Warts are common epidermal growths caused by human papillomavirus that often cause significant discomfort and embarrassment. Current treatment options include topical therapies, cryotherapy, laser vaporization, and surgical excision. Many of these options are destructive and may result in scarring, while less aggressive approaches can lead to lesion recurrence. Additionally, these local modalities are not practical for patients with a large number of warts. Systemic approaches such as immunotherapy have demonstrated success in treating multiple lesions by combining a targeted approach with upregulation of the host immune system. An extensive literature review was performed to evaluate the various vaccine antigens that have been used intralesionally to treat cutaneous and anogenital warts. The specific intralesional immunotherapies that have been studied include: Candida albicans; measles, mumps, and rubella; Trichophyton; and tuberculin antigens such as purified protein derivative, Mycobacterium w vaccine, and Bacillus Calmette-Guerin. Intralesional vaccine injection represents a safe, effective, and tolerable treatment for warts, including recalcitrant and anogenital warts. This approach has been somewhat overlooked in the past despite substantial evidence of high response rates with a low side effect profile. Large comparative trials are necessary to determine the most effective immunotherapy treatment option as well as the most appropriate dosing parameters.

IMPORTANCE Hedgehog pathway inhibitors (HPIs) were made available by US Food and Drug Administration approval in 2012 for vismodegib and 2015 for sonidegib. Both target the Smoothened molecule and are indicated for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC). OBJECTIVE To evaluate clinical experience with HPIs, including efficacy and adverse effects. DATA SOURCES We conducted a systematic review in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EMBASE, using search terms "vismodegib," "sonidegib," "Erivedge," "Odomza," "basal cell carcinoma," and "BCC." STUDY SELECTION We included clinical trials, retrospective medical record reviews, and prospective case series that used HPIs for the treatment of laBCC or mBCC in human subjects. Individual case reports and limited, retrospective case series were excluded from our review. DATA EXTRACTION AND SYNTHESIS Data were extracted independently by 2 reviewers on a predesigned, standardized form. MAIN OUTCOMES AND MEASURES The following data were recorded: number of patients with laBCC or mBCC, dose and frequency of drug administration, median duration of treatment, clearance and recurrence rates, and adverse effects. RESULTS Eleven vismodegib articles (published between 2009 and 2015) met criteria for inclusion, and 8 articles were able to be pooled for analysis. The 8 pooled articles included 744 total patients with 704 patients clinically evaluable. Sonidegib did not yield enough publications for a formal analysis. Objective response to vismodegib for laBCC had a weighted average of 64.7% (95% CI, 63.7%-65.6%); complete response averaged 31.1% (95% CI, 30.4%-31.8%). Objective response for mBCC was 33.6% (95% CI, 33.1%-34.2%); complete response averaged 3.9% (95% CI, 3.3%-4.4%). Median duration of therapy was 35.8 weeks (95% CI, 35.1-36.5 weeks). CONCLUSIONS AND RELEVANCE In a systematic review of HPIs for laBCC and mBCC, vismodegib, but not sonidegib, had enough studies to warrant a pooled analysis. Vismodegib was identified to have a significant, consistent effect on the median duration of therapy of laBCC and mBCC. While mBCC responses are superior to any traditional approach, the response rate for laBCC might be considered in the context of other standard treatment options including surgery and radiation therapy.

Striae distensae (SD) are common dermatologic lesions that often arise as a result of rapid weight change, certain endocrine conditions, or prolonged exposure to steroids. SD initially present as raised edematous plaques (striae rubra), after which they become white and atrophic (striae alba) owing to local breakdown and reorganization of collagen and elastin. There currently exists no reliable treatment option, though numerous topical applications have been attempted. Lasers and light represent emerging noninvasive therapies that have demonstrated some success targeting vascular chromophores in striae rubra and stimulating collagen and elastin production in striae alba. An extensive literature review was performed to gather all available articles studying laser and light treatments for SD. Lasers and light can significantly improve the appearance of both striae rubra and striae alba. Generally, striae rubra are more responsive to therapy and can be treated successfully with a variety of lasers without major adverse effects. Fractional lasers exhibit the strongest results for striae alba repigmentation and collagen induction, and several other lasers produce temporary repigmentation. Lasers in combination with other modalities such as topical agents and additional energy devices have also demonstrated promising preliminary results; however, large comparative studies are necessary to validate these outcomes.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) induces degradation of low-density lipoprotein receptor (LDLR) in the liver. It is being pursued as a therapeutic target for LDL-cholesterol reduction. Earlier genome-wide gene expression studies showed that PCSK9 over-expression in HepG2 cells resulted in up-regulation of genes in cholesterol biosynthesis and down-regulation of genes in stress response pathways; however, it was not known whether these changes were directly regulated by PCSK9 or were secondary to PCSK9-induced changes to the intracellular environment. In order to further understand the biological function of PCSK9 we treated HepG2 cells with purified recombinant wild type (WT) and D374Y gain-of-function PCSK9 proteins for 8, 24, and 48 h, and used microarray analysis to identify genome-wide expression changes and pathways. These results were compared to the changes induced by culturing HepG2 cells in cholesterol-free medium, mimicking the intracellular environment of cholesterol starvation. We determined that PCSK9-induced up-regulation of cholesterol biosynthesis genes resulted from intracellular cholesterol starvation. In addition, we identified novel pathways that are presumably regulated by PCSK9 and are independent of its effects on cholesterol uptake. These pathways included "protein ubiquitination," "xenobiotic metabolism," "cell cycle," and "inflammation and stress response." Our results indicate that PCSK9 affects metabolic pathways beyond cholesterol metabolism in HepG2 cells.

Hypertrophic (HTSs) and keloid scars are common dermatological complaints produced by disruption of the normal wound-healing process. Despite a wide array of therapeutic options available to treat these lesions, HTSs and keloids continue to pose a significant challenge to clinicians in everyday practice. The chemotherapeutic drug 5-fluorouracil (5-FU) is a well-known treatment option reserved for recalcitrant HTSs and keloid lesions. We present clinicians with a comprehensive review of the published data concerning the use of 5-FU in the treatment of HTSs and keloids. The current evidence suggests that 5-FU is a safe and practical alternative for the treatment of HTSs and keloids as it may substantially improve the appearance of proliferative scars and reduce the chance of recurrence. This therapeutic option is most effective in conjunction with adjuvant therapy such as corticosteroids. Additional randomized controlled clinical trials with large sample sizes should be conducted to corroborate the existing efficacy and safety data in patients with HTSs and keloids.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-016-0118-5) contains supplementary material, which is available to authorized users.