Eosinophilic Esophagitis — Climbing to New Understandings
By Valerie Yeager
Today’s Dietitian
Vol. 8 No. 5 P. 28

The thought of a child needing nutrition support is a tough one to swallow. But that’s one treatment method for this little-known, severe allergic condition that wages a war in the esophagus.

Eosinophilic esophagitis (EE) is a rapidly emerging chronic illness in both pediatric and adult gastroenterology. Often misdiagnosed as gastroesophageal reflux disease (GERD) in the past, recent research and new diagnostic techniques have proven EE to be an entity all its own.

Most commonly caused by a food allergy, EE is a serious condition that can cause chronic feeding problems. Treatment to control the disease has become a widely discussed and often controversial topic—especially among RDs, physicians, allergists, and gastroenterologists.

Etiology of EE
A growing health problem affecting as many as one in every 2,000 children worldwide, EE is characterized by an abnormal accumulation of eosinophils in the lining of the esophagus.1 An eosinophil is a type of white blood cell that defends against certain types of infections, such as parasites.2 Various problems—including food and environmental allergies, infections, eosinophil-associated gastrointestinal disorders, and leukemia—can cause a high number of eosinophils in the blood. For patients with EE, the most common cause is an allergy to milk, eggs, soy, corn, wheat, beef, chicken, shellfish, peanuts, or potatoes.

EE affects people of all ages, regardless of gender or ethnic background, but most patients are in early childhood or aged 20 to 40. Eighty percent of cases are males.3

Symptoms
Although they vary for each individual, the following are the most common symptoms of EE:

• dysphagia;

• food impaction;

• nausea and vomiting;

• failure to thrive (poor growth and/or weight loss);

• abdominal or chest pain;

• poor appetite;

• malnutrition; and

• difficulty sleeping.

Nausea and vomiting are the most common symptoms for children, while dysphagia accompanied by solid food impaction is most prevalent in adults.4

Vomiting, dysphagia, and abdominal pain are also symptoms of GERD, making it easy to misdiagnose EE as the reflux disease. Distinguishing the two illnesses is important because patients with EE do not respond to GERD treatments.

The symptoms of EE appear intermittently while GERD symptoms are persistent. The results of a pH probe will return normal for patients with EE and abnormal for those with GERD. An acid blockage will be unresponsive in someone with EE whereas it will be responsive in someone with GERD.3

GERD also causes eosinophils in the esophagus, but typically far less than for patients with EE. According to Steven Yannicelli, PhD, RD, the esophageal biopsy of a person with EE will find a “significant infiltration” of eosinophils.

Diagnosis
Though diagnosing EE is a complicated and frustrating procedure, the use of endoscopy has made the task a bit easier. Patients are often treated for reflux before receiving an endoscopy since symptoms for the two diseases are so similar. When reflux treatments, such as proton pump inhibitors or histamine-2 receptor blockers, fail to relieve symptoms, an upper endoscopy with biopsies is used to screen for EE.2

An upper endoscopy looks at the esophagus, stomach, and duodenum through an endoscope (a small tube inserted through the mouth) and takes multiple small tissue samples. Even if the esophagus appears normal, the biopsies may show an abnormal accumulation of eosinophils. The pathologist will also examine the biopsy for tissue injury, swelling, and thickening of esophageal layers.

Once the diagnosis is confirmed, the next step is a visit to an allergist. Skin prick/scratch testing to different foods is used to look for immunoglobulin E (IgE)-mediated allergies (immediate reaction) while patch testing measures non-IgE (delayed) reactions.
Although there may be no obvious, immediate reaction, causative foods can trigger an accumulation of eosinophils over a period of days to weeks that will cause inflammation and injury.

Treatment
Easily the most controversial aspect of EE is its treatment. Among the suggested treatment plans are removing causative foods from the diet, consuming a liquid elemental formula, or taking pharmaceuticals.

Most children and adult patients have a significantly favorable response to dietary treatment. However, controversy arises when naysayers say the dietary plans are too restrictive—especially for young children.

Elimination Diets
During an elimination diet, all foods that tested positive on allergy tests, as well as other foods likely to cause problems, are removed from the diet. According to Michele Shuker, MS, RD, CSP, LDN, coordinator of the Center for Eosinophilic Disorders at the Children’s Hospital of Philadelphia, an elimination diet will significantly improve the symptoms in roughly 70% of cases.

“As part of their nutrition assessment, we get a diet history and preferences. Based on what they tell us, we will try to work out the most balanced diet possible with the foods that remain in the diet,” says Shuker.

Elemental Diets
If developing a balanced diet with the remaining foods of an elimination diet is impossible, or if the child has a history of feeding difficulties or food refusal, an elemental diet is suggested.

During an elemental diet, all sources of protein are removed and a formula lacking any whole or partial proteins is consumed. Elemental formulas are made of amino acids, fats, sugars, vitamins, and minerals.

Adults generally rely on an elemental diet for partial nutrition and may still intake other foods; children are more likely to rely on an elemental diet as their soul source of nutrition.

This may seem a simple solution, but the quantity of formula required is often difficult for many patients to consume. In such a circumstance, patients may require enteral support to maintain proper nutrition. The amount of formula consumed is unique to each patient, based on his or her estimated need for weight gain and growth.

Food Reintroduction
Patients who respond favorably to an elemental or elimination diet may then undergo a food trial. This involves reintroducing one pure food to the diet at a time, beginning with those that tested negative on allergy tests and are least likely to cause a reaction (see Chart 1: “Food Reintroduction — Sample Progression”). The foods are added every one to three weeks with reevaluation after several foods have been resumed.2

Medication Therapy
The most common type of medication therapy is oral topical corticosteroids. Other medications include cromolyn sodium and leukotrine inhibitors that help reduce inflammation in the esophagus.5 Faubio et al treated 21 children with oral steroids for one month, and almost all experienced near total symptom relief within one week.5

Nutrition vs. Medication
Strong arguments and evidence support both sides of the nutrition vs. medication therapy debate. Nutrition management is complicated. It involves clinicians of several different specialties, detailed communication and planning, and a very disciplined and tolerant patient; yet, it works. Medication, meanwhile, provides quick and effective results without the demands of a restrictive diet. Nevertheless, these medications aren’t suggested for long-term use and the eosinophils will return when medication is stopped.

Healthcare providers who support nutrition therapy argue that the pharmaceutical approach should not be the first course of treatment. If nutrition therapy can almost always diminish symptoms completely, why risk the side effects of medication therapy?

“Steroids, especially the systemic ones, have been very effective at reducing both clinical systems and the number of eosinophils. The problem is that once you stop, those come back. The symptoms come back and EE does return. So the issue is that, yes, they are effective, but they aren’t recommended for long-term use. If you stay on a diet, it works. It balances against the negative effects of drugs, and there are a number of those,” says Yannicelli.

The side effects of steroid therapy to treat EE include decreased growth, protein breakdown, joint necrosis, osteoporosis, behavioral changes, glucose intolerance, increased risk of cataracts, and headaches. “These are all time-dependent and dose-dependent side effects, but they’re well documented. There’s not really an argument—they’re there,” says Shuker.

“There’s currently no specific drug to treat this disease. Although the drugs are effective, the evidence doesn’t support daily use. Everything that’s coming out now really says that diet and [elemental] formulas are the best way forward. With drugs, there aren’t long-term studies to show if it makes a difference in clinical outcome,” says Yannicelli.

Those who favor using pharmaceuticals to treat EE argue that children cannot be trusted to follow such a restrictive diet, including older children who aren’t under constant parental supervision. Children may become bored with the diet, worry about fitting in with peers, and may not have the discipline to follow such a prohibitive diet.

Also, nutrition management may be very expensive, whereas a pharmaceutical approach will almost always be covered by insurance. Elemental diets require compliance, and if the patient’s family cannot afford the formula, the physician is unlikely to recommend the diet.

“I’m not going to say that in any way, shape, or form an elimination or elemental diet is easy by any means. It is very challenging and does require a team approach,” says Nicole Perna, RD. Though elemental diets may be a hindrance to a child’s lifestyle, it will resolve the issue in almost all cases, according to Shuker. It will remove most of the eosinophils from the esophagus and keep them from returning.

However, there are circumstances in which dietary therapy is unsuccessful. Most RDs are not opposed to using pharmaceutical therapy—just not as a first option. “Steroids are very effective. They work, but when you stop steroids, the cells come back. Sometimes people will want to take a break from dietary therapy—during vacations or holidays. It doesn’t happen often, but it happens,” says Shuker.

Choosing the Best Option
Christopher Liacouras, MD, of the Children’s Hospital of Philadelphia, says that quality of life is the main concern when choosing a treatment option. There is no right answer for all patients collectively—it depends on each patient’s level of discomfort and subsequent willingness to change his or her lifestyle.

Although Liacouras ultimately supports nutrition therapy, he argues that patients who are very ill, are losing weight, and can’t function on a normal level should consider pharmaceuticals to alleviate their symptoms. Nutrition therapy does work, but the lifestyle associated with making such drastic dietary changes doesn’t work for everyone. According to Liacouras, “Some people would just rather not be on tube feeding or an elemental formula.”

It’s not that changing dietary habits wouldn’t work for these patients—they just choose to not travel that route. Some patients, for various reasons, would simply rather continue their regular eating patterns with the help of medication. While not a long-term option, the aid of pharmaceuticals is an option required for some and chosen by others.
Perna suggests the best route to successfully combating EE is to present the treatment options in an unbiased manner to the patients and their families so they can decide “not based on what sounds easier but what is actually a better choice for their lifestyle.

“We need to let the family decide what’s best for them and what they would like to do, whether it be a diet or not. We need to take extra care and present all the options that we think are appropriate, and it’s up to us [as dietitians] to decide what’s appropriate, and then to present those appropriate treatments,” says Perna.

If nutritional management is the chosen treatment program, it’s important that a team approach is taken and that doctors are working in conjunction with RDs. “RDs are vital to the success of the process because dietitians are your nutrition experts. They’re going to know how to make sure the kids know which foods may have an ingredient in it that may affect the eosinophils,” says Perna.

Perna suggests removing the eliminated foods from the household to remove temptation. Hopefully, in turn, patients will make healthy decisions outside the home as well. “It definitely takes all the clinicians, the parents, and the child [for successful treatment]. Compliance is one of the biggest problems of staying on a diet like this,” says Yannicelli.

“The good news is that there are so many more products available these days that are free of certain allergens. The kids who play sports can have energy bars that are wheat-free, soy-free, and egg-free. Education is key. We work with every family on an individual basis to recommend products and find ways to make a restricted diet more liveable,” says Shuker. “It will still be hard, but there are people and products to help.”

Yannicelli says that most clinicians who support pharmaceutical treatments don’t do so because they are against nutritional therapy. They do so because nutrition management takes a complicated and labor-intensive team approach, and many physicians simply don’t have the time. “You have to individualize [the nutritional management] for any patient with a chronic disorder who’s on a diet. That just goes with the game,” says Yannicelli. “But if you take a team approach and you have a great dietitian, the diet for a patient with EE is very doable ... and you have to weigh that with the long-term effects of drugs,” he adds.

To reach ultimate success, education, communication, and advocacy are paramount. “It’s really just a matter of educating the families. The big thing in food allergies, or any field really, is focusing on what the child can have,” says Shuker. “Communication is key. It’s crucial to developing an effective plan and staying on the same page.”

“The message has to be ‘how are we going to do this?’ rather than ‘this is going to be hard to do … let’s do something else.’” says Yannicelli.

According to Shuker, “Dietary manipulation will remedy the problem in almost every case of EE that results from a food allergy. Sometimes we need to use steroids, and we will if we need to.” She recommends using steroids when necessary, but relying on nutrition therapy as the first course of action. “We do not recommend nutrition therapy for these patients merely because we're dietitians; we recommend it because it works.”

— Valerie Yeager is an editorial assistant at Today’s Dietitian.

References
1. Silverman RG. New Discovery Gives Buffalo Grove Girl Some Hope. Chicago Daily Herald. February 10, 2006.

2. American Partnership for Eosinophilic Disorders. Available at: http://www.apfed.org. Accessed March 28, 2006.

3. Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116:536-547.

4. Arora AS, Yamazaki K. Eosinophilic esophagitis: Asthma of the esophagus? Clinical and Gastroenterology and Hepatology. 2004;2:523-530.

5. Food Allergies May Cause Chronic Vomiting. Newswise. Children’s Hospital of Philadelphia. November 4, 2003.

Helpful Online Resources for Families
• Allergy & Asthma Disease Management Center, www.aaaai.org

• American Partnership for Eosinophilic Disorders, www.apfed.org

• Children’s Hospital of Philadelphia, www.chop.edu

• Cincinnati Children’s Hospital Medical Center, www.cincinnatichildrens.org

• The National Eosinophilic Enteritis Disease Foundation, http://c4isr.com/NEED