1. ¹Center for Skin Biology, Stiefel Laboratories Inc., Palo Alto, California, USA
2. ²Stiefel Research Australia, Melbourne, Victoria, Australia

Correspondence: Dr Hans E.J. Hofland, Center for Skin Biology, Stiefel Laboratories Inc., 3160 Porter Drive, Palo Alto, California 94304, USA. E-mail: hans.hofland@stiefel.com

Received 21 December 2006; Revised 21 May 2007; Accepted 23 May 2007; Published online 19 July 2007.

Abstract

Oral acitretin is currently indicated for the treatment of severe psoriasis in adults, but its use is limited by systemic side effects and teratogenicity. Topical administration of acitretin may lessen the risk of systemic toxicity while increasing local bioavailability in the skin. The effects of topical acitretin on reconstructed human epidermis (RHE) and Rhino mice were investigated and compared to those of currently marketed topical retinoids: tretinoin and tazarotene. In acitretin-treated RHE cultures, there was a reduction in keratohyalin granules and filaggrin expression in the stratum granulosum, a loss of keratin 10 expression in the stratum spinosum, and an increase in keratin 19 expression in all viable cell layers. All retinoids showed similar signs of activity in RHE cultures. Furthermore, the release of pro-inflammatory cytokines IL-1 and IL-8 in RHE cultures was less pronounced with acitretin compared to tretinoin- and tazarotene-containing formulations, suggesting that acitretin may be less irritating. In Rhino mice, acitretin induced a local, dose-dependent reduction in utricle diameter after seven daily dermal doses. A similar effect was observed in tretinoin- and tazarotene-treated mice. Our data suggest that topical application of acitretin may have a therapeutic benefit in the local management of keratinization disorders.