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