Clinical outcomes of gentamicin therapy in dystrophic Epidermolysis Bullosa: a case-based literature review

Abstract

Introduction: Epidermolysis bullosa (EB) comprises a group of inherited disorders characterized by skin fragility and blister formation resulting from mutations in proteins essential for dermoepidermal adhesion. Dystrophic EB (DEB), particularly its recessive form (RDEB), is caused by mutations in the COL7A1 gene, leading to defective type VII collagen and impaired anchoring fibrils. Clinically, severe forms are associated with chronic wounds, scarring, pseudosyndactyly, mucosal involvement, and increased risk of cutaneous squamous cell carcinoma. Current therapeutic options remain limited and largely supportive. Gentamicin has emerged as a potential disease-modifying therapy due to its ability to induce translational readthrough of nonsense mutations, restoring partial production of functional collagen VII. This study aims to analyze published cases of EB treated with gentamicin and identify patterns in clinical response and therapeutic outcomes. Methodology: A case-based literature review was conducted, including studies published between 2020 and 2026, retrieved from the PubMed and SciELO databases, in English, Portuguese, and Spanish. Patients with severe generalized dystrophic epidermolysis bullosa treated with gentamicin were included. Extracted variables comprised age, sex, EB subtype, genetic mutation, route of administration (topical or intravenous), treatment duration, methods used to assess response (including immunofluorescence, quality of life scales, and pain scores), collagen VII expression before and after treatment, clinical improvement, adverse effects, and follow-up duration. Data from four studies were compiled into a comparative table to identify trends in therapeutic response and safety outcomes. Discussion: Across the analyzed cases, gentamicin therapy was consistently associated with increased expression of type VII collagen and corresponding clinical improvement, including enhanced wound healing and reduction of mucocutaneous lesions. These findings support its mechanism of action as a readthrough agent that partially restores protein synthesis in patients with nonsense mutations in COL7A1. Both topical and intravenous routes demonstrated therapeutic benefit, although with different clinical profiles. Topical administration was predominantly associated with localized improvement, particularly in oral and cutaneous lesions, reflecting its direct action on treated areas. In contrast, intravenous administration was associated with more systemic effects. Despite these promising findings, variability in treatment response was observed, likely influenced by mutation type, disease severity, and differences in treatment protocols. Additionally, methodological heterogeneity across studies, such as variation in biopsy sites, outcome measures, and duration of therapy, limits direct comparability. Importantly, no significant adverse effects were reported across the included studies, suggesting a favorable short-term safety profile. Some studies also demonstrated maintenance of collagen VII expression after treatment discontinuation, although without evidence of progressive improvement over time. Conclusion: Gentamicin appears to be a promising therapeutic strategy for patients with dystrophic epidermolysis bullosa, particularly those with nonsense mutations in COL7A1. The available evidence demonstrates increased collagen VII expression and associated clinical improvement, regardless of the route of administration. The absence of significant adverse effects supports its short-term safety. However, further large-scale and controlled studies are needed to establish standardized treatment protocols and confirm long-term efficacy.