Management of Erythema Multiforme
Erythema multiforme is a self-limited immune-mediated condition best managed by identifying and treating the underlying trigger (most commonly HSV infection), providing symptomatic relief with topical corticosteroids and antihistamines for acute episodes, and initiating prophylactic antiviral therapy for recurrent HSV-associated cases. 1, 2
Initial Assessment and Diagnosis
Distinguish erythema multiforme from Stevens-Johnson syndrome immediately, as they are separate disorders requiring different management approaches. 3
Key diagnostic features of erythema multiforme:
- Target or iris lesions distributed symmetrically on extremities (especially extensor surfaces) spreading centripetally 2, 4
- Lesions remain fixed for minimum of 7 days (versus urticaria which resolves within 24 hours) 2
- May involve one mucosa (EM minor) or two or more mucosae (EM major) 5
- Does not progress to widespread erythematous/purpuric macules with extensive blistering characteristic of SJS/TEN 3, 2
Obtain detailed history focusing on:
- Preceding HSV infection (most common trigger) 1, 6, 5
- Mycoplasma pneumoniae infection, especially in children 6, 4
- Medication exposure within past 2 months, including OTC products (allopurinol, phenobarbital, phenytoin, sulfonamides, penicillins, NSAIDs, statins, TNF-α inhibitors) 3, 6
- Recent vaccinations or immunotherapy 6
Acute Episode Management
First-Line Treatment
Stop any suspected causative medication immediately and treat identified infections before initiating symptomatic therapy. 1, 2
Topical corticosteroids (high-potency formulations) applied to cutaneous lesions for symptom control 1, 2
Oral antihistamines for pruritus and discomfort 1, 2
Mucosal Involvement
For oral or genital mucosal lesions:
- Antiseptic or anesthetic solutions (lidocaine-based mouthwashes) for pain relief 1
- Maintain adequate hydration 2, 4
- Monitor for ability to maintain oral intake 2
Hospitalization is indicated when severe mucosal involvement prevents adequate oral hydration or requires intravenous fluid and electrolyte repletion 2
Recurrent Erythema Multiforme
HSV-Associated Recurrent Disease
Prophylactic antiviral therapy is first-line treatment for recurrent HSV-associated erythema multiforme. 1, 2
- Initiate continuous suppressive antiviral therapy (acyclovir, valacyclovir, or famciclovir) 1, 6
- Note: Topical acyclovir prophylaxis does not prevent recurrent episodes 6
- If resistance develops to one antiviral agent, switch to an alternative virostatic drug 6
Antiviral-Refractory Cases
For patients non-responsive to antiviral prophylaxis:
Second-line options include:
- Dapsone as immunosuppressive therapy 6
- JAK inhibitors (emerging evidence) 6
- Apremilast (novel option) 6
- Other immunosuppressive agents, antibiotics (for non-HSV infectious triggers), or antimalarials 1
Systemic corticosteroids may be considered for severe recurrent cases, though evidence is limited and controversial 1, 5
Critical Clinical Pitfalls
Do not confuse erythema multiforme with Stevens-Johnson syndrome - EM has typical target lesions on acrally-distributed sites and does not progress to widespread epidermal detachment. 3, 2
Avoid using topical acyclovir for prophylaxis - it is ineffective at preventing recurrent EM episodes; systemic antiviral therapy is required. 6
Do not delay stopping suspected causative medications - immediate discontinuation is essential before initiating symptomatic treatment. 3, 1
Recognize that EM is self-limiting - most acute episodes resolve without aggressive intervention when the trigger is addressed. 1, 4