Key Facts

Erythema multiforme (EM) is an important condition to recognise because of its characteristic morphology and its distinction from the more serious SJS/TEN spectrum. The vast majority of cases are infection-triggered (HSV) rather than drug-triggered.

Epidemiology

• Common: exact incidence uncertain
• Peak age: 20–40 years
• M:F ~3:2
• Recurrence: ~20–30% (driven by recurrent HSV)

Aetiology

• HSV (~90%): HSV-1 (most common) or HSV-2; EM occurs 1–3 weeks after HSV reactivation
• Mycoplasma pneumoniae: especially in children; may cause EM major
• Other infections: EBV, hepatitis viruses, histoplasmosis
• Drugs (rare): NSAIDs, sulfonamides — but most drug-induced mucocutaneous reactions are SJS/TEN, not EM
• Idiopathic: ~10% of cases

Pathophysiology

• HSV DNA fragments deposited in skin by circulating mononuclear cells → HSV polymerase detected in keratinocytes
• Cell-mediated immune response (CD4+ Th1) to viral antigen in skin → IFN-gamma → keratinocyte apoptosis
• Interface dermatitis at dermal-epidermal junction → characteristic target morphology
• Distinct pathogenesis from SJS/TEN (which involves granulysin-mediated massive apoptosis)

EM Minor (No Mucosal Involvement)

• Typical target lesions: three distinct zones — central dusky/bullous, pale intermediate ring, outer erythematous halo
• Predominantly on extremities: dorsum of hands, palms, soles, extensor forearms
• May affect face; trunk less commonly
• Acute onset; lesions appear in crops over 3–5 days
• Mildly pruritic or burning
• Preceding cold sore (herpes labialis) — often 1–3 weeks before rash

EM Major (With Mucosal Involvement)

• Target lesions on skin PLUS oral erosions (most common mucosal site)
• Lips: erosions, crusting, haemorrhagic
• Buccal mucosa: erosions, pain
• Ocular, genital mucosal involvement less common
• Often triggered by Mycoplasma pneumoniae (especially in children)
• Systemic upset: fever, malaise

Red Flags

• Widespread atypical target lesions on trunk → consider SJS (NOT EM)
• Nikolsky sign positive → SJS/TEN
• Respiratory symptoms in child with EM → Mycoplasma pneumoniae
• Rapidly progressive mucosal involvement → SJS/TEN

Bedside

• Clinical diagnosis: typical target lesions on extremities — often no investigations needed
• Nikolsky sign: should be NEGATIVE in EM

Bloods

• Not routinely required for typical EM minor
• Mycoplasma serology/PCR: if EM major in child/adolescent
• HSV serology: if clinical history not clear (most diagnosed clinically)

Biopsy

• Skin biopsy: if diagnostic uncertainty — interface dermatitis, keratinocyte necrosis, perivascular lymphocytic infiltrate
• Not routinely necessary for classic presentation

Special Tests

• HSV PCR (viral swab): from any active herpes lesion
• CXR: if Mycoplasma suspected (community-acquired pneumonia symptoms)

Non-Pharmacological

• Reassurance: EM minor is self-limiting; resolves in 2–4 weeks
• Supportive care: emollients, oral antiseptic mouthwash if oral involvement
• Soft diet: if oral mucosal involvement impairs eating

Pharmacological

EM minor:

• Usually no specific treatment needed
• Topical corticosteroids: for symptomatic relief
• Oral antihistamines: for pruritus

EM major:

• Potent topical corticosteroids
• Oral prednisolone 0.5–1 mg/kg for 1–2 weeks: if severe mucosal involvement (controversial — limited evidence)
• Treat underlying infection: azithromycin 500 mg day 1, then 250 mg days 2–5 for Mycoplasma

Recurrent EM (HSV-driven):

• Prophylactic aciclovir 400 mg BD: for 6–12 months — prevents HSV-triggered recurrences
• Valaciclovir 500 mg OD: alternative with better bioavailability

Referral Criteria

• Dermatology: diagnostic uncertainty (EM vs SJS), severe EM major
• Ophthalmology: if ocular involvement
• Paediatrics: child with EM major (consider Mycoplasma)

• EM minor: excellent; self-limiting in 2–4 weeks; no scarring
• EM major: resolves in 2–6 weeks; oral erosions may be slower
• Recurrence: ~20–30% (HSV-driven); reduced with aciclovir prophylaxis
• No mortality associated with EM (unlike SJS/TEN)
• Pigmentary changes (PIH): common after resolution, particularly in darker skin
• Distinct from SJS/TEN — EM does not progress to TEN

EM vs SJS — Key Differences

Common Triggers