment with a proton pump inhibitor (PPI) is no longer a diagnostic criterion for eosinophilic esophagitis. The rationale for exclusion of a PPI trial is that patients with eosinophilic esophagitis who are PPI-responsive do not appear to be clinically distinct from patients who are not PPI-responsive, and their management should not differ. 

The diagnosis of eosinophilic esophagitis requires all of the following:

● Symptoms related to esophageal dysfunction

● Eosinophil-predominant inflammation on esophageal biopsy, characteristically consisting of a peak value of ≥15 eosinophils per high power field (or 60 eosinophils per mm3)

● Exclusion of other causes that may be responsible for or contributing to symptoms and esophageal eosinophilia

The International Gastrointestinal Eosinophil Researchers (TIGERS) Summary of 2011 eosinophilic esophagitis updated consensus recommendations
Below is a summary version of the 2011 consensus recommendations for eosinophilic esophagitis (EoE) diagnosis and treatment.[1] Since 2007, the number of EoE publications doubled, providing new disease insight. A panel of 33 physicians with expertise in pediatric and adult allergy/immunology, gastroenterology and pathology conducted a systematic review of the EoE literature (since September 2006) using electronic databases. Based on the literature review and expertise of the panel, a summary of the recommendations is provided here.
Conceptual definition - To refine perceptions and hypotheses for future EoE studies, the following conceptual definition was developed: "Eosinophilic esophagitis represents a chronic, immune/antigen mediated, esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation."
Diagnostic guidelines - Taking into account increasing clinical experiences and research, the following guidelines were proposed: "Eosinophilic esophagitis is a clinico-pathological disease. Clinically, EoE is characterized by symptoms related to esophageal dysfunction. Pathologically, one or more biopsies must show eosinophil predominant inflammation.* With few exceptions, 15 eosinophils/hpf (peak value) is considered a minimum threshold for a diagnosis of EoE. The disease is isolated to the esophagus and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor (PPI)-responsive esophageal eosinophilia. (Table A). The disease should remit with treatments of dietary exclusion and/or topical corticosteroids. EoE should be diagnosed by clinicians taking into consideration all clinical and pathologic information; neither of these parameters should be interpreted in isolation.
Summary statements
History and physical - History should focus on difficulties with eating and swallowing (Table B) and a thorough physical examination should focus on growth and nutrition parameters and to assess potential other causes of esophagitis (Table A).
Endoscopy - Endoscopy with esophageal biopsy is considered the only reliable EoE diagnostic. Two to four biopsies each from the proximal and distal esophagus should be obtained. Gastric and duodenal biopsies should be examined to exclude other potential causes of eosinophil associated gastrointestinal disease (Table A). Endoscopic features can suggest but cannot diagnose EoE.
Radiography - An upper gastrointestinal series is useful to characterize anatomic abnormalities that may escape endoscopic detection such as proximal strictures and long segment narrowing.
Histopathology - See Diagnostic guidelines and Table C.
Allergic evaluation - An evaluation by an allergist or immunologist is recommended to document aeroallergen sensitization and seasonal variability as it may pertain to EoE and to control concurrent atopic diseases. Serum IgE and/or skin prick testing for immediate type hypersensitivity reactions to foods are warranted to help identify food allergic disease in patients with EoE. Medically supervised food reintroduction may be necessary for patients with previous allergic reactions to a food or IgE-mediated sensitivity documented by IgE testing. Skin prick tests, serum IgE tests, and food patch tests may be used to help identify foods that are associated with EoE, but are not sufficient to make the diagnosis of food allergy driven EoE. Foods that trigger EoE can only be identified by documenting disease remission and recrudescence after specific food elimination and addition.
Genetics - EoE runs in families and although specific genes that pre-dispose to EoE susceptibility have been identified (thymic stromal lymphopoietin [TSLP], eotaxin-3), they are not yet ready for usage in clinical settings.
Treatments - (Table D).
Dietary therapy - Amino acid based formulas and dietary elimination are effective therapies for children with EoE and their use in adults requires further study. Patient's lifestyle, adherence to therapy and family resources should be considered when instituting these treatments. Consultation with a registered dietitian is strongly encouraged. EoE foods triggers may need to be restricted indefinitely.
Steroids - Topical corticosteroids are effective therapy for EoE in children and adults. Systemic corticosteroids may be used for emergent situations (severe dysphagia, hospitalization, weight loss) but caution is warranted for chronic management of EoE.
Other treatments - Cromolyn sodium, leukotriene receptor antagonists, and immunosuppressives (azathioprine or 6-mercaptopurine) are not recommended treatments for EoE. Biologic agents require further clinical studies and are currently not recommended for routine use.
Dilation - Esophageal dilation can provide relief of dysphagia in selected EoE patients. If high-grade esophageal stenosis is not present, a trial of medical or dietary therapy prior to esophageal dilation is reasonable.
Table A.[1] Conditions associated with esophageal eosinophilia
Gastroesophageal reflux disease (GERD)
Eosinophilic esophagitis (EoE)
Eosinophilic gastrointestinal diseases (EGIDs)
Celiac disease
Crohn's disease
Hypereosinophilic syndrome (HES)
Drug hypersensitivity
Pemphigoid vegetans
Connective tissue disease
Graft versus host disease
Table B.[1] Symptoms related to EoE
Dysphagia and feeding dysfunction
Coping mechanisms - Avoiding highly textured foods such as meats and bulky foods such as bagels, cutting food in small pieces, lubricating foods before eating with liquids or butter, extensive chewing of foods, washing food down with liquids, prolongation of mealtimes
Food impaction
Coping mechanisms - Drinking liquid to wash food down, raising hands above head, jumping up and down, waiting for food to dissolve or to pass
Chest pain
Coping mechanisms - Avoiding foods or liquids that exacerbate pain such as highly textured or bulky foods, alcohol or acidic drinks
GERD like symptoms recalcitrant to medical and surgical GERD management
Abdominal pain
Anorexia and early satiety
Table C.[1] Histological characteristics of EoE
Mucosal eosinophilia
Eosinophil microabscesses
Superficial layering of eosinophils
Extracellular eosinophil granules
Surface epithelial desquamation
Basal zone hyperplasia
Rete peg elongation
Dilated intercellular spaces
Subepithelial fibrosis/sclerosis/lamina propria fibrosis
Table D.[1] Recommended initial treatments for EoE
Topical swallowed corticosteroids (initial doses)[2-4]
Fluticasone (spray metered dose inhaler directly in mouth then swallow)
Adults: 440 to 880 mcg twice daily
Children: 88 to 440 mcg twice to four times daily (maximum 1760 mcg per day)
Budesonide (as a compounded viscous suspensionΔ)
Children (<10 years): 1 mg daily
Older children and adults: 2 mg daily
Following administration, patients should not rinse the mouth or eat or drink for 30 minutes
Systemic corticosteroids (severe disease)
Prednisone: 1 to 2 mg/kg per day by mouth in one or two divided doses (maximum 60 mg per day), taper after week 4[4]
Education, advocacy, and/or research support resources:
American Academy of Allergy, Asthma, and Immunology:
American Partnership for Eosinophilic Disorders:
Campaign Urging Research for Eosinophilic Disorders:
Children's Digestive Health and Nutrition Foundation:
Food Allergy & Anaphylaxis Network:
North American Society of Pediatric Gastroenterology and Nutrition:
Registry for Eosinophilic Gastrointestinal Disorders:
TIGERS is grateful to the American Partnership for Eosinophilic Disorders for providing financial support of this summary document. APFED ( is a 501(c)3 non-profit dedicated to education, advocacy, support and advancing research to improve the lives of those with eosinophil associated diseases. Content summarized by TIGERS.
EoE: eosinophilic esophagitis.
* For optimal pathological evaluation, multiple biopsies from the proximal and distal esophagus should be obtained and evaluated for a variety of pathological features. Pathologists should report all abnormalities associated with EoE such as the peak eosinophil count (obtained from the area with the highest density of eosinophils), eosinophilic microabscesses, surface layering of eosinophils, extracellular eosinophil granules, basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. In a few circumstances, patients may have strong clinical evidence for EoE and have less than 15 eosinophils/hpf with other histological features indicative of eosinophilic inflammation.
¶ An emerging body of literature and clinical experience describes a subset of patients whose symptoms and histopathologic findings are responsive to PPI treatment and who may, or may not, have well documented gastroesophageal reflux disease (GERD). Until more is known, these patients should be diagnosed as "PPI-responsive esophageal eosinophilia."
Δ Viscous budesonide can be compounded by mixing two 0.5 mg/2 mL budesonide inhalation (Pulmicort Respule) ampules for nebulization with sucralose (Splenda), ten 1-gram packets per 1 mg of budesonide, creating a volume of approximately 8 mL[3].
  1. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011; 128:3.
  2. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology 2006; 131:1381.
  3. Dohil R, Newbury R, Fox L, Bastian J, Aceves SS. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology 2010; 139:418.
  4. Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol 2008; 6:165.
  5.  Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference. Gastroenterology. 2018; Dellon - Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: