Last week I was interviewed by a reporter from the Wall Street Journal. The topic was food allergy. The reporter came across this website and thought that I be a good resource for her article. We had a delightful talk that went on for 45 minutes. Questions were asked about the increase in food allergy; is it real or is it possibly due to the over use of diagnostics (allergy testing).

Needless to say I was excited about the prospect of being quoted in the Journal.

My hopes were dashed. The reporter had to cutback on material. My name did not appear in the article. The article was very well done and did quote a number of outstanding leaders in the field of food allergy (Drs. Hugh Sampson and Robert Wood).

I do encourage you to read the article written by Melinda Beck.

FEL

N. Nicolaou, M Poorafshar, C Murray,  A Simpson, H Winell, G Kerry, A Woodcock, S Ahlstadt, and A Custovic.  Journal of Allergy and Clinical Immunology(JACI) 2010;125:191-7.

This article appeared in the most recent JACI. Almost as soon as I read the article, I began to put together this review (I am excited about the approach and ideas in this work). This paper states very clearly the problem of positive allergy tests for peanut (sensitization) and demonstrating clinical relevance- that is allergy to peanut. It addresses this problem using a new test for determining sensitization, component-resolved diagnostics.

Background:

          A few very important facts are noted about peanuts;

            1. Peanut is a nutritious and inexpensive food

            2. Peanut is one of the most common food allergies

            3. The prevalence of peanut allergy is increasing

            4. Peanut allergy is usually life-long

            5. Peanut avoidance is the current management of this allergy

            6. Accidental peanut exposure is common

            7. Peanut exposure in the allergic child can be life-threatening

Peanut allergy diagnosis issues:

            1. An accurate diagnosis is very important- sensitized or truly allergic?

            2. The gold standard for the diagnosis of peanut allergy is the

               ‘double-blind placebo-controlled food challenge (DBPCFC)

            3. DBPCFC are costly, time consuming, and dangerous

            4. The diagnosis is made with a suggestive history of what happens after exposure,

                supported by a skin prick test or by the determination of specific IgE in the blood

            5. These tests detect the presence of antibody (sensitization)

            6. Positive allergy tests does not equate to the presence of allergic symptoms after exposure-

                known as clinical allergy

            7. Current tests –both skin prick tests (SPT) and specific IgE tests (sIgE-blood) use crude peanut

                 extracts and contain a mix of the allergic proteins and non-allergic proteins that may

               cross-react with other allergens.

            8. Bottom line- peanut sensitization may not equal peanut allergy

Solving this problem:

            1. A new blood test to detect antibody production by the child to the important proteins in peanut that cause

                allergic symptoms has been developed

            2. This is called component-resolved diagnostics (CRD) – developed by Phadia

            3. This may be a more accurate tool to assess food allergy (vs. sensitization)

The purpose of the paper was to look at the CRD to correctly identify children with peanut allergy.

Methods:

A birth cohort of children enrolled in the Manchester Asthma and Allergy Study (Manchester, England) was evaluated. Information on exposure and reactivity to peanut was collected.  Peanut sensitization was measured by skin prick testing and by Phadia specific IgE.

There were 110 children (cohort contained 1085) who were sensitized and were asked to undergo a more extensive evaluation of their reactivity to peanut. This included more extensive history, skin testing, specific IgE, a DBPCFC, and the CRD.

The definition of peanut allergy included two very specific sets of criteria.

                        1. Sensitization and a positive oral challenge or

                        2. A convincing history and specific peanut IgE >15 kU/L and/ or a skin prick test that was greater than

                           an 8 mm wheal (this group did not have an oral challenge).

Results:

The cohort included 1085 children, 1029 were evaluated at age 8 years. There were 17 (1.6%) who had a history of peanut allergy.

Skin-testing was performed in 919 of the children with 47 (5.1%) having a positive SPT. Sensitization to grass pollen was noted in 59.6% of the children.

Blood studies were performed on 582 children with 71 (12.2%) having a detectable level of specific IgE to peanut. Grass sensitization was found in 67 (94.4%).

Overall, of the 933 children who had either a SPT or sIgE 110 or 11.8% were considered to be sensitized to peanut.

From this group of 110, 108 agreed to participate in the program. Seventeen did not consent to a food challenge. From the remaining 91 children, 12 had convincing histories and SPT/sIgE criteria to fit the definition of peanut allergy. Food challenges were performed in 79.

In the 79 oral food challenges to peanut, 66 had no symptoms with the exposure. Of the 13 who developed symptoms, 7 had two or more signs/symptoms and were declared peanut allergic. The breakdown on these number was- 66 were peanut tolerant and 19 were had peanut allergy (12 not challenged plus the 7 with a positive challenge).

The proportion of children with peanut allergy among those sensitized was 22.4%.

Peanut allergic and peanut tolerant children were compared.

            1. Asthma, eczema, and food allergies were more common in the peanut allergy group.

            2. Allergic rhinitis was more common in the peanut tolerant group.

            3. Peanut tolerant children had lower peanut sIgE and higher grass sIgE.

The CRD results differentiated the peanut allergic from the peanut tolerant group. The peanut allergic group had higher values to the major peanut proteins Ara h 1-3. The peanut tolerant group had higher reaction values to grass components. The response to the peanut protein Ara h 2 was the best discriminator.

A model was developed to discriminate between children with peanut allergy and peanut sensitization. The model misclassified only 2 (6.9%) with peanut allergy and 4 (7.7%) peanut tolerant children.

Conclusions:

The majority of children who have peanut sensitization based on SPT or sIgE do not have peanut allergy. The CRD may help the diagnosis of peanut allergy.

Reviewers Comments:

This is exciting work. In the practice of allergy we struggle with positive tests and their clinical relevance. The authors very clearly point out the differences between sensitization and allergy. The test makes no one allergic. The test only tells us that specific IgE is being made. The history and/or a food challenge help define that clinical relevance in making the diagnosis of food allergy.

Phadia has developed a very specific assay which will help in making the diagnosis of peanut allergy. I am excited about the prospects for CRD. Phadia’s science is at the cutting edge of food allergy and I look forward to using this assay for the large number of children we see in our practice with a positive test for peanut antibody. I have always had the greatest respect for Phadia’s science; it is the marketing part that I have issues with (topic of a few of my posts).

The authors point out the strengths of this study. They performed a very extensive evaluation and used the DBPCFC for verification.

The small number of children reported is a recognized weakness. The authors encourage replication of their work.

The study looked at 8 year old children. I wonder about why that age and from the paper my guess is that this was the most recent year of evaluation on their cohort. This birth cohort attended the clinic at ages 1, 3, 5, and 8 years. In our clinic we use age 5 as our cut-off for peanut challenges. At this age, most children are able to communicate with us regarding the subtle aspects of allergic reactions.

Look at the rate of positive tests for peanut. The testing of a population of children revealed that almost 12% will have a positive test for peanut.

The last paragraph in the paper goes as follows; “The majority of children within the general population with positive skin test or measurable serum IgE to peanut do not have clinical peanut allergy.

 The article did contain something that I strongly feel needs to be critiqued and clarified. The content expert for the quote was an associate professor of family practice at Michigan State University. Dr. Reinhardt is quoted as saying that the National Heart, Lung, and Blood Institutes (NHLBI) Guidelines for the Diagnosis and Management of Asthma 2007 advocates the use of the Phadia test to determine whether a person has allergies to common indoor allergens. He also states that too few clinicians are using this test.

 The first comment is out of context with other considerations that need to be addressed prior to ordering an expensive and perhaps unreliable laboratory test. The comment supports one commercially available product (fair balance). It assumes that this commercial product is the one the Guidelines recommend. As to the last comment regarding the use of the Phadia test for inhalant allergens, this is most probably because clinicians may be aware of the problems with this approach to allergy.

 The 2007 asthma guidelines do not specific the Phadia test for determining allergy. On page 168 of the NHLBI Asthma Guidelines Key Points clearly indicate that there are more steps involved- a relevant history, skin testing or in vitro testing, and an assessment of the significance of the test results. The guidelines do not mention specifically the Phadia test in the Key Points. This test has value, but only in the context of a patient’s history. The Phadia test for inhalant allergens is frequently falsely positive. In a recent national survey (JACI 2009;123:1163-9) 20% had symptoms of allergic disease. The Phadia test for inhalants demonstrated that 50% of the population had a positive test (for more on this article see ‘Incidence of Allergy in Children: Using Allergy Testing Panels (Pharmacia ImmunoCap) or Symptoms?’ one of my earlier posts on this topic). It is very important to point out that any test used in allergy only tells us that antibodies are produced. It is the history of symptoms plus the results of the test together that fulfill the criteria for allergy. A test result alone makes no one allergic and is only as useful as the history that supports it.

 In my opinion the reason why the Phadia test is not being used is because clinicians are aware of the need of taking a history, they dislike the obligatory panel of analysis offered by the Phadia panel, there is worry about the cost, and the test declares many more positive than actually have symptoms.

 Do we let the laboratory test dictate the diagnosis/treatment or the patient’s history matched to relevant laboratory studies to decide how to manage asthma?

I am old school- I make sure that I understand the history of the condition and the environmental exposures. From this I decide what tests for allergy are relevant and use testing to verify my clinical impression. Sometimes we don’t need to test. Sometimes we have to take the test results and re-evaluate the history and exposures to make sense of it all. Health care is expensive, laboratory tests for specific IgE is expensive. The consequences of questionable results taken out of context can have a cost as well. Allergen-environmental control is a big business. Consider the hidden costs of extra work, alteration of living environments, and the status of pets. Seek out consultation of experts who can sort through both a medical and environmental history and make sense of what to test for. You also need to consider what the gold standard is for the assessment of allergic sensitization and that is the allergen skin prick test. Look also to the credentials of the providers that you are working with.

Fred Leickly

A young African-American girl of 11 months presented upon the recommendation of her pulmonologist. The pulmonologist saw the need for a flu shot however there was some concern about a positive allergy test to egg. This little girl had a ‘Phadia Specific IgE’ set of food allergy panels performed for about 31 foods (the bill to the mother was >$800). The test was performed because of a concern for a constant runny nose. The child was tested to the usual suspects for food allergy in young children. The test array went significantly further. As I have talked about previously, because of the marketing of these allergy blood tests to include extra items (at more expense) these are in most cases irrelevent. Many of the foods tested are not part of a young child’s diet. The test included foods that this young lady of 11 months has never ingested; lobster, shrimp, tree nuts, shrimp, and clams to name a few. So in the end mother was at risk to pay for information that was not relevent to the child’s situation or exposures. There is also the argument within this case regarding the pursuit of a food allergy for the complaint of a runny nose in an 11 month old child.

The test for egg was 0.51 kU/L. The cutoff for a negative response is <0.35 kU/L. When you look at the literature for critical cut-off levels for doing an egg challenge, this value would indicate that the child will have a high probability of a negative and successful egg challenge.

Now the real kicker. As we all know there is no better test for a food allergy than the challenge; give the food and see what happens. We do have to be careful depending upon the history of previous reactions for those challenges. In this baby’s history she had been eating scrambled eggs without any problems. There was no history of a cause/effect relationship with egg exposure.

Now let us add in the variable of the flu shot. The flu shot contains egg protein. The recommendations from the CDC and the AAP are to not give the flu shot if there is a history of a severe reaction. This pertains to what happened when egg was ingested. It does not pertain to the presence or size of an allery test for egg. In this case, cooked eggs have been ingested without any reactions. So in my opinion, the history of egg exposure and having no serious reactions with that exposure should clear the way for the flu immunization. For those children who have serious reactions to egg but can eat heated egg products, there is a need for considering a desensitization for the fluogen. The egg in the vaccine is more like cooked egg (scrambled, hard boiled, over easy etc) than heated egg (cakes, cookies, muffins, and waffles). The history of eating products with heated egg should not be considered a ‘safe’ for those with serious egg reactions.

The children need to be immunized for this upcoming flu season.

My humble opinion,

Fred Leickly