The Janus kinase-signal transducer and activator of transcription (JAK-STAT) intracellular signaling pathway is implicated in the pathogenesis of a number of inflammatory dermatoses. Clinical trials ...and other studies have demonstrated the efficacy of JAK inhibitors in the treatment of a variety of dermatologic conditions. Here we review JAK inhibitors currently under investigation for the treatment of alopecia areata, vitiligo, sarcoidosis, necrobiosis lipoidica, granuloma annulare, and systemic lupus erythematosus with a special emphasis on safety and the implications of JAK inhibitors during the novel coronavirus 2019 pandemic.
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.
Cutaneous photobiology studies have focused primarily on the ultraviolet portion of the solar spectrum. Visible light (VL), which comprises 50% of the electromagnetic radiation that reaches the ...Earth's surface and, as discussed in Part I of this CME, has cutaneous biologic effects, such as pigment darkening and erythema. Photoprotection against VL includes avoiding the sun, seeking shade, and using photoprotective clothing. The organic and inorganic ultraviolet filters used in sunscreens do not protect against VL, only tinted sunscreens do. In the United States, these filters are regulated by the Food and Drug Administration as an over-the-counter drug and are subject to more stringent regulations than in Europe, Asia, and Australia. There are no established guidelines regarding VL photoprotection. Alternative measures to confer VL photoprotection are being explored. These novel methods include topical, oral, and subcutaneous agents. Further development should focus on better protection in the ultraviolet A1 (340-400 nm) and VL ranges while enhancing the cosmesis of the final products.
Until recently, the primary focus of photobiology has centered on the impact of UV radiation on skin health, including DNA damage and oncogenesis; however, the significant effects of visible light ...(VL) on skin remain grossly underreported. VL has been reported to cause erythema in individuals with light skin (Fitzpatrick skin types FSTs I-III) and pigmentary changes in individuals with dark skin types (FSTs IV-VI). These effects have importance in dermatologic diseases and potentially play a role in conditions aggravated by sun exposure, including phototoxicity in patients with FSTs I to III and post-inflammatory hyperpigmentation and melasma in patients with FSTs IV to VI. The induction of free radicals, leading to the generation of reactive species, is one driving mechanism of VL-induced skin pathologies, leading to the induction of melanogenesis and hyperpigmentation. Initial clinical studies have demonstrated the effectiveness of topical sunscreen with antioxidant combinations in inhibiting VL + UV-A1-induced erythema in FSTs I to III and reducing pigmentation in FSTs IV to VI. Antioxidants may help prevent the worsening of pigmentary disorders and can be incorporated into photoprotective strategies. It is essential that dermatologists and the public are aware of the impact of VL on skin, especially in patients with skin of color, and understand the available options for VL protection.
Sunscreen and frontal fibrosing alopecia: A review Robinson, Gabrielle; McMichael, Amy; Wang, Steve Q. ...
Journal of the American Academy of Dermatology,
March 2020, 2020-Mar, 2020-03-00, 20200301, Letnik:
82, Številka:
3
Journal Article
Recenzirano
Frontal fibrosing alopecia (FFA) is a cicatricial alopecia of unknown etiology. The incidence of FFA appears to be increasing with time, leading to suspicion of a possible environmental trigger. ...Observational studies have reported a positive correlation between facial sunscreen use and FFA. This finding raises the question of whether sunscreen use plays a role in disease development. In this article, we review the available literature on the association of sunscreen with FFA. There is insufficient evidence to establish a direct causal relationship between sunscreen and FFA. Further studies are required to better characterize the role of sunscreen and the environment in the pathogenesis of this unique disease.
Availability of new UV filters in the United States lags behind the European Union (EU), partly due to differing approval processes.
To review available human safety data of all US- and EU-approved ...UV filters.
Data from Food and Drug Administration and EU regulatory guidelines, federal governmental documentation, databases, reviews, and opinions for approval and ongoing safety evaluation were analyzed.
Currently, there are 17 US UV filters and 29 EU UV filters (18 EU-approved only filters). Almost all US filters possessed sensitization data (94%, 16/17) with the majority (76%, 13/17) showing minimal skin sensitization. The minority of EU-approved only filters (33%, 6/18) possessed sensitization data, all showing no sensitization. Some filters possessed dermal absorption data (US: 76%, 13/17; EU: 44%, 8/18). Oxybenzone, octinoxate, octisalate, homosalate, and octocrylene, approved in the US and EU, were shown to have plasma levels exceeding the Food and Drug Administration exposure threshold.
Proprietary manufacturer human data were unavailable.
Many new UV filters are available in the EU, but not yet in the United States. Rigorous US and EU guidelines ensure that UV filters provide adequate photoprotection assuming consumers follow American Academy of Dermatology SPF (sun protection factor) and broad-spectrum recommendations. Human data are limited, but known human risks of sunscreen appear minimal.
Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive ...therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients.
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•Loss of EGFR signaling leads to senescence-like dormancy in EGFR-mutant lung cancer•YAP promotes survival and dormancy in the absence of EGFR downstream signaling•YAP/TEAD/SLUG suppress apoptosis through transcriptional repression of BMF•A TEAD inhibitor enhances EGFR inhibitor-mediated apoptosis and prevents dormancy
Kurppa et al. show that YAP activation mediates resistance to combined EGFR/MEK inhibition by inducing dormancy in non-small-cell lung cancer cells. Targeting the YAP pathway, in part by using a newly developed covalent TEAD inhibitor, promotes apoptosis of the dormant therapy-resistant cancer cells.
In addition to the naturally occurring, physical, and systemic photoprotective agents reviewed in part I, topical ultraviolet radiation filters are an important cornerstone of photoprotection. ...Sunscreen development, efficacy, testing, and controversies are reviewed in part II of this continuing medical education article.
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