Reducing Carbon Dioxide Laser-Induced Postinflammatory Hyperpigmentation with Prophylactic Photobiomodulation: A Case Study.

Objective: This study aimed to investigate the effectiveness of prophylactic photobiomodulation (PBM) in reducing postinflammatory hyperpigmentation (PIH) induced by carbon dioxide (CO2) laser resurfacing in a patient with periorbital syringomas. Background: PIH is a common condition characterized by abnormal skin pigmentation after an inflammatory process occurring in up to 20-30% of patients undergoing CO2 laser resurfacing. Methods: The patient was treated with PBM using a pulsed home-use device at 630 nm before and after CO2 laser treatment. The patient was asked to treat the right periorbital area before and after the CO2 laser treatment, which was continued once a day for 2 consecutive weeks. Results: At 12 weeks, PIH was significantly reduced on the treated side compared with the contralateral untreated side (leading to persistent erythema at 6 months). Conclusions: This is the first report of prophylactic treatment of CO2 laser-induced dyschromia using PBM.

Low-Intensity Visible and Near-Infrared Light-Induced Cell Signaling Pathways in the Skin: A Comprehensive Review.

Objective: To describe current knowledge regarding established and putative cell signaling pathways involved in skin photobiomodulation. Background: The skin is the largest and most accessible organ of the body. It is the first line of defense against the external environment, including solar radiation. Among solar rays, visible and infrared non-ionizing photons may reach human skin and trigger a cascade of non-thermal cell signaling pathways called photobiomodulation (PBM). The use of PBM using artificial light sources has been known for more than 50 years, but it has not yet been widely accepted due to uncertainty about the cellular mechanisms of action. However, much knowledge has been gained in this field in recent years, which will be summarized in this review. Methods: An extensive literature review was performed using Medline, Embase, and Google Scholar as research databases to acquire relevant publications in this particular field. Results: A comprehensive description of chromophores, primary and secondary effectors is provided in addition to a visual representation of known and putative cell signaling mechanisms involved in such complex light-skin interactions. Also, a summary of clinical indications of skin PBM, key light parameters, and promising skin applications (local and systemic) are mentioned. Conclusions: In PBM, skin cells are the first to absorb photons, triggering specific cell-signaling pathways through primary and secondary effectors, leading to enhanced cell repair and survival, notably in hypoxic or stressed cells. A better understanding of the mechanisms of action will help us optimize known indications and discover new ones.

Near-Infrared Light and Skin: Why Intensity Matters.

Infrared light (760 nm-1 mm) constitutes approximately 40% of the solar radiation reaching the ground at sea level. Shortest wavelength near-infrared (NIR) photons (NIR or IR-A: 760-1,400 nm) can penetrate the epidermis, dermis, and subcutaneous tissue with numerous biological effects. NIR used to have a bad reputation on the basis of past studies using high-intensity artificial light sources (above the solar IR-A irradiance threshold) at high doses leading to detrimental effects (i.e., upregulation of matrix metalloproteinase-1). However, when looking at the other side of the coin and what we can learn from the sun, NIR intensity matters. Hence, mimicking sunlight NIR intensity (30-35 mW/cm2) will rather trigger beneficial cutaneous effects. It is likely that intensity is more important than the fluence (dose) delivered. Moreover, the law of reciprocity (i.e., the biological effect is directly proportional to the total dose irrespective of intensity) does not always apply when considering tissue response in photobiology. In fact, the biphasic dose curve (Arndt-Schulz curve) of photobiomodulation establishes that if irradiance is lower than the physiological threshold value for a given target, it does not produce beneficial effects, even when -irradiation duration is extended. Also, photo-inhibitory deleterious effects may occur at higher irradiances. Remarkably, the beneficial "sweet spot" in between corresponds to the irradiance of the sun. NIR might even precondition the skin from an evolutionary standpoint as exposure to early morning NIR wavelengths in sunlight may prepare the skin for upcoming mid-day harmful UVR. Consequently, NIR light appears to be the solution, not the problem.

The Efficacy and Effectiveness of Non-ablative Light-Based Devices in Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that may be treated with non-ablative light-based devices; however, no systematic reviews on the topic exist to date. We conducted a systematic review and meta-analysis to determine efficacy of non-ablative light-based devices in treating HS. Specifically, a systematic review was conducted using MEDLINE, EMBASE, Web of Science and CINAHL. We analyzed the use of non-ablative light-based devices in the treatment of HS. At least two investigators performed title/abstract review and data extraction. Meta-analysis was conducted using comprehensive meta-analysis software. 5 RCTs and 11 case reports/series were included (n = 211 unique patients). No observational studies were found. For Nd:YAG laser, meta-analysis of 3 RCTs reported improvement in modified HS Lesion Area and Severity Index (HS-LASI) when compared to control subjects. In addition, three case reports/series reported HS-LASI, Physician Global Assessment (PGA) scores and number-of-lesion improvements in treated patients. For intense pulsed light (IPL), two RCTs reported HS-LASI and Dermatology Life Quality Index (DLQI) score improvements. For Alexandrite laser, one case report showed lesion improvement. In conclusion, meta-analysis of Nd:YAG laser in HS patients suggests significant improvement in HS-LASI scores. For IPL, evidence is limited, but suggests improvement in HS-LASI and DLQI scores. For Alexandrite laser, evidence precludes conclusions. Given small sample sizes and inconsistent reporting scales, larger RCTs are required to better determine the efficacy of these modalities in treating HS.

Beneficial Effects of Near-Infrared Light Photobiomodulation in Linear Morphea: A Case Report.

Background: Linear morphea is a variant of scleroderma limited to the skin and underlying tissues secondary to an autoimmune inflammation leading to excess collagen deposition and fibrosis. Apart from topical or oral medications, successful light-based treatments have been reported using phototherapy including Psoralen plus ultraviolet A, photodynamic therapy, carbon dioxide laser, pulsed dye laser, and visible/infrared light. Methods: We report a patient with biopsy-proven infraorbital linear morphea responding to 940 nm near-infrared light photobiomodulation treatments. Results: The patient had excellent cosmesis without textural changes or hypopigmentation despite her darker skin complexion (Fitzpatrick phototype III) after tri-weekly treatments for 8 months. Conclusions: Linear morphea, therefore, may be potentially amenable to home use light-based therapy by using nonthermal nonablative 940 nm photons. To our knowledge, this home-based treatment approach has not been previously reported.

Multiple miliary osteoma cutis treatment response to Q-switched Nd:YAG laser: A case report.

Facial multiple miliary osteoma cutis is a variant of osteoma cutis usually occurring in women with a previous history of acne vulgaris. Successful ablative laser treatment has been reported using both CO2 and Er:YAG lasers among other invasive treatment modalities, like surgical removal. We report a patient with biopsy-proven facial multiple miliary osteoma cutis responding to non-ablative Q-switched Nd:YAG laser therapy. The patient had excellent cosmesis without textural changes or hypopigmentation despite her Asian background after three sessions over 6 months. Multiple miliary osteoma cutis is therefore now amenable to non-surgical non-ablative therapy by using Q-switched Nd:YAG laser therapy reducing the risk of textural changes and hypopigmentation, especially in dark complexion and high-risk individuals. To our knowledge, this treatment approach has not been previously reported.

Current trends in needle-free jet injection: an update.

BACKGROUND: Jet injection can be defined as a needle-free drug delivery method in which a high-speed stream of fluid impacts the skin and delivers a drug. Despite 75 years of existence, it never reached its full potential as a strategic tool to deliver medications through the skin. OBJECTIVE: The aim of this review was to evaluate and summarize the evolution of jet injection intradermal drug delivery method including technological advancements and new indications for use. METHODS: A review of the literature was performed with no limits placed on publication date. RESULTS: Needleless injectors not only reduce pain during drug delivery but also confine the drug more evenly in the dermis. Understanding skin properties of the injection site is a key factor to obtain optimal results as well as setting the right parameters of the jet injector. Until the advent of disposable jet injectors/cartridges, autoclaving of the injector remains the only reliable method to eliminate the risk of infection. Needle-free intradermal injection using corticosteroids and/or local anesthetics is well documented with promising indications being developed. LIMITATIONS: Limitations of the review include low-quality evidence, small sample sizes, varying treatment parameters, and publication bias. CONCLUSION: New developments may help reconsider the use of jet injection technology. Future studies should focus on measurable optimized parameters to insure a safe and effective outcome.

Dual Effect of Photobiomodulation on Melasma: Downregulation of Hyperpigmentation and Enhanced Solar Resistance-A Pilot Study.

Overview. Melasma is a resistant, sun-induced facial hyperpigmentation capable of remaining present for decades with ensuing psychological distress. Treatment is difficult and focuses on an array of measures to reduce skin hyperpigmentation resulting from triggered hyperactive melanocytes. The pathogenesis of melanoma is not clearly understood but it has been reported that some growth factors and specific cell-signaling pathways are involved. Objective. The objective of the current study was to evaluate the use of pulsed photobiomodulation to modulate melasma via the regulation of gene expression pertaining to skin pigmentation. Methods. We evaluated a two-step approach via a spilt-face pilot study involving seven patients with bilateral dermal melasma who had formerly undergone unsuccessful treatments. During treatment, the initial mobilization phase with microdermabrasion was closely followed by the modulation phase, delivering low-energy pulsed photons (940nm) to downregulate highly metabolic melanocytes in the dermis. A weekly treatment was performed for eight consecutive weeks. White light pictures, ultraviolet pictures, melanin index scores, and Melasma Area and Severity Index scores were obtained at baseline and at Week 12. Results. The pulsed photobiomodulation-treated side versus the control side showed statistically significant results for pigment reduction. Conclusion. This pilot study shows that dermal melasma can be significantly improved with pulsed photobiomodulation. Interestingly, it might also precondition the skin, helping it to build a resistance to future solar ultraviolet ray exposure.

Infrared and skin: Friend or foe.

In the last decade, it has been proposed that the sun's IR-A wavelengths might be deleterious to human skin and that sunscreens, in addition to their desired effect to protect against UV-B and UV-A, should also protect against IR-A (and perhaps even visible light). Several studies showed that NIR may damage skin collagen content via an increase inMMP-1 activity in the same manner as is known for UVR. Unfortunately, the artificial NIR light sources used in such studies were not representative of the solar irradiance. Yet, little has been said about the other side of the coin. This article will focus on key information suggesting that IR-A may be more beneficial than deleterious when the skin is exposed to the appropriate irradiance/dose of IR-A radiation similar to daily sun exposure received by people in real life.IR-A might even precondition the skin--a process called photo prevention--from an evolutionary standpoint since exposure to early morning IR-A wavelengths in sunlight may ready the skin for the coming mid-day deleterious UVR. Consequently IR-A appears to be the solution, not the problem. It does more good than bad for the skin. It is essentially a question of intensity and how we can learn from the sun. © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Pulsed versus continuous wave low-level light therapy on osteoarticular signs and symptoms in limited scleroderma (CREST syndrome): a case report.

Limited cutaneous systemic sclerosis (lcSSc) was formerly known as CREST syndrome in reference to the associated clinical features: calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasias. The transforming growth factor beta has been identified as a major player in the pathogenic process, where low-level light therapy (LLLT) has been shown to modulate this cytokine superfamily. This case study was conducted to assess the efficacy of 940 nm using millisecond pulsing and continuous wave (CW) modes on osteoarticular signs and symptoms associated with lcSSc. The patient was treated two to three times a week for 13 weeks using a sequential pulsing mode on one elbow and a CW mode on the other. Efficacy assessments included inflammation, symptoms, pain, health scales, patient satisfaction, clinical global impression, and adverse effects monitoring. Considerable functional and morphologic improvements were observed after LLLT, with the best results seen with the pulsing mode. No adverse effects were noted. Pulsed LLLT represents a treatment alternative for osteoarticular signs and symptoms in limited scleroderma (CREST syndrome).

Low fluence-high repetition rate diode laser hair removal 12-month evaluation: reducing pain and risks while keeping clinical efficacy.

BACKGROUND AND OBJECTIVE: High fluence diode lasers with contact cooling have emerged as the mainstay modality for hair removal. However, the use of these devices is associated with pain and side effects, especially in patients with dark or tanned skin. A novel concept of depilation at low fluence using 810 nm diode laser has been introduced as a solution to these shortcomings. The purpose of this study was to evaluate the lasting efficacy and safety of low-level fluence 810 nm (15 J/cm(2) ) and high repetition rate (5 Hz) F1 Diode Laser™ therapy on hair reduction in patients with various skin types. STUDY DESIGN/MATERIALS AND METHODS: This randomised, controlled, bilaterally paired within-patient, double-blind study compared low level fluence 810 nm (15 Joules/cm(2) ) laser diode therapy to nontreated shaved control areas on long-term hair reduction. Seventeen patients with skin type II-V were treated four times at 1 month intervals. Hair count was assessed monthly over 10 months using an objective computerised method. Safety and tolerability were assessed by adverse reactions monitoring. RESULTS: Statistically significant differences in hair count between treated and control sites were observed at each follow-up visit. The majority of patients reported a slight but bearable sensation of heat during the laser treatment, and transient erythema post-treatment. CONCLUSIONS: This study showed that laser hair removal with the F1 Diode Laser™ system was generally well tolerated, safe, and efficacious in this small sample study of patients with various skin types. After just four treatments, permanent hair reduction following one complete hair cycle has been shown. Controlled studies on larger groups of patients within each skin phototype are needed to confirm these promising results.

No-needle jet intradermal aminolevulinic Acid photodynamic therapy for recurrent nodular Basal cell carcinoma of the nose: a case report.

Photodynamic therapy (PDT) with aminolevulinic acid (ALA) to treat nodular basal cell carcinoma (BCC) has been shown to be beneficial. The success rate of ALA-PDT in the treatment of nodular BCC is dependent on optimal penetration of the photosensitizing agent and subsequent PpIX production. To enhance topical delivery of drugs intradermally, a needleless jet injection (NLJI), which employs a high-speed jet to puncture the skin without the side effects of needles, was used in one patient with recurrent BCC of the nose. Photoactivation was then performed using red light emitting diode [CW @ λ 630 nm, irradiance 50 mW/cm(2), total fluence 51 J/cm(2)] for 17 minutes. Excellent cosmesis was obtained. Aside from mild crusting present for six days, no other adverse signs were noted. Clinically, there was no recurrent lesion up two years postintervention. Additional studies in larger samples of subjects are needed to further evaluate this promising technique.

Importance of pulsing illumination parameters in low-level-light therapy.

The influence of emission parameters in low-level-light therapy on cellular responses is not yet fully understood. This study assessed the impact of various light delivery modes on collagen production in human primary fibroblast cultured in monolayers after three treatments with red light-emitting diode illumination (630 nm, 8 J/cm(2)). Human type I collagen was measured in cell culture supernatants with procollagen type I C-peptide enzyme immunoassay. Results demonstrated that, 72 h post-baseline, specific microsecond pulsing patterns had a more favorable impact on the ability of fibroblasts to produce collagen de novo than comparative conditions of continuous wave, pulsed 50% duty cycle, and millisecond pulsing domains. The cascade of events leading to collagen production by red illumination may be explained by the photodissociation of nitric oxide from cytochrome c oxidase. Short and intermittent light delivery might enhance this cellular event.

Prophylactic low-level light therapy for the treatment of hypertrophic scars and keloids: a case series.

BACKGROUND AND OBJECTIVES: Hypertrophic and keloid scars result from alterations in the wound healing process. Treating abnormal scars remains an important challenge. The aim of this case series was to investigate the effectiveness of near infrared (NIR) light emitting diode (LED) treatment as a prophylactic method to alter the wound healing process in order to avoid or attenuate the formation of hypertrophic scars or keloids. STUDY DESIGN/PATIENTS AND METHODS: Three patients (age 27-57) of phototypes I-III with hypertrophic scars or keloids due to acne or surgery participated in this case series. Following scar revision by surgery or CO(2) laser ablation on bilateral areas, one scar was treated daily by the patient at home with non-thermal, non-ablative NIR LED (805 nm at 30 mW/cm(2)) for 30 days. Efficacy assessments, conducted up to a year post-treatment, included the Vancouver Scar scale (VSS), clinical global assessment of digital photographs, and quantitative profilometry analysis using PRIMOS. Safety was documented by adverse effects monitoring. RESULTS: Significant improvements on the NIR-treated versus the control scar were seen in all efficacy measures. No significant treatment-related adverse effects were reported. CONCLUSION: Possible mechanisms involved are inhibition of TGF-beta I expression. Further studies in larger group of patients are needed to evaluate this promising technique.

Radiant near infrared light emitting Diode exposure as skin preparation to enhance photodynamic therapy inflammatory type acne treatment outcome.

BACKGROUND AND OBJECTIVE: An alternative approach in the treatment of acne vulgaris is photodynamic therapy (PDT) that uses light and aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) production to eradicate Propionibacterium acnes found in acne lesions. PpIX formation is dependent on ALA percutaneaous penetration. In this study, to enhance ALA penetration and subsequent accumulation of PpIX, skin temperature was increased with radiant infrared (IR) prior to ALA-PDT application and compared to ALA-PDT alone in the treatment of inflammatory acne. STUDY DESIGN/MATERIALS AND METHODS: Ten patients exhibiting inflammatory acne with a lesion count of > or =10 were assigned to a split face or split back group. One side was pre-treated for 15 minutes with radiant IR light emitting diode (LED) (970 nm), while the other side was used as control. ALA was then applied after which PDT LED (630 nm) was performed on the entire face or back surface. Blinded lesion counts and clinical global assessment of severity were performed based on digital photographs before and 4 weeks after the PDT procedure. RESULTS: This randomized, controlled, and rater-blinded trial revealed a significant difference in median reduction of inflammatory lesions on the IR pre-treated (73%, 95% confidence interval (CI) 51-81%) versus the control side (38%, 95% CI 8-55%) 1 month after PDT (P<0.0001). Clinical assessment of severity was also significantly lower on the IR-treated side than on the control side (median 1, 95% CI 0.74-1.34 vs. 2, 95% CI 1.17-1.72). No unusual treatment-related adverse effects were observed. CONCLUSION: The reported therapeutic effects may be due to enhanced induction of alterations in transcutaneous diffusion kinetics of the photosensitizer at higher skin temperature and/or conversion of ALA to PpIX. Pre-PDT radiant IR LED exposure appears to be a promising method to enhance PDT efficacy for the treatment of acne lesions.

Regulation of skin collagen metabolism in vitro using a pulsed 660 nm LED light source: clinical correlation with a single-blinded study.

It has been reported that skin aging is associated with a downregulation in collagen synthesis and an elevation in matrix metalloproteinase (MMP) expression. This study investigated the potential of light-emitting diode (LED) treatments with a 660 nm sequentially pulsed illumination formula in the photobiomodulation of these molecules. Histological and biochemical changes were first evaluated in a tissue-engineered Human Reconstructed Skin (HRS) model after 11 sham or LED light treatments. LED effects were then assessed in aged/photoaged individuals in a split-face single-blinded study. Results yielded a mean percent difference between LED-treated and non-LED-treated HRS of 31% in levels of type-1 procollagen and of -18% in MMP-1. No histological changes were observed. Furthermore, profilometry quantification revealed that more than 90% of individuals showed a reduction in rhytid depth and surface roughness, and, via a blinded clinical assessment, that 87% experienced a reduction in the Fitzpatrick wrinkling severity score after 12 LED treatments. No adverse events or downtime were reported. Our study showed that LED therapy reversed collagen downregulation and MMP-1 upregulation. This could explain the improvements in skin appearance observed in LED-treated individuals. These findings suggest that LED at 660 nm is a safe and effective collagen-enhancement strategy.

LED photoprevention: reduced MED response following multiple LED exposures.

BACKGROUND AND OBJECTIVES: As photoprotection with traditional sunscreen presents some limitations, the use of non-traditional treatments to increase skin resistance to ultraviolet (UV) induced damage would prove particularly appealing. The purpose of this pilot study was to test the potential of non-thermal pulsed light-emitting diode (LED) treatments (660 nm) prior to UV exposure in the induction of a state of cellular resistance against UV-induced erythema. STUDY DESIGN/MATERIALS AND METHODS: Thirteen healthy subjects and two patients with polymorphous light eruption (PLE) were exposed to 5, 6, or 10 LED treatments (660 nm) on an EXPERIMENTAL anterior thigh region. Individual baseline minimal erythema doses (MED) were then determined. UV radiation was thereafter performed on the LED EXPERIMENTAL and CONTROL anterior thigh areas. Finally, 24 hours post-UV irradiation, LED pre-treated MED responses were compared to the non-treated sites. RESULTS: Reduction of erythema was considered significant when erythema was reduced by >50% on the LED-treated side as opposed to CONTROL side. A significant LED treatment reduction in UV-B induced erythema reaction was observed in at least one occasion in 85% of subjects, including patients suffering from PLE. Moreover, there was evidence of a dose-related pattern in results. Finally, a sun protection factor SPF-15-like effect and a reduction in post-inflammatory hyperpigmentation were observed on the LED pre-treated side. CONCLUSIONS: Results suggest that LED based therapy prior to UV exposure provided significant protection against UV-B induced erythema. The induction of cellular resistance to UV insults may possibly be explained by the induction of a state a natural resistance to the skin via specific cell signaling pathways and without the drawbacks and limitations of traditional sunscreens. These results represent an encouraging step towards expanding the potential applications of LED therapy and could be useful in the treatment of patients with anomalous reactions to sunlight.

Light-emitting diodes (LEDs) in dermatology.

Light-emitting diode photobiomodulation is the newest category of nonthermal light therapies to find its way to the dermatologic armamentarium. In this article, we briefly review the literature on the development of this technology, its evolution within esthetic and medical dermatology, and provide practical and technical considerations for use in various conditions. This article also focuses on the specific cell-signaling pathways involved and how the mechanisms at play can be put to use to treat a variety of cutaneous problems as a stand-alone application and/or complementary treatment modality or as one of the best photodynamic therapy light source.