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Background: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety., Objectives: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability., Methods: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically., Results: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions., Conclusions: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment., (© 2018 British Association of Dermatologists.)

The pathogenesis of keratinocyte carcinoma following organ transplantation is multifactorial, and recent evidence suggests a complex and often synergistic interplay between the carcinogenic effects of ultraviolet radiation, compromised immune surveillance, direct pro- and anticarcinogenic effects of drugs, oncogenic viruses (in particular, beta-genus human papillomaviruses) and host genetic susceptibility factors. We present an overview of those factors for which there is currently the most convincing evidence and highlight important gaps in our knowledge. In particular, a clear understanding of the interdependence and relative contributions of these co-factors is currently lacking, yet has important implications for rational development of clinically relevant biomarkers and targeted strategies for treatment and prevention of post-transplant keratinocyte cancers., (© 2017 British Association of Dermatologists.)

Background: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs., Objectives: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs., Methods: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis., Results: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC., Conclusions: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC., (© 2016 British Association of Dermatologists.)