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Journal of the American Academy of Physician Assistants:
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Eosinophilic esophagitis: A practical primer for an atypical disease

Shakouri, Alireza A. MD; Ortiz, Gabriel MPAS, PA‐C; Casillas, Adrian M. MD

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Author Information

Alireza Shakouri is a fellow‐in‐training in the Section of Allergy Immunology, Louisiana State University Health‐Shreveport. Gabriel Ortiz practices at Pediatric Pulmonary Services, El Paso, Texas, and is the AAPA liaison to the American Academy of Allergy, Asthma and Immunology. Adrian Casillas is an associate professor of pediatrics at Louisiana State University Health‐Shreveport.

No relationships to disclose.

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Abstract

LEARNING OBJECTIVES:

* Apply current consensus recommendations related to the diagnosis of EoE

* Identify confounding factors that complicate diagnosis and differences among clinical features at various developmental stages

* Discuss management approaches for patients with EoE

Experience with eosinophilic esophagitis is limited, and it remains an incompletely understood disease with confounding factors that can puzzle clinicians.

Eosinophilic esophagitis (EoE) is a relatively new disorder that is being increasingly diagnosed. It is characterized by eosinophilic inflammation of the esophagus leading to clinical esophageal dysfunction.1

EoE is a clinicopathologic disease.1 Symptoms range widely from vague chest pain, heartburn, and dysphagia to acute food impaction. The hallmark of EoE is marked tissue eosinophilia of the esophagus on biopsies obtained via endoscopy. Esophageal eosinophilia is not specific to EoE, however, and other GI diseases need to be considered1 (Table 1). Chief among these disorders is gastroesophageal reflux disease (GERD), the symptoms of which can mimic those of EoE, with similar histology characterized by eosinophilia on esophageal biopsy.

Table 1
Table 1
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EPIDEMIOLOGY

The prevalence of eosinophilic esophagitis is unknown, but the incidence has been increasing.2,3 One report that showed an annual incidence of one case of EoE per 10,000 children in 2000 finished the year 2003 with a prevalence of 4.296 cases per 10,000 children.2 A study that examined the incidence of EoE over 3 decades found that the incidence had increased from 0.35 per 100,000 person‐years (1991‐1995) to 9.45 per 100,000 person‐years (2001‐2005).4 In 2006, the prevalence of EoE was 55 per 100,000 persons.4

EoE has been described in children and adults. In adults, it is seen more commonly in males, with a male‐to‐female ratio of 3:1. Patients are usually white and 20 to 30 years of age. On average, their symptoms have been present for 4.5 years prior to diagnosis.5,6 Similar to adults, children with EoE are more commonly male and white. Although EoE is not a classic allergic disease, approximately 70% of patients have a personal history of atopy to environmental or food allergens.1 Some patients have a family history of eosinophilic GI disease.2

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PATHOPHYSIOLOGY

Figure. Stacked circ...
Figure. Stacked circ...
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A chronic immune/antigen‐mediated disorder, EoE manifests with symptoms of esophageal dysfunction and histologic findings of eosinophil‐predominant inflammation.1 The exact pathogenesis of EoE is not known, and confounding factors, such as genetics and the environment, may be in play. In a recent review, Elitsur reported on a study that found African American patients were younger at diagnosis, leading the authors to propose that race/ethnicity plays a role in EoE.7,8 Familial clustering has been observed, with characteristics similar to those of sporadic cases, and genes that may predispose susceptible individuals to EoE have been identified.1 Additionally, the incidence of EoE is higher in the Northeast United States than in the Southeast and in urban areas versus rural areas, suggesting the potential influence of air pollution or aeroallergens.8 Furthermore, a seasonal variation is possible, with the greatest number of EoE diagnoses occurring during peak aeroallergen exposure months.4 In genetically predisposed individuals, the eosinophilia may be an immune system response to food and environmental antigens. Eosinophil recruitment and chronic inflammation over time can lead to irreversible remodeling of the esophagus with a decrease in number of eosinophils, fibrosis, and stricture formation. Research currently under way will increase our knowledge of EOE.

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DIAGNOSIS

The primary elements in the diagnosis of EoE are evidence of esophageal dysfunction, presence of an eosinophil‐rich inflammation in the esophagus, and elimination of other diagnoses that share a similar clinical picture. Chief among these is GERD, although a recently identified disease, proton pump inhibitor‐responsive eosinophilic esophagitis (PPI‐REE), also warrants consideration. A history of food or environmental allergy supports the diagnosis of EoE.

History Ask if the patient is having difficulty swallowing. In adults, the most common symptoms of EoE are dysphagia, refractory heartburn, chest pain, and food impaction1 (Table 2). Symptoms may be unrecognized for years. In children, symptoms of EoE are more nonspecific and dominated by feeding difficulties, including vomiting and abdominal pain9 (Table 3). Ask the parents of a very young child if he or she has any history of gastroesophageal reflux or difficulty feeding. Feeding dysfunction, with aversion to solid foods and failure to advance from a liquid diet to a solid diet, can be indicative of underlying EoE in very young children. To investigate the possibility of aeroallergen sensitivity, ask if the patient's symptoms vary with the seasons. Aeroallergen sensitivity can manifest in seasonal variability of symptoms of EoE, along with other possible atopic symptoms of allergic rhinitis and/or atopic asthma.4,10,11

Table 2
Table 2
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Table 3
Table 3
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Physical examination In general, no physical examination findings are characteristic of or specific to EoE, and the oropharyngeal, chest, and abdominal examinations are typically unremarkable. The physical examination in children should focus on growth and nutrition deficiencies, which may be indicative of underlying feeding dysfunction. Any findings of comorbid allergic disease should also be noted.

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KEY POINTS

- Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation of the esophagus leading to clinical esophageal dysfunction.

- The pathogenesis of EoE may include such factors as race, genetics, geographic location, and allergy.

- Endoscopy and esophageal biopsy is the only definitive method to diagnose EoE. Biopsy specimens must be taken from the distal esophagus, as well as the proximal and/or midesophagus, where eosinophilia is not seen in gastroesophageal reflux disease.

- Treatment begins with dietary modification, followed by pharmacologic therapy with topical corticosteroids, systemic corticosteroids, and endoscopic intervention.

Endoscopy and esophageal biopsy Evaluation by a trained gastroenterologist using endoscopy and esophageal biopsy is the only definitive method to diagnose EoE. Visual findings on endoscopy that may be suggestive of EoE include stacked circular rings (“feline” esophagus), proximal strictures, and linear furrowing of the esophagus. White exudates or papules that represent accumulations of eosinophil pus and microabscesses may be seen throughout the esophagus.

Biopsy specimens must be taken from the distal esophagus, as well as the proximal and/or midesophagus, where eosinophilia is not seen in GERD. A threshold of 15 eosinophils or greater per high‐power field (hpf) is required for the diagnosis of EoE.1 Histologically, EoE is distinguished from GERD by more marked eosinophilia (usually >15/hpf), involvement of the proximal and/or midesophagus, and lack of eosinophilia resolution by therapy with proton pump inhibitors (PPIs). In fact, after the initial finding of distal esophageal eosinophilia, an 8‐ to 12‐week trial of PPI therapy may be initially recommended to rule out GERD and PPI‐REE, with subsequent repeat endoscopy and biopsy to document resolution or persistence of eosinophilia, as seen in EoE.1

Radiography An upper GI series with barium is not sufficiently sensitive for use in diagnosis. However, barium studies can provide valuable information regarding esophageal anatomy, such as the presence of proximal strictures and esophageal narrowing.1 An esophagus with a ringed appearance on barium study is suggestive of EoE.2

Laboratory evaluation No laboratory tests can definitively diagnose EoE, but some findings may support its diagnosis. For example, mild eosinophilia in the peripheral blood may be related to EoE or concomitant atopic disease. Elevation of total serum immunoglobulin (Ig)E can suggest an underlying atopic diathesis,9 and elevations of specific IgE levels may indicate allergens to which the patient is sensitive.1

Allergy testing Evaluation by an allergist/immunologist is recommended after diagnosis to document food allergy and/or aeroallergen sensitization that may be driving the underlying inflammation and symptoms of EoE. Skin prick testing, patch testing, and/or specific IgE testing can help identify possible food allergens.1,12 Any potential food allergens will need to be further evaluated by eliminating them from the diet and monitoring for subsequent resolution of symptoms and esophageal eosinophilia. Sequential food reintroduction can identify causative factors.13

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TREATMENT

Treatment of EoE requires a multidimensional approach consisting of dietary modification, pharmacotherapy, and endoscopic intervention (reserved for complex cases).

Dietary modification The first step in treating EoE is dietary modification. This approach may be particularly effective in children, who tend to have more food allergies than adults.10 Prior to introducing dietary changes, referral to an allergist/immunologist experienced in diagnosis and management of food and environmental allergies is recommended. The usual approach to dietary therapy begins with allergy skin prick and/or serology for IgE to multiple foods, including the most commonly allergenic foods (eg, cow's milk, eggs, soy, wheat, peanut, and tree nuts), with the addition of any other foods suspected by history. Food allergen skin patch testing may also be performed.12 Any food(s) that produce positive results on skin tests or serology should be eliminated from the diet and the patient monitored for symptomatic improvement.1 An alternative approach is to empirically eliminate all the aforementioned foods and then gradually reintroduce them one by one every few weeks; note that this approach may cause unnecessary avoidance of many foods.10

Elemental diet therapy consisting of a synthetic amino acidbased dietary formula is an effective approach that may be used in some children to strictly limit exposure to food protein allergens.1 Elemental diets may be impractical, however, because they are expensive, have an unpleasant taste, and may have adverse psychosocial effects on children.13 Patients on dietary elimination or elemental diet therapy need to be monitored closely for potential nutritional deprivation and/or unnecessary aversion to foods.1 Consultation with a certified dietitian or nutritionist is highly recommended in children who undergo elimination or elemental diet therapy.

Dietary modification therapies are also recommended in motivated adult patients. As is the case for children, food allergy testing may be clinically useful to guide in finding suspected trigger foods.13 The duration of diet elimination therapies is not well‐defined, but they are generally followed long‐term, if not indefinitely. Their use is guided by change in patient symptoms upon sequential reintroduction of the foods, as well as by changes in endoscopy findings.

Pharmacologic therapy To date, the FDA has not approved any drugs for the treatment of EoE. However, topical corticosteroids, which are swallowed to coat the esophagus, are effective and well‐tolerated in improving both symptoms of EoE and the underlying esophageal eosinophilia in children and adults. Most patients respond within the first few days of treatment; however, symptoms usually recur once the corticosteroids are discontinued. The optimal duration of therapy is not yet known.1 The two most studied formulations are fluticasone via metered‐dose inhaler and viscous budesonide suspension, which is usually mixed with sucralose (Splenda) for a thicker consistency to coat the esophagus. Usually, five to 10 packets of sucralose (each 1‐g packet contains 11.9 mg of sucralose) are mixed with every 1‐mg respule of budesonide and then swallowed. The currently recommended doses and methods of topical corticosteroid administration are presented in Table 4. Though generally well‐tolerated, topical corticosteroid therapy has reported side effects that can be limited to the immediate area, including infectious fungal and viral esophagitis, and systemic side effects, such as cataracts, impaired growth in children, and adrenal insufficiency (with very high doses). These effects vary with duration of therapy. As is always the case, the recommendation is to use the lowest effective dose possible.1

Table 4
Table 4
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Systemic corticosteroids are a more effective from of treatment for EoE than topical corticosteroids. However, a greater systemic side‐effect profile limits the use of these agents to more emergent situations, such as occur with severe dysphagia, hospitalization, and weight loss.1 The recommended doses are 1 to 2 mg/kg per day, which can be divided into twice‐daily doses. Long‐term use is not recommended.

Since patients with EoE usually have an overall atopic diathesis, other allergic disorders, such as allergic rhinitis or atopic asthma, will also need to be aggressively treated. However, no direct evidence indicates that treatment of other allergic disorders improves the symptoms of EoE.

PPI therapy is not recommended specifically for treatment of EoE, although it may help to treat coexistent GERD and/or PPI‐REE.1 The mechanism of PPI therapy is unclear. It may help decrease acid‐induced injury to the inflamed esophagus in EoE. Some authors have suggested a possible effect on the immune/antigen‐mediated pathogenesis of EoE.14

Investigational treatments Other treatments that show promise and are currently being researched include anti‐IgE therapy with omalizumab and anti‐interleukin 5 therapy with mepolizumab.1

Endoscopic intervention Esophageal dilatation can provide relief of dysphagia symptoms in patients with strictures or those who have not been responsive to other treatments.15 It does not treat the underlying inflammation and can be associated with esophageal mucosal tears and perforation. In patients without high‐grade or significant stenosis, an initial trial of dietary or medical therapy is warranted.

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PROGNOSIS

The long‐term prognosis of EoE patients is not known because of limited data on long‐term outcomes. In general, the disease may continue with chronic symptoms or it may be episodic.6,10 EoE in children may persist into adulthood, but such persistence is not well‐established. Some adults with EoE may progress to a fibrotic stage with persistent dysphagia. Currently, EoE is not thought to be associated with increased risk of esophageal cancer.

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REFERENCES

1. 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.e6.

2. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004;351(9):940-941.

3. Erwin EA, Asti L, Hemming T, Kelleher KJ. A decade of hospital discharges related to eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2012;54(3):427-429.

4. Prasad GA, Alexander JA, Schleck CD, et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin Gastroenterol Hepatol. 2009;7(10):1055-1061.

5. Croese J, Fairley SK, Masson JW, et al. Clinical and endoscopic features of eosinophilic esophagitis in adults. Gastrointest Endosc. 2003;58(4):516-522.

6. Straumann A, Spichtin HP, Grize L, et al. Natural history of primary eosinophilic esophagitis: a follow-up of 30 adult patients for up to 11.5 years. Gastroenterology. 2003;125(6):1660-1669.

7. Sperry SLW, Woosley JT, Shaheen NJ, Dellon ES. Influence of race and gender on the presentation of eosinophilic esophagitis. Am J Gastroenterol. 2012;107(2):215-221.

8. Elitsur Y. Confounding factors affect the pathophysiology of eosinophilic esophagitis. World J Gastroenterol. 2012;18(33):4466-4469.

9. Liacouras CA. Clinical presentation and treatment of pediatric patients with eosinophilic esophagitis. Gastroenterol Hepatol (N Y). 2011;7(4):264-267.

10. 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.

11. Roy-Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2008;6(5):531-535.

12. Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol. 2012;130(2):461-467.e5.

13. 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): 1451-1459.e1.

14. Hirano I. Should patients with suspected eosinophilic esophagitis undergo a therapeutic trial of proton pump inhibition? Am J Gastroenterol. 2013;108(3):373-375.

15. Schoepfer AM, Gonsalves N, Bussmann C, et al. Esophageal dilation in eosinophilic esophagitis: effectiveness, safety, and impact on the underlying inflammation. Am J Gastroenterol. 2010; 105(5):1062-1070.

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Section Description

EARN CATEGORY I CME CREDIT by reading this article and the article beginning on page 24 and successfully completing the posttest on page 58. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of May 2013.

© 2013 Lippincott Williams & Wilkins, Inc.

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