Erythema multiforme (EM) is an immune-mediated inflammatory skin condition associated with several viral infections, that appears with red patches evolving into target lesions, typically on both hands.

[1][2][3] It is a type IV hypersensitivity reaction in which T-lymphocytes target skin keratinocytes due to the presence of specific proteins that resemble antigens of HSV, Mycoplasma, or other pathogens and foreign substances.

Individuals with persistent (chronic) erythema multiforme will often have a lesion form at an injury site, e.g. a minor scratch or abrasion, within a week.

[citation needed] Erythema multiforme typically arises as a type IV hypersensitivity reaction to certain infections or, rarely, certain medications.

[8] Stevens–Johnson syndrome and toxic epidermal necrolysis used to be considered part of the erythema multiforme "spectrum," but EM is now recognized as a fundamentally different condition.

HSV DNA is also detected in nearly half of patients with idiopathic EM, suggesting that the true frequency is even higher than traditionally thought.

Acute cases of erythema multiforme are often diagnosed clinically, based on symptom presentation, and treated with systemic steroid medications.