Melanoma Metabolism: Molecular Mechanisms and Therapeutic Implications in Cutaneous Oncology.

BACKGROUND: Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and a high metastatic potential, presenting significant challenges in clinical oncology. A critical aspect of melanoma biology is its metabolic reprogramming, which supports tumor growth, survival, and therapeutic resistance. OBJECTIVE: This review aims to explore the key molecular mechanisms driving metabolic alterations in melanoma and their implications for developing therapeutic strategies. METHODS: A Pubmed search was conducted to analyze literature discussing key mechanisms of the Warburg effect, mitochondrial dysfunction, enhanced lipid metabolism, epigenetic modifications, and the tumor microenvironment. RESULTS: Metabolic reprogramming supports melanoma growth, proliferation, and survival. Understanding these complex metabolic dynamics provides valuable insights for developing targeted therapeutic strategies. CONCLUSION: Potential therapeutic interventions aimed at disrupting melanoma metabolism highlight the promise of precision medicine in improving treatment outcomes in cutaneous oncology. By targeting metabolic vulnerabilities, novel treatment approaches could significantly enhance the clinical management and prognosis of melanoma.

Psychosocial impact of alopecia areata in paediatric and adolescent populations: A systematic review.

Alopecia areata is an autoimmune disorder characterised by sudden hair loss, and can range from patchy baldness to more severe forms such as alopecia totalis and universalis. Hair loss can have a profound impact on self-esteem and body image, particularly during childhood and adolescence. Understanding the psychosocial impact of alopecia areata in paediatric and adolescent populations is crucial to address the emotional and social challenges faced by these patients. The aim is to review the existing literature for clinical studies and reports investigating the psychosocial impact of alopecia areata in paediatric and adolescent populations. A systematic review of the literature was performed using PubMed, Cochrane and Embase databases from inception to July 2023. Included articles assessed the psychosocial impact of alopecia areata in paediatric and adolescent populations. Of 79 total articles, 10 were identified as meeting the inclusion criteria. Several studies highlighted self-esteem, emotional distress and social challenges as features of psychosocial manifestations. Factors such as stress, psychiatric comorbidities and familial issues are significantly associated with alopecia areata in these populations. The heterogeneity of studies precluded data synthesis and analysis. A majority of the included studies evaluated short-term findings. Alopecia areata has significant psychosocial impacts in paediatric and adolescent populations, with studies emphasising the negative effects on self-esteem, body image and quality of life. Additional research is required to better elucidate this relationship and draw meaningful conclusions to guide clinical support and interventions.

Acne and the cutaneous microbiome: A systematic review of mechanisms and implications for treatments.

Acne vulgaris is a pervasive skin disease characterized by inflammation of sebaceous units surrounding hair follicles. It results from the complex interplay between skin physiology and the intricate cutaneous microbiome. Current acne treatments, while effective, have major limitations, prompting a shift towards microbiome-based therapeutic approaches. This study aims to determine the relationship between acne and the cutaneous microbiome, assess the effects of current treatments on the cutaneous microbiome and explore the implications for developing new therapies. A systematic review was performed using PubMed and SCOPUS databases within the last 10 years. Methodological quality was assessed independently by two authors. The search retrieved 1830 records, of which 26 articles met the inclusion criteria. Meta-analysis of alpha diversity change was assessed using fixed and randomized effect models per therapeutic group. Eight studies pertain to the role of the cutaneous microbiome in acne, identifying C. acnes, S. aureus and S. epidermidis as key contributors through overproliferation, commensalism or dysbiosis. Eleven studies discuss current acne treatments, including doxycycline (1), topical benzoyl peroxide (BPO) (4), isotretinoin (2), sulfacetamide-sulfur (SSA) (2) and aminolevulinic acid-photodynamic therapy (ALA-PDT) (2), identified as modulating the cutaneous microbiome as a mechanism of efficacy in acne treatment. Seven studies discuss new treatments with topical probiotics, plant derivatives and protein derivatives, which contribute to acne clearance via modulation of dysbiosis, inflammatory markers and diversity indexes. A meta-analysis of the effects of existing therapeutics on the cutaneous microbiome identified benzoyl peroxide as the only treatment to facilitate significant change in diversity. Despite the heterogeneity of study types and microbiome classifications limiting the analysis, this review underscores the complexity of microbial involvement in acne pathogenesis. It delineates the effects of acne therapeutics on microbial diversity, abundance and composition, emphasizing the necessity for personalized approaches in acne management based on microbiome modulation.

A comparison of the safety and efficacy of tapinarof and roflumilast topical therapies in the management of mild-to-moderate plaque psoriasis.

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles. MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment. RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed more frequent but mild adverse effects, while roflumilast had less frequent but more severe side effects. DISCUSSION: Tapinarof and roflumilast offer once-daily dosing and successful treatment in restricted areas, potentially enhancing patient adherence. Cost remains a limiting factor, necessitating future comparative studies to evaluate the efficacy, safety, and cost-effectiveness between the two drugs. CONCLUSION: Tapinarof and roflumilast present promising topical treatments for psoriasis, showing efficacy and manageable safety profiles. Further research is crucial to fully elucidate their comparative benefits and drawbacks in clinical practice.

Artificial intelligence in psychodermatology: A brief report of applications and impact in clinical practice.

BACKGROUND: This report evaluates the potential of artificial intelligence (AI) in psychodermatology, emphasizing its ability to enhance diagnostic accuracy, treatment efficacy, and personalized care. Psychodermatology, which explores the connection between mental health and skin disorders, stands to benefit from AI's advanced data analysis and pattern recognition capabilities. MATERIALS AND METHODS: A literature search was conducted on PubMed and Google Scholar, spanning from 2004 to 2024, following PRISMA guidelines. Studies included demonstrated AI's effectiveness in predicting treatment outcomes for body dysmorphic disorder, identifying biomarkers in psoriasis and anxiety disorders, and refining therapeutic strategies. RESULTS: The review identified several studies highlighting AI's role in improving treatment outcomes and diagnostic accuracy in psychodermatology. AI was effective in predicting outcomes for body dysmorphic disorder and identifying biomarkers related to psoriasis and anxiety disorders. However, challenges such as limited dermatologist knowledge, integration difficulties, and ethical concerns regarding patient privacy were noted. CONCLUSION: AI holds significant promise for advancing psychodermatology by improving diagnostic precision, treatment effectiveness, and personalized care. Nonetheless, realizing this potential requires large-scale clinical validation, enhanced dataset diversity, and robust ethical frameworks. Future research should focus on these areas, with interdisciplinary collaboration essential for overcoming current challenges and optimizing patient care in psychodermatology.

Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.

Skin Manifestations of VEXAS Syndrome and Associated Genotypes.

Importance: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations. Objective: To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features. Design, Setting, and Participants: This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland. Main Outcomes and Measures: To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS. Results: Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]). Conclusions and Relevance: Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.

Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies.

The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1ß, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors' use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.

Artificial intelligence in dermatology: advancements and challenges in skin of color.

Artificial intelligence (AI) uses algorithms and large language models in computers to simulate human-like problem-solving and decision-making. AI programs have recently acquired widespread popularity in the field of dermatology through the application of online tools in the assessment, diagnosis, and treatment of skin conditions. A literature review was conducted using PubMed and Google Scholar analyzing recent literature (from the last 10 years through October 2023) to evaluate current AI programs in use for dermatologic purposes, identifying challenges in this technology when applied to skin of color (SOC), and proposing future steps to enhance the role of AI in dermatologic practice. Challenges surrounding AI and its application to SOC stem from the underrepresentation of SOC in datasets and issues with image quality and standardization. With these existing issues, current AI programs inevitably do worse at identifying lesions in SOC. Additionally, only 30% of the programs identified in this review had data reported on their use in dermatology, specifically in SOC. Significant development of these applications is required for the accurate depiction of darker skin tone images in datasets. More research is warranted in the future to better understand the efficacy of AI in aiding diagnosis and treatment options for SOC patients.

From tugs to treatments: a systematic review on pharmacological interventions for trichotillomania.

BACKGROUND: Trichotillomania (TTM) is a psychiatric disorder with dermatological consequences, characterized by recurrent hair pulling. It affects 1-3% of the population, and often coexists with other psychiatric disorders, leading to emotional distress. Effective management of TTM can be challenging because of underdiagnosis, symptom heterogeneity and stigma. Pharmacological interventions, including selective serotonin reuptake inhibitors and N-acetyl cysteine (NAC) are commonly used. OBJECTIVES: To assess the existing literature on pharmacotherapy for TTM and identify potential avenues for future research and treatment advancements. METHODS: A systematic review of the literature was performed using PubMed and Scopus databases within the past 10 years (PROSPERO: CRD42023454009). Included studies assessed pharmacotherapy for TTM and provided insights into current evidence and potential directions for future research and treatment advancements. RESULTS: In total, 23 articles were identified that met inclusion criteria. The most successful interventions were NAC, aripiprazole and monoamine oxidase inhibitors. NAC was identified as the most impressive adjunctive therapy to selective serotonin reuptake inhibitors and behavioural therapies in treatment through its mechanism of decreased glutamate-induced excitatory neuronal damage, with adjunctive antioxidant properties. Most of the other therapeutics that were identified require further research and controlled trials to validate their findings. CONCLUSIONS: Even if successful therapeutic outcomes are achieved, it is important to consider the patient's comorbidities and to combine pharmacological interventions with behavioural therapy interventions to comprehensively manage TTM.

Evaluating the clinical efficacy of pulsed dye laser with sirolimus for treatment of capillary malformations: A systematic review.

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits. The search was limited to the English language and human-subject studies conducted between 1 January 2000 and 1 June 2023. Inclusion criteria included studies evaluating SIRO as an adjunct to PDL in patients with PWS. Data extraction and quality assessment were performed by two independent reviewers. A total of nine studies met the inclusion criteria, which included randomized controlled trials (3), case series (2), case reports (3), and a prospective intrapatient study (1), which represented a total of 58 patients. Five studies showed improvement of a measured post-treatment PDL parameter including shortening treatment time and less frequent dosing. A subset of studies (4/9) which did not demonstrate significant clinical improvements exhibited significant photographic evidence of improvement. Heterogeneity among the studies highlights the need for further research and standardization. While adjunctive SIRO shows promise, larger studies and comprehensive evaluation methods are required to establish conclusive safety and efficacy guidelines to shape clinical decision-making.

Unraveling the mirage of fairness cream commercials: A cross-sectional analysis of commercials from South Asia.

BACKGROUND: Fairness products are an essential component of daily beauty routines for many individuals in subcontinental Asia. However, it is important to be aware that these products often contain ingredients that can be detrimental to the skin and are banned in several developed countries. OBJECTIVE: Our study aims to analyze the content of fairness cream commercials in order to gain a deeper understanding of the information used to persuade and influence consumers to use these products. METHODS: Fairness cream commercials originating from countries in subcontinental Asia, including India, Pakistan, Bangladesh, Sri Lanka, and Nepal, were specifically searched and analyzed on the YouTube platform. RESULTS: An analysis of 152 fairness cream commercials on YouTube identified 84.21% of commercials targeted female consumers, while only 15.79% targeted male consumers. 77.63% of commercials used celebrities in their commercials and 47.37% of commercials mentioned specific ingredients. CONCLUSIONS: Based on our findings, it is crucial for dermatologists to take an active role in educating patients and consumers about the potential risks associated with certain ingredients found in fairness creams. Dermatologists should emphasize the importance of prioritizing overall skin health rather than solely focusing on skin lightening.