What is the treatment for erythema multiforme?

Treatment of Erythema Multiforme

Erythema multiforme is primarily managed with supportive care, identification and treatment of the underlying trigger (most commonly herpes simplex virus or drugs), and symptomatic relief with topical corticosteroids and analgesics for mild cases, while systemic corticosteroids are reserved for severe mucosal involvement. 1, 2, 3

Immediate Management Priorities

Identify and Eliminate the Trigger

• Discontinue any suspected culprit medications immediately if drug-induced EM is suspected 4, 2
• Document all medications taken in the previous 2 months, including over-the-counter and complementary therapies 4
• Common drug triggers include allopurinol, phenobarbital, phenytoin, antibacterial sulfonamides, penicillins, NSAIDs, and TNF-α inhibitors 2
• Test for herpes simplex virus (HSV) serology, as HSV is the most common infectious trigger 2, 5, 3
• Consider Mycoplasma pneumoniae testing, particularly in children and young adults with respiratory symptoms 2, 6, 3

Assess Disease Severity

• Examine all mucosal sites (oral cavity, eyes, genitalia) for involvement 4, 6
• Document extent of skin involvement and presence of target lesions 4
• Severe mucosal involvement affecting feeding, hydration, or voiding requires more aggressive management 6

Treatment Algorithm by Severity

Mild Cutaneous Disease (Skin Only, Limited Mucosal Involvement)

Supportive Care:

• Maintain adequate hydration 3
• Apply emollients and skin moisturizers to affected areas 4
• Use topical corticosteroids (e.g., hydrocortisone cream) for symptomatic relief of skin lesions 4, 1
• Provide oral analgesics for pain control 3

Specific Treatment:

• If HSV-associated: Consider acyclovir 400 mg orally 2-3 times daily for acute episodes 5, 6
• If Mycoplasma pneumoniae-associated: Azithromycin or other appropriate antibiotic 6
• Most cases are self-limited and resolve within 2-4 weeks with supportive care alone 2, 3

Moderate to Severe Disease (Extensive Mucosal Involvement)

Systemic Corticosteroids:

• Prednisone 0.5-1 mg/kg/day orally is indicated for severe cases with significant mucosal inflammation 1, 6, 7
• The FDA label specifically lists "severe erythema multiforme (Stevens-Johnson syndrome)" as an indication for prednisone 1
• Taper over 2-3 weeks as symptoms improve 6, 7

Mucosal-Specific Management:

• Oral involvement: Aluminum hydroxide/magnesium hydroxide/simethicone mouthwash (400 mg/400 mg/40 mg) for oral lesions 6
• Ocular involvement: Immediate ophthalmology referral to prevent long-term sequelae (symblepharon, trichiasis, punctal stenosis) 6
• Genital/urethral involvement: Topical 2% lidocaine gel with applicator for urinary discomfort 6
• Apply petroleum jelly (Vaseline) to open lesions to prevent secondary infection 6

Pain Management:

• Systemic analgesics as needed; fentanyl may be required for severe pain 6
• Topical lidocaine for localized painful areas 6

Recurrent Erythema Multiforme

First-Line Prophylaxis

For HSV-associated recurrent EM (most common):

• Continuous suppressive acyclovir 400 mg orally twice daily is the first-line prophylactic treatment 5, 7
• Trial for at least 6-12 months 5
• Approximately 50% of patients achieve complete remission with acyclovir monotherapy after the first course 5
• If relapse occurs, repeat acyclovir cycles (patients may require 2-6 cycles) 5

Second-Line Options for Acyclovir-Refractory Cases

When acyclovir fails or provides only partial response:

• Add dapsone 50-100 mg daily to acyclovir for combined therapy 5, 7
• Nine of 33 patients in one series required dapsone due to partial acyclovir response 5
• Monitor for dapsone adverse effects (hemolysis, methemoglobinemia) 5

Alternative if dapsone not tolerated:

• Thalidomide 50-100 mg daily can be used as adjuvant therapy 5, 7
• Four of 33 patients required thalidomide due to dapsone adverse effects 5
• Requires strict pregnancy prevention protocols and monitoring for neuropathy 5

Third-Line Immunosuppressive Therapy

For severe refractory cases:

• Mycophenolate mofetil provided partial or complete response in 6 of 8 patients in one series 7
• Consider azathioprine or other immunosuppressants for frequent relapses 7
• Newer options include JAK inhibitors or apremilast for resistant cases 2

Critical Clinical Pitfalls

Common Errors to Avoid

• Do not confuse EM with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): EM has typical target lesions with acral distribution, while SJS/TEN has widespread epidermal detachment and atypical targets 4
• Do not delay ophthalmology referral when ocular mucosa is involved, as permanent sequelae can develop rapidly 6
• Do not assume topical acyclovir prevents recurrent EM: Systemic continuous suppressive therapy is required for prophylaxis 2
• Do not continue NSAIDs if they are the suspected trigger, and avoid structurally similar drugs 6
• Do not overlook Mycoplasma pneumoniae in children and young adults with respiratory symptoms, as this is the second most common infectious trigger after HSV 2, 3

Monitoring and Follow-Up

• Reassess after 2 weeks of treatment; if worsening or no improvement, escalate therapy 4
• For recurrent EM on prophylactic therapy, follow-up every 3-6 months to assess disease control 5
• Long-term follow-up with ophthalmology is essential for patients with ocular involvement 6
• Mean follow-up duration in recurrent EM should be at least 7-8 years, as this is a chronic relapsing condition 5