Usually when I review an article I go directly to that part of the introduction that deals with the purpose of the study. However, the background information provided in the introduction I thought was very helpful in understanding food allergy, noting the concerns regarding food allergy, and sharing how experts in the field of food allergy handle it (especially as they see a significant number of food allergic children in their referral center).

Identified problems with food allergy;

1.  Availability of serum IgE tests for foods
2.  Use of allergy tests to direct avoidance diets
3.  Consequences of avoidance diets
   • Poor weight gain
   •  Malnutrition
4.  Idea that food allergy is the exclusive cause of atopic dermatitis
5.  Food allergy focus leads to neglect of skin care

The allergy test result, whether by skin prick test or by serum IgE (formerly known as RAST) antibody levels, predict the chance of having a reaction with exposure to that food (they also demonstrate the presence of IgE directed against that food). These probabilities have been established for just a few foods; cow’s milk, hen’s egg, fish, peanut, and tree nuts. For all the other foods the levels that predict the chance of the child having a positive reaction have not been established.

Another significant issue that clouds the picture is that both allergic skin testing and serum specific IgE levels obtained from a blood test frequently detect sensitization that is not associated with any symptoms when the food is ingested. The false positive rate- when the test is positive and the story is that there were no problems with ingestion – is 50%! The gold standard for a food allergy is the double-blind placebo-controlled challenge. In other words, the best indicator is the history- what happens when the food is ingested.

The Purpose of the Study- was to raise awareness about the overreliance on serum immunoglobulin results as the primary indicator for establishing a food elimination diet in children (with atopic dermatitis).

Methods-This was a retrospective chart review of children who were seen for atopic dermatitis and food allergy. The number evaluated was 125.

Results

The median age of the children was 4 years. Most of had atopic dermatitis (96%). The severity of the atopic dermatitis varied- 30% were mild, 24% were moderate, and 42% were severe.

There were 364 oral food challenges performed on foods that were avoided at the time of the evaluation. That is almost 3 food challenges per child. Most of these challenges were negative- 325/364 (89%). Of note that during these food challenges, if there was a reaction, it occurred within a 2-hour observation period. Also, there were no documented flares of the skin condition.

Those 364 food challenges occurred in three different groups of children; 111 in whom foods were avoided due to a positive allergy test, 122 in whom a food was avoided due to a previous reaction to a food, and the last grouping was 131 children in whom a food was avoided for other reasons (not a history of a reaction or a positive allergy test). This last group included those who avoided a food because of lack of prior exposure, another family member with an allergy to that food, parental fear, refusal to eat the food, worsening of atopic dermatitis was uncertain with exposure, being too young for the food, and uncertain reasons.

In the group who avoided a food due to a positive allergy test (n=44 children) – with wheat being an exception (at 77% negative), 80% or more of the food challenges were negative. When there was a positive food challenge, the foods involved included egg, banana, peanut, soy, and wheat.

There were 122 food challenges done in a group of children (n=67 children) who had a history of a reaction to the food. When peanut and oats are excluded, more than 75% of the food challenges were negative. The positive food challenges were to; egg, chicken, milk, oat, peanut, soy, pea, wheat, beans, and pork & beans. This group of children had an array of food reactions by history; anaphylaxis (5%), gastrointestinal reactions (17%), lower respiratory tract reactions (8%), upper respiratory tract reactions (10%), and skin reactions (76%).

In the last group, those who avoided a food for other reasons, (n=131) more than 90% of the challenges were negative. There were 11 positive food challenges. The positive foods included egg, fruits (strawberry), meats (beef, chicken), milk, shellfish (shrimp), soy, barley, and Alimentum.

The levels of specific IgE antibody to the food were used to divide those who were challenged versus those who were not challenged. The following table shows the serum IgE level, the offering of a food challenge, and the result of the food challenge. When the serum IgE levels were elevated, no challenges were offered. For these three foods everyone who was below the critical cut-off point passed the food challenge. The decision levels for doing a food challenge were as follows- egg:< 2years of age -2 kU/L and >2 years of age 7 kU/l, Milk:< 2 years of age -5 kU/L and > 2 years of age a5 kU/l, peanut: 14 kU/L.

84-93% of foods that were avoided for a variety of reasons were returned to the child’s diet after a successful food challenge.

Conclusions- the authors concluded that in the absence of a history of anaphylaxis, the primary reliance on serum food-specific IgE testing to establish the need for a food elimination diet is not sufficient, especially within the population of children with atopic dermatitis. Oral food challenges are indicated to confirm the presence of a food allergy.

Many of the children seen were on overly restrictive diets that were inclusive of foods they never had exposure to or foods that were eaten without a problem. This restriction was based on food blood test results. The successful food challenge demonstrated that specific food restriction was not necessary in most instances. A food challenge discerns sensitization from true allergy.

The authors point out that it is important to optimize skin care and clearing to accurately sort out the impact of a food on the condition. It is also stated that there is a significant overreliance on allergy test results in making the diagnosis of food allergy especially in the children with atopic dermatitis. Allergy test results, if not supported by a food challenge, can lead to unnecessary food restrictions. To quote the authors, ‘misinterpretation of food allergy immunoassays, for which there is no correlation between the level and the probability of reacting to a food, is leading       unnecessary dietary restrictions that could result in nutritional deficiencies.’

Reviewer’s Comments- After my first read of the article, I felt that this was a very strongly worded statement against the indiscriminate use of serum IgE testing.  After numerous reads, that opinion of the article has not changed. This work is a strong statement against serum IgE testing for allergy.

It is important to point out that the vast majority of children who were in the study had atopic dermatitis (aka eczema). This clinical condition is notorious for having many false positive food allergy tests. During the 1980’ there were many studies that linked food allergy with atopic dermatitis. During my fellowship at Duke we watched children with severe atopic dermatitis react during the double-blind placebo-controlled food challenges. These studies led to the observation that there were 6 foods commonly associated with the condition; egg, milk, wheat, soy, peanut, and fish. Subsequently, many children with a range of presentations of atopic dermatitis have undergone allergy testing both by the skin prick method and by serum testing.  That has led to the concerns presented in this article.

The current ‘state of the art’ noted in the NHLBI Guidelines for the Diagnosis and Management of Food Allergy  suggests that food allergy considerations should include egg and any other food that the family feels is causative to the skin condition.

The authors point out that the availability of immunoassay food allergy panels to identify possible food allergy has added to the ongoing potential for misinterpretation of the results.

We also have that issue that continuously plagues us- sensitization vs. allergy. The laboratory test tells us that IgE is being made. The significance of that IgE has to be determined by the clinician. Taking a history is one way to begin establishing significance. The food challenge would be the bottom line for establishing relevance and significance of a positive IgE test for a food.

There are many messages within this study. The concerns regarding restrictive diets and avidly pursing food allergy diagnostics can lead to;

1. Failure to thrive due to food restrictions
2. Parental perceptions about unclear messages about which foods must be avoided
3. Attempts to treat atopic dermatitis by diet alone and not proper skin care
4. Pressure from parents to get these blood tests for food allergy
5. Incomplete understanding about the class designations
6. Applying the well-established food specific IgE values to foods that have not been rigorously evaluated

These concerns are seen with parents, primary caretakers, and yes, even allergists.

 When an allergy test for a food is positive yet the food is eaten without any clinical reaction, the test was a false positive. We should not let the laboratory result dictate the care of the child. Specific food allergy testing can be done for the food of interest. Select the test based on the story that supports it.

I think the role of the allergist in the near future will be to clear many of these positive tests. Here at Riley hospital we have an extensive experience in doing food challenges. Most of the time we perform a food challenge to demonstrate that a food allergy has been outgrown. We offer them in a controlled clinical environment. Everything is in place to take care of a reaction. In the near future I am sure we will be doing more food challenges to demonstrate the irrelevance of positive allergy test results.

The serum tests for IgE to food have helped with the decision to offer a food challenge for some foods. I look to the serum tests for food to decide the chance of a reaction and whether or not an oral food challenge should be scheduled. It is always perplexing to have a child present who has had a panel performed. All too often we struggle with results deemed high due to the ‘H’ notation after the specific concentration. We struggle with positive results from foods that the child has never ingested. We very frequently struggle with results on foods that the child has eaten with impunity and never had a problem. The food challenge helps to sort the well from the worried well.

Many times I have witnessed the joy of having the yoke (not yolk) of a food allergy removed by doing the food challenge.

FEL

Our Indianapolis Star posted a story from Shari Roan. Ms Roan is reporter for the Los Angeles Times. The title of the article in the Star was ‘You may be allergic to a food . . . or not’ . The original article by Ms. Roan had a slightly different title.

The article coincided with the announcement of the publications of the ‘New Guidelines for the Diagnosis and Management of Food Allergy’. This document represented the efforts of a group of food allergy experts working with the National Institute of Allergy and Infectious Diseases. In one of my earlier posts I commented on a draft of this document. The final product is now available.

What struck me after reading the article was the need for us to undo what has been done. There are  many children out there who have had extensive food allergy testing performed and struggle with numerous positive food allergy test results. Are they all truly allergic to all those foods? Are they being deprived of adequate nutrition? Can we help them and their families?

‘A lot of physicians order large numbers of blood tests of various foods, and when they find small amounts of antibody present, they indicate to the patient  that they are allergic to this food and should not ingest it,’ according to Dr. Hugh Sampson- an internationally recognized expert in food allergy. The article goes to state that many children are placed on highly restricted diets that are probably not necessary.

It is also important to point out that the same consequence can be seen with the results of skin testing.

The New Guidelines state that oral food challenges will be needed to sort out the relevance of the positive food allergy test. The oral food challenge is required to make an accurate diagnosis. These guidelines point out that a positive test result only shows sensitization. The test result must be used together with a history for a correct diagnosis of food allergy.

Stated a bit more firmly, these New Guidelines advise against making the diagnosis of food allergy solely based on the results of skin prick tests or blood tests.

 I foresee pediatric allergy practices becoming more involved with doing food challenges. A child presents with an array of positive food allergy tests, restrictive dietary advice, and accompanied by scared and frustrated parents. All too often many of the foods they have been told to avoid had been eaten with impunity- there was absolutely no observed reactions with ingestion, but there was a positive allergy test. This is very confusing.

In  pediatric allergy we sort through the history of exposure and the appearance of reactions that are IgE-mediated (the antibody detected by food allergy testing). We look for that constancy of cause/effective relationships with the food. We also need a sense of the timing between exposure and reaction. From that history, the proper selection of food allergy tests is then made.

So now we need to verify clinical reactivity to food allergy test results that revealed sensitization. For some foods we have been given guidance regarding the chance of having a reaction. For many other foods we do not have that information. Many of these challenges will be adventures in uncharted waters. In our practice we have done many challenges for milk, egg, soy, wheat, and peanut. We have also challenged to beef.  For the other foods we can put together a protocol for the safe introduction of a ‘challenge’ food.

Take a look at these New Guidelines for the Diagnosis and Management of Food Allergy.

FEL

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

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