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Notes: Abstract: In skin biology, matrix metalloproteinases (MMPs) have been implicated in inflammatory matrix remodeling, neovascularization, wound healing and malignant transformation. Psoriasis is histologically characterized by keratinocyte hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-α, IL-1β, TGF-α, and IFN-γ, also capable of regulating MMP transcription. To investigate the role of stromelysins-1 and -2, matrilysin, metalloelastase, collagenases-1 and -3 and 92-kDa gelatinase as well as their inhibitors, TIMPs-1 and -3, in psoriasis, we performed in situ hybridization using 35S-labeled cRNA probes on 29 psoriatic lesions and 9 samples of normal looking skin from psoriatic patients. Metalloelastase mRNA was detected in 21/27 samples in macrophages that had migrated into the epidermis or in the inflammatory infiltrates of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in basal keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in basal keratinocytes of the same samples, suggested that stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for stromelysin-2 or collagenase-3 was found and only sweat glands were positive for matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the inflammatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP-3 was expressed perivascularly in 9/16 samples. Our results suggest that overexpression of the investigated MMPs by keratinocytes is not associated with psoriasis. However, macrophages express MMPs in psoriatic skin. Also TIMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.

Notes: Summary  Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 µg g−1) and betamethasone dipropionate (0·5 mg g−1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. Objectives The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. Methods This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. Results There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68·6% once daily, 73·8% twice daily) than in both the twice daily calcipotriol group (58·8%) and the vehicle group (26·6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9·9% combined formulation once daily, 10·6% combined formulation twice daily, 19·8% calcipotriol, 12·5% vehicle). Conclusions No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.

Notes: Background  Long-term use of topical trimethylpsoralen (TMP) psoralen bath plus ultraviolet A (bath PUVA) is considered safe with regard to the risk of skin cancer. However, the potential for severe phototoxicity limits its use. Objectives  To study the effect of dilution of the TMP bath on the minimal phototoxic dose (MPD). Methods  Fifteen volunteers participated in the study. The MPD tests were performed for three TMP concentrations: 0·33 mg L−1, 0·1 mg L−1 and 0·033 mg L−1 at 2-week intervals. Geometric UVA dose series increasing by a factor of √2 were used for the testing on the previously unexposed buttock skin. The MPD72 h was assessed at 72 h from the bath. Results  For the highest TMP concentration of 0·33 mg L−1, the median MPD72 h was 0·14 J cm−2 (95% confidence interval (CI), 0·10–0·14 J cm−2). For the diluted TMP bath concentration of 0·1 mg L−1, the median MPD72 h increased to 0·29 J cm−2 (95% CI, 0·2–0·41 J cm−2) and for 0·033 mg L−1 to 0·81 J cm−2 (95% CI, 0·57–1·15 J cm−2), respectively. Thus, diluting the labelled concentration of 0·33 mg L−1 1 : 10 increased the median MPD72 h 5·6-fold. Conclusions  With regard to the safety and practicality of the TMP bath PUVA, the lower concentrations of TMP may be of clinical importance, and this needs to be validated in future controlled clinical trials.

Notes: The effect of heliotherapy on psoriasis skin lesions and arthritis was studied in a trial comprising 4 weeks of therapy in the Canary Islands and a 6-nionth follow-up period, A total of 373 patients participated in the heliotherapy and in patients completed the follow-up period. The severity of skin lesions was evaluated using a psoriasis severity index (PSI), and that of the arthropathy by using an arthritis index (AI).During heliotherapy, the PSI decreased significantly from the initial median value of 4.5 to the final value of 0.2, A reduction in the PSI of at least 75% was achieved in 84% of the patients. Guttate psoriasis improved significantly better than plaque-type or erythrodermic psoriasis. There was no correlation between skin type and improvement. Initially, 129 patients had symptoms of arthritis. During heliotherapy, the AI decreased significantly from the initial median value of 6 to the final value of 2.The median time until starting another treatment after heliotherapy was 80 days, and the PSI had returned to its original value in 49% of the patients in 6 months. In patients with joint symptoms the AI returned to the pretreatment level within 6 months.A 4-week heliotherapy period effectively cleared psoriasis, alleviated joint symptoms, and reduced both morbidity and treatment requirement to a considerable extent in the ensuing 6-month period.