Toxic epidermal necrolysis: Pathophysiology and therapeutic advances

Toxic epidermal necrolysis is a rare and severe cutaneous adverse drug reaction. The histologic hallmark of this reaction is necrosis with detachment of the epidermis resulting in skin blistering. This is a life-threatening emergency with up to 30 % deaths in the acute phase. The percentage of blistering skin determines two clinical entities: Stevens-Johnson syndrome, in which detachment is less than 10 %, and Lyell's syndrome, in which it is greater than 30 %. The development of late complications, notably mucous synechiae, is frequent and must be systematically prevented. The pathophysiologic mechanism consists of a delayed drug hypersensitivity reaction in which cytotoxic T-lymphocytes play a major role. Genetic background is also very important with HLA-drug associations having been reported, notably in Asian populations. Treatment remains highly debated, with systemic steroids, cyclosporine or intravenous immunoglobulins all being commonly used. Some studies also suggest that TNF-alpha inhibitors are of value in treating this disease.