This prospective long-term cohort study investigated the incidence of malignancies in severe psoriasis patients treated with cyclosporine. A total of 1252 patients were followed prospectively for up to 5 y. Malignancies were recorded prospectively. Incidence rates for malignancies were compared with the general population using standardized incidence ratios. The effect of duration of exposure to cyclosporine and to previously administered anti-psoriatic treatments on the incidence of malignancies was investigated using Poisson regression models. The mean age of patients was 43 y and on average, patients received cyclosporine for 1.9 y. Malignancies were diagnosed in 47 patients (3.8%), 49% of them had skin malignancies. The standardized incidence ratio in the study cohort was 2.1 as compared with the general population. The higher incidence of malignancies was attributed to a 6-fold higher incidence of skin malignancies, most of which were squamous cell carcinoma. The incidence of nonskin malignancy overall was not significantly higher in this study than in the general population. Duration of exposure to cyclosporine, exposure to psoralen and ultraviolet A, exposure to methotrexate, and exposure to immunosuppressants showed a significant effect on the incidence of nonmelanoma skin malignancies. In conclusion, treatment of psoriasis with cyclosporine is associated with an increased risk of nonmelanoma skin cancer. Patients treated for more than 2 y with cyclosporine were shown to have a higher risk. In addition, exposure to psoralen and ultraviolet A and to other immunosuppressants was shown to contribute to the overall risk.

PKC isoforms t, α, and β play fundamental roles in the activation of T cells and other immune cell functions.Here we show that the PKC inhibitor AEB071 both abolishes the production of several cytokines by activated human T cells, keratinocytes, and macrophages in vitro and inhibits an acute allergic contact dermatitis response in rats. To translate these findings into humans, single and multiple ascending oral doses of AEB071 were administered to healthy volunteers and patients with psoriasis, respectively. AEB071 was well tolerated with no clinically relevant laboratory abnormalities. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression. Clinical severity of psoriasis was reduced up to 69% compared with baseline after 2 weeks of treatment, as measured by the Psoriasis Area Severity Index (PASI) score. The improvement in psoriasis patients was accompanied by histological improvement of skin lesions and may be partially explained by a substantial reduction of p40 + dermal cells, which are known to mediate psoriasis. These data suggest that AEB071 could be an effective novel treatment regimen for psoriasis and other autoimmune diseases, and that AEB071 warrants long-term studies to establish safety and efficacy.

Acne is principally a disorder of adolescence but persists into middle age in a small minority of individuals. There is some evidence, primarily from twin studies, to suggest that acne may be an inherited disease. We have carried out an investigation of the familial risk of persistent adult acne by studying the occurrence of this condition in first-degree relatives of patients with adult persistent acne compared with the relatives of unaffected matched controls. Two hundred and four patients over the age of 25, referred to our department with facial acne which had persisted from adolescence, were included in the study. For each patient, a detailed pedigree which included all first-degree relatives was drawn up. For all relatives over the age of 25, demographic details and the presence or absence of facial acne was recorded. One hundred and forty-four unaffected controls were recruited. These were matched with the patient group in terms of age, social class and ethnic origin. The same questions were asked of controls as of the cases, and they provided the same information on their first-degree relatives. In total, 204 acne cases and 144 non-acne control volunteers were studied, contributing 1203 and 856 first-degree relatives, respectively. Two hundred and three first-degree relatives of cases were affected with facial acne, compared with 42 first-degree relatives of volunteers. The risk of adult acne occurring in a relative of a patient with adult acne was significantly greater than for the relative of an unaffected individual (odds ratio 3.93, 95% confidence interval 2.79-5.51; P < 0.001). Our study suggests that familial factors are important in determining individual susceptibility to adult persistent facial acne. Genetic factors may determine the failure of acne-prone follicles to evolve into acne-resistant follicles in early adult life.

Adults with acne represent an increasingly important population of acne sufferers referred for treatment. Acne, in these patients, is generally mild or moderate in severity but tends to be resistant to conventional antibiotic therapy. A study was carried out to assess the efficacy of intermittent moderate dose isotretinoin as a treatment for acne. Eighty consecutive patients, over the age of 25 years, referred with acne unresponsive to, or relapsing rapidly after three or more courses of conventional antibiotic therapy were recruited. Acne severity was assessed on the face, chest and back using the Leeds grading scale and the number of inflamed lesions was counted at the site showing the highest acne grade. The patients were 22 men and 58 women. The treatment regimen consisted of isotretinoin, 0.5 mg/kg per day for 1 week in every 4 week for a total period of 6 months. Seventy-five patients completed the study. The therapy was very well tolerated with mild cheilitis as the only side-effect. At the end of treatment, both total acne grade and lesion counts were significantly reduced (P < 0.0001). The acne had resolved in 68 (88%) patients. Twelve months after treatment, acne grades and inflamed lesion counts remained significantly improved (P < 0.0001) in the 68 patients who responded; however, 26 (39%) patients had relapsed. There was a significantly higher incidence of relapse in patients with predominantly truncal acne (P = 0.01). Patients who relapsed also had a significantly higher total acne grade, lesion count (P < 0.0001) and sebum excretion rate (P < 0.001) compared with those whose acne resolved. This study suggests that intermittent moderate dose isotretinoin may be a cost-effective alternative to full dose isotretinoin in a carefully selected group of adult patients with-acne. Selection criteria should include predominantly facial acne, total acne grade less than 1, inflamed lesion count less than 20 and sebum excretion rate less than 1.25 micrograms/cm2 per min.

Adults with acne represent an increasingly important population of acne sufferers referred for treatment. Acne, in these patients, is generally mild or moderate in severity but tends to be resistant to conventional antibiotic therapy. A study was carried out to assess the efficacy of intermittent moderate dose isotretinoin as a treatment for acne. Eighty consecutive patients, over the age of 25 years, referred with acne unresponsive to, or relapsing rapidly after three or more courses of conventional antibiotic therapy were recruited. Acne severity was assessed on the face, chest and back using the Leeds grading scale and the number of inflamed lesions was counted at the site showing the highest acne grade. The patients were 22 men and 58 women. The treatment regimen consisted of isotretinoin, 0.5 mg/kg per day for 1 week in every 4 week for a total period of 6 months. Seventy-five patients completed the study. The therapy was very well tolerated with mild cheilitis as the only side-effect. At the end of treatment, both total acne grade and lesion counts were significantly reduced (P < 0.0001). The acne had resolved in 68 (88%) patients. Twelve months after treatment, acne grades and inflamed lesion counts remained significantly improved (P < 0.0001) in the 68 patients who responded; however, 26 (39%) patients had relapsed. There was a significantly higher incidence of relapse in patients with predominantly truncal acne (P = 0.01). Patients who relapsed also had a significantly higher total acne grade, lesion count (P < 0.0001) and sebum excretion rate (P < 0.001) compared with those whose acne resolved. This study suggests that intermittent moderate dose isotretinoin may be a cost-effective alternative to full dose isotretinoin in a carefully selected group of adult patients with-acne. Selection criteria should include predominantly facial acne, total acne grade less than 1, inflamed lesion count less than 20 and sebum excretion rate less than 1.25 micrograms/cm2 per min.