Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis

被引:86
作者
Jensen, Jens-Michael [1 ]
Pfeiffer, Stephan [2 ]
Witt, Magdalena [1 ]
Braeutigam, Matthias [3 ]
Neumann, Claudia [1 ]
Weichenthal, Michael [1 ]
Schwarz, Thomas [1 ]
Foelster-Holst, Regina [1 ]
Proksch, Ehrhardt [1 ]
机构
[1] Univ Kiel, Dept Dermatol, D-24105 Kiel, Germany
[2] Microscopy Serv, Flintbek, Germany
[3] Novartis Pharma GmbH, Clin Res, Nurnberg, Germany
关键词
Atopic dermatitis; skin barrier; pimecrolimus; corticosteroid; skin penetration; TRANSEPIDERMAL WATER-LOSS; STRATUM-CORNEUM; PERMEABILITY BARRIER; EPIDERMAL DIFFERENTIATION; LANGERHANS CELLS; UNINVOLVED SKIN; IN-VIVO; FILAGGRIN; ECZEMA; PENETRATION;
D O I
10.1016/j.jaci.2009.03.032
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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. (J Allergy Clin Immunol 2009;123:1124-33.)
引用
收藏
页码:1124 / 1133
页数:10
相关论文
共 52 条
[1]   IMPROVEMENT OF SKIN BARRIER FUNCTION DURING TREATMENT OF ATOPIC-DERMATITIS [J].
AALTOKORTE, K .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1995, 33 (06) :969-972
[2]  
AGNER T, 1992, ACTA DERM-VENEREOL, P1
[3]   The pathophysiology of atopic eczema [J].
Allam, JP ;
Novak, N .
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 2006, 31 (01) :89-93
[4]   PATHOGENESIS OF ATOPIC ECZEMA [J].
BOS, JD ;
KAPSENBERG, ML ;
SMITT, JHS .
LANCET, 1994, 343 (8909) :1338-1341
[5]   The immunogenetics of asthma and eczema: A new focus on the epithelium [J].
Cookson, W .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (12) :978-988
[6]  
Elias P M, 1999, Am J Contact Dermat, V10, P119, DOI 10.1016/S1046-199X(99)90054-4
[7]   Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms [J].
Elias, Peter M. ;
Hatano, Yutaka ;
Williams, Mary L. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 121 (06) :1337-1343
[8]  
ELIAS PM, 1991, ADV LIPID RES, V24, P1
[9]   PERMEABILITY BARRIER IN MAMMALIAN EPIDERMIS [J].
ELIAS, PM ;
FRIEND, DS .
JOURNAL OF CELL BIOLOGY, 1975, 65 (01) :180-191
[10]  
Elias PM, 2001, ARCH DERMATOL, V137, P1079