Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of lowdensity lipoprotein. PCSK9, which promotes the degradation of low-density lipoprotein receptors and, therefore, the increased concentration of circulating low-density lipoprotein, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying small interfering RNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients and imiquimod-induced psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated mice, and we also used cultured human keratinocytes to investigate the role of PCSK9 in regulating cell proliferation and apoptosis. We found that PCSK9 is overexpressed in psoriatic lesions and that suppressing Pcsk9 can decrease the inflammatory reaction induced by imiquimod treatment and inhibit hyperproliferation of keratinocytes. We also found that suppressing PCSK9 can significantly alter the cell cycle and induce apoptosis of human keratinocytes. Taken together, our findings indicate that PCSK9 plays an important role in psoriasis and may be a therapeutic target.

Background Systemic sirolimus (rapamycin) has recently been found effective in treating complex vascular anomalies by reducing the size and associated complications. Many vascular anomalies have a cutaneous component, and thus, we sought to determine whether topical administration of sirolimus may be an effective therapy, as data on the use of topical sirolimus are limited. Objective We reviewed the efficacy and tolerability of topical formulations of sirolimus in the treatment of various simple and combined vascular malformations and tumors. Methods Eighteen patients with any vascular anomaly treated exclusively with topical sirolimus were retrospectively reviewed. Results Eleven patients had combined venous lymphatic malformations, three had tufted angiomas, two had a lymphatic malformation, one had a venous malformation, and one had a verrucous venous malformation. All (100%) patients reported some degree of improvement and 50% of patients reported marked improvement in one or more symptoms, most commonly blebs and lymphatic drainage, and bleeding. Limitations The retrospective nature, small number of patients, and differences in topical preparations limit the broad application of the results. Conclusion Topical sirolimus appears to be a safe and useful non‐invasive therapy that is well‐tolerated in the treatment of the cutaneous portion of a variety of vascular anomalies.

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and melanoma skin cancers are increasing rapidly in the United States likely because of increased UV light exposure. Sunless tanning is a safe alternative to achieve tanned skin that might help reduce skin cancer incidence by deterring risky behaviors. However, limited data exist on the characteristics and associated skin cancer risk behaviors of sunless tanners in the United States. OBJECTIVE To assess the demographic characteristics and skin cancer risk behaviors of sunless tanners among adults in the United States. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a cross-sectional study used data from the 2015 National Health Interview Survey, a population-based survey of the US noninstitutionalized civilian population. Participants included 27 353 men and women 18 years or older. MAIN OUTCOME AND MEASURES Participant demographics and skin cancer risk behaviors, including indoor tanning, skin cancer screening, sunburn, and sun protection behaviors. RESULTS Of the 27 353 adults (representative of more than 198 million US adults; mean [SE] age, 46.0 [0.2] years) studied, 6.4% (SE, 0.2%) reported sunless tanning. Factors associated with sunless tanning included being young, female, non-Hispanic white, college educated, nonobese, and sun sensitive, living in the western United States, and having a family history of skin cancer. Sunless tanners were more likely to report indoor tanning (adjusted prevalence odds ratio [aPOR], 3.77; 95% CI, 3.19-4.43; P < .001), recent sunburn (aPOR, 1.55; 95% CI, 1.31-1.83; P < .001), use of sunscreen (β = 0.19; 95% CI, 0.09-0.28; P < .001), and having had a full-body skin examination (aPOR, 1.77; 95% CI, 1.51-2.08; P < .001) but less likely to seek shade (β = −0.12; 95% CI, −0.19 to −0.04; P = .001) or use protective clothing when outdoors (long pants: β = −0.18; 95% CI, −0.26 to −0.11; P < .001; long sleeves: β = −0.10; 95% CI, −0.18 to −0.03; P = .01). Among indoor tanners, sunless tanners compared with those who did not sunless tan reported increased frequency of indoor tanning (mean [SE], 19.2 [1.9] vs 14.9 [1.2] sessions in the past 12 months; P = .04) but no differences in other skin cancer risk behaviors.CONCLUSIONS AND RELEVANCE This study suggests that sunless tanning is associated with risky skin cancer-related behaviors. Longitudinal studies are needed to assess whether sunless tanning changes UV exposure behaviors to better determine whether sunless tanning represents an effective public health strategy to reduce rates of skin cancer in the United States.

Objective:In order to explore the use of Skindex scoring in NF1 patients across multiple clinical sites, and inform design of additional quality of life measures, we analysed correlations between skindex, site and clinical parameters for 79 patients with NF1 from specialised clinics in Sydney, NSW Australia (RNS) and Minneapolis Minnesota, USA (UMN).Methods:The relationship between the clinical factors and Skindex scores were explored by clinic site and overall.Results:40 subjects were recruited from RNS and 39 from UMN. Female sex, total number of cNFs, and whether cNFs were present on the face, correlated highly with skindex and not Riccardi scores. The UMN site had lower average scores, but these differences were almost entirely removed after adjusting for age, sex, facial CNFs and total CNF number.Conclusions:The development of cutaneous neurofibromas (cNFs) in adolescence and adulthood in neurofibromatosis, type 1 (NF1) often lead to progressive disfigurement and discomfort, and are among one of the most common reasons for patients to seek medical treatment. Skindex has been used to assess skin related quality of life in NF1 previously but is not specific to NF1. These findings highlight the need for a low threshold for referral to Dermatologists for all patients with Neurofibromatosis Type 1 regardless of the severity of disease. The finding that facial CNFs and higher total number of CNFs correlates with poorer skin related quality of life, may benefit design of more specific NF1 skin related quality of life measures.