Extension Phase of a Multi-Center, Randomized, Blinded Clinical Study Evaluating the Efficacy and Safety of a Novel Topical Product for Facial Dyschromia.

BACKGROUND: Dyschromia can be associated with increased production and/or reduced clearance of pigmentation in the skin. Multiple pathways are involved in causality. A novel topical product was recently developed, which contains actives that have been validated through in-vitro and clinical studies to counteract pigmentation related to photodamage, PIH, and melasma. This study further evaluates the safety and efficacy of this product for facial dyschromia during an additional 3-month extension period following the completion of the previous 12-week multi-center trial.  Study Design: Subjects from the previous multi-center trial with mild to severe facial dyschromia at baseline were eligible to participate in this 3-month extension study upon completion of that trial. This extension study evaluated the continued use of the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) over a 3-month period. Subjects who were previously randomized to the novel topical product continued using it and for those previously randomized to hydroquinone 4% discontinued its use. Both cohorts continued daily sunscreen use. Blinded investigators assessed subjects at follow-up visits at 16, 20, and 24 weeks. RESULTS: Twenty-six (26) subjects completed the extension phase of the pivotal trial, with 13 subjects in each of the AL and HQ-BREAK cohorts. Significant improvements were seen within the AL cohort from weeks 12 to 24 for facial dyschromia (P=0.0158) and skin tone/clarity/evenness (P=0.0067), while there were no significant improvements seen in the HQ-BREAK cohort. The HQ-BREAK cohort had more subjects who worsened with facial dyschromia and skin tone/clarity/evenness. For the mMASI, the HQ-BREAK cohort demonstrated regression at week 24 compared to week 12, while the AL cohort instead experienced continued improvement. This difference was found to be significant (P=0.02). No study-related adverse events were reported for either cohort.  Conclusion: A novel topical product designed to counteract various steps in pigmentation pathways using PATH-3 Technology has been demonstrated to be safe and effective in treating facial dyschromia on a long-term basis. In contrast to the significant rebound experienced by subjects with HQ, the AL cohort continued to demonstrate ongoing improvement. J Drugs Dermatol. 2024;23(1):1266-1270.     doi:10.36849/JDD.7622.

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.

Multicenter evaluation of a topical hyaluronic acid serum.

BACKGROUND: A new hyaluronic acid (HA) formulation was developed based on high molecular weight (MW) compounds used on the surface of the skin while using peptides to stimulate the high MW HA production by fibroblasts and keratinocytes from within the skin layers. Detailed science has been submitted to this journal in a previous publication. This multicenter study aims to validate the science by demonstrating the safety and efficacy of the product in the clinical realm. OBJECTIVES: This study evaluated the efficacy and safety of a topical HA serum in facial skin. METHODS: An open-label clinical study was undertaken over 4 months from November 2021 to March 2022. Participants applied the topical serum twice daily and were provided a gentle cleanser and an SPF 30+ to use in the morning. Follow-up visits were conducted at weeks 2, 4, and 8. At every visit, participants were measured for hydration post 15 minutes of cleansing the skin and post 15 minutes of product application for cumulative skin hydration sensor measurements. Additional procedures included participant assessments and satisfaction, investigator assessments, biopsies, and photography. RESULTS: At each follow-up visit, there was an increase in hydration measurements compared to baseline, in both immediate scores and cumulative long-term scores. At weeks 4 and 8, there was a statistically significant increase in hydration compared to baseline and the prior visit. Participants' assessments progressively increased over 2-, 4-, and 8-week intervals with significantly favorable ratings in all measured parameters. Similarly, investigator assessment grades were statistically significant (p < 0.0001) for decreased fine lines/wrinkling, crepiness, texture, erythema, and dryness, and increased (p < 0.0001) for moisture/hydration. Histology revealed increased CD44 staining in 6 of the 7 participants biopsied, denoting increased HA stimulation. In all of the participant biopsies, H&E staining demonstrated improvement in solar elastosis. Photography revealed remarkable improvement in erythema, tone, and texture. CONCLUSIONS: The study results demonstrated that the formulation produced significant improvements in immediate and long-term hydration effects on the skin as measured by the skin hydration sensor, 'wearifi' technology, comparison of before and after biopsies, and participant and investigator assessments. This high MW HA formulation produced excellent clinical improvement in skin health and hydration.

Intraarterial Degradation of Calcium Hydroxylapatite Using Sodium Thiosulfate - An In Vitro and Cadaveric Study.

BACKGROUND: The most severe complications following soft tissue filler injections result from the intraarterial administration of the filler product. Although hyaluronic acid-based filler can be trans-arterially dissolved with hyaluronidase, no information is available on calcium hydroxylapatite (CaHA)-based fillers. OBJECTIVE: The authors sought to test whether CaHA-based fillers can be trans-arterially dissolved by sodium thiosulfate (STS) when evaluated in cadaveric and in vitro models. METHODS: Human cadaveric facial arterial segments were each filled with 0.2 cc of commercially available CaHA product and submerged for 24 hours in 4 different STS-containing solutions: 10 cc STS (300 mg/cc) (pure, 1:1 dilution, 1:2 dilution), 0.9% saline and 10 cc STS (300 mg/cc), and 300 IU (bovine) hyaluronidase in a 1:1 ratio. RESULTS: Intraarterial CaHA was detected in human facial artery segments after 24 hours independent of the STS concentration employed. Submerging the arterial segments in STS (300 mg/cc) and 300 IU (bovine) hyaluronidase (1:1 ratio) also did not dissolve the intraarterial CaHA product. Gray scale analyses did show, however, that increasing concentrations of STS resulted in increased disintegration of CaHA in an in vitro experimental setting. CONCLUSIONS: The results of this study indicate that STS is limited in its potential to dissolve intraarterial CaHA of cadaveric human facial arteries, despite the fact that it appears effective when in direct contact with the CaHA. Adverse events caused by intraarterial administration of CaHA-based fillers still lack a suitable antidote.

Clinical evidence of the efficacy and safety of a new 3-in-1 anti-aging topical night serum-in-oil containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate: 103 females treated from 28 to 84 days.

BACKGROUND: Topical melatonin is a potent antioxidant, yet there have been few clinical studies on its anti-aging effects on the skin. OBJECTIVES: To clinically assess the anti-aging efficacy and safety of a new 3-in-1 night facial serum (NFS) combining melatonin with bakuchiol, a novel retinol-like ingredient, and ascorbyl tetraisopalmitate, in all skin types. METHODS: Five clinical studies were performed, with a total of 103 subjects treated from 28 to 84 days. Under dermatologist supervision, a 3-month efficacy and safety study evaluated anti-aging properties by clinical scoring and instrumental evaluations. Two studies evaluated skin hydration properties for 12 hours after a single application of NFS. Two studies were performed in oily skin: a 1-month efficacy and safety study and a 1-month comedogenesis study. RESULTS: After 12 weeks, clinical evaluation showed a statistically significant decrease in wrinkles (11%), an increase in skin firmness (8%), a reduction in redness (70%; P < 0.01 for all), and an overall improvement in skin quality and complexion. The reduction in wrinkles and the increase in skin firmness were also supported by instrumental evaluations (Dermatop and Dynaskin). Hydration levels increased significantly from 30 minutes until 12 hours and transepidermal water loss significantly decreased after 4H and 6H. Subjects favorably evaluated the efficacy and cosmetic properties of the serum, and it was well tolerated in all skin types including oily skin. CONCLUSIONS: This 3-in-1 NFS showed significant clinical anti-aging effects when applied once daily and was well tolerated.

Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: Findings from the 52-week open label REVEAL trial.

BACKGROUND: Limited treatments are available for persistent erythema of rosacea. OBJECTIVE: To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema. METHODS: Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52. RESULTS: Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation. LIMITATIONS: A vehicle-control group was not included. CONCLUSION: This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea.

Noninvasive body contouring.

In a society where stigma surrounds cosmetic procedures and yet a thin and sculpted physique is idealized, noninvasive body contouring satisfies the demand to reduce excess and undesired body fat in areas that persist despite exercise and diet. Numerous devices are available to meet this need; however, choosing the "perfect" device is challenging because the science and data are often limited with variable results. In this paper, we review 7 US Food and Drug Administration-approved noninvasive body contouring therapies in hopes of providing some clarity to this area.

Cellulite: a review of pathogenesis-directed therapy.

Cellulite is a condition that affects the majority of postpubertal women and can negatively impact quality of life. This review discusses several proposed pathophysiologies of cellulite, and examines treatment options that have been utilized, focusing on the etiologic factor targeted by the therapies. This approach aims to help clarify the pathogenesis of cellulite and provide a road map for developing effective treatment paradigms for patients.

Randomized, Split-Face/Décolleté Comparative Trial of Procedure Enhancement System for Fractional non-Ablative Laser Resurfacing Treatment.

INTRODUCTION: A topical proprietary procedural enhancement system (PES) containing a combination of active ingredients including a tripeptide and hexapeptide (TriHex Technology™, Alastin Procedure Enhancement Invasive System, ALASTIN Skincare™, Inc., Carlsbad, CA) has been used successfully to aid in healing and improve symptomatology following resurfacing procedures.

METHODS: PES (Gentle Cleanser, Regenerating Skin Nectar with TriHex Technology™, Ultra Nourishing Moisturizer with TriHex Technology™, Soothe + Protect Recovery Balm, Broad Spectrum 30+ Sunscreen) was compared to a basic regimen (Aquaphor™, Cerave™ cleanser, Vanicream™, Alastin Broad Spectrum 30+ Sunscreen) in a split face/ décolleté trial following fractional non-ablative thulium-doped resurfacing treatment to the face or décolleté. The skin was pre-conditioned and treated during and after the procedure using the two regimens.

RESULTS: A blinded investigator rated the PES statistically superior to the basic regimen on healing post-laser treatment on day 4 based on lentigines, texture, and Global Skin Quality. Subjects also reported 'better looking and feeling' skin on the PES side.

CONCLUSION: PES appears to improve healing post-non ablative thulium-doped resurfacing treatment to the face/décolleté in comparison with standard of care.

J Drugs Dermatol. 2017;16(7):707-710.

Midodrine-induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is an acute sterile pustular eruption most commonly induced by medications. We present a case of AGEP with erythroderma following use of midodrine in a 58-year-old man. Although antibiotics are most commonly implicated in AGEP, we emphasize that nonantibiotic agents also may cause AGEP, which often manifests after a longer time interval compared to antibiotic-associated AGEP.

Cosmetic concerns and management strategies to combat aging.

Multiple modalities with varying degrees of complexity and risks exist in the treatment of the aging face. Paramount to all treatment paradigms is photoprotection to prevent further damage. Intervetions should be geared towards addressing the intrinsic and extrinsic signs of aging and can include topical retinoid therapy, superficial chemical and laser resurfacing, botulinum toxin and soft tissue fillers. The combination of these primary, secondary, and tertiary therapies will address the underlying pathophysiologic changes of the aging face and thus will provide the optimal aesthetic outcome.

Symmetric aplasia cutis congenita associated with fetus papyraceus: report of two cases.

We present two cases of neonates born with symmetric aplasia cutis congenita associated with intrauterine fetal demise of cotwins during the early second trimester. Fetus papyraceus resulting in aplasia cutis congenita is a rare association with many clinical presentations, including extratruncal symmetric lesions and small linear, arcuate, and triangular lesions when twin intrauterine demise occurs after the first trimester.

Young-Simpson syndrome (YSS), a variant of del(1)(p36) syndrome?

The Young-Simpson syndrome (YSS) and 1p36 deletion syndrome are both characterized by facial and heart abnormalities, congenital hypothyroidism, and severe growth and developmental retardation. However, the YSS is characterized by the presence of blepharophimosis and epicanthus inversus, findings not described in monosomy 1p36 patients. We describe a girl with YSS, who presented with the typical facial findings, global retardation, congenital hypothyroidism, and congenital dilated cardiomyopathy. Comparative genomic hybridization chromosomal microarray analysis showed a 1p36.3 deletion, a finding not previously reported in other YSS cases. We propose that YSS is a variant of the 1p36 deletion syndrome.