-Review-

A Review of the Pathogenesis of Toxic Epidermal Necrolysis

Yuri Kinoshita and Hidehisa Saeki

Department of Dermatology, Nippon Medical School, Tokyo, Japan

Toxic epidermal necrolysis (TEN) is a rare skin condition, most often drug-induced, known for its skin detachment and high mortality. In general, acute TEN is considered a T-cell mediated, type IV hypersensitivity disorder. It mostly results from a cumulative effect of risks from the drug structure, drug metabolism, HLA alleles and T cell clonotypes. However, the precise mechanism of TEN is still unknown. Apoptosis or necroptosis causes keratinocytes to lose their shape and adhesion, and necrosis predominates within a few days. Total epidermal necrosis separates the epidermis from the dermis. TEN is regarded as an immune reaction with predominantly CD8+ T lymphocytes, monocytes/macrophages, and natural killer cells. Impaired regulatory T-cells, T-helper 17 cells, cytotoxic granules such as perforin-granzyme and granulysin, tumor necrosis factor α, annexin, microRNA-18a-5p, and drug metabolites are all thought to be involved. From what is known, it can be assumed their mechanism is complex, and there is still much to be investigated. New findings will contribute to the identification of effective active methods of intervention.

J Nippon Med Sch 2016; 83: 216-222

Keywords
Fas-Fas ligand, apoptosis, pathogenesis, tumor necrosis factor α, toxic epidermal necrolysis

Correspondence to
Yuri Kinoshita, MD, MSc, Department of Dermatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
yuri-kino@nms.ac.jp

Received, September 13, 2016
Accepted, October 26, 2016