Upcoming topical TRPV1 anti-pruritic compounds.

Transient receptor potential vanilloid type 1 (TRPV1) is found on sensory neurons, keratinocytes, sebocytes, and dendritic cells. Activated TRPV1 channels are believed to help propagate the itch sensation. Therefore, there has been great interest in targeting TRPV1 to treat pruritus. Since oral formulations aimed at TRPV1 have led to adverse effects such as hyperthermia, there has been emphasis on developing novel topical agents. Several companies are investigating topical TRPV1 anti-pruritic compounds and the initial data has been very promising. These drugs have the potential to be important treatment options for the management of itch. This paper reviews topical products in current development for pruritus that target TRPV1 channels.

Harnessing the gatekeepers of glucocorticoids for chemoprevention of non-melanoma skin cancer.

Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients suffer from tissue damage, scarring, or even disfigurement; thus, there is a need for chemopreventive approaches. Because of the complex interplay between glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role of 11ß-hydroxysteroid dehydrogenase 1 and 2 (11ßHSD1 and 2) in regulating GCs during skin cancer development and progression. 11ßHSDs modulate the activation of GCs in a tissue-specific manner and have been reported to play a role in development and progression of other types of cancer, but their role has not yet been reported in NMSC. Here, we found a significant upregulation of 11ßHSD2 protein in skin cancer cells when compared to normal skin cells, suggesting a role for this enzyme in the multifactorial process of skin cancer development. In addition, inhibition of 11ßHSD2 with siRNA resulted in significant reduction in colony formation in vitro. Finally, our in vivo study elucidated that inhibition of 11ßHSD2 with pharmacological inhibitor, Glycyrrhetinic acid (GA) could significantly diminish tumorigenesis in a well-studied in vivo mouse model of NMSC. Overall, these studies highlight for the first time a potential novel role for 11ßHSD2 in NMSC development and may allow for new GC treatment approaches capable of avoiding deactivation by the enzyme. If 11ßHSD2 can be inhibited as we have done here, or circumvented using modified GCs, this may lead to more efficacious outcomes for NMSC patients by preventing deactivation of the GC and minimizing resistance.

Hydroxyurea-induced hyperpigmentation with iron deposition.

Hydroxyurea is a chemotherapeutic agent that is used in the treatment of various hematological diseases including chronic myelogenous leukemia, polycythemia vera, and sickle cell anemia. Hydroxyurea is also used to treat psoriasis. Drug-induced hyperpigmentation is a known cutaneous side effect of hydroxyurea along with xerosis, dermal ulcers, and dermatomyositis-like eruptions. Hyperpigmentation has been observed in the oral mucosa, nails, and in a generalized or a diffuse pattern. The mechanism of hyperpigmentation related to hydroxyurea is believed to be correlated with increased melanin. Classically, clinical types of diffuse hyperpigmentation owing to iron deposition in the dermis have been associated with minocycline and not with hydroxyurea. We report a novel case in which hydroxyurea hyperpigmentation is associated with iron deposition.

Transgenerational transmission of hyperactivity in a mouse model of ADHD.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder affecting children and adults. Genetic and environmental factors are associated with the etiology of ADHD. Among the environmental factors, exposure of the developing brain to nicotine is considered a major risk factor. Recent evidence suggests that environmental influences on the brain and behavior may be transmitted from one generation to the next. We used a prenatal nicotine exposure (PNE) mouse model of ADHD to test the hypothesis that PNE-induced hyperactivity, a proxy for human ADHD phenotype, is transmitted from one generation to the next. Our data reveal transgenerational transmission of PNE-induced hyperactivity in mice via the maternal but not the paternal line of descent. We suggest that transgenerational transmission is a plausible mechanism for propagation of environmentally induced ADHD phenotypes in the population.

Botanical Briefs: Daffodils (Narcissus Species).

Daffodils (Narcissus species) are the most common cause of irritant contact dermatitis among florists. Calcium oxalate crystals contained in the sap of the daffodil plants lead to irritant contact dermatitis on the skin. Daffodil rash commonly presents with fissuring, scaling, and erythema of the fingertips, hands, and forearms. The best preventative measure is to wear appropriate protective gloves and clothing.

Social Media and Dermatology During the COVID-19 Pandemic: Analyzing User-Submitted Posts Seeking Dermatologic Advice on Reddit.

INTRODUCTION: Reddit, a popular social media website, has numerous forums where users may discuss healthcare-related topics and request diagnostic and treatment advice for dermatologic conditions. We sought to analyze and grade user-submitted requests for dermatologic advice and their top responses on Reddit. METHODS: User-submitted posts requesting diagnostic advice and their respective responses on two popular Reddit forums, SkinCareAddiction (ScA) and DermatologyQuestions (DQ), were reviewed by three board-certified dermatologists using a grading rubric designed for this study. RESULTS: 300 posts and comments were reviewed. Diagnoses among all graders matched in 52.3% of posts with a mean grader confidence score of 4/5 (95% CI 3.89-4.11). 31% of responder's comments recommended a diagnosis not included by any reviewer. Mean scores for the top comment's accuracy, appropriateness, and potential to be misleading/dangerous were 3.28/5 (95% CI 3.12-3.45), 3.3/5 (95% CI 3.14-3.45), and 2.33/5 (95% CI 2.18-2.48), respectively. CONCLUSION: Reddit may be informative to patients requesting dermatologic advice. However, responses should be taken with caution as the information provided may be inaccurate or insufficient for treatment recommendations. Dermatologists should be aware of these resources used by patients.

Oral Janus kinase inhibitors in the treatment of atopic dermatitis: A systematic review and meta-analysis.

Background: Janus kinase (JAK) inhibitors are being evaluated as promising upcoming treatments for atopic dermatitis (AD). Objectives: To systematically assess the efficacy of oral JAK inhibitors in patients with AD and provide comparisons among JAK inhibitors. Methods: A systematic literature review of JAK inhibitors in the treatment of AD was conducted and reported based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses using PubMed, ClinicalTrials.gov, CENTRAL, MEDLINE/Ovid, Embase and sponsor websites from inception to 30 September 2021. References of relevant articles were reviewed by two authors. Only RCTs of JAK inhibitors for treating AD with more than one study were included. Data was extracted and the meta-analysis was performed using the metan procedure in STATA version 12.1. Risk of bias was assessed with the Cochrane Risk of Bias Tool. The four outcomes analysed included Eczema Area Severity Index (EASI)-75 response (≥75% improvement of EASI score from baseline), percent change in EASI score, percent of subjects achieving Investigator Global Assessment (IGA) of clear or almost clear (IGA 0/1), and ≥ 4-point improvement in pruritus numerical rating scale (NRS). Results: Fourteen randomized controlled trials (7051 subjects) assessing three different oral JAK inhibitors (abrocitinib, baricitinib and upadacitinib) in patients with moderate-to-severe AD were included in the meta-analysis. Abrocitinib (100 and 200 mg), baricitinib (1, 2 and 4 mg) and upadacitinib (15 and 30 mg) were all found to be more efficacious compared to placebo in all four outcomes analysed. Upadacitinib 30 mg was more effective than all other dosages of JAK inhibitors in achieving EASI-75, decrease in percent change of EASI, IGA 0/1 response rate, and ≥ 4-point improvement in pruritus NRS. Conclusions: JAK inhibitors were found to be an effective treatment for AD. Upadacitinib, at 30 mg, was found to be the most efficacious oral JAK inhibitor for AD. More clinical trial studies with comparisons among JAK inhibitors are needed to confirm these results as well as explore long-term efficacy and safety of these molecules.

Phytophotodermatitis due to a Citrus-Based Hand Sanitizer: A Case Report.

Phytophotodermatitis, a cutaneous reaction caused by direct contact with photosensitive substances in plants and subsequent exposure to ultraviolet light, is commonly caused by psoralens in plants, including citrus fruits. We describe a case of phytophotodermatitis caused by a hand sanitizer containing a blood orange (Citrus sinensis) extract. To our knowledge, this is the first reported case of phytophotodermatitis caused by a hand sanitizer. A 41-year-old woman presented with a 2-week history of pruritic cutaneous eruptions on her right thigh. Approximately 24 hours prior to the onset of her symptoms, she applied a new citrus-based hand sanitizer. Immediately after applying the hand sanitizer, her right thigh was exposed to sunlight for approximately 5 hours. Extracts from oranges are used in many cosmetics, including perfumes and fragrances. With the increased use of hand sanitizers during the coronavirus disease 2019 pandemic, physicians should note that phytophotodermatitis due to scented hand sanitizers may occur more frequently.

Botanical Briefs: Tulipalin A.

Contact dermatitis is a common issue for many floral employees. Tulips are one of the most common causes of hand dermatitis. Tulipalin A is the main sensitizer in tulips and also is found in the Peruvian lily. "Tulip fingers" is the most typical clinical presentation of hand dermatitis from tulips and is characterized by erythematous scaling seen in periungual skin and between the first and second fingertips of the dominant hand. The best prevention for tulip contact dermatitis is to avoid exposure to the inciting plants or use nitrile gloves.

CADASIL disease, an inherited slowly progressive vascular dementia: case report with radiologic and electron microscopic findings.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) disease, a genetically determined arteriopathy, is a rare cause of vascular dementia. We present a case report of a 50-year-old man with migraines associated with left-sided weakness since age 34 years, a stroke at age 43 years, followed by progressive dementia. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes. Skin biopsy was performed because of clinical suggestion of CADASIL and positive family history. Electron microscopy revealed granular osmophilic material deposits in dermal arterioles, diagnostic for CADASIL disease. A brief discussion of reasons for false-negative skin biopsy findings, differential diagnosis, and treatment of patients with CADASIL disease is presented.

Impact of flavonoids on matrix metalloproteinase secretion and invadopodia formation in highly invasive A431-III cancer cells.

Metastasis is a major cause of mortality in cancer patients. Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs). Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT) phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells. We also observed enhanced phosphorylation levels of cortactin and Src in A431-III cells; these phosphorylated proteins have been reported to be the main regulators of invadopodia formation. Flavonoids, almost ubiquitously distributed in food plants and plant food products, have been documented to exhibit anti-tumor properties. Therefore, it was of much interest to explore the effects of flavonoid antioxidants on the metastatic activity of A431-III cells. Exposure of A431-III cells to two potent dietary flavonoids, namely luteolin (Lu) and quercetin (Qu), caused inhibition of invadopodia formation and decrement in ECM degradation. We conclude that Lu and Qu attenuate the phosphorylation of cortactin and Src in A431-III cells. As a consequence, there ensues a disruption of invadopodia generation and the suppression of MMP secretion. These changes, in concert, bring about a reduction in metastasis.