The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial.

BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.

Phenotypic/genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression.

Dominant-negative mutations in the KRT1 and KRT10 genes cause epidermolytic hyperkeratosis, a rare form of ichthyosis sometimes associated with palmoplantar keratoderma. Although there is no permanent cure, some patients improve on retinoid therapy. More knowledge is needed, however, about the mechanism of action of retinoids and the genotypic/phenotypic correlations in this disease. Thirteen patients from 10 families with generalized disease and 2 sporadic patients with nevoid lesions were studied, probably representing most of the patients in Sweden and Norway. All patients, except one nevoid case, were known to have KRT1 or KRT10 mutations. Those with mutated keratin 1 (K1) invariably had associated keratoderma (n=6). In contrast, only 1 of 7 patients with K10 mutations had this problem (p = 0.0047). Five out of 6 patients with KRT10 mutations benefited from treatment with oral acitretin (5-25mg/day) or topical tretinoin/tazarotene, but none of the patients with KRT1 mutations derived any benefit. Quantitative analysis of K1 and K10 mRNA in skin biopsies obtained before and after retinoid therapy (n=8) showed no consistent down-regulation of mutated keratin that would explain the therapeutic outcome. Instead, the mRNA expression of K2e (a normal constituent of the upper epidermis) diminished especially in nonresponders. In contrast, K4 mRNA and protein (marker of retinoid bioactivity in normal epidermis) increased in almost all retinoid-treated patients. In conclusion, our study confirms a strong association between KRT1 mutations and palmoplantar keratoderma. Retinoid therapy is particularly effective in patients with KRT10 mutations possibly because they are less vulnerable to a down-regulation of K2e, potentially functioning as a substitute for the mutated protein in patients with KRT1 mutations.

[Pathological findings in the eye of children with facial nevus]. / Patologiske funn i øyet hos barn med fødselsmerke i ansiktet.

BACKGROUND: Port-wine stains distributed to the trigeminal area may be associated with eye and/or central nervous system complications. Visual loss may be prevented with screening for eye pathology at an early age with adequate intervention. MATERIAL AND METHODS: 45 children with port-wine stains in the trigeminal area were examined by an ophthalmologist under general anaesthesia. RESULTS: Seven of 30 patients with one or both eyelids affected had a choroidal vascular anomaly. Four patients had glaucoma. These four patients had both eyelids affected. Two children with a vascular anomaly had only upper eyelid involvement. INTERPRETATION: Patients with facial port-wine stains affecting the eyelids should be screened for eye pathology at an early age.

[Pyoderma gangrenosum--possible diagnosis in therapy-resistant wounds]. / Pyoderma gangrenosum--aktuell diagnose ved terapiresistente sår.

Pyoderma gangrenosum is a chronic ulcerative inflammatory skin disease. The condition is often associated with inflammatory bowel disease. We report three patients with pyoderma gangrenosum successfully treated with cyclosporin. There were difficulties in establishing the diagnosis, and antibiotics, surgical excisions and different wound dressings had been used without effect.

Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study. The PISCES Study Group.

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan-Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.

Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis.

BACKGROUND: Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids. OBJECTIVES: To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol. METHODS: Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas. RESULTS: Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect. CONCLUSIONS: Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.

Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.

OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.

A multicentre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris.

In a double-blind, parallel group study we compared fluconazole 150 mg once weekly with griseofulvin 500 mg once daily for 4-6 weeks in the treatment of tinea corporis or tinea cruris. Eighty-four of 114 patients (74%) (39% after 3 weeks) were clinically cured in the fluconazole group compared with 72 of 116 (62%) (39% after 3 weeks) in the griseofulvin group (P = 0.06). In the fluconazole group 78% were mycological cured compared with 80% in the griseofulvin group. In the fluconazole group nine patients (7.5%) had treatment related adverse events and in the griseofulvin group 15 patients (12.5%) had adverse events. Fluconazole 150 mg once weekly for 6 weeks is both clinically and mycologically effective in the treatment of tinea corporis and tinea cruris and few side-effects were reported.

[Nevus flammeus in small children treated pulsed dye laser]. / Nevus flammeus hos små barn behandlet med pulset fargelaser.

We report the results of treating 30 children less than 7.5 years old for port wine stains of the face and neck using pulsed dye laser with a wave length of 585 nm. The children were given a general anaesthetic. In five children the stains disappeared completely and in 21 there was marked improvement (> 75% lighter). The younger age group, 7 months to 4 years, required fewer treatment sessions (mean 3.7) than the older age group, 4 to 7 years (mean 5.1 sessions), indicating the benefit of early treatment. No side effects were seen except for transient hyperpigmentation.

Efficacy and skeletal side effects of two years' acitretin treatment.

In this prospective study, 51 patients suffering from psoriasis and ichthyosis were treated with acitretin for 2 years. The average dose was 0.5 mg/kg/day. We have evaluated the efficacy and side effects, focusing on skeletal side effects. X-ray examinations were done before treatment and after 1 and 2 years. Forty-five patients completed the study. Acitretin had a good clinical effect, with 75% improvement in 35 of the patients. Apart from the well-known side effects affecting the mucous membranes, one patient developed biopsy- proven toxic hepatitis. In 2 patients we observed unusual skeletal calcifications located in the forearms and in the hip. These were considered to be caused by the drug. In this study, which included patients up to 71 years, only radiographs of the pelvis and the forearms were of value as routine follow-up films.

An open, parallel groups, study of the importance of thoroughness of application in the treatment of psoriasis with a dithranol cream (Micanol).

Earlier studies have suggested that the rate of healing is somewhat slower for the new microencapsulated dithranol formulation, Micanol, than for petrolatum or paraffin based formulations. The less smeary Micanol formulation may need more vigorous application. A population of 29 patients with chronic, stable plaque-type psoriasis was divided into two groups, both receiving short contact treatment. One group received standard patient information while the other received information stressing the importance of being thorough when rubbing the dithranol cream into the lesions. Regarding composite sign severity score, there was a significant difference (about 50%) in favour of the extra information group after 6 weeks. This result suggests that thoroughness of application is an important factor for the rate of healing in short contact treatment of psoriasis with Micanol.

[Dermatological laser treatment]. / Dermatologisk laserbehandling.

This article reviews the different lasers used in dermatology. Special emphasis is placed on the treatment of naevus flammeus ("portwine stain") where lasers are the treatment of choice. Argon laser and pulsed dye laser are the main lasers used in vascular skin diseases, and the article focuses on these two types. Copper vapour laser, neodymium-YAG-laser and CO2-laser are also presented. Information is provided about the availability of laser technology in the different health regions in Norway.

A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study.

Acitretin, the free acid of etretinate, is less lipophilic and has a much shorter terminal half-life than the parent compound. The present double-blind, randomized study compared the therapeutic effectiveness and the tolerability of acitretin (n = 127) and etretinate (n = 41) in psoriasis. Patients were treated with 40 mg daily for the first 4 weeks and with an individually adjusted dose for the subsequent 8 weeks. The average daily doses of acitretin (0.54 mg/kg/day) and etretinate (0.65 mg/kg/day) were similar. The PASI (Psoriasis Area and Severity Index) scores improved in parallel in the 2 treatment groups. At the completion of the study, the PASI score improvement was 75.8% for acitretin and 70.8% for etretinate. Both acitretin and etretinate resulted in mucocutaneous side effects. Assessments of tolerability by investigators and patients showed a statistically significant difference in favour of etretinate. These results demonstrate that acitretin and etretinate have similar therapeutic effectiveness in psoriasis. Although the tolerance to acitretin was lower than to etretinate, acitretin offers the important advantage of a much shorter period of potential teratogenicity and is, therefore, to be preferred in women of childbearing potential.

Effect of UVA and PUVA on alloactivating and antigen-presenting capacity of human epidermal Langerhans cells.

Human epidermal cell suspensions (EC), obtained with a suction blister technique and enzyme digestion, were irradiated with various doses of UVA with (PUVA) or without previous incubation with 8-methoxypsoralen (8-MOP). EC were then cocultured with allogeneic T cells or pulsed with the soluble antigen purified protein derivative of tuberculin (PPD) for 90 min before being cocultured with autologous T cells. While low doses of UVA induced a small but significant increase in the PPD-specific T-cell response, both PUVA and higher doses of UVA induced dose-dependent reductions. The allogeneic T-cell responses were reduced with PUVA, as well as with UVA, in a dose-dependent fashion. PUVA was far more effective than UVA in reducing both allogeneic and antigen-specific T-cell responses. There were no differences between numbers of DR-positive cells in EC before, immediately after or 24 h after PUVA or UVA radiation, and quantitative determination of EC HLA-DR molecules using an indirect radioimmunoassay (RIA) technique did not reveal any difference between PUVA-treated and non-irradiated cells.