Oral Manifestations and Challenges in Dental Treatment of Epidermolysis Bullosa Dystrophica

Source: Journal of Dentistry for Children - Category: Dentistry Authors: Tags: Case Reports Source Type: research

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Granzyme B (GzmB) is a serine protease that exhibits both intracellular and extracellular roles in immune cell-mediated apoptosis and extracellular proteolysis, respectively. GzmB-positive neutrophils are abundant in areas proximal to blisters in autoimmune subepidermal blistering diseases and may contribute to pathology. In the current study, the function of GzmB in blistering was assessed in an anti-collagen VII IgG passive transfer murine model of epidermolysis bullosa acquisita (EBA) using both wild type C57Bl/6 (WT) and GzmB knockout (GzmBKO) mice.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Adaptive and Auto-Immunity Source Type: research
The treatment of autoimmune diseases still relies on immunosuppression and is associated with severe side-effects. The development of drugs abrogating pathogenic pathways more specifically is, therefore, most desirable. In nature, such specificity is exemplified, e.g., by the soft-tick-derived lipocalin Coversin, which locally suppresses immune responses by simultaneously inhibiting the complement factor C5 and leukotriene B4 (LTB4). C5a, a proteolytic fragment of C5, and LTB4have been highlighted as critical drivers of skin inflammation in pemphigoid diseases (PDs), a group of autoimmune blistering skin diseases.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Adaptive and Auto-Immunity Source Type: research
The most lethal complication of recessive dystrophic epidermolysis bullosa (RDEB) is the development of aggressive cSCCs, which lead the high mortality rates in RDEB patients. RDEB results from mutations in COL7A1 which impair the function of type VII collagen (C7), resulting in blister formation. C7 deficiency directly interferes with the healing process by altering the wound microenvironment. These abnormalities increase TGF- ß1 signaling and lead to a constitutively active JAK-STAT pathway. Currently, the available treatments for locally advanced or metastatic cSCC are very limited.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
Squamous cell carcinoma (SCC) develops in more than 80% of individuals with the skin blistering disorder recessive dystrophic epidermolysis bullosa (RDEB). In contrast with UV-induced SCC, RDEB SCC has a high proliferative and metastatic rate, with five-year survival near zero. RDEB dermal fibroblasts were found with higher expression of the myofibroblast markers α-smooth muscle actin (6/8 pairs), Fibronectin (7/8 pairs), and periostin (7/8 pairs) compared to matched donors. RDEB fibroblasts were also found to have higher expression of MCP-1 (3/4 pairs) and TGFβ1 (3/4 pairs), indicative of increased TGFβ1 secretion.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from recalcitrant, painful blistering and open wounds, however, a systematic natural history of RDEB wounds with patient reported outcomes such as pain and itch has not been conducted. We hypothesized that RDEB patients have 2 major types of wounds, chronic wounds, defined as those that stay open for ≥ 12 weeks, and recurrent wounds, which heal but reblister easily, and that these wounds differ in size, pain, and itch. Recruited from Stanford's EB clinic, 40 patients completed a questionnaire to evaluate the size, duration, and associated symptoms of chro...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Epidemiology Source Type: research
Genome editing represents a promising strategy to correct COL7A1 gene mutations that cause recessive dystrophic epidermolysis bullosa (RDEB). Previously, we used programmable nucleases that create double-stranded DNA breaks (DSBs) to repair COL7A1 mutations through homology-directed repair (HDR) with an exogenous repair template. Delivery of this template can be cytotoxic and DSBs induce undesired insertions and deletions (indels) that compete with desired HDR. To overcome these limitations, we used base editors (BE), a CRISPR/Cas9-based system that uses naturally occurring or laboratory-evolved deaminating enzymes to dire...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering disorder caused by mutations in the COL7A1 gene, encoding type VII collagen (C7). Reduced functional or absent C7 leads to fragile skin. QR-313 is an antisense oligonucleotide designed to skip exon 73 from COL7A1 mRNA, thereby excluding mutations in this exon from the transcript. This leads to the formation of a slightly shorter C7 (C7 Δ73) protein. We previously demonstrated the functionality of C7Δ73 using isolated protein, and the efficacy of QR-313 in cell cultures.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
We report long term follow-up results of a single-center phase 1/2a study of 7 RDEB patients who underwent grafting of gene-corrected epidermal grafts from 2013-2017. Autologous keratinocytes were isolated from patient biopsies and transduced with GMP-grade retrovirus carrying full-length human COL7A1.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe genetic disorder characterized by large recurrent and chronic open wounds. RDEB patients lack functional type VII collagen (C7) owing to mutations in the gene COL7A1, the main component of anchoring fibrils (AF) required for epidermal-dermal cohesion. Over 700 alterations in COL7A1 have been reported to cause Dystrophic Epidermolysis Bullosa (DEB), which may be autosomal dominant or recessive. The most common subtypes are dominant DEB (DDEB), recessive DEB severe (RDEB-GS), and recessive DEB generalized other (RDEB-GO).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Epidemiology Source Type: research
Epidermolysis bullosa (EB) causes mucocutaneous blisters predisposing the host to polymicrobial colonization with potentially resistant organisms. Limited data are available on the microbiology and antibiotic susceptibility in EB patients. Understanding the skin flora in EB may direct clinical care. We reviewed wound cultures from patients with EB to identify their isolates and susceptibilities patterns. Patients, aged 0-22 years were recruited through the EB clinic at the University of Minnesota between 2007 and 2017.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Innate Immunity, Microbiology, and Microbiome Source Type: research
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