Types Of Epidermolysis Bullosa Research Articles

Descriptive Study of the Clinical and Molecular Features of Epidermolysis Bullosa Patients in a Romanian European Reference Network-Skin Affiliated Reference Center.

During the last 10 years, in Romania, progress has been made for the welfare of patients suffering from epidermolysis bullosa (EB). In five university hospitals, affiliated with the National Program for the Treatment of Rare Diseases, highly trained specialists diagnose and treat patients with this rare condition. Regarding diagnosis, limitations still exist as immunofluorescence mapping and molecular genetic analysis are not accessible, and generally not reimbursed. Our objective is to present the experience in diagnosing EB patients at Colentina Clinical Hospital, highlighting genotype-phenotype correlations observed in our cohort of patients. The records of the patients enrolled between 2012 and 2024 were analyzed considering clinical aspects, and, when available, immunofluorescence mapping, transmission electron microscopy, and genetic molecular analysis. Fifty-six patients were identified, of whom 31 cases were of dystrophic EB, threewere of junctional EB, and 11 were of simplex EB. For 11 cases, the EB type could not be determined. Regarding EB simplex, two patients with KRT5 mutations and three patients with KRT14 mutations with various clinical expressions, from mild phenotype to severe forms, were identified. Three severe junctional EB patients were registered in our database and for one of the patients, two previously unreported mutations in the LAMA3 gene were identified. Regarding dystrophic EB, 31 cases were identified, of which 25 were recessive dystrophic casesand six were dominant dystrophic cases. Molecular genetic testing was performed for 15 patients, and the most common variant was c.425A>G, identified in six cases. Two previously unreported mutations were identified, namely,COL7A1 c.5416G>C, a heterozygous missense variant in a patient with a mild phenotype, mainly with nail involvement, and COL7A1 c.5960del, a variant that generates a frameshift in exon 72 resulting in a premature stop codon; this variant was identified in two siblings with a severe recessive dystrophic. Important steps have been made in identifying the correct and complete diagnosis, as well as the characterization of EB patients addressing our reference center. The findings underscore the pivotal role of molecular genetic testing in confirming diagnoses and elucidating inheritance patterns, especially in cases with atypical presentations or de novo mutations.

Bone marrow transplantation and bone marrow-derived mesenchymal stem cell therapy in epidermolysis bullosa: A systematic review.

Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life-threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM-MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft-versus-host disease, and renal insufficiency. Allogeneic BMT is a high-risk procedure with possible benefits and adverse events. BM-MSCs revealed favorable outcomes to improve the safety of EB cell-based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment's long-term effects and clarify the risk/benefit ratio of procedure versus conventional therapy.

IL-6 levels dominate the serum cytokine signature of severe epidermolysis bullosa: A prospective cohort study.

Systemic inflammation is considered a major player in the pathogenesis of epidermolysis bullosa (EB), but its pattern has only been described in small heterogeneous cohorts. There is controversy if and how systemic inflammation should be therapeutically targeted. We examined serum proinflammatory, anti-inflammatory, and itch related cytokines in a paediatric cohort of 29 patients with junctional and dystrophic EB. The cytokine that emerged as the most relevant was measured in a validation cohort of 42 patients during follow-up visits over 2 years. IL-6 showed the most consistent and highest aberration dominating systemic inflammation. IL-6 correlated with wound body surface area (BSA) in both, finding and validation cohorts. Patients with less than 3% wound BSA had normal IL-6, while IL-6 levels significantly increased at more than 5% and 10% of wound BSA. TGF-β was only marginally elevated in patients with severe recessive dystrophic EB, while TNF-α, IFN-γ and IL-1β varied inconsistently. Patients reporting itch showed elevations in type 2 immunity (IgE, TSLP, IL4 and/or IL-31, respectively). Our data suggest a dominant skin barrier and wound healing inflammatory pattern in junctional and dystrophic EB that depends on the wound area and not on the EB type. In EB, itch mediators may be similar to other pruritic disorders.

Translation, cultural adaptation and validation of the German Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire.

Epidermolysis bullosa (EB) is a rare disease characterised by skin fragility and a wide variety of symptoms. The Quality of Life in Epidermolysis Bullosa (QOLEB) score is an English 17-item EB-specific validated measurement tool with two dimensions: functioning and emotions. The aim of this cross-sectional study was to develop and validate a culturally adapted German QOLEB. The following steps were carried out: translation, expert evaluation, back translation, linguistic and cultural adaptation, sample-based psychometric testing and evaluation. Data analysis was performed with n = 46 patients across all EB types. The reliability and internal consistency of the translated German QOLEB were excellent (α = 0.901). Regarding convergent validity, the QOLEB correlated highly with the iscorEB (r = 0.879; p < 0.001). Structural similarity with the English original version was confirmed through exploratory factor analysis. In conclusion, the German QOLEB demonstrates internal reliability and construct validity and is suitable to assess the quality of life in German-speaking EB patients.

IscorEB-p: A patient-reported outcome measure for Epidermolysis bullosa. Psychometric properties of the Patient Score from the Instrument for Scoring Clinical Outcome of Research for EB.

In contrast to clinical diagnosis via external examination, patient-related outcome measures allow to access the patients' internal perception. Particularly, in the case of epidermolysis bullosa (EB), a rare disease characterized by a wide variety of symptoms and individual courses of disease, it is central to integrate the patient's perspective into diagnostic processes. The Instrument for Scoring Clinical Outcome of Research for EB (iscorEB) is an EB-specific measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). The aim of this study is to establish the iscorEB-p as an independent patient-related outcome measure tool by exploring its psychometric properties. The following steps were performed on data collected via a multinational online cross-sectional study: sample-based psychometric testing and evaluation. Data analysis was performed with n=95 participants across all EB types. The reliability and internal consistency of the iscorEB-p was excellent (α=0.90). A principal component analysis with a varimax rotation resulted in a two-factor solution, explaining 55.6% of the total variance, with the distinct factors "everyday life functioning" and "specific EB symptoms". Convergent validity was shown by high correlations to the SWLS (r=-0.52, p<0.001), the QOLEB (r=0.72, p<0.001) and EB-BoD (r=-0.73, p<0.001). In conclusion, the iscorEB-p is a reliable and valid instrument to assess the patient-reported view on the health status of EB patients.

Full-thickness Skin Grafts for Hand Contractures in an Adult Patient with Junctional Epidermolysis Bullosa: A Case Report

Epidermolysis bullosa is a group of inherited skin fragility disorders with blister formation in the basement membrane zone. Chronic scarring after repeated blistering of the hands causes narrowing of the first web, flexion contractures of the digits, and pseudosyndactyly. Junctional epidermolysis bullosa is a type of epidermolysis bullosa that is characterized by blister formation in the lamina lucida. This condition is associated with survival into adulthood. In adult survivors, hand function might be required in order to participate in normal social activities. However, there is a lack of literature on the management of hand surgery for adult patients with junctional epidermolysis bullosa. We herein describe an adult patient with junctional epidermolysis bullosa who had pseudosyndactyly and flexion contractures in both hands. Five surgeries were performed. Contractures were released and reconstructed using split- or full-thickness skin grafts. Delayed wound healing was always observed due to epidermal necrosis in the graft. After epithelialization, a satisfactory functional outcome was obtained.

Harmonization of outcomes in epidermolysis bullosa: report of the Core Outcome Sets for Epidermolysis Bullosa (COSEB) kick-off meeting.

The COSEB kick-off meeting was organized in April 2023, and highlighted the stakeholder perspectives on the unmet and urgent need to work towards reasonable harmonization of outcome measurement in epidermolysis bullosa (EB) by developing core outcome sets for the different EB types. Standardized and uniform outcome assessment holds great promise to reduce selective reporting, improve the comparability and pooling of treatment outcomes, and enhance the efficacy of future research in EB.

Analysis of the state and problems of pharmaceutical supply for patients with epidermolysis bullosa

Aim. To analyze medical technologies (MT) for the treatment of epidermolysis bullosa (EB) and their availability to patients and the healthcare system.&#x0D; Materials and methods. The study objects were scientific publications, normative legal acts, guidelines (protocols), statistical data, the Orphanet network, official data of the Ministry of Health and the State Enterprise “Medical Procurement of Ukraine”, marketing information. The methods of content analysis, structural and logical, comparison, generalization, marketing analysis were used.&#x0D; Results. Modern approaches to the classification of types of EB were studied; epidemiological indicators were analyzed; recommendations of clinical protocols were summarized. It has been found that currently there are no available specific MT in the world for the treatment of this severe chronic disease. International clinical guidelines recommend the use of medicines and medical products to relieve symptoms (wound care, reduce pain and itching), prevent secondary pathologies and improve the quality of life of patients with EB. The cost of treating EB depends on the severity of the disease and the patient’s age. The burden of the disease and the impact on the budget are assessed to be high. The state cannot provide 100 % of the need for the necessary medicines and medical products due to budget constraints. The analysis of the national legal framework for providing patients with rare (orphan) diseases, including EB, with the necessary medicines and medical products was carried out. It has been determined that only 9 INNs of the seven groups of medicines recommended by the protocol are included in the National List and can be purchased for budget funds. The annual need, nomenclature and volumes of purchases of drugs for the treatment of EB were studied. According to the State Enterprise “Medical Procurement of Ukraine” in 2023, for patients with EB it is planned to purchase eight groups of medical products for skin and wound care under 20 names in the amount of UAH 119.8 million.&#x0D; Conclusions. In order to improve approaches to the pharmaceutical provision of patients with EB, it is extremely important to use health technology assessment (HTA) to identify the most effective and economically feasible medicines and medical products.

Epidermolysis bullosa in a twins infant: a rare case

Background: Epidermolysis bullosa (EB) is a rare hereditary genodermatosis characterized by blisters due to trauma and temperature. Cases of EB in twin infants are rare. This report will discuss EB in twin infants to improve our knowledge about this genodermatosis. Case: A baby boy with a twins history aged 4 months was consulted by the Pediatric Department with complaints of fluid-filled blisters that have been present since birth. During examination, bullae appeared on the upper and lower extremities. The gram examination and culture results showed Staphylococcus aureus infection and gentamicin sensitivity. The histopathology results showed a subepidermal blister with the dermis layer showed lymphocytic infiltration, which was in accordance with EB. The baby was hospitalized for 5 days and then came back to the outpatient unit with his twin, who had the same complaint. Examination of the second infant revealed multiple erosions and hypopigmented macules on the superior and inferior extremities. Both babies were born at term, normal, adequate weight, and are the first twins. Direct immunofluorescence did not show immunoglobulin G (IgG) and complement C3 deposits in the basement membrane zone. Both infants received symptomatic therapy. Conclusion: Epidermolysis bullosa is a rare case, especially in twins. Electron microscopy is a gold standard for determining EB type. Symptomatic treatment is the main therapy in this population of EB.

Evaluation of Clinical and Oral Findings in Patients with Epidermolysis bullosa.

Introduction: Epidermolysis bullosa (EB) is a genetically inherited disease characterized by recurrent bullae and erosions on the skin with numerous signs of dental caries and poor oral hygiene. The aim of this study was to investigate the general clinical and oral findings of patients with EB. Materials and Methods: In this prospective study, the clinical and oral findings and family history of 26 cases with EB were evaluated. The type of EB, gender, age, parental consanguinity, dental caries, oral findings, distribution of lesions and presence of associated anomalies, clinical and oral findings correlated with gender were recorded. Results: All 26 patients with EB had a history of consanguinity and siblings with EB to varying degrees. In our study, malnutrition, anemia and growth retardation, gastrointestinal system complications, hair thinning, hand and nail deformity, ocular problems and renal disease (in one case) were observed with variable frequencies. When the intraoral findings of the patients were investigated, extensive dental caries in all EB types, enamel hypoplasia in junctional EB (JEB) and the presence of tooth-root to be extracted in dystrophic EB (DEB), intraoral bullae and lesions, ankyloglossia, vestibular sulcus insufficiency, microstomia and maxillary atrophy were observed. Three cases had restorative treatment and one case had prosthetic rehabilitation. Conclusions: Oral involvement can be seen with varying frequencies depending on the type of EB and the severity of the disease. It may result from delayed oral and dental rehabilitation due to physical disabilities, limitations and more pressing medical problems. Microstomy, pain from mucosal lesions, and restricted access to the mouth can be caused by poor oral hygiene. Oral complications and caloric needs of individuals with EB should be determined, and individual prophylaxis should be applied to prevent caries formation and protect teeth.

A Retrospective Study on the Clinical, Laboratory, and Nutritional Status of Pediatric Epidermolysis Bullosa in a Tertiary Referral Hospital in West Java, Indonesia.

Epidermolysis bullosa (EB) is a genodermatosis disease with bullae and erosions of the skin and mucous membrane that can last for a lifetime and decrease quality of life. Oral and gastrointestinal disorders inhibit the patients' ability to achieve optimal nutrition, making the patients prone to infection, leading to prolonged wound healing, and delayed growth and developmental process. However, there has been no research on the clinical, laboratory, and nutritional status of pediatric EB patients in Indonesia. This study aims to describe the clinical, laboratory, and nutritional characteristics of pediatric EB patients treated in Dr. Hasan Sadikin General Hospital Bandung, Indonesia. This was a retrospective descriptive study of pediatric EB patient records in Dermatology and Venereology Outpatient of Dr. Hasan Sadikin General Hospital Bandung, Indonesia, from April 2018-March 2020. Study results showed 12 pediatric EB patients consisting of 7 dystrophic EB (DEB) (4 recessive dystrophic EB [RDEB] patients and 3 dominant dystrophic EB [DDEB]), 3 junctional EB (JEB), and 2 EB simplex (EBS). The most extensive EB wounds was found affecting 10-20% of the body surface area with a <10% infected wound area. Pain was found in all patients. The most frequent abnormalities in laboratory examination were anemia and low zinc levels. Severe malnutrition was found in almost half of the patients. RDEB is the most commonly found type of pediatric EB. Wounds on the skin, tooth decay, hand deformity, pain when changing dressings, low zinc levels, and low hemoglobin levels are the clinical features and laboratory findings that contribute to the development of moderate and severe malnutrition in RDEB patients.

Oral health status in patients with inherited epidermolysis bullosa: a comparative multicenter study.

Epidermolysis bullosa (EB) is a rare genetic mucocutaneous disorder characterized by epithelial fragility leading to blister formation on skin and mucous membranes with even minor mechanical trauma. Most EB oral health publications give fragmented information, focusing on only one oral health aspect or one EB type. The aim of this study was to expand the knowledge of the overall oral health status of individuals with dystrophic, junctional, and simplex EB. A comparative multicenter study, including a control group, and based on questionnaires and clinical examinations, was undertaken in three EB expert centers. Most EB (90.2%) participants brushed their teeth at least once a day despite the pain. The prevalence of enamel defects and caries experience did not differ between the 42 EB participants and the 42 age-/sex-matched healthy controls. Gingival inflammation unrelated to dental plaque accumulation was found in EB participants. Blisters, erythema, and erosion/ulceration mainly involved gingiva, buccal mucosa, lips, and palate, with different topographic patterns according to EB type. EB patients whatever the age showed a similar lesion distribution. Simplex and dystrophic EB patients under 12 years old displayed higher lesion severity than junctional EB ones. Only dystrophic type exhibited microstomia and ankyloglossia. Oral health status seemed to benefit from a close collaboration between dental practitioner and dermatologist, and from regular dental examination, starting at a young age and with a focus on prevention. The new appreciation of oral health involvement highlighted by this study is essential for EB patients care, regarding comorbidities and quality of life.

A Case study showing a Novel gene mutation in LAMB3 causing Junctional Epidermolysis Bullosa [Intermediate/Severe

ABSTRACT Background: Junctional epidermolysis bullosa (JEB) is a type of Epidermolysis Bullosa, a group of genetic conditions that cause the skin to be very fragile and to blister easily. It is categorized into Herlitz type and Non-Herlitz types. JEB is inherited in an autosomal recessive pattern and the most common genetic mutations associated are LAMB3, COL17A1, or LAMC2, and LAMA3 genes. Case presentation: This study reports a consanguineous couple, who are carriers for pathogenic variant for LAMB3 gene, with an affected child with a homozygous mutation in the LAMB3 gene causing Herlitz type of Junctional epidermolysis Bullosa/ Non-Herlitz type of junctional epidermolysis bullosa. Furthermore, prenatal diagnosis for the Gravida also showed the same pathogenic variant. Conclusion: For autosomal recessive genetic conditions, it is advisable to perform a Trio whole-exome sequencing or next-generation sequencing to detect the genes associated with the disease. Depending on the type of variants involved prenatal diagnosis for the next pregnancy and treatment or management (if available) options can be offered/discussed.

Clinical features and outcomes of epidermolysis bullosa in thai children: A 20-Year review from a Tertiary Care Center

Background: Epidermolysis Bullosa (EB) is a heterogeneous genetic disorder with skin fragility. Only a few cases have been reported in Thailand. This study aims to determine the clinical characteristics, complications, and outcomes of EB stratified by subtype. Methods: A retrospective single-center study of EB patients at the Dermatology Unit, Queen Sirikit National Institute of Child Health, was reviewed from January 1, 2002, to December 31, 2021. Diagnosis is based on clinical manifestations and some skin biopsies. Results: There were 38 enrolled patients, age range from 0 to 25 years with a male-to-female ratio of 1.1:1. Family history of EB and consanguineous marriage were found in 6 cases and 2 cases, respectively. The most common type of EB was dystrophic EB (DEB) (26 cases) (68.4%), including recessive DEB in 15 cases (39.5%) and dominant DEB in 11 cases (28.9%). Other types were EB simplex in 10 cases (26.3%) and junctional EB in 2 cases (5.3%). Common complications were cutaneous bacterial infection (39.5%), anemia (31.6%), failure to thrive (18.4%), and protein energy malnutrition (15.8%). Musculoskeletal (21.1%), gastrointestinal (13.2%), and eye complications (7.9%) were exclusively found in DEB. Nineteen patients (50%) received regular follow-ups with a median duration of 9 months (range = 0.5 to 248 months). The mortality rate was 31.6% (6/19). Five cases died from bacterial sepsis, while one case died from metastatic squamous cell carcinoma. Conclusion: DEB is the most common type of EB in Thai children, and bacterial sepsis is the predominant cause of death. Further multicenter and molecular genetic studies are recommended for a definite diagnosis.

Whole exome sequencing in a sample of Peruvian patients diagnosed with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a complex and heterogeneous dermatological disease. Four main types of EB have been described, each of them with distinct characteristics: EB simplex (EBS), dystrophic EB (DEB), junctional EB (JEB) and Kindler EB (KEB). Each main type varies in its manifestations, severity, and genetic abnormality. We sought mutations in 19 genes known to cause EB and 10 genes associated with other dermatologic diseases in 35 Peruvian pediatric patients of a rich Amerindian genetic background. Whole exome sequencing and bioinformatics analysis was performed. Thirty-four of 35 families revealed an EB mutation. Dystrophic EB was the most frequently diagnosed type, with 19 (56%) patients, followed by EBS (35%), JEB (6%), and KEB (3%). We found 37 mutations in seven genes; 27 (73%) were missense mutations; 22 (59%) were novel mutations. Five cases changed their initial diagnosis of EBS. Four were reclassified as DEB and one as JEB. Inspection into other non-EB genes revealed a variant, c.7130C&gt;A, in the gene FLGR2, which was present in 31 of the 34 patients (91%). We were able to confirm and identify pathological mutations in 34 of 35 patients.

Epidemiology of inherited epidermolysis bullosa in Germany.

Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity. Epidemiological data from different countries have been published, but none are available from Germany. In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization. Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries. Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.

Bart’s Syndrome: A Case Report

Bart's syndrome (BS) is a genetic disorder characterized by the absence of localized skin (present at birth), epidermolysis bullosa (EB) and ungueal changes [1]. Clinically Bart's syndrome is associated with epidermolysis bullosa (EB). It may be associated with any type of EB but is mostly reported with dominant dystrophic form. Diagnosis is obvious clinically but requires ultrastructural microscopy. Treatment suffices to conservative measures [1].

Clinical characteristics, healthcare use, and annual costs among patients with dystrophic epidermolysis bullosa

BackgroundDystrophic epidermolysis bullosa (DEB) is a serious, ultra-rare, genetic blistering disease that requires a multidisciplinary care team and lifelong, proactive disease management. To organize and optimize care, we comprehensively examined diagnoses, healthcare use, and annual costs in patients with DEB across all healthcare settings.MethodsA retrospective study was performed using electronic health record (EHR) data from Optum Clinical Database (January 1, 2016, through June 30, 2020). Patients with an epidermolysis bullosa (EB) diagnosis between July 1, 2016, and December 31, 2019, with ≥ 6 months of baseline and 12 months of follow-up activity were included. Patients were stratified by EB type: recessive DEB (RDEB), dominant DEB (DDEB), DEB (type unknown), and EB unspecified. Demographics, comorbid conditions, and healthcare resource utilization were identified from EHR data. Cost of bandages and total medical costs (US$) were identified from linked claims data.ResultsA total of 412 patients were included, classified as having DDEB (n = 17), RDEB (n = 85), DEB (type unknown; n = 45), and EB unspecified (n = 265). Mean age was 38.4 years, and 41.7% had commercial insurance coverage. The most common comorbidities were mental health disorders, malnutrition, and constipation. Rates of cutaneous squamous cell carcinoma ranged from 0% (DDEB) to 4.4% (RDEB). Prescriptions included antibiotics (56.6%), pain medications (48.3%), and itch medications (50.7%). On average, patients had 19.7 ambulatory visits during the 12-month follow-up, 22.8% had an emergency department visit, and 23.8% had an inpatient stay. Direct medical costs among patients with claims data (n = 92) ranged from $22,179 for EB unspecified to $48,419 for DEB (type unknown).ConclusionsThis study demonstrated the range of comorbidities, multiple healthcare visits and prescription medications, and treatment costs during 1 year of follow-up for patients with DEB. The results underscore that the clinical and economic burden of DEB is substantial and primarily driven by supportive and palliative strategies to manage sequelae of this disease, highlighting the unmet need for treatments that instead directly address the underlying pathology of this disease.

Burden of caregivers and out-of-pocket expenditures related to epidermolysis bullosa in France.

Inherited epidermolysis bullosa (EB) is a heterogeneous group of genodermatoses characterized by localized or generalized skin and/or mucosal fragility. The objective of this work was to evaluate in France the burden of disease and out-of-pocket (OOP) expenditures for families with a child affected by EB. A digital questionnaire was built and distributed to parents of children with EB in partnership with the patients' association DEBRA France. The questionnaire collected clinical and socioeconomic characteristics including the estimated amount of money caregivers had to pay out of their own pockets. The burden of caregivers was assessed using the validated Epidermolysis Bullosa Burden of Disease (EB-BoD) tool. Linear univariate regression models were conducted to search for factors associated with higher burden and higher OOP. Between October and December 2021, 77 parents answered the questionnaire. The responder was the child's mother in 77% (n=59) of cases. Parents represented 40 girls and 37 boys with a mean age of 7.5 years and with different EB types and disease severity. The mean BE-BOD score was 63.9 ± 20.2. The mean score observed in children with severe EB was 69.0 ± 21 versus 59.0 ± 18.6 for moderate/mild. Similarly, the mean BE-BOD scores observed in parents performing daily wound care were 67.9 ± 19.6. All parents (100%) reported OOP expenses. The mean annual OOP cost was 4129€ ± 4321€. Linear regression demonstrated that for each one-point increase in the EB-BoD score, OOP expense increases by 91.1 euros (35.1-147) p=0.002. EB places a considerable burden on families' daily lives. This burden is closely associated with OOP expenditures to manage EB which were on average 20 times higher compared with the French population.

Novel compound heterozygous mutations in the PLEC gene in a neonate with epidermolysis bullosa simplex with pyloric atresia.

Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by the blistering of the skin and mucous membranes. Although the molecular basis of EB has been significantly elucidated, the precise phenotypes of the lethal types of EB have not been completely characterized. Herein, we report a severe case of EB with pyloric atresia (PA). The patient was a Japanese boy who not only had skin lesions but also various complications such as PA, dysphagia, hypotonia, infectious keratitis with corneal ulcer, obstructive uropathy and protein-losing enteropathy. Genetic analysis led to the identification of two novel compound heterozygous mutations in the last exon of the plectin (PLEC) gene. Based on this finding, EB simplex with PA was diagnosed. Immunostaining with anti-plectin antibodies revealed truncated plectin proteins lacking the C-terminus in the patient's skin. We also conducted a prenatal diagnosis in subsequent pregnancy. Our report further highlights the crucial role of plectin in many organs and provides valuable information regarding the phenotypes resulting from mutations in the PLEC gene.