Accumulating evidence suggests that psoriasis may be a genetically determined immunogenic, inflammatory disorder based on an ongoing autoreactive Th-1 response. Systemic immunosuppressive therapy is highly effective but fraught with longterm side effects. Our research therefore focuses on therapeutic strategies that induce local immunosuppression in the skin by topical, transepidermal delivery of immunosuppressive drugs. SDZ 281-240 is a newly developed macrolide of the ascomycin type. It is immunosuppressive by mechanism of action similar to that of FK506 but has no antiproliferative activity against keratinocytes in vitro. To evaluate whether SDZ 281-240 exhibits antipsoriatic activity when applied topically, we tested 15 patients with severe, recalcitrant psoriasis, using a microplaque assay in randomized, double-blind, placebo-controlled study, comparing the therapeutic efficacy of the macrolide with a potent halogenated corticosteroid and vehicle. All patients showed a significant improvement of psoriatic lesions treated with two concentrations of the macrolide and, as expected, with the corticosteroid but not with placebo. Both concentrations of the macrolide led to clearing of psoriasis after 10 days of treatment and biopsies confirmed a reversal of the histopathological and immunopathological phenotype of psoriasis to that of normal skin. Thus, an immunosuppressive agent that interferes with early T cell activation can be designed to penetrate into psoriatic lesions when applied topically and to be functionally active within the skin to suppress the ongoing psoriatic process.

Based on available information that melanocytic skin lesions presenting a junctional component are more susceptible to the influence of ultraviolet radiation, this study compares the seasonal differences between the excision rates of melanocytic skin lesions with a junctional component to those without. The histological diagnoses of 1230 patients with melanocytic skin lesions were retrospectively analysed. Depending on the histological diagnosis four groups were formed: melanomas, dysplastic naevi, common naevi (junctional and compound naevi), and dermal naevi. All dates of operations were allocated to summer or winter halves of the year. The collected data were computer analysed for statistical description. The number of excisions of melanocytic lesions with a junctional component (melanoma, dysplastic naevi, common naevi) showed an impressive seasonal variation, with a peak during the summer months, while the excision frequency of dermal naevi was approximately constant during the year. In conclusion, we suggest that ultraviolet radiation may contribute to the seasonal pattern of excision of melanoma and naevi only when a junctional component is present.