Epidermolysis Bullosa Research Articles

Reconstruction of hand surgical wounds after correction of pseudo-syndactyly or squamous cell carcinoma resection in patients affected from epidermolysis bullosa: a monocentric experience with a collagen-elastin dermal matrix dermal substitute

In patients with Epidermolysis Bullosa (EB), surgery may be required to remove Squamous Cell Carcinoma (SCC) of the hands or to correct pseudo-syndactyly. Dermal substitutes may represent a suitable tool to promote the healing of surgical wounds in EB. We review our experience with a collagen-elastin dermal matrix to promote surgical wound healing due to hand surgery to correct pseudo-syndactyly or SCC resection in patients affected by EB. Overall, 12 patients (mean age, 29±11 years, range 13-51; four females) with EB were considered, with a total of 25 different interventions (16 SCC removals; three amputations for recurrent infiltrating SCC; six pseudo-syndactyly corrections). All patients received a collagen-elastin dermal matrix sheet. Neodermis was achieved in all patients, and no adverse events potentially associated with the graft occurred. No SCC recurrence was reported at sites operated for either SCC resection or amputation. The opening of the first or second commissure appears to be maintained for over 1 year after the procedure, preserving digital function. We believe that the application of a dermal substitute, together with a close dressing protocol, may represent a suitable strategy for obtaining physiological tissue regeneration and maintaining proper hand function in patients with EB.

Application of biomedical cell products in the treatment of congenital epidermolysis bullosa

Congenital epidermolysis bullosa is a phenotypically and genetically heterogeneous group of genodermatoses, which which is clinically manifested by the development of blisters on the skin and mucous membranes after mechanical injury. The presence of long-term erosive and ulcerative defects in patients with congenital epidermolysis bullosa reduces the quality of patients` life and also leads to malignancy of the lesions, as a result of constant stimulation of regenerative processes.Currently, there are a lot of publications describing the use of skin substitutes, three-dimensional tissue-engineered structures based on auto- and allogeneic cells that promote rapid epithelization of wounds in patients with congenital epidermolysis bullosa. The most prospective and at the same time the least studied direction of congenital epidermolysis bullosa treatment is the use of a combined skin equivalent created on the basis of keratinocytes and fibroblasts, which mixes the advantages of epidermal and dermal grafts.

Pregabalin for Neuropathic Pain and Itch in Recessive Dystrophic Epidermolysis Bullosa

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience neuropathic pain and itch. There is a lack of evidence on any treatment for these symptoms in patients with RDEB. To test the efficacy of pregabalin in the treatment of neuropathic pain and itch in patients with RDEB. A randomized, double-blinded, crossover trial of oral pregabalin (50-300 mg/d) vs placebo was conducted at 2 sites, Toronto (Canada) and Santiago (Chile) from January 1, 2019, to December 31, 2020. Patients eligible to participate were diagnosed with RDEB, aged 8 to 40 years, not pregnant or lactating (if female), and had evidence of probable neuropathic pain and itching defined as distal thermal sensory loss (confirmed by thermal roller), score of 4 or greater on the Douleur Neuropathique 4 questionnaire (DN4), and score greater than 4 on the 10-point visual analog scale [VAS]). Patients with a clinically important or poorly controlled medical or psychiatric condition or pregabalin intolerance or allergy were excluded. Of 41 patients screened, 3 were not eligible and 28 declined enrollment. Data analyses were performed in 2021 through 2023. Participants received both pregabalin and matched placebo (titrated to a maximum-tolerated dose of 300 mg/day) in a randomized sequence so that comparisons could be made within participants and between groups. Difference in the mean pain and itch scores between pregabalin and placebo treatment (measured using VAS) before and after intervention. In all, 10 participants were randomized to 2 groups, 6 patients (mean [SD] age, 26.7 [8.1] years; 3 females [50%]) in group 1, and 4 patients (mean [SD] age, 26.5 [7.8] years, 2 females [50%]) in group 2. Group 1 received a sequence of pregabalin-placebo while group 2 received placebo-pregabalin. Pregabalin significantly reduced mean (SD) pain scores by 1.9 (1.5) points when controlling for sequence and treatment period vs baseline, while placebo had 0.1 (2.0) points of reduction. The effect of pregabalin was a mild but significant reduction in itch compared to baseline (mean [SD] points, 0.9 [2.2]), whereas the placebo produced no reduction (0.1 [2.5]). The mean pregabalin dose was generally well tolerated. The results of this randomized crossover trial indicate that pregabalin significantly reduced pain and itch scores from baseline compared to placebo in patients with RDEB. This feasibility study provided preliminary data on the efficacy of pregabalin in managing pain and itch in RDEB and gathered essential data to inform the design of a larger cohort trial. ClinicalTrials.gov Identifier: NCT03928093.

Oesophageal Dilation Using Combined Fluoroscopy Guidance and Neonatal Scope: Overcoming Narrow Lumen Challenges in Paediatric Cases- Two Case Reports

This report highlights the management of two complex oesophageal strictures using an innovative combined endoscopic and fluoroscopic technique. The first case involves a 12-year-old boy with epidermolysis bullosa, where conventional endoscopic methods were inadequate. The second case details a premature infant with an anastomotic stricture post-oesophageal atresia repair. Both patients underwent successful dilation with a neonatal endoscope and fluoroscopic guidance, overcoming significant technical challenges. This approach demonstrates a promising alternative for handling severe and refractory oesophageal strictures.

Evaluation of a Risk Model for Sepsis Early Prediction in Infants with Epidermolysis Bullosa

Abstract Objective Epidermolysis bullosa (EB) is a severe hereditary condition characterized by fragile skin that can lead to complications, including severe infections such as sepsis. Current research on sepsis in children with EB is limited, and there is a need for specific biomarkers that can aid in early detection and management. Methods This study analyzed blood samples from 92 children diagnosed with EB, 42 of whom developed sepsis. We investigated various inflammatory proteins and clinical parameters as potential biomarkers. Multivariate analysis was used to determine predictors of sepsis occurrence. Results Elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), lactate, and decreased oxygen saturation were significantly associated with sepsis in children with EB. The predictive model displayed an area under the receiver operating characteristic curve of 0.80 in the training set and 0.77 in the validation set, indicating good predictive accuracy. Conclusion Our findings suggest that CRP, IL-6, lactate, and oxygen saturation are reliable predictors of sepsis in children with EB. These biomarkers should be monitored closely to facilitate early diagnosis and improve outcomes in this vulnerable population. The study underscores the need for tailored research and diagnostic strategies for children with EB at risk of sepsis.

Identification of a novel variant in the LAMB3 gene in a patient with a distinct junctional epidermolysis bullosa laryngo-onycho-cutaneous syndrome phenotype.

Junctional epidermolysis bullosa (JEB) represents a rare mechanobullous genodermatosis, characterized by fragility and blister formation of the skin and mucous membranes. Within the JEB spectrum, laryngo-onycho-cutaneous (LOC) syndrome is a rare subtype that manifests with excess granulation tissue of the eyes, nails, skin, and larynx. Thus far, the LOC subtype has been linked predominantly to mutations in LAMA3, disrupting the epidermal basement membrane zone. We present a unique case of a congenitally affected female with numerous cutaneous eroded plaques, oral ulcers, nail dystrophy, and laryngeal involvement phenotypically consistent with the rare JEB LOC subtype. Genetic testing revealed a previously unreported homozygous variant in the LAMB3 gene (p.C316Y) highlighting a novel variant in the LAMB3 gene and its association with the LOC phenotype of JEB.

Case Report: Alpha6 Integrin Disorder Presenting in Childhood with Nail Dysplasia and Onycholysis But No History of Fragile or Bullous Skin Changes

AbstractWe report a 7-year-old girl born with pyloric atresia but without congenital epidermolysis bullosa or skin fragility. Nail dysplasia developed at age 8 months and throughout childhood she suffered from onycholysis and mild nail hypertrophy. Whole-exome sequencing demonstrated biallelic mutations in alpha6 integrin (ITGA6): p. Q139* and R153W. ITGA6 normally forms a protein heterodimer with beta4 integrin (ITGB4), and this dimer participates in anchoring the basal skin cells to the extracellular matrix. Biallelic mutations in each gene are well known to cause epidermolysis bullosa and pyloric atresia. However, this child had ostensibly normal skin without any evidence of skin fragility. In a literature search, we identified 11 cases involving ITGA6 mutations, and all had epidermolysis skin changes. Thus, this case adds to the reported phenotype of ITGA6 disease since it is the first to show absence of an epidermolysis bullosa phenotype in the setting of pyloric atresia and nail dysplasia.

PROSPECTS FOR THE USE OF MESENCHYMAL STEM CELLS IN THE TREATMENT OF CONGENITAL EPIDERMOLYSIS BULLOSA

Epidermolysis bullosa (EB) is a hereditary orphan pathology caused by mutations in genes encoding structural cellular proteins necessary for the integrity of the skin and mucous membranes. As a result of minor mechanical stress, blisters with serous and/or hemorrhagic contents, long-term non-healing wounds and scars form on the skin. Such injuries have a high risk of infectious complications and often lead to disability of the patient. Current treatment methods are primarily palliative in nature and aimed at preventing complications, which emphasizes the relevance in new therapeutic strategies. Mesenchymal stem cells (MSCs) offer a promising therapeutic approach. MSCs are known for their multipotency, immunomodulatory properties, and ability to promote tissue repair, a potential treatment for epidermolysis bullosa. This literature review evaluates the therapeutic potential of MSCs in the treatment of VEB, highlighting key findings from recent studies.

“EPIDERMÓLISE BOLHOSA DISTRÓFICA RECESSIVA.”

This study addresses Recessive Dystrophic Epidermolysis Bullosa (RDEB), a rare genetic disorder characterized by extreme fragility of the skin and mucous membranes. The objective is to explore the clinical, genetic, and psychosocial implications for patients with RDEB, with an emphasis on emerging therapies such as gene and biotechnological interventions. Using a qualitative methodology and a literature review from reputable scientific databases, the study will analyze the effectiveness of these new therapies and their impact on patients’ quality of life. The main expected outcomes include validating the new therapies and formulating guidelines to improve the management of RDEB. It is concluded that emerging therapeutic approaches have the potential to transform the prognosis of RDEB, although further studies are necessary to consolidate these strategies.

Pain in recessive dystrophic epidermolysis bullosa (RDEB): findings of the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES)

BackgroundPain is common in the genetic skin fragility disorder epidermolysis bullosa (EB), from skin and mucosal injury and inflammation as well as extra-mucocutaneous sites. Individuals living with EB have identified pain as a priority for better treatments.ObjectivesThe Prospective EB Longitudinal Evaluation Study (PEBLES) is a prospective register study exploring the natural history of RDEB across all ages from birth to death. Here, we investigated the characteristics and treatment of pain in different RDEB subtypes.MethodsInformation was collected from individuals with different RDEB subtypes over an 8-year period. Data included visual analogue scale (VAS) ratings of background and procedural pain, its location, intensity and impact on sleep, as well as pain medication. Disease severity scores and quality of life measures were correlated to pain scores.ResultsSixty-one participants (13 children, 48 adults) completed a total of 361 reviews. Pain was common, experienced by 93% of participants at index review, with 80% suffering both background and procedural pain. Across all RDEB patients, the median VAS for background pain was 40 (out of 100) [interquartile range 20,60] and for those having regular dressing changes, median procedural pain was 52 [40,80]. Severe (RDEB-S) and pruriginosa (RDEB-Pru) groups had the greatest increase in procedural compared to background pain of 20 and 22 VAS points, respectively. Correlations between disease severity and quality of life impairment were observed across most groups, particularly RDEB-S. Over half of those studied experienced pain frequently or constantly, and in one third pain disturbed sleep at least 4 nights per week. Skin was the commonest source of pain in all subtypes except inversa RDEB where the mouth was the main site. Despite frequent and severe pain, one third of participants used no medication for pain and, in those that did, pain levels remained high suggesting ineffectiveness of current pain management approaches and a significant unmet need in RDEB.ConclusionThe frequency, severity, and impact of pain in all RDEB patients is significant, particularly in RDEB-S and RDEB-Pru. Our findings highlight that current RDEB pain management is poorly effective and that further research is needed to address this symptom.

New Recessive Dystrophic Epidermolysis Bullosa intermediate variant resulting from alternative splicing of exon 19 and truncation in FN III-like domain of type VII collagen.

Here we described two unrelated cases of a new pathogenic variant in COL7A1, the deletion c.2588-3_2588delCAGC. The variant causes alternative splicing in the preceding exon and results in truncation of fibronectin III (FN-III) like domain of C7. This new variant is distinct from previously documented variants as it does not completely exclude exon 19, restores open reading frame of COL7A1 and results in a less severe form of RDEB intermediate.

Parents’ perception of challenges of caring of children with Epidermolysis bullosa: a qualitative study

ObjectiveThe present study was investigate parents’ experiences of children with Epidermolysis bullosa. So, this descriptive phenomenological qualitative study was conducted on 17 parents of children with EB from five hospitals affiliated with the University of Medical Sciences, west of Iran. Data was collected through semi-structured interviews. COLAIZZI’s method was also used to analyze the data.ResultsThree main themes were extracted in this study: invasion of psychological crisis, alive but no living, and comprehensive support, including 10 categories. The parents of these children are the target of psychological crises that severely reduce their quality of life. In this regard, they need extensive support to improve their living conditions. Therefore, it is suggested to provide cultural and institutional contexts in which all components of the children’s dignity are emphasized.

Suspected epidermolysis bullosa simplex with anonychia and sepsis in a malnourished 7-month-old infant in Katsina, northwest Nigeria: A case report.

Epidermolysis bullosa (EB) is an uncommon hereditary cutaneous disorder inherited largely in an autosomal dominant manner. Epidermolysis bullosa simplex (EBS) typically presents at birth or early childhood, and common presenting complaints include blistering, skin fragility, and non-healing wounds inconsistent with mechanical trauma. It is associated with several complications such as sepsis, malnutrition, malignancy, and so on. The management of EBS is mainly supportive. The prognosis is good with early detection, wound care, infection control, nutritional support, and counseling. We present a case of suspected EBS-Dowling Meara type with acquired anonychia and sepsis in a malnourished 7-month-old infant in Katsina, and to the best of our knowledge the first reported case in northwest Nigeria

Treatment methods for oesophageal strictures in paediatric patients with epidermolysis bullosa: a systematic review

BackgroundEpidermolysis bullosa (EB) is a collection of rare, inherited disorders that require treatment in specialised centres by multidisciplinary teams knowledgeable about the unique features and challenges of EB manifestations and...

Management of excessive submandibular abscess and anesthesia in epidermolysis bullosa

Management of excessive submandibular abscess and anesthesia in epidermolysis bullosa

Oral Manifestations and Dental Management of Dystrophic Epidermolysis Bullosa

Oral Manifestations and Dental Management of Dystrophic Epidermolysis Bullosa

Healing of Recalcitrant Chronic Ulcers by Hair Follicle-Containing Punch Grafts in Epidermolysis Bullosa.

Healing of Recalcitrant Chronic Ulcers by Hair Follicle-Containing Punch Grafts in Epidermolysis Bullosa.

Advancing Management of Oral Lesion Patients with Epidermolysis Bullosa: In Vivo Evaluation with Optical Coherence Tomography of Ultrastructural Changes after Application of Cord Blood Platelet Gel and Laser Photobiomodulation

Advancing Management of Oral Lesion Patients with Epidermolysis Bullosa: In Vivo Evaluation with Optical Coherence Tomography of Ultrastructural Changes after Application of Cord Blood Platelet Gel and Laser Photobiomodulation

Advances and challenges in gene therapy for dystrophic epidermolysis bullosa: Insights from therapeutic strategies and animal models

Dystrophic epidermolysis bullosa (DEB) is a severe monogenic skin disorder resulting from mutations in the COL7A1 gene, which disrupts the synthesis of type VII collagen. This leads to impaired anchoring fibrils and results in dermoepidermal separation. The clinical manifestation of DEB varies significantly, ranging from localized blistering in milder forms to extensive blistering with subsequent severe complications such as vision loss and squamous cell carcinoma in more severe cases. Despite the recent approval of the first gene replacement therapy by the U.S. Food and Drug Administration, the majority of DEB patients still depend on palliative care, an indication of the continued unmet therapeutic needs. In the past two decades, there has been a rapid advancement of gene therapy techniques, extensive research efforts, and pre-clinical studies focusing on the correction of DNA, RNA, and protein defects specific to DEB. In this review, we provide a comprehensive update on the current state of gene engineering strategies for DEB, including gene replacement, pre-mRNA regulatory therapies, and gene editing techniques. In addition, this review critically evaluates the role and development of animal models in DEB research, which are crucial for the progression of therapeutic strategies. Our discussion aims to delineate the existing challenges and emphasize ongoing advancements in the gene therapy landscape for DEB, providing insights that may guide future research and clinical approaches.

Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa.

This detailed review describes innovative strategies and current products for gene and cell therapy at different stages of research and development to treat recessive dystrophic epidermolysis bullosa (RDEB) which is associated with the functional deficiency of collagen type VII alpha 1 (C7) caused by defects in the COL7A1 gene. The use of allogenic mesenchymal stem/stromal cells, which can be injected intradermally and intravenously, appears to be the most promising approach in the field of RDEB cell therapy. Injections of genetically modified autologous dermal fibroblasts are also worth mentioning under this framework. The most common methods of RDEB gene therapy are gene replacement using viral vectors and gene editing using programmable nucleases. Ex vivo epidermal transplants (ETs) based on autologous keratinocytes (Ks) have been developed using gene therapy methods; one such ET successively passed phase III clinical trials. Products based on the use of two-layer transplants have also been developed with both types of skin cells producing C7. Gene products have also been developed for local use. To date, significant progress has been achieved in the development of efficient biomedical products to treat RDEB, one of the most severe hereditary diseases.