Managing epidermolysis bullosa during the coronavirus pandemic: Experience and ideals.
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ABSTRACT:
SUBMITTER: Ramirez-Quizon M
PROVIDER: S-EPMC7849544 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous skin fragility disorder characterized by trauma-induced skin dissociation and the development of painful wounds. So far, mutations in 20 genes have been described as being associated with more than 30 clinical EB subtypes. The era of whole-exome sequencing has revolutionized EB diagnostics with gene panels being developed in several EB centers and allowing quicker diagnosis and prognostication. With the advances of gene editing, more focus has been placed on gene editing-based therapies for targeted treatment. However, their implementation in daily care will still take time. Thus, a significant focus is currently being placed on achieving a better understanding of the pathogenetic mechanisms of each subtype and using this knowledge for the design of symptom-relief therapies, i.e. treatment options aimed at ameliorating and not curing the disease.
| S-EPMC6051194 | biostudies-literature
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| S-EPMC7435522 | biostudies-literature
Project description:BACKGROUND:Little information is available regarding the burden of living with and managing epidermolysis bullosa, including the distinct challenges faced by patients with different disease types/subtypes. METHODS:A 90-question/item survey was developed to collect demographics, diagnostic data, management practices, and burden of illness information for patients with epidermolysis bullosa living in the United States. Recruitment was conducted via email and social media in partnership with epidermolysis bullosa patient advocacy organizations in the United States, and the survey was conducted via telephone interview by a third-party health research firm. Respondents aged ??18 years with a confirmed diagnosis of epidermolysis bullosa or caring for a patient with a confirmed diagnosis of epidermolysis bullosa were eligible to participate in the survey. RESULTS:In total, 156 responses were received from patients (n?=?63) and caregivers (n?=?93) representing the epidermolysis bullosa types of simplex, junctional, and dystrophic (subtypes: dominant and recessive). A large proportion of patients (21%) and caregivers (32%) reported that the condition was severe or very severe, and 19% of patients and 26% of caregivers reported a visit to an emergency department in the 12?months prior to the survey. Among the types/subtypes represented, recessive dystrophic epidermolysis bullosa results in the greatest wound burden, with approximately 60% of patients and caregivers reporting wounds covering >?30% of total body area. Wound care is time consuming and commonly requires significant caregiver assistance. Therapeutic options are urgently needed and reducing the number and severity of wounds was generally ranked as the most important treatment factor. CONCLUSIONS:Survey responses demonstrate that epidermolysis bullosa places a considerable burden on patients, their caregivers, and their families. The limitations caused by epidermolysis bullosa mean that both patients and caregivers must make difficult choices and compromises regarding education, career, and home life. Finally, survey results indicate that epidermolysis bullosa negatively impacts quality of life and causes financial burden to patients and their families.
| S-EPMC6942340 | biostudies-literature
Project description:Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Patients with EBA suffer from chronic inflammation as well as blistering and scarring of the skin and mucous membranes. Current treatment options rely on non-specific immunosuppression, which in many cases, does not lead to a remission of treatment. Hence, novel treatment options are urgently needed for the care of EBA patients. During the past decade, decisive clinical observations, and frequent use of pre-clinical model systems have tremendously increased our understanding of EBA pathogenesis. Herein, we review all of the aspects of EBA, starting with a detailed description of epidemiology, clinical presentation, diagnosis, and current treatment options. Of note, pattern analysis via direct immunofluorescence microscopy of a perilesional skin lesion and novel serological test systems have significantly facilitated diagnosis of the disease. Next, a state-of the art review of the current understanding of EBA pathogenesis, emerging treatments and future perspectives is provided. Based on pre-clinical model systems, cytokines and kinases are among the most promising therapeutic targets, whereas high doses of IgG (IVIG) and the anti-CD20 antibody rituximab are among the most promising "established" EBA therapeutics. We also aim to raise awareness of EBA, as well as initiate basic and clinical research in this field, to further improve the already improved but still unsatisfactory conditions for those diagnosed with this condition.
| S-EPMC6335340 | biostudies-literature
Project description:The term epidermolysis bullosa (EB) refers to a group of hereditary skin blistering diseases. The group is clinically and genetically heterogeneous, but all EB forms are associated with mechanically induced skin blistering and fragility. The causative gene mutations of most EB types are known. The current international consensus classification contains four main types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome (KS). The classification is based on the morphological level of blister formation. In EBS, the split is intra-epidermal, in JEB along the basement membrane and in DEB below the basement membrane. In Kindler syndrome, the dermal-epidermal junction is disorganized, and blisters can occur on all three levels. Each major EB type has further subtypes which may differ in terms of their genetic, biological or clinical characteristics. Traditionally, EB treatments have been symptomatic, but increasing understanding of disease etio-pathogenesis is facilitating development of novel evidence-based therapy approaches. First gene- and cell-based therapies are being tested at preclinical level and in clinical trials. New knowledge on secondary disease mechanisms has led to development and clinical testing of urgently needed symptom-relief therapies using small molecules and biologicals.
| S-EPMC6536064 | biostudies-literature
Project description:ObjectiveThe COVID-19 pandemic has forced healthcare providers worldwide to bring in changes in the way cancer patients are cared for. Many cancer departments globally have brought in changes to their daily practice. This article is about our experience of evolving "COVID 19 PROTOCOL" devised in our department and taking a shape to suit a health care system with limited budget.Materials and methodsAll the patient census & details of department of surgical oncology, Royapettah cancer hospital, from month of March 2020 to July 2020, who were subjected to COVID protocol were compared to patient census of similar duration in immediate past five months of October 2019 to February 2020. The data from out-patient department, ward in-patient census and healthcare personnel data was analyzed.ResultsThere was a drop to 63.5% in OP census and 61.6% in IP census. There was a drop to 64.5% in number of major cases operated during initial phases of COVID pandemic. Health care workers were also infected with the COVID but cross infectivity can be checked if proper steps to adhere to an institutional protocol based on general measures of cleanliness are taken.ConclusionAdherence to an institutional protocol based on compliance to general measures of masking, hand washing and social distancing plays a major role in minimizing disease spread. The Royapettah COVID protocol, though in process of evolution, can be recommended for any health care center with limited resources.
| S-EPMC7834458 | biostudies-literature
Project description:Epidermolysis bullosa (EB) is the umbrella term for a group of rare inherited skin fragility disorders caused by mutations in at least 20 different genes. There is no cure for any of the subtypes of EB resulting from different mutations, and current therapy only focuses on the management of wounds and pain. Novel effective therapeutic approaches are therefore urgently required. Strategies include gene-, protein- and cell-based therapies. This review discusses molecular procedures currently under investigation at the EB House Austria, a designated Centre of Expertise implemented in the European Reference Network for Rare and Undiagnosed Skin Diseases. Current clinical research activities at the EB House Austria include newly developed candidate substances that have emerged out of our translational research initiatives as well as already commercially available medications that are applied in off-licensed indications. Squamous cell carcinoma is the major cause of death in severe forms of EB. We are evaluating immunotherapy using an anti-PD1 monoclonal antibody as a palliative treatment option for locally advanced or metastatic squamous cell carcinoma of the skin unresponsive to previous systemic therapy. In addition, we are evaluating topical calcipotriol and topical diacerein as potential agents to improve the healing of skin wounds in EBS patients. Finally, the review will highlight the recent advancements of gene therapy development for EB.
| S-EPMC6900197 | biostudies-literature
Project description:The craniofacial and oral manifestations of the different epidermolysis bullosa (EB) types vary markedly in character and severity depending largely on the EB type. The tissues affected and the phenotypes displayed are closely related to the specific abnormal or absent proteins resulting from the causative genetic mutations for these disorders. In this article, the major oral manifestations are reviewed for different EB subtypes and are related to the causative genetic mutations and gene expression.
| S-EPMC2787479 | biostudies-literature
Project description:Recessive dystrophic epidermolysis bullosa (RDEB) is characterized by a functional deficit of type VII collagen protein due to gene defects in the type VII collagen gene (COL7A1). Gene augmentation therapies are promising, but run the risk of insertional mutagenesis. To abrogate this risk, we explored the possibility of using engineered transcription activator-like effector nucleases (TALEN) for precise genome editing. We report the ability of TALEN to induce site-specific double-stranded DNA breaks (DSBs) leading to homology-directed repair (HDR) from an exogenous donor template. This process resulted in COL7A1 gene mutation correction in primary fibroblasts that were subsequently reprogrammed into inducible pluripotent stem cells and showed normal protein expression and deposition in a teratoma-based skin model in vivo. Deep sequencing-based genome-wide screening established a safety profile showing on-target activity and three off-target (OT) loci that, importantly, were at least 10?kb from a coding sequence. This study provides proof-of-concept for TALEN-mediated in situ correction of an endogenous patient-specific gene mutation and used an unbiased screen for comprehensive TALEN target mapping that will cooperatively facilitate translational application.
| S-EPMC3677309 | biostudies-literature
Project description:The blistering skin disorder epidermolysis bullosa simplex (EBS) results from dominant mutations in keratin 5 (K5) or keratin 14 (K14) genes, encoding the intermediate filament (IF) network of basal epidermal keratinocytes. The mechanisms governing keratin network formation and collapse due to EBS mutations remain incompletely understood. Drosophila lacks cytoplasmic IFs, providing a 'null' environment to examine the formation of keratin networks and determine mechanisms by which mutant keratins cause pathology. Here, we report that ubiquitous co-expression of transgenes encoding wild-type human K14 and K5 resulted in the formation of extensive keratin networks in Drosophila epithelial and non-epithelial tissues, causing no overt phenotype. Similar to mammalian cells, treatment of transgenic fly tissues with phosphatase inhibitors caused keratin network collapse, validating Drosophila as a genetic model system to investigate keratin dynamics. Co-expression of K5 and a K14(R125C) mutant that causes the most severe form of EBS resulted in widespread formation of EBS-like cytoplasmic keratin aggregates in epithelial and non-epithelial fly tissues. Expression of K14(R125C)/K5 caused semi-lethality; adult survivors developed wing blisters and were flightless due to a lack of intercellular adhesion during wing heart development. This Drosophila model of EBS is valuable for the identification of pathways altered by mutant keratins and for the development of EBS therapies.
| S-EPMC4519992 | biostudies-literature