Erythema multiforme

Last updated: March 14, 2023

Summarytoggle arrow icon

Erythema multiforme (EM) is a rare, acute hypersensitivity reaction most commonly triggered by herpes simplex virus (HSV) infections. Other triggers include M. pneumoniae infection, certain drugs, and immunizations. EM is mainly seen in adults between 20–40 years of age. Clinical features include a rash of varied appearance, beginning as macules and papules, which evolve into characteristic target lesions. The rash first appears on the dorsal aspect of the hands and feet then extends proximally. If mucous membrane involvement and systemic symptoms occur, the condition is defined as EM major. The diagnosis is often clear on history and physical examination, whereas serology for underlying infectious causes and/or skin biopsy may be necessary in doubtful or recurrent cases. EM is usually self-limiting and resolves spontaneously within a month; symptomatic treatment with NSAIDs, antihistamines, and topical steroids is generally sufficient. In severe cases of EM major, hospitalization to treat dehydration, severe pain, and possible bacterial superinfection may be necessary.

Epidemiologytoggle arrow icon

  • Incidence: < 1% per year
  • Age: mainly adults 20–40 years
  • Sex: slight male predominance


Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Erythema multiforme is a type IV hypersensitivity reaction; which can be triggered by the following.


Clinical featurestoggle arrow icon

  • Rash
  • Distribution
    • Symmetrical distribution
    • Affects backs of hands and feet first → spreads proximally and can affect the entire body, including palms and soles
    • Mucous membrane involvement
      • EM minor: no/minimal involvement of mucus membranes
      • EM major: painful ulcers of the oral (most common), ocular, genital mucosa
  • Further symptoms: fever, myalgia, and arthralgia in cases of EM major


Diagnosticstoggle arrow icon

The diagnosis is mainly clinical and should be suspected (especially) if there is a history of recurrent labial herpes, recent drug intake, or immunizations.


Differential diagnosestoggle arrow icon


The differential diagnoses listed here are not exhaustive.

Treatmenttoggle arrow icon

In most cases of EM, no treatment is necessary because the condition is self-limiting.


Prognosistoggle arrow icon

  • EM is usually self-limiting; rash spontaneously disappears within a month
  • Some patients may have a recurrence of EM.


Referencestoggle arrow icon

  1. Lamoreux MR, Sternbach MR, Hsu WT. Erythema multiforme. Am Fam Physician. 2006; 74 (11): p.1883-1888.
  2. Kaur S, Handa S. Erythema multiforme following vaccination in an infant. Indian J Dermatol Venereol Leprol. 2008; 74 (3): p.251-253.
  3. Erythema Multiforme. Updated: October 1, 2015. Accessed: May 16, 2017.
  4. Wetter DA. Pathogenesis, Clinical Features, and Diagnosis of Erythema Multiforme. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: November 15, 2016. Accessed: May 16, 2017.
  5. Shiohara T. Fixed Drug Eruption. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: August 1, 2016. Accessed: May 16, 2017.
  6. Valente Duarte de Sousa IC. Fixed drug eruption. N Engl J Med. 2011; 365: p.e12.doi: 10.1056/NEJMicm1013871 . | Open in Read by QxMD
  7. Fixed Drug Eruption. Updated: January 1, 2001. Accessed: May 16, 2017.

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