Management of Erythema Multiforme Major
Erythema multiforme major (EMM) is a self-limited condition requiring supportive care, treatment of the underlying trigger, and symptomatic management—it does not progress to Stevens-Johnson syndrome and typically has excellent outcomes without need for hospitalization unless severe mucosal involvement prevents oral intake or hydration. 1
Critical Distinction from Stevens-Johnson Syndrome
EMM must be distinguished from SJS/TEN, as these are entirely different diseases with different prognoses and management:
- EMM presents with typical target lesions starting on acral surfaces (hands, feet) and progressing proximally, with mucosal erosions typically confined to the mouth 1
- Patients with EMM are constitutionally well, make good recovery, and rarely have long-term complications 1
- EMM does not progress to SJS/TEN 1
- In contrast, SJS/TEN presents with purpuric macules, widespread blisters, and epidermal detachment rather than true target lesions, with extensive mucosal involvement and systemic illness 2
Identification and Treatment of Underlying Trigger
The most critical management step is identifying and treating the precipitating cause:
- Herpes simplex virus is the most common trigger 3, 4, 5
- Mycoplasma pneumoniae is a frequent cause, especially in children 3, 4
- Medications are the second most common cause, including NSAIDs, allopurinol, anticonvulsants, antibiotics, and TNF-α inhibitors 3
When the trigger is unclear, empirically treat both HSV and Mycoplasma while awaiting laboratory confirmation: 6
- Start acyclovir for HSV-1 6
- Start azithromycin for Mycoplasma pneumoniae 6
- Discontinue any recently started medications, particularly NSAIDs and similarly-structured drugs 6
Symptomatic Management
Cutaneous Lesions
- Apply petrolatum (Vaseline) to open lesions for wound care 6
- Topical corticosteroids may reduce inflammation, though evidence is limited 4
- Oral antihistamines for pruritus if present 4
Oral Mucosal Involvement
- Use aluminum hydroxide/magnesium hydroxide/simethicone mouthwash (400 mg/400 mg/40 mg) for oral lesions 6
- Maintain adequate hydration and nutrition—severe cases preventing oral intake require hospitalization for IV fluids and electrolyte repletion 4
Urethral/Genital Involvement
- Apply topical 2% lidocaine gel with applicator to assist with urinary discomfort during voiding 6
Pain Control
- Systemic analgesics including opioids (fentanyl) may be necessary for severe pain 6
When to Hospitalize
Hospitalization is indicated when:
- Severe mucosal involvement prevents adequate oral intake or hydration 4
- Pain is uncontrolled with oral medications 6
- Patient cannot void due to urethral involvement 6
Ophthalmologic Involvement
Urgent ophthalmology referral is mandatory for any ocular involvement: 6
- EMM can cause long-term ocular sequelae including trichiasis, symblepharon, and punctal stenosis 6
- Do NOT start corticosteroids before ophthalmology evaluation if eye involvement is present, as this may worsen infectious causes like herpetic keratitis or mask accurate diagnosis 7
Recurrent Herpes-Associated EMM
For patients with recurrent HSV-associated EMM:
- Prophylactic oral antiviral therapy is recommended to prevent recurrences 4
- Topical acyclovir prophylaxis does not prevent further episodes 3
- If resistant to one antiviral, switch to an alternative agent 3
- For patients non-responsive to antivirals, consider dapsone, JAK-inhibitors, or apremilast 3
Common Pitfalls to Avoid
- Do not confuse EMM with SJS/TEN—EMM has true target lesions, acral distribution, constitutional wellness, and does not progress to widespread epidermal detachment 1, 2
- Do not start steroids before ruling out infectious causes, particularly if ocular involvement is present 7
- Do not use topical acyclovir for prophylaxis—only systemic antivirals are effective 3
- Recurrence is common (up to 18% in children) because the precipitant is usually infection rather than drugs 1