Food Allergy and Eosinophilic Esophagitis

There is an excellent, easy to read review on this topic in the January, 2010 edition of the Cleveland Clinic Journal of Medicine (volume 77, number 1, pages 51-59)written by Sandra Hong and Nicola Vogel. As a review article the authors bring together a number of concepts from an evaluation of 58 perr-reviewed publications on this very interesting and frustrating subject. I will highlight the important and noteworthy issues. The text in italics are my comments on this topic.

Key Points

Food allergies can be classified as IgE-mediated, non-IgE-mediated, or mixed.
The diagnosis is made from a complete history and performing directed testing.
Despite new developments in treatment, for now it is only avoidance.

Purpose of the article

The purpose of this article is to review the current state of knowledge regarding the mechanisms, the diagnosis, and the treatment of food allergy and eosinophilic esophagitis.

Background

Food allergy affects 6-8% of children and 3-4% of adults. The prevalence of food allergy is increasing.

Any food can cause a reaction. There are a few foods that account for most reactions; cow’s milk, soy, wheat, eggs, peanuts, tree nuts, fish, and shellfish.

Most food allergy presents in the first few years of life.

Almost 80% of children resolve allergies to milk, egg, wheat, and soy. Far fewer resolve tree nut allergy (about 9%) and peanut allergy (20%). Allergies to fish and shell fish tend to persist into the adult years.

A major risk factor for the development of food allergy is a family history of allergy. The presence of allergy in the parents, not extended family member is the risk factor.

Becoming allergic or tolerant

Food allergy may be more prevalent in children due to; an immature gut barrier, low IgA levels in the gut, lower stomach acid levels (high pH), and low levels of digestive enzymes. There are also immune mechanisms in play that suppress an immune response that can lead to developing a food allergy. Normally, the immune system works to achieve food tolerance. Alterations to the immune system checks this drive towards tolerance and can lead to sensitization and food allergy.

Factors that contribute to food allergy

The dose of the food
The structure of the food
Processing of the food
The route of the initial exposure
The gut flora (bacteria in the gut)
The acidity of the stomach
Genes

High doses and low doses of food can lead to tolerance (no allergy), but how this happens varies to the food. Food allergens that are soluble (dissolve) are less sensitizing. Dry-roasted peanuts are more allergenic than raw or boiled peanuts (less soluble).

Gut flora refers to bacteria in the gastrointestinal system. Current research with germ-free mice suggests that they are prone to develop more food allergy or fail to develop food tolerance. The use of antibiotics in these germ free mice leads to the development of sensitization to food and subsequent food allergy. The acidity of the gut may be too high not allowing for proper digestion of food. The use of antacids increases the risk of developing food allergy.

Types of Immune Responses to Food

Metabolic- lactose intolerance
Pharmacologic- chemicals/contaminants
Bacterial- food poisoning
Psychological- food aversion
Immunologic- allergy (IgE, non-IgE, mixed)

The Diagnosis of IgE-mediated Food Allergy

The most important aspect in making the diagnosis is the history- NOT THE LABORATORY RESULT!

Food allergy is not subtle. The appropriate questioning will tease out the exposures.

What are the potential food culprits?
How much was eaten?
What was the timing between exposure and symptoms?
What were the symptoms- are they consistent with an IgE-mediated reaction?
Any related factors- exercise, alcohol, medication use

The symptoms of an IgE-mediated reaction (predictable by allergy testing) will generally occur soon after the exposure, but may be delayed for a few hours.

The symptoms of a non-IgE-mediated reaction will occur several hours to days later.

The ‘gold standard’ for the diagnosis of a food allergy is the double-blind, placebo-controlled food challenge.

Allergy Testing- Commercially available skin prick tests are a rapid and sensitive way to screen for food allergy. Negative allergy skin prick tests have more than a 95% negative predictive value- when I show that the skin test is negative to a food, I have a 95% chance of being correct and 5% chance of being wrong with this study.

The positive test indicates the presence of IgE antibody against the food and SUGGESTS a clinical food allergy. The specificity of the test is 50% making a positive result more difficult to interpret than the negative skin test result. This is why we need to be careful in selecting allergy tests.

The size of the skin test response does not necessarily correlate with the potential severity of a reaction- You cannot say a child is very allergic based on the size of their test. You can say that they make a significant amount of antibody.

Allergy Testing- Immunoassays

DO NOT USE THE WORD ‘RAST’ ANY MORE. The tests no longer use radioactive materials. They are tests for specific IgE.

These blood tests for allergy are generally less sensitive, more expensive, and the results are not immediately available.

Threshold values for food specific-IgE have been established for a few foods. When the value exceeds the critical cutoff value, there is an increased risk of a reaction. Only a few foods have these critical cutoff values established.

Note that an undetectable specific IgE by an immunoassay has a low negative predictive value. Reactions can occur in 10-25% of patients who have undetectable specific IgE to a food.

Managing Food Allergy

Current management involves the following. Anything else is experimental.
Avoidance
Education
Medical alert jewelry
Medications for reactions- epinephrine, diphenhydramine

Experimental treatments

Humanized monoclonal anti-IgE- use limited in food allergy
Oral Immunotherapy- recent work suggests this may induce tolerance

The Oral Immunotherapy must be considered investigational- more studies are needed to address the effect and the safety of this form of treatment.

The Role of Food Allergy in Eosinophilic Esophagitis (EE)

This is a clinical condition that has increased in frequency. Symptoms include; difficulty feeding, failure to thrive, vomiting, epigastric/chest pain, dysphagia, and food impaction.

The diagnostic criteria are;

Clinical symptoms
>15 eosinophils per high powered field on biopsy
No response to a proton-pump inhibitor for 1-2 months or a normal pH probe study
Exclusion of other causes

The cause of this condition is not completely understood. Atopy (tendency towards allergy) has been implicated as a factor with >50% of EE patients having an atopic condition. Most patients improve with either dietary restrictions or elemental diets, so food sensitization appears to play a role.

A review of responses to dietary manipulation revealed the percent of patients who had symptom improvement/resolution from 96-100% in four studies that used an elemental diet and 57-94% improvement/resolution with restricted or 6- food elimination diets. A study with only wheat or rye avoidance demonstrated only 17% with improvement/resolution.

How to identify potential food triggers of EE

Potential food triggers have been hard to identify in EE.

A recent consensus report did not recommend in vitro food allergy testing (specific IgE) due to a lack of positive or negative predictive values for food-specific IgE level testing in EE. Furthermore, the absence of IgE does not eliminate a food as a potential trigger. Non-IgE mechanisms may play a role.

With skin prick testing, 2/3 patients with EE had positive reactions to at least one food such as cow’s milk, egg, soy, wheat, and peanut, but also to rye, beef, and bean.

Atopy patch testing may show some usefulness in identifying foods that may elicit a non-IgE response. Currently these types of tests are not validated and have only been evaluated in a very small number of studies (these are all from the same research group). There are no standardized materials, methods of application, or interpretation of results. Also, importantly there has been no study that has included a control (non-sick) population to validate atopy patch testing.

Reviewers comments- This was a fun article to read and review for you. Two huge areas, food allergy and eosinophilic esophagitis were condensed in a very scholarly fashion. This is a contemporary review that included many references. It eagerly and cautiously points out strengths and weaknesses of what is going on in diagnostics for food allergy problems. I applaud the points made about blood tests for allergy especially the limitations for their use in EE. There is interest in patch tests for food reactions, however the major proponents of its utility tend to be from only one group that publishes on the topic. The patch testing for foods does need validation in the proper population.

For those of you who are interested in food allergy, you should look at this article.

FEL

January 13, 2010 Tags: Food Allergy Epidemiology Posted in: Food Allergies, Gastrointestinal Allergy