Erythema multiforme is a type of hypersensitivity (allergic) reaction that occurs in response to medications, infections, or illness. Medications associated with erythema multiforme include sulfonamides, penicillins, barbiturates, and phenytoin. Associated infections include herpes simplex and mycoplasma infections.

The exact cause is unknown. The disorder is believed to involve damage to the blood vessels of the skin with subsequent damage to skin tissues. Approximately 90% of erythema multiforme cases are associated with herpes simplex or Mycoplasma infections. The disorder occurs primarily in children and young adults.