Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss.

Collagen VII maintains proteostasis in dermal fibroblasts by scaffolding TANGO1 cargo.

Lack of type VII collagen (C7) disrupts cellular proteostasis yet the mechanism remains undescribed. By studying the relationship between C7 and the extracellular matrix (ECM)-associated proteins thrombospondin-1 (TSP1), type XII collagen (C12) and tissue transglutaminase (TGM2) in primary human dermal fibroblasts from multiple donors with or without the genetic disease recessive dystrophic epidermolysis bullosa (RDEB) (n=31), we demonstrate that secretion of each of these proteins is increased in the presence of C7. In dermal fibroblasts isolated from patients with RDEB, where C7 is absent or defective, association with the COPII outer coat protein SEC31 and ultimately secretion of each of these ECM-associated proteins is reduced and intracellular levels are increased.

Hematohidrosis, Hemolacria, and "Trichorrhage": A Systematic Review.

Introduction: Hematohidrosis and hemolacria are 2 conditions surrounded in religiousness, mysticism, and supernatural superstitions. While the mechanism is still unclear, these cases have amazed physicians for centuries.

Methods: We performed a systematic review in PubMed from 2000 to mid-2021 accounting for 75 studies from which we included 60 cases in 53 articles which were described.

T-cell activation and bacterial infection in skin wounds of recessive dystrophic epidermolysis bullosa patients.

Recessive dystrophic epidermolysis bullosa (RDEB) patients develop poorly healing skin wounds that are frequently colonized with microbiota. Because T cells play an important role in clearing such pathogens, we aimed to define the status of adaptive T cell-mediated immunity in RDEB wounds. Using a non-invasive approach for sampling of wound-associated constituents, we evaluated microbial contaminants in cellular fraction and exudates obtained from RDED wounds.

Laser in surgical scar clearance: An update review.

Scar formation is a consequence of wound healing that developed from damaged tissue either from physical injury or surgical incision. A hypertrophic scar develops due to an abnormal healing response to trauma. It might lead to serious functional and cosmetic disability.

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited.

Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime.

A novel AAGAB mutation in a Peruvian family with punctate palmoplantar keratoderma.

Buschke-Fischer-Brauer (BFB) disease is a rare keratoderma characterized by multiple hyperkeratotic lesions on the palms and soles, with an autosomal dominant pattern. In several countries, some genetic alterations have been associated with this clinical entity. A 68-year-old Peruvian woman presenting with hyperkeratotic lesions on both her palms and soles was diagnosed with BFB keratoderma.

Cutaneous adverse effects due to personal protective measures during COVID-19 pandemic: a study of 101 patients.

Background: Coronavirus Disease 2019 (COVID-19) is a viral illness caused by the novel coronavirus SARS-CoV-2 which spreads via droplets from an infected person. There has been an unprecedented rise in the use of personal protective equipment and practice of personal hygiene measures against COVID-19. The extended use of protective measures (PM) can lead to ill effects on the skin.

Aberrant recruitment of leukocytes defines poor wound healing in patients with recessive dystrophic epidermolysis bullosa.

Background: Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches.

Objectives: To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks.

CRISPR/Cas9-based targeted genome editing for correction of recessive dystrophic epidermolysis bullosa using iPS cells.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin disorder caused by mutations in the gene encoding type VII collagen (C7). The spectrum of severity depends on the type of mutation in the gene. C7 is the major constituent of anchoring fibrils (AFs) at the basement membrane zone (BMZ).

Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation.

Regenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a danger-associated molecular pattern contributing to inflammatory pathologies. We show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives tumor formation.

Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma.

Purpose: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need. We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC.

Thrombospondin-1 Is a Major Activator of TGF-β Signaling in Recessive Dystrophic Epidermolysis Bullosa Fibroblasts.

Mutations in the gene encoding collagen VII cause the devastating blistering disease recessive dystrophic epidermolysis bullosa (RDEB). RDEB is characterized by severe skin fragility and nonhealing wounds aggravated by scarring and fibrosis. We previously showed that TSP1 is increased in RDEB fibroblasts.

The importance of diagnostic imaging of mycetoma in the foot.

Background: Mycetoma is a chronic, localized infection caused by fungi and bacteria. It usually affects the skin, subcutaneous tissue, and bone of exposed areas with deformity of the affected limb, ulcers, and fistula; however, pain is not severe, therefore the patient comes late to hospital for care.

Objective: To establish the diagnosis of mycetoma in the foot by imaging and identify the principal radiological signs.

Overexpression of Desmoglein 2 in a Mouse Model of Gorlin Syndrome Enhances Spontaneous Basal Cell Carcinoma Formation through STAT3-Mediated Gli1 Expression.

Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1 mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1 mice) or the superficial epidermis (Inv-Dsg2/Ptc1 mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively.

APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors.

Beta-2 Microglobulin in Whole Unstimulated Saliva Can Effectively Distinguish Between Sjögren's Syndrome and Non-Autoimmune Sicca Symptoms.

Objectives: This study aims to describe salivary beta-2 microglobulin (sB2M) levels in our setting and to assess the performance of sB2M for the diagnosis of Sjögren's syndrome (SS).

Patients And Methods: This cross-sectional, comparative study included 192 SS patients (2 males, 190 females; mean age 53.1 years; range 23 to 84 years) and 64 healthy controls (1 male, 63 females; mean age 46.

Preclinical comparison of proteasome and ubiquitin E1 enzyme inhibitors in cutaneous squamous cell carcinoma: the identification of mechanisms of differential sensitivity.

Proteasome inhibitors have distinct properties and the biochemical consequences of suppressing ubiquitin E1 enzymes and the proteasome differ. We compared the effects of the proteasome inhibitors bortezomib, ixazomib and carfilzomib and the ubiquitin E1 enzyme inhibitor MLN7243/TAK-243 on cell viability and cell death in normal keratinocytes and cutaneous squamous cell carcinoma (cSCC) cell lines. The effects of both a pulse of treatment and more extended incubation were investigated.

Bullosis Diabeticorum: A Neglected Bullous Dermatosis.

A 75-year-old African-American man presented with a 3-year history of painless, fluid-filled blisters, for which his primary care physician had treated him with doxycycline, cephalexin, and topical corticosteroids, with no significant improvement. The blisters had ruptured spontaneously and healed with scarring. He denied antecedent trauma.