Divya Sharma BS,a Mary-Margaret Kober MD,b and Whitney P. Bowe MDc
The body of evidence demonstrating the beneficial effects of probiotics on the skin continues to grow in the published literature. Insights into their effects at the molecular level, in animal models, and in human clinical trials build the case for their role in slowing the skin manifestations of both intrinsic and extrinsic aging. The reports reviewed in this manuscript demonstrate that probiotics can restore acidic skin pH, alleviate oxidative stress, attenuate photoaging, improve skin barrier function, and enhance hair quality.
J Drugs Dermatol. 2016;15(1):9-12.
Jill S. Waibel MD,a Ashley Rudnick,a Carlos Nousari MD,b and Dhaval G. Bhanusali MDc
BACKGROUND: Topical drug delivery is the foundation of all dermatological therapy. Laser-assisted drug delivery
(LAD) using fractional ablative laser is an evolving modality that may allow for a greater precise depth of penetration
by existing topical medications, as well as more efficient transcutaneous delivery of large drug molecules. Additional
studies need to be performed using energy-driven methods that may enhance drug delivery in a synergistic manner. Processes such as iontophoresis, electroporation, sonophoresis, and the use of photomechanical waves aid in penetration. This study evaluated in vivo if there is increased efficacy of fractional CO2 ablative laser with immediate acoustic pressure wave device.
METHODS: Five patients were treated and biopsied at 4 treatment sites: 1) topically applied aminolevulinic acid (ALA) alone; 2) fractional ablative CO2 laser and topical ALA alone; 3) fractional ablative CO2 laser and transdermal acoustic pressure wave device delivery system; and 4) topical ALA with transdermal delivery system. The comparison of the difference in the magnitude
of diffusion with both lateral spread of ALA and depth diffusion of ALA was measured by fluorescence microscopy.
RESULTS: For fractional ablative CO2 laser, ALA, and transdermal acoustic pressure wave device, the protoporphyrin
IX lateral fluorescence was 0.024 mm on average vs 0.0084 mm for fractional ablative CO2 laser
and ALA alone. The diffusion for the acoustic pressure wave device was an order of magnitude greater.
CONCLUSION: We found that our combined approach of fractional ablative CO2 laser paired with the transdermal acoustic pressure wave device increased the depth of penetration of ALA.
J Drugs Dermatol. 2016;15(1):14-21.
Noelani Gonzalez MD and Maritza Perez MD
As Dermatologists caring for patients with hyperpigmentation problems, we are always looking for more alternative therapies. Hydroquinone (HQ) is still the standard of care. However, traditional depigmenting agents such as HQ and corticosteroids, although highly effective, can raise safety concerns including exogenous ochronosis, atrophy, carcinogenesis and local and systemic untoward effects with long term use. Therefore, we need to investigate non-prescription natural alternatives. This manuscript presents many of the natural ingredients found in cosmeceuticals for the treatment of hyperpigmentation and their mechanisms of action. It will also describe the melanocyte activation pathways and how each of these ingredients interferes with it.
J Drugs Dermatol. 2016;15(1):26-34.
Hilary Reich MD,a,b Irmina Wallander BA,a Lacie Schulte MS BA,a Molly Goodier BS,a and Brian Zelickson MDa
SUMMARY BACKGROUND: Many over the counter topical products claim to reverse the signs of cutaneous photo-damage. To date, the two most studied ingredients for improving the texture, tone, and pigmentation of the skin are topical retinoids and hydroquinone.1
OBJECTIVE: This split face study compares a mass market skincare regimen with a prescription skin care regimen for improvement in photo damaged skin.
METHODS: Twenty-seven subjects with moderate photo damaged facial skin were enrolled. Each subject was consented and assigned with the mass market anti-aging system (Treatment A) to one side of the face and the prescription anti-aging system (Treatment B or Treatment C) to the other side of the face. Treatment B contained 13 subjects whom did not use 0.025% Retinol cream. Treatment C contained 14 subjects who used a 0.025% Retinol Cream. Subjects had 4 visits over 12 weeks for digital photography and surveys. Photographs were evaluated by blinded physicians.
RESULTS: Physician objective analysis showed all three systems to have a statistically significant clinical improvement in photoaged skin seen in as little as 4 weeks of use. Participant’s surveys rated the mass market system higher than both of the professional systems for visible skin changes, ease of use, and likelihood to recommend to a friend. Twelve of twenty-seven subjects preferred the mass market system for overall improvement while twelve thought each system gave the same improvement.
CONCLUSION: This study demonstrates that a mass marketed skin care system can give similar clinical improvements in photo-aged skin as a professionally dispensed prescription system and the majority of participants preferred the mass-marketed system.
J Drugs Dermatol. 2016;15(1):37-44.
Joel Schlessinger,a MD, Barbara Green RPh MS,b Brenda L. Edison BA,b Lynn Murphy MA,b and Yamini Sabherwal PhDb
BACKGROUND: Noninvasive antiaging neck and décolletage treatments are highly sought after by aging patients. A topical cosmetic antiaging cream was formulated with skin matrix building and smoothing ingredients to help reverse visible signs of aging on the neck and décolletage, including laxity, crepiness, deep lines, and hyperpigmentation.
OBJECTIVE: A clinical study was conducted to evaluate the efficacy and safety of the antiaging neck/décolletage cream over a 16-week treatment period.
METHOD: Caucasian women with moderate texture (including wrinkles, fine lines, laxity, and/or crepiness) on the neck and hyperpigmentation on the décolletage used the test cream for 16 weeks. At weeks 0, 8, 12 and 16, the dermatologist investigator graded neck texture, décolletage texture and décolletage pigmentation using a 0-5 scale, and irritation/tolerability using a 0-4 scale. Subjects were photographed and provided self-assessment of their aging parameters as well as product tolerability. Chromameter measurements were collected in triplicate on the chest at weeks 0, 8, and 16 to quantitatively and objectively assess pigmentation.
RESULTS: Forty-two women completed the study. All dermatologist-graded aging parameters were significantly improved at each time point, P<0.001. Chromameter measurements demonstrated significant improvements in brightness (L*) and redness (a*), P<0.05. Self-assessed aging parameters were significantly improved on the décolletage and neck, P<0.05. Digital photography demonstrated obvious antiaging effects including improved texture of neck and décolletage areas, reduced appearance of lines and wrinkles, reduced mottled hyperpigmentation, and a more youthful, firm appearance. The test cream was well-tolerated with no significant changes in irritation parameters throughout the study.
CONCLUSION: The antiaging neck/décolletage cream delivered significant firming and smoothing effects with reduced appearance of hyperpigmentation and can be considered an effective topical homecare treatment option for patients seeking rejuvenation of this challenging area.
J Drugs Dermatol. 2016;15(1):47-52.
BACKGROUND: Radiofrequency has long been successfully employed for medical and, more recently, aesthetic indications due to its ability to cause tissue contraction by thermal induction of neocollagenesis and the subsequent wound healing cascade, leading to collagen
remodeling and a tightening effect. Percutaneous RF treatment provides therapeutically relevant thermal stimulation directly to the tissue target in a minimally invasive manner, which is therapeutically ideal because of limitations inherent in transcutaneous RF heating. A novel device combines percutaneous RF with thermistor-controlled temperature regulation and external tissue temperature monitoring, providing the ability to safely deliver RF energy.
METHODS: Percutaneous subdermal RF treatment was performed on 48 samples of abdominoplasty tissue; samples were marked to standardize measurement of surface area in the treatment zones, and a subdermal temperature target of 51°C was preprogrammed into the treatment device. The treatment cannula was inserted parallel to the dermal plane at four points with a single pass per insertion.
Surface area was then re-measured.
RESULTS: Approximate average reduction in surface area was 91.23±19.33 mm2, ranging between 124.45 mm2 and 35.39 mm2 (median 96.83 mm2). Results were statistically significant (P<0.0001). Statistical analysis via analysis of variance (ANOVA) plus Tukey post-hoc testing revealed no statistically significant difference between the sides in all comparisons, demonstrating symmetry in contracture.
CONCLUSION: Percutaneous subdermal monopolar RF creates dramatic, immediate tissue contraction in vitro and is a viable technology for tissue tightening.
J Drugs Dermatol. 2016;15(1):55-58.
Brian P. Hibler BS, Jonathan Schwitzer MD, and Anthony M. Rossi MD
BACKGROUND: Detecting clinically meaningful change from the patients' perspective is critical to evaluating a successful cosmetic procedure. FACE-Q is a patient-reported outcome instrument for use in patients undergoing cosmetic procedures.
OBJECTIVE: We sought to determine the impact of laser resurfacing and injectable treatment (neurotoxin or fillers) on patient perceived improvement in facial appearance.
METHODS and MATERIALS: Patients were asked to complete FACE-Q scales (Satisfaction with Facial Appearance, Satisfaction with Facial Skin, and Appraisal of Facial Lines) at their pre-procedure consultation and/or at post-procedural follow-up. Item means (range 1-4) and Rasch transformed scores (range 0-100) were compared pre to post-procedure using two sample t-tests. Higher FACE-Q scores indicated greater satisfaction.
RESULTS: Overall, patients experienced a statistically significant improvement in all three scales pre- to post-procedure (P <0.05). Sub-group analysis showed statistically significant improvement in Satisfaction with Facial Appearance and Satisfaction with Facial Skin for both the laser resurfacing group and injectables group with moderate effect sizes. Improvement on Appraisal of Facial Lines trended toward improvement but did not reach statistical significance.
CONCLUSION: Our results support the ability to directly measure and quantify meaningful improvement in appearance among facial cosmetic dermatology patients using FACE-Q scales. Reporting this data is important, as this is the first step towards evidence-based cosmetic procedures in dermatology.
J Drugs Dermatol. 2016;15(1):62-67.
Yan Wu MD PhD,a Jinhua Xu PhD,b Yi Jia MD MSc PhD,c and Diane K. Murphy MBAd
BACKGROUND: The hyaluronic acid (HA) dermal filler, Juvéderm® Ultra, which employs Hylacross® technology, produces a gel with a smooth consistency and has demonstrated effectiveness in correcting nasolabial folds (NLFs) in Caucasian populations.
OBJECTIVE: To evaluate the safety and effectiveness of Juvéderm Ultra vs Restylane® for the correction of moderate NLFs in Chinese subjects.
METHODS: In this double-blind randomized study, adult Chinese subjects with moderate NLFs received Juvéderm Ultra (24 mg/mL) in 1 NLF and Restylane injectable gel (20 mg/mL) in the other NLF. NLFs were evaluated using the validated 5-point photonumeric Allergan NLF Severity Scale (NLFSS); scores ranged from 0 (“no wrinkle”) to 4 (“very deep wrinkle”). Response was defined as ≥1-point improvement at 6 months. Investigator-assessed responder rate (primary outcome), NLF mean improvement, and subject-assessed responder rate and preference were assessed.
RESULTS: Among the 104 subjects who completed the study, median initial volumes (mL) were 0.8 (range, 0.2–1.4) for Juvéderm Ultra and 0.8 (0.3–1.5) for Restylane; median touch-up volumes were 0.3 (0.1–0.5) and 0.3 (0.1–0.5), respectively. At 6 months, investigator-assessed responder rates were 87.3% for both products, indicating that Juvéderm Ultra was noninferior to Restylane; mean improvement
in NLFSS scores from baseline was 1.0 for both products. At 6 months, Juvéderm Ultra and Restylane subject-assessed responder
rates were 86.3% and 79.4%, respectively, and mean improvement in NLFSS scores from baseline was 1.2 and 1.0, respectively. Among subjects who expressed a preference, 57.9% preferred Juvéderm Ultra. For both products, the most commonly reported treatment
site responses were swelling, firmness, and tenderness; treatment site responses were generally mild or moderate in severity. Juvéderm Ultra had fewer severe responses than Restylane.
CONCLUSIONS: Juvéderm Ultra is noninferior to Restylane and is a safe and effective treatment for correcting moderate NLFs in Chinese subjects.
J Drugs Dermatol. 2016;15(1):70-76.
Linda Stein Gold MD,a Jerry Tan MD,b and Leon Kircik MDc
BACKGROUND: Outcomes for success in acne interventional trials include statistically significant differences from baseline between treatment arms in lesion counts (comedonal, inflammatory and/or total) and in thresholds of categorical improvement in investigator global assessments (IGA).
OBJECTIVES: We evaluated differences in outcome measures and definition of success in acne trials; and their impact on FDA approval and indications for acne medications.
METHODS: Review of acne clinical trial literature, prescribing information and regulatory guidelines for currently approved acne medications in the United States.
RESULTS: Numerous IGA scales exist with variations in specific categorical definitions. There are also differences in definitions of global success. Outcome success may not be accurately translated into corresponding terminology for indications.
CONCLUSIONS: Variability in IGA scales and definitions of success confound comparison of trial results for acne treatments. Harmonization and standardization of these factors will facilitate meta-analytics and treatment selection in patient care. Outcome measure success has not consistently been incorporated into acne medication indications.
J Drugs Dermatol. 2016;15(1):79-86.
Tracey C. Vlahovic DPM,a Dina Coronado BS,b Sanjay Chanda PhD,b Tejal Merchant MPharm,b and Lee T. Zane MDb
INTRODUCTION: Patients with onychomycosis may mask infected nails with polish. Tavaborole topical solution, 5% is a boron-based, small-molecule pharmaceutical approved for the treatment of toenail onychomycosis caused by Trichophyton rubrum and Trichophyton mentagrophytes; efinaconazole topical solution, 10% is approved for the same indication. Nail polish appearance after application of tavaborole (dropper) or efinaconazole (brush); respective applicator appearance; presence of color transfer from respective applicators; and color transfer to remaining solutions after dosing of polished nails were evaluated.
METHODS: Twelve ex vivo human cadaver fingernails were cleaned, polished with two coats of L’Oréal® Nail Color, Devil Wears Red #420, and mounted on floral foam. Nails were treated with tavaborole or efinaconazole solutions once daily for 7 days. Dropper and brush applicators were applied to white watercolor paper immediately after dosing to evaluate color transfer from polished nails. On day 7, remaining solutions were transferred to clear glass vials to evaluate color transfer from applicators to solutions. Nails, applicators, and papers were photographed daily following application; remaining solutions were photographed after 7 days of dosing.
RESULTS: Tavaborole-treated polished nails showed no polish discoloration, and tavaborole applicators did not change in appearance during treatment. No color transfer from polished nails was evident to applicator, paper, or remaining solution. Efinaconazole-treated polished nails showed substantial polish changes after the first day of treatment, with polish appearance and discoloration progressively
worsening over 7 days of treatment. Color transfer from nails was evident to applicator, paper, and remaining solution.
CONCLUSIONS: Daily dropper application of tavaborole to ex vivo polished nails did not alter polish appearance. Brush application of efinaconazole
produced visible changes in polish appearance and color transfer to applicators, paper, and remaining solution. Tavaborole topical solution, 5% may not alter nail polish appearance; the impact of nail polish on tavaborole clinical efficacy has not been evaluated.
J Drugs Dermatol. 2016;15(1):89-94.
Amanda A. Cyrulnik MD,a,b,* Aron J. Gewirtzman MD,a,c,* Karin Blecher Paz MD,a Jaimie B. Glick MD,b
Anika K. Anam MD,b Daniel A. Carrasco MD,c Alan R. Shalita MD,b and Steven R. Cohen MD MPHa
BACKGROUND: The observance during acne follow-ups that information stored within iPLEDGE was discordant with medical charts prompted this study.
OBJECTIVE: To evaluate the information acquired and stored within iPLEDGE as it compares to medical charts with a goal of assessing the efficacy of iPLEDGE as a database.
METHODS: This is a multicenter retrospective chart review analyzing congruence and discrepancies between medical chart documentation and iPLEDGE data for all patients who received at least a single dose of isotretinoin from the primary investigators between January 2006 and November 2010.
RESULTS: A total of 357 charts were analyzed. Overall congruence between medical chart documentation and iPLEDGE data was observed in only 73.1% of cases. The discrepancy (N=96) was due to a missed dose (prescription recorded in chart but not in iPLEDGE) in 81.4% of cases, or an addition (medication dispensed per iPLEDGE without corresponding chart documentation) in the remainder of cases. Of note, several charts had multiple discrepancies (N=249 total discrepancies).
LIMITATIONS: Retrospective chart review study.
CONCLUSION: Given the large percentage of discordant data, our findings question the efficacy of the iPLEDGE system, which is designed to monitor every dispensed isotretinoin dose.
J Drugs Dermatol. 2016;15(1):97-102.
Hiroyasu Koga PhD,a Yasuko Nanjoh,a Tetsuo Toga PhD,a Radhakrishnan Pillai PhD,b William Jo PhD,b and Ryoji Tsuboi PhDc
OBJECTIVE: To compare drug concentrations in the stratum corneum following daily application of luliconazole and terbinafine cream in a guinea pig tinea pedis model.
METHODS: Luliconazole 1% cream or terbinafine 1% cream were topically applied once daily to hind limbs of guinea pigs for 14 days. Drug concentration in stratum corneum of plantar skin was measured by HPLC-UV on days 1, 3, 7, 10, and 14. Separately, creams were applied daily for 5 days to the hind limbs of guinea pigs and skin drug release determined. In addition, drug retention in the stratum corneum was assessed by infecting guinea pigs with Trichophyton mentagrophytes, 14 and 21 days after a single application of luliconazole or terbinafine creams.
RESULTS: Luliconazole stratum corneum concentrations were higher than those of terbinafine throughout the study. Concentrations of luliconazole and terbinafine were 71.6μg/g and 36.6μg/g, respectively, after a single application (P<.05), reaching steady state after 10 days. Cumulative release of luliconazole from the stratum corneum was 4.5 times greater than with terbinafine. Unlike terbinafine, no fungal invasion of the stratum corneum was seen 14 days post-treatment with luliconazole.
CONCLUSIONS: Drug concentrations of luliconazole in the stratum corneum and subsequent release are greater than those achieved with terbinafine and may contribute to clinical efficacy. Luliconazole may also provide greater protection against disease recurrence.
J Drugs Dermatol. 2016;15(1):104-108.