What is the relationship between photosensitizing drugs and skin cancer?

ABSTRACT: Many medications are associated with phototoxicity or photoallergy, the two types of photosensitivity. Recently, a warning related to increased skin cancer risk was added to the labeling of the popular diuretic hydrochlorothiazide. This article reviews some photosensitizing medications and describes patient education on preventing and recognizing photosensitivity reactions and skin cancer.

An Added Benefit of Masks During the COVID-19 Pandemic: Ultraviolet Protection.

The widespread use of masks during the COVID-19 pandemic presents a new avenue for protecting the lower half of the face from the harms of sun exposure. The increased social acceptability of masks, which may persist post-pandemic, has the potential to impact prevention of photosensitive disorders, photoaging, and skin cancer. The authors sought to review clinically relevant information on the ultraviolet (UV) shielding properties of masks. This synthesis of current research will help physicians counsel patients on optimal mask choices, from both dermatological and public health viewpoints. The variables impacting the UV protection of masks were reviewed, including fabric type, construction, porosity, and color. Other factors related to wear and use such as moisture, stretch, laundering, and sanitization are discussed in the context of the pandemic. Black, tightly woven, triple-layered polyester cloth masks were determined to be optimal for UV protection. The most protective choice against both SARS-CoV-2 and UV radiation is a medical mask worn underneath the aforementioned cloth mask. In order to preserve the filtration capacity of the fabric, masks should be changed once they have become moist. Washing cotton masks before first use in laundry detergents containing brightening agents increases their UV protection. Overall, cloth masks for the public that are safest against SARS-CoV-2 are generally also the most protective against UV damage. People should be encouraged to procure a high-quality mask to simultaneously help reduce the spread of SARS-CoV-2 and shield against sun exposure. Further investigation is needed on the UV-protective properties of medical masks.

Violet-blue light exposure of the skin: is there need for protection?

Advocates of skin protection against blue light express concern about exposure to indoor lighting and electronic screens as well as natural outdoor exposure. However, the nature of adverse effects in skin is unclear and the doses to induce effects are unknown. We aimed to reveal whether there is a scientific basis for promoting skin protection against violet-blue light (400-500 nm, VBL). Based on published literature, we determined the time to reach a threshold dose that induced a biological response in human skin. In the absence of an action spectrum for effects on skin, we used a hand held probe with a defined spectral response and measurements of the unweighted exposure between 400 and 500 nm to estimate the exposure by a selection of artificial light sources and solar light. For comparison, an outdoor threshold erythemally weighted UV dose was set to 1 SED (standard erythema dose). Outdoor, weighted irradiances were obtained using a radiative transfer model. Induction of pigmentation in human skin tissue was the only consistently reported endpoint after VBL exposure of about 65 Jcm-2. This threshold dose was reached in 0.5 to 20 months of exposure to indoor lighting sources. In comparison, specialised medical sources reached this dose in 0.5 min to 45 h. The time outdoors to reach 1 SED was shorter than the time to reach a VBL threshold dose throughout all seasons. Skin protection against VBL is superfluous for exposures to domestic lighting sources or screens and for solar radiation; however, it may be advantageous for patients suffering from photosensitive diseases or taking photosensitising medication.

Protective effects of liquiritin on UVB-induced skin damage in SD rats.

Overexposure to ultraviolet B (UVB) rays can cause damage to the skin. Liquiritin has a variety of pharmacological effects, such as anti-inflammatory and antioxidant. In the present study, the effect of liquiritin on UVB irradiated rat skin was investigated. Results showed that UVB irradiation caused erythema and wrinkles on the skin surface, as well as thickening and loss of elasticity of the epidermis and a significant increase in the level of ROS in the skin tissue. At the same time, western blot detected an increase in nuclear factor kappa-B (NF-κB) and matrix metalloproteinases (MMPs) and Elisa also detected an increase in pro-inflammatory factors. Therefore, we hypothesized that UVB irradiation-induced damage is associated with inflammation. Interestingly, application of liquiritin to exposed skin of rats reduced the increase in ROS, pro-inflammatory factors, and MMPs caused by UVB irradiation and increased the levels of Sirtuin3 (SIRT3) and Collagen α1. In addition, after intraperitoneal injection of the SIRT3 inhibitor 3-TYP in rats, the protective effect of liquiritin against UVB damage was found to be diminished. These results suggested that promotion of SIRT3 with liquiritin inhibits UVB-induced production of pro-inflammatory mediators, possibly acting through the SIRT3/ROS/NF-κB pathway. In conclusion, this study suggests that liquiritin is an effective drug candidate for the prevention of UVB damage.

Photoprotection beyond ultraviolet radiation: A review of tinted sunscreens.

Ultraviolet radiation and visible light both have biologic effects on the skin. Visible light can induce erythema in light-skinned individuals and pigmentation in dark-skinned individuals. Broad-spectrum sunscreens protect against ultraviolet radiation but do not adequately protect against visible light. For a sunscreen to protect against visible light, it must be visible on the skin. Inorganic filters (also known as mineral filters), namely, zinc oxide and titanium dioxide, are used in the form of nanoparticles in sunscreens to minimize the chalky and white appearance on the skin; as such, they do not protect against visible light. Tinted sunscreens use different formulations and concentrations of iron oxides and pigmentary titanium dioxide to provide protection against visible light. Many shades of tinted sunscreens are available by combining different amounts of iron oxides and pigmentary titanium dioxide to cater to all skin phototypes. Therefore, tinted sunscreens are beneficial for patients with visible light-induced photodermatoses and those with hyperpigmentation disorders such as melasma and postinflammatory hyperpigmentation.

Photoprotective habits in children with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can involve multiple organ systems. Exposure to ultraviolet radiation (UVR) can exacerbate pre-existing SLE, and can even induce systemic manifestations. This study aimed to investigate the photoprotective habits of children with SLE and the factors that significantly influence those photoprotective habits. METHODS: This questionnaire-based cross-sectional study included paediatric SLE patients being treated at the Department of Paediatrics at Siriraj Hospital, Mahidol University, between September 2018 and September 2019. Data were obtained from medical records and a face-to-face interview. RESULTS: Ninety-six patients were enrolled, with a female-to-male ratio of 8:1. The mean age of patients at enrollment was 13.7 ± 2.4 years. Of the 96 patients, 70 (72.9%) reported being directly exposed to sunlight for less than two hours per day, but 39% of patients spent time in the sun during the peak hours of UVR. Up to 95% of patients used sunscreen. However, only 64% of patients applied it every day, and only 35% of patients used an adequate amount of sunscreen. Girls were significantly more likely to apply sunscreen every day than boys were (p = 0.041). SLE patients with a shorter disease duration had significantly greater exposure to sunlight than patients with a disease duration of more than four years (p = 0.040). CONCLUSION: Sunscreen was the most common photoprotective method. However, most patients used sunscreen inappropriately. A shorter disease duration was significantly associated with more sunlight exposure. Regular evaluation and emphasis of the importance of photoprotection should be encouraged among paediatric SLE.

Successful Liver Transplantation for Liver Failure With Erythropoietic Protoporphyria by Covering the Operating Theater Lights With Polyimide Film: A Case Report.

BACKGROUND: Erythropoietic protoporphyria is a rare disease of heme biosynthesis resulting in excessive accumulation of protoporphyrin in various organs. The most typical symptom is photosensitivity caused by activated protoporphyrins (wavelength ~400 nm). Accumulated protoporphyrin in the liver also causes liver failure, and liver transplantation is the only life-saving treatment. Phototoxic injury to abdominal organs has been reported during liver transplantation. Thus, to avoid phototoxic injury during liver transplantation, it has previously been conducted with only shadowless lights and ceiling lights off in the operating theater. Here, we report a case of a safe and successful liver transplantation in a patient with erythropoietic protoporphyria where the operating theater lights were covered with polyimide film. CASE PRESENTATION: A 50-year-old man presented with hepatic failure owing to erythropoietic protoporphyria. Before liver transplantation, the shadowless lights and ceiling lights in the operating theater were covered entirely with polyimide film. This filter completely blocked the harmful wavelength of light (400-470 nm). Orthotopic liver transplantation was safely and successfully performed with adequate illumination and patient monitoring. The patient followed a normal postoperative course without phototoxic injuries or protoporphyrin re-accumulation. CONCLUSION: Covering not only shadowless lights but also all ceiling lights in the operating theater with the polyimide film allowed safe surgery, safe anesthesia, and safe monitoring of the patient who underwent liver transplantation for severe liver failure owing to erythropoietic protoporphyria.

UV-responsive AKBA@ZnO nanoparticles potential for polymorphous light eruption protection and therapy.

Polymorphous light eruption (PLE) is one of the acquired idiopathic photodermatosis mainly induced by immoderate UV radiation. In order to realize UV protection and medicine administration simultaneously for polymorphous light eruption protection and therapy, Acetyl-11-keto-ß-boswellic acid (AKBA) loaded Zinc Oxide (ZnO) nanoparticles of which drug release behavior is UV-controlled has been successfully synthesized. Such nanoparticles can not only reflect UV but also transfer the energy to release AKBA which presents an excellent antioxidant and anti-inflammatory effects. In addition, they are biocompatible to HaCaT cells. As a result, they have a great potential in combining UV protection and medicine administration simultaneously for PLE protection and therapy.

Protective effect of a topical sunscreen formulation fortified with melatonin against UV-induced photodermatitis: an immunomodulatory effect via NF-κB suppression.

Objective: Melatonin and pumpkin seed oil, along with US FDA approved UV filters were incorporated into a formulation for enhancement of UV protection by exerting an antioxidant effect. The objective of this study was to assess the protective effect of this formulation against ultraviolet (UV) radiation-induced photo dermatitis in rats, which is an established model to study the aetiopathogenic mechanisms in psoriasis vulgaris, as the former exhibits the same features to those of clinical psoriasis vulgaris in humans. Materials and methods: The animals were segregated into five groups (6/group) and all received their respective formulations dermally prior to chronic UV irradiation for 28 days. The test, placebo, and standard groups; received the test, placebo, and standard formulations respectively; whereas the positive control group received only UV radiation. A normal control group was also maintained. Disease and treatment status were analyzed using various techniques by euthanizing the rats after 28 days. Results: The test formulation was able to ameliorate the UV-induced increase in skin fold, epidermal thickness, and skin edema; inhibit the reduction of hydroxyproline content and incidence of LPO within the skin tissues of exposed animals. The formulation was also able to inhibit the release of proinflammatory cytokines; IFN-γ, IL-1ß, IL-6, and TNF-α; and upregulation of NF-κB and COX-2 genes caused by chronic UV exposure. Conclusion: It can be stated that melatonin included in the newly formulated sunscreen was able to inhibit the induction of photodermatitis via immunoregulation of inflammatory cytokines along with NF-κB and COX-2 genes.

Drug and chemical induced photosensitivity from a clinical perspective.

Drug photosensitivity is a relatively common occurrence and a range of mechanisms may be involved. Some of these mechanisms will be discussed, including the most common, that of drug phototoxicity. Different types of photosensitivity are addressed with respect to clinical presentation, mechanisms and additionally the contribution to our understanding through clinically directed investigations and regulatory requirements. Repeated controlled therapeutic use of drug phototoxicity, with psoralen-UVA (PUVA) photochemotherapy and photodynamic therapy (PDT) will also be discussed. Finally, the potential for drug-induced photocarcinogenesis will also be covered.

Fotoprotección y fotodaño en la niñez y la adolescencia / Photoprotection and photodamage in the childhood and adolescence

Durante las últimas décadas se ha incrementado la incidencia del cáncer de piel, debido fundamentalmente a la exposición a las radiaciones solares, por lo cual es importante la protección desde las edades tempranas. Teniendo en cuenta lo anterior, se realizó una revisión bibliográfica con el objetivo de describir los efectos que estas ocasionan en los seres humanos y las formas de protección adecuadas. Se concluyó que el conocimiento y la implementación de las recomendaciones para la fotoprotección, son necesarias para prevenir los efectos causados por dichas radiaciones.

During the last decades the incidence of the skin cancer has been increased, due fundamentally to the exposure to the sun radiations, reason why it is important the protection since early ages. Keeping this in mind, a literature review was carried out with the objective of describing the effects that they cause in the human beings and the appropriate protection forms. It was concluded that the knowledge and the implementation of the recommendations for photoprotection, are necessary to prevent the effects caused by these radiations.

Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye.

Although immune responses are essential to protect the body from infection, they can also harm tissues. Certain tissues and organs, including the eye, constitute specialized microenvironments that locally inhibit immune reactivity. Dedicator of cytokinesis protein 2 (DOCK2) is a Rac-specific guanine nucleotide exchange factor (GEF) that is predominantly found in hematopoietic cells. DOCK2 plays a key role in immune surveillance because it is essential for the activation and migration of leukocytes. DOCK2 mutations cause severe immunodeficiency in humans. We found that DOCK2-mediated Rac activation and leukocyte migration were effectively inhibited by cholesterol sulfate (CS), but not by cholesterol or other sulfated steroids. CS bound to the catalytic domain of DOCK2 and suppressed its GEF activity. Mass spectrometric quantification revealed that CS was most abundantly produced in the Harderian gland, which provides the lipids that form the oily layer of the tear film. Sulfation of cholesterol is mediated by the sulfotransferases SULT2B1b and, to a lesser extent, SULT2B1a, which are produced from the same gene through alternative splicing. By genetically inactivating Sult2b1, we showed that the lack of CS in mice augmented ultraviolet- and antigen-induced ocular surface inflammation, which was suppressed by administration of eye drops containing CS. Thus, CS is a naturally occurring DOCK2 inhibitor and contributes to the generation of the immunosuppressive microenvironment in the eye.

Nanoencapsulation of Cyanidin-3- O-glucoside Enhances Protection Against UVB-Induced Epidermal Damage through Regulation of p53-Mediated Apoptosis in Mice.

Excess ultraviolet (UV) radiation causes numerous forms of skin damage. The aim of the present study was to assess and compare the photoprotective effects of cyanidin-3- O-glucoside (C3G) alone and encapsulated in chitosan nanoparticles (Nano-C3G) in a UVB-induced acute photodamage mouse model. Nano-C3G was developed from chitosan and sodium tripolyphosphate (TPP) by ionic gelation. The particle size, zeta potential, entrapment efficiency, drug loading, and in vitro release in 6 days were determined. Kunming (KM) mice were treated with Nano-C3G (125, 250, 500 µM) or C3G (500 µM) after part of the dorsal skin area was dehaired and then exposed to 2 J/cm2 of UVB. The nanocapsules were successfully produced and had a uniform and complete spherical shape without agglomeration. The size, zeta potential, entrapment efficiency, and drug loading of Nano-C3G was 288 nm, +30 mV, 44.90%, and 4.30%, respectively. C3G in the nanocapsules was released quite rapidly, and the release rate slowed down at higher pH. The animal experiment demonstrated that Nano-C3G could effectively reduce the UVB-induced lipid peroxidation, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine contents; downregulate p53, Bcl-2-associated X (Bax), and caspase-3 and -9 expression; and balance the B-cell lymphoma-2/leukemia-2 ratio. Moreover, Nano-C3G (125, 250, 500 µM) improved the visual appearance, skin moisture, histologic appearance, and apoptotic index (based on TUNEL staining) under UVB exposure. In conclusion, these results suggest that Nano-C3G can reduce UVB-induced epidermal damage through the p53-mediated apoptosis signaling pathway. Moreover, Nano-C3G was more efficient than C3G at the same concentration (500 µM).

Polymorphous Light Eruption.

Polymorphous light eruption (PLE) is the commonest immuno-mediated photodermatosis. It occurs after solar or artificial UV-light exposure and affects only the sun-exposed areas with preference of the V-area of the chest, of arms and forearms, legs, upper part of the back, and rarely the face. The lesions are itching or burning, and vary morphologically from erythema to papules, vesico-papules and occasionally blisters, plaques, sometimes erythema multiforme-like, insect bite-like wheals and purpura. The clinical manifestations befall within a few hours to days from light exposure, last a few days, and subside in about a week without sequelae. Its diagnosis is based on history, morphology and phototests. PLE is considered as a delayed hypersensitivity response to newly UV induced, but still unidentified, antigen(s). Usually, MED is normal, but the provocative phototests with UVA or UVB reproduce the spontaneous lesions in about 50% of the patients. Broad spectrum sunscreens and antioxidants, photohardening with PUVA or narrow band UVB may be beneficial to prevent the disease. Therapy is based mainly on topical or systemic corticosteroids.

Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients.

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.

Sucrose esters improve the colloidal stability of nanoethosomal suspensions of (-)-epigallocatechin gallate for enhancing the effectiveness against UVB-induced skin damage.

Nanoethosomal suspensions, composed of phospholipids, ethanol, and water, are novel lipid carriers. These suspensions have been reported to enhance the permeation of drugs into the skin as a result of the interdigitation effect of ethanol on the lipid bilayer of liposomes and by increasing the fluidity of lipids in the stratum corneum. The physical stability of the nanoethosomal suspension is still a critical research problem until now. This study investigated the commercial palm sucrose esters to improve the colloidal stability of nanoethosomal suspensions. The results indicated that palm sucrose esters (PSE) were effective for stabilizing nanoethosomal suspension of (-)-epigallocatechin gallate (EGCG) from green tea. A PSE concentration of 0.15% was optimal for a nanoethosomal suspension which gave mean diameter 75.5 ± 3.5 nm, zeta potential -30.8 ± 3.2 mV and polydispersity index 0.207 ± 0.017. Moreover, the effectiveness of stabilization was influenced by the degree of esterification of the sucrose esters: the sucrose polyesters could prolong the stability of nanoethosomes loaded with EGCG to a year, but the sucrose monoesters only provided less than 6 months of stabilization. EGCG nanoethosomal suspension stabilized by sucrose polyesters shows better inhibition effectiveness against UVB-induced skin damage than native EGCG. The nanoethosomal suspension has the potential for its utilization as skin care and other products. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2416-2425, 2017.