This supplement to the Journal of Drugs in Dermatology was made possible through an educational grant provided by SkinMedica.

The Future is Now With SkinMedica’s Lytera™

The gold standard for the treatment of abnormal melanin accumulation has long been 4% hydroquinone, but, given the proliferating safety concerns posed by hydroquinone, the search for novel skin brighteners has been ongoing. Several studies have demonstrated that the future for skin brighteners is now, because of the skin brightening efficacy of SkinMedica’s Lytera™, a hydroquinone-free skin-brightening complex. Lytera includes a series of formulations that utilize a multi-modal treatment approach, and it is as effective as hydroquinone over the course of 24 weeks for the treatment of facial hyperpigmentation without the concomitant toxicities of the latter.

Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface.
SkinMedica’s HA⁵ Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles.
Pre-clinical studies demonstrated that HA⁵ induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA⁵ application. Initial clinical studies showed that within 15 minutes of application, HA⁵ instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA⁵ (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies present in HA⁵ promotes restoration of endogenous epidermal HA while delivering instant smoothing effects.

J Drugs Dermatol. 2016;15(1 Suppl 2):s24-s37.

BACKGROUND: Photoaged skin, characterized by mottled, irregular areas of pigmentation, is a common skin condition that is often difficult to treat. The areas of hypermelanosis are an aesthetic concern to subjects and may lead to social distress and quality of life issues. There are many commercial hyperpigmentation regimens marketed to lighten dark spots and improve overall skin dyschromia. However, data to support efficacy of such kits are often lacking.
OBJECTIVE: This investigator-blinded, randomized trial was conducted to compare a new hydroquinone (HQ)-free hyperpigmentation regimen against a leading HQ-based hyperpigmentation regimen for the treatment of facial hyperpigmentation and photoaging.
METHODS: Subjects with mottled pigmentation and photodamaged facial skin were randomized to treatment with either the new 4-product (HQ-free) SkinMedica® Hyperpigmentation System (SKM; SkinMedica, an Allergan Company, Carlsbad, CA) kit or the 7-product (HQ-containing) Obagi Nu-Derm System (OMP; Obagi Medical Products, Long Beach, CA) kit. Subjects were evaluated by a blinded investigator for clinical efficacy and tolerability using grading scales at baseline and at weeks 4, 8, and 12. Standardized digital photographs were taken at baseline and week 12. Self-assessment questionnaires were completed at week 12.
RESULTS: Thirty-six female subjects (16: SKM; 20: OMP) completed the 12-week comparative study. Both hyperpigmentation regimens significantly reduced Overall Hyperpigmentation, Mottled Pigmentation Area and Severity Index (MoPASI), global photoaging, and sallowness at week 12 compared to baseline. Significant reductions in tactile roughness were seen with the OMP regimen at week 12. In these investigator-blinded assessments, there were no significant differences between treatment groups, nor was there a difference in global response to treatment. Investigator assessments of tolerability showed mean scores were mild or below for all parameters with both treatment regimens.
CONCLUSION: A new 4-product (HQ-free) regimen was shown to be as effective and tolerable as a 7-product (HQ-based) regimen in reducing facial hyperpigmentation and photoaging in females with mottled pigmentation and photodamaged facial skin.

J Drugs Dermatol. 2013;12(3 suppl 1):s32-s37.

For more than a century, solar radiation has been known to contribute significantly to the extrinsic aging of skin. Until recently, this was almost exclusively attributed to the photodamage caused by ultraviolet (UV) light. However, a growing body of evidence now indicates that both infrared (IR) and visible light may also contribute to extrinsic skin aging. Infrared radiation, comprised of IR-A, IR-B, and IR-C, accounts for 54.3% of the total solar radiation reaching the skin. Studies have shown that IR radiation is also responsible for skin aging. Thus, IR-A radiation regulates hundreds of genes in skin, with roles in extracellular matrix (ECM) homeostasis regulation, apoptosis, cell growth, and stress responses. IR-B and IR-C radiation are primarily responsible for the increase in skin temperature associated with solar exposure, and are implicated in heat-related skin destruction of collagen and elastin, which is characterized by an increase in the expression of matrix metalloproteinases (MMPs). The contribution of visible light to photoaging is less well understood; however, some preliminary indication associates visible light with the upregulation of MMPs’ expression, DNA damage, and keratinocyte proliferation. Interestingly, the common denominator that links skin damage to the different solar wavelengths is the enhanced production of reactive molecule species (RMS) and therewith increased oxidative stress. SkinMedica® Total Defense + Repair (TD+R; SkinMedica Inc., an Allergan company, Irvine, CA) is a “superscreen,” which combines broad spectrum UV protection with a unique blend of antioxidants (SOL-IR Advanced Antioxidant Complex™) that provide protection from IR radiation while promoting skin repair. Preclinical studies have indicated that TD+R SPF34 prevents the formation of UV-induced sunburn cells and cyclobutane pyrimidine dimers while preserving or improving the expression of ECM genes. In addition, it prevents IR-A-triggered fragmentation of elastin fibers and expression of MMP-1. Initial clinical studies indicate that TDR+R SPF34 reduces the increase in surface temperature seen with IR radiation. A significant improvement in the appearance of lines and wrinkles was reported as early as week 2 in patients using TDR+R SPF34. In summary, we observed that the unique blend of antioxidants present in TD+R acts in harmony with SPF active ingredients, expanding solar protection beyond UV radiation and counterbalancing the deleterious effects of free radicals on skin cells by promoting endogenous repair.

J Drugs Dermatol. 2015;14(suppl 7):s3-s11.

A recent and growing body of evidence now indicates that, along with ultraviolet (UV) light, both infrared (IR) and visible light from solar radiation may also contribute to extrinsic skin aging.

Currently, sunscreens play an important role in maintaining the health of the skin by providing “broad spectrum” protection against the harmful effects of UV radiation. However, this does not protect human skin from 94.2% of solar radiation (comprised of visible and IR lights), and nor does it prevent heat accumulation damage. Thus, none of the commercially-available sunscreens is able to block 100% of UV radiation.

Inspired by the need to provide patients with a more comprehensive solar protection, SkinMedica® has created Total Defense + Repair (TD+R), which combines broad spectrum UV protection with a unique blend of antioxidants (SOL-IR Advanced Antioxidant Complex^TM) that provide protection from IR radiation while promoting skin repair. These antioxidants are the product of scientific research and breakthrough technology, providing the next generation of multifunctional skin care products.

There are numerous common skin disorders involving hyperpigmentation, including solar lentigines, postinflammatory hyperpigmentation, melasma, freckles, and dyschromia from photoaging. While these conditions are of an aesthetic nature, there is great interest in newer, safer, and more effective treatment modalities. Topical hydroquinone (HQ) has been the gold standard of skin lighteners for many years. However, regulatory authorities around the world are now questioning its safety. A randomized, double-blind, half-face study was conducted in females having moderate to severe facial hyperpigmentation to assess the efficacy and tolerability of 3 new skin brightener formulations containing SMA-432, a prostaglandin E2 inhibitor, compared with 4% HQ. Each subject was assigned 2 of the 4 test materials and was instructed to apply the product on the assigned side of the face twice daily for 12 weeks. Evaluation visits were conducted at baseline and at 4, 8, and 12 weeks. At each visit, subjects were evaluated by a blinded investigator for clinical efficacy and tolerability using grading scales. Standardized digital photography and Chroma Meter assessments were also taken. Self-assessment questionnaires were completed at weeks 4, 8, and 12. Sixty-eight Caucasian subjects (136 half faces) completed the study. All test materials significantly reduced Overall Hyperpigmentation and improved the Investigator's Global Hyperpigmentation Improvement rating at weeks 4, 8, and 12 compared with baseline. SMA-432 exhibited a dose-dependent improvement in hyperpigmentation. There were no major tolerability issues with any of the test materials. Self-assessments were generally favorable for all test materials. At the completion of the trial, subjects rated one of the tested multimodality brightener compositions as the most favorable product and 4% HQ as the least favorable. This study demonstrated that the new non-HQ-containing skin brightener formulations were as effective and equally well tolerated as the gold standard, 4% HQ, in females with facial hyperpigmentation.

J Drugs Dermatol. 2012;11(12):1478-1482.

Background: Hyperpigmentary disorders are common aesthetic skin conditions that can be very concerning to patients and both challenging and time-consuming for the physician to treat. Several companies commercialize hyperpigmentation kits for the lightening of dark spots and improvement of overall skin dyschromia. Unfortunately, clinical data from controlled studies to support the efficacy and tolerability of these kits are typically lacking
Objective: This investigator-blinded, randomized trial was undertaken to compare two commercial hyperpigmentation systems (kits) used for the treatment of facial hyperpigmentation and photo-aging.
Methods: Female subjects with at least mild facial hyperpigmentation and photo-aging were randomized to treatment with either the four product SkinMedica (SKM) regimen or the 7-product Obagi (OMP) regimen. Evaluations were conducted at baseline, 4, 8, and 12 weeks. Subjects were evaluated by the blinded investigator for clinical efficacy and tolerability using grading scales. Standardized digital photographs were taken at baseline and week 12. Self-assessment questionnaires were completed at week 12. Thirty-five females (SKM=17, OMP=18) completed the 12-week study.
Results: Both treatment regimens showed a significant improvement at week 12 (compared to baseline) for Overall Hyperpigmentation, Global Photo-aging and Sallowness. At week 12, there was no significant difference between treatment groups in Global Response to Treatment. Tolerability was good for both regimens based on investigator assessments. Subject self-assessments showed no consistent differences in efficacy between the two regimens. Similarly, there was no significant difference in subject satisfaction or intent to continue use between the two regimens.
Conclusion: This clinical study demonstrated that both systems were equally effective at reducing hyperpigmentation and global photo-aging in females with mottled pigmentation and photodamaged facial skin.

J Drugs Dermatol. 2012;11(8):964-968.

The combination of in-office procedures such as chemical peels with topical maintenance therapies has been shown to provide greater efficacy than either treatment by itself in the management of melasma. A series of 3 case studies were conducted to evaluate the efficacy and tolerability of one superficial chemical peel (containing a proprietary blend of resorcinol, lactic acid, salicylic acid, and retinol) combined with a topical multimodal, hydroquinone-free skin brightener as postpeel maintenance therapy. Patients presented with moderate to severe facial hyperpigmentation. At baseline, subjects received the superficial chemical peel treatment followed by a standard postpeel skin care regimen (cleanser, moisturizer, and SPF 30+ sunscreen). Approximately 1 week after the peel procedure, subjects initiated twice-daily application of the skin brightener. Subjects were then evaluated for Global Improvement in Hyperpigmentation by the investigator for up to 7 weeks postpeel. Standardized digital photographs of the subjects facial skin and in vivo reflectance confocal microscopy (RCM) images were taken of a target hyperpigmented lesion at baseline and at follow-up. Standardized photography and in vivo RCM images at baseline and at postpeel show the improvements observed by the investigator. Results from these case studies suggest that the combination of a superficial chemical peel with topical maintenance and the multimodal skin brightener may provide an effective treatment approach for subjects with moderate to severe facial hyperpigmentation.

J Drugs Dermatol. 2013;12(3 suppl 1):s38-s41.

Melasma is a chronic, relapsing disorder that can be disfiguring and can have adverse effects on quality of life. Recently, a unique hydroquinone-free topical product addressing multiple pathways involved in pigmentation was shown to have similar efficacy and equally well tolerated as 4% hydroquinone in females with facial hyperpigmentation. The goal herein was to further assess the efficacy and tolerability of this new multimodality product for the control of moderate melasma in skin of color.

Six female subjects with Fitzpatrick skin types IV-V in good general health between the ages of 46 and 63 years with moderate epidermal facial melasma are presented herein. Subjects applied the skin brightener twice daily, morning and evening, and returned to the clinic at weeks 4, 8, and 12. By week 12, Investigator Overall Hyperpigmentation scores and MASI scores improved by an average of 22% and 38% from baseline, respectively. Additionally, 100% of subjects showed at least a 25% increase in Global Improvement at week 12. The skin brightener was well tolerated with no reports of erythema, edema, scaling, burning/stinging, or itching.

Results from these case studies suggest that this multimodality skin brightener may provide an alternative treatment to hydroquinone for moderate melasma in skin of color. However additional clinical studies would be needed.

J Drugs Dermatol. 2014;13(3):364-366.

To assess the treatment of hyperpigmentation, a series of 5 case studies were conducted to evaluate the efficacy and tolerability of a novel hydroquinone-free treatment regimen combining a multimodal skin brightener with a cleanser, high strength retinol product and sunscreen SPF 30+. Patients presented with moderate to severe facial hyperpigmentation as determined by a score of 4 to 8 on the Overall Hyperpigmentation scale. Physician-graded Overall Hyperpigmentation, Global Improvement in Hyperpigmentation, and standardized photography were conducted at weeks 3, 6, and 12. At week 12, the majority of patients demonstrated Global Improvements in Hyperpigmentation of at least 50%, with at least a 2-grade reduction in Overall Hyperpigmentation scores, as assessed by the physician. Standardized photographs also support the physician and patient findings. Results from these case studies demonstrate that this unique 12-week treatment regimen can provide an effective and simple option for patients with facial hyperpigmentation.

J Drugs Dermatol. 2013;12(3 suppl 1):s42-s44.

Vitamin A and its derivatives (commonly termed retinoids) are widely used in topical anti-aging products. Certain retinoids such as retinol and its esters are available without a prescription, while others such as tretinoin are available only via prescription. A randomized, double-blind, controlled clinical study was conducted to compare the efficacy and tolerability of a tri-retinol 1.1% gradual release cream vs. tretinoin 0.025% cream in females with mild-to-moderate facial photodamage. Subjects applied the test product to the entire face in the evening after cleansing in a progressively increasing frequency starting twice weekly for the first week, followed by three times weekly during the second week and then daily as tolerated for the third week and beyond. Treatment was continued for a total of three months. Clinical evaluations and standardized digital photographs were performed at baseline and after four, eight, and 12 weeks of treatment. Self-assessment questionnaires were completed by the subjects at four, eight, and 12 weeks to assess perceived efficacy of the test products. Thirty-four subjects (16: tri-retinol and 18: tretinoin) completed the study. Both test products significantly improved signs of photodamage, including fine and coarse periocular wrinkles, skin firmness, skin tone, mottled pigmentation, tactile roughness, overall photodamage and global photodamage improvement. There were no significant differences in efficacy between the two products for these assessments. The adverse effects (which were graded as mild or less) were those typically seen with topical retinoids. Subjects reported >93 percent overall satisfaction with both products at weeks 8 and 12.

J Drugs Dermatol. 2012;11(1):64-69.

Acne therapies that are able to show efficacious treatment of acne lesions as well as to address the issues of oiliness and shine control may be particularly appropriate for the treatment of patients with acne vulgaris that is accompanied by oily skin and facial shine. The microsphere delivery system (MDS), a novel delivery technology for topical therapy, can be customized to optimize product attributes, including oil absorption. Clinical trials have clearly established the efficacy and tolerability of such MDS formulations in the treatment of acne. In addition, studies have shown that the use of products formulated with an MDS provides a more significant reduction in facial shine than non-MDS acne therapy, as well as a reduction in facial sebum accumulation relative to control. Future clinical research should aim to further delineate the effect of individual topical acne treatment formulations on oiliness and shine.

J Drugs Dermatol. 2013;12(11):1268-1270.

Retinol, has been shown to improve the appearance of photodamaged skin when applied topically, and is generally considered to be approximately ten times less potent than tretinoin. To assess this theory, three cosmetic formulations containing 0.25%, 0.5%, and 1.0% retinol were developed to correspond to the three commonly prescribed concentrations of tretinoin (0.025%, 0.05%, and 0.1%). A randomized, double-blind, split-face comparison study was conducted to compare the three concentrations retinol (Ret) including 0.25%, 0.5%, and 1.0%, against the respective three strengths of tretinoin (Tret) 0.025%, 0.05%, and 0.1% in subjects with moderate to severe facial photodamage. Subjects were randomized into three groups: Group 1 (Ret 0.25% vs. Tret 0.025%); Group 2 (Ret 0.5% vs. Tret 0.05%); and Group 3 (Ret 1.0% vs. Tret 0.1%). Within each group, subjects were randomized to apply Ret on one half of the face (left or right) and Tret on the other facial side, for a duration of twelve weeks. Clinical evaluations for efficacy and tolerability, as well as standardized digital photographs were conducted at baseline and at weeks 4, 8, and 12. Sixty-five subjects completed the twelve-week study (Group 1: n=24, Group 2: n=20, and Group 3: n=21). At week 12 in all treatment groups, both Ret and Tret produced statistically significant improvements from baseline in all efficacy parameters, including overall photodamage, fine lines/wrinkles, coarse lines/wrinkles, skin tone brightness, mottled pigmentation, and tactile roughness (all P<0.001). There were no significant differences in efficacy between Ret and Tret in these efficacy parameters. Results from this comparison study suggest that this sustained-release retinol complex containing multiple agents for optimal irritation control provides comparable improvements to tretinoin in the appearance of photodamage.

J Drugs Dermatol. 2015;14(1):24-30.

There are numerous common skin disorders involving hyperpigmentation, including solar lentigines, postinflammatory hyperpigmentation, melasma, freckles, and dyschromia from photoaging. While these conditions are of an aesthetic nature, there is great interest in newer, safer, and more effective treatment modalities. Topical hydroquinone (HQ) has been the gold standard of skin lighteners for many years. However, regulatory authorities around the world are now questioning its safety. A randomized, double-blind, half-face study was conducted in females with moderate to severe facial hyperpigmentation to assess the efficacy and tolerability of 3 new skin brightener formulations containing SMA-432, a prostaglandin E2 inhibitor, compared with 4% HQ. Each subject was assigned 2 of the 4 test materials and was instructed to apply the product on the assigned side of the face twice daily for 12 weeks. Evaluation visits were conducted at baseline and at 4, 8, and 12 weeks. At each visit, subjects were evaluated by a blinded investigator for clinical efficacy and tolerability using grading scales. Standardized digital photography and Chroma Meter assessments were also taken. Self-assessment questionnaires were completed at weeks 4, 8, and 12. Sixty-eight Caucasian subjects (136 half faces) completed the study. All test materials significantly reduced Overall Hyperpigmentation and improved the Investigator's Global Hyperpigmentation Improvement rating at weeks 4, 8, and 12 compared with baseline. SMA-432 exhibited a dose-dependent improvement in hyperpigmentation. There were no major tolerability issues with any of the test materials. Self-assessments were generally favorable for all test materials. At the completion of the trial, subjects rated one of the tested multimodality brightener compositions as the most favorable product and 4% HQ as the least favorable. This study demonstrated that the new non-HQ-containing skin brightener formulations were as effective and equally well tolerated as the gold standard, 4% HQ, in females with facial hyperpigmentation.

J Drugs Dermatol. 2013;12(3 suppl 1):s21-s26.

Objective: To assess the safety and efficacy of clobetasol propionate 0.05% emulsion formulation (EF) foam in subjects with mild-to-moderate chronic hand dermatitis.
Methods: This was a single-center, open-label pilot study of 30 adults with chronic hand dermatitis. Subjects were treated with clobetasol propionate 0.05% EF foam twice-daily and returned for assessment at day 8 and day 15. The primary efficacy endpoint was the proportion of subjects who achieved treatment success, defined as improvement of ≥1 grade in their chronic hand dermatitis as per the Investigator's Static Global Assessment (ISGA) from baseline to day 15. Safety and quality-of-life measures were also assessed.
Results: A minimum 1-grade improvement in the ISGA was achieved by 96.7 percent (29/30) of subjects at day 15, with 80 percent (24/30) of subjects achieving a score of 0 (clear) or 1 (almost clear). Clobetasol propionate 0.05% EF foam appeared to be safe and well-tolerated, with only four subjects experiencing treatment-related adverse events. No pattern of adverse event occurrence or predisposition could be delineated from this study.
Conclusion: Clobetasol propionate 0.05% EF foam appeared to be safe and effective for the treatment of chronic hand dermatitis.

J Drugs Dermatol. 2011;10(12):1398-1402.

BACKGROUND: Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of moderate to severe inflammatory facial acne vulgaris.
METHODS: This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥2 score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count.
RESULTS: A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo. The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne. Also, the study was not prospectively powered to show efficacy differences.
CONCLUSION: Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe inflammatory acne.

J Drugs Dermatol. 2013;12(6):658-663.

Clinical Trial Review is a JDD department designed to provide physicians with information on drugs and devices undergoing clinical testing. It is our goal to inform the reader of the status of select drug and device studies relevant to the practice of dermatology before this information is available through standard channels. To participate in or learn more about these and additional trials, visit www.clinicaltrials.gov.

BACKGROUND and OBJECTIVE: Skin lightening preparations are used by people all over the world for a diverse range of dermatologic indications. Hydroquinone (HQ) is the gold standard and remains the only prescription product available in the United States for the treatment of generalized facial hyperpigmentation. Irritation and the risk of exogenous ochronosis are the main adverse effects for concern. Therefore, there has been a constant search for new treatment alternatives. Understanding the molecular mechanisms involved in pigmentation has resulted in the development of a series of formulations that utilize a multimodal treatment approach. These proprietary formulas combine skin lightening agents that act via different mechanisms of action. The actives included 4-ethoxybenzaldehyde (anti-inflammatory and prostaglandin E2 suppressor), licorice extract (tyrosinase inhibitor), tetrahexyldecyl ascorbate (antioxidant), niacinamide (melanosome transport inhibitor), ethyl linoleate (tyrosinase inhibitor; enhances turnover of epidermis), hexylresorcinol (tyrosinase inhibitor), and retinol (tyrosinase transcription inhibitor; enhances turnover of epidermis).
METHODS: Select formulations were tested in several studies using the MelanoDerm™ Skin Model (MatTek Corporation, Ashland, MA) to assess the ability of the product to reduce melanin production and distribution. A single-center, double-blind comparison clinical study of 18 subjects was conducted to evaluate the efficacy of the product in reducing ultraviolet-induced hyperpigmentation. Test sites were irradiated with 1.0, 1.5, 2.0, and 2.5 minimal erythema doses. After 5 days, to allow for pigmentation development, the product or 4% HQ cream was applied to the respective test sites, once daily for 4 weeks. Chroma Meter measurements (L* brightness) and standardized digital photographs were taken of the test sites twice a week.
RESULTS: The test product resulted in greater reduction in melanin as measured by melanin content and histological staining compared with the positive control in the MelanoDerm Skin Model. The product also demonstrated statistically significant reductions in pigmentation compared with baseline (all P≤.0001) at the end of the clinical study, and produced greater increases in L*, compared with 4% HQ. Results from these studies indicate that a product designed to affect multiple pathways of melanogenesis and melanin distribution may provide an additional treatment option beyond HQ for hyperpigmentation.

J Drugs Dermatol. 2013;12(3 suppl 1):s16-s20.

An excess of 70 million cutaneous surgical procedures are conducted annually in the United States that may result in scarring. Skin scars are a normal outcome of the tissue repair process. However, individuals with abnormal scarring may have aesthetic, psychological, and social consequences. As a result, there is a high patient demand for products that will reduce the scarring.

The principles underlying scar formation are now better understood. Products are being developed to address those critical components of the wound-healing process, namely inflammation, hydration, and collagen maturation. A multicomponent scar product was previously shown effective in preventing exaggerated scarring in patients undergoing various surgical procedures. The present outpatient study was conducted in patients undergoing shave biopsies. Following reepithelialization, this investigator-blinded, randomized, 8-week trial compared twice-daily application of either the scar product or the standard of care, white petrolatum. Evaluation visits were conducted at baseline and at weeks, 1, 2, 4 and 8. Subjects were evaluated by the blinded investigator for clinical efficacy and tolerability using grading scales. Standardized digital photographs were taken at each visit, and subjects completed a self-assessment questionnaire regarding treatment effectiveness and satisfaction. Twenty-eight subjects completed the 8-week study. The scar product provided earlier improvements than the white petrolatum. At week 1, 70% of subjects receiving the scar product demonstrated at least 50% global improvement in scar appearance vs only 42% of the subjects receiving white petrolatum. The more rapid improvement was accompanied by greater reductions in stinging/burning and itching with the scar product at all visits. Importantly, there was also greater subject satisfaction with the scar product at all visits. This scar product may be useful in hastening the healing of cutaneous shave biopsies and reducing the stinging/burning and itching associated with the normal healing process.

J Drugs Dermatol. 2013;12(1):86-90.

BACKGROUND: Topical dapsone gel, 5% is approved for treatment of acne vulgaris but has not been studied specifically in women with skin of color (SOC; Fitzpatrick skin types IV, V, or VI).
OBJECTIVE: Evaluate safety and efficacy of dapsone gel, 5% applied topically twice daily for 12 weeks in women with SOC.
METHODS: Females with SOC aged 18 years and older with facial acne participated in a multicenter, open-label, single-group, 12-week pilot study of twice-daily monotherapy with dapsone gel, 5%. The investigator-rated 5-point Global Acne Assessment Score (GAAS) was used to assess efficacy. The impact of acne on subjects was assessed using the validated Acne Symptom and Impact Scale (ASIS).
RESULTS: The study enrolled and treated 68 women with SOC and facial acne. GAAS decreased significantly from baseline to week 12 (mean, -1.2 [95% CI, -1.4, -1.0]; P<.001), a 39.0% improvement. Overall, 42.9% of subjects were responders based on a GAAS of 0 or 1 at week 12. Subjects also experienced significant reductions in mean total lesions (52% decrease), inflammatory lesions (65%), and comedo counts (41%; all P<.001). Dapsone gel, 5% monotherapy was associated with significant improvement in subject-assessed acne signs (P<.001) and impact on quality of life (QOL; P<.001), based on ASIS. Dapsone gel, 5% used twice daily was well tolerated, with no treatment-related adverse events. The local dermal tolerability scores tended to remain stable or decrease from baseline to week 12.
CONCLUSIONS: Monotherapy with dapsone gel, 5% administered twice daily was safe and effective for treatment of facial acne in women with SOC. Significant improvement in overall acne severity and both inflammatory lesions and comedones was observed. Further, study subjects reported considerable improvement in both acne signs and impact on QOL.

J Drugs Dermatol. 2016;15(2):197-204.

BACKGROUND: Abnormal accumulation of melanin is a common aesthetic skin concern. For years, the gold standard for the treatment of hyperpigmentary disorders has been 4% hydroquinone (HQ). Due to regulatory agencies around the world questioning the safety of HQ, there has been interest in developing new HQ-free skin brightening/lightening products. A multimodality product (skin brightening complex) addressing various pathways for melanogenesis was developed as an alternative to HQ.
OBJECTIVE: The skin brightening complex was studied for efficacy and tolerability in subjects with moderate to severe facial hyperpigmentation.
METHODS: Subjects were instructed to apply skin brightening complex to the entire face twice daily and to follow a standard skin care regimen (facial cleanser, moisturizer, and sunscreen) during the course of the study. The study was conducted over a 12-week period and consisted of evaluation visits at baseline and at weeks 4, 8, and 12. At each visit, subjects were evaluated by an investigator for clinical efficacy and tolerability using grading scales. Standardized digital photographs and spectrophotometric assessments were also taken. Self-assessment questionnaires were completed at weeks 4, 8, and 12. To assess longer-term safety and efficacy, 10 subjects elected to continue treatment for an additional 12 weeks (24 weeks total), with evaluations at weeks 18 and 24.
RESULTS: Twenty-six subjects completed the 12-week study, and 8 subjects completed treatment for an additional 12 weeks (24 weeks in total). In the 12-week study, the skin brightening complex was shown to be effective and significantly improved Overall Hyperpigmentation at weeks 4, 8, and 12 compared with baseline. The skin brightening complex also significantly improved the Mottled Pigmentation Area and Severity Index ([MoPASI], a modified Melasma Area and Severity Index [MASI] scale) at weeks 8 and 12 compared with baseline. These efficacy benefits continued at 24 weeks. The product was well tolerated at all evaluation visits. Subject questionnaires showed 80% or more of the subjects reporting pigmentation improvement and satisfaction with the skin brightening complex at all evaluation visits.
CONCLUSION: This HQ-free skin brightening complex was effective and well tolerated in subjects with facial hyperpigmentation who were treated for as long as 24 weeks.

J Drugs Dermatol. 2013;12(3 suppl 1):s27-s31.

No abstract details for the moment.

No abstract details for the moment.

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.

J Drugs Dermatol. 2014;13(3):309-314.

Anti-aging cosmeceutical efficacy is hampered by lack of active ingredient purity and lack of dosing standardization. These are two important key factors necessary to insure consistent, reproducible, and documentable skin effects. Without this type of standardization, it is not possible for cosmeceutical science to advance. Growth factors are interesting cosmeceutical ingredients with established cosmetic skin effects that can now be standardized due to the recent ability to manufacture recombinant epidermal growth factor. The concomitant use of a recombinant epidermal growth factor with a filler grade hyaluronic acid (EGF/RHA) was studied over 12 weeks in 60 females with mild to moderate photoaging as compared to a currently marketed spent fibroblast growth media and moisturizer (TNS). Investigator, noninvasive, and subject assessments were collected at baseline and weeks 2, 4, 8, and 12. The blinded investigator noted a statistically significant preference for the EGF/RHA at week 2 in terms of smoothness (P =0.003) and firmness (P =0.003). This improvement continued into weeks 4 and 8 with continued superior EGF/RHA results in fine lines (P =0.002), radiance (P =0.014), and overall appearance (P =0.027) by week 12. Transepidermal water loss was reduced for the EGF/RHA over the TNS at week 12 (P =0.005). The subjects gave high ratings to both study products. This research demonstrates the utility of recombinant growth factors, when combined with hyaluronic acid hydration, in improving skin cosmetic attributes. The ability to manufacture consistent pure recombinant growth factors lays the foundation for improved scientific study of this category of cosmeceutical actives.

J Drugs Dermatol. 2016;15(6):738-741.

Etanercept is approved for the treatment of plaque psoriasis at a subcutaneous (SC) dosage of 50 mg twice-weekly for three months, followed by 50 mg SC once-weekly thereafter. It is of note, however, that many patients experience loss of efficacy when they step down to etanercept 50 mg/week, often instigating a switch to another biological. The current pilot study investigated the adjunctive use of a topical calcipotriene 0.005% and betamethasone dipropionate 0.064% combination ointment, approved for the treatment of psoriasis, to sustain the original efficacy of etanercept by augmenting response to the 50 mg/week SC dose, thus stabilizing the disease.
Trial Design: In this single-center, open-label study, subjects (n=20) underwent 12 weeks treatment with etanercept 100 mg/week (50 mg, 2x week; weeks –12 to -1), followed by etanercept 50 mg/week maintenance therapy for 40 weeks (weeks 0 to 40). Subjects were followed at four-week intervals. Starting at week 4, subjects who demonstrated an increase from baseline (week 0) body surface area (BSA) of >2% initiated therapy with calcipotriene 0.005% and betamethasone dipropionate 0.064% ointment for four weeks. The study is limited by its small sample size, open-label nature, and lack of blinding.
Findings: Mean BSA involvement decreased significantly from week –12 to 0 with etanercept 50 mg twice a week. At week 4, on the etanercept 50 mg/week dose, mean BSA increased to 9.42±9.39 compared to week 0. With introduction of calcipotriene 0.005%/betamethasone dipropionate 0.064% ointment at week 4, mean BSA decreased to 4.62±8.19 by week 24 and was relatively stable for the remainder of the study period. Similarly, mean PASI (Psoriasis Area and Severity Index) scores improved from week -12 to week 0, increased at week 4, then decreased significantly by week 24 with adjunctive topical treatment.
Conclusion: Topical calcipotriene 0.005% and betamethasone dipropionate 0.064% ointment is a safe and effective adjunct to etanercept 50 mg/week maintenance therapy.

J Drugs Dermatol. 2011;10(8):881-885.

Purpose: Though hydroquinone (HQ) remains the gold standard for treatment of hyperpigmentation, concerns about its safety have prompted the development of HQ-free topical skin lightening systems. Objective: To compare the efficacy and tolerability of a new HQ-free system and a popular HQ-based system for the improvement of facial hyperpigmentation and photoaging in darker skin types. Methods: This investigator-blinded trial randomized 30 subjects of Fitzpatrick skin types III to VI with moderate to severe hyperpigmentation to a new 7-product HQ-free system or a 7-product HQ-based system for 12 weeks. At 4, 8, and 12 week follow-up visits, a blinded investigator assessed efficacy and tolerability using standardized scales. Subjects also performed a self-assessment at each visit. Summary: Both the HQ-free and HQ-based systems produced significant improvements in Overall Hyperpigmentation that were sustained through week 12 (P=0.008, 0.0003). The HQ-based system demonstrated better improvement in overall hyperpigmentation at weeks 4, 8, 12 (P=0.01, 0.001, 0.003, respectively). Mottled Pigmentation Area Severity Index (MoPASI) scores improved with both systems (P=0.02, 0.01), with no statistically significant differences between the two treatment groups. Subject-rated hyperpigmentation was not different between groups. Subjects reported significantly more discomfort with the HQ-free system at week 8 (P=0.02); otherwise, measures of irritation were the same between groups. All irritation was described as mild to moderate. At week 12, 100% of subjects in the HQ-free group and 92.3% of subjects in the HQ-based group were satisfied with their outcome. Conclusion: Both a new HQ-free skincare system and a widely-available HQ-based system improved hyperpigmentation in Fitzpatrick skin types III to VI. Though the HQ-based system produced greater improvement in hyperpigmentation when compared to the HQ-free system, there was no difference in MoPASI scores between the treatment groups. Subjects were satisfied with both treatments and reported only mild to moderate irritation using either system.

J Drugs Dermatol. 2017;16(11):1127-1132.

Background: Acne vulgaris is a common dermatologic disease that most frequently affects adolescents and young adults. Over-the-counter (OTC) acne treatment regimens are increasingly being used by individuals with acne.
Objectives: To compare the efficacy, user satisfaction, and tolerability of the OTC regimens MaxClarity™, Proactiv^®, and Murad^® in the treatment of mild and moderate acne. Methods: Two randomized, evaluator-blinded, split-face studies were conducted, each involving 20 subjects with acne, to evaluate MaxClarity against Proactiv (study 401) and MaxClarity against Murad (study 404) over 8 weeks.
Results: Clinically and statistically significant reductions in acne lesion counts were achieved at 8 weeks compared with baseline for each regimen using MaxClarity, Proactiv, and Murad. Similar reductions in lesion counts and improvements in Investigator's Static Global Assessment grades were observed between MaxClarity and either Proactiv or Murad, in the respective studies. MaxClarity was well tolerated, with no treatment-related adverse events observed in any treatment group and no discontinuations due to adverse events. Overall, most subjects were satisfied with all study treatments.
Conclusions: MaxClarity is an effective alternative to either Proactiv or Murad for use in the treatment of mild and moderate acne.

J Drugs Dermatol. 2013;12(2):180-185.

Dyschromia is one of the primary complaints for patients with skin of color. Treatments need to achieve a balance between tolerability and efficacy to address existing hyperpigmentation without causing additional damage that could trigger post-inflammatory hyperpigmentation (PIH). An open-label, single-center study was conducted to assess the efficacy of a novel comprehensive pigmentation control serum (LYT2) combined with a series of three very superficial chemical peels (VP) in skin of color subjects. Seventeen female and male subjects aged 36 to 69 years with Fitzpatrick Skin Types III-VI and moderate to severe facial hyperpigmentation were enrolled in the 12-week clinical study. Subjects identified as Asian, Hispanic, African American, or Caucasian ethnicities. Subjects received a series of 3 VP treatments every 4 weeks. LYT2 was applied twice-daily in between VP treatments. Investigator assessments for overall hyperpigmentation, overall photodamage, and skin tone unevenness, as well as standardized digital photography and subject self-assessment questionnaires were conducted at all visits (baseline and weeks 4, 8, and 12). In vivo reflectance confocal microscopy (RCM) of a target lesion was conducted (in a subset of subjects) at baseline and week 12. Fourteen subjects completed the study. The treatment regimen provided statistically significant improvements in all efficacy parameters at weeks 8 and 12 (all P less than equal to 0.03, student’s t-test). Standardized digital photography and RCM images support the improvements in overall hyperpigmentation observed by the investigator. At the end of treatment, the regimen was highly rated by subjects with 100% of subjects (strongly agree/agree) that the combination “decreased the appearance of uneven skin tone and discolorations” and “reduced the appearance of sun damage.” In addition to this clinical study, independent case studies with this combination treatment regimen at a separate study site were also conducted with results that corroborate the formal clinical study findings. The comprehensive results from these studies suggest that the combination of a comprehensive pigmentation control serum with a series of 3 very superficial chemical peels may provide an effective treatment approach for hyperpigmentation in skin of color patients.

J Drugs Dermatol. 2017;16(4):301-306.

Dyschromia is one of the most common dermatological concerns in patients with darker skin.1 Disorders of hyperpigmentation, including postinflammatory hyperpigmentation, melasma, solar lentigines, and miscellaneous causes of facial hyperpigmentation, are the most frequently treated dyschromias and can have a considerable psychosocial impact. Given the high prevalence of hyperpigmentation and the considerable demand for an even complexion, newer treatment options for hyperpigmentation are of growing interest among consumers, manufacturers, and dermatologists. Blinded, controlled studies demonstrating skin lightening effects in soy, niacinamide, n-acetylglucosamine, licorice extract, arbutin, vitamin c, kojic acid, emblica extract, lignin peroxidase, and glutathione have led to the development of a growing list of non-prescription skin care products that can be incorporated (mostly as adjuncts) in the management of hyperpigmentation.

J Drugs Dermatol. 2013;12(suppl 9):s123-s127.

The treatment of tinea pedis with hyperkeratosis has always been challenging due to presence of thick scales even after the resolution of active fungal infection. Patients usually identify hyperkeratosis with active disease. Therefore, a regimen of an antifungal and a keratolytic agent would be useful not only clearing the skin clinically but also addressing patients’ perceptions.

J Drugs Dermatol. 2014;13(2):162-165.

Introduction: A 4% hydroquinone/10% L-ascorbic acid treatment system aims to treat early signs of photodamage in normal to oily skin and help prevent further photodamage. The system also contains vitamin E, witch hazel, aloe barbadensis leaf juice, penetration-enhancing ingredients, micronized zinc oxide, and octinoxate.
Methods: Patients with minimal or mild facial photodamage and hyperpigmentation, and normal to oily facial skin, used the treatment system for 12 weeks.
Results: Of 34 females enrolled, 30 completed. Median scores for the overall integrated assessment of photodamage, overall intensity of pigmentation, fine lines and wrinkles, tactile roughness, and laxity were significantly improved at week 12 compared with baseline. Furthermore, ≥90 percent of patients considered their skin was smoother, softer, more evenly toned, and more radiant, and 100 percent were satisfied with the overall appearance of their skin.
Conclusion: The treatment system can help to ameliorate early signs of photodamage in normal to oily skin.

J Drugs Dermatol. 2011;10(12):1455-1461.

Background: Non-surgical fat reduction through cold application, cryolipolysis, is an extremely popular procedure. Apoptosis of the fat cell content may take around 3 months to resolve.

Objective: A topical test product was compared to a bland emollient as an adjunct to the cryolipolysis procedure of the upper arms to determine if the product could hasten outcomes in these patients. The product includes a peptide combination thought to stimulate autophagic breakdown of lipid droplets, thus speeding up the apoptotic process seen after cryolipolysis.

Methods: A randomized, double-blind, comparator-controlled study in 11 patients compared the test product to a bland emollient on the upper arms of patients following cryolipolysis. Subjects were followed at 1, 4, 8, 12, and some at 24-weeks post treatment. Assessments were made through subjective and objective photographic analysis of the treated areas comparing changes in both arms.

Results: The test product appeared to speed up the process of contour improvement with results at 8 weeks matching those attained at 12 weeks by the comparator and long-term results at 24 weeks appearing to maintain this advantage. When measured objectively using pixel analysis, 8 and 24-week contour improvement was statistically better than the comparator. Skin laxity was also improved. In additional assessments using 3D volume analysis, cases showed improved reduction of fat tissue on the treated sides.

Conclusion: This pilot study introduces a potential advance in adjuvant topical therapy aiding the outcome of non-invasive fat reduction procedures.

J Drugs Dermatol. 2019;18(4):342-348.

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Benzoyl peroxide (BPO) is a widely used over-the-counter (OTC) topical acne treatment often used in combination with salicylic acid (SA) to achieve better comedone control than that achieved with BPO alone. MaxClarity™ is an OTC acne treatment system comprising BPO and SA in an aqueous foam delivery vehicle, VersaFoam AF™. This paper describes 2 open-label, single-arm studies conducted to assess the efficacy, safety, tolerability, and patient preference of MaxClarity in the treatment of mild, moderate, and severe acne. Subjects applied MaxClarity twice daily for 8 weeks in study 402 and for 12 weeks in study 405. Reductions in all lesion types were seen throughout both studies. At week 8 (study 402), there was a mean reduction from baseline of –56.9 ± 32.7% in total lesions in subjects with mild, moderate, or severe acne. At week 12 (study 405), there was a reduction from baseline of –61.6 ± 22.0% in total lesions in subjects with moderate or severe acne. Overall, both studies demonstrated that MaxClarity is a generally well tolerated and effective treatment for mild, moderate, and severe acne.

J Drugs Dermatol. 2013;12(3):259-264.

Topical tretinoin has been a standard treatment for acne vulgaris for more than 4 decades. While tretinoin has demonstrated proven efficacy in the treatment of acne lesions, it also is associated with the potential for skin irritation. Newer formulations have been designed to optimize both the drug concentration and the delivery vehicle with the aim to enable clinicians to provide increasingly effective acne treatment that minimizes irritation. These therapies include formulations with varying concentrations of tretinoin and vehicles that utilize a microsponge delivery system, hydrogels and micronized tretinoin, or propolymers. The purpose of this review is to evaluate different formulations and combinations of tretinoin in the treatment of acne vulgaris. While these advanced formulations were designed for controlled release of active ingredient, and have the potential to reduce cutaneous irritation relative to standard tretinoin cream and gel formulations, there is a need for comparative studies to evaluate the relative benefits of each of these advanced tretinoin formulations in optimizing acne treatment.

J Drugs Dermatol. 2014;13(4):466-470.

INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery.
METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months.
RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P=.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P=.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment.
CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.

J Drugs Dermatol. 2014;13(6):741-747.

INTRODUCTION: Cryosurgery is the most common treatment for actinic keratosis (AK) in the United States. Efficacy with cryosurgery is variable, and is a modality for treating individual, visible lesions while failing to treat subclinical lesions.
METHODS: FIELD Study 1 (NCT01541553) is a phase 3, multicenter, randomized, double-blind study that evaluated the short- (11-week) and long- (12-month) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel, versus cryosurgery followed by vehicle.
RESULTS: Overall, 329 patients were randomized to ingenol mebutate 0.015% gel (n=167) or vehicle (n=162) 3 weeks after cryosurgery. Baseline characteristics were balanced across groups. At week 11, complete clearance rate (100%) in the treatment area was higher for ingenol mebutate gel compared with vehicle (60.5% vs 49.4%, respectively; P=.04). Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel (82.7% vs 75.6%). A general reduction from baseline lesion count was observed 3 weeks after cryosurgery. Treatment after cryosurgery was well tolerated.
CONCLUSIONS: Short-term (11-week) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone.

J Drugs Dermatol. 2014;13(2):154-160.

Skin care products may use various active ingredients to support skin rejuvenation including growth factors and other molecules that help to regenerate extracellular matrix (ECM) and promote skin repair. The biological effect of skin care products with a strong anti-aging claim was assessed in gene expression analyses using an in vitro human skin model. Application of products containing human fbroblast-derived growth factors resulted in signifcant upregulation of genes encoding ECM components including collagens and elas-tin. Human fbroblasts cultured under hypoxic conditions show increased gene expression of stem cell markers, and their conditioned media could possibly further support skin rejuvenation. Furthermore, a double-blind, randomized, placebo-controlled study was con-ducted in subjects with moderate to severe facial photodamage to assess the cosmetic clinical effcacy of a product containing human fbroblast-derived growth factors. The test product group demonstrated signifcantly greater reductions in the appearance of fne lines/wrinkles, coarse line/wrinkles, and overall photodamage, compared to the placebo group. Altogether, the results suggest that human fbroblast-derived growth factors support skin rejuvenation by stimulating dermal fbroblasts to generate ECM.

J Drugs Dermatol. 2017;16(12):1190-1196.

Approximately 20-25% of the population worldwide is affected by superficial cutaneous mycoses (SCM). SCM are cutaneous fungal infections with a wide array of systemic and topical treatment options. However, successful therapeutic outcomes are limited by patient non-adherence, medication side effects, potential drug interactions, antifungal resistance and disease recurrence. Advances in formulation technology have allowed for the development of more effective and safer therapies. In this article we will review several new and emerging pharmacotherapeutics for onychomycosis and tinea pedis.

J Drugs Dermatol. 2014;13(4):391-395.

BACKGROUND: This multicenter, open-label pilot study evaluated safety, efficacy and tolerability of a topical formulation containing a multipotent growth factor resignaling complex (MRCx), when applied to infraorbital and lateral canthal skin.
METHODS: Thirty-nine female subjects with mean age of 56.8 years who had periorbital lines and wrinkles, uneven skin texture, puffiness, and lack of skin firmness were enrolled, and 38 completed the study. All subjects applied the multipotent growth factor formulation bilaterally to the periorbital area, twice daily for 60 days. Efficacy and treatment-related adverse events were evaluated at Baseline and days 14, 30, and 60. Investigators rated the periorbital areas based on 10-point scales.
RESULTS: Subjects’ self-reported compliance with treatment was greater than 99% throughout the study. At day 60, all subjects had improvement in infraorbital brightness (≥ 2 points), moistness (≥ 2 points), wrinkles (≥ 1 point), sallowness (≥ 1 point), crepiness (≥ 1 point), smooth texture (≥ 1 point), skin tightness (≥ 1 point), and skin tone (≥ 1 point). Investigator-rated assessments showed ≥ 1-point improvement for lateral canthal wrinkles, dyschromia/mottled pigmentation, skin tone, overall brightness, and moistness. Investigator-rated scoring on the Global Aesthetic Improvement Scale (GAIS) demonstrated that 67.6% of subjects were much improved/improved at day 14, and 63.1% remained improved at day 60. Overall, 76.2% and 79.0% of subjects were very pleased/pleased/mostly pleased with the appearance of their infraorbital and lateral canthal areas at day 60. Adverse events comprised one case of mild canthal erythema, and one case of mild eye irritation, both of which were respectively resolved.
CONCLUSIONS: This pilot study demonstrated that the topical multipotent growth factor formulation was safe, effective and well tolerated for periorbital skin rejuvenation.

J Drugs Dermatol. 2015;14(12):1410-1417.

Poly-L-lactic acid (PLLA) was approved for use in Europe in 1999. In the United States, it was approved by the Food and Drug Administration in 2004 for the treatment of facial lipoatrophy associated with human immunodeficiency virus, and in 2009 for cosmetic indications in immune-competent patients. The need for consistent, effective PLLA usage recommendations is heightened by an increased consumer demand for soft tissue augmentation and a shift toward a younger demographic. Over the past 14 years, considerable experience has been gained with this agent, and we have come to better understand the clinical, technical, and mechanistic aspects of PLLA use that need to be considered to optimize patient outcomes. These consensus recommendations regarding patient selection, proper preparation and storage, optimal injection techniques, and other practical considerations reflect the body of evidence in the medical literature, as well as the collective experience of this author group.

J Drugs Dermatol. 2014;13(suppl 4):s44-s51.

According to the United States national survey data, acne vulgaris is the leading dermatologic diagnosis among African Americans, Hispanics/Latinos, and Asians/Pacific Islanders. This patient population, collectively referred to as having skin of color, exhibits clinical and therapeutic nuances that are relevant in the management of acne. Understanding the nuances in clinical presentation, safety considerations, cultural factors, and desired treatment endpoints is key to ensuring successful outcomes.

J Drugs Dermatol. 2014;13(suppl 6):s61-s65.

BACKGROUND: Topical products with epidermal lipids in a ceramide-dominant ratio were originally developed to address atopic dermatitis. They have been used by extension to address the barrier deficits of aging skin, and after laser resurfacing and other barrier-disrupting procedures. The purpose of this study was to evaluate efficacy, tolerability, and safety of a novel formulation containing high levels of physiological barrier lipids, in a unique cholesterol-dominant ratio hypothesized to directly address the specific epidermal lipid imbalances of aging skin. METHODS: An 8-week, single-center study was conducted on females aged 55 to 75 with mild to moderate fine lines and wrinkles, and other stigmata of facial photodamage. Evaluations were performed at baseline, immediately after rst use of the cholesterol-dominant test formulation, and at weeks 4 and 8. Efficacy evaluations comprised blinded expert grading of 9 skin attributes, bioinstrumental measurements of trans-epidermal water loss (TEWL) and stratum corneum hydration, standardized digital imaging, and self-assessment questionnaires. Tolerability was scored objectively and subjectively, and by grading of skin dryness. Adhesive tape extracts were analyzed biochemically for epidermal lipids, and by double-staining to detect mature vs. immature corneocytes. In a separate study, the effects of pre- or post-treatment with the test formulation on barrier recovery following traumatic tape stripping of forearm skin were assessed via measurements of TEWL and stratum corneum hydration. RESULTS: Statistically significant improvements occurred in all facial skin attributes (weeks 4 and 8), TEWL (week 8), and stratum cor- neum hydration (weeks 4 and 8). There were significant increases in total ceramides and cholesterol, including ceramide isoforms not present in the test formulation itself; and a statistically significant increase in the ratio of mature to immature corneocytes at week 8. Forearm skin treated with the test formulation after traumatic tape stripping recovered barrier function significantly faster than untreated skin. Pre-treatment for 1 week prior to traumatic tape stripping had a significant protective effect. Tolerability and safety of the test formulation were excellent. CONCLUSIONS: This cholesterol-dominant lipid formulation offers a new paradigm of primary skin barrier repair specifically targeted to- ward aging skin. Correction of age-related epidermal lipid deficits directly addresses the underlying cause and the profound sequelae of barrier dysfunction in aging skin. This may also be of utility to optimize skin tolerance, response and recovery from aesthetic procedures and other topical treatments, and for dermatoses associated with barrier dysfunction, such as rosacea. The formulation achieved sustained improvements in barrier function throughout the course of the 8-week study, had a protective effect when applied prior to barrier insult, and mediated more rapid recovery when applied after barrier insult. Significant increases in total epidermal ceramides, cholesterol and triglycerides, and in mature versus immature corneocytes, indicated both structural and functional normalization of the skin barrier, and possibly a broader-based stimulation of ceramide synthesis. The formulation had excellent tolerability and safety profiles, even in subjects with sensitive skin. J Drugs Dermatol. 2016;15(12):1513-1523.

BACKGROUND: Hyaluronic acid (HA) is a popular ingredient in topical formulations for cosmetic improvement of the skin. Most formulations contain linear, non-crosslinked HA oligomers, low molecular weight (LMW) HA, and/or high molecular weight (HMW) HA. Crosslinking of HA enhances its clinical longevity and mechanical characteristics. The objective of this study was to characterize the topical effects of a new, crosslinked resilient HA (RHA) that is also available as a cohesive, tissue-integrating injectable filler, compared with non-crosslinked HMW HA and LMW HA. Living human skin explants that preserve the 3-dimensional structure of in vivo skin were used to maximize clinical relevance.
METHODS: Standardized doses of each HA product were applied daily for 9 days to human skin explant surfaces. Untreated explants served as controls. Water content of the stratum corneum and entire epidermis was analyzed by Raman spectroscopy. Transepidermal water loss (TEWL) was measured to assess skin barrier function. Explant morphology and microrelief were evaluated by optical and scanning electron microscopy.
RESULTS: Crosslinked RHA achieved a significant increase in epidermal water content (7.6%) over the control. Spectral cartography confirmed a higher epidermal water content with RHA than with HMW HA or LMW HA. TEWL was reduced by 27.8% with RHA, and by 15.6% with HMW HA, but increased by 55.5% with LMW HA. Cutaneous microrelief improved with RHA. Corneocyte cohesion improved with RHA and HMW HA.
CONCLUSIONS: This comparative, multimodal study demonstrated greater benefits of topical crosslinked RHA over linear HMW HA or LMW HA in reducing TEWL, retaining and redistributing water within the epidermis, maintaining skin integrity, and improving skin barrier structure and function. RHA was a more efficacious humectant than LMW HA, and a more efficacious occlusive moisturizer than HMW HA. These integrative epidermal repair activities are of significant value for addressing primary deficits of aging skin, improving tolerance to retinoids and other topical agents, and optimizing procedural outcomes. A combination of topical and injectable HA provides an elegant model of synergistic, multi-level skin restoration.

J Drugs Dermatol. 2016;15(4):434-441.

Background: Acne pathogenesis is multifactorial and includes inflammation. Combining drugs targeting multiple components of acne pathogenesis is standard practice.
Objective: To assess the safety and efficacy of dapsone gel 5%, an anti-inflammatory agent, in combination with tazarotene cream 0.1% for treatment of acne vulgaris.
Methods: Patients were randomized to receive combination therapy (dapsone gel 5% twice-daily plus tazarotene cream 0.1% daily) or monotherapy (tazarotene cream 0.1% daily). Efficacy and safety data were collected after 1, 2, 4, 8, and 12 weeks of treatment.
Results: Patients in both arms (n=86, dapsone + tazarotene; n=85, tazarotene) showed significant reductions from baseline in inflammatory, noninflammatory and total lesion counts (P<.001 for all). At 12 weeks, patients treated with dapsone plus tazarotene showed a greater reduction from baseline in noninflammatory (comedonal) and total lesion counts than tazarotene-treated patients (noninflammatory, 59.7 percent vs. 46.5 percent, P=.01; total, 63.3% vs. 53.6%, P=.02). The percentage of patients achieving treatment success (an investigator subjective score of 0 [none] or 1 [minimal]) was greater in dapsone plus tazarotene-treated patients (42.2%) than in tazarotene-treated patients (21.8%;P=.01). Both treatments were well tolerated.
Conclusion: Combination therapy with dapsone gel 5% plus tazarotene cream 0.1% was more effective than tazarotene monotherapy for treatment of comedonal acne. The results suggest that anti-inflammatory agents such as dapsone can effectively treat early stages of acne (both comedonal and noncomedonal) when used in combination with a retinoid.

J Drugs Dermatol. 2011;10(7):783-792.

The pathophysiology of rosacea has undergone renewed interest over the past decade, with a large body of evidence supporting the role of an abnormal innate immune response in rosacea. Many mechanisms interact with the cutaneous innate immune system that may be operative. A variety of potential triggers stimulate this immune detection system which is upregulated and hyper-responsive in facial skin of patients with rosacea as compared to normal skin. Based on the most current data, two conclusions have been reached. First, the major presentations of rosacea appear to be inflammatory dermatoses. Second, the presence of a microbial organism is not a primary or mandatory component of the pathogenesis of rosacea. Available therapies for rosacea exhibit reported modes of action that appear to correlate with the inhibition of inflammatory processes involved in the pathophysiology of at least some presentations of rosacea.

J Drugs Dermatol.2012;11(6):694-700.

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.

Periorbital hyperpigmentation (POH) is a common worldwide problem. It is challenging to treat, complex in pathogenesis, and lacking straightforward and repeatable therapeutic options. It may occur in the young and old, however the development of dark circles under the eyes in any age is of great aesthetic concern because it may depict the individual as sad, tired, stressed, and old. While “dark circles” are seen in all skin types, POH is often more commonly seen in skin of color patients worldwide.1 With a shifting US demographic characterized by growing number of aging patients as well as skin of color patients, we will encounter POH with greater frequency. As forecasted by the US Census, by 2030 1 in 5 Americans will be 65 plus years old and greater than 50% of the population will possess ethnic skin of color.2 The disparity in the medical community’s understanding of POH versus popular demand for treatment is best illustrated when you have only 65 cited articles to date indexed on PubMed line3 compared to the 150,000,000 results on Google search engine.4 Most importantly POH may be a final common pathway of dermatitis, allergy, systemic disorders, sleep disturbances, or nutritional deficiences that lends itself to medical, surgical, and cosmeceutical treatments. A complete medical history with ROS and physical examination is encouraged prior to treating the aesthetic component. Sun protection is a cornerstone of therapy. Safety issues are of utmost concern when embarking upon treatments such as chemical peeling, filler injection, and laser therapy as not to worsen the pigmentation. Without intervention, POH usually progresses over time so early intervention and management is encouraged. The objective of this study was to review the current body of knowledge on POH, provide the clinician with a guide to the evaluation and treatment of POH, and to present diverse clinical cases of POH that have responded to different therapies including non-ablative fractional photothermolysis in two skin of color patients.

J Drugs Dermatol. 2014;13(4):472-482.