Erythema Multiforme

Definition

• Erythema multiforme is a self-limiting, immune-mediated condition affecting mucocutaneous surfaces. It often presents with target-like lesions and may be isolated, recurrent, or persistent. Typically seen in young adults, though it can occur at any age. The incidence is relatively low (~1%), but precise figures vary. Lesions are usually symmetrical and predominantly located on extensor surfaces.

Aetiology & Causes

• Idiopathic: No identifiable trigger (relatively common)

• Infections:

  • Herpes simplex virus (HSV): The most common trigger

  • Mycoplasma pneumoniae: The second most frequent cause, particularly in children and adolescents

  • Other infectious agents: COVID-19, CMV, EBV

• Drugs:

  • Sulphonamides (e.g. co-trimoxazole)

  • Penicillins (especially amoxicillin)

  • Anticonvulsants (phenytoin, carbamazepine, lamotrigine)

• Systemic disease: SLE, Hodgkin’s lymphoma (rare association)

• Vaccinations: Occasionally reported post-immunisation

Clinical Features

• Skin Lesions:

  • Symmetrical rash primarily on the extensor surfaces of arms, legs, and dorsal hands/feet

  • Target lesions: Characteristic with three distinct zones:

    • Dusky or purplish centre (epidermal necrosis)

    • Pale oedematous ring

    • Outer erythematous halo

  • May be painful, pruritic, or swollen

• Mucosal Involvement:

  • Formation of blisters leading to shallow ulcers with a white membranous covering

  • Commonly affects oral mucosa, causing discomfort with eating or swallowing

  • May also affect lips, ocular mucosa, or genital mucosa

Diagnosis

• Largely clinical, based on the typical target lesions and relevant triggers (e.g. HSV infection, recent medication use).

• Ophthalmic assessment if concern for keratitis, conjunctival inflammation, or uveitis (especially in cases with eye discomfort or vision changes).

Differential Diagnosis

• Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN): More severe mucosal damage, extensive skin peeling, and systemic involvement.

• Urticaria: Usually more fleeting lesions, intense pruritus, no target lesions.

• Viral exanthem: Tends to be more diffuse and not target-shaped.

• Fixed drug eruption: Typically single or few round, well-demarcated patches that recur at the same site with re-exposure.

• Bullous pemphigoid or paraneoplastic pemphigus: Usually seen in older patients, with tense bullae or widespread erosions.

• Polymorphous light eruption (PMLE): Photosensitive rash, different morphological pattern.

• Rowell syndrome: A rare variant of cutaneous lupus with erythema multiforme-like lesions.

Management

• Usually Self-Limiting: Mild forms require no specific therapy beyond addressing discomfort.

• Symptomatic Care:

  • Itch: Oral antihistamines, topical corticosteroids, cool compresses

  • Pain relief in mouth lesions: Local anaesthetic mouthwashes or gels (e.g. benzydamine rinse)

  • Eye involvement: Urgent ophthalmology review if red or painful eye, blurred vision, or photosensitivity

• Recurrent or Severe Cases:

  • Oral antivirals (e.g. aciclovir) if HSV is the confirmed or highly suspected trigger

  • Antibiotics if an active Mycoplasma pneumoniae infection is identified

  • Rarely, short-course systemic corticosteroids in severe inflammatory cases (controversial and typically specialist-led)

Prognosis

• Minor Erythema Multiforme usually resolves spontaneously within 2–3 weeks, leaving no scar.

• Erythema Multiforme Major (with significant mucosal involvement) may last up to 6 weeks.

• Progression to SJS/TEN is rare but can occur. Ocular involvement may lead to chronic complications (e.g. dry eyes, vision impairment).

Notes

• Erythema multiforme is typically less severe than SJS/TEN, but watch closely for increasing mucosal involvement or systemic symptoms.

• Eye involvement: Potential for corneal ulceration or uveitis. Early specialist referral is crucial for preventing long-term damage.

• Recurrence is common, especially if triggered by HSV. Consider prophylactic antivirals in frequent recurrences.