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The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study.Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers.
Dendritic Cells (DC) are important inducers and regulators of T cell responses. They are able to activate- and modulate the differentiation of CD4+ and CD8+ T cells. In the skin there are at least five phenotypically distinct DC subpopulations that can be distinguished by differential expression of the cell surface markers CD207, CD103 and CD11b. Previous studies have suggested, that dermal CD11b−CD207+ conventional type 1 DC (cDC1) are indispensable for the priming of a skin homing cytotoxic T lymphocyte (CTL) response.
Activation of the Hedgehog (Hh) pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCC), with loss of function of Patched1 (Ptc1) being the most common genomic lesion. Sporadic BCCs also overexpress desmoglein-2 (Dsg2), a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively.
Vitiligo results from CD8+ T cell targeting of melanocytes, leading to patchy depigmentation. Upon cessation of therapy, depigmentation recurs at the same locations, implicating resident autoimmune memory T (TRM) cells. Indeed, Richmond and colleagues found that vitiligo patients have antigen-specific autoreactive TRM cells in lesional skin. As interleukin (IL)-15 is critical for generation of TRM cells, these investigators examined the effects of blocking IL-15 signaling via an antibody to the IL-15 CD122 subunit, which is expressed on autoreactive TRM cells in vitiligo.
Simpson and colleagues examined the clinical and physiological features and serum biomarkers in adult atopic dermatitis (AD) patients with and without Staphylococcus aureus colonization. AD patients colonized by S. aureus exhibited a distinct clinical phenotype and endotype, marked by more severe disease, greater epidermal function impairment, more pronounced defects in permeability and skin hydration, increased immune activation, type 2 immunity, and more extensive tissue damage than non-AD patients colonized by S. aureus.
Animal models have been developed to study the complex cellular and biochemical processes of wound repair and to evaluate the efficacy and safety of potential therapeutic agents. Several factors can influence wound healing. These include aging, infection, medications, nutrition, obesity, diabetes, venous insufficiency, and peripheral arterial disease. Lack of optimal preclinical models that are capable of properly recapitulating human wounds remains a significant translational challenge. Animal models should strive for reproducibility, quantitative interpretation, clinical relevance, and successful translation into clinical use.
The “Research Techniques Made Simple” (RTMS) series has covered nearly 75 research topics in the past 6 years to help readers build a foundation from which to understand the vast array of basic science and clinical research tools used in the field of dermatology. The early RTMS articles published in late 2012 through 2014 covered fundamental techniques including flow cytometry (Jahan-Tigh et al., 2012), PCR (Garibyan and Avashia, 2013), how a transgenic mouse is made (Scharfenberger et al., 2014), and basics of systematic reviews and meta-analyses (Abuabara et al., 2012).
The JID Connector was established to do just that—connect. It was in that spirit that “Research Techniques Made Simple” (RTMS) was born. The initial concept, conceived by Barbara Gilchrest of Harvard University and implemented by Kathy Schwarzenberger of the University of Tennessee Health Science Center, was to increase the accessibility of articles that appeared in the Journal of Investigative Dermatology (JID). It was recognized, however, that to reach trainees, interested clinicians, and non-cognoscenti, the science had to be more accessible and understandable.
“Education is not the filling of a pail, but the lighting of a fire.”—W.B. Yeats
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 Miller et al (https://doi.org/10.1016/j.jid.2018.02.018).
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical images above, while additional questions concern the findings reported in the JID article by Lauffer et al (https://doi.org.com/10.1016/j.jid.2018.02.034).
The letters “Interpretation of the Outputs of Deep Learning Model trained with Skin Cancer Dataset” and “Automated Dermatological Diagnosis: Hype or Reality?” highlight the opportunities, hurdles, and possible pitfalls with the development of tools that allow for automated skin lesion classification. The potential clinical impact of these advances relies on their scalability, accuracy, and generalizability across a range of diagnostic scenarios.
The impact of antiseptics on the skin microbiota is poorly understood. SanMiguel et al. (2018) use a sequencing-based approach to compare treatment effects and find that they are dependent on interpersonal and body site–specific community differences. While treatment results in an immediate depletion of the skin microbiota, not all bacterial families are affected equally.
Tyrosine kinase inhibitors (TKI) have emerged as therapeutic option for rheumatic diseases such as systemic sclerosis (SSc). Since TKs like c-Abl kinase are important for fibroblast activation and fibrosis development in SSc, the c-Abl inhibitor imatinib was proposed for SSc treatment. Transporters for organic cations have become increasingly recognized as an important determinant for uptake and efficacy of TKI. Therefore, we investigated the role of organic cation transporters in the uptake of imatinib.
Keloids mark a chronic inflammatory disease characterized by a fibroproliferative disorder of the skin. A genome-wide association study (GWAS) has revealed that single nucleotide polymorphism (SNP) rs8032158 in the neural precursor cell expressed, developmentally down-regulated 4 (NEDD4) gene, which has six protein-coding transcript variants (TV), is genetically linked with keloid. Here we show a high frequency of the risk allele C in rs8032158 in keloid patients is associated with a selectively higher expression of TV3 of NEDD4 to activate the NFκB pathway.
Kindler syndrome (KS) is an autosomal recessive genodermatosis that results from mutations in the FERMT1 gene encoding t kindlin-1. Kindlin-1 localises to focal adhesion and is known to contribute to the activation of integrin receptors. Most cases of KS show a reduction or complete absence of kindlin-1 in keratinocytes, resulting in defective integrin activation, cell adhesion and migration. However, roles for kindlin-1 beyond integrin activation remain poorly defined. In the current study we show that skin and keratinocytes from KS patients have significantly reduced expression levels of the epidermal growth factor receptor (EGFR), resulting in defective EGF-dependent signalling and cell migration.