Erythema Multiforme



  • Erythema multiforme (EM) is an acute, self-limited mucocutaneous eruption characterized by distinct targetoid lesions on the skin.
  • Although classically defined by the presence of target lesions, at various stages of evolution, EM may appear as erythematous macules, papules, vesicles, or bullae.
  • EM is considered an immune-mediated reaction, usually to infectious triggers; numerous additional triggers have been reported in the literature.
  • Ranges from relatively mild cutaneous disease (EM minor) to severe forms with significant mucosal involvement (EM major)
  • Historically viewed as a spectrum of diseases, most authors now regard EM to be a separate entity from Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS and TEN are distinguished from EM by differing patterns of mucocutaneous involvement, precipitating factors, and prognosis.


  • Predominantly affects healthy young adults but can affect people of all ages, including young children
  • Possible seasonal variation with increased frequency in spring and summer. The more severe form has been reported to occur more frequently in winter.
  • Recurrences are common.


  • ~90% of cases are caused by an infectious agent, most commonly herpes simplex virus (HSV) or Mycoplasma pneumoniae.
  • <10% of cases are secondary to drug exposure. Common culprits include NSAIDs, sulfonamides, antiepileptics, and antibiotics.
  • Reported causes are numerous. Rare precipitants include the following:
    • Chemical and physical exposures
    • Immunizations
    • Autoimmune disease
  • Often, the causative factor is not identified.
  • HSV is the major cause of recurrent EM.
  • M. pneumoniae is associated with a distinct phenotype in children, characterized by more severe mucosal involvement, particularly oral and ocular, with less severe cutaneous findings. The term Mycoplasma-induced rash and mucositis, (MIRM) has been proposed to describe this particular presentation.

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