BACKGROUND: Long-term exposure to sunlight, including ultraviolet A and B, produces signs associated with photoaging and photodamage, including laxity and discoloration of the skin. Initial laser treatment for dyspigmentation included the use of ablative lasers, followed by Q-switched lasers and more recently fractional lasers.
OBJECTIVE: We investigated the safety and efficacy of a fractionated 1927nm non-ablative thulium laser for the treatment of photo-induced pigmentation.
METHODS: Prospective multi-center study of subjects with clinically identifiable photopigmentation. The study protocol was approved by BioMed Institutional Review Board (San Diego, CA). Subjects received two treatments with a non-ablative 1927nm fractionated thulium laser (Fraxel Dual 1550/1927 Laser System, Solta, Hayward CA), energy level of 10mJ, coverage of 40% and 4-6 passes. Subject pain, erythema and edema were recorded immediately after treatment. Two dimensional photography was obtained before each treatment and at one and three month follow up visits. Independent blinded physician assessment was performed evaluating overall improvement in appearance as well as pigment specific improvement.
RESULTS: Forty men and women, ages 30 to 80 years, Fitzpatrick skin types I-IV, with photo-induced facial pigmentation were enrolled and treated, and 39 completed the three month follow up visit. Mean pain sensation for subjects during laser treatments was reported to be 4.3 on a 10-point scale. Mean scores for erythema, edema, and skin roughness throughout all treatments indicated moderate erythema, mild edema and mild skin roughness. Assessment of overall improvement was graded as moderate to very significant in 82% of subjects at one month and in 69% of subjects at three months after the second treatment. Assessment of lentigines and ephelides demonstrated moderate to very significant improvement in approximately 68% of subjects at the one month and in 51% of subjects at three months after the second treatment. Independent blinded physician assessment of randomized photography also demonstrated a durable response at three month follow up visit. Treatment was well tolerated and no serious adverse events related to treatment were observed or reported. Study limitations included a limited number of male subjects, lack of Fitzpatrick skin types V and VI, and decrease in improvement at 3 months post-treatment.
CONCLUSIONS: Two treatments with a 1927nm non-ablative fractionated thulium laser produced moderate to marked improvement in overall appearance and pigmentation with high patient satisfaction. The response to treatment was maintained at one and three months follow up.
J Drugs Dermatol. 2014;13(11):1317-1322.
BACKGROUND AND OBJECTIVES: Non-ablative fractional lasers cause little down-time, however, some patients want more noticeable results with fewer treatments. The 1940 nm wavelength matches one of the water absorption peaks in the mid infrared band of electromagnetic energy. The skin absorption is much stronger than other non-ablative wavelengths (1410-1550 nm) and weaker than ablative wavelengths (Er:YAG or CO2). The objective of this study was to characterize clinical efficacy using this technology to treat photodamaged skin in human subjects.
MATERIALS AND METHODS: Under an IRB approved study, eleven subjects with facial photodamage (1 male and 10 female) were enrolled and completed the study. The fractional 1940 nm laser was comprised of a thulium rod pumped by a pulsed alexandrite laser. The fractional patterns were generated by four separate handpieces (two dot (0.48mm and 0.76mm dot-to-dot distance or pitch) and two grid geometries) whereby a larger beam was broken up into smaller microbeams by a microlens system or reflective square grids. The low -pitch circular dot array handpiece, which is used most frequently, has a macro-spot size of 12 mm and a total applied energy of approximately 2-5 J (~ 4-10 mJ per beamlet). Contact skin cooling (5-20degC) was provided via a sapphire window at the distal end of handpiece. Pulses from the dot handpieces were applied with 20% overlap. The microspot size for the dot handpieces was ~ 0.2-0.3 mm. The two grid pattern handpieces included 0.4 mm wide lines with 45% and 0.7 mm wide lines with 65% coverage. Each subject received 3 full-face treatments 4-6 weeks apart. Anesthesia was achieved by 5% lidocaine cream and a cold air chiller. Typical treatments were carried out with two passes. Outcome assessments included changes in pigment, rhytides, laxity, elastosis, and texture, using a diffuse pigmentation scale and the Alexiades-Armenakas Comprehensive Grading Scale of Rhytides, Laxity, and Photodamage. Photographs of each patient from prior to treatment, and 3 months after treatment were analyzed by 3 blinded physician raters. A paired t-test was applied for each category comparing the pre treatment and 3-month post treatment results.
RESULTS: Three months after the final treatment, (a) mean pigment improvement was 21.1%, (b) rhytides were reduced by 14.3%, (c) laxity was reduced by 8.9%, elastosis was reduced by 22.3%, and (e) texture scores were unchanged. Reductions in pigmentation, rhytides, and elastosis were statistically significant (P ≤ 0.05). Clinical downtime was 3-5 days. Pain was variable (mean of 2.8/10) and side effects included two cases of mild focal vesiculation. No long-term side effects were noted. Histological analysis showed focal damage that extended about 200 μm deep to the surface.
CONCLUSION: The 1940nm thulium laser is safe, well tolerated, and results in reduced downtime compared to traditional resurfacing. The study demonstrated that the 1940 nm thulium laser could achieve injury patterns capable of skin rejuvenation.
J Drugs Dermatol. 2014;13(11):1324-1329.
As the aging population in our society continues to grow, new technologies and procedures promising a more youthful appearance are continuously sought. The utilization of radiofrequency technology remains a novel method for the treatment of many aesthetic and medical dermatological indications. Innovative applications are constantly identified, expanding treatment options for various patient concerns including aging of the hands, cellulite, non-invasive lipolysis, and postpartum skin laxity. Non-invasive treatments are ideal for busy patients seeking minimal recovery time and so called lunch-time procedures. Furthermore, new developments in treatment devices enhance efficacy while decreasing patient discomfort.
J Drugs Dermatol. 2014;13(11):1331-1335.
BACKGROUND: The purpose of this study was to demonstrate the effect of monopolar, focused radiofrequency (RF) with embedded cooling on subcutaneous skin structures. Specifically, the study was to prove that the monopolar RF with cooling can selectively heat fat, causing disintegration of adipocytes and programmed cell death (apoptosis) of the subcutaneous fat cells.
METHODS: A non-invasive monopolar RF device with cooling (Exilis Elite, BTL Industries, Framingham, MA) was used to reduce abdominal fat in a porcine model. The study was done on 3 Vietnamese pigs in a certified veterinary facility. The treatment was delivered to an area the size of 20 x 10cm. The treatment duration was 11 minutes, 30 seconds. Biopsy samples were taken before the first treatment, 1 hour post each treatment, as well as 8 and 20 hours post each treatment. Programmed cell death (apoptosis) was monitored using the TUNEL method. The temperature was measured on the skin surface by an infrared thermal imager and built-in IR thermometer, and by an internal probe inserted into various depths of the subcutaneous layer. The internal probe placement was monitored by diagnostic ultrasound examination.
RESULTS: The temperature in the treated adipose tissue was higher compared to the skin surface temperature. The average temperature gradient observed was 3.1°C. Due to the temperature gradient the skin surface remained intact, while subcutaneous layers showed significant changes. The TUNEL method proved large-scale apoptosis of fat cells after each treatment. The apoptotic index increased from 7% before the first treatment to an average of 53.4%, 39.6%, 40.2%, and 44.7% respectively for each treatment. In the three-month follow up the apoptotic index dropped back to 11.7%. Histology, blood biochemistry and hematology samples showed mild to no signs of inflammation in the treated area.
CONCLUSION: The study has shown that use of monopolar, focused radiofrequency can induce substantial apoptotic process in a porcine model. The data suggests that the monopolar, focused radiofrequency device can be used for reduction of fat and body shaping.
J Drugs Dermatol. 2014;13(11):1336-1340.
BACKGROUND: In the last decade, energy-based aesthetic treatments, using light, radiofrequency (RF), and ultrasound, have gained scientific acceptance as safe and efficacious for non-invasive treatment for aesthetic skin disorders. The phase-controlled multisource radiofrequency technology (3DEEP™), which is based on the simultaneous use of multiple RF generators, was proven to allow significant pigment-independent dermal heating without pain or the need of epidermal cooling. This study was performed in order to evaluate the efficacy and safety of a new handheld device delivering multisource radiofrequency to the skin for wrinkle reduction and skin tightening in the home setting.
PATIENTS AND METHODS: A total of 69 participants (age 54.3 years ± 8.09; age range 37-72 years) were enrolled in the study after meeting all inclusion/exclusion criteria (100%) and providing informed consent. Participants were provided with the tested device together with a user manual and treatment diary, to perform independent treatments at home for 4 weeks. The tested device, (Newa™, EndyMed Medical, Cesarea, Israel) emits 12 W of 1Mhz, RF energy through six electrodes arranged in a linear fashion. Independent control of RF polarity through each one of the 6 electrodes allows significant reduction of energy flow through the epidermis with increased dermal penetration.
Participants were instructed to perform at least 5 treatments a week, for one month. Four follow-up visits were scheduled (once a week) during the period of independent treatments at home, following 4 weeks of home treatments, 1 month follow-up visit (1 month after treatment end) and at 3 months follow-up (3 months following treatment end).
Analysis of pre-and post treatment images was conducted by three uninvolved physicians experienced with the Fitzpatrick Wrinkle and Elastosis Scale. Fitzpatrick Wrinkle and Elastosis score of each time point (4 weeks following home use treatments; 1 month follow-up, 3 months follow-up) was compared to baseline.
Participants were asked a series of questions designed to explore usability concerns and level of satisfaction regarding the device use and subjective efficacy.
RESULTS: Altogether, 62 subjects completed the study course and follow-up visits. No unexpected adverse effects were detected or reported throughout the independent treatment. All study participants did not experience any difficulties while operating the tested device for independent wrinkle reduction treatments. Photographic analysis of pre- and post-one month of independent home use treatments, and one and three months follow-up after end of treatment course, was conducted by three uninvolved board certified dermatologists. Analysis of results revealed improvement (downgrade of at least 1 score according to the Fitzpatrick scale) in 91.93%, 96.77%, and 98.39% of study subjects (according to the first, second, and third reviewer, respectively). Results were found to be statistically significant. The majority of study participants were very satisfied from the results of the independent treatment using the tested device for wrinkle reduction.
J Drugs Dermatol. 2014;13(11):1342-1347.
BACKGROUND: Molluscum contagiosum (MC) is a benign contagious viral skin infection that typically resolves without treatment within months. For cases where treatment is recommended or requested, a number of options are available. Over the last 2 decades, a number of case reports and case series have described cases of MC lesions that were successfully treated with pulsed dye laser (PDL); however, a review of these studies has not been reported in the dermatologic literature.
OBJECTIVES: To review the use of PDL for the treatment of MC.
MATERIALS AND METHODS: A search of the National Library of Medicine’s PubMed Database and the SCOPUS Database was performed to find articles that detailed the treatment of MC with PDL.
RESULTS: Eight articles met criteria for inclusion in this review. These articles represented 161 patients with over 4200 MC lesions that were treated with PDL. Each article was reviewed and summarized in a table.
LIMITATIONS: The main limitation of this review is the small number of published studies, which reflects the importance of this review of the dermatology literature.
CONCLUSIONS: PDL offers a novel and effective treatment for MC. However, the articles reviewed herein suggest PDL is a safe, effective, quick and well-tolerated treatment for clearing MC lesions that does not cause scarring or permanent pigment change.
J Drugs Dermatol. 2014;13(11):1349-1352.
OBJECTIVE: This randomized, 3-group study compared the efficacy and tolerability of 3 treatment modalities for facial actinic keratoses.
METHODS: Twenty-four healthy adult male and female subjects who had 4 to 8 clinically visible and discrete actinic keratoses on the face in a contiguous 25cm2 treatment area. Subjects were randomized into one of three treatment groups: 2 treatments with 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT), 1 ALA-PDT treatment and 1 course of ingenol mebutate (ingenol mebutate) 0.015% gel daily for 3 consecutive days, or 1 course of ingenol mebutate gel alone. Actinic keratoses in the treatment field were counted at the baseline visit, and at the completion of the study (day 57 or day 71). At the site of application, local site reactions were graded at each visit.
RESULTS: Subjects in the two ALA-PDT treatment group had a 97.5% mean reduction (P<0.00001) from the number of baseline actinic keratosis; ALA-PDT plus ingenol mebutate gel group had an 86.7% mean reduction (P<0.00001); while subjects in the ingenol mebutate gel alone group had a 91.7% mean reduction from the number of baseline actinic keratoses. The peak composite LSR score was 4.625 for the ALA-PDT group, 10.375 for the ALA-PDT followed by ingenol mebutate gel group, and 12.625 for the ingenol mebutate gel alone group (P=0.0004 and 0.001, respectively).
CONCLUSION: ALA-PDT, ingenol mebutate gel, and a combination of the two treatment modalities are successful topical therapies for the reduction of actinic keratoses on the face. The group of subjects receiving 2 consecutive treatments with ALA-PDT, compared to treatment with ingenol mebutate gel alone or sequentially after one course of ALA-PDT had a significantly lower mean composite LSR score and a non-significant trend for greater efficacy.
J Drugs Dermatol. 2014;13(11):1353-1356.
INTRODUCTION: Multiple topical therapies are available for mild to moderate acne vulgaris. The role of antibiotics and their resistance in the treatment of acne was reviewed by an expert panel of dermatologists who practice in Canada.
METHODS: Prior to the consensus meeting, the panel members filled out a survey on their current practice using topical treatment for acne. A literature review was carried out using information obtained from PubMed, Cochrane Library, Medline, and EMBASE. During a consensus meeting organized at the Spring Dermatology Update on April 27, 2014 in Toronto, ON, the panel had a blind vote on the issues at hand.
RESULTS: The panel reached consensus on: 1) Antibiotics are an integral part of acne treatment not only due to their antibiotic effect but also by their anti-inflammatory action. 2) Oral antibiotics should be used for a short period of time if possible. 3) Topical antibiotics should not be used in monotherapy. 4) Retinoids are effective in reducing antibiotic resistance. 5) A benzoyl peroxide wash is as effective as topical benzoyl peroxide in reducing antibiotic resistance. 6) Therapy needs to be re-evaluated in 6-8 weeks versus 12 weeks. The recommendations given by the panel are to be disseminated to both general practitioners and dermatologists.
CONCLUSION: For mild to moderate acne treatment, topical antibiotics in monotherapy are not to be used but may be combined with a retinoid or BPO to safely achieve more successful outcomes.
J Drugs Dermatol. 2014;13(11):1358-1364.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder that results in areas of dry, itchy skin. Several cultivation-dependent and –independent studies have identified changes in the composition of microbial communities in these affected areas over time and when compared to healthy control individuals. However, how these communities vary on affected and unaffected skin of the same individual, and how these communities respond to emollient treatment, remains poorly understood. Here we characterized the microbial communities associated with affected and unaffected skin of 49 patients with AD before and after emollient treatment using high-throughput sequencing of the 16S rRNA gene. We found that microbial diversity and community composition was different between affected and unaffected skin of AD patients prior to treatment. Differences were driven primarily by the overabundance of Staphylococcus species on affected skin and a corresponding decrease in bacterial diversity. After 84-days of emollient treatment, the clinical symptoms of AD improved in 72% of the study population. Microbial communities associated with affected skin of these treatment responders more closely resembled unaffected skin after treatment as indicated by increased overall diversity and a decrease in the abundance of Staphylococcus species. Interestingly, Stenotrophomonas species were significantly more abundant in the communities of ‘responders’, suggesting a possible role in restoration of the skin microbiome in patients with AD. We demonstrated that the comparison of affected and unaffected skin from the same individual provides deeper insight into the bacterial communities involved in the skin dysbiosis associated with AD. These data support the importance of emollients in the management of AD although future studies should explore how emollients and other treatments help to restore skin dysbioses.
J Drugs Dermatol. 2014;13(11):1365-1372.
BACKGROUND: Treatment with calcipotriene plus betamethasone dipropionate (CBD) fixed-combination topical suspension has been shown to be effective and well tolerated in patients with psoriasis vulgaris.
AIM: To document experiences with CBD topical suspension in a US clinical dermatology setting using patient-reported outcomes (PROs).
METHODS: In total, 147 patients were enrolled in this 8-week, prospective, noninterventional, multicenter, one-arm study. Data were collected at baseline and week 8 at the office, and at one time at home (week 2). PROs were assessed using the Dermatology Life Quality Index (DLQI), Patient’s Global Assessment of disease severity (PtGA) using a 5-point Likert scale, patient-reported level of itching using a 0–100 graduated visual analog scale, and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Treatment adherence and adverse events (AEs) were assessed at week 8.
RESULTS: After 8 weeks of treatment, DLQI score significantly improved compared with baseline (–5.5 ± 5.93; P<.0001), starting as early as week 2 (–4.2 ± 5.28; P<.0001). The level of itching was significantly reduced from baseline to week 2 (–19% ± 25.94%; P<.0001) and week 8 (–28.6% ± 29.14%; P<.0001). The percentage of patients with “controlled disease” (PtGA score of “clear” or “very mild”) was 34.1% at week 2 and 60.2% at week 8. At the end of treatment, mean TSQM-9 scores for effectiveness, convenience, and satisfaction domains ranged from 68 to 74. Patients reported the need to use CBD topical suspension for an average of 53.62 ± 8.05 days. Treatment-emergent AEs occurred in 3 patients.
CONCLUSION: The results of this noninterventional study are consistent with previously reported data from interventional trials and suggest that treatment with CBD topical suspension is efficacious and well tolerated and improves quality of life in patients with psoriasis vulgaris.
J Drugs Dermatol. 2014;13(11):1374-1379.
Papulopustular rosacea (PPR) is characterized by facial erythema and inflammatory lesions believed to be primarily caused by dysregulation of the innate immune system. More recent evidence also suggests that Demodex folliculorum mites may contribute to the etiology of PPR. Ivermectin (IVM) 1% cream is a novel topical treatment developed to treat PPR. Two phase 3 trials have demonstrated that IVM 1% cream was significantly better than vehicle at investigator global assessment (IGA) success rate and lesion reductions and that it was safe and well tolerated. Two 40-week extension studies of those trials were conducted to assess the long-term safety of IVM 1% cream vs azelaic acid (AzA) 15% gel. Subjects originally treated with IVM 1% continued on IVM 1% and those originally treated with vehicle switched to AzA 15% gel. IVM 1% cream was safe throughout the study with a lower incidence of related adverse events (AEs) compared to AzA 15% gel. No subjects in the IVM 1% cream group discontinued either study due to a related AE. IVM 1% also continued to be efficacious during the 40-week extension studies as the percentage of subjects with IGA scores of clear or almost clear was higher at the end of the study compared to baseline. The results of these 40-week extension studies support the use of IVM 1% cream as a long-term therapy for PPR as IVM 1% cream was shown to be safe and effective for up to 52 weeks of total treatment.
J Drugs Dermatol. 2014;13(11):1380-1386.
BACKGROUND: Effective transungual delivery of topical antifungal agents in onychomycosis has been hampered by poor nail permeation. To be effective they must have antifungal efficacy, and effectively permeate through the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. The therapeutic efficacy of efinaconazole topical solution, 10% has been established in two phase 3 clinical trials in distal lateral subungual onychomycosis.
OBJECTIVE: To investigate the transungual delivery of efinaconazole in onychomycosis patients and its fungicidal activity in the toenail.
METHODS: Concentrations of efinaconazole were determined as part of a multi-center, open label study in forty onychomycosis patients following repeated application of efinaconazole topical solution, 5% and 10% to the toenails over 28 days, with a 2-week follow-up. Fungicidal activity against T. rubrum in the ventral layer of human nails was determined using an in vitro human nail infection model (ChubTur®).
RESULTS: Efinaconazole concentrations in the nail were four orders of magnitude higher than MIC values of efinaconazole against dermatophytes. Further, nail drug concentrations were not influenced by the presence of disease or nail thickness, and maintained at high antifungal levels post-treatment. Efinaconazole was effective in reducing fungal viability, suggesting that sufficient amounts of efinaconazole were being delivered into the ventral layer of the nail plate.
CONCLUSIONS: Effective transungual delivery of efinaconazole was demonstrated. The high efinaconazole concentrations in patient toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase 3 studies.
J Drugs Dermatol. 2014;13(11)1388-1392.
OBJECTIVE: To evaluate the ability of efinaconazole vehicle to reach the site of toenail onychomycosis by spreading through the subungual space between the nail plate and nail bed. Lacquer-based vehicles are primarily limited to application on the nail plate and dependent on nail plate permeation.
METHODS: 11 patients (mean age 48.5 years) were entered with clinically determined onychomycosis. Presence of fungal infection was confirmed by KOH testing in eight patients. Two separate applications of vehicle (with fluorescein incorporated for better visualization) were applied at the hyponychium, avoiding application to the exterior nail plate surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the underside of the nail. Spread of formulation was assessed under visible and UV light conditions by photographing target toenails after vehicle application, and after nail clipping.
RESULTS: Assessments under both visible and UV light indicated that the vehicle had spread into the subungual space, with deposition of flourescein wherever vehicle had reached, including in the nail bed. Nail clippings also indicated deposition to the underside of the nail plate.
LIMITATIONS: The relative contributions of spreading into the subungual space, or permeation through the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed.
CONCLUSIONS: This study suggests that the vehicle developed for efinaconazole topical solution, 10%, when applied at the hyponychium, spreads into the subungual space between the nail plate and nail bed, reaching the site of infection.
J Drugs Dermatol. 2014;13(11):1394-1398.
OBJECTIVE: To evaluate the efficacy of sequential therapy of cryotherapy and sinecatechins 15% ointment BID versus cryotherapy alone in treatment of external genital warts (EGW).
METHODS: Forty-two subjects with at least two EGW lesions underwent cryotherapy to all lesions. One week following cryotherapy, subjects were randomized 1:1 to receive either no additional treatment or treatment with sinecatechins 15% ointment BID up to 16 weeks or until complete clearance. The total number of visible baseline and new EGW were recorded at each visit. Subjects were followed for a total of 65 weeks post-treatment.
RESULTS: There was a significant reduction in mean number of lesions from baseline after 16 weeks of treatment in the cryotherapy-sinecatechins ointment group compared to cryotherapy alone (-5.0 lesions vs -2.1 lesions respectively, P=0.07).
CONCLUSION: Cryotherapy plus sinecatechins 15% ointment BID resulted in a significant improvement in the reduction of EGW compared to cryotherapy alone. Clinicaltrials.gov registration identifier: NCT02147353
J Drugs Dermatol. 2014;13(11):1400-1405.