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Simple Summary: Outgrowth of skin tumors in cancer patients who receive therapies with BRAF inhibitors is frequently observed as an undesired side effect. Infection with certain human papillomaviruses may play a role in BRAF-inhibitor-associated skin tumor development. In this study, the impact of BRAF inhibitors and Ultraviolet B (UVB) light on tumor growth was investigated in laboratory mice after infection of their skin with a murine papillomavirus. We could show that the combination of BRAF inhibitor treatment and UVB exposure resulted in higher numbers of virus-induced tumors compared with virus-infected mice that had received only BRAF inhibitors, only UVB irradiation or no additional treatment. This shows that BRAF inhibitors, particularly when combined with UVB light, support skin tumor growth in mice and may represent a novel way by which BRAF inhibitors contribute to skin cancer development. The development of keratinocytic skin tumors, presumably attributable to paradoxical activation of the MAPK pathway, represents a relevant side effect of targeted therapies with BRAF inhibitors (BRAFis). The role of cutaneous papillomavirus infection in BRAFi-associated skin carcinogenesis, however, is still inconclusive. Employing the Mus musculus papillomavirus 1 (MmuPV1) skin infection model, the impact of BRAFis and UVB exposure on papillomavirus induced skin tumorigenesis was investigated in immunocompetent FVB/NCrl mice. Systemic BRAF inhibition in combination with UVB light induced skin tumors in 62% of the MmuPV1-infected animals. In contrast, significantly fewer tumors were observed in the absence of either BRAF inhibition, UVB irradiation or virus infection, as demonstrated by lesional outgrowth in 20%, 5% and 0% of the mice, respectively. Combinatory exposure to BRAFis and UVB favored productive viral infection, which was shown by high numbers of MmuPV1 genome copies and E1^E4 spliced transcripts and an abundance of E6/E7 oncogene mRNA and viral capsid proteins. BRAF inhibition, but not viral infection or UVB light, activated ERK1/2, whereas γH2AX expression, inducible by UVB light, remained unaltered by BRAFis. These results provide experimental evidence that BRAF inhibition and UVB irradiation synergistically promote MmuPV1-induced skin tumor development in vivo. This indicates an alternative pathway by which papillomavirus skin infection may contribute to BRAFi-associated skin tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Scabies is an itchy, parasitic infection of the skin. Recent reports indicate there is a decreasing efficacy of the standard treatment of choice, topical 5% permethrin cream. Objective: To evaluate the comparative efficacy, safety and tolerability of topical benzyl benzoate (BB) with oral ivermectin in the treatment of scabies. Methods: Patients with dermoscopy‐verified scabies visiting the dermatologic outpatient clinic were assessed for enrolment in the study. In total, 224 patients were enrolled and sequentially randomized into two equally sized groups. Group A received topical 25% or 10% BB for the daily use over a period of three consecutive days, group B received oral ivermectin (200 μg/kg body weight) twice, 1 week apart. Treatment outcome was evaluated by dermoscopy at a 3‐week follow‐up visit. Results: Treatment resulted in a cure rate of 87% in group A and 86% in group B. After initial therapy failure in group A, six out of eight patients showed treatment response upon repeated application of BB, five of five when retreated with ivermectin and two of two with BB plus ivermectin, respectively. In group B, successful retreatment was observed in three out of three patients with ivermectin, two of two patients with BB and 11 of 11 patients with the combination of BB plus ivermectin, respectively. Tolerability and safety profile of oral ivermectin was excellent, while BB produced short burning sensations in 14%. Conclusion: Topical BB and oral ivermectin have shown comparable good therapeutic efficacy. Therefore, both agents constitute an adequate first‐line therapy in the treatment of scabies. A combination of both agents may be considered in recalcitrant and extensively infested cases, additionally to crusted scabies. [ABSTRACT FROM AUTHOR]

Cathelicidins have been reported to inhibit human papillomavirus infection in vitro; however, nothing is known about their activity in vivo. In this study, experimental skin infection with Mus musculus papillomavirus 1 resulted in robust development of cutaneous papillomas in cyclosporine A-treated C57BL/6J mice deficient for the murine cathelicidin-related antimicrobial peptide (CRAMP), in contrast to wild-type controls. Analysis of the underlying mechanisms revealed moderate disruption of virion integrity and lack of interference with viral entry and intracellular trafficking by a synthetic CRAMP peptide. Differences in the immune response to Mus musculus papillomavirus 1 infection were observed between CRAMP-deficient and wildtype mice. These included a stronger reduction in CD4+ and CD8+ T-cell numbers in infected skin, and lack of Mus musculus papillomavirus 1-specific neutralizing antibodies in response to cyclosporine A in the absence of endogenous CRAMP. CRAMP has modest direct antipapillomaviral effects in vitro, but exerts protective functions against Mus musculus papillomavirus 1 skin infection and disease development in vivo, primarily by modulation of cellular and humoral immunity. [ABSTRACT FROM AUTHOR]

Patients receiving tumour necrosis factor alpha (TNF-α) inhibitors are at increased risk of exacerbation of (myco-)bacterial and some viral infections. However, information on anogenital human papillomavirus (HPV) infection in these patients is sparse or conflicting. In this study 222 patients with psoriasis or inflammatory bowel disease (IBD), who received either anti-TNF-α inhibitors or alternatives (purine-, folic acid analogues, phototherapy, fumaric ester, mesalazine) continuously for at least 6 months, were evaluated for the presence of anogenital HPV-induced lesions, mucosal HPV DNA, and serological status of mucosal low-risk HPV6 and high-risk HPV16/HPV18. Hallmarks of anogenital HPV infection were more frequently detected in patients with psoriasis than in those with IBD. HPV-induced lesions, viral DNA, and seroprevalence were not elevated in participants with psoriasis or IBD, who received TNF-α inhibitors for a mean duration of 31.4 months (range 6-96 months) compared with recipients of alternative or no treatment. TNF-α blockade for a mean period of 31.4 months does not increase detectable anogenital HPV infection or disease. [ABSTRACT FROM AUTHOR]