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The International Bullous Diseases Group has created this excellent consensus paper on diagnostic criteria for epidermolysis bullosa acquisita (EBA). They start by explaining that EBA is a complex autoimmune bullous disease that has variable clinical presentations; multiple possible diagnostic tests mean that international consensus on the diagnosis of EBA is needed. A standardized system of face-to-face discussion followed by voting was used to achieve consensus. However, the differential diagnosis of bullous systemic lupus erythematosus was not addressed.
The International Investigative Dermatology (IID) 2018 meeting was held at the Rosen Shingle Creek resort in Orlando, Florida from May 16–19, 2018. This tri-continental endeavor, a collaboration between the Society for Investigative Dermatology (SID), the European Society for Dermatological Research (ESDR), and the Japanese Society for Investigative Dermatology (JSID), brought together more than 2,300 prominent skin biology investigators and clinicians to share cutting-edge research, establish international collaborations, and shape the future of investigative dermatology.
Sample size and power calculations help determine if a study is feasible based on a priori assumptions about the study results and available resources. Trade-offs must be made between the probability of observing the true effect and the probability of type I errors (α, false positive) and type II errors (β, false negative). Calculations require specification of the null hypothesis, the alternative hypothesis, type of outcome measure and statistical test, α level, β, effect size, and variability (if applicable).
Although collagen XVII (COL17) is expressed in both skin and oral mucosa, autoantibodies targeting COL17 cause lesions almost exclusively in skin. Kamaguchi and colleagues reported that COL17 is much more abundant in oral mucosa than skin. In addition, oral mucosa keratinocytes exhibited stronger adhesion to culture plates, and knockdown of COL17 in these cells reduced the numbers of adherent cells, suggesting that COL17 protein is associated with basal cell attachment strength. The authors concluded that increased expression of COL17 in the oral mucosa relative to skin attenuates COL17 depletion induced by pemphigoid autoantibodies, influencing the clinical phenotype of blistering diseases.
Recent clinical trials demonstrated the efficacy of novel biologics as metastatic melanoma treatments. These drugs include ipilimumab, an antibody that targets CTLA4 as well as pembrolizumab and nivolumab, antibodies that target programmed death 1 (PD-1). Following approval of ipilimumab and nivolumab as effective agents for adjuvant therapy, Eggermont and colleagues initiated a study to compare pembrolizumab treatment with matching placebo as adjuvant therapy for patients with resected, high-risk stage III melanoma.
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 image above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.
Epidermal desquamation is the highly regulated process of invisible shedding of corneocytes from the outermost layers of the stratum corneum. This occurs through the interplay between proteases and their inhibitors that control the degradation of corneodesmosomes. Skin peeling refers to exaggerated visible superficial desquamation and can occur in inherited and acquired conditions. The illumination of the molecular basis of genetic disorders with skin peeling sheds light on the biological mechanisms of epidermal desquamation and skin barrier homeostasis.
The SATB1 protein has been the focus of two recent studies of cutaneous T-cell lymphomas. Fredholm et al. observed a stage-related decrease of SATB1 expression in epidermotropic cutaneous T-cell lymphomas. SATB1 was negatively regulated by STAT5 through microRNA-155, which in turn triggered enhanced expression of T helper type 2 cytokines such as IL-5 and IL-9. In parallel, Sun et al. found that SATB1 expression was up-regulated by promoter demethylation in a subset of cutaneous anaplastic lymphoma and was associated with T helper type 17 polarization in patients with better therapeutic responses.
The cytokine IL-17 plays a critical role in host defense against fungal infections. So far, clinical relevance for IL-17 antifungal activity focused on mucocutaneous candidiasis. Burstein and colleagues now provide evidence that type 17 immunity is also essential for defense against dermatophytosis.
Pandeya et al. report that nevus-associated melanoma is associated with a specific phenotype, namely, young age, high number of nevi, non-brown eye color and slight dermal elastosis. Potential implications regarding differences between nevus-associated melanomas and de novo melanomas are discussed.
The advancement of genetic and preclinical studies has uncovered the mechanisms involved in the pathogenesis of alopecia areata (AA). The development of targeted therapies using small molecules blocking specific pathways for the treatment of AA is underway. By repurposing Food and Drug Administration–approved small molecule JAK inhibitors as treatments for AA, it has been demonstrated that JAK inhibitors can effectively reverse hair loss in patients with moderate to severe AA. In this review, we summarize and discuss the current preclinical and clinical studies on JAK inhibitors, as well as the prospects of using JAK inhibitors for the treatment of AA.
Human T-cell leukemia virus type-1 (HTLV-1) propagates within and between individuals via cell-to-cell transmission, and primary infection typically occurs across juxtaposed mucosal surfaces during breastfeeding and sexual intercourse. It is therefore likely that dendritic cells (DCs) are among the first potential targets for HTLV-1. However, it remains unclear how DCs contribute to virus transmission and dissemination in the early stages of infection. We show that an HTLV-1-infected cell line (MT-2) and naturally-infected CD4+ T-cells transfer p19+ viral particles to the surface of allogeneic DCs via cell-to-cell contacts.
Several studies have emphasized the importance of immune composition of the melanoma microenvironment for the clinical outcome. The contribution of IL4-induced gene 1 (IL4I1), a phenylalanine oxidase with immunoregulatory functions, has not been yet explored. Here we studied a primary cutaneous melanoma series from stage I-III patients in order to investigate the association between in situ IL4I1 expression and clinical parameters or tumor infiltrating T-cell subsets. IL4I1 was detected in 87% of tumors and was mainly expressed by tumor-associated macrophages and very rare FoxP3+ regulatory T cells (Tregs).
The incidence and survival of melanoma have increased over the last several decades, with a growing population of patients who develop multiple primary melanomas (MPM). To determine risk factors for developing MPM and compare the survival of patients with MPM to those with single primary melanomas (SPM), a prospective, multidisciplinary database of patients with melanoma at a single tertiary care institution was retrospectively reviewed. From 1985 to 2013, 6963 patients with SPM and 305 patients with MPM were identified.
Human HSP70iQ435A carries a single amino acid modification within the dendritic cell (DC) activating region and tolerizes DCs in vitro. The underlying DNA was used to prevent and treat disease in vitiligo mouse models through reduced dendritic cell activation and diminished skin T cell infiltration, suggesting the same may be useful for patients. Physiologic differences between mouse and human skin then called for studies in large animals with human-like skin. We established the efficiency of DNA jet injection into swine skin before subcloning HSP70iQ435A into clinically suitable vector pUMVC3.
Biologic therapies have shown high efficacy in psoriasis, but individual response varies and is poorly understood. To inform biomarker discovery in the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) study, we evaluated a comprehensive array of omics platforms across three time-points and multiple tissues in a pilot investigation of ten severe psoriasis patient, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used RNA-sequencing to analyse mRNA and small-RNA transcriptome in blood, lesional and non-lesional skin and the Somascan platform to investigate the serum proteome.
The major modifiable risk factor in melanomagenesis is UV exposure and mutagenesis of melanocytes. Other UV-induced events that contribute to early tumorigenesis are poorly understood. Herein we show the repeated exposure of human primary melanocytes to UVB results in a sustained senescence response, increases in expression of STAT1, MX1, OAS2 and IRF7 proteins of up to 75-fold, and resistance to subsequent UVB-induced apoptosis. In the setting of UVB-induced DNA damage, we detected time-dependent increases in the release of damage-associated molecular patterns (DAMPs) such as HMGB1.
High-risk skin cancer is a rare, but severe, complication associated with discoid lupus erythematosus (DLE). Chronic scar, inflammation, ultraviolet radiation and immunosuppressive medications are proposed explanations for this heightened skin cancer risk; however, the exact mechanism driving skin carcinogenesis in DLE is unknown. The distinct co-localization of multiple independent skin cancers with areas of active inflammation in two DLE patients followed over eight years strongly suggested that lupus inflammation promotes skin carcinogenesis in DLE.