Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis - 12/08/11

Doi : 10.1016/j.jaci.2009.07.015

Jens-Michael Jensen, MD ^a, Stephan Pfeiffer, Dipl Ing ^b, Magdalena Witt, MD ^a, Matthias Bräutigam, MD ^c, Claudia Neumann, BTA ^a, Michael Weichenthal, MD ^a, Thomas Schwarz, MD ^a, Regina Fölster-Holst, MD ^a, Ehrhardt Proksch, MD, PhD ^a,^⁎
^a Department of Dermatology, University of Kiel, Kiel, Germany
^b Microscopy Services, Flintbek, Germany
^c Novartis Pharma GmbH, Clinical Research, Nuremberg, Germany

Reprint requests: Ehrhardt Proksch, MD, PhD, Department of Dermatology, University of Kiel, Schittenhelmstr. 7, 24105 Kiel, Germany.

Abstract

Background

Genetic defects leading to skin barrier dysfunction were recognized as risk factors for atopic dermatitis (AD). It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens.

Objectives

We investigated the effect of 2 common treatments, a calcineurin inhibitor and a corticosteroid, on the skin barrier.

Methods

In a randomized study 15 patients with AD were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks.

Results

Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier, improved in both groups. Dye penetration, a marker of the outside-inside barrier, was also reduced in both drugs. Electron microscopic evaluation of barrier structure displayed prevalently ordered stratum corneum lipid layers and regular lamellar body extrusion in pimecrolimus-treated skin but inconsistent extracellular lipid bilayers and only partially filled lamellar bodies after betamethasone treatment. Both drugs normalized epidermal differentiation and reduced epidermal hyperproliferation. Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning.

Conclusion

The present study demonstrates that both betamethasone and pimecrolimus improve clinical and biophysical parameters and epidermal differentiation. Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD.

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Key words : Atopic dermatitis, skin barrier, pimecrolimus, corticosteroid, skin penetration

Abbreviations used : AD, pEASI, TEWL

Plan

Methods

Patients and treatment regimens

Clinical assessment

Biophysical measurements of stratum corneum hydration and transepidermal water loss

Dye penetration

Histologic analysis

Immunohistochemistry and proliferation assay

Chemical fixation and ultramicrotomy for transmission electron microscopy

Statistical analysis

Results

Clinical assessment and stratum corneum hydration

TEWL and dye penetration

Epidermal proliferation and thickness

Epidermal differentiation

Skin barrier structure and lamellar body extrusion evaluated by means of transmission electron microscopy

Discussion

	Supported by grants of the Deutsche Forschungsgemeinschaft (SFB415/B2 and SFB617/A7, A21) and Novartis Pharma, Nürnberg (Germany), given to E. Proksch and J.-M. Jensen. T. Schwarz and E. Proksch have acted as consultants to Novartis. M. Bräutigam is employed by Novartis.
	Disclosure of potential conflict of interest: J.-M. Jensen has received a travel grant from Novartis. T. Schwarz has received grants from Novartis and Therakos and has served as an advisor for Novartis. The rest of the authors have declared that they have no conflict of interest.