The role of aryl hydrocarbon receptor agonists in the treatment of vitiligo.

Vitiligo is a chronic autoimmune disorder characterized by progressive skin depigmentation. Vitiligo significantly impacts patients' quality of life, contributing to psychological and social burdens. Despite readily available therapeutic options, many cases remain refractory to treatment, highlighting the critical need for safer and more effective therapies. Currently, ruxolitinib is the only FDA-approved medication for vitiligo; however, it carries a black box warning for serious adverse effects, including infections, malignancy, and major cardiovascular events, limiting its use. Recent studies have identified the aryl hydrocarbon receptor (AhR) as a promising therapeutic target, suggesting that AhR agonists could address the multifaceted pathogenesis of vitiligo. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search to analyze the role of AhR agonists in the treatment of vitiligo on PubMed, Cochrane, Embase, MEDLINE, and Web of Science databases on April 15, 2024. Fourteen studies met the inclusion criteria, comprising two clinical trials, two case reports, and nine basic science studies. Our search revealed that culturing AhR agonists with melanocytes upregulates melanin-synthesizing enzymes, reduces reactive oxygen species, and modulates pro-inflammatory cytokines such as IL-17A and IL-22. Tapinarof, a topical AhR agonist used commonly for the treatment of psoriasis, demonstrated clinical efficacy in repigmentation with a favorable safety profile compared to long-term steroid use. Although limited by the number of clinical studies, this review underscores the potential of using AhR agonists, such as tapinarof, as a transformative approach to vitiligo management. Future clinical trials are necessary to evaluate the safety, efficacy, and long-term outcomes of AhR agonists.

The potential cutaneous benefits of bentonites and montmorillonites.

Bentonites and montmorillonites, natural clay minerals originating from volcanic ash, possess unique properties that have traditionally been utilized in industrial applications. Recently, their potential biomedical applications, particularly in dermatology, have garnered significant interest. This review explores the cutaneous benefits of bentonites and montmorillonites, highlighting their anti-inflammatory, wound-healing, oil-absorbing, drug delivery, photoprotective, and anti-aging effects. Evidence from in vitro experiments, animal studies, and preliminary clinical trials demonstrate that these clays can significantly reduce inflammation, accelerate wound healing, absorb excess oil, enhance drug delivery, protect against ultraviolet radiation, and improve skin hydration and elasticity. Larger scale randomized clinical trials (RCTs) are needed to further establish the safety and efficacy of bentonites and montmorillonites. Given the increasing consumer demand for natural ingredients in skincare, bentonites and montmorillonites present a promising area for further research and development in dermatologic applications.

The role of IL-17 and Th17 cells in keloid pathogenesis.

Keloids are characterized histologically by excessive fibroblast proliferation and connective tissue deposition, and clinically by scar tissue extending beyond the original site of skin injury. These scars can cause pruritus, pain, physical disfigurement, anxiety, and depression. As a result, keloid patients often have a diminished quality of life with a disproportionate burden on ethnic minorities. Despite advances in understanding keloid pathology, there is no effective Food and Drug Administration (FDA)-approved pharmacotherapy. Recent studies have highlighted the possible pathologic role of T helper (Th)17 cells and interleukin (IL)-17 in keloid formation, as well as their implication in other inflammatory disorders. This systematic review characterizes the role of Th17 cells and IL-17 in keloid pathogenesis, highlighting this pathway as a potential therapeutic target. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search on PubMed, Embase, MEDLINE, and Web of Science databases on June 5, 2024. The search included terms related to Th17 cells, IL-17, and keloids. Thirteen studies met the inclusion criteria, comprising basic science and bioinformatic studies focusing on Th17 cells and IL-17. Key findings include increased Th17 cell infiltration and IL-17 expression in keloids, IL-17's role in amplifying the inflammatory and fibrotic response via the promotion of IL-6 expression, and IL-17's involvement in upregulating fibrotic markers via SDF-1 and HIF-1α pathways. IL-17 also activates the transforming growth factor beta (TGF-ß)/Smad pathway in keloid fibroblasts. Th17 cells and IL-17 significantly contribute to the inflammatory and fibrotic processes in keloid pathogenesis. Therefore, targeting the IL-17 pathway offers a potential new therapeutic target to improve keloid patients' outcomes. Future research could further elucidate the role of Th17 cells and IL-17 in keloid pathogenesis and assess the safety and efficacy of targeting this pathway in human studies.

Outstanding user reported satisfaction for light emitting diodes under-eye rejuvenation.

The under-eye region is an area of significant cosmetic concern. Photobiomodulation (PBM) has emerged as an effective, safe, inexpensive, and convenient treatment for skin rejuvenation. Herein, we aim to evaluate the safety and efficacy of a LED under-eye device for under-eye rejuvenation, as measured by objective and patient reported outcomes. Eleven participants self-administered treatment using a commercially available LED device emitting red (633 nm) and near infrared (830 nm) light for six weeks. Standardized photographs and questionnaires were administered at baseline and six weeks. Photographic digital analysis indicated an improvement in under-eye wrinkles at six weeks compared to baseline, with a reduction in wrinkle score from 20.05 to 19.72. However, this finding was not statistically significant. Participants self-reported consistent improvements in under-eye wrinkles, texture, dark circles, bags, pigmentation, and erythema. All participants reported a high degree of comfortability, ease of use, and satisfaction with the eye device. The participants noted no moderate or severe adverse events and few reports of transient expected outcomes such as mild erythema. The participants' self-reported improvements and high user satisfaction, and the device's favorable safety profile, highlights the benefits of at-home LED devices for under-eye rejuvenation. Future randomized controlled trials with larger sample sizes could further establish the safety and efficacy of at-home LED under-eye treatments.

Systematic review of dupilumab safety and efficacy for treatment of keloid scars.

Keloids, characterized by excessive scar formation following dermal inflammation, pose a therapeutic challenge due to high recurrence rates. Radiation therapy, contraindicated in children, can minimize recurrence post-surgical removal. Dupilumab, which inhibits the pro-fibrotic interleukin-4/interleukin-13 axis, may effectively manage keloids when intralesional corticosteroid injections are unsuccessful. It may also prevent recurrence post-surgery in pediatric patients. This systematic review assesses the efficacy and safety of dupilumab for the treatment of keloids. Through a systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified and analyzed outcomes from three case reports and three case series studies, totaling 15 patients. Results indicate variable responses to treatment, including significant improvements, no clinical change, and worsening of keloid symptoms. Additional research is needed to recommend using dupilumab to treat keloids (Grade D). Treatment response variability may be linked to differences in interleukin-4/interleukin-13 activity between active and inactive keloids. Additionally, the unintended promotion of T helper 17 cell differentiation by dupilumab may worsen keloids.

Inverse Eruptive Syringoma in a Skin of Color Patient.

Syringomas are benign neoplasms derived from eccrine sweat glands. Eruptive syringomas are a subtype of syringomas and are typically located on the chest, neck, and abdomen during puberty or childhood. Herein, we present a 20-year-old African American female with an atypical case of eruptive syringomas, characterized by an unusual distribution on her chest, abdomen, and anterior and posterior bilateral extremities. This case underscores the importance of recognizing diverse presentations of skin conditions in patients with skin of color and adds to the limited reports of eruptive syringoma in these populations. We present and emphasize this atypical manifestation of eruptive syringomas in an individual with darker skin to promote awareness and improve diagnosis and patient outcomes.J Drugs Dermatol. 2024;23(7):564-566. doi:10.36849/JDD.8103.

Updates on the Molecular Basis of Photoaging in All Skin Types.

Photoaging is a complex, ongoing process that clinically manifests as cutaneous rhytides, atrophy, laxity, dyspigmentation, telangiectasias, roughness, and mottled appearance of the skin. There is an abundance of research establishing the mechanism of ultraviolet (UV) - induced photodamage as it is a significant source of photoaging and skin cancers. While UV damage is known to induce photoaging, it is important to understand how other forms of light radiation also contribute to this process. UV only constitutes 5 to 10% of solar radiation that reaches the earth's surface. The remaining nearly 90% is evenly split between infrared and visible light radiation. Early research shows that varied skin types may elicit different photobiologic responses to light. This article presents the mechanisms and biomarkers of photodamage induced by light from across the spectrum, including UV, visible light, and infrared to better prevent and reverse the damage of photoaging in all skin types.J Drugs Dermatol. 2024;23(7):504-509.  doi:10.36849/JDD.7438.

Systematic review of topical, laser, and oral treatments in acanthosis nigricans clinical trials.

Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis Nigricans negatively affects psychological well-being and particularly impacts skin of color individuals. Addressing the underlying cause of acanthosis nigricans, as current guidelines recommend, is often challenging. This highlights the importance of skin directed treatment for acanthosis nigricans. This systematic review evaluated topical, laser, and oral treatments for acanthosis nigricans and provides evidence-based recommendations for clinical use. Adhering to PRISMA guidelines, we evaluated 19 clinical trials investigating topical, oral, and laser interventions for acanthosis nigricans. Oxford Centre for Evidence-Based Medicine guidelines were used to make clinical recommendations. We strongly recommend topical tretinoin (grade A) and endorse the appropriate use of adapalene gel, urea cream, and fractional carbon dioxide laser therapy (grade B). Further research is essential to enhance our understanding of alternative treatments to determine additional evidence-based recommendations. This review aims to guide clinicians in managing acanthosis nigricans, especially when direct treatment of underlying conditions is impractical.

Sunscreen Practices and Preferences of Skin of Color Patients.

Sunscreen is an essential way to protect against photodamage from ultraviolet (UV) radiation. Despite the recognized benefits of sunscreen in preventing skin damage from UV light, its use varies across different patient groups. This cross-sectional, questionnaire-based study aims to uncover the sunscreen usage patterns, preferences, and barriers among non-Hispanic White (NHW) and skin of color (SOC) individuals. Our findings demonstrate that NHW individuals are more likely to wear sunscreen daily (31% NHW vs 25% SOC) and reapply sunscreen at least once a day (76% NHW vs 45% SOC) compared with SOC individuals. SOC individuals demonstrate a willingness to use sunscreen, but they face barriers such as cost (2% NHW vs 16% SOC), lack of knowledge in finding suitable products (22% NHW vs 41% SOC), and concerns about white cast (7% NHW vs 25% SOC). SOC individuals are less likely to know the difference between mineral and chemical sunscreen (49% NHW vs 29% SOC), less likely to learn about sunscreen from dermatologists (36% NHW vs 22% SOC), and more likely to prefer sunscreen from brands owned by people of color (13% NHW vs 47% SOC).  In addition to analyzing the broader categories of NHW and SOC, subgroup analysis was conducted on specific subgroups, including Black, Asian, and Hispanic groups. Herein, we highlight differences in motivations, sunscreen preferences, sources of information, and knowledge levels about sun protection between NHW and SOC individuals. By uncovering the unique needs and challenges faced by SOC individuals, we aim to improve culturally competent patient education and promote effective sun protection practices across diverse populations. J Drugs Dermatol. 2024;23(6):456-462.     doi:10.36849/JDD.8268.

Gender, racial, ethnic, and Fitzpatrick skin type representation in Acanthosis nigricans clinical trials.

Acanthosis nigricans (AN) is characterized by dark, velvety patches and thin plaques primarily in the body folds. AN is more prevalent in skin of color populations, including Black/African American, Native American, and Hispanic patients. As the U.S. population becomes increasingly diverse, the need for inclusive dermatologic research becomes more pressing. Given the increased prevalence of AN in skin of color patients, there is a need to evaluate representation in AN clinical trials. This study aims to uncover gender, race, ethnicity, and Fitzpatrick skin type (FST) representation in AN clinical trials. A systematic literature search was performed across PubMed, Embase, and Cochrane databases to identify participant characteristics in clinical trials focused on AN treatment. Our review yielded 21 clinical trials, totaling 575 participants, with an identified predominance of female participants (69.0%) and a surprising absence of race or ethnicity data. Out of the 11 studies that included FST data, 1.2% of participants were type II, 20.6% were type III, 50.0% were type IV, and 28.2% were type V. None of the participants were FST I or VI. Herein, we highlight a predominate inclusion of female and FST III-V patients in AN clinical trials, the populations most impacted by this condition. We also highlight the need for improved race and ethnicity reporting and the importance of including all FSTs in clinical studies. Addressing this gap is critical for developing safe, efficacious, patient-centered, and equitable treatments for all AN patients. Future research should prioritize comprehensive inclusion of race, ethnicity, and the full spectrum of FSTs.

Investigating the Relationship Between Acne and Vasodilatory Medications in a Hospital-Wide Adult Population.

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.

Cosmeceuticals for antiaging: a systematic review of safety and efficacy.

Cosmeceuticals, the bridge between pharmaceuticals and cosmetics, contain biologically active ingredients that may improve the skin's overall appearance. As the market, accessibility, and popularity of cosmeceuticals increase, it is essential to understand the safety and efficacy of such products. This systematic review aims to examine published clinical studies involving the use of cosmeceuticals for antiaging to provide evidence-based recommendations based on available efficacy and safety data. PubMed, Embase, and Cochrane were systematically searched on January 1, 2023 using PRISMA guidelines. Strength of evidence was graded using the Oxford Centre for Evidence-Based Medicine guidelines. Clinical recommendations were made based on the quality of the existing literature. A total of 153 articles regarding the use of cosmeceuticals for treatment of antiaging were identified. After screening of titles, abstracts, and full text, 32 studies involving 1236 patients met inclusion criteria, including 20 randomized controlled trials (RCTs) and 12 non-randomized open-label clinical trials for Vitamin C, Retinol, Bakuchiol, Tetrahydrojasmonic acid, Growth Factors, Methyl Estradiolpropanoate, Timosaponin A-III (TA-III), Protocatechuic acid, Grammatophyllum speciosum, and Jasmine rice panicle extract. Retinol and vitamin C for antiaging received a Grade A for recommendation. Methyl estradiolpropanoate, bakuchiol, tetrahydrojasmonic acid, and growth factors received a recommendation grade of C. The remaining ingredients were assigned an inconclusive grade of recommendation due to lack of evidence. Cosmeceuticals included in the review had favorable safety profiles with few significant adverse events. The review analyzes numerous different ingredients to provide an evidence-based approach to decision-making for consumers and physicians on the use of cosmeceuticals for antiaging. Limitations to our review include a limited number of randomized controlled trials and a need for long-term data on each cosmeceutical's efficacy and safety. Future research is needed to establish the long-term effectiveness and safety of cosmeceuticals.

An Analysis of Dermatology-Related Red-Light Therapy Patient Questions on Reddit.

BACKGROUND: Reddit is one of the world's most popular social media platforms and is increasingly used as a health information resource for patients on topics such as red-light (RL) therapy. OBJECTIVE: In this article, the authors present an analysis of prevalent patient questions and concerns regarding RL therapy. METHODS: All posts on the "Hot" page of the r/redlighttherapy subreddit were analyzed and categorized. RESULTS: A total of 930 questions from 664 posts were analyzed. The most commonly asked question category was related to product recommendations or feedback (29.7%), followed by usage instructions (15.3%), safety and side effects (12.6%), and indications and efficacy (12.3%). CONCLUSION: Understanding patient concerns and questions about RL, as expressed on online platforms like Reddit, can help clinicians improve patient satisfaction, education, and clinical outcomes. The study offers an innovative approach by using social media to uncover valuable patient insights that might not be easily observable within clinical settings.

Systematic review of randomized controlled trials of topicals for actinic keratosis field therapy.

Cutaneous field cancerization in dermatology describes the anatomic region of photodamaged skin with actinic keratoses (AKs) or cutaneous squamous cell carcinoma (cSCC) that is surrounded by cellular atypia, forming a dysplastic field. The concept of field cancerization is especially relevant in dermatology, as actinic keratoses and the surrounding dysplastic region can progress to carcinomas, necessitating the treatment of the field. Recent research has focused on field-directed therapy using topical agents. This study aims to systematically review randomized controlled trials on topical treatments for actinic keratosis field cancerization, following the PRISMA guidelines. Clinical recommendations were based on the Oxford Centre for Evidence-Based Medicine. We identified 20 original randomized controlled trials for topical cutaneous field therapy. 0.5% 5-Fluorouracil/salicylic acid and 0.5% 5-fluorouracil received a clinical recommendation grade of A, while diclofenac sodium received a clinical recommendation grade of B. Calcipotriol/5-fluorouracil, Imiquimod, sunscreen combination therapies, and tirbanibulin received a recommendation grade of C. This review provides a framework for clinicians when considering topical treatments for patients with field cancerization.

Blue light aminolevulinic acid photodynamic therapy downregulates cell division and proliferation pathways in cutaneous squamous cell carcinoma.

5-Aminolevulinic acid (5-ALA) photodynamic therapy (PDT) is a treatment for actinic keratosis (AK) and has been studied as a treatment for noninvasive cutaneous squamous cell carcinoma (cSCC). PDT induces apoptosis and necrosis in AKs and cSCC. 5-ALA blue light PDT may modulate gene expression and pathways in surviving cells. In this study, differential gene expression and pathway analysis of cSCC and human dermal fibroblasts were compared before and after 5-ALA blue light PDT using RNA sequencing. No genes were differentially expressed after correcting for multiple testing (false discovery rate < 0.05). As a result, transcription factor, gene enrichment, and pathway analysis were performed with genes identified before multiple testing (p < 0.05). Pathways associated with proliferation and carcinogenesis were downregulated. These findings using 5-ALA blue light PDT are similar to previously published studies using methyl-aminolevulinic and red light protocols, indicating that surviving residual cells may undergo changes consistent with a less aggressive cancerous phenotype.

An analysis of keloid patient questions on Reddit.

Reddit is one of the world's leading social media platforms, fostering active community discussions on a variety of topics including keloids. The prevalence and reach of conversations on Reddit underscore the need to investigate and understand patient perspectives and gaps in knowledge. Herein, we present an in-depth analysis of questions and concerns of Reddit users on keloids, offering valuable insights into patient experiences, knowledge gaps and treatment preferences. The study presents a distinct approach by harnessing the power of social media data to understand patient perspectives, which may not be readily apparent in clinical settings. All posts on the 'Hot' page of the subreddit r/Keloids were analyzed. Questions were categorized and subcategorized to reveal common themes. A total of 644 questions from 513 posts between 26 March 2017 and 28 August 2023 were identified and analyzed. Reddit users most frequently asked questions regarding keloid management (57.5%). Other common categories included uncertainty regarding diagnosis or symptoms (15.1%), living with keloids (7.5%) and causes or triggers (6.2%). This analysis highlights critical areas of patient knowledge gaps and potential misconceptions regarding keloids. For dermatologists, understanding these patient questions is crucial. Such insights allow for patient-centric education and treatments, ensuring more effective and comprehensive care.

Photobiomodulation CME part I: Overview and mechanism of action.

Photobiomodulation (PBM), previously known as low-level laser light therapy, represents a noninvasive form of phototherapy that utilizes wavelengths in the red light (RL, 620-700 nm) portion of the visible light (VL, 400-700 nm) spectrum and the near-infrared (NIR, 700-1440 nm) spectrum. PBM is a promising and increasingly used therapy for the treatment of various dermatologic and nondermatologic conditions. Photons from RL and NIR are absorbed by endogenous photoreceptors including mitochondrial cytochrome C oxidase (COX). Activation of COX leads to the following changes: modulation of mitochondrial adenosine triphosphate (ATP), generation of reactive oxygen species (ROS), and alterations in intracellular calcium levels. The associated modulation of ATP, ROS and calcium levels promotes the activation of various signaling pathways (eg, insulin-like growth factors, phosphoinositide 3-kinase pathways), which contribute to downstream effects on cellular proliferation, migration, and differentiation. Effective PBM therapy is dependent on treatment parameters (eg, fluence, treatment duration and output power). PBM is generally well-tolerated and safe with erythema being the most common and self-limiting adverse cutaneous effect.

Photobiomodulation CME part II: Clinical applications in dermatology.

Photobiomodulation (PBM) is an emerging treatment modality in dermatology with increasing office and home-based use. PBM is the use of various light sources in the red light (620-700 nm) and near-infrared (700-1440 nm) spectrum as a form of light therapy. PBM is often administered through low-level lasers or light-emitting diodes. Studies show that PBM can be used effectively to treat conditions secondary to cancer therapies, alopecia, ulcers, herpes simplex virus, acne, skin rejuvenation, wounds, and scars. PBM offers patients many benefits compared to other treatments. It is noninvasive, cost-effective, convenient for patients, and offers a favorable safety profile. PBM can be used as an alternative or adjuvant to other treatment modalities including pharmacotherapy. It is important for dermatologists to gain a better clinical understanding of PBM for in-office administration and to counsel patients on proper application for home-use devices to best manage safety and expectations as this technology develops. PBM wavelengths can induce varied biological effects in diverse skin types, races, and ethnicities; therefore, it is also important for dermatologists to properly counsel their skin of color patients who undergo PBM treatments. Future clinical trials are necessary to produce standardized recommendations across conditions and skin types.

The potential cutaneous benefits of edible bird's nest.

Edible bird's nest (EBN) is composed of the solidified saliva of swiftlet birds. EBN has been extremely popular in Asian culture for centuries. They are often consumed as a delicacy in the form of bird's nest soup and are believed to have numerous skin benefits. In light of EBN's growing popularity and significant cultural importance, we aim provide a comprehensive review of EBN's potential dermatologic benefits and role in photoaging, anti-inflammation, wound healing, skin barrier enhancement, and skin whitening. While in vitro, in vivo, and preliminary clinical trial results are promising, there is a need for future human clinical research to further validate these findings and establish EBN's efficacy and safety for dermatologic applications.