Filaggrin epidermal barrier protein shows promise for treating pediatric AD tx

March 1, 2007

The prevalence of atopic dermatitis has steadily increased over the past 40 years, and in children born after 1980, the rate has increased 15 percent to 20 percent.

"Some parents saw the reports and became concerned, but I also saw new patients brought in by parents who were happy with the treatment, but whose physicians were the ones who were now apprehensive," Dr. Treadwell says.

She is an investigator for Novartis' Study of the Atopic March (SAM) that is currently under way. The six-year study of 1,100 infants with eczema is investigating whether the use of the nonsteroidal TIM pimecrolimus (Elidel, Novartis) at the first sign of eczema can prevent the subsequent development of asthma, a consequence of the so-called atopic march.

Hopes are high that topical immunomodulators can offer an alternative to steroidal treatments, which can carry such side effects as the thinning of the skin and increased risk of infection.

TIM safety concerns

But the use of TIMs in infants under 2 years of age raises its own safety concerns, such as the potential for increasing the risk of infections, including chickenpox, by suppressing the immune system.

The SAM study will also evaluate those safety concerns.

Regarding the research linking TIMs with cancer that prompted the FDA's "black box" requirement, Dr. Treadwell says she explains to patients that the research did not involve topical medications, and she adds that if the FDA were that concerned about the risks, the agency would have stopped the SAM study, which it didn't.

Aside from TIMs, researchers continue to look for new alternatives for pediatric atopic dermatitis, but with one of the more intriguing possibilities in recent years - probiotics - the progress has been a case of one step forward, two steps back.

Preliminary probiotics study

In the preliminary probiotics study published in October 2006, researchers at the University of Western Australia, Perth, reported that, at six months of age, 58 high-risk infants who were given the probiotic Lactobacillus acidophilus (LAVRI-A1, Probiomics), showed immunomodulatory effects, compared to a placebo group of 60 children.

"The children who received probiotics showed reduced production of IL-5 and TGF-beta in response to polyclonal stimulation (P=0.044 and 0.015, respectively)," the researchers wrote (Clin Exp Allergy. 2006 Oct; 36(10):1227-1235).

They also reported that children receiving probiotics showed significantly lower IL-10 responses to TT vaccine antigen compared with the placebo group, and not due to vaccination differences.

However, the research group reported that, in follow-up at 12 months of age, not only was there no reduction of AD in infants in the probiotics group, but the supplementation was in fact associated with increased allergen sensitization (J Allergy Clin. Immunol. 2007 Jan;119[1]:184-191. Epub 2006 Oct 13).

In other AD developments, researchers at the University of Dundee, Scotland, reported that two loss of function genetic mutations in the gene encoding for the epidermal barrier protein filaggrin are strong disposing factors for AD, as well as for asthma associated with AD (Nat Genet. 2006 Apr:38[4]:441-446). The researchers say the findings underscore the importance of the skin barrier in preventing allergic sensitization. In addition, they help explain family links to AD.