What Is Erythema Multiforme?

Erythema multiforme (EM) is a skin condition caused by a reaction to infection, usually herpes simplex virus (HSV), or occasionally to medication. It is characterized by red, raised skin patches that often have a bull's-eye appearance and usually last two to four weeks. EM affects less than 1% of the population and is most common in adults between the ages of 20 to 40 years of age.

This article will discuss the types of EM, its symptoms and causes, how it is diagnosed and treated, and its prognosis.

Types of Erythema Multiforme

The two types of EM are:

• EM minor is the more common form. It typically involves just the skin, though sometimes mouth sores can occur.
• EM major is a rare but serious form of EM involving skin and mucus membranes. It often starts with a fever and joint aches and can affect the skin, mouth, eyes, genitals, the lung's airways, and gut. EM major can be life-threatening.

Erythema Multiforme Symptoms

The most common symptom of EM is a rash that starts suddenly then develops over a few days. This rash:

• Usually starts on the arms, hands, legs, and feet and then spreads to the neck, body, and face
• Begins as small red spots which can develop into raised patches that are a few centimeters in size
• Often has patches with a dark red or purplish-gray center (that may blister or crust), surrounded by a pale pink ring and a darker ring around the pale ring, giving it a bull's-eye appearance
• May be symmetrical (appear evenly on both sides of the body)
• Can be mildly itchy or uncomfortable
• May have patches that join to become large, red areas that can feel raw and painful (in more severe cases)
• Typically lasts about two to four weeks
• In more severe cases, it can cause sores in the mouth, on the genitals, and other areas such as the eyes or lung airways

Other symptoms of EM (more common with EM major) may include:

• Fever
• Joint and/or muscle aches
• Headache
• Fatigue
• Feeling generally unwell
• Swollen, crusted lips
• Cold sores
• Puffy hands or feet
• Vision problems, such as sensitivity to light and/or blurred vision
• Red, bloodshot, sore, burning, itching, and/or dry eyes (may have discharge)
• Painful urination (if there are sores on the genitals)
• Sore throat
• Cough
• Runny nose

Causes of Erythema Multiforme

EM can be triggered by a number of factors, which are outlined below.

Infections

The most common cause of EM is a reaction to an infection and is responsible for up to 90% of EM cases.

Infectious triggers associated with EM include:

• HSV 1 (the most common trigger for EM)
• HSV 2
• Cytomegalovirus (a common virus that remains in the body for life)
• Epstein-Barr virus (human herpesvirus 4)
• Influenza virus (virus causing the flu)
• Vulvovaginal candidiasis (yeast infection caused by candida)
• SARS-CoV-2 (virus causing COVID-19)
• Orf virus (a type of poxvirus)
• Bacteria (such as Mycoplasma pneumoniae which can cause lung infection)
• Fungi (such as Histoplasma capsulatum, which can cause the lung infection histoplasmosis)

Medications

Reactions to medications can also cause EM. The severe form of EM is often caused by medication rather than infection.

Medication triggers for EM may include:

• Antibiotics (such as sulfonamides, tetracyclines, penicillins, amoxicillin, and ampicillin)
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil/Motrin (ibuprofen)
• Anticonvulsants/antiepileptics (such as phenytoin and barbiturates)
• Some vaccines
• Anesthesia
• Allopurinol (used for gout)

Other Conditions

Some medical conditions associated with EM include:

• Inflammatory bowel disease (Crohn's disease and ulcerative colitis)
• Systemic lupus erythematosus (lupus, an autoimmune disease)
• Hepatitis C (causes liver inflammation that can lead to liver damage)
• Leukemia (blood cancers)
• Lymphoma (cancers starting in the lymph system)
• Solid organ cancer malignancy
  

How Erythema Multiforme Is Diagnosed

To make a diagnosis of EM, a healthcare provider will:

• Ask about symptoms
• Discuss medical history, including recent infections, illnesses, and medications
• Do a physical examination

This may be enough to diagnose EM, but other tests may be necessary if the diagnosis is unclear. These may include:

• Complete blood count (CBC)
• Liver functions tests
• Erythrocyte sedimentation rate (ESR) to look for inflammation
• Serological testing (antibody tests)
• Chest X-ray
• Skin biopsy and examination of skin tissue under a microscope
• Testing for HSV and/or other infections or conditions

Treatment for Erythema Multiforme

EM usually goes away on its own and doesn't require treatment. The underlying infection may be treated if that causes the EM symptoms. If the EM is due to a reaction to medication, a healthcare provider may suggest stopping or changing medications. Do not stop or change medications unless advised by your healthcare provider.

If necessary, treatment may include:

• Antihistamines to help with itching
• Pain medication for discomfort and/or fever
• Applying moist compresses to the skin
• Cool baths or showers
• Antibiotics if a bacterial infection is present
• Antiviral medication if viral infection is present
• Topical or oral steroid medication for inflammation
• Eye medication if eyes are affected
• Anesthetic mouthwash if mouth sores are painful
  

While rare, severe cases may require hospitalization for intravenous fluids, wound care, and/or more intensive treatment.

If EM is recurrent, treatment such as six or more months of continuous oral antiviral therapy (often acyclovir/aciclovir) may be recommended.

Prognosis for Erythema Multiforme

EM typically fully resolves within a few weeks without further problems. The skin heals without scarring, but hyperpigmentation (areas of darker skin) may last for several months.

EM may come back, particularly when caused by HSV.

Complications are possible in severe cases. These may include:

• Cellulitis (skin infection)
• Permanent skin damage or scarring
• Sepsis (the body's extreme response to an infection)
• Inflammation of internal organs (such as the liver or lungs)
• Permanent eye damage/visual impairment
  
• Keratitis (inflammation/irritation of the cornea)
• Conjunctival scarring (damage to the membrane that covers part of the front of the eye and inside the eyelids)
• Uveitis (inflammation of the middle layer of the eye)
  

Summary

Erythema multiforme is a skin condition usually caused by a reaction to infection (such as HSV) but can be caused by medication or a medical condition. EM causes a rash of red, raised skin patches that often have a bull's-eye appearance. In more severe cases, symptoms such as fever, mouth, eye sores, or large areas of affected skin may be present.

EM typically resolves on its own in two to four weeks, but medications such as antihistamines, pain medications, or steroids may be used if necessary. EM is usually minor but can be serious or life-threatening. See a healthcare provider if you have symptoms of EM.