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Notes: Abstract. Objective: Dapsone (4,4'diaminodiphenylsulfone) is effective in treating leprosy, chronic inflammatory conditions and opportunistic infections in HIV patients. By the oral route, the sulfone is metabolized to monoacetyldapsone (MADDS) and dapsone hydroxylamine (DDS-NOH). We have addressed the question as to whether these dapsone metabolites have anti-inflammatory properties of their own in vivo.¶Treatment and Methods: After two weeks topical pre-treatment with MADDS (1%), DDS-NOH (1%) and clobetasol proprionate (CP; 0.05%) dissolved in acetone, as a reference, 10 ng leukotriene B4 (LTB4) were applied on the upper arms of eight healthy volunteers. After 24 h, biopsies were taken and the polymorphonuclear leukocytes (PMN) were quantified fluorometrically using elastase as marker enzyme.¶Results: MADDS did not show any inhibitory activity on trafficking of PMN compared to the corresponding control and nontreated area (untreated: 790 ± 450 PMN/10 μg skin; p 〉 0.05, acetone: 840 〉 578 PMN/10 μg skin; MADDS: 1099 〉 556 PMN/10 μg skin), whereas DDS-NOH caused a statistically significant inhibition of PMN accumulation as did the reference CP (DDS-NOH: 128 〉 143 PMN/10 μg skin; CP: 86 〉 131 PMN/10 μg skin, p 〈 0.01).¶Conclusions: These results indicate that DDS-NOH has anti-inflammatory potential which might contribute to the effectiveness of dapsone therapy.

Notes: Background  Based on the increasing knowledge of T-cell-mediated pathogenesis in atopic dermatitis (AD), systemic immunosuppressive drugs are increasingly applied. The chronic, relapsing course of severe AD necessitates a drug, both efficacious and safe in long-term application. Leflunomide is a pyrimidine de novo synthesis-inhibiting immunosuppressant exhibiting an extremely long in vivo half life of its active metabolite.Objectives  To evaluate the efficacy of leflunomide in long-term treatment of AD.Methods  As a proof of principle, we treated two patients with severe AD, recalcitrant to different systemic treatment modalities, for 20 months with leflunomide (loading dose 100 mg daily during 3 days; maintenance dose 20 mg daily). At regular visits physical examination, eczema area and severity index (EASI), visual analogue scale (VAS) for itching, and laboratory findings were assessed with according adjustment of the leflunomide dose.Results  At the initiation of leflunomide therapy, both patients presented with almost erythrodermic AD (patient 1, EASI 40·0, VAS 10; patient 2, EASI 43·0, VAS 8). Partial remission was observed within 4 and 7 weeks, respectively, and maintained over 20 months (patient 1, median EASI 4·2, median VAS 2; patient 2, median EASI 8·4, median VAS 2) except for one episode of exacerbation in each case. In one patient, remission was stable even after cessation of drug dosing. Severe adverse events were not observed.Conclusions  Leflunomide was efficient in the long-term treatment of recalcitrant AD. Controlled studies will be necessary to evaluate the subset of severe AD patients benefiting most from this drug.

Notes: Background  A two-compound ointment containing calcipotriol 50 µg g−1 and betamethasone dipropionate 0·5 mg g−1 has recently been shown to be an effective treatment for psoriasis.Objectives  This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet®/Dovobet®; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 µg g−1 ointment (Daivonex®/Dovonex®; LEO Pharma).Methods  In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment.Results  The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73·3% for group 1, 68·2% for group 2 and 64·1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55·3% for group 1, 47·7% for group 2 and 40·7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 (P 〈 0·001), whereas group 2 did not differ significantly from group 3. The difference between group 1 and group 2 was statistically significant with regard to PASI but not regarding the proportion of patients with absent/very mild disease. Patients receiving initial therapy with the two-compound product achieved the fastest treatment response, and the maximum treatment effect for these patients was seen after 5 weeks. This effect was maintained with continued treatment with the two-compound product for up to 8 weeks. After 12 weeks of treatment, no significant differences were seen between the three groups with regard to reduction in PASI, whereas the proportion of patients with absent/very mild disease in group 2 was superior to that in group 3. Patients receiving therapy with the two-compound product experienced fewer lesional/perilesional adverse drug reactions than the calcipotriol-treated patients (P 〈 0·001): 10·9% in group 1, 11·5% in group 2 and 22·3% in group 3.Conclusions  Two different short-term treatment regimens employing a recently developed two-compound product (calcipotriol/betamethasone dipropionate) provided rapid and marked clinical efficacy and were shown to be safe therapies for psoriasis vulgaris.

Notes: Summary Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pre-treated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.