Types Of Epidermolysis Bullosa Research Articles

Immunofluorescence mapping, electron microscopy and genetics in the diagnosis and sub-classification of inherited epidermolysis bullosa: a single-centre retrospective comparative study of 87 cases with long-term follow-up.

Epidermolysis bullosa (EB) comprises a heterogeneous group of skin fragility disorders, classified in four major types based on skin cleavage level, i.e. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, and in more than 30 subtypes defined by the combination of laboratory and clinical data, including disease course. Our aims were to address whether, in the age of genomics, electron microscopy (TEM) has still a role in diagnosing EB, and whether the genotype per se may be sufficient to sub-classify EB. A thoroughly characterized single-centre EB case series was retrospectively evaluated to compare the power of TEM with immunofluorescence mapping (IFM) in establishing the EB type, and the ability of TEM, IFM and genetics to predict selected EB subtypes, i.e. severe dominant EBS (DEBS), severe JEB, severe recessive DEB (RDEB) and DEB self-improving, using genetic and final diagnosis, respectively, as gold standard. The series consisted of 87 patients, including 44 newborns, with a median follow-up of 54months. Ninety-five mutations were identified in EB-associated genes, including 25 novel variants. Both IFM and TEM were diagnostic in about all cases of JEB (21/21 for both) and DEB (43/44 for IFM, 44/44 for TEM). TEM sensitivity was superior to IFM for EBS (19/20 vs. 16/19). As to EB subtyping, IFM performed better than genetics in identifying severe JEB cases due to laminin-332 defect (14/14 vs. 10/14) and severe RDEB (eight/nine vs. seven/nine). Genetics had no role in self-improving DEB diagnosis; it almost equalled TEM in predicting severe DEBS (eight/nine vs. nine/nine) and enabled to discriminate dominant from recessive non-severe DEB phenotypes and to identify special subtypes, e.g. DEBS with KLHL24 mutations. Transmission electron microscopy remains relevant to the diagnosis of EBS. IFM and genetics are essential and complementary tools in the vast majority of EB cases.

A comparison study of outcome measures for epidermolysis bullosa: Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and the Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB)

BackgroundThe success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared.ObjectiveTo compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools.MethodsAn observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures.ResultsThe intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other.ConclusionBoth scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities.

An analysis of the prevalence of osteoporosis and osteopenia in patients with epidermolysis bullosa: A cross-sectional study.

Epidermolysis bullosa (EB) patients have multiple risk factors for osteoporosis. There is limited literature describing the prevalence of bone health in EB, particularly in adults and less severe EB types. To investigate the prevalence of osteopenia or osteoporosis in EB patients from the Australasian Epidermolysis Bullosa Registry (AEBR). Of 417 AEBR patients, 72 underwent a dual energy X-ray absorptiometry scan. Bone mineral density (BMD) T and Z-scores, EB Disease Activity and Scarring Index (EBDASI), and Quality of Life in EB (QOLEB) scores were obtained. T-scores of RDEB patients were significantly lower than the diagnostic cut-off value for osteopenia. EBDASI and QOLEB scores were inversely correlated with Z-scores. The prevalence of osteoporosis in adults was 75% in severe EB types (RDEB and JEB). In adults with less severe types (EBS and DDEB), the prevalence of osteopenia was 50% and 33%, respectively. This is the largest study of osteoporosis in EB to date and the first to include adult patients with EBS. The high prevalence of osteoporosis and osteopenia identified in these patients warrants larger, collaborative international studies. Nevertheless, EB patients with high disease severity and QOL scores, irrespective of type, should receive early osteoporosis screening and prophylaxis.

Inherited epidermolysis bullosa: epidemiology and patient care in Slovenia with a review of the updated classification

Inherited epidermolysis bullosa (EB) is a heterogeneous group of rare genetic skin disorders characterized by fragility of the skin and mucous membranes. The prevalence of all types of EB is estimated at approximately 11 per million, based on recent data from the American National Epidermolysis Bullosa Registry. A national registry of EB has not yet been established in Slovenia. Because all cases of EB are diagnosed and treated at our department, we have collected data on all known cases of EB in Slovenia. Based on our data, the prevalence of all EB types in Slovenia is about 20 per million. As of December 2020, our data consist of 29 EB simplex, three junctional EB, 10 dominant dystrophic EB, and four recessive dystrophic EB patients. The prevalence of all EB types in Slovenia is higher compared to the estimated prevalence in the United States. The multidisciplinary care of EB patients in Slovenia has been developed based on patients' needs, including a wide group of various specialists, and it has been adapted to the resources and treatment options available. This article also reviews the up-to-date classification and diagnostic protocol for EB, and international recommendations for interdisciplinary patient care.

Utility of Immunofluorescence Antigen Mapping in Hereditary Epidermolysis Bullosa.

Background:Epidermolysis bullosa (EB) is characterized by blisters and erosions on the trauma-prone areas of the body. It occurs as a result of mutation in the genes encoding structural proteins. Transmission electron microscopy (TEM) is considered the gold standard test in the laboratory diagnosis of EB. However, this test requires a lot of expertise and is not widely available. Immunofluorescence antigen mapping (IFM) is considered a suitable alternative with comparable sensitivity and specificity. However, there is paucity of studies analyzing the utility of IFM in the diagnosis of EB.Aims and Objectives:To study the utility of IFM in the laboratory diagnosis of EB.Materials and Methods:A cross-sectional study was conducted involving 179 biopsy specimens of patients with EB. IFM was carried out using a panel of monoclonal antibodies against K14, laminin 332, type IV collagen, and type VII collagen.Results:Diagnosis of EB simplex (EBS), junctional EB (JEB), and dystrophic EB (DEB) was made in 104, 28, and 26 biopsy specimens, respectively. The overall concordance rate was 41.3% with higher concordance rates in EBS.Conclusion:The present study is conducted to assess the efficacy of IFM in the diagnosis of EB with large sample size. Our study serves to establish IFM as an important tool in the diagnostic armamentarium of EB as the prognosis mainly rests on diagnosing the type of EB.

EPIDERMOLYSIS BULLOSA: CLINICAL OBSERVATION AND PRACTICAL ASPECTS OF TREATMENT

Epidermolysis bullosa (EB) is a heterogenous group of hereditary diseases characterized by blisters on the skin and mucous membranes resulting in scarring. General occurrence rate of the disease is 8-10 cases per 1 000 000 of childbirths, with the 1:1 ratio between boys and girl. In the majority of patients clinical signs of the disease appear at birth and under 1 year. There are four main EB types: simple, functional, dystrophic and Kindler syndrome. Nowadays more than 1000 mutations of 14 structural genes have been identified resulting in the development of different EB phenotypes. Pathogenesis of the disease is based on abnormal, lost or insufficient level of a specific protein, which plays a crucial role in adhesion of the epidermis and dermis. This case report presents a clinical case of EB in a newborn girl and practical aspects of its treatment at the early neonatal period. The girl was born from the II pregnancy, II delivery in normal physiological term of gestation assessed as having 8-9 scores by Apgar scale. Some areas of disturbed skin integrity on the lower limb with some aplasia, penicilli and exfoliation of the oral mucosa were found at birth. These areas underwent changes in the dynamics of the disease, but new ones continuously appeared. Individual topical treatment was prescribed considering the stage of wound healing; partial parenteral feeding was carried out with gradual transition to enteral feeding with breast milk through the orogastric tube. Consultations with specialists providing medical aid to children suffering from EB and close contacts with parent organizations promote professional care to these patients, especially at the early neonatal period.

EPIDERMOLYSIS BULLOSA: A RARE CASE MULTISCIPLINARY APPROACH

Epidermolysis bullosa is a rare inherited disease, which manifests as mucocutaneous blisters from minimal trauma. According to the genetic mutation, the site of histologic cleavage and the sites of lesion appearance, the epidermolysis bullosa type can be classified as simple, junctional, or dystrophic. The diagnosis made by electronic microscopy is fundamental for the institution of multidisciplinary treatment. A case of a 5-year-old child admitted to pediatric, dermatologic, and dental care since the age of 2 years, diagnosed with recessive dystrophic epidermolysis bullosa, associated with anemia, severe malnutrition, low weight and height, and presenting oral cavity caries, calculus, and mucosal ulcers. Dental follow-up is of extreme importance for these patients to provide oral health and relieve symptoms caused by large numbers of ulcers, allowing better nutrition and quality of life.

A World of Scientific Endeavors and Friendships

To give readers a sense of the important contributions of the European Society for Dermatological Research (ESDR) in the development of individuals’ careers from the early 90s through the early 2000s, we asked Eugene Healy (University of Southampton, UK), Sarolta Karpati (Semmelweis University, Budapest, Hungary), and Lajos Kemeny (University of Szeged, Hungary) to share their experience in leadership positions in the Society during that period. They were posed several questions, presented in bold, and their responses follow their initials in the paragraphs that follow.

Genotype-phenotype correlations on epidermolysis bullosa with congenital absence of skin: A comprehensive review.

Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype-phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype-phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch-like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non-collagenous interruptions of the triple-helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon.

Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population.

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.

A study into growth and anaemia in children with epidermolysis bullosa

Severe subtypes of epidermolysis bullosa (EB) are devastating conditions that cause extremely fragile skin and mucosal membranes and lots of wounds. So far, no cure for EB exists. About 5,000 people in the U.K. and 500,000 people worldwide suffer from different EB types. Apart from skin problems, children with EB often have trouble gaining weight, and they develop anaemia (deficiency of iron). As wound healing works best when the body is strong, researchers needed to see how exactly children with EB grow and what factors may stop them from growing properly. To address this, a research group from the German EB reference centre, has looked back at weight, height and blood measurements of 200 children with EB. 157 had a type of EB called recessive dystrophic EB (RDEB) and 43 had junctional EB (JEB). The researchers calculated growth charts that allowed better comparison with growth of healthy children and can help to find EB‐specific growth patterns. The researchers found that the growth of children with RDEB was impaired from the second year of life (age 18 months+). In JEB, growth resembled that of healthy children. Anaemia was present from the second year of life onwards in RDEB and JEB. Children with RDEB who suffered from anaemia and deficiency of proteins, vitamins and certain minerals in the blood had impaired growth compared to those who did not. A lot of inflammation in the body also compromised the growth of children with EB. The EB growth charts from this study will help doctors and families in making decisions on feeding, like giving extra vitamins or tube feeding. The results are also important now that therapies for EB are being developed, so that we can compare how growth will improve in line with such therapies. The direct results of this study are printable growth charts that can be used throughout the world immediately, to assess and counsel children with EB. This is a summary of the study: Natural history of growth and anaemia in children with epidermolysis bullosa: a retrospective cohort study

Absence of tongue papillae as a clinical criterion for the diagnosis of generalized recessive dystrophic epidermolysis bullosa types

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

Quality of life in people with epidermolysis bullosa: a systematic review.

Individuals with epidermolysis bullosa (EB) present with various clinical manifestations of different severities that affect quality of life (QoL). This systematic review synthesizes the current evidence about the QoL of individuals with EB. We included observational studies with people of all age groups, both sexes, and any EB type. Studies with qualitative methodology, chapters of books, meeting proceedings, and abstracts were excluded. In this study, 12 articles comprising 745 individuals were included. More than half of the articles observed lower QoL in individuals with recessive dystrophic EB (RDEB) or junctional EB (JEB). Three articles indicated that EB affected QoL more in women than in men, and one article identified that children with EB suffered more than adults with the disease. Pain was frequently reported. Seven articles identified difficulty in sports, two identified a need for bathing assistance, and three identified eating difficulties. Additionally, participants reported that family relationships and friendships were affected, and they experienced feelings of anxiety and depression. Some of the instruments used evaluated QoL in general dermatologic conditions, and one was specific to EB. QoL is more affected in people who have RDEB and JEB. Regarding sex and age, women and children need special care in their monitoring. It is necessary that guidelines on pain management be more disseminated and put into practice. Future studies should use standardized specific instruments to assess the QoL in EB individuals, while considering the particularities of the different age groups.

The challenges of living with and managing epidermolysis bullosa: insights from patients and caregivers

BackgroundLittle information is available regarding the burden of living with and managing epidermolysis bullosa, including the distinct challenges faced by patients with different disease types/subtypes.MethodsA 90-question/item survey was developed to collect demographics, diagnostic data, management practices, and burden of illness information for patients with epidermolysis bullosa living in the United States. Recruitment was conducted via email and social media in partnership with epidermolysis bullosa patient advocacy organizations in the United States, and the survey was conducted via telephone interview by a third-party health research firm. Respondents aged ≥ 18 years with a confirmed diagnosis of epidermolysis bullosa or caring for a patient with a confirmed diagnosis of epidermolysis bullosa were eligible to participate in the survey.ResultsIn total, 156 responses were received from patients (n = 63) and caregivers (n = 93) representing the epidermolysis bullosa types of simplex, junctional, and dystrophic (subtypes: dominant and recessive). A large proportion of patients (21%) and caregivers (32%) reported that the condition was severe or very severe, and 19% of patients and 26% of caregivers reported a visit to an emergency department in the 12 months prior to the survey. Among the types/subtypes represented, recessive dystrophic epidermolysis bullosa results in the greatest wound burden, with approximately 60% of patients and caregivers reporting wounds covering > 30% of total body area. Wound care is time consuming and commonly requires significant caregiver assistance. Therapeutic options are urgently needed and reducing the number and severity of wounds was generally ranked as the most important treatment factor.ConclusionsSurvey responses demonstrate that epidermolysis bullosa places a considerable burden on patients, their caregivers, and their families. The limitations caused by epidermolysis bullosa mean that both patients and caregivers must make difficult choices and compromises regarding education, career, and home life. Finally, survey results indicate that epidermolysis bullosa negatively impacts quality of life and causes financial burden to patients and their families.

Terapija bola tokom previjanja kod novorođečeta sa buloznom epidermolizom - prikaz slučaja

Epidermolysis bullosa (EB) is a genetic disease characterized by blisters on the skin and mucous membranes as a result of mechanical fragility. There are four types of EB: simplex (EBS), junctional (JEB), dystrophic forms (DEB), and Kindler syndrome. Simple analgesics such as paracetamol and ibuprofen in EB are also sufficient to reduce pain. Opioids and anxiolytics are necessary for severe pain during wound dressings. In this report, a case of JEB and its pain management at home during dressing by an anesthetist is presented.

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives.

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone. Disease hallmarks are skin fragility and unremitting blistering. The most disabling EB (sub)types show defective wound healing, fibrosis and inflammation at lesional skin. These features expose patients to serious disease complications, including the development of cutaneous squamous cell carcinomas (SCCs). Almost all subjects affected with the severe recessive dystrophic EB (RDEB) subtype suffer from early and extremely aggressive SCCs (RDEB-SCC), which represent the first cause of death in these patients. The genetic determinants of RDEB-SCC do not exhaustively explain its unique behavior as compared to low-risk, ultraviolet-induced SCCs in the general population. On the other hand, a growing body of evidence points to the key role of tumor microenvironment in initiation, progression and spreading of RDEB-SCC, as well as of other, less-investigated, EB-related SCCs (EB-SCCs). Here, we discuss the recent advances in understanding the complex series of molecular events (i.e., fibrotic, inflammatory, and immune processes) contributing to SCC development in EB patients, cross-compare tumor features in the different EB subtypes and report the most promising therapeutic approaches to counteract or delay EB-SCCs.

Syndromes with skin fragility

Syndromic disorders with skin fragility belong to different groups of genodermatoses: epidermolysis bullosa (EB), Ehlers-Danlos syndrome and porphyria. The genetic defects mainly concern structural proteins which assure the mechanical stability of the skin and other tissues. Depending on the expression pattern of the affected protein in the skin, cutaneous fragility may manifest as superficial erosions, blisters, wounds, wound healing defects or scars. Extracutaneous manifestations are manifold and involve the heart, skeletal muscles, intestine, kidneys, blood vessels or the skeleton. Syndromic types of EB include in addition to skin blistering: (i)cardiomyopathy in case of desmoplakin, plakoglobin, or kelch-like protein mutations; (ii) muscular dystrophy in case of plektin mutations; (iii) pyloric atresia in case of integrin α6β4 or plectin mutations; (iv) nephrotic syndrome in case of CD151 or integrin α3 mutations. Lysyl hydroxylase3 mutations affect posttranslational modifications of collagens and lead to adystrophic epidermolysis bullosa-like multisystemic disorder. Ehlers-Danlos syndromes are due to defects of dermal collagens or their processing and affect the skin, joints and blood vessels. Finally porphyrias are complex metabolic disorders with photosensitivity and sometimes skin fragility, liver or neurologic problems. Their pathogenesis relies on the accumulation of precursors in the tissues. Although these syndromes are rare in clinical practice, knowledge of the syndromic constellation contributes to early diagnosis and detection of complications.

Challenges of the differential diagnosis between the subtypes of the junctional epidermolysis bullosa: presentation of two clinical cases

Background: Epidermolysis bullosa (EB) is a rare hereditary skin disease. It is subdivided into EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome. JEB is diagnosed in 2 per 1,000,000 of the population. There are few descriptions of clinical JEB cases in the literature. Clinical diagnosis of JEB and its subtypes is a challenge, especially in the early age. The paper presents 2 clinical cases of JEB in patients of the West Slavonic origin. Clinical case No. 1 was a girl of Ukrainian ethnicity, with confirmed definitive diagnosis of severe generalized JEB. Molecular genetic tests identified mutations of the LAMA3 gene that had not been described previously. The patient died at the age of 24 months from acute respiratory failure. When the patient was alive, her EB type and subtype was not possible to identify, because she had a combination of clinical manifestations typical for various JEB subtypes. Despite such symptoms as hoarse voice, stenoses, granulation tissue of typical location, laryngeal granulations, the girl was steadily gaining weight, with some periods of relative stabilization of the skin disease; she also had longer life longevity than was common for patients with severe generalized JEB. All this made a precise diagnosis difficult. Clinical case No. 2: an ethnic Russian boy with non-classified JEB. Molecular genetic testing helped to identify a homozygote mutation in the LAMA3 gene that had not been previously described; reliable determination of the subtype was not possible. The patient had mixed clinical manifestation similar both to generalized severe JEB and to laryngo-onycho-cutaneous (LOC) syndrome. During his lifetime, the patient was clinically diagnosed with Hallopeau acrodermatitis and LOC syndrome. The differential diagnostic problems were associated with the presence of signs not typical for each of the subtypes. Significant life longevity of the proband is not characteristic for severe generalized JEB (at the time of the publication the patient is 13 years old), whereas for LOC syndrome the absence of eye involvement is not typical, as well as severe laryngeal involvement at adolescence.Conclusion: Detailed descriptions of phenotype of JEB subtypes including rare and minimal clinical signs can be useful to study the clinical manifestations and natural course of the disease, including its differential diagnosis.

Isolation and Culture of Epidermolysis Bullosa Cells and Organotypic Skin Models.

Isolation and culture of keratinocytes from patients with different types of epidermolysis bullosa are sometimes challenging, because of the inherent adhesion defects of these cells. We routinely employ a well-established protocol for in vitro culture of these cells from small skin samples remaining after diagnostic procedures are performed. Keratinocytes and fibroblast can be used for downstream expression and functional studies or for construction of in vitro organotypic cocultures. These cells maintain main common characteristics of spreading, adhesion, migration, and survival, which depend on the underlying molecular defect.

Newer Treatment Modalities in Epidermolysis Bullosa.

The term epidermolysis bullosa (EB) refers to a group of hereditary skin blistering diseases. The group is clinically and genetically heterogeneous, but all EB forms are associated with mechanically induced skin blistering and fragility. The causative gene mutations of most EB types are known. The current international consensus classification contains four main types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome (KS). The classification is based on the morphological level of blister formation. In EBS, the split is intra-epidermal, in JEB along the basement membrane and in DEB below the basement membrane. In Kindler syndrome, the dermal-epidermal junction is disorganized, and blisters can occur on all three levels. Each major EB type has further subtypes which may differ in terms of their genetic, biological or clinical characteristics. Traditionally, EB treatments have been symptomatic, but increasing understanding of disease etio-pathogenesis is facilitating development of novel evidence-based therapy approaches. First gene- and cell-based therapies are being tested at preclinical level and in clinical trials. New knowledge on secondary disease mechanisms has led to development and clinical testing of urgently needed symptom-relief therapies using small molecules and biologicals.