Erythema Multiforme
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Erythema multiforme is a hypersensitivity reaction, causing a character in skin rash. It is typically the result of an infection – usually from herpes simplex virus, and sometimes from mycoplasma pneumoniae.

It usually resolves itself within a few weeks, without any specific intervention. It does not leave scarring, but there may be some skin mottling or discolouration. Most cases resolve within2  weeks, but it can last up to 6 weeks.

  • If the eyes become involved it can lead to blindness (rare)

Sometimes it can be hard to differentiate from the much more serious Stevens-Johnson Syndrome (SJS). Erythema multiforme does NOT progress to SJS.

Epidemiology and Aetiology

  • Most common in young adults age 20-40
  • Can occur at any age
  • M>F
  • Genetic predisposition
  • 90% of cases are due to infection
    • HSV – typically type 1 (mouth and lips)
    • HSV infection typically starts 3-14 days before erythema multiforme is seen
    • Mycoplasma pneumoniae – a bacteria that causes atypical pneumonia¬†has also been implicated
    • Many other types of infection can also cause erythema multiforme
      • Parvovirus
      • Herpes zoster (chickenpox / shingles)
      • HIV
      • CMV
      • Viral vaccines
      • Fingal infections (rare)
  • Can be recurrent – especially when the cause is HSV1 infection


  • May be preceding symptoms:
    • Fever
    • Joint aches
    • Muscle weakness

Skin lesions

  • Lesions can be many sizes and shapes –¬†multiforme
  • Anywhere between a handful and hundred
  • Typically appear within a 24 hour period
  • Start on back of hands and top of feet
  • Spread towards and including the trunk
  • Upper limbs more commonly affected
  • Palms and soles maybe involved
  • Face and neck may also be involved
  • Itchy
  • Mucous membranes may be involved – typically several days after the onset of the rest of the rash
  • Lesions:
    • Well demarcated
    • Round
    • Red
    • Initially flat, then become raised
    • Up to several cm diameter
    • Evolve over 72 hours
    • Target lesions –¬†pale in the middle, red ground the outer edge – like a target
Erythema multiforme - Small target lesions, coalescing
Erythema multiforme – Small target lesions, coalescing. Image from and used in accordance with the licensing requirements of Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (New Zealand).
Erythema multiforme - typical rash
Erythema multiforme – Typical rash. Image from and used in accordance with the licensing requirements of Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (New Zealand).
Erythema multiforme - target lesions
Erythema multiforme – target lesions. Image from and used in accordance with the licensing requirements of Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (New Zealand).


  • Usually a clinical diagnosis
  • A skin biopsy may be performed which has a characteristic histology but is not always diagnostic


  • Usually self-limiting – typically no treatment is required
  • Treat any underlying infection
    • e.g. Antivirals for HSV – such as valaciclovir or aciclovir
    • Antibiotics for mycoplasma – e.g. erythromycin
  • If a drug cause is suspected – cease the offending drug
  • Supportive measures
    • Anti-histamines for itch
    • Local anaesthetic mouth wash for oral lesions
  • Eye involvement – should be referred to ophthalmologist
  • In rare cases with severe mucosal involvement, then oral fluid intake may be affected and IV fluids may be required
  • Steroids¬†have not been proven to be effective, but are often prescribed, particularly in severe cases. It may be more effective if used earlier in the presentation

Recurrent erythema multiforme

  • Often treated with 6 months of continuous antivirals – e.g. aciclovir 10mg/Kg/d – divided into two doses
  • It may recur when the antiviral medication is ceased
  • Other possible treatments for recurrent erythema multiforme include:
    • Dapsone 100-150 mg/day orally
    • Hydroxychloroquine
    • Azathioprine
    • Cyclosporin
    • Typically these would be supervised by a dermatologist in tricky recurrent cases


  • Murtagh‚Äôs General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
  • Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
  • Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy
  • Erythema multiforme - DermnetNZ

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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