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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 Fan et al. (2019) (https://doi.org/10.1016/j.jid.2019.06.135).
Although UV light is the main cause of skin cancers, beta human papillomavirus (β-HPV) has been associated with squamous cell carcinoma risk, especially in immunocompromised patients such as transplant recipients. To probe this relationship in more detail, Strickley et al. investigated the role of these commensal viruses in skin cancer in a mouse papillomavirus type 1 infection system. Infected wild-type immunocompetent mice exhibited a delay in skin tumor onset and developed fewer tumors overall in response to either chemical or UVR exposure.
Pigmentation of the skin and hair represents the result of melanin biosynthesis within melanosomes of epidermal melanocytes, followed by the transfer of mature melanin granules to adjacent keratinocytes within the basal layer of the epidermis. Natural variation in these processes produces the diversity of skin and hair color among human populations, and defects in these processes lead to diseases such as oculocutaneous albinism. While genetic regulators of pigmentation have been well studied in human and animal models, we are still learning much about the cell biological features that regulate melanogenesis, melanosome maturation, and melanosome motility in melanocytes, and have barely scratched the surface in our understanding of melanin transfer from melanocytes to keratinocytes.
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.
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).
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.
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.
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.
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.
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).
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.
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.
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).
The loss of primary cilia on melanocytes is a useful biomarker for the distinction of melanoma from conventional melanocytic nevi. It is unknown whether ciliation status is beneficial for diagnosing spitzoid tumors - a subclass of melanomas that present inherently ambiguous histology and are challenging to classify. We evaluated ciliation index (CI) in 68 cases of spitzoid tumors ranging from Spitz nevi (SN) and atypical Spitz tumors (AST) to spitzoid melanoma (SM). We found a significant decrease in CI within the SM group when compared to either the SN or AST groups.
RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs hBD-2 and LL-37 promote TLR9-mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. Stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase of IP-10 production.
To the Editor, The regular use of sunscreen products protects against sunburn, photo-aging and skin cancer (Waldman and Grant-Kels, 2019). A recent Australasian Sunscreen Summit recommended that sunscreens should be applied daily when the UV index is expected to be 3 or more to decrease future skin cancer incidence (Whiteman et al., 2019). However, although Australia has one of the highest rates of skin cancer in the world, only 55 percent of Australians believed it was safe to use sunscreen every day (Cancer Council Australia, 2017).
Melanoma is cancer caused by the neoplastic transformation of melanocytes. The last decade has witnessed a surge in treatment options for advanced melanoma patients, especially immunotherapeutic interventions; nonetheless, issues such as drug resistance, limited efficacy, and high-toxicity ensue (Luke et al., 2017). Understanding the mechanisms underpinning melanoma progression and invasion is, therefore, vital for the development of treatment strategies.