Double Blind, Placebo Controlled Evaluation of a Novel Skin Lightening Agent.

Melasma remains a troubling problem for physicans and patients alike. It is a chronic irregular, symmetric hyperpigmentation seen most often in women. In this study, a unique combination of ingredients with non-irritating properties was tested for treatment of melasma. In a double blind, placebo controlled, split face trial, 17 patients with melasma were treated on one half of the face, left or right, while the other received placebo control. All patients used sunscreen on both sides. Measurement with a colorimeter (Mexameter) was taken at baseline and after 8 weeks of daily use. The active side showed an objective decrease in hyperpigmentation of 14.60% while the control side showed a decrease of 9.82%. We conclude the product provides a non-irritating effective therapy for melasma.

J Drugs Dermatol. 2018;17(1):113-115.

Microneedling Prior to Levulan PDT for the Treatment of Actinic Keratoses: A Split-Face, Blinded Trial.

INTRODUCTION: Photodynamic Therapy (PDT) with topical Levulan is an approved and efficacious method for treating actinic keratoses. This therapy depends on the ability of the Levulan (delta amino levulinic acid) to penetrate the stratum corneum and enter the cells of the epidermis. Microneedling is an increasing popular cosmetic therapy in which an array of tiny needles is used to make holes in the epidermis and presumably induce a wound healing cascade that leads to cosmetic improvement of the skin. We were interested to know if prior microneedling would enhance the penetration of topical Levulan and thus enhance the PDT treatment, and if a cosmetic improvement beyond the PDT alone would be seen when it is used in conjunction with microneedling.
METHODS: 20 patients each with at least 4 non hyperkeratotic AKs on each side of their face were enrolled. All patients were randomized to receive multiple passes with a microneedling device to ½ of their face, left or right, followed by application of Levulan to the entire face. The Levulan was allowed to incubate 1 hour followed by exposure to blue light (Blu U) for 1000 seconds.
RESULTS: 19 patients completed the study with 4-month follow up. The mean percentage reduction in AKs was 89.3% on the microneedling side versus 69.5% on the PDT alone side, a significant difference. A physician's global cosmetic assessment was performed based on Canfield Visia photographs: 15 of the 19 patients had a noticeable improved cosmetic appearance on one side of the face versus the other, and in 13 of these patients the improved side was the microneedled side.
DISCUSSION: Prior microneedling significantly enhances the effect of Levulan PDT. It also seems to provide a cosmetic benefit above and beyond the PDT alone. It was safe and well tolerated in this study.

J Drugs Dermatol. 2016;15(9):1072-1074.

Advancing the Care of Post-Acne Scarring: Expert Insights Into New Treatment Options.

Most patients with acne have some degree of facial scarring even after their acne resolves, extending the period of psychosocial distress. Unfortunately, management of acne scars remains challenging. Many treatments for post-acne scarring including chemical peels, skin needling, laser resurfacing, surgical repair, subcision lifting, and punch elevation lifting, are limited by moderate and unpredictable results, significant morbidity, and substantial patient investments in time and money. The most recent addition to the armamentarium is tissue augmentation with soft tissue fillers, including a recently approved polymethylmethacrylate-collagen filler. Matching individual patient needs to the appropriate treatment is crucial. While many patients with acne scars have unrealistic expectations about treatment outcomes, open, honest, and realistic dialogue regarding their treatment options and concerns can facilitate realistic expectations. This article is based on a consensus discussion by the authors, who all have experience managing post-acne scarring, as well as the content of a series of live CME-accredited symposia in connection with major dermatology meetings.

J Drugs Dermatol. 2016;15(5):518-525.

Topical imiquimod clears invasive melanoma.

Malignant melanoma has continually shown a pattern of increased incidence and mortality in the last 50 years. Currently, wide local excision is the mainstay of treatment of primary cutaneous melanomas. Imiquimod has been shown to clear cases of melanoma in situ, but its role in the treatment of invasive cutaneous melanomas is unknown. We present the case of a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod.

A regional survey of purse-string sutures for partial and complete closure of Mohs surgical defects.

BACKGROUND: The purse-string suture is a method for partial and complete closure of circular surgical defects. OBJECTIVE: Short-term and long-term efficacy and cosmesis were assessed to evaluate the utility of purse-string closure as the sole method of closure of Mohs defects in different locations. MATERIALS AND METHODS: Sixty-six circular wounds from Mohs surgery were closed with a running intradermal suture traversing the circumference of the wound. Preoperative and immediate postoperative wound areas were measured. Long-term cosmetic appearance was also assessed. RESULTS: An immediate decrease in average wound area was observed, most notably in the neck and arm. Long-term cosmetic results were best in the head and neck and were remarkably similar for a given anatomic area. CONCLUSION: The purse-string suture is rapid, simple, and associated with little morbidity. In properly selected cases, it is an excellent alternative for partial and complete closure of circular defects resulting from Mohs surgery.

From DNA repair to proteome protection: new molecular insights for preventing non-melanoma skin cancers and skin aging.

Non-melanoma skin cancers (NMSC) are the most common human neoplasms and continue to represent an important public health issue with greater than one million cases diagnosed each year. The primary factor contributing to the molecular pathogenesis of NMSC is unprotected skin exposure to ultraviolet (UV) radiation, ie, UVA (wavelength: 315-400 nm) and UVB rays (wavelength: 280-315 nm) with additional albeit less damaging factors of infrared radiation (wavelength: ~750 nm-1 mm) and environmental pollutants. Skin carcinogenesis by DNA damage is the current predominant paradigm of UV toxicity, which may be caused by direct damaging effects of energy deposited by photons or indirect oxidative action of short-lived reactive oxygen species (ROS) formed from water that reacts with biomacromolecules. UV rays are capable to induce direct both DNA damages, mainly consisting in the formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPDs), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8OHdG). Growing evidence also suggests that the efficiency of DNA repair after exposure to UV radiation is crucially dependent on the levels of oxidative protein damage, including but not limited to DNA repair proteins. Besides DNA lesions, UV-induced oxidative stress can indeed result in carbonylation of proteins, a major form of irreversible protein damage that inactivates their biological function. Interestingly, microorganisms characterized by extreme resistance to UV rays have an intrinsic capacity to protect their proteome, rather than genome, from radiation-induced damage, suggesting that protein carbonylation (PC) may serve as a reliable and innovative biomarker of UV photodamage. This review discusses the main DNA and protein markers of UV-induced damage (eg, CPDs, 8OHdG, and PC) and their relationship and importance to the current understanding of skin carcinogenesis. The identification of key DNA and protein signatures of photodamage may represent a therapeutic target for translational studies of innovative therapeutic and preventive approaches for reducing both skin aging and the morbidity and mortality associated with NMSC.

An experimental double-blind irradiation study of a novel topical product (TPF 50) compared to other topical products with DNA repair enzymes, antioxidants, and growth factors with sunscreens: implications for preventing skin aging and cancer.

The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.

Current status of surgery in dermatology.

An article titled "Current issues in dermatologic office-based surgery" was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein.

Topical formulation engendered alteration in p53 and cyclobutane pyrimidine dimer expression in chronic photodamaged patients.

While the clinical attributes of photoaging are well characterized in the literature, the pathogenic mechanisms that underlie these changes are incompletely elucidated. At the molecular level, p53 tumor-suppressor gene product mediated excision repair of ultraviolet (UV)-induced DNA damage is a critical effector in xeroderma pigmentosum (XP) and potentially in conventional photoaging. We examined p53 activity and measured UV-induced DNA damage via cyclobutane pyrimidine dimers (CPDs) quantitatively in 20 volunteers before and after an 8-week, open-label prospective topical application of a proprietary DNA recovery serum (Celfix). There was a statistically significant decrease in immunohistochemically determined p53 and CPD levels. While these data are preliminary, the findings lend support to the theoretical possibility of a topical agent reversing the effects of photodamage at the molecular level and, potentially, an ameliorative outcome clinically.

Clearance of invasive melanoma with topical imiquimod.

A 93-year-old woman presented with biopsy-proven invasive melanoma of 2.75 mm depth, arising from a melanoma in situ. Standard treatment of this depth would be an extensive and mutilating excision, which presented a therapeutic dilemma. Imiquimod has the ability to clear melanoma in situ, but its effect on invasive melanoma is unknown. After a thorough discussion with the patient, we decided to attempt to treat the melanoma in situ with topical imiquimod and then excise the smaller invasive component. Following 5 weeks of topical imiquimod therapy, the area where the nodular melanoma had previously been was excised. Histological examination of the excisional specimen revealed no residual melanoma detected. In this case, it appears that 5 weeks of topical imiquimod therapy completely cleared an invasive melanoma of 2.75 mm depth, as well as clearing the component of melanoma in situ. The patient was followed for 14 months with no evidence of recurrence.

Clindamycin phosphate 1.2% and tretinoin 0.025% gel for rosacea: summary of a placebo-controlled, double-blind trial.

Rosacea is a common, chronic, and poorly understood dermatological condition characterized by an inflammatory component composed of papules and pustules and a vascular component composed of flushing and erythema. Current treatment options include topical, systemic, and light-based methods, each of which focuses on either the inflammatory or the vascular component. Retinoids are not routinely indicated as treatment because of the common conception that they would be too inflammatory for the sensitive rosacea patient. However, photodamage may play a role in rosacea and tretinoin is well-known to repair photodamage. Thirty rosacea subjects were enrolled to assess their response to the use of clindamycin phosphate 1.2% and tretinoin 0.025% gel (ZIANA; Medicis Pharmaceutical Corporation, Scottsdale, AZ) for a period of 12 weeks. The results showed a dramatic decrease in pustules and papules without any significant inflammation or overall intolerance. No improvement in facial redness was achieved. Based on our results, more investigation of topical retinoids for rosacea treatment is prudent.

Adverse effects of ultraviolet radiation from the use of indoor tanning equipment: time to ban the tan.

The incidence of melanoma skin cancer is increasing rapidly, particularly among young women in the United States. Numerous studies have documented an association between the use of indoor tanning devices and an increased risk of skin cancer, especially in young women. Studies have shown that ultraviolet exposure, even in the absence of erythema or burn, results in DNA damage. Countries and regulatory bodies worldwide have recognized the health risks associated with indoor tanning. In the United States, 32 states have passed legislation to regulate the indoor tanning industry, but there is an urgent need to restrict the use of indoor tanning devices at the federal level. The Food and Drug Administration is currently reviewing the classification of these devices. For all of these reasons, the Food and Drug Administration should prohibit the use of tanning devices by minors and reclassify tanning devices to at least class II to protect the public from the preventable cancers and other adverse effects caused by ultraviolet radiation from indoor tanning.

Adverse effects of ultraviolet radiation from the use of indoor tanning equipment: time to ban the tan.

The incidence of melanoma skin cancer is increasing rapidly, particularly among young women in the United States. Numerous studies have documented an association between the use of indoor tanning devices and an increased risk of skin cancer, especially in young women. Studies have shown that ultraviolet exposure, even in the absence of erythema or burn, results in DNA damage. Countries and regulatory bodies worldwide have recognized the health risks associated with indoor tanning. In the United States, 32 states have passed legislation to regulate the indoor tanning industry, but there is an urgent need to restrict the use of indoor tanning devices at the federal level. The Food and Drug Administration is currently reviewing the classification of these devices. For all of these reasons, the Food and Drug Administration should prohibit the use of tanning devices by minors and reclassify tanning devices to at least class II to protect the public from the preventable cancers and other adverse effects caused by ultraviolet radiation from indoor tanning.

Effects of immobilization stress and hormonal treatment on nociception.

The purpose of this study was to evaluate the effects of stress and estradiol (E2) on pain tolerance. Ovariectomized rats were assigned to treatment groups based on a 2 x 4 factorial design comprising stress (nonstress x stress) and hormone treatment vehicle x E2 [0.25 mg/kg/d]) x estrogen receptor alpha (ERalpha)-selective agonist propyl pyrazole triol (1 mg/kg/d) x estrogen receptor beta (ERbeta)-selective agonist diarylpropionitrile (1 mg/kg/d). Stressed animals underwent daily 60-minute immobilization for 22 days. Pain tolerance was assessed with the hot plate test, an acute thermal pain test. In this study, stressed rats showed increased (P < .05) pain tolerance compared with nonstressed rats (25.0 +/- 1.92 s vs 20.4 +/- 1.02 s, respectively). Increased (P < .05) pain threshold was observed in nonstressed and stressed rats treated with E2 and the ERalpha agonist compared with vehicle-treated rats. Interestingly, the ERbeta agonist only increased (P < .10) pain thresholds in stressed rats. Stressed rats exhibited higher (P < .05) beta-endorphin levels compared with nonstressed rats in all hormone-treatment groups. With the exception of stressed rats treated with the ERbeta agonist, there was no hormone effect on beta-endorphin levels. These studies suggest that E2's effect on pain thresholds may be mediated via the ERalpha, while the interaction between chronic stress and ERbeta may also enhance pain threshold.

Correction of atrophic scars with artefill: an open-label pilot study.

BACKGROUND: Artefill, a novel permanent filler approved by the U.S. Food and Drug Administration (FDA), has been used as an injectable implant for the correction of nasolabial folds. Fillers are considered a first line treatment for atrophic scars. OBJECTIVE: The authors evaluated the degree of correction and subject satisfaction of correction of atrophic acne scar(s) after injection of Artefill. METHODS: Fourteen qualified subjects participated in a single-center, open-label, pilot study. Atrophic acne scars were evaluated prior to injection. Subscision was performed, and then Artefill was injected into the scar. The degree of improvement was measured at weeks 2 and 4 and month 8. Subjects were asked to fill out a satisfaction survey at their eight-month visit. RESULTS: Investigator ratings after eight months post procedure indicated that 96 percent of the atrophic acne scars showed some degree of improvement. There was no improvement in two out of a total of 57 scars evaluated. The majority of patients reported a moderate correction, correlating with a 51-75 percent improvement in their acne scars at eight months. No adverse events or side effects were noted. CONCLUSION: Artefill demonstrated to be both an efficacious and safe therapy for the treatment of atrophic acne scars.

Case series: evaluation of a liquid silicone gel on scar appearance following excisional surgery--a pilot study.

Efforts to improve the size and appearance of scars have included therapies as varied as laser treatments and onion extract gels. Silicone gel sheeting is well know to improve the appearance of hypertrophic scars, and may have a role in the management of routine surgical and traumatic scars. By varying the degree of cross linking, silicone elastomer can be a solid sheet or a liquid gel. In this pilot series, seven patients applied a liquid silicone gel twice a day to one half of a new surgical scar for three months. At the end of this time, the treated side was noticeably better in appearance in five of seven patients while two of seven had no difference. In no patient was the silicone treated side worse in appearance.

Practical applications of a new botulinum toxin.

The injection of Clostridium botulinum type A neurotoxins is among the most commonly performed cosmetic procedures, both in the U.S. and worldwide. The U.S. Food and Drug Administration (FDA) approval of a new botulinum neurotoxin type A in April 2009 (BoNT-A, Dysport, Medicis, Scottsdale, AZ-hereafter referred to as "Dysport") has broadened the neurotoxin market and provides new therapeutic alternatives to practitioners. The introduction of this product raises questions about how to best use it. In this supplement, the authors address critical similarities and differences between onabotulinumtoxinA (Botox, Allergan, Irvine, CA--hereafter referred to as "Botox") and abobotulinumtoxinA (Dysport). The authors also provide practical guidelines for the use of Dysport based on clinical experience and peer-reviewed, published clinical trials. In the authors' opinion, Botox and Dysport can be used for similar "on-" and "off-label" applications. Judicious use of either product requires an understanding of how the two products differ in order to avoid side effects and achieve optimal results. Common Questions: Are these two toxins the same or different and how? How are inter-product "unit" conversions addressed? Does injection technique differ? Does one product result in greater adverse events? Does one product last longer or "diffuse" better than the other? What other toxins can be expected on the market in the future?