A few things to add. I prefer the use of the term ‘peanut-safe’ in deference to ‘peanut-free’. The terms safe and free may have the same intent, however they may be practiced differently. For example, peanut free would mean that no peanuts would pass through the threshold of the institution- that is the policy, that is the law. Now consider ‘peanut-safe’. When you are peanut-safe, it includes the previous concept and adds the idea of continued vigilance; always checking, always looking, being active about keeping peanuts away from those who may have life-theatening events with exposure.

The other item I would add is that at this time, since I write all the material for allergy at Riley, you would have to check out this website for more information. The www.RileyHospital.org gets you to the children’s hosptial website and how to access the children’s hospital. They are working on topic postings.

Thanks for looking,

Fred Leickly (12-11-2011)

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

The July issue of Pediatrics has an article entitled, ‘The Prevalence, Severity, and Distribution of Childhood Food Allergy in the United States’ by R S Gupta, E E Springston, M R Warrier, B Smith, R Kumar, J Pongracic, and J L Holl. The bottom line from this work is that the prevalence and severity of food allergy is greater than previous reports would indicate and this was a fairly large nationwide survey designed to address the question of prevalence. The authors also conclude that disparities exist with the clinical diagnosis of the condition.

Purpose of the paper- to determine the prevalence, severity, and distribution of food allergy in children.

Methods-The authors created a survey that was population-based and cross-sectional. It was administered to a representative sample of the United States population between June 2009 and February 2010. This survey was carefully developed and evaluated prior to its use. It was not a previously used, standardized tool.

Recruiting and survey administration was performed by a survey research company. Internet access was required to participate.

Completion of 40,000 surveys would give the study significant power (0.9) at a significance level of 0.5 to detect overall and allergen-specific food allergy prevalence (between 1-9%) and prevalence variability from 1-7% in groups as small as 1% of the sample.

Outcome Measures

The primary outcomes were food allergy prevalence and severity.

Food allergy was defined as a report of a confirmed or a convincing story of an allergy.

A convincing food allergy was based on at least one of the following;

1. Anaphylaxis- defined as a severe reaction that could lead to death
2. Angioedema (swelling) of the lips, eyes, or face
3. Other Angioedema
4. Coughing
5. Other oropharnygeal symptoms
6. Eczema
7. Flushing
8. Hives
9. Low blood pressure
10. Pruritis (itching)
11. Trouble breathing
12. Vomiting
13. Wheezing

A confirmed food allergy had the above criteria and included a report of a physician-diagnosis with serum-specific IgE, skin prick test results, or the result of an oral food challenge.

The severity of a food reaction was based on the nature of the symptoms;

Mild-moderate food allergy symptoms were limited to;

1. Angioedema of the lips, eyes, or face
2. Other angioedema
3. Coughing
4. Other oropharyngeal symptoms
5. Eczema
6. Flushing
7. Hives
8. Pruritis
9. Vomiting

Severe food allergy symptoms were;

1. Any report of anaphylaxis
2. Low blood pressure
3. Trouble breathing
4. Wheezing
5. Vomiting and angioedema, and coughing in combination

Results

The final sample size was 38,480 children.

The prevalence of food allergy in children was 8%. Multiple food allergies were reported in 2.4% (approximately 1/3 children of those with food allergy had more than one food to report).

Allergen prevalence was as follows;

Peanut- 767/3339 (23% of the reports) 52% had severe reactions, 48% had mild-moderate reactions

Milk- 702/3339 (21% of the reports) 31% had severe reactions, 69% had mild-moderate reactions

Shellfish- 509/3339 (15% of the reports) 47% had severe reactions, 53% had mild-moderate reactions

There was an age variation reported (the highest percentage reporting a specific food allergy);

Peanut- 30% in the 3-5 years of age group

Milk- 32% in the 0-2 years of age group

Shellfish- 24% in the > 14 year old age group

Tree nuts- 15% in the 11-13 year old age group

Egg – 16% in the 0-2 year old age group

Fish (fin) – 7% in the >14 year old age group

Strawberry- 8% in the 0-2 year old age group

Wheat- 8% in the 11-13 year old age group

Soy- 7% in the 11-13 year old age group

Severity of the Food Reactions

The prevalence of a severe reaction to a food was 3.1% of the surveyed population. This translates to 38.7% of the food allergy population. These severe reactions were reported more frequently in the children who had peanut or tree nut allergy. From the note above- 52% of the peanut and 53% of the tree nut allergic group had severe reactions.

When it happens to you or your child- it is 100%. The reassurance factor- just over 1/3 have serious reactions, most do not. Serious reactions are seen just over half the time with peanuts and tree nuts.

Food Allergy Associations- Odd/Risk Factors

The odds of having a food allergy were-

1. Higher in Asian and black children as compared to white children.
2. Higher in all age groups compared to children aged 0-2 years.
3. Higher in geographic areas outside the Midwest.
4. Lower with household incomes <$50,000.
5. Gender did not make a difference
6. Higher for a confirmed food allergy compared to a convincing food allergy history in those children with multiple food allergies.
7. Lower for confirmed food allergy in Asian, black, and Hispanic as compared to white children.
8. Lower for confirmed food allergy in households with incomes <$50,000.
9. Higher for a severe reaction among children in all age groups compared to children 0-2 years of age,  boys compared to girls, and those with compared to those without multiple food allergies.

Conclusions

Eight percent of children have food allergy with 38.7% having a severe reaction and 30.4% having multiple food allergies.

The disparity regarding food allergy diagnosis was seen with race, age, and income.

Reviewer’s Comments

Prevalence refers to the proportion of individuals with the clinical condition in a population at a specific moment in time. It provides an estimate of the risk or probability that an individual will have the condition. This would be the number of cases divided by the total population at a given moment.

When looking over the information there are a few points that need to be stressed. First was the sample truly representative?

The study was not performed on the entire pediatric population of the United States. The population was recruited from 6100 participants through a Web-enabled panel and an additional 33,900 came from on online sample of households with children; they all had access to the internet. This specific population is reported to be representative of U.S. households with children. So the first concern has been answered. However, a question arises as to selection bias. Do families who have children with food allergy have more computer access? Did the lack of computer (internet access) lead to non-selection for the study?

The second point was the definition of a food allergy. This was by the family’s report of a reaction or a confirmed food allergy. This was not a medical record review nor was this a bone-fide food challenge. The authors do point out that another bias; recall bias may be at work.

This was the largest study conducted looking at food allergy prevalence- a uniqueness to the work.

The article points out a number of helpful ‘between the lines’ points. About half of the children with a peanut allergy had a severe reaction. You can have mild-moderate reactions to peanut. The same relationship was seen with shellfish allergy.

The authors used multiple logistic regression models to establish odds. This statistical tool looks at the degree of association between having the condition after adjusting for factors that may be confounding. When the odds equal 1, then there is no increased/decreased relationship. When confidence interval include the number one, then there is no strong statistical difference. There seems to be a tendency for disparity, however I would be cautious due to the stated confidence intervals. The disparities that look clear are

Race- Asian, Black for having food allergy

Less confirmed vs. convincing cases with Asians

Age-compared to two year olds, more food allergy in all other ages

Age- compared to two year olds, more severe food allergy in all other age groups

Income- household income lower than $50,000 was protective for having food allergy, for having fewer confirmed vs. convincing histories, and having less severe food allergy. (In these instances the odds was less than one)

Geographic regions- compared to the Midwest, there was more food allergy in the Northeast, South, and West.

As for summarizing discrepancies in a few sentences- if the child was Asian or Black there was a higher chance of having food allergy, and less of a chance that it was confirmed if the child was Asian. Children over the age of two years have more reported food allergies and they tend to be more severe in the older age groups. If your family made less than $50,000, there was less of a chance that there would be a food allergy (poverty protects?). Lastly, there is less food allergy in the Midwest that in other regions of the country.

I enjoyed reading and reviewing this article. As with many good studies it stimulates more questions.

Respectfully submitted,
FEL

Now she also has nasal allergy that is very well controlled on an antihistamine. She ate almonds with impunity, but had one experience with cashew that caused the same symptoms.

We tested her for cashew and peanut- they were positive. We also tested her for birch and alder tree pollen, hazelnut, celery, apple, peach, and carrot. Birch and hazelnut (food) were also positive. I felt very sure that she had peanut- induced oral allergy syndrome. She was given injectable epinephrine, information regarding the Food Allergy and Anaphylaxis Network, and information on medical alert bracelets.

I only wished that I could have ordered a few additional blood tests to help provide some guidance regarding the seriousness of her peanut reaction.

We are currently working with a large group of children who have been seen at Riley Hospital for Children with peanut positive skin prick tests. This group of 76 children (from the 350 we have seen over the past year who have had a positive skin test to peanut) had wide variety of clinical presentations for their peanut allergy. Phadia has performed their microarray assay on these children. Now I am eagerly working on the information looking for associations, frequencies, odds ratios, and predictive values. This project and what I read in the literature, indicates that reactions to specific peanut proteins may help predict who will have a serious reaction to peanut. What we see is that the skin test for peanut and even the blood test for peanut tend to be rather crude tests and may measure antibody responses to a wide variety of proteins in peanut, not all of which are important in causing serious reactions. Positive peanut test results may be due to proteins in peanut that are shared with other members of the plant kingdom. So a child may have a positive screening test, by skin prick or by blood, but not show reactivity to the proteins associated with serious reactions and may show possible cross-reactivity to birch or alder tree pollen or the foods celery, carrot, apple, peach, or hazelnut.

My guess is that this young lady has the oral allergy syndrome due to peanut. I await her ImmunoCap specific IgE to peanut- her value may be low enough, below the critical cut-off point, to allow her to undergo a safe peanut challenge. However, I would have relished the opportunity to evaluate her responses via the Phadia microarray. This may help with my diagnosis and guidance. Knowing the specifics of her response may help with the family’s fear of a more serious peanut reaction, it may help with her socialization at school, and it may obviate the need for having injectable epinephrine.

Just another day in clinic!

FEL

FOOD ALLERGY

Of course the biggest event in 2010 was the publication of the National Institute of Allergy and Infectious Diseases (NIAID) sponsored ‘Guidelines for the diagnosis and management of food allergy in the United States’. Previous postings on this site go into more detail on those guidelines. The review states that these guidelines should provide tremendous guidance for improved diagnosis and management of food allergy. I think we as allergists may be very busy in the next few years making sure that food allergy was the correct diagnosis. Allergists will be performing more food challenges to test the relevance of test results.

Food Allergy Epidemiology and Risk Factors

For the United States the prevalence of specific food allergy was (percent of the population);

•                 Peanut- 0.8%
•                 Tree Nut- 0.6%
•                 Sesame seed- 0.1%

These were from telephone surveys and are self-reports.

Food allergy in children has increased (self-reported survey data);

                      Food                                             Year

                                            1997                       2002                       2008

                Tree nuts             0.6%                      1.2%                      2.1%

                Peanut                 0.4%                      0.8%                      1.4%

Rates of clinical food allergy risk (National Health and Nutrition Examination Survey 2005-2006)

•                 Food                      Rate
•                 Milk                       0.4%
•                 Egg                         0.2%
•                 Peanut                 1.3%
•                 Shrimp                  1.0%

In this study, children 1-5 years of age, clinical allergy to milk, egg, and peanut was 1.8% for each.

It needs to be pointed out that this information was from surveys and/or from specific IgE levels. They were not the results of a food challenge. So there is the possibility that this represents sensitization only and may be an over-estimate.

Risk factors for food allergy

                Food allergy may be due to deficiency in vitamin D.

Vitamin D has been a most popular topic over the past year. The standards for daily intake of vitamin D are changing; we may need more of this vitamin in our diets. Relative vitamin D deficiency has been reported in a number of clinical conditions.

                Prolonged avoidance of certain foods to infants at risk of developing food allergy has been the standard advice, however two studies were published that shake this concept, at least for milk and egg allergy. When milk exposure was delayed beyond the 15^th day of life, the odds ratio for milk allergy was 19.3. (Odds ratios are the odds that an event will occur compared to the odds that it will not occur). The OR gives an idea of how strongly a variable is associated with an outcome. In this example the odds of milk allergy was 19.3 times more likely to have milk allergy.

When egg was introduced at 4-6 months of life compared to introduction beyond the first year of life, the odds ratio was 3.4 for allergy to egg with late introduction (after age 1 year). The comment was made that oral exposure may promote tolerance and that excessive delays in introducing food allergens may be counterproductive and may allow sensitization to occur via intermittent exposure to the food and possible environmental exposure.

                A study from the Consortium of Food Allergy Research reported that mother’s ingestion of peanut during pregnancy had a positive dose-response association with the infant having increase peanut specific IgE antibodies to peanut. The more peanuts the mother ate, the higher the peanut- specific antibody levels. The reviewers point out that this is sensitization (the blood test only). The children are being followed to see if true peanut allergy appears over time.

Food Allergy Treatment

                Now what about those food labels for allergens. Specifically, when it says may contain an allergen or when there are no warning labels at all on the product. The review commented on a study in which 401 foods were evaluated for egg, milk, and peanut. The foods either had no indication that it contained one of these foods or the label stated that the food may contain an allergen.  Overall, just over 5% of the products that had an advisory label had detectable protein and almost 2% of the food products with no label were contaminated with the food. Food allergen levels were low, but this could still be an exposure risk.

                Avoidance has been the mainstay of food allergy treatment, however that may be changing. A study on peanut oral immunotherapy was published in 2010. There were 23 children who participated in the study. If a peanut has 300 mg of protein, in this study 1 child tolerated 6 peanuts (2000 mg), 5 tolerated 3 peanuts (1000 mg), and 8 had a peanut and a half (500 mg). So 14 of the 23 tolerated peanut- they did not have a serious reaction up to their limit of tolerance.

                A very important editorial appeared in the JACI about peanut oral immunotherapy. The editorial stated that this procedure is not ready for clinical use at this time. There are still concerns about safety, efficacy, and a number of other practical issues. Be excited about the prospects, but be patient as well.

ANAPHYLAXIS

                An updated practice parameter appeared this year on this topic. The highlights stressed the importance of a medical history, the early use of epinephrine, and prevention strategies.

                A very detailed epidemiologic study from England revealed the following;

•                                 Anaphylaxis is more common in those with asthma
•                                 Anaphylaxis is more common in women
•                                 Drug and food reactions were the most common causes

ATOPIC DERMATITIS

                Mechanisms of barrier dysfunction

                                The presence of an abnormal skin barrier is a major feature of this condition. A protein called filaggrin may have abnormal function. Filaggrin defects can lead to the absorption of allergens or enhance the colonization of the skin with bacteria leading to chronic inflammatory changes in the skin.

                Management and Natural History

                                The initial step is to make the correct diagnosis.  Hyper-IgE syndrome can look and act like atopic dermatitis.

                                Treatment includes skin barrier repair, allergen avoidance, infection control, and the use of anti-inflammatory agents. Keeping the skin well hydrated and preventing skin water loss is important. Betamethasone was great at decreasing symptoms but did cause thinning of the skin. The topical steroids are of help in gaining control followed by topical calcineruin inhibitors for long-term therapy.

                                Using probiotics to treat atopic dermatitis is a very controversial area. A study from Europe suggested that formula supplementation with a very specific prebiotic helped to reduce the occurrence of atopic dermatitis in ‘low-atopy-risk infants’.

URTICARIA and ANGIOEDEMA

                Anti-histamines are the first line treatments for urticaria. Higher doses of an anti-histamine may be required for symptom relief. In one report, levocetirizine (Xyzal) or desloratidine (Clarinex) were increased by 5 mg a week to a maximum dose of 20 mg or 20 mg of the other agent was used if there was no relief of symptoms. This increase of the dose did relief symptoms with 75% responding. The authors of this anti-histamine study suggested up to a 4-fold increase may be needed for symptom control and this can be achieved without safety issues.

                Another study looked at cyclosporine at low-dose as an option.

                In pursuit of a cause for chronic urticaria, low vitamin D levels may be causative and supplementing with vitamin D may help.

This was a nice review that summarized 113 articles that appeared in the JACI in 2010.

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

The title was ‘A Practical Approach to Food Allergy’. Slide copy can be found by clicking on the link which will take you to Google Documents. References for the talk can be found by clicking the link.

FEL

S. Sicherer, R. Wood, D. Stablein, R. Lindblad, W. Burks, A. Liu, S. Jones, D. Fleischer, D. Leung, and H. Sampson. JACI 2010 in press

How does peanut sensitization occur? How can we prevent peanut sensitization? What are the risk factors associated with the development of peanut allergy?

There are  very few proven answers to these questions. The number of theories to explain this abound. Thankfully we are seeing more clinical research intent on finding answers to this common problem of peanut allergy (sensitization). Of note, many of our recommendations for preventing peanut allergy/sensitization have been challenged. This is in part due to the existence of a paucity of data to support current recommendations and conflicting results from newer studies. This article is the latest on the topic of risk factors for the development of peanut sensitization. The article will be published in the Journal of Allergy and Clinical Immunology 2010.

Current recommendations from the American Academy of Pediatrics (American Academy of Pediatrics, Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics 2000;106:346-349.)are that peanuts should be avoided during pregnancy and lactation for an infant at risk for developing allergy. Two studies (published in 1996 and 2003) challenged that concept and concluded that peanut consumption during pregnancy/lactation was not a risk factor. We now have a much larger study performed with specific attention to mother’s dietary history that has concluded that peanut ingestion during pregnancy is indeed a risk factor.

The Purpose of the Study

The study came from the Consortium of Food Allergy Research. Five sites contributed to the work. This is a report on the clinical, demographic, and immunologic factors that were associated with an elevated specific IgE (value greater than 5 kU/L) to peanut (done by a blood test for peanut antibody) in a large group of children with known egg or milk allergy (without previously known peanut allergy). The specific interest was the discovery of a behavior that could be modified if relevant- mother’s ingestion of peanuts during pregnancy and the frequency of that ingestion.

Methods and Subjects in the Study

The cohort group was 512 infants and children, 3-15 months of age at enrollment (average age 9.4 months). To be in this group, the children had to have an allergic reaction and a positive allergy skin prick test to egg and/or milk. No child with a known peanut allergy or with a positive peanut specific IgE (blood test) done prior to the study was enrolled.

Questions were answered about the diet, the social situation, and the environment. There were five categories for maternal peanut ingestion; total avoidance, ingested <2 times/week, ingested more than 2 times/week, ingested daily, or unknown. The term ‘frequent’ meant that peanuts were eaten 2 or more times in a week.

Allergy testing included skin testing, blood tests for specific IgE, and tests for specific IgG to peanut.

What they found

A specific IgE of 5 kU/L or greater was selected as the cut-off point for evaluation. This was the level that was associated with more than a 70% chance of having a reaction to peanut (taken from other studies). There were 140 children (27.8%) who had a peanut specific IgE to peanut >5 kU/L.

The results were presented in a number of different ways; univariate analyses, multivariate analyses, and an analysis for receiver operator characteristics.

Looking at how a number of variables that could act alone as risk factors: there was no association between peanut IgE >5 kU/L and age at enrollment, age when formula was introduced, age when solid food was introduced, household income, parent education level, atopic disease in the parent, exposure to soy formula, breastfeeding, type of birth delivery, or use of antibiotics.

The variables that have a significant association included the following; male sex, race, atopic dermatitis severity, and peanut consumption during pregnancy >2 times/week. Peanut specific IgE was highly correlated to egg and milk specific IgE levels.

There was a dose-response associated with mother’s peanut consumption and peanut specific IgE >5 kU/L- the more peanuts consumed-the greater chance of having a child with a peanut specific IgE >5 kU/L. Further analyses showed peanut consumption during breast feeding to have no association with peanut IgE in one model of analysis.

Using a linear regression analysis and adjusting for egg IgE, milk IgE, severity of atopic dermatitis, sex, study site, and race, only peanut ingestion during pregnancy predicted peanut specific IgE.

The ratio of IgE to IgG for food has been noted to decrease for those who have achieved natural tolerance or in those who have undergone oral immunotherapy. A high IgE to IgG ratio may be related to a higher risk of demonstrating allergic reactions.

Conclusions

In a dose-dependent fashion (increase the amount eaten by the mother leads to an increase in sensitization of the child) mothers eating peanuts during pregnancy was associated with an increased chance of peanut allergy developing in the child known to have egg and/or milk allergy.

The factors that have been associated with this included; male sex, nonwhite race, and elevated milk/egg IgE levels.

Cautions and Concerns

The observation that boys tend to have more food allergy is well known. In regards to race, Asians tended to be at higher risk. The association with egg /milk allergy as a risk factor was not unexpected. Sensitization to these multiple foods is known from previous work.

Atopic disease was not a risk factor; however this group of children was selected for having atopic disease. There was no association with soy ingestion and peanut sensitization (both are legumes). There was also no association with the use of medications to suppress gastric acid. Having peanuts in the home was also not a risk factor in this group.

The authors point out that this was an observational study. They found associations or risk factors- not causative factors. To prove allergy, a peanut challenge would be required.

My comments

This report is to be published in an excellent peer-reviewed journal with authors who have national if not international reputations for excellent science in the world of peanut allergy.

The problems with other studies similar to this were identified in the discussion part of this study. One of the problems is the recall of peanut exposure during pregnancy by the mother. Here the enrollment and history was taken soon after birth. It was hoped that dietary exposure history would be less biased with this approach.

The study also points out that this was sensitization to peanut and not clinical peanut allergy: there was no history of a peanut reaction in these children. They worked with a laboratory value that was associated with a high risk of having an allergic reaction taken from a different group of children. So there was a very good chance that a reaction could occur.

The results also pertain to a specific population. The study was performed in a group of children who were selected due to known egg/milk allergy.

So the mothers of children who currently suffer with egg/milk allergy should not have eaten peanuts 2 or more times per week during pregnancy. This sounds like advice given too late to make a difference. The point however is the association of peanut ingestion in pregnancy with peanut sensitization in known egg/milk sensitive children.

The AAP recommendation is that mothers with infants at risk for atopy should not eat peanuts during pregnancy.  So that ‘at risk’ infant would be one with one parent and/or two parents, and/or a sibling with allergy.

Clearly more work is needed before declaring these associations as recommendations. This is the latest work on risk factors.  Mothers that eat peanuts less than twice a week may decrease the risk of peanut sensitization, if the child goes on to have egg/milk allergy. They may also not worry about eating peanuts during breast feeding of a child who has known egg/milk allergy.  

This also begs the question of how many peanuts were eaten. This is a frequency factor (>2 times per week). Perhaps there is a quantity factor as well. My guess is that a serving work be considered the standard exposure. One resource lists one ounce of peanuts or two tablespoons as a serving. The authors point out that this group needs to be followed with a peanut challenge in their future.

This was a fascinating study to read and review.

FEL

I came across this article ‘Peanut Allergy’ by M Pansare and D Kamat published in Current Opinion in Pediatrics 2010. This is a review article and the authors did a very nice job summarizing a number of import facts about peanut allergy. They have included many references for their statements which helps when trying to figure out what was said. Since this may be a somewhat difficult article to find, I thought I would summarize what this review highlights regarding the world of peanut allergy. My comments follow the statements in italics.     

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