DENVER—Bacterial or viral skin infections affect about 30% of patients with atopic dermatitis but only 7% of those with psoriasis, even though the skin barrier is compromised in both conditions. Why are skin infections more likely in atopic dermatitis?

“An antimicrobial peptide deficiency in the skin may explain this,” says Donald Y. M. Leung, MD, PhD, Head of Pediatric Allergy-Immunology at the National Jewish Medical and Research Center in Denver. Dr. Leung’s group recently found that two antimicrobial peptides—a cathelicidin and a ß2-defensin (HBD-2)—are abundant in skin samples from psoriasis patients, but their levels are markedly reduced in the skin of atopic dermatitis sufferers.[1]

Testing showed that the combined concentration of these peptides was sufficient to kill Staphylococcus aureus in psoriatic lesions but not in atopic lesions. Skin infections in patients with atopic dermatitis are very often caused by S aureus, the researchers noted.

PEPTIDE CONCENTRATION AND ANTIMICROBIAL ACTIVITY

Dr. Leung and colleagues compared the cathelicidin LL-37 and HBD-2 expression in skin samples from eight patients who had moderate to severe atopic dermatitis affecting 20% to 60% of the total skin area and from 11 psoriasis patients with 15% to 40% skin involvement. The study also included six healthy controls.

Skin LL-37 and HBD-2 concentrations were measured using immunohistochemical staining, Western and immunodot blot analysis, and a quantitative real-time reverse-transcriptase polymerase chain reaction assay. The antimicrobial activity of the two peptides against S aureus was assessed with a colony-forming assay.

UNEXPECTED FINDINGS

The decline in antimicrobial peptides associated with atopic dermatitis was unexpected, the researchers noted. Previous investigations had demonstrated that levels of LL-37 and HBD-2 are markedly increased in patients with other inflammatory skin conditions.

The deficiency may have been related to the elevated concentrations of the T-helper 2 (TH2) cytokines interleukin 4 (IL-4) and IL-13 known to occur in eczematous skin. In the study, IL-4 and IL-13 were highly effective at inhibiting HBD-2 gene expression.

The study “provokes many questions and highlights the importance of the protective shield that antimicrobial peptides provide on our epithelial surfaces,” remarked Michael A. Zasloff, MD, PhD, in an editorial.[2] Among the questions that must be addressed, said Dr. Zasloff, Dean of Research and Translational Science at Georgetown University Medical Center in Washington, DC, are: To what extent are the signs and symptoms of eczema caused by antimicrobial peptide deficiency? And, can the study findings be extended to bronchial asthma?

How should the antimicrobial peptide deficiency be treated? “Based on our findings, it may be possible to replace the peptides or neutralize the TH2 response that suppresses their production,” Dr. Leung suggested.

—Timothy Begany