Awareness of the outside-inside aspect of atopic dermatitis is creating a swing in treatment choices away from a sole reliance on immunologic therapy, such as corticoids or immunomodulators such as tacrolimus.
"Atopic dermatitis is now seen as an outside-inside disease, rather than as a primary immunologic disease," Peter Elias, M.D., department of dermatology, University of California, San Francisco, tells Dermatology Times. "We're in the midst of a huge paradigm shift in how inflammatory skin conditions are viewed. They are no longer just immunologic entities with the epidermis as an innocent bystander. Instead, they are seen as having the primary abnormality in the epidermis, with the immune system serving as a downstream secondary participant."
This secondary participant creates a vicious circle of immune abnormalities causing further abnormalities, according to Dr. Elias, and this, in turn, gives dermatologists new choices in how to treat AD.
"Then, as patients experience a sustained accumulation of insults such as psychological stress, high PH soaps, reduced environmental humidity, and repeated exposure to antigens like house dust mites, the ichthyosis phenotype develops an inflammatory phenotype, and you have the manifestations of atopic dermatitis," he says. "So AD is a disease where inherited and acquired stressors converge to drive disease expression."
Outside the box
Awareness of the outside-inside aspect of the disease is creating a swing in treatment choices away from a sole reliance on immunologic therapy, such as corticoids or immunomodulators such as tacrolimus (Prograf, Astellas) or pimecrolimus (Elidel, Novartis).
Treatment can be administered either toward treating the immunologic disorder - inside-out approach - or by treating the primary barrier abnormality - outside-in approach, according to Dr. Elias.
"Obviously, the inside-out treatment of the immunologic abnormalities inherently has more risk of long-term and short-term toxicity. In contrast," he says, "treatment of the primary barrier abnormality, with restoration of barrier function, is inherently completely safe, and this approach improves disease, alleviates symptoms and can provide dramatic relief, without reliance on immunotherapy.
"While short-term immunologic therapy should be initiated initially in combination with barrier repair therapy, such as EpiCeram emulsion (Promius), long-term treatment with barrier repair therapy should suffice as soon as the patient begins to improve," he adds.
EpiCeram is composed of the three lipids that make up the barrier in normal stratum corneum with a further increase in ceramide, which makes it a ceramide-dominant triple lipid mixture.
"The difference between EpiCeram and anything else that's on the market for AD," Dr. Elias says, "is that it's targeted and designed to correct the biochemical abnormality in AD, which is responsible for the barrier defect which drives the disease."
Mixing it up
However, combination therapy should be used initially in all patients with moderate to severe AD, Dr. Elias says. In combination, the treatments improve disease more rapidly, because they work by different mechanisms. The combination should be used for the first two to three weeks, until the disease is under control, for moderate to severe disease.
"I think that most doctors will use combination therapy initially, because they want patients to get better faster," he says. "Many patients or family members are terrified of steroids and immunomodulators, in part for good reason. They will feel much reassured once they have moved over to the safer form of barrier repair therapy alone.
"Once the patient improves, the patient should switch over to EpiCeram for further treatment and also for maintenance and preventive therapy," he adds. "In the mild disease, there is no reason why primary therapy with EpiCeram alone should not be employed."