Fixed drug eruption: the dark side of activation of intraepidermal CD8+ T cells uniquely specialized to mediate protective immunity.

Fixed drug eruption (FDE) is generally regarded as representing the mild end of drug-induced dermatitis, but the clinical importance of recognizing this disease as an abortive, localized variant of toxic epidermal necrolysis has received increasing attention in recent years. FDE often presents with a wide spectrum of clinical manifestations indistinguishable from those of other skin diseases, such as erythema multiforme, Stevens-Johnson syndrome /toxic epidermal necrolysis, cellulitis, paronychia, lichen planus, and parapsoriasis en plaques. These unusual forms of FDE are likely to be overlooked unless the possibility of a drug etiology is routinely considered in the differential diagnosis of any patient with these diseases. Clinical awareness and recognition of these unique forms are essential for avoiding a misdiagnosis. Intraepidermal CD8+ T cells resident in the FDE lesions that have the capacity to rapidly produce large amounts of IFN-γ are likely to have a key role in mediating localized epidermal injury, while they may represent a T cell subset uniquely specialized to mediate protective immunity against various pathogens.