Richard L. Gallo MD PhD,a Vivian W. Bucay MD,b Ava T. Shamban MD,c Janice Lima-Maribona DO,d Amy B.
Lewis MD,e Cherie M. Ditre MD,f Flor A. Mayoral MD,g Michael H. Gold MDh
Heparan sulfate is an essential glycosaminoglycan that plays important roles in development, homeostasis, and disease. As a group, the glycosaminoglycans provide mechanical strength to skin, as they can absorb water and occupy the space between elastin fibers and collagen. Heparan sulfate is also a key participant in cell proliferation, cell migration, collagen fiber formation, basement membrane regeneration, granulation tissue formation, and cell adhesion associated with wound healing. A variety of dermatological disorders are associated with changes in glycosaminoglycans or their associated proteoglycans. A new topical formulation of low molecular weight heparan sulfate glycosaminoglycan has been shown to penetrate the epidermis, basement membrane, and dermis within 24 hours of application. In an 8-week study, 15 patients using this new formulation showed improvement in skin hydration, skin firmness, skin elasticity, skin barrier function, and global fine lines and wrinkles. Incorporating low molecular weight heparan sulfate into topically applied formulations may represent a new approach to improving the appearance of photodamaged skin.
J Drugs Dermatol. 2015;14(7):669-674.
Tracey Vlahovic DPM,a Tejal Merchant MPharm,b Sanjay Chanda PhD,b Lee T. Zane MD,b and Dina Coronado BSb
BACKGROUND: Onychomycosis is a common infection of the toenails that causes nail thickening and discoloration. The physical appearance
of the infected nail can diminish self-image and negatively impact quality of life. Patients may use nail polish to mask the appearance of infected nails.
OBJECTIVE: To evaluate the in vitro nail penetration properties of tavaborole topical solution, 5%, through nail polish using ex vivo, non-diseased human fingernails.
METHODS: In study 1, tavaborole penetration was evaluated over 20 days of dosing using the Franz finite dose technique and modified
Franz diffusion cells. Nails received either 1 coat of over-the-counter (OTC) typical polish or were left unpolished (controls). In study 2, tavaborole penetration was measured over 14 days of dosing using the finite dose technique and vertical diffusion cells. Nails were polished with either 4 coats or 1 coat of salon typical polish or with 2 coats or 1 coat of OTC typical polish, or they were left unpolished.
RESULTS: In study 1, the mean ± standard deviation (SD) cumulative tavaborole penetration at day 21 was numerically higher,
though not statistically significant, through polished nails (3,526 ± 1,433 μg/cm2) vs unpolished nails (2,661 ± 1,319 μg/cm2). In study 2, the mean cumulative tavaborole penetration was also numerically higher (statistical significance not assessed) through all nails that received polish vs unpolished nails. At day 15, mean ± SD cumulative tavaborole nail penetration
was 1,179 ± 554 μg/cm2 through 4 coats of salon typical polish, 1,227 ± 974 μg/cm2 through 1 coat of salon typical polish, 1,493 ± 1,322 μg/cm2 through 2 coats of OTC typical polish, 1,428 ± 841 μg/cm2 through 1 coat of OTC typical polish, and
566 ± 318 μg/cm2 through unpolished nails.
CONCLUSION: Results from these in vitro studies demonstrated that tavaborole penetrated through human nails with up to 4 layers of nail polish.
J Drugs Dermatol. 2015;14(7):675-678.
Yi Chun Lai BSa and Yik Weng Yew MBBS MPHa,b
Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases.
J Drugs Dermatol. 2015;14(7):681-684.
Amit Verma DrPH MPH, Babajide Olayinka MSc, Alan B. Fleischer Jr. MD
BACKGROUND: Tinea pedis is the most common superficial fungal infection. Naftifine hydrochloride is a topical antifungal of the allylamine
class, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects. Clinical data on topical antifungal therapy using naftifine for tinea pedis in a pediatric population is limited.
OBJECTIVE: To assess trends in efficacy, tolerability, safety, and to quantify the pharmacokinetics (PK) of topical naftifine hydrochloride gel 2% in pediatric subjects with tinea pedis.
METHODS: Twenty-eight subjects (22 pediatric and 6 adult controls) were enrolled and treated in the study. Approximately 2 grams of naftifine hydrochloride gel 2% was applied to each foot (4 grams total) for subjects with tinea pedis. Pharmacokinetic blood and urine samples were collected at various time points throughout the study. Efficacy was assessed based on potassium hydroxide, dermatophyte
culture, and signs and symptom results at days 7, 14, and 28. Adverse event information was collected routinely.
RESULTS: The rate and extent of systemic exposure among the pediatric and adult control subjects was low. Adverse events were minimal
and were not related to treatment. Positive results were observed as early as day 7; however the proportion of subjects achieving success generally increased over time through day 28 in both treatment groups.
CONCLUSIONS: Naftifine hydrochloride gel 2% was found to be well tolerated and safe. Trends in clinical benefit were observed throughout
the treatment period; however, continued improvement in efficacy rates were observed during the post-treatment period.
J Drugs Dermatol. 2015;14(7):686-691.
INTRODUCTION: Successful treatment of onychomycosis is both a clinical and therapeutic challenge. Effective patient education and reassurance are critical. This post hoc analysis aims to provide some guidance to physicians based on initial disease severity and influencing factors.
METHODS: A post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled studies evaluating the efficacy and safety of efinaconazole topical solution, 10% in mild to moderate onychomycosis. Outcomes were assessed based on baseline severity (20%-29%, 30%-39%, 40%-49%, and ≥50% affected target toenail).
RESULTS: Overall, the mean percent affected toenail following efinaconazole treatment decreased from 36.4% to 20.6% (a 43% reduction). The percent reduction in mean percent affected toenail (range, 43.6% to 59.8%) with efinaconazole was similar irrespective of baseline severity. Improvement was only seen in the very mildest patients with vehicle and not before week 36. Improvement was influenced by gender (females did better) and disease duration (long standing disease responding less well).
CONCLUSIONS: Our onychomycosis patients treated with efinaconazole might expect a 50% improvement in their disease within a year, and this will be seen as significant by many, especially those who have suffered for many years. Many will do better, but they will need to be reminded of the slow growth of the toenail.
J Drugs Dermatol. 2015;14(7):694-698.
James H. Herndon Jr. MD,a Lily Jiang PhD,a Tatiana Kononov BS MBA,b Theresa Fox BSb
An open label clinical trial was conducted to determine the effectiveness of a multi-ingredient anti-aging moisturizer designed to improve
the appearance of facial skin. Parameters studied included fine lines and wrinkles, clarity/brightness, visual roughness, tactile roughness, evenness of skin tone (redness), evenness of skin tone (hyperpigmentation) and overall appearance. Thirty-seven female subjects, ages 35-60 years completed the study. Effective ingredients incorporated into the facial anti-aging moisturizer include: Astragalus membranaceus root extract, a peptide blend including palmitoyl tripeptide-38, standardized rosemary leaf extract (ursolic acid), tetrahexyldecyl ascorbate (THD ascorbate) and ubiquinone (coenzyme Q10). Subjects were instructed to apply the moisturizer
twice daily, once in the morning and once in the evening. Subjects were evaluated at baseline and after 4, 8, and 12 weeks of product usage. Clinical evaluations were conducted at each visit. A self-assessment questionnaire was conducted at week 4, week 8, and week 12. The self-assessment questionnaire included product efficacy inquiries and product aesthetic inquiries. Digital photography was conducted at baseline, week 8, and week 12. After 8 weeks of twice daily use, clinical evaluation results show that the multi-ingredient anti-aging moisturizer produced a statistically significant improvement in the scores of all clinical grading parameters assessed compared to baseline. A greater statistically significant improvement was seen at 12 weeks. At week 12, there was a statistically significant percentage of favorable results versus unfavorable results in all product efficacy and product aesthetic self-assessment questionnaire results. Digital photography supported the clinical grading and self-assessment questionnaire results. Additionally, the multi-ingredient anti-aging moisturizer is judged to be mild and well tolerated. Several tolerability parameters were assessed at all time points with no statistically significant increase in any of the scores compared to baseline.
J Drugs Dermatol. 2015;14(7):699-704.
Kim Papp MD PhD,a Alice B. Gottlieb MD PhD,b Luigi Naldi MD,c David Pariser MD,d Vincent Ho MD,
e Kavitha Goyal MD,f Steven Fakharzadeh MD PhD,f Marc Chevrier MD PhD,g Stephen Calabro MS,f
Wayne Langholff PhD,g and Gerald Krueger MDh
BACKGROUND: Safety surveillance is needed for biologic therapies for psoriasis.
OBJECTIVE: To assess the risk of adverse events of special interest (AEoSIs) with ustekinumab and other psoriasis treatments in a real-world setting using 2014 Psoriasis Longitudinal Assessment and Registry (PSOLAR) data. AEoSIs included malignancy (excluding nonmelanoma skin cancer), major adverse cardiovascular events (MACE), serious infection, and all-cause mortality.
METHODS: Cumulative rates of AEoSIs/100 patient-years (PY) are reported for ustekinumab, infliximab, other biologics (mostly adalimumab/etanercept), and non-biologics based on pre-specified analyses using attribution rules biased against ustekinumab. Risk factors for AEoSIs, including treatments, were determined using multivariate statistical analysis.
RESULTS: A total of 12,093 patients (40,388 PY) were enrolled in PSOLAR. Overall incidence rates were 0.68/100PY for malignancy, 0.33/100PY for MACE, 1.60/100PY for serious infection, and 0.46/100PY for mortality. Unadjusted rates of serious infection for infliximab (2.91/100PY) and other biologics (1.91/100PY) were numerically higher compared with ustekinumab (0.93/100PY). Exposure to the combined group of biologics other than ustekinumab was significantly associated with serious infection (hazard ratio=1.96, P<.001). None of the biologics was associated with increased risk of malignancy, MACE, or mortality.
LIMITATIONS: Observational data have inherent biases.
CONCLUSION: Analysis of 2014 PSOLAR data identified no increased risk of malignancy, MACE, serious infection, or mortality with ustekinumab.
J Drugs Dermatol. 2015;14(7):706-714.
Emily Stamell Ruiz MD,a Amber Ingram BS,b Angelo Landriscina BA,b Jiaying Tian MD MPH,b Robert S. Kirsner MD PhD,c and Adam Friedman MDb,d
IMPORTANCE: As restoration of the integument is paramount to wound healing, dermatologists should be central to managing wounds; yet this is often not the case. If a training gap exists during residency training, this may account for the observed discrepancy.
OBJECTIVES: To identify United States (US) dermatology residents’ impressions regarding their preparedness to care for wounds, and to assess the amount and type of training devoted to wound care during residency.
DESIGN, SETTING, AND PARTICIPANTS: An online survey among current US dermatology residents enrolled in a residency training program.
MAIN OUTCOMES AND MEASURES: The primary goal was to determine whether dermatology residents believe more wound care education
is needed, evaluate preparedness to care for wounds, and identify future plans to manage wounds.
RESULTS: Responses were received from 175 of 517 (33.8%) US Dermatology residents contacted. The majority of residents did not feel prepared to manage acute (78.3%) and chronic (84.6%) wounds. Over three quarters (77.1%) felt that more education is needed. Fewer than half (49.1% and 35.4%) of residents planned to care for acute and chronic wounds, respectively, when in practice.
CONCLUSIONS AND RELEVANCE: There is a gap in wound care education in US dermatology residency training. This translates to a low percentage of dermatology residents planning to care for wounds in future practice. Dermatology residents need to receive focused wound care training in order to translate the underpinnings of wound healing biology and ultimately better serve patients.
J Drugs Dermatol. 2015;14(7):716-720.
Tagai Musaev BA,a Angelo Landriscina BA,a Jamie Rosen BA,a and Adam J. Friedman MDa,b,c
BACKGROUND: Burns are a major cause of morbidity and mortality worldwide. Most burn patients are treated in an outpatient setting. However, the type of burn injuries, frequency of burn injuries treated by dermatologists, and therapeutic approach is unknown.
OBJECTIVE: To assess burn injury incidence in a single center academic dermatology practice, and describe demographic characteristics of burn patients seen by dermatologists.
METHODS: A retrospective chart review analysis of 51 patients seen by 7 dermatologists from April 2010 to July 2014.
RESULTS: Of the 51 patients seen, burns from hot metal were the main mechanism of injury followed by contact with hot liquids. Silver sulfadiazine was the most commonly prescribed treatment. At the time of the visit 84.3% (n=43) had other dermatological conditions.
CONCLUSION: Our study demonstrates that burns are not frequently seen by dermatologists. We hypothesize that longer wait times in specialty practices, the lack of burn-specific training and the complexities of burn care prevent dermatologists from being first line providers in this arena. A larger epidemiological study is needed to further elucidate these issues.
J Drugs Dermatol. 2015;14(7):721-724.
Angelo Landriscina BA,a* Tagai Musaev BA,a* Jamie Rosen BA,a Anjana Ray PhD,b Parimala Nacharaju PhD,c Joshua D. Nosanchuk MD,b and Adam J. Friedman MDa,c
BACKGROUND: The treatment of cutaneous wounds in the clinical setting continues to be a clinical challenge and economic burden, with burn wounds being especially formidable. Direct mechanical injury coupled with the transfer of thermal energy leads to tissue necrosis,
pro-inflammatory cytokine release and the eventual expansion of an initial wound. Our current therapeutic armamentarium falls short of options to help prevent wound expansion, and therefore new modalities are required. Nitrosating substances such as RSNOs have been proven to be effective in promoting wound closure due to their ability to modulate inflammation, cytokine production and vascular function.
OBJECTIVE: We aim to evaluate the efficacy of n-actetylcysteine s-nitrosothiol nanoparticles (NAC-SNO-np) on thermal burn wounds and associated expansion.
METHODS: A multi-burn model was utilized to induce three burn wounds on the dorsal surface of BALB/c mice, allowing for evaluation of the burn itself and peripheral tissue. Wounds were excised and processed for histology and immunohistochemistry on day 7 following
RESULTS: Following treatment with NAC-SNO-np, burn wound expansion was attenuated and wound healing was accelerated. Histological
analysis revealed increased collagen deposition as well as increased macrophage and decreased neutrophil infiltration into the wound bed.
CONCLUSION: NAC-SNO-np represents a platform that harnesses the nitrosative properties of NAC-SNO in order to accelerate the transition
from inflammatory to proliferative wound healing. Further studies are needed in order to translate to the clinical setting.
J Drugs Dermatol. 2015;14(7):726-732.
Alejandra Vivas MD,a Joshua D. Fox BS,a Katherine L. Baquerizo Nole MD,a Andrea D. Maderal MD,a Evangelos Badiavas MD PhD,a D. Innes Cargill PhD,b Herbert B. Slade MD,b Steven R. Feldman MD PhD,c Robert S. Kirsner MD PhDa
INTRODUCTION: Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development.
METHODS: On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined.
RESULTS: Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze-time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained.
DISCUSSION: This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies.
Clinicaltrials.gov identifier: NCT01253135.
J Drugs Dermatol. 2015;14(7):734-738.
Angelo Landriscina BA,a* Jamie Rosen BA,a* and Adam J. Friedman MDa,b,c
Chronic wounds are a major source of morbidity and mortality within the United States. Wound dressings remain a cornerstone of dermatologic
therapy. Selection of the proper wound dressing proves difficult given the range of wounds encountered and the numerous dressing options available to the clinician. Nevertheless, selection of a proper wound dressing is a crucial step in management that can significantly alter the course of wound healing. There are a variety of wound dressings available, including moisture retentive/occlusive dressings as well as dressings impregnated with antimicrobial agents. Here we outline the characteristics and indications of specific wound dressings in order to provide clinicians with a basic understanding of the types of dressings available. This review provides a tool for dermatologists to better assess and treat chronic wounds. Using the algorithm provided, clinicians will be able to select the appropriate dressing in order to accelerate wound healing, prevent infection and improve health outcomes.
J Drugs Dermatol. 2015;14(7):740-744.