This 41-year-old African-American woman had recurrent bouts of erythema multiforme, each approximately one year apart. She has a history of elevated Herpes simplex virus (HSV) titers in her blood. Recurrent erythema multiforme is associated with HSV infection, and less often drugs. When the disease process advances beyond simple targetoid lesions, the necrosis can lead to separation of the epidermis from the dermis, causing blister formation. Although bullous erythema multiforme is not necessarily common, this case demonstrates the typical histopathology. A clue to the diagnosis is looking at the epidermis away from the blister, to find a classic erythema-multiforme-reaction pattern. The roof of the blister may become completely necrotic, resembling toxic epidermal necrolysis. In fact, there is a histologic continuum from targetoid erythema multiforme to bullous erythema multiforme to Stevens-Johnson syndrome and toxic epidermal necrolysis. The histologic differential diagnosis in this case would also include a bullous fixed drug eruption.
Histologic sections of skin demonstrate separation of the epidermis in a subepidermal plane. At low power, the blister cavity appears to contain a few inflammatory cells. There is a mild but present inflammatory infiltrate within the dermis.