Erythema Multiforme

Essentials

• Erythema multiforme (EM) is an independent syndrome usually triggered by a viral or bacterial infection, most commonly by Herpes simplex or mycoplasma. Especially in children, a COVID-19 infection can trigger EM. A drug can also act as a trigger (in less than 10% of the cases). However, the aetiology frequently remains unknown.
  • According to current knowledge, drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are two forms of a separate syndrome that includes EM-like mucosal changes but the skin symptoms are different.
• Patients with Stevens-Johnson syndrome or TEN must be referred immediately to specialist care.

Symptoms

• Erythema multiforme
  • EM minor: symmetrical lesions predominantly on the limbs and face with a characteristic cockade pattern (target lesions) of 1-2 cm in diameter, which may have a small central vesicle (pictures ).
  • EM major: the rash is more severe, the vesicles are large and mucosal involvement is present (pictures ).
  • Patients are usually young adults.
  • Lesions develop over a few days and do not change their location.
  • Mild disease forms heal spontaneously within 1-3 weeks.
  • Symptoms may recur.
  • EM will not progress into toxic epidermal necrolysis.
  • The patient usually has mild fever as a general symptom and feels generally ill.
  • Particularly mycoplasma and Chlamydia pneumoniae infections may cause, especially in children, a clinical picture where the primary symptom consists of breaks in the oral mucosa and there are only few or no findings on the skin.
• Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN)
  • Different degrees of the same drug reaction
  • Stevens-Johnson syndrome (picture) is a drug reaction with purpuric lesions involving less than 10% of total body surface area. Eroding vesicles are present on the skin and mucous membranes.
  • Toxic epidermal necrolysis (Lyell's syndrome) (picture ) is a serious drug reaction with epidermal detachment involving over 30% of total body surface area and mucosal erosions. The patient will have systemic symptoms and need aggressive treatment.
  • The most common triggering agents are non-steroidal anti-inflammatory drugs, antimicrobial drugs, antiepileptics and allopurinol.

Diagnosis

• Diagnosis is based on the clinical picture.
• Histopathological findings are non-specific.

Treatment

• EM minor
  • Mild forms of EM resolve without treatment.
  • If the bacterial infection that triggered the reaction is known, it should be treated.
  • If the reaction was triggered by a drug, the drug is discontinued.
• EM major
  • Systemic glucocorticoids for 3-4 weeks are generally prescribed, even though no clear evidence is available on their efficacy. The starting dose of prednisone or prednisolone is 30-60 mg/day.
  • A dermatologist should be consulted for appropriate topical treatment.
  • An ophthalmologist should be consulted if the patient has eye symptoms.
  • Frequently recurring episodes of EM caused by the Herpes simplex virus may be an indication for prophylactic medication against herpes.
• Stevens-Johnson syndrome: immediate referral to hospital
• Toxic epidermal necrolysis: the patient needs high dependency/intensive care.

Pictures