Applications of nitric oxide-releasing nanomaterials in dermatology: Skin infections and wound healing.

Nitric oxide (NO) is produced in most cells in the skin and is an important regulator of essential cutaneous functions, including responses to UV irradiation, microbial defense, wound healing, melanogenesis and epidermal permeability barrier homeostasis. Harnessing the physiological activities of NO for therapeutic use is difficult because the molecule is highly reactive and unstable. A variety of exogenous NO delivery platforms have been developed and evaluated; however, they have limited clinical applications in dermatology due to instability and poor cutaneous penetration. NO-releasing nanomaterials overcome these limitations, providing targeted tissue delivery, and sustained and controlled NO release. This review provides a comprehensive and up-to-date evaluation of the use of NO-releasing nanomaterials in dermatology for the treatment of skin and soft tissue infections and wound healing.

Perceptions, Utilization, and Cost Assessment of Sebaceous Hyperplasia Treatment Modalities: A Pilot Survey.

BACKGROUND: Sebaceous hyperplasia (SH) is a common, benign but cosmetically bothersome skin condition preferentially affecting older adults. Despite multiple treatment options, there is no universally accepted first-line treatment for SH nor standard pricing for said approaches.  Methods: A survey aimed at evaluating treatment approaches and their respective costs was disseminated on the Orlando Dermatology Aesthetic and Clinical Conference email listserv.  Results: Out of 224 dermatologists who participated in the survey (response rate 9.2%), most treated patients with SH (95.98%). In-office procedures were used more than pharmacologic treatments (P=<0.05). Treatments most used by respondents included electrodesiccation (ED; 83.9%), cryosurgery (35.3%), oral isotretinoin (32.6%), and carbon dioxide (CO2) laser (19.2%). Cryosurgery and ED priced between <$200 to $400. Most reported 1 to 2 sessions to achieve lesion clearance for ED, CO2 laser, and cryosurgery. Twenty-one percent reported 3-4 sessions with cryosurgery. Chemical peels, diode lasers, and photodynamic therapy required between 2-4 sessions. Respondents indicated lesions were most unlikely to recur with ED and CO2 laser. Most dermatologists (86.39%) agreed or strongly agreed that they were exposed to new treatments methods for SH through this survey and 86.49% of dermatologists were interested in learning about treatments employed by others. CONCLUSION: SH is a common issue that presents in the dermatologist's office. These data highlight the perception that ED is the most common approach employed, associated with lower costs, and requiring fewer sessions to achieve resolution. More data is needed and wanted to better determine best practices for the management of SH.J Drugs Dermatol. 2024;23(2):29-37.  doi:10.36849/JDD.7734.

Stasis Dermatitis: The Burden of Disease, Diagnosis, and Treatment.

Stasis dermatitis (SD), an inflammatory dermatosis occurring on the lower extremities, is a cutaneous manifestation of chronic venous insufficiency (CVI). SD is associated with a significant burden of disease. Symptoms such as pain, swelling, and itching can be debilitating for patients, leading to poor sleep, loss of mobility, and the inability to perform daily activities, and can interfere with work and leisure activities. Moreover, SD is a progressive disease with serious secondary complications such as ulcerations, which increase the patients' morbidity, reduce their quality of life, and increase health care burden. Challenges in diagnosing patients may have both short- and long-term sequalae for the patients due to unnecessary treatment and management. In addition, misdiagnosis may result in hospitalizations, placing additional burden on health care professionals in terms of time and financial burden on the health care system. Compression therapy and leg elevation represent the mainstay of treatment for CVI; however, it is also difficult to self-manage, which places a substantial burden on patients and caregivers. Moreover, compression therapy may cause discomfort and exacerbate itching. Subsequent nonadherence may result in disease progression that places additional burden on the physicians who manage these patients and the health care system in terms of resources required and costs incurred. A large proportion of patients with SD develop allergic contact dermatitis because of innate immune signals and altered skin barrier predisposing to sensitization to topical prescriptions, over-the-counter medications, and compression devices used to treat SD. Other than topical corticosteroids, there are no approved pharmacological options to treat inflammation in SD.

Stasis Dermatitis: An Overview of Its Clinical Presentation, Pathogenesis, and Management.

Stasis dermatitis is a chronic inflammatory skin disease of the lower extremities. It typically occurs in older individuals and is the cutaneous manifestation of venous hypertension caused by venous reflux. Such retrograde venous blood flow is the result of incompetent venous valves, valve destruction, or venous obstruction. Stasis dermatitis is eczematous. The associated impairment of venous valves may cause swelling of the legs, leading to serious conditions including venous ulcerations. Diagnosis can be challenging because of its clinical resemblance to other skin conditions and poor clinical recognition by physicians. The cornerstones of stasis dermatitis treatment are compression therapy to ameliorate pain and swelling, topical treatments to alleviate secondary skin changes, and interventional treatment options to correct the underlying causes of venous reflux. Given the central role of inflammation of the lower extremities in driving the cutaneous changes characteristic of stasis dermatitis, new therapeutic approaches that target the inflammation are under clinical evaluation in patients with stasis dermatitis.

Stasis dermatitis is a skin disease that can affect a person for a long time. It affects the legs of older people who have a disease called chronic venous insufficiency. This is when a person's veins have difficulty sending blood from their limbs back to their heart. Stasis dermatitis is caused by increased pressure inside a person's veins. Its signs and symptoms are skin discoloration, itch, dryness, and scaling and can be similar to the signs and symptoms of cellulitis and allergic contact dermatitis. Cellulitis is a common skin infection caused by bacteria. Cellulitis causes redness, swelling, and pain. Allergic contact dermatitis is an itchy skin rash caused by contact with something that irritates the skin. Stasis dermatitis is usually diagnosed after a healthcare provider has looked at person's skin and their medical history. Treatment for stasis dermatitis should treat the chronic venous insufficiency that causes the disease. It should also treat the skin lesions caused by stasis dermatitis. One way to treat stasis dermatitis is to reduce pain and swelling. This is done by applying pressure with compression stockings or bandages. Minor surgery can treat the venous insufficiency that causes stasis dermatitis. No treatments have been approved for the skin symptoms associated with stasis dermatitis. New ways to treat such symptoms need to be developed.

Treating Cutaneous Immune-Related Adverse Events from Immune Checkpoint Blockade.

Immune checkpoint inhibitors (ICPis) have revolutionized outcomes in various advanced malignancies. Therapeutic restoration of a robust T-cell response against malignant cells is also at the root of distinct cutaneous immune-related adverse events (cirAEs). As approved indications for ICPis increase and interdisciplinary collaboration with oncology grows, identifying the most common skin toxicities from ICPis, particularly on melanin-rich skin,1 and understanding treatment strategies are increasingly crucial for dermatologists. This brief review highlights common cirAEs and summarizes the latest evidence for interventions.

Nitric Oxide-Releasing Nanoparticles Are Similar to Efinaconazole in Their Capacity to Eradicate Trichophyton rubrum Biofilms.

Filamentous fungi such as Trichophyton rubrum and T. mentagrophytes, the main causative agents of onychomycosis, have been recognized as biofilm-forming microorganisms. Nitric oxide-releasing nanoparticles (NO-np) are currently in development for the management of superficial and deep bacterial and fungal infections, with documented activity against biofilms. In this context, this work aimed to evaluate, for the first time, the in vitro anti-T. rubrum biofilm potential of NO-np using standard ATCC MYA-4438 and clinical BR1A strains and compare it to commonly used antifungal drugs including fluconazole, terbinafine and efinaconazole. The biofilms formed by the standard strain produced more biomass than those from the clinical strain. NO-np, fluconazole, terbinafine, and efinaconazole inhibited the in vitro growth of planktonic T. rubrum cells. Similarly, NO-np reduced the metabolic activities of clinical strain BR1A preformed biofilms at the highest concentration tested (SMIC50 = 40 mg/mL). Scanning electron and confocal microscopy revealed that NO-np and efinaconazole severely damaged established biofilms for both strains, resulting in collapse of hyphal cell walls and reduced the density, extracellular matrix and thickness of the biofilms. These findings suggest that biofilms should be considered when developing and testing new drugs for the treatment of dermatophytosis. Development of a biofilm phenotype by these fungi may explain the resistance of dermatophytes to some antifungals and why prolonged treatment is usually required for onychomycosis.

Supporting Underrepresented in Medicine (UIM) and non-UIM Trainees Applying into Dermatology: A Qualitative Analysis.

BACKGROUND: Recently, there have been calls to improve diversity among the dermatology workforce, with emphasis placed on the resident selection process and trainee pipeline. However, there is limited data on the perspectives of dermatology applicants, especially among UIM trainees, and the support that they need and want to successfully apply in dermatology. METHODS: To assess trainee perspectives, we disseminated a survey to medical students, interns (matched into dermatology), and dermatology residents asking how dermatology residency programs can best support trainees through the dermatology application process. We developed a codebook drawing upon grounded theory methodology, and consensus coded all qualitative responses. RESULTS: We received 224 qualitative responses from underrepresented in medicine (UIM) (65, 29.0%) and non-UIM trainees (159, 70.9%). UIM trainees were more likely to mention diversity and inclusion initiatives (46.2% vs 3.8%, P<0.001), transparency in program information (40.0% vs 24.5%, P=0.021), holistic review (30.8% vs 6.3%, P<0.001), UIM student outreach/pipeline programs (23.1% vs 0.6%, P<0.001), and mentorship (21.5% vs 8.2%, P=0.009). CONCLUSION: Improving programmatic efforts to address unique challenges UIM trainees face when applying into dermatology is instrumental to mitigating barriers. We highlight opportunities for dermatology residency programs to create a more fair and equitable dermatology application process and support a more diverse pipeline of future dermatologists. J Drugs Dermatol. 2021;20(7):795-797. doi:10.36849/JDD.6043.

Evaluating provider knowledge, perception, and concerns about cannabinoid use in pediatric dermatology.

As the use of medical cannabinoids expands, the value and acceptance in pediatric dermatology is poorly characterized. To better assess the current climate, this survey evaluated pediatric dermatologists' familiarity and knowledge about medical cannabis and their interest to research and use cannabinoids. While the fund of knowledge and acceptance was high, providers voiced concerns about psychoactive effects of cannabis and substance abuse among their pediatric patients.

A Predictive Self-Organizing Multicellular Computational Model of Infant Skin Permeability to Topically Applied Substances.

Computational models of skin permeability are typically based on assumptions of fixed geometry and homogeneity of the whole epidermis or of epidermal strata and are often limited to adult skin. Infant skin differs quantitatively from that of the adult in its structure and its functional properties, including its barrier function to permeation. To address this problem, we developed a self-organizing multicellular epidermis model of barrier formation with realistic cell morphology. By modulating the parameters relating to cell turnover reflecting those in adult or infant epidermis, we were able to generate accordingly two distinct models. Emerging properties of these models reflect the corresponding experimentally measured values of epidermal and stratum corneum thickness. Diffusion of an externally applied substance (e.g., caffeine) was simulated by a molecular exchange between the model agents, defined by the individual cells and their surrounding extracellular space. By adjusting the surface concentration and the intercellular exchange rate, the model can recapitulate experimental permeability data after topical exposure. By applying these parameters to an infant model, we were able to predict the caffeine concentration profile in infant skin, closely matching experimental results. This work paves the way for a better understanding of skin physiology and function during the first years of life.

Patient Perceptions and Satisfaction With Teledermatology During the COVID-19 Pandemic: A Survey-Based Study.

BACKGROUND: The COVID-19 pandemic has drastically changed the practice of dermatology as social distancing guidelines have led to a shift from in-office care to virtual telehealth (teledermatology). We aimed to determine patient satisfaction, perceived barriers, as well as indications for teledermatology appointments during the COVID-19 pandemic. METHODS: A survey was sent out via SurveyMonkey's online platform to patients of the George Washington Medical Faculty Associates' Dermatology department who attended telehealth appointments during the COVID-19 pandemic. RESULTS: Out of 894 invitations sent, 168 patients completed our survey.The most common reasons for making a telehealth appointment were for a new rash (11.6%), eczema (9.8%), and psoriasis (9.1%). The most common reasons respondents liked telehealth were because of time efficiency (81.1%), not requiring transportation (74.2%), and maintaining social distancing (73.6%). The most common reasons respondents did not like telehealth were due to lack of physical touch (26.8%) and feeling they received an inadequate assessment (15.7%). Very few patients reported that they were unlikely to undertake another telehealth visit (9.94%) or recommend a telehealth visit to others (6.92%). CONCLUSION: Dermatology patients likely perceive telehealth visits as a convenient and safe method for quality care during the COVID-19 pandemic. The lack of physical touch, inability to provide close inspection and/or procedural intervention can be frustrating for patients and therefore meaningful selection of appropriate cases for telehealth visits can optimize the patient experience. Overall, telemedicine represents an effective and safe vehicle for delivering care especially during a global pandemic. J Drugs Dermatol. 2021;20(2):178-183. doi:10.36849/JDD.5714.