Turning the page on atopic dermatitis
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New guidelines move toward treatment partnership with patients

Even after an exhaustive review of the evidence, definitive answers to some of the most fundamental questions around the care of patients with atopic dermatitis continue to elude the experts. That makes educating AD patients about routine care and treatment regimens that are supported by the evidence all the more critical, said Robert Sidbury, MD, division chief in the department of pediatrics and associate professor of dermatology at Seattle Children’s Hospital. Dr. Sidbury co-chaired a workgroup of 17 dermatologists who recently updated the AAD’s guidelines for the management of AD; he cited the importance of education in eczema care as one of the key messages he took from their meetings.

“In discussing a number of really important core principles and issues regarding both diagnosis and treatment of AD, this group of people who know a lot about the condition couldn’t always come up with a uniform way to agree on certain ideas,” he said. “And if that’s the case in a roundtable of experts — not about genetic minutiae or the latest laboratory marker, but basic things like whether or not to bathe every day — imagine how that plays out in clinic rooms across the country with dermatologists and pediatricians and family practitioners and confused parents.” In fact, the evidence didn’t support a recommendation for any particular frequency or duration of bathing, but moisturizing after bathing (“soak and seal”) was deemed critical, Dr. Sidbury said. 

Parents and patients are getting mixed messages from friends, from the Internet, and from practitioners they’ve consulted before arriving at the dermatologist’s office, he noted. “It’s really important to recognize that patients often come in to our offices entirely flummoxed about some basic things. And we’ve got to take the time, not to hit them over the head with dogma — because often there’s not a real good basis to do that — but to give them our opinion, and then try to explain why.”

Acknowledging that an office visit may be too short to instruct patients appropriately, Dr. Sidbury pointed to formats such as nurse-run AD clinics and “eczema schools” as interventions that have proven to benefit patients. The guidelines cite numerous studies showing that structured education programs can positively affect patient outcome, and recommend them as an adjunct to conventional therapy. The problem is that “while it’s a great recommendation, not many of these programs exist yet in this country,” said Julie Block, chief executive officer of the National Eczema Association and a member of the guidelines workgroup. “There’s a wealth of data from other countries that have established that eczema schools do improve disease outcomes, and the National Eczema Association is working to help advance the progress of such programs here.” In the meantime, the AAD is developing a guide for patients to inform them about what is new or changing in the treatment of AD. According to Wendy Smith Begolka, the AAD’s senior manager of guidelines, research, and appropriate use criteria, the guide will focus on helping patients “participate in informed decision-making, improve compliance with treatment regimens, and contribute to their own care through the actions they take at home.”

Patient advocacy

Block’s participation marked the first time the AAD included a patient representative in a guideline workgroup. As a result, the group “made an effort to attempt to address things that were very important to patients,” said Timothy G. Berger, MD, professor of clinical dermatology at the University of California, San Francisco School of Medicine. “It’s not just about direct dermatologic management, but it’s this broad-spectrum, total approach to the atopic patient. So there’s a section on diet, and skin testing, and those kinds of things that patients bring up and may not be at the tip of every dermatologist’s knowledge.” [pagebreak]

Because the workgroup set a high bar for evidence that would lead to a recommendation, not every issue of concern to patients could be addressed through a recommendation, Dr. Sidbury said. “As head of the National Eczema Association, Julie is a tremendously effective advocate for atopic dermatitis patients, and she was never shy about raising her voice to say, maybe the evidence doesn’t support addressing that particular question, but patients want to know.’ She always kept our eyes on the prize, making sure that these recommendations were going to be practical.” Some topics, while not included in the recommendations due to a dearth of strong evidence, are nevertheless discussed in the body of the guidelines. “All the adjunctive and complementary approaches we discussed thoroughly, and the guidelines suggest there’s inconsistent or no evidence [on which to base a recommendation],” Block said. “These are things I wanted to bring forward, because eczema patients and their caregivers are very interested in these topics. I was really struck by how compassionate and patient-centric the members of the workgroup were. The discussions were very validating to the patients’ point of view.”

AD and allergies

One of the most contentious debates around AD, and one that the workgroup wrestled with, is the role of allergies, Dr. Sidbury said. “There was a paper published in the mid-’90s whose title summarized it perfectly: Atopic dermatitis: is it an allergic disease or a disease with allergies?’” he noted. “Parents come in with a ton of guilt because they’ve been told their child with AD must be allergic to something, you’re just missing it.’ So there’s a lot of elimination dieting, restriction dieting, sometimes to the point of iatrogenic malnutrition.” In fact, “there’s no doubt that allergies and atopic dermatitis keep company, and there are some patients for whom it’s influential on the course of disease. But there are other patients who, when tested, show sensitivities in the lab, but their parents will say they take that every day and it doesn’t seem to affect the course of their eczema.”

The guidelines section on allergic disease and allergy testing notes that “the role of allergens in eliciting and maintaining AD skin lesions is complex;” discusses testing for and clinical associations with food allergies, inhalant allergies, and allergic contact dermatitis; and sets forth three recommendations for testing (one, for example, is: If significant concerns for allergy are identified [i.e. hives, urticaria, etc.], assessment can be undertaken. Allergy testing independent of history is not recommended.). “It turns out that food allergies are relevant in very young children — sometimes,” Dr. Berger said. “They’re rarely a problem in adults. On the other hand, over time people with AD use a lot of products, so developing allergy to products is a bigger problem for adults than for kids. So we say, in the child who’s under five and has refractory atopic dermatitis, you might think about food allergies. In the adult, you need to think about, not food allergies, but contact allergy.” [pagebreak]

Systemic therapy

Differences between children and adults also come into play when practitioners consider systemic therapy for AD. “There are very few of the highest-quality trials for pediatric indications,” said Kelly M. Cordoro, MD, associate professor of dermatology and pediatrics at UCSF School of Medicine and the workgroup leader for systemic therapy. “Where evidence really lags behind is in using systemic therapy, even phototherapy to some extent, in very young children with atopic dermatitis. In clinical practice, we often look to the evidence and experience gained from treating children with indications other than atopic dermatitis with systemic therapy. For example, much of our safety data for immunosuppressive drugs such as methotrexate and cyclosporine derive from use in children with rheumatologic or oncologic diseases. We also apply what we have learned from long-term use of these medications in adult patients. Though this is not ideal, we feel fairly comfortable about safety, but it’s efficacy for which we don’t have head-to-head studies for kids with AD.” In prescribing cyclosporine in particular, “it’s important for physicians to be aware that kids metabolize differently,” Dr. Cordoro explained. “A child can tolerate, and often requires, higher doses of cyclosporine than an adult would due to differences in the pharmacokinetics of the drug in children. The guidelines don’t get into the granular details of that, but we do include a pediatric subsection in each guideline that tries to address pediatric issues specifically and speaks to some of the differences.”

Dermatologists reading the guidelines may be surprised to learn that among four drugs recommended to treat AD systemically, cyclosporine has not proven to be more effective than methotrexate, mycophenolate, or azathioprine, Dr. Sidbury said. “For kids and adults with severe, severe atopic dermatitis, when they’ve failed everything and you’re getting to the point where you’re thinking about oral agents, I suspect most dermatologists would start with cyclosporine,” he remarked. “Looking at the evidence, we found that we really couldn’t recommend cyclosporine over the other three agents. Most of us around the table use cyclosporine first, and we kind of assumed that was because it’s proven to be better.” Dr. Sidbury added that “there’s been a little more evidence in recent years for methotrexate being used for atopic dermatitis, whereas heretofore it’s been more in the province of psoriasis.”

The role of non-sedating antihistamines in eczema was an important point of discussion in the new guideline, Dr. Cordoro said. “We know that the itch in atopic dermatitis is not histamine-driven,” she explained. “Antihistamines help to treat the symptoms of comorbid conditions such as allergic rhinitis, but they are not very helpful for the itch of AD. However, using sedating antihistamines at night is very useful for minimizing nighttime scratching, which we know propagates the itch-scratch cycle of AD. The new guidelines are more clinically nuanced as we understand itch more.”

Proactive treatment

While the guidelines don’t recommend drastic departures from current methods of treatment, they do present dermatologists with some new strategies to manage their more difficult cases, Dr. Berger said. “There’s evidence that intermittent, chronic treatment [with a topical agent] in areas where patients tend to flare actually stabilizes those patients.” Dr. Cordoro elaborated: “First you would use adequately potent topicals to control the inflammation. As the skin clears, a lower potency topical steroid or alternative, such as a calcineurin inhibitor, may be used intermittently on the most severe, recurrent areas as a proactive tactic to minimize flares.” [pagebreak]

Filaggrin and the barrier defect

European researchers identified a mutation of the filaggrin gene as a possible culprit in atopic dermatitis 10 years ago, Dr. Berger said. “Filaggrin is a protein on the surface of the skin. A portion of atopic dermatitis patients, though not all, have a mutation that causes them to lack this protein,” he explained. “It doesn’t explain all cases of eczema, because a bunch of people with eczema don’t have the mutation. But what filaggrin does is to stay inside the cell and get broken down into something called natural moisturizing factor.’ And it’s what keeps the skin hydrated. When this protein is absent, the skin can’t hold water in as well, and it can’t tolerate stress to the surface, so it’s more easily irritated.”

With a better understanding of the science underlying atopic dermatitis, “maintaining the barrier and repairing the barrier becomes a cornerstone of the treatment.” The filaggrin studies didn’t change the treatment regimen so much as it changed the emphasis, Dr. Berger said. “We used to tell people to use their medicine, and now every eczema patient gets a basic discussion of moisturizing. Because atopic dermatitis is a problem of the epidermis, the best treatment is to treat the epidermis. It sounds so simple, but it takes a lot of science to prove that. And having the patient advocacy groups with us to give the same message to patients creates a powerful synergy.”

Using the guidelines

Key differences between the new guidelines and the previous version, Dr. Berger said, are that “one, the information is more practical; two, the recommendations are more patient-centered; and three, the recommendations are more evidence-based and allow physicians to make therapeutic decisions. In the past, we might have said, if you have this situation you can use all these therapies. Now they’ll read something that says, these are the treatment options, this will happen if you do this, this is the result if you do that. I think every dermatologist should read it once, and then have it as a ready reference.” For Dr. Cordoro, one of the highlights of the workgroup experience was that “we were addressing not only the science of the treatment but the art of management. When it comes down to being a doctor with a patient in a room, a guideline is not enough — you have to examine the whole patient, understand the history, and make decisions relevant to the individual situation. I think this message will come across in the guideline, as it is very patient-centered. The goal is to help dermatologists and other care providers treat these patients in a more comprehensive way. There is an enormous need for this approach.” 



Guide to the guidelines