Oral Manifestations and Challenges in Dental Treatment of Epidermolysis Bullosa Dystrophica
We report 2 cases of BPP cicatricial alopecia with histopathology of subepidermal blister formation, different clinical presentation, and different salt-split test results. One patient had features of bullous pemphigoid (BP) with important oral mucosal involvement (not yet reported in the literature), and the second patient had typical features of epidermolysis bullosa acquisita (EBA). The secondary cicatricial alopecia may be due to different antigens associated with either BP or EBA. The phenomenon of epitope spreading could explain the association between 2 distinctive bullous diseases in the same patient, justifying th...
A gene therapy company has received a designation for one of its treatments from the European Medicines Agency. Krystal Biotech, developing and commercializing novel treatments for dermatological diseases, announced that KB103, a treatment for a severe skin disorder, was granted an Orphan Medicinal Product Designation by the agency, according to a news release. In November 2017, the FDA granted the same de signation for the treatment, which is meant for dystrophic epidermolysis bullosa, an incurable…
A central pacemaker coordinates a network of endogenous circadian clocks. The skin itself features a self-sustained, intrinsic clock which may affect our first-line defense against intruders over the course of the day. Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disease caused by autoantibodies to type-VII collagen. Treatment options are not yet considered satisfactory. Against this background, we aimed at investigating the role of circadian clocks in EBA. We hypothesized that the migration of neutrophils into the skin, which controls the severity of autoantibody-induced tissue damage, is gated by pe...
Osteopenia and osteoporosis are one of the comorbidities in patients with severe forms of epidermolysis bullosa (EB) due to the many extracutaneous manifestations that predisposes EB patients to have poor bone health. Currently, there is scarce literature on studies describing the prevalence of osteopenia and osteoporosis in EB; mainly in the severe forms of EB such as Recessive Dystrophic EB (RDEB) and Junctional EB (JEB). The aim of this study is to describe the prevalence of osteopenia and osteoporosis in all EB types using patients from the Australasian Epidermolysis Bullosa Registry(AEBR) via a quantitative descriptive study.
In this study we investigated IgE antibodies in EBA. We enrolled 109 EBA cases in this study based on: (i) compatible clinical features, (ii) IgG reaction on the dermal side by indirect immunofluorescence (IIF) of salt-split skin, and (iii) detection of IgG antibodies to COL7 by western blotting and/or ELISA.
Recessive dystrophic epidermolysis bullosa (RDEB) is a skin blistering disease caused by mutations in the COL7A1 gene. RDEB patients experience severe blistering and fragility of the skin and mucous membranes, leading to pseudosyndactyly, susceptibility to infections, esophageal strictures, and aggressive cutaneous squamous cell carcinoma (SCC), which accounts for more than two thirds of RDEB patient deaths. RDEB patients can have multiple primary tumors and these tumors develop and metastasize much more quickly than in the general population.
Recessive dystrophic epidermolysis bullosa (RDEB) patients develop highly aggressive squamous cell carcinoma (SCC) at sites of persistent wounds owing to repeated cycles of wounding, infection, and chronic inflammation in these areas. Arising tumors are difficult to detect, as they resemble non-healing wounds or exuberant granulation tissue, and require invasive biopsies of the suspect wounds to confirm diagnosis. Development of novel detection assays based on minimally invasive sampling techniques are desired to facilitate regular patient screening.
RDEB is caused by mutations in COL7A1 encoding type VII collagen, which links the epidermal basement membrane to the underlying dermis. In RDEB, the anchoring fibrils are functionally abnormal or absent, resulting in chronic skin fragility, bullae formation and progressive tissue fibrosis. Development of aggressive SCC at repetitively wounded and scarred sites is a dangerous complication in RDEB, leading to metastatic disease, frequently resulting in death. Our understanding of the molecular mechanisms operative in the metastatic process is limited, but it is highly likely that tumor/matrix interactions are an important feature.
This study was powered by the sample size calculation that 10 RDEB and 20 healthy volunteers would show a statistically significant difference in blister formation time (10 min and 30 min, respectively).
We report the results of the ongoing Phase 1/2 clinical trial of an ex vivo gene therapy for the treatment of RDEB. Five adult subjects enrolled in this trial carried various null COL7A1 mutations resulting in undetectable C7 expression by immunofluorescence microscopy (IF) and a lack of intact anchoring fibrils (AF) by electron microscopy (EM).