Sunscreens: Misconceptions and Misinformation.

Over the past 70 years, sunscreens have evolved from beach products designed to prevent sunburn to more cosmetically elegant skincare products intended to protect against multiple long-term adverse consequences of characteristically low-intensity daily UV and visible light exposure. Sunscreen testing and labeling intended to quantify such protection are unfortunately often misunderstood by users and have also led to illegal misleading and potentially dangerous industry practices. Changes in regulatory requirements, better policing, and more informative sunscreen labeling would benefit users and their physician advisors.

Actinic Keratoses: Reconciling the Biology of Field Cancerization with Treatment Paradigms.

This Perspective briefly reviews the relationship between UV-induced mutations in habitually sun-exposed human skin and subsequent development of actinic keratoses (AKs) and skin cancers. It argues that field therapy rather than AK-selective therapy is the more logical approach to cancer prevention and hypothesizes that treatment early in the process of field cancerization, even prior to the appearance of AKs, may be more effective in preventing cancer as well as more beneficial for and better tolerated by at-risk individuals. Finally, the Perspective encourages use of rapidly advancing DNA analysis techniques to quantify mutational burden in sun-damaged skin and its reduction by various therapies.

Interdisciplinary Perspectives on Sun Safety.

Overexposure to the sun is associated with an increased risk of melanoma and nonmelanoma skin cancer, but indications of improvements in sun protection behavior are poor. Attempts to identify emerging themes in skin cancer control have largely been driven by groups of experts from a single field. In December 2016, 19 experts from various disciplines convened for Interdisciplinary Perspectives on Skin Cancer, a 2-day meeting hosted by the National Academy of Sciences. The group discussed knowledge gaps, perspectives on sun exposure, implications for skin cancer risk and other health outcomes, and new directions. Five themes emerged from the discussion: (1) The definition of risk must be expanded, and categories for skin physiology must be refined to incorporate population diversities. (2) Risky sun exposure often co-occurs with other health-related behaviors. (3) Messages must be nuanced to target at-risk populations. (4) Persons at risk for tanning disorder must be recognized and treated. (5) Sun safety interventions must be scalable. Efficient use of technologies will be required to sharpen messages to specific populations and to integrate them within multilevel interventions. Further interdisciplinary research should address these emerging themes to build effective and sustainable approaches to large-scale behavior change.

Changes in Self-Perceptions of Photoaging Severity and Skin Cancer Risk After Objective Facial Skin Quality Analysis.

Background: Despite public education efforts, many people at risk for skin cancer do not practice safe sun behaviors.

Objective: To determine whether machine-based evaluation of UV-induced alterations (VISIA scan) changes self-assessment of facial photoaging, skin cancer risk, and willingness to improve sun protective habits. In addition, to determine whether VISIA scan analysis reveals differences between those with versus without a history of skin cancer, men versus women, those older than 50 versus less than 50 years of age, and Fitzpatrick skin types I-III versus IV-VI.

Methods: Volunteers attending a health expo were recruited and queried about their perceived risk of skin cancer and degree of skin photoaging. All participants underwent facial skin quality analysis of both sides of the face, and then completed a follow-up survey.

Results: Participants' scored self-perceptions of overall skin aging were all statistically significantly worse after VISIA scan analysis. There was no change in perceived skin cancer risk, but most participants expressed intent to improve their sun protection habits.

Limitations: Limitations to this study include selection bias, recall-misclassification bias, and social desirability bias.

Conclusion: Intervention with facial skin analysis can positively affect subjects' stated intent to use sun protection, indicating the importance of appearance in these health decisions.

J Drugs Dermatol. 2017;16(5):453-459.

Effective blue light photodynamic therapy does not affect cutaneous langerhans cell number or oxidatively damage DNA.

BACKGROUND: Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin. OBJECTIVE: To determine whether broad-area short incubation (BASI)-ALA-PDT using blue light immunosuppression immunosuppresses treated skin. METHODS: Patients were evaluated clinically and by standardized facial biopsies of non-AK skin before, 24 hours and 1 month after customary blue light BASI-ALA-PDT. All biopsies were stained for markers of epidermal atypia and Langerhans cells (LCs); and at 24 hours to detect oxidative DNA damage. RESULTS: Patients had an 81% reduction in AKs and slight improvement in clinical and histologic signs of photoaging after 1 month. The biopsied chronically photodamaged skin without clinically detectable AKs showed no effect of PDT on the LC number, distribution, or morphology; and no oxidative DNA damage, in contrast to the changes reported after customary red light PDT. CONCLUSION: Customary blue light BASI-ALA-PDT does not affect the LC number or produce oxidative DNA damage, the sequelae of red light PDT responsible for immunosuppression in treated skin.

Collagenase followed by compression for the treatment of earlobe keloids.

BACKGROUND: Many therapeutic options are available for treating keloids, but success rates vary widely, and the keloids often recur. The Food and Drug Administration has recently approved intralesional collagenase for the treatment of Dupuytren's contracture. This medication has not been explored for the treatment of earlobe keloids, a common problem. OBJECTIVE: To evaluate the safety and clinical efficacy of intralesional collagenase followed by compression for the treatment of earlobe keloids. MATERIALS AND METHODS: Six earlobe keloids in six patients were injected with a commercial collagenase preparation. Study participants were asked to use compression earrings daily thereafter. Patients were examined and photographed 1 day, 2 weeks, 4 weeks, 10 months, and 12 months after injection. Adverse events were assessed at each visit, and the keloids were measured and photographed. RESULTS: All patients had a decrease in the size of their earlobe keloid by an average of 50% (p = .02). Three of the six participants chose to have their earlobe keloids surgically excised for cosmetic reasons 6, 8, and 11 months after enrollment, so measurements for data analysis for these patients were taken after only 1, 1 and 10 months. All participants returned for follow-up at the last study visit 1 year after study commencement. The three patients who completed the study were pleased with the improvement of their earlobe keloid, although complete clearance was not achieved. Side effects included injection site swelling, tenderness, and one ulceration that spontaneously resolved within 2 weeks. CONCLUSION: Intralesional collagenase followed by compression appears to be a safe and modestly effective treatment for earlobe keloids. This approach warrants further investigation in larger studies with longer follow-up in motivated patients who decline surgical excision.

What you and your patients need to know about vitamin D.

"Vitamin D" is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compound is then hydroxylated sequentially in the liver and kidney to produce the active hormone 1,25(OH)(2)D that binds its nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases and the nuclear receptor have been identified in many tissues, suggesting previously unrecognized roles for vitamin D. Some epidemiologic studies have also correlated low levels of the inactive storage form 25(OH)D with an increased incidence or prevalence of a variety of diseases, suggesting that large oral supplements and/or increased ultraviolet (UV) exposure might therefore improve individual health. However, randomized, prospective controlled trials comparing vitamin D supplements with placebo have not supported this belief. Moreover, current evidence supports the conclusion that protection from UV radiation does not compromise vitamin D status or lead to iatrogenic disease. In contrast, high vitamin D levels appear to incur a risk of kidney stones and other adverse effects. In the case of true vitamin D deficiency, supplements are a more reliable and quantifiable source of the vitamin than UV exposure.

Acute New World cutaneous leishmaniasis presenting as tuberculoid granulomatous dermatitis.

Acute primary cutaneous leishmaniasis typically presents microscopically with a lymphohistiocytic infiltrate containing admixed plasma cells, parasitized macrophages and abundant organisms. Tuberculoid granulomatous changes may occur in the later phases of primary infection. A 23-year-old male presented 1 month after visiting Peru with classic clinical findings of acute primary cutaneous leishmaniasis, while histopathology showed a tuberculoid granulomatous process that lacked any organisms in hematoxylin-eosin and fungal stains. Polymerase chain reaction (PCR) analysis and tissue cultures confirmed the diagnosis of cutaneous leishmaniasis with Leishmania (Viannia) panamensis infection. A pauci-organism tuberculoid granulomatous process may uncommonly be the presenting histopathology in the acute infectious phase of cutaneous leishmaniasis. Clinicians and dermatopathologists should be aware of this atypical presentation, which may cause diagnostic confusion and delay proper treatment. PCR testing should be employed in cases with high clinical suspicion when histopathology is not definitive.

Ultraviolet-fluorescent tattoo location of cutaneous biopsy site.

BACKGROUND: Cutaneous biopsies often heal with little or no scarring. Prior studies have shown an alarming percentage of patients who incorrectly identify biopsy sites at the time of surgery. OBJECTIVE: To investigate the safety and utility of an ultraviolet (UV)-fluorescent tattoo for biopsy site identification. MATERIALS AND METHODS: A preclinical proof of concept was established with skin culture. An UV-fluorescent tattoo was applied to discarded neonatal foreskin in culture medium. The stability of the tattooed skin was examined clinically and histologically. One patient with a recurrent basal cell carcinoma in a difficult-to-identify location underwent tattoo application at the time of biopsy to demarcate the site. The patient was monitored for tattoo reaction and referred for surgical excision. RESULTS: The cultured tissue exhibited stable UV fluorescence with daily washing. Tissue histology demonstrated tattoo particles lining the skin edge under fluorescent microscopy. The patient was reluctant to undergo another surgical procedure and instead returned to our clinic at 3 months and 17 months after the biopsy for management of other tumors. The patient had no symptoms of allergic reaction to the tattoo dye. The fluorescent tattoo remains invisible under visible light and visible only under Wood's light. CONCLUSION: The present study documents the utility of an UV-fluorescent tattoo to locate a biopsy site.

Iatrogenic effects of photoprotection recommendations on skin cancer development, vitamin D levels, and general health.

Ultraviolet (UV) radiation is an established carcinogen that causes skin cancers and other cutaneous photodamage. Vitamin D is produced in the skin after UV exposure and may also be obtained from dietary and supplemental sources. The effect of recommendations for UV protection, as well as for very large vitamin D supplements, and possible adverse effects of both are explored. Current evidence supports the conclusion that protection from UV radiation reduces the incidence of skin cancers and photodamage, but generally does not compromise vitamin D status or lead to iatrogenic disease. Conversely, risks of maintaining very high vitamin D levels have not been adequately studied. Vitamin D obtained from diet and supplements is functionally identical to that produced after UV exposure, and is a more reliable and quantifiable source of the vitamin.

Radiosensitization of mammary carcinoma cells by telomere homolog oligonucleotide pretreatment.

INTRODUCTION: Ionizing radiation (IR) is a widely used approach to cancer therapy, ranking second only to surgery in rate of utilization. Responses of cancer patients to radiotherapy depend in part on the intrinsic radiosensitivity of the tumor cells. Thus, promoting tumor cell sensitivity to IR could significantly enhance the treatment outcome and quality of life for patients. METHODS: Mammary tumor cells were treated by a 16-base phosphodiester-linked oligonucleotide homologous to the telomere G-rich sequence TTAGGG (T-oligo: GGTTAGGTGTAGGTTT) or a control-oligo (the partial complement, TAACCCTAACCCTAAC) followed by IR. The inhibition of tumor cell growth in vitro was assessed by cell counting and clonogenic cell survival assay. The tumorigenesis of tumor cells after various treatments was measured by tumor growth in mice. The mechanism underlying the radiosensitization by T-oligo was explored by immunouorescent determination of phosphorylated histone H2AX (γH2AX) foci, ß-galactosidase staining, comet and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assays. The efficacy of the combined treatment was assessed in a spontaneous murine mammary tumor model. RESULTS: Pretreatment of tumor cells with T-oligo for 24 hours in vitro enhanced both senescence and apoptosis of irradiated tumor cells and reduced clonogenic potential. Radiosensitization by T-oligo was associated with increased formation and/or delayed resolution of γH2AX DNA damage foci and fragmented DNA. T-oligo also caused radiosensitization in two in vivo mammary tumor models. Indeed, combined T-oligo and IR-treatment in vivo led to a substantial reduction in tumor growth. Of further significance, treatment with T-oligo and IR led to synergistic inhibition of the growth of spontaneous mammary carcinomas. Despite these profound antitumor properties, T-oligo and IR caused no detectable side effects under our experimental conditions. CONCLUSIONS: Pretreatment with T-oligo sensitizes mammary tumor cells to radiation in both in vitro and in vivo settings with minimal or no normal tissue side effects.

Inhibition of melanoma angiogenesis by telomere homolog oligonucleotides.

Telomere homolog oligonucleotides (T-oligos) activate an innate telomere-based program that leads to multiple anticancer effects. T-oligos act at telomeres to initiate signaling through the Werner protein and ATM kinase. We wanted to determine if T-oligos have antiangiogenic effects. We found that T-oligo-treated human melanoma (MM-AN) cells had decreased expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, angiopoeitin-1 and -2 and decreased VEGF secretion. T-oligos activated the transcription factor E2F1 and inhibited the activity of the angiogenic transcription factor, HIF-1alpha. T-oligos inhibited EC tubulogenesis and total tumor microvascular density matrix invasion by MM-AN cells and ECs in vitro. In melanoma SCID xenografts, two systemic T-oligo injections decreased by 60% (P < .004) total tumor microvascular density and the functional vessels density by 80% (P < .002). These findings suggest that restriction of tumor angiogenesis is among the host's innate telomere-based anticancer responses and provide further evidence that T-oligos may offer a powerful new approach for melanoma treatment.