Refractory solar lentigines successfully treated with 532-nm nanosecond Nd:YAG Vasculature Salvage Laser Surgery (VSLS) system: Case series.

BACKGROUND: Solar lentigo, a common epidermal hyperpigmented lesion found in sun-exposed areas, results from the proliferation of melanocytes and the accumulation of melanin. Although various treatments for solar lentigo have been explored, they often lead to complications, including prolonged erythema and post-inflammatory hyperpigmentation (PIH), posing significant concerns. OBJECTIVES AND METHODS: This study evaluated the safety and efficacy of the Vasculature Salvage Laser Surgery (VSLS) system. We treated six Korean patients, each with solar lentigo, in a single session using the 532-nm nanosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) VSLS system, with follow-up periods ranging from 3 to 10 weeks. RESULTS: The treatment led to the complete removal of pigmented lesions in all patients without resulting in PIH, even in cases where previous laser treatments had failed. The only side effect observed was mild erythema, which resolved over the long term in most instances. CONCLUSIONS: The VSLS system emerges as a safe and effective treatment for pigmented lesions, including refractory solar lentigines. Nonetheless, additional studies are required to verify its long-term efficacy.

Anti-melanogenic effect of exosomes derived from human dermal fibroblasts (BJ-5ta-Ex) in C57BL/6 mice and B16F10 melanoma cells.

Exosomes are involved in intercellular communication by transferring cargo between cells and altering the specific functions of the target cells. Recent studies have demonstrated the therapeutic effects of exosomes in several skin diseases. However, understanding of the effects of exosomes on anti-pigmentation is limited. Therefore, we investigated whether BJ-5ta exosomes (BJ-5ta-Ex) derived from human foreskin fibroblasts regulate melanogenesis and delineated the underlying mechanism. Interestingly, treatment with BJ-5ta-Ex induced decreased melanin content, tyrosinase (TYR) activity, and expression of melanogenesis-related genes, including microphthalmia-related transcription factor (MITF), TYR, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, BJ-5ta-Ex downregulated the cAMP/PKA and GSK-3ß/ß-catenin signaling pathways and upregulated the MAPK/ERK signaling pathway. Notably, treatment with BJ-5ta-Ex inhibited α-melanocyte-stimulating hormone-induced melanosome transport and decreased the expression of key proteins involved in melanosome transport, namely, rab27a and melanophilin (MLPH). To further confirm the depigmenting effects of BJ-5ta-Ex, we conducted experiments using a three-dimensional reconstituted human full skin model and ultraviolet B (UVB)-irradiated mouse model. Treatment with BJ-5ta-Ex improved tissue brightness and reduced the distribution of melanosomes. In UVB-irradiated mouse ears, BJ-5ta-Ex reduced the number of active melanocytes and melanin granules. These results demonstrate that BJ-5ta-Ex can be useful for the clinical treatment of hyperpigmentation disorders.

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.

Needleless laser injector versus needle injection for skin enhancement and rejuvenation effect of dermal filler.

BACKGROUND AND OBJECTIVES: A needleless laser-induced microjet injector is a novel transdermal drug delivery system that can rapidly inject a very small and precise drug dose into the skin with minimal pain and downtime. In this study, we aimed to compare the laser-induced microjet injection versus needle injection of polylactic acid/hyaluronic acid filler for skin enhancement and rejuvenation. PATIENTS AND METHODS: A 24-week prospective, single-center, assessor-blinded, randomized, split-face study was conducted. The enrolled patients underwent one treatment session of dermal filler injection using a laser-induced microjet injector on one half of the face or a traditional needle injection on the other half of the face. Evaluation was conducted at baseline before treatment and at 4, 12, and 24 weeks after treatment. RESULTS: A single treatment of filler injection with a laser-induced microjet injector resulted in similar improvements in skin hydration and elasticity as a single treatment of filler injection by using manual needle injection, with reduced pain, side effects, and decreased treatment time. CONCLUSIONS: Laser-induced microjet injector enabled not only the application of a controlled dose and filler depth but also even distribution, improved clinical efficacy, reduced pain and side effects, and sufficient time for clinicians to perform treatment.

Adipose-derived stem cell exosomes for treatment of dupilumab-related facial redness in patients with atopic dermatitis.

BACKGROUND: Dupilumab facial redness (DFR) is a side effect of dupilumab treatment that has only been recently reported. We previously reported on two patients with DFR who were successfully treated with a topical formulation containing human adipose tissue-derived mesenchymal stem cell-derived exosomes (ASCEs). OBJECTIVES: The study aimed to evaluate the efficacy and safety of ASCEs in DFR. PARTICIPANTS AND METHODS: We performed 12-week prospective study at single center. Twenty adult atopic dermatitis patients diagnosed with DFR were enrolled. They were treated with a topical application of the exosome formulation every week for five consecutive weeks. RESULTS: After exosome treatment, both the average investigator global assessment score and clinical erythema assessment scale scores decreased. 19 patients (95%) were satisfied with the treatment. Compared to baseline, erythema index at week 4 were decreased by 31, 27, 13, and 25 units on the forehead, chin, right and left cheek respectively. The analysis of stratum corneum samples revealed the expression of IL-1α and human thymic stromal lymphopoietin was suppressed after exosome treatment, whereas filaggrin and vascular endothelial growth factor expression increased. CONCLUSIONS: This study suggests topical formulation containing ASCEs can alleviate DFR by downregulating local inflammation and restoring skin barrier function.

A Randomized, Prospective, Split-Face Pilot Study to Evaluate the Safety and Efficacy of 532-nm and 1,064-nm Picosecond-Domain Neodymium:Yttrium-Aluminum-Garnet Lasers Using a Diffractive Optical Element for Non-Ablative Skin Rejuvenation: Clinical and Histological Evaluation.

BACKGROUND: The advent of fractionated picosecond (ps) lasers has provided an opportunity to explore new ways of creating microinjuries in the skin to induce skin rejuvenation. OBJECTIVE: To compare the efficacy and safety of diffractive optical element (DOE)-assisted ps neodymium: yttrium-aluminum-garnet (Nd:YAG) lasers with 532-nm and 1,064-nm wavelengths (532-nm and 1,064-nm Nd:YAG P-DOE) using a novel fractional handpiece for the treatment of photoaged skin. METHODS: An ex vivo guinea pig skin experiment was performed by evaluating the histology of the skin after 532-nm Nd:YAG P-DOE irradiation. A randomized, prospective, split-face study was performed on eight subjects with 532-nm and 1,064-nm Nd:YAG P-DOE. RESULTS: Based on the histological evaluation using ex vivo guinea pig skin, a reasonable safety profile and the potential to generate effective skin rejuvenation was observed using the 532-nm Nd:YAG P-DOE. Results demonstrated that both 532- and 1,064-nm Nd:YAG P-DOE were similarly effective in improving skin texture and skin pores; however, 532-nm Nd:YAG P-DOE was more effective in treating dyspigmentation. CONCLUSION: At a preliminary level, this study revealed that 532-nm and 1,064-nm ps Nd:YAG lasers using DOE fractional technology may improve photoaged skin. In conclusion, 532-nm Nd:YAG P-DOE may be especially beneficial for skin with epidermal pigmentary lesions.

Combination of Non-Ablative Fractional Laser with Q-Switched Laser for the Treatment of Becker's Nevus: Efficacy and Limitations.

Becker's nevus (BN) is a benign hamartoma that may present as a distressing cosmetic problem. The treatment of BN poses a significant challenge as current therapeutic modalities are suboptimal and have an increased risk of adverse effects, such as scarring and dyspigmentation. We present the use of non-ablative fractional laser therapy combined with Q-switched Nd:YAG laser as a possible therapeutic option for BN treatment and review relevant literature to discuss its efficacy and limitations.

Utilization of Ultrasonography in Dermatology: Two Case Reports of Calcinosis Cutis.

Development of newer generation of cost-effective ultrasonic devices in recent years has increased the use of ultrasonography in dermatology. Several lesions can be diagnosed and managed using ultrasonography. Calcinosis cutis involves the deposition of insoluble calcium salts in the cutaneous and subcutaneous tissues. On ultrasonography, it specifically presents as hyperechoic deposits with a posterior acoustic shadowing artifact due to the acoustic properties of calcium. A 62-year-old female patient presented with a solitary, skin-colored, palpable nodule on the inner side of the right lower leg. The lesion was beneath the intact skin and detectable only on palpation. However, ultrasonography demonstrated a clear delineation of the lesion, showing hyperechoic deposits with a posterior acoustic shadow (15 MHz, linear probe). Skin biopsy and curettage were performed, revealing histological features consistent with calcinosis cutis. Four weeks after the procedure, ultrasonography performed to evaluate the outcome of treatment, showed recurrence. Another 18-year-old female patient presented with a skin-colored deep-seated nodule on the left temple. On ultrasonography, linear hyperechoic deposits with a posterior acoustic shadow were visible. Skin biopsy was performed, and histopathologic features showed calcified material in the subcutaneous tissue. These two cases of calcinosis cutis highlight the diagnostic value of ultrasonography in dermatology.

Split-face comparative trial of 785-nm picosecond neodymium:yttrium-aluminum-garnet laser and precision cryotherapy combination treatment for facial benign pigmented lesions.

Cryotherapy (or cryosurgery) has been performed to treat various skin lesions in the field of dermatology; however, to the best of our knowledge, no study has investigated its efficacy and safety for benign pigmented lesions. Therefore, we conducted a split-face study to evaluate the efficacy and safety of cryotherapy in the treatment of benign pigmented lesions. A total of five subjects were included. Picosecond laser therapy was performed to treat the whole face and cryotherapy for half the face. Four weeks after completing the treatment sessions, patients showed more clinical improvement on the laser and cryotherapy combination treatment side than on the laser-only side, with no adverse events. Our study demonstrated that cryotherapy is a potential adjuvant therapeutic modality for benign pigmented lesions.

Exosomes derived from human adipose tissue-derived mesenchymal stem cells for the treatment of dupilumab-related facial redness in patients with atopic dermatitis: A report of two cases.

BACKGROUND: Atopic dermatitis is a chronic, pruritic, and inflammatory dermatosis that affects approximately 20% of children and 10% of adults worldwide. Dupilumab facial redness is gaining attention as additional cases are coming to light in the medical literature. OBJECTIVES AND METHODS: Exosomes are nano-sized vesicles that are constantly released by almost all cells. They can travel between cells and transport their cargo (lipids, proteins, and nucleic acids), making them a possible cell-free therapeutic option for various diseases. Herein, we investigated whether topical application of human adipose tissue-derived mesenchymal stem cell-derived exosomes could reduce dupilumab facial redness in patients with severe atopic dermatitis. RESULTS: Two patients with atopic dermatitis and refractory dupilumab facial redness were successfully treated with electroporation-assisted topical application of human adipose tissue-derived mesenchymal stem cell-derived exosomes. Six repeated sessions of treatment, with an interval of 1 week between each session, led to marked improvement in erythematous facial lesions. CONCLUSIONS: We suggest that human adipose tissue-derived mesenchymal stem cell-derived exosomes may serve as an effective agent in the management of dupilumab facial redness. However, further controlled studies with a larger number of patients are necessary to confirm the efficacy and safety of this agent, as well as the optimal treatment protocol.

Phase I/III Clinical Trial to Evaluate the Safety and Efficacy of a New Botulinum Toxin (HU-014) Versus OnabotulinumtoxinA in Subjects With Moderate-to-Severe Crow's Feet Lines.

BACKGROUND: HU-014, a newly introduced botulinum toxin type A, has not been investigated for its efficacy and safety in crow's feet line (CFL) treatment. OBJECTIVE: Here, we compared the efficacy and safety of HU-014 and onabotulinumtoxinA in CFL treatment. METHODS: This was a randomized, double-blind, active drug-controlled, multicenter, 16-week, Phase I/III study designed to determine the noninferiority of HU-014 compared with onabotulinumtoxinA in moderate-to-severe CFL treatment. In the Phase III study, 290 subjects were randomized at a 1:1 ratio to receive a single treatment of HU-014 or onabotulinumtoxinA. The primary endpoint was the proportion of subjects achieving Grade 0 or 1 in the facial wrinkle scale on maximum smile at Week 4. RESULTS: The primary endpoint was achieved by 72% of the subjects with HU-014 and onabotulinumtoxinA treatments, supporting the noninferiority of HU-014 compared with onabotulinumtoxinA. All secondary efficacy outcomes were achieved by the subjects. The 2 groups showed no significant differences in the safety analysis. CONCLUSION: HU-014 has noninferior efficacy and safety compared with onabotulinumtoxinA in the treatment of CFL.

Potency and Quality of Reconstituted Botulinum Neurotoxin Type A According to Storage Temperatures.

BACKGROUND: In clinical practice, one of the most important issues regarding the use of botulinum neurotoxin A (BoNT-A) is the proper storage conditions and the change in potency and quality over time after reconstitution. OBJECTIVE: This study aimed to investigate the change in potency and quality of reconstituted prabotulinumtoxin A (PraBoNT-A) over time when stored at different storage temperatures. MATERIALS AND METHODS: ICR/CD-1 mice and PraBoNT-A were used for the mouse intraperitoneal lethal dose 50% (LD50) test. A thorough quality evaluation of the product was performed. RESULTS: All of the reconstituted PraBoNT-A stored at different temperatures met the evaluation criteria for the suggested limits of estimated potency and for the quality assessment at every evaluated time point. When the stability of reconstituted PraBoNT-A was evaluated by regression analysis, the shelf life of reconstituted PraBoNT-A was found to be 99.24, 73.80, and 16.34 weeks in the case of PraBoNT-A stored at freezing, refrigeration, or room temperatures, respectively. CONCLUSION: Based on the results, the authors conclude that the efficacy and quality of the reconstituted PraBoNT-A product are not compromised at least for a certain period of time and that the shelf life of reconstituted PraBoNT-A is longest when stored at the freezing temperature.

Successful Treatment of Pigmentary Disorders in Asians With a Novel 730-nm Picosecond Laser.

BACKGROUND AND OBJECTIVE: Until recently, quality-switched nanosecond lasers have been the workhorse lasers in treating pigmented lesions. However, the recently commercialized picosecond lasers have provided physicians with a novel method to manage pigmented lesions. Most recently, the first picosecond laser with a 730-nm wavelength was developed to specifically target melanin and melanocytes. STUDY DESIGN/MATERIALS AND METHODS: We report on two Asian patients with freckles, lentigines, and melasma who were successfully treated with a novel 730-nm Ti:Sapphire picosecond laser (Picoway®; Syneron Candela, Corp). The clinical outcome was measured by the global percent of clearance, which was evaluated by blinded observers by comparing the post-treatment photographs with the baseline photographs. RESULTS: In both patients, a significant pigmentary reduction was achieved with only one treatment session. In both patients, the treatments were well tolerated with minimal discomfort even without topical anesthesia. No post-inflammatory hyperpigmentation or repigmentation was observed until the 6-week follow-up. The pigmentary conditions treated included freckles, lentigines, and melasma. Both subjects showed clinical improvement, with the best results observed for the treatment of freckles such that 95% of the lesions achieved excellent response (75-94% lightening). CONCLUSION: The results of this case report indicate that a novel 730-nm Ti:Sapphire picosecond laser may be effective and safe in treating pigmentary disorders in darker-skinned patients. Therefore, further well-designed, prospective clinical trials are warranted to establish the potential of 730-nm picosecond lasers and determine the optimal treatment parameters in comparison to existing laser and light modalities. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

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.