Allergy Testing for EoE & EGE

I have spent the last several days researching information and trying to compose this blog regarding the allergy testing Tylyn will receive at the end of this month. I’m anxiously waiting for the testing to be done, as her trouble swallowing has become increased and itchiness is driving both her and me bonkers.

True to everything Eosinophilic Eosphagitis (EoE) and Eosinophilic Gastroenteritis (EGE), there is little information out there, but what is published is conflicting.

Almost all the data supports that EoE is caused by allergies or more clearly a food hypersensitivity, as a true food allergy requires the presence of IgE antibodies (to be explained below). The treatment for children results in the following remission rates of EoE below.

Diet related:

Amino Acid-based Formula (Elemental diet)- 96-100%

Empiric Elimination (6-food elimination)- 50-74%

Direct Elimination Diet (SPT & APT based)- 69%

Pharmaceutical Related:

Systemic- 93-95%

Topical (flucticasone, budesonide)- 50-95%

Now if I have caused confusion, let me explain some of the definitions above.

Types of allergy testing for EoE:

SPT- Skin Prick testing (or Scratch test)- Used for over 100 years,  this is the most commonly performed allergy testing and can be done in a physician’s office setting. This is great for identifying  Type I Hypersensitivity . With this test a few drops of the suspected allergen (ex. food, pet dander, dust, pollen, dust mites etc) are pricked on a patient’s skin, with the most ideal location being the forearm. Results are available in a few minutes and can be performed on patients as young as four months.

Skin Prick above testing with several positive reactions
 Histamine is the positive control.

Some doctor’s offices do testing on the back, though it is a more sensitive area than the forearm. I had allergy testing done as a child and they performed it on my back. When it was done as an adult they did it on my upper arm near the bicep area.

This test is performed also with a control to ensure that there are not false negatives.

However, this particular test is not 100% accurate as a negative response maybe attributed to the following factors:

-         Not enough concentration was used to evoke a response in the body

-         The test is technique dependent

-         The allergy is non-IgE- mediated (see Patch Test below) such as a reaction to food additives

In addition the following points must be considered:

-         SPT is for identifying an IgE-mediated allergy, meaning that the allergic response is immediate and rapid in onset, may present themselves as wheezing, hives, itching and anaphylaxis.

-         A positive SPT may also indicate a food sensitization but not necessarily a food allergy. 50% of patients with food sensitization are tolerant to food when ingested.

-         Foods most identified with SPT are: cow’s milk, egg, peanut, shellfish, peas, beef, fish, rye, tomato and wheat.

-         Fewer reported successes when an elimination diet is based on the SPT for EoE patients

-         Requires stopping of certain allergy medications to perform testing

-         Yields only a positive or negative result.

-         Some food allergens such as: fruit and vegetable allergens are unstable and denature very quickly.

-         Negative result very reliable, positive result is reliable in only 50% of patients

Radioallergosorbent test (RAST or newer versions called ImmunoCAP)- Also utilized for Type I hypersensitivity food allergies, this is a blood test that specially measures IgE in the serum for a suspected allergic. Posing no risk of allergic reaction which can occur with SPT, this can be used as an alternative in the case of a possible anaphylactic reaction, in addition patients do not have to stop any allergy medications.

This test is more expensive than skin prick testing, yields the same results, is applicable to over 150 foods for a single sample, provides the best reproducibly and is extremely sensitive due to its high specificity. Researchers have been able to provide “predictive values” for some of the more common foods.

However, this particular test is not 100% as a negative response maybe attributed to the following factors:

-         Not enough concentration was used to evoke a response in the body

-         The test is technique dependent

-         The allergy is non-IgE- mediated (see Patch Test below) as some food additives are

In addition the following points must be considered:

-         RAST is for identifying IgE-mediated allergies, meaning that the allergic response is immediate and rapid in onset, may present themselves as wheezing, hives, itching and anaphylaxis.

-         Fewer reported successes when an elimination diet is based on the SPT for EoE patients

-         RAST testing can show the amount of IgE present to each allergen.

-         Negative test yields a 90% chance of being non-allergic but a positive reaction may not necessarily confirm and allergy but rather a sensitization (less than 50%)

-         Because IgE is an antibody response it has a memory, which means it may indicate that a patient maybe has positive IgE years after exposure and after they have outgrown the allergy.

-         Usefulness in low-level (1-5uL) sensitization is unclear

RAST Rating, Response & Levels of IgE

0          <0.35                      Absent or undetectable

1          0.35-0.69                Low Level

2          0.70-3.49                Moderate Level

3          3.50-17.49              High Level

4          17.50-49.99            Very High Level

5          50.00-100.00          Very High Level

6          >100.00                   Extremely High Level

Atopy Patch Test (APT): A newer technique and more controversial, this type of testing is used for identifying Type IV Hypersensitivity.  Because this testing is specific for non-IgE mediated responses, or more commonly known as cell-mediated responses, the first step to is to re-expose the patient. A cell mediated response appears 7-14 days after initial sensitization and reactivates within 2-5 days of re-exposure. 

With this test a few drops of the suspected allergen are placed in an aluminum chamber (or called the Finn Chamber) that is adhered to tape. They are then placed on the patient’s skin and left on for 48 hours with, with the most ideal location being the back. After the two required days the chambers are removed and results are read. They are also re-read at 72 or 96 hours. If applied correctly by an experienced physician’s office or facility, reliable and reproducible results can be obtained.

Above: APT with Chambers taped to patient's skin



Above: Several positive results from APT



However, this particular test is not 100% as a negative response maybe attributed to the following factors:

-         Not enough concentration was used to evoke a response in the body

-         The test is technique dependent

-         The allergy is IgE- mediated (see Skin & RAST testing above)

In addition the following points must be considered:

-         APT is for identifying a non IgE-mediated food intolerance, meaning that the response is delayed and may take several days or a week to present a response.

-         A positive APT may also indicate a sensitization at some point of the patient’s life.  

-         Foods most identified with APT are: wheat, corn, beef, cow’s milk, egg, chicken, rye, soy, oats, barley and potato. .

-         APT is not standardized for the type of foods to use (fresh versus extract)

-         Requires stopping of certain allergy medications and steroids to perform testing

Results are reported as:

Negative (-)

Irritant Reaction (IR)- Follicular pustules & burn like reactions

Equivocal/uncertain (+/-)- Pink area under the test chamber

Weak Positive (+)- slightly elevated and pink or red plaques usually with mild vesiculation

Strong Positive (++)- are ‘papulovesicles’ or papules that change into a blister

Extreme Reaction (+++)- spreading redness, severe itching and blisters or ulcers

Problems food that are present with EoE & EGE:

Food Allergy:  Invokes an immune response due to a reaction with a food protein. This occurs when the immune symptom mistakes protein of foods as being harmful causing the body to have a reaction. An example of non food allergies is latex sensitivity.

This is also called IgE mediated immune response. Food Allergies can range from mild to severe with a more rapid onset of symptoms ranging from seconds to one hour.  Classified as a Type I hypersensitivity it is an antibody mediated response.

Common symptoms of food allergies:

Itching (mouth, lips, tongue, throat, eyes, skin)

Hives

Difficulty swallowing

Runny or congested nose

Wheezing or shortness of breath

Nausea

Vomiting

Abdominal pain/cramps

Lightheadedness

Fainting

Anaphylaxis

Causes: Mostly food and directly related to the food protein in the case of eggs, where patients are most frequently allergic to the white instead of the yolk.  

Over 90% of the food allergies are attributed to eight foods: milk, eggs, peanuts, tree nuts, seafood, shellfish, soy and wheat. Allergies can also be regional in the case of increasing number of rice allergies in East Asia. In addition allergies to seeds, especially sesame are on the rise.

Other foods that can have allergenic proteins associated with them besides the ones listed above are derivatives of those foods, for example cheese, vegetables, spices, fruits, synthetic and natural colors and chemical additives. In addition patients that have a birch allergy may react to additional classes of families such as fresh apples, cherries and peaches.

There is also data which supports cross reactivity. Some patients who are allergic to cow’s milk also show sensitivity to soy-based products. Often patients with latex allergies develop allergies to foods such as bananas, kiwi, avocados and other foods.

Diagnosis: Easier than food intolerances because reactions are more apparent, linking ingestion of food or contact with allergen to symptoms. SPT, RAST and food challenges are the most common types of allergy testing.

Food Intolerance (Food Sensitivity): A negative reaction in response to food, beverage, additive or compound found in food (like dye or preservative) that produces symptoms in the body. This also can include a gastro-intestinal response to foods.

This is also called Non-IgE mediated food hypersensitivity. Non-IgE or Food Intolerance is more chronic and more difficult to diagnose. Unlike a food allergy, intolerance symptoms usually begin about a ½ hour after ingestion but symptoms may be delayed for 48 hours. Classified as a Type IV hypersensitivity it is a cell mediated response.

Many of these food intolerances are directly related to the food protein as shown in milk-soy protein intolerance (MSPI). MSPI is a non medical term that describes a food intolerance to milk and/or soy protein during infancy and early childhood. Tylyn had this.

Common symptoms of food intolerance:

Skin Rash

Hives

Dermatitis

Eczema

Asthma

Unproductive Cough

Sinusitis

Nasal Congestion

Abdominal Cramps

Nausea

Gas

Intermittent Diarrhea

Constipation

Anaphylaxis (less common)

Causes: Both natural and artificial ingredients, chemical intolerances, viral infection, illnesses to environmental exposure, deficiencies in digestive enzymes, and autoimmune diseases such as Celiac disease which results in gluten intolerance. Food sensitivity may be linked to chemicals mimicking hormones, as it occurs more commonly with women. This is perplexing due to EoE occurs in males more than females.

Diagnosis: More difficult than with allergy or IgE mediated immune responses. SPT & RAST testing are not used as diagnostic tools for food intolerance as it is a non-IgE mediated immune response. .

Alternative testing includes APT testing due to the delayed reactions that can not be captured with SPT. The least expensive and less scientific elimination or empiric diet can be followed, although it may take up to 6 weeks before relief of symptoms can be seen.

In addition, IgG testing and  ELISA/ ALCAT (or ACT) testing for IgG-mediated immune response can be used. This is mostly for delayed allergic reactions of Type III hypersensitivity.

Controlling a patient’s diet for food allergies/sensitivities are the following strategies:

Elemental Diet- is a liquid diet that is usually composed of amino acids, fats, sugars, vitamins and minerals, providing all the nutrients the body needs. It is ingested or in more severe cases, uses of a gastric feeding tube or intravenous feeding This diet lacks whole or partial protein due to its ability to cause an allergic reaction, therefore put no stress on the digestive system. Very harsh and not very palatable.

Empiric Diet- The big 6- Removal of  the most common food allergy triggers from the diet: dairy, nuts, wheat, eggs, soy, and seafood.

Direct Elimination Diet- These allergic foods are removed from the diet based on SPT and APT-based testing.

Worth mentioning here is 70-80% of patients with EoE have had postive SPT or RAST results. Patients with atopic EGE often have multiple food sensitizations with positive SPT. However of the three subtypes of EGE, mucosal, muscularis and serousal, the first tend to have IgE-mediated food allergies.

Tylyn's allergist (the nice one) has decided to include chicken in the patch testing based on my data from Tylyn’s food diary. Although they have not adminstered this with the patch testing she will contact a colleague at CHOP (Children’s Hospital in Philadelphia) about obtaining the material to test.

As a mom and scientist I am very interested in the tests and the results.

CH in Denver called today as well. Tylyn has been rescheduled for November. She advised me that Tylyn will have to undergo repeat allergy testing while she is at the facility but understands that I am trying to provide some temporary relief until our appointment. In addition she did mention there are only so many tests that can be performed per day and there is a lot of testing to be done.

After all my research do I believe Tylyn has a “food allergy”? Maybe, maybe not. I am leaning more towards food intolerance due to symptoms and lack of any responses on her SPT performed previously.
Sure her results revealed a high allergy to dust mites, pollen and a few other things but nothing other than a slight 2+ reaction of milk that was subsequently proven negative by a RAST test. As confirmed the SPT is false positive in 50% of the results.

As Tylyn counts down to her new job and I count down to getting answers. Thirteen days.