Wm. Philip Werschler MD FAAD FAACS,a Julius W. Few Jr. MD,b Carolyn I. Jacob MD FAAD,c
John H. Joseph MD,d James M. Spencer MD MS,e and Amy Forman Taub MDf
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.
Daniel J. Aires MD JD,*a Jo Wick PhD,*b Tarek S. Shaath MD,*c Anand N. Rajpara MD,a Vikas Patel MD,a Ahmed H. Badawi PhD,c Cicy Li MS,c Garth R. Fraga MD,d Gary Doolittle MD,e and Deede Y. Liu MDa
New melanoma drugs bring enormous benefits but do so at significant costs. Because melanoma grows deeper and deadlier over time, deeper lesions are costlier due to increased sentinel lymph node biopsy, chemotherapy, and disease-associated income loss. Prior studies have justified pigmented lesion biopsies on a “value per life” basis; by contrast we sought to assess how many biopsies are justified per melanoma found on a purely economic basis. We modeled how melanomas in the United States would behave if diagnosis were delayed by 6 months, eg, not biopsied, only observed until the next surveillance visit. Economic loss from delayed biopsy is the obverse of economic benefit of performing biopsy earlier. Growth rates were based on Liu et al. The results of this study can be applied to all patients presenting to dermatologists with pigmented skin lesions suspicious for melanoma. In-situ melanomas were excluded because no studies to date have modeled growth rates analogous to those for invasive melanoma. We assume conservatively that all melanomas not biopsied initially will be biopsied and treated 6 months later. Major modeled costs are (1) increased sentinel lymph node biopsy, (2) increased chemotherapy for metastatic lesions using increased 5-yr death as metastasis marker, and (3) income loss per melanoma death at $413,370 as previously published. Costs avoided by diagnosing melanoma earlier justify 170 biopsies per melanoma found. Efforts to penalize “unnecessary” biopsies may be economically counterproductive.
J Drugs Dermatol. 2016;15(5):527-532.
Brian Berman MD PhDa,b and Eggert Stockfleth MD PhDc
There is a need for early, effective field treatments for actinic keratosis (AK) that target subclinical as well as clinically visible lesions to minimize the recurrence and emergence of new lesions. Ingenol mebutate gel is an effective and well-tolerated topical field therapy that has demonstrated sustained clearance and long-term reduction of AKs. This article reviews findings from the FIELD study program and highlights health-related quality of life (HRQoL) outcomes for patients receiving ingenol mebutate. Efficacy data from the FIELD study program are discussed and the tolerability profile of ingenol mebutate in the treatment of areas of up to 100 cm2 is considered. These findings are then placed in the context of HRQoL outcomes and their relevance for patients.
J Drugs Dermatol. 2016;15(5):535-542.
Adam Meekings BSc,a Sarah Utz BA,d Martina Ulrich MD,f Amanda Bienenfeld BA,d,e Naveen Nandanan MD,e Juliya Fisher MD,c Gordon McKenzie PhD,b Daniel M. Siegel MD FAAD,c Eleanor Feldman BA,c and Orit Markowitz MD FAADc
BACKGROUND: Optical coherence tomography (OCT) is a technique that enables real-time in-vivo examination of tissue. This technology provides the clinician with the potential to use a non-invasive tool in the identification and diagnosis of many skin lesions. However, the diagnostic features of basal cell carcinoma have not yet been described with comparison to their histopathology.
OBJECTIVES: To identify and describe key features of basal cell carcinoma (BCC) and its subtypes as they present in multi-beam Swept Source – OCT (MSS-OCT), and to correlate those against conventional histopathology.
METHODS: A total of 40 lesions were assessed by MSS-OCT prior to biopsy. 60-slice OCT images of the lesions were obtained and correlated with histology sections taken in the same plane. OCT scans were assessed retrospectively by a panel to determine the OCT criteria for BCC and its subtypes.
RESULTS: The following diagnostic criteria were identified: hyporeflective ovoid structures (40/40), dark halo boundaries (38/40), epidermal thinning (28/40), and collagen compression (14/40). Lesional tissue also showed a destruction of layers when compared to the surrounding normal tissue. In addition to the shared criteria, other subtypes showed distinct diagnostic criteria.
CONCLUSION: With its higher sensitivity, using MSS-OCT allowed for non-invasive, accurate identification of the key diagnostic features of BCC and its subtypes with high correlation to the histopathologic features found with biopsy.
J Drugs Dermatol. 2016;15(5):545-550.
Linda F. Stein Gold MD,a Michael T. Jarratt MD,b Alicia D. Bucko DO,c Steven K. Grekin DO,d
Joshua M. Berlin MD,e Michael Bukhalo MD,f Jonathan S. Weiss MD,g David R. Berk MD,h
Joan–En Chang–Lin PhD,h Vince Lin PhD,h and Alexandre Kaoukhov MDh
BACKGROUND: Treatment of acne vulgaris (acne) with dapsone gel, 5% requires twice-daily dosing, and some patients may not adhere to this regimen.
OBJECTIVE: The objective of this study was to assess the efficacy and safety of a new, once-daily formulation of dapsone gel, 7.5%, with a 50% higher dapsone concentration, versus vehicle over 12 weeks in patients with acne.
METHODS: This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients with moderate acne aged 12 years and older with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized to receive topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
RESULTS: The intent-to-treat population comprised 2102 patients, 1044 in the dapsone gel, 7.5% group and 1058 in the vehicle group. At week 12, 29.9% of patients in the dapsone gel, 7.5% group and 21.2% in the vehicle group (P<.001) had GAAS success. Mean inflammatory lesions decreased by 55.5% and 49.0%, noninflammatory lesions decreased by 44.4% and 38.4%, and total lesions decreased by 48.7% and 42.4% in the dapsone gel, 7.5% and vehicle groups (all P<.001), respectively, at week 12. The incidence of adverse events was similar in the dapsone gel, 7.5% (19.1%) and vehicle (20.6%) groups. Most events in both groups were mild or moderate in severity. Most patients receiving dapsone gel, 7.5% and vehicle had a severity rating of “none” for stinging/burning, dryness, scaling, and erythema scales at all time points.
CONCLUSIONS: Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne.
J Drugs Dermatol. 2016;15(5):553-561.
Craig L. Leonardi MD,a Kristina Unnebrink PhD,b and Wendell C. Valdecantos MDc
INTRODUCTION: We evaluated post hoc the relationship between Humira® (adalimumab) therapy and high-sensitivity C-reactive protein (hs-CRP) levels in patients with moderate-to-severe hand and/or foot psoriasis from the 16-week placebo-controlled period of REACH.
METHODS: REACH was a phase 4, multicenter, randomized, double-blind trial, evaluating adalimumab treatment for patients with psoriasis of the hands and/or feet. Adults were randomized 2:1 to adalimumab 40 mg every other week (following 80 mg at week 0) or matching placebo from weeks 1 to 16, followed by a 12-week, open-label extension. In this post hoc analysis, changes in hs-CRP were reported as observed from baseline to week 16.
RESULTS: Of the 72 patients (23 placebo, 49 adalimumab) who participated in REACH, 63 (19 placebo, 44 adalimumab) with hs-CRP measurements at baseline and at week 16 were included in this analysis. Baseline median hs-CRP values were 1.6 mg/L (placebo) and 2.2 mg/L (adalimumab), and were 3 times higher for patients with, as compared with those without, psoriatic arthritis (5.45 vs 1.8 mg/L). At week 16, the adalimumab group showed greater improvements (median reduction) from baseline than the placebo group in hs-CRP overall (−0.55 vs +0.10 mg/L), regardless of achievement of PGA of the hands and/or feet (hfPGA) 0 or 1 at week 16 (−0.80 vs 0 mg/L for patients who achieved hfPGA 0/1; −0.40 vs +0.30 mg/L, patients who did not achieve hfPGA 0/1), baseline psoriatic arthritis history (−2.35 mg/L with history [adalimumab group; no history for placebo group]; −0.40 vs +0.10 mg/L without history), and body mass index (BMI) category (defined by median BMI) (−0.80 vs +0.20 mg/L for BMI <30.28 kg/m2; −0.40 vs 0 mg/L for BMI ≥30.28 kg/m2).
CONCLUSION: Treatment with adalimumab 40 mg every other week resulted in greater overall reductions in hs-CRP levels among patients in this post hoc analysis, compared with placebo at 16 weeks regardless of baseline characteristics.
ClinicalTrials.gov Registry for REACH: NCT00735787
J Drugs Dermatol. 2016;15(5):562-566.
M. Alan Menter MD,a Kim A. Papp MD,b Jennifer Cather MD,c Craig Leonardi MD,d David M. Pariser MD,e
James G. Krueger MDM,f Johannes Wohlrab MD,g Mario Amaya-Guerra MD,h Andrzej Kaszuba MD,i
Oleg Nadashkevich MD,j Tsen-Fang Tsai MD,k Pankaj Gupta PhD,l Huaming Tan PhD,l
Hernan Valdez MD,m Lotus Mallbris MD,n and Svitlana Tatulych MDl
BACKGROUND: Tofacitinib is a Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. We report efficacy of tofacitinib in patient subgroups based on pooled data from two Phase 3 trials (NCT01276639, NCT01309737).
OBJECTIVES: To assess consistency of treatment effects of tofacitinib versus placebo in subgroups defined by baseline characteristics, and to ascertain whether baseline characteristics are of value in optimizing tofacitinib use.
METHODS: Pooled data from the two trials were used to evaluate ≥75% reduction in PASI from baseline (PASI75 response) in subgroups defined by age, age at psoriasis onset, gender, race, geographical region, weight, body mass index, diabetes, metabolic syndrome, tobacco/alcohol use, psoriatic arthritis, disease activity, and prior therapy.
RESULTS: Week 16 PASI75 response rates (N=1843) were 43%, 59% and 9% with tofacitinib 5 and 10mg twice daily (BID) and placebo, respectively (each P<0.0001 versus placebo). Tofacitinib 5 and 10mg BID were effective regardless of baseline characteristics. Across subgroups, tofacitinib generally produced greater response rates with the 10 versus 5mg BID dosage. Lower absolute response rates were seen in heavier patients and patients with prior biologic experience.
CONCLUSIONS: Both tofacitinib dosages demonstrated consistent efficacy versus placebo across subgroups. Lower response rates were seen in heavier patients and those with prior biologic experience. Tofacitinib 10mg BID resulted in a substantial proportion of responders regardless of baseline characteristics.
J Drugs Dermatol. 2016;15(5):568-580.
Gabriel Nistor MD,a Aleksandra J. Poole PhD,a Zoe Draelos MD,b Mary Lupo MD,c Thomas Tzikas MD,d Jerome H. Liu MD,e and Hans S. Keirstead PhDa
These studies were designed to determine the effect of stem cell-derived skin lineage precursor secretions on the intrinsic and extrinsic symptoms of human skin aging.
Human stem cells cultivated in balanced conditions were differentiated into skin lineage precursors, and shown to secrete large amounts of fetuin as well as multiple growth factors beneficial for human skin development and maintenance. The cell secretions were incorporated in two simple cosmetic formulations (serum and lotion) and investigated in an IRB-approved 12-week human trial that included 25 subjects in each group. Subjects were examined at 2, 4, 8, and 12 weeks by a dermatologist to evaluate safety, trans-epidermal water loss, wrinkles, firmness, radiance, texture, softness, and overall appearance. A sub-group of subjects from each group consented for biopsies for histological analyses.
Protein analyses in the cell secretions revealed a high concentration of the multifunctional alpha 2-HS glycoprotein (fetuin) along with a multitude of protein factors involved in the development and maintenance of healthy human skin. Clinical investigation demonstrated significant amelioration of the clinical signs of intrinsic and extrinsic skin aging, findings that were confirmed by significant changes in skin morphology, filaggrin, aquaporin 3, and collagen I content.
Our data strongly support our hypothesis that cosmetic application of stem cell-derived skin lineage precursor secretions containing fetuin and growth factors beneficial for human skin development and maintenance, positively influence intrinsic and extrinsic aging.
J Drugs Dermatol. 2016;15(5):583-598.
Patrick Micheels MD,a Didier Sarazin MD,b Christian Tran MD,c and Denis Salomon MDd
BACKGROUND: The mechanical, rheological, and pharmacological properties of hyaluronic acid (HA) gels differ by their proprietary crosslinking technologies.
OBJECTIVE: To examine the different properties of a range of HA gels using simple and easily reproducible laboratory tests to better understand their suitability for particular indications.
METHODS AND MATERIALS: Hyaluronic acid gels produced by one of 7 different crosslinking technologies were subjected to tests for cohesivity, resistance to stretch, and microscopic examination. These 7 gels were: non-animal stabilized HA (NASHA® [Restylane®]), 3D Matrix (Surgiderm® 24 XP), cohesive polydensified matrix (CPM® [Belotero® Balance]), interpenetrating network-like (IPN-like [Stylage® M]), Vycross® (Juvéderm Volbella®), optimal balance technology (OBT® [Emervel Classic]), and resilient HA (RHA® [Teosyal Global Action]).
RESULTS: Cohesivity varied for the 7 gels, with NASHA being the least cohesive and CPM the most cohesive. The remaining gels could be described as partially cohesive. The resistance to stretch test confirmed the cohesivity findings, with CPM having the greatest resistance. Light microscopy of the 7 gels revealed HA particles of varying size and distribution. CPM was the only gel to have no particles visible at a microscopic level.
CONCLUSION: Hyaluronic acid gels are produced with a range of different crosslinking technologies. Simple laboratory tests show how these can influence a gel’s behavior, and can help physicians select the optimal product for a specific treatment indication.
Versions of this paper have been previously published in French and in Dutch in the Belgian journal Dermatologie Actualité. Micheels P, Sarazin D, Tran C, Salomon D. Un gel d’acide hyaluronique est-il semblable à son concurrent? Derm-Actu. 2015;14:38-43.
J Drugs Dermatol. 2016;15(5):600-606.
Leslie Baumann MDa and Brian Zelickson MDb
BACKGROUND: A novel device using micro-focused ultrasound with high-resolution ultrasound visualization (MFU-V) produces non-invasive lifting and tightening of lax skin on the face and neck when treatment is delivered at a single focal depth (Ulthera® System; Ulthera, Inc., Mesa, AZ).
OBJECTIVE: The following study was performed to test the hypothesis that customized application of MFU-V at two focal depths will produce clinical results that are superior to treatment at a single focal depth.
METHODS AND MATERIALS: Adult subjects (N=71) with skin laxity in the lower face and neck were enrolled; 64 met all entrance criteria and received treatment. On the basis of physical and anatomical characteristics, patients were assigned in nonrandomized fashion to one of three treatment groups to undergo treatment on the submental, submandibular, lower neck, and platysmal areas with MFU-V at single or dual depths.
RESULTS: Among evaluable subjects (N=64), investigator-assessment and subject-self-assessment demonstrated improved aesthetic changes at 60, 90, and 180 days after treatment. Overall, subjects that received MFU-V at two focal depths to the entire treatment area achieved slightly greater aesthetic improvement than subjects receiving MFU-V at single focal depths. There were no unexpected adverse events.
CONCLUSION: Applying treatment with MFU-V at two focal depths may provide improved aesthetic results in some subjects.
J Drugs Dermatol. 2016;15(5):607-614.
Mario A. Trelles MD PhD,a,* Patricia Almudever PhD,b,* Justo M. Alcolea MD,a
Julio Cortijo PhD,b Gabriel Serrano MD,c Inmaculada Expósito MD,c Josefina Royo MD,d
and Franck Marie Leclère MD PhDe
BACKGROUND: Photothermolysis of unwanted hair depends on the presence of melanin in the hair follicle as the chromophore, but is not effective in patients with non-pigmented, melanin-sparse hair shafts and follicles. This split-scalp, double-blind study was to monitor the efficacy of melanin bound in nanosomes to inject exogenous melanin into the hair follicles thus potentiating successful photothermolysis.
MATERIAL AND METHODS: Twelve patients, phototypes II-III, with white or very fair hair, were treated with a compound containing melanin encapsulated in nanosomes (Melaser®) together with a fluorescent marker. Two equal 6 cm² areas were marked on each side of the occiput of the subjects. The compound was applied to a randomly selected experimental side on each patient (area A), and a saline solution applied in the same manner to the contralateral control side (area B). Penetration of the melanin into the hair follicle was assessed using optical and fluorescence microscopy. Also, condition of hair structure was checked in vivo after standard laser settings used for epilation.
RESULTS: A slight transient erythema was observed in those areas where the compound was applied with some perifollicular edema. No such effects were noticed in those areas where saline solution was applied. No persistent complications such as scarring, hypo- or hyperpigmentation were observed in any of the experimental or control areas. Under fluorescence microscopy, the hair structures in the areas to which the compound had been applied showed a clear melanin deposit confirmed by the immunofluorescence intensity, which was highest at 2 hours after application. By optical microscopy, external melanin was deposited in hair follicles. Tests with standard settings for epilation were efficacious in damaging melanin-marked white hair.
CONCLUSION: This study strongly suggests the safety and efficacy of the application of nanosomes encapsulating melanin for the introduction of melanin into hair follicles. Changes noticed in the hair structure compromising its viability indicated potential application of this external melanin marker for white hair photoepilation.
J Drugs Dermatol. 2016;15(5):615-625.
Boni E. Elewski MD,a Aditya K. Gupta MD PhD FRCPC,b Ted Rosen MD,c Bryan D. Caldwell DPM,d David M. Pariser MD,e Leon H. Kircik MD,f Neal Bhatia MD,g and Antonella Tosti MDh
BACKGROUND: There is no general agreement as to what constitutes cure or treatment success in onychomycosis. Regulatory guidelines differ in the United States and Europe, and outcomes reported in clinical trials do not consistently report secondary endpoints.
METHODS: We reviewed definitions of onychomycosis cure to develop a less stringent and more practical approach to assess improvement and treatment success.
RESULTS: Complete cure (totally clear nail and mycologic cure) remains an important regulatory standard. Mycologic cure (negative fungal culture and negative potassium hydroxide) is the only consistently reported outcome in clinical trials, however the potential for discrepancies between microscopy and culture can be problematic. We propose a more practical approach to assessing improvement in infected nails that relies on both physician and patient input in a similar fashion to other skin diseases.
CONCLUSIONS: Treatment success should be based on both physician and patient assessment of improvement in the affected toenails and negative fungal culture.
J Drugs Dermatol. 2016;15(5):626-632.
Adam J. Friedman MD FAAD,a Erika C. von Grote PhD,b Matthew H. Meckfessel PhDb
Urea is an important hygroscopic component of the epidermis, where it participates in the maintenance of skin hydration as part of the skin’s source of natural moisturizing factor (NMF) in the outer most layers. Xerotic skin, which is frequently characterized as NMF-deficient, is a unifying trait of dermatoses such as atopic dermatitis (AD), psoriasis, and ichthyosis vulgaris. The reduced hygroscopic potential of pathologically dry skin leads to unregulated transepidermal water loss (TEWL), epidermal hyperproliferation, and inhibited desquamation; all which clinically translate to hyperkeratotic and possibly pruritic skin. Common underlying etiologies link these dermatoses to aberrant expression of genes encoding epidermal structural and catalytic proteins. Intervention of dry skin pathologies with topical moisturizer formulations is a foundational management strategy. For over a century urea-containing formulations have been used in a concentration-dependent manner to restore skin hydration, thin hyperkeratosis, debride dystrophic nails, and enhance topical drug penetration. Recently, urea’s role in skin hydration and repair has expanded to include regulation of epidermal genes necessary for proper barrier function. Taken together, urea’s versatility in topical formulations and broad range of therapeutic mechanism highlights its utility to clinicians and benefit to patients.
J Drugs Dermatol. 2016;15(5):633-639.
Jacqueline E. Greb BA MS4,a Joseph Merola MD MMSC,b Amit Garg MD,c John Latella, Leah Howard JD,d Nayan Acharya MBBS MRCP MFPM, and Alice B. Gottlieb MD PhDa
A collaborative exchange of ideas occurred at The Psoriatic Disease Payer Advisory Panel sponsored by International Dermatology Outcomes Measures (IDEOM) and The National Psoriasis Foundation (NPF) in January, 2016. Patient, provider, payer, pharmaceutical industry, IDEOM board member, and NPF leader representatives shared perspectives to address the unmet needs in the treatment of psoriatic patients. The payers who play a crucial role in controlling treatment access and improving patient outcomes played a pivotal role in the discussion. Progress made during the Payer Advisory Panel will ultimately advance psoriatic initiatives and help to address the persistent challenges of all vested stakeholders.
J Drugs Dermatol. 2016;15(5):641-644.