Erythema multiforme is an immune-mediated reaction that causes a raised, red, target-like rash on the skin or mucous membranes. Its name combines the Latin “erythema” (redness), “multi” (many), and “forme” (shapes) and describes its main symptom.

Erythema multiforme can affect people of any age, with children representing 20 percent of cases. However, it most commonly occurs in young adults between 20 and 30 years old. It is more prevalent in men, affecting five men for every one woman.

Erythema multiforme can be minor or major. Erythema multiforme minor is usually a mild condition that causes a rash on the skin. Erythema multiforme major can be severe, affecting the mucous membranes, and typically requires more extensive treatment.

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Erythema multiforme rash. Erythema multiforme usually results from an immune system response to an infection, medication, or vaccination.
Photography by DermNet New Zealand
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Widespread erythema multiform rash. The erythema multiforme rash usually appears over 3 to 5 days and gets better in about 2 weeks.
Photography by DermNet New Zealand
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Erythema multiforme minor (note the blanching centers of the lesions).
James Heilman, MD/Wikimedia Commons
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Erythema multiforme rash on a child. Rarely, low fever, joint pains, body aches, and itching accompany the erythema multiforme rash.
Grook Da Oger/Wikimedia Commons

Erythema multiforme is an immune reaction of the skin that develops in response to a viral infection. It can sometimes occur as a result of medications or other factors.

What does it look like?

Erythema multiforme minor presents as a bulging, rash-like lesion that is red, pink, or purple. It may look like a hive or a somewhat round bull’s-eye target. The center of the lesion is typically darker with lighter pink edges.

The lesion is often circular and less than 3 centimeters (cm) in size, though it may be larger or smaller. The outermost circle has a well-defined border, while the center may be a blister. The condition almost always involves the palms of the hands.

People may think erythema multiforme major looks similar to erythema multiforme minor. However, the most significant difference in the major type is the amount of mucus and the size of the affected areas.

With erythema multiforme major, at least two mucous membranes will have lesions. The rash is still shaped like a bull’s-eye in the major type, but it may be slightly larger, and the circles may run into each other. The lesions are more likely to blister and burst, and these areas of skin may be sore and oozing.

Where does it appear?

Erythema multiforme minor may affect the feet, face, ears, palms, and back of the hands. It often presents initially on the hands or feet before moving toward the torso.

Erythema multiforme major typically affects the mouth, genitals, anus, or eyes.

A person with erythema multiforme may also experience the following symptoms:

  • itching and burning rash, which is the most common symptom
  • fever or body temperature of 100.4°F (38°C) or higher
  • headache
  • general feeling of being unwell, sometimes before the rash appears
  • joint pain and swelling
  • sores in the moth
  • sores and redness in the eyes
  • sensitivity to light
  • joint pain

A person may experience coughing and difficulty breathing as signs of an underlying infection causing the condition, but this is rare.

Most erythema multiforme lesions are not painful, although some people may experience a burning sensation. Lesions involving mucous membranes, such as those on the mouth, throat, genitals, or eyes, can be painful.

Erythema multiforme can occur due to an allergic reaction to an infection, medications, or other types of illnesses that elicit an immune response. The most common causes are:

Herpes simplex virus

Herpes infection is the primary cause of erythema multiforme. The herpes simplex virus (HSV) is present in 70 percent of recurrent erythema multiforme cases.

Both types of herpes simplex virus (HSV-1 and HSV-2) can cause the condition, but HSV-1, which also causes cold sores, is responsible for most cases.

Herpes outbreaks typically happen 7 to 10 days before erythema multiforme develops. However, it is possible to develop erythema multiforme without herpes symptoms.

Mycoplasma pneumoniae

Another cause of erythema multiforme is Mycoplasma pneumoniae infection, a contagious respiratory infection with Mycoplasma pneumoniae (M. pneumoniae) bacteria. In children, erythema multiforme is a complication in 2–10% of cases of M. pneumoniae infection.

If doctors suspect M. pneumoniae is causing erythema multiforme, they will likely treat it immediately.

Other infectious causes

Other common causes of erythema multiforme include viral infections such as:

  • cytomegalovirus
  • influenza
  • Epstein-Barr, which causes mono
  • adenovirus
  • hepatitis
  • HIV
  • parapoxvirus

Medications

In rarer cases, medication can lead to erythema multiforme. Medications associated with erythema multiforme include:

  • barbiturates, sometimes prescribed for anxiety
  • nonsteroidal anti-inflammatory drugs (NSAIDs)
  • phenothiazines for the treatment of mental and emotional disorders
  • sulfonamides, penicillin, and nitrofurantoin
  • anticonvulsants
  • statins, which help reduce cholesterol

It is rare for medications to cause erythema multiforme. However, if a person develops a rash from a medication, they should see their doctor right away. A rash can be a sign of a severe drug reaction called Stevens-Johnson syndrome or toxic epidermal necrolysis.

Other causes

Other rare causes include vaccines and cancers. Vaccines associated with erythema multiforme include the MMR (measles, mumps, and rubella) vaccine, and those for smallpox, hepatitis B, varicella, and influenza.

Cancers such as leukemia, lymphoma, renal cell carcinoma, and gastric adenocarcinoma have been linked to erythema multiforme.

Erythema multiforme is not contagious in itself. A person cannot get the rash from coming in contact with someone who has it.

However, if the underlying cause is a viral infection, that condition may be transmittable.

Erythema multiforme minor usually resolves by itself, but treatment is sometimes necessary. A doctor might prescribe topical steroids if symptoms persist.

Erythema multiforme major requires much more treatment. People with oozing lesions will need bandages and pain relievers.

If a person is losing a lot of fluid from the blisters, they may also need to receive intravenous fluids through an IV line — possibly in a hospital setting if the lesions are extensive. Doctors might also prescribe steroids, mouthwashes with topical anesthetic, and eye drops.

If HSV causes the skin reaction, some doctors suggest using an oral antiviral medication called acyclovir. Acyclovir can be particularly beneficial as a prevention method for recurrent cases of erythema multiforme resulting from HSV.

If M. pneumoniae infection is responsible for the rash, doctors may prescribe antibiotics such as a macrolide, tetracycline, or azithromycin.

Blood tests are not necessary to diagnose erythema multiforme. Doctors can usually identify it by observing the lesions.

Occasionally, a skin biopsy may be necessary to rule out other conditions. To do this, a doctor will take a small sample of skin from the affected area and send it to a laboratory for analysis.

Doctors may do a chest X-ray if they suspect M. pneumoniae is the cause.

People sometimes confuse erythema multiforme with Stevens-Johnson syndrome or toxic epidermal necrolysis, as skin reactions of this type have similar symptoms. These conditions are medical emergencies.

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Toxic epidermal necrolysis is a life threatening skin disorder that presents as blistering and peeling of the skin, leaving large areas of dermis exposed. This leads to infection, pain, loss of fluids, and possibly death.
Wikimedia Commons

Erythema migrans is a skin condition specifically associated with Lyme disease. It appears as a bull’s-eye rash on the skin with a central clearing.

Unlike the lesions of erythema multiforme, those of erythema migrans are bigger in size, ranging from about 5–68 cm on average. The lesions will usually appear 3 days to a month after a person is bitten by a tick and contracts Lyme disease.

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Erythema migrans is a rash that has a strong association with Lyme disease. This rash presents as a circular red area with a clearing in the middle, forming a bull’s-eye. It can appear all over the torso and can be painless.
Photography courtesy of CDC/James Gathany/Wikimedia

Erythema multiforme is a skin condition that develops in response to infection or, in rare cases, certain medications. In its minor form, erythema multiforme will usually get better in 2-4 weeks.

Doctors will try to identify and treat the cause of erythema multiforme, but they may also prescribe topical treatments for the rash.

Erythema multiforme major requires more extensive treatment, which can consist of wound management, pain medication, and potentially hospitalization.