An Unusual Case Report of Dystrophica Epidermolysis Bullosa in a Child

Epidermolysis bullosa (EB) is a genetically inherited severe skin disease involving dermal-epidermal junction. Based on the appearance and involvement, it is grouped into simplex, junctional & dystrophic forms. These disorders represent heterogeneous phenotypes and are correlated with a variable range of complications, from localized skin fragility to neonatal death. Genetic testing had made a precise diagnosis and it requires only supportive and symptomatic therapy. Here we report an atypical case of dystrophica epidermolysis bullosa in a 6-year-old male child. Epidermolysis bullosa (EB) is a general term used for heterogeneous group of congenital, genetic blistering disorders. It has a wide spectrum of clinical presentations. 1 It is characterized by induction of blisters by trauma, exacerbation of blistering in warm weather and healing with scarring. EB can be categorized under three major groups - epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB). EB simplex has an incidence and a prevalence rate of 10.75 and 4.65, 2.04 and 0.44 of junctional EBs and 2.86 and 0.99 of dystrophic EBs and recessive dystrophic EB 2.04 and 0.92 respectively.2 The dystrophic forms are characterized by deformities of the skin including coalescence of the fingers, nail changes and milia formation.3 This case report highlights the rare presentation of recurrent episodes of blisters and limb deformities in 6 - year - old male children.

Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of devastating genetic diseases characterized by skin and mucosal fragility and formation of blisters, which develop either spontaneously or in response to minor mechanical trauma. There is no definitive therapy for any form of EB. Intermediate junctional EB (JEB) caused by mutations in the gene LAMB3 has been the first genetic skin disease successfully tackled by ex vivo gene therapy. Here, we present a multicenter, open-label, uncontrolled phase II/III study that aims at confirming the efficacy of Hologene 5, a graft consisting of cultured transgenic keratinocytes and epidermal stem cells and meant to combine cell and gene therapy for the treatment of LAMB3-related JEB. Autologous clonogenic keratinocytes will be isolated from patients’ skin biopsies, genetically corrected with a gamma-retroviral vector (γRV) carrying the full-length human LAMB3 cDNA and plated onto a fibrin support (144cm2). The transgenic epidermis will be transplanted onto surgically prepared selected skin areas of at least six JEB patients (four pediatric and two adults). Evaluation of clinical efficacy will include, as primary endpoint, a combination of clinical parameters, such as percentage of re-epithelialization, cellular, molecular, and functional parameters, mechanical stress tests, and patient-reported outcome (PRO), up to 12months after transplantation. Safety and further efficacy endpoints will also be assessed during the clinical trial and for additional 15years in an interventional non-pharmacological follow-up study. If successful, this clinical trial would provide a therapeutic option for skin lesions of JEB patients with LAMB3 mutations and pave the way to a combined cell and gene therapy platform tackling other forms of EB and different genodermatoses.Clinical Trial Registration: EudraCT Number: 2018-000261-36.

Case Report: Crown Resorption in a Patient With Junctional Epidermolysis Bullosa and Amelogenesis Imperfecta With LAMB3 Gene Mutations

Background: Epidermolysis bullosa (EB) corresponds to a series of conditions characterized by extreme fragility of the skin and/or mucous membranes. Of the four main types of EB, junctional EB (JEB) is the most associated with alterations in the teeth. The purposes of this study were to determine the clinical, histopathological, and ultrastructural characteristics of teeth with amelogenesis imperfecta (AI) in a patient with JEB, and compare them with control teeth, and correlate the findings with the mutations present in the patient.Case Report: The study was conducted on a 10-year-old patient with JEB carrier of two recessive mutations in the LAMB3 gene and absence of the laminin-332 protein (LM-332), determined by immunofluorescence on a skin biopsy. The patient presents hypoplastic AI with very thin and yellow-brown colored enamel. Extraction of two permanent molars was performed due to pain and soft tissue covering the crown, resembling pulp polyp or hyperplastic gingiva. Light and scanning electron microscopy (SEM) revealed very thin enamel varying from complete absence to 60 μm, absence of normal prismatic structure, and presence of a cross-banding with a laminated appearance. The histopathological study revealed granulation tissue causing external crown resorption.Conclusion: Although coronary resorption has been reported in patients with syndromic and non-syndromic AI, this is the first clinicopathological report of coronary resorption in partially erupted teeth in patients with JEB with mutations in the LAMB3 gene and hypoplastic AI. In patients with this condition, the presence of partially erupted teeth with soft tissue covering part of the crown, without a periodontal pocket, and with a radiographic image of partial coronal radiolucency should lead to suspicion of external coronary resorption.