Practical guide to skin prick tests in allergy to aeroallergens

I was alerted to this article by my partner Dr. Vitalpur. It comes from Allergy (European Journal of Allergy and Clinical Immunology) 2011 . The purpose of the article was to provide ‘pocket guidelines’ from a consensus report regarding the use of allergy skin prick tests for inhalant or aeroallergens.

The skin prick test (SPT) is a widely used, major diagnostic tool used for the diagnosis of allergy. The introduction of the article points out the many complexities in performing SPTs and recommends that they should be performed only by trained health professionals.

As for the methods used to create the guide; it was a combined effort from the Global Allergy and Asthma European Network (GA²LEN) and the Allergic Rhinitis and its Impact on Asthma (ARIA) task force. Once the document was created, it was reviewed by the membership of the networks. The authors point out that this is not an evidence-based guideline. It should be looked at as ‘…clear-cut answers to frequently asked questions by practitioners and patients.’ The evidence-based aspect follows the guide-in future reports.

The article is broken down into a series of 21 specific questions:

1. What are the indications for skin tests in clinical practice?
2. Which skin tests are recommended?
3. What role do intradermal tests play?
4. What is the recommended skin prick test technique?
5. Which treatments suppress skin tests?
6. Which diseases affect skin tests?
7. Which allergen extracts to choose?
8. Which allergen extracts should be tested?
9. What area of the body should be chosen and what is the ideal distance between tests?
10. Which negative and positive controls are recommended?
11. Which results are regarded as positive?
12. How do skin tests compare with serum-specific IgE?
13. How to interpret skin test results?
14. Which skin tests are recommended in adolescents and adults?
15. Which skin tests are recommended in the elderly?
16. Which skin tests are recommended in young children?
17. What is the role of skin tests in primary care?
18. How can skin tests be used in developing countries?
19. Are skin tests needed in allergen immunotherapy follow-up?
20. Can skin tests be used in research?
21. What are the future needs?

Each question has a short, concise answer. These are common concerns and questions. I would like to point out a few of them for this review. The link will direct the reader to questions not covered here.

1. What are the indications for skin tests in clinical practice?

Asthma and allergic rhinitis are the indications for aeroallergen testing. The SPTs can be used from infancy to old age. The repeating of SPTs is done to detect new sensitizations in children and when changes in symptoms have occurred. 

2.Which skin tests are recommended?

Prick skin tests have a high degree of correlation with symptoms. There is high specificity (a negative test when you do not have the disease) and sensitivity (when the test is positive when you have the condition) with the skin pricks used for inhalant allergy.

 Table 1 Performance of skin prick tests

1. Use standardized extracts when available (We have grass, house dust mites, and cat as standardized extracts.)
2. Include a positive and a negative control solution (histamine is the positive control)
3. Perform tests on normal skin (not on skin affected by severe eczema or urticaria)
4. Evaluate the patient for dermatographism (Means skin writing- pressure to the skin will cause a hive, this is a common reason for someone to allergic to everything including the negative control.)
5. Determine and record medications taken by the patient and the time of the last dose
6. Record the reactions after 15 minutes
7. Measure the longest wheal diameter

Skin prick testing may cause systemic reactions

The common errors in skin testing are listed in table 2

• Tests are placed too close together and overlapping reactions cannot be separated visually.
• Induction of bleeding, leading possibly to false-positive results.
• Insufficient penetration of the skin by the puncture instrument, leading to false-negative results. This occurs more with plastic devices.
• Spreading allergen solutions during the test or when the solution is wiped away.

 3. What role do intradermal tests play?

Intradermal skin tests (when a needle is used to inject the extract- almost like a TB test) are not useful for allergy diagnosis with inhalant allergens. The clinical value is unknown in patients who only have positive intradermal tests. They are less safe to perform. There are practices where this is the only type of test done or they are performed when the SPTs are negative. We use this type of test ONLY in the ‘Bee Clinic’- the protocol for pursuing stinging insect allergy utilizes the intradermal test.

4. Which treatments suppress skin tests?

Drugs can suppress skin tests.

 Antihistamines- have a significant impact on skin test results. They should be avoided for 7 days

Imipramine- anti-depressants, sometimes used for bed wetting- can affect skin test results for 21 days

Steroid ointments and creams- minimal if any effect on skin testing

UltraViolet light – used to treat skin condition, can effect skin test results for up to 4 weeks

Table 3 Inhibitory effect of various treatments on skin prick tests show other agents that may impact skin test results.

5. Which diseases affect skin tests?

Patients with widespread eczema or hives cannot be tested in areas of affected skin. Neurological disorders and infectious diseases (e.g. leprosy) can lead to false-negative results.

6. Which allergen extracts to choose?

The quality of the allergen extract is of key importance as variations in the quality and/or potency of commercially available extracts exists, in particular for animal mites, animal dander, and molds, but even pollens. Use standardized extracts if available.  

7. Which allergen extracts should be tested?

This varies per region. This answer was relevant to Europe. I comment on this at the end of the review.

 8. What area of the body should be chosen and what is the ideal distance between tests?

Usually, the skin tests are performed on the forearms depending on the age of the patient. The distance between tests should be 2 cm. We have used the child’s back for testing. There is a larger surface area to work with. If needed, more items could be evaluated using the larger space. It is also an area which would not be frequently treated with a topical steroid.

 9. Which results are regarded as positive?

The wheal and erythema have been used to assess the positivity of the skin test. However, only the wheal is needed. The largest size of the wheal is considered to be sufficient. Wheal diameters equal to or larger than 3 mm are considered positive in SPTs.  

Redness alone is not a significant response. There needs to be a wheal (swollen area) of proper size to be called significant. In our clinic, the physician who ordered the test reads them and decides on the significance. All too often, slight red marks are interpreted as positives.

 10. How do skin tests compare with serum-specific IgE?

Serum-specific IgE, SPTs and allergen challenge do not have the same biological and clinical relevance and are not interchangeable. Low levels of serum-specific IgE are less often associated with symptoms than higher levels, but they do not exclude allergic symptoms particularly in very young children.

Note- the paper did not use the term RAST. The proper term is serum-specific IgE- that blood test for allergy. I thought that the answer to this question was not as complete as it should have been.

 11. Are skin tests needed in allergen immunotherapy follow-up?

Skin test reactivity decreases with allergen-specific immunotherapy to inhalant allergens, but skin tests cannot be used to assess the efficacy of immunotherapy in practice. Moreover, skin tests cannot be used to decide the cessation of immunotherapy.

Reviewer’s Comments-From the original 21 questions, I chose 11 that tend to be more frequently brought up in our practice. Many of the questions that I omitted dealt with issues unique to Europe or to the adult population.

In a nutshell the skin prick tests for aeroallergens (inhalant allergens) are:

• Indicated for respiratory tract symptoms
• Can be done in very young children
• Should be done with the proper extracts and application technique
• Can be done if a few medications are out of the child’s system
• There may be a problem finding clear skin to do them on a child who has eczema or hives
• May be done on the arms,
• Are considered positive if the wheal (swollen area) is of proper size (redness alone does not qualify)
• Should not be used to monitor an allergy shot program.

This was a very neat, concise, and well done synopsis of how things are done in Europe. An additional tidbit was the answer to the question- Which allergens should be tested? The quick answer is that it depends on the allergen exposure for the area and that a common, standardized battery of tests should be recommended for Europe. The list was short;

• Pollens- Birch, Cypress, Grass (one species or a mix), Mugwort, Olive (or Ash), Parietaria, Plane, and Ragweed
• Mites- two species
• Animals- Cat and Dog
• Mold- Alternaria and Cladosporium (Aspergillus extract is not available in all countries).
• Insects- Cockroach

That panel for respiratory tract allergens would contain only 15 aeroallergens plus the two controls- 17 skin tests done to assess allergen sensitization.

A reference was also made to the National Health and Nutrition Examination Survey (NHANES) performed in the United States (2005) – 10 allergens were used.

FEL

11-30-2011

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

I was intrigued to see a recent article in the American Journal of Respiratory and Critical Care Medicine (Volume 183. pages 582-588, 2011) that dealt with asthma and swimming pools. The title of the article was ‘Swimming Pool Attendance, Asthma, Allergies, and Lung Function in the Avon Longitudinal Study of Parents and Children Cohort’ written by Font-Ribera and others. What follows are a number of interesting points about swimming pools and asthma that appear in the article.

Background

There is the suggestion that swimming in chlorinated swimming pools is a risk factor for developing asthma. The theory was that cleaning products had an effect on the airway which could lead to the development of asthma. Studies were references showing increased asthma in lifeguards and a higher prevalence of asthma in elite swimmers.

These observations were also thought to be due to ‘reverse causation (where the effect preceded the cause)’- swimming is recommended for those with asthma.

There have been many epidemiologic studies done in Europe regarding swimming as a risk factor for asthma, however the results are conflicting. Of note is the statement “….there is agreement on the complexity of the potential role of swimming asthma etiology and the important public health implications.

Asthma is one of the most common chronic conditions in childhood and swimming is one of the most popular sports/activities. So, a study was done to address some of these issues

The purpose of the study

To examine whether swimming at different periods during early childhood is associated with the prevalence of asthma and allergy symptoms.

How they did it

This was part of a large cohort study. In such a study a group of children are recruited and watched over time for events to occur. This was done as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) and comes from the United Kingdom. More than 5,700 children were evaluated. Asthma symptoms were reported using a standardized tool (the International Study of Asthma and Allergies in Children- ISAAC). Lung function was measured and a methacholine challenge was performed (measures airway hyper-reactivity)

Swimming frequency was asked at various times of the child’s life. There were a variety of possible confounding variables looked at as well; sex, birth weight, number of siblings, atopy, maternal education, maternal and paternal social class, maternal age at delivery, maternal asthma, allergy and hay fever, contact with pets, hours of TV watching, exposure to environmental smoke, and body mass.

What they found

The total number of children in the study was 5,738. Only 12% of the mothers had asthma. Positive allergy skin tests were seen in 21.4%. Asthma was present in 20%.

The crude and an adjusted model looked at using a variety of variables and both gave similar results. When all the confounders were accounted for, swimming was not associated with ever having asthma. Interestingly, swimming was associated with a lower prevalence of currently having asthma and currently using asthma medication at age 7 years. There was also no significant association seen between swimming and current wheezing, eczema, nasal symptoms, or eye symptoms at age 7 or at age 10 years.

The data was looked at from the perspective of the effect of swimming when there were previous respiratory tract symptoms at different ages. The protective effect of swimming was only seen among children who wheezed prior to age 3.5 years.

Of note, there was no significant association between swimming and bronchial hyper-reactivity.

Swimming also did not increase the risk of any respiratory tract symptom in children who were atopic.

Conclusions

This large prospective birth cohort study did not find that swimming increased the risk for asthma, atopy, or any respiratory/allergic symptom in British children. Swimming was associated with better lung function and decrease asthma prevalence in children who had previous respiratory tract symptoms.

The authors do point out a few problems with the study. The questionnaire asked about swimming and not swimming pool attendance. It was assumed that since this was done in the United Kingdom and the weather being what it is, the assumption was that the affirmative answer did refer to pools. Chlorine is the most commonly used disinfectant. However, no information was collected regarding the amount of chlorine exposure.

Reviewers Note

This was a large study and a prospective study that looked into a very practical question. The more children the study, the stronger the conclusions.
Swimming did not make things worse and in fact lung function was better and the risk of asthma symptoms and medication used was lower in those children who were known to have wheezing when they were younger.

Swimming is a good thing!

FEL

Article by A. Carbone, A. Siu, and R. Patel in The Annals of Pharmacotherapy 2010 Volume 44:

The medical management of atopic dermatitis

This ‘website’ has an analytic program attached to it, Google Analytics (GA). With GA I get feedback regarding which pages or topics are viewed. Those topics that involve ‘Atopic Dermatitis’ (AD) are frequently looked at, indicating that this is an area of concern. This condition is of special interest to me and seemingly to many others. I participate along with Dr. Travers (dermatology) and Laura Dean (nutrition) in the Atopic Dermatitis Signature Center at Riley. So we (the team)  are constantly looking for new information and twists on old information to help children with this condition. The review posted here involves a critique on the medical management of atopic dermatitis. This appeared or will appear in the September 2010 journal The Annals of Pharmacotherapy. The authors are A. Carbone, A. Siu, and R. Patel from the Ernest Mario School of Pharmacy at Rutgers, the State University of New Jersey.

The purpose of the paper

This was a review of the available medical treatment options for atopic dermatitis.

Methods

A review of the literature from 1950 to February 2010 was conducted using the key words ‘atopic dermatitis’. The search was restricted to articles that involved children <18 years of age and were written in English. The review was further refined with only articles that appeared in the literature within the past 5 years included. The authors also included articles that were older if they felt they were pertinent.

The reference list has 47 articles. The oldest article is from 1983.

Background Facts

This condition affects 17% of children. It most commonly starts at around 2-3 months of life. About half will declare themselves with the condition by their first year. Almost all will be diagnosed by age 5 years.

In this literature, the terms eczema and dermatitis are used interchangeably (and after the descriptor atopic).

The incidence of atopic dermatitis is increasing; the reason is unknown and theories abound.

There is no cure for atopic dermatitis. However, the incidence and prevalence decrease as the child ages.

Medical Management

There are a number of options here;

•                 Non-pharmacologic
•                 Pharmacologic

The non-pharmacologic treatments were not the focus of this paper but are worth mentioning. This is a multi-faceted condition. There is no ‘one’ thing, no ‘one’ golden treatment that takes care of it entirely. It is also recognized that each child will be different. So success in control involves many options that should be done together – the non-pharmacologic with the pharmacologic treatments.

Non-pharmacologic Treatment (individualized)

•                 Removal of allergens
•                 Identification of trigger factors
•                 Balanced nutrition

Pharmacologic Treatments

•                 Emollients- moisturizing agents
•                 Topical Corticosteroids
•                 Topical Calcineurin inhibitors
•                 Systemic Treatments
•                 Oral antihistamines
•                 Bandages
•                 Phototherapy
•                 Bleach baths

Emollients

These are moisturizing agents that work to inhibit water loss from the skin and provide a protective coating. There are a number of choices here; the first table in the paper lists 21 choices. The choice should be one that is unscented and a large amount should be used.

There are no recommendations regarding the amount and frequency of the use of emollients. There are also no studies that compare them to placebo.

These products are lotions, creams, and ointments. The active ingredients are mineral oil, petrolatum, ceramide, and urea.

The article (authors without conflict of interest) reviewed studies that involved Mimyx and Skin Barrier (EpiCeram).

Topical Corticosteroids

A table lists ‘some’ of these products. There were 67 topical steroids listed according to potency

•                 Super-high
•                 High
•                 Medium-high
•                 Medium
•                 Medium-low
•                 Low
•                 Lowest

The side effects of these products included (noted as being rare if used properly);

•                 Stinging
•                 Thinning of the skin (atrophy)
•                 Acne
•                 Folliculitis (hair follicles become inflamed)
•                 Bacterial infection of the skin
•                 Hypertrichosis (increased hair)

For those children who have frequent flares (2-3 times per month) but are not currently active, the use of the topical steroids 1-2 days per week to frequently affected areas may help reduce flares.

The article talks about a few studies that compared topical steroids alone to topical steroids with emollients. There were also a number of studies that compared the various topical corticosteroids.

Topical Calcineurin Inhibitors

Tacrolimus and pimecrolimus (Protopic and Ellidel) work on specific cells of the immune system (T-cells) to decrease inflammation.

These agents have been recommended for children (>2 years of age) who do not respond to topical corticosteroids. They have also been recommend for  those with adverse reactions to the topical steroids or with irreversible skin atrophy (thinning). Facial eczema may also be a reason for considering these agents.

These agents are not to be considered first-line therapy. There are reports of associated malignancy (black box warning).

Systemic Treatments

Oral steroids have been used to treat this condition. There is improvement, however rebound flaring of the condition occurs often. The need to taper the oral steroid to prevent rebound was gone over with a number of examples of tapering when the exposure is 1 week, 1-2 weeks, or more than 1 month. The side-effects of the oral steroids include; adrenal suppression, growth suppression, glucose intolerance, and hypertension.

Oral Antihistamines

I think this is an area of great confusion. These agents may not relieve the itch or urticaria associated with atopic dermatitis. Supporting evidence in the literature regarding the efficacy of these agents in children is lacking (for relief of itching). However, the sedating effect of the antihistamine helps with a child’s sleep, specifically the quality of sleep.

Within this therapeutic category you would be seeking out antihistamines with sedating effects to help sleep. The new, non-sedating agents would not be viable choices since they lack to some degree that affect you seek- sedation. These agents also cost more than the older generation-sedating agents.

Pick an agent to help with sleep and use the product at night alone. The half-life of some of the anti-histamines is long enough for single or once a day dosing.

Bandages

I have been more familiar with the wet bandage or wet wrap. This article reviewed the evidence for both dry and wet bandaging.

For the dry bandaging, there are no clinical trials that report their efficacy in the management of atopic dermatitis.  In theory, the dry bandage allow the emollients to remain on the site.

Wet wraps (bandages) can be used in children with extremely dry skin, severe atopic dermatitis, for exacerbations not well controlled by topical agents, or for those children who tend to scratch extensively at night.

In the literature reviewed for this article, clinical trials did not show any evidence that wet wraps is any better than conventional treatment with topical corticosteroids and emollients.

Phototherapy

Listed as an option, however there is minimal information regarding its effectiveness.

Bleach Baths

Staphylococcal bacteria is on the skin of almost all of these children.  Oral antibiotics help to reduce the colonization of staphylococcus, however in this review  the evidence for clinical improvement is minimal.

The bleach bath is analogous to the chlorinated swimming pool. Studies have shown that this decreases the need for oral antibiotics.
Summary (author’s)

Children with atopic dermatitis are encouraged to;

•                 Avoid triggers such as allergens and irritants
•                 Maintain a balanced diet
•                 Use emollients
•                 Use topical corticosteroids- low strength with adjustments in potency as needed
•                 Calcineurin inhibitors- for non-responders or children with adverse effects
•                 Systemic oral corticosteroids- last resort
•                 Anti-histamines for sleep, they may not help the itch
•                 Phototherapy- when all else fails
•                 Bandages- may work
•                 Bleach baths- decrease severity

The health care professional taking care of the child needs to assess and consider the quality of life when deciding which treatment is appropriate.

Reviewer’s comments

We come across patients who have been on a wide array of therapies for atopic dermatitis and we come across a number of health care providers who swear by certain therapeutic approaches as if they were gospel. I have noted that there seems to be an inverse relationship between published studies on efficacy and the voracity with which a therapy is touted.

 I fully understand that some therapies work for individuals and I have no problem with setting on a course of therapy that may not have published evidence to support it, however I think that there should be defined clinical outcomes and timelines set to achieve those outcomes. As you can see from my numerous posts I do tend to be abide by what is evidence-based and if it is not evidence-based I explain that to the parents. I also go over the timeline for benefit, adverse effects, and I am conscious of the cost of the plan both in direct financial costs and on quality of life costs. Let us return to my review of the content of the article.

My background is in pharmacology- if things had gone a different way I would have had a career as a PhD in Pharmacology. I am very familiar with the journal  in which this article appeared.

I liked the comments on allergens which were to identify relevant allergens and help with avoidance measures.

Maintaining a balanced diet was mentioned a number of times. My guess is that this comes from concerns about allergy testing and applying those results as restrictive diets. After reviewing this work, I think we need something of quality on these non-pharmacologic treatment options.

I also liked the comments about the anti-histamines.  This suggests that we should go with the older, cheaper, agents that are associated with sedation. The child may need that. There is a current trend to use sedating antihistamines at night and non-sedating anti-histamines during the day. As medicine seemingly can go in circles and if you are old enough, you may see things pass by for a second time. When these new  anti-histamines (non-sedating) agents first appeared (you may remember Seldane), many third party payers balked at the expense and mandated that they would be okayed for daytime use but they would not pay for the second dose and suggested a first generation anti-histamine (over-the -counter). Studies appeared that concluded that this was not an effective form of treatment and side-effects still occurred during the day. It has been 15-20 years since I saw use and the advocating of two different anti-histamines. From pharmacologic standpoint, the histamine receptor is probably fairly well blocked with one agent. Ask why they (the antihistamines) are being used. Ask about the use of two agents. If they have been prescribed for itch, try it and see if it works and not, give it up. Most of the misery happens at night. Help the child sleep at night with the appropriate type of anti-histamine.

My take on the oral steroid is more cautious. Children have come to Riley who have been on oral steroids for this condition for months and even years. Yes it works, but look at the consequences and the risks; rebound, adrenal and growth suppression, glucose intolerance, and high blood pressure. Ask if other things have been tried. Consider asking for a referral to a center of excllence for the condition.

The allergy dogma (legacy) has been that those with atopic dermatitis do poorly in winter months and tend to do great in the summer. This paper offered two reasons for that observation. The summer reprieve  could be due to the sun and natural phototherapy along with a contribution to all those chlorinated swimming pools. Bleach baths may be akin to this to those swimming spots. The contemporary thoughts on pools/bathing is to encourage frequent use of water on the skin.

In the AD Signature Center we have been doing wet wraps. This article introduced dry bandages as an option. It also stated that wet/dry bandages/wraps use are without evidence to support efficacy.

Keep in mind that the treatment is very individualized. Find out what works and go with it.

FEL

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

Authors: Amy Branum and Susan Lukacs

Reference: Pediatrics Volume 124 (6) December 2009

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

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

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

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

Results (what the study found):

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

Conclusions:

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

Commentary:

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

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

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

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

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

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

Fred Leickly

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

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

Fred Leickly