Immunobiology of acute cytotoxic drug reactions

While relatively rare, the clinical presentation of toxic epidermal necrolysis (TENS) is often very dramatic and unfortunately it frequently results in the loss of life due to extensive epidermal necrosis and subsequent complications. The etiology of TENS is fairly well known and linked to ingestion of various medications. However, the pathophysiology and treatment of TENS is less well understood, but abnormal immunological mechanisms have been implicated by some investigators. The purpose of this chapter is to review the clinical features of TENS, followed by dermatopathological and immunopathological aspects of the skin lesions. A review of basic skin biology as regards regulation of keratinocytes' life and death is provided with emphasis on premature cell death. After a review of the immunopathogenic theories for TENS, a discussion of possible therapeutic interventions concludes the chapter. Clearly, many new insights are required at multiple levels of understanding to better manage and perhaps even prevent TENS.