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Pruritus is one of the most debilitating symptoms for patients with epidermolysis bullosa (EB). This study aimed to assess the burden of itch and to address its dimensions across patients with EB. Forty-six patients with EB were recruited from the Saudi EB registry to participate. All participants completed the Leuven Itch Scale. The sample included 5 patients with EB simplex (EBS), 3 with junctional EB (JEB), 34 with dystrophic EB (DEB), and 4 patients had unknown type. Overall, 97.8% patients reported itch. In patients with itch, 73.3% reported that it was often or always present, longer than 2 h Itch episodes was reported by JEB (66.7%) and recessive DEB (RDEB) (3.2%). Itch, in all its dimensions, was worst in patients with JEB and DEB than EBS. Itch occurred mostly in a hot environment (80%), when sweating (71.1%), in healing wounds (40%), and during dressing change (35.6%) whereas cold environment resulted in itch in only (2.2%). The burden of pruritus increased with increasing age. This study highlights a challenging area in EB care with a need for specific treatments.

The discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system has revolutionized gene editing research. Through the repurposing of programmable RNA-guided CRISPR-associated (Cas) nucleases, CRISPR-based genome editing systems allow for the precise modification of specific sites in the human genome and inspire novel approaches for the study and treatment of inherited and acquired human diseases. Here, we review how CRISPR technologies have stimulated key advances in dermatologic research. We discuss the role of CRISPR in genome editing for cutaneous disease and highlight studies on the use of CRISPR-Cas technologies for genodermatoses, cutaneous viruses and bacteria, and melanoma. Additionally, we examine key limitations of current CRISPR technologies, including the challenges these limitations pose for the widespread therapeutic application of CRISPR-based therapeutics.

Hailey-Hailey disease is a rare, chronic, autosomal dominant skin disorder characterized by recurrent painful erosions and macerated plaques, primarily affecting intertriginous areas. It is caused by mutations in the ATP2C1 gene, leading to impaired calcium homeostasis and keratinocyte adhesion. Many patients experience poor disease control despite conventional therapies. We report a case of a female in her 60s with refractory Hailey-Hailey disease affecting the perianal, inguinal, and cervical folds, with painful, eroded plaques resistant to conventional treatments. Despite multiple failed therapies, including methotrexate, dapsone, acitretin, and naltrexone, she showed rapid improvement within 2 weeks of abrocitinib (100 mg daily), a JAK1 inhibitor, with sustained control at 2 months follow-up. JAK inhibitors, initially approved for inflammatory diseases such as atopic dermatitis, are emerging as promising therapies for genodermatoses. By suppressing IL-4/IL-13-driven inflammation, JAK1 inhibition may restore epithelial integrity and reduce chronic skin inflammation. This case adds to growing evidence that JAK inhibitors, particularly abrocitinib, may serve as an effective targeted therapy for refractory Hailey-Hailey disease. Further clinical trials are needed to confirm its long-term efficacy and safety.

Monogenic genodermatoses encompass a diverse group of over 400 distinct disorders, presenting significant therapeutic challenges. Recent advancements in the clinical application of biological agents have heralded a new era in the management of these conditions. A plethora of clinical studies and case reports have demonstrated the efficacy of TNF‐α, IL‐1, IL‐4Rα, IL‐17A, IL‐12/23, and IL‐6R inhibitors in the management of monogenic genodermatoses. To elucidate the current landscape of biological agent utilization and their putative mechanisms of action in the context of monogenic genodermatoses, we conducted a review of the literature.

Genodermatoses encompass a wide range of inherited skin diseases, many of which are monogenic. Genodermatoses range in severity and result in early-onset cancers or life-threatening damage to the skin, and there are few curative options. As such, there is a clinical need for single-intervention treatments with curative potential. Here, we discuss the nascent field of gene editing for the treatment of genodermatoses, exploring CRISPR–Cas9 and homology-directed repair, base editing, and prime editing tools for correcting pathogenic mutations. We specifically focus on the optimisation of editing efficiency, the minimisation off-targets edits, and the tools for delivery for potential future therapies. Honing each of these factors is essential for translating gene editing therapies into the clinical setting. Therefore, the aim of this review article is to raise important considerations for investigators aiming to develop gene editing approaches for genodermatoses.

Gene therapies are powerful tools to prevent, treat, and cure human diseases. The application of gene therapies for skin diseases received little attention so far, despite the easy accessibility of skin and the urgent medical need. A major obstacle is the unique barrier properties of human skin, which significantly limits the absorption of biomacromolecules, and thus hampers the efficient delivery of nucleic acid payloads. In this review, we discuss current approaches, successes, and failures of cutaneous gene therapy and provide guidance toward the development of next-generation concepts. We specifically allude to the delivery strategies as the major obstacle that prevents the full potential of gene therapies – not only for skin disorders but also for almost any other human disease. Gene therapies are powerful tools for the treatment of inflammatory, genetic, and cancer-related skin diseases.The skin barrier function and the low number of cells that get transfected are the main hurdles for cutaneous gene therapy and contribute to the fact that gene therapies for skin diseases are an underexplored area.Gene editing provides an approach to cure rare and severe genodermatoses-like epidermolysis bullosa. First studies demonstrate the potential and invaluable impact these treatments may have even if only a small percentage of the gene function can be restored.Recent advancements demonstrate the power of non-viral delivery systems for the delivery of gene therapeutics to the skin. They may prove superior to viral vectors, the current gold standard, because their use is not limited by packaging size, serious safety concerns, or manufacturing issues.

People with genodermatoses face physical pain, social discrimination, and daily life challenges, all of which have an impact on their emotional and psychological well-being. The assessment of anxiety and the development of coping strategies are crucial. This study aimed to compare state and trait anxiety between healthy adults ( n  = 30) and patients with Mendelian Disorders of cornification (MeDOC) ( n  = 29). Using the State and Trait Anxiety Inventory and Coping in Stressful Situations Questionnaire, we compared anxiety levels and coping strategies between patients with MeDOC and healthy controls. Given the rarity of MeDOC, the study group is small, but the findings are highly relevant and can significantly improve patients’ well-being. Average or high levels of trait anxiety were significantly more common in the study group compared to the control group (25 vs. 18 cases; 86.2% vs. 60%, respectively; p  = 0.0488). It was estimated that the risk of average or a high level of trait anxiety was over 4 times higher in the study group than in the control group (OR = 4.2, 95% CI 1.1–15; p  = 0.0293). High-level emotion-oriented coping was significantly more frequent in the study group compared to the control group (8 vs. 1 case; 27.6% vs. 3.3%; p  = 0.0259), with the risk being 11 times higher in the study group (OR = 11, 95% CI 1.3–95.2; p  = 0.0288). No significant correlation was found between demographic, social, educational, clinical factors, and anxiety levels or avoidant-distracted coping. Patients with MeDOC have an increased risk of experiencing anxiety. Understanding the emotions and behaviors of patients with this disease is essential for clinical specialists to guide their coping strategies effectively.

Background Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds. Methods Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5 × 7 cm (35 cm 2 ) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for ≥ 12 weeks. Results Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9 years (range 4–8 years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated ≥ 50% wound healing compared to baseline by investigator global assessment. No sites with ≥ 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing ( p  < 0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9 years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up. Conclusions Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming. Trial registration ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379