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Abstract Introduction Exosomes are extracellular vesicles that transport bioactive substances during normal and abnormal cellular physiological processes. The unique properties of exosomes can be exploited for use as biomarkers and targeted drug delivery vehicles, and are, for this reason, gaining increasing attention in the field of dermatology. This review aims to synthesise the existing evidence supporting exosomes in regenerative and cosmetic dermatology. Method A comprehensive PubMed search for the period of 2010–2023 was performed using the MeSH terms "exosome" and "skin.” The initial search yielded 246 studies, which were then refined to 178 studies following title and abstract screening. Studies were confined to human or animal studies published in English that evaluated the use of exosomes in medical/cosmetic dermatology. A subsequent full‐text review based on these criteria yielded 34 studies, which were then reviewed. Results Exosomes can be derived from a variety of biological sources and show potential application in wound healing, scar prophylaxis, photodamage prevention, skin regeneration, improved grafting success, hair loss mitigation, and as biomarkers and drug carriers. Conclusion Exosomes are gaining traction in regenerative and cosmetic dermatology. However, their widespread clinical application is hindered by cost, a complex isolation process, lack of uniform protocols, limited assessment of infective potential, and a paucity of clinical evidence. Further research in this area is needed, especially by way of clinical studies evaluating the efficacy of exosome‐based treatments on human skin.

In the era of artificial intelligence and machine learning, computer-aided diagnostic frameworks are data-hungry and require large amounts of annotated data to automate the disease diagnosis procedure. Moreover, to enhance the performance and accuracy of disease diagnosis, procedures need to be automated to ensure timely and accurate diagnosis. We are providing a whole slide image repository comprising unstained skin biopsy images acquired using a brightfield microscope, along with Hematoxylin and Eosin chemically and virtually stained image samples, to virtualize the staining procedure and enhance the efficiency of the disease diagnosis pipeline. The dataset was utilized to train a Dual Contrastive GAN to generate virtually stained image samples. The trained model achieved an FID score of 80.47 between virtually stained and chemically stained image samples, indicating a high correlation of content between synthesized and original images. In contrast, FID scores of 342.01 and 320.40 were observed between unstained images and virtually stained slides, and between unstained images and chemically stained images, respectively, indicating less similarity in content.

Abstract Background Theclinical presentation of atopic dermatitis (AD) varies in different skin phototypes and has been evaluated previously using reflectance confocal microscopy (RCM). Line‐field confocal optical coherence tomography (LC‐OCT) is a new noninvasive imaging modality with additional capabilities. Objectives This prospective cohort study aimed to assess the capabilities of LC‐OCT and RCM in visualizing and quantifying microscopic features of AD lesions. Methods Ten patients with clinically diagnosed AD and visible active lesions were included in the study. LC‐OCT and RCM imaging were performed on lesional and perilesional skin during routine dermatology visits. Image analysis included quantitative measurements of living and total epidermal thickness and dermo‐epidermal junction (DEJ) undulation using LC‐OCT, as well as visual assessment of characteristic features such as spongiosis, exocytosis, perivascular inflammation, and atypical blood vessels using both LC‐OCT and RCM. Results LC‐OCT provided precise measurements of epidermal landmarks and shared similar microscopic features compared to RCM. AD lesions exhibited increased stratum corneum thickness, living epidermis thickness, total epidermis thickness, and DEJ undulation compared to clinically normal skin. Spongiosis, exocytosis, perivascular inflammation, blood vessel proliferation, and dilation were prominent features observed in AD lesions on both LC‐OCT and RCM images. Interestingly, some inflammatory features were also detected in the visually normal skin of AD patients. Conclusions LC‐OCT showed potential as a fast and noninvasive imaging tool for assessing inflammatory skin pathologies, including AD. Its ability to visualize microscopic features and quantify epidermal changes may aid in diagnosis and treatment monitoring. These findings suggest that LC‐OCT could provide valuable insights, particularly for patients with darker skin types where clinical severity assessment may be challenging. Further studies are warranted to explore the full potential of LC‐OCT and its integration into clinical practice.

Abstract Transgender individuals experience elevated mental health issues and a diminished quality of life compared to the general population. While gender‐affirming dermatology treatments hold promise in addressing these challenges, there is a notable dearth of research in this area. Therefore, the objective of this study was to provide a comprehensive summary of the existing literature on the psychosocial effects of gender‐affirming dermatology treatments in transgender populations. A systematic review of original research on gender‐affirming dermatology treatments in transgender populations was conducted from PubMed (including Medline), Cochrane Library and Embase following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 2020 guidelines. The search was limited to studies published after 1 January 2013 and was conducted on 26 June 2023. Relevant reviews were excluded but had their references screened. All studies that met the inclusion criteria also had their references screened. Article screening involved two steps: initial abstract/title screening using Rayyan.ia, followed by full‐text screening for selected articles. Risk of bias was assessed using Joanna Briggs Institute critical appraisal checklists. Thirteen studies were analyzed and most revealed a positive association between gender‐affirming dermatology treatments and favorable psychosocial outcomes. However, there was a large imbalance in the focus on transfeminine versus transmasculine individuals, alongside disparities in gender identification methods. Hair removal followed by nonsurgical injectables were the primary treatments studied. Most studies faced notable limitations, preventing a definitive causal relationship between gender‐affirming dermatology treatments and psychosocial effects. Across studies, there were discrepancies in the type of psychosocial outcome studied and a lack of standardized assessment tools. Despite these limitations, gender‐affirming dermatology treatments appear to have psychosocial benefits for transgender individuals, but further robust studies are needed for a comprehensive understanding of this relationship.

Abstract Pemphigus represents a spectrum of autoimmune‐mediated blistering diseases associated with high morbidity, mortality and reduced quality of life (QoL). Despite an increase in pemphigus clinical trials, the varied instrument measurements of disease severity and QoL outcomes make comparisons between studies challenging. This study aimed to evaluate trends in the use of disease severity and QoL outcome measurements in pemphigus clinical trials. A review of pemphigus clinical trials was conducted using the PubMed, Embase, Cochrane Reviews and ClinicalTrials.gov databases up until September 2023. Only pemphigus randomized clinical trials that assessed at least one disease severity and/or QoL outcome were included. Overall, 53 clinical trials were eligible for this review. All clinical trials evaluated a disease severity outcome, with the Pemphigus Disease Area Index being the most used validated questionnaire (28.3% of trials) and more popular after 2015 (47.8% of trials since). The autoimmune bullous skin disorder intensity score (7.6%) and visual analogue measurements (7.6%) have fallen out of favour. Most studies now include lab parameters (56.5% of trials after 2015), with anti‐desmoglein 1 and 3 antibody levels (30.2%), immunoglobulins (IgG and/or IgM and IgA) (11.3%), and anti‐drug antibody levels (7.6%) being frequently evaluated. A small portion of trials evaluated QoL (26.5% of studies), with the autoimmune bullous quality of life being the most common (15.1%), however QoL utilization as an outcome measure has been increasing since 2015 (61.1% of trials since). Standardising the use of validated outcome measurements allows for better data interpretation, comparability and clinical application of results.

Approximately 0.7% of patients taking angiotensin-converting enzyme inhibitors (ACEIs) develop ACEI-induced angioedema (ACEI-IA). With no approved treatments for ACEI-IA, the risk of complications is concerning. Tranexamic acid (TXA) has the potential to prevent intubations and resolve ACEI-IA by inhibiting the downstream production of bradykinin. In this review, we aim to evaluate the safety and efficacy of TXA use in ACEI-IA. We queried the PubMed database for studies involving TXA for ACEI-IA from January 2003 to January 2023. Seven studies met the study inclusion criteria. Our results demonstrate that TXA may improve angioedema symptoms and prevent intubation. In addition, its availability, low cost, and safety profile support its use for improving the symptoms and complications of ACEI-IA in an emergency setting.

Abstract Background Dermal filler injections pose serious risks when administered by untrained individuals or when food and drug administration (FDA) guidelines are not adhered to. This issue may potentially be compounded by a growing reliance on social media platforms for health information. Objective Our objective was to analyze the quality of health information in videos published on dermal filler on TikTok. Methods We searched three hashtags, #filler (2.4 billion views), #dermalfiller (132.8 million views), and #fillersinjection (137.0 million views) and assessed the top videos returned by TikTok's algorithm that met inclusion criteria. The quality of health information was evaluated using the DISCERN instrument, a validated tool that uses a 1 to 5 scale to assess consumer health information. Results Videos received a mean DISCERN score of 1.64 (SD 0.33), indicating significantly low quality. 7% of the videos promoted non‐FDA‐approved uses of filler. Notably, videos posted by physician assistants or physicians received the highest mean scores (1.92 and 1.72) as well as videos categorized as educational (1.99). Conclusion Dermatologists should be aware of the high viewership of low‐quality TikTok videos on dermal filler. Dermatologists shall, therefore, understand the importance of their role in providing education to patients on this topic.

Abstract Staining is a crucial step in histopathology that prepares tissue sections for microscopic examination. Hematoxylin and eosin (H&E) staining, also known as basic or routine staining, is used in 80% of histopathology slides worldwide. To enhance the histopathology workflow, recent research has focused on integrating generative artificial intelligence and deep learning models. These models have the potential to improve staining accuracy, reduce staining time, and minimize the use of hazardous chemicals, making histopathology a safer and more efficient field. In this study, we introduce a novel three-stage, dual contrastive learning-based, image-to-image generative (DCLGAN) model for virtually applying an "H&E stain" to unstained skin tissue images. The proposed model utilizes a unique learning setting comprising two pairs of generators and discriminators. By employing contrastive learning, our model maximizes the mutual information between traditional H&E-stained and virtually stained H&E patches. Our dataset consists of pairs of unstained and H&E-stained images, scanned with a brightfield microscope at 20 × magnification, providing a comprehensive set of training and testing images for evaluating the efficacy of our proposed model. Two metrics, Fréchet Inception Distance (FID) and Kernel Inception Distance (KID), were used to quantitatively evaluate virtual stained slides. Our analysis revealed that the average FID score between virtually stained and H&E-stained images (80.47) was considerably lower than that between unstained and virtually stained slides (342.01), and unstained and H&E stained (320.4) indicating a similarity virtual and H&E stains. Similarly, the mean KID score between H&E stained and virtually stained images (0.022) was significantly lower than the mean KID score between unstained and H&E stained (0.28) or unstained and virtually stained (0.31) images. In addition, a group of experienced dermatopathologists evaluated traditional and virtually stained images and demonstrated an average agreement of 78.8% and 90.2% for paired and single virtual stained image evaluations, respectively. Our study demonstrates that the proposed three-stage dual contrastive learning-based image-to-image generative model is effective in generating virtual stained images, as indicated by quantified parameters and grader evaluations. In addition, our findings suggest that GAN models have the potential to replace traditional H&E staining, which can reduce both time and environmental impact. This study highlights the promise of virtual staining as a viable alternative to traditional staining techniques in histopathology.

Background/Objectives: Hypertrophic and atrophic skin aging represent two distinct phenotypes: hypertrophic aging is marked by deep wrinkles and a leathery texture, whereas atrophic aging is characterized by overall skin thinning, increased vascularity, and a higher risk of non-melanoma skin cancers. This study aims to elucidate the characteristics and differences between hypertrophic and atrophic facial aging subtypes using two non-invasive imaging devices: VISIA® and dynamic optical coherence tomography (D-OCT). Methods: We retrospectively evaluated patients who had presented to the outpatient dermatological clinic at Policlinico Umberto I hospital in Rome, Italy for a non-invasive facial imaging check-up. We included 40 patients aged 60–75 who were imaged with VISIA® and dynamic optical coherence tomography (D-OCT). Based on the number of UV spots and amount of red found on VISIA®, subjects were grouped into four subgroups (PIGM, RED, CONTROL, PIGM + RED), and trends among them were analyzed. Results: We found a strong correlation between VISIA® red area scores and D-OCT vascular density at 300 µm depth, confirming VISIA®’s effectiveness for assessing facial vascularity. Wrinkle count was highest in areas with UV spots, particularly in the PIGM and PIGM + RED groups. Conversely, low attenuation coefficients and dermal density were observed in regions with low UV spots but high red areas. Intermediate subgroups (CONTROL and PIGM + RED) displayed varying parameters. Conclusions: Non-invasive imaging devices are effective in evaluating facial aging and distinguishing between aging subtypes. This study identified two intermediate aging types in addition to the hypertrophic and atrophic subtypes.

Abstract 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.

Abstract Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti‐programed death‐1 (PD1) and anti‐cytotoxic T‐lymphocyte‐associated protein (anti‐CTLA4). However, a significant percentage of patients develop resistance to these immunotherapy drugs. Therefore, novel strategies were developed to target other aspects of the immune response. Lymphocyte activation gene‐3 (LAG‐3) is a cell‐surface molecule found on natural killer cells and activated T‐cells which negatively regulates T‐cell proliferation and function. LAG‐3 inhibitors interact with LAG‐3 ligands on the surface of T‐cells to block T‐regulatory (Treg) cell activity, suppress cytokine secretion and restore dysfunctional effector T‐cells which subsequently attack and destroy cancer cells. This review reports the dermatologic side effects associated with LAG‐3 inhibitors used in the treatment of melanomas. Using PRISMA 2022 guidelines, a comprehensive literature review of PubMed, Google Scholar, Embase, Cochrane, and Web of Science databases was conducted. Three studies were identified that demonstrated that the use of LAG‐3 inhibitors, whether as a single agent or in combination with other immune checkpoint inhibitors, resulted in stomatitis, pruritus, rash, dry skin, erythema, and vitiligo. Further research is warranted to assess the cutaneous adverse events observed with LAG‐3 inhibitors in treating melanoma and to identify populations most vulnerable to such side effects.

Abstract We investigated a method for automatic skin tissue characterization based on optical coherence tomography (OCT) imaging. We developed a manually scanned single fiber OCT instrument to perform in vivo skin imaging and tumor boundary assessment. The goal is to achieve more accurate tissue excision in Mohs micrographic surgery (MMS) and reduce the time required for MMS. The focus of this study was to develop a novel machine learning classification method to automatically identify abnormal skin tissues through one-class classification. We trained a deep convolutional neural network (CNN) with a U-Net architecture for automatic skin segmentation, used the pre-trained U-Net as a feature extractor, and trained one-class support vector machine (SVM) classifiers to detect abnormal tissues. The novelty of this study is the use of a neural network as a feature extractor and the use of a one-class SVM for abnormal tissue detection. Our approach eliminated the need to engineer the features for classification and eliminated the need to train the classifier with data obtained from abnormal tissues. To validate the effectiveness of the one-class classification method, we assessed the performance of our algorithm using computer synthesized data, and experimental data. We also performed a pilot study on a patient with skin cancer.

Key Clinical Message We present the first case of metastatic renal cell carcinoma visualized via reflectance confocal microscopy (RCM). This case describes the RCM features of such a tumor, in an effort to improve noninvasive characterization of cutaneous metastases.

Human-trafficking survivors suffer significant physical, mental, and social health consequences, prompting them to seek health care services. Although there is research regarding identification protocols for human-trafficking victims, there is no framework outlining the dermatologic patterns of survivors of human trafficking. We sought to identify the dermatologic signs reported in human-trafficking victims to create a framework for dermatologists and the broader medical community to appropriately screen patients at risk. After screening 577 pertinent records in the PubMed and Google Scholar databases for information about the physical signs of human trafficking in health care, 10 final studies were selected. Significant findings of rashes and brandings, such as tattoos, were more likely in sex-trafficked patients, whereas burns, injuries, and deep cuts were more likely to be found in labor-trafficked patients. This review outlines important identification guidelines that dermatologists and the broader medical community can use to recognize victims and take appropriate action while also raising awareness of human trafficking as an emerging public health issue.

Abstract Tinea versicolour, used interchangeably with pityriasis versicolour (PV), is a superficial fungal infection of the stratum corneum caused by Malassezia furfur, a fungus of the normal flora of the skin. PV occurs when conditions favour proliferation of the organism's mycelial form, such as in environments with high temperatures/humidity, in immunodeficient/immunocompromised states, and during pregnancy. PV presents as numerous well‐ demarcated macules with a powdery scale. Prior epidemiologic studies have indicated that underrepresented groups defined by race experience a higher burden of PV as compared to White patients. However, the burden of PV in other underrepresented groups has not previously been examined, as underrepresented groups are frequently excluded from studies evaluating the impact of dermatologic disease. The new National Institute of Health All of Us Research Program (AoU) aims to build one of the world's largest and most diverse databases to promote elucidation of health disparities, particularly in communities that have been historically excluded from biomedical research.

Abstract Optical coherence tomography (OCT) is a cross-sectional imaging modality based on low coherence light interferometry. Within dermatology, it has found applications for in vivo diagnostic imaging purposes, as well as to guide Mohs micrographic surgery (MMS), due to its ability to visualize skin morphology up to several millimeters in depth. However, standard OCT probes have a large footprint and capture an extended area of the skin, making it difficult to precisely pinpoint clinically relevant location being imaged. Mohs surgeons stand to benefit from a handheld in vivo imaging device that can accurately trace surgical margins. In this study, we demonstrate the use of a single fiber OCT (sfOCT) instrument. Our imaging system features a miniature common path single fiber probe, and a novel speckle decorrelation technique that generates distortion free 2D images from manual scanning.By manually moving the single-fiber probe across the region of interest, the user can perform a lateral OCT scan while visualizing the location of the probe during data acquisition. Using the sfOCT, we have identified normal skin morphology, qualitatively correlated features of basal cell carcinoma and squamous cell carcinoma with histopathology, and quantified the disruption of the dermo-epidermal junction OCT pattern in skin tumors—each demonstrating the potential of utilizing sfOCT to differentiate tumor from normal skin. Using this imaging tool, a Mohs surgeon can enhance determination of surgical margins for the first stage of MMS, potentially decreasing the time and number of stages required for complete tumor removal.

Abstract Findings obtained on objective assessments to evaluate sensitive skin do not correlate well with the symptomatology. We utilized reflectance confocal microscopy (RCM) to compare transepidermal application of zinc in sensitive and non-sensitive skin. Thirty-six subjects participated in this study. They were divided into groups based on lactic acid sting test (LAST):‘stinger’ and ‘non-stinger’; transepidermal water loss (TEWL) measurements; and sensitivity self-assessments: ‘sensitive’ and ‘non-sensitive’. RCM images were taken to visualize transepidermal application of topically-applied zinc. The intensity of zinc reflectance at different depths was measured by ImageJ software. Based on LAST scores, the ‘stinger’ group showed significantly higher reflectance of zinc at 8 µm (stratum corneum) [face (P

Cutaneous and adnexal fungal infections are typically diagnosed with potassium hydroxide (KOH) skin scrapings, fungal cultures, and Periodic acid-Schiff (PAS) biopsy staining. All three current methods of fungal diagnosis require sample processing and turnover time which leads to a delay in diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive, in vivo skin imaging technology that provides real-time dermatologic diagnoses. We present an updated systematic review of the applications of RCM in diagnosing fungal infections in an effort to explore the utility of RCM as an adjunct clinical tool in detecting cutaneous and adnexal fungi We systematically searched the MEDLINE (via PubMed) for studies published from January 2000 to October 2022 that described the utility of RCM in the setting of fungal infections. Of the 25 studies that met the inclusion criteria, 202 patients were included. The following information on the application of RCM in the setting of fungal infections was extracted from each study, if reported: study type, year published, number of patients included, diagnosis/diagnostic methods, and RCM description. Concordant within all included studies, fungal infections presented on RCM as bright, linear, branching, filamentous structures at the level of stratum corneum. A limitation of this review is that 11 of 25 studies were case reports (n = 1). Larger scale studies should be conducted to explore the utility of RCM in diagnosing fungal infections and to enrich the RCM descriptions of specific fungal conditions.

Pagetoid spread of melanocytes in the epidermis is a common indicator of melanocytic atypia, both histopathologically and with reflectance confocal microscopy (RCM). Specifically on RCM, large, bright, atypical dendritic and/or roundish cells are characteristic of melanoma. However, intraepidermal Langerhans cells (ILC) create the potential for diagnostic ambiguity on RCM. We describe one case of a pigmented facial lesion that was initially diagnosed as lentigo maligna (LM) due to numerous atypical perifollicular dendritic cells on RCM. Additionally, we present the findings of a literature review for similar reported cases conducted by searching the following terms on PubMed: reflectance confocal microscopy, RCM, lentigo maligna, melanoma, Langerhans cells, dendritic cells, and atypical cells. In our case, the lesion was determined to be a solar lentigo on histopathology. Immunohistochemistry (IHC) with CD1a identified the atypical-appearing cells as ILC, as it did in 54 reported cases of benign lesions (benign melanocytic nevus, Sutton/halo nevus, labial melanotic macule, and solar lentigo) misdiagnosed as malignant on RCM (melanoma, lip melanoma, lentigo maligna, and LM melanoma). According to our case and the literature, both ILC and atypical melanocytes can present with atypical-appearing dendritic and/or roundish cells under RCM. Currently, there is no method to distinguish the two without IHC. Therefore, the presence of pagetoid cells should continue to alert the confocalist of a potential neoplastic process, prompting biopsy, histopathologic diagnosis, and IHC differentiation.