Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited blistering skin disorders characterized by skin fragility following minor trauma, usually present since birth. EB can be categorized into four classical subtypes, EB simplex, junctional EB, dystrophic EB and Kindler EB, distinguished on clinical features, plane of blister formation in the skin, and molecular pathology. Treatment for EB is mostly supportive, focusing on wound care and patient symptoms such as itch or pain. However, therapeutic advances have also been made in targeting the primary genetic abnormalities as well as the secondary inflammatory footprint of EB. Pre-clinical or clinical testing of gene therapies (gene replacement, gene editing, RNA-based therapy, natural gene therapy), cell-based therapies (fibroblasts, bone marrow transplantation, mesenchymal stromal cells, induced pluripotential stem cells), recombinant protein therapies, and small molecule and drug repurposing approaches, have generated new hope for better patient care. In this article, we review advances in translational research that are impacting on the quality of life for people living with different forms of EB and which offer hope for improved clinical management.
Background
Epidermolysis bullosa (EB) is a heterogeneous group of hereditary skin diseases characterized by skin fragility. Primary data on Taiwanese population remain scarce.
Methods
We gathered clinical information from EB patients at National Cheng Kung University Hospital from January, 2012, to June, 2021. Diagnostic tests including transmission electron microscopy, immunofluorescence studies, and whole-exome sequencing (WES) were performed. The pathogenicity of novel splice-site mutations was determined through reverse transcriptase-PCR of skin mRNA followed by Sanger and/or RNA sequencing.
Results
Seventy-seven EB patients from 45 families were included: 19 EB simplex, six junctional EB, and 52 dystrophic EB. Pathogenic variants were identified in 37 of 38 families (97.4%), in which WES was used as a first-line tool for mutational analysis; RNA sequencing determined pathogenic variants in the remaining one family. A total of 60 mutations in EB-related genes were identified, including 22 novel mutations. The mutations involved KRT5, KRT14, PLEC, COL17A1, LAMB3, LAMA3, ITGB4, and COL7A1. Over one-quarter of DEB patients had EB pruriginosa.
Conclusions
The distinct clinical presentation and molecular pathology of EB in Taiwan expand our understanding of this disorder. WES was an effective first-line diagnostic tool for identifying EB-associated variants. RNA sequencing complemented WES when multiple potentially pathogenic splice-site mutations were found.
Psoriasis in different body regions displays varying therapeutic responses to biologics, whereas currently relevant studies remain scarce. We retrospectively reviewed the treatment responses of patients with moderate-to-severe psoriasis, who completed the two-year reimbursed ustekinumab or secukinumab treatment in two medical centers in Southern Taiwan. Demographic profiles and body regional PASI scores (head/neck, trunk, upper and lower limbs) along the treatment course were recorded. The proportions of patients attaining PASI 75, 90, 100 and the extent of body regional PASI score improvements were compared in biologic naïve or experienced patients. A total of 57 and 67 patients receiving ustekinumab and secukinumab injections, respectively, were included. Overall, patients receiving secukinumab showed higher degrees of PASI score improvements along the two-year treatment course. The lower limbs had the highest, and the upper extremities and head/neck
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