Epidermal deletion of Kindlin-1 drives matrix changes in the mouse skin and altered responses to ultraviolet radiation.

Inherited epidermolysis bullosa comprises a heterogeneous group of skin fragility diseases, presenting with a range of manifestations and complications that profoundly affect quality of life (QoL). A disease-specific instrument, Quality of Life in EB (QOLEB), has been developed to assess the impact of epidermolysis bullosa signs and symptoms on QoL. The aim of this cross sectional study, conducted as part of a European project - BUR-EB, was to test the psychometric properties of the Italian version of the QOLEB and to assess QoL in Italian epidermolysis bullosa patients. Demographic, clinical, and QOLEB data of 56 Italian patients aged ≥11 years participating in the BUR-EB online survey were analysed. Principal component analysis showed excellent internal consistency of Italian QOLEB, and high convergent validity with the generic questionnaire EQ-5D. About 40% of patients reported severe to very severe disease burden, and a strong correlation was observed between disease severity and QOLEB scores. Independent variables associated with worse QoL were pain, chronic wounds, wheelchair use and patient organization membership. Our study confirms the good psychometric properties of the Italian QOLEB. In addition to depicting the major impact of epidermolysis bullosa on QoL, it identifies pain, chronic wounds and functional disability as major targets for therapeutic interventions.

Epidermolysis bullosa (EB) is a debilitating genetic disorder characterized by extreme skin fragility and chronic wound formation, often complicated by bacterial infections. Current wound dressings provide limited protection against infection and may induce cytotoxicity or mechanical trauma. Herein, we report a multifunctional nanofibrous dressing based on casein/poly(vinyl alcohol) (PVA) integrated with an aggregation-induced emission (AIE) photosensitiser (PS) for enhanced antibacterial performance. Bilayer nanofibrous mats were fabricated via multi-nozzle electrospinning, combining a mechanically robust PVA support layer with a bioactive casein-rich surface. Post-fabrication, glutaraldehyde crosslinking improved structural stability, while plasma polymerization enabled immobilization of an AIE PS (TPAQ-PF6) onto the fiber surface. The resulting materials exhibited tunable wettability, preserved nanofibrous morphology, and stable AIE fluorescence. Under light irradiation, AIE-functionalised dressings generated reactive oxygen species (ROS), leading to significant antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Fluorescence imaging confirmed enhanced ROS production at the material surface. Importantly, cytocompatibility assays using keratinocytes and fibroblasts demonstrated good cytocompatibility, highlighting suitability for potential wound-contact applications. Overall, this work presents a biocompatible, photodynamically active dressing platform that integrates natural polymers with advanced AIE technology, offering a promising strategy for infection control in fragile skin conditions such as EB.

Introduction: Epidermolysis Bullosa (EB) is a rare genetic condition with skin and mucosal fragility. Patients with EB present extra- and intraoral manifestations that can limit their access to dental treatment, including orthodontic treatment. This research aims to determine the barriers, benefits and complications of orthodontic treatment reported by a group of patients living with EB. Materials and Methods: This observational study included n = 101 patients with a genetic diagnosis of EB. After their regular dental consultation, they were interviewed about factors they considered barriers to accessing orthodontic treatment. Those who underwent orthodontic treatment (n = 24) reflected about their perceived benefits and complications from the therapy. Data were analysed with descriptive statistics and multiple Fisher’s exact tests with false discovery rate (FDR) correction. Results: The most prevalent barrier was that most patients with EB had never been evaluated by an orthodontist (74.3%), even if the teams had an orthodontist. Other barriers included distance to the treatment centre (42.6%), poor oral hygiene (27.7%) and poor oral health status (26.7%). Patients with limited mouth opening perceived greater treatment benefit compared to those without this limitation (φ = −0.28, p = 0.0242), while an increasing age was associated with a reduced perception of treatment benefit (Cramér’s V = 0.29, p = 0.0404). Among those who underwent orthodontic treatment, the most prevalent benefits of orthodontic treatment were aesthetic improvement (62.5%), oral hygiene improvement (20.8%) and occlusal stability (12.5%), while the most prevalent complications were wounds and ulcers (75.0%), gingivitis (54.1%), poor oral hygiene (41.6%) and caries (33.3%). Discussion: People living with EB reported different barriers to orthodontic treatment relating to psychosocial and professional aspects, which vary according to the EB type and severity. The involvement of orthodontists in multidisciplinary special care teams and the reduction in access barriers to dental specialities can be facilitated by a more comprehensive understanding of conditions such as EB.

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare genetic skin condition causing fragile skin, blistering, and scarring. It leads to chronic pain, slow wound healing, and severe limitations, profoundly impacting patient and family quality of life. Umbilical cord tissue-derived mesenchymal stromal cells (UC-MSC) have shown therapeutic promise. The Mission EB trial (ISRCTN14409785; registration date 25/03/2021) assessed UC-MSC safety and effectiveness in children with RDEB in a placebo-controlled, double-blinded, crossover study. This study used a qualitative research design with semi-structured interviews and thematic analysis, to explore Mission EB trial treatment impact on the quality of life of patients and parents. Parents and patients were interviewed at two time points (approximately 3- and 12-months post-randomisation). Purposive sampling included 10 parents and 6 children; 13 individuals (8 adults, 5 children) were interviewed twice (once in each study period). Interviews were transcribed verbatim, independently coded, with overall impressions agreed upon prior to unblinding. RDEB significantly impacted daily life, marked by pain and itch. Participants were hopeful of the trial, willing to pursue minor improvements. UC-MSC infusions led to reduced pain/itchiness, improved wound healing, and resulted in fewer self-reported dressing changes. These benefits often translated to increased energy, improved eating, and greater daily activity participation. Benefits were more pronounced with active treatment. Negative effects were minimal, primarily venous access difficulties. Blinded participants could discern active UC-MSC from placebo based on symptom changes; 10 of 13 showed clear differences aligning with treatment. All parents interviewed expressed willingness for their child to receive treatment again. This qualitative research provides valuable insights into perceived benefits of UC-MSC treatment for children with RDEB. Interview findings regarding symptom improvement and participants' ability to discern active treatment shed light on its perceived benefit in RDEB, especially in milder RDEB patients. The study highlights the critical importance of qualitative methodologies in adding to quantitative trial outcomes and capturing the meaningful impact of interventions on the lives of patients and families particularly where quantitative measures may not fully reflect lived experience.

Pretibial injuries manifest as lacerations or haematomas. Despite differences in pathogenesis and treatment, these entities have been mixed together in previous classifications. No classification for pretibial haematomas exists, and the Modified Dunkin Classification includes a Type V category that conflates lacerations with haematomas. To present the Sinuhe Classification-a comprehensive system categorising pretibial lacerations and haematomas with evidence-based treatment recommendations-and propose the umbrella term 'dermatoporotic wounds' to encompass the full spectrum of cutaneous injuries arising from chronic skin fragility. A narrative literature review of PubMed, MEDLINE and EMBASE was conducted. Treatment recommendations and clinical findings were synthesised from the available literature, including a doctoral thesis on pretibial injuries. The Sinuhe Classification categorises pretibial lacerations into linear lacerations; flap lacerations (vital, i.e., with adequate perfusion and non-vital, i.e., with flap necrosis); and total skin loss. Pretibial haematomas are classified into open (ruptured), closed and necrotic haematomas. Each subtype is paired with specific treatment guidance. The classification eliminates the Modified Dunkin Type V category and provides a classification framework for pretibial haematomas. The Sinuhe Classification offers a unified yet distinct framework for diagnosing and treating pretibial injuries. Adoption into clinical practice and medical education is recommended.

Porphyrias are rare metabolic disorders caused by inherited or acquired enzymatic defects in the heme biosynthesis pathway, resulting in the accumulation of heme precursors or toxic porphyrin intermediates. The cutaneous porphyrias arise from enzymatic defects in later steps of the heme biosynthesis pathway, which lead to the build-up of photoactive porphyrins in the skin and liver, such as coproporphyrins, protoporphyrins, and uroporphyrins. These photoactive porphyrins generate reactive oxygen species that drive the characteristic cutaneous manifestations, including painful photosensitivity, skin fragility, and blistering. The cutaneous porphyrias encompass both blistering and non-blistering subtypes, which include erythropoietic protoporphyria, X-linked protoporphyria, congenital erythropoietic porphyria, porphyria cutanea tarda, and hepatoerythropoietic porphyria, each distinguished by specific biochemical patterns and clinical features. Acute hepatic porphyrias, which include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and aminolevulinic acid dehydratase deficiency porphyria, result in the accumulation of neurotoxic precursors, such as δ-aminolevulinic acid and porphobilinogen. While acute neurovisceral attacks predominate in acute hepatic porphyrias, certain subtypes, such as variegate porphyria and hereditary coproporphyria, may present with blistering photosensitivity, creating a significant diagnostic overlap between cutaneous porphyrias and other photodermatoses. This overlap underscores the importance of awareness of acute hepatic porphyrias among dermatologists, who may be the first clinicians to encounter patients with these disorders. In addition, recent treatment breakthroughs will likely bring patients with porphyrias to pursue care, changing the likely underestimated disease prevalence rates. This narrative review provides a comprehensive overview of the pathobiology, clinical features, diagnostic strategies, and management approaches for the cutaneous and acute hepatic porphyrias.

Prevalence and associated factors of skin tears among hospitalized older adults in a hospital in Türkiye: A point prevalence study.

Extracting and standardizing phenotypic information from free-text medical reports remains a main challenge in biomedical natural language processing (NLP). Conceptual normalization, which maps textual mentions to standardized vocabularies such as the UMLS or HPO, is a key step for deep phenotyping. Dystrophic epidermolysis bullosa (DEB) is a rare severe and heterogeneous skin disorder causing skin and mucosal fragility that leads to early morbidity and mortality. To better understand the disease's natural history and severity spectrum, it is important to comprehensively identify DEB-related phenotypes. This study aimed to assess a pipeline for automatically mapping clinical terms from textual reports to the UMLS Metathesaurus and to evaluate how well the UMLS covers DEB-related phenotypes. The study was conducted at Necker-Enfants Malades Hospital in Paris, a reference center for rare diseases, using its "Dr Warehouse" database, containing more than 11 million clinical documents. It involved 198 patients with dystrophic epidermolysis bullosa (DEB). Phenotypes were automatically extracted from clinical texts using named entity recognition (NER) and then normalized using a cosine similarity method. Among the 198 DEB patients followed at Necker Hospital, 14,734 documents were analyzed, allowing the extraction of 33,347 phenotypes using an NER model. Of these phenotypes, 13,485 were correctly mapped to a UMLS or HPO concept, while 19,862 were not. A manual evaluation of 300 unmapped phenotypes revealed five main causes of failure: overly specific phenotypes (72%), missing synonyms in terminologies (30%), multiple phenotypes within a single extraction (15%), absence of a real phenotype (9%), missing concepts in terminologies (3%), or spelling/grammatical errors (3%). Despite the initial association failure, a significant proportion of overly specific or poorly formulated phenotypes actually corresponded to existing concepts. These results highlight the limitations of current ontologies and the challenges of automatic medical language processing.

Epidermolysis bullosa (EB) is a rare inherited disorder characterized by skin and mucosal fragility, with severe implications for physical, psychological, and social well-being. Research on quality of life (QoL) in EB remains limited, particularly in Italy, where systematic patient-reported outcome measures are lacking. To address this gap, Fondazione REB ETS developed a patient-centered QoL questionnaire (QoL-REB) constructed directly by patients and caregivers, with support from clinicians and researchers. We conducted a cross-sectional online survey between March and April 2024, recruiting Italian EB patients and caregivers through Fondazione REB and Debra Italia mailing lists. Participants completed the QoL-REB questionnaire, which assesses seven dimensions of QoL: physical health, autonomy, emotional well-being, family dynamics, social interactions, work/school life, and care experience. Responses were rated on a 4-point scale, with overall QoL assessed on a 0-10 scale. Forty-seven individuals with EB (38 adults, 9 minors; 55% female) participated, representing multiple EB subtypes, predominantly dystrophic EB (62.4%). Mean overall QoL was rated 6/10. Pain, itching, and reduced mobility emerged as the most frequent physical challenges. Over 70% of adults reported limited autonomy in daily activities, while children experienced difficulties with walking, dressing, and sports participation. Emotional distress was common, with patients expressing concerns about future prospects, body image, and dependence on others; 43% reported a need for psychological support. Family burden was evident, with both adults and minors perceiving themselves as a strain on relatives. Social limitations, workplace and school difficulties, and dissatisfaction with healthcare services-particularly a lack of EB-specific expertise in non-reference centers-were also reported. This first Italian patient-led assessment highlights the pervasive and multidimensional burden of EB on QoL. Findings underscore the need for integrated, patient-centered care models that combine medical, psychological, and social support. The QoL-REB questionnaire provides a novel, comprehensive tool to capture the lived experience of EB and may serve as a framework for international adaptation and implementation.

Engineered natural extracellular matrix platform for modelling skin diseases and identifying therapeutic targets.

Observations of dystrophic epidermolysis bullosa patients with collagen VII NC2 truncation provide new insights into anchoring fibril assembly.

BackgroundBed baths are commonly used to maintain skin hygiene in older hospitalized patients whose skin may be affected by disease, treatment, and aging. The effects of bed baths on the skin barrier function, particularly in the lower limbs, in older patients with heart disease who may have fragile skin remain unclear. This quasi-experimental (crossover) study investigated the effects of bed baths with weak wiping pressure using cotton and disposable towels on the skin barrier function of the lower limbs and forearms in older hospitalized patients with heart disease.MethodsThirty-three older hospitalized patients with heart disease were evaluated. Participants received two randomly ordered wipes (AB or BA): (A) bed baths of the lower limbs and forearms using disposable towels; and (B) bed baths of the lower limbs and forearms using cotton towels. Weak wiping pressure was used (10–20 mmHg). Skin barrier function was measured before, 15 min after, and the day after bed bath using transepidermal water loss (TEWL), stratum corneum hydration (SCH), and overall dry skin score (ODS). Mixed-effects models for repeated measures were used to compare the changes over time between the two types of bed baths.ResultsSCH and TEWL were lower in the lower limbs than in the forearms, while ODS was higher. An interaction for TEWL was observed in the lower limbs (F[2,25] = 4.0, P = 0.030); however, TEWL did not differ significantly across time points or towel types. No interaction or main effects of time or towel type on lower limb SCH and forearm TEWL were noted. Only the main effect of time on forearm SCH was observed, which was significantly lower 15 min after the cotton towel bed bath than before (t = 3.2, P = 0.004, MD [95% CI]: − 3.5, − 0.8). ODS at baseline and the following day demonstrated no difference.ConclusionChanges in TEWL and SCH over time revealed that a single bed bath with weak wiping pressure did not cause sustained impairment of skin barrier function by the following day. However, transient SCH decreases, and limited intervention periods require further mechanistic investigation.Trial registrationUMIN R000061354 (date of registration: March 3, 2024).Supplementary InformationThe online version contains supplementary material available at 10.1186/s40101-026-00433-x.

Systemic clinical-grade recombinant decorin reduces disease burden and fibrosis in advanced recessive dystrophic epidermolysis bullosa

Epidermolysis Bullosa (EB) is a rare, inherited skin disorder characterized by skin fragility, leading to painful blisters and wounds. While protective measures are essential for managing EB, they can inadvertently restrict physical activity and social participation. Recognizing this dilemma, the current psychosocial care guidelines for EB emphasize the need to support social participation as a key priority. Accordingly, this study explores barriers and facilitators influencing participation in education, employment, and economic life, as conceptualized by the International Classification of Functioning, Disability, and Health (ICF). A qualitative research design using biographical interviews was employed. Twelve adults with EB were recruited via purposive sampling. Interviews were transcribed and analysed through deductive qualitative content analysis, guided by the ICF framework. During the early stages of education, peer attitudes and bullying were identified as major barriers, while parental advocacy, supportive teachers, and peers helped mitigate exclusion. In the later stages of education (higher education and vocational training), frequent transitions in teachers, classrooms, and peers required participants to continuously renegotiate adjustments, which before used to be a one-time task. In employment, barriers included discrimination during job applications and inadequate support from employment agencies, whereas flexible arrangements (e.g., remote work) promoted participation. In economic life, complex bureaucratic procedures hindered access to social security benefits and medical reimbursements, increasing participants’ financial and psychological burden. Patient organizations significantly alleviated these burdens by assisting with paperwork and administrative navigation. Living with EB necessitates constant care to avoid physical stressors, yet protective measures can unintentionally restrict participation. This study identifies 17 environmental factors shaping participation across education, employment, and economic life, with uninformed attitudes emerging as a persistent barrier in all life areas. Supporting patient organizations in their advocacy efforts may help reduce stigma, improve awareness, and ultimately enhance social participation of individuals with EB.

Ectopic Cushing syndrome is a rare cause of ACTH-dependent hypercortisolism, with pancreatic neuroendocrine tumors representing an exceptional origin. We report the case of a 48-year-old woman presenting with severe Cushing syndrome, characterized by central obesity, hirsutism, secondary amenorrhea, and marked skin fragility. Laboratory evaluation confirmed pronounced ACTH-dependent hypercortisolism, and imaging revealed a suspicious pancreatic lesion. The patient was being prepared for surgical resection; however, her condition deteriorated rapidly, culminating in fatal septic shock before surgery. Pancreatic ectopic Cushing syndrome is associated with high morbidity due to metabolic, infectious, and cardiovascular complications. Diagnosis relies on elevated plasma ACTH, normal pituitary MRI, and targeted functional imaging. Optimal management involves surgical excision, with medical therapy to control hypercortisolism while awaiting intervention. This case underscores the potentially severe course of pancreatic ectopic Cushing syndrome and highlights the importance of early recognition and multidisciplinary management.

Epidermolysis bullosa (EB) is a rare genetic disorder that causes extreme skin fragility, chronic pain, and functional impairment, with major psychosocial and economic consequences. Health-related quality of life (HRQoL) data is critical to capture the full burden of EB. Health utilities derived from preference-based generic instruments such as the EQ-5D-5L provide standardized health status utility values that enable cross-disease comparisons and provide input data for cost-utility analyses to inform resource allocation. There is a notable lack of multinational, up-to-date utility data for EB. This cross-sectional study aimed to assess HRQoL in adults with EB across seven European countries (Austria, Bulgaria, Germany, Hungary, Italy, France, and Spain) using the EQ-5D-5L. A total of 328 adults with EB participated in the survey, 61% were female, 37% were between 18 and 30 years old and 46% had dystrophic EB. Based on self-reported symptoms, 58% were classified as severe EB. Pain/discomfort was the most affected EQ-5D-5L dimension (92% reporting problems; 27% severe or extreme). The mean EQ-5D value (health utility) was 0.63 (SD 0.32), ranging from 0.57 in Spain to 0.71 in Bulgaria. Patients with severe EB reported significantly lower utilities than non-severe cases (0.52 vs. 0.78, p < 0.001). Mean EQ VAS score was 60 (SD 23.2). Compared to general population norms, EB patients in all countries had markedly lower HRQoL (p < 0.005), with large effect sizes for the EQ-5D value (Cohen's d ≥ 0.8). Symptomatic burden and functional deterioration were the primary drivers of HRQoL impairments. This multinational study provides the most extensive and current health utility data for adults with EB in Europe. Findings reveal the profound HRQoL impairment in EB, particularly in severe cases. These standardized utility values fill a major evidence gap, supporting their use in health economic evaluations, cross-disease comparisons, and policy development.

INTRODUCTION: Epidermolysis bullosa (EB) encompasses a rare, inherited group of skin disorders characterised by skin fragility, leading to painful, chronic wounds. While recent international studies have reported reduced microbial diversity and altered bacterial composition in EB blistered skins, no microbiome or antimicrobial resistance data is available for Australian EB patients. The objectives of this study were to characterise the wound microbiome of Australian EB patients and identify bacterial pathogens and their associated antimicrobial resistance profiles. METHODS: A total of 15 chronic wound swabs were collected from 10 EB patients. Bacterial identification was performed using standard culture methods and MALDI-TOF; for a selected resistant subset, whole-genome sequencing (WGS) was conducted on two strains, and full-length 16S rRNA gene sequencing was performed on 10 swab samples. Antimicrobial susceptibility profiles were determined using disk diffusion assays. RESULT: PacBio Full-length 16S rRNA sequence analysis revealed a high relative abundance of the genera Staphylococcus and Streptococcus, with Staphylococcus aureus being the most frequently detected species. Among the 27 cultured bacterial isolates, 81.5% exhibited resistance to at least one antibiotic, and 22.2% were classified as multidrug resistance (MDR). WGS of two selected resistant strains harboured blaZ, mecA, ermC and mupA genes conferring resistance to penicillins, cefoxitin, clindamycin and high-level mupirocin, respectively. CONCLUSIONS: This is the first study to profile the wound microbiome and antimicrobial resistance in Australian EB patients. The findings provide the descriptive microbial profiles and resistance patterns, with implications for clinical management of patients in a specific healthcare setting.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) is a disorder caused by autosomal-dominant mutations in the TP63 gene. AEC is characterised by the presence of severe and painful skin erosions that can take years to heal. Current treatment options for these devastating lesions are limited, highlighting the need for new therapeutic strategies. We previously generated keratinocytes from patient-derived induced pluripotent stem cells (iPSC-K) and identified defects in several cell adhesion complexes, including desmosomes, hemidesmosomes and focal adhesions. In the present study, we developed a complementary invitro model using NTERT keratinocytes transduced with lentiviral constructs expressing AEC-related TP63 mutations (N-AEC). This model allows for the large-scale production of disease-relevant material, overcoming the limitations of iPSC-derived keratinocytes, which have the characteristics of primary keratinocytes, including limited cell doublings and lifespan. We demonstrate that N-AEC keratinocytes exhibit key defects observed in AEC iPSC-K and AEC patient skin, including downregulation of cell adhesion proteins. In addition, 3D epidermal equivalents generated from these cells replicate pathological features seen in AEC patient skin, such as intra-epidermal cysts, reduced desmosomal protein expression and altered expression of differentiation markers. Our N-AEC model provides a valuable tool for investigating the mechanisms underlying skin fragility in AEC and other genetic skin disorders and advances the potential for novel therapeutic development.

African spiny mice (Acomys spp.) are an emerging animal model for regeneration due to their remarkable healing capabilities. Defining characteristics of these species include fragile skin that sloughs easily and shedding of the tail skin when grabbed, making handling and administration of parenteral drugs difficult in conscious animals. In addition, many studies in spiny mice involve painful procedures. To our knowledge, there are no reports regarding analgesia in Acomys spp. This prospective study aimed to assess 3 sustained-release buprenorphine formulations-lipid-bound extended-release buprenorphine (XRB), polymeric sustained-release buprenorphine (SRB), and long-acting transdermal buprenorphine (TB)-in spiny mice. Adult male and female Cairo spiny mice (Acomys cahirinus) were included and administered 1 of the 3 treatments (XRB 3.25 mg/kg, SRB 1 mg/kg, or TB 20 mg/kg). Tail flick assays to assess nociception and terminal blood collection for pharmacokinetic analysis were performed at baseline and a set timepoint following treatment administration (1, 2, 4, 8, 24, 48, and 72 hours) (n = 3 of each sex per timepoint per treatment group). Additional animals underwent repeated serial tail flick assays at 1, 2, 4, 8, 24, 48, and 72 hours following the administration of treatment or sterile saline (n = 5-8 of each sex per treatment group). XRB displayed the longest duration at which mean plasma buprenorphine concentrations were >1 ng/mL, with the drug remaining above this level for 48-72 hours, compared with 24-48 hours in spiny mice receiving TB and 8 hours in those receiving SRB. On serial tail flick assays, the mean percentage of maximum possible efficacy was highest at all timepoints up to 72 hours in the TB group, followed by the XRB group, suggestive of greater analgesic efficacy. Several spiny mice receiving SRB developed ulcerative skin lesions within 24 hours of administration, so this treatment is not recommended in Acomys without additional evaluation. XRB and TB are promising analgesic therapies in spiny mice, and treatment selection should be based on whether duration of action or ease of application is the priority.