The Gastrointestinal Microbiome and Immune Checkpoint Inhibitors: A Review of Human Interventional Studies Among Melanoma Patients.

Immune checkpoint inhibitors (ICI) are widely utilized for the treatment of malignant melanoma. Interestingly, gastrointestinal microbiome composition has emerged as a predictive biomarker of immunotherapy outcomes. This review seeks to assess the effect of microbiota-modulatory interventions on the clinical and immunological response of metastatic melanoma treated with ICIs. A systematic search was performed to retrieve studies and cases involving any microbiota-modulating intervention. Three studies assessed the effect of fecal microbiota transplantation (FMT) on ICI efficacy, and one case report assessed its effect on clearance of ICI-associated colitis. Overall, 37.5% of melanoma patients who had been previously refractory to ICI immunotherapy demonstrated complete or partial response following FMT and subsequent immunotherapy. 65% of immunotherapy-naïve melanoma patients demonstrated an objective response. No severe FMT-associated adverse events were reported, and FMT depicted efficacy in the remission of ICI-associated colitis. The results suggest that FMT may be a safe and moderately effective microbiota-modulating intervention to improve the efficacy of therapy in ICI-treated melanoma patients. Large, randomized, controlled trials are needed to determine optimal FMT donors and assess other microbiota-modulating interventions, such as pre- and probiotics, in melanoma patients.  J Drugs Dermatol. 2024;23(2):78-84.     doi:10.36849/JDD.7674.

A photoaging smartphone application to promote sun safety behaviors among youth in late childhood and adolescence.

BACKGROUND: Ultraviolet (UV)-exposure behaviors can directly impact an individual's skin cancer risk, with many habits formed during childhood and adolescence. We explored the utility of a photoaging smartphone application to motivate youth to improve sun safety practices. METHODS: Participants completed a preintervention survey to gather baseline sun safety perceptions and behaviors. Participants then used a photoaging mobile application to view the projected effects of chronic UV exposure on participants' self-face image over time, followed by a postintervention survey to assess motivation to engage in future sun safety practices. RESULTS: The study sample included 87 participants (median [interquartile (IQR)] age, 14 [11-16] years). Most participants were White (50.6%) and reported skin type that burns a little and tans easily (42.5%). Preintervention sun exposure behaviors among participants revealed that 33 (37.9%) mostly or always used sunscreen on a sunny day, 48 (55.2%) experienced at least one sunburn over the past year, 26 (30.6%) engaged in outdoor sunbathing at least once during the past year, and zero (0%) used indoor tanning beds. Non-skin of color (18 [41.9%], p = .02) and older (24 [41.4%], p = .007) participants more often agreed they felt better with a tan. Most participants agreed the intervention increased their motivation to practice sun-protective behaviors (wear sunscreen, 74 [85.1%]; wear hats, 64 [74.4%]; avoid indoor tanning, 73 [83.9%]; avoid outdoor tanning, 68 [79%]). CONCLUSION: The findings of this cross-sectional study suggest that a photoaging smartphone application may serve as a useful tool to promote sun safety behaviors from a young age.

Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature.

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

Reflectance confocal microscopic visualization of melanocytic bodies in the stratum corneum overlying acral lentiginous melanoma.

BACKGROUND: We present a case of RCM evaluation of ALM surgical margins demonstrating intracorneal melanocytic bodies overlying subsequently confirmed melanoma in situ by histopathology. CASE PRESENTATION: A 73-year-old male with a history of acral lentiginous melanoma (ALM) of the right great toe presented to our clinic for evaluation of positive surgical margins. The positive margin was localized for examination and subsequent biopsy with reflectance confocal microscopy (RCM) which allowed targeted re-resection of the area of concern. Three punch biopsies were obtained in the area of concern, which confirmed residual melanoma in situ. Immunostains confirmed the cellular remnants in the stratum corneum were melanocytic. To correlate the intra stratum corneum findings seen with confocal to the histopathology, a 3D rendering of a stack of images was used to demonstrate the location. DISCUSSION: Typically, acral surfaces are challenging to examine with RCM due to the limited ability of light to penetrate thickened stratum corneum; however, we observed unique cellular features with confocal. Scattered hyper-reflective pleomorphic cells consistent with melanocytes were observed in the stratum corneum, although the visualized underlying epidermis appeared normal. Confocal microscopy may aid in diagnosis and management of ALM, especially in the context of positive surgical margins.

Bacteriophages and the Microbiome in Dermatology: The Role of the Phageome and a Potential Therapeutic Strategy.

Bacteriophages, also known as phages, are viruses that selectively target and infect bacteria. In addition to bacterial dysbiosis, dermatologic conditions such as acne, psoriasis, and atopic dermatitis are characterized by a relative reduction in the abundance of phages and the overgrowth of the corresponding bacteria. Phages often exhibit high specificity for their targeted bacteria, making phage-replacement therapy a promising therapeutic strategy for the control of pathogenic bacteria in dermatologic disease. Novel therapeutic strategies regulating pathogenic bacteria are especially necessary in light of growing antibiotic resistance. In this review, we aimed to review the medical literature assessing phage dysbiosis and therapeutic trials in dermatology. Ultimately, studies have depicted promising results for the treatment of acne, psoriasis, and atopic dermatitis but are limited by low sample sizes and the omission of control groups in some trials. Additional work is necessary to validate the efficacy depicted in proof-of-concept trials and to further determine optimal treatment vehicles, administration mechanisms, and dosing schedules. This review provides the necessary framework for the assessment of phage efficacy in future trials.

Treatment of post-burn pruritus - A systematic review and meta-analysis.

BACKGROUND: Post-burn pruritus is one of the most common complaints reported by patients with limited evidence for a gold-standard treatment. OBJECTIVE: To review the literature and assess the efficacy of various interventions in treating post-burn pruritus. METHODS: PubMed, MEDLINE, CINAHL, Web of Sciences, Ovid Databases, and ClinicalTrials.Gov were searched. The articles were scored by two assessors for inclusion with a third independent assessor resolving conflicting scores. RESULTS: The present systematic review and meta-analysis synthesised findings from a total of nine studies, representing a pool of 323 patients. The standardized mean effect size for the various categories of interventions was: naltrexone at 1.47 (95 % CI of 0.75-2.20, p < 0.0000), coverings at 0.94 (95 % CI of 0.40-1.48, p = 0.006), topical ozonated oil at 2.64 (95 % CI of 1.94-3.34, p < 0.00001), lasers at 2.34 (95 % CI of 1.60-3.09, p < 0.00001), current stimulation at 1.03 (95 % CI of -0.04 to 2.10, p = 0.06), and lemon balm tea at 0.54 (95% CI of 0.12-0.96, p = 0.01). CONCLUSIONS: Current evidence suggests that current modalities have a statistically significant, but not clinically significant, reduction in pruritus. This review highlights the limited quality of evidence in the literature and the poor quality of reporting among excluded studies.

A Review of Current and Pipeline Drugs for Treatment of Melanoma.

Malignant melanoma is the most aggressive form of skin cancer. Standard treatment options include surgery, radiation therapy, systemic chemotherapy, targeted therapy, and immunotherapy. Combining these modalities often yields better responses. Surgery is suitable for localized cases, sometimes involving lymph node dissection and biopsy, to assess the spread of the disease. Radiation therapy may be sometimes used as a standalone treatment or following surgical excision. Systemic chemotherapy, while having low response rates, is utilized as part of combination treatments or when other methods fail. The development of resistance to systemic chemotherapies and associated side effects have prompted further research and clinical trials for novel approaches. In the case of advanced-stage melanoma, a comprehensive approach may be necessary, incorporating targeted therapies and immunotherapies that demonstrate significant antitumor activity. Targeted therapies, including inhibitors targeting BRAF, MEK, c-KIT, and NRAS, are designed to block the specific molecules responsible for tumor growth. These therapies show promise, particularly in patients with corresponding mutations. Combination therapy, including BRAF and MEK inhibitors, has been evidenced to improve progression-free survival; however, concerns about resistance and cutaneous toxicities highlight the need for close monitoring. Immunotherapies, leveraging tumor-infiltrating lymphocytes and CAR T cells, enhance immune responses. Lifileucel, an FDA-approved tumor-infiltrating lymphocyte therapy, has demonstrated improved response rates in advanced-stage melanoma. Ongoing trials continue to explore the efficacy of CAR T-cell therapy for advanced melanoma. Checkpoint inhibitors targeting CTLA-4 and PD-1 have enhanced outcomes. Emerging IL-2 therapies boost dendritic cells, enhancing anticancer immunity. Oncolytic virus therapy, approved for advanced melanoma, augments treatment efficacy in combination approaches. While immunotherapy has significantly advanced melanoma treatment, its success varies, prompting research into new drugs and factors influencing outcomes. This review provides insights into current melanoma treatments and recent therapeutic advances.

Integrative and Mechanistic Approach to the Hair Growth Cycle and Hair Loss.

The hair cycle is composed of four primary phases: anagen, catagen, telogen, and exogen. Anagen is a highly mitotic phase characterized by the production of a hair shaft from the hair follicle, whereas catagen and telogen describe regression and the resting phase of the follicle, respectively, ultimately resulting in hair shedding. While 9% of hair follicles reside in telogen at any time, a variety of factors promote anagen to telogen transition, including inflammation, hormones, stress, nutritional deficiency, poor sleep quality, and cellular division inhibiting medication. Conversely, increased blood flow, direct stimulation of the hair follicle, and growth factors promote telogen to anagen transition and subsequent hair growth. This review seeks to comprehensively describe the hair cycle, anagen and telogen balance, factors that promote anagen to telogen transition and vice versa, and the clinical utility of a variety of lab testing and evaluations. Ultimately, a variety of factors impact the hair cycle, necessitating a holistic approach to hair loss.

Clinical Efficacy of Topical or Oral Soy Supplementation in Dermatology: A Systematic Review.

Soybean, a legume native to Southeast Asia, serves many nutritional and medical purposes due to its rich source of phytochemicals and its antioxidant activity. Many animal and in vitro studies have demonstrated its potential impact on dermatologic health. The objective of this review is to investigate the clinical response of soy-based oral supplementation or topical application on dermatologic outcomes. A systematic review of studies assessing soy supplementation or application was performed in January 2023. Databases included PubMed, Embase, Cochrane, and Natural Medicines, and studies assessing any formulation that included soybean or associated products were included. Thirty studies met the inclusion criteria and are included in the review; 13 of these studies assessed oral supplementation and 17 assessed topical application. Topical and oral supplementation demonstrated efficacious results for a variety of dermatologic parameters, including chronological or photoaging parameters, skin barrier status, hydration, hyperpigmentation, dermal network composition, erythema, hair and nail parameters, acne lesion counts, and vulvar lichen sclerosis scores. Factors associated with aging, such as wrinkle area and depth, were most frequently assessed among the studies, and both topical and oral studies demonstrated efficacy. Effects are likely mediated by dermal compositional changes, such as increased collagen and/or elastic fiber numbers. Transepidermal water loss measurements, an indicator of skin barrier status, were frequently obtained among the studies, although improvement was more likely achieved with topical application compared to oral supplementation. The results of this review highlight the utility of soy-based products for a variety of dermatologic applications, although future studies are required to determine optimal formulations and application routes for intended outcomes.

Efficacy and safety of topical treatments for seborrheic keratoses: a systematic review.

Seborrheic keratoses (SKs) are benign epidermal neoplasms presenting as waxy, brown to black papules and plaques. Patients often seek removal for cosmetic reasons or irritation. The objective of this systematic review is to assess the efficacy and safety of topical treatments for SKs. Studies involving any topical medication indicated for SK removal were retrieved from Embase, Scopus, PubMed, and Cochrane. The final search was conducted on November 9, 2021, and 26 reports met inclusion criteria. A quality rating scheme was utilized to assess evidence quality. Heterogeneity of treatments and outcome measures precluded meta-analysis. Topical treatments that yielded a good-to-excellent response include hydrogen peroxide, Maxacalcitol 25 µg/g, BID Tazarotene 0.1% cream, 5% potassium dobesilate cream, 1% diclofenac sodium solution, urea-based solution, and 65% and 80% trichloroacetic acid. Local skin reactions were often mild and transient. Topical hydrogen peroxide showed the greatest evidence for clinical clearance of SKs, although there are no studies to our knowledge that directly compared hydrogen peroxide to current first-line treatments (e.g. cryotherapy or shave excision). The results of this review suggest viable and safe treatment of SK with topical therapies; however, there remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies.Key PointsQuestion: Are safe and efficacious topical treatments for seborrheic keratoses available?Findings: Topical treatments for seborrheic keratoses yield different responses and may be associated with local skin reactions. Topical hydrogen peroxide shows the greatest evidence for clinical clearance of seborrheic keratoses and may be a viable option for patients requesting noninvasive removal. No studies to our knowledge directly compare hydrogen peroxide to current first-line treatments.Meaning: There remains demand for topical treatments that reliably equate or exceed the efficacy of current first-line therapies.

Systematic Review of Psychological Interventions for Quality of Life, Mental Health, and Hair Growth in Alopecia Areata and Scarring Alopecia.

Alopecia is associated with significant psychological burden. There is limited evidence on the use of psychological interventions in conditions of hair loss. This manuscript systematically reviews the current state of literature on psychological treatments for quality of life, mental health, and hair growth in various forms of alopecia. PubMed and Embase were searched with predefined inclusion and exclusion criteria. Reference lists were also examined for relevant studies. Nine articles met our criteria and are included in this review. Eight of the articles related to alopecia areata and one related to scarring alopecia. Mindfulness-based stress reduction (MBSR) was found to improve quality of life-related subjective symptoms, relationship impacts, anxiety, phobia, distress, and psychological symptom intensity. Alopecia-specific collocated behavioral health (CLBH) treatment showed a trend for psychosocial improvement in areas such as appearance shame, activity avoidance, negative emotions, and coping. Hypnotherapy was found to improve anxiety and depression, quality of life measures, and alexithymia. There was also some evidence for significant hair growth with hypnosis, but the data are mixed. Psychotherapy combined with immunotherapy led to more hair growth, and supported self-confidence. Finally, coping strategies modulated the subjective burden of alopecia, and were associated with disease improvement. Further research will be necessary to better establish the efficacy and optimal administration of these interventions in alopecia.

Regulatory miRNAs and lncRNAs in Skin Cancer: A Narrative Review.

Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the current review with an eye toward potential therapeutic treatments. LncRNAs are remarkably adaptable, acting as scaffolding, guides, or decoys to modify key signaling pathways (i.e., the Wnt/ß-catenin pathway) and gene expression. As post-transcriptional gatekeepers, miRNAs control gene expression by attaching to messenger RNAs and causing their degradation or suppression during translation. Cell cycle regulation, cellular differentiation, and immunological responses are all affected by the dysregulation of miRNAs observed in skin cancer. NcRNAs also show promise as diagnostic biomarkers and prognostic indicators. Unraveling the complexity of the regulatory networks governed by ncRNAs in skin cancer offers unprecedented opportunities for groundbreaking targeted therapies, revolutionizing the landscape of dermatologic care.

Systematic review and estimated cost-efficacy of biologics compared with narrowband ultraviolet B light for the treatment of moderate to severe psoriasis and atopic dermatitis.

Psoriasis and atopic dermatitis are chronic inflammatory skin conditions, each affecting about 2-3% of the United States adult population. Phototherapy, such as narrowband ultraviolet-B (NB-UVB) therapy have been employed for the treatment of both psoriasis and atopic dermatitis for decades. More recently, systemic biologics have been approved by the Food and Drug Administration (FDA), representing a great advancement in dermatology. No comprehensive study to date has compared the cost efficacy of phototherapy compared to FDA-approved biologics for the treatment of psoriasis and atopic dermatitis. We pursued a systematic review of the literature for studies assessing efficacy of NB-UVB or biologics with endpoints including the Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI). Thirty-four studies including 55 treatment regimens and 5,123 patients were included in the analysis. Phototherapy costs were estimated with Medicare fee schedules for phototherapy-related current procedural terminology code (CPT), and biologic costs were estimated with wholesale acquisition cost (WAC). Total costs to achieve PASI 75 or EASI 75 in each study were standardized to a single month, the "adjusted cost," and exploited to a year, the "effective yearly cost," allowing direct cost-efficacy comparison despite different durations of treatment described in studies. The psoriasis analysis found NB-UVB to be the most cost-effective therapy, with an adjusted monthly cost of $1714.00 per PASI 75. Infliximab was the least expensive biologic, with an adjusted monthly cost of $2076.00 to $2502.00 per PASI 75. For atopic dermatitis, no NB-UVB studies utilized EASI 75 as their outcome measure, hindering the ability to directly compare cost effectiveness for the treatment of atopic dermatitis. However, all NB-UVB studies depicted a reduced treatment cost per treatment period compared to studies assessing biologics, although this comparison does not account for efficacy. The results depict NB-UVB to be the most cost effective for the treatment of psoriasis and the least expensive per treatment period for the treatment of atopic dermatitis. However, certain factors need to be taken into account. Biologics may be more effective for more severe disease, do not require multiple weekly clinic visits, and the ease for patient compliance may lead some to favor biologic therapy. This study is necessary to allow physicians, patients, and health systems to make informed decisions regarding cost-efficacy for a variety of treatment options.

A review of the use of beeswax in skincare.

BACKGROUND: Beeswax is a naturally occurring product secreted from worker bees that has varied uses in modern day. In skincare, its function ranges from its role as an occlusive, helping to create a semi-occlusive skin barrier that minimizes transepidermal water loss; as a humectant, locking in hydration; and an emollient to soften and soothe the skin. As a natural substance, its use has been shown to help alleviate symptoms associated with common cutaneous conditions like dermatitis, psoriasis, and overgrowth of normal skin flora. AIMS: In this narrative review, we aim to describe current uses of beeswax in skincare that has been published in the literature. MATERIALS AND METHODS: A review of beeswax related publications was performed by searching the PubMed database studies. RESULTS: A total of five clinical studies were included with three studies on animals and two studies in humans. DISCUSSION: Several studies show the benefits of topical beeswax in supporting the skin barrier. CONCLUSION: Beeswax can be a low-cost, natural ingredient for use in products. Further studies with topical beeswax are warranted.

Effect of Pulsing Digital Heating Devices on Skin Parameters, Subjective Pain, Mood, and Anxiety.

A common pitfall of many conventional heat therapy methods is the propensity to lose heat over time and the need for reheating and reapplication. Pain-relieving digital heating devices are now available that can be held in place on the body via adhesive or magnet and provide pulsed heat. However, the safety of such devices among different ages and skin types must be established. We conducted a prospective, open-label study to assess the effect of three consecutive thirty-minute treatment cycles on skin parameters and pain. Effects on mood and anxiety were secondarily assessed. 22 adult participants (20 female, 2 male; mean 58 ± 17.63 years) were recruited. The participants attended one visit with heating device intervention and a follow-up visit after 7-10 days. A 97% significant increase in transepidermal water loss was observed immediately following intervention (p = 8.04487 × 10-7), although significance was not sustained at follow-up. There was an increase along the red/green axis at 13/14 treatment locations immediately following treatment, although only four locations remained significantly increased at follow-up. Pain non-significantly decreased immediately following treatment (p = 0.057). A 38.6% decrease in subjective anxiety was observed immediately after treatment (p = 0.0139), and scores remained non-significantly reduced at follow-up (19.3% reduction from baseline; p = 0.1397). The heating devices elicit temporary changes to the skin, although the lack of significance at follow-up suggests that the devices can be safely used without long-term changes in skin color or barrier status.

Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review.

Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 articles were selected for review. Qualitative analysis revealed that nanoscale systems demonstrate significant antineoplastic and anti-metastasis properties: increased drug bioavailability, reduced toxicity, enhanced permeability and retention effect, as well as tumor growth inhibition, among others. Nanoformulations for skin cancers have largely lagged behind those tested in other cancers-several of which have commercialized formulae. However, emerging evidence has indicated a powerful role for these carriers in targeting primary and metastatic skin cancers.

Cutaneous Manifestations of Rheumatoid Arthritis: Diagnosis and Treatment.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammatory arthritis and periarticular structural damage. Available evidence suggests that RA results from complex interactions between genetic susceptibility (e.g., HLA-DRB1), environmental factors (e.g., smoking), and immune dysregulation. Alongside joint-related symptoms, individuals with RA may also experience a wide array of skin issues, including the development of nodules, neutrophilic dermatoses, vasculitis, and vasculopathy. Treatment strategies for these manifestations vary but routinely involve corticosteroids, disease-modifying anti-rheumatic drugs, and biologics, with individualized approaches guided by disease severity. In this review, we provide comprehensive insights into the skin-related issues associated with RA, outlining their clinical characteristics and histopathological findings. Our aim is to facilitate early diagnosis and personalized treatment to improve the quality of life of affected individuals.

Effects of Spinal Deformities on Hiatal Hernia Occurrence and Recurrence.

BACKGROUND: Spinal deformities such as kyphosis, lordosis, and scoliosis have demonstrated a possible association between these deformities. Our hypothesis is that the presence of spinal deformities will increase the risk of hiatal hernia recurrence after repair. METHODS: The following data was retrospectively gleaned for patients undergoing hiatal hernia repair (1997-2022): age, sex, date of hiatal hernia repair, presence and type of spinal deformity, Cobb angle, type of hiatal hernia and size, type of hiatal hernia repair, recurrence and size, time to recurrence, reoperation, type of reoperation, and time to reoperation. RESULTS: Spinal deformities were present in 15.8% of 546 patients undergoing hiatal hernia repair, with a distribution of 21.8% kyphosis, 2.3% lordosis, 58.6% scoliosis, and 17.2% multiple. There was no difference in sex or age between groups. Spinal deformity patients were more likely to have types III and IV hiatal hernias (52.3% vs. 38.9%, p = 0.02) and larger hernias (median 5 [3-8] vs. 4 [2-6], p = 0.01). There was no difference in access, fundoplication use, or mesh use between groups. However, these patients had a higher recurrence rate (47.7% vs 30.0%, p = 0.001) and a shorter time to recurrence (months) (10.3 [5.6-25.1] vs 19.2 [9.8-51.0], p = 0.02). Cobb angle did not affect recurrence. CONCLUSIONS: Spinal deformity patients were more likely to have more complex and larger hiatal hernias. They were at higher risk of hiatal hernia recurrence after repair with shorter times to recurrence. This is a group that requires special attention with additional preoperative counseling and possibly use of surgical adjuncts in repair.