What is the treatment for Erythema multiforme?

Treatment of Erythema Multiforme

Immediate Management Approach

For acute erythema multiforme, symptomatic treatment with topical corticosteroids or antihistamines is the primary approach, while simultaneously identifying and treating the underlying trigger—most commonly herpes simplex virus or Mycoplasma pneumoniae. 1, 2

Identifying and Treating the Underlying Cause

• Stop any suspected causative medications immediately, including antibiotics (sulfonamides, penicillins, erythromycin, tetracyclines), anticonvulsants (phenobarbital, phenytoin, valproic acid), NSAIDs, allopurinol, or statins 3
• Test for and treat herpes simplex virus infection, as HSV is the most common infectious trigger and appears 10 days before EM lesions develop 4, 1
• Consider Mycoplasma pneumoniae, particularly in children, as this is the second most common infectious cause and carries a better prognosis 4, 3
• Other infectious triggers to consider include hepatitis C virus, Coxsackie virus, and Epstein-Barr virus 3

Symptomatic Treatment for Acute Episodes

Topical corticosteroids:

• Apply high-potency topical corticosteroids to cutaneous lesions 2
• For mucosal involvement, use topical antiseptic or anesthetic solutions 2

Systemic therapy for severe cases:

• Systemic corticosteroids (prednisone) are indicated for severe erythema multiforme (Stevens-Johnson syndrome) per FDA labeling 5
• Systemic corticosteroids proved effective in controlling outbreaks in all patients in a retrospective study of 22 patients 6
• Oral antihistamines can provide symptomatic relief for pruritus 1

Hospitalization Criteria

Severe mucosal involvement requires hospitalization for intravenous fluids and electrolyte repletion when patients cannot maintain adequate oral intake 1

Management of Recurrent Erythema Multiforme

First-Line Prophylactic Treatment

For recurrent HSV-associated erythema multiforme, prophylactic antiviral therapy is the recommended first-line treatment 1, 2

• Continuous antiviral prophylaxis with acyclovir, valacyclovir, or famciclovir prevents recurrent episodes 2
• Important caveat: Topical acyclovir prophylaxis does NOT prevent further EM episodes—only systemic antivirals are effective 3
• If resistance develops to one antiviral agent, switch to an alternative antiviral drug 3

Second-Line Therapies for Refractory Cases

For patients who do not respond to antiviral prophylaxis:

• Dapsone can be considered for patients non-responsive to antiviral agents 3, 2
• JAK inhibitors represent a novel treatment option for refractory cases 3
• Apremilast may be considered as an alternative immunomodulatory agent 3
• Other immunosuppressive agents, antibiotics, anthelmintics, and antimalarials have been used as second-line options 2

Critical Diagnostic Considerations

Confirming the Diagnosis

Histopathologic examination is essential when clinical diagnosis is uncertain, as conditions like granuloma annulare can masquerade as erythema multiforme 4, 7

• Look for the characteristic three-zone target configuration: central dark papule/vesicle, pale zone, and erythematous halo 4
• EM lesions remain fixed for a minimum of 7 days, distinguishing them from urticaria where individual lesions resolve within 24 hours 4, 1
• Lesions present symmetrically on extremities (especially extensor surfaces) and spread centripetally 1

Differentiating from Stevens-Johnson Syndrome/TEN

EM typically presents with typical target lesions or raised atypical targets predominantly on limbs and extremities, while SJS/TEN features flat atypical targets or purpuric macules with epidermal detachment and positive Nikolsky sign 4

• EM is mostly HSV-related with lower mortality and better prognosis compared to SJS/TEN 4
• SJS/TEN is usually drug-triggered and requires immediate drug discontinuation 4

Common Pitfalls to Avoid

• Do not use topical acyclovir for prophylaxis—it is ineffective; only systemic antivirals prevent recurrence 3
• Do not confuse persistent itching after treatment with treatment failure—mild symptoms can persist for days after the trigger is eliminated 1
• Do not assume all targetoid lesions are EM—obtain histopathology when uncertain, as granuloma annulare and other conditions can mimic EM clinically 7
• Do not use systemic corticosteroids as maintenance therapy—their role is limited to controlling acute outbreaks 6