1. Eosinophilic Esophagitis
Nisha Patel, MD
Eugene Vortia, MD
Jonathan Moses, MD
Cleveland Clinic
Reviewed by Sandeep Gupta, MD of the Professional Education Committee

2. Definition
Chronic immune and antigen mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation*
* J Allergy Clin Immunol 2011;128:3–20

3. Epidemiology Male to Female ratio - 3:1
Familial clustering - 3% have an affected parent or sibling
Overall prevalence 1:2000
Incidence - ~ 1: 10,000 per year*
Among patients undergoing upper endoscopy for any indication, prevalence is ~ 7%
* N Engl J Med 2004; 351: , Gastroenterology 2008;134:

4. Causes of Esophageal Eosinophilia
Caustic injury
Chronic (non-eosinophilic) esophagitis
Churg-Strauss Syndrome
Drugs (anti-convulsants, immunosuppressants)
EoE
Gastro-esophageal reflux disease
Hypereosinophilic syndrome
Inflammatory bowel disease
Lymphoma
Parasitic and fungal infections
Scleroderma

5. Diagnostic Criteria* Clinical symptoms of esophageal dysfunction
> 15 eosinophils per high-power field (eos/HPF) in biopsy specimens
Exclusion of GERD by a normal pH probe study or lack of response to high-dose proton pump inhibitors
Exclusion of other disorders associated with similar clinical, histological, or endoscopic features
* NASPGHAN / AGA Consensus Recommendations- Gastroenterology 2007;133:

6. Role of Food and Aeroallergens
50% have history of atopy *
2 out of 3 have food or aeroallergen sensitivity **
Milk, egg, soy, wheat, seafood and peanuts most frequently implicated foods
** JPGN 48:30– 36, 2009,
* Curr Opin Allergy Clin Immunol 2007;7:264–268

7. Clinical Symptoms Symptoms vary according to age:
Feeding dysfunction (median age 2 years)
Vomiting (median age 8 years)
Abdominal pain (median age 12 years)
Dysphagia (median age 13 years)
Food impaction (median age 17 years)
Many patients develop strictures over several years
N Engl J Med. 2004;351(9):940

8. Natural History
Liacouras et al. JPGN 48:30– 36, 2009

9. Dysphagia and Food Impaction
Dysphagia is the most frequent symptom in older children
Other complications include
Esophageal food impaction
esophageal stricture formation
Presence of food impaction among adults with EoE ranges from 30%–55%
Gastrointest Endosc 2006;64:313–319
Clin Gastroenterol Hepatol 2008;6:598–600

10. Upper Endoscopy Findings
Normal in 20%*
Abnormal findings (80%)
Linear furrowing (vertical lines)
White exudates, white specks, nodules
Circular rings (felinization, trachealization)
Linear shearing, crepe-paper mucosa
Stricture (in proximal, mid or distal esophagus)
*Eur J Gastroenterol Hepatol Feb; 18(2):211-7

11. Diagnosis
Endoscopic pictures showing rings (trachealization), white exudates, linear furrowing
Arch Pathol Lab Med. 2010;134:815–825

12. Biopsy Procurement
EoE is a patchy disease and sensitivity of diagnosis varies based on number of biopsies
Recommendation is to obtain 2-4 biopsies each from both mid and distal esophagus*
Using 15 eos/hpf as the threshold, the sensitivity of 2, 3 and 6 biopsies was found to be 84%, 97% and 100%, respectively**
*J Allergy Clin Immunol 2011;128:3-20
**Am J Gastroenterol 2009; 104:716–721

13. Histopathology Consensus criteria Other criteria
Peak eos count of >15 per 40x eos/HPF
Other criteria
Eosinophilic micro-abscesses - cluster of > 4 eos
Superficial layering - preferential distribution of eos in the upper ½ to ⅓ of epithelium
Basal zone hyperplasia - > 20% of epithelium
Papillary elongation
Lack of correlation between symptoms and histologic findings

14. Histopathology Esophageal Eosinophilia
Arch Pathol Lab Med. 2010;134:815–825

15. Schematic representation of the characteristic histology of EoE*
Histopathology
Schematic representation of the characteristic histology of EoE*
*Arch Pathol Lab Med. 2010;134:815–825

16. Treatment Acid suppression Dietary elimination Elemental diet
Allergy evaluation
Topical steroids
Leukotriene inhibitors
Systemic steroids and Biologics
Esophageal dilatation

17. Acid Suppression Useful part of diagnostic evaluation
GERD can coexist with EoE
May help with symptoms
Some patients have PPI-responsive esophageal eosinophilia and so EoE can be excluded in these patients*
*J Allergy Clin Immunol 2011;128:3-20

18. Food Elimination Empiric 6 food elimination diet
Based on milk, soy, eggs, wheat, peanuts/tree nuts, and seafood (6 most common foods)
Foods are reintroduced with monitoring of symptoms and endoscopy/hisstopathology
Skin prick and atopy patch-directed elimination
Culprit foods identified and then eliminated
6-food elimination diet or targeted elimination leads to complete histologic remission in 50% of patients *
A food was considered to cause EoE if its elimination led to resolution of esophageal eosinophilia or reintroduction led to reoccurrence of EoE.
*J Allergy Clin Immunol 2012 Aug; 130 (2): 461 – 467. e500 18

19. Elemental diet Elemental amino acid-based diet
Superior at inducing histologic remission compared with 6-food elimination and skin test–directed diets.
Remission occurred in 96%, 81%, and 65% of patients on elemental, 6-food elimination, and directed diets.
J Allergy Clin Immunol 2012;129:1570-8

20. Allergy evaluation and avoidance
Evaluation by an allergist and/or immunologist recommended for all patients
Skin prick testing (SPT) and atopy patch testing (APT) useful in effective avoidance/elimination strategies
Evidence does not currently support serum specific IgE-based food allergen testing
J Allergy Clin Immunol 2012 Aug; 130 (2): 461 – 467. e5 20

21. Topical Steroids
Provide short term resolution of clinical and pathologic features
Small risk of systemic side effects (1% absorbed)
Esophageal candidiasis occurs in 15-20% after 3 months of therapy
Fluticasone (MDI) and Budesonide (viscous) are most commonly used

22. Fluticasone Propionate
Shown to be safe and effective in Pediatric randomized controlled trials ±*
Dose: μg MDI swallowed daily without the use of a spacer
No rinsing, eating or drinking for 30 minutes afterward, and then drink small amount of liquid
*Gastroenterology 2006;131:1381–1391
± Clinical Gastroenterology and Hepatology 2008;6: 165–73

23. Oral viscous Budesonide
Good option in younger children (<4 yrs)
Dosing: 1 mg - 2 mg of 0.5 mg/2ml Budesonide nebulizer suspension mixed with 10 gm of sucralose (Splenda® – 1 gm/packet) orally at bedtime
Dosed according to height <5ft (1mg) or >5ft (2mg)
No eating, drinking or rinsing mouth for 30 minutes, and then drink small amount of liquid
* Gastroenterology 2010;139:

24. Leukotriene Inhibitors
May help symptoms in some patients
Studies show no impact on esophageal eosinophilia
Symptoms usually recur on discontinuation
* Gut 2003 Feb; 52(2): 181-5

25. Oral Steroids and Biologics
Systemic corticosteroids may be used for emergent situations (severe dysphagia, hospitalization, weight loss)*
Chronic use of steroids in management of EoE results in systemic side effects, sometimes severe
Mepolizumab and Reslizumab (anti-IL5) are biologics studied in trials for treatment of EoE
Safety and sustained efficacy of biologics not fully established
J Allergy Clin Immunol 2011;128:3-20

26. Esophageal Dilatation
Used in symptomatic patients who have strictures with critical esophageal narrowing
Increased risk of mucosal tearing and rarely, perforation during procedure
After dilation, strictures with dysphagia recurs in half of the patients after 2 years*
* Gastroenterology 2003;125:

27. Summary
EoE is an increasingly recognized esophageal disorder characterized dysphagia and in severe cases food impaction; characteristic endoscopic findings; and intraepithelial eosinophilia not responsive to PPI therapy
Exact pathogenesis remains under investigation, but food allergens, aeroallergens, genetics and acid exposure have been implicated
Accepted treatments include allergy testing/dietary changes, topical steroids, dilation, and PPI.
Complications include esophageal strictures
Based on current evidence, there does not appear to be malignant potential