BASICS
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated, inflammatory esophageal disease characterized clinically in adults by dysphagia, food impaction, and heartburn and in children with nonspecific abdominal complaints, abdominal pain, and failure to thrive. Histologically, EoE is characterized by eosinophilic predominate inflammation (1)[A].
EPIDEMIOLOGY
All ages, most common in 20s to 30s; male > female, 3:1
Incidence
Incidence in general population is approximately 1 case in 10,000 persons per year (2)[A].
Prevalence
Gradually increasing, perhaps due to better case finding, understanding of EoE in multiple clinical guises; 45 to 55/100,000
- Increased prevalence in those with celiac disease.
ETIOLOGY AND PATHOPHYSIOLOGY
- Believed to be an atopic inflammatory disease, whose pathogenesis is an aberrant immune response to antigenic stimulation
- Like eczema and asthma, T-helper 2 (TH2) lymphoctyes play a role, as do mixed IgE and non-IgE-mediated allergic responses to food and environmental allergens.
- Although not well-understood, the pathophysiology of EoE is postulated to be due to increased recruitment and activation of eosinophils in the esophagus. Eosinophil chemoattractants include eotaxin-3, IL-5, and IL-13.
Genetics
- EoE susceptibility may be caused by polymorphisms in thymic stromal lymphopoietin protein (TSLP) (3)[A].
- Potential new subphenotype of EoE (may also overlap with GERD): proton pump inhibitor (PPI)-responsive esophageal eosinophilia, where PPIs may act to decrease the inflammatory response in EoE (3)[A]
RISK FACTORS
- EoE is commonly associated with atopy/allergic disorders, such as asthma, hay fever, or eczema (1,4)[A].
- High rate of associated food antigen allergies/anaphylaxis
DIAGNOSIS
There are no pathognomonic findings for EoE. A definitive diagnosis is made by esophageal endoscopy and biopsy.
HISTORY
- Solid food dysphagia and food impaction are the most common symptoms and are usually present for 3 to 4 years prior to the diagnosis.
- Patients may also have reflux symptoms. Often, the diagnosis is entertained after patients fail a trial of antireflux medications. Other common complaints include nausea or vomiting, regurgitation, chest pain, upper abdominal pain, or decreased appetite.
- Patients may also have a history of food or environmental allergies, as well as asthma or atopic conditions (e.g., dermatitis).
PHYSICAL EXAM
No specific physical exam findings are associated with the diagnosis. However, signs and symptoms of allergies or asthma with symptoms of ongoing dysphagia or GERD-like symptoms should raise suspicion; some patients will have signs indicating weight loss or malnutrition.
DIFFERENTIAL DIAGNOSIS
- GERD
- Associated with EoE; diseases may coexist in individual patients.
- PPI-responsive esophageal eosinophilia (PPI-REE)
- Characteristics of PPI-REE
- Shows classic EoE symptoms
- Diagnosis of GERD has been excluded.
- Responds to PPIs clinically and histologically
- Secondary causes of esophageal eosinophilia including celiac disease, Crohn esophagitis, infection, vasculitis, PPIs, achalasia, connective tissue disease, eosinophilic gastrointestinal diseases
- Functional dyspepsia
- Congenital rings
- Esophageal carcinoma
- Esophageal motility disorders
DIAGNOSTIC TESTS & INTERPRETATION
- To exclude PPI-REE, patients with suspected EoE should be given a 2-month course of PPI followed by endoscopy with biopsies.
- Solid food dysphagia is an indication for esophagogastroduodenoscopy (EGD), as are other concerning or "red-flag" symptoms, many of which occur in patients with EoE; they include the following:
- Odynophagia
- Weight loss
- Early satiety or vomiting
- Aspiration/wheezing or cough
- GI bleeding
- Unexplained iron deficiency anemia
- Male >45 years with long-standing symptoms
- GERD patients who show no symptomatic improvement after 8 to 12 weeks of a PPI should also be considered for EGD and biopsy.
- Serum IgE levels are elevated in 70% of patients.
- Peripheral eosinophilia occurs in 10-50% of patients.
Follow-Up Tests & Special Considerations
Testing for asthma and IgE-mediated food/inhalant allergies, if clinically relevant, can help manage coexisting atopic conditions:
- Serum IgE, skin prick test, or atopy patch test
Diagnostic Procedures/Other
EGD: 17% of biopsy-proven cases of EoE had an endoscopically normal exam (5)[A].
- Endoscopic findings: esophageal rings (trachealization), strictures, white plaques or exudates, linear furrows, narrow-caliber esophagus, and pallor or decreased vasculature
- Esophageal biopsies are required for diagnosis; two to four biopsies from both proximal and distal esophagus. At initial diagnosis, biopsies should be obtained from antrum and/or duodenum to rule out other causes of esophageal eosinophilia in all children and adults with gastric or small intestinal symptoms or endoscopic abnormalities (1)[A].
- Biopsy specimen: Pathologic findings may include surface layering of eosinophils, eosinophilic microabscesses, subepithelial lamina propria fibrosis, or basal cell hyperplasia.
- Barium contrast radiography
- Can help to identify anatomic abnormalities in EoE but has a low sensitivity for diagnosis
- May be an alternative to repeated endoscopies in previously treated patients who have changing symptoms
- pH monitoring: may be helpful in differentiating EoE from GERD
- Consensus American Gastroenterologic Association guidelines for diagnosis of EoE (1)[A]
- Clinical symptoms of esophageal dysfunction
- ≥15 eosinophils in 1 high-power field on biopsy
- Mucosal eosinophilia is isolated to esophagus and persists after PPI use.
- Secondary causes of esophageal eosinophilia are excluded.
TREATMENT
Endpoints of therapy of EoE include improvements in clinical symptoms and reducing esophageal eosinophilic inflammation. Defining evidence-based endpoints in EoE is still an area of active research (1)[A].
MEDICATION
First Line
- Corticosteroids
- Topical steroids (swallowed, not inhaled) are first-line pharmacologic treatment.
- Initial dosing for treatment of EoE: Swallowed fluticasone dose in adults is 880 to 1,760 Ī¼g/day in a divided dose and in children is determined based on age or weight. Swallowed budesonide dose in adults is 2 mg/day, typically in divided doses; in children determined based on age or weight. Initial duration of treatment is 8 weeks. Medication should be discontinued if patient develops side effects or other intolerances. Patients have relapsed after withdrawal of the medication. Inhaled topical steroid trials are ongoing.
- Systemic steroids: Prednisone can be helpful if topical steroids are not effective or for patients who require a more rapid improvement to symptoms, such as those with refractory dysphagia and in patients who are hospitalized. Long-term toxicity limits use (1)[A].
- Diet
- Dietary elimination is considered initial therapy in both children and adults.
- Three dietary regimens have been shown to be effective in treatment of EoE: (i) elemental amino acid-based diet; (ii) elimination diet based on various food allergy tests; and (iii) six-food elimination diet of the most common food groups known to trigger EoE: wheat, soy, cow's milk, eggs, nuts, and seafood. All three methods have been shown to be effective in children for both clinical and histologic improvement, with the elemental diet being most effective:
- In children, success rates of 77-98% have been reported for clinical and histologic remission using an elemental amino acid formula. A retrospective chart review comparing the three diets showed that the elemental diet was superior, with 96% remission (6)[B]. Yet, this treatment has not gained popularity because of its high cost, impaired quality of life, and overall practicality.
- In adults, food allergy plays an important role in EoE, and six-food elimination diet (SFED) is an effective therapy (7)[B]:
- Gonsalves et al. evaluated SFED in adult patients with EoE and demonstrated clinical, endoscopic, and histologic improvement. Symptoms improved in 94% of patients. Reintroduction of eliminated food caused reactivation of EoE with wheat (60%) and cow's milk (50%) as the leading causative agents. Skin-prick allergy testing was only 13% predictive in identifying food triggers.
Second Line
- Endoscopic esophageal dilation
- May be used effectively in symptomatic patients with strictures that are resistant to medical or dietary treatments and initially in patients with severe and symptomatic esophageal stenosis (1)[A]
- A systematic review showed that 92% of patients treated with dilation had improvement in dysphagia symptoms for up to 1 to 2 years.
- Patients should be informed of the risks of esophageal dilation. The most common risk being postprocedure chest pain, which occurs in 75% of patients. The perforation rate for dilation is 0.3%, contrary to early reports which showed higher rates of perforation. Bleeding requiring endoscopic intervention or blood products is very rare, with only one occurence reported to date (1,4)[A].
ISSUES FOR REFERRAL
Refer to an allergist and/or nutritionist to help identify/manage allergic disorders and diet regimens.
ADDITIONAL THERAPIES
Other pharmacologic therapies
- Montelukast, mepolizumab (IL-5 monoclonal antibody), acid suppression therapy, purine analogues, anti-TNF therapy. Biologic agents have been well-tolerated with low adverse effects (AEs); yet, no studies have shown prolonged symptomatic relief (1)[A].
- Antihistamines: Case studies showed no benefit.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- EoE is a chronic disease with symptom recurrence after discontinuing treatment the rule rather than the exception. Prevention of progression of esophageal dysfunction is primary. Maintenance therapy with swallowed topical corticosteroid therapy, and/or dietary restriction should be considered in all patients after clinicopathologic remission indefinitely or PRN (1)[A]. This is not yet standardized; only one RCT maintenance study has been done using low-dose budesonide (0.25 mg BID) versus placebo after remission for 50 weeks. Those maintained on budesonide had modest reduction in eosinophilia and fewer symptom recurrences, but there was still significant recurrence (8)[A]. As such, ongoing therapy needs to be tailored to individual patient cases.
- Patient should be counseled on the high likelihood of symptom recurrence after discontinuing treatment.
Patient Monitoring
- No guidelines yet established. It is reasonable to order periodic endoscopy based on symptoms or after completing a recent therapeutic regimen.
- There is no evidence to date of esophageal malignancy or hypereosinophilic syndromes associated with EoE.
- Esophageal candidiasis is a common side effect of chronic corticosteroid therapy.
PROGNOSIS
EoE does not seem to affect life expectancy. Quality of life is affected to some extent due to the chronic nature of the disease, difficulty in adhering to a restrictive diet, and so forth. Nutritional status can be maintained with appropriate care and diligence.
COMPLICATIONS
- Food impaction
- Esophageal stricture/ring/narrowing
- Nutritional deficiencies
- Subglottic stenosis or laryngeal edema is very rare.
REFERENCES
11 Dellon ES, Gonsalves N, Hirano I, et al. ACG clinical guidelines: evidenced based approach to diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108(5):679-692.22 Dellon ES. Epidemiology of eosinophilic esophagitis. Gastroenterol Clin North Am. 2014;43(2):201-218.33 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.e6-20.e6.44 Bohm ME, Richter JE. Review article: oesophageal dilation in adults with eosinophilic oesophagitis. Aliment Pharmacol Ther. 2011;33(7):748-757.55 Kim HP, Vance RB, Shaheen NJ, et al. The prevalence and diagnostic utility of endoscopic features of eosinophilic esophagitis: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10(9):988.e5-996.e5.66 Henderson CJ, Abonia JP, King EC, et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129(6):1570-1578.77 Gonsalves N, Yang GY, Doerfler B, et al. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012;142(7):1451.e1-1459.e1.88 Straumann A, Conus S, Degen L, et al. Long-term budesonide maintenance treatment is partially effective for patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2011;9(5):400.e1-409.e1.
ADDITIONAL READING
- Dellon ES, Jensen ET, Martin CF, et al. Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol. 2014;12(4):589.e1-596.e1.
- Stewart MJ, Shaffer E, Urbanski SJ, et al. The association between celiac disease and eosinophilic esophagitis in children and adults. BMC Gastroenterol. 2013;13:96.
CODES
ICD10
K20.0 Eosinophilic esophagitis
ICD9
530.13 Eosinophilic esophagitis
SNOMED
235599003 eosinophilic esophagitis (disorder)
CLINICAL PEARLS
- Food impaction or recurrent solid food dysphagia in a young, adult male: Think EoE.
- EoE commonly mimics disorders like GERD and PPI-REE.
- A PPI trial is now required prior to the diagnosis of EoE.
- Remember "red flags" in patients with GERD: dysphagia, odynophagia, weight loss, early satiety or vomiting, aspiration/wheezing/cough, GI bleeding, unexplained iron deficiency anemia, age >50 years. Each "red flag" justifies EGD.