Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.

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 micro g 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.

PUVA and cancer risk: the Swedish follow-up study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Pinch grafting of leg ulcers. A retrospective study of 412 treated ulcers in 146 patients.

In a retrospective study of 412 leg ulcers in 146 patients treated with pinch grafting, with a mean duration of follow-up of 32 months (range 2-84), the overall healing rate was 38%. The healing rate was best in the vasculitic ulcers (56%), followed by venous ulcers (38%), arteriosclerotic ulcers (33%), mixed ulcers (33%) and "other ulcers" (20%). In the series as a whole, the mean duration of ulcer problems was 8 years, and that of the 412 ulcers treated 2.5 years; the mean recurrence rate was 28%, and the mean remission time 12.5 months. In the ulcers that were still healed at close of the study (comprising 27% (112/412) of the series), the remission time was > or = 26.6 months. Thus we consider pinch grafting to be a successful complement to conservative therapy in most types of ulcers.

Comparison of the carcinogenic potential of trioxsalen bath PUVA and oral methoxsalen PUVA. A preliminary report.

BACKGROUND AND DESIGN: There is an increasing concern about the long-term carcinogenic effect of oral psoralen with long-wave UV radiation in the A range (PUVA). Most follow-up investigations indicate a definite risk of squamous cell carcinoma of the skin with long-term PUVA treatment. In a recently published study of 4799 Swedish patients who had received PUVA, it was noted that 833 patients who had received trioxsalen bath or oral trioxsalen did not show any increased risk of skin cancer in contrast to oral methoxsalen. This finding has been further investigated in this study. We compared four dermatologic university clinics in Sweden with regard to the carcinogenic potential of the PUVA regimen used. One clinic used trioxsalen bath PUVA exclusively and the other three used oral methoxsalen. Information on their PUVA-treated patients was collected and linked with information from the Swedish Cancer Registry to identify individuals with squamous cell carcinoma of the skin. RESULTS: A total of 18 squamous cell carcinomas of the skin were reported in 2975 PUVA-treated patients until 1987. The expected number was 3.1. The center using bath PUVA only had no increased risk of squamous cell carcinoma of the skin in contrast to the three centers using oral methoxsalen-PUVA. The increased risk for male subjects from those centers varied from six to 13 times that in the general population, but for female subjects a significant increased relative risk was found only at one center. CONCLUSION: In this preliminary report, PUVA treatment with trioxsalen bath seems to be less carcinogenic than the oral dosage. However, differences in the patient populations might also have affected the outcome of the study. More information on this field is needed.

Sex differences in skin pigmentation illustrated in art.

In different cultures of the world, many artists have made their female models lighter skinned than male models. There exists a biologic truth behind these observations. Several spectrophotometric studies have found that female skin reflectance is 2-3 percentage points above (that is, paler skin) that of males in diverse populations in Europe, Asia, Africa, and North and South America. The sex difference in skin pigmentation is, however, subtle and often difficult to appreciate. Probably artists have used pigmentation to emphasize sexual differences between men and women in the same way they use body size and musculature.

Short-contact treatment at home with Micanol.

The efficacy of home treatment of psoriasis with a new dithranol formulation, Micanol, was investigated in three studies. They were carried out according to a randomized, within-patient comparison design. In a 4-week pilot study Micanol was compared with placebo (10 patients) and in two 6-week studies Micanol was compared with dithranol 1% in petrolatum (33 patients) and with dithranol 1% in Amitase stick (16 patients). Micanol was found to be effective and well suited for treatment at home in all studies. The vehicle itself did not improve the psoriasis plaques. The rate of clinical improvement was faster for dithranol in petrolatum and Amitase stick than for Micanol. The prevalence and severity of erythema, burning and staining of skin and clothing were far less for Micanol. Approximately half the number of patients preferred dithranol in petrolatum or Amitase stick and the other half preferred Micanol.

PUVA and cancer: a large-scale epidemiological study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) therapy for treatment of skin disorders. A study of 4799 Swedish patients (2343 males, 2056 females; mean age at first treatment 45.3 years, range 6-93; mean follow-up 6.9 years males, 7.2 years females) who received PUVA between 1974 and 1985 showed a dose-dependent increase in the risk of squamous cell cancer of the skin. Male patients who had received more than 200 treatments had over 30 times the incidence of squamous cell cancer found in the general population. Significant increases (p less than 0.05) were also found in the incidences of respiratory cancer in males and females, pancreatic cancer in males, and kidney and colonic cancer in females. This study confirms previous reports of a dose-dependent increase in the incidence of squamous cell cancer in patients treated with PUVA.

Darier's disease with involvement of both submandibular glands.

Salivary gland obstruction in association with Darier's disease is described. Histological examination of both submandibular glands revealed squamous metaplasia of the ducts with suprabasal cleft formation and occlusion of the lumen.

Halo dermatitis around tumours.

Circular dermatitis around different benign or malignant lesions were examined in 19 patients. The morphological picture was the same whether it occurred around an acquired naevus cell naevus, a congenital naevus cell naevus, a seborrheic keratosis, a stucco-keratosis, a keloid, a benign lentigo, an insect bite, a basal cell carcinoma, or a squamous cell carcinoma. The central lesions were macroscopically unaffected by the surrounding inflammation.

Hydrogen peroxide cream for the prevention of white pressure areas in UVA sunbeds.

A single application of 1% hydrogen peroxide in a stabilized lipid cream during 2 min before UVA exposure prevents white spots in anoxic pressure areas in sunbed use, causing an almost normal pigmentation. During maintenance exposure with UVA once a week this pigmentation will remain unchanged if the pressure areas are pretreated with hydrogen peroxide before each irradiation. White spots will appear 3-4 weeks after finishing hydrogen peroxide pretreatment in the pressure areas thus exposed to UVA alone.

Biochemical observations in UV-induced pigmentation.

The biochemical events in the melanocytes resulting from stimulation of pigmentation by exposure to ultraviolet (UV) irradiation are correlated to changes in specific metabolites in the plasma and in the urine. A compound produced in the melanocyte by nucleophilic addition of cysteine to dopaquinone, 5-S-cysteinyldopa, is present in increased quantities in the plasma and in the urine after different types of pigment-producing UV exposure. Similarly, a methylated indolic metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid, appears in increased amounts in the urine after UV exposure of the skin. UVA does not produce inflammation or pigmentation in skin that is anoxic at the time of irradiation. In contrast, inflammation and pigment response to UVB and PUVA are not dependent on oxygenation of the skin at the time of exposure.

Polymorphous light eruption in hypopigmented pressure areas with a UVA sunbed.

In two persons a papular dermatitis was provoked by UVA on an area of the back which was subjected to high pressure and therefore did not tan. The inflammation observed had the appearance of a polymorphous light eruption, but neither of the individuals had a history of any pathological light reaction.

Trichochromuria in melanosis of melanoma.

Two patients with metastasizing melanoma and diffuse melanosis have previously been reported to excrete large quantities of trichochromes in the urine. The present study describes 2 further melanoma patients with diffuse melanosis and trichochromuria. The hair of one of the patients which had been red in childhood and turned brown in adult age returned to red with the appearance of melanosis. Normal excretion of a methylated melanocytic metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid, was observed in this patient, possibly indicating exhaustion of the methylating system. The other patients excreted large quantities of 6-hydroxy-5-methoxyindole-2-carboxylic acid. Both patients showed highly increased excretion of 5-S-cysteinyldopa. Both patients with melanosis exhibited fine electrone-dense granules in lysosomes of dermal histiocytes. The findings support the concept that trichochromes or similar pigments in dermal histiocytes are responsible for diffuse melanosis in melanoma patients.