Abstract Background Anti‐p200 pemphigoid (P200) is a rare subepidermal autoimmune blistering disease (AIBD) related to anti‐laminin γ1 autoantibodies (Abs). It has been recently reported that laminin β4 was frequently recognized by sera from patients with P200. Objectives To evaluate the incidence of P200 in France using a new recombinant anti‐laminin β4 serological assay. Methods This multicentre retrospective study was conducted in the Immunology Laboratory of the French reference centre for AIBD from January 2018 to March 2023. Sera suspected of corresponding to P200 were tested using the new anti‐LAMB4 cell‐based immunoassay (CBIA) and/or immunoblotting (IB) on dermal extract. The incidence of P200 was then estimated based on its incidence rate relative to those of BP and pemphigus over the same period. Results 116 patients with sera labelling the dermal side of salt‐split skin by IIF and negative for other junctional AIBD were recorded. Among them, 23 patients' sera had already been tested positive for P200 by dermal IB. Thus, 93 patients' sera were tested with both the anti‐LAMB4 CBIA and IB: 85 were positive with the CBIA (91%) vs. 44 with IB (47%, p < 0.0001). Only two were positive with IB alone. Overall, 110 patients had anti‐p200 Abs. Subsequently, we compared the frequency of serological detection of P200 to that of BP and pemphigus based on data from centres that exhaustively submitted their sera to our reference laboratory. According to the incidence of BP and pemphigus in France (21.7 and 1.85 cases per million inhabitants per year, respectively), the incidence of P200 was estimated to range from 0.23 to 0.83 cases per million inhabitants per year. This corresponds to approximately 16–57 new cases annually in France, which is approximately 2‐ to 4‐fold more frequent than epidermolysis bullosa acquisita . Conclusions This study shows that P200 may be much more frequent than initially estimated.

Crusted scabies is a severe and highly contagious variant of scabies, characterized by extensive infestation of Sarcoptes scabiei var. hominis within the epidermis. It typically occurs in individuals with compromised immune responses to parasitic infections. Crusted scabies in patients with epidermolysis bullosa, particularly recessive dystrophic epidermolysis bullosa (RDEB), is rarely reported. Here, we describe a 14-year-old girl with severe RDEB who developed crusted scabies. Treatment with a combination of ivermectin and losartan led to significant clinical improvement.

Part I. The role of Staphylococcus aureus in the pathophysiology of dermatologic disease.

Quantifying Itch and Sleep in Epidermolysis Bullosa and Ichthyosis: Sensor-Based Outcomes in a Dupilumab Study

Evaluation of the effect of iron therapy on nutritional and hematological parameters, disease extension, and patient- reported outcomes in pediatric patients with epidermolysis bullosa

Hyaluronidase Injections for Treatment of Microstomia in Recessive Dystrophic Epidermolysis Bullosa

271P Efficacy and safety of cemiplimab in the treatment of cutaneous squamous cell carcinoma in patients with dystrophic epidermolysis bullosa

Clinical and molecular spectrum of inherited epidermolysis bullosa in a Thai cohort: a 12-year retrospective study

Enhancing the therapeutic potential of intravenous recombinant collagen VII as a protein replacement therapy for recessive dystrophic epidermolysis bullosa

Recent years have seen rapid progress in biological treatments for genetic diseases, as well as conditions like type 1 diabetes that lack an obvious genetic component. The authors sought to explain why this progress has emerged at this particular moment. The best way to illustrate this is by showcasing a wide range of therapies targeting diverse diseases. This progress has been driven by technological advances in genetically modified CAR-T and CAR-NK cells (e.g., using CRISPR or transgenes), which have led to significant improvements in cancer therapy. A key trend now is the emergence of "off-the-shelf" approaches aimed at generating cellular therapies compatible with a range of recipients by mitigating alloreactivity and immune rejection. Different diseases impose distinct biological and logistical limitations; thus, treatment of each patient requires an appropriate strategy. Emerging advances include the modification of therapeutic cells, either ex vivo or in vivo. Current options for transgene delivery mainly comprise lipid nanoparticles (LNPs), adeno-associated virus (AAV) vectors, and lentiviral vectors. Researchers also focus on selecting suitable promoters for specific expression in selected cell types. Altogether, these advances have led to remarkable progress in treating various diseases in recent years. This publication discusses the development of biological therapies, with particular emphasis on cell and gene therapies, illustrated by viable examples across various disorders. It covers implemented solutions for several types of cancer, as well as selected hereditary diseases and syndromes, including Huntington's disease, carbamoyl phosphate synthetase 1 (CPS1) deficiency, hemiplegia, epidermolysis bullosa, chronic granulomatous disease, and congenital deafness. Emerging applications in heart diseases and diabetes are also summarized, along with therapeutic strategies involving tRNA gene editing. Although numerous strategies exist, only the most representative, practical, and up-to-date examples are emphasized.

We conducted a randomised, double-blind, placebo-controlled crossover trial of sublingual 10% THC/5% CBD in eight adults with epidermolysis bullosa and chronic pain. No significant change in pain affect occurred, but 75% reported ≥30% global pain reduction. Analgesic use halved during active treatment. Mild adverse events were common; larger trials are warranted.

Currently, there is no permanent treatment for the group of severe monogenic fragile skin conditions epidermolysis bullosa (EB). The recent USFood and Drug Administration (FDA)-approved in vivo gene replacement therapy beremagene geperpavec (Vyjuvek®) provides a promising solution, but it requires ongoing application and is not applicable to all forms of EB. Targeted gene editing approaches directly addressing pathogenic mutations hold great promise for the development of durable personalized therapies. Here, we comprehensively describe the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) gene editing landscape for EB, critically review the advantages and limitations of emerging therapeutic strategies, and present some future perspectives. We find that the widespread application of Cas9 nuclease is currently hindered by off-target genotoxicity, which can be mitigated using Cas9 nickases. Further, new tools including prime editing have recently emerged and hold significant potential for EB gene therapy. Ongoing developments in gene editing technologies focused on improving safety and editing precision offer significant promise for the future clinical translation of potentially lifelong treatments for people with EB.

Background/Objectives: Cannabinoids are increasingly recognised for their therapeutic potential beyond well-established indications such as chronic pain, multiple sclerosis, and specific epileptic syndromes. Recent advances have highlighted their possible role in less-common or orphan diseases, opening new avenues for pharmaceutical research and clinical application. Methods: This review provides a critical synthesis of the most recent evidence (2020-2025), available in PubMed and Scopus, regarding the use of cannabinoids in conditions including refractory epilepsies beyond Dravet and Lennox-Gastaut syndromes, movement disorders such as dystonia and Tourette syndrome, rare dermatological diseases like epidermolysis bullosa, and emerging data in Crohn's disease. Results: Negative outcomes, such as those reported in Fragile X syndrome trials, are also discussed as instructive examples of methodological and pharmacological challenges. Particular attention is given to the optimisation of pharmaceutical formulations and advanced separation technologies, including oromucosal sprays, transdermal gels, and novel nanocarrier systems, which aim to overcome issues of bioavailability and variability in patient response. Finally, safety concerns, regulatory aspects, and the need for robust clinical trials are addressed. Conclusions: Overall, cannabinoids represent a promising yet underexplored therapeutic option in rare and complex disorders, warranting further investigation supported by innovative pharmaceutical approaches.

Epidermolysis bullosa (EB) is a group of rare genetic blistering skin diseases, with EB simplex (EBS) being the most common subtype, accounting for around 70% of cases. Although there is no cure for EB, recent advancements led to the historic FDA-approvals of two treatments for dystrophic and junctional EB in 2023 and a third for dystrophic EB in 2025. However, no approved treatments exist for EBS despite its relative prevalence. Here, we outline established and emerging therapies for EBS. Supportive EBS management focuses on five key areas: skin-directed wound care, sweating reduction, keratoderma management, EBS-severe specific considerations, and blister reduction/prevention. Environmental measures target friction and moisture control to prevent blistering with the proper socks, footwear, and ambulation assistive device use. Wound care strategies include draining blisters without unroofing, nonstick dressing protection, and dilute vinegar or bleach baths to prevent infection and mitigate itch. Absorptive powders, glycopyrrolate, oxybutynin, and botulinum toxin target hyperhidrosis reduction. Painful keratoderma management, while challenging, includes mechanical debridement and topical keratolytic agents; targeted treatments including topical sirolimus have been explored in early phase study. A number of emerging treatments targeting EBS inflammatory pathways under investigation include apremilast, dapsone, diacerein ointment, deucravacitinib, and topical broccoli sprout extract. Tetracycline antibiotics are commonly used off-label for blister prevention. Ongoing bench research and gene-editing techniques like siRNA, TALEN, and CRISPR-Cas9 offer hope for translational advancements.

Oral healthcare is severely hampered in patients with epidermolysis bullosa simplex (EBS), a rare inherited genodermatosis marked by mucocutaneous fragility and blister formation. This case report describes the dental management of a six-year-old female child clinically diagnosed with EBS presenting with severe periodontal manifestations such as extensive calculus accumulation, gingival bleeding, halitosis, and poor oral hygiene as a result of frequent oral ulcerations. Meticulous behaviour modification technique and atraumatic periodontal intervention were employed to minimize soft tissue injury. This report highlights the importance of early dental referral, preventive-focused care, and a multidisciplinary approach in managing pediatric patients with EBS.

Abstract Tsukamurella species are rare, aerobic, gram-positive actinomycetes that are increasingly recognized as opportunistic pathogens affecting immunocompromised patients, such as those suffering from epidermolysis bullosa. Epidermolysis bullosa is a rare genetic disorder characterized by skin fragility that predisposes patients to chronic wounds and recurrent skin infections. The case of interest in this work was a 22-year-old male with a complex medical history, including the aforementioned disorder. He was admitted to the hospital’s emergency department, presenting with fluctuating low-grade fever and recurrent bleeding of the skin lesion on his flank. Infectious workup was sent, after which appropriate intravenous fluids were administered for resuscitation, along with broad-spectrum antibiotics. During the patient’s hospitalization, he was found to have Tsukamurella pulmonis and methicillin-resistant Staphylococcus aureus bacteremia, which was treated with vancomycin administered intravenously. Treatment resulted in significant improvement. This case adds to the limited body of studies describing T. pulmonis as a human pathogen. It highlights the importance of considering such rare opportunistic infectious agents in immunocompromised patients with chronic wounds and indwelling catheters. The study serves as a reference for clinicians, emphasizes the therapeutic challenges encountered in managing this infection in high-risk populations, and sheds the light on the need for established policies and clinical guidelines.

Moxifloxacin, a fluoroquinolone antibiotic with immunomodulatory activity, has not been evaluated for effects on autoantibody-driven inflammation. Pemphigoid diseases are a group of autoimmune blistering skin diseases driven by pathogenic autoantibodies and granulocytes. With current treatments for pemphigoid diseases associated with substantial adverse effects, there is a high medical need for new treatment strategies. We investigated the effect of moxifloxacin on skin inflammation in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita. Moxifloxacin attenuated skin inflammation in this model markedly. Invitro, moxifloxacin inhibited responses of neutrophils to fixed IgG immune complexes, including the release of leukotriene B4 (LTB4), a lipid mediator essential for disease propagation in this model. Moxifloxacin also reduced the maximal respiration rate of mitochondria and inhibited mitochondrial complex I. Consistent with a hypothetical direct link between mitochondrial complex I actions and the release of LTB4, the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)-decyltriphenylphosphonium (SkQ1; visomitin) reduced the immune complex-induced release of LTB4 from neutrophils dose-dependently. Collectively, our results demonstrate that moxifloxacin can ameliorate autoantibody-induced granulocytic skin inflammation. The disruption of select mitochondrial functions and of the immune complex-induced release of LTB4 from neutrophils might contribute to these therapeutic effects. Hence, moxifloxacin should be assessed as a drug for the treatment of patients with pemphigoid diseases.

This study aimed to uncover the genetic variations and their corresponding clinical features in a Chinese family affected by epidermolysis bullosa (EB). We enrolled a Chinese family clinically diagnosed with EB and conducted whole-exome sequencing on the proband to identify genetic variations. I-TASSER and PyMOL software were used to examine the structural and functional implications of the identified mutant proteins. The study identified an autosomal-dominant form of epidermolysis bullosa simplex (EBS) in the family, attributed to a novel missense variation c.A527G (D176G) in the ITGB4 gene. By bioinformatics analyses, we found that the wild-type D176 forms one hydrogen bond with a distance of 3.1 Å from F201, one hydrogen bond with a distance of 2.7 Å from K177, and two hydrogen bonds with a distance of 3.2 Å from Y304; however, the mutant G176 only forms one hydrogen bond with F201 at a distance of 3.2 Å. This study confirms the dominant mode of inheritance of the missense ITGB4 mutation observed in EB. The novel missense variation c.A527G (D176G) in ITGB4 involves a transition from a polar to non-polar amino acid and a decrease in intermolecular hydrogen bonding, which was associated with EB development.

Abstract Epidermolysis bullosa (EB) is a rare genetic disease defined by high fragility of the skin. The impact of this chronic disease extends beyond the physical and affects the psychosocial well-being and quality of life of not only the affected individuals but also their families. The Epidermolysis Bullosa Burden of Disease (EB-BoD) questionnaire aims to assess the impact of the disease on the family of those affected. Whereas the questionnaire has been partially validated in French, there is no validated English translation. Additionally, the original version is limited to assessing the quality of life of parents only. The objective of this study was to revise the EB-BoD to ensure its applicability to all relatives of individuals with EB, and to translate, culturally adapt and validate it in English. The EB-BoD revised was developed in three stages: (1) translation and cross-cultural adaptation, (2) content revision and thematic adjustment and (3) sample-based testing with 64 relatives of patients with all EB types to establish the psychometric properties of the English EB-BoD-R. The revised EB-BoD exhibits excellent reliability and internal consistency, with a Cronbach’s α of 0.93. Exploratory factor analysis resulted in two distinct factors, Circumstances and Emotions . Convergent validity was demonstrated by strong correlations with the iscorEB-p and the SWLS (both p < .001). Divergent validity was found in relation to social support F-SozU (ρ=−0.17, p = .228). In conclusion, the English EB-BoD-R is an effective and reliable instrument for assessing the quality of life of relatives of EB patients.

Dominant dystrophic epidermolysis bullosa (DDEB) is a hereditary genetic disorder with a mutation of the type VII collagen gene (COL7A1), leading to a destabilized dermal-epidermal junction. Current treatments for DDEB are supportive, and new gene therapies are being developed to target DDEB. However, gene therapy can be expensive. A 59-year-old woman presented with eroded blisters on her right lower extremity. Genetic testing identified a pathogenic COL7A1 mutation, confirming the diagnosis of DDEB. She was treated with 6 weeks of gentian violet and trichloroacetic acid peel, resulting in significant improvement of her lesions. DDEB is characterized by dysregulated inflammation of chronic wounds and aberrant fibroblast activity. Gentian violet and trichloroacetic acid may address inflammation while reducing fibroblast activity and preventing infection. The treatment worked well for the patient, and there was minimal pain with the application of these topical therapies. &nbsp.