Eosinophilic Esophagitis – Children vs. Adults

Eosinophilic esophagitis in children and adults: what is the same and what is different.

Straumann, Aceves, Blanchard, Collins, Furuta, Hirano, Schoepfer,Simon, and Simon

This was a very interesting review article on a very frustrating clinical condition, Eosinophilic Esophagitis (EE). There were nine authors from the United States and from Switzerland. The specialties represented by the authors were gastroenterology, pathology, allergy, dermatology, and pharmacology. This was a very interesting diverse mix of expertise for this topic. Italics will be used for my elaborations.

The article starts with a historical review. Case reports appeared in the early 1990s on what was to be EE. Over the last 10 years it has been shown that this is a T-helper cell, type 2 (Th2) inflammatory cell condition or response. The inflamed esophagus repairs or remodels in response to the inflammation. The remodeling causes abnormal functioning of the esophagus. Symptoms arise from food impacting in the inflamed, remodeled esophagus.

The authors report on concurrent allergic conditions such as allergic rhinitis, asthma, atopic dermatitis, and atopy (positive allergy tests without clinical correlation). The point is made that classic allergic problems are seen along with those who struggle with EE. A difference between the children and the adults who have EE is the propensity for this to be a food antigen-driven condition in the child, whereas in the adult the tendency is towards this being due to inhaled allergens. This is a very interesting separation.

The introduction of the paper refers to the 3 Ds of therapy for this condition; drugs, diet, and dilation.

Symptoms- in adults and teenagers there can be vague symptoms, compensatory behavior, or flagrant episodes of food impaction. In this group, the diagnosis can be delayed for 4-5 years. The complaints just do not point to any one clinical condition.

In children there is a wider array of presentations including; irritability, feeding problems, vomiting, and abdominal pain. The older child may have more of the adult presentations with dysphagia, heartburn, or food impaction.

Symptoms in Children

Abdominal pain
Chest pain
Heartburn
Coughing
Food sticking in the esophagus
Food refusal (eating is associated with discomfort)
Choking/gagging
Nausea
Regurgitation
Sleep difficulties
Throat pain

Symptoms in Adults

Food sticking (hard to pass a food bolus)
Food impaction (the food bolus does not move)
Retrosternal pain (mimicking heart issues)

Physical examination

You really cannot evaluate the esophagus on a physical examination. However, there may be features of concomitant allergic problems such as asthma, atopic dermatitis, and nasal allergy that are amenable to examination. A child may have problems with failure to thrive.

Laboratory Evaluation

A blood count may show high levels of the inflammatory cell involved with the condition- the eosinophil. Percent eosinophils can range from 5-50%. About 70% will have an elevation of IgE- the antibody that mediates allergic conditions.

Endoscopy

This is the first diagnostic step in the work-up of eosinophilic esophagitis. You have to go into the esophagus to see what is going on and to perform a biopsy. In children active inflammation is usually found. In adults the inflammation appears to be more chronic- of longer duration.

A biopsy is needed to confirm the diagnosis.

Immunopathogenesis

The authors refer to a landmark study published in 2001 that demonstrated what immune cells are involved in EE. Biopsies show the eosinophil, T-cells, B-cells (lymphocytes), and mast cells which have IgE linked to the surface. These findings point to the possibility of allergy being involved. Links with atopy have been demonstrated, however there is an intrinsic (non-IgE mediated) form of the condition seen in both children and adults. In these cases, no relevant allergen was identified. The article has a very erudite discussion on the cells and mediators involved. At this point it is important to discern what a relevant allergen is. When an allergy test is positive and that food is removed from the diet two things may happen; improvement may be seen due to avoidance of a causative agent or no change due to the food being an irrelevant agent. If there is improvement with avoidance of a food and re-introduction of that food causes symptoms to return, then the food allergen is relevant. The food allergy test was positive however avoiding that food made no difference and symptoms did not return when the food was re-introduced. Food allergy tests are a starting point. Once positive food tests are discovered, the relevance of that food to the condition needs to be established.

Allergic Profile in Adults and Children with Eosinophilic Esophagitis

In the introduction to this section, the authors suggest that EE may be a new manifestation of atopy. (A new allergic condition has evolved.) For the children, this is a food antigen-driven condition with the majority responding to elimination of common dietary antigens (food protein that causes an immunologic reaction) and when the food is re-introduced, the condition returns (food challenge). Key points here are common dietary antigen. At one time I would skin test to those six foods that have been associated with well over 90% of food allergy in children; egg, milk, wheat, soy, peanut, and fish. Additional foods were added to our test array due to what others were reporting on. We got up to 25 foods that were tested. More recently, I hand the skin test sheet to the family and ask them to pick out foods that the child is actually exposed to. Relevance of exposure is important in selecting diagnostic studies. Food allergy panels include foods that are not usually or ever a part of the child’s diet. The best test for a food allergy is to perform a food challenge. There is no better way to establish relevance of a food trigger than to give the food and see what happens. One problem is that we do not have a surrogate for endoscopy/biopsy to see what is happening to the esophagus. Food challenges in the allergy clinic rely on symptoms.

The adult with eosinophilic esophagitis may also be driven by food however aeroallergen (inhalant allergens) is the predominant causative stimulus. It is pointed out that this observation follows the known shifts in allergic sensitization; children with more food allergy and adults with more respiratory tract allergy.

More than 50% of those with eosinophilic esophagitis have a history of atopy (positive allergy test). In the literature, the criteria and severity of the concurrent allergic conditions is not standardized. The criteria for these other conditions vary. The best estimates for the incidence of known allergic conditions are as follows;

Allergic Rhinitis- 40-75%
Asthma – 14-70%
Eczema – 4-60%

The point is made that the ranges are very wide.

Of note, despite this allergic tendency, immediate hypersensitivity to foods using guidelines for anaphylaxis is reported in up to 24%. This was an interesting point. I was unsure if 24% were indeed having signs and symptoms of anaphylaxis or did this refer to the point that for a food to cause an allergic reaction the criteria would be that with every exposure there would always be symptoms that would occur in a very short period of time after the exposure. Did the authors mean that 24% did have a real food allergy? This bothered me enough to pursue reference #36 . That reference is a letter to the editor. The article did not say anything about defining immediate hypersensitivity to food. In fact the words anaphylaxis and guidelines do not appear in the article. The letter has food sensitization in the population. This is an important issue- a critical reader who is concerned about the role of immediate hypersensitivity reactions to a food in EE should be able to review what the criteria were. Some other article must have the diagnostic criteria. The reference #54 is from Australia- it is this reference that shows that 24% of children with EE had anaphylaxis to a food. This paper also showed that food sensitization prevalence decreased as the age of the patient increased.

The literature shows that 24% can have anaphylaxis to food. However, what percent of children have a relevant food allergy (not sensitization) accounting for the EE?

Adults Eosinophilic Esophagitis and Allergen Sensitization

Reports indicate that elevated IgE is seen in 70% and other allergic diseases are seen in 77% of the adults with EE. In 63% of adults sensitized to food, cross-reactivity was seen. This was a different type of cross-reactivity. This concept can refer to problems between food groups- peanut sensitive patients cross-reacting to some of the tree nuts. Here the concept is aeroallergen and botanically related foods. For example grass as the aeroallergen and wheat and rye (both grasses) as the food allergen. However, in a small study of these adults, avoiding wheat and rye did not improve their symptoms. Recent work has shown that 86-93% of adults with this condition are sensitized to aeroallergens (point of sensitized vs. allergic) and 50-82% were sensitized to food. The common foods were;

Peanut
Soybean
Egg White
Cow’s Milk
Tree Nuts
Wheat
Tomato
Carrots
Onions

Pediatric Eosinophilic Esophagitis and Food Sensitization

Similar to what has been reported in adults more than 70% of the children has an elevation of IgE, the antibody that mediates type one allergic reactions. The track record on this measure, the total IgE, does not support the need to analyze or follow total IgE levels. A total IgE level is of no value in the evaluation of EE.

Children can be sensitized to allergens of the indoor and outdoor world. Grass pollen and mold (Alternaria) spore sensitization is seen in 26-37%. Fewer are sensitized to cockroach (16%) and house dust mites (19%). There may be seasonal changes with the symptoms of eosinophilic esophagitis, but the link between pollen and the presentation of the condition in children remains unclear.

Foods tend to be more of a problem with the children. The paper points out a continually perplexing problem with allergy testing for foods. The serum or blood tests finds more positives than skin prick testing, with the clinical usefulness and the clinical significance of the increased detection is unclear. At this time, we do not know what this means.

To date (up to the time the article was accepted-12-2011- not too long ago) there have been no studies published that document any correlation between the blood test values for food IgE with instigation(starting/causing) or propagating (continuing) EE. There are very few studies that use the blood tests results for any kind of elimination diet/intervention.

The patch test has been used to detect a delayed food reaction. Patch testing for food has been done for children with EE. The combination of skin prick tests and food patch test results has had a high degree of success in predicting food allergens that may trigger EE. The point is made that the patch test may help in creating a directed (a diet that focuses on foods that were positive by testing) elimination diet, the test (patch testing) still needs standardization and validation for its use in children with EE. Of note, certain foods have been commonly found to be positive with all three diagnostic measures (skin prick, serum, and patch). These foods are;

Milk
Egg
Wheat

These three were on my original skin test profile for food testin.

Using prick skin tests and patch tests the following foods were commonly positive with both techniques;

Corn
Beef
Chicken
Barley
Oat
Rice

This group of foods are more unusual and not commonly discovered when taking a history of cause/effect relationships with food exposures.

Importantly, the article points out that an empiric (this is a very appropriate word, it pertains to the use of practical experience to gain knowledge) elimination diet- the child is not given cow’s milk, egg, soy, wheat, peanuts, tree nuts, fish, and shellfish (with the exception of the shellfish and tree nuts, this empiric diet are those same foods that have been established a long time ago as the common culprits for food allergy in children.) followed by reintroduction has shown that four foods are the major culprits in most children- milk, wheat, egg, and soy. These are the ones to stay away from and see if there is improvement.

Treatment of EE

It was pointed out that there is a debate regarding the endpoint of treatment. Should the program be directed against symptoms or resolution of the abnormal biopsy. The authors give three reasons to do both- make the symptoms go away and clear the inflammation;

To improve the quality of life

To reduce the risk of injury to the esophagus

To prevent esophageal damage

Treatment is the 3 Ds- Drugs, Diet, and Dilation.

Drugs-

Proton pump inhibitors-never to be used alone

Steroids- oral prednisone, topical fluticasone

Leukotriene modifiers- not recommended

Biologic agents/Immunosuppressants-mixed reports on preliminary use

Diet

A 1995 study, noted as a landmark study by the authors, demonstrated the role of food in pediatric EE. The use of an elemental formula was found to be highly effective in >96% of children.

One previously mentioned problem is the occurrence of multiple food sensitizations determined by skin prick testing or by blood testing. These are not accurate and better diagnostics are a real need to help these children. Looking at the results of skin prick tests (not blood tests) combined with the patch test, the positive predictive value varied between 50-92% and the negative predictive value varied 41-100% for a variety of foods. The positive predictive value is the probability that the food causes the illness when the test for that food is positive. The negative predictive value is the probability that the food does not cause a problem with the test for that food is negative. The wide variation in predictability underscores the need for standardizing and validating the tests that are used for food allergy in managing EE.

The empiric diet- complete elimination of the common allergenic foods- milk, egg, soy, wheat, peanut, fish, shellfish, and tree nuts was successful in clearing the abnormal biopsy and relieving symptoms in 74%. When symptoms returned, milk, wheat, egg, and soy were the most common problematic foods. Milk was 18 times more likely to precipitate/cause a reaction than any other food.

This was a great article to review. There are many more questions out there than answers. There are real needs for better tests to find the relevant causative agents. This review focused on the allergy issues.

FEL 5-3-2012

May 2, 2012 · fleickly · No Comments
Tags: Article Review, Eosinophilic esophagitis, Food Allergy, Gastrointestinal Allergy · Posted in: Allergies, Article Review, Food Allergies, Gastrointestinal Allergy