Journal Of Investigative Dermatology

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YKL-40 promotes proliferation of CTCL tumor cells through extracellular signal-regulated kinase pathways

Mon, 2019-10-14 00:00
YKL-40, one of the chitinase-like proteins, is associated with the pathogenesis of wide variety of human diseases through modulation of inflammation and tissue remodeling by its diverse roles in cell proliferation, differentiation, and survival. Emerging evidence shows that aberrantly expressed YKL-40 promotes the development of malignancies by inducing proliferation of tumor cells, cytokine production, and angiogenesis by acting on various stromal cells, immune cells, and tumor cells. In this study, we investigated the expression and function of YKL-40 in cutaneous T-cell lymphoma (CTCL).

The Evolution of Melanoma – Moving beyond Binary Models of Genetic Progression

Mon, 2019-10-14 00:00
To date, over 1000 melanocytic neoplasms, spanning all stages of tumorigenesis, have been sequenced, offering detailed views into their -omic landscapes. This has coincided with advances in genetic engineering technologies that allow molecular biologists to edit the human genome with extreme precision and new mouse models to simulate disease progression. In this review, we describe how these technologies are being harnessed to provide insights into the evolution of melanoma at an unprecedented resolution, revealing that prior models of melanoma evolution, in which pathways are turned ‘on’ or ‘off’ in a binary fashion during the run-up to melanoma, are oversimplified.

Interpretability of the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ)

Thu, 2019-10-10 00:00
The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) is used to measure impairment of health-related quality of life (HRQoL) in hand eczema. Here, we prospectively studied the interpretability of international QOLHEQ scores at three time points: baseline, after 1-3 days (T1) and after 4-12 weeks (T2). Adult patients with hand eczema completed the QOLHEQ and anchor questions for overall assessment of HRQoL impairment. Interpretability of single scores was assessed at baseline by defining severity bands based on agreement with the anchor questions.

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.

A distinct pre-treatment immune gene signature in lentigo maligna is associated with imiquimod response

Mon, 2019-09-30 00:00
Lentigo Maligna (LM) is a common subtype of in-situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Whilst surgery is the standard treatment, there is associated morbidity and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both prior to and following treatment with imiquimod to better identify likely responders.

MicroRNA Ratios Distinguish Melanomas from Nevi

Mon, 2019-09-30 00:00
The use of microRNAs as biomarkers has been proposed for many diseases, including the diagnosis of melanoma. Although hundreds of microRNAs have been identified as differentially expressed in melanomas as compared to benign melanocytic lesions, a limited consensus has been achieved across studies, constraining the effective use of these potentially useful markers. In this study, we applied a machine learning-based pipeline to a dataset consisting of genetic features, clinical features, and next-generation microRNA sequencing from micro-dissected formalin-fixed paraffin embedded melanomas and their adjacent benign precursor nevi.

Topical Application Of A Mast Cell Stabilizer Improves Impaired Diabetic Wound Healing

Fri, 2019-09-27 00:00
Impaired wound healing in the diabetic foot is a major problem often leading to amputation. Mast cells have been shown to regulate wound healing in diabetes. We developed an indole-carboxamide type mast cell stabilizer, MCS-01, which proved to be an effective mast cell degranulation inhibitor in vitro and can be delivered topically for prolonged periods through controlled release by specifically designed alginate bandages. In diabetic mice, both pre- and post-wounding, topical MCS-01 application accelerated wound healing comparable to that achieved with systemic mast cell stabilization.

Inherited Melanoma Risk Variants Associated with Histopathologically Amelanotic Melanoma

Fri, 2019-09-27 00:00
Amelanotic melanoma (AM) accounts for 2-20% of cutaneous melanomas but a disproportionately high number of melanoma-related deaths because of a more advanced stage at diagnosis (Strazzulla et al., 2019, Thomas et al., 2014, Wee et al., 2018). AM is defined by lacking pigment upon clinical inspection or melanin upon histopathological examination; and, in some studies, includes both hypo- and non-pigmented lesions. We reported in the Genes, Environment and Melanoma Study (GEM) that carriage of MC1R variants, absent back nevi, many freckles, red hair, lighter eyes, and decreased tannability were associated with histopathologically AM relative to pigmented melanoma (PM) (Vernali et al., 2017), consistent with other studies (Rayner et al., 2019, Strazzulla et al., 2019, Wee et al., 2018).

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).

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