Barrier repair: New generation of therapy works outside, inside to fight AD

Key Points

The nonsteroidal treatment is targeted biochemical corrective therapy that decreases inflammation by repairing the barrier.

The new generation of technology basically maintains that in AD, a global deficiency exists in the three lipids - ceramide, cholesterol and free fatty acids, as well as a further reduction in ceramides.

The key is to replace lipids with a ceramide-dominant, triple lipid formulation, which can correct the underlying lipid biochemical abnormality.

"By fixing the barrier, you decrease inflammation in AD in three different mechanisms," says Peter M. Elias, M.D., a dermatologist at Veterans Affairs Medical Center in San Francisco, and inventor of the new technology.

Mechanisms of repair

Decreasing inflammation AD is provided by three mechanisms.

The first mechanism shuts off the cytokine cascade, which is the signaling mechanism that always attempts to repair the barrier, but ultimately causes inflammation in all inflammatory dermatoses.

"In other words, AD starts from the outside-inside," Dr. Elias tells Dermatology Times.

"It's the same with psoriasis, which appears often on the elbows and knees - it starts from trauma from the outside, signaling downward, that ultimately causes inflammation.

"Secondly, by fixing the barrier, you prevent the ability of antigens, the things that provoke AD, and possibly asthma and allergic rhinitis, from getting across the epidermis.

"It's now known that the antigens that cause asthma and allergic rhinitis are also being absorbed across the skin, explaining the so-called 'atopic march,'" Dr. Elias says. "So, fixing the barrier also prevents access of the bad antigens from coming in."

Thirdly, by fixing the permeability barrier, you simultaneously fix the antimicrobial barrier, thus, preventing the colonization with Staphylococcus aureus.

"This step shuts off all the staph toxin-mediated mechanisms that stimulate pruritis and inflammation," Dr. Elias says.

Products

Approaches to restoring barrier function range from use of general moisturizers to application of serine protease (SP) inhibitors to specific lipid-replacement therapy.

The latter approach represents a potentially new model of treatment that is both highly effective and inherently safe as therapy for AD.

Compared to the older, emollient products that provide symptomatic relief of AD for one to four hours after application, the new generation of products addresses and corrects the biochemical abnormality responsible for the barrier defect.

In a review published recently in the journal Expert Reviews in Dermatology, Dr. Elias compared various barrier-repair therapies, including Mimyx (Stiefel), EpiCeram (Skin Barrier Emulsion, Promius Pharma) and Atopiclair (Sinclair Pharmaceuticals) with mixed results.

"Although (these new products) offer potential new ways to treat AD, only one product currently demonstrates biochemical corrective therapy for the underlying barrier abnormality in AD," he says.

"Corrective lipid replacement with a new, ceramide-dominant, triple-lipid mixture - EpiCeram - improves barrier function not only in mice with AD, but also in clinical status, itch severity and sleep habits in an investigator-blinded, five-center study of 121 pediatric patients with moderate-to-severe AD," Dr. Elias says.

This product, approved by the Food and Drug Administration (FDA), has been on the market in the United States since late September.

Awareness

Promius Pharma, the marketer of EpiCeram, is working hard to get word out about the product.

Already, hundreds of patient testimonials similar to the following have attested to the product's effectiveness.

"Right now, there are a lot of physicians who are using (EpiCeram) and a lot of physicians who don't know a thing about it," Dr. Elias says.

"We are in AD season now, and I hope that people learn about this product when they can still use it widely this year," he says.

Dr. Elias' take-away message to dermatologists is twofold. "First, paying attention to the principal functions of tissue and the tissue that drives the inflammation in not only AD, but in other inflammatory dermatoses, is crucial," Dr. Elias says.

"Secondly, we no longer have to use drugs with significant and substantial side effects. This is the future of dermatology," he says.

Disclosures: Dr. Elias is the inventor of the lipid-replacement technology. He is also a consultant to Ceragenix Corporation and to Promius Pharma. He received no funding from either company, other than a consulting stipend.