The Medical Management of Atopic Dermatitis in Children

Pediatric Atopic Dermatitis: A Review of the Medical Management

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

July 18, 2010 · fleickly · No Comments
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The Allergic March- Children who start with Atopic Dermatitis and go on to have Asthma and Allergic Rhinitis

Redefining who goes on the Atopic March

Does improvement management of atopic dermatitis influence the appearance of respiratory allergic diseases? A follow-up study. Clinical and Molecular Allergy 2010 8:8 Published June 30, 2010. Authors- G Ricci, A Patrizi, A Giannetti, A Dondi, B Bendandi, and M Masi.

Background and purpose of the study

Atopic dermatitis (AD) is one of the most common skin conditions that affect children. AD is characterized by dry, itchy, rough, and flaky skin. Between 70-80% of children who have AD have an elevation of the antibody associated with allergy- IgE and antibodies to foods/inhalants.  Many children outgrow this condition and in some it persists into their adulthood. In some children AD is the first step along the allergic march; going on to have asthma and allergic rhinitis. Depending upon who you ask or quote, 25-80% go on to have asthma. That is a huge range. The authors of this study published a 10 year follow-up study in 2006 looking at this issue. They showed that the AD disappeared in 60%, 34% developed asthma, and 58% developed nasal allergy. So some, not all finish the allergic march with a better chance of having nasal allergy and about a 1/3 chance of developing asthma. This begs the question as to whether or not anything can be done about it.

This current study looked at the effect of clinical management on the subsequent development of other allergic conditions and they used more standardized and contemporary measures of the conditions in asking what are the risk factors in children who have AD that may predict the development of other allergic conditions.

This is a study from Italy. It was a retrospective analysis; children who had AD between 9-16 months of age were contacted for participation. They had to have been seen in the clinic between 1993-2002.

Methodology

The assessment included;

1. Diagnosis of AD based on Hanifin and Rajka criteria (well established for this condition)

2. AD was evaluated by the SCORAD index at the first visit ( a measure of disease severity)

The clinical management program involved;

1. Environmental management- house dust mite avoidance, high-filtration vacuum cleaning,

2. Skin care- emollients, topical corticosteroids, calcineurin inhibitors, oral steroids, immunosuppressants, biologicals, antibiotics, antihistamines, and leukotriene inhibitors

Allergy Assessment;

1. Skin prick tests (SPT), total IgE  and specific IgE tests- milk, egg, soybean, wheat, peanut, nut, codfish, apple, grass pollen, house dust mite, cat dander, and dog dander. A positive was any value >0.35 for the blood test and a wheal response on the SPT.

Telephone interviews

Results

Telephone interviews were conducted with the families of 176 children. Their ages ranged from 6-12 years. The average age at the time of the first evaluation was about 1 year.

One hundred of the 176 (57%) showed a sensitization by SPT to at least one of the foods/inhalants.

One hundred and three of the 176 (58.5%) had an elevation at least one specific IgE blood test.

After an average of 7.5 years 84 (48%) still had AD- it disappeared in 52%. In the group of children who still had AD, 44% had a single site involved (mostly on a limb) and 18% had multiple locations of AD.

When AD disappeared on the average, the child was 3.25 years old.

In this group of children, respiratory allergy conditions appeared in 66/176 (37.5%).The specific respiratory ailments were; 36 (20.5%) developed only nasal allergy, 18 (10%) developed only asthma, and 12 (7%) developed both.

The nasal allergy appeared at 4.8 years of age. The mean age of appearance of asthma was 3.33 years. Asthma tended to precede the development of the nasal allergy.

A mathematical model, logistic regression, was used to predict the occurrence of asthma. A child who developed nasal allergy or was positive to at least one inhalant (serum specific IgE >0.35) at the time of the first evaluation had a greater risk to develop asthma (odds ratio was 4.219).

Conclusions (authors’)

The results of this study were compared to their earlier study in which disease-specific management was not evaluated. In the current study, the use of integrated management of AD did not seem to influence the natural course of AD. However, the early diagnosis and improved management at specialty centers decreased the percentage of children who went on to develop respiratory allergic disease. The presence of early allergic sensitization at age 1 year may predict the development of respiratory allergy.

                                Percentage of Children with Allergic Conditions – Comparing the two studies

                                1981-1989 study                                                                               1993-2002 study

Resolved AD             60.5%                                                                                                  52%*

Asthma                     34.1%                                                                                                  17%

Nasal Allergy            57.6%                                                                                                  27%

* not significantly different

In the present study at age 8 years (mean age of the children) 15% already had asthma. In the previous study, 29% had asthma by age 8 years. The management program accounted for a reduction in the appearance of asthma in this group. Similarly, the percentage with nasal allergy fell from about 35% to 17%. This could be due to better management of the AD.

This study used quantitative evaluations with determinations of specific IgE sensitivities and the use of improved clinical tools for assessing AD (SCORAD index, environmental prevention, integrated management) that helped with the early diagnosis, appropriate therapy, and monitoring of children with AD. This may have been  helpful in decreasing the numbers who go on to have respiratory allergy.

Reviewer’s comments

I was surprised at the wide range of children who go on from Atopic Dermatitis to Asthma to Allergic Rhinitis. More definitive epidemiologic work is needed to have a more precise estimate. I hear all too often from other allergists that it is an absolute fact; if the child has AD they will have…..This group of investigators had previously  looked at this evolution to other allergic conditions in the 1980s. This earlier study served as a nice comparison group for the current study.

Back in the80′s the tools and criteria differed. The current study tries to standardize the diagnosis of the allergic conditions. The entire group of children were evaluated with the same tools for AD severity and for respiratory allergy.

This study looks at the impact of early evaluation and the impact of management programs on the occurrence of detouring children who may have been on that allergic march. The first detour was asthma and the second change of course was allergic rhinitis.

Evaluation and management seems to re-direct some of these children away from respiratory allergy. it is not known if these conditions appear later in life. That will be a paper for review perhaps 10 years from now.

 The foods that were important were eggs and milk. A specific IgE level was >2.0KU/L to milk or egg was found to be predictive of sensitization to inhalants in late infancy.

Other considerations are that this is a group of children from Italy- the genetics may differ and certainly the environment differs. Such a study needs to done on our population of children to see if the results can be replicated.

As noted by the authors, demographic information was lacking making it a bit more difficult to describe and characterize the population.

Do we need to be more aggressive with our AD children? When should all these evaluations be performed. In this study many of the children had progressed and were very severe at the time they presented to the specialty clinic. The study did not look at how long treatment should be tried before embarking on a more Allergy/Dermatology Specialty oriented evaluation.

I like the selection of allergy tests here. Nut and apple were a surprise for a first evaluation for specific IgE to food at age 1 year. We did not see shrimp or scallops as a choice here.  Also, the evaluation for the inhalants was looking at sensitization- has the child begun to make antibodies towards these items? The study used these as associations and not necessarily as cause/effect items.

I think we need to re-think about the number of children who march from AD to other allergic conditions. It never was 100% – here is it about a third of children who do this. A take home message here is to consider being more aggressive with our evaluations, monitor more frequently, and carefully in hopes of halting that march from AD to Asthma to Allergic Rininits.

FEL

July 8, 2010 · fleickly · No Comments
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Increased Asthma Frequency and Asthma Severity in Children: The Asssociation with Atopy

Asthmatic children with atopy have more frequent and more severe virus-induced illnesses.

During a career you hear many words of wisdom from your mentors who are with you seeing children in the office and from meetings, curbside conversations/consultations, and from the literature. The adage that allergic children get sick easier, more frequently, and have more severe illnesses has been out there for many years. There are a number of theories for this contention. Children with allergy tend to remedy their itchy nose with internal manipulation, otherwise known as nose-picking. The finger serves as the vector for direct inoculation of viral particles onto the respiratory tract. Also, a number of years ago a publication reported that allergic noses actually had more receptors for the cold virus than non-allergic noses.

The May issue of the  Journal of Allergy, Asthma, and Immunology (Volume 125 No 5.) has an article by Jaime Olenec, ‘Weekly monitoring of children with asthma for infections and illness during common cold seasons’ concluded that atopic (showing IgE antibodies) children with asthma do have more frequent and more severe asthma exacerbations due to the common cold. The bottom line for me is the impact that the specialty of allergy and the determination of sensitization to allergens can make on children with asthma. The study did not address allergen control measure effects on frequency/severity of asthma symptoms.

My review of the study-

The group who did this is excellent and has a long established research track record and publication record regarding the role of viruses and allergy in pediatric asthma.

The journal in which this was published is peer-reviewed and a top-notch allergy journal. Also of note is that the manuscript was submitted in September, 2010 and was accepted for publication four months later.

The support for the work was from the National Institutes of Health.

The purpose of the study was to look at the impact of viral infections and allergic sensitization on the loss of asthma control during the peak ‘cold’ season.

The study involved 58 children between the ages of 6-8 years who were known to have asthma. These children were followed for three years. Skin testing and specific IgE testing was performed on all. Nasal samples were collected and analyzed for human rhinovirus infection. Diary cards were kept for symptoms. Cold and asthma symptom scores were collected along with peak flow value recordings and notations of the frequency albuterol (rescue inhaler) usage.

There were 42 children who had at least one season of complete data. The average age was 6.5 years and there were 30 boys and 12 girls. In this group 50% had one or more positive skin prick test for an allergen. Of note is that 69% had one or more positive blood tests for an allergen. Additional baseline information included; daily asthma controller medications used by 88%, and oral corticosteroids were used by 57% in the past year. Fifty five percent of the mothers and 40% of the fathers had allergy.

The number of viral illnesses per season was higher in the allergen sensitized group; 47% more virus-associated illness per season. During documented viral infections (viral cultures were frequently performed), the non-atopic children commonly reported no or mild cold symptoms. In the sensitized (atopic) children symptoms tended to be more moderate or severe. Also, almost half of the viral infections in the sensitized children caused moderate or severe asthma symptoms.

The author’s conclusions were that respiratory tract illnesses (asthma symptoms) due to viruses were more severe and were more frequent in children who are atopic.

These were children with asthma who had a positive allergy test. The terms sensitized and atopy were used to describe the group. Asthma frequency and asthma severity was increased in those who have made at least one IgE antibody to something.

This was a small study which was done in only one site. Larger studies in a variety of populations need to be done to confirm these observations.

This work re-affirms my practice of being aggressive with my allergic asthmatic children when the first signs of a cold occur. I advocate stepping-up the treatment program and continuing it for up to 14 days. One of the charts shows that the average duration of cold symptoms was 8.1 +/- 5.6 days and the average duration of asthma symptoms was 7.2 +/- 7.8 days in those who had a documented rhinovirus infection. For me this fits nicely with what I advise- on the average cold symptoms may begin the day prior to asthma symptoms and at the extremes of the range, asthma symptoms may last 14 days in some children.

FEL

June 10, 2010 · fleickly · No Comments
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House Dust- It is worse than we thought!

All too frequently I hear  someone saying that they are allergic to ‘Dust’. Just what is ‘Dust’ and is my ‘Dust’ the same as your ‘Dust’? More importantly is dust, specifically house dust, a harmless nuisance?

When I was at Henry Ford Hospital, Dennis Ownby, MD analyzed the house dust material that was used in the immunotherapy program. Of note is that there was more cat allergen in the house dust mix than what was available in the cat preparation that was available at the time. This house dust extract came from homes. I learned that dust is a mixture of many things.

During my fellowship we went on a field trip across the state of North Carolina to Greer labs. The house dust used for allergen diagnostics and for treatment sets came from collections from a large number of homes. The house dust extract had cat, dog, house dust mite fecal material, roach, other insects, food, mold, and IgA from human spittle.

The June issue of the journal Pediatrics had a quip from the editor emeritus, Jerold F. Lucey, MD regarding the ‘Dirt on Dust’. Dust is a big deal in allergy so this interested me. The note starts with the statement that simple house dust may not be as simple as all that. His source was a text box by Andrew Grant which was part of a more elaborate article by Michael Tennesen in the May 2010 issue of Discover magazine.

Mr. Grant reports that we are responsible for our own house dust. A scientific analysis of house dust reveals that it contains fibers from clothing, crumbs from food, and human dander. Hopefully, so far this is not too disgusting.

House dust has the remnants of other living creatures- plants, bacteria, mold, fungi, decaying insect carcasses, and fecal droppings from house dust mite (yes that is poop!). Had enough? It gets worse.

Our open windows and our shoes bring in the chemical villains. A study by the US Geological Survey from January, 2010 reported on numerous harmful chemicals discovered in house dust. Included in the samples were polycyclic aromatic hydrocarbons. This is used to coat parking lots. DDT, a pesticide banned 40 years ago was detected in house dust samples. Reference was made to another study in which arsenic and lead contaminated soil was found in house dust samples. The lesson here is that we track it in to our home on our shoes.

Clearly, dust is not so simple. It is a hodgepodge of items- biological and chemical. Some can elicit an allergic response; some can cause illness in other ways.

This has caused me to wonder about dust. My wonderment has lead to a few questions;

  • If the house dust has all this stuff from our shoes, I wonder what is lurking on the mat at the front door?
  • Are there enough food particles in house dust to trigger an allergic reaction in someone sensitive to food?
  • What is the composite listing of what is in house dust? Endotoxins would be on that list.
  • What is the seasonal variation in house dust composition?
  • How do various methods of cleaning change what is in house dust? Now that we have been scared, what can we do about it?
  • Are certain types of homes more conducive to certain dust components.

Good studies and information always beget more questions. I am now removing my workday shoes prior to walking into my home!

Fred Leickly

June 9, 2010 · fleickly · One Comment
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Child Care Conference Lecture-Food Allergy Testing

On May 19th, 2010 I participated in the Child Care Conference. This has been a Riley tradition for many years. My colleague in Pediatric Gastroenterology, Dr. Sandeep Gupta put this idea together on ‘Puzzling, Perplexing, Problematic Allergies in Children. He wanted pediatric allergy, dermatology, and gastroenterology to present together issues common to each specialty that have been problems for practitioners. Dr. Jeffery Travers spoke on Atopic Dermatitis. Dr. Gupta spoke on Eosinophilic Esophagitis, and I spoke on Allergy Testing- specifically allergy testing for food.

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

May 24, 2010 · fleickly · No Comments
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Critically Reviewing the Literature on Food Allergy

Diagnosing and Managing Common Food Allergies: A systematic review.

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

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

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

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

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

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

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

The results were as follows;

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

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

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

                Dietary restriction

                Nutritional problems

                Anxiety/worry

                Social challenges due to food allergy

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

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

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

FEL

May 16, 2010 · fleickly · No Comments
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Welcoming a New Family Member

Miles

We are proud to announce that we are grandparents for the second time. Miles was born on April 28, 2010 in Falls Church, Virginia. He joins his his now two year old sister Stella making the family a foursome. I spent the first part of my vacation visiting Miles and playing with Stella. She really is interested in this new family addition. They are a beautiful family indeed!

Welcome to the world Miles!

May 9, 2010 · fleickly · 2 Comments
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Peanut Allergy Misdiagnosed in 2 out of 3 Cases ?

 
Attacking Peanut Allergy

 

Peanut Allergy Misdiagnosed in 2 out of 3 Cases  

This title from Medical News Today April 13, 2010 caught my attention.  It has always been a mystery as to why peanut allergy has increased dramatically over the years. This publication may shed some light on that mystery.   

There are a number of factors in the peanut allergy equation  and a recalculation may be necessary. First we need to be careful in discerning peanut allergy from peanut sensitization. Peanut allergic children would be those who have symptoms with exposure and evidence of a positive allergy test (skin prick test or specific IgE to peanut determined by a blood test). The sensitizated child is one with a positive test and no clinical correlate.   

Secondly, the use of allergy tests has become more frequent and is being done by many other specialties. The manufacturers of blood tests for allergy market to primary caretakers an array of food allergen diagnostic panels that contain peanut along with many other foods. If the history was hives occurring after eating egg, a panel would include egg but would also have a number of additional foods. Sometimes these add-on foods return as positives (despite no history of a problem with ingestion) and the diagnosis of allergy is made.  

Thirdly, this news report indicates that the diagnosis of peanut allergy was wrong in 66% of the patients.   

A reworking of the prevalence of peanut allergy has a potential confounding variable; faulty diagnostic tools.   

This news article began with a poignant comment- peanut allergy has always been associated with a deep anxiety, especially in the parents of peanut allergic children. I have many patients who will attest to that.  

“Many people are being told that they are allergic to peanut, that they must avoid them and all foods that contain them at all costs, are actually not allergic to the nut at all” says Professor Wickman (Stockholm, Sweden). Dr. Wickman reported that 2/3 who are considered allergic to peanuts experience mild symptoms or none at all. A cross-reactive protein from birch tree pollen was thought responsible for the peanut reaction.   

This report included the shortcomings of the materials used for allergen skin testing and those used for testing the blood for allergy.   

To address this issue, a new diagnostic test was used on 4000 children to determine the specific proteins that are cross-reactive. It is known that specific peanut proteins are responsible for allergic reactions to peanut. The new test looks at antibody (IgE) production to the allergy-causing proteins. This allergy component test was used to show that 2/3 children who were diagnosed with peanut allergy were not allergic. Their positive test to peanut was due to some other protein that cross-reacted.  

Now this was a news report and not a peer-reviewed article and I know how reporters can get things wrong or misquote. In regards to the report, remember peanut is a legume, not a nut.   

In the report a statement is made that…” up to 7.5% of children seemed to be allergic to peanut at age 8 based on routine tests”. This made me wonder if they were truly allergic (symptoms by history) or they were declared allergic because a test was positive (done routinely for allergy?).   

Now for a few critical comments- both positive and negative;  

1. The capability of sorting out reactivity to the important proteins is applauded. We may be able to go back and de-diagnose a seemingly large proportion of peanut allergic people. The peanut-free tables at the schools are still essential but will be smaller by 2/3.  

2. How would this been all different if the diagnostics, both skin prick tests and specific IgE would have been done only in those who had a history of exposure and reactivity with exposure? If the patient’s history directed our choice of individual tests, would we have so many peanut sensitive/allergic people? Avoid doing food allergen panels. Pick out the pertintent allergens- it will be less confusing and it will save money (one example from a local sendout laboratory -$300 for the panel and $25 for the individual allergen).   

3. Look at the consequences of marketing panels or doing standard groupings of skin tests or blood tests- in 66% diagnosed perhaps falsely the families have an emotional burden, a nutritional burden, an isolation burden, and a financial burden. The peanut allergic person needs to have self-injected epinephrine available.  

4. We always have to be careful in applying the findings from one area to another. This report on the 4000 children was from Sweden. There may be significant differences in our population. I would relish the opportunity to sort out our population of peanut sensitive children.  

I am an advisor to the Southside Indianapolis Food Allergy Support Group. In March when I presented an update on food allergy, I promised that I would look at our peanut positive population. This has been quite a task.  I am creating a database to characterize the population in the hopes of being able to participate in a peanut study. We have 360 positive skin tests for peanut from January 1, 2009 through March 31, 2010-15 months of clinic visits. The spreadsheet has a number of epidemiologic parameters including the age and type of reaction to peanut. Many of the children were diagnosed based on a panel that was performed because of atopic eczema or due to blood test panels and referred by primary caretakers for further evaluation. A few had anaphylaxis.This project is fascinating and I think will be very informative. It hopefully will catch the eye of those in the allergen diagnostic community or someone looking for a large population to enroll in a peanut immunotherapy study. These families are highly motivated to make a difference and to help others with this problem.  

The new technology may help to address a historical and continuing over-enthusiastic and unfocused use of allergy tests, both skin prick test and blood test for peanut allergy. The tests we have now only tell us that antibody (IgE) is being made. The significance of that antibody is left to the clinician and must be based on the history and exposure to the allergen making sure that the clinical condition fits the template of IgE-mediated reactions. I for one eagerly await the arrival of more definitive diagnostic tools. 

  

FEL  

April 25, 2010 · fleickly · 3 Comments
Tags: , , , ,  Â· Posted in: Allergies, Allergy Testing, Food Allergies

Indy Food Allergy Support Groups

This past Tuesday (March 16, 2010) I was asked to speak to the Southside Indianapolis Food Allergy Support Group. Last spring I talked about food challenges and what Dr. Vitalpur and I are doing at Riley hospital regarding food challenges. This time I gave an update from the annual meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI) on food allergy topics. I also shared with the group the request for public commentary on a draft of “Guidelines for the Diagnosis and Management of Food Allergy”. This was a great meeting. I had a very attentive audience who asked many great and probing questions. I reformatted my notes from the conference gave this presentation without any slides to hide behind- now that is a great accomplishment.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Respectfully submitted,

Fred Leickly

March 18, 2010 · fleickly · 2 Comments
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Measuring Allergic Airway inflammation in Asthma

What is new for asthma diagnosis and treatment.

A message was forwarded to me about a news broadcast from Chicago that highlighted a tool that can be used to help with asthma diagnosis and management. The FDA has recently approved this according to the message. This tool is the measurement of exhaled nitric oxide (eNO). In allergic asthma  airway inflammation involves numerous inflammatory cells especially eosinophils. These inflammatory cells have a marker for their involvement and activation called nitric oxide. We are able to measure this by-product of airway inflammation in the breath. I also received another link on this measure of airway inflammation. In this second newsbroadcast Dr. Wolfe, an allergist, does a nice job in explaining this test, this measure, and allergic asthma.

This is not a new procedure. At Riley Hospital our group has been using this measurement in the care of children with asthma. It is nice to see that the concept of eNO is catching on and its value is appreciated.

I feel that a measure of eNO offers a significant amount of information regarding the role of allergy and the level of control patients with asthma have. I use eNO measures frequently in my Allergy/Asthma practice.

FEL

March 12, 2010 · fleickly · No Comments
Tags: ,  Â· Posted in: Asthma, Uncategorized