Journal Of Investigative Dermatology

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Clinical Snippets

Sat, 2020-02-01 00:00
Zhou and colleagues detected ectopic lymphoid structures (ELS) that resemble tertiary lymphoid organs in pemphigus vulgaris and pemphigus foliaceous lesions. ELS were characterized by B cells reactive to the desmoglein 3 autoantigen, and were associated with active disease and B cell expansion. B cell differentiation in ELS was supported by the detection of centroblasts, plasmablasts, and plasma cells in these lesions. Chemokines that may induce B cell migration to pemphigus lesions were also detected in ELS.

SnapshotDx Quiz: February 2020

Sat, 2020-02-01 00:00
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx 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 Callewaert et al. (2019) (https://doi.org/10.1016/j.jid.2019.05.024).

Survival in Mycosis Fungoides and Sezary Syndrome: How Can We Predict Outcome?

Sat, 2020-02-01 00:00
Early-stage mycosis fungoides (MF) has been associated with long survival. A recent meta-analysis including 6,279 patients with MF and Sezary syndrome found that about 10–20% of stage IB patients don’t survive 5 years, whereas patients with advanced-stage MF and Sezary syndrome have a 5-year survival chance of about 20–60%. Identifying prognostic markers to better identify those at risk of limited survival may allow improved management choices and this, coupled with newer treatments, could improve survival.

Is Local Production of Autoantibodies in Skin Lesions Relevant in Pemphigus?

Sat, 2020-02-01 00:00
Pemphigus is an autoimmune bullous disease characterized by IgG production against desmogleins. The major sites of autoantibody production are thought to be lymph nodes, spleen, and bone marrow. Previously, it has been suggested that autoreactive B cells might exist in the skin lesions in pemphigus and produce autoantibodies. In their report, Zhou et al. expanded their previous studies and reported that ectopic lymphoid-like structures were found in pemphigus skin lesions, wherein B-cell differentiation and lesional B-cell expansion might progress.

Noncoding Variants as Genetic Contributors to Autoimmune Disease Pathogenesis

Sat, 2020-02-01 00:00
Understanding the functions of disease-associated noncoding variants is essential for understanding the molecular mechanisms driving diseases with a genetic cause and for identifying therapeutic targets. Combined computational and experimental analyses have demonstrated that IRF5 is hyperactivated by a pathogenic allele of TNPO3 through long-distance chromatin looping. This finding identifies a molecular mechanism contributing to the polygenic autoimmune diseases of systemic lupus erythematosus and systemic sclerosis.

Spherical Nucleic Acids as Emerging Topical Therapeutics: A Focus on Psoriasis

Sat, 2020-02-01 00:00
Systemically delivered targeted biologics have revolutionized the treatment of moderate-to-severe psoriasis. For milder forms of psoriasis, topical therapies, primarily corticosteroids, remain the mainstay of treatment to reduce the risks and off-target side effects associated with systemic therapies. Most newly developed biologics, including monoclonal antibodies, are structurally complex and are unable to penetrate the skin barrier. Recently developed liposomal spherical nucleic acids overcome this barrier and enable topical delivery of antisense oligonucleotides capable of specifically targeting inflammatory pathways underlying psoriasis pathogenesis.

Interaction between Smoking and HLA-C*06:02 on the Response to Ustekinumab in Psoriasis

Fri, 2020-01-31 00:00
HLA-C*06:02, is the genetic variant that affords the highest susceptibility for psoriasis, increasing the odds for the disease approximately five times (Strange et al., 2010). Its effect may be modified by a number of factors, including smoking (Jin et al., 2009).

PAR2 mediates itch via TRPV3 signaling in keratinocytes

Tue, 2020-01-28 00:00
Animal studies have suggested that transient receptor potential (TRP) ion channels and G protein-coupled receptors (GPCRs) play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists.

A Phase II, Open Label Study of Bermekimab in Patients with Hidradenitis Suppurativa Shows Resolution of Inflammatory Lesions and Pain

Tue, 2020-01-28 00:00
To evaluate the safety and efficacy of bermekimab, an interleukin-1⍺ inhibitor, in the treatment of hidradenitis suppurativa (HS). Design and Setting: This study was a phase 2, multi-center, open-label study of two dose cohorts of bermekimab in patients naïve to or have failed prior anti-TNF therapy with moderate-to-severe HS.

AURKA Enhances Autophagy of ADSCs to Promote Diabetic Wound Repair via Targeting FOXO3a

Tue, 2020-01-28 00:00
AURKA (Aurora kinase A) regulates apoptosis and autophagy in a diverse range of disease and exhibited a promising clinical efficacy. But the role of AURKA in regulating ADSCs (Adipose derived stem cells) repairing diabetic wound remains unclear. Here, we showed that ADSCs subjected to high glucose stress displayed an obvious induction of AURKA, FOXO3a and a significant increase in autophagy and apoptosis. The AURKA was confirmed to regulate autophagy through FOXO3a. AURKA mediated autophagy inhibited high glucose-induced apoptosis of ADSCs.

Apremilast in combination to narrowband UVB in the treatment of vitiligo. A 52 weeks monocentric prospective randomized placebo-controlled study

Tue, 2020-01-28 00:00
Scientific rationale and encouraging first clinical results suggest the interest of using apremilast for treating vitiligo.

Enhanced glycogen metabolism supports the survival and proliferation of HPV-infected keratinocytes in condylomata acuminata

Tue, 2020-01-28 00:00
Condylomata acuminata (CA) is caused by HPV infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here we report that HPV infection develops a hypoxic microenvironment in CA warts, inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a HIF-1α dependent pathway.

Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms

Tue, 2020-01-28 00:00
The newest WHO classification suggests eliminating cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). We aimed to better characterize the genomics of Spitz neoplasms and assess whether integrating genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). NGS data was used to reclassify tumors by moving BRAF/NRAS-mutated cases to MSF.

Long non-coding RNA GAS5 regulates macrophage polarization and diabetic wound healing

Tue, 2020-01-28 00:00
A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages. Using in vivo and in vitro analyses, we have tested the hypothesis that lncRNA GAS5 (Growth Arrest-Specific 5) is dysregulated in diabetic wounds. We have assessed the contribution of GAS5 to the M1 macrophage phenotype, as well as the functional consequences of knocking down its expression. We found that expression of GAS5 is significantly increased in diabetic wounds and in cells isolated from diabetic wounds.

Wif1 suppresses the generation of suprabasal cells in acanthotic skin and growth of basal cell carcinomas upon forced overexpression

Fri, 2020-01-24 00:00
We analyzed the role of Wnt inhibitory factor 1 (Wif1) in normal and acanthotic epidermis of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans-retinoic acid (ATRA)-treated and basal cell carcinoma (BCC)-bearing mice. Wif1 protein is located in the follicular infundibulum and interfollicular epidermis (IFE) in murine back skin. Within the hyperplastic epidermis of TPA- or ATRA-treated or BCC-bearing murine skin, Wif1 and K10 overlap in Ki67neg suprabasal layers, while basal epidermal layers expressing Ki67, and BCCs expressing Wif1 mRNA, are free of Wif1 protein.

Palmoplantar keratoderma with leukokeratosis anogenitalis caused by KDSR mutations

Fri, 2020-01-24 00:00
Hereditary keratodermas and ichthyoses comprise a large collection of genodermatoses for which underlying mutations in more than 100 genes have been identified (Oji et al., 2010). The implicated genes are involved in a multitude of biological pathways. Ceramides are important for cutaneous barrier function (Borodzicz et al., 2016) and cutaneous proliferation and differentiation (Uchida, 2014). In most organisms they are synthesized by three different biochemical pathways, named de novo, sphingomyelinase and salvage pathways (Hannun and Obeid, 2008, Kihara, 2016, Kitatani et al., 2008).

Phenotypic plasticity of cutaneous squamous cell carcinoma mediated by cyclooxygenase-2

Wed, 2020-01-22 00:00
To the Editor, Squamous cell carcinomas (SCCs) are the most common type of cancer capable of metastasis (Yan et al., 2011). The enzymatic activity of Cox-2 (Cyclooxygenase 2, also called Ptgs2), contributes to the synthesis of prostanoids and is upregulated in numerous types of cancers, including cutaneous SCCs (cSCCs) (Subbaramaiah and Dannenberg, 2003; Sobolewski et al., 2010; Hua et al., 2015). Cox-2 is an important regulator of tumor development and progression in ultraviolet and chemical carcinogenesis models of cSCC (Jiao et al., 2014b; a; Elmets, Ledet and Athar, 2014).

Human Polyomavirus 6 with the Asian/Japanese Genotype in Cases of Kimura Disease and Angiolymphoid Hyperplasia with Eosinophilia

Wed, 2020-01-22 00:00
Some human polyomaviruses (HPyVs) have been associated with inflammatory skin conditions (Ho et al., 2015; Nguyen et al, 2017). More investigation is needed to identify further presentations of pathological cases of patients with cutaneous HPyVs (Nguyen et al., 2019; Sheu et al., 2019). Kimura disease (KD) is a rare form of chronic inflammatory disorder involving subcutaneous tissue, and frequently associated with regional lymphadenopathy (Leiferman and Peters, 2018). KD is seen predominantly in East Asian populations, especially Japanese and Chinese individuals (Chen et al., 2004; Long et al., 2016), but the underlying cause is still unknown.

Identification of a human skin commensal bacterium that selectively kills Cutibacterium acnes

Wed, 2020-01-22 00:00
The microbiome represents a vast resource for drug discovery as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes (C. acnes) is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C.

Association of HLA-A*11:01 with sulfonamide-related severe cutaneous adverse reactions in Japanese patients

Wed, 2020-01-22 00:00
Sulfonamides are pharmaceuticals with an SO2-NH2 group, used mainly for treating infectious and inflammatory diseases. Their main active ingredient is sulfanilamide (SN), a metabolite that can inhibit folic acid synthesis in bacteria. In Japan, common sulfonamides include sulfamethoxazole (SMX) and salazosulfapyridine (SASP). Sulfonamides can cause severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DIHS) (Schnyder and Pichler, 2013).

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