The current clinical guidelines as published by the American College of Gastroenterology (ACG) on the diagnosis and management of Eosinophilic Esophagitis (EoE) are summarized below:

EoE is an increasingly recognized and prevalent condition and important cause of esophageal symptoms. It is presumed to result from eosinophilic activation to dietary antigens, which is limited to the esophagus. Inflammatory strictures, secondary dysmotility and resulting dysphagia are common problems. Current management includes food exclusion diets, swallowed topical steroids and proton pump inhibitors. Strictures may require endoscopic dilatation. Relapse is common and strategies for maintaining remission are being developed.

Definition and Causes of Esophageal Eosinophilia

• Esophageal eosinophilia, the finding of eosinophils in the squamous epithelium of the esophagus, is abnormal and the underlying cause should be identified.
• EoE is clinicopathologic disorder diagnosed by clinicians taking into consideration both clinical and pathologic information without either of these parameters interpreted in isolation, and defined by the following criteria:

1. Symptoms related to esophageal dysfunction.
2. Eosinophil-predominant inflammation on esophageal biopsy; peak value of ≥15 eosinophils per high-power field (eos/hpf).
3. Mucosal eosinophilia is isolated to the esophagus and persists after a PPI trial.
4. Secondary causes of esophageal eosinophilia excluded.
5. A response to treatment (dietary elimination; topical corticosteroids) supports the diagnosis.

• Esophageal biopsies are required to diagnose EoE. 2-4 biopsies should be obtained from both the proximal and distal esophagus to maximize the likelihood of detecting esophageal eosinophilia in all patients in whom EoE is being considered.
• At the time of initial diagnosis, biopsies should be obtained from the antrum and/or duodenum to rule out other causes of esophageal eosinophilia in all children and in adults with gastric or small intestinal symptoms or endoscopic abnormalities.

Diagnostic Challenges: PPI-responsive esophageal eosinophilia and GERD

• Proton-pump inhibitor esophageal eosinophilia (PPI-REE) should be diagnosed when patients have esophageal symptoms and histologic findings of esophageal eosinophilia, but demonstrate symptomatic and histologic response to proton-pump inhibition.
• At this time, the entity is considered distinct from EoE, but not necessarily a manifestation of GERD.
• To exclude PPI-REE, patients with suspected EoE should be given a 2-month course of a PPI followed by endoscopy with biopsies.
• A clinical, endoscopic and/or histologic response to a PPI does not establish gastroesophageal reflux as the cause of esophageal eosinophilia. To determine whether reflux is contributing to esophageal eosinophilia, additional evaluation for GERD, as per standard clinical practice, is recommended. This may include ambulatory pH testing in selected cases.

Pharmacologic Treatments

• Topical steroids (i.e., fluticasone or budesonide, swallowed rather than inhaled, for an initial duration of 8 weeks) are a first-line pharmacologic therapy for treatment of EoE.
• Prednisone may be useful to treat EoE if topical steroids are not effective or in patients who require rapid improvement in symptoms. Patients without symptomatic and histologic improvement after topical steroids might benefit from a longer course of topical steroids, higher doses of topical steroids, systemic steroids, elimination diet, or esophageal dilation.
• There are few data to support the use of mast cell stabilizers or leukotriene inhibitors, and biologic therapies remain experimental at this time.

Fluticasone

• Children b 88 – 440 mcg / day in a divided dose
• Adults 880 – 1760 mcg / day in a divided dose

Budesonide

• Children 1 mg/day
• Adults 2 mg day, typically in a divided dose

Dietary Treatments

• Dietary elimination can be considered as an initial therapy in the treatment of EoE in both children and adults.
• The decision to use a specific dietary approach (elemental, empiric, or targeted elimination diet) should be tailored to individual patient needs and available resources.
• Clinical improvement and endoscopy with esophageal biopsy should be used to assess response to dietary treatment when food antigens are either being withdrawn from or reintroduced to the patient.
• Gastroenterologists should consider consultation with an allergist to identify and treat extraesophageal atopic conditions, assist with treatment of EoE, and to help guide elemental and elimination diets.

Strategies for Dietary Elimination

1. Total elimination of all food allergens with elemental or amino-acid-based formula.
2. Targeted elimination diet guided by allergy testing, typically skin prick testing or patch testing.
3. Empiric six-food elimination diet: soy, egg, milk, wheat, nuts, and seafood.

• The duration of the treatment is usually 4-8 weeks, followed by a reintroduction period once remission has been achieved. One food or food group can be introduced every 2-4-6 weeks with observation of clinical symptoms and a subsequent endoscopy if no change in symptoms occur. A food trigger is identified based on the recurrence of symptoms and esophageal eosinophilia. Because patients typically have more than one food trigger, the process is continued until all foods have been added or an acceptable diet is reached. Patients who are treated with an elemental formula undergo a substantially longer reintroduction process. Once food triggers are identified, patients are advised to eliminate these agents from their diet completely.

Endoscopic Treatment

• Esophageal dilation may be used as an effective therapy in symptomatic patients with strictures that persist in spite of medical or dietary therapy. Patients should be well informed of the risks of esophageal dilation in EoE including post-dilation chest pain (up to 75% of patients), bleeding, and esophageal perforation.

Maintenance Therapy

• While knowledge of the natural history of EoE is limited, patients should be counseled about the high likelihood of symptom recurrence after discontinuing treatment due to the chronic nature of this disease.
• The overall goal of maintenance therapy is to minimize symptoms and prevent complications of EoE, preserve quality of life, with minimal long-term adverse effects of treatments.
• Maintenance therapy with topical steroids and/or dietary restriction should be considered for all patients, but particularly in those with severe dysphagia or food impaction, high-grade esophageal stricture and rapid symptomatic/histologic relapse following initial therapy.
• The endpoints of therapy of EoE include improvements in clinical symptoms and esophageal eosinophilic inflammation. While complete resolution of symptoms and pathology is an ideal endpoint, acceptance of a range of reductions in symptoms and histology is a more realistic and practical goal in clinical practice. Symptoms are an important parameter of response in EoE, but cannot be used alone as a reliable determinant of disease activity and response to therapy, given that compensatory dietary and lifestyle factors can mask symptoms.

Diseases Associated with Esophageal Eosinophilia

1. Eosinophilic gastrointestinal diseases
2. PPI-responsive esophageal eosinophilia
3. Celiac disease
4. Crohn’s disease
5. Infection
6. Hypereosinophilic syndrome
7. Achalasia
8. Drug hypersensitivity
9. Vasculitis
10. Pemphigus
11. Connective tissue diseases
12. Graft vs. host disease
13. PPI, proton-pump inhibitor.

Proposed Classification/Grading System for the Endoscopic Assessment of Esophageal Features of EoE

Major features
Edema (decreased vascular markings, mucosal pallor)

• Grade 0: Absent. Distinct vascularity present
• Grade 1: Loss of clarity or absence of vascular markings

Fixed rings (concentric rings, corrugated esophagus, corrugated rings, ringed esophagus, trachealization)

• Grade 0: None
• Grade 1: Mild-subtle circumferential ridges
• Grade 2: Moderate-distinct rings that do not impair passage of a standard diagnostic adult endoscope (outer diameter 8 – 9.5 mm)
• Grade 3: Severe-distinct rings that do not permit passage of a diagnostic endoscope

Exudates (white spots, plaques)

• Grade 0: None
• Grade 1: Mild-lesions involving less than 10 % of the esophageal
• surface area
• Grade 2: Severe-lesions involving greater than 10 % of the esophagealsurface area

Furrows (vertical lines, longitudinal furrows)

• Grade 0: Absent
• Grade 1: Vertical lines present

Stricture

• Grade 0: Absent
• Grade 1: Present (specify estimated luminal diameter)

Minor features
Crepe paper esophagus (mucosal fragility or laceration upon passage of endoscope, not after esophageal dilation)

• Grade 0: Absent
• Grade 1: Present

Narrow-caliber esophagus (reduced luminal diameter of the majority of the tubular esophagus)

• Grade 0: Absent
• Grade 1: Present