What is the best management approach for erythema multiforme?

Management of Erythema Multiforme

Immediately discontinue any suspected culprit medications and begin supportive care with topical corticosteroids and emollients as first-line therapy. 1

Initial Assessment and Immediate Actions

Critical first steps:

• Stop all suspected medications immediately, documenting everything taken in the previous 2 months including over-the-counter and complementary therapies 1
• Examine all mucosal sites (oral, genital, ocular) and document the extent of skin involvement and presence of target lesions 1
• Distinguish EM from Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), as these require entirely different management—EM patients remain constitutionally well and do not progress to SJS/TEN 2

Key distinguishing features of EM:

• Typical target lesions starting on acral surfaces (hands, feet) progressing proximally 2, 3
• Usually triggered by infection (most commonly herpes simplex virus) 3, 4
• Patients are constitutionally well, even with mucosal involvement 2
• Individual lesions remain fixed for minimum 7 days (unlike urticaria which resolves within 24 hours) 3

First-Line Treatment

Topical therapy forms the foundation:

• Apply topical corticosteroids (hydrocortisone cream) for symptomatic relief of skin lesions 1
• Use emollients and skin moisturizers liberally to affected areas 1
• Topical antihistamines may provide additional symptomatic relief 3

For mucosal involvement:

• Severe oral mucosal disease may require hospitalization for intravenous fluids and electrolyte repletion 3

Treating the Underlying Cause

When herpes simplex virus is identified (most common trigger):

• For acute episodes: treat the active HSV infection 3, 4
• For recurrent HSV-associated EM: initiate prophylactic antiviral therapy with acyclovir 3, 5
• Acyclovir monotherapy achieves complete remission in approximately 67% of patients after the first course 5
• Patients who relapse may require 2-6 additional cycles of acyclovir 5

Important caveat: Topical prophylactic acyclovir does not prevent further EM episodes; systemic therapy is required 4

When Mycoplasma pneumoniae is suspected (especially in children):

• Treat the underlying infection appropriately 4, 6

Management of Refractory Cases

For patients with partial or no response to acyclovir:

• Add dapsone as combination therapy (effective in patients who partially respond to acyclovir alone) 5
• If dapsone causes adverse effects, consider thalidomide as an alternative adjuvant 5
• Mycophenolate mofetil provides partial or complete response in 75% of refractory cases (6 of 8 patients) 7
• Emerging options include JAK-inhibitors or apremilast for virostatic-resistant cases 4

If one antiviral fails, switch to an alternative agent before abandoning the antiviral approach 4

Monitoring Protocol

Reassess after 2 weeks of treatment:

• If worsening or no improvement, escalate therapy 1
• For recurrent EM, mean follow-up should extend 7-8 years given the chronic relapsing nature 5

Common Pitfalls to Avoid

Do not confuse EM with SJS/TEN:

• SJS/TEN presents with widespread erythematous or purpuric macules with blisters, not true target lesions 3
• SJS/TEN patients are systemically ill and require ICU-level care 2

Do not rely solely on topical antivirals for HSV-associated recurrent EM:

• Systemic prophylactic therapy is necessary for prevention 4

Do not give up on antiviral therapy prematurely:

• Many patients require multiple cycles or combination therapy before achieving sustained remission 5

Recognize features of recalcitrant cases early:

• No identifiable cause found 7
• Lack of improvement with continuous antiviral therapy 7
• Severe oral involvement requiring extensive corticosteroid therapy 7
• These patients may need immunosuppressive agents sooner rather than later 7