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Background: Genome diagnostics is considered gold standard diagnostics for epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous group of rare disorders characterized by blistering and wounding of mucocutaneous tissues. EB is caused by pathogenic variants in genes encoding proteins of the dermo‐epidermal junction. Accurate genetic diagnosis of EB is crucial for prognostication, counselling and precision‐medicine. Genome diagnostics for EB started in 1991 with the introduction of Sanger sequencing (SS), analysing one gene at a time. In 2013, SS was superseded by next‐generation sequencing (NGS), that allow for high‐throughput sequencing of multiple genes in parallel. Several studies have shown a beneficial role for NGS in EB diagnostics, but its true benefit has not been quantified. Objectives: To determine the benefit of NGS in EB by systematically evaluating the performance of different genome diagnostics used over time based on robust data from the Dutch EB Registry. Methods: The diagnostic performances of SS and NGS were systematically evaluated in a retrospective observational study including all index cases with a clinical diagnosis of EB in whom genome diagnostics was performed between 01 January 1994 and 01 January 2022 (n = 308), registered at the Dutch EB Expertise Centre. Results: Over time, a genetic diagnosis was made in 289/308 (94%) EB cases. The diagnostic yield increased from 89% (SS) to 95% (NGS). Most importantly, NGS significantly reduced diagnostic turnaround time (39 days vs. 211 days, p < 0.001). The likelihood of detecting variants of uncertain significance and additional findings increased from 5% and 1% (SS) to 22% and 13% (NGS) respectively. Conclusions: Our study quantifies the benefit of NGS‐based methods and demonstrate they have had a major impact on EB diagnostics through an increased diagnostic yield and a dramatically decreased turnaround time (39 days). Although our diagnostic yield is high (95%), further improvement of genome diagnostics is urgently needed to provide a genetic diagnosis in all EB patients. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Inherited epidermolysis bullosa (EB) comprises a group of genetic disorders characterized by skin fragility and unique oral features. It requires interdisciplinary care from several health professionals, including oral health teams. Modern dentistry encompasses a wide range of therapeutic options performed by specialists from different fields.To guide clinicians caring for patients with different types of EB to seek care from different dental services.Dental treatment needs for patients with EB were identified based on a systematic literature review. A panel of experts was consulted and invited to provide additional information through an open‐ended question over 7 months. A Delphi study was applied over two rounds to the resulting pathways design. The threshold of consensus was set a priori at 75%. Patients' representatives revised the final document.The panel (n = 17) agreed on a total of 55 recommendations divided into six groups according to the severity of oral compromise in EB (52 recommendations were agreed on in round 1, and three were agreed on in round 2).Dental care pathways are presented for each type of EB. Specific considerations are discussed according to clinical features, including age of first referral, frequency of follow‐up appointments, and list of dental specialties involved in the care of patients with EB. [ABSTRACT FROM AUTHOR]

When surgery is performed in patients with EB, risks of blisters and epidermal detachment are always present. The Heineke‐Mikulicz pyloroplasty cannot always be performed because of anatomical constraints. In such cases, it is necessary to select a more time‐consuming surgical procedure (i.e., Roux‐en‐Y gastrojejunal anastomosis) with adequate fluid management. [ABSTRACT FROM AUTHOR]

Dystrophic epidermolysis bullosa (DEB) is a rare, but severe, subtype of epidermolysis bullosa. It is characterized mainly by blisters and miliary rashes of the skin, while oral mucosa‐dominated cases are extremely rare. Here, we report the characteristics of oral mucosa lesions in a Chinese familial case of DEB with a novel compound heterozygous COL7A1 mutation. We further analyzed the genetic and molecular features of the proband and the two related mutation carriers. Our study further elucidates the genetic and phenotypic heterogeneity of DEB. [ABSTRACT FROM AUTHOR]

The characteristics of epidermolysis bullosa (EB) demand higher than average provider support for transition from pediatric to adult care. We administered an online Qualtrics survey to members of the Epidermolysis Bullosa Clinical Research Consortium (EBCRC), a group of providers who care for patients with EB, in order to examine their practices and perspectives on transition of care (TOC) and identify barriers to successful implementation. Sixteen of eighteen medical centers completed the survey. Eighty‐eight percent of center representatives expressed concerns about their patients transitioning/transferring from the pediatric to adult‐centered care. Thirty‐eight percent of providers reported having a formal TOC program in place. Our findings support the desire for formal TOC programs, the need for a team‐based approach and, in particular, identification of adult providers to participate in the transition to improve this often challenging time. [ABSTRACT FROM AUTHOR]

The cutaneous microbiome represents a highly dynamic community of bacteria, fungi and viruses. Scientific evidence, particularly from the last two decades, has revealed that these organisms are far from being inconsequential microscopic hitchhikers on the human body, nor are they all opportunistic pathogens waiting for the chance to penetrate the skin barrier and cause infection. In this review, we will describe how dermatological diseases have been found to be associated with disruptions and imbalances in the skin microbiome and how this new evidence had shaped the diagnosis and clinical practice relating to these disorders. We will identify the microbial agents which have been found to directly exacerbate skin diseases, as well as those which can ameliorate many of the symptoms associated with dermatological disorders. Furthermore, we will discuss the studies which suggest that bacteriotherapy, either by topical use of probiotics or by bacteria‐derived compounds, can rectify skin microbial imbalances, thereby offering a promising alternative to antibiotic treatment and reducing the risks of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and the metastatic disease is associated with poor prognosis. Cancer‐associated fibroblasts (CAFs) promote progression of cancer, but their role in cSCC is largely unknown. We examined the potential of CAF markers in the assessment of metastasis risk and prognosis of primary cSCC. We utilized multiplexed fluorescence immunohistochemistry for profiling CAF landscape in metastatic and non‐metastatic primary human cSCCs, in metastases, and in premalignant epidermal lesions. Quantitative high‐resolution image analysis was performed with two separate panels of antibodies for CAF markers and results were correlated with clinical and histopathological parameters including disease‐specific mortality. Increased stromal expression of fibroblast activation protein (FAP), α‐smooth muscle actin, and secreted protein acidic and rich in cysteine (SPARC) were associated with progression to invasive cSCC. Elevation of FAP and platelet‐derived growth factor receptor‐β (PDGFRβ) expression was associated with metastasis risk of primary cSCCs. High expression of PDGFRβ and periostin correlated with poor prognosis. Multimarker combination defined CAF subset, PDGFRα−/PDGFRβ+/FAP+, was associated with invasion and metastasis, and independently predicted poor disease‐specific survival. These results identify high PDGFRβ expression alone and multimarker combination PDGFRα−/PDGFRβ+/FAP+ by CAFs as potential biomarkers for risk of metastasis and poor prognosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Genetic testing is the gold standard for diagnosing different epidermolysis bullosa (EB) subtypes; however, testing rates are low. We conducted a pilot study to test feasibility of a novel, home‐based registry that involved patients with EB submitting self‐reported clinical symptoms using secure, online surveys (REDCap) and submitting buccal swabs for exome sequencing of EB‐related genes (GeneDx). In total, 50 EB participants were enrolled, with an average age of 17 years and an average distance of 198 miles from EB specialty centers. All buccal swabs (N = 24) provided sufficient DNA for sequencing without causing mucosal trauma and 80% of participants were found to have pathogenic variants in COL7A1, the gene mutated in DEB. Participants with recessive dystrophic EB (RDEB) reported a higher prevalence of esophageal dilations (65.7% vs. 0%, p =.009) and mitten deformities of the feet (57.1% vs. 0%, p =.047) compared to non‐RDEB participants. [ABSTRACT FROM AUTHOR]

The pemphigoid disease epidermolysis bullosa acquisita (EBA) is an autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7), immune cell infiltrates at the dermal–epidermal junction and subepidermal blistering. Proteases, particularly granzyme B (GzmB), have been established as therapeutic targets for the treatment of EBA and other pemphigoid diseases. We investigated the impact of the novel GzmB inhibitor SNT‐6935 on anti‐COL7 IgG‐induced subepidermal blistering in a well‐established EBA ex vivo model. Our findings demonstrate that pharmacological targeting of GzmB with its selective inhibitor SNT‐6935 significantly reduced autoantibody‐induced dermal–epidermal separation in human skin cryosections. Interestingly, treatment of skin cryosections with recombinant human GzmB alone did not cause dermal–epidermal separation, suggesting that additional mechanisms alongside GzmB are required for tissue damage in EBA. In conclusion, our study highlights the significant contribution of GzmB to the pathogenesis of EBA and supports the notion of GzmB as a therapeutic target in EBA and other pemphigoid diseases. [ABSTRACT FROM AUTHOR]

This document is an interview with Professor John McGrath, a prominent figure in the field of dermatology and venereology. The interview provides information about McGrath's academic education, professional career, memberships in various societies, and awards and honors he has received. McGrath discusses his journey into dermatology, his most important teachers and mentors, his best publications, and his achievements and disappointments in his professional life. He also shares his thoughts on the future of dermatology, the next breakthroughs in the field, and offers advice to younger colleagues. [Extracted from the article]

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

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross‐sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1–67 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analysed the interrelationship of infection history, standard inflammatory markers, systemic cytokines and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C‐reactive protein as an excellent biomarker for disease severity in RDEB. A type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4/IL13 pathways as potential evidence‐based therapeutic targets. Moreover, the complete inflammatory scenario aligns with Staphylococcus aureus virulence mechanisms. Concurrently, abnormalities in IgG, IgE and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB. [ABSTRACT FROM AUTHOR]

Split paw pad disease is a scarcely defined phenotype characterized by skin lesions on the paw pads of dogs. We studied a family of German Shepherd dogs, in which four dogs developed intermittent paw pad lesions and lameness. The paw pads of two of the affected dogs were biopsied and demonstrated cleft formation in the stratum spinosum and stratum corneum, the outermost layers of the epidermis. Whole genome sequencing data from an affected dog revealed a private heterozygous 18 bp in frame deletion in the KRT5 gene. The deletion NM_001346035.1:c.988_1005del or NP_001332964.1:p.(Asn330_Asp335del) is predicted to lead to a loss of six amino acids in the L12 linker domain of the encoded keratin 5. KRT5 variants in human patients lead to various subtypes of epidermolysis bullosa simplex (EBS). Localized EBS is the mildest of the KRT5‐related human diseases and may be caused by variants affecting the L12 linker domain of keratin 5. We therefore think that the detected KRT5 deletion in dogs represents a candidate causal variant for the observed skin lesions in dogs. However, while the clinical phenotype of KRT5‐mutant dogs of this study closely resembles human patients with localized EBS, there are differences in the histopathology. EBS is defined by cleft formation within the basal layer of the epidermis while the cleft formation in the dogs described herein occurred in the outermost layers, a hallmark of split paw pad disease. Our study provides a basis for further studies into the exact relation of split paw pad disease and EBS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This document is an interview with Professor Leena Bruckner-Tuderman, a pioneer in the field of Dermatology and Venereology. The interview provides information about her academic education, professional career, memberships in various societies, awards and honors she has received, and her achievements and disappointments in her professional life. Professor Bruckner-Tuderman also discusses her interests outside of dermatology, her predictions for the future of the field, and the message she wants to give to younger colleagues. [Extracted from the article]

Gene therapy based on the CRISPR/Cas9 system has emerged as a promising strategy for treating the monogenic fragile skin disorder recessive dystrophic epidermolysis bullosa (RDEB). With this approach problematic wounds could be grafted with gene edited, patient‐specific skin equivalents. Precise gene editing using homology‐directed repair (HDR) is the ultimate goal, however low efficiencies have hindered progress. Reframing strategies based on highly efficient non‐homologous end joining (NHEJ) repair aimed at excising dispensable, mutation‐harboring exons offer a promising alternative approach for restoring the COL7A1 open reading frame. To this end, we employed an exon skipping strategy using dual single guide RNA (sgRNA)/Cas9 ribonucleoproteins (RNPs) targeted at three novel COL7A1 exons (31, 68, and 109) containing pathogenic heterozygous mutations, and achieved exon deletion rates of up to 95%. Deletion of exon 31 in both primary human RDEB keratinocytes and fibroblasts resulted in the restoration of type VII collagen (C7), leading to increased cellular adhesion in vitro and accurate C7 deposition at the dermal‐epidermal junction in a 3D skin model. Taken together, we extend the list of COL7A1 exons amenable to therapeutic deletion. As an incidental finding, we find that long‐read Nanopore sequencing detected large on‐target structural variants comprised of deletions up to >5 kb at a frequency of ~10%. Although this frequency may be acceptable given the high rates of intended editing outcomes, our data demonstrate that standard short‐read sequencing may underestimate the full range of unexpected Cas9‐mediated editing events. [ABSTRACT FROM AUTHOR]

Self‐improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self‐improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self‐improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases. [ABSTRACT FROM AUTHOR]

The article discusses a case of systemic amyloidosis presenting with blisters as the primary skin manifestation. The patient had various symptoms, including chronic diarrhea, postural hypotension, and weight loss, leading to a diagnosis of stage II AL amyloidosis. Early detection of systemic amyloidosis is crucial for timely treatment and preventing organ damage. Dermatologists should consider amyloidosis as a possible differential diagnosis for vesiculobullous diseases to facilitate early management. [Extracted from the article]

The article discusses a case of alopecic and eroded scalp plaque in a newborn female, diagnosed as erosive pustular dermatosis of the scalp (EPDS). EPDS is an inflammatory disease typically seen in elderly individuals but can also occur in pediatric cases. The condition may manifest after trauma, surgery, or other skin injuries, leading to scarring alopecia. Treatment with topical corticosteroids was effective in this case, emphasizing the importance of early recognition and intervention in such cases. [Extracted from the article]

ABSTRACT Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by fragility of the skin and mucous membranes due to alterations in the dermal epidermal junction. This condition manifests as mechanically induced bullous lesions that heal with hypertrophic granulation tissue and/or atrophic scars. Here, we report two brothers carrying a homozygous LAMB3 missense variant, p.Gly254Asp, which affects the N‐terminal end of the laminin‐332 (LM332) β3 chain, previously described in another JEB family sharing a common ethnic origin and LAMB3 haplotype with the siblings reported here. Moreover, all affected patients with p.Gly254Asp mutation from both families exhibits a distinct phenotype consisting of a few localized long‐standing skin lesions characterized by excessive granulation tissue formation or keloid scars, without new blistering, and associated with amelogenesis imperfecta. Our patients also showed nail dystrophy, expanding the phenotypic spectrum and confirming the peculiar role of the N‐terminal end of the β3 chain in regulating the granulation tissue response associated with the wound healing process. [ABSTRACT FROM AUTHOR]

Objective: Although Ireland has one of the highest levels of well‐being in Europe, having a health condition has been found to have a direct negative impact. The aim of this study is to evaluate the current situation and the experiences of patients with epidermolysis bullosa (EB), a rare genetic skin disease, and their relatives living in Ireland, with a focus on burdens and helpful practices. Methods and Measures: In a mixed‐methods design, a series of standardised questionnaires were combined with open‐ended questions. Via an online survey, data from n = 59 EB patients and relatives of EB patients living in Ireland were collected. Results: EB affects both the patients and their relatives. Burdens were found in relation to the visibility of EB, the degree of severity, the current health status, reduced mobility, the financial impact of EB, the psychosocial impact and personal and social resources. The paper also analyses existing resources and highlights opportunities for support and needs of improvement. Conclusion: Quality of life with EB is influenced by somatic symptoms and the psychosocial burden. Individual helpful practices in dealing with this rare disease can be considered as mediators, but they need to be supported by structural and healthcare improvements. Patient or Public Contribution: The perspective of EB patients, their relatives and EB experts were taken into account in the development of the study design via two feedback loops with the EB patient organisations DEBRA Ireland and DEBRA Austria. The design was adapted accordingly. Additionally, by including open‐ended questions, patients and relatives could contribute their individual perspectives and add insights into their lives with EB that might not have been captured with the structured online survey alone. [ABSTRACT FROM AUTHOR]

Nutritional compromise, low levels of vitamin D, chronic inflammation, abnormal growth, and physical inactivity affect bone metabolism and compromise long‐term bone health in individuals with epidermolysis bullosa (EB). The result is a high risk for osteopenia, osteoporosis, and pathologic fractures, but this important consequence of EB has been the focus of few investigations. Our scoping review found 21 publications that assessed the current understanding and clinical practices for monitoring of osteoporosis and its treatment in EB. Recommendations summarized from 13 of these publications include early nutritional and weight assessments before 2 years of age; bloodwork every 6–12 months starting at birth; Tanner stage assessments every 6 months to detect any pubertal delay; DEXA scans starting at age 6 years with repeated scans every 1–2 years, except in mild cases; and vitamin D supplementation of 80–320 IU daily for children 0–7 years and 720 IU for patients >8 years. [ABSTRACT FROM AUTHOR]

Background: Pruritus is a highly burdensome symptom in patients with epidermolysis bullosa, especially recessive dystrophic epidermolysis bullosa (RDEB); however, only a few studies have assessed the molecular pathogenesis of RDEB-associated pruritus. Interleukin (IL)-31 is a key cytokine implicated in pruritus associated with dermatologic diseases such as atopic dermatitis and prurigo nodularis. Objective: To investigate the role and cellular source of IL-31 in RDEB-associated pruritus. Methods: Serum and skin samples were obtained from 11 RDEB patients and 11 healthy controls. Pruritus visual analogue scale scores were determined. Serum levels of IL-31 and thymic stromal lymphopoietin (TSLP) were examined by enzymelinked immunosorbent assay (ELISA). The expression of IL-31 and other pruritus mediators in the skin were examined through immunofluorescence staining, and their correlation with pruritus severity was analysed. Results: Serum IL-31 and TSLP were elevated in RDEB patients. IL-31 expression was increased in RDEB skin and positively correlated with pruritus severity. Most of the IL-31-expressing cells were mast cells, and some were CD206(+) M2-like macrophages. The number of substance P(+) cells was also increased in the patients' skin, and most of them were mast cells. The number of substance P(+) mast cells was correlated with the number of IL-31(+) dermal infiltrates. The number of IL-4Rα-and IL-13-expressing cells and expression of TSLP and periostin increased in RDEB skin, but without a correlation to pruritus score. Conclusion: The increased production of skin IL-31 from mast cells and M2-like macrophages may be the mechanism underlying pruritus in RDEB. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion affecting the skin and mucous membranes, predominantly affects females in their fifth and sixth decades of life. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. PV should always be considered in the differential diagnosis of oral ulcerative and vesiculobullous lesions in both children and adolescents. [ABSTRACT FROM AUTHOR]

Introduction: Epidermolysis bullosa (EB) is a rare genetic disorder characterized by skin fragility and blister formation. The phenotypic presentation is broad with four major types, being Recessive Dystrophic EB (RDEB) the most severe, including oral anomalies such as severe microstomia, ankyloglossia, vestibule obliteration and occlusal anomalies, turning orthodontic treatment into a challenge. Aim: This case report aims to present the comprehensive treatment of a patient with severe RDEB, including periodontal surgery, orthodontic fixed braces with mini‐screws and oral rehabilitation with anterior veneers. Case Report: A 27‐year‐old female patient with severe RDEB received orthodontic treatment in the upper jaw to improve malalignment and anterior crossbite. After 13 months of treatment with fixed appliances, miniscrews were placed in the anterior segment to intrude and procline the upper incisors. Oral surgery was performed to increase the vestibule depth of the upper lip. Once edge‐to‐edge occlusion was obtained, anterior veneers were placed to improve aesthetic and stabilize occlusion, especially with the lack of posterior support. Discussion: The multidisciplinary treatment approach, involving orthodontic treatment, periodontal surgery and oral rehabilitation, played a crucial role in achieving favorable results. This case highlights the successful use of miniscrews as a viable orthodontic approach for patients with severe RDEB. [ABSTRACT FROM AUTHOR]

The article presents the development and validation of two new scoring systems, the Keratosis Pilaris Area Index (KPAI) and the Keratosis Pilaris Investigator Global Assessment (KP-IGA), for assessing the severity of keratosis pilaris (KP). KP is a common skin condition that affects a significant percentage of adolescents and adults, causing keratotic papules and other symptoms. The study involved 15 patients with KP and nine dermatologists/dermatology fellows who assessed the patients using the new scoring systems. Both scores demonstrated high reliability and feasibility, with the KPAI showing excellent reliability. These validated scoring systems can be used in clinical trials to evaluate disease severity and assess the efficacy of new treatments for KP. [Extracted from the article]

A retrospective bicentric study in France evaluated the efficacy of dupilumab, a monoclonal antibody, in treating pruritus (itching) in patients with dystrophic epidermolysis bullosa (DEB). The study included 29 patients with different subtypes of DEB, and the severity of itching and its impact on sleep were assessed using visual analogue scales. The results showed that dupilumab was effective in reducing pruritus severity and improving sleep in most patients, with some variability in response. The treatment was generally well-tolerated, and further studies are needed to confirm these findings. [Extracted from the article]

This clinical correspondence discusses a case of primary urogenital tuberculosis with papulonecrotic tuberculid in a 32-year-old male. The patient presented with recurrent episodes of ulcerations and atrophic scars on the shins, as well as nail deformity. The diagnosis was initially considered to be epidermolysis bullosa acquisita, but further examination revealed ulceration on the penis and a positive Mantoux test. Biopsy results confirmed the presence of caseous granulomas and leukocytoclastic vasculitis. The patient was started on antitubercular therapy and showed improvement after 5 months of follow-up. This case highlights the importance of considering cutaneous tuberculosis in atypical presentations, particularly in countries where tuberculosis is endemic. [Extracted from the article]

Introduction: At a single‐center pediatric hospital, the neurokinin‐1 receptor antagonist aprepitant was used to treat refractory pruritus in epidermolysis bullosa (EB) and atopic dermatitis (AD). Methods: Thirty‐seven patients were included (24 EB patients, 13 AD patients), ages 10 months to 37 years. Results: 58% (14/24) of patients with EB and 85% (11/13) of patients with AD reported aprepitant was effective in decreasing their pruritus, with age‐related differences in efficacy observed in EB patients, and access to the medication by insurance denial or availability of the drug as a barrier to use. Conclusions: Aprepitant shows promise in controlling refractory pruritus in pediatric EB and AD patients and deserves further study. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a patient with severe epidermolysis bullosa acquisita (EBA), a rare autoimmune disease characterized by auto-antibodies against type-VII collagen. The patient had previously tried various treatments without success, but achieved sustained clinical remission (CR) for 5 years after receiving rituximab infusions. Rituximab, a monoclonal antibody targeting B lymphocytes, has shown promise in inducing long-term remission for patients unresponsive to conventional therapies. The article highlights the patient's improvement in symptoms, decrease in disease activity scores, and improved quality of life following rituximab treatment. This case adds to the existing evidence for rituximab as an effective treatment for severe EBA. [Extracted from the article]

This article discusses the phenotypic differences between two brothers with junctional epidermolysis bullosa (JEB) caused by homozygous LAMC2 mutations. The brothers' parents are carriers of the same LAMC2 variant, and they share a cousin who died from JEB. The elder brother had a more severe phenotype and died at the age of 24, while the younger brother has a milder phenotype at the age of 28. Further genetic testing revealed a variant in the COL17A1 gene that may act as a modifier of the disease. The article also mentions previous research on the phenotypic variation of EB and the effect of genetic modifiers on the disease. [Extracted from the article]

The Indian Association of Dermatologists, Venereologists, and Leprologists (IADVL) has established the I-CuReD registry in India to collect data on rare skin disorders. The registry has recorded 323 patients with genodermatoses, with epidermolysis bullosa and congenital ichthyosis being the most common diseases. The article provides detailed information on the demographics, symptoms, and diagnostic methods used for these patients. The study found a lower number of cases compared to other countries and highlights the need for further research in this area. The authors acknowledge the limitations of their study and hope for more comprehensive studies in the future. [Extracted from the article]

This document is a letter to the editor discussing the evaluation of the antipruritic effects of serlopitant, a neurokinin 1 receptor antagonist, in patients with epidermolysis bullosa (EB). Pruritus, or itching, is a significant symptom in EB, and current treatments are not effective in relieving itch. A previous pilot study showed that serlopitant reduced itch compared to a placebo. In this phase 2 randomized controlled trial, serlopitant was further evaluated, and although the sample size was small, some participants experienced a reduction in itch. The study suggests that neurokinin 1 receptor antagonists may be worth considering for the treatment of EB-related pruritus, but larger studies are needed. [Extracted from the article]

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL‐6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL‐6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL‐6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll‐like receptor (TLR) ligands, pathogen‐associated and damage‐associated molecular pattern molecules. In vitro, TLR ligands induced IL‐6 expression via NF‐κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL‐6 via TLR1/2 and NF‐κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR‐mediated persistent skin inflammation might increase the risk of IL‐6‐related systemic complications, including RDEB. [ABSTRACT FROM AUTHOR]

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

Key Clinical Message: Bart Syndrome, characterized by congenital skin absence, blistering, and nail abnormalities, presents complex neonatal challenges. This rare condition demands a multidisciplinary approach for accurate diagnosis and comprehensive care. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a heritable skin blistering disease caused by variants in genes coding for proteins that secure cell–cell adhesion and attachment of the epidermis to the dermis. Interestingly, several proteins involved in inherited EB are also associated with autoimmune blistering diseases (AIBD). In this study, we present a long‐term follow‐up of 15 patients suffering from recessive dystrophic or junctional EB. From these patients, 62 sera were analysed for the presence of autoantibodies associated with AIBD. We show that patients suffering from recessive dystrophic EB (RDEB) are more susceptible to developing autoantibodies against skin proteins than patients suffering from junctional EB (70% vs. 20%, respectively). Interestingly, no correlation with age was observed. Most patients showed reactivity to Type XVII collagen/linear IgA bullous dermatosis autoantigen (n = 5; 33%), followed by BP230 (n = 4; 27%), Type VII collagen (n = 4; 27%) and laminin‐332 (n = 1; 7%). The pathogenicity of these autoantibodies remains a subject for future experiments. [ABSTRACT FROM AUTHOR]

Background: Epidermolysis bullosa (EB) is a group of rare, congenital skin disorders, characterized by skin fragility and formation of blisters. The gross motor outcomes of children with EB are not known. Objectives: The primary objective of the study was to measure the proportion of gross motor delay in children with EB. The secondary objectives were to measure the difference in gross motor outcomes between EB sub‐types and change in gross motor outcomes over time. Methods: Children with EB, aged between one month and five and a half years of age, attending the Sydney Children's Hospital, Epidermolysis Bullosa Clinic, were eligible. Carers completed Ages and Stages Questionnaires, Third Edition, on behalf of their children. Questionnaires were scored, and outcomes were compared to age‐expected norms. Results: There were 24 participants to complete a questionnaire. Eleven participants completed additional questionnaires over the 24 month study duration. The proportion of children with EB with gross motor delay was greater than age‐expected norms (29.17% vs. 2.5%). The delay occurred in children with recessive dystrophic (80%) and epidermolysis bullosa simplex (33.33%) sub‐types, but not dominant dystrophic (0%). No children with Junctional EB or Kindler EB joined this study. Conclusions: This study demonstrates a difference in gross motor outcomes in children with EB. Children with recessive dystrophic and epidermolysis bullosa simplex should be prioritized for monitoring of, and intervention for, gross motor outcomes through multidisciplinary care. Further research investigating long‐term outcomes for children with EB and the effectiveness of interventions would be beneficial. [ABSTRACT FROM AUTHOR]

This article reports on two sisters with recessive dystrophic epidermolysis bullosa (RDEB) caused by novel variants in the COL7A1 gene. The sisters experienced symptoms such as intense cutaneous pruritus, skin blistering, erosion, and ulceration on their hands and feet, as well as nail dystrophy. Whole-exome sequencing revealed two heterozygous variants in COL7A1, which were inherited from their parents and segregated with the phenotype in the family. These variants were classified as uncertain significance but were believed to affect the fibronectin III-like domains in the NC-1 domain of the protein, resulting in a milder phenotype. This study contributes to the understanding of genotype-phenotype correlation in RDEB. [Extracted from the article]

This article discusses two cases of palmoplantar keratoderma, a skin condition characterized by thickened and hardened skin on the palms and soles. The patients presented with linear distribution of verrucous and keratotic plaques on their hands, feet, and other areas of the body. Genetic analysis revealed pathogenic variants in the HRAS gene, which is associated with various skin disorders. The article suggests that the clinical presentation of HRAS-associated nevus (HAN) can vary widely, from isolated linear palmoplantar keratoderma to widespread lesions covering the skin in a mosaic pattern. [Extracted from the article]

This article discusses a novel enzyme-linked immunosorbent assay (ELISA) system for the diagnosis and monitoring of anti-integrin β4 mucous membrane pemphigoid (MMP). MMP is an autoimmune blistering disease that primarily affects mucous membranes. The ELISA system utilizes the epidermal basement membrane zone protein complex derived from keratinocytes and can detect autoantibodies targeting integrin β4. The study presents a case of a patient with MMP and demonstrates the potential of the ELISA system to detect and quantify MMP autoantibodies and monitor disease activity. [Extracted from the article]

Epidermolysis bullosa (EB) is a group of inherited blistering disorders that primarily affect the skin and mucous membranes of the digestive tract, which can lead to poor nutritional status. Dietary supplements and nutritional support methods, such as nasogastric tubes and gastrostomy, have been employed to improve the nutritional status of patients with EB; however, few foods are suitable for enjoyable eating with family and friends. Here, we introduce a nutritionally balanced, melt‐in‐the‐mouth chocolate called andew, which was specifically designed for patients with EB. The andew chocolate is nutritionally superior and melts more easily than traditional chocolates, thus it is suitable for patients with EB, who are prone to oral erosions. Patients responded more favorably to the taste and texture of andew than to those of other dietary supplements. Not only does andew provide nutritional benefits, but it also promotes enjoyable eating with family members and friends, which could positively impact patients' mental health. [ABSTRACT FROM AUTHOR]

Background: Inherited epidermolysis bullosa (EB) is a group of genodermatoses with considerable clinical and genetic heterogeneity. Clinical diagnosis of the EB subtypes is frequently imprecise and requires confirmation with genetic testing. There is still limited study using genetic testing to identify EB subtypes in Indonesia. This study aims to identify the pathogenic variants of inherited EB patients at the Department of Dermatology and Venereology, Universitas Padjadjaran—Dr Hasan Sadikin General Hospital in Bandung, West Java, Indonesia and to describe the correlation between the phenotype and genotype of our patients. Methods: Twelve patients clinically diagnosed with EB were included in this study. Genetic testing was performed in collaboration with KK Women's and Children's Hospital, Singapore. Results: Pathogenic variants were identified in the COL7A1 gene in seven patients, namely Dominant Dystrophic EB (DDEB) with mutation types c.5945G>T, c.6218G>A, Recessive Dystrophic EB (RDEB) c.2005C>T, c.6081dup, c.1268C>T, c.1784C>T which are all known mutations. Novel mutations were found in the COL7A1 gene in two patients namely DDEB c.6253G>T and RDEB c.6740C>T. Two EB Simplex (EBS) patients showed mutation KRT14 gene as c.356T>C, c.373C>T which are known mutation. In addition, a novel mutation in LAMA3 gene c.2649del was found in one Junctional EB (JEB) patient. Conclusion: The molecular diagnoses of 12 Indonesian EB patients were identified, of which three were novel pathogenic variants. Concordance between the initial clinical diagnosis and genetic testing was only 33%. This demonstrated the importance of early genetic testing for accurate diagnosis, prognostication, management and genetic counselling. [ABSTRACT FROM AUTHOR]

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano‐technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in‐depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody‐ (I‐III), cell‐mediated (IVa‐c), tissue‐driven mechanisms (V‐VI) and direct response to chemicals (VII). Types I‐III are linked to classical and newly described clinical conditions. Type IVa‐c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V‐VI involve epithelial barrier defects and metabolic‐induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime. [ABSTRACT FROM AUTHOR]

Background: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal‐epidermal junction, EB is sub‐classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB‐associated genes reported to date. Methods: We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds. Results: The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14‐associated EBS as compared to EBS due to KRT5 mutations (p <.05). Mutations in COL17A1 and laminin 332‐encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332‐associated JEB (p <.05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p <.001). Conclusions: EB patients of Middle Eastern origin were found to feature specific phenotype–genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region. [ABSTRACT FROM AUTHOR]

Background: Dystrophic epidermolysis bullosa (DEB) is a subtype of an inherited skin disorder characterized by skin and mucosal fragility due to collagen VII (COL7A1) gene mutations. Esophageal strictures leading to chronic dysphagia and acute episodes are well recognized complications within this subtype. Sloughing of esophageal mucosa and the treatment of this emergency have heretofore received limited attention in the EB literature. Methods: We retrospectively reviewed the electronic medical records of the patients who had an acute episode of sloughing of the esophageal lining between 2008 and 2021 and extracted the information regarding their clinical presentation and management. Results: Six patients out of 210 with recessive DEB severe (RDEB‐S) (n = 4), RDEB intermediate (RDEB‐I) (n = 1) and dominant DEB (DDEB) (n = 1) were identified. The mean age at the time of the episode was 2.7 years. All patients had early‐onset severe gastroesophageal reflux. Clinically, they presented with a coughing episode (n = 6), hematemesis (n = 6), vomiting (n = 6), and choking (n = 3), followed by coughing up a string like tissue of variable length, part of the esophageal mucosal lining. Four patients recovered with medical management only, two patients required gastrostomy insertions for feeding due to severe persistent dysphagia and one also required a Nissen's fundoplication to manage severe reflux. One patient had aspiration pneumonia. Conclusions: Sloughing of varying lengths of segments of the esophagus is an emergency. The lining coughed up needs to be cut at the mouth not pulled and the emergency services called immediately for urgent assessment and management. Expert multidisciplinary care is needed to manage this rare but serious condition. [ABSTRACT FROM AUTHOR]

Background: Variants in COL7A1 cause an extremely rare and clinically heterogeneous syndrome known as dystrophic epidermolysis bullosa pruriginosa (DEB‐Pr). Duplilumab, a fully humanized anti‐IL‐4Ra monoclonal antibody, can inhibit IL‐4 and IL‐13‐driven signaling. Methods: Ethical Compliance: Following our Institutional Review Board, genetic testing has been made available after completing a signed informed consent form. This article presents the case study of a DEB‐Pr patient who received dupilumab therapy. Genomic DNA was extracted from the peripheral blood of the patient. Results: The findings showed that a unique COL7A1 mutation was discovered in the patient who underwent genetic testing. As a result of the patient receiving dupilumab treatment, the individual reported experiencing significantly less itching and considerably improved erythema, less severe scales, crusts, and flattening of plaques. Conclusion: In conclusion, the current investigation showed that to the best of our knowledge, this is the first DEB‐Pr patient with heterozygous COL7A1 (NM_000094.3:c.8110G>A [p. Gly2704Arg]) who responded positively to dupilumab treatment without experiencing any serious side effects. [ABSTRACT FROM AUTHOR]