RESPONSE OF THE CLINICALLY UNINVOLVED SKIN OF PSORIATIC PATIENTS TO REPEATED TAPE STRIPPING DURING CYCLOSPORINE-A TREATMENT

It is well established that cyclosporin A (CyA), a widely used immunos uppressant in human organ transplantation, is an effective drug in the treatment of psoriasis. Although it has been postulated that the effe ct of CyA in psoriasis is mediated through antilymphocyte activity, th ere is also evidence suggesting that CyA exerts a direct cytostatic ef fect on epidermal keratinocytes, but results of studies relating to th e latter have been contradictory. Using immunohistochemical methods we investigated the influence of systemic CyA on proliferation and diffe rentiation in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity of studying epidermal regenera tion in the absence of a significant accumulation of T lymphocytes. We addressed the question of whether CyA (3-5 mg/kg/day) modulates epide rmal proliferation and differentiation following standardized injury i n uninvolved skin of psoriatic patients. Ten patients with severe psor iasis participated in this study. The dosages of CyA were sufficient t o induce a marked and statistically significant improvement (PASI, wee k 0, 20.5+/-4.4; PASI, week 16, 4.3+/-0.6). Before CyA treatment, and during week 16 of treatment, Sellotape stripping was carried out on a 2-cm(2) area of the uninvolved skin of psoriatic patients. After 48 h punch biopsies were taken. Immunohistochemical assessment of recruitme nt of cycling cells (Ki-67), filaggrin, involucrin, T lymphocytes and tenascin, was carried out. We did not find any significant alteration during the treatment period in the tape-stripped uninvolved skin of ps oriatic patients. We conclude that epidermal hyperproliferation and ab normal keratinization are not modulated directly by CyA at therapeutic doses in vivo. Furthermore, our study provides indirect evidence that the antipsoriatic effect of CyA is mediated by the immune system.