Erythema multiforme is an immune-mediated reaction that causes a raised, red, target-like rash on the skin or mucous membranes. It often resolves on its own but may require medical treatment.

Its name combines the Latin “erythema” (redness), “multi” (many), and “forme” (shapes) and describes its main symptom.

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.

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

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

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.

What does it look like?

Erythema multiforme minor presents as bulging, rash-like lesions that may be red or pink on lighter skin tones and dark brown or purple on darker skin tones. They may look like hives or somewhat round bull’s-eye targets. The center of the lesions is typically darker with lighter edges.

In erythema multiforme minor, lesions are often circular and less than 3 centimeters (cm) in size, though they 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, there are differences.

With erythema multiforme major, at least two mucous membranes will have lesions. Mucous membranes include the mouth, vagina or genitals, anal area, or conjunctiva of the eye. Lesions in these areas open into painful ulcers that contain fluid.

Lesions are still shaped like a bull’s-eye in the major type, but they 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.

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 illnesses that elicit an immune response. The most common causes are:

Herpes simplex virus

Herpes infection is the primary infectious cause of erythema multiforme. The herpes simplex virus (HSV) is present in 70% 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 (M. pneumoniae) infection, a contagious respiratory infection. In children, erythema multiforme is a complication in 2% to 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 causes of erythema multiforme include viral infections such as:

Medications

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

If a person develops a rash from a medication, they should see a 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.

The erythema multiforme rash is not contagious. 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 treatment. People with oozing lesions will need bandages and pain relief medications.

If a person is losing a lot of fluid from the blisters, they need to rehydrate. If drinking is painful due to mouth lesions, they may 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 preventive 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.

Optum Perks is owned by RVO Health. By clicking on this link, we may receive a commission. Learn more.

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 skin sample 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.

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 gradually enlarge, reaching up to 30 cm across. The lesions will usually appear 3 days to a month after getting a tick bite that causes Lyme disease.

In its minor form, erythema multiforme usually improves in 2 to 3 weeks and typically does not cause scarring.

Erythema multiforme major typically resolves in 4 to 6 weeks as mucosal lesions, such as mouth ulcers, take longer to heal. Scarring usually does not occur, but skin discoloration might persist.

Erythema multiforme is a skin condition that develops in response to infection or, in rare cases, certain medications.

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.