When the presentations were finished, we had a panel discussion and took questions from the audience. This 20 minute Q & A went close to 45 minutes.

I have linked to Google Documents this presentation. It is entitled ‘Allergy Testing and Referral to the Allergist’.  This presentation was completed in April. You will notice slides with red titles. It has been a rule for speakers, especially in Continuing Medical Education (CME) offerings to not make changes. An article in JAMA was published the week prior to this presentation. In an attempt to provide the 50 learners at the seminar with the most up-to-date information, I quickly added these slides.

The reference list for the presentation (Food Allergy Testing Reference List)  is also available via a link to google documents.

FEL

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.

Authors: Amy Branum and Susan Lukacs

Reference: Pediatrics Volume 124 (6) December 2009

This title caught my eye. The impression in clinical practice is that more and more children have food allergy. This article looks at the prevalence of food allergy in children. I wanted to get this review posted this week. I am off to Santa Fe to moderate an AAP Practical Pediatrics Course. This AAP meeting is similar to the one I reported on earlier on this home page (Rhode Island). This meeting has an excellent cast of presenters. I plan to take notes and post a few updates upon my return.

Purpose of the article: To describe trends in the prevalence of food allergy and food allergy-related health care utilization in children in the United States.

Methods (how was this study conducted?): Data from a number of national health surveys were reviewed.

• Food allergy prevalence was evaluated in children 0-17 years of age from surveys conducted over the years 1997-2007. The question asked about food allergy was “During the past 12 months has the child had any kind of food or digestive allergy?”
• Blood tests for IgE antibodies to foods were taken from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. Specific IgE antibodies to peanut, egg, and milk were measured using the Pharmacia ImmunoCap 1000 System. Specific IgE to shrimp was measured only in children over the age of 6 years. The range of specific IgE values was 0.35 to 1000 kU/L.
• Information regarding food allergy-related visits to physician offices and hospital facilities was taken from two additional surveys.
• The results were analyzed using rather sophisticated statistical tools that included weighing the data for the analysis of trends.

Results (what the study found):

• The prevalence of reports of food allergy in children has increased from 3.3% in 1997 to 3.9% in 2007.
• Peanut IgE antibodies were found in 9.3%, egg IgE antibodies were found in 6.7%, milk IgE antibodies in 12.2%, and shrimp specific IgE was found in 5.2% of children.
• Ambulatory care visits for food allergies tripled between 1993 and 2006. Between the years 2003 and 2006 there were 317,000 visits/years to emergency departments and outpatient offices. Hospitalizations with a recorded diagnosis related to food allergy increased from 2600 to 9500 discharges/year.

Conclusions:

                These national surveys show that food allergy prevalence and/or food allergy awareness has increased in recent years.

Commentary:

                The authors point out a number of limitations in the study, however the major contribution here is reporting on what these surveys reveal about the parent’s report regarding food allergy. Food allergy may be rising however it is possible that the results may be due to increased food allergy awareness which is also a very good thing. This is a report of prevalence and does not go into the possible reasons for the increases.

                It is important to note that this was a survey. A simple question was asked. These were not absolutely proven cases of food allergy. The question included digestive allergy which has the potential to include a number of clinical conditions that are more common and may or may not be allergy; lactose intolerance, eosinophilic esophagitis, and celiac disease for example. This was a report on what a parent thought about food allergy in their child.

                The report has a few ‘between the lines’ issues as well. The conclusion is that food allergy and digestive tract allergy has a prevalence of 3.9%. The study also included a survey in which a blood test for allergy was performed. Using the blood test the prevalence of peanut, egg, milk, and shrimp ‘allergy’ exceeds the overall food allergy prevalence. The authors do point out this difference and are very careful about what is allergy and what sensitization to food is.  “Although serum IgE measurements cannot be used alone to determine the prevalence of food-specific allergies or to predict reactions to certain foods, they give an indication of increased atopy and risk for allergic reactions to food.” I define allergy and atopy on my allergy testing page.

                We also need to be a bit careful on the hospital data. The information on health care utilization included children who had a diagnosis of a food allergy. This did not necessarily mean that they were in the health care facility for a food allergy issue. There is a tendency in coding encounters to include as many codes as possible and to include codes that will help with health care utilization reimbursements.

                The statistical analyses on papers like this always fascinate me. During my MPH training I had a number of biostatistics courses. The weighing of the data is frequently done and when it is done, differences can be found. Sometimes it is interesting to see what the results were before any weighing. I have also wondered what went into the ‘weighing’ of the data. What elements of the data were assigned a ‘weight’ to make them work into the analysis?

                This was a nicely done paper and does answer some questions however as many quality studies also do it has us asking many more questions about food allergy in children.

Fred Leickly

I should be receiving my copy of the journal soon. I am concerned about how food allergy will be defined in the paper: will the diagnosis of food allergy be based on a history of exposure confirmed with appropriate allergy testing or will this be based on only laboratory results and no history?

As soon as I have this in hand I will post a commentary.

Fred Leickly

The story goes as follows. I have subscribed to a newsletter called ‘Bottom Line Personal’. This publication has short articles on a variety of topics. For example, the last issue has quips on investing, real estate, psychotherapy, painkillers, career starting, bed sharing, and dangers in your garage (as I listed these it made me wonder why I subscribe). There is a page that talks about the purpose of the publication which is to bring to the reader the best information from the most knowledgeable sources in the world in helping the reader gain “greater wealth, better health, more wisdom, extra time and increased happiness” (this is a direct quote). Way at the bottom of the disclosure panel is the statement that they publish the opinions of expert authorities in the fields. I came across an article in the news column that started “If you think you are allergic to a certain food…..” That certainly caught my eye. As I read on my interest turned to rage (not really rage but my feathers were rattled). The first line continued “….. but you aren’t sure which food-consider having a blood test for the immunoglobulin IgG, says the author of a book called ‘The Source: Unleash Your Natural Energy, Power Up Your Health and Feel Ten Years Younger’”.

So I am concerned that my newsletter (one I subscribe to) which focuses on saving money and promoting health would promote this book specifically this concept of IgG to food as being something of value and something well established in health care. So I carefully composed a letter citing references from the Food Allergy and Anaphylaxis Network (FAAN) and from the American Academy of Allergy, Asthma, and Clinical Immunology. I also did a literature search on the author of the book using PubMed and OVID. My letter explained that the measurement of IgG to food is unproven as a diagnostic test and should be considered experimental. It is known that IgG to foods does not sort out a healthy from a sick population. The thought is that we see IgG to food in healthy people. To date, this is a test looking for a disease.

Thinking that I may have missed something, my search for published articles by the author on this topic in peer-reviewed journals came up with nothing.

I went on to point out that IgG to food is on a rather long list of unproven diagnostic tests for allergy. I pointed out that prior to publishing their review on the topic that they should have done more research on the topic, utilizing position statements from the major organization involved with allergy and perhaps used a literature review of evidence-based medicine to see the value of a test for IgG directed to foods.  My bottom line was that this was not money well spent and could possibly lead to more harm for someone. I even went so far as to make some analogy to the use and sale of snake oil.

I carefully looked over my 750 word editorial, criticized the editors for violating their own standards and sent it off. Needless to say, I thought I was doing a service in pointing out my concerns.

Respectfully submitted,

Fred Leickly

Story continued- I got a response from ‘Bottom Line’- “Thank you for your email.  We welcome your feedback.  We find that on occasion even well-respected experts disagree and this appears to be one of those times. Again, I thank you for taking to the time to explore this topic with us.”

Ugh! I still feel better for the effort!

Up until a week ago, I had never heard of fenugreek.  On my first day back at Riley to start the 2009 new year, I had a young man, just under 2 years of age who presented with concerns about reactions to legumes. The list of suspects included peas, green beans, black beans, baked beans, and lentils. The mother also shared with me that during breast feeding she used ‘fenugreek’. This product is used to help nursing mothers. In our discussion, the mother brought up the concern that the fenugreek may have contributed to the legume reactions.

I had not heard of ‘fenugreek’ prior to this. I have been involved with allergy long enough to know that any food product ingested by mankind for as long as we have been on the planet has been implicated in an allergic response. I wanted to know more about this ‘fenugreek’.

I consulted my online food ‘Allergy Advisor’ regarding fenugreek and got a wealth of information to get me started. To my surprise later that week the Journal of Allergy and Clinical Immunology (JACI) had an article from a group in Norway regarding fenugreek.

Fenugreek (aka Greek hay, Greek fennel, Bird’s foot, Greek hay-seed) is a legume. It is used as a flavoring in many foods including curry, blends of spice, and even tea. As an herbal medication it has been touted as being helpful in initiating and maintaining milk production. There are references for its use in diabetes and hypertension. Importantly, it is a legume and many legumes share certain proteins and may be cross-reactive in some patients.

The purpose of the JACI article was to evaluate the allergenicity and antigenicity of the proteins in fenugreek. There were 29 patients in the study who had specific IgE antibodies to legumes, peanut, soy, pea, lupin, and fenugreek. These patients ranged from 1 to 53 years of age. High levels of antibody to both peanut and fenugreek were found in most patients and the sensitization to fenugreek was believed to be due to cross-reactivity in those patients with peanut allergy. In this study, the reactivity to the other legumes was weaker. Here the other legumes (specifically peanut) were implicated in causing sensitization to fenugreek. With the young lad that I saw I wondered if there is the possibility that the fenugreek may have worked in the opposite direction – fenugreek exposure causing sensitization to the other legumes.

I was not aware of this association: fenugreek and peanut. In my clinic notes I debated about doing the peanut test since he had no exposure, but since he reacted to a large number of the other legumes I had the skin test placed. His response was positive to peanut.

The world of IgE-mediated reactions to foods is growing significantly. Our diets are changing with significantly more opportunities for ingredients in foods from other lands becoming part of our lives. Herbal supplements may contain a variety of items that could lead to sensitization. It is important to inquire about the use of such products.