Toxic Epidermal Necrolysis and Antifolate Drugs in Cancer Chemotherapy

Claudine      Pierard-Franchimont; Marianne      Lesuisse; Philippe      Humbert; Philippe      Delvenne; Gerald      E. Pierard

Abstract

Folates are one-carbon donors essential for synthesizing purines, pyrimidines, serine, and methionine. They correspond to anionic hydrophilic molecules essential for DNA synthesis in mammalian cells. The latter cells lack the capacity to synthesize folates. In some patients, high dosages of antifolate drugs (eg: methotrexate, pemetrexed) used in cancer chemotherapy alter the keratinocytes, endothelial cells and Factor XIIIa+ dermal dendrocytes in a range of various severities. Such conditions clinically designed under the heading antifolate cytotoxic skin reaction (ACSR) occasionally resemble the toxic epidermal necrolysis (TEN) / Stevens-Johnson syndrome (SJS) spectrum. Whether or not the TEN/SJS presentation of ACSR is a regular condition similar to that induced by other drugs or a variant condition supported by a unique pathomechanism is unsettled.

Keywords: Antifolate, methotrexate, pemetrexed, cancer, folate metabolism, toxic epidermal necrolysis, Stevens-Johnson syndrome, Folates, necrosis, lymphocytes, macrophages