Improvements in Submental Contour up to 3 Years After ATX-101: Efficacy and Safety Follow-Up of the Phase 3 REFINE Trials.

BACKGROUND: ATX-101 (deoxycholic acid) significantly reduced submental fat (SMF) severity in two 24-week Phase 3 studies (REFINE-1 and REFINE-2). OBJECTIVES: The aim of this study was to evaluate the durability of effect and long-term safety of ATX-101. METHODS: REFINE study patients who maintained ≥1-grade improvement on the Clinician-Reported SMF Rating Scale (CR-1 responders) 12 weeks after their last REFINE treatment were eligible for enrollment in this multicenter, double-blind, nontreatment, long-term, follow-up study (NCT02163902). The primary endpoint was CR-1 response at Years 1, 2, and 3. Patient-reported satisfaction, psychological impact, and adverse events were monitored. RESULTS: In total, 224 patients (ATX-101, n = 113; placebo, n = 111) were enrolled. Maintenance of CR-1 response was significantly better in the ATX-101 group than in the placebo group at Year 1 (86.4% vs 56.8%; P < 0.001), Year 2 (90.6% vs 73.8%; P = 0.014), and Year 3 (82.4% vs 65.0%; P = 0.03). Most (74%) ATX-101‒treated patients satisfied at 12 weeks remained satisfied at Year 3. Significant reductions from baseline in psychological impact scores were sustained through Year 3 (P < 0.001). No new treatment-related adverse events were reported. CONCLUSIONS: Improvements in submental contour achieved with ATX-101 are maintained for 3 years in most patients. No new safety signals emerged.

Human Pharmacokinetics and Safety of Subcutaneous Collagenase Clostridium Histolyticum in Women.

BACKGROUND: Clostridium collagenase histolyticum (CCH) is being evaluated in women as a cellulite treatment. OBJECTIVE: To report preclinical safety and human pharmacokinetics (PK) and safety data for CCH. METHODS: Across 3 PK studies, 41 women received 12 subcutaneous injections per thigh/buttock in 1 session (up to 3.36 mg/dose). Blood samples were taken at baseline; at 5, 10, 20, and 30 minutes postdose; and at 1, 2, 4, 8, 12, 24, 48, 168, and 504 hours postdose. In a preclinical study, rats received 0, 0.029, 0.13, or 0.29 mg/dose of CCH intravenously (IV) every other day (QOD) for 16 days (total, 8 doses) and were evaluated for histopathologic changes. RESULTS: In human PK studies, no quantifiable plasma concentrations of AUX-I or AUX-II were observed postdose (n= 39 evaluable). Adverse events were injection site–related (bruising [97.6%], pain [87.8%], and edema/swelling [46.3%]). Antidrug antibodies were seen in most women at 504 hours postdose. In rats, plasma concentrations of AUX-I and AUX-II (CCH components) were measurable for 30 minutes and 1-2 hours, respectively, after IV administration. At ≥43× proposed human therapeutic dose on a mg/kg basis, rats experienced elevated liver enzyme levels, increased liver weights, and histologic changes that were mostly reversed during a 14-day recovery period. CONCLUSIONS: In human studies, no quantifiable circulating CCH levels were observed after a single subcutaneous dose of CCH up to 3.36 mg. Preclinical data indicated that repeat IV dosing (QOD; 8 doses) at ≥43× proposed human dose on a mg/kg basis for CCH was generally well tolerated.J Drugs Dermatol. 2020;19(9):852-856. doi:10.36849/JDD.2020.5048THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

A Consensus on Minimizing the Risk of Hyaluronic Acid Embolic Visual Loss and Suggestions for Immediate Bedside Management.

BACKGROUND: Hyaluronic acid fillers have a satisfactory safety profile. However, adverse reactions do occur, and rarely intravascular injection may lead to blindness. Currently there is no internationally recognized consensus on the prevention or management of blindness from hyaluronic acid filler. OBJECTIVES: The authors sought to give guidance on how to minimize the risk and optimize the management of this rare but catastrophic adverse reaction. METHODS: A multinational group of experts in cosmetic injectables from multiple disciplines convened to review current best practice and develop updated consensus recommendations for prevention and bedside intervention if visual loss occurs after cosmetic injection of hyaluronic acid filler. RESULTS: The consensus group provided specific recommendations focusing on the consenting process, prevention, and early management of visual impairment related to intravascular hyaluronic acid filler injection. CONCLUSIONS: Although visual loss due to filler injections is rare, it is important that both patient and physician be aware of this risk. In this paper the authors describe methods and techniques available to reduce the risk and also document suggested initial management should a clinician find themselves in this situation.

Patient perception on the usage of smartphones for medical photography and for reference in dermatology.

BACKGROUND: With increasing use of smartphones in the practice and delivery of dermatologic care, little is known on patient perceptions regarding its applications in the clinical setting. OBJECTIVE: To survey patient viewpoints regarding medical photography and the usage of smartphone applications during a medical encounter. MATERIALS AND METHODS: Cross-sectional survey of adult patients in urban academic and private practice clinics. Patients responded to questionnaires tailored to identify respondent characteristics, preferences of photographing procedure and smartphone uses, and concerns regarding smartphone camera use. RESULTS: Of the 300 patients surveyed, the majority preferred a hospital-owned camera (97.7%) over the use of personal photographing equipment including a physician's digital camera (27.5%) or a physician's smartphone camera (27.2%). The majority found personal smartphones to be an acceptable reference tool (69.7%) and means to provide information to the patient (75.3%). CONCLUSION: Patients appear to have clear preferences in the equipment used for medical photography and acceptable applications of smartphones, highlighting the importance of feedback in shaping patient-physician interactions. In light of patient opinions on camera preferences, it may be prudent to make a conscientious effort to refrain from using smartphones as a camera in the clinical setting until patient concerns regarding its use can be addressed.

Rapid treatment of mild acne with a novel skin care system containing 1% salicylic acid, 10% buffered glycolic acid, and botanical ingredients.

The biggest hurdle in the treatment of acne vulgaris is patient non-compliance that is due in large part to poor tolerability to common acne medications. As such, new acne treatments must be developed that balance good anti-acne efficacy with excellent tolerability in order to ensure patient adherence and by extension ensure good clinical outcomes. The goal of the present study was to determine the tolerability and efficacy of a novel skin care system, composed of a cleanser, containing 1% salicylic acid and botanical ingredients, and a treatment gel, containing 1% salicylic acid, 10% buffered glycolic acid and botanical ingredients for the treatment of mild acne. In this single-center, open-label clinical study, 25 male and female volunteers used the test cleanser and test gel twice daily over six weeks. Tolerability assessments showed that the skin care regimen was very well tolerated by all study volunteers. Acne severity was significantly reduced by two acne grades at six weeks. Inflammatory lesion counts were significantly reduced, on average, by 59.06% (P ≤ 0.0001), 91.62% (P ≤ 0.0001), 90.85% (P ≤ 0.0001) and by 98.55% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Non-inflammatory lesion counts were reduced, on average, by 13.54% (ns), 38.95% (P ≤ 0.0001), 44.48% (P ≤ 0.0001), and by 56.10% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Standardized photography also demonstrated a progressive reduction in acne lesions over time. In conclusion, results of the present study suggest that the tested skin care regimen offers rapid acne clearance and excellent tolerability that together may help to improve patient adherence as well as treatment outcome.

Characterization of Tissue Histology for the Injectable Cellulite Treatment Collagenase Clostridium Histolyticum-aaes: Results in Swine.

Background: Cellulite is a common aesthetic condition that affects predominantly females. Collagenase clostridium histolyticum-aaes (CCH-aaes) injections disrupt native collagen structures, resulting in an improvement in cellulite appearance. However, injection-site bruising is a frequently occurring adverse event with CCH-aaes treatment. Objectives: To characterize tissue histology following CCH-aaes injection in Yorkshire pigs. Methods: In an animal study, female swine with 10 defined dosing sites on the ventral-lateral aspect received 1 or 2 CCH-aaes (0.07 mg/0.3 mL) or placebo subcutaneous injections at a single site at designated time points before tissue sampling. Results: Injection with CCH-aaes was associated with lysis of mature, collagen-rich septa in the subcutaneous layer at and adjacent to the injection site as early as Day 1. On Day 4, an increase in inflammatory cells and a decrease in hemorrhage (vs Day 2) were observed, with inflammation and hemorrhage decreased by Day 8. By Day 21, deposition of new collagen and reorganization of fat lobules were observed. Observations with repeat CCH-aaes treatment were comparable with 1 course of CCH-aaes treatment. Conclusions: In this animal study, targeted enzymatic subcision of collagenous bands and remodeling of subcutaneous tissue were observed following CCH-aaes injection.

Treatment of mild to severe acne with 1726 nm laser: A safe alternative to traditional acne therapies.

INTRODUCTION: Acne is the most common reason for dermatology consultation in adolescents and young adults. Consultation is often delayed despite unsuccessful self-treatment. Postponing effective treatment places acne sufferers at higher risk for permanent acne scars and post-inflammatory pigment changes. AIM: This review discusses clinical challenges with present therapeutic options for acne treatment and the role of a 1726 nm laser for acne. METHODS: Current acne treatment guidelines were reviewed. A literature review was conducted for trials of light-based acne therapy. The selectivity of previous light-based therapies was reviewed. RESULTS: Available acne therapy is effective, but treatment-related side effects are common. Acne treatment guidelines do not include recommendations for light-based treatments. Different types of light-based treatments have been tried but until now no wavelength specifically targeted sebaceous glands. CONCLUSION: The 1726 nm laser is safe and effective for treating mild to severe acne in all Fitzpatrick skin types. Acne resolution is apparent within the first month and improves for up to 2 years beyond treatment.

Real-world effectiveness and safety of collagenase clostridium histolyticum-aaes injections for the treatment of thigh cellulite in women: An open-label study interim analysis.

BACKGROUND: Collagenase clostridium histolyticum-aaes (CCH-aaes) is approved in the United States for moderate-to-severe cellulite in the buttocks of adult women. AIM: Interim analysis to evaluate efficacy/safety of CCH-aaes in the treatment of thigh cellulite. METHODS: Data were analyzed from a phase 3, open-label study (REAL). Women with mild-to-moderate cellulite on both thighs (Clinician Reported Photonumeric Cellulite Severity Scale score, 2 or 3) received ≤0.84 mg (volume, 18 ml) of CCH-aaes subcutaneously, in up to 12 dimples per posterolateral thigh, in up to 3 treatment sessions (Days 1, 22, and 43). Follow-up was on Day 90 (interim cutoff). A subset of women participated in the concurrent study (PIXELS), which included high-definition photography and 3D-image scanning of treatment areas. RESULTS: Twenty-two women (44 thighs) were included in the interim analysis (mean age, 42.3 years; thighs with mild cellulite, 68.2%). Investigators reported high percentages of responders (score of "improved" or better on Investigator Global Aesthetic Improvement Scale) at Day 90 for either thigh (86.4%; primary endpoint) or both thighs (72.7%). Patient-reported bother due to cellulite was reduced at Day 90; mean change was 15.3 points (85.5% reduction) in BODY-Q Appraisal of Cellulite Scale total score (possible range, 11-44). In PIXELS analysis, Day 90 3D-image scans showed improvement from baseline in skin roughness in some of the treated thigh areas. The most commonly reported adverse events were injection-site bruising and pain (95.5% and 50.0% of patients, respectively). CONCLUSIONS: CCH-aaes treatment of mild-to-moderate thigh cellulite was effective and generally well tolerated, with markedly reduced cellulite-related bother.

Paradoxical hypertrichosis after laser therapy: a review.

BACKGROUND: Laser hair removal is a safe and effective procedure for the treatment of unwanted body hair but is not exempt from side effects. A rare but significant adverse effect with this treatment modality is paradoxical hypertrichosis. OBJECTIVE: To evaluate the potential etiologies, risk factors, related laser types, and treatment options for the development of excess hair after laser therapy. MATERIALS AND METHODS: An analysis of previously published case studies and review articles along with our own experience was used to gather information regarding this phenomenon. RESULTS: Paradoxical hypertrichosis has a low incidence, ranging from 0.6% to 10%, and most commonly occurs on the face and neck. All laser and light sources have the potential to cause hair induction, especially in individuals with darker skin types (III-VI); with dark, thick hair; and with underlying hormonal conditions. Possible causes include the effect of inflammatory mediators and subtherapeutic thermal injury causing induction of the hair cycle. Treatment for paradoxical hypertrichosis is laser therapy of the affected area. CONCLUSIONS: Paradoxical hypertrichosis is a rare side effect of laser hair removal; the pathogenesis of this event remains widely unknown. We recommend further large-scale studies to investigate this effect. The authors have indicated no significant interest with commercial supporters.

Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures.

BACKGROUND: Hypochlorous acid (HOCl), a naturally occurring molecule produced by the immune system, is highly active against bacterial, viral, and fungal microorganisms. Moreover, HOCl is active against biofilm and increases oxygenation of the wound site to improve healing. Natural HOCl is unstable; through technology, it can be stabilized into an effective topical antiseptic agent. AIM: This paper focuses on the use of topical stabilized HOCl in wound and scar management for pre-, peri-, and postprocedures-including its ability to reduce the occurrence hypertrophic scars and keloids. The role of the product in other skin conditions is beyond the scope of this article. METHODS: A panel comprising clinicians with experience in cosmetic and surgical procedures met late 2018 to discuss literature search results and their own current clinical experience regarding topical stabilized HOCl. The panel of key opinion leaders in dermatology and plastic surgery defined key insights and consensus statements on the direction of use for the product. RESULTS: Topical stabilized HOCl provides an optimal wound healing environment and, when combined with silicone, may be ideal for reducing scarring. Additionally, in contrast to chlorhexidine, HOCl, used as an antiseptic skin preparation, raises no concerns of ocular- or ototoxicity. CONCLUSIONS: For wound care and scar management, topical stabilized HOCl conveys powerful microbicidal and antibiofilm properties, in addition to potency as a topical wound healing agent. It may offer physicians an alternative to other less desirable wound care measures.

Review of the efficacy, durability, and safety data of two nonanimal stabilized hyaluronic acid fillers from a prospective, randomized, comparative, multicenter study.

BACKGROUND: Nonanimal stabilized hyaluronic acid (NASHA)-based fillers are currently the criterion standard for cosmetic soft tissue augmentation. OBJECTIVE: To report the efficacy, durability, and safety data of a large-particle NASHA filler and a small-particle NASHA filler. METHODS & MATERIALS: A blinded, prospective, randomized subject and evaluator study was conducted at 17 sites in the United States with 248 subjects enrolled. One of the two products was injected into both nasolabial folds and, if deemed necessary, the oral commissures of each subject. A 2-week touch-up injection was provided if necessary. Subjects returned for follow-up visits 2, 6, 12, and 24 weeks after receiving their last injection. Assessments were done using a subject diary, blinded investigator's Wrinkle Severity Rating Score (WSRS), and palpability of product. RESULTS: Both products demonstrated similar efficacy, durability, and safety profiles. CONCLUSION: Although both NASHA fillers demonstrated similar efficacy, durability, and safety, the fanning injection technique, and a faster rate of injection played a key role in the increase in incidence of adverse experiences. Furthermore, the safety of each NASHA product was demonstrated at volumes well beyond the volume range listed on the product inserts.

Topical methyl aminolevulinate photodynamic therapy using red light-emitting diode light for multiple actinic keratoses: a randomized study.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AKs). Light-emitting diodes (LEDs) offer practical advantages when treating multiple lesions. OBJECTIVE: To evaluate the efficacy and tolerability of PDT using a LED and topical methyl aminolevulinate (MAL) for treatment of multiple AKs. METHODS AND MATERIALS: One hundred thirty-one patients with four to 10 non-pigmented, previously untreated thin or moderately thick AKs on the face or scalp were enrolled in this multicenter, double-blind, randomized, placebo-controlled study. MAL or matching placebo cream was applied to the débrided lesion surface for 3 hours before illumination with noncoherent red light (630 nm, light dose 37 J/cm(2)). Treatment was repeated 1 week later. RESULTS: Efficacy was evaluated in 57 patients with 418 lesions treated with MAL PDT and 58 with 414 lesions treated with placebo PDT. Sixteen patients were excluded as protocol violators (not randomized). MAL PDT was superior (p< .001) to placebo PDT in lesion complete response rates (83.3%, 95% confidence interval (CI)=79.3-86.7%, vs 28.7%, 95% CI=24.4-33.4%) and patient complete response rates (all lesions showing complete response; 68.4%, 95% CI=54.8-80.1% vs 6.9%, 95% CI=1.9-16.7%). CONCLUSIONS: Topical MAL PDT using a LED is an effective treatment for multiple AKs.

The role of topical vitamin K oxide gel in the resolution of postprocedural purpura.

BACKGROUND AND OBJECTIVE: Facial purpura is a frequent barrier to patient acceptance and satisfaction with the results of various cosmetic procedures. Methods to shorten the duration of purpura after such procedures are often sought by patients. This study evaluated the efficacy and safety of a topical gel containing vitamin K oxide in the resolution of laser induced purpura. METHODS: In this randomized, double-blinded, placebo-controlled split-face study, 20 subjects with bilateral facial telangiectasia were treated with a pulsed dye laser (PDL) device at purpuric settings. The test articles, a gel containing vitamin K oxide and placebo (vehicle), were each randomly assigned to one side of the subject's face. Subjects applied the test articles twice a day for the following 9 +/- 1 days. Improvement in both focal and general field purpura on each side of the face was assessed by the investigator using photographs. A scale of -100% (worsening) to 100% (improving) was used to rate photos against a baseline photograph obtained 15-30 minutes after treatment with the PDL device. RESULTS: Resolution of the field of purpura was consistently greater with the vitamin K oxide gel after the second day of treatment. The greatest difference between the vitamin K oxide gel and placebo scores occurred on the fourth day after treatment. Although differences in active versus placebo scores did not reach statistical significance during the nine-day study period, a trend toward faster resolution of purpura with the active product was seen. Treatment-related adverse effects were not observed in any subject. CONCLUSION: Vitamin K oxide gel appears to hasten the resolution of pulsed dye laser-induced purpura in subjects being treated for bilateral facial telangiectasia, and may well be useful in accelerating resolution of facial bruising from other cosmetic procedures such as fillers used for soft-tissue augmentation as well as other types of cutaneous surgical procedures.

Online patient-reported reviews of Mohs micrographic surgery: qualitative analysis of positive and negative experiences.

Mohs micrographic surgery (MMS) is the gold standard for treating high-risk skin cancers and skin cancers in areas where skin sparing is essential. However, relatively little is known about patient-reported satisfaction with this procedure. In this study, we used qualitative research methods to determine themes of patient-reported satisfaction and dissatisfaction with MMS on one popular online resource (RealSelf). Real-world patient feedback provides an opportunity for physicians to explore the patient mind-set and to target areas of potential improvement in MMS patient satisfaction.

Nevus spilus: is the presence of hair associated with an increased risk for melanoma?

Nevus spilus (NS), also known as speckled lentiginous nevus, is characterized by background café au lait-like lentiginous melanocytic hyperplasia speckled with small, 1- to 3-mm, darker foci. Nevus spilus occurs in 1.3% to 2.3% of the adult population worldwide. Reports of melanoma arising within hypertrichotic NS suggest that hypertrichosis may be a marker for the development of melanoma. We present a case of a hypertrichotic NS without melanoma and also provide a review of previously reported cases of hypertrichosis in NS. We believe that NS has a lower risk for malignant degeneration than congenital melanocytic nevi (CMN) of the same size, and it is unlikely that hypertrichosis is a marker for melanoma in NS.

Topical 5-aminolevulinic acid combined with intense pulsed light in the treatment of photoaging.

BACKGROUND: The adjunctive use of 5-aminolevulinic acid (5-ALA) with intense pulsed-light (IPL) treatments has been suggested to increase the benefit of IPL for photoaging; however, to our knowledge, no controlled trials have been performed. DESIGN: A prospective, randomized, controlled, split-face study was designed. Twenty subjects participated in a series of 3 split-face treatments 3 weeks apart in which half of the face was pretreated with 5-ALA followed by IPL treatment while the other half was treated with IPL alone. Two additional full-face treatments (with IPL alone) were then delivered 3 weeks apart. Assessment of global photodamage, fine lines, mottled pigmentation, tactile roughness, and sallowness (on a scale of 0-4) was performed by a blinded investigator before each treatment and 4 weeks after the final treatment. Patients also completed an assessment at the conclusion of the study comparing their results with pretreatment photographs. RESULTS: All 20 volunteers completed the study. Pretreatment with 5-ALA resulted in more improvement in the global score for photoaging (16 [80%] subjects vs 9 [45%] subjects; P = .008) and mottled pigmentation (19 [95%] subjects vs 12 [60%] subjects; P = .008) than IPL treatment alone. More successful results were achieved on the side pretreated with 5-ALA compared with the side treated with IPL alone for fine lines (12 [60%] subjects vs 5 [25%] subjects; P = .008) and mottled pigmentation (17 [85%] subjects vs 4 [20%] subjects; P < .001). While there was noticeable improvement over baseline scores with respect to tactile roughness and sallowness, pretreatment with 5-ALA did not seem to enhance the results of the IPL treatment. The final investigator cosmetic evaluations (P=.0002) and subject satisfaction scores (P=.005) were significantly better for the 5-ALA-pretreated side. Both treatments were well tolerated, with little difference in the incidence or profile of adverse effects with or without 5-ALA pretreatment. CONCLUSIONS: The adjunctive use of 5-ALA in the treatment of facial photoaging with IPL provides significantly greater improvement in global photodamage, mottled pigmentation, and fine lines than treatment with IPL alone, without a significant increase in adverse effects. This combination treatment enhances the results of photorejuvenation and improves patient satisfaction.