Validation of Dermaphot(®) for the assessment of steroid-induced skin atrophy.

Currently, there are no accurate and simple methods available to measure this risk of atrophy in patients treated with topical glucocorticosteroids. In the present clinical trial, we validated a new score (Dermaphot(®) score) to assess the atrophogenic potential of glucocorticosteroids. 36 healthy adult volunteers were included in an investigator-initiated, blinded, randomized, intra-individual comparison, vehicle controlled multi-centre study. Subjects were treated in a randomized manner for 3 weeks with pimecrolimus cream 1 %, mometasone furoate (1 mg/g), clobetasol propionate 0.05 % and vehicle. In addition, ultrasound examination for skin thickness was performed. Data demonstrated a direct correlation of the achieved Dermaphot(®) score and the ultrasound thickness measurements. Our study shows that the Dermaphot(®) score can be used as a simple method to evaluate the atrophogenic potential of glucocorticosteroids. Respectively, we showed that the new score is an easy, valid and sensitive new tool for early detecting and quantifying even subclinical glucocorticosteroid-induced skin damage. We demonstrated that the score is able to differentiate the extent of skin atrophy (damage) after 3 weeks of topical glucocorticosteroid application with different levels of skin transparency and levels of telangiectasia.

Effective continuous systemic therapy of severe plaque-type psoriasis is accompanied by amelioration of biomarkers of cardiovascular risk: results of a prospective longitudinal observational study.

BACKGROUND: Severe psoriasis is associated with significant cardiovascular mortality. OBJECTIVES: We investigated the effects of continuous systemic therapy on the cardiovascular risk of patients with severe plaque-type psoriasis. METHODS: A total of 42 consecutive patients receiving systemic treatment for their severe plaque-type psoriasis were included. The clinical course was monitored over 24 weeks. Initially as well as after 12 and 24 weeks, oral glucose tolerance tests were performed along with comprehensive laboratory monitoring. RESULTS: Responding patients, defined as a Psoriasis Area and Severity Index (PASI)-50 response, showed correlations between the PASI and high-sensitive C-reactive protein (r = 0.45, P = 0.03) as well as with vascular endothelial growth factor (r = 0.76, P = 0.007). The adipokine resistin was positively and the potentially cardio-protective adiponectin was negatively correlated with the PASI (r = 0.50, P = 0.02 and r = -0.56, P = 0.007, respectively). Oral glucose tolerance tests yielded a correlation between the PASI and plasma levels for C-peptide (r = 0.73, P = 0.02) at t = 120 min in patients with a pathological Homeostasis Model Assessment (>2.5), indicating that the state of peripheral insulin resistance is driven at least in part by the severity of the psoriatic inflammation. Correlations between the change of adipokine levels and change in PASI were more pronounced among patients with better clinical improvement (PASI-75 vs. PASI-50). CONCLUSIONS: We document an amelioration of biomarkers of cardiovascular risk in patients with severe plaque-type psoriasis responding to continuous systemic therapy. The impact on the patients'metabolic state was found to be better if the psoriatic inflammation was controlled for longer. Future studies need to compare the cardioprotective effects of different treatment modalities, based on hard clinical endpoints.

Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial.

Renal transplant recipients (RTR) have a 50-200-fold higher risk for nonmelanoma-skin cancer (NMSC) causing high rates of morbidity and sometimes mortality. Cohort-studies gave evidence that a sirolimus-based immunosuppression may inhibit skin tumor growth. This single-center, prospective, assessor-blinded, randomized trial investigated if switching to sirolimus treatment inhibits the progression of premalignancies and moreover how many new NMSC occur compared to continuation of the original immunosuppressive therapy. Forty-four RTR (mean age 59.9 years, mean duration of immunosuppression 229.5 months) with skin lesions were randomized to sirolimus or continuation of their original immunosuppression. Blinded dermatological assessment at month 6 and 12 by the same dermatologist evaluated the clinical change compared to baseline. Biopsy was performed in suspected malignancy. Already the 6-month-assessment showed significant superiority of sirolimus-therapy: a stop of progression, even regression of preexisting premalignancies (p < 0.0005). This effect was increased at month 12 (p < 0.0001). Nine patients developed histologically confirmed NMSC: one in the sirolimus group, eight in the control group, p = 0.0176. Sirolimus-based immunosuppression in RTR, even when established many years after transplantation, can delay the development of premalignancies, induce regression of preexisting lesions and decelerate the incidence of new NMSC.

Treatment of moderate-to-severe plaque psoriasis.

Psoriasis, a chronic common immune-mediated disease with frequent remitting/relapsing courses, has a high negative impact on the quality of life, especially in patients moderately or severely affected by the disease. It is also associated with various co-morbidities resulting in a decreased life expectancy and remarkable socioeconomic costs. At least one third of the patients who suffer from it has moderate or severe psoriasis and require continuous treatment to control disease activity. The therapeutic approach in daily practice is usually determined by the severity of the disease. Whether the definition of disease severity is not always clear, there is a considerable number of patients requiring systemic treatment to control the symptoms of psoriasis. The treatment options available for the management of moderate-severe psoriasis have dramatically increased over the past decade, and now range from phototherapy to traditional systemic treatments to biologics. Available data from clinical trials and growing number of patients treated with biologics shows that this new agent are effective and relatively safe to control psoriasis, and are coupled with improved tolerability, convenience and improvement in quality of life. This review shortly presents the characteristics, safety and efficacy profile of the conventional and newer systemic drugs used in moderate-to-severe psoriasis.