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AD: New understanding, new treatments


Louisville, Ky. - Recent insights into the pathogenesis of atopic dermatitis (AD) and its role as a possible precursor to food and other allergies are driving treatments that seek to restore the skin's barrier function, experts say.

"The prevalence of AD is increasing, and it affects between 10 percent and 17 percent of the total United States population," with 80 percent to 90 percent of patients being diagnosed before age five and about half of them eventually outgrowing it (Ann Allergy Asthma Immunol. 1997 Sep;79(3):197-211), says Leon Kircik, M.D., clinical associate professor of dermatology at Indiana University, Indianapolis.

One in five affected

"And 60 percent of affected infants continue to have symptoms in adulthood (Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93)," Dr. Kircik says.

"Most of the time, patients with AD also suffer from secondary infections," including those caused by community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), Dr. Kircik notes.

Therefore, he says, "I suggest culturing every secondary infection" occurring with AD.

AD also can be a marker for other atopic diseases such as asthma, food allergies, hay fever, allergies and rhinitis, Dr. Kircik asserts.

There's also a theory that if one prevents AD from developing or from becoming severe, one will be able to prevent asthma developing later in life. The concept is called the atopic march (BMJ. 2002 Jun 8;324(7350): 1376-1379), Dr. Kircik explains.

Research inroads

Over the past several years, research into the pathogenesis of AD also has focused on the possibility that patients with this disease have a functional problem with their skin barrier, says Amy E. Gilliam, M.D., assistant clinical professor of pediatrics and dermatology at the University of California, San Francisco.

In particular, she says researchers have shown that this barrier dysfunction in patients with AD correlates with a reduction in ceramides, one of the three key stratum corneum lipids.

"Ceramides may also influence inflammatory responses, in addition to their contribution to effective barrier function," Dr. Gilliam says.

"Another recent development in the understanding of the pathogenesis of AD involves a study showing that there may be a genetic predisposition for AD," she says.

In particular, researchers have shown that an inherited reduction in the expression of filaggrin, a key protein involved in the formation of the skin barrier, is a major predisposing factor in AD (Nat Genet. 2006 Apr;38[4]:441-446. Epub 2006 Mar 19).

"This genetic mutation in filaggrin in affected families further supports the hypothesis that an impaired skin barrier plays a key role in the pathogenesis of AD," Dr. Gilliam says.

Similarly, Dr. Gilliam notes other studies have shown that the skin of patients with AD is deficient in certain antimicrobial peptides, specifically beta defensins and cathelicidins, which contribute to the skin's barrier against infection (J Invest Dermatol. 2005 Jul;125[1]:9-13).

Pharmaceutical armamentarium

In keeping with the foregoing developments, manufacturers have begun offering ceramide-based moisturizing creams and other barrier repair formulations, sources say.

Ceramide-based creams include TriCeram (Osmotics), EpiCeram (Ceragenix) and TriXera (Eau Thermale Avene), while products that have earned Food and Drug Administration (FDA) approval include Atopiclair (Sinclair Pharmaceuticals Ltd./Chester Valley) and Mimyx (PEA, Steifel), Dr. Gilliam says.

"Atopiclair and Mimyx do not contain ceramides, but multiple other agents that have anti-inflammatory and anti-pruritic properties," she tells Dermatology Times.

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