Novel 40 µm spot size 3050/3200 nm DFG laser versus CO2 laser for laser-assisted drug delivery.

BACKGROUND AND OBJECTIVES: The use of ablative fractional lasers to enhance the delivery of topical drugs through the skin is known as laser-assisted drug delivery. Here, we compare a novel 3050/3200 nm difference frequency generation (DFG) fiber laser (spot size: 40 µm) to a commercially used CO2 laser (spot size: 120 µm). The objective is to determine whether differences in spot size and coagulation zone (CZ) thickness influence drug uptake. MATERIALS AND METHODS: Fractional ablation was performed on ex-vivo human abdominal skin with the DFG (5 mJ) and CO2 (12 mJ) lasers to generate 680 µm deep lesions. To evaluate drug delivery, 30 kDa encapsulated fluorescent dye was topically applied to the skin and histologically analyzed at skin depths of 100, 140, 200, 400, and 600 µm. Additionally, transcutaneous permeation of encapsulated and 350 Da nonencapsulated dye was assessed using Franz Cells. RESULTS: The DFG laser generated smaller channels (diameter: 56.5 µm) with thinner CZs (thickness: 22.4 µm) than the CO2 laser (diameter: 75.9 µm, thickness: 66.8 µm). The DFG laser treated group exhibited significantly higher encapsulated dye total fluorescence intensities after 3 h compared to the CO2 laser treated group across all skin depths (p < 0.001). Permeation of nonencapsulated dye was also higher in the DFG laser treated group vs the CO2 laser treated group after 48 h (p < 0.0001), while encapsulated dye was not detected in any group. CONCLUSION: The DFG laser treated skin exhibited significantly higher total fluorescence uptake compared to the CO2 laser. Additionally, the smaller spot size and thinner CZ of the DFG laser could result in faster wound healing and reduced adverse effects while delivering similar or greater amount of topically applied drugs.

Full-thickness skin rejuvenation by a novel dual-length microneedle radiofrequency device: A proof-of-concept study using human skin.

BACKGROUND: A novel dual-length microneedle radiofrequency (DLMR) device has been developed to achieve full-thickness skin rejuvenation by stimulating the papillary and reticular dermis simultaneously. This device's dual-level targeting concept need to be validated on human skin, although its clinical efficacy has been demonstrated in a previous study. OBJECTIVES: This study evaluated the dual-depth targeting capability and the ability to induce rejuvenation in each layer of vertical skin anatomy, that is, the epidermis, papillary dermis, and reticular dermis, using full-thickness human facial skin samples. METHODS: Human facial skin samples were obtained from 13 Asian patients who had facelift surgery. To validate the dual-depth targeting concept, DMLR-treated skin samples were analyzed using a digital microscope, thermal imaging, and hematoloxylin and eosin (H&E) staining immediately after DLMR application. On samples stained with H&E, Masson's tricrome, and Verhoeff-Van Gieson, histological observation and morphometric analysis were performed. Total collagen assay (TCA) and quantitative real-time polymerase chain reaction (qPCR) were used to assess changes in total collagen content and mRNA expression levels of collagen types I/III and vimentin, respectively. RESULTS: The DLMR device successfully induced thermal stimulation in the papillary and reticular dermis. The thickness, stacks, and dermal-epidermal junction convolution of the epidermis treated with DLMR were significantly increased. Collagen bundles in the dermis treated with DLMR exhibited a notable increase in thickness, density, and horizontal alignment. Dermal collagen levels were significantly higher in the morphometric and TCA data, as well as in the qPCR data for dermal matrix proteins. CONCLUSIONS: Our DLMR device independently and precisely targeted the papillary and reticular dermis, and it appears to be an effective modality for implementing full-thickness rejuvenation.

Low-intensity cold atmospheric plasma reduces wrinkles on photoaged skin through hormetic induction of extracellular matrix protein expression in dermal fibroblasts.

BACKGROUND: Recent evidence indicates that cold atmospheric plasma (CAP) can upregulate the production of extracellular matrix (ECM) proteins in dermal fibroblasts and enhance transdermal drug delivery when applied at a low intensity. OBJECTIVES: The aim of this study was to evaluate the effect of low-intensity CAP (LICAP) on photoaging-induced wrinkles in an animal model and the expression profiles of ECM proteins in human dermal fibroblasts. METHODS: Each group was subjected to photoaging induction and allocated to therapy (LICAP, topical polylactic acid (PLA), or both). The wrinkles were evaluated via visual inspection, quantitative analysis, and histology. The expression of collagen I/III and fibronectin was assessed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunofluorescence. The amount of aqueous reactive species produced by LICAP using helium and argon gas was also measured. RESULTS: Wrinkles significantly decreased in all treatment groups compared to those in the untreated control. The differences remained significant for at least 4 weeks. Dermal collagen density increased following LICAP and PLA application. LICAP demonstrated a hormetic effect on ECM protein expression in human dermal fibroblasts. The production of reactive species increased, showing a biphasic pattern, with an initial linear phase and a slow saturation phase. The initial linearity was sustained for a longer time in the helium plasma (~60 s) than in the argon plasma (~15 s). CONCLUSION: LICAP appears to be a novel treatment option for wrinkles on the photodamaged skin. This treatment effect seems to be related to its hormetic effect on dermal ECM production.

Intralesional Electrocoagulation With Insulated Microneedle for the Treatment of Periorbital Syringomas: A Retrospective Analysis.

BACKGROUND: Conventional treatment options for periorbital syringomas are often unsatisfactory because of inevitable surface damage from the procedure and frequent recurrence rate of the tumors. OBJECTIVES: The authors sought to ascertain the efficacy and safety of intralesional electrosurgery utilizing a monopolar radiofrequency device with a single insulated microneedle for the treatment of periorbital syringomas. METHODS: A retrospective analysis was performed employing data from medical records, routine questionnaires, and clinical photographs of 55 patients with periorbital syringoma who underwent intralesional electrosurgery. RESULTS: Approximately one-half of the patients (50.9%) experienced marked resolution after 1 treatment. The lesion clearance rate increased and lesion severity decreased each time the treatment was repeated. No persistent therapy-related adverse event was found except transient erythema or crusting. CONCLUSIONS: Intralesional electrosurgery with insulated microneedle is an effective and safe treatment option for periorbital syringomas.

Selective Sebaceous Gland Electrothermolysis Using a Single Microneedle Radiofrequency Device for Acne Patients: A Prospective Randomized Controlled Study.

BACKGROUND AND OBJECTIVES: The selective electrothermolysis of the sebaceous glands was suggested as a novel therapeutic option for facial acne. However, there has been no randomized controlled trial to evaluate the effectiveness and safety of the monopolar radiofrequency (RF) device using single microneedle with proximal insulation. The objective of the study was to evaluate the efficacy and tolerability of intralesional electrothermolysis using monopolar RF device and proximally-insulated single microneedle in acne patients. STUDY DESIGN/MATERIALS AND METHODS: The prospective randomized controlled clinical trial was performed to treat moderate-to-severe facial acne. Subjects randomized to the treatment group received three treatments at 4-week intervals with an RF device, whereas the control group received micro-needling and extraction. For efficacy evaluation, reduction rate of acne lesions were evaluated by two independent physicians. RESULTS: Sixty-three patients completed the study and the results showed statistically significant improvement of inflammatory acne at 12 weeks. The number of inflammatory lesions was significantly reduced at 12 weeks (20.86 vs. -5.13; P = 0.03) compared with controls. CONCLUSIONS: Selective sebaceous gland electrothermolysis can be a safe and effective method of achieving consistent improvement in acne. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Case series of post-purpuric darkness on the periorbital area after aesthetic surgery.

Periorbital hyperpigmentation (POH) is a common condition encountered in dermatology practice. POH is caused by various exogenous and endogenous factors including excessive pigmentation, postinflammatory hyperpigmentation (PIH) secondary to eczema, periorbital edema, excessive vascularity, and aging. Recently, we have experienced several patients who complained of POH with an unusual pattern. Their pigmented lesions had several features in common. The pigmentation occurred bilaterally after aesthetic surgery involving the periorbital region. Periorbital post-purpuric darkness should be distinguished from common POH. Practitioners should ask patients about history of prior aesthetic surgery and make their patients aware that the dark colors are composed of various pigments such as hemosiderin, which make treatment troublesome. Conservative management with expectations for gradual spontaneous regression or laser therapy with multiple wavelengths including 1,064-nm laser for PIH and 650 or 694-nm laser targeting heme-derived pigments may be considered as treatment options.

A case of successful treatment of Fordyce spots with a single insulated microneedle radiofrequency device.

Fordyce spots are ectopic sebaceous glands which typically present as asymptomatic, multiple whitish, or yellowish 1-3-mm sized papules on the lips. Several therapeutic approaches have been proposed such as laser, electrical or chemical ablation, and micropunch excision. However, these modalities pose the risk of scarring from inevitable surface damage. In this report, we present a case of Fordyce spots which was successfully treated with intralesional electrocoagulation using a proximally insulated microneedle and monopolar radiofrequency device, resulting in marked cosmetic improvements without surface damage.

Topical brimonidine-assisted laser treatment for the prevention of therapy-related erythema and hyperpigmentation.

Postinflammatory hyperpigmentation (PIH) and erythema are the most common adverse effects associated with laser treatment, particularly in dark-skinned individuals. Several methods have been used to prevent or minimize these adverse effects; however, to date, no definitive precautions/strategies are known to prevent post-laser PIH and erythema. We investigated whether the topical application of the α-adrenergic receptor agonist brimonidine could reduce laser treatment-related complications such as erythema and PIH.

Impending skin necrosis after dermal filler injection: A "golden time" for first-aid intervention.

Vascular compromise with impending skin necrosis is one of the most serious potential complications. Early recognition of vascular occlusion and swift and aggressive treatment are required to avoid any irreversible changes. However, initial symptoms of a vascular event are often dismissed as simple post-procedural discomfort. If more than 3 days pass after filler injection, crust formation is initiated over the erythematous base along with a rim of fibrous tissue. Due to the replacement of normal tissues by fibrous material, the healing process may result in scar formation in spite of debridement and aggressive dressing changes. Scars often cause contracture and subsequent cosmetic disfigurement, which results in a traumatic burden to the patient. By sharing our experience of the patients with filler induced skin necrosis, we suggest that treatment should be initiated no later than 3 days after the procedure.

Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles.

Hyaluronic acid (HA) has an immediate volumizing effect, due to its strong water-binding potential, and stimulates fibroblasts, causing collagen synthesis, with short- and long-term effects on wrinkle improvement. We investigated the efficacy and safety of HA microneedle patches for crow's feet wrinkles. Using a randomized spilt-face design, we compared microneedle patches with a topical application containing the same active ingredients. We enrolled 34 Korean female subjects with mild to moderate crow's feet wrinkles. The wrinkle on each side of the subject's face was randomly assigned to a HA microneedle patch or HA essence application twice a week for 8 weeks. Efficacy was evaluated at weeks 2, 4, and 8. Skin wrinkles were measured as average roughness using replica and PRIMOS. Skin elasticity was assessed using a cutometer. Two independent blinded dermatologists evaluated the changes after treatment using the global visual wrinkle assessment score. Subjects assessed wrinkles using the subject global assessment score. Skin wrinkles were significantly reduced and skin elasticity significantly increased in both groups, although improvement was greater in the patch group at week 8 after treatment. In the primary and cumulative skin irritation tests, the HA microneedle patch did not induce any skin irritation. The HA microneedle patch is more effective than the HA essence for wrinkle improvement and is a safe and convenient without skin irritation.

The effect of low-intensity cold atmospheric plasma jet on photoaging-induced hyperpigmentation in mouse model.

BACKGROUND: Cold atmospheric plasma (CAP) produces reactive oxygen/nitrogen species (RONS) in the target and can induce cytoprotective effects by activating hormesis-related pathways when its intensity is in the low range. OBJECTIVES: The aim of this study is to evaluate the effect of low-intensified CAP (LICAP) on skin with photoaging-induced hyperpigmentation in an animal model. METHODS: Changes in cell viability and RONS production following LICAP treatment were measured. For the in vivo study, 30 hairless mice underwent antecedent photoaging induction followed by the allocated therapy (i.e., LICAP, topical ascorbic acid (AA), or both). During the first 4 weeks of the treatment period (8 weeks), ultraviolet (UV)-B irradiation was concurrently administered. Visual inspection and measurement of the melanin index (MI) were performed to assess the change in skin pigmentation at Weeks 0, 2, 4, 6, and 8. RESULTS: RONS production increased linearly until the saturation point. Cell viability was not significantly affected by LICAP treatment. At Week 8, MI was significantly decreased in every treatment group compared with the values at Week 0 and Week 4. The treatment effect of the concurrent therapy group was superior to that of the LICAP and AA groups. CONCLUSION: LICAP appears to be a novel modality for photoprotection and pigment reduction in photodamaged skin. LICAP treatment and topical AA application seem to exert a synergistic effect.

Non-Invasive Diagnosis of a Facial Tumor Using Dermoscopy and Successful Treatment with 595 nm Pulsed Dye Laser.

Clear cell acanthoma (CCA) is an uncommon, benign epithelial tumor presenting as a well-defined, slow-growing solitary nodule. The diagnosis of CCA is usually based on clinical and histopathological evaluation of the tumor. However, when such type of benign tumor occurs on an exposed area, a biopsy is not always the best diagnostic option since it may leave scar. The recent advent of dermoscopy has offered an accurate and non-invasive method to diagnose CCA without resorting to skin biopsy. A 40-year-old male presented with a shiny, erythematous-to-brown, flattened nodule on the left cheek. Dermoscopic examination revealed a 'string of pearls' vascular pattern, a characteristic dermoscopic feature of CCA. Under the clinical and dermoscopic impression of CCA, a 595 nm pulsed dye laser (PDL) therapy targeting the vascular tissue in the superficial dermis of the lesion was chosen for a minimally invasive treatment. After repeated sessions of PDL, an optimal cosmetic outcome was achieved and no recurrence was recorded during the follow-up period. Herein, we report a case of presumed CCA which was successfully diagnosed and treated by utilizing non-invasive modalities.

A randomized, patient/evaluator-blinded, split-face study to compare the efficacy and safety of polycaprolactone and polynucleotide fillers in the correction of crow's feet: The latest biostimulatory dermal filler for crow's feet.

BACKGROUND: No data on the clinical results and safety profiles of the polycaprolactone (PCL) -based dermal filler for crow's feet correction have been published. AIMS: This study was designed to compare the efficacy and safety of a novel PCL-based dermal filler, DLMR01, with that of RJR, a purified polynucleotide dermal filler. PATIENTS/METHODS: A total of 30 subjects with symmetric crow's feet of 2-4 points on the Crow's Feet Grading Scale (CFGS) were enrolled in this randomized, patient/evaluator-blinded, split-face study. Each subject was randomized to receive injections of DLMR01 or RJR in their right or left crow's feet. At 4 and 12 weeks, all participants were evaluated via CFGS, Global Aesthetic Improvement Scale (GAIS), and PRIMOS software system. RESULTS: No significant difference in CFGS, GAIS, and Ra value was detected between DLMR01 side and RJR at 12 weeks (improvement rate in CFGS from baseline at week 12-DLMR01: 48.28% [14/29], RJR: 41.38% [12/29]). CONCLUSION: The novel PCL-based dermal filler DLMR01 shows suitable efficacy and safety, widening the selection possibilities for clinicians and patients in the treatment crow's feet.

Diffuse Systemic Sclerosis in a Patient with Primary Biliary Cirrhosis and Autoimmune Hepatitis Overlap Syndrome: A Case Report.

Systemic sclerosis (SSc) is a chronic systemic disease of unknown etiology characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and other internal organs. Although its etiology remains elusive, approximately one third of SSc patients presents with additional autoimmune disease, which suggests that an autoimmune mechanism is a major component of the underlying pathophysiology. On the other hand, primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) are two main autoimmune liver diseases. A 41-year-old female previously diagnosed with PBC/AIH overlap syndrome presented with multiple, painful brownish to erythematous firm patches on the hands, arms, axillae, neck, abdomen, and thighs. Laboratory work-up yielded positive results for anti-nuclear antibody, anti-Ro/Sjögren's-syndrome-related antigen A autoantibodies, and perinuclear anti-neutrophil cytoplasmic antibodies while punch biopsy of her left hand showed characteristics that are consistent with scleroderma. Herein, we report the first case of a patient with diffuse cutaneous SSc and concurrent PBC/AIH overlap syndrome and suggest that this coexistence of multiple autoimmune diseases is not a coincidence but rather that a common autoimmune pathogenesis may exist.

The Effect of Adiponectin on the Regulation of Filaggrin Expression in Normal Human Epidermal Keratinocytes.

BACKGROUND: Adiponectin, an adipokine secreted from adipocytes, affects energy metabolism and also shows anti-diabetic and anti-inflammatory properties. Recent studies have reported that adiponectin plays a role in regulating skin inflammation. OBJECTIVE: This study aimed to investigate the effect of adiponectin on the expression of filaggrin (FLG) in normal human epidermal keratinocytes (NHEKs). METHODS: NHEKs were serum-starved for 6h before being treated with adiponectin. Afterward, cell viability was assessed by MTT assay. We also treated with calcium, interleukin (IL)-4, and IL-13 to provide positive and negative comparative controls, respectively. Gene mRNA expression was quantified using real time reverse transcription polymerase chain reaction, and protein expression was evaluated using Western blot. To evaluate the relationship among mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1), and FLG, we also treated cells with inhibitors for MAPKs JNK, p38, and ERK1/2. RESULTS: FLG and FLG-2 mRNA expression in NHEKs significantly increased after treatment with 10 µg/ml adiponectin. Adiponectin also restored FLG and FLG-2 mRNA expression that was otherwise inhibited by treatment with IL-4 and IL-13. Adiponectin induced FLG expression via AP-1 and MAPK signaling. CONCLUSION: Adiponectin positively regulated the expression of FLG and could be useful as a therapeutic agent to control diseases related to disrupted skin barrier function.

Topical administration of EGF suppresses immune response and protects skin barrier in DNCB-induced atopic dermatitis in NC/Nga mice.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by a complex, heterogeneous pathogenesis including skin barrier dysfunction, immunology, and pruritus. Although epidermal growth factor (EGF) is essential for epithelial homeostasis and wound healing, the effect of EGF on AD remains to be explored. To develop a new therapy for AD, the anti-AD potential of EGF was investigated by inducing AD-like skin lesions in NC/Nga mice using 2,4-dinitrochlorobenzene (DNCB). EGF was administrated to NC/Nga mice to evaluate its therapeutic effect on DNCB-induced AD. EGF treatment improved dermatitis score, ear thickness, epidermal hyperplasia, serum total immunoglobulin E level, and transepidermal water loss in NC/Nga mice with DNCB-induced AD. In addition, levels of skin barrier-related proteins such as filaggrin, involucrin, loricrin, occludin, and zonula occludens-1 (ZO-1) were increased by EGF treatment. These beneficial effects of EGF on AD may be mediated by EGF regulation of Th1/Th2-mediated cytokines, mast cell hyperplasia, and protease activated receptor-2 (PAR-2) and thymic stromal lymphopoietin (TSLP), which are triggers of AD. Taken together, our findings suggest that EGF may potentially protect against AD lesional skin via regulation of skin barrier function and immune response.