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Erythema Multiforme (EM)

Erythema multiforme (EM) is a dermatological condition characterised by red patches that evolve into target lesions, typically appearing on both hands. It is considered to be mediated by the deposition of immune complexes, predominantly IgM-bound complexes, in the superficial microvasculature of the skin and oral mucous membranes, often following an infection or drug exposure.

EM is an uncommon disorder, peaking in incidence during the second and third decades of life. The condition has various forms and presentations, which is reflected in its name (multiforme, "multiform").

Erythema multiforme minor of the hands (note the blanching centres of the lesion)
Erythema multiforme minor of the hands (note the blanching centres of the lesion)

Signs and Symptoms

The clinical presentation of EM varies, ranging from a mild, self-limited rash known as erythema multiforme minor to a severe, life-threatening form called erythema multiforme major, which also involves the mucous membranes. The classification of EM can be summarised as follows:

  • Erythema multiforme minor: Characterised by typical target lesions or raised, edematous papules distributed acrally.
  • Erythema multiforme major: In addition to the typical target lesions or raised, edematous papules distributed acrally, this form involves one or more mucous membranes. Epidermal detachment in these cases involves less than 10% of the total body surface area.

Stevens–Johnson syndrome and toxic epidermal necrolysis were previously considered part of the EM spectrum but are no longer classified as such.

The mild form of EM typically presents with mildly itchy (though itching can be severe), pink-red blotches that are symmetrically arranged, starting on the extremities. The lesions often take on a target-like appearance, with a pink-red ring surrounding a pale centre. Usually, the condition resolves within 7–10 days.

Target lesion
Target lesion
Erythema Multiforme target lesions on the leg
Erythema Multiforme target lesions on the leg
Erythema multiforme of tongue
Erythema multiforme of tongue
Erythema multiforme of head and limbs
Erythema multiforme of head and limbs


Numerous etiologic factors can trigger EM, including:

  • Infections: Bacterial (e.g., Streptococci, Neisseria meningitidis), fungal (e.g., Coccidioides immitis), parasitic (e.g., Trichomonas species, Toxoplasma gondii), and viral (especially herpes simplex virus).
  • Drug reactions: Common culprits include antibiotics (sulphonamides, penicillin), anticonvulsants (phenytoin, barbiturates), aspirin, modafinil, antituberculoids, and allopurinol.
  • Physical factors: Radiotherapy, cold, and sunlight.
  • Others: Collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia, multiple myeloma, myeloid metaplasia, and polycythaemia.

EM minor is often triggered by herpes simplex virus (HSV), accounting for almost all cases. HSV also accounts for 55% of EM major cases. Mycoplasma infection is another common cause.


EM is frequently self-limiting and may not require any treatment. The use of glucocorticoid therapy is sometimes debated due to the difficulty in predicting the course of the condition. Suppression or prophylaxis of herpes simplex virus with antiviral medications such as acyclovir has been shown to prevent recurrent EM eruptions.

Self-assessment MCQs (single best answer)

What is the primary characteristic of erythema multiforme (EM)?

Which immune complexes are predominantly involved in the pathogenesis of EM?

What is the most common age of incidence for erythema multiforme?

Which of the following is NOT a form of erythema multiforme?

In erythema multiforme major, what is the maximum percentage of total body surface area that can be involved?

Which of the following is a common cause of EM minor?

What is the typical appearance of the lesions in erythema multiforme?

Which of the following treatments is commonly used to prevent recurrent eruptions of erythema multiforme?

Which of the following drugs is NOT commonly associated with triggering erythema multiforme?

Which type of infection is most commonly associated with erythema multiforme minor?


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