Increased healthcare burden and comorbidity risks of pediatric patients with dystrophic epidermolysis bullosa: Analysis of Nationwide Emergency Department Sample 2015-2019.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) describes a rare genetic blistering disorder characterized by fragile skin. This study aimed to classify the frequency, demographics, cost, and comorbidities associated with emergency department (ED) visits due to DEB. METHODS: The Nationwide Emergency Department Sample (NEDS) was analyzed for pediatric (age <18) ED visits from 2015 to 2019. DEB was identified with ICD-10-CM code Q81.2. Weighted frequency, prevalence, and 95% confidence intervals (CIs) of comorbidities were determined among ED visits with and without a DEB diagnosis. RESULTS: From 2015 to 2019, 53 (weighted 242) cases of DEB among 27,223,220 pediatric ED visits were captured. Patients with DEB were more likely to visit the ED in summer compared with those without a diagnosis of DEB (35.7% vs. 21.4%, P < .05). More than half of patients with DEB were admitted to the hospital (56.2%, 95% CI: 39.3-72.5, P < .001) versus only 3.4% (95% CI: 3.1-3.7) of other patients. For ED visits with a secondary DEB diagnosis, the top three primary diagnoses were fever, constipation, and bone marrow transplant aftercare. Patients with DEB had higher rates of hypertension, cellulitis, sepsis, acute and chronic kidney injury, esophageal obstruction, gastroesophageal reflux disease, cardiomyopathy, and anxiety, compared to patients without DEB (all P < .001). CONCLUSIONS: DEB is a complex blistering disorder with multisystemic manifestations. Patients with DEB have significantly higher admission rates and commonly present with infectious or gastrointestinal complications. Understanding the features of ED visits due to DEB can better prepare healthcare teams and improve patient outcomes.

Ancestral patterns of recessive dystrophic epidermolysis bullosa mutations in Hispanic populations suggest sephardic ancestry.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis caused by mutations in the gene coding for type VII collagen (COL7A1). More than 800 different pathogenic mutations in COL7A1 have been described to date; however, the ancestral origins of many of these mutations have not been precisely identified. In this study, 32 RDEB patient samples from the Southwestern United States, Mexico, Chile, and Colombia carrying common mutations in the COL7A1 gene were investigated to determine the origins of these mutations and the extent to which shared ancestry contributes to disease prevalence. The results demonstrate both shared European and American origins of RDEB mutations in distinct populations in the Americas and suggest the influence of Sephardic ancestry in at least some RDEB mutations of European origins. Knowledge of ancestry and relatedness among RDEB patient populations will be crucial for the development of future clinical trials and the advancement of novel therapeutics.

Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: A global cross-sectional survey.

BACKGROUND: A spectrum of skin disease severity exists in patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVE: To characterize the patient-reported outcomes and quality of life (QOL) in patients with RDEB. METHODS: A cross-sectional study of patients with RDEB surveyed through the global EBCare Registry. Patient-reported outcomes included skin disease severity, wound characteristics, pain, itch, extracutaneous symptoms, and medications. QOL was measured by using the validated Quality of Life in Epidermolysis Bullosa instrument. RESULTS: A total of 85 patients with RDEB reported 1226 wounds (937 recurrent wounds and 289 chronic open wounds). Overall skin disease severity was self-reported as mild (26%; 22/83), moderate (48%; 40/83), or severe (25%; 21/83). Worsening skin disease severity was significantly associated with larger wounds, increased opiate use, anemia, gastrostomy tube use, infections, osteoporosis, and squamous cell carcinoma. Larger wound size was associated with worse quality of life scores. LIMITATIONS: All data were self-reported from an online epidermolysis bullosa patient registry. CONCLUSIONS: This study shows a significant correlation between larger wound size with worsening skin disease severity and quality of life in participants with RDEB. Worsening skin disease severity significantly correlated with key clinical manifestations. These results show that patients with RDEB are able to self-report their skin disease severity and wounds.

Genotype-Phenotype Correlations of Dystrophic Epidermolysis Bullosa in India: Experience from a Tertiary Care Centre.

Recent advances in the field of genomics have seen the successful implementation of whole exome sequencing as a rapid and efficient diagnostic strategy in several genodermatoses. The aim of this study was to explore the potential of molecular studies in dystrophic epidermolysis bullosa (DEB) in India. Whole exome sequencing was performed using genomic DNA from each case of epidermolysis bullosa, followed by massively parallel sequencing. Resulting reads were mapped to the human reference genome hg19. Sanger sequencing subsequently confirmed the potentially pathogenic mutations. Whole exome sequencing of 18 patients with DEB from 17 unrelated Indian families revealed 20 distinct sequence variants in the COL7A1 gene including 2 widely prevalent mutations. Dominant inheritance was seen in 7 patients, while 11 patients showed a highly variable recessive DEB. This preliminary study using exome sequencing is clearly encouraging and will serve as the basis for future large-scale molecular studies to actively identify and understand DEB in the Indian population.

Epidemiology of inherited epidermolysis bullosa in Romania and genotype-phenotype correlations in patients with dystrophic epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) is a rare and so far incurable genetic disease, affecting mainly the skin and mucosal membranes, manifesting with blisters triggered by minor mechanical trauma. Since only few epidemiological data on EB are available, we established a Registry for EB and implemented molecular diagnostic methods. OBJECTIVE: We present epidemiologic data from the EB Registry and genotype-phenotype correlations. METHODS: In 2006, a registry of patients with EB was initiated in the Department of Dermatology of the University of Medicine, as well as molecular diagnostic tools. The patients were diagnosed on clinical bases, and whenever possible, immunofluorescence mapping and molecular analysis were performed. RESULTS: 89 EB patients were enrolled in the study from 2006 to 2012: 58 patients with dystrophic EB (DEB), 20 with EB simplex, one patient was diagnosed with Kindler syndrome; in 10 patients, the type of EB could not be determined. DISCUSSION AND CONCLUSION: We have estimated, the total number of EB patients in Romania and we have estimated the incidence and the prevalence of EB. We have also managed to approximate the distribution of EB types in Romania. Moreover, we performed a phenotypic and genotypic characterization in some of the patients included in the EB register.

Prevalence of dystrophic epidermolysis bullosa in Spain: a population-based study using the 3-source capture-recapture method. Evidence of a need for improvement in care.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a rare disease that represents a heavy burden for both the patient and the health care system. There are currently no data on the prevalence of DEB in Spain. OBJECTIVE: To determine the prevalence of DEB in Spain. METHODS: We used data from 3 incomplete population-based sources (hospital dermatology departments, diagnostic laboratories performing antigenic mapping, genetic testing or both, and the Spanish Association of Epidermolysis Bullosa Patients [DEBRA]) and combined them using the 3-source capture-recapture methodology. RESULTS: We identified 152 living DEB patients. The estimated prevalence of DEB was 6.0 cases per million (95% CI, 4.2-11.8) in adults and 15.3 (95% CI, 10.4-40.8) in children under 18 years of age. The data indicated that 77% of the patients were not being followed up in specialized centers of reference; 65% had not had a genetic diagnosis, and 76% were not members of DEBRA. CONCLUSIONS: The prevalence of DEB in Spain is 6.0 patients per million (95% CI, 4.2-11.8), a figure higher than previous estimates in many areas, but similar to those found in other southern Europe countries. The north-south difference may represent real geographic differences in prevalence, but it might be due to the fact that most of the data come from registries with a lower than expected catchment. Many patients are not being followed up in centers of reference, do not have genetic diagnosis, and are not members of patients' associations, suggesting that there is room for considerable improvement in their care.

The international dystrophic epidermolysis bullosa patient registry: an online database of dystrophic epidermolysis bullosa patients and their COL7A1 mutations.

Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder that can be inherited autosomal dominantly (DDEB) or recessively (RDEB) and covers a group of several distinctive phenotypes. A large number of unique COL7A1 mutations have been shown to underlie DEB. Although general genotype-phenotype correlation rules have emerged, many exceptions to these rules exist, compromising disease diagnosing and genetic counseling. We therefore constructed the International DEB Patient Registry (http://www.deb-central.org), aimed at worldwide collection and sharing of phenotypic and genotypic information on DEB. As of May 2011, this MOLGENIS-based registry contains detailed information on 508 published and 71 unpublished patients and their 388 unique COL7A1 mutations, and includes all combinations of mutations. The current registry RDEB versus DDEB ratio of 4:1, if compared to prevalence figures, suggests underreporting of DDEB in the literature. Thirty-eight percent of mutations stored introduce a premature termination codon (PTC) and 43% an amino acid change. Submission wizards allow users to quickly and easily share novel information. This registry will be of great help in disease diagnosing and genetic counseling and will lead to novel insights, especially in the rare phenotypes of which there is often lack of understanding. Altogether, this registry will greatly benefit the DEB patients.

Restrictions in oral functions caused by oral manifestations of epidermolysis bullosa.

Several forms of epidermolysis bullosa (EB) present oral manifestations. Blistering of the (peri)oral mucosa affects the opening of the mouth, the mobility of the tongue and lips, thereby restricting oral functions. We describe the prevalence and characteristics of oral manifestations of EB in relation to loss of oral functions in a cross-sectional study of different types of EB patients using standardized measurement techniques. Twenty-two patients were included. The mobility of the mandible, lips and tongue was measured, the mandibular function impairment questionnaire (MFIQ) was filled out and additional questions regarding hindrance of EB during oral hygiene and intelligibility of speech (being understood) were asked in structured interviews. The median age was 11.8 yrs. Mobility of the mandible, tongue and lip was restricted, oral hygiene procedures were hindered in most patients. A data comparison was made between the recessive dystrophic EB (RDEB) and junctional EB (JEB) groups. Mandibular function was impaired in both groups but more severely in the RDEB-population. Intelligibility in both groups was almost unaffected. Restrictions in mobility of the mouth, tongue and lips are frequently present in EB patients. These are most severe in the RDEB group and support the clinical relevance of optimizing symptomatic treatment.

Novel glycine substitution mutations in COL7A1 reveal that the Pasini and Cockayne-Touraine variants of dominant dystrophic epidermolysis bullosa are allelic.

Mutations in the type VII collagen gene (COL7A1) have been shown to underlie dystrophic epidermolysis bullosa (DEB). The dominantly inherited forms of DEB have been divided into two clinical subcategories, the Pasini (DDEB-P) and the Cockayne-Touraine (DDEB-CT) variants, on the basis of the presence or absence of albopapuloid lesions. In this study, we have examined the molecular basis of DDEB in two Japanese families, one with DDEB-P and the other with DDEB-CT. Mutation detection strategy consisted of polymerase chain reaction amplification of COL7A1 from genomic DNA, followed by heteroduplex analysis and direct nucleotide sequencing. The results revealed heterozygous glycine substitution mutations, G2076D and G2034R, in these families, respectively. Thus, these two variants of DDEB are allelic, and subtle differences in the clinical presentation may reflect the precise position of the mutation along the type VII collagen molecule. Alternatively, the nature of the substituting amino acid (D versus R) may influence the clinical phenotype. This is the first demonstration of a COL7A1 mutation in DDEB-P, and brings the total number of dominant DEB variants with underlying glycine substitutions in COL7A1 to five, including the pretibial and localized variants as well as the Bart's syndrome, in addition to DDEB-P and DDEB-CT.

Type VII collagen DNA linkage analysis in a Japanese family with dominant dystrophic epidermolysis bullosa.

Type VII collagen, a major component of anchoring fibrils in the basement membrane zone, is now considered to be a primary genetic factor in the pathogenesis of dominant dystrophic epidermolysis bullosa (DDEB). In this study, we performed genetic linkage analysis in a Japanese family with DDEB using a PvuII polymorphism in the type VII collagen gene. The pedigree consisted of 10 affected and 13 unaffected living individuals and was diagnosed as having Cockayne-Touraine type of DDEB. Electron microscopic examination of the skin demonstrated a diminished number and rudimentary structure of anchoring fibrils. PCR-based detection of PvuII polymorphism resulted in 3 genotypes and co-segregated with DDEB phenotype in this pedigree. The maximum lod score was 2.10 at recombination fraction (theta) of 0. The absence of recombination between DDEB and type VII collagen gene locus, as well as the observation of altered anchoring fibrils, suggested that type VII collagen is a candidate gene for the Japanese family with DDEB, although the lod score was statistically not significant.

Dental caries risk in hereditary epidermolysis bullosa.

Epidermolysis bullosa (EB) is a clinically diverse group of conditions characterized by skin fragility and, in certain types, marked dental involvement. The purpose of this study was to determine the prevalence of dental caries in EB and control populations. Healthy individuals and participants from the Southern Clinical Center of the National EB Registry were examined with artificial light and a #23 dental explorer. Caries levels were evaluated by chi-square analysis, regression analyses, and ANOVA (P < 0.05 being significant). The study included 252 individuals with EB, aged 2.3-71 years, and 57 similarly aged controls. The prevalence of dental caries, scored as DMFS (decayed, missing, filled surfaces), was significantly higher in the junctional (mean = 58.6) and recessive dystrophic (mean = 37.6) EB types than controls (mean = 23.2). The simplex (mean = 25.6) and dominant dystrophic (mean = 21.6) EB groups had DMFS levels similar to the control group. Individuals with recessive dystrophic EB had the most severe oral blistering and scarring and did not have generalized enamel hypoplasia. In contrast, junctional EB always was associated with generalized enamel hypoplasia yet the intraoral blistering rarely involved scarring. This study shows that dental caries is increased in dystrophic and junctional EB compared with unaffected individuals or other EB types. While rampant caries appears related to the soft tissue and enamel involvement in these two EB types, other as yet unclear cofactors also must be involved.

Epidermolysis bullosa: where do we stand?

Epidermolysis bullosa, a genetically determined skin fragility disorder can severely incapacitate the life of the afflicted patient. Although the clinical features are multiple and varied, treatment still remains a major challenge. There have been major changes in the classification of the disease recently. Although there is still a long way to go, good nursing care, and gene therapy could possibly significantly alleviate the suffering of the patients in the future.

Epidermolysis bullosa in Australia and New Zealand.

This article describes the clinical services for EB in Australia and New Zealand. The history and epidemiology of EB in Australia is described. Current treatment and research achievements are described.

Epidermolysis bullosa in Northern Ireland.

Cases of epidermolysis bullosa (EB) diagnosed in Northern Ireland during a 23-year period (1962-84) were identified from dermatology clinic files, paediatric hospital notes and cases known by general practitioners. A total of 48 confirmed new cases of EB were diagnosed during the screening period. This involved 31 families, with identification of 36 further cases. The distribution of incident EB subtypes was: simplex 31 (65%), junctional 1 (2%), dystrophic 12 (25%) and acquisita 4 (8%). The incidence rate of new cases of EB diagnosed per year is 1.4/million and prevalence of all forms estimated at 32/million. The prevalence of simplex, junctional and dystrophic forms is 28, 0.7 and 3/million, respectively.