2026-08-11 | Topical gene therapy for severe recessive dystrophic epidermolysis bullosa: clinical outcomes and multidisciplinary management in three patients treated with beremagene geperpavec (B-VEC) in Italy - a case series.

Recessive dystrophic epidermolysis bullosa is a severe inherited blistering disorder characterized by chronic wounds, fibrosis and systemic complications. Beremagene geperpavec (B-VEC), a topical HSV1-based gene therapy delivering full-length COL7A1, has shown efficacy in clinical trials; however, real-world data remain limited. This retrospective, descriptive case series reports on three patients with genetically confirmed recessive dystrophic epidermolysis bullosa - two children and one young adult - treated between 2024 and 2026 at two Italian tertiary centres. All patients had extensive chronic skin involvement and received weekly topical B-VEC. Clinical data included wound characteristics, response to therapy, supportive care and adverse events. All patients showed clinically meaningful improvement in target wound healing. One child achieved ~70% reduction in the wound area needing treatment; the second had ~50% with shallower morphology and reduced bleeding. The adult, previously enrolled in the GEM-3 trial, achieved over 60% wound closure after reinitiating B-VEC via Italy's 5% Italian Medicines Agency (AIFA) access programme. No treatment-related adverse events occurred. Adjunctive care included wound hygiene optimization, nutritional and iron support, and pain control. In this small descriptive case series, B-VEC was well tolerated and associated with clinically meaningful improvement in wound healing though outcomes were more variable and, in some cases, less pronounced than those reported in pivotal trials, nevertheless supporting its integration into a comprehensive care model that addresses infection risk, anaemia, nutrition, and wound management.

Open article ↗

2026-07-27 | A Systematic Review of Topical and Systemic Gentamicin for Wound Healing in Patients With Junctional and Dystrophic Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is an inherited mechanobullous genodermatosis caused by a mutation in genes encoding proteins integral to skin integrity. Premature termination codon readthrough therapies, such as gentamicin, have promise in facilitating full-length protein expression in patients with EB. We conducted a systematic review of the effectiveness and adverse effects of gentamicin for wound healing in EB. Six databases were searched to 01 September 2025 for clinical trials investigating gentamicin for EB. Risk of bias was assessed using the ROBINS-I tool, and data were synthesised descriptively. This study was registered with PROSPERO (CRD42024496582). Five studies involving 24 patients with junctional EB or dystrophic EB were included; four were open-label and one was double-blinded. Nineteen of the 24 patients had a known nonsense mutation. Gentamicin was administered topically (two studies), intravenously (two studies) and both topically and intradermally (one study). Wound healing was heterogeneously measured across studies, with all but one showing improved outcomes. All patients demonstrated increased expression of glycoprotein or collagen in skin biopsy specimens after gentamicin treatment. No adverse events were noted. However, four of five studies were at serious risk of bias on ROBINS-I, primarily owing to lack of blinding and absence of control groups, increasing the risk of bias for subjective outcomes such as wound healing. The available evidence suggests gentamicin may improve wound healing in EB caused by nonsense mutations, but the small number of heterogeneous studies precludes high-level evidence. Larger, blinded, randomised trials are required to confirm efficacy and long-term safety.

Open article ↗

2026-07-08 | Esophageal Stricture in a 5-Year-Old Child with Epidermolysis Bullosa: Case Report of a Rare Complication at a Very Young Age.

Epidermolysis bullosa (EB) represents a group of rare inherited mechanobullous disorders characterized by extreme skin and mucosal fragility. Dystrophic EB (DEB), caused by mutations in the COL7A1 gene, often leads to cycles of blistering, healing, and scarring with multisystem involvement, including the gastrointestinal tract. Esophageal strictures are not uncommon in recessive DEB (RDEB), appearing after the first decade of life (∼12.6 years). We describe a relatively early complication in a 5-year-old child. A 5-year-old girl with genetically confirmed RDEB presented with 4 months of progressive dysphagia, vomiting, and retrosternal pain, more pronounced with solids. Her disease history included severe skin fragility since birth, scarring, and autoamputation of toes. Examination showed multiple healed ulcers, mitten deformities of all limbs, dental caries, and bilateral corneal opacities. Laboratory evaluation revealed anemia (Hb 7.7 g/dL). Barium swallow demonstrated a short mid-esophageal stricture; upper gastrointestinal endoscopy confirmed focal narrowing at 14 cm from the incisors. Endoscopic balloon dilatation up to 8 mm using a controlled radial expansion was performed, and the patient was initiated on oral losartan (8 mg/day) to reduce transforming growth factors-β-mediated fibrosis and stricture recurrence. Serial dilatations were planned at 3-week intervals. This case represents one of the youngest reported presentations of esophageal stricture in RDEB. The combination of early endoscopic balloon dilatation and adjunct antifibrotic therapy with losartan may reduce recurrence and improve nutritional outcomes. Monitoring for early esophageal involvement in young patients with RDEB is essential for timely intervention.

Open article ↗

2026-06-26 | Use of Tramadol in Pain Management of Neonates with Epidermolysis Bullosa: A Single-Center Experience.

Background: Inherited Epidermolysis Bullosa (EB) is a wide group of rare genetic disorders characterized by mucocutaneous fragility and blister formation. In neonates with EB, pain control is particularly complex because painful skin lesions coexist with developmental vulnerability, repeated handling, and the need for frequent wound care. Traditional opioid use carries a risk of adverse effects such as respiratory depression. Tramadol, a centrally acting weak opioid with a dual mechanism of action, may offer a safer alternative. Methods: This retrospective observational study analyzed neonates with different EB subtypes admitted to our tertiary neonatal care center between January 2020 and October 2022. Genetic diagnosis was confirmed via next-generation sequencing. Pain was assessed using the Neonatal Infant Pain Scale (NIPS). Tramadol was administered intravenously (1-2 mg/kg bolus or 0.1-0.2 mg/kg/h infusion) before daily wound dressings, then transitioned to oral dosing when appropriate. Pain scores before and after tramadol administration were compared. Results: Six neonates with various EB subtypes were included. All patients received tramadol for procedural pain control. No significant differences in NIPS scores were observed before and after tramadol administration (p = 0.997), indicating adequate pain control, although baseline pain scores were low, limiting interpretation of analgesic efficacy. No immediate adverse events were observed during hospitalization or reported during follow-up. Conclusions: Scheduled tramadol administration appears to be a safe and effective option for pain management in neonates with EB, with no observed hemodynamic or respiratory complications. Given the scarcity of data in this population, our findings highlight the need for multicenter studies to establish standardized analgesia protocols for EB neonates.

Open article ↗

2026-06-23 | O2 Innate immune dysregulation drives recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma

Abstract Introduction and aims Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited, immunologically active, skin disorder, characterized by skin fragility and chronic inflammation, predisposing patients to aggressive early-onset squamous cell carcinoma (cSCC). Despite this, immunopathogenic mechanisms driving tumour progression remain poorly understood, while current treatments fail to address cancer initiation. This study aimed to characterize the RDEB-cSCC innate immune landscape to identify targetable pathways for therapeutic intervention. Methods We performed an integrated immune analysis using bulk RNA sequencing of matched nonlesional, perilesional and lesional biopsies as a strategy to model disease progression. This was complemented by peripheral blood immunophenotyping of healthy donors, patients with RDEB and patients with RDEB-cSCC to identify innate immune alterations associated with disease severity. To validate therapeutic targets, a patient-derived three-dimensional immunocompetent spheroid model was established, designed to recapitulate key tumour-promoting immune features, observed in patients with RDEB-cSCC. Results Transcriptomic profiling revealed a severity-dependent macrophage enrichment and activation of the immunoregulatory pathway, Janus kinase/signal transducer and activator of transcription (JAK/STAT)3, previously identified as a promising target in RDEB-cSCC. Lesional tissue and patient plasma exhibited concurrent upregulation of both pro- and anti-inflammatory cytokine signatures, indicating a dysregulated immune response. Peripheral immune profiling further revealed a significant shift towards alternatively activated monocytes, expressing CD163 and Tim4, suggesting a prepriming of precursor tumour-associated macrophages, linked to aggressive disease progression. Uniform manifold approximation and projection analysis identified unique monocyte clusters specific to RDEB-cSCC, associated with aggressive tumour behaviour. To functionally validate these tumour-promoting immune features, an immunocompetent spheroid model was developed recapitulating protumour macrophage differentiation and cytokines release associated with JAK/STAT3 activation. Targeting the model with the clinically approved JAK1/2 inhibitor, ruxolitinib, resulted in reduced spheroid growth, increase necrosis and a significant shift in monocyte polarization towards antitumour phenotype. Conclusions These findings highlight the innate immune dysregulation as a central driver of RDEB-cSCC, and targeting the monocyte–macrophage plasticity via the JAK/STAT3 pathway could be a potential early intervention strategy for treating RDEB-cSCC.

Open article ↗