title: The response of normal human skin to single and repeated applications of dithranol cream: an immunohistochemical assessment.
abstract: The irritative response of uninvolved skin is a serious limitation of dithranol therapy in psoriasis. A characterisation in cell biological terms may be helpful in finding an effective counteraction to this well-known irritation. Therefore, we studied the effect of single and repeated applications of dithranol on normal human skin. Besides a clinical evaluation, we studied aspects of epidermal proliferation, differentiation and inflammation. On day 2, after single dithranol challenge, we observed an induction of both the cornified envelope precursor protein involucrin and the cross-linking enzyme transglutaminase I. Subsequently, epidermal hyperproliferation was observed with a maximum on day 8. The epidermal response to dithranol appears to be a reinforcement of the barrier function. Remarkably, however, filaggrin was found to be decreased. Profilaggrin breakdown might be an attempt to compensate for xerosis of uninvolved skin that accompanies dithranol therapy. T lymphocytes and to a lesser extent polymorphonucleocytes were found to be significantly increased. The reduction of Langerhans cells suggests a dose-dependent toxic effect of dithranol or one of its metabolites on Langerhans cells. The dynamics in the induction of changes after repeated challenge are comparable with those after single challenge. However, the induction of hyperproliferation following repeated application appeared to continue between day 8 and 12. Based on the dynamics of dithranol-induced irritation, it may be of interest to study the efficacy of intermittent dithranol treatment. Our results indicate that an optimal timing for biopsies in future dithranol irritation studies lies between 4 and 8 days after the first dithranol challenge.
authors.affiliation: Department of Dermatology, University Medical Centre Nijmegen, The Netherlands. O.Swinkels@derma.zn.nl
authors.forename: O Q J
authors.initials: OQ
authors.lastname: Swinkels
authors.forename: M
authors.initials: M
authors.lastname: Prins
authors.forename: L W J
authors.initials: LW
authors.lastname: Birker
authors.forename: M J P
authors.initials: MJ
authors.lastname: Gerritsen
authors.forename: P G M
authors.initials: PG
authors.lastname: van der Valk
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000875:Anthralin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000187:drug effects* / Q000473:pathology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D000875:Anthralin