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InflammatoryHypersensitivityICD-10 L51.0

Erythema multiforme

EM · erythema multiforme minor / major

Erythema multiforme is an acute immune-mediated hypersensitivity reaction characterised by target lesions, usually triggered by herpes simplex virus reactivation (HSV-1 > HSV-2) in over 50% of cases. Mycoplasma pneumoniae is the second most common trigger, particularly in paediatric cases. EM minor lacks mucosal involvement; EM major includes mucosal disease but is distinct from SJS / TEN — recent consensus (Bastuji-Garin) treats EM major as a separate entity rather than the mild end of the SJS-TEN spectrum.

CurrentLast reviewed 16 May 2026
Clinical image of Erythema multiforme
Erythema multiforme. Image sourced from DermNet New Zealand. Used under CC BY-NC-ND 4.0. No endorsement implied.

Aetiology

  • Infections (~90%):
    • Herpes simplex virus (HSV-1 > HSV-2) — commonest; recurrent EM often herpetic.
    • Mycoplasma pneumoniae — second commonest; paediatric mucositis prominent (formerly MIRM: Mycoplasma-induced rash and mucositis — now recognised as related entity).
    • Other viral: EBV, CMV, parvovirus B19, COVID-19.
    • Fungal: histoplasmosis, coccidioidomycosis.
  • Drugs (<10%): NSAIDs, sulfonamides, anticonvulsants, antibiotics — although these more often cause SJS/TEN.
  • Other: malignancy, autoimmune disease, radiation, vaccination, photodermatosis, contact (e.g. poison ivy).

Clinical features

  • Acute onset within 1-3 weeks of trigger.
  • Target lesions — classic three-zone:
    • Central dusky / vesicular zone.
    • Pale oedematous middle ring.
    • Peripheral erythematous halo.
  • Distribution: acral; dorsal hands, palms, extensor forearms, knees, elbows; face / neck less common.
  • Symmetric.
  • Prodrome: mild flu-like symptoms.
  • EM minor: no mucosal involvement; mild systemic symptoms.
  • EM major: ≥1 mucosal site involved (oral, ocular, genital) but ≤10% BSA detachment (distinct from SJS).
  • Self-limiting; resolves in 2-4 weeks; recurrent disease in 30-50% with HSV.

Differentials

  • SJS / TEN — full-thickness epidermal detachment; centripetal distribution; drug-induced; mucosal predominant.
  • Urticaria — wheals; transient; itch dominates.
  • Fixed drug eruption — recurrent same-site.
  • Bullous pemphigoid (urticarial phase).
  • Polymorphic light eruption — sun-exposed sites.
  • Rowell syndrome: lupus + EM-like lesions + anti-Ro / La / RNP / speckled ANA.
  • Erythema annulare centrifugum.
  • Targetoid haemosiderotic / hobnail haemangioma.

Investigations

  • Clinical diagnosis usually adequate.
  • Skin biopsy in atypical / persistent / severe cases: interface dermatitis with apoptotic keratinocytes; perivascular lymphocytic infiltrate; subepidermal vesiculation.
  • HSV serology / PCR from lesional / oral swab.
  • Mycoplasma serology / PCR (especially in children with prominent mucositis).
  • FBC, U&E, LFT, CXR, throat swab in severe / multisystem cases.
  • Drug history.
  • Recurrent disease: investigate triggers (HSV, Mycoplasma, drug, occupational).

Management

  • Treat trigger:
    • Acute HSV: aciclovir 400 mg 5× daily for 5-7 days.
    • Mycoplasma: macrolide (clarithromycin) or tetracycline (adult).
  • Symptomatic:
    • Analgesia, antihistamines, bland emollients.
    • Mid-potency topical corticosteroids.
    • Mouthwash (e.g. chlorhexidine, benzydamine, lidocaine) for oral disease.
  • Severe:
    • Short-course oral prednisolone 30-60 mg / day taper.
    • IVIG, ciclosporin in extreme cases.
  • Recurrent disease (≥5 episodes / year):
    • Continuous oral antiviral suppression: aciclovir 400 mg BD or valaciclovir 500 mg OD for 6-12 months.
    • If antiviral-refractory: consider dapsone, methotrexate, azathioprine, mycophenolate.
  • Counsel: distinguish from SJS/TEN; self-limiting; recurrence common with HSV; prophylactic antiviral if frequent recurrence.

References

  1. Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Int J Dermatol. 2012;51:889-902.
  2. Bastuji-Garin S et al. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129:92-96.
  3. Schalock PC, Dinulos JGH. Mycoplasma pneumoniae-induced cutaneous disease. Int J Dermatol. 2009;48:673-681.
  4. Tatnall FM et al. A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme. Br J Dermatol. 1995;132:267-270.

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