Basics
Description
- Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease characterized clinically by variable symptoms of esophageal dysfunction and pathologically by localized eosinophilic inflammation.
- The diagnosis is established in symptomatic patients who have the following:
- At least 15 eosinophils/HPF isolated to the esophagus on endoscopic biopsies
- Persistent eosinophilic infiltrate in esophageal biopsies after a trial of proton pump inhibitor (PPI) therapy
Epidemiology
- Incidence rates range from 0.7 to 10 per 100,000 person-years, and prevalence from 0.2 to 43 per 100,000.
- 3:1 male-to-female ratio
- Peaks of onset in childhood and 3rd-4th decade
Pathophysiology
- The exact pathophysiology of EoE is unknown but likely involves an immune response to environmental antigens in genetically predisposed individuals.
- Environmental factors (food and possibly aeroallergens) trigger inflammatory response mediated by type 2 T-helper (Th2) cells.
- Genetic polymorphisms which predispose to EoE include eotaxin-3, thymic stromal lymphopoietin, and filaggrin.
Diagnosis
Alert
Any patient who presents with esophageal food impaction should be evaluated for EoE. More than half of patients with food impaction are ultimately diagnosed with EoE.
History
Symptoms of EoE vary with age:
- In younger children, symptoms may include feeding difficulty or refusal (median age 2 years), vomiting (median age 8 years), and abdominal pain (median age 12 years).
- Assess for:
- Failure to thrive (poor weight gain, weight loss)
- Feeding difficulties (not advancing past liquids, refusal of previously tolerated solids)
- Gastroesophageal reflux (arching, irritability/fussiness)
- Vomiting
- In adolescents and adults, symptoms include dysphagia, food impaction, refractory heartburn, epigastric abdominal pain, chest pain.
- Questions to assess dysphagia:
- Sensation of difficulty swallowing or food getting stuck?
- Is the child a slow eater? Does the child overchew or overcut food? Does the child avoid specific foods?
- Personal history of esophageal food impaction?
- EoE is often associated with atopic disease (asthma, allergic rhinitis, atopic dermatitis, food allergy). Ask about the following:
- Personal or family history of atopic disease?
- Family history of EoE, dysphagia, refractory GERD, esophageal food impactions or dilations?
- No relief of symptoms after acid-blocking medication (minimum 8 weeks)
Physical Exam
- Typically normal
- Growth failure (rare but may occur if feeding dysfunction or significantly decreased appetite)
- Signs of comorbid atopic disease: allergic shiners, wheezing, eczematous skin lesions
Diagnostic Tests & Interpretation
Lab
- Blood tests:
- No diagnostic serum markers for EoE
- Peripheral eosinophilia observed in <50% of patients
- Elevated serum IgE present in 50-60%.
- Food allergy testing
- Performed after biopsies confirm EoE
- In vitro-specific IgE testing: serum testing for food-specific IgE antibodies; no studies of predictive value, limited or no role
- Skin prick testing (SPT): assesses for IgE-mediated reactions; good specificity (>82%) for identifying EoE triggers, but poor sensitivity
- Atopy patch testing (APT): assesses for non-IgE-mediated reactions; application of fresh or rehydrated food in occlusive chambers for 48 hours on back; similar specificity as SPT but better sensitivity
- Combination of SPT and APT identified causative food antigens in 70% of patients at one center. More studies, especially prospective randomized controlled studies, are needed.
- Aeroallergen testing
- SPT may identify aeroallergen triggers of EoE and inform timing of follow-up endoscopies relative to pollen seasons.
Imaging
- Upper GI series fluoroscopy
- Provides complementary information to an upper endoscopy
- Evaluates esophageal anatomy for strictures, hiatal hernia, Schatzki ring (lower esophageal ring), and achalasia
- Is not sufficient to make a diagnosis of EoE
- Use upper GI series to evaluate worsening dysphagia for development of stricture that may require dilation.
Diagnostic Procedures/Other
- Esophagogastroduodenoscopy (EGD)
- Required for diagnosis of EoE
- Used to evaluate appearance of esophagus and obtain biopsies for pathology
- As some forms of EoE are responsive to high doses of PPI, the diagnostic endoscopy is usually performed after an 8-week trial of a twice daily PPI.
- 4-6 esophageal biopsies are obtained by cold forceps. The distal and proximal esophagus should be sampled separately. A pathologist experienced with the diagnosis of EoE should examine the biopsies for the presence of ≥15 eosinophils/HPF. Corroborating features include surface layering of eosinophils, eosinophilic microabscesses, extracellular eosinophilic granules, basal zone hyperplasia, dilated intercellular spaces, and lamina propria fibrosis.
- Gastric and duodenal biopsies should also be obtained to rule out other causes of esophageal eosinophilia. In EoE, there is no associated gastric or duodenal eosinophilic infiltrate.
- pH/impedance probe
- Use in diagnosis and management of EoE is unclear.
- Some patients clearly suffer from both pathologic reflux and EoE. pH/impedance monitoring may clarify who should be treated with PPI.
- Endoscopic ultrasound
- Findings include thickened mucosal and muscular layer.
Differential Diagnosis
- GERD
- Crohn disease
- Eosinophilic gastroenteritis
- Parasitic infection
- Connective tissue disease
- Drug allergy
- Hypereosinophilic syndrome
- Autoimmune enteropathy
- Candida esophagitis
- Viral esophagitis (HSV, CMV)
- Achalasia
- Peptic stricture
Treatment
Medication
- Proton pump inhibitors (PPIs)
- Part of the diagnostic criteria for EoE is that the esophageal eosinophilia persists after treatment with high-dose PPI (e.g., omeprazole, pantoprazole, esomeprazole, lansoprazole, dexlansoprazole, or rabeprazole). If the eosinophilia persists after an 8-week course of PPI, then the diagnosis of EoE is applied.
- Useful as adjunctive therapy to treat associated reflux symptoms
- Insufficient to treat EoE
- Non-systematic corticosteroids
- Description
- Swallowed topical steroids (fluticasone propionate and budesonide) are an alternative to dietary therapy.
- Discontinuation is associated with recurrence of disease. They are safe for short-term administration.
- Local fungal infections are known complications.
- Data on long-term safety are lacking.
- Fluticasone propionate
- Use metered-dose inhaler.
- Dose is sprayed into mouth and swallowed.
- Initial doses:
- Adults: 440-880 mcg twice daily
- Children: 88-440 mcg 2-4 times daily
- Avoid eating or drinking for 30 minutes after each dose.
- Budesonide (viscous suspension)
- Liquid budesonide inhaled solution ampules are mixed with sucralose/maltodextrin (e.g., Splenda, 5 packets per ampule) or other sweetener to form thick slurry that coats the esophagus when ingested (see Liacouras CA, Furuta GT, Hirano I, et al, 2011 in "Additional Reading").
- Initial doses:
- Adults: 2 mg daily
- Children (<10 years): 1 mg daily
- Avoid eating or drinking for a minimum of 30 minutes after dose.
- Bedtime dosing is optimal.
- Systemic corticosteroids
- Are effective but should only be used in cases of severe dysphagia and weight loss affecting growth
- Long-term use should be avoided.
- Prednisone or methylprednisolone: 1-2 mg/kg/24 h (max 60 mg daily)
Dietary Therapy
- Elemental diet
- Use amino acid-based formula for 100% of caloric requirements.
- Highest efficacy for clearing eosinophilic inflammation
- Reintroduction of foods into diet should be stepwise and guided by allergist.
- Six food elimination diet (SFED)
- Avoid most common food allergens: (1) milk, (2) soy, (3) wheat, (4) egg, (5) peanuts and tree nuts, (6) fish and shellfish.
- Efficacy not as high as with elemental diet but comparable to topical swallowed steroids
- Targeted elimination diet
- Use results from multimodal allergy testing to guide food eliminations from diet.
- Efficacy comparable to SFED
When reintroducing foods into the diet following one of the above dietary therapies, caution should be taken to do so stepwise with reevaluation of esophageal biopsies after each food reintroduction to determine the actual dietary trigger that should continue to be avoided.
Ongoing Care
Complications
- Failure to thrive
- Esophageal strictures
- Small-caliber esophagus
- Esophageal perforation
- Esophageal fungal or viral superinfection
Endoscopic Therapy
- Dilation of esophageal strictures
- Useful in alleviating dysphagia
- Does not address underlying problem
- A trial of medical or dietary therapy is advisable prior to dilation unless a high-grade stricture is present.
- Complications include chest pain (5%) and esophageal rupture (<1-5%).
- Removal of esophageal food impaction
- Should be performed within 24 hours of food impaction to decrease risk of esophageal rupture
Additional Reading
- Greenhawt M, Aceves SS, Spergel JM, et al. The management of eosinophilic esophagitis. J Allergy Clin Immunol Pract. 2013;1(4):332-340. [View Abstract]
- Kagalwalla AF, Shah A, Li BU, et al. Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr. 2011;53(2):145-149. [View Abstract]
- Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3-20. [View Abstract]
- Soon IS, Butzner JD, Kaplan GG, et al. Incidence and prevalence of eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr. 2013;57(1):72-80. [View Abstract]
- Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr. 2009;48(1):30-36. [View Abstract]
Codes
ICD09
- 530.13 Eosinophilic esophagitis
ICD10
- K20.0 Eosinophilic esophagitis
SNOMED
- 235599003 eosinophilic esophagitis (disorder)
FAQ
- Q: What are the goals of EoE treatment?
- A: There is no agreed upon definition of EoE remission. Treatment goals include symptom reduction, decrease in esophageal eosinophilia to <15 eosinophils/HPF, and improvement in histologic and visual endoscopic changes. However, several studies show discordance between symptoms and histologic findings.
- Q: Do patients who have symptom response but persistent esophageal eosinophilia require further treatment?
- A: There is insufficient natural history data to answer this question. The concern is that untreated esophageal eosinophilia may progress to dysphagia, strictures, and esophageal fibrosis, but predictors of this progression are not well-defined.
- Q: Why might the SFED and targeted elimination diet have similar efficacy?
- A: The targeted elimination diet is guided by allergy testing (SPT and APT) results, but data on their diagnostic use are poorly reproducible. For certain foods (milk, wheat), they have poor reliability. Also, the APT process is not standardized and interpretation may be subjective and variable. More prospective controlled trials are needed to evaluate the diagnostic use of these tests.
- Q: What is the best 1st-line therapy for EoE?
- A: The approach to each patient is individualized, as there is no agreement on the single best 1st-line therapy for EoE. Younger children may be more amenable to dietary restrictions. Children with failure to thrive benefit from elemental formula either as monotherapy, or as a nutritional supplement in conjunction with either an elimination diet or topical corticosteroids. Dietary compliance in teenagers makes topical corticosteroids a popular option.