Atopic dermatitis: Emerging knowledge enhances clinical practices

October 1, 2008

Recent developments in pediatric atopic dermatitis include the discovery of filaggrin gene mutations and their possible role, a new appreciation of the epidermis' role in the immune system and renewed emphasis on patient education, an expert says.

Key Points

And as clinicians' and researchers' understanding of AD has evolved, so has clinical practice.

"Recognizing the evidence regarding how the disease can disturb quality of life, two things I do differently than in the past are that I always ask patients about sleep disturbance and the impact of eczema on the individual and family," says Lawrence F. Eichenfield, professor, pediatrics and dermatology, and chief, pediatric and adolescent dermatology, Rady Children's Hospital, San Diego, and the University of California, San Diego.

"The most exciting information to emerge over the last few years relates to filaggrin," Dr. Eichenfield tells Dermatology Times.

More specifically, researchers now know that mutations in this gene cause the fairly common condition ichthyosis vulgaris.

"It's been shown that filaggrin mutations are responsible for barrier dysfunction in a significant subset of AD patients as well," Dr. Eichenfield says.

Moreover, having this filaggrin mutation is a very significant risk factor for AD and for asthma in patients with AD (Smith FJ et al. Nat Genet. 2006;38:337-342), though it's not a risk factor for asthma without AD.

As researchers around the world build upon studies that began in Europe, Dr. Eichenfield says, "It has been interesting to see that there are various different types of mutations that are present in AD. It's still uncertain how common these mutations are among all AD patients, with different mutations and differing prevalence regionally."

However, he says there is evidence that filaggrin mutations are associated with a tendency to develop more allergies (and allergic AD) over time, as well as with a higher risk of having persistent AD into older adolescence and adulthood.

Skin's role

Researchers' appreciation of the epidermis' role in the immune system also is evolving.

"People used to think of the epidermis as a passive location for immune activity - that cells would percolate up from the dermis to respond to antigens," Dr. Eichenfield says.

But now, researchers know that a significant amount of immune activity occurs in the skin; that keratinocytes express toll-like receptors; and that the epidermis plays an active role in regulating innate immune activity and in interacting with cathelicidins, he says.

At the same time, he says, "I am very interested in the research from Dr. Richard Gallo's group that has studied how vitamin D may mediate cathelicidins in the skin (Schauber J et al. J Clin Invest. 2007;117(3):803-811)."

Since vitamin D appears to upregulate the innate immune system, Dr. Eichenfield says, "It will be interesting to see whether oral or topical vitamin D can influence skin immunity and perhaps the course of AD."

In keeping with dermatologists' growing appreciation of the skin's role in the immune system, Dr. Eichenfield says, "I am trying to get people to think of the skin's barrier function as not just a structural barrier, but also a functional one."

Along with physically blocking intrusion, he says, the skin also can signal the body to mount a response to such intrusions or barrier breakdowns.