Eosinophilic Esophagitis (EoE): Questions and Answers

What is EoE?

Eosinophilic (ee-uh-sin-uh-fil-ik) esophagitis (EoE) is an allergic swallowing disorder. EoE affects the esophagus, the part of the gastrointestinal tract (gut) that connects the back of the throat to the stomach. EoE occurs when a type of white blood cell called eosinophil collects in the esophagus. It is often triggered by food. EoE may be triggered by pollen as well. Both children and adults can have EoE.

Eosinophils are a special type of white blood cell. Eosinophils help us fight off certain types of infections, such as parasites or hookworms. However, eosinophils also are involved in other conditions, including allergies, cancer and other problems. The eosinophil is a cell that serves many roles. Some roles are specific and some not specific, which means that there are a number of different processes in the body that can cause eosinophils to be present. An eosinophilic disorder may be present when eosinophils are found in high numbers in the blood or part of the body for a long period of time without a known cause. Generally, this means more than 6 months.

Eosinophilic disorders can occur in different areas of the gastrointestinal (GI) tract. For instance, eosinophilic esophagitis (EoE) means abnormal numbers of eosinophils in the esophagus. Eosinophils are not normally present in the esophagus. Eosinophils are normally found in small numbers in other areas of the GI tract.

A variety of triggers may cause this abnormal production and collection of eosinophils. Foods can be one of those triggers in some people in EoE. Other diseases can cause eosinophils in the esophagus and these sources must be considered as well. Some other causes include:

• Gastroesophageal reflux diseases (GERD)
• Other forms of esophagitis that damage the lining of the esophagus
• Infection
• Inflammatory bowel disease

EoE affects people of all ages, gender and ethnic backgrounds. In certain families, there may be an inherited (genetic) tendency.

It is common for people with EoE to have other allergic diseases such as asthma or eczema.

Image 1: Upper gastrointestinal tract

What are the symptoms of EoE?

Symptoms vary from one person to the next. The symptoms may differ depending on age. Symptoms in young children may include problems with eating, vomiting and poor weight gain. Older children and adults may experience reflux, chest pain and difficulty swallowing. The symptoms can occur days or even weeks after eating a food allergen. However, symptoms may wax and wane, meaning they are not always present. This can be confusing. Common symptoms include:

• Reflux that does not respond to usual therapy (this includes proton pump inhibitors, a medicine which stops acid production in the stomach)
• Difficulty swallowing (dysphagia)
• Food impactions (food gets stuck in the throat)
• Nausea and vomiting
• Failure to thrive (poor growth or weight loss)
• Abdominal or chest pain
• Poor appetite
• Malnutrition
• Difficulty sleeping

How is EoE diagnosed?

Unfortunately, EoE cannot be diagnosed by symptoms alone. Symptoms often guide your physician as to when to begin evaluation for EoE. EoE is diagnosed through a test called an upper endoscopy. During an upper endoscopy, a small tissue sample, or biopsy, of the esophagus is taken and studied for eosinophils. A specialist called a gastroenterologist performs the endoscopy. The endoscopy is often performed after trying reflux medications to relieve the symptoms. Medications for reflux include proton pump inhibitors (PPI) such as Prevacid.^® Another type of reflux medicine is histamine-2 (H2) blockers such as Zantac.^®

During an upper endoscopy, the specialist looks at parts of the GI tract – the esophagus, stomach and duodenum. The specialist also takes biopsies from several parts of these areas. A pathologist reviews these tissue samples under the microscope.

When the specialist performs the procedure, the surface of the esophagus may appear very abnormal. It could appear very red and inflamed. It could be very narrowed. It could have multiple white bumpy patches. It might even have a Slinky or accordion-like appearance.

Sometimes, it looks quite normal. However, even if the esophagus appears normal, the biopsies may show EoE. A high number of eosinophils greater than 15, counted per high power viewing field on a microscope, suggest the diagnosis of EoE.

GERD also causes eosinophils in the esophagus, but typically far fewer than in EoE. Currently, experts have not decided what range of eosinophils definitely indicates severe reflux or a process that may respond best to anti-acid medication, and what range clearly indicates EoE. Unfortunately, no other cell or tissue findings have been identified to help clarify this situation.

The pathologist will also look for tissue injury, swelling and thickening. With EoE, the eosinophils are only present in the esophagus and not found in other areas. Also, other causes of eosinophils must be excluded. After a diagnosis of EoE is made, food and pollen allergy testing is usually recommended. This testing helps to guide treatment as these may be triggers in some individuals.

Treatment

Many children and adults with EoE respond well to changes in the diet, though not all do. Foods that cause symptoms are generally removed from the diet, especially those associated with difficulty swallowing (“dysphagia”) or even becoming stuck (“impaction”). Food allergy testing may help to determine which foods need to be avoided.

Two types of tests may be applied—prick skin tests (“scratch tests’) and patch tests. There are between 10-15 “common” foods that are well-associated with EoE. These are the foods that are first tested. Researchers now know how likely a negative or positive test indicates that one of these particular foods is a trigger for EoE.

Sometimes, foods that people eat regularly may be triggers, even ones that were never associated with symptoms. This is the difficult part of EoE. In “regular” food allergy, there would be no cause to test someone to a food they eat without symptoms. But with EoE, the case is different. Eosinophils can be triggered by a food with minimal - or in some cases - no symptoms.

If a food is positive on testing, the specialist usually recommends that the food be removed from the diet. Once symptoms are gone and the eosinophil counts have gone away, foods are added back to the diet, one by one.

Dietary Therapy

There are actually three styles of dietary therapy. Dietary therapy is a form of treatment based on making changes in a person’s diet. All of these dietary therapies are aimed at removing triggers of EoE from the diet. These include:

Elimination diets. Allergy testing is used to determine what foods are likely triggers. Experts recommend that all foods one tests positive to are removed from the diet.

Elemental diets. An elemental diet is a formula based diet. This special formula does not include any food-based sources of protein. The elemental diet includes only an amino acid formula such as Neocate^® or Elecare.^® Simple sugars, salt, oils, and selected fruits may be the only foods allowed on an elemental diet. Some children and adults require a feeding tube to help with these diets.

6-Food elimination diets. This is a cleverly effective treatment that involves avoiding the 6 major food allergens. These six allergens are milk, egg, wheat, soy, “nuts,” and “seafood.” If you count, it is actually a greater-than-40 food elimination diet when you consider each individual nut or seafood item. This diet can be used without any allergy testing. Newer versions of this diet have simplified this to a 4-food elimination of just milk, egg, wheat, and soy.

Food trials. This involves adding back one ingredient at a time to determine specific foods causing a reaction. The food is tried for a period of days to weeks, followed by a repeat biopsy to check if eosinophils returned (or symptoms returned). Food trials begin after symptoms resolve and eosinophils have cleared.

A quick note on dietary therapy. The good news is that all three diet styles appear to work quite well to get rid of both symptoms and eosinophils. The bad news is that it is not clear which style is the best. No study has directly compared each one in a way that would allow for a true “champion” to be crowned. However, having three choices gives us many options to explore. These three choices allow each provider and family to select an option that works best for them.

Dietary therapy may be used as the only therapy for EoE, or it can be combined with medication.

Medical Therapy

In the early days of EoE, before it was clear that food allergens may play a role, the earliest therapies used were steroids. Very rarely do large doses of oral steroids (the same doses used for asthma attacks) need to be used now. Most EoE can be treated with topical steroids. Topical means the patient swallows doses of inhaled steroids. The same dose is used for daily control of asthma such as Flovent^® or Pulmicort^®.

Pulmicort^® (budesonide) respules can be squirted into a cup and thickened with various substances such as Splenda,® honey or syrup to make a “slurry.” The slurry is then swallowed. The goopy steroid slurry slowly passes over the esophagus and provides “topical” therapy.

Flovent^® (fluticasone proprionate) or other steroid inhalers can be “gulped” and swallowed when used without a spacer device, which also coats the esophagus.

Both styles work quite well in both children and adults.

Steroid therapy can be used alone, or in combination with dietary therapy. Like dietary therapy, there is no clear proven “winner” between Pulmicort^® and Flovent^®. Both work quite well. There are no clear rules as to how long to treat someone with steroids.

Some specialists use a six-to-12 week course of steroid as a starting point, but that varies. Some individuals may require months of treatment, not unlike in asthma.

Topical steroid use in EoE has not been shown to stunt growth or have any long-term effects. The doses used are equivalent to those used in asthma, and both Pulmicort and Budesonide are of the “safe” steroid class in terms of stunting growth. The doses used for both EoE and asthma are much lower than when taken as a pill or liquid and do not carry the same risk of side effects. As with any condition in which steroids are recommended for treatment, long-term monitoring and consideration for ‘stepping down’ therapy are important to consider over time.

Medications for reflux include proton pump inhibitors (PPI) such as Prevacid.^® Another type of reflux medicine is histamine-2 (H2) blockers such as Zantac.^®

These are important additional medicines that help to control any reflux that may be present. Reflux can cause eosinophils, as well as cause symptoms. Most specialists will not perform the first endoscopy to diagnose EoE without the patient being on anti-reflux medicine for 8 weeks. This approach will exclude other causes of the eosinophils that could be treated by these medications. It is equally important to remain on reflux medication in the active treatment of EoE, even if the patient does not have symptoms of reflux.

Experimental Therapies

Many potential therapies are being studied right now. Researchers are looking at including drugs that target the specific signals that eosinophils need to grow and develop (IL-5 and IL-13). You can find out more at www.clinicaltrials.gov. Search for “eosinophilic esophagitis” to learn more about these studies.

At present, diet, steroid, and anti-acid medications are the only proven therapies.

Ongoing Care

Patients with EoE may need more endoscopies to check how the esophagus is responding to treatment. Symptoms are not a reliable way to monitor one’s EoE. Repeat biopsies are necessary to directly see how an individual responds to treatment.

There are rules to help specialists know how many follow up procedures are necessary, or how often to do these procedures.

Patients on dietary therapy should meet with a registered dietician or nutritionist. A dietitian will make sure that a patient’s daily needs for vitamins, minerals, and calories are being met. A dietitian also helps patients explore alternative foods.

EoE can be frustrating in that it may come and go. EoE is not like an infection that can be treated with antibiotics. It is a lot like asthma, in that it may not go away for several years. However, it may not always be active, either.

No one knows exactly for how long someone must be treated to get rid of EoE. Short courses for around six weeks of treatment have been found to result in EoE coming back. Most providers start with 12 weeks (3 months) of treatment and then re-check their patients.

The specialist’s collective goal in treating patients is to treat for as short a time period as possible, but for as long as needed, making sure patients no longer have symptoms or eosinophils. It is not enough to no longer have symptoms or no longer have eosinophils alone to be considered fully treated. Periodic follow up is necessary to stay on top of this condition.

Reviewed by Matthew Greenhawt, MD, MBA, MSc, FAAP, member of the Kids With Food Allergies Medical Advisory Team, in August 2014.

Published in collaboration with the American Partnership for Eosinophilic Disorders (APFED).

About APFED

American Partnership for Eosinophilic Disorders (APFED) is a non-profit organization whose mission is to passionately embrace, support, and improve the lives of patients and families affected by eosinophil-associated diseases through education and awareness, research, support, and advocacy. Learn more at www.apfed.org.