Peanut Allergy vs. Peanut Sensitization

Allergy or tolerance in children sensitized to peanut: Prevalence and differentiation using component-resolved diagnostics.

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.

January 24, 2010 · fleickly · 4 Comments
Tags: , ,  · Posted in: Food Allergies, Phadia Allergy Tests

4 Responses

  1. Rita - August 23, 2010

    Are children who are sensitized to peanuts more likely to develop a peanut allergy with continued exposure?

  2. fleickly - August 23, 2010

    Very interesting question. Sensitization means making an antibody against something. In this context, a person with a positive skin test or a positive blood test for peanut has evidence that an IgE antibody is being made.
    Now for that person to be allergic, symptoms will occur with exposure. So to be allergic you have the symptoms consistent with a type I allergic reaction and evidence of having the antibody.
    One of my postings reviews an article about misdiagnosing peanut allergy in 2/3 children. The thought here is that they are sensitized to other proteins and perhaps not those associated with servere allergic reactions.
    Patients who ‘tolerate’ peanuts- eat them with great regularity, may have a positive allergy test to peanut. The theory is that as long as the immune system sees the peanut proteins with some frequency the features or symptoms of allergy do not occur- they are tolerant.
    In a round about way to answer your question- if a peanut sensitized child eats peanuts daily, I would think that child is ‘tolerant’ to the peanut. If the exposure to peanuts is stopped or becomes very sporadic, then ‘tolerance’ may be lost and allergy can happen.
    Phadia is working on an assay (see prior reports on Microarray) that may help to sort out what proteins the child is reacting to. This may be of great help.
    We have seen 321 children with a positive skin test to peanut since January 1, 2009- very few of the group who only had an allergy test for peanut (no history of a reaction to peanut) went on to have an allergic reaction.
    Great question- as you can see the answer is not clear-cut. We are still looking for more definitive statements from those who are doing peanut research.
    Thanks for posting the question,
    FEL

  3. Rita - August 23, 2010

    I was unable to open the link about misdiagnosing peanut allergies…but would like to read it. My 2.5 year old has never actually eaten peanuts, his only exposure would have been via breastmilk and prior to birth. At 18 months he was picked up by someone who had just eaten peanuts and developed hives. His skin prick test was positive. He did have a blood test for all major allergens several months earlier (with a different doctor than the skin prick) which was negative. Would a child who is sensitized to peanuts react with hives when their skin comes into contact with peanut proteins or is that more indicative of an allergy? I am just curious if we should try to pursue CRD at our next appointment or if I am just being overly hopeful that this may not be an issue for him…

    Thanks!

  4. fleickly - August 23, 2010

    From the home page you can scroll down to reach the article. Or you can use a title/topic link on the left for food allergy topics. Contact urticaria (hives) can occur with many foods and with many other items. I have a few patients who can eat a P&J sandwich and do just fine. However, if the sandwich touch the skin (usually the cheeks next to the lips) they get hives. Some foods were not meant to be worn. Looking at the specific IgE via a blood test may help predict the chances of a reaction. Your pediatric allergist can select the appropriate test for peanut. The allergist should have a handle on what levels of peanut specific IgE have a significant risk of a reaction. If the sensitivity/allergy is outgrown the specific IgE levels decrease over time.
    FEL