EM is a type of allergic reaction. In most cases, it occurs in response to an infection. In rare cases, it is caused by certain medicines or body-wide (systemic) illness.

Infections that may lead to EM include:

• Viruses, such as herpes simplex that cause cold sores and genital herpes (most common)
• Bacteria, such as Mycoplasma pneumoniaethat cause lung infection
• Fungi, such as Histoplasma capsulatum, that cause histoplasmosis

Medicines that may cause EM include:

• NSAIDs
• Allopurinol (treats gout)
• Certain antibiotics, such as sulfonamides and aminopenicillins
• Anti-seizure medicines

Systemic illnesses that are associated with EM include:

• Inflammatory bowel disease, such as Crohn disease
• Systemic lupus erythematosus

EM occurs mostly in adults 20 to 40 years old. People with EM may have family members who have had EM as well.

Symptoms of EM include:

• Low-grade fever
• Headache
• Sore throat
• Cough
• Runny nose
• General ill feeling
• Itchy skin
• Joint aches
• Many skin lesions (sores or abnormal areas) 

Skin sores may:

• Start quickly
• Come back
• Spread
• Be raised or discolored
• Look like hives
• Have a central sore surrounded by pale red rings, also called a target, iris, or bulls-eye
• Have liquid-filled bumps or blisters of various sizes
• Be located on the upper body, legs, arms, palms, hands, or feet
• Include the face or lips
• Appear evenly on both sides of the body (symmetrical)

Other symptoms may include:

• Bloodshot eyes
• Dry eyes
• Eye burning, itching, and discharge
• Eye pain
• Mouth sores
• Vision problems

There are two forms of EM:

• EM minor usually involves the skin and sometimes mouth sores.
• EM major often starts with a fever and joint aches. Besides the skin sores and mouth sores, there may be sores in the eyes, genitals, lung airways, or gut.

Your health care provider will look at your skin to diagnose EM. You'll be asked about your medical history, such as recent infections or medicines you've taken.

Tests may include:

• Skin lesion biopsy
• Examination of skin tissue under a microscope

EM usually goes away on its own with or without treatment.

Your provider will have you stop taking any medicines that may be causing the problem. But, don't stop taking medicines on your own without talking to your provider first.

Treatment may include:

• Medicines, such as antihistamines, to control itching
• Moist compresses applied to the skin
• Pain medicines to reduce fever and discomfort
• Mouthwashes to ease discomfort of mouth sores that interferes with eating and drinking
• Antibiotics for skin infections
• Corticosteroids to control inflammation
• Medicines for eye symptoms

Good hygiene may help prevent secondary infections (infections that occur from treating the first infection).

Use of sunscreen, protective clothing, and avoiding excessive exposure to sun may prevent the recurrence of EM.

Mild forms of EM usually get better in 2 to 6 weeks, but the problem may return.

Complications of EM may include:

• Patchy skin color
• Return of EM, especially with HSV infection

Contact your provider right away if you have symptoms of EM.

EM; Erythema multiforme minor; Erythema multiforme major; Erythema multiforme minor - erythema multiforme von Hebra; Acute bullous disorder - erythema multiforme; Herpes simplex - erythema multiforme

Duvic M. Urticaria, drug hypersensitivity rashes, nodules and tumors, and atrophic diseases. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier; 2020:chap 411.

Holland KE. Acquired rashes in the older child. In: Kleigman RM, Toth H, Bordini BJ, Basel D, eds. Nelson Pediatric Symptom-Based Diagnosis. 2nd ed. Philadelphia, PA: Elsevier; 2023:chap 61.

Lalor L, Shah KN. Urticaria and erythema multiforme. In: Long SS, ed. Principles and Practice of Pediatric Infectious Diseases. 6th ed. Philadelphia, PA: Elsevier; 2023:chap 71.

Rubenstein JB, Spektor T. Conjunctivitis: infectious and noninfectious. In: Yanoff M, Duker JS, eds. Ophthalmology. 5th ed. Philadelphia, PA: Elsevier; 2019:chap 4.6.

Updated by: Elika Hoss, MD, Assistant Professor of Dermatology, Mayo Clinic, Scottsdale, AZ. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.