Oral R115866 in the treatment of moderate to severe plaque-type psoriasis.

BACKGROUND: R115866 (Rambazole) is a new generation all-trans retinoic acid metabolism blocking agent, highly specific against the retinoic acid 4-hydroxylase. The drug alleviates hyperproliferation and normalizes differentiation of the epidermis in animal models of psoriasis. OBJECTIVE: To explore the efficacy, safety and tolerability of systemic R115866 in patients with moderate to severe plaque-type psoriasis. PATIENTS AND METHODS: In this open label, single-arm trial, patients were treated with R115866, 1 mg/day for 8 weeks, followed by a 2-week treatment-free follow-up period. Patients were monitored for efficacy and safety. RESULTS: Nineteen patients (intent-to-treat population) were treated and 14 completed the entire study. Two patients discontinued due to lack of efficacy and three due to adverse events. At the end of the treatment, 26% of the patients showed at least 50% reduction in Psoriasis Area Severity Index (PASI) compared to baseline. Further improvement was observed at the end of the 2-week follow-up period where 47% of the patients showed a 50% or greater reduction in PASI. Kinetic data showed no evidence of accumulation of either R115866 or retinoic acid in plasma. The most common adverse events were pruritus, xerosis, cheilitis and an increase in blood triglycerides. The majority of adverse events were mild to moderate. No deaths or serious adverse events were reported. CONCLUSION: Eight-week daily treatment with 1 mg R115866 resulted in a significant reduction in PASI from baseline to end of therapy. Additional improvement was seen after the 2-week follow-up period. The drug was well tolerated. R115866 merits further evaluation to optimize its clinical efficacy and safety profile in moderate to severe plaque-type psoriasis.

[Behçet's disease in a Dutch boy with painful skin lesions]. / De ziekte van Behçet bij een Nederlandse jongen met pijnlijke huidafwijkingen.

A 14-years-old Dutch boy had pain in both calves, recurrent oral ulcers, fever, hoarseness and erythema nodosum-like skin lesions. Laryngoscopic examination revealed a vocal cord ulcer and leukocytoclastic vasculitis was visible in a skin biopsy. Based on the clinical picture, the diagnosis of 'incomplete juvenile Behçet's disease' was established. During treatment with colchicine, genital ulcers developed. These disappeared after local treatment with corticosteroids. Juvenile Behçet's disease is rare in Western Europe and the diagnosis is often difficult. Diagnostic criteria have been formulated, but in most cases there is a delay before these criteria are fulfilled due to the slow clinical course of the disease. All organ systems may be affected; mucocutaneous and skin lesions are the most frequent manifestations. Therapy depends on the severity and the symptoms of the disease.