Budapest, Hungary The calcineurin inhibitor pimecrolimus exerted more beneficial effects than betamethasone on the disrupted epidermal barrier of atopic dermatitis both structurally and immunologically, according to the results of a small randomized, double-blind study.
The take-away message from this study is that pimecrolimus (Elidel) may be the better option for long-term management of atopic dermatitis, Dr. Jens-Michael Jensen said at the annual congress of the European Society for Dermatological Research.
He reported on 15 atopic dermatitis patients with symmetrical lesions on their upper arms.
The patients were randomized to 3 weeks of twice-daily topical therapy with pimecrolimus 1% on one arm and betamethasone valerate cream 0.1% on the other.
Changes in epidermal barrier function were probed via electron microscopy, immunohistochemical staining, and gene array analysis of protein expression.
Betamethasone resulted in significantly greater clinical improvement and a more pronounced reduction in the epidermal hyperproliferation that is a hallmark of atopic dermatitis.
That being said, the change in epidermal proliferation induced by betamethasone went too far, with suppression to below-normal levels and epidermal thinning, whereas epidermal proliferation in the pimecrolimus-treated lesions was akin to that seen in healthy skin, according to Dr. Jensen.
The treatment-related ultrastructural changes seen through the electron microscope were more favorable with pimecrolimus, as were the changes in expression of genes playing key roles in skin immunologic function, according to Dr. Jensen of the University of Kiel (Germany).
Electron microscopy showed extensive baseline disruption of the lipid bilayers at the stratum granulosum and stratum corneum interface in lesional skin.
The integrity of this lipid bilayer is critical to a well-functioning skin barrier, he explained.
After pimecrolimus therapy, the lipid bilayer architecture became regular and continuous, as in normal skin, while after betamethasone therapy, the lipid bilayer remained irregular and disrupted.
At baseline, lesional skin contained just 9% physiological lamellar bodies, while healthy skin contained 91%.
After treatment with pimecrolimus, 82% of lamellar bodies identified on electron microscopy were categorized as physiological.
In contrast, following betamethasone therapy only 9% of lamellar bodies were categorized as physiologicalthe same as in untreated atopic dermatitis.
Current thinking is that barrier repair prevents penetration of allergens into the skin, with subsequent immune sensitization and inflammation.
The emerging concept of atopic dermatitis is that barrier disruption is not a secondary event occurring in response to immunologic reaction, but rather is a primary event, he explained.
The expression of psoriasin, a chemotactic protein that plays an important role in fighting off penetration of the skin by Escherichia coli, essentially disappeared after 3 weeks of betamethasone therapy. So did expression of other antimicrobial peptides involved in innate immunity, including human beta-defensin-2 and -3 and RNase 7. The expression of genes controlling for stratum corneum keratin production was suppressed as well.
"This decrease is related to broad downregulation of general protein synthesis by the corticosteroid, which is not what we see with pimecrolimus," Dr. Jensen noted.
The expression of antimicrobial peptides was only mildly to moderately suppressed following pimecrolimus therapy. And the gene expression pattern for keratins became normalized, he said.
Dr. Jensen disclosed that the study was supported by Novartis (manufacturer of Elidel), which provided him with a travel grant.