Erythema multiforme is a skin condition often associated with an overreaction to an infection (usually herpes simplex) or medication. It can affect skin throughout the body. Erythema multiforme has two forms:

  • Erythema multiforme minor—most common, is generally mild and may go away on its own, and usually caused by a virus
  • Erythema multiforme major—rare, usually has other symptoms, is more severe, is less likely go away on its own, and usually caused by medications


Erythema multiforme is an overreaction of the immune system to a certain trigger. Some erythema multiforme is associated with an infection or certain medications, though the exact trigger may not be known half the time. It is not clear why some people have this reaction.


Erythema multiforme is more common in young adults.

Factors that may increase your chance of getting erythema multiforme include:

  • History of erythema multiforme
  • Infection or history of infection caused by:
    • Virus—herpes infection is the main cause in erythema multiforme minor
    • Bacteria
    • Fungus
    • Parasite
  • Certain medications (usual cause of erythema multiforme major), such as:
    • Antibacterials
    • Anticonvulsants
    • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Certain vaccinations including:
    • Diphtheria and tetanus vaccine
    • Hepatitis B vaccine
    • Smallpox vaccine

Red Blistered Skin

Skin blister boil
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Symptoms can vary from mild to severe. Both erythema multiforme minor and major cause skin lesions that:

  • Feel itchy or burning
  • Typically develop over 3-4 days, but at different times. Lesions will look different in various places of the body.
  • Often start on hands and feet and spread to legs, arm, and face
  • Start out as small, red areas, and grow to circular, raised areas. The middle is often a dark red which fades to a pale pink and is surrounded by a bright red edge. The different colors make the lesions look like mini targets.
  • May have a blister or crust in the center
  • Appears equally on both sides of the body
  • May develop in one mucus membrane such as the lips, inside the mouth, or the eyes

Erythema multiforme major may also cause:

  • General ill feeling, fever, and achy joints before the rash appears
  • More extensive rash
  • Lesions that develop in two or more mucus membranes such as the lips, inside the mouth, or the eyes


You will be asked about your symptoms and medical history. A physical exam will be done. You may be referred to a dermatologist.

Most cases can be diagnosed based on your medical history and skin exam. The target lesions are usually a key for diagnosis. However, the skin lesions may not be typical and a sample of the skin may be taken. The skin sample is examined under a microscope to look for findings of erythema multiforme.


Erythema multiforme will usually go away on its own in 4-6 weeks. Mild forms usually will not need treatment.

Treatment may be needed to treat an underlying infection. This may include antiviral, antibiotic, or antifungal medications. If the erythema multiforme is related to a current medication, your doctor will work with you to stop the medication and find a replacement if needed.

Severe lesion due to erythema multiforme major may also require:

  • Treatment to prevent infections of the lesions
  • Hospitalization for hydration if mouth lesions are severe

Management of symptoms

Moist compresses and medications may help relieve discomfort from lesions. Medication options may include:

  • Oral antihistamines to help control itching
  • Topical steroid creams to help discomfort and itching
  • Acetaminophen to reduce pain and fever
  • Medicated mouthwash for lesions in the mouth


If the lesions were due to the herpes simplex virus, there are ways to prevent outbreaks:

  • Talk to your doctor about a daily prescription of an oral antiviral medication.
  • Apply sunscreen and zinc sulfate solution to the site of the herpes simplex to help prevent relapse.