Herpes Zoster Following COVID-19 Vaccination.

Vaccination is an important intervention in preventing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Messenger RNA (mRNA) vaccines from Pfizer™ and Moderna™ are the first to market in the United States, and while cutaneous adverse events have been reported in clinical trials for both of these vaccines, they have not been well characterized. Here we report a case of a patient who developed herpes zoster after receiving the Moderna™ COVID-19 vaccine. Dermatologists should familiarize themselves with this and other potential cutaneous adverse events associated with COVID-19 vaccination. J Drugs Dermatol. 2021;20(8):898-900. doi:10.36849/JDD.6146.

Nanoparticle-Encapsulated Doxorubicin Demonstrates Superior Tumor Cell Kill in Triple Negative Breast Cancer Subtypes Intrinsically Resistant to Doxorubicin.

The effect of size and release kinetics of doxorubicin-nanoparticles on anti-tumor efficacy was evaluated in a panel of human cancer cell lines, including triple-negative breast cancer (TNBC) cells that frequently demonstrate resistance to doxorubicin. Different nano-formulations of sol-gel-based Doxorubicin containing nanoparticles were synthesized. Increased cell kill in chemoreffactory triple-negative breast cancer cells was associated with the smallest size of nanoparticles and the slowest release of Dox. Modeling of dose-response parameters in Dox-sensitive versus Dox-resistant lines demonstrated increased EMax and area under the curve in Dox-resistant mesenchymal TNBC cells, implying potentially favorable activity in this molecular subtype of breast cancer. Mesenchymal TNBC cells demonstrated a high rate of fluorescent bead uptake suggestive of increased endocytosis, which may partially account for the enhanced efficacy of Dox-np in this subtype. Thus, manipulation of size and release kinetics of this nanoparticle platform is associated with enhanced dose-response metrics and tumor cell kill in therapeutically recalcitrant TNBC cell models. This platform is easily customizable and warrants further exploration.

Topical nitric oxide releasing nanoparticles are effective in a murine model of dermal Trichophyton rubrum dermatophytosis.

Systemic therapies are preferred for treating dermal dermatophytosis due to inadequate penetration of topical agents. However, systemic antifungals are associated with off-target effects and limited tissue penetration, and antimicrobial resistance is a growing concern. To address this, we investigated topical nitric oxide-releasing nanoparticles (NO-np), which have been used against superficial fungal infections and bacterial abscesses. In addition to enhanced penetration and permeation conferred by nanoparticles, nitric oxide, a broad-spectrum multi-mechanistic antimicrobial agent, offers decreased likelihood of resistance development. In the current study, NO-np inhibited Trichophyton rubrum in vitro, as well as in a murine model of dermal dermatophytosis. In mice, NO-np reduced fungal burden after three days, with complete clearance after seven. Furthermore, NO-np decreased tissue IL-2, 6, 10 and TNFα, indicating earlier attenuation of the host inflammatory response and decreased tissue morbidity. Thus, topical NO-np represent an attractive alternative to systemic therapy against dermal T. rubrum infection.

Bensal HP Attenuates the Inflammatory Response in Hair Shaving Associated Dermatitis.

Shaving is an ubiquitous practice, and cutaneous irritation and inflammation are common sequelae, which may be worsened by underlying skin conditions or poor hair removal techniques. Moisturizing shaving creams and aftershaves are available to help maintain or restore the epidermal barrier; however, many continue to suffer from post-shave redness, itching, and pain. To reduce post-shave inflammation, some products have included botanical and other natural ingredients, which are often favored by consumers. We evaluated Bensal HP, an ointment containing 3% oak bark extract, 3% salicylic acid, and 6% benzoic acid, which has documented anti-inflammatory and antimicrobial properties, in a murine model of shave irritation to determine whether it would be useful in this clinical setting. Shaving dermatitis was simulated using a depilatory agent and electric clippers, and the shaved area was photographed and treated with Bensal HP daily for four days. Compared to untreated controls, mice treated with Bensal HP experienced a visible reduction in skin irritation and inflammation. These findings were mirrored on histology, as Bensal HP-treated areas demonstrated increased epidermal integrity and decreased dermal inflammatory infiltrate compared to untreated skin. Using immunohistochemistry, fewer neutrophils and macrophages were noted, and cytokine analysis also revealed decreased IL-6 in Bensal HP-treated skin at 24 and 96 hours after shaving. These results highlight the potential of Bensal HP as an anti-inflammatory treatment for shave irritation. Given the product's application against a variety of inflammatory and infectious skin disorders, its use against shave irritation may also improve comorbid skin conditions, such as pseudofolliculitis barbae.

J Drugs Dermatol. 2016;15(7):836-840.

Psoriasis-associated fatigue: pathogenesis, metrics, and treatment.

Fatigue, a substantial symptom of psoriasis, is triggered by complex interactions of inflammation in psoriatic disease, both directly via inflammatory cytokines and indirectly via psychological and physiological factors. We provide data and observations that highlight the importance of qualifying and quantifying fatigue among patients with psoriasis and psoriatic arthritis and underscore the need to develop novel therapeutics to target this debilitating element of a multisystem disease.

Integrating lifestyle-focused approaches into psoriasis care: improving patient outcomes?

Psoriasis is one of the most well described cutaneous disorders, with a large body of literature devoted to describing its pathogenesis and treatment. In recent years, attention has turned toward the mechanisms by which lifestyle can impact psoriatic disease, and how lifestyle interventions may help to alleviate cutaneous, rheumatological, and comorbid disease in the setting of psoriasis. The following review explores our current understanding of the interaction between lifestyle factors and psoriasis and describes outcomes of interventions meant to target these factors.

Bensal HP Treatment for Burn and Excision Wounds: An In-Vivo Assessment of Wound Healing Efficacy and Immunological Impact.

Natural ingredients are of increasing interest within the field of dermatology. Bensal HP, an ointment containing 3% oak bark extract, 3% salicylic acid, and 6% benzoic acid, is believed to be efficacious against a variety of inflammatory and infectious dermatidites. Here we evaluate Bensal HP's ability to influence wound healing, which has yet to be studied in this setting. Bensal HP applied to burn wounds on the dorsal surface of BALB/c mice significantly attenuated wound expansion in the first few days post-injury as compared to controls. Histological analysis mirrored these findings with accelerated maturation of the wound bed and increased collagen deposition by the end of the study period. Cytokine analysis revealed decreased IL-6 and TNFα secretion in the Bensal HP-treated burns as compared to controls. Similarly, excisional wounds treated with Bensal HP demonstrated comparable wound healing as compared to controls with positive histologic features and increased collagen deposition. Furthermore, IL-6 production was attenuated in the Bensal-HP treated wounds at day 3, with no differences appreciated in IL-6 at day 7 or in TNFα at either time point. While Bensal-HP represents a therapeutic strategy to enhance the histologic and immunologic milieu in burn and excisional wounds, further study is needed to fully elucidate the full potential of this treatment.

Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1ß, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 ß secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1ß secretion was through inhibition of caspase-1 and IL-1ß gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response.

Identifying an Education Gap in Wound Care Training in United States Dermatology.

IMPORTANCE: As restoration of the integument is paramount to wound healing, dermatologists should be central to managing wounds; yet this is often not the case. If a training gap exists during residency training, this may account for the observed discrepancy. OBJECTIVES: To identify United States (US) dermatology residents' impressions regarding their preparedness to care for wounds, and to assess the amount and type of training devoted to wound care during residency. DESIGN, SETTING, AND PARTICIPANTS: An online survey among current US dermatology residents enrolled in a residency training program. MAIN OUTCOMES AND MEASURES: The primary goal was to determine whether dermatology residents believe more wound care education is needed, evaluate preparedness to care for wounds, and identify future plans to manage wounds. RESULTS: Responses were received from 175 of 517 (33.8%) US Dermatology residents contacted. The majority of residents did not feel prepared to manage acute (78.3%) and chronic (84.6%) wounds. Over three quarters (77.1%) felt that more education is needed. Fewer than half (49.1% and 35.4%) of residents planned to care for acute and chronic wounds, respectively, when in practice. CONCLUSIONS AND RELEVANCE: There is a gap in wound care education in US dermatology residency training. This translates to a low percentage of dermatology residents planning to care for wounds in future practice. Dermatology residents need to receive focused wound care training in order to translate the underpinnings of wound healing biology and ultimately better serve patients.

The Management of Burn Injuries by Dermatologist: A Single Center Pilot Study.

BACKGROUND: Burns are a major cause of morbidity and mortality worldwide. Most burn patients are treated in an outpatient setting. However, the type of burn injuries, frequency of burn injuries treated by dermatologists, and therapeutic approach is unknown. OBJECTIVE: To assess burn injury incidence in a single center academic dermatology practice, and describe demographic characteristics of burn patients seen by dermatologists. METHODS: A retrospective chart review analysis of 51 patients seen by 7 dermatologists from April 2010 to July 2014. RESULTS: Of the 51 patients seen, burns from hot metal were the main mechanism of injury followed by contact with hot liquids. Silver sulfadiazine was the most commonly prescribed treatment. At the time of the visit 84.3% (n=43) had other dermatological conditions. CONCLUSION: Our study demonstrates that burns are not frequently seen by dermatologists. We hypothesize that longer wait times in specialty practices, the lack of burn-specific training and the complexities of burn care prevent dermatologists from being first line providers in this arena. A larger epidemiological study is needed to further elucidate these issues.

N-acetylcysteine S-nitrosothiol Nanoparticles Prevent Wound Expansion and Accelerate Wound Closure in a Murine Burn Model.

BACKGROUND: The treatment of cutaneous wounds in the clinical setting continues to be a clinical challenge and economic burden, with burn wounds being especially formidable. Direct mechanical injury coupled with the transfer of thermal energy leads to tissue necrosis, pro-inflammatory cytokine release and the eventual expansion of an initial wound. Our current therapeutic armamentarium falls short of options to help prevent wound expansion, and therefore new modalities are required. Nitrosating substances such as RSNOs have been proven to be effective in promoting wound closure due to their ability to modulate inflammation, cytokine production and vascular function. OBJECTIVE: We aim to evaluate the efficacy of n-actetylcysteine s-nitrosothiol nanoparticles (NAC-SNO-np) on thermal burn wounds and associated expansion. METHODS: A multi-burn model was utilized to induce three burn wounds on the dorsal surface of BALB/c mice, allowing for evaluation of the burn itself and peripheral tissue. Wounds were excised and processed for histology and immunohistochemistry on day 7 following wounding. RESULTS: Following treatment with NAC-SNO-np, burn wound expansion was attenuated and wound healing was accelerated. Histological analysis revealed increased collagen deposition as well as increased macrophage and decreased neutrophil infiltration into the wound bed. CONCLUSION: NAC-SNO-np represents a platform that harnesses the nitrosative properties of NAC-SNO in order to accelerate the transition from inflammatory to proliferative wound healing. Further studies are needed in order to translate to the clinical setting.

Systematic Approach to Wound Dressings.

Chronic wounds are a major source of morbidity and mortality within the United States. Wound dressings remain a cornerstone of dermatologic therapy. Selection of the proper wound dressing proves difficult given the range of wounds encountered and the numerous dressing options available to the clinician. Nevertheless, selection of a proper wound dressing is a crucial step in management that can significantly alter the course of wound healing. There are a variety of wound dressings available, including moisture retentive/occlusive dressings as well as dressings impregnated with antimicrobial agents. Here we outline the characteristics and indications of specific wound dressings in order to provide clinicians with a basic understanding of the types of dressings available. This review provides a tool for dermatologists to better assess and treat chronic wounds. Using the algorithm provided, clinicians will be able to select the appropriate dressing in order to accelerate wound healing, prevent infection and improve health outcomes.

Characterization and assessment of nanoencapsulated sanguinarine chloride as a potential treatment for melanoma.

Sanguinarine has a history of use in both folk medicine and early dermatology for the treatment of cutaneous neoplasms. Applied indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue necrosis. However, when used in a controlled fashion, sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/ murine melanoma. To exploit sanguinarine's observed activity against melanoma, a targeted delivery system is required. We present a sol-gel based nanoparticulate platform for encapsulating sanguinarine chloride(sang-np)-a targeted therapeutic capable of steady, reliable delivery of predictable quantities of drug over a sustained time period with minimal undesirable effects. Size and release kinetics of sang-np were characterized using dynamic light scattering and ultraviolet-visible spectroscopy respectively. In vitro efficacy of sang-np was assessed. At both 2 and 24 hours, free sanguinarine killed > 90% of B16 melanoma cells, assessed via MTT assay. At 2 hours, sang-np killed a portion of melanoma cells, increasing to percentages comparable to free sanguinarine by 24 hours. Control(empty) nanoparticles exerted minimal toxicity to melanoma cells at both time points. TUNEL assay revealed that treatment with both sanguinarine and sang-np induces apoptosis in B16 melanoma cells, suggesting that both treatments act via the same mechanism of action. These data confirm controlled release of sanguinarine from sang-np, as well as comparable efficacy and mechanism of action to sanguinarine alone. This suggests that nanoparticle delivery of sanguinarine may be a unique approach to capitalize on this potent agent's inherent anti-tumor activity and overcome many of the limitations with its current formulation.

Biodegradable chitosan nanoparticles in drug delivery for infectious disease.

Increasing rates of antimicrobial resistance have left a significant gap in the standard antimicrobial armament. Nanotechnology holds promise as a new approach to combating resistant microbes. Chitosan, a form of deacetylated chitin, has been used extensively in medicine, agriculture and industry due to its ease of production, biocompatibility and antimicrobial activity. Chitosan has been studied extensively as a main structural component and additive for nanomaterials. Specifically, numerous studies have demonstrated its potent microbicidal activity and its efficacy as an adjuvant to vaccines, including mucosally administered vaccines. In this review, we present fundamental information about chitosan and chitosan nanoparticles as well as the most recent data about their antimicrobial mechanism and efficacy as a nanotechnology-based drug delivery system.

Trichophyton rubrum is inhibited by free and nanoparticle encapsulated curcumin by induction of nitrosative stress after photodynamic activation.

Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use against Trichophyton rubrum, a dermatophytic fungus with increasing incidence and resistance, has not been well characterized. Our aim was to evaluate the mechanism of action of aPI against T. rubrum using curcumin as the PS in both free and nanoparticle (curc-np) form. Nanocarriers stabilize curcumin and allow for enhanced solubility and PS delivery. Curcumin aPI, at optimal conditions of 10 µg/mL of PS with 10 J/cm² of blue light (417 ± 5 nm), completely inhibited fungal growth (p<0.0001) via induction of reactive oxygen (ROS) and nitrogen species (RNS), which was associated with fungal death by apoptosis. Interestingly, only scavengers of RNS impeded aPI efficacy, suggesting that curcumin acts potently via a nitrosative pathway. The curc-np induced greater NO˙ expression and enhanced apoptosis of fungal cells, highlighting curc-np aPI as a potential treatment for T. rubrum skin infections.

Biafine topical emulsion accelerates excisional and burn wound healing in mice.

Macrophages play a fundamental role in wound healing; therefore, employing a strategy that enhances macrophage recruitment would be ideal. It was previously suggested that the mechanism by which Biafine topical emulsion improves wound healing is via enhanced macrophage infiltration into the wound bed. The purpose of this study was to confirm this observation through gross and histologic assessments of wound healing using murine full-thickness excisional and burn wound models, and compare to common standards, Vaseline and silver sulfadiazine (SSD). Full-thickness excisional and burn wounds were created on two groups of 60 mice. In the excisional arm, mice were divided into untreated control, Biafine, and Vaseline groups. In the burn arm, mice were divided into untreated control, Biafine, and SSD groups. Daily treatments were administered and healing was measured over time. Wound tissue was excised and stained to appropriately visualize morphology, collagen, macrophages, and neutrophils. Collagen deposition was measured and cell counts were performed. Biafine enhanced wound healing in murine full-thickness excisional and burn wounds compared to control, and surpassed Vaseline and SSD in respective wound types. Biafine treatment accelerated wound closure clinically, with greater epidermal/dermal maturity, granulation tissue formation, and collagen quality and arrangement compared to other groups histologically. Biafine application was associated with greater macrophage and lower neutrophil infiltration at earlier stages of healing when compared to other study groups. In conclusion, Biafine can be considered an alternative topical therapy for full-thickness excisional and burn wounds, owing to its advantageous biologically based wound healing properties.

A surprising case of Mycobacterium avium complex skin infection in an immunocompetent patient.

An acute inflammatory nodule of unknown etiology can pose a formidable diagnostic challenge. Here, we highlight the importance of including Mycobacterium avium intracellulare complex (MAC) and other atypical mycobacterial infections in the differential diagnosis of a cutaneous nodule in an immunocompetent individual. We also explore the implications of eczema in the development of a mycobacterial infectious process. We report a case of MAC skin infection in an immunocompetent individual. The patient is a 49-year-old male with a history of dyshidrotic eczema presenting with a fluctuant, non-draining nodule on his right forearm for 2 to 3 weeks, identified by tissue DNA probe to be a cutaneous MAC infection without systemic complications, as serologies and chest X-ray were unremarkable. MAC should be included in the broader differential diagnosis of deep fungal vs atypical mycobacterial skin infections. Nucleic acid-based assays are an important tool in making a definitive diagnosis, allowing for utilization of appropriate therapy for the specific etiologic pathogen. Given the patient's preceding diagnosis of eczema, it is possible that the compromised skin barrier and dampened cytotoxic Th1 activity predisposed the patient to this infection, typically appreciated in the immunosuppressed, warranting further investigation into the relative risk for atypical mycobacterial infections in the setting of eczema.