Association of Acetaminophen With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Pharmacologic Considerations and Treatment Options.

Acetaminophen is an extremely common drug with many implications for its analgesic and antipyretic properties. It has a unique mechanism of action and downstream effects that separate it categorically from non-steroidal anti-inflammatory drugs. These differences come with potential adverse effects that range from mild drug reactions to severe life-threatening emergencies. While acetaminophen's toxic liver effects are well known, a lesser-known adverse effect of this drug is its association with the development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These dermatological emergencies involve similar pathological processes, including apoptosis of the epidermis and sloughing of the dermis and mucosa from the underlying layers with a positive Nikolsky sign. Currently, SJS and TEN are considered immune-mediated type IV hypersensitivity reactions predominantly involving CD8+ T lymphocytes. Other immune mediators, including regulatory T cells, natural killer cells, interleukins, and drug metabolites are speculated to be involved, but their mechanisms have not been entirely determined. These conditions are differentially diagnosed by the percentage of body area affected with SJS and TENS, involving <10% and >30%, respectively. Genomic variations in human leukocyte antigens (HLA) genes have been implicated in the susceptibility and severity of acetaminophen-induced SJS/TENS, however, details of these interactions remain unclear. Acetaminophen's widespread use and the morbidity of its associated skin pathologies SJS and TENS warrant an in-depth examination of the causative processes involved in their pathogenesis. It is critical that both physicians and patients be made aware that while acetaminophen is widely tolerated by most individuals, severe and potentially fatal interactions do occur, and further investigation is necessary to reduce these adverse effects.