Journal Of Investigative Dermatology

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BJD Editor's Choice

Tue, 2019-10-01 00:00
Accurate counting of nonmelanoma skin cancer in fair-skinned populations remains challenging due to high event rates. In the past, epidemiology data have often been limited to collection of the number of people affected, rather than the number of tumours. Venables and coauthors report on pathology data from across the U.K., which identified the first basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) each year in 2013–2015 across the U.K. European age-standardized incidence rates of the first BCC and cSCC per patient per annum were 285 and 77 per 100 000 person-years, respectively.

Table of Contents

Tue, 2019-10-01 00:00

Subscription Information

Tue, 2019-10-01 00:00

Editorial Board

Tue, 2019-10-01 00:00

Cells to Surgery Quiz: October 2019

Tue, 2019-10-01 00:00
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery 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 Kobayashi et al. (2019) (https://doi.org/10.1016/j.jid.2019.02.016).

Editors’ Picks

Tue, 2019-10-01 00:00
The unique distribution of RNAs in cells underlies local protein organization, chromatin features, and organismal development. On a quest for new methods to map the spatial localization of thousands of endogenous RNAs simultaneously in living cells, Fazal and colleagues developed APEX-seq, which involves direct proximity labeling of RNA with the APEX2 peroxidase. Advantages of this novel method include the ability to assess localization in live cells and in organelles that are not readily purified for analysis, and the analysis of diverse RNA transcripts, including lncRNAs, antisense RNAs, and untranslated RNAs.

Clinical Snippets

Tue, 2019-10-01 00:00
Hörer and colleagues uncovered variants in the phospholipase enzyme C δ1 gene (PLCD1) in blood from 35 affected individuals from 12 Tunisian families with trichilemmal cysts, which are benign scalp tumors derived from the hair follicle outer root sheath. These high-risk inherited alleles were associated with the presence of trichilemmal cysts, which are known to be inherited in an autosomal dominant manner with incomplete penetrance. Comparison of cyst tissue and blood DNA revealed an additional cyst-specific PLCD1 variant that occurred in cis with the other predisposing variants, and this variant was associated with reduced protein function.

SnapshotDx Quiz: October 2019

Tue, 2019-10-01 00:00
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx/Cells to Surgery 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 a JID article by Langton et al. (2019) (https://doi.org/10.1016/j.jid.2018.10.026).

Research Techniques Made Simple: Feature Selection for Biomarker Discovery

Tue, 2019-10-01 00:00
Molecular biomarkers can be powerful tools for aiding in the efficiency and precision of clinical decision-making. Feature selection methods, machine-learning, and biostatistics have been applied to discover subsets of molecular markers that identify target classes of clinical cases. For example, in the field of dermatology, these approaches have been used to develop predictive models that identify skin diseases, ranging from melanoma to psoriasis, based upon a variety of biomarkers. However, a continuous increase in the variety and size of datasets from which candidate biomarkers can be derived, and limitations in the computational tools used to analyze them, have hindered the interpretability of biomarker discovery studies.

PLCD1 and Pilar Cysts

Tue, 2019-10-01 00:00
Trichilemmal or “pilar” cysts are commonly found on the scalp and are derived from the outer root sheath of the hair follicle. Multiple trichilemmal cysts present in an autosomal dominant pattern of inheritance, yet the genetic mechanism has remained elusive. In this issue, Hörer et al. (2019) highlight predisposing variants in PLCD1 in such families and propose a monoallelic mutational mechanism that drives cyst formation.

ILC2s and Basophils Team Up to Orchestrate IL-33–Induced Atopic Dermatitis

Tue, 2019-10-01 00:00
In this issue, Imai et al. (2019) provide new insights into the pathophysiology of AD-like inflammation using their model (Imai et al., 2013) and ask how ILC2s and basophils contribute to the IL-33–induced AD-like inflammation. Their findings show that continuous expression of IL-33 in keratinocytes is sufficient to cause AD-like inflammation in mice, and that this occurrence is largely independent of adaptive immune cells and is mediated by basophils and ILC2s.

Tracing the Equilibrium Phase of Cancer Immunoediting in Epidermal Neoplasms via Longitudinal, Intravital Imaging

Thu, 2019-09-19 00:00
Recognition of transformed cells by the immune system can sometimes generate a rate-limiting “equilibrium phase,” wherein tumor outgrowth is prevented without complete neoplasm elimination. Targeting premalignancies during this immune-controlled bottleneck is a promising strategy for rational cancer prevention. Thus far, immune equilibrium has been difficult to model in a traceable way and most immunoediting systems have been limited to mesenchymal tumor types. Here, we introduce a mouse model for fluorescent tracing of somatic, epithelial transformation.

Cells of myeloid origin partly mediate the association between psoriasis severity and coronary plaque

Tue, 2019-09-17 00:00
Psoriasis, a chronic inflammatory skin disease is associated with heightened immune activation, accelerated cardiovascular (CV) risk as well as increased acute coronary syndromes, most evident in young adults (Gelfand et al., 2006). This inflammatory skin disease confers an independent risk for myocardial infarction (MI) beyond traditional CV risk factors (Mehta et al., 2010) and on average leads to a decreased lifespan of five years (Gelfand et al., 2006). One explanation is the susceptibility of psoriasis patients to develop unstable, lipid-rich non-calcified coronary plaques (NCB) that are vulnerable to rupture (Lerman et al., 2017).

Skin microbiota perturbations are distinct and disease severity-dependent in hidradenitis suppurativa

Tue, 2019-09-17 00:00
Hidradenitis Suppurativa (HS) is a prevalent and debilitating inflammatory skin disease characterized by painful and recurrent nodules and abscesses, malodorous purulent drainage, and disfiguring sinus tract and scar formation involving intertriginous body sites. Microorganisms have been implicated in HS pathogenesis, and broad-spectrum antimicrobial therapy is one of the mainstays of HS management. However, bacteria have been identified in only ∼50% of HS lesions using conventional culture-based methods and no consistent organism has been cultured from HS lesions.(Brook and Frazier, 1999, Gener et al., 2009, Jemec, 2003, Join-Lambert et al., 2011, Leach et al., 1979)

Interleukin-36 promotes systemic Type-I IFN responses in severe forms of psoriasis

Tue, 2019-09-17 00:00
Psoriasis is an immune-mediated skin disorder associated with severe systemic co-morbidities. While IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extra-cutaneous disease manifestations remain poorly understood.To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalised pustular psoriasis (GPP), a clinical variant associated with pervasive up-regulation of IL-36 signalling.

Staphylococcus aureus Lipoteichoic Acid Initiates a TSLP-Basophil-IL4 Axis in the Skin

Tue, 2019-09-17 00:00
Atopic Dermatitis (AD) is an inflammatory skin disease associated with increased levels of type 2 cytokines. In addition, the skin of AD patients is frequently colonized with Staphylococcus aureus and increased levels of this pathogen are associated with increased disease severity and elevated type 2 allergic responses (Leung et al., 2019). Recent studies have also shown that the onset of S. aureus colonization correlates with the onset of type 2 responses (Meylan et al., 2017, Nakatsuji et al., 2016), however, a mechanism to explain the induction of type 2 responses by S.

Pathogenic CD8+ epidermis-resident memory T cells displace dendritic epidermal T cells in allergic dermatitis

Tue, 2019-09-10 00:00
The skin is our interface with the outside world and consequently it is exposed to a wide range of microbes and allergens. Recent studies have indicated that allergen-specific skin-resident memory T (TRM) cells play a role in allergic contact dermatitis (ACD). However, the composition and dynamics of the epidermal T cell subsets during ACD are not known. Here we show that exposure of the skin to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB) results in a displacement of the normally occurring dendritic epidermal T cells (DETC) concomitant with an accumulation of epidermal CD8+CD69+CD103+ TRM cells in mice.

Somatic mosaic NLRP3 mutations and inflammasome activation in late-onset chronic urticaria

Mon, 2019-09-09 00:00
Chronic urticaria is a common skin disorder with heterogeneous causes. In the absence of physical triggers, chronic urticarial rash is called idiopathic or spontaneous. The objective of the current study was to identify the molecular and cellular bases of a disease condition displayed by two unrelated patients aged over 60 years who presented for two decades with a chronic urticaria resistant to standard therapy which occurred in the context of systemic inflammation not triggered by cold. In both patients, a targeted sequencing approach using a next generation technology identified somatic mosaic mutations in NLRP3, a gene encoding a key inflammasome component.

Exploratory Assessment Of Oxygen Flow Assisted Cutaneous Administration Of Methotrexate For Superficial Basal Cell Carcinoma, Mycosis Fungoides And Extramammary Paget’s Disease

Mon, 2019-09-09 00:00
The molecular weight of methotrexate (MTX) makes cutaneous penetration difficult. Oxygen flow could enhance the skin permeation of MTX diluted in the LP3 carrier system. This pilot study aims to assess the efficacy, safety and tolerance of oxygen-flow-administered (OFA)-LP3-MTX3% for treating superficial skin cancers. Patients with superficial basal cell carcinoma (sBCC)(n=12), extramammary Paget’s disease (EMPD)(n=5), mycosis fungoides classic type (CMF) (n=10) and folliculotropic (FMF) (n=6) were included in the study and were treated with 4 weekly applications of OFA-LP3-MTX3%.

IL-1β-primed Mesenchymal Stromal Cells improve epidermal substitute engraftment and wound healing via MMPs and TGF-β1

Mon, 2019-09-09 00:00
Since the 1980s, deep and extensive skin wounds and burns are treated with autologous Split-Thickness Skin Grafts, or Cultured Epidermal Autografts (CEAs) when donor sites are limited. However, the clinical use of CEAs often remains unsatisfactory due to poor engraftment rates, altered wound healing and reduced skin functionality.In the past few decades, Mesenchymal Stromal Cells (MSCs) have raised much attention due to their anti-inflammatory, pro-trophic and pro-remodeling capacities. More specifically, gingival MSCs have been shown to possess enhanced wound healing properties compared to other tissue sources.

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