Topical Corticosteroids
Currently, topical glucocorticosteroids (TCS) or topical calcineurin inhibitors (TCI) are the usual first-line treatments of vitiligo. The TCS have been used widely as topical and sometimes intralesional therapy in viti-ligo since their introduction in de
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3.2.1 3.2
3.2.1
J. P. Wietze van der Veen, Bas S. Wind, and Alain Taïeb
Contents 3.2.1.1 Introduction ........................................................... 327 3.2.1.2 Mode of Action and Rationale for Use in Vitiligo .................................................. 327 3.2.1.3 Studies .................................................................... 328 3.2.1.4 Application Scheme............................................... 329 3.2.1.5 Side Effects ............................................................ 329 3.2.1.6 Safety Issues........................................................... 329
3.2.1.1 Introduction Currently, topical glucocorticosteroids (TCS) or topical calcineurin inhibitors (TCI) are the usual first-line treatments of vitiligo. The TCS have been used widely as topical and sometimes intralesional therapy in vitiligo since their introduction in dermatology in the 1950s. However, based on current criteria for clinical trials, the studies are of poor quality and since 1977, no randomized controlled trial (RCT) has been published.
References ........................................................................... 329
3.2.1.2 Mode of Action and Rationale for Use in Vitiligo
J.P.W. van der Veen () Netherlands Institute for Pigment Disorders and Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands e-mail: [email protected]
The classical, genomic mechanism of glucocorticoid (GC) action can be divided into transrepression, which is responsible for a large number of desirable antiinflammatory and immunomodulating effects, and transactivation, which is associated with frequently occurring side effects as well as with some immunosuppressive activities [17]. After cell-membrane passage, GC interacts with the cytosolic glucocorticoid receptor (cGCR). Chaperones and co-chaperones are transported with the receptor into the nucleus where they modulate the action of the receptor. Transactivation is largely mediated through binding of the receptor as homodimer to specific sequences in the promoter or enhancer regions of GC-responsive genes. Dimerization of the GR is a prerequisite for the activation of gene expression. Other mechanisms of activation occur possibly through the activation function domains 1 and 2 of the receptor [17]. Transrepression mechanisms are not fully understood, but the receptor can inhibit the activity of other
M. Picardo and A. Taïeb (eds.), Vitiligo, DOI 10.1007/978-3-540-69361-1_3.2.1, © Springer-Verlag Berlin Heidelberg 2010
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transcription factors such as activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and interferon regulatory factor-3 (IRF-3), which regulate the expression of proinflammatory genes. The negative regulation of those transcription factors by the GR has become a paradigm for the antiinflammatory and immunosuppressive action of GCs. Some of the immunosuppressive and antiinflammatory activities of GCs are also mediated by MAP kinase phosphatase-1 [17]. TCS have well-known
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