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Erythema Multiforme

Essentials

  • Erythema multiforme (EM) is an immune-mediated mucocutaneous syndrome usually triggered by a viral or bacterial infection, most commonly by Herpes simplex or Mycoplasma pneumoniae. A COVID-19 infection or vaccine can trigger EM. A drug, such as an NSAID, antiepileptic or antimicrobial, can rarely act as a trigger (in less than 10% of the cases). However, the aetiology frequently remains unknown.
    • 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 with a characteristic cockade pattern (target lesions) of 1-2 cm in diameter, which may have a small central vesicle (pictures 1 2 3 4 5 6). The rash can spread to the face and body, but covers no more than 10% of the skin. There are no or few mucosal symptoms.
    • EM major: the rash is more severe and extensive, the vesicles are large and mucosal involvement, most often in the mouth, is present (pictures 7 8 9 10 11).
    • Patients are usually young adults.
    • Patients' ethnic background does not affect the incidence of the syndrome.
    • Lesions develop over a few days and do not change their location.
    • Mild disease forms heal spontaneously within 1-3 weeks, but skin hyperpigmentation may persist for months.
    • 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.
    • Mycoplasma and Chlamydia pneumoniae infections may cause, especially in children, a clinical picture where breaks in the oral mucosa are the primary symptom and there are only few or no findings on the skin. This is considered a distinct syndrome, different in pathophysiology from other mucocutaneous diseases.
  • Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN)
    • Different degrees of the same drug reaction
    • Stevens-Johnson syndrome (picture12) 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 13) 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 patient history and 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 2-4 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 of the skin and mucosae.
    • Promptly consult an ophthalmologist to avoid permanent eye damage 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.

    References

    • Yousefian M, Khadivi A. Occurrence of erythema multiforme following COVID-19 vaccination: a review. Clin Exp Vaccine Res 2023;12(2):87-96 [PubMed]
    • Daneshgaran G, Dubin DP, Gould DJ. Cutaneous Manifestations of COVID-19: An Evidence-Based Review. Am J Clin Dermatol 2020;21(5):627-639.[PubMed]
    • Trayes KP, Love G, Studdiford JS. Erythema Multiforme: Recognition and Management. Am Fam Physician 2019;100(2):82-88 [PubMed]
    • Bassetti M, Massone C, Vena A, et al. Skin manifestations in patients with coronavirus disease 2019. Curr Opin Infect Dis 2022;35(2):88-94 [PubMed]
    • Mayor-Ibarguren A, Feito-Rodriguez M, González-Ramos J, et al. Mucositis Secondary to Chlamydia pneumoniae Infection: Expanding the Mycoplasma pneumoniae-Induced Rash and Mucositis Concept. Pediatr Dermatol 2017;34(4):465-472 [PubMed]
    • Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol 2012;51(8):889-902. [PubMed]