Erythema multiforme (EM) is a self-limited hypersensitivity reaction of the skin and mucous membranes that is characterized by the acute onset of persistent lesions of concentric color change (target lesions). Two subtypes of EM exist: EM minor and EM major. Key differences between the EM subtypes include mucosal involvement and systemic symptoms such as fever, arthralgias, and asthenias seen in the major subtype. In the past, EM, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) were considered a continuum, but it is now recognized that EM does not progress to TEN. Typically, all cutaneous lesions appear within 24-72 hours and persist for 1-4 weeks before fading. The eruption often recurs on repeated exposure to the inciting agent.

In older children and adults, herpes simplex virus (HSV) is a common etiology; however, HSV has not been reported as a significant etiology in infants. EM in neonates and infants is exceedingly rare. Reported triggers for infantile EM have included drugs (particularly penicillin), hepatitis, hepatitis B vaccination, Candida, and cow's milk.