Erythema Multiforme

Erythema multiforme (EM) is an acute, self-limited, immune mediated mucocutaneous eruption characterised by target lesions, and clearly distinguished from SJS and TEN.

• Incidence is about 1 per 1,000 per year; affects mainly young adults, more men.
• Triggers: herpes simplex virus (HSV-1 more common than HSV-2; about 60 to 70% of cases, often recurrent), Mycoplasma pneumoniae (children), orf, and less commonly drugs (NSAIDs, sulfonamides, anticonvulsants).
• Forms: EM minor (skin only, minimal or no mucosal), EM major (one or more mucosal sites with systemic symptoms).
• Recurrences 1 to 4 per year in recurrent HSV-associated EM.

• Abrupt onset of fixed, round, three zone target lesions: dusky or blistered centre, oedematous pale ring, and erythematous outer ring.
• Symmetric acral distribution (dorsal hands, forearms, feet, knees, elbows), face, spreading centripetally; palms and soles frequently involved; lesions persist for 7 or more days.
• EM major: oral erosions and haemorrhagic crusted lips, with fever and arthralgia.
• Lesions resolve in 2 to 4 weeks without scarring; post-inflammatory hyperpigmentation can persist.

• Clinical diagnosis based on morphology and distribution.
• Biopsy if uncertain: interface dermatitis with keratinocyte necrosis and dermal lymphocytic infiltrate.
• Investigate triggers: HSV PCR or history of preceding herpes labialis (1 to 3 weeks earlier), Mycoplasma serology/PCR, and drug history.
• Exclude SJS/TEN (atypical flat targets, extensive epidermal detachment), urticaria (transient, non-fixed lesions), fixed drug eruption, urticarial vasculitis, and Sweet syndrome.

• Remove causative drug or treat precipitant (macrolide or doxycycline 100 mg twice daily for Mycoplasma).
• Symptomatic: topical corticosteroids (clobetasol 0.05% for skin; triamcinolone dental paste for mouth), oral antihistamines, analgesic mouthwash (benzydamine or lidocaine 2%), soft diet, and hydration.
• EM major with severe mucosal disease: prednisolone 0.5 mg/kg for 7 to 10 days (limited evidence; avoid if HSV active without antiviral).
• Recurrent HSV-associated EM: continuous suppressive therapy with valaciclovir 500 mg daily (or 500 mg twice daily) or aciclovir 400 mg twice daily for 6 to 12 months; this prevents 70% of recurrences.
• Resistant recurrent disease: azathioprine 1 to 2.5 mg/kg, mycophenolate 1 g twice daily, dapsone, apremilast 30 mg twice daily, or hydroxychloroquine 200 mg twice daily.
• Ophthalmological review for ocular involvement.