The influence of a topical corticosteroid on short-contact high-dose dithranol therapy.
BACKGROUND
Dithranol (anthralin) has been known to be effective in the treatment of psoriasis for more than 80 years. However, perilesional and uninvolved skin often show irritation during dithranol treatment, which limits its use. As the relapse rate of psoriasis is worsened by adding corticosteroids to a dithranol regimen, the use of topical corticosteroids to reduce dithranol irritation is controversial.


OBJECTIVE
The aim of the present study was to investigate the clinical and cell biological effect of clobetasol-17-propionate 0.05% ointment on dithranol-treated lesional and perilesional skin.


METHODS
For 17 consecutive days, 2% dithranol cream was applied on two test sites. A third site was left untreated on all participating patients (n = 8). All sites consisted of a psoriasis lesion as well as a 3-cm zone of perilesional skin localized on the back. After 1 h, the cream was washed off, and subsequently one of the dithranol-treated sites was treated once a day with clobetasol-17-propionate 0.05% ointment. The second site was treated once daily with the vehicle. On day 17, punch biopsies were taken from all three lesions and from the perilesional zone of all test sites in order to perform an immunohistochemical investigation, using markers to assess proliferation, differentiation and inflammation.


RESULTS
The SUM score (erythema + induration + scaling) of the lesion treated with dithranol/clobetasol showed a pronounced reduction, which was significantly greater than the SUM score of the lesion treated with dithranol/vehicle. However, the scores of both sites were equal by 6 weeks of follow-up. Comparing the two treated lesions, we observed a lower number of cycling epidermal cells in the dithranol/clobetasol lesion and a significantly lower perivascular dermal score of T lymphocytes. Comparing the perilesional skin of the two treated sites we observed less cycling epidermal cells in the dithranol/clobetasol-treated site. Regarding perilesional differentiation, the interpapillary involucrin expression was higher in the dithranol/clobetasol-treated site. With respect to perilesional inflammation the expression of dermal polymorphonuclear leucocytes, monocytes, macrophages and T lymphocytes in the dermal infiltrate were significantly lower in the dithranol/clobetasol-treated site.


CONCLUSIONS
The addition of clobetasol-17-propionate enhanced the antipsoriatic efficacy of dithranol by interfering with T-cell accumulation and epidermal proliferation. The addition of a corticosteroid reduced perilesional dithranol inflammation at the cellular level, although clinically detectable dithranol erythema was not reduced.
Swinkels
O Q
OQ
Department of Dermatology, University Hospital Nijmegen, P.O.Box 9101, 6500 HB Nijmegen, The Netherlands. O.Swinkels@derma.azn.nl
Prins
M
M
Tosserams
E F
EF
Gerritsen
M J
MJ
Van Der Valk
P G
PG
Van De Kerkhof
P C
PC
D000287:Administration, Topical; D000875:Anthralin / Q000009:adverse effects / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002990:Clobetasol / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004817:Epidermis / Q000473:pathology; D005500:Follow-Up Studies; D005938:Glucocorticoids; D006801:Humans; D007124:Immunoenzyme Techniques; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D002990:Clobetasol; D000875:Anthralin