Immunological mechanisms of epidermal damage in toxic epidermal necrolysis.

PURPOSE OF REVIEW

The purpose of the present review is to introduce recent findings on the pathomechanisms of toxic epidermal necrolysis (TEN), which is characterized by widespread epidermal detachment due to keratinocyte apoptosis.

RECENT FINDINGS

In the mechanism of epidermal damage, the roles of drug metabolites, cytotoxic lymphocytes, and apoptosis-inducing factors have been noted. In addition, recent studies have focused on monocytes/macrophages, which may participate in epidermal damage through the production of apoptosis-inducing factors and the expression of costimulatory factors with the ability to activate CD8 T cells.

SUMMARY

Epidermal keratinocyte death is a hallmark of TEN. In a very high proportion of cases, drugs are responsible for TEN. It has been suggested that toxic drug metabolites produced by keratinocytes act like electrophilic agents to induce apoptosis and inflammation. Next, cytotoxic lymphocytes and monocytes function in the development of widespread epidermal damage through direct or indirect cytotoxic pathways. In addition, T-cell activation may be strengthened by the impairment of regulatory T-cell function and activated monocytes. The development of epidermal damage in TEN may require the coordinated action of these factors.