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Erythema multiforme (EM) is a skin condition considered to be a hypersensitivity reaction to infections or drugs[1] . It presents as a dermatological eruption featuring iris or target lesions, although other forms of skin lesion can occur - hence the name. It is usually an acute, self-limiting disease that affects the skin. Mucosal lesions are present in 25% to 60% of patients with erythema multiforme.

EM must be distinguished from the rare but more serious and life-threatening conditions, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)[2] .

There is no register or valid estimate of the number of cases of EM; however, it may represent 1% of dermatology outpatient attendance. Males are affected slightly more often than females. Most patients are aged under 40 with 20% occurring in children and adolescents.


  • Herpes simplex virus (HSV) 1 and 2 infections (account for >50% of cases).
  • Mycoplasma pneumonia infections.
  • Fungal infections.
  • Other viruses (varicella-zoster virus, cytomegalovirus, hepatitis C virus, and HIV).

Drug reactions

  • Barbiturates.
  • Penicillins.
  • Phenothiazines.
  • Sulfonamides.
  • Anticonvulsants.
  • Non-steroidal anti-inflammatory drugs.
  • Vaccinations (diphtheria-tetanus, hepatitis B, smallpox).


  • There may be either no prodrome or a mild upper respiratory tract infection. The rash starts abruptly, usually within three days. It starts on the extremities, being symmetrical and spreading centrally.
  • There may be some mild burning or itching sensation but the skin is not tender.
  • Recurrent EM is thought to be usually due to reactivation of HSV.
  • Half of children with the rash have recent herpes labialis. It usually precedes the EM by 3 to 14 days but it can sometimes be present at the onset.


The iris or target lesion is the classical feature of the disease.

  • Initially, there is a dull red macule or urticarial plaque that enlarges slightly up to 2 cm over 24-48 hours. In the middle, a small papule, vesicle or bulla develops, flattens, and then may clear. The intermediate ring forms and becomes raised, pale and oedematous. The periphery slowly becomes violaceous and forms a typical concentric target lesion.
  • The lesions can expand to form plaques which are several centimetres in diameter.
  • Some lesions are atypical targets with only two concentric rings. Polycyclic or arcuate lesions may occur.

    Erythema multiforme

    Erythema multiforme
    Grook Da Oger, CC BY-SA 3.0, via Wikimedia Commons
    By Grook Da Oger, CC BY-SA 3.0, via Wikimedia Commons

    Erythema multiforme

    Erythema multiforme
    Alborz Fallah (Own work), via Wikimedia Commons
    By Alborz Fallah (Own work), via Wikimedia Commons

  • Köbner's phenomenon may occur. This lesion occurs along the line of previous skin trauma.
  • Lesions appear first on the extensor surfaces of the periphery and extend centrally. The palms, neck and face are often involved but the soles and flexures of the extremities less often.
  • There may be mucosal involvement but it tends to be mild and limited to just one mucosal surface. Oral lesions are most common with lips, palate and gingiva affected.
  • Occasionally the mucosal involvement is marked with few skin lesions.
  • Usually, no specific investigations are indicated.
  • Skin biopsy can be indicated in an atypical presentation or where there is recurrent EM without an obvious trigger.
  • Investigations may be required to discover the underlying cause - eg, CXR, drug history, atypical pneumonia titres.

It is associated with the infections listed above.

  • If a drug is thought to be responsible, it must be withdrawn. If an infection is suspected, it should be treated.
  • In recurrent disease due to HSV, antiviral therapy is beneficial[5] .
  • Symptomatic treatment may include analgesics, mouthwash and local skin care. Steroid creams may be used.
  • It may be helpful to emphasise to patients or parents that, although an underlying infection may be contagious, EM itself is not.
  • If the mouth is very sore, attention may have to be given to hydration and nutrition.
  • Dilute antiseptics, such as chlorhexidine, may help to prevent secondary infection. Lubricating drops for the eyes may be required.

Secondary infection of lesions may occur. Serious complications are unusual in an immunocompetent patient. A very sore mouth may lead to dehydration and poor nutrition. Genitourinary lesions may result in urinary retention. If the eye is involved it is important to prevent infection or conjunctival scarring.

Skin lesions usually heal without complication, but skin hyperpigmentation may occur. Some episodes of erythema multiforme have been documented to persist for up to five weeks, and recurrent and more persistent forms may occur.

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Further reading and references

  1. Trayes KP, Love G, Studdiford JS; Erythema Multiforme: Recognition and Management. Am Fam Physician. 2019 Jul 15100(2):82-88.

  2. Harr T, French LE; Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010 Dec 165:39.

  3. Trayes KP, Savage K, Studdiford JS; Annular Lesions: Diagnosis and Treatment. Am Fam Physician. 2018 Sep 198(5):283-291.

  4. Drug allergy: diagnosis and management of drug allergy in adults children and young people; NICE Clinical guideline (September 2014 updated November 2018).

  5. Sladden MJ, Johnston GA; More common skin infections in children. BMJ. 2005 May 21330(7501):1194-8.