BACKGROUND:Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis characterized by skin fragility and systemic complications, including anemia, inflammation, and nutritional deficiencies. The prevalence and age of onset of monitoring laboratory tests remain poorly defined in the current literature. OBJECTIVE:To characterize the frequency of nutritional deficiencies and earliest age of laboratory abnormalities in a cohort of RDEB patients. METHODS:A retrospective chart review of 122 patients with RDEB seen at a tertiary care EB center (2010-2021) was conducted. Laboratory and anthropometric data from initial visits were stratified by age group and compared to institutional reference ranges. RESULTS:Inflammatory markers were frequently elevated: C-reactive protein (CRP) (100%, 74/74) and ESR (81%, 71/88), including in patients < 2 years. Anemia (86%, 98/114) and iron deficiency (84%, 80/95) were highly prevalent. Hypoalbuminemia was present in 69% of patients (77/112), particularly among those younger than 16 years. Thrombocytosis occurred in 41% (49/120). Anthropometric measures revealed early declines in weight-for-age and height-for-age percentiles and persistently low BMI. Mean height-for-age percentile decreased sharply from the 61st to the 30th %ile between ages 0-1.99 and 2-3.99 years. Vitamin D deficiency (using a 30 ng/mL cutoff) affected 49% (44/90), especially those > 8 years. Zinc and carnitine levels declined with increasing age, but the majority of patients had values within normal limits. Magnesium, selenium, phosphorus, and thyroid studies were within normal limits for most patients. CONCLUSIONS:Nutritional, hematologic, and inflammatory abnormalities are common and often present, even in infancy, among patients with RDEB. These findings underscore the need for standardized, age-specific laboratory monitoring protocols beginning in early childhood. Early recognition of and intervention for abnormalities may improve long-term outcomes in this medically complex population.

Epidermolysis bullosa with associated pyloric atresia (EB-PA) is a rare subtype of epidermolysis bullosa with a high mortality characterized by skin fragility, pyloric atresia, as well as renal and ureteral abnormalities. We present a unique case of EB-PA in a newborn male further complicated by esophageal atresia and nephrotic syndrome. We review the previously reported nine cases of EB-PA with esophageal atresia. However, to our knowledge, this case represents a previously unreported phenotype of EB-PA with esophageal atresia and nephrotic syndrome.

BACKGROUND:Epidermolysis bullosa (EB) is a rare genetic condition characterized by skin and mucosal fragility. The clinical phenotype is highly variable. Severe types and subtypes, such as junctional EB (JEB), kindler EB (KEB), and recessive dystrophic EB (RDEB), are considered to present a high risk of oral health problems, including malocclusions. Despite this, the literature on orthodontic treatment in patients with EB is scarce and is limited to a few case reports. OBJECTIVE:To provide the users with information on the current best practices for orthodontic and dentofacial orthopedic diagnosis and treatment for patients with EB. METHODS:Current information regarding orthodontic treatment in patients with EB was identified based on a systematic literature review. A panel of experts was invited to provide additional information based on their experience through an open-ended form. Later, a Delphi study was performed over two rounds with a consensus threshold at 75%. Members of the medical team and patient representatives revised the final document. RESULTS:The panel (n = 12) agreed on a total of 15 recommendations, divided into three categories: general information on EB and orthodontics; orthodontic diagnosis and orthodontic treatment. A fourth category on perspectives was developed based on the feedback provided by non-dental members of the medical team (n = 4) and patients (n = 2). CONCLUSIONS:Orthodontic treatment guidelines for patients living with EB are presented, including general aspects of EB, orthodontic diagnosis, and orthodontic treatment.

BACKGROUND:Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic disorder caused by pathogenic variants in COL7A1. OBJECTIVES:To determine the association between different COL7A1 variants and clinical disease severity in 236 North American patients with RDEB. METHODS:Published reports or in silico predictions were used to assess the impact of pathogenic variants in COL7A1 on type VII collagen (C7) protein function. Three impact categories were postulated: genotypes that would be likely to cause a low impact on C7 function (splice B/missense, missense/missense); a medium impact [premature termination codon (PTC)/splice B, splice A/splice B, PTC/missense, splice A/missense, splice B/splice B]; and a high impact (PTC/PTC, PTC/splice A, splice A/splice A). Splice A variants are predicted to cause downstream PTCs, while splice B variants cause in-frame exon skipping and are therefore less deleterious. RESULTS:The severity of functional impact was significantly associated with a history of gastrostomy tube placement, oesophageal dilation, hand surgery, anaemia, renal disease, chronic wounds, diffuse skin involvement and a history of squamous cell carcinoma. The odds of death were 3.5 time higher in the high-impact vs. medium-impact group (95% confidence interval 1.24-8.50; P = 0.02). Patients in the high-impact group had worse clinical outcomes. CONCLUSIONS:Functional genotype categories are a feasible approach to risk-stratify patients based on predicted C7 function.

Patients with dystrophic epidermolysis bullosa have pathogenic variants in COL7A1, leading to skin fragility. Beremagene geperpavec-svdt (B-VEC) is a modified, herpes simplex virus type 1-based gene therapy vector that topically delivers COL7A1 to dystrophic epidermolysis bullosa wounds. In a phase III study, B-VEC significantly improved wound healing at 3 and 6 months compared with placebo. We aimed to evaluate the safety and tolerability of B-VEC beyond 6 months in patients with dystrophic epidermolysis bullosa. An open-label extension study was conducted with 47 subjects (24 rollover from phase III; 23 treatment naïve) receiving B-VEC weekly to target wound areas for up to 112 weeks (median 81 weeks). Safety was assessed by adverse events. Treatment satisfaction and quality of life were assessed with patient-reported outcomes as exploratory measures of efficacy. Selected wounds from phase III rollover subjects were assessed for closure. Thirty-five subjects (74.5

A patient with woolly hair nevus syndrome, presented with epidermal facial nevi by the age of 12 years. Despite transient improvement with topical 1% sirolimus cream, the facial nevus grew larger. The patient was then treated with topical 1% everolimus cream resulting in a reduction in the size of the nevus. This case highlights a novel use of topical 1% everolimus cream, which previously has not been used to treat epidermal nevi.

Emily S. Gorell has worked as a consultant for Abeona Therapeutics, Krystal Biotech, and Amryt Pharma (now Chiesi Global Rare Diseases). No other conflicts of interest to report. Data for this manuscript is available from the corresponding author upon reasonable request.

BACKGROUND:Epidermolysis bullosa (EB), characterized by skin fragility and blistering, often requires hospitalization. Training for inpatient management of EB is limited, with no unified recommendations available in North America. OBJECTIVE:To develop consensus-derived best practices for hands-on inpatient management of EB in both the neonatal and postneonatal period. METHODS:A modified Delphi method (expert-based input via 2 surveys and a final review) was implemented. Available guidelines from EB Clinical Research Consortium centers were analyzed to determine areas of focus and formulate statements to be voted on by EB Clinical Research Consortium members, experienced EB nurses, and select family members. Study participants evaluated statements using a Likert scale: statements with at least 70% agreement were accepted; statements with 30% or more disagreement were rejected. RESULTS:Ten areas of focus were identified. Delphi participants included 15 dermatologists, 8 nurses, and 6 nonhealth care caregivers. Consensus was established on 103/119 neonatal statements and 105/122 postneonatal statements; no statements were rejected. Most recommendations applied to both age groups. LIMITATIONS:Recommendations may require adjustment based on individual patient's clinical context. CONCLUSION:Using the Delphi method, a consensus-derived resource for hospital-based health care professionals who manage patients with EB has been developed to improve the quality of inpatient care.

BACKGROUND/PURPOSE:Dystrophic epidermolysis bullosa (DEB), a rare genetic skin disease caused by loss-of-function mutations in COL7A1, the gene encoding type VII collagen (COL7), is characterized by skin blistering, scarring, and extracutaneous manifestations that markedly reduce patient quality-of-life. Beremagene geperpavec-svdt ('B-VEC') is a gene therapy employing a non-integrating, replication-defective herpes simplex virus type 1 (HSV-1)-based vector encoding two copies of full-length human COL7A1 to restore COL7 protein after topical administration to DEB wounds. B-VEC was approved in the United States in 2023 as the first topical gene therapy and the first approved treatment for DEB. However, few providers have experience with use of this gene therapy.METHODS:Data was obtained through literature review and the experience of providers who participated in the B-VEC clinical study or initiated treatment after B-VEC approval.RESULTS:This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient's home.CONCLUSIONS:By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

The primary objective was to assess pain catastrophizing and functional disability in pediatric patients with epidermolysis bullosa (EB) and their parents/guardians. Secondary objectives included examining relationships between pain catastrophizing, functional disability, and correlations with other factors (e.g., age, disease severity, and percent of body surface area (BSA) involved).

Background Epidermolysis bullosa (EB) is a group of rare genetic skin conditions that result in skin fragility. EB can be quite severe with chronic inflammation and malnutrition impairing growth and pubertal development. These factors have potential consequences for skeletal health. We aimed to determine the prevalence of delayed puberty and low bone mineral density (BMD) for age in children and young adults with EB. Methods Electronic medical records (EMR) of patients with confirmed EB <30 years of age at time of initial encounter at Cincinnati Children's Hospital Medical Center between January 1, 2010 and September 30, 2020 were reviewed. Natural language processing software was used to categorize pubertal status of patients with EB as early, normal or delayed. BMD was measured by dual energy x-ray absorptiometry and categorized as low if height adjusted Z-score was <-2.0 using age, sex and race specific reference ranges. Results 29% of individuals with EB had low BMD with most cases occurring prior to 10 years of age. Of patients who reached adolescence, 23% failed to develop any signs of puberty in the normal range (before age 13 in females or 14 in males) and BMD Z-scores further declined in these individuals. Conclusion Delayed puberty is an under-recognized comorbidity of individuals with EB, especially in those with recessive dystrophic EB, and can have a significant impact on BMD.

Background and Objectives: To describe the prevalence, severity, and management of anemia in a cohort of children with recessive dystrophic epidermolysis bullosa (RDEB) and to highlight the use of soluble transferrin receptor (sTfR) to diagnose iron deficiency in this chronic inflammatory state. Methods: We studied a cohort of 114 patients with RDEB followed at a pediatric hospital-based Epidermolysis Bullosa Center from 2010 to 2020; data were prospectively tracked in a comprehensive clinical database that captured all visits, laboratory tests, iron infusions, and transfusions. The primary outcome was occurrence of anemia, which was assessed by age and sex, with and without transfusion support. Secondary outcomes included iron status using a combination of ferritin and sTfR levels, the cumulative incidence of parenteral iron therapy and transfusions, and survival. Results: In RDEB, anemia begins in the first year of life and becomes more frequent and severe with age. The prevalence of iron deficiency anemia (IDA) estimated by ferritin was 33.6% (37/110), but the sTfR/log(10)-ferritin ratio indicated a 1.5-fold higher true prevalence of IDA of 50.6% (41/81). 53.5% (61/114) received parenteral iron infusions, transfusions, or both. Higher ferritin was associated with earlier mortality. Conclusions: Individuals with RDEB have a high burden of anemia (IDA and anemia of inflammation) that requires frequent medical interventions. The sTfR/log(10)-ferritin ratio improves the detection of iron deficiency in the context of inflammation and guides therapy.

BACKGROUND:Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling.OBJECTIVE:To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB.METHODS:A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal.RESULTS:A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%).LIMITATIONS:Retrospective design.CONCLUSIONS:Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Importance A comprehensive, user-friendly system to assess global ichthyosis disease burden is imperative to improving the care of patients with ichthyosis, identifying appropriate participants for clinical trials, and quantifying treatment outcomes. To our knowledge, there is currently no validated scale to objectively and systematically measure ichthyosis severity across the entire body. Objective To create and evaluate a comprehensive and user-friendly instrument to measure total body ichthyosis severity in adults and children. Design, Setting, Participants In this qualitative study, ichthyosis experts participated in the content development of the Ichthyosis Scoring System (ISS). The body was divided into 10 regions, and Likert scales (0-4) were created to quantify scale and erythema, with extensive descriptors and photographic standards. An 83-image teaching set was created from photographs of participants with ichthyosis. Two cohorts of dermatologists (11 total) independently scored all test photographs twice to evaluate interrater and intrarater reliabilities. Participants were enrolled worldwide from referral centers and patient advocacy groups. Participants of all ages, races, and ethnicities were included in the creation of ISS, and dermatologists with varying experience and areas of expertise participated as raters to evaluate the ISS. The study was conducted from 2019 to 2021, and the data were analyzed in 2021. Main Outcomes and Measures Intraclass correlation coefficients determined overall reliabilities. Results Across both cohorts of 11 dermatologists in total, the intraclass correlation coefficients for total, scale and erythema scores were greater than 0.90 (95% CI, 0.77-0.97), greater than 0.91 (95% CI, 0.79-0.98), and greater than 0.88 (95% CI, 0.72-0.97), respectively. Most body sites exhibited moderate to good interrater reliabilities for scale and erythema. Intrarater reliabilities were good to excellent. Conclusions and Relevance The results of this qualitative study demonstrate reproducibility and suggest that the ISS is a reliable system to measure global ichthyosis severity in adults and children.