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

This week I am presenting at a seminar at the Riley Child Care Conference. The seminar was the idea of Dr. Sandeep Gupta (pediatric gastroenterology). The title is “Puzzling, Perplexing, Problematic Allergies in Children”. The third lecturer is Dr. Jeff Travers (dermatology). I have the task of talking about allergy testing and referral to the allergist. Food and specifically food allergy is the common ground for the three specialties. My focus will be on food allergy evaluations and management.

I have been putting this presentation together for a number of weeks. I was ahead of deadline and sent my slide copy and handouts to the organizers for inclusion in the syllabus. For those involved in continuing medical education (CME) programs, that is what is called being a good citizen. However, I just changed major parts of my talk due to the appearance of an article in the Journal of the American Medical Association (JAMA) this past week. The article is entitled ‘Diagnosing and Managing Common Food Allergies: A systematic review’ by J Schneider Chafen and colleagues (JAMA, May 12, 2010- Vol 303, No 18, pages 1848-1856). I know that I am in trouble for doing this because showing slides that are not part of the syllabus has always been a most dangerous behavior for a CME speaker. The audience tends to yell at the speaker for this violation, however I will take the hits in favor of providing the most up to date information.

The idea of a ‘systematic review’ is a very specific and intense look at the literature on a specific topic. First a few basic questions are established. This is followed by an extensive review of everything in the literature on the topic/question. There are strict inclusion criteria. The data from the studies is abstracted, the quality of the study is assessed, and the data is then synthesized. The hope is that those studies which have substantial numbers of cases in randomized controlled studies were evaluated and included in the review. This is done to present the best, the most valid, and most convincing work.

This systematic review caused me to revise my talk and add seven slides that will truly reflects the most current information.

This review was sponsored by the National Institute for Allergic and Infectious Diseases (NIAID). It is the prelude to the establishment of National Food Allergy Diagnosis and Management Guidelines, a topic I have talked about previously. There were 12,378 literature citations on food allergy found between the January 1988 and September 2009. From this, only 72 articles qualified for this review. That represents approximately 0.05% of the starting total. This is important to note. Almost all of the articles pulled did not fit the purpose of this review. The specific topics that were sorted inclluded; food allergy prevalence, studies of diagnostic tests, and studies on management and food allergy prevention. Further restriction involved looking at studies that dealt with specific food allergies; milk, egg, peanut, tree nut, fish, and shellfish (50% of all food allergy).

The overall summary was that the literature/evidence regarding food allergy prevalence, diagnosis, and management is voluminous, diffuse, and according to this review is also critically limited by the lack of uniformity on what food allergy is (lacking uniformity for criteria for the diagnosis of food allergy). The point is that when looking at an article on food allergy we have to be sure what is being talked about. All too often the diagnosis is based on laboratory study results alone. This lack of defining food allergy has severely limited making conclusions regarding the best practices for managing and preventing food allergy.

It may come as a surprise, but food allergy has no universally accepted definition. The NIAID suggested definition is “an adverse immune response that occurs reproducibly on exposure to a given food and is distinct from other adverse responses to food, such as food intolerances, pharmacologic reactions, and toxin-mediated reactions.

The results were as follows;

• Prevalence- food allergy affects more than 1-2% of the population but less than 10%.
• Diagnosing- food challenges, skin prick tests (SPT), & serum food-specific IgE (blood tests for food allergy) all have a role in making the diagnosis, but no one test has sufficient ease of use or sensitivity or specificity to be recommended over the other tests. The food challenge suffers from not being easy to use in general clinical practice.
• Management (elimination diets)- only 1 randomized controlled trial (RCT), established as the more scientifically rigorous test,  was identified for the effect of elimination diets. RCT are generally lacking for atopic dermatitis and eosinophilic espophagitis. The benefits for elimination diets are uncertain based on published evidence, and potential benefits need to be weighed against the potential nutritional risks especially in children. It is important to point out that this is not referring to trials for serious life-threatening food allergy reactions, such a trial would be unnecessary and unethical.
• Immunotherapy- not a currently licensed method for treating food allergy. May be effective in generating desensitization. The effect on long-term tolerance needs to be determined.
• Prevention- In high-risk infants hydrolyzed formula may prevent against cow’s milk allergy, but standard definitions of high risk and hydrolyzed formula do not exist.

There were a few general comments made that are worth noting.

• There is the potential for the over-diagnosis of food allergy
• Consequences

                Dietary restriction

                Nutritional problems

                Anxiety/worry

                Social challenges due to food allergy

There were a few final comments in this paper that are worth consideration.

• Proper interpretation of SPTs and serum food-specific IgE results requires evaluation of the data within the context of the clinical history and physician understanding of symptoms consistent with clinical food allergy to separate true positives for food allergy.
• The over-diagnosis or misdiagnosis of food allergy by medical practitioners obscures the substantial morbidity caused by patients truly affected by immune-mediated food allergy and serves to perpetuate some public misperceptions that food allergy is a trivial medical condition.

We all have a significant amount of work to sort this all out. The first steps are coming to some consensus as to what a food allergy is and what it is not. We then need to perform a detailed medical history to tease out a reproducible immune response with exposure to a food. Next we need a diagnostic tool or tools to be used to confirm our impression. The food challenge has been the gold standard for this, however it is not easy to perform food challenges. The next need is a plan of management. There has always been avoidance. We can add ‘Father Time’ as some food allergies can be outgrown. We eagerly look forward to immunotherapy that not only provide desensitization but will lead to tolerance.

FEL

We talked about the findings at the meeting. We shared  experiences and concerns and we talked about a number of great ideas to help children with food allergy. One of the most thought provoking topics was looking at food allergy as a public health problem. This is definitely a public health problem. As an aside, the request for comments on the ‘ Food Allergy Mangement…’ draft began with a very effective attention getting statement-’Food allergy is an important public health problem….’ . To my dismay (that recent Masters of Public Health degree affecting my perspective again), the guidelines’ intention was to help with diagnosing and managing food allergy and not the public health issues. I applaud this work and the work of the committee that put this together. I have never made any responses to requests for comments on guideline drafts in the past. This draft of the guidelines stimulated me to offer a few comments. The acceptance of these food allergy guidelines is  important and desperately needed before we can be effective in any public health approach to food allergy. We need to critically look at what food allergy is and what is not food allergy. We need to listen to the story of what happens with exposures to food and carefully select the appropriate tools/tests to make the diagnosis. We also need to support efforts to help treat current food allergy issues and hopefully prevent the development of food allergy.

I shared with the group a review by Scott Sicherer on ‘What is New in Pediatric Allergy’. In this session Dr. Sicherer selected a few key articles that have appeared over the past year dealing with food allergy. A few of the food allergy topics included; The Natural History of Wheat Allergy (Keet, 2009), Food Protein-Induced Enterocolitis Syndrome (Mehr, 2009), Timing of Food Introduction and the Development of Atopy (Nwaru, 2010), and Dietary Advice, Dietary Adherence, and the Acquisition of Tolerance in Egg-allergic Children (Allen, 2009).

1. Wheat allergy resolved faster than egg or milk allergy.

2. FPIES- depending on the population studied, different foods are causitive and there seems to be differences in the rate of resolution. The overall prognosis is good.

3. Sensitization (having a positive allergy test, not necessarily symptomatic with exposure) was seen with the late introduction of a number of foods in this cohort of children from Finland.

4. Dietary advice is not uniformly followed, the advice given did not correlate with outgrowing egg allergy, adherence to the advice did not correlate with resolution, and accidental exposures to egg did not affect the outcome (outgrowing the allergy).

We also talked about research projects and protocols that involve food desensitization and food tolerance. Wes Burks from Duke University presented information on a number of studies. This work is ongoing at Duke, University of Arkansas, and at Mt.Sinai (New York). It is important to understand the differences between achieving a state of desensitization or tolerance.

1. Desensitization is the temporay increase of the amount of a food that would trigger an allergic reaction. This would offer protection from a life-threatening event due to an exposure.

2. Tolerance is the permanent loss of allergic reactivity due to changes in the immune system.

Desensitization and tolerance may work through similar mechanisms. Small exposures would not cause life threatening events in the desensitized child, however only the tolerant child could eat larger amounts of the culprit food without consequences.

The enthusiasm for participation in studies that may end the fear of a food reaction was intense. I was very impressed. A mother mentioned that she would donate her home if her child could participate in a program that would lead to desensitization/tolerance for peanut.

I shared the findings from an abstract of a study from the University of Michigan (abstract # 746). This was a report from a survey that represented the US population. In this survey 3-4% of those responding had a child with a life-threatening food allergy. Twenty five percent of responders knew someone with a food allergy. Of the families who had a child with a food allergy, 80% were accommodated by the school or daycare and of those, 50% of the staff had specific training in food allergy. Nearly 50% of the responders said that they were not at all inconvenienced by measures needed to protect the food allergic child, 25% were somewhat inconvenienced, and a few said it was very inconvenient for them.

We spent some time talking about this. Some of us were surprised by the findings. The charge to the group and the charge to anyone involved with children with food allergy is to advocate and to make others aware of the issues. The Southside Food Allergy Support Group offers an excellent program called
PAC- Protect Allergic Children. PAC has a detailed presentation that can be given in a number of venues.  The programs are ‘Food Allergy Safety in Schools’ and ‘Creating a Safe Home for Food Allergic Families’. Information on these programs can be obtained from the Southside Food Allergy Support Group.

One topic for a future meeting most certainly will be a summary of the final Food Allergy Guidelines.

My thanks to the Southside Food Allergy Support Group for the invitation to speak (as a disclosure, I am an advisor to the group as well). Keep the kids safe!!

Respectfully submitted,

Fred Leickly

This young lady’s mother had with her an article that escaped my attention. The article was written by known experts in the field of Allergy (the lead author was Anna Nowak-Wegrzyn with Hugh Sampson, Robert Wood, and Scott Sicherer as contributing authors). The paper was a nice review of FPIES and a study of 14 special children. I think that any allergist who sees young children should review this paper. These young children can present with signs that are possibly consistent with anaphylaxis.

 The article was published in the journal Pediatrics in 2003. It is a review of 14 children who presented over a five year period at the Mount Sinai Pediatric Allergy and Immunology Clinic (New York, NY) and to the Allergy Clinic at Johns Hopkins Children’s Center (Baltimore, MD). The reactions that these children experience include severe diarrhea and vomiting which can lead to dehydration and shock. This is a clinical diagnosis; there are no specific laboratory tests that make the diagnosis. A food challenge can confirm the diagnosis.

Milk and soy have been the most commonly implicated foods causing FPIES. This article shows that other foods specifically solid foods have been shown to be associated with this syndrome; rice, oat, barley, peas, string beans, squash, sweet potato, chicken, and turkey. These children underwent food challenges to show the cause-effect relationship between the exposure and the symptoms. There were many combinations of foods causing the problem; cow’s milk alone, soy milk alone, both cow and soy milk, a single solid food, and more than one grain. The group was compared to children who were only milk/soy sensitive.

                The profile of the Solid Food FPIES population was as follows;

• Age at onset of the reaction:    5.5 months (range 3-7 months)
• Age at resolution:                      24 months (range 14-44 months)

                The Milk/Soy FPIES profile was the following;

• Age at onset of the reaction:   1.0 months (range 2 days to 12 months)
• Age at resolution:                      28 months (range 14-21 y)

This was the first published study of FPIES triggered by solid food. Oat was the most common food causing solid-food FPIES. The study also showed that breast-feeding may have a protective role in preventing/delaying the development of FPIES. The diagnosis of solid-food FPIES was not made until after two reactions. It was also noted that these reactions were severe. The delay in diagnosis was attributed to a number of possible factors; low incidence of the disorder, a presentation that looks like septic shock, and the belief that solid foods such as grains, vegetables, and poultry are of low allergenic potential. It was also noted that the time course of the reaction may delay making the correct diagnosis. The daily feeding of milk – cows and soy, leads to chronic problems. The re-introduction of the milk causes symptoms two hours after the exposure.  As mentioned previously another problem is the lack of any test (other than avoidance and a food challenge) to confirm the diagnosis.

Another point that was made was that almost half of the children in this series had multiple food sensitivities. Children who were already on a casein hydrolysate formula had a median of four solid-foods that they were sensitive to.

No infant developed FPIES with exclusive breast feeding in this series.  The authors pointed out that they were unaware of any reports of FPIES during breast feeding with absolutely no direct oral feeding of an offending food. No infant developed FPIES to milk/soy after age 1 years and the oldest child who had the solid-food FPIES was 7 months old. There were no ‘predictors’ of which child with milk/soy FPIES would go on to develop solid-food FPIES.

The Bottom Line-

The reaction of vomiting/diarrhea possibly leading to shock can be consistent with an IgE-mediated reaction and these are perhaps more common than FPIES. Such a reaction would lead to an allergy evaluation which will be negative if the diagnosis is FPIES. However, the infant is still at risk for a severe reaction with re-exposure.

Board certified allergists are credentialed in the care of allergic conditions in both pediatrics and internal medicine. Some of us went into allergy after completing training in pediatrics and others were trained in internal medicine. FPIES would not have been a clinical entity seen during internal medicine training. It may have been seen/talked about for a pediatric oriented allergist. FPIES favors infants. My point to all this is that although very rare, we need to keep this type of presentation in mind when seeing young infants with scary episodes of vomiting leading to shock with solid-food exposure. Their evaluation will show no evidence of allergic sensitization. We can help by teasing out the history of exposures and clinical course. We can offer recommendations for avoidance of the common foods that have triggered solid food-induced FPIES. This profile of young infants reacting in such a violent way needs to be considered in the evaluation especially if they have had issues with cow’s milk or soy milk.

This young lady made an impression on me. Her story was very scary. She caused me to go back to the literature and review what is known about her presentation.

Fred Leickly

We have seen many children who were evaluated for food allergy and/or who were brought by parents to be evaluated for food allergy because of redness to the cheeks that is observed after eating.

What I haven’t heard about is a syndrome called ‘Frey’s Syndrome’. 

In the January edition of Postgraduate Medicine there is a case report, pictures, and a review of this syndrome which frequently precipitates an allergy evaluation. The problem is not due to allergy. It is an allergy-pretender.

Frey’s syndrome is also called the auriculotemporal nerve syndrome.  It involves redness over the cheeks after eating or drinking. The cause is abnormal nerve regeneration which can happen with forceps delivery or after parotid-gland surgery.  The actual incidence of the syndrome is unknown and it is by this report rare in children. Sucking on a lemon brings out the facial flushing. The use of starch/iodine brings sweating which is seen more in the adult.

The facial flushing with eating, gustatory flushing, may mimic food allergy and lead to unnecessary testing and the consequence of restrictive diets.

The clinical course is benign in children. The authors point out that it is important to recognize it so unnecessary evaluations are avoided.

The treatment is explanation and reassurance.

If you can see the paper, there  pictures of this flushing. The reaction looks distinctly delineated. It follows the distribution of the nerve.  The young lady would experience the flushing after eating sweets, citrus fruit, grapes, tomato sauce, fruit-flavored ice cream, and spicy foods. She had no history of any trauma to the area of the auriculotemporal nerve. There were no other symptoms besides this flushing. There was no personal history of allergy. Her teachers thought that this was a food allergy issue. In the clinic, the flush was seen one minute after eating a citrus-flavored sweet.

 I had not heard of Frey’s syndrome before, but I have seen a good number of red-cheeked children who had no other signs/symptoms of a food allergy. In this case, the types of food that elicited the problem, the timing of the flush in relation to eating, and the specific distribution help with the diagnosis of Frey’s syndrome.

We will start stocking sweet citrus-flavored candies for test purposes only. I am soliciting suggestions. So far I think Skiddles may work. If you can think of a candy that is has more of the citrus bite, let me know.

My thanks to the authors N Hussain, M Dhanarass, and W Whithouse for this article (Postgraduate Medicine Journal January 2010 Vol 86 N0 1011 page 62.)

Fred Leickly

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.

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

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