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Erythema Multiforme

Last updated May 4, 2018

Approved by: Maulik P. Purohit MD MPH

Erythema Multiforme (EM) is an acute, benign skin condition with a sudden onset that usually occurs due to medications, infections, illnesses, or for unknown reasons.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Dermatostomatitis, Erythema Multiforme Type
  • EM (Erythema Multiforme)
  • Herpes Iris, Erythema Multiforme Type

What is Erythema Multiforme? (Definition/Background Information)

  • Erythema Multiforme (EM) is an acute, benign skin condition with a sudden onset that usually occurs due to medications, infections, illnesses, or for unknown reasons. It is described as an immune-mediated type IV hypersensitivity reaction (abnormal sensitivity to a substance)
  • Typically, the condition is a self-limiting and non-progressive illness, but may recur in up to a third of the individuals
  • It is classified clinically into many types: (controversy still exists regarding how it is classified)
    • Erythema Multiforme Minor with skin involvement
    • Erythema Multiforme Major with less than 10% skin involvement (of the whole body) and involvement of the mucous membrane
    • Steven-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN): This is the most severe form of Erythema Multiforme. Historically it has been considered as type of EM, but currently researchers believe it to be a different entity altogether
  • The classic skin lesion is described as "target" lesions, with 3 circumferential zones of erythematous color change with central clearing like a “bulls-eye”. There may or may not be mucosal surface, such as oral cavity, involvement
  • The management of Erythema Multiforme mainly involves treating the symptoms, stopping the offending agents, such as medications, and treating the underlying condition that caused EM
  • Prognosis of Erythema Multiforme Minor is usually good with skin lesions disappearing spontaneously in 2-6 weeks. Whereas, the prognosis of other severe forms of EM depend on how much skin area is involved and on the prognosis of the underlying conditions. In severe cases, it may even result in death

Who gets Erythema Multiforme? (Age and Sex Distribution)

  • Erythema Multiforme is most commonly seen in adults in their 20s to 40s and children
  • The condition is slightly more common in males than females
  • It is seen worldwide and there is no ethnic or racial preference noticed

What are the Risk Factors for Erythema Multiforme? (Predisposing Factors)

The risk factors of Erythema Multiforme may include:

  • Infections are one of most common risk factors of Erythema Multiforme. The most common infections implicated are herpes simplex virus, mycoplasma, Epstein-Barr virus, adenovirus, streptococci, and many other pathogens
  • Medications that increase one’s risk EM include sulfonamides antibiotics, many medications used for epileptic fits, such as carbamazepine, penicillin group of antibiotics, etc.
  • Other clinical situations which can increase one’s risk include pregnancy, cancer, collagen diseases, exposure to substances such as poison ivy and nickel
  • The male gender and children are at a slightly increased risk than other individuals
  • Certain individuals possess factors on a molecular or cellular level that increases one’s susceptibility to EM. These factors include HLAB12, HLADQ3, etc.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Erythema Multiforme? (Etiology)

The exact cause and mechanism of Erythema Multiforme development is currently unknown. However, scientists believe that certain substances trigger an immune-mediated destruction of the epidermal (skin) cells and cause Erythema Multiforme. Such substances or triggers may include:

  • Infections: Most commonly herpes simplex virus and mycoplasma
  • Medications: Barbiturates, penicillin, phenytoin, sulfonamides, carbamazepine, some preservatives found in food, and other substances
  • Contact irritants such as poison ivy, nickel, etc.
  • Diseases and conditions that may include cancer, pregnancy, systemic lupus erythematosus (SLE), and many other conditions
  • In up to 50% of the individuals, the cause remains unknown; though, subclinical (no signs or symptoms) diseases may be a possibility in these individuals.

What are the Signs and Symptoms of Erythema Multiforme?

The signs and symptoms of Erythema Multiforme may include:

Overall illness or feeling sick:

  • Fever
  • Itching
  • Joint aches
  • Vision defects: Eyes that may appear bloodshot, dry, with burning or itching sensation, eye discharge and eye pain
  • Mouth sores

Skin lesions

  • There may be multiple skin lesions with rashes that show color or texture change. The skin lesions usually appear suddenly and may appear as:
    • Hives (red raised welts on skin that are often itchy)
    • Nodules (raised solid bumps that are wider than 10 mm)
    • Papules (solid raised spot that is less than 10 mm wide)
    • Macules (flat and distinctly colored area of skin that is frequently less than 10 mm wide and does not change in thickness or color)
    • Some may have blisters or vesicles (smaller blisters)
  • “Target”, “iris”, or “bull’s-eye” appearance: Pale red rings surround the central, darker area, which is the most characteristic lesion of Erythema Multiforme. Even though, it may not be present in some individuals
  • The skin lesions are usually located on the upper body, arms, hands, palms, legs, or feet. They are sometimes present on the face or lips too
  • They are usually symmetrical in presentation (distributed evenly on the right and left sides of the body)

How is Erythema Multiforme Diagnosed?

The following tests and procedures may be used to diagnose Erythema Multiforme:

  • Thorough evaluation of the individual’s medical history and a complete physical examination, along with skin examination
  • During history taking the physician may want to know the following:
    • When the symptoms began and whether they are becoming worse
    • List of prescription and over-the-counter medications currently being taken
    • Personal and family history of skin diseases, cancer, other conditions, etc.
  • During physical exam the healthcare provider may try to elicit Nikolsky’s sign. This is considered positive if the top layers of the skin “slip away” from the lower layers when they are gently rubbed
  • The diagnosis is mainly based on the physical appearance of the skin lesions. Consultation with a dermatologist may become necessary, if they resemble other skin conditions
  • Skin lesion biopsy: In this procedure, the physician removes a sample of the skin tissue and sends it to the laboratory for a histopathological examination. The pathologist examines the biopsy under a microscope and arrives at a definitive diagnosis after a thorough evaluation of the clinical and microscopic findings, as well as by correlating the results of special studies on the tissues (if required)
  •  Diagnostic tests to confirm or rule-out other EM associated medical conditions and disorders

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Erythema Multiforme?

The complications of Erythema Multiforme could include:

  • Skin infection
  • Sepsis: It is a body-wide infection due to blood poisoning
  • Shock, due to the loss of body fluids
  • The skin lesions can occasionally cause:
    • Myocarditis (heart inflammation)
    • Pneumonitis (lung inflammation)
    • Nephritis (kidney inflammation)
    • Hepatitis (liver inflammation)
    • Permanent skin scarring or skin damage

How is Erythema Multiforme Treated?

The goal of treatment of Erythema Multiforme is to treat the underlying disease that caused EM, or discontinue the medication(s) that resulted in EM, and treat the symptoms of the disorder.

In order to treat mild Erythema Multiforme, the following may be considered:

  • Antihistamines may be taken for itching
  • Applying moist compresses to the skin can help relieve discomfort
  • If EM is caused by herpes simplex, oral antiviral medications is used
  • If fever is present, then over-the-counter medications can be used to reduce the fever and discomfort
  • If mouth lesions are present, topical anesthetics will help decrease discomfort caused while eating or swallowing liquids

In order to treat severe Erythema Multiforme, the following may be considered:

  • Skin infections may be treated with antibiotics
  • Inflammation may be controlled through corticosteroids
  • Intravenous immunoglobulins (IVIG) may be tried in some individuals
  • If large parts of the skin are infected, then skin grafting (surgery to transplant skin) may be helpful

How can Erythema Multiforme be Prevented?

The preventative measures of Erythema Multiforme could include:

  • In certain individuals the condition may be prevented by avoiding substances that trigger EM. For example, by not taking sulfonamides for infections, but rather choosing a different class of antibiotics
  • Treating underlying diseases or conditions that trigger EM
  • In some individuals prophylactic antiviral medications (medications taken before the condition sets in) may help prevent herpes simplex infections from occurring, or from progressing further
  • In individuals with EM, good hygiene and staying away from those who are ill, can help to prevent secondary infections from taking place

Note: Not all cases of Erythema Multiforme (EM) can be prevented, especially if the offending agent is not apparent or remains unknown.

What is the Prognosis of Erythema Multiforme? (Outcomes/Resolutions)

  • Most Erythema Multiforme minor skin lesions often resolve in about 2-6 weeks. However, these may return or recur in over 30% of the individuals
  • The prognosis of severe forms of Erythema Multiforme depends on the prognosis of the underlying disease, the extent of skin and or mucous membrane involvement, and the presence of complications such as sepsis
  • In some cases, severe EM can result in death

Additional and Relevant Useful Information for Erythema Multiforme:

Erythema Multiforme has different forms, such as Erythema Multiforme Minor, which is not very serious when compared to Erythema Multiforme Major (Stevens-Johnson syndrome), a more severe and sometimes fatal condition.

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 28, 2015
Last updated: May 4, 2018