Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited blistering skin disease, resulting from biallelic mutations in COL7A1, the gene encoding type VII collagen (C7). At mucocutaneous barriers, tissue integrity relies upon linked extracellular matrix (ECM) proteins forming a physiologic suture, connecting basal epidermal keratinocytes to the underlying dermis. C7 secreted from epidermal keratinocytes and dermal fibroblasts homotrimerizes in the upper dermis to form anchoring fibrils, a critical component of this suture. Clinical manifestations of RDEB are apparent at birth and include exquisite skin fragility, pain and itch, high metabolic demand, and complications downstream of systemic inflammation. Dermal fibrosis is a critical complication of RDEB. Repeated cycles of mechanical injury and healing trigger characteristic fibrotic changes. In addition to functional limitations from joint strictures and pseudosyndactyly formation, dermal fibrosis in RDEB is a nidus for and potential driver of aggressive squamous cell carcinoma (SCC), the leading cause of death in RDEB. A greater understanding of fibrosis in RDEB promises to inform impactful, life-prolonging clinical trials in this patient population with no proven systemic therapy or cure.

中文翻译：

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解构隐性营养不良性大疱性表皮松解症的进行性炎症纤维化

隐性营养不良性大疱性表皮松解症 (RDEB) 是一种遗传性水疱性皮肤病，由 COL7A1 中的双等位基因突变引起，编码 VI​​I 型胶原蛋白 (C7) 的基因。在皮肤粘膜屏障处，组织完整性依赖于连接的细胞外基质 (ECM) 蛋白，形成生理缝合线，将基底表皮角质形成细胞连接到下面的真皮。从表皮角质形成细胞和真皮成纤维细胞分泌的 C7 在真皮上部同三聚化以形成锚定原纤维，这是这种缝合线的关键组成部分。RDEB 的临床表现在出生时就很明显，包括精致的皮肤脆弱、疼痛和瘙痒、高代谢需求以及全身炎症下游的并发症。皮肤纤维化是 RDEB 的严重并发症。机械损伤和愈合的重复循环触发特征性纤维化变化。除了关节狭窄和假并指形成的功能限制外，RDEB 中的真皮纤维化是侵袭性鳞状细胞癌 (SCC) 的病灶和潜在驱动因素，SCC 是 RDEB 死亡的主要原因。对 RDEB 中纤维化的更深入了解有望为该患者群体中的有影响力的、延长生命的临床试验提供信息，这些临床试验尚未得到证实的全身治疗或治愈。