Erythema Multiforme Major

February 1, 2017

Erythema multiforme is a hypersensitivity reaction usually triggered by infections, most commonly herpes simplex virus (HSV). It presents with a skin eruption characterised by a typical target lesion. There may be mucous membrane involvement. It is acute and self-limiting, usually resolving without complications.

Erythema multiforme has 2 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 more severe, less likely go away on its own, and usually caused by medications

A variety of factors have been implicated in the pathogenesis of EM. The disorder is most commonly induced by infection, with herpes simplex virus being the most frequent precipitator. The clinical course of EM is usually self-limited, resolving within weeks without significant sequelae. However, in a minority of cases, the disease recurs frequently over the course of years.

The rash is made of spots that are red welts, sometimes with purple or blistered areas in the center. It often also affects the mouth, eyes and other moist surfaces. Erythema multiforme has been so named because of the “multiple forms” it appears in; there is a large degree of variety in its clinical presentation. This variation has led to EM being divided into two overlapping subgroups (EM minor and Stevens-Johnson syndrome). These are different faces of the same disease.

EM is relatively common problem for a dermatologist. Half the cases are in young people (under 20). It rare both under the age of 3 and over the age of 50. Males are slightly more affected than females and there is no racial predilection. One third of EM sufferers will have a recurrence of the disease. Seasonal epidemics are common.


It is thought that erythema multiforme is caused by damage to tissues and blood vessels on the skin. This may result from infection with the herpes simplex virus, infection with mycoplasma bacteria, or a reaction to a medication. Minor cases of erythema multiform are more commonly associated with a herpes simplex infection, whereas severe cases are more commonly associated with reactions to medication.

The herpes simplex virus that causes erythema multiforme is also responsible for cold sores. The virus can lie dormant unless activated by a trigger that causes a flare-up. Some people may develop a cold sore in the days before a rash appears.

Severe erythema multiforme is most often caused by a reaction to certain types of medications. Penicillin antibiotics such as amoxicillin and ampicillin, anticonvulsants, barbiturates, sulphonamides, tetracyclines, and non-steroidal anti-inflammatory drugs (NSAIDs) have all been known to cause erythema multiforme.

Risk Factors

Factors that may increase the 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
  • Non-steroidal anti-inflammatory drugs

Certain vaccinations including –

  • Diptheria and tetanus vaccine
  • Hepatitis B vaccine
  • Smallpox vaccine


Symptoms of erythema multiforme include –

  • Fever
  • General ill feeling
  • Itchy skin
  • Joint aches
  • Multiple 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


Some complications of erythema multiforme are –

  • Body-wide infection (sepsis)
  • Loss of body fluids (shock)
  • Lesions on internal organs, causing inflammation of the heart (myocarditis), lung (pneumonitis), kidney (nephritis), and liver (hepatitis)
  • Permanent skin damage and scarring
  • Skin infection (cellulitis)


Treatment of severe symptoms may include –

  • Antibiotics for skin infections
  • Corticosteroids to control inflammation
  • Treatment in an intensive care or burn care unit for severe cases, Stevens-Johnson syndrome, and toxic epidermal necrolysis (top layer of skin separates from the lower layers)
  • Intravenous immunoglobulins (IVIG, an injection of healthy cells from donors into a vein) to stop the disease process

Good hygiene and staying away from other people may help prevent secondary infections (infections that occur from treating the first infection).

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

Alternative Treatment

Reference –

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