Synchronizing the Nomenclature Surrounding Synchronous Primary Cutaneous Melanomas: A Systematic Review.

Objective: There is little consensus regarding the nomenclature and prognostic implications of synchronous melanomas. Here, we present a case of synchronous cutaneous melanoma and perform a systematic review of similar cases in the literature. Methods: Pubmed and EMBASE databases were queried for relevant English-language articles published from inception until 2023. Cases of "multiple primary cutaneous melanomas" that occurred within a time frame of three months or less were included. Exclusion criteria included non-cutaneous melanomas and cases without specific time intervals or those occurring beyond a three-month period. Data including patient age, sex, risk factors, cutaneous melanoma (CM) anatomic location, CM clinicohistologic features, and prognosis were extracted from relevant articles. Results: Nineteen case reports/series documenting 22 patients with multiple primary melanomas (MPM) occurring within a three-month interval. Overall, 66 melanomas were diagnosed, with an average of three (SD±2.1, median: 2) per patient. A majority (63%) of patients had one or more risk factors for skin cancer. Subsequent CM found within three-month interval were thinner than the first found (index) CM, more likely to be melanoma in situ (MMis) and have highest degree of anatomic concordance if the index lesion was first found on the trunk (50%). Two retrospective cohort studies (n=4,703; n=13) of melanomas occurring within three-month interval found similar results. Limitations: Limitations to our review included inconsistent reporting in the literature and use of terminology and a limited number of case reports and case series found in the literature. Conclusion: Synchronous primary cutaneous melanomas are a heterogenous collection of terminologies that may limit the ability of dermatologists to accurately diagnose, prognosticate, and treat high-risk patients. Given lack of guidelines, we recommend the use of the term "synchronous" to delineate additional primary cutaneous melanomas found within a three-month interval.

Red Light Phototherapy Using Light-Emitting Diodes Inhibits Melanoma Proliferation and Alters Tumor Microenvironments.

Background: Total annual cancer rates have decreased due to improved treatment and prevention. However, the incidence of melanoma is rising, and not all patients respond to immune and targeted approaches. Therefore, we sought to determine the efficacy of red light (RL) phototherapy in preclinical models of melanoma. Methods: Melanoma cells (A375, B16F10, MNT-1) were irradiated with RL. Melanoma proliferation, apoptosis, oxidative stress, and p53 phosphorylation were measured in vitro. In C57BL/6 mice, phototherapy safety, B16F10 tumor growth, and immunocyte infiltration were assessed following RL. Results: In vitro, 640 J/cm2 RL decreased cellular proliferation without increasing apoptosis, while 1280 J/cm2 increased apoptosis. RL increased intracellular reactive oxygen species generation and p53 phosphorylation. In animal models, 2560 J/cm2 RL significantly prevented melanoma growth and increased the expression of CD103+ dendritic cells. 1280 and 1920 J/cm2 RL decreased tumor volume, but not significantly. RL did not cause skin inflammation or erythema in normal skin. Conclusion: RL represents a potentially safe and effective melanoma therapeutic. RL prevented tumor growth and increased the expression of immune markers, such as CD103, that are associated with favorable melanoma outcomes. Further research is needed to determine the optimal clinical treatment regimen for melanoma using RL.

"COVID toes": A true viral phenomenon or a diagnosis without a leg to stand on?

"COVID toes" is the colloquial name of chilblain-like lesions thought to be a sequela of COVID-19 infection. Over two years and approximately 300 publications later, this association remains controversial. Here, we summarize key clinical, serological, biological, histological, and immunological evidence that supports and rejects this relationship and discuss alternate theories underlying the pathogenesis of chilblain-like lesions.

High-fluence light emitting diode-red light inhibits cell cycle progression in human dermal fibroblasts.

Skin fibrosis is a debilitating feature of several systemic and dermatologic diseases. While current treatment options carry significant risk of side effects and recurrence, high-fluence light emitting diode-generated red light (LED-RL) is an alternative therapeutic that is safe, non-invasive, and accessible. We previously demonstrated LED-RL decreases fibroblast proliferation, a key pathogenic component of fibrosis. However, the cellular mechanism by which high fluence LED-RL modulates fibroblast proliferation is unclear. Herein, we explored the effects of high fluence LED-RL on human dermal fibroblast cell cycle progression. We demonstrate that LED-RL at 640 J/cm2 induced significant arrest of cells in G0 /G1 compared to temperature-matched control. This was accompanied by a corresponding increase in expression of checkpoint regulator p53 in irradiated cells. These data demonstrate high fluence LED-RL may exert its anti-proliferative effect on fibroblasts by inducing G0 /G1 arrest. Further, this study provides insight into the molecular mechanism underlying LED-RL as an anti-fibrotic therapeutic.

Light Emitting Diode Phototherapy for Skin Aging.

Skin aging is associated with changes that include atrophy, pigmentation, decreased ability for wound healing, and rhytides. Recently, there has been growing research interest and consumer demand for minimally invasive cosmetic procedures involving light and energy-based devices, particularly for facial skin rejuvenation. Light emitting diode (LED) phototherapy is a promising treatment modality for photorejuvenation as it is safe, noninvasive, accessible, and can be easily combined with other treatment options. LED irradiation alters intrinsic cellular activity via absorption by chromophores located in the skin and may result in desirable photorejuvenation effects. In this review, we discuss the physiologic process of cutaneous aging, how visible light phototherapy with LEDs may be used to treat aging skin, and the importance of photoprotection. J Drugs Dermatol. 2020;19(4):359-364. doi:10.36849/JDD.2020.4711.

Light-Emitting Diode-Based Photodynamic Therapy for Photoaging, Scars, and Dyspigmentation: A Systematic Review.

BACKGROUND: Light-emitting diodes (LEDs) may be used as an activating light source for photosensitizers in photodynamic therapy (PDT), a form of noninvasive phototherapy. Photodynamic therapy for aesthetic dermatologic conditions has demonstrated skin rejuvenating effects. OBJECTIVE: To evaluate the safety and efficacy of PDT using LEDs to treat aesthetic dermatologic conditions including photoaged skin, scarring, and dyspigmentation. MATERIALS AND METHODS: A search of PubMed and EMBASE databases was conducted through May 31, 2019, to identify studies that used LEDs as a light source for PDT and evaluated cosmetic improvements as the primary outcome measure. RESULTS: A total of 24 original articles were included in the authors' systematic review. The available evidence supports methyl aminolevulinate or 5-aminolevulinic acid incubation followed by LED treatment for global improvement of skin quality, including smoother texture, reduction of rhytides, and improvement of scars. Histologic analysis for global skin improvement demonstrated increased collagen fibers and decreased elastin fibers after LED-mediated PDT. CONCLUSION: Light-emitting diode-based PDT seems to have beneficial effects for photoaging, scars and dyspigmentation. A paucity of high-quality studies using LED-based PDT for aesthetic outcomes was found, highlighting the need for well-designed randomized control trials on this topic.

Facial rejuvenation using photodynamic therapy with a novel preparation of ALA and hyaluronic acid in young adults.

Photodynamic therapy (PDT) is a well-established, non-invasive treatment modality that has shown desirable effects such as improvement of fine lines, dyspigmentation, and other signs of photodamage. Many patients seek to decrease, or reverse, effects of sun damage on the skin. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan found in the body, has enormous potential to bind water which allows the skin to retain moisture and maintain elasticity. Topical application of HA has been found to produce anti-wrinkle effects. We conducted a pilot case series evaluating the safety and efficacy of a commercially available 2% 5-aminolevulinic acid (ALA) gel with hyaluronic acid (ALA-HA) and light-emitting diode-red light (LED-RL) for facial rejuvenation as determined by clinical assessments and digital skin analysis of rhytides, pore size, and erythema. All patients noted improvement of their skin and experienced minimal pain during PDT. Evaluation by dermatologists demonstrated significant improvement in overall skin appearance. Digital analysis of photographs revealed improvement of skin spots, wrinkles, pores, texture, UV spots, brown spots, red areas, and porphyrins. Our findings demonstrated safety and efficacy of this novel preparation of photodynamic gel with HA and subsequent activation with LED-RL.

Variability in Wound Care Recommendations Following Dermatologic Procedures.

BACKGROUND: Dermatologists routinely perform office-based surgical procedures that result in cutaneous wounds. Wound care instructions are an important resource for postoperative patients. As there is no consensus on the ideal wound care regimen after dermatologic procedures, recommendations may vary. OBJECTIVE: To evaluate the current recommendations for wound care following dermatologic procedures. METHODS: The authors conducted a cross-sectional assessment of dermatology wound care handouts available online. The handouts were evaluated based on predefined parameters: topical agent recommendations for wound healing, caution against topical antibiotic use, and discussion of scarring, infection, bleeding, analgesia, and lifestyle considerations. RESULTS: A total of 169 handouts were evaluated. The majority (84%) recommended the application of petrolatum-based products, specifically Vaseline (75%) and Aquaphor (43%). Nearly half (43%) recommended the use of topical antibiotics, whereas 24% advised patients to avoid antibiotic ointments. Handouts variably addressed scarring (36%), infection (72%), bleeding (69%), pain (66%), and lifestyle modifications (64%). CONCLUSION: The instructions provided in dermatology patient handouts are highly variable, with various topical agents being recommended for wound healing. Topical antibiotics are not indicated for prophylaxis in clean dermatologic procedures but are still widely used. Greater efforts should be made to ensure that patients receive consistent and evidence-based wound care guidance.

The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets.

Skin fibrosis, characterized by excessive fibroblast proliferation and extracellular matrix deposition in the dermis, is the histopathologic hallmark of dermatologic diseases such as systemic sclerosis, hypertrophic scars, and keloids. Effective anti-scarring therapeutics remain an unmet need, underscoring the complex pathophysiologic mechanisms of skin fibrosis. The Th2 cytokines interleukin (IL)-4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders. The goal of this article is to summarize the current understanding of the role of the IL-4/IL-13 axis in wound healing and skin fibrosis. We conducted a literature search to identify research studies investigating the roles of IL-4 and IL-13 in fibrotic skin diseases. While transforming growth factor-beta has long been regarded as the main driver of fibrotic processes, research into the cellular and molecular biology of wound healing has revealed other pathways that promote scar tissue formation. IL-4 and IL-13 are important mediators of skin fibrosis, supported by evidence from in vitro data, animal models of fibrosis, and clinical studies. Overactive signaling of the IL-4/IL-13 axis contributes to the initiation and perpetuation of fibrotic skin diseases. Further insights into the IL-4/IL-13 axis may reveal potential targets for the development of novel therapies that prevent or treat fibrotic skin diseases.

Updates on Treatment Approaches for Cutaneous Field Cancerization.

PURPOSE OF REVIEW: Field cancerization describes the phenomenon that multiple heterogenous mutations may arise in an area exposed to chronic carcinogenic stimuli. Advances in the understanding of cutaneous field cancerization have led to novel therapeutic approaches to the management of actinic keratoses (AKs). Herein, we review the literature on the pathophysiology and emerging research of field cancerization in dermatology. RECENT FINDINGS: The classification systems for grading AK lesions are being refined with investigations focusing on their clinical utility. There is a growing shift towards field-directed treatment for AKs as the importance of field cancerization becomes clearer. Current field-directed therapies are being optimized and novel therapeutic modalities are being studied. SUMMARY: Field cancerization underlies the transformation of photodamaged skin into AKs and potentially cutaneous SCC (cSCC). Clinically meaningful classification systems for AKs are needed to better inform decisions regarding treatment. As we learn more about the role of field characterization in photodamage, AKs and cSCCs, therapeutic strategies are becoming more field-directed rather than lesion-directed.

Patient-reported outcomes in lasers and light therapy.

As the prevalence of lasers and light devices to treat dermatologic conditions increases, patient reported outcomes (PROs) will be an essential component of evaluating clinical efficacy and patient satisfaction. PROs may be used to identify patients' values, weigh risks and benefits of various therapies, identify barriers to treatment and help guide the development of new therapies. Utilizing patient and physician assessments may help determine if a new treatment is objectively better than currently available therapies. In creating a patient-centered treatment plan using laser and light modalities, it is critical to evaluate side effects using PROs. Determining and resolving barriers to treatment has benefits at the individual level and the population level. Many PRO measures (PROMs) are available to use for general and specific dermatologic conditions. The Dermatologic Life Quality Index, Skindex, and FACE-Q are PROMs that have been used in laser and light therapy studies. Selecting the proper instrument should be based on study aims to yield high quality data. Herein, we assess PROs use in laser and light treatment protocols to improve patient care, increase patient satisfaction and reduce barriers to care, and review dermatology PRO measures (PROMs) used in published laser and light clinical studies.