Erythema Multiforme

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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

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. Mucous membranes, however, are affected little, if at all. (EM was previously described as having minor and major forms. The major form - more serious and with more extensive involvement of both skin and mucosa - is now known as Stevens-Johnson syndrome (SJS).)

It is considered by some as being part of a spectrum of disease which includes, in order of severity, EM, SJS and toxic epidermal necrolysis (TEN), diagnosed by the extent of skin and mucous membrane involvement.[2]However, others argue that these conditions should not be classified as part of the same disease spectrum.[3]

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 on feet
    Erythema multiforme bulls eye lesions
  • Köbner's phenomenon may occur. This is where a 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, 6]
  • 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.

EM usually resolves within 3-5 weeks without sequelae, but may recur.[1]

In 1860, Ferdinand von Hebra initially described EM as an acute, self-limited condition with characteristic red papular skin lesions.[7] A more serious variant was first described by Stevens and Johnson in 1922 as febrile erosive stomatitis, severe conjunctivitis, and disseminated cutaneous eruption.[8]In 1950, Thomas coined the terms 'erythema multiforme minor' and 'erythema multiforme major' to describe the condition.

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Further reading and references

  1. Lamoreux MR, Sternbach MR, Hsu WT; Erythema multiforme. Am Fam Physician. 2006 Dec 174(11):1883-8.

  2. Bastuji-Garin S, Rzany B, Stern RS, et al; Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993 Jan129(1):92-6.

  3. Becker DS; Toxic epidermal necrolysis. Lancet. 1998 May 9351(9113):1417-20.

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

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

  6. Woo SB, Challacombe SJ; Management of recurrent oral herpes simplex infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar103 Suppl:S12.e1-18.

  7. Hebra F; On diseases of the skin, including the exanthemata, London, New Sydenham Society, 1866-80

  8. Stevens AM, Johnson FC; A new eruptive fever associated with stomatitis and ophthalmia: report of two cases in children. Am J Dis Child 1922 24: 526-33

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