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

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