Journal Of Investigative Dermatology

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Updated: 2 hours 31 min ago

Cells to Surgery Quiz: December 2018

Sat, 2018-12-01 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 above, while additional questions concern the findings reported in a JID article by Kuonen et al (

Progress in Understanding Atopic Dermatitis

Sat, 2018-12-01 00:00
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, and its realm of basic mechanisms and predisposing factors is similarly wide. The Journal of Investigative Dermatology (JID) has recently published a surprisingly numerous collection of articles, comments, and reviews that scan the universe of basic information about AD. This review is directed toward using the JID Collections to provide a background and melding of research focuses in the current setting. This online commentary will attempt to consolidate and interweave some of the featured studies that have emerged.

SnapshotDx Quiz: December 2018

Sat, 2018-12-01 00:00
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 above, while additional questions concern the findings reported in the JID article by Imanishi et al (

BJD Editor’s Choice

Sat, 2018-12-01 00:00
This team of researchers, led by Moss explain that midface toddler excoriation syndrome (MiTES) is a newly described condition. It is characterized by habitual scratching from the first year of life creating deep, chronic, scarring wounds around the nose and eyes. An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to MiTES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII (HSAN8), PRDM12.

NLRP1 Is the Key Inflammasome in Primary Human Keratinocytes

Sat, 2018-12-01 00:00
The epidermis is the primary area of contact between the body and the environment, and it distinguishes between harmful exposures and those that should be tolerated. Discrimination between insults, and in particular the recognition of danger signals such as UVB, is mediated by innate immune receptors. Inflammasomes are one major innate mechanism that activate inflammatory caspases. In human keratinocytes, the importance of inflammasomes and the sensing of UVB and other danger signals are a matter of debate.

Treatment with Modified Heat Shock Protein Repigments Vitiligo Lesions in Sinclair Swine

Sat, 2018-12-01 00:00
HSP70i is secreted by stressed melanocytes, is associated with human vitiligo lesions, and functionally contributes to a mouse model of vitiligo. Henning et al. report that treatment with a modified version of the protein reversed depigmentation in Sinclair swine, a useful animal model of vitiligo. These studies provide the rationale for testing in human studies.

Impact of secukinumab on endothelial dysfunction and other cardiovascular disease parameters in psoriasis patients over 52 weeks

Fri, 2018-11-30 00:00
Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown.CARIMA was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomized to 300 mg or 150 mg secukinumab until week 52, or placebo until week 12 then 300 mg or 150 mg secukinumab until week 52.

Cyclophosphamide pulse therapy normalizes vascular abnormalities in a mouse model of systemic sclerosis vasculopathy

Fri, 2018-11-30 00:00
Intravenous cyclophosphamide pulse, a standard treatment for systemic sclerosis (SSc)-related interstitial lung disease (ILD), elicits a disease-modifying effect on SSc vasculopathy, such as fostering microvascular de-remodeling. To investigate the molecular mechanism by which cyclophosphamide mitigates SSc vasculopathy, we employed endothelial cell-specific Fli1 knockout (Fli1 ECKO) mice that mimic the functional and structural vascular abnormalities characteristic of SSc. Biweekly cyclophosphamide injection improved vascular permeability and structural abnormalities of Fli1 ECKO mice in 2 weeks and in 3 months, respectively.

Activation of aryl hydrocarbon receptor negatively regulates thymic stromal lymphopoietin gene expression via PKCδ-p300- NF-κB pathway in keratinocytes under inflammatory conditions

Thu, 2018-11-29 00:00
Epithelial-derived TSLP (thymic stromal lymphopoietin) plays an important role in pathogenesis in several types of dermatitis. Recently, the anti-inflammatory effects of AhR (aryl hydrocarbon receptor) have been reported in inflamed skin. In this study, keratinocytes were stimulated with TNFα or flagellin in combination with AhR ligands or antagonist. TSLP gene expression and recruitment of transcriptional regulator to TSLP gene promoter were determined. The effects of AhR activation were also studied in DNFB (1-fluoro-2, 4-dinitrobenzene)-induced dermatitis model.

Non-Invasive Analysis of High-Risk Driver Mutations and Gene Expression Profiles in Primary Cutaneous Melanoma

Tue, 2018-11-27 00:00
Tools that help reduce the number of surgical biopsies performed on benign lesions have the potential to improve patient care. The pigmented lesion assay (PLA) is a non-invasive tool validated against histopathology that helps rule out melanoma and the need for surgical biopsies of atypical pigmented skin lesions. Genetic information is collected using adhesive patches and the expression of two genes, LINC00518 and PRAME, is measured. Using genetic material collected non-invasively and to further validate the PLA, somatic hotspot mutations in genes known to be drivers of early melanoma development (BRAF other than V600E, NRAS and the TERT promoter) can also be identified.

Online Care versus In-Person Care for Improving Quality of Life in Psoriasis: A Randomized Controlled Equivalency Trial

Sat, 2018-11-24 00:00
This 12-month, pragmatic, randomized controlled equivalency trial evaluated whether an online, collaborative connected-health model results in equivalent improvements in quality of life as compared to in-person care for psoriasis. 296 adults with physician-diagnosed psoriasis from ambulatory clinics were randomized to either online or in-person care; all were analyzed for outcomes. In the online group, patients and primary care providers (PCPs) sought dermatologists’ care directly and asynchronously online.

A microRNA-29 mimic (remlarsen) represses extracellular matrix expression and fibroplasia in the skin

Thu, 2018-11-22 00:00
MicroRNA-29 negatively regulates fibrosis, and miR-29 is downregulated in multiple fibrotic organs and tissues, including in the skin. miR-29 mimics prevent pulmonary fibrosis in mouse models but have not previously been tested in the skin. This study aimed to identify pharmacodynamic (PD) biomarkers of miR-29 in mouse skin, to translate those biomarkers across multiple species and to assess the PD activity of a miR-29b mimic (remlarsen) in a clinical trial. miR-29 biomarkers were selected based on gene function and mRNA expression using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR).

Perspective: Mutations in Recessive Congenital Ichthyoses Illuminate the Origin and Functions of the Corneocyte Lipid Envelope

Wed, 2018-11-21 00:00
The corneocyte lipid envelope (CLE), a monolayer of ϖ-hydroxyceramides, whose function(s) remain(s) uncertain, is absent in autosomal recessive congenital ichthyoses (ARCI) with mutations in enzymes that regulate epidermal lipid synthesis. Secreted lipids fail to transform into lamellar membranes in certain ARCI epidermis, suggesting the CLE provides a scaffold for the extracellular lamellae. But since cornified envelopes (CEs) are attenuated in these ARCI, the CLE may also provide a scaffold for subjacent CE formation, evidenced by restoration of CEs after CLE ‘rescue.’ We provide multiple lines of evidence that the CLE originates as lamellar body (LB) limiting membranes fuse with the plasma membrane: i) ABCA12 patients and Abca12-/- mice display normal CLEs; ii) CLEs are normal in Netherton syndrome, despite destruction of secreted LB contents; iii) CLEs are absent in VSP33B-negative patients; iv) limiting membranes of LBs are defective in lipid-synthetic ARCI; and v) lipoxygenases, lipase activity and LIPN co-localize within putative LBs.

Targeting PAR2 with Pepducins

Wed, 2018-11-21 00:00
Itch, inflammation, and atopic dermatitis are associated with activation of PAR2. Affecting PAR2 activity presents a number of challenges. Here, a cell-penetrating peptide, termed a pepducin, circumvents these challenges by preventing the receptor from coupling to G proteins. The pepducin modulates several models of itch, inflammation, and atopic dermatitis.

A Role for the E3 Ubiquitin Ligase NEDD4 in Keloid Pathogenesis

Wed, 2018-11-21 00:00
The molecular pathomechanisms that drive keloid formation are only partially understood. Genetic studies have provided evidence for a genetic predisposition to keloid formation, and a keloid risk allele has been reported in the gene locus for the E3 ubiquitin ligase NEDD4. Fujita et al. (2018) explore the consequences of this genetic risk allele in NEDD4 for inflammation in the skin and for keloid pathogenesis. This study implicates a specific transcript variant of NEDD4, NEDD4-TV3, as a regulator of NF-κB/STAT3–mediated inflammation and provides evidence that an increase in NEDD4-TV3 promotes keloid formation.

Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients

Tue, 2018-11-20 00:00
Pseudoxanthoma elasticum (PXE) is a heritable disease caused by ABCC6 deficiency. Patients develop ectopic calcification in skin, eyes and vascular tissues. ABCC6, primarily found in liver and kidneys, mediates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a potent inhibitor of calcification. PXE patients and Abcc6-/- mice display reduced PPi levels in plasma and peripheral tissues. PXE is currently incurable, although some palliative treatments exist. In recent years, we have successfully developed therapeutic methodologies to compensate the PPi deficit in animal models and humans.

Skin-Derived SPINK9 Kills Escherichia coli

Tue, 2018-11-20 00:00
Antimicrobial peptides (AMP) play a critical role in the barrier function of human skin. They offer a fast response to invading microorganisms and hence protect from external microbial infection. Here we showed the isolation of the KLK5 inhibitor SPINK9 as a major antibacterial factor from healthy stratum corneum. Totally, six N-terminal SPINK9 variants were identified in the stratum corneum. Whereas all variants exhibited similar inhibition activities against KLK5, only three variants with either lysine or glutamine as their first N-terminal residues were able to kill various Escherichia coli (E.coli) strains but not other bacteria or fungi.