Efficacy of Botulinum Toxin in the Treatment of Cutaneous Flushing: A Systematic Review and Meta-Analysis.

BACKGROUND: Flushing is a common dermatologic complaint and can be resistant to many treatments. As the utility of botulinum toxin continues to expand, recent data suggest that it may also be a therapeutic option for flushing. OBJECTIVE: To evaluate the efficacy of botulinum toxin for the treatment of cutaneous flushing. MATERIALS AND METHODS: A systematic search of Medline, Embase, Cochrane CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted to identify studies evaluating the effect of botulinum toxin on flushing 1 month after treatment. Prespecified outcome measures included a clinical flushing score, dermatology life quality index (DLQI), and erythema index (EI). Meta-analysis was performed to calculate the mean differences in these outcomes before and after treatment at 1-month follow-up. RESULTS: Nine studies (132 patients) were included in the analysis of this study (2 randomized controlled trials and 7 nonrandomized studies). All studies had a low risk of bias (high quality). The most frequent outcome reported was a clinical flushing score, which significantly decreased by 1.25 points overall (95% confidence interval [CI]: -2.47; -0.04) 1 month after treatment with botulinum toxin. Mean DLQI scores decreased (i.e., improved) by 9.02 points (95% CI: -19.81; 1.77) 1 month after botulinum toxin injections. The EI (measured by Mexameter) before and after botulinum toxin was evaluated in 2 studies; however, not enough statistical information was provided to analyze with meta-analytic techniques. CONCLUSION: Based on this meta-analysis, botulinum toxin significantly improves clinical flushing scores 1 month after treatment.

A Pilot Study of the Safety and Effectiveness of a Novel Device in Subjects With Axillary Hyperhidrosis.

BACKGROUND: One-third of U.S. adults are bothered by excessive sweating and 5% suffer from hyperhidrosis, both of which negatively affect quality-of-life (QoL). A single-use disposable patch using the novel targeted alkali thermolysis (TAT) technology is being developed to address this condition. OBJECTIVE: Assess the efficacy and safety of the TAT patch for the treatment of excessive sweating using a randomized, double-blind, sham-controlled study design. MATERIALS AND METHODS: Adults with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 ( n = 16) were treated with an active or sham patch for up to 3 minutes (as established in a previous unpublished feasibility study) and evaluated weekly for 6 weeks post-treatment. The primary effectiveness measure was improved HDSS at Week-4. RESULTS: The study met its objective. For the primary efficacy measure, 83% of TAT-treated subjects reported HDSS scores of 1 or 2 at Week-4 versus 0% of sham-treated subjects ( p = .0032). Furthermore, 67% of TAT-treated subjects had a 2-point improvement in HDSS scores versus 0% of sham-treated subjects ( p = .0123). Quality-of-life improvement correlated with HDSS. The TAT patch seemed to be well-tolerated; one transient moderate adverse event that resolved without sequelae was reported. CONCLUSION: The TAT patch successfully demonstrated efficacy and was well-tolerated.

Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A.

Botulinum toxin type A (BoNTA) products are widely used for therapeutic and aesthetic indications, but there is a need for longer-lasting treatments that maintain symptom relief between injections and reduce the frequency of re-treatment. DaxibotulinumtoxinA for Injection (DAXI) is a novel BoNTA product containing highly purified 150-kDa core neurotoxin and is the first to be formulated with a proprietary stabilizing excipient peptide (RTP004) instead of human serum albumin. The positively charged RTP004 has been shown to enhance binding of the neurotoxin to neuronal surfaces, which may enhance the likelihood of neurotoxin internalization. DAXI produces robust, extended efficacy across both aesthetic and therapeutic indications. In an extensive glabellar lines clinical program, DAXI showed a high degree of efficacy, a consistent median time to loss of none or mild glabellar line severity of 24 weeks, and median time until return to baseline of up to 28 weeks. In adults with cervical dystonia, DAXI at 125 U and 250 U significantly improved Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores, with a median duration of efficacy of 24 and 20 weeks, respectively, which compares favorably with the 12-14 weeks' duration reported for approved BoNTA products. Overall, DAXI was well tolerated, and the consistent extended duration of effect suggests that DAXI has the potential to improve the management of both aesthetic and therapeutic conditions.

Botulinum toxin is used to block the nerve signals that cause muscles to contract. Products containing botulinum toxin are commonly given by injection to treat muscle spasms (such as cervical dystonia, a painful condition where the neck muscles contract involuntarily) and for cosmetic treatment of frown lines. However, the effects of the currently approved botulinum toxin products typically wear off about 3­4 months after injection and so the injections must be repeated regularly. A new product called DAXI (DaxibotulinumtoxinA for Injection) has been developed. In this product, the botulinum toxin is formulated with a unique protein (called RTP004) that has been designed to help deliver the botulinum toxin to the nerve cells. Research suggests that the RTP004 protein in DAXI adheres the botulinum toxin to the nerves close to the injection site, potentially making its effect last longer. To date, DAXI has been studied in over 3800 patients. The studies have shown that DAXI is effective for treating neck spasms (cervical dystonia) and for reducing the appearance of frown lines. Importantly, the effects of DAXI lasted up to 6 months, which is longer than seen with other botulinum toxin products. The side effects seen with DAXI are consistent in nature and frequency with those seen with other botulinum toxin products. These findings suggest that DAXI can improve both medical and cosmetic treatments due to its longer-lasting effect.

Deformation of Needle Tips During Facial Soft Tissue Filler Injections: An Electron-Microscopic Study.

BACKGROUND: Injectable soft tissue fillers are used on a global scale for a variety of aesthetic indications. Despite their widespread use, there is a dearth of information regarding needle deformation following injection procedures. Repeated injections with the same needle could lead to progressive needle tip deformation, potentially resulting in decreased precision and increased patient discomfort. OBJECTIVES: The objective of this study was to quantify the magnitude of needle tip deformation utilizing scanning electron microscopy (SEM) image analysis. METHODS: An observational study was performed evaluating 4 differently sized needles following soft tissue filler injections for 5 different aesthetic indications (zygomatic arch, infraorbital, midcheek, nasolabial sulcus, and perioral) in patients aged 36 to 64 years. Following treatment, each needle was visualized and imaged through SEM, and the percentage of deformation in relation to the total amount of needle tip surface was calculated. RESULTS: The factor most influencing needle tip damage was revealed to be the number of injection passes, ie, dermal transitions. Per injection procedure, an increase in needle tip damage of 4.7% occurred. Touching the bone deformed the needle tip by 9.6% and an increase in needle size resulted in 0.13% more damage. CONCLUSIONS: To the authors' knowledge, this is the first SEM investigation to provide objective evidence for the deformation of needle tips after repeated facial soft tissue filler injections. These data may help improve patient safety and comfort during these minimally invasive procedures.

CME: Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update.

Since initial US Food and Drug Administration approval of botulinum toxin type A (BoNT-A) for aesthetic use in 2002, clinical evidence and experience with BoNT-A and understanding of facial anatomy have greatly increased, leading to rapid advances in treatment planning and implementation. BoNT-A use has expanded from the upper face to the midface, lower face, and neck, so that BoNT-A injection is the most common cosmetic procedure worldwide. Trends in facial aesthetics reflect growing patient diversity with respect to age, gender, and ethnicity. In October 2019, a multidisciplinary panel of 6 experts in minimally invasive injectable procedures in the specialties of dermatology and plastic surgery convened at the 2019 American Society for Dermatologic Surgery (ASDS) meeting in Chicago, IL. Their goal was to discuss recent advances in BoNT-A use in facial aesthetics, including implications of the introduction of new agents in light of an evolving patient population. J Drugs Dermatol. 2020;19(4 Suppl 1):s5-15To receive a CME certificate of participation, you should: •Read the entire publication, including the CME information. •Register or log in at www.paradigmmc.com/822 to complete and submit the online posttest and evaluation. Following online completion of the posttest and evaluation, a certificate of participation will be available for download/printing immediately.Erratum published for this article here.

Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update

Since initial US Food and Drug Administration approval of botulinum toxin type A (BoNT-A) for aesthetic use in 2002, clinical evidence and experience with BoNT-A and understanding of facial anatomy have greatly increased, leading to rapid advances in treatment planning and implementation. BoNT-A use has expanded from the upper face to the midface, lower face, and neck, so that BoNT-A injection is the most common cosmetic procedure worldwide. Trends in facial aesthetics reflect growing patient diversity with respect to age, gender, and ethnicity. In October 2019, a multidisciplinary panel of 6 experts in minimally invasive injectable procedures in the specialties of dermatology and plastic surgery convened at the 2019 American Society for Dermatologic Surgery (ASDS) meeting in Chicago, IL. Their goal was to discuss recent advances in BoNT-A use in facial aesthetics, including implications of the introduction of new agents in light of an evolving patient population. J Drugs Dermatol. 2020;19(4 Suppl 1):s5-15 To receive a CME certificate of participation, you should: •Read the entire publication, including the CME information. •Register or log in at www.paradigmmc.com/822 to complete and submit the online posttest and evaluation. Following online completion of the posttest and evaluation, a certificate of participation will be available for download/printing immediately.

Impact of Smoking and Alcohol Use on Facial Aging in Women: Results of a Large Multinational, Multiracial, Cross-sectional Survey.

Objective: Data on associations between facial aging and smoking or alcohol consumption are generally derived from small studies, and therefore, vary. The aim of this large multinational study was to determine more accurately which clinical signs of skin- and volume-related facial aging are associated with tobacco and alcohol use in women. Design: This was a subanalysis of a global, cross-sectional, Internet-based survey of self-reported facial aging. Participants: Women aged 18 to 75 years old (n=3,267) from the United States, Australia, Canada, and the United Kingdom who described themselves as white, Asian, black, or Hispanic were included. Measurements: Using a mirror, participants determined their own aging severity on photonumeric rating scales for 11 facial characteristics. Linear regressions were used to assess associations between each feature's severity and smoking status (never vs. current and former smoker); smoking pack years (0 versus 1-10, 11-20, and >20 years); alcohol use (none vs. moderate and heavy); and alcoholic beverage type, after controlling for body mass index, country, age, and race. Results: Smoking was associated with an increased severity of forehead, crow's feet, and glabellar lines; under-eye puffiness; tear-trough hollowing; nasolabial folds; oral commissures; perioral lines; and reduced lip fullness (p≤0.025) but not midface volume loss or visible blood vessels. Heavy alcohol use (≥8 drinks/week) was associated with increased upper facial lines, under-eye puffiness, oral commissures, midface volume loss, and blood vessels (p≤0.042). Conclusion: Smoking and alcohol consumption significantly but differentially impact skin and volume-related facial aging.

Clinical Assessment of 2 Licensed AbobotulinumtoxinA Injection Volumes for the Treatment of Glabellar Lines.

BACKGROUND: Two licensed reconstitution volumes may be used to achieve the recommended abobotulinumtoxinA (ABO) dose for glabellar line correction. OBJECTIVE: Comparison of efficacy, safety, and subject satisfaction concerning treatment of moderate to severe glabellar lines with 2 different ABO reconstitution volumes. MATERIALS AND METHODS: Phase IV, prospective, randomized, multicenter, subject- and evaluator-blinded study: 60 subjects received 1 ABO (50 units) treatment, administered as a 1.5- or 2.5-mL reconstitution. Primary objective was Day 30 improvements (≥1-point) in glabellar line severity. Onset of effect, duration, subject satisfaction, and treatment-related adverse events (AEs) were assessed. RESULTS: At Day 30, 90.0% and 86.7% of subjects achieved ≥1-point improvements with 1.5- and 2.5-mL reconstitutions, respectively. Median time to onset of effect was 48 hours after treatment. At 24 hours, 26.7% achieved ≥1-point improvements with the 2.5-mL reconstitution versus 6.7% with the 1.5-mL reconstitution. Maximum response was at Day 14, and >40% maintained efficacy through Day 120 in each group. High subject satisfaction was sustained throughout observation. Most AEs were mild. No serious AEs were reported. CONCLUSION: Both ABO reconstitutions were well tolerated and effective in correcting glabellar lines with no significant differences concerning efficacy or duration of effect. No serious AEs were reported.

Topical Oxymetazoline Cream 1.0% for Persistent Facial Erythema Associated With Rosacea: Pooled Analysis of the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Background: Rosacea is a chronic dermatologic condition with limited treatment options. Methods: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Conclusion: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated. J Drugs Dermatol. 2018;17(11):1201-1208.

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial.

Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(3):290-298.

New Uses of AbobotulinumtoxinA in Aesthetics.

BotulinumtoxinA (BoNT-A) is now widely established for the main approved indication of reducing glabellar lines, and is also widely used off-label to improve the appearance of wrinkles and lines in other parts of the face. The number of aesthetic procedures continues to increase as the patient population becomes more diverse, in particular with increasing numbers of people of color and men. Further developments in treatment may continue to expand the audience for BoNT-A by making procedures more comfortable and by delivering a more natural, less static appearance. These may be achieved through use of combinations of BoNT-A with other aesthetic procedures, tailoring the dose of toxin to the patient's muscle mass or by using novel injection and application techniques. Beyond amelioration of facial lines, encouraging results have been seen with the use of BoNT-A to improve the appearance of hypertrophic and keloid scars and even to prevent them. Studies have been conducted with scars in various parts of the body and further research is ongoing. Dermatological and other medical uses for BoNT-A are also active areas of research. Injections of BoNT-A have been shown to reduce signs and symptoms of acne, rosacea, and psoriasis, to reduce neuromuscular pain, and to bring about significant improvements in a number of rare diseases that are caused or exacerbated by hyperhidrosis. This paper reviews these new uses for BoNT-A, looking at the rationale for their use and discussing the results of published case studies and clinical trials. These areas have shown great promise to date, but more and larger clinical studies will be required before these treatments become a clinical reality. To this end details are also provided of clinical trials currently listed in the main clinical trials database to highlight research areas of particular interest.

Combining Microfocused Ultrasound With Botulinum Toxin and Temporary and Semi-Permanent Dermal Fillers: Safety and Current Use.

BACKGROUND: A microfocused ultrasound system with visualization (MFU-V) is currently indicated for use as a noninvasive dermatological aesthetic treatment to lift the eyebrows, lax submental and neck tissue, and improve lines and wrinkles of the décolleté. OBJECTIVE: To determine the existence of any safety signals when combining MFU-V with botulinum toxin-A and/or semipermanent and temporary dermal fillers. MATERIALS AND METHODS: A retrospective chart review was performed using subjects who received aesthetic treatments including incobotulinumtoxinA injection, cohesive polydensified matrix hyaluronic acid (CPM HA) dermal fillers, and calcium hydroxylapatite (CaHA) dermal fillers within 6 months of treatment with MFU-V in the same or different anatomic areas. RESULTS: All subjects (N = 101; 96 female; 25-70 year old) received MFU-V, 18% received incobotulinumtoxinA injections, and 81% were treated with CPM HA and/or CaHA fillers. Seven adverse events (7%) were reported: bruising/purpura (n = 4), swelling (n = 1), paresthesia (n = 1), and herpes simplex virus (HSV) outbreak (n = 1). Only the HSV outbreak was considered to be related to combined treatments. CONCLUSION: Although limited by relatively few subjects, the results of the present study suggest that the safety profile of MFU-V combined with other aesthetic products is consistent with the safety profiles of the individual treatments.

Therapeutic approaches to cellulite.

Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution.

Laser and Light-Based Aesthetics in Men.

Men represent an important evolving segment of the cosmetic market. With the growing acceptability of cosmetic procedures along with societal and workplace pressure to maintain youthfulness, men increasingly seek the advice of aesthetic practitioners. Despite this so-called "Menaissance," there is a paucity of published literature regarding laser and light treatments of male skin. Herein the differences in male cutaneous physiology are addressed, followed by a review of light-based treatment of conditions largely unique to male skin, pseudofolliculitis barbae, and rhinophyma. Next, the publications related to laser treatment of male skin specifically are examined. We conclude with a discussion of personal observations derived from clinical experience with laser and light-based treatments in men.

Nonablative fractional resurfacing.

Since its introduction in 2004 by Manstein et al, fractional resurfacing has revolutionized the manner in which we treat photoaging. Fractional resurfacing delivers microscopic beams of light to the skin resulting in coagulation or vaporization of fragments of the epidermis and dermis. The wavelengths of these devices may vary, yielding different clinical results. This article will discuss the various uses of fractional ablative and nonablative devices available today.

Picosecond lasers: the next generation of short-pulsed lasers.

Selective photothermolysis, first discussed in the context of targeted microsurgery in 1983, proposed that the optimal parameters for specific thermal damage rely critically on the duration over which energy is delivered to the tissue. At that time, nonspecific thermal damage had been an intrinsic limitation of all commercially available lasers, despite efforts to mitigate this by a variety of compensatory cooling mechanisms. Fifteen years later, experimental picosecond lasers were first reported in the dermatological literature to demonstrate greater efficacy over their nanosecond predecessors in the context of targeted destruction of tattoo ink. Within the last 4 years, more than a decade after those experiments, the first commercially available cutaneous picosecond laser unit became available (Cynosure, Westford, Massachusetts), and several pilot studies have demonstrated its utility in tattoo removal. An experimental picosecond infrared laser has also recently demonstrated a nonthermal tissue ablative capability in soft tissue, bone, and dentin. In this article, we review the published data pertaining to dermatology on picosecond lasers from their initial reports to the present as well as discuss forthcoming technology.

Laser principles.

Since the construction of the first laser in the 1960s, the role that lasers play in various medical specialities, including dermatology, has steadily increased. However, within the last 2 decades, the technological advances and the use of lasers in the field of dermatology have virtually exploded. Many treatments have only become possible with the use of lasers. Especially in aesthetic medicine, lasers are an essential tool in the treatment armamentarium. Due to better research and understanding of the physics of light and skin, there is now a wide and increasing array of different lasers and devices to choose from. The proper laser selection for each indication and treatment requires a profound understanding of laser physics and the basic laser principles. Understanding these principles will allow the laser operator to obtain better results and help avoid complications. This chapter will give an in-depth overview of the physical principles relevant in cutaneous laser surgery.

Fractional photothermolysis.

The novel concept of 'fractional photothermolysis' was introduced to the market in 2003, and has since gained tremendous popularity and importance for numerous clinical indications. Its development and introduction were driven by the need for an effective yet safe and low-risk resurfacing technique, in contrast to the ablative and non-ablative lasers available at the time. The first device that was introduced to the market used non-ablative wavelengths. In 2007, the technology was further developed with ablative wavelengths leading to vaporization of tissue. This new technology has revolutionized the field of laser skin resurfacing and resulted in the development of numerous non-ablative and ablative fractional devices. There is little doubt that fractional technology is here to stay, as (when used properly) it allows the operator to obtain significant clinical results with minimal post-treatment recovery and hence fewer complications.

1550-nm nonablative laser resurfacing for facial surgical scars.

OBJECTIVE: To investigate the efficacy of 1550-nm (Fraxel SR1500 RE:Store; Solta Medical, Hayward, California) nonablative laser treatment of facial surgical scars. METHODS: In this prospective clinical study, a volunteer sample of 13 adults with Fitzpatrick skin types I to III and facial surgical scars with a postoperative duration longer than 6 months were enrolled. Subjects were treated once every 4 weeks for a total of 4 treatments. Initial settings for the 1550-nm nonablative laser were at energy level 40 mJ and treatment level 4 and were subsequently increased on each visit according to the patients' tolerance level. Using a previously validated Patient and Observer Scar Assessment Scale (POSAS), the study subject and an independent evaluator completed assessments of the scar at each visit. RESULTS: According to the Friedman test on ratings across all occasions after the first treatment to the last evaluation, there was a statistically significant improvement in the patient's assessment of the color, stiffness, thickness, and irregularity of the scar but not for pain or itching. For the observer's ratings, there was a statistically significant improvement in pigmentation, thickness, relief, and pliability but not for vascularization. CONCLUSIONS: Preliminary data suggest improved aesthetic results, demonstrating the potential use of fractional photothermolysis as a scar revision technique. Future studies with a longer follow-up period could elucidate the role of fractional photothermolysis in more permanent scar improvements.