Erythema multiforme is a skin immune reaction that an infection or medication can trigger. Its name combines the Latin “erythema” (redness), “multi” (many), and “forme” (shapes) and describes the main symptom, which is a rash on the body where each mark resembles a bullseye.

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 skin rash. Erythema multiforme major can be more severe and typically requires more extensive treatment.

What is erythema multiforme?

Erythema multiforme is a skin immune reaction that develops in response to infection but can sometimes occur as a result of medication.

What does it look like?

Erythema multiforme minor presents as a bulging, rash-like lesion that is red, pink, purple, or brown.

It is usually circular, less than 3 centimeters in size, and similar to a bullseye in appearance. The outermost circle has a well-defined border, while the center may be a blister.

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.

The rash is still bullseye-shaped 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. Depending on their location, the lesions may also produce mucus.

With erythema multiforme major, at least two areas on the body will typically have lesions with mucus. One of these areas is often the mouth.

Where does it appear?

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

Erythema multiforme major may occur in the same areas, but it can also affect the mouth, lips, throat, eyes, and genitals. The lesions in these areas will usually contain mucus.

Other symptoms

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

  • a cough and difficulty breathing that are signs of the infection causing the condition
  • a fever or body temperature of 38°C or higher
  • a general feeling of being unwell, sometimes before the rash appears
  • joint pain and swelling
  • painful lesions if mucus is present

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

Causes

In most cases, an infection triggers erythema multiforme. Very rarely, medications can cause this immune reaction.

Herpes simplex virus

Herpes simplex is the primary cause of erythema multiforme, and the virus is present in 70 percent of recurrent erythema multiforme cases.

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

Herpes outbreaks normally happen 7 to 10 days before the development of erythema multiforme. However, it is possible to develop erythema multiforme without having any herpes symptoms.

Mycoplasma pneumonia

Another cause of erythema multiforme is mycoplasma pneumonia, a contagious respiratory infection with Mycoplasma pneumoniae bacteria. In children, erythema multiforme is a complication in 2 to 10 percent of mycoplasma pneumonia cases.

If doctors suspect mycoplasma pneumonia to be the cause of erythema multiforme, they are likely to treat it immediately.

Other infectious causes

Other causes of erythema multiforme include viral infections such as:

  • adenoviruses
  • influenza, or the flu
  • Epstein-Barr, which causes mono
  • hepatitis
  • Coxsackie that can lead to hand, foot, and mouth disease
  • parvovirus
  • HIV

Other bacterial infections that may cause erythema multiforme include:

Medications

In very rare cases, medication can lead to erythema multiforme.

Medications that have an association with erythema multiforme include:

  • sildenafil (Viagra)
  • barbiturates, sometimes prescribed for anxiety or sleep disorders
  • hydantoins used to treat some cases of epilepsy
  • nonsteroidal anti-inflammatory drugs, often pain relievers
  • penicillins
  • phenothiazines, for the treatment of mental and emotional disorders
  • sulfonamides, antibacterials that doctors may use to treat ulcerative colitis

Diagnosis

Blood tests are not necessary to diagnose erythema multiforme, which doctors can usually identify by looking at the rash.

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 mycoplasma pneumonia 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.

Treatment

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 a lot more treatment. People with oozing lesions will need bandages and pain relievers. If they are 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.

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 mycoplasma pneumonia is responsible for the rash, doctors may prescribe antibiotics such as a macrolide, tetracycline, or azithromycin.

Outlook

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 to 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.