The impact, perceptions and needs of parents of children with epidermolysis bullosa.

BACKGROUND:  Epidermolysis bullosa (EB) is a rare, incurable genodermatosis that presents with blistering and skin fragility. Complications can be localised or generalised, limited to the skin or have systemic effects resulting in death. Caring for a child with this painful condition can have a profound effect on the quality of life of parents and the family. There is currently no published research on the lived experience of parents caring for a child with EB in a resource-limited environment in Africa. METHOD:  This qualitative research used interpretative phenomenological analysis with the aim of understanding the lived experiences of parents caring for children with EB. Semi-structured interviews were conducted with 13 participants between May 2022 and October 2023. Guba's framework of trustworthiness was used to ensure rigour. RESULTS:  Seven experiential themes with associated sub-themes were identified. The themes were (1) grappling with understanding EB, (2) the psychological experience, (3) living with the responsibility, (4) barriers to feeling supported, (5) changing relational dynamics, (6) experience of healthcare professionals and (7) parental needs. CONCLUSION:  Parents caring for children with EB face emotional, physical, psychosocial and financial challenges. Addressing parents' needs and concerns will go a long way in decreasing this burden. A biopsychosocial approach with an awareness of cultural context is essential for family-centred holistic EB care.Contribution: This is the first study in Africa that focussed on the lived experiences of parents caring for a child with EB.

Epidermolysis Bullosa in Spain: A Qualitative Analysis of Its Social Impact on Families With Diagnosed Minors.

BACKGROUND: Epidermolysis bullosa (EB) comprises a group of rare types of genodermatoses characterized by extreme mucocutaneous fragility, leading to blistering and/or erosions, even with minimal trauma. Continuous care through wound management is an integral part of daily life for the families and individuals affected. The aim of this study was to assess the social reality and impacts on families of having minor members diagnosed with EB in Spain. METHODS: A qualitative methodology was employed, utilizing four focus groups entailing participation by 24 parents (19 mothers and five fathers) of minors diagnosed with EB in Spain. RESULTS: Negative impacts on the family nucleus were evident in four priority areas of analysis: sociorelational, economic-labour, physical and psychoemotional, with significant differences observed based on the severity of the symptoms. CONCLUSION: Impacts on the family nucleus are noticeable from birth, influencing all other daily life routines and complicating family planning and organization. There is an imperative need to enhance the availability of sociohealth resources and to adopt an interdisciplinary approach to address their biopsychosocial needs. PATIENT OR PUBLIC CONTRIBUTION: The active participation of relatives of minors diagnosed with Epidermolysis Bullosa (EB) is invaluable to sociohealth professionals, legislators and researchers. A team member conducts their professional activities at DEBRA España (national patient association dedicated to enhancing the quality of life for individuals with EB and their families), actively engaging in all study phases.

Review: the spectrum of antimicrobial resistance in bacteria isolated from wounds of patients with epidermolysis bullosa.

Purpose: Cutaneous infection in epidermolysis bullosa (EB) can cause significant morbidity, mortality, and dangerous sequelae. This review article aims to delve into the known epidemiology of EB, highlight the disease's primary causative agents and their antimicrobial resistance spectrum.Materials and methods: A thorough literature search was conducted using Medline, EMBASE, JBI and PubMed to gather data on the microbial landscape of EB wounds. The focus was on identifying the most common bacteria associated with EB infections and assessing their antimicrobial resistance profiles.Results: The analysis revealed that Staphylococcus aureus is the most frequently identified bacterium in EB wounds, with a notable prevalence of methicillin-resistant strains (MRSA). Specific studies on mupirocin resistance further indicated rising rates of mupirocin-resistant Staphylococcus aureus, with one study reporting rates as high as 16.07%. Additionally, high resistance to other antibiotics, such as levofloxacin and trimethoprim/sulfamethoxazole, was observed in MRSA isolates.Conclusions: The findings highlight the critical need for regular resistance surveillance and the prudent use of mupirocin to manage infections effectively in EB. The multi-drug resistant nature of pathogens in EB presents a significant challenge in treatment, highlighting the importance of antimicrobial stewardship. Ultimately, given the sparse literature and the rarity of large-scale studies, further longitudinal research on the antimicrobial resistance profile of bacteria isolated from EB wounds is essential.

[A case of Neonatal generalized atrophic benign epidermolysis bullosa due to variants of COL17A1 gene].

OBJECTIVE: To diagnose and explore the genetic etiology of a neonate with Hereditary epidermolysis bullosa. METHODS: A neonate who was admitted to Suqian Hospital Affiliated to Xuzhou Medical University on July 10, 2021 was selected as the study subject. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. And target gene capture and next-generation sequencing were carried out. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The child was found to harbor compound heterozygous variants of the COL17A1 gene, namely c.997C>T (p.Q333X) and c.3481dupT (p.Y1161fs*2), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic. CONCLUSION: The child was diagnosed with Generalized atrophic benign epidermolysis bullosa due to the compound heterozygous variants of the COL17A1 gene.

Facing the complex challenges of people with epidermolysis bullosa in Austria: a mixed methods study on burdens and helpful practices.

BACKGROUND: With approximately 500 people affected in Austria, epidermolysis bullosa (EB) is a rare genetic skin disease reducing the quality of life of those affected and their relatives. The intensive efforts of the patient organisation DEBRA Austria during the last decades have led to a unique situation of those affected and their relatives, with increased support and broader knowledge about the disease in the general population. The aim of the study is to evaluate the current situation of patients and their relatives living in Austria, with a focus on burdens and helpful practices. RESULTS: The mixed-methods study consisted of two parts: a qualitative interview study to identify psychosocial aspects of EB in those affected and their relatives, and a subsequent online survey to further assess those aspects in a larger sample, resulting in a total of n=78 Austrian participants. The impact of EB on the quality of life of EB patients and their relatives in Austria is related to the current health status, psychological burden, mobility, visibility, financial situation as well as job prospects. Personal and social resources and external support have a significant influence on the individual situation. CONCLUSIONS: The outcome is mapped to concrete implications regarding targeted support for EB patients and their relatives on an individual level and their needs in regard to the Austrian health care system.

"Quality of Life in Epidermolysis Bullosa" and "Epidermolysis Bullosa Burden of Disease": Italian translation, cultural adaptation, and pilot testing of two disease-specific questionnaires.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of skin fragility disorders characterized by blister formation following minor trauma. Four major types are distinguished based on the level of cleavage within the skin. Most EB forms present severely disabling cutaneous and systemic signs and symptoms. Management relies on daily time-consuming and distressing topical medications, and symptomatic treatment of systemic findings. Disease manifestations, symptoms, and daily care strongly affect patient and caregiver quality of life (QoL). To date, there are two validated EB-specific questionnaires, the "Quality of Life in Epidermolysis Bullosa" (QOLEB) and the "Epidermolysis Bullosa Burden of Disease" (EB-BoD) for the evaluation of patient and family disease burden, respectively. The aim of our study was to develop an Italian translation of the two questionnaires and to pilot-test them. METHODS: The guidelines for translation and cross-cultural adaptation of health-related QoL measures were followed. Initially, two separate translations were generated for each questionnaire, and subsequently reconciled by an expert committee. This was followed by a back-translation process. The original texts and all translations underwent revision by the expert committee, resulting in definitive versions. The final versions were then tested in a pilot study involving cognitive debriefing in a group of 17 families, representative of all EB major types. RESULTS: The translation and reconciliation process led to minor changes to obtain semantic/idiomatic/cultural equivalence of the Italian versions with the original ones and to reconcile the questions with the answer options. The cognitive debriefing process showed a good understanding and did not require text modifications. CONCLUSIONS: The Italian versions of the QOLEB and EB-BoD provide valuable tools in everyday clinical practice of reference centers, and they allow the participation in multicenter international real-life observational studies as well as in controlled clinical trials. They enable the identification of disease-specific psychological and socioeconomic challenges for EB patients and their families, guiding targeted interventions to ensure appropriate and timely care.

Epidermolysis Bullosa: Two rare case reports of COL7A1 and EBS-GEN SEV KRT14 variants with review of literature.

EPIDERMOLYSIS: Bullosa is a rare hereditary skin condition that causes blisters. Genes encoding structural proteins at or near the dermal-epidermal junction are mutated recessively or dominantly, and this is the primary cause of EB. Herein, two Chinese boys were diagnosed with the condition, each with a different variant in a gene that serves as a reference for EB genetic counseling. Skincare significantly impacted their prognosis and quality of life. CASE PRESENTATION: Two Chinese boys, with phenotypically normal parents, have been diagnosed with distinct blister symptoms, one with Dominant Dystrophic Epidermolysis Bullosa and the other with a severe form of Epidermolysis Bullosa Simplex. The first patient had a G-to-A variant in the COL7A1 allele, at nucleotide position 6163 which was named "G2055A". The proband is heterozygous for Dystrophic Epidermolysis Bullosa due to a COL7A1 allele with a glycine substitution at the triple helix domain. A similar variant has been discovered in his mother, indicating its potential transmission to future generations. Another patient had severe Epidermolysis Bullosa Simplex with a rare c.377T > A  variant resulting in substitution of amino acid p.Leu126Arg (NM_000526.5 (c.377T > G, p.Leu126Arg) in the Keratin 14 gene. In prior literature, Keratin 14 has been associated with an excellent prognosis. However, our patient with this infrequent variant tragically died from sepsis at 21 days old. There has been a reported occurrence of the variant only once. CONCLUSION: Our study reveals that Epidermolysis Bullosa patients with COL7A1 c.6163G > A and KRT14 c.377T>A variants have different clinical presentations, with dominant forms of Dystrophic EB having milder phenotypes than recessive ones. Thus, the better prognosis in the c.6163G > A patient. Furthermore, c.377T>A patient was more prone to infection than the patient with c.6163G>A gene variant. Genetic testing is crucial for identifying the specific variant responsible and improving treatment options.

Advances in Treatments for Epidermolysis Bullosa (EB): Emphasis on Stem Cell-Based Therapy.

Epidermolysis bullosa (EB) is a rare genetic dermatosis characterized by skin fragility and blister formation. With a wide phenotypic spectrum and potential extracutaneous manifestations, EB poses significant morbidity and mortality risks. Currently classified into four main subtypes based on the level of skin cleavage, EB is caused by genetic mutations affecting proteins crucial for maintaining skin integrity. The management of EB primarily focuses on preventing complications and treating symptoms through wound care, pain management, and other supportive measures. However, recent advancements in the fields of stem cell therapy, tissue engineering, and gene therapy have shown promise as potential treatments for EB. Stem cells capable of differentiating into skin cells, have demonstrated positive outcomes in preclinical and early clinical trials by promoting wound healing and reducing inflammation. Gene therapy, on the other hand, aims to correct the underlying genetic defects responsible for EB by introducing functional copies of mutated genes or modifying existing genes to restore protein function. Particularly for severe subtypes like Recessive Dystrophic Epidermolysis Bullosa (RDEB), gene therapy holds significant potential. This review aims to evaluate the role of new therapeutic approaches in the treatment of EB. The review includes findings from studies conducted on humans. While early studies and clinical trials have shown promising results, further research and trials are necessary to establish the safety and efficacy of these innovative approaches for EB treatment.

Orofacial Anomalies in Kindler Epidermolysis Bullosa.

Importance: Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe orofacial manifestations of Kindler epidermolysis bullosa, including early oral squamous cell carcinoma, have been reported. Objective: To determine whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa. Design, Settings, and Participants: This longitudinal, 2-center cohort study was performed from 2003 to 2023 at the Epidermolysis Bullosa Centre, University of Freiburg, Germany, and the Special Care Dentistry Clinic, University of Chile in association with DEBRA Chile. Participants included a convenience sampling of all patients with a diagnosis of Kindler epidermolysis bullosa. Main Outcomes and Measures: The primary outcomes were the presence of hypoplastic pitted amelogenesis imperfecta, intraoral wounds, gingivitis and periodontal disease, gingival hyperplasia, vestibular obliteration, cheilitis, angular cheilitis, chronic lip wounds, microstomia, and oral squamous cell carcinoma. Results: The cohort consisted of 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]) with Kindler epidermolysis bullosa. The follow-up ranged from 1 to 24 years. The enamel structure was assessed in 11 patients, all of whom presented with enamel structure abnormalities. The severity of hypoplastic pitted amelogenesis imperfecta varied from generalized to localized pitting. Additional orofacial features observed include gingivitis and periodontal disease, which was present in 90% (27 of 30 patients) of those assessed, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), cheilitis (22 of 34 patients [65%]), gingival overgrowth (17 of 26 patients [65%]), microstomia (14 of 25 patients [56%]), and vestibular obliteration (8 of 16 patients [50%]). Other features included chronic lip ulcers (2 patients) and oral squamous cell carcinoma with lethal outcome (2 patients). Conclusions and Relevance: These findings suggest that hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa and underscore the extent and severity of oral manifestations in Kindler epidermolysis bullosa and the need for early and sustained dental care.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis. Variants in laminin subunit alpha-3 (LAMA3) were found in 10/15 patients where genotype was available. LAMA3 encodes a subunit of the laminin-332 heterotrimeric extracellular matrix protein complex and is expressed by airway epithelial basal stem cells. We investigated the benefit of restoring wild-type LAMA3 expression in primary EB patient-derived basal cell cultures. EB basal cells demonstrated weak adhesion to cell culture substrates, but could otherwise be expanded similarly to non-EB basal cells. In vitro lentiviral overexpression of LAMA3A in EB basal cells enabled them to differentiate in air-liquid interface cultures, producing cilia with normal ciliary beat frequency. Moreover, transduction restored cell adhesion to levels comparable to a non-EB donor culture. These data provide proof of concept for a combined cell and gene therapy approach to treat airway disease in LAMA3-affected EB.

Stop codon readthrough as a treatment option for epidermolysis bullosa-Where we are and where we are going.

In the context of rare genetic diseases caused by nonsense mutations, the concept of induced stop codon readthrough (SCR) represents an attractive avenue in the ongoing search for improved treatment options. Epidermolysis bullosa (EB)-exemplary for this group of diseases-describes a diverse group of rare, blistering genodermatoses. Characterized by extreme skin fragility upon minor mechanical trauma, the most severe forms often result from nonsense mutations that lead to premature translation termination and loss of function of essential proteins at the dermo-epidermal junction. Since no curative interventions are currently available, medical care is mainly limited to alleviating symptoms and preventing complications. Complementary to attempts of gene, cell and protein therapy in EB, SCR represents a promising medical alternative. While gentamicin has already been examined in several clinical trials involving EB, other potent SCR inducers, such as ataluren, may also show promise in treating the hitherto non-curative disease. In addition to the extensively studied aminoglycosides and their derivatives, several other substance classes-non-aminoglycoside antibiotics and non-aminoglycoside compounds-are currently under investigation. The extensive data gathered in numerous in vitro experiments and the perspectives they reveal in the clinical setting will be discussed in this review.

Advantages of whole-exome sequencing over immunomapping in 67 Brazilian patients with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involves a skin biopsy. Most recently, whole exome sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. OBJECTIVE: To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. METHODS: Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing from skin biopsies. RESULTS: 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS), and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1 associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the results were concordant with exome results in 37 (62%), discordant in 13 (22%), and inconclusive in 9 patients (15%). STUDY LIMITATIONS: Even though EB is a rare disease, for statistical purposes, the number of patients evaluated by this cohort can still be considered limited; other than that, there was a significant difference between the proportion of types of EB (only one case with JEB, against more than 50 with DEB), which unfortunately represents a selection bias. Also, for a small subset of families, segregation (usually through Sanger sequencing) was not an option, usually due to deceased or unknown parent status (mostly the father). CONCLUSION: Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in about 1/3 of the patients. This study shows that WES is an effective method for the diagnosis and genetic counseling of EB patients.