Drug-induced photosensitivity associated with anticancer therapies.

INTRODUCTION: Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event. EVIDENCE ACQUISITION: A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. EVIDENCE SYNTHESIS: A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies. CONCLUSIONS: Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.

Botanical Briefs: Fig Phytophotodermatitis (Ficus carica).

Patients presenting with a linear, erythematous, blistering eruption may experience a sudden painful sunburn that seems to get worse rather than better with time. In warm climates, exposure to the common fig tree (Ficus carica) may be the culprit. Dermatologists should recognize fig phytophotodermatitis as a possible cause and help the patient connect their symptoms with the inciting agent as well as administer proper treatment.

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells-In Vitro Studies on Melanocytes and Fibroblasts.

Hypertension is known to be a multifactorial disease associated with abnormalities in neuroendocrine, metabolic, and hemodynamic systems. Poorly controlled hypertension causes more than one in eight premature deaths worldwide. Hydrochlorothiazide (HCT) and furosemide (FUR), being first-line drugs in the treatment of hypertension, are among others the most frequently prescribed drugs in the world. Currently, many pharmacoepidemiological data associate the use of these diuretics with an increased risk of adverse phototoxic reactions that may induce the development of melanoma and non-melanoma skin cancers. In this study, the cytotoxic and phototoxic potential of HCT and FUR against skin cells varied by melanin pigment content was assessed for the first time. The results showed that both drugs reduced the number of metabolically active normal skin cells in a dose-dependent manner. UVA irradiation significantly increased the cytotoxicity of HCT towards fibroblasts by approximately 40% and melanocytes by almost 20% compared to unirradiated cells. In the case of skin cells exposed to FUR and UVA radiation, an increase in cytotoxicity by approximately 30% for fibroblasts and 10% for melanocytes was observed. Simultaneous exposure of melanocytes and fibroblasts to HCT or FUR and UVAR caused a decrease in cell viability, and number, which was confirmed by microscopic assessment of morphology. The phototoxic effect of HCT and FUR was associated with the disturbance of redox homeostasis confirming the oxidative stress as a mechanism of phototoxic reaction. UVA-irradiated drugs increased the generation of ROS by 10-150%, and oxidized intracellular thiols. A reduction in mitochondrial potential of almost 80% in melanocytes exposed to HCT and UVAR and 60% in fibroblasts was found due to oxidative stress occurrence. In addition, HCT and FUR have been shown to disrupt the cell cycle of normal skin cells. Finally, it can be concluded that HCT is the drug with a stronger phototoxic effect, and fibroblasts turn out to be more sensitive cells to the phototoxic effect of tested drugs.

Lime Dermatitis.

Phytophotodermatitis are skin eruptions caused by contact with a plant substance and exaggerated by exposure to sunlight. They are due to the presence of furocoumarins (psoralens, xanthotoxins, and bergaptenes) in the plant and involve 2 mechanisms of skin photosensitivity: phototoxicity or photoallergy.

Sap and Sun: A Case of Phytophotodermatitis.

We report a case of phytophotodermatitis caused by cow parsnip (Heracleum maximum) exposure affecting a hiker in Colorado. Phytophotodermatitis is a phototoxic skin reaction to UV-A rays after contact with photosensitizing plant substances that presents as a burning, painful rash, often with blisters. Treatment is supportive, including wound hygiene, analgesia, and anti-inflammatories. Avoiding offending plants, protecting the skin from sun, and immediate washing with soap and water after plant contact are the primary means of prevention. We have included a table and photos of plants found in the United States that can cause phytophotodermatitis. Medical providers should include phytophotodermatitis in the differential diagnosis of blistering rashes in patients who have been outdoors with possible exposure to offending plants.

Phototoxicity─Medicinal Chemistry Strategies for Risk Mitigation in Drug Discovery.

Phototoxicity is a common safety concern encountered by project teams in pharmaceutical research and has the potential to stop progression of an otherwise promising candidate molecule. This perspective aims to provide an overview of the approaches toward mitigation of phototoxicity that medicinal chemists have taken during the lead optimization phase in the context of regulatory standards for photosafety evaluation. Various strategies are laid out based on available literature examples in order to highlight how structural modification can be utilized toward successful mitigation of a phototoxicity liability. A proposed flowchart is presented as a guidance tool to be used by the practicing medicinal chemist when facing a phototoxicity risk. The description of available tools to consider in the drug design process will include an overview of the evolution of in silico methods and their application as well as structure alerts for consideration as potential phototoxicophores.

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.

Development of a GCN-based model to predict in vitro phototoxicity from the chemical structure and HOMO-LUMO gap.

The interaction between sunlight and drugs can lead to phototoxicity in patients who have received such drugs. Phototoxicity assessment is a regulatory requirement globally and one of the main toxicity screening steps in the early stages of drug discovery. An in silico-in vitro approach has been utilized mainly for toxicology assessments at these stages. Although several quantitative structure-activity relationship (QSAR) models for phototoxicity have been developed, in silico technology to evaluate phototoxicity has not been well established. In this study, we attempted to develop an artificial intelligence (AI) model to predict the in vitro Neutral Red Uptake Phototoxicity Test results from a chemical structure and its derived information. To accomplish this, we utilized an open-source software library, kMoL. kMoL employs a graph convolutional neural networks (GCN) approach, which allows it to learn the data for the specified chemical structure. kMoL also utilizes the integrated gradient (IG) method, enabling it to visually display the substructures contributing to any positive results. To construct this AI model, we used only the chemical structure as a basis, then added the descriptors and the HOMO-LUMO gap, which was obtained from quantum chemical calculations. As a result, the assortment of chemical structures and the HOMO-LUMO gap produced an AI model with high discrimination performance, and an F1 score of 0.857. Additionally, our AI model could visualize the substructures involved in phototoxicity using the IG method. Our AI model can be applied as a toxicity screening method and could enhance productivity in drug development.

Putative antimicrobial-associated phototoxicity in three dogs.

This case series describes putative doxycycline phototoxicity in three dogs, with one also undergoing a possible sulfamethoxazole phototoxic reaction.

Cette série de cas décrit la possible phototoxicité de la doxycycline chez trois chiens, à laquelle s'ajouterait une possible réaction phototoxique au sulfaméthoxazole chez l'un des chiens.

Está serie de casos describe una posible reacción de fototoxicidad en tres perros, junto con otro también sufriendo una posible reacción fototóxica por administración de sulfametoxazol.

Esta série de casos descreve a fototoxicidade putativa da doxiciclina em três cães, sendo que um também passou por uma possível reação de fototoxicidade por sulfametoxazol.

The Assessment of the Phototoxic Action of Chlortetracycline and Doxycycline as a Potential Treatment of Melanotic Melanoma-Biochemical and Molecular Studies on COLO 829 and G-361 Cell Lines.

Melanoma is still one of the most dangerous cancers. New methods of treatment are sought due to its high aggressiveness and the relatively low effectiveness of therapies. Tetracyclines are drugs exhibiting anticancer activity. Previous studies have also shown their activity against melanoma cells. The possibility of tetracycline accumulation in pigmented tissues and the increase in their toxicity under the influence of UVA radiation creates the possibility of developing a new anti-melanoma therapy. This study aimed to analyze the phototoxic effect of doxycycline and chlortetracycline on melanotic melanoma cells COLO 829 and G-361. The results indicated that tetracycline-induced phototoxicity significantly decreased the number of live cells by cell cycle arrest as well as a decrease in cell viability. The simultaneous exposure of cells to drugs and UVA caused the depolarization of mitochondria as well as inducing oxidative stress and apoptosis. It was found that the combined treatment activated initiator and effector caspases, caused DNA fragmentation and elevated p53 level. Finally, it was concluded that doxycycline demonstrated a stronger cytotoxic and phototoxic effect. UVA irradiation of melanoma cells treated with doxycycline and chlortetracycline allows for the reduction of therapeutic drug concentrations and increases the effectiveness of tested tetracyclines.

Phytophotodermatitis as a clinical problem and as a therapeutic option: Case report and review of the literature.

BACKGROUND: Phytophotodermatitis is a contact photodermatitis to furocoumarins, which act as sensitizing psoralens, from certain plants, especially citrus and fig trees. This photosensitizing effect has traditionally been used for the treatment of cutaneous viral warts, a reflection of traditional medicine. However, there are hardly any studies that support this fact. Otherwise, on certain occasions, especially in extensive exposures, they can cause a generalized severe condition that can even put the patient's life at risk. CASE PRESENTATION: We report the case of a 28-year-old man with severe phytophotodermatitis after generalized photoexposure with the manipulation of a fig tree, which required hospital management in a burn unit. RESULTS: A traditional method for the treatment of warts in some rural areas, especially in Iran, comprises the use of fig tree (ficus carica) latex as a local treatment; however, there is no scientific evaluation of its efficacy. It bases its effectiveness on physical destruction due to the sensitizing effect of furocoumarins. Though, in generalized exposures of this tree, as the case of our patient, can cause fatal symptoms. The essential therapeutic pillar is the avoidance of exposure to this tree and of sun exposure. Symptomatically, topical corticosteroids and systemic antihistamines are used. In severe cases, admission to a burn unit may be necessary. CONCLUSION: In conclusion, we highlight the importance the importance of early detection of phytophotodermatitis, an entity that can be caused by the daily handling of trees, including fig trees, a traditional remedy for viral warts and which, without adequate supervision in its application, can cause severe generalized symptoms.

Ficus carica L photodermatitis: a report of five cases with histopathologic study and review of the literature.

Phytophotodermatitis is a condition caused by contamination of the skin with phototoxic plant substances, followed by exposure to ultraviolet rays. Ficus carica L 1753, belonging to the Moraceae family, can be responsible for acute photodermatitis. We present five cases of photodermatitis caused by contact with Ficus carica L and subsequent exposure to sunlight. A histopathologic study and review of the literature are included.