Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an isolated infiltration of eosinophils into the epithelium of the esophagus and is triggered by specific allergens. Patients should undergo an upper endoscopy with biopsy after 6 to 8 weeks of treatment with a proton pump inhibitor in order to make the diagnosis of EoE. Eosinophilic gastroenteritis is a pathologic eosinophilic infiltration of any portion of the gastrointestinal tract, and eosinophilic proctocolitis is an eosinophilic infiltration in the colon alone.
Key points
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Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an isolated infiltration of eosinophils into the epithelium of the esophagus.
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A diagnosis of EoE requires an esophageal biopsy while on a proton pump inhibitor for at least 6 to 8 weeks.
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Proton pump inhibitor–responsive esophageal eosinophilia should always be differentiated from EoE.
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Both medication and dietary therapy options should be considered in patients with EoE.
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Eosinophilic gastroenteritis is described as a pathologic eosinophilic infiltration of any portion of the gastrointestinal tract, and eosinophilic proctocolitis is defined as an abnormal number of eosinophils in the colon alone.
Eosinophilic esophagitis
Introduction
Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an isolated infiltration of eosinophils into the epithelium of the esophagus. EoE is triggered by specific allergens, almost always food antigens; there has been significant research in this area over the past 30 years in order to determine the nature of these specific allergens.
Definition
The 2013 revised guidelines for the diagnosis and management of this disease state that EoE is defined as a clinicopathologic disorder that meets the following criteria :
- 1.
Presence of symptoms related to esophageal dysfunction
- 2.
Presence of greater than or equal to 15 eosinophils per high-power field on esophageal biopsy after a trial of a proton pump inhibitor (PPI)
- 3.
Isolation of this mucosal eosinophilic predominance to the esophagus
Of note, symptoms of EoE are often similar to those of gastroesophageal reflux; therefore, the presence of eosinophils on esophageal biopsy is needed to make the diagnosis of EoE.
Prevalence
EoE has increased in prevalence over the past 10 years. The reported prevalence of EoE in 2003 was 4.3 per 10,000 children aged 0 to 19 years. The pediatric male to female ratio is approximately 3:1.
Cause
EoE is thought to occur in genetically susceptible individuals through predominantly non–immunoglobulin E (IgE)-mediated allergic responses to allergens. These allergens are thought to be predominantly food, although other studies have suggested additional environmental allergens, such as aeroallergens, as potential triggers. In general, when food allergens enter the body through a disrupted epithelial barrier, it is postulated that local esophageal antigen presenting cells interact with this antigen. Subsequently, a cascade of proinflammatory cytokines, such as interleukin (IL)-5 and IL-13, as well as chemokines, such as eotaxin-1 and eotaxin-3, are triggered. This trigger results in recruitment of eosinophils to the esophagus.
The first EoE genetic susceptibility locus was recently described at locus 5 q 22. One of the genes at this locus is thymic stromal lymphopoietin, a T-helper 2 proinflammatory cytokine gene that has been associated with other allergic diseases in the past.
Clinical Symptoms
Symptoms of EoE are detailed in Table 1 and Box 1 .
| Younger Children | Older Children and Adolescents |
|---|---|
| Vomiting Chronic nausea Regurgitation Irritability/feeding difficulties | Heart burn Epigastric pain Dysphagia Nighttime cough Food impaction |
Growth failure
Hematemesis
Esophageal dysmotility
Failure to thrive
Malnutrition
Some children drink an overabundance of fluids with meals or chew their food excessively in order to compensate for these symptoms. Additional allergic symptoms, such as asthma, eczema, and allergic rhinitis, are present in up to 50% of patients. Complications of EoE include hiatal hernia as well as esophageal strictures, perforation, and fungal infection. Because heartburn is a common symptom of EoE, it is important to consider EoE in patients who have chronic reflux symptoms.
Diagnosis
When considering this diagnosis, patients should be placed on a PPI. After at least 6 to 8 weeks on the PPI, patients should undergo an upper endoscopy with biopsy. An esophageal biopsy is always necessary in order to diagnose EoE. Specifically, at least 15 eosinophils per high-powered field must be present on biopsy, and these eosinophils must be isolated to the esophagus. Although the distal esophagus is typically most affected, biopsies should be taken from multiple levels of the esophagus, as EoE is a patchy disease. In order to make a diagnosis of EoE, biopsies must also be taken from the stomach and duodenum to be sure that excessive eosinophilia is not present. Increased eosinophilia in the stomach or duodenum would instead suggest eosinophilic gastroenteritis.
Visual endoscopic findings include concentric ring formation (called trachealization), vertical linear furrows, and white patches or plaques scattered along the mucosal surface. These findings are present in up to 70% of patients with EoE but are not pathognomonic for the disease. The remaining 30% of those with EoE have visually normal esophageal mucosa. These facts reinforce the need to obtain an esophageal biopsy in order to make the diagnosis of EoE ( Box 2 ).
Eosinophilic gastrointestinal diseases
Proton pump inhibitor–responsive esophageal eosinophilia
Celiac disease
Crohn disease
Infection
Hypereosinophilic syndrome
Achalasia
Drug hypersensitivity
Vasculitis
Pemphigus
Connective tissue diseases
Graft versus host diseases
There are no current serologic, radiologic or stool tests that have been shown to be diagnostic of EoE.
Allergy Testing
In addition to an evaluation by a gastroenterologist, consultation with an allergist is often helpful because patients often have other features of atopy including asthma, eczema, allergic rhinitis and IgE-mediated food allergies. Although allergy testing is not diagnostic of EoE, skin prick testing (SPT) should be considered in order to identify IgE-mediated food allergens and, less frequently, aeroallergens. These allergens may also crossover and be potential EoE allergen triggers. In addition to SPT, atopy patch testing may be considered in order to identify non–IgE-based food allergens, as the food reactions in EoE are due to these cell-mediated reactions.
Proton Pump Inhibitor–Responsive Esophageal Eosinophilia
PPI–responsive esophageal eosinophilia (REE) should always be differentiated from EoE. PPI-REE is either related to gastroesophageal reflux, an independent disorder, or a possible subset of EoE. Despite not understanding the exact cause of PPI-REE, it is important to determine if esophageal eosinophilia do not respond to a PPI, as the following treatment approach for EoE mandates this course of action. Ngo and colleagues identified several patients with esophageal eosinophilia that normalized after administration of a PPI for 1 month. Short-term aggressive dosing of the PPI should be considered; the pediatric dosage of the PPI can be up to 1 mg/kg twice daily (maximum 30–40 mg twice a day) and should be administered for 6 to 12 weeks before upper endoscopy and biopsy.
Management of Eosinophilic Esophagitis
Both medical and dietary therapy should be considered in patients with EoE. Historically, systemic steroids were the first medication that mitigated symptoms as well as normalized the number of eosinophils in the esophageal mucosa in these patients. However, chronic systemic corticosteroids cannot be used long-term because of side effects, such as decreased linear growth, increased appetite, hypertension, bone changes, and mood alterations. Although this is not currently recommended as a first-line treatment in EoE, oral corticosteroids are still a useful short-term treatment approach for patients with severe dysphagia, poor weight gain, and small-caliber esophagus.
Current first-line medical treatment of EoE is swallowed, topical corticosteroids. These medications include fluticasone propionate, which is sprayed into the pharynx and swallowed rather than inhaled, and swallowed viscous budesonide. Swallowed topical corticosteroids are delivered along the surface of the esophagus, which leads to symptom improvement and histologic normalization within several weeks. Recommended dosing for fluticasone is age and weight based and varies from 110 to 880 mg twice daily; dosing for swallowed budesonide is 0.5 to 1.0 mg twice a day. Patients should not eat, drink, or rinse the mouth for 20 to 30 minutes after use. The initial treatment course is 2 to 3 months, followed by a repeat upper endoscopy. If patients have achieved histologic remission, then the steroids can be weaned (followed by another upper endoscopy). The disease almost always recurs once the medication is discontinued. The side effects of topical corticosteroids are significantly decreased compared with those of systemic steroids. However, some patients develop epistaxis, dry mouth, or esophageal candidiasis.
Dietary modification has also been found to be an effective treatment. After identifying the appropriate dietary antigens, patients experience both an improvement in symptoms and histologic resolution. Potential dietary modifications include initiation of a hypoallergenic, elemental diet, eliminating the 6 most common food allergens (milk, eggs, wheat, soy, nuts, shellfish) or selectively eliminating particular foods from the diet. Kelly, Markowitz, and Liacouras demonstrated that greater than 95% of children completely resolve their EoE if given a strict amino acid–based formula as the sole source of dietary nutrition. Children on this diet ingest only this formula for a period of time to allow the esophagus to heal. After the esophageal mucosa normalizes, foods are systematically reintroduced. Clinical symptoms may take up to several weeks to recur after reintroduction of a particular food. This diet is often difficult to adhere to for older children because of the large volume of formula required to meet caloric needs and the inability to eat solid foods while on the diet. Most pediatric patients on this regimen cannot tolerate this formula by mouth and instead require administration via a nasogastric tube.
Alternatively, in the mid 2000s the idea of using targeted elimination diets was introduced. Kagalwalla and colleagues showed that a 6-food elimination diet without allergy testing resulted in resolution of EoE symptoms and improvement, but not elimination, of the esophageal eosinophil count in approximately 75% of patients. These targeted elimination diets are executed in conjunction with serial endoscopy with biopsy. After specific foods are removed from the diet for at least 6 to 8 weeks, patients then undergo a repeat endoscopy to assess the esophageal eosinophil count. If the count has normalized, then these foods must be assessed individually to determine the exact food allergen that triggers the disease. On the other hand, if there is no improvement in the eosinophil count after removal of the foods, further dietary restriction must be initiated. This process continues for several cycles until the exact EoE food allergen triggers have been identified and removed and the esophageal eosinophil count has normalized. The most common EoE trigger foods identified through this process are dairy, eggs, soy, corn, wheat, and beef.
Other Therapy
New medications that target specific cytokines and immune mediators are being studied as potential treatment options for patients with severe EoE. These medications include anti-IL-5, very late activating antigen, and monoclonal eotaxin antibody.
Eosinophilic esophagitis
Introduction
Eosinophilic esophagitis (EoE) is an atopic disease that is characterized by an isolated infiltration of eosinophils into the epithelium of the esophagus. EoE is triggered by specific allergens, almost always food antigens; there has been significant research in this area over the past 30 years in order to determine the nature of these specific allergens.
Definition
The 2013 revised guidelines for the diagnosis and management of this disease state that EoE is defined as a clinicopathologic disorder that meets the following criteria :
- 1.
Presence of symptoms related to esophageal dysfunction
- 2.
Presence of greater than or equal to 15 eosinophils per high-power field on esophageal biopsy after a trial of a proton pump inhibitor (PPI)
- 3.
Isolation of this mucosal eosinophilic predominance to the esophagus
Of note, symptoms of EoE are often similar to those of gastroesophageal reflux; therefore, the presence of eosinophils on esophageal biopsy is needed to make the diagnosis of EoE.
Prevalence
EoE has increased in prevalence over the past 10 years. The reported prevalence of EoE in 2003 was 4.3 per 10,000 children aged 0 to 19 years. The pediatric male to female ratio is approximately 3:1.
Cause
EoE is thought to occur in genetically susceptible individuals through predominantly non–immunoglobulin E (IgE)-mediated allergic responses to allergens. These allergens are thought to be predominantly food, although other studies have suggested additional environmental allergens, such as aeroallergens, as potential triggers. In general, when food allergens enter the body through a disrupted epithelial barrier, it is postulated that local esophageal antigen presenting cells interact with this antigen. Subsequently, a cascade of proinflammatory cytokines, such as interleukin (IL)-5 and IL-13, as well as chemokines, such as eotaxin-1 and eotaxin-3, are triggered. This trigger results in recruitment of eosinophils to the esophagus.
The first EoE genetic susceptibility locus was recently described at locus 5 q 22. One of the genes at this locus is thymic stromal lymphopoietin, a T-helper 2 proinflammatory cytokine gene that has been associated with other allergic diseases in the past.
Clinical Symptoms
Symptoms of EoE are detailed in Table 1 and Box 1 .
| Younger Children | Older Children and Adolescents |
|---|---|
| Vomiting Chronic nausea Regurgitation Irritability/feeding difficulties | Heart burn Epigastric pain Dysphagia Nighttime cough Food impaction |
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