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Background Esophageal strictures are the common gastrointestinal complications in patients with epidermolysis bullosa (EB) requiring dilation. There is limited information on the best type of intervention, outcomes, and predictors for re-stenosis. Objectives We aimed to investigate the frequency, clinical presentation of esophageal strictures in EB patients, and to ascertain the predictors of re-stenosis. Methods We conducted a retrospective, multicenter cohort study involving 7 specialized, international EB centers on patients who were 0 to 50 years of age. Descriptive statistics and hazard risks for re-stenosis were calculated. Results We identified 125 patients with 497 esophageal stricture episodes over a mean period of observation of 17 (standard deviation [SD] = 11.91) years. Dilations were attempted in 90.74% of episodes, using guided fluoroscopy 45.23%, retrograde endoscopy 33.04%, and antegrade endoscopy 19.07%. Successful dilation was accomplished in 99.33% of attempts. Patients experienced a median of 2 (interquartile range [IQR]: 1-7) stricture episodes with a median interval between dilations of 7 (IQR: 4-12) months. Predictors for re-stenosis included: number of strictures (2 vs 1 stricture: χ = 4.293, P = 0.038, hazard ratio [HR] = 1.294 (95% confidence interval [CI]: 1.014--1.652 and 3 vs 1 stricture:χ = 7.986, P = 0.005, HR = 1.785 [95% CI: 1.194, 2.667]) and a long (≥1 cm) segment stricture (χ = 4.599, P = 0.032, HR = 1.347 (95% CI: 1.026--1.769). Complications were more common with the endoscopic approach (8/86, antegrade endoscopy; 2 /149, retrograde endoscopy vs 2/204, fluoroscopy; χ = 17.39, P-value Conclusions We found excellent dilation outcomes irrespective of the dilation procedure; however, with higher complications in the endoscopic approach. Long (>1 cm) segment involvement and multiple locations were predictive of stricture reoccurrence.

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in granulocytes in chronic wounds, and we show that patients with the junctional form of EB have significantly more cells infiltrating their wounds compared with patients with recessive dystrophic EB. Finally, we identify subsets of granulocytes and T lymphocytes present in all wounds paving the way for single cell profiling of innate and adaptive immune cells with relevance to wound pathologies. In summary, our study delineates findings in EB that have potential relevance for all chronic wounds, and presents a method of cellular isolation that has wide reaching clinical application.

Objectives To present early teeth extractions as a treatment option in severe dental crowding in patients with generalized recessive dystrophic epidermolysis bullosa (RDEB). Materials and methods Three patients with generalized RDEB were treated with early teeth extractions to prevent severe dental crowding. Results Two patients had bilateral upper first premolars extraction, and the third patient had permanent maxillary canine extraction. Crowding was avoided, and no further orthodontic treatment was necessary. Conclusion Considering the challenges of severe mucosal fragility and microstomia in patients with generalized RDEB, early teeth extractions are a reasonable option as an orthodontic management. This approach reduces the severity of dental crowding as the child gets older and reduces the need for orthodontic appliances. Individual factors such as access to dental care, general health, and oral health have an important impact on the decision‐making process. Orthodontic treatment planning should include a multidisciplinary team.

Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) Initiation into Research grant, Chile 11140440

Background/objectives Epidermolysis bullosa is a group of diseases caused by mutations in skin structural proteins. Availability of genetic sequencing makes identification of causative mutations easier, and genotype-phenotype description and correlation are important. We describe six patients with a keratin 5 mutation resulting in a glutamic acid to lysine substitution at position 477 (p.Glu477Lys) who have a distinctive, severe and sometimes fatal phenotype. We also perform in silico modeling to show protein structural changes resulting in instability. Methods In this case series, we collected clinical data from six patients with this mutation identified from their national or local epidermolysis bullosa databases. We performed in silico modeling of the keratin 5-keratin 14 coil 2B complex using CCBuilder and rendered with Pymol (Schrodinger, LLC, New York, NY). Results Features include aplasia cutis congenita, generalized blistering, palmoplantar keratoderma, onychodystrophy, airway and developmental abnormalities, and a distinctive reticulated skin pattern. Our in silico model of the keratin 5 p.Glu477Lys mutation predicts conformational change and modification of the surface charge of the keratin heterodimer, severely impairing filament stability. Conclusions Early recognition of the features of this genotype will improve care. In silico analysis of mutated keratin structures provides useful insights into structural instability.

Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 11140440

Epidermolysis bullosa (EB) is an inherited connective tissue disease causing blisters in the skin and mucosal membranes. In severe cases, EB may be associated with renal damage through several mechanisms, mainly immunological ones. The present case described a young male with dystrophic recessive EB who developed an advanced chronic renal damage secondary to tubulointerstitial nephritis that was demonstrated by a renal biopsy. Unpublished previously, this complication should be considered among the possible causes of renal damage in EB. Also it is recommended a protocoled surveillance of renal and urinary tract complications in children with EB.

Background Down syndrome (DS) is the most common autosomal chromosomal disorder. Epidermolysis bullosa (EB) is a rare genodermatosis characterized by skin and mucous membrane fragility, with formation of blisters and erosions after minor trauma. Dystrophic EB (DEB) is inherited as an autosomal dominant (DDEB) or recessive (RDEB) trait. Both forms are caused by mutations in COL7A1, the gene coding for the type VII collagen. We report a patient affected by both conditions: DS and DDEB. Methods A patient with DS developed generalized blisters at the age of three months. Cytogenetic study was performed to confirm DS. Skin biopsies were examined with immunohistochemical and electron microscopy techniques to determine EB subtype. Genomic DNA was extracted from peripheral blood samples. COL7A1 mutations were screened by heteroduplex analysis using conformation-sensitive gel electrophoresis and sequencing. Results Karyotype analysis revealed trisomy 21. Histological study agreed with a DEB diagnosis. Mutational analysis showed a heterozygous c.6127G>T mutation in COL7A1, which is compatible with DDEB. Parental study suggests that c.6127G>T arises as a de novo mutation. Conclusions This report demonstrates that EB can be associated with other common conditions and reports the case of a patient who suffered two de novo independent genetic conditions. It also contributes to expanding the knowledge and database of clinical and molecular aspects of DDEB.

In animal models it has been shown that mesenchymal stromal cells (MSC) contribute to skin regeneration and accelerate wound healing. We evaluated whether allogeneic MSC administration resulted in an improvement in the skin of two patients with recessive dystrophic epidermolysis bullosa (RDEB; OMIM 226600). Patients had absent type VII collagen immunohistofluorescence and since birth had suffered severe blistering and wounds that heal with scarring. Vehicle or 0.5 x 10(6) MSC were infused intradermally in intact and chronic ulcerated sites. One week after intervention, in MSC-treated skin type VII collagen was detected along the basement membrane zone and the dermal-epidermal junction was continuous. Re-epithelialization of chronic ulcerated skin was observed only near MSC administration sites. In both patients the observed clinical benefit lasted for 4 months. Thus intradermal administration of allogeneic MSC associates with type VII collagen replenishment at the dermal-epidermal junction, prevents blistering and improves wound healing in unconditioned patients with RDEB.