Journal Of Investigative Dermatology

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Second primary cancers in patients with invasive and in situ squamous cell skin carcinoma, Kaposi sarcoma and Merkel cell carcinoma: role for immune mechanisms?

Sat, 2019-07-06 00:00
Second primary cancers (SPCs) are becoming a common cancer entity, which may interfere with survival in relatively benign first primary cancers. We wanted to examine the hypothesis that immune dysfunction may contribute to SPCs by assessing SPCs associated with known immune responsive skin cancers, invasive and in situ squamous cell carcinoma (SCC), Kaposi sarcoma (KS) and Merkel cell carcinoma (MCC). Cancers were identified from the Swedish Cancer Registry from the years 1958 through to 2015. Standardized relative risks (RRs) were calculated bi-directionally for any SPC after skin cancer and for skin cancer as SPC.

MCPyV Large T antigen induced atonal homolog 1 (ATOH1) is a lineage-dependency oncogene in Merkel cell carcinoma

Fri, 2019-07-05 00:00
Despite the fact that the transcription factor atonal homolog 1 (ATOH1) is a master regulator of Merkel cell development, its role in Merkel cell carcinoma (MCC) carcinogenesis remains controversial. Here, we provide several lines of evidence that ATOH1 is a lineage-dependency oncogene in MCC. Luciferase assays revealed binding of ATOH1 and subsequent activation to the promoter of miR-375, i.e. one of the most abundant microRNAs in MCCs. Overexpression of ATOH1 in variant MCC cell lines and fibroblasts induced miR-375 expression, whereas ATOH1 knockdown in classical MCC cell lines reduced miR-375 expression.

Oxygen-mediated control of the keratinocyte proliferation-differentiation axis

Fri, 2019-07-05 00:00
The epidermis differentiates and functions in direct contact with the atmosphere (21% oxygen), leading to the common practice of maintaining keratinocytes in vitro at this oxygen level. However, studies have reported that the in vivo oxygen level in skin is much lower (<10%) (Evans et al. 2006).

Cutaneous wound healing in diabetic mice is improved by topical mineralocorticoid receptor blockade

Wed, 2019-07-03 00:00
Skin ulcers resulting from impaired wound healing are a serious complication of diabetes. Unresolved inflammation, associated with the dysregulation of both the phenotype and function of macrophages, is involved in the poor healing of diabetic wounds. Here, we report that topical pharmacological inhibition of the mineralocorticoid receptor (MR) by canrenoate or MR siRNA can resolve inflammation to improve delayed skin wound healing in diabetic mouse models; importantly, wounds from normal mice are unaffected.

Peripheral sensitisation and loss of descending inhibition is a hallmark of chronic pruritus

Tue, 2019-07-02 00:00
Neurophysiological mechanisms leading to chronicity of pruritus are not yet fully understood and it is not known whether these mechanisms diverge between different underlying diseases of chronic pruritus. This study aimed to detect such mechanisms in chronic pruritus of various origins. One-hundred and twenty patients with chronic pruritus of inflammatory origin (atopic dermatitis), neuropathic origin (brachioradial pruritus) and chronic prurigo of nodular type, the latter as a model for chronic scratching, as well as 40 matched healthy controls participated in this study.

Conditional Alox12b knockout: degradation of the corneocyte lipid envelope in a mouse model of autosomal recessive congenital ichthyoses

Tue, 2019-07-02 00:00
The skin barrier defect underlying autosomal recessive congenital ichthyoses (ARCI) leads to excessive transepidermal water loss immediately after birth. Affected infants are often born as collodion babies reflecting a physical compensation for the defective permeability barrier. In the available knockout mouse models, however, extrauterine survival is limited to a few hours. These animals therefore do not allow evaluation of any postnatal therapy.

The Long Noncoding RNA UCA1 Negatively Regulates Melanogenesis in Melanocytes

Tue, 2019-07-02 00:00
The long noncoding RNA UCA1 was first discovered in bladder cancer, and is known to regulate the proliferation and migration of melanoma. However, its role in melanogenesis is unclear. In this study, we aimed to explore the role and mechanism of UCA1 in melanogenesis. Our findings showed that the expression of UCA1 was negatively correlated with melanin content in melanocytes and pigmented nevus. Overexpression of UCA1 in melanocytes decreased melanin content and the expression of melanogenesis-related genes, whereas knockdown of UCA1 in melanocytes had the opposite effect.

Nanoparticle Targeting to Scalp Hair Follicles – New Perspectives for a Topical Therapy of Alopecia Areata

Tue, 2019-07-02 00:00
Alopecia Areata (AA) is a hair follicle (HF) disorder, where the immune system attacks the HF and causes reversible hair loss. Even though AA is not a life-threatening disease, an association with psychosocial diseases and a severe drop in quality of life is common (Pratt et al., 2017). Today, there is no approved medicine in the therapy of AA. New potent drugs, like Janus kinase (JAK) inhibitors, show promising results but bear severe adverse effects (Wang et al., 2018). For such drugs, the necessity for targeted delivery to the site of action is demanding.

IL-17A dissociates inflammation from fibrogenesis in systemic sclerosis (scleroderma)

Tue, 2019-07-02 00:00
Interleukin-17A (IL-17A) is abundant in scleroderma but its role in fibrogenesis is controversial. We interrogated the role of IL-17A in extracellular matrix deposition (ECM) and inflammation by investigating its effects on keratinocytes and fibroblasts cross-talk and in organotypic skin cultures. Keratinocyte-conditioned media (KCM) of resting, IL-17A- and/or transforming growth factor-β (TGF-β)-primed primary keratinocytes were used to stimulate healthy donors (HD) and scleroderma fibroblasts.

BJD Editor’s Choice

Mon, 2019-07-01 00:00
This systematic review from the U.K. set out to analyse studies evaluating the early detection of skin cancer, using skin self-examination interventions. They found 18 relevant studies with 6836 participants. Meta-analysis demonstrated the impact of the intervention on the degree of skin self-examination activity from five studies, especially in the short term, but with small effect sizes. Risk-of-bias assessment indicated that 61% of the studies (n = 11) were of weak quality. This study found that some interventions can enhance skin self-examination activity and so are more likely to aid early detection of skin cancer.

Table of Contents

Mon, 2019-07-01 00:00

Subscription Information

Mon, 2019-07-01 00:00

Editorial Board

Mon, 2019-07-01 00:00

Psoriasis Caught in the NET

Mon, 2019-07-01 00:00
A report in the June 2019 issue of the Journal of Investigative Dermatology reveals a role of neutrophil extracellular traps (NETs) in the induction of T helper type 17 cell responses and shows the relevance of this pathway in patients with psoriasis carrying a common risk variant in the TRAF3IP2 gene (Lambert et al., 2019). This work provides a new piece to the puzzle that links neutrophils to the T helper type 17–mediated pathogenesis of psoriasis.

SnapshotDx Quiz: July 2019

Mon, 2019-07-01 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 shown, while additional questions concern the findings reported in the JID article by Kim et al. (2019) (

Cells to Surgery Quiz: July 2019

Mon, 2019-07-01 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 Ferris et al. (2018) (

Clinical Snippets

Mon, 2019-07-01 00:00
Basal cell carcinomas (BCC) depend on deregulated Hedgehog (HH) signaling, which relies on the primary cilium. HH inhibitors, such as Smoothened inhibitors, prevent BCC growth, but development of resistance is common. Kuonen and colleagues showed a correlation between BCC resistance and loss of primary cilia. This study also revealed an inverse relationship between the primary cilium and Ras/mitogen-activated protein kinase (MAPK) activation, implicating a switch from HH to Ras/MAPK pathway as a mechanism of BCC resistance to HH inhibitors.

Editors’ Picks

Mon, 2019-07-01 00:00
Actinic keratoses (AKs) are frequent nonmalignant skin lesions that may develop into squamous cell carcinomas (SCCs) if left untreated. However, it is currently not possible to determine which lesions will progress. For that reason, field-directed treatments, including fluorouracil cream, imiquimod cream, methyl aminolevulinate photodynamic therapy, and ingenol mebutate gel, are commonly used to treat multiple AKs. The preferred methods for, and the long-term outcomes of, these treatments are still under study.

Research Techniques Made Simple: Using Genetic Variants for Randomization

Mon, 2019-07-01 00:00
Observational epidemiological studies have identified associations between a number of modifiable exposures and outcomes, including in dermatology, such as between smoking and psoriasis. However, it is challenging to determine if such relationships are causal because of the potential of confounding and reverse causation. Mendelian randomization (MR) is a statistical method that can be used to investigate the causal relationships between an exposure and outcome by using a genetic instrument that proxies the exposure.

Fueling Melanocytes with ATP from Keratinocytes Accelerates Melanin Synthesis

Mon, 2019-07-01 00:00
Melanocyte homoeostasis and their response to ultraviolet radiation (UVR) are mediated to a large extent by keratinocyte-derived factors, many of which have been well-characterized. Lee et al. describe novel effects of adenosine 5′-triphosphate (ATP), which is secreted by keratinocytes and can stimulate melanogenesis by melanocytes following UVA exposure. The investigators attribute the melanogenic effect of ATP to binding purinergic receptors type 2 X7 (P2X7), which are expressed on human melanocytes, leading to activation of the protein kinase C pathway.