Nitric oxide (NO) is omnipresent in the body and synthesized by 3 isoenzymes (nNOS, eNOS and iNOS), all detected in human skin. NO can be stored in a pool of compounds readily converted to NO following skin irradiation by UVR and blue light. This non-enzymatic (without NOS involvement) photolytic reaction mobilizes cutaneous stores of NO derivatives to the bloodstream, lowering blood pressure. However, with the likelihood of skin deleterious effects caused by UVR/blue light, safer wavelengths in the red/near-infrared (NIR) spectrum are becoming potential contenders to release cutaneous NO, possibly via NOS temperature-dependent effects. The use of red/NIR light to mobilize NO stores from the body's largest organ (the skin) is auspicious. This review focuses on UVR, blue, red, and NIR spectra and their capacity to release NO in human skin. PubMed and Google Scholar were used as article databases to find relevant publications related to this particular field.

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.

Hypopigmented mycosis fungoides (HMF) is a form of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of extranodal non-Hodgkin’s lymphomas. HMF has a unique set of defining features that include light colored to achromic lesions, a predilection for darker skin phototypes, an early onset of disease, and predominance of CD8⁺ T-cells, among others. In the current review, we detail the known pathways of molecular pathogenesis for this lymphoma and posit that an active Th1/cytotoxic antitumor immune response in part explains why this variant is primarily seen in children/adolescents and young adults, who do not exhibit signs of immunosenescence. As a result of this potent cytotoxic response, HMF patients experience mostly favorable overall prognosis, while hypopigmentation may in fact represent a useful surrogate marker of cytotoxic immunity targeting the malignant cells. Understanding the molecular processes behind the specific features that define HMF may lead to improved diagnostic accuracy, personalized prognosis by risk stratification, and improved management of HMF. Moreover, improving our knowledge of HMF may aid our further understanding of other cutaneous lymphomas.

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.

Significance: This study investigates the therapeutic potential of photobiomodulation (PBM) using visible and near-infrared (NIR) light on nitric oxide (NO) release from intact human skin. Given NO's critical role in physiological processes such as wound healing, inflammation control, and vasodilation, this research could lead to innovative non-invasive treatments. Aim: The primary aim was to explore how PBM at different wavelengths affects NO release from human skin. Custom-built airtight sleeves equipped with gas ports were used to measure NO levels, assessing the impact of three specific wavelengths of light (455 nm, 660 nm, and 850 nm). Approach: Eighteen healthy participants had their forearms enclosed in airtight sleeves. The skin was irradiated with the specified wavelengths at a fluence of 45 J/cm² and an irradiance of 50 mW/cm² for 15 minutes. NO levels were quantified after irradiation using chemiluminescence detection (CLD), which measures the chemiluminescent reaction of NO with ozone (O3) for real-time analysis. Results: Significant differences in NO release were observed among the wavelengths tested, indicating that PBM stimulates NO release from intact human skin. Conclusions: The study provides strong evidence that PBM using visible and NIR light can enhance NO release from human skin, suggesting potential therapeutic applications for conditions involving NO. Further research is needed to understand the mechanisms behind PBM-induced NO release and its clinical implications.

NO is a crucial signaling molecule involved in skin health, the immune response, and the protection against environmental stressors. This study explores how different wavelengths of light, namely blue (455 nm), red (660 nm), and near infrared (NIR, 850 nm), affect nitric oxide (NO) production in skin cells. Primary keratinocytes and fibroblasts from three donors were exposed to these wavelengths, and NO production was quantified using a DAF-FM fluorescent probe. The results demonstrated that all three wavelengths stimulated NO release, with blue light showing the most pronounced effect. Specifically, blue light induced a 1.7-fold increase in NO in keratinocytes compared to red and NIR light and a 2.3-fold increase in fibroblasts compared to red light. Notably, fibroblasts exposed to NIR light produced 1.5 times more NO than those exposed to red light, while keratinocytes consistently responded more robustly across all wavelengths. In conclusion, blue light significantly boosts NO production in both keratinocytes and fibroblasts, making it the most effective wavelength. Red and NIR light, while less potent, also promote NO production and could serve as complementary therapeutic options, particularly for minimizing potential photoaging effects.