Photobiomodulation CME part II: Clinical applications in dermatology.

Photobiomodulation (PBM) is an emerging treatment modality in dermatology with increasing office and home-based use. PBM is the use of various light sources in the red light (620-700 nm) and near-infrared (700-1440 nm) spectrum as a form of light therapy. PBM is often administered through low-level lasers or light-emitting diodes. Studies show that PBM can be used effectively to treat conditions secondary to cancer therapies, alopecia, ulcers, herpes simplex virus, acne, skin rejuvenation, wounds, and scars. PBM offers patients many benefits compared to other treatments. It is noninvasive, cost-effective, convenient for patients, and offers a favorable safety profile. PBM can be used as an alternative or adjuvant to other treatment modalities including pharmacotherapy. It is important for dermatologists to gain a better clinical understanding of PBM for in-office administration and to counsel patients on proper application for home-use devices to best manage safety and expectations as this technology develops. PBM wavelengths can induce varied biological effects in diverse skin types, races, and ethnicities; therefore, it is also important for dermatologists to properly counsel their skin of color patients who undergo PBM treatments. Future clinical trials are necessary to produce standardized recommendations across conditions and skin types.

Photobiomodulation CME Part I: Overview and Mechanism of Action.

Photobiomodulation (PBM), previously known as low-level laser light therapy, represents a non-invasive form of phototherapy that utilizes wavelengths in the red light (RL, 620-700 nm) portion of the visible light (VL, 400-700 nm) spectrum and the near-infrared (NIR, 700-1440 nm) spectrum. PBM is a promising and increasingly used therapy for the treatment of various dermatologic and non-dermatologic conditions. Photons from RL and NIR are absorbed by endogenous photoreceptors including mitochondrial cytochrome C oxidase (COX). Activation of COX leads to the following changes: modulation of mitochondrial adenosine triphosphate (ATP), generation of reactive oxygen species (ROS), and alterations in intracellular calcium levels. The associated modulation of ATP, ROS and calcium levels promotes the activation of various signaling pathways (e.g., insulin-like growth factors, phosphoinositide 3-kinase pathways), which contribute to downstream effects on cellular proliferation, migration and differentiation. Effective PBM therapy is dependent on treatment parameters (e.g., fluence, treatment duration and output power). PBM is generally well-tolerated and safe with erythema being the most common and self-limiting adverse cutaneous effect.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.

Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.

Systemic therapies in vitiligo: a review.

Vitiligo is characterized by the development of depigmented macules and patches. Autoimmunity has been established as a factor in disease pathogenesis, leading to utilization of immunosuppressive agents. Topical immunosuppressants are commonly used; however, this treatment modality is often cumbersome and inefficient, as many patients have active disease with extensive body surface area involvement. Prompt and aggressive treatment of vitiligo is important, as this may prevent progression and improve quality of life. To meet these challenges and improve patient outcomes, interest in systemic therapies has grown. Currently, oral therapies are rarely prescribed, likely due to concerns with systemic side effects and unclear efficacy. This article provides a brief overview on the use of systemic agents in treating vitiligo in order to provide additional therapeutic options to clinicians.

Photoprotection for all: Current gaps and opportunities.

The effects of solar radiation on human skin differ based on the skin phototype, presence or absence of photodermatoses, biologic capacity to repair DNA damage, wavelength, intensity of sun exposure, geographic latitude, and other factors, underscoring the need for a more tailored approach to photoprotection. To date, the focus of photoprotection guidelines has been to prevent sunburn and DNA damage induced by UV radiation, both UVB and UVA; however, several recent studies have shown that visible light also generates reactive oxygen and nitrogen species that can contribute to skin damage and pigmentation on the skin, particularly in people with skin of color. Therefore, individuals with dark skin, while naturally better protected against UVB radiation by virtue of the high eumelanin content in melanocytes, may need additional protection from visible light-induced skin damage. The current options for photoprotection products need to expand, and potential strategies against visible light include the addition of iron oxide, titanium dioxide, and biologically relevant antioxidants to sunscreen formulations as well as supplementation with orally active antioxidants.

The potential effect of Polypodium leucotomos extract on ultraviolet- and visible light-induced photoaging.

Photoaging induced by both ultraviolet and visible light has been shown to lead to increased inflammation and dysregulation of the extracellular matrix. Standardized extract of the Polypodium leucotomos fern, PLE, possesses anti-inflammatory and antioxidant properties, and has been shown to potentially mitigate photoaging through various mechanisms. This comprehensive review presents the data available on the effects of P. leucotomos extract on UV and VL-induced photoaging in vitro as well as in vivo in murine and human models.

Visible light. Part I: Properties and cutaneous effects of visible light.

Approximately 50% of the sunlight reaching the Earth's surface is visible light (400-700 nm). Other sources of visible light include lasers, light-emitting diodes, and flash lamps. Photons from visible light are absorbed by photoreceptive chromophores (e.g., melanin, heme, and opsins), altering skin function by activating and imparting energy to chromophores. Additionally, visible light can penetrate the full thickness of the skin and induce pigmentation and erythema. Clinically, lasers and light devices are used to treat skin conditions by utilizing specific wavelengths and treatment parameters. Red and blue light from light-emitting diodes and intense pulsed light have been studied as antimicrobial and anti-inflammatory treatments for acne. Pulsed dye lasers are used to treat vascular lesions in adults and infants. Further research is necessary to determine the functional significance of visible light on skin health without confounding the influence of ultraviolet and infrared wavelengths.

Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Role of phototherapy in the era of biologics.

Phototherapy is a safe and effective treatment for many dermatologic conditions. With the advent of novel biologics and small molecule inhibitors, it is important to critically evaluate the role of phototherapy in dermatology. Surveys have shown that many dermatology residency programs do not dedicate time to teaching residents how to prescribe or administer phototherapy. Limitations of phototherapy include access to a center, time required for treatments, and insurance approval. Home phototherapy, a viable option, is also underused. However, it should be emphasized that modern phototherapy has been in use for over 40 years, has an excellent safety profile, and does not require laboratory monitoring. It can be safely combined with many other treatment modalities, including biologics and small molecule inhibitors. In addition, phototherapy costs significantly less than these novel agents. Dermatologists are the only group of physicians who have the expertise and proper training to deliver this treatment modality to our patients. Therefore, to continue to deliver high-quality, cost-effective care, it is imperative that phototherapy be maintained as an integral part of the dermatology treatment armamentarium.

Photobiomodulation for the management of hair loss.

Photobiomodulation, otherwise known as low-level laser (or light) therapy, is an emerging modality for the management of hair loss. Several randomized trials have demonstrated that it is safe and potentially effective on its own or in combination with standard therapies. These devices come in many forms including wearable caps or helmets that afford hands-free and discreet use. Models with light-emitting diodes (LEDs) are less expensive compared to laser-based devices and do not require laser safety considerations, thus facilitating ease of home use. Limitations include cost of the unit, risk of information bias, and lack of standardized protocols. Finally, as with any hair loss treatment, patients' expectations with regards to therapeutic outcomes must be managed.

Phototherapy in the Evaluation and Management of Photodermatoses.

Ultraviolet light (UV) and visible light are important components in the diagnosis of photodermatoses, and UV has the unique ability to also be used to manage photodermatoses. Phototesting, provocative light testing, and photopatch testing can provide important information in diagnosing patients with photodermatoses; phototesting can be used to determine the starting dose for phototherapy in these patients. Once photosensitivity is established, narrowband UVB and UVA1 therapy have helped to improve the quality of life of photosensitive patients, such as those with polymorphous light eruption, chronic actinic dermatitis, and solar urticaria.

Oral Polypodium Leucotomos Extract and Its Impact on Visible Light-Induced Pigmentation in Human Subjects

BACKGROUND: Visible light (VL) has multiple effects on the skin that currently available sunscreens do not protect against. Polypodium leucotomos extract (PLE) has properties that may offer protection against VL. OBJECTIVES: To determine the effectiveness of PLE in preventing VL-induced effects. METHODS: Twenty-two subjects with Fitzpatrick skin phototype IV-VI were enrolled. On day 0, subjects were irradiated with VL. Clinical Investigator's Global Assessment (IGA) scoring and spectroscopic evaluations were performed immediately, 24 hours, and 7 days after irradiation. Subjects then received a 28-day supply of PLE (480 mg daily). Irradiation and evaluation were repeated. Three 4-mm punch biopsies were obtained for immunohistochemistry analysis: one from normal unirradiated skin and the other two twenty-four hours after irradiation, pre- and post-PLE, from sites irradiated with highest dose of VL. RESULTS: All subjects had immediate pigment darkening, persistent pigment darkening, and delayed tanning both pre- and post-PLE. For the highest VL dose (480 J/cm²) spectroscopic assessments demonstrated a statistically significant decrease in persistent pigment darkening and delayed tanning post-PLE. In addition, there was a significant decrease in cyclooxygenase-2, and a trend towards decreases in the markers for cellular damage post-PLE. While there was a trend towards lower IGA scores post-PLE, statistical significance was not reached possibly due to lack of sensitivity of the visual IGA scoring system in detecting small changes. CONCLUSIONS: Spectroscopic data and immunohistochemistry indicate an effect of PLE on visible light induced effects. As such, PLE may be used as an adjuvant to traditional means of photoprotection to protect against the effects of VL. Clinical trial registration number: NCT02904798. J Drugs Dermatol. 2019;18(12):1198-1203.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

The potential role of antioxidants in mitigating skin hyperpigmentation resulting from ultraviolet and visible light-induced oxidative stress.

Oxidative stress is an integral element that influences a variety of biochemical reactions throughout the body and is known to play a notable role in melanogenesis. Exogenous triggers of oxidative stress, such as ultraviolet radiation (UVR) and visible light (VL), lead to pigment formation through somewhat different pathways, but both share a common endpoint-the potential to generate cosmetically undesirable hyperpigmentation. Though organic and inorganic sunscreens are available to protect against the UVR portion of the electromagnetic spectrum, coverage is lacking to protect against the VL spectrum. In this manuscript, we review the phases of tanning, pathways of melanogenesis triggered by UVR and VL, and the associated impact of oxidative stress. We also discuss the known intrinsic mechanisms and paracrine regulation of melanocytes that influence their response to UVR. Understanding these mechanisms and their role in UVR-induced hyperpigmentation should potentially lead to identification of useful targets that can be coupled with antioxidant therapy to alleviate this effect.