Light-emitting diodes in dermatology: A systematic review of randomized controlled trials.

OBJECTIVE: In dermatology, patient and physician adoption of light-emitting diode (LED) medical technology continues to grow as research indicates that LEDs may be used to treat skin conditions. The goal of this systematic review is to critically analyze published randomized controlled trials (RCTs) and provide evidence-based recommendations on the therapeutic uses of LEDs in dermatology based on published efficacy and safety data. METHODS: A systematic review of the published literature on the use of LED treatments for skin conditions was performed on September 13th 2017. RESULTS: Thirty-one original RCTs were suitable for review. CONCLUSIONS: LEDs represent an emerging modality to alter skin biology and change the paradigm of managing skin conditions. Acne vulgaris, herpes simplex and zoster, and acute wound healing received grade of recommendation B. Other skin conditions received grade of recommendation C or D. Limitations of some studies include small patient sample sizes (n < 20), absent blinding, no sham placebo, and varied treatment parameters. Due to few incidences of adverse events, affordability, and encouraging clinical results, we recommend that physicians use LEDs in clinical practice and researchers continue to explore the use of LEDs to treat skin conditions. Lasers Surg. Med. 9999:1-16, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

High-Fluence Light-Emitting Diode-Generated Red Light Modulates the Transforming Growth Factor-Beta Pathway in Human Skin Fibroblasts.

BACKGROUND: Skin fibrosis is a significant medical problem with limited available treatment modalities. The key cellular characteristics include increased fibroblast proliferation, collagen production, and transforming growth factor-beta (TGF-B)/SMAD pathway signaling. The authors have previously shown that high-fluence light-emitting diode red light (HF-LED-RL) decreases cellular proliferation and collagen production. OBJECTIVE: Herein, the authors investigate the ability of HF-LED-RL to modulate the TGF-B/SMAD pathway. MATERIALS AND METHODS: Normal human dermal fibroblasts were cultured and irradiated with a commercially available hand-held LED array. After irradiation, cell lysates were collected and levels of pSMAD2, TGF-Beta 1, and TGF-Beta I receptor were measured using Western blot. RESULTS: High-fluence light-emitting diode red light decreased TGF-Beta 1 ligand (TGF-B1) levels after irradiation. 320 J/cm HF-LED-RL resulted in 59% TGF-B1 and 640 J/cm HF-LED-RL resulted in 54% TGF-B1, relative to controls. 640 J/cm HF-LED-RL resulted in 62% pSMAD2 0 hours after irradiation, 65% pSMAD2 2 hours after irradiation, and 95% 4 hours after irradiation, compared with matched controls. High-fluence light-emitting diode red light resulted in no significant difference in transforming growth factor-beta receptor I levels compared with matched controls. CONCLUSION: Skin fibrosis is a significant medical problem with limited available treatment modalities. Light-emitting diode-generated red light is a safe, economic, and noninvasive modality that has a body of in vitro evidence supporting the reduction of key cellular characteristics associated with skin fibrosis.

Thermal Ultra Short Photodynamic Therapy: Heating Fibroblasts During Sub-30-Minute Incubation of 5-Aminolevulinic Acid Increases Photodynamic Therapy-Induced Cell Death.

BACKGROUND: Actinic keratoses (AKs) prevalence was estimated at 39.5 million Americans in 2004, and the cost to treat AKs that year was approximately 1 billion dollars. Photodynamic therapy (PDT) is an FDA-approved therapy for the treatment of AK. Recent studies have focused on reducing PDT treatment time while maintaining efficacy. OBJECTIVE: To investigate the use of thermal modulation to improve the efficacy of ultra short aminolevulinic acid (ALA) incubation PDT. MATERIALS AND METHODS: Human dermal fibroblasts (HDFs) were incubated for 10, 15, or 20 minutes with 0.5-mM ALA at various temperatures (21, 24, 27, 30, 33, 36, 39, and 42°C). After ALA incubation, samples were treated for 1,000 seconds with blue light (417 ± 5 nm) resulting in a fluence of 10 J/cm. Samples were collected and stained for apoptosis/necrosis with annexin-V and 7-aminoactinomycin D (7-AAD), then analyzed by flow cytometry. RESULTS: Human dermal fibroblast treated with 10-minute ALA-PDT had no statistically significant changes in apoptosis at all temperatures. Human dermal fibroblast treated with 15- or 20-minute ALA-PDT had statistically significant increases in apoptosis at 39 and 42°C (p < .05). CONCLUSION: These results suggest the use of thermal modulation may improve ultra short ALA incubation PDT efficacy.

Efficacy of ultra short sub-30 minute incubation of 5-aminolevulinic acid photodynamic therapy in vitro.

BACKGROUND AND OBJECTIVE: The estimated incidence of cutaneous squamous cell carcinoma (SCC) is 700,000 cases per year. In the US, SCC incidence is highest among fair skinned adults older than 50 years of age. Thus, as the population ages, the reported number of SCCs will likely increase in the future. Photodynamic therapy (PDT) is an FDA approved therapy for treatment of actinic keratoses (AKs), a precursor to cutaneous SCC lesions. The FDA approved incubation time of the photosensitizing agent 5-aminolevulinic acid (ALA) is 14-18 hours. Recent studies have investigated short ALA incubation times of 1-3 hours with ALA and PDT demonstrating treatment success. Therefore, the question exists whether ALA incubation periods of less than 30 minutes are efficacious. Herein, we evaluate the efficacy of short ALA incubation periods by measuring apoptosis after 10, 15, and 20 minutes of ALA incubation. STUDY DESIGN/MATERIALS AND METHODS: AG13145 normal human dermal fibroblasts HDFs were incubated with 10, 15, or 20 minute of ALA at various concentrations (0, 0.05, 0.075, 0.1, 0.25, 0.375, 0.5, 1, and 2 mM). After ALA incubation, samples were treated with 1,000 seconds (16 minutes 40 seconds) of Blu-U fluorescent blue light (417 ± 5 nm) for a fluence of 10 J/cm2 . Immediately following treatment with blue light, samples were collected and stained for apoptosis and necrosis with annexin-V and 7-aminoactinomycin D (7-AAD), and then analyzed by flow cytometry. RESULTS: HDFs incubated with ALA for 10 minute at 36 °C followed by 10 J/cm2 of blue light had no statistically significant changes in apoptosis. HDFs incubated with ALA for 15 or 20 minutes at 36 °C followed by 10 J/cm2 of blue light had statistically significant increases in the percentages of cells positive for apoptosis in the 0.5, 1.0, and 2.0 mM ALA doses (P < 0.05). CONCLUSIONS: We found that incubation of ALA for at least 15 minutes followed by 10 J/cm2 of blue light resulted in a statistically significant increase in apoptosis. Lasers Surg. Med. 49:592-598, 2017. © 2017 Wiley Periodicals, Inc.

The Combination of Resveratrol and High-Fluence Light Emitting Diode-Red Light Produces Synergistic Photobotanical Inhibition of Fibroblast Proliferation and Collagen Synthesis: A Novel Treatment for Skin Fibrosis.

BACKGROUND: Skin fibrosis is a debilitating condition that significantly impacts patient quality of life. Ultraviolet phototherapy is currently used to treat several diseases featuring skin fibrosis. High-fluence light-emitting diode-generated red light (HF-LED-RL) does not cause DNA damage associated with skin cancer, and it is generally regarded as safe, portable, and cost-effective. Early clinical observations suggest that LED-generated light may possess antifibrotic effects, although these findings are largely unexplored. Previously published research demonstrated that HF-LED-RL decreases fibroblast proliferation and collagen in vitro. OBJECTIVE: The goal of this study was to compare the combination effects of HF-LED-RL alone with HF-LED-RL in combination with resveratrol. MATERIALS AND METHODS: It is hypothesized that resveratrol, an active ingredient in red wine, a potent antioxidant scavenger of reactive oxygen species, and an inhibitor of collagen production, may synergistically decrease fibroblast proliferation and collagen production when combined with HF-LED-RL. RESULTS: In this study, evidence is provided that resveratrol combined with HF-LED-RL acts synergistically to decrease fibroblast proliferation and procollagen 1A1 production, and this represents a new potential therapeutic modality that is termed the "photobotanical" effect due to the combined light and botanical properties observed. CONCLUSION: The study, discovery, and use of photobotanical combinations may usher in new therapeutics or phototherapy adjuvants for the treatment of dermatologic diseases.

Striae Distensae: Preventative and Therapeutic Modalities to Improve Aesthetic Appearance.

BACKGROUND: Striae distensae (SD) are aesthetically troublesome to patients and therapeutically challenging. OBJECTIVE: Herein, the authors comprehensively review the literature pertaining to the history, pathogenesis, clinical presentation, clinical rating scales, and laboratory, imaging, and histologic features of SD. METHODS AND MATERIALS: A review of PubMed, MEDLINE, Scopus, Embase, and Google scholar was conducted, including literature published from 1773 to August 6, 2016. RESULTS: The authors identified 68 articles that met inclusion and exclusion criteria. CONCLUSION: There are few randomized controlled trials evaluating the long-term efficacy and safety of various topical and energy-based devices. Based on clinical and anecdotal experience, both nonablative and ablative fractionated lasers have shown modest SD improvement compared with other treatment modalities (including Excimer laser, CuBr laser, pulsed dye laser, and 1,064-nm Nd:YAG laser). In the authors' experience, 1,540-nm nonablative fractionated laser is a worthy first-line modality for the treatment of SD. Future researchers may consider greater focus on enhanced study design, including larger, long-term split-body, or split-SD head-to-head randomized comparative trials with objective outcome measures and end points, such as biopsy and molecular studies demonstrating increased collagen and elastic fibers that correlate to clinical improvement.

A Systematic Review of Light Emitting Diode (LED) Phototherapy for Treatment of Psoriasis: An Emerging Therapeutic Modality.

Background: Psoriasis is a chronic, inflammatory skin condition. The economic burden of psoriasis is approximately $35.2 billion in the United States per year, and treatment costs are increasing at a higher rate than general inflation. Light emitting diode (LED) phototherapy may represent a cost-effective, efficacious, safe, and portable treatment modality for psoriasis.

Objective: The goal of our manuscript is to review the published literature and provide evidence-based recommendations on LED phototherapy for the treatment of psoriasis.

Methods & Materials: A search of the databases Pubmed, EMBASE, Web of Science, and CINAHL was performed on April 5, 2016. Key search terms were related to psoriasis and LED-based therapies.

Results: A total of 7,793 articles were generated from the initial search and 5 original articles met inclusion criteria for our review. Grade of recommendation: B for LED-blue light. Grade of recommendation: C for LED-ultraviolet B, LED-red light, and combination LED-near-infrared and LED-red light.

Conclusion: We envision further characterizing the effects of LED phototherapy to treat psoriasis in patients may increase adoption of LED-based modalities and provide clinicians and patients with new therapeutic options that balance safety, efficacy, and cost.

J Drugs Dermatol. 2017;16(5):482-488.

Resveratrol Prevents Reactive Oxygen Species-Induced Effects of Light-Emitting Diode-Generated Blue Light in Human Skin Fibroblasts.

BACKGROUND: Light-emitting diode-generated blue light (LED-BL) is part of the visible light spectrum that does not cause DNA damage and may represent a safer alternative to ultraviolet phototherapy. Previous research demonstrated that LED-BL can inhibit adult human skin fibroblast proliferation and migration speed and is associated with increased reactive oxygen species (ROS) generation in a dose-dependent manner. In addition, resveratrol possesses potent intracellular antioxidative effects on ROS-free radicals in human skin fibroblasts. OBJECTIVE: The authors studied the effects on migration speed as a surrogate to measure LED-BL effects on fibroblast function. The authors hypothesized that resveratrol, a potent scavenger of ROS, could prevent the effects of LED-BL on fibroblast migration speed. This would implicate ROS as the mechanistic driver of LED-BL effects on human skin fibroblasts. METHODS: To demonstrate that resveratrol could prevent the effects of LED-BL (415-nm), fibroblasts were incubated with resveratrol (Sigma-Aldrich, St. Louis, MO) at concentrations of 0.001% and 0.0001% for 24 hours and then irradiated with LED-BL at fluences of 30, 45, and 80 J/cm. Postirradiation fibroblast migratory speed was assayed in an environment-controlled computer-assisted video microscopy system. Reactive oxygen species levels were measured by flow cytometric analysis of dihydrorhodamine. Statistical analyses with analysis of variance and Student t-test were performed to compare individual treatment arms and matched controls. RESULTS: The experimental results demonstrate that pretreatment of skin fibroblasts with resveratrol at concentrations of 0.001% and 0.0001% prevents the effects of 30, 45, and 80 J/cm of LED-BL on fibroblast migration speed. The authors found that LED-BL at a fluences of 30, 45, and 80 J/cm significantly increased ROS, whereas pretreatment with 0.001% resveratrol significantly reduced ROS generation. CONCLUSION: The findings demonstrate that LED-BL-induced decreases in fibroblast migration speed can be prevented by pretreating cells with resveratrol. This finding supports the hypothesis that ROS generation is the most likely driver of LED-BL-induced alterations in migration speed and suggests that ROS generation may be responsible for a number of other alterations seen after LED-BL phototherapy, such as decreases in cellular migration, cytokine levels, and myofibroblast differentiation. The authors hypothesize that their findings may result in greater understanding of the fundamental mechanisms underlying visible light interaction with skin and they hope dermatologists and other researchers may use these pathways for patient benefit.

Successful Treatment of Traumatic Onychodystrophy and Associated Pterygium Unguis With Fractionated Carbon Dioxide Laser: Case Report and Review of the Literature.

Onychodystrophy is a common, chronic malformation of the nail that is aesthetically displeasing and can signi cantly impact patient quality-of-life. Onychodystrophy can be associated with pterygium unguis that contributes to pain and appears as a V-shaped exten- sion of the proximal nail fold skin. Treatment options are limited, and topical or intralesional corticosteroids have minimal ef cacy and cause signi cant patient discomfort. Surgical revision of onychodystrophy is complex, and symptomatic or aesthetic improvements are difficult to achieve. There is limited published literature on laser treatment of noninfectious onychodystrophy or associated pterygium unguis. We present a case of a 68-year-old man with a 10-year history of painful traumatic onychodystrophy with associated pterygium unguis, who was successfully treated after three treatments of fractionated carbon dioxide (CO2) laser. Additionally, we review the medical literature on laser treatment of noninfectious onychodystrophy and pterygium unguis. To our knowledge, this is the first reported successful treatment of painful traumatic onychodystrophy and associated pterygium unguis using fractionated CO2 laser. We hope clinicians consider this treatment modality to relieve pain and improve aesthetics associated with traumatic onychodystrophy and associated pterygium unguis. We envision additional research investigating the mechanism of action of fractionated CO2 laser may con rm this treatment option for the management of traumatic onychodystrophy and associated pterygium unguis. J Drugs Dermatol. 2016;15(11):1461-1464..

Light emitting diode-generated blue light modulates fibrosis characteristics: fibroblast proliferation, migration speed, and reactive oxygen species generation.

BACKGROUND AND OBJECTIVE: Blue light is part of the visible light spectrum that does not generate harmful DNA adducts associated with skin cancer and photoaging, and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode (LED) red and infrared light inhibits proliferation of skin fibroblasts. Moreover, different wavelengths of light can produce different biological effects. Furthermore, the effects of LED blue light (LED-BL) on human skin fibroblasts are not well characterized. This study investigated the effects of LED-BL on human skin fibroblast proliferation, viability, migration speed, and reactive oxygen-species (ROS) generation. METHODS AND MATERIALS: Irradiation of adult human skin fibroblasts using commercially-available LED-BL panels was performed in vitro, and modulation of proliferation and viability was quantified using the trypan blue dye exclusion assay, migratory speed was assessed using time-lapse video microscopy, and intracellular ROS generation was measured using the dihydrorhodamine flow cytometry assay. Statistical differences between groups were determined by ANOVA and Student's t-test. RESULTS: Human skin fibroblasts treated with LED-BL fluences of 5, 10, 15, 30, and 80 J/cm(2) demonstrated statistically significant dose-dependent decreases in relative proliferation of 8.4%, 29.1%, 33.8%, 51.7%, and 55.1%, respectively, compared to temperature and environment matched bench control plates, respectively. LED-BL fluences of 5, 30, 45, and 80 J/cm(2) decreased fibroblast migration speed to 95 ± 7.0% (P = 0.64), 81.3 ± 5.5% (P = 0.021), 48.5 ± 2.7% (P < 0.0001), and 32.3 ± 1.9% (P < 0.0001), respectively, relative to matched controls. LED fluences of 5, 10, 30, and 80 J/cm(2) resulted in statistically significant increases in reactive oxygen species of 110.4%, 116.6%, 127.5%, and 130%, respectively, relative to bench controls. CONCLUSION: At the fluences studied, LED-BL can inhibit adult human skin dermal fibroblast proliferation and migration speed, and is associated with increased reactive oxygen species generation in a dose-dependent manner without altering viability. LED-BL has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation.

Light-emitting diode-generated red light inhibits keloid fibroblast proliferation.

BACKGROUND: Red light is part of the visible light spectrum that does not generate DNA adducts associated with skin cancer and photoaging and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode-generated red light (LED-RL) inhibits proliferation of skin fibroblasts. The effects of LED-RL on keloidal skin are not well characterized. OBJECTIVE: To determine the effect of LED-RL on keloid-derived fibroblast proliferation and viability in vitro. METHODS: Irradiation of primary keloid-derived human skin fibroblasts using LED-RL panels was performed in vitro, and modulation of proliferation and viability was quantified using trypan blue dye exclusion assay. Statistical analysis was performed using analysis of variance to compare treatment arms and the Student t-test to compare each treatment arm with the paired bench control arm. RESULTS: Keloid fibroblasts treated with LED-RL 240, 320, and 480 J/cm demonstrated statistically significant dose-dependent decreases in relative proliferation rate of 12.4%, 16.5%, and 28.9%, respectively, compared with matched nonirradiated controls (p < .05) and did not significantly alter viability relative to the matched nonirradiated controls. CONCLUSION: Light-emitting diode-generated red light can inhibit keloid fibroblast proliferation in a dose-dependent manner without altering viability. Light-emitting diode-generated red light has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation.

Optical Coherence Tomography Imaging of Normal, Chronologically Aged, Photoaged and Photodamaged Skin: A Systematic Review.

BACKGROUND: Optical coherence tomography (OCT) is capable of providing a noninvasive real-time cross-sectional image of the skin through light-based interferometry, a method sometimes described as "light-based ultrasound." One key application of OCT in dermatology is the visualization of dermal collagen during chronological aging, photoaging, or photodamage. These skin conditions are typically managed by the practitioner's subjective assessment of severity and response to therapy. OBJECTIVE: The purpose of this review is to present available evidence on the ability of OCT to image normal, chronologically aged, photoaged and photodamaged skin in human subjects. METHODS AND MATERIALS: The authors have searched Medline, PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Library databases for published literature on the imaging of skin collagen by OCT using the following search terms: "optical coherence tomography," "OCT," "skin," "collagen," "photoaging," "wrinkles," and "photodamage." RESULTS: The search resulted in 23 articles investigating OCT-based skin collagen imaging, which met their search criteria. CONCLUSION: The authors anticipate tremendous growth in the field of OCT-based skin imaging that will parallel the development ultrasound technology has experienced over the past 30 years. They foresee that the use of OCT imaging to evaluate skin aging will not only help identify pathological changes earlier, but will also assist in the evaluation of the response to therapy longitudinally without biopsy.

Inhibition of fibroblast proliferation in vitro using red light-emitting diodes.

BACKGROUND: Red light is part of the visible light spectrum. The effects of light-emitting diode (LED)-generated red light on human skin are not well-characterized. OBJECTIVE: To study the effect of red LED-generated low-level light therapy (LLLT) on fibroblast proliferation and viability in vitro. METHODS AND MATERIALS: Irradiation of normal human skin fibroblasts using red LED panels was performed in vitro, and modulation of proliferation and viability was quantified using trypan blue dye exclusion assay. RESULTS: Statistically significant decreases in cell proliferation were noted at the following fluences (time): 160 J/cm2 (30 minutes, 34 seconds), 320 J/cm2 (61 minutes, 07 seconds) and 640 J/cm2 (122 minutes, 14 seconds) (Figure 1). Irradiation at the 160- (98.5 ± 1.2%) and 320-J/cm2 (98.0 ± 3.1%) doses did not significantly alter viability. CONCLUSION: At certain fluences, red LLLT can effectively inhibit fibroblast proliferation in vitro without altering viability and holds promise for the treatment of scars and other proliferative skin diseases.

The active natural anti-oxidant properties of chamomile, milk thistle, and halophilic bacterial components in human skin in vitro.

The number of skin cancers continues to rise, accounting for approximately 40% of all cancers reported in the United States and approximately 9,500 deaths per year. Studies have shown reactive oxygen species (ROS) type free radicals are linked to skin cancer and aging. Therefore, it is important for us to identify agents that have anti-oxidant properties to protect skin against free radical damage. The purpose of this research is to investigate the anti-oxidant properties of bisabolol, silymarin, and ectoin that are components from chamomile, milk thistle, and halophilic bacteria, respectively. We measured the ability of bisabolol, silymarin, and ectoin to modulate the hydrogen peroxide (H2O2)-induced upregulation of ROS free radicals in normal human skin fibroblasts in vitro. Using a flow cytometry-based assay, we demonstrated that varying concentrations of these natural components were able to inhibit upregulation of H2O2-generated free radicals in human skin fibroblasts in vitro. Our results indicate components of chamomile, milk thistle, and halophilic bacteria exhibit anti-oxidant capabilities and warrant further study in clinical trials to characterize their anti-cancer and anti-aging capabilities.

Light emitting diode-red light for reduction of post-surgical scarring: Results from a dose-ranging, split-face, randomized controlled trial.

Scarring has significant esthetic and functional consequences for patients. A need exists for anti-scarring therapeutics. Light emitting diode-red light (LED-RL) has been shown to modulate skin fibrosis. The aim of this study is to evaluate the safety and efficacy of LED-RL to reduce post-operative scarring. Cutaneous Understanding of Red-light Efficacy on Scarring was a randomized, mock-controlled, single-blind, dose-ranging, split-face phase II clinical trial. Starting 1 week post-surgery, patients received LED-RL irradiation and temperature-controlled mock therapy to incision sites at fluences of 160, 320 or 480 J/cm2 , triweekly for 3 weeks. Efficacy was assessed at 1, 3 and 6-12 months. The primary endpoint was difference in scar pliability between LED-RL-treated and control sites. Secondary outcomes included Patient and Observer Scar Assessment Scale, collagen and water concentration, and adverse events. There were no significant differences in scar pliability between treated and control scars. At certain fluences, treated scars showed greater improvements in observer rating and scar pliability, reflected by greater reductions in induration, from baseline to 6 months compared to control scars. Treatment-site adverse events included blistering (n = 2) and swelling (n = 1), which were mild and resolved without sequelae. LED-RL phototherapy is safe in the early postoperative period and may reduce scarring.

Transcriptome analysis of human dermal fibroblasts following red light phototherapy.

Fibrosis occurs when collagen deposition and fibroblast proliferation replace healthy tissue. Red light (RL) may improve skin fibrosis via photobiomodulation, the process by which photosensitive chromophores in cells absorb visible or near-infrared light and undergo photophysical reactions. Our previous research demonstrated that high fluence RL reduces fibroblast proliferation, collagen deposition, and migration. Despite the identification of several cellular mechanisms underpinning RL phototherapy, little is known about the transcriptional changes that lead to anti-fibrotic cellular responses. Herein, RNA sequencing was performed on human dermal fibroblasts treated with RL phototherapy. Pathway enrichment and transcription factor analysis revealed regulation of extracellular matrices, proliferation, and cellular responses to oxygen-containing compounds following RL phototherapy. Specifically, RL phototherapy increased the expression of MMP1, which codes for matrix metalloproteinase-1 (MMP-1) and is responsible for remodeling extracellular collagen. Differential regulation of MMP1 was confirmed with RT-qPCR and ELISA. Additionally, RL upregulated PRSS35, which has not been previously associated with skin activity, but has known anti-fibrotic functions. Our results suggest that RL may benefit patients by altering fibrotic gene expression.

The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets.

Skin fibrosis, characterized by excessive fibroblast proliferation and extracellular matrix deposition in the dermis, is the histopathologic hallmark of dermatologic diseases such as systemic sclerosis, hypertrophic scars, and keloids. Effective anti-scarring therapeutics remain an unmet need, underscoring the complex pathophysiologic mechanisms of skin fibrosis. The Th2 cytokines interleukin (IL)-4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders. The goal of this article is to summarize the current understanding of the role of the IL-4/IL-13 axis in wound healing and skin fibrosis. We conducted a literature search to identify research studies investigating the roles of IL-4 and IL-13 in fibrotic skin diseases. While transforming growth factor-beta has long been regarded as the main driver of fibrotic processes, research into the cellular and molecular biology of wound healing has revealed other pathways that promote scar tissue formation. IL-4 and IL-13 are important mediators of skin fibrosis, supported by evidence from in vitro data, animal models of fibrosis, and clinical studies. Overactive signaling of the IL-4/IL-13 axis contributes to the initiation and perpetuation of fibrotic skin diseases. Further insights into the IL-4/IL-13 axis may reveal potential targets for the development of novel therapies that prevent or treat fibrotic skin diseases.

Facial rejuvenation using photodynamic therapy with a novel preparation of ALA and hyaluronic acid in young adults.

Photodynamic therapy (PDT) is a well-established, non-invasive treatment modality that has shown desirable effects such as improvement of fine lines, dyspigmentation, and other signs of photodamage. Many patients seek to decrease, or reverse, effects of sun damage on the skin. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan found in the body, has enormous potential to bind water which allows the skin to retain moisture and maintain elasticity. Topical application of HA has been found to produce anti-wrinkle effects. We conducted a pilot case series evaluating the safety and efficacy of a commercially available 2% 5-aminolevulinic acid (ALA) gel with hyaluronic acid (ALA-HA) and light-emitting diode-red light (LED-RL) for facial rejuvenation as determined by clinical assessments and digital skin analysis of rhytides, pore size, and erythema. All patients noted improvement of their skin and experienced minimal pain during PDT. Evaluation by dermatologists demonstrated significant improvement in overall skin appearance. Digital analysis of photographs revealed improvement of skin spots, wrinkles, pores, texture, UV spots, brown spots, red areas, and porphyrins. Our findings demonstrated safety and efficacy of this novel preparation of photodynamic gel with HA and subsequent activation with LED-RL.

Safety of light emitting diode-red light on human skin: Two randomized controlled trials.

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.