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(Erythema Multiforme Minor; Erythema Multiforme Major)


Erythema multiforme is an inflammation of the skin. It can happen on any part of the skin. There are two types:

  • Erythema multiforme minor—the most common, is generally mild
  • Erythema multiforme major—rare, is more severe


Erythema multiforme is an overreaction of the immune system. The cause is not always known. The minor type may be triggered by an infection. The major type may be triggered by medicine.

Risk Factors

Erythema multiforme is more common in young adults.

Things that may raise the risk are:

  • A history of erythema multiforme
  • A current or previous infection caused by a:
    • Virus—especially herpes infection
    • Bacterium
    • Fungus
    • Parasite
  • Certain medicines (usual cause of erythema multiforme major), such as:
    • Antibiotics
    • Seizure medicines
    • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Certain vaccines, such as:
    • 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 spots that:

  • Feel itchy or burning
  • Typically develop over 3 to 4 days
  • Often start on hands and feet—then spread to legs, arm, and face
  • Start out as small, red areas that:
    • Grow to circular, raised areas
    • Have a dark red center that fades to a pale pink
    • Are surrounded by a bright red edge—they look like mini targets.
  • May have a blister or crust in the center
  • Appear on both sides of the body
  • May develop on the lips, eyes, or inside the mouth

Erythema multiforme major may also cause:

  • General ill feeling, fever, and achy joints
  • A rash that covers more of the body


The doctor will ask about your symptoms and health history. A physical exam will be done. This may be enough to make the diagnosis. You may be sent to a skin doctor.


Erythema multiforme often goes away on its own in 4 to 6 weeks.

Treatment options may be:

  • If medicine triggered the condition—stopping and replacing the medicine
  • Treating an underlying infection with medicines, such as:
    • Antiviral medicine
    • Antibiotics
    • Antifungal medicine
  • Medicines to ease symptoms, such as:
    • Antihistamines—to reduce itching
    • Corticosteroid ointments—to reduce itching and pain
    • Special mouthwash—to treat sores in the mouth

Severe erythema multiforme major may also need:

  • Treatment to prevent infections of the skin
  • Supportive care in the hospital


If the condition was triggered by the herpes simplex virus, the risk may be lowered by:

  • Taking a daily antiviral medicine
  • Applying sunscreen and zinc sulfate to the area


American Academy of Dermatology 

Family Doctor—American Academy of Family Physicians 


Canadian Dermatology Association 

Health Canada 


Erythema multiforme. EBSCO DynaMed website. Available at: . Accessed February 18, 2021.

Erythema multiforme. DermNet New Zealand website. Available at: Accessed February 18, 2021.

Trayes KP, Love G, et al. Erythema multiforme: recognition and management. Am Fam Physician. 2019;100(2):82-88.

Revision Information

  • Reviewer: EBSCO Medical Review Board Mary Beth Seymour, RN
  • Review Date: 01/2021
  • Update Date: 02/18/2021