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Ciguatera fish poisoning (CFP) is caused by the consumption of fish contaminated with ciguatoxins (CTXs). The most distressing symptoms are cutaneous sensory disturbances, including cold dysesthesia and itch. CTXs are neurotoxins known to activate voltage-gated sodium channels (Nav) but no specific treatment exists. Peptidergic neurons have been critically involved in CFP sensory disturbances. Protease-activated receptor-2 (PAR2) is an itch- and pain- related G protein-coupled receptor whose activation leads to a calcium-dependent neuropeptide release.
The aging process deleteriously alters the structure and function of dermal collagen. These alterations result in thinning, fragility, wrinkles, laxity, impaired wound healing, and a microenvironment conducive to cancer. However, the key factors responsible for these changes have not been fully elucidated and relevant models for the study of skin aging progression are lacking. CCN1, a secreted extracellular matrix (ECM) associated matricellular protein, is elevated in dermal fibroblasts in aged human skin.
Congenital melanocytic nevi (CMN) are heterogeneous in their clinical appearance, implications, and range in size from small through to large/giant. Large/giant CMN (LGCMN) have an increased risk of malignant transformation, and the most severe complication manifests as a melanoma of the central nervous system. Mutations in the oncogene NRAS are the most frequently observed, however this post-zygotic mutation is not present in all subtypes of CMN. In a study of LGCMN, Martins da Silva et al. (Martins da Silva et al., 2019) performed RNA-seq and multiregional sequencing (median coverage approximately x 19,000) using a targeted panel of genes (see Supplementary Material) and discovered that ∼60% harbored an NRAS mutation, but other rare events like gene fusions were identified.
Cancer cells are known to reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) to act as tumor supporters. The presence and role of CAFs in mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma, are unknown. This study sought to characterize CAFs in MF and their cross talk with the lymphoma cells using primary fibroblast cultures from punch biopsies of patients with early-stage MF and healthy subjects. MF cultures yielded significantly increased levels of FAPα, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and MMP2.
We have previously shown that gain-of-function mutations in TRPV3 underlay Olmsted syndrome (OS), a rare hyperkeratotic skin channelopathy. Here, we attempt to establish a genotype-phenotype correlation in OS, which has been unclear due to the rarity and heterogeneity of the condition. We identified five previously unreported TRPV3 mutations (R416Q, R416W, L655P, W692S, and L694P) and three recurrent mutations (G568D, G568V, and L673F) in nine unrelated patients. These mutants were expressed in HEK293 cells and channel behavior was characterized electrophysiologically, with results compared to the clinical severity.
Pilomatricoma, a benign skin appendage tumor, also known as calcifying epithelioma, consists of islands of epithelial cells histologically that contain anucleated cells in the center surrounded by basophilic cells, and partial calcification. Sporadic pilomatricoms commonly have somatic mutations in the gene CTNNB1, but causative genes from germline and the underlying pathophysiology are unclear. Here, we identified a germline missense variant of PLCD1 encoding phospholipase C delta 1 (PLCδ1), c.1186G>A (p.Glu396Lys), in a large Chinese family with autosomal dominant multiple pilomatricomas.
Melorheostosis (OMIM #155950) is a rare disease of benign bone overgrowth (Freyschmidt, 2001) (Supplementary figure 1). We recently described somatic activating mutations in MAP2K1 in affected bone as a cause of disease in nearly 60% of our cohort(Kang et al., 2018). Mosaicism for the mutation was also detected in some patients in skin directly overlying the affected bone. However, unlike the proliferative changes seen in bone, overlying skin is characterized by patchy erythematous lesions but no overgrowth (Jha et al., 2018).
The cells of myeloid origin, mature granulocytes and monocytes, are generally acknowledged with innate functions in pathogen clearance, however they possess great capacity to modulate T cell immunity (Chen and Flies 2013). Alternatively, exposure to weak and sustained proinflammatory mediators from chronic pathological conditions as such observed in cancer and autoimmunity may create an imbalance in favor of immature myeloid cells (Veglia et al. 2018) (Zhao et al. 2016). Accordingly, immature myeloid cells’ egress from bone marrow are increased and these cells accumulate in circulation, secondary immune organs and sites of inflammation (Bronte et al.
Vitiligo is a complex disease in which autoimmune destruction of epidermal melanocytes results in patches of depigmented white skin. Vitiligo has an estimated prevalence of about 0.2–2% in different populations and approximately 0.4% in the European-derived white (EUR) population. The fraction of disease risk attributable to genetic variation, termed heritability, is high, with estimates from family studies in EUR of 0.75–0.83 and from SNP based studies estimated at 0.78. About 70% of genetic risk comes from common genetic variants and about 30% from rare genetic variants.
BRAF V600E is the most common driver mutation in human cutaneous melanoma and is frequently accompanied by loss of the tumor suppressing phosphatase PTEN. Recent evidence suggests a co-operative role for RAC1 activity in BRAF V600E -driven melanoma progression and drug resistance. However, the underlying molecular mechanisms and the role of RAC1 downstream targets are not well explored. Here, we examine the role of the NCKAP1 subunit of the pentameric cytoskeletal SCAR/WAVE complex, a major downstream target of RAC1, in a mouse model of melanoma driven by BRAF V600E; PTEN loss.
We present heightened skin reactivity in vivo to two MRGPRX2 drug ligands in patients with chronic spontaneous urticaria. Selectivity for the MRGPRX2 pathway by drug ligands was demonstrated by the loss of drug activation in MRGPRX2-KO LAD2 cells.
Sturge-Weber syndrome (Online Mendelian Inheritance in Man #185300) is a capillary malformation condition (Bichsel and Bischoff, 2019, Comi, 2015). Affected regions include the skin (typically with facial cutaneous vascular malformations called port-wine birthmarks), brain (often resulting in seizures, intellectual disability, and recurrent stroke-like episodes), and eye (often causing glaucoma). We (Shirley et al., 2013) and others (Frigerio et al., 2015, Nakashima et al., 2014) reported that 90% of individuals with SWS or nonsyndromic PWB have a mosaic, activating mutation in GNAQ, encoding G protein subunit alpha q (Gαq).
SATB1 is an important T-cell specific chromatin organizer in cutaneous T cell lymphoma, while its expression and function in Mycosis fungoides (MF) remain ambiguous. Our study aimed to investigate the clinicopathological significance of SATB1 in a cohort of 170 MF patients. SATB1 expression was heterogeneous among MF patients in each clinical stage. High SATB1 expression was associated with epidermal hyperplasia, eosinophil infiltration, less large-cell transformation, and favorable prognosis in MF cases.
To the Editor, Fumaric acid ester(FAE) formulations are considered a first-line treatment for psoriasis and multiple sclerosis. Small case series and case reports document the use of FAE in various other, mostly granulomatous, diseases(Meissner et al.,2012). A common denominator of these clinically diverse diseases is that neutrophil (polymorphonuclear) granulocyte(PMN) and tumor necrosis-factor α(TNF-α) signaling are thought to contribute to their pathogenesis(McCoy and Tansey,2008,Nestle et al.,2009,Piette and Rosenbach,2016).
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 Quan et al. (2020) (https://doi.org/10.1016/j.jid.2019.12.031).
Rab11b Mediates Melanin Transfer between Donor Melanocytes and Acceptor Keratinocytes via Coupled Exo/Endocytosis
We are deeply saddened by the long-standing structural racism and injustice suffered by the Black community and mourn the loss of George Floyd, Breonna Taylor, Ahmaud Arbery, and many others.