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The current issue of the BJD contains a set of scholarly reviews on acne, with an editorial from the guest editor Maurice van Steensel. These can be found at the links below.
Basosquamous carcinomas (BSCs), which comprise 1.2–2.7% of skin carcinomas, are aggressive skin tumors that feature histopathologic characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BSC origin and genetic etiology remain controversial. Chiang and colleagues reported underlying PTCH and SMO mutations in BSCs, suggesting that Hedgehog signaling drives BSC similar to BCC. Principal component analysis indicated that BSC has greater genetic similarity to BCC than to SCC, supporting the concept that BSCs are derived from BCCs.
Although laboratory mice have enabled important immunological advances, divergent microbiota often contribute to variable results at different institutions and limit translational relevance. Rosshart and colleagues implanted C57BL/6 embryos into wild mice to generate a wild mouse microbial genome on an isogenic laboratory strain background. The microbiome of these “wildlings” resembled wild mice at barrier sites in the gut, skin, and vagina and was stable for generations. These “natural” microbiota were resilient to antibiotic and microbiological challenge.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Atkinson et al. (2019) (https://doi.org/10.1016/j.jid.2018.10.038).
Psoriasis is a chronic inflammatory disease of the skin, nails, and joints. In the last two decades, there has been enormous progress in our understanding of the genetics, immunology, and associated comorbidities (Figure 1). This has been accompanied by a marked improvement in the number of therapeutic agents and their effectiveness. Much of this progress has been outlined in numerous articles, commentaries and reviews in the Journal of Investigative Dermatology (JID) over the years (Figure 2). This commentary, which is part of the JID Collections, serves to outline how we have arrived at our present state of knowledge on psoriasis and provides an overview of some exciting future directions.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Witte-Händel et al. (2019) (https://doi.org/10.1016/j.jid.2018.11.018).
This article aims to provide an overview of drug discovery with a focus on application within dermatology. The term “drug” can be used to describe a wide variety of agents, including small molecules, cell therapies, and antibodies, which may be dosed intravenously, orally, topically, or by other routes of administration. We summarize the economics and risks involved in drug discovery. Understanding the needs of patients and clinicians through use of a target product profile before initiating drug discovery can reduce time and effort spent developing a poor or unneeded drug.
Tunneling nanotubes (TNTs) have been described as a novel mechanism for intercellular communication. However, the ability of epidermal cells to utilize TNTs remains a mystery. In this issue, Su and Igyártó (2019) showed that Langerhans cells (LCs) obtain mRNA from keratinocytes (KC) in vivo presumably via TNTs. The demonstration of exchange of genetic material from KC to LC in vivo is an an unexpected method of antigen acquisition by LC and also an important consideration when analyzing transcriptomic data.
Basosquamous carcinoma (BSC) is a rare form of skin cancer with both basaloid and squamous morphology. Chiang et al. (2019) genetically define BSCs and demonstrate that BSCs likely originate as basal cell carcinomas that partially squamatize through accumulation of ARID1A mutations and RAS/MAPK pathway activation.
The lipids covalently bound to the cornified envelope of corneocytes are essential for the human skin barrier (Swartzendruber et al., 1987). Together with the unbound lipids they form a matrix regulating the permeability for water and pathogens through the stratum corneum (SC). Three main lipid classes are observed in the SC: sterols, fatty acids, and ceramides. Bound ceramides are a subset of the unbound ceramides and have an ultra-long omega-hydroxyl chain (OCer)(Farwanah et al., 2007, Hill et al., 2006).
Nutrition is considered an essential factor in the management of inflammatory skin diseases such as psoriasis (Barrea et al., 2016; Ford et al., 2018). A recent study identified saturated fatty acid (FA) intake as a significant risk factor for exacerbation of psoriasis, independent of adipocytokine levels, fat mass, and glucose homeostasis (Herbert et al., 2018). In line with this observation, another study showed that in mice fed a high-fat diet (60% of kcal from fat) in which there was still a substantial amount of carbohydrates (20% of kcal), T-cells accumulated in the skin and promoted psoriasis via IL-17A production (Nakamizo et al., 2017).
Keloid disorder, a recently coined term, refers to a group of fibroproliferative disorders affecting the skin (Tirgan, 2019a). The clinical spectrum of such conditions include keloids and hypertrophic scars, as well as acne keloidalis and keloidalis nuchae, in which cutaneous nodules and tumors develop as a result of trauma and inflammation (Figure 1). Keloids are relatively common, particularly affecting certain ethnic groups. Individuals of African ancestry have a very high incidence of keloids, reported to affect 4-16% of people in such populations, i.e., about 15 times higher than in individuals of European ancestry (Brown et al.
Current patient-reported outcome measures for itch are limited and may not capture its full impact on health-related quality of life (HRQOL). We sought to develop, calibrate and validate banks of questions assessing the HRQOL impact of itch as part of Patient-Reported Outcomes Measurement Information System® (PROMIS®). A systematic process of literature review, content-expert review, qualitative research, testing in a sample of 600 adults, classical test theory methods, and item response theory (IRT) analyses were applied.
Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease characterized by a type 2 cytokines secreted by T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s). Despite a high degree of heterogeneity, AD is still explained by type 2 immunity, and the role of interleukin (IL)-17A, which is increased in acute, pediatric, or Asian patients with AD, remains poorly understood. Here, we aimed to investigate the role of IL-17A-producing ILC3s, which are unexplored immune cells, in the pathogenesis of AD.
Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the bothersome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of IL-31 generation.
Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway.
Melanoma cells can switch between distinct gene expression profiles, resulting in “proliferative” and “invasive” phenotypes. Signaling pathways involved in this switch were analyzed by gene expression profiling of a cohort of 22 patient-derived melanoma cell lines. E-cadherin/CDH1 negativity was identified as a surrogate marker for the invasive phenotype. CDH1 expression could be turned on and off by modulating activity of p38 or its downstream target MK2, suggesting that this pathway controls melanoma progression.