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Erythema multiforme

What is erythema multiforme?

Erythema Multiforme (EM) 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 (iris) lesion. There may be mucous membrane involvement. It is acute and self-limiting, usually resolving without complications.

Erythema multiforme is divided into major and minor forms and is now regarded as distinct from Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).

Who gets erythema multiforme?

Erythema multiforme most commonly affects young adults (20-40 years of age), however all age groups can be affected. There is a male predominance but no racial bias.

There is a genetic tendency to EM. Certain tissue types are more often found in people with herpes-associated EM (HLA-DQw3) and recurrent EM (HLA-B15, -B35, -A33, -DR53, -DQB1*0301).

What triggers it?


Infections are probably associated with at least 90% of cases of EM.

The single most common trigger for developing EM is herpes simplex virus (HSV) infection, usually herpes labialis (cold sore on the lip) and less often genital herpes. HSV type 1 is more commonly associated than type 2. The herpes infection usually precedes the skin eruption by 3-14 days.

Mycoplasma pneumonia (a lung infection caused by Mycoplasma pneumoniae) is the next most common trigger.

Many different virus infections have been reported to trigger EM including:

Dermatophyte fungal infections (tinea) have also been reported in association with EM.


Medications are probably an uncommon cause (<10%) of EM. If this diagnosis is being seriously considered then alternative drug eruptions should be excluded such as SJS/TEN, generalised fixed drug eruption, polymorphic exanthematous drug eruption and urticaria.

Many drugs have been reported to trigger EM including barbiturates, non-steroidal anti-inflammatory drugs, penicillins, sulphonamides, phenothiazines and anticonvulsants.

Clinical features

General symptoms

There are usually no prodromal symptoms (EM minor). However, sometimes with EM major there may be mild symptoms such as fever or chills, weakness or painful joints.

Skin lesions

Few to hundreds of skin lesions erupt within a 24-hour period. The lesions are first seen on the backs of hands and/or tops of feet, then spread along the limbs towards the trunk. The upper limbs are more commonly affected than the lower. Palms and soles may be involved. The face, neck and trunk are common sites. Skin lesions are often grouped on elbows and knees. There may be an associated mild itch or burning sensation.

The initial lesions are sharply demarcated, round, red/pink and flat (macules) which become raised (papules/palpable) and gradually enlarge to form plaques (flat raised patches) up to several centimetres in diameter. The centre of the papule/plaque darkens in colour and develops surface (epidermal) changes such as blistering or crusting. Lesions usually evolve over 72 hours.

The typical target (iris) lesion of EM has a sharp margin, regular round shape and three concentric colour zones:

Atypical targets show just 2 zones and/or an indistinct border.

The eruption is polymorphous (many forms), hence the ‘multiforme’ in the name. Lesions may be at various stages of development with both typical and atypical targets present at the same time. A full skin examination may be required to find typical targets as these may be few in number.

Lesions show the Köbner (isomorphic) phenomenon, meaning they can develop at sites of preceding (but not concurrent or subsequent) skin trauma.

There is no associated swelling of face, hands or feet, despite these being common sites of rash distribution. However the lips are often swollen, especially in EM major.

Target lesions Target lesions Target lesions
Erythema multiforme

More pictures of EM ...

Mucous membrane involvement

Mucosal lesions, if present, typically develop a few days after the skin rash begins.

In EM minor, mucous membrane involvement is absent or mild. Mucosal changes, if present, consist initially of redness of the lips and inside cheek. Sometimes blisters develop and quickly break to form erosions and ulcers.

In EM major, one or more mucous membranes are typically affected, most often the oral mucosa:

Other mucosal sites affected may include:

Mucosal lesions consist of swelling and redness with blister formation. The blisters break quickly to leave large, shallow, irregular shaped, painful ulcers that are covered by a whitish pseudomembrane. Typically the lips are swollen with haemorrhagic crusts. The patient may have difficulty speaking or swallowing due to pain.

With mycoplasma pneumonia, the mucous membranes may be the only affected sites (mucositis). This can be severe and require hospitalization due to difficulty eating and drinking. Whether this is a limited form of EM has not been determined.

Erythema multiforme of lips Erythema multiforme of lips Erythema multiforme of eye
Erythema multiforme: mucosal involvement

Recurrent EM

Erythema Multiforme can be recurrent with multiple episodes per year for many years. This is believed to be nearly always due to HSV-1 infection.

How is the diagnosis made?

Erythema multiforme is a clinical diagnosis although skin biopsy may be required to exclude other conditions. The histology of EM is characteristic but not diagnostic. It varies with the age of the lesion, its appearance, and which part is biopsied.

Other tests may be done looking for infections commonly seen in association with EM such as for Mycoplasma pneumoniae.

For more detail, see: Erythema multiforme: histology & mechanisms.

Treatment of erythema multiforme

For the majority of cases, no treatment is required as the rash settles by itself over several weeks without complications.

Treatment directed to any possible cause may be required such as oral aciclovir (not topical) for HSV or antibiotics (e.g. erythromycin) for Mycoplasma pneumoniae. If a drug cause is suspected then the possible offending drug should be ceased.

Supportive/symptomatic treatment may be necessary.

The role of oral corticosteroids remains controversial as no controlled studies have shown any benefit. However for severe disease 0.5-1mg/kg/d prednis(ol)one is often used early in the disease process.

Recurrent EM is usually treated initially with continuous oral aciclovir for 6 months at a dose of 10mg/kg/d in divided doses (e.g., 400mg twice daily), even if HSV has not been an obvious trigger for the patient's EM. This has been shown to be effective in placebo-controlled double blind studies. However EM may recur when the aciclovir is ceased. Other antiviral drugs such as valciclovir (500-1000mg/d) and famciclovir (250mg twice daily) should be tried if aciclovir has not helped; these drugs are not readily available in New Zealand.

Other treatments (used continuously) that have been reported to help suppress recurrent EM include:

What is the outlook?

Erythema multiforme usually resolves spontaneously without scarring over 2-3 weeks for the EM minor form, and up to 6 weeks for EM major. EM does not progress to SJS/TEN.

There may be residual mottled skin discolouration. Significant eye involvement in EM major may result in serious eye problems including blindness, as seen with SJS/TEN.

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Author: In 2009, Dr Delwyn Dyall-Smith updated an original article written by Dr Amanda Oakley.

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If you have any concerns with your skin or its treatment, see a dermatologist for advice.