Atypical epidermolysis bullosa simplex with a missense keratin 14 mutation p.Arg125Cys

Abstract

Epidermolysis bullosa (EB) is a group of hereditary autosomal dominant bullous diseases. EB is divided into four major phenotypes: intraepidermal EB (or EB simplex), junctional EB, dermolytic EB and mixed EB (Kindler syndrome). EB simplex is further divided into three subtypes: localized EB simplex, Dowling-Meara EB simplex and other generalized EB simplex. We report a 28-year-old man with EB simplex with a missense keratin 14 mutation p.Arg125Cys associated with clumping of keratin filaments and acantholysis in mainly the spinous cells and basal cells. Immunohistochemistry revealed that the broader expression of keratin 5 and 14 was observed in the epidermis, while the expression of keratin 1/10 was quite normal. Dysregulated expression of keratin 5/14 may hinder some functions or roles of keratin 1/10, namely filament assembly of keratin 1/10 in spinous cell integrity, although the expression of keratin 1/10 was not affected and this has not been demonstrated before.

MMP-9 and CXCL8/IL-8 Are Potential Therapeutic Targets in Epidermolysis Bullosa Simplex

“…Hypothetically, kallikreins could play a role in acantholysis, the separation of cell-cell contacts, but there are only few reports of Dowling-Meara patients that show signs of acantholysis [26], [27]. Nevertheless, since we did not observe any differences in KLK5 and KLK7 expression in patients blister fluids vs. controls, their role as potential therapeutic targets can not be suggested.…”

Mimickers of classic acantholytic diseases

“…Patients present with widespread, often hemorrhagic, blistering at birth, sometimes displaying arciform or grouped configurations. Nail, hair and dentition abnormalities are also present . A case with clinical and ultrastructural features consistent with DM‐EBS has been reported, with prominent acantholysis‐mimicking pemphigus vulgaris or LAEB .…”

“…Rare cases of DM-EBS with prominent acantholysis have been reported. 13,19 DM-EB is a severe type of classic EBS, resulting from mutations in genes encoding basal keratinocyte intermediate filaments 5 and 14 (KRT5/14) with the unique ultrastructural abnormality of clumped tonofilaments, as seen on electron microscopy. 13,[19][20][21] Patients present with widespread, often hemorrhagic, blistering at birth, sometimes displaying arciform or grouped configurations.…”

“…13,[19][20][21] A case with clinical and ultrastructural features consistent with DM-EBS has been reported, with prominent acantholysis-mimicking pemphigus vulgaris or LAEB. 19 Though the exact mechanism of acantholysis is not clearly understood, additional findings of dyskeratosis due to tonofilament clumping, somewhat similar to that seen in Darier's disease, and the observation that severe keratin mutations downregulate other cell junction proteins, including desmosomal proteins, may suggest that severe keratin mutations induce acantholysis indirectly. 22 A single case described as "acantholytic epidermolysis bullosa" reported a kindred with an acrally distributed mechanobullous disease closely resembling Weber-Cockayne EBS.…”