What is the treatment for erythema multiforme (EM) rash?

Treatment for Erythema Multiforme

For erythema multiforme, provide symptomatic treatment with topical corticosteroids for skin lesions and oral antihistamines for pruritus, while identifying and treating the underlying trigger—most commonly herpes simplex virus (requiring prophylactic antivirals for recurrent cases) or medications (requiring immediate discontinuation). 1, 2

Immediate Management Approach

Assess Disease Severity

• Erythema multiforme minor: Classic target lesions on extremities with or without oral erosions—treat conservatively 3, 1
• Erythema multiforme major (Stevens-Johnson syndrome): Atypical skin lesions with erosions on multiple mucosal surfaces—requires hospitalization and more aggressive management 4, 3

Identify and Address the Trigger

• Herpes simplex virus is the most common cause, particularly in recurrent cases 1, 2
• Mycoplasma pneumoniae is an important trigger, especially in children 1, 2
• Medications are the second most common cause—immediately discontinue any suspected drugs including allopurinol, anticonvulsants (phenobarbital, phenytoin, valproic acid), sulfonamides, penicillins, NSAIDs, and TNF-α inhibitors 2

Symptomatic Treatment

For Skin Lesions

• Apply topical corticosteroids such as prednicarbate cream 0.02% or hydrocortisone to affected areas to reduce inflammation and erythema 5, 1
• Use emollients and moisturizers daily to prevent skin dryness and maintain skin barrier function 5
• Avoid alcohol-containing lotions or gels; use oil-in-water creams or ointments instead 5

For Pruritus

• Oral antihistamines (cetirizine, loratadine, fexofenadine, or clemastine) for grade 2/3 pruritus 5, 1
• Topical polidocanol-containing lotions can soothe itching 5

For Oral Mucosal Lesions

• Topical corticosteroids applied directly to oral erosions 6, 7
• Maintain oral hygiene with gentle, soap-free cleansers 8
• Antibiotics only if secondary bacterial infection (purulent lesions)—take bacterial swabs and start targeted antibiotic therapy 5, 3

Systemic Corticosteroid Therapy

Indications for Systemic Steroids

• Severe erythema multiforme (grade 3-4) with extensive mucosal involvement 4, 6
• Stevens-Johnson syndrome/erythema multiforme major 4, 3
• Prednisone is FDA-indicated for "severe erythema multiforme (Stevens-Johnson syndrome)" 4

Important Caveats

• Early systemic corticosteroids may prevent further damage in severe cases, but risks versus benefits must be carefully weighed 3
• Avoid systemic steroids in typical erythema multiforme minor—conservative symptomatic care is preferred 3
• Short-term oral systemic steroids are recommended only for grade 3 erythema and desquamation 5

Treatment for Recurrent Erythema Multiforme

Prophylactic Antiviral Therapy

• For herpes simplex virus-associated recurrent cases: Prophylactic antiviral therapy with acyclovir, valacyclovir, or famciclovir 1, 2
• If resistance develops to one antiviral agent, switch to an alternative drug 2

Alternative Options for Refractory Cases

• Dapsone for patients non-responsive to antiviral agents 2
• Consider JAK-inhibitors or apremilast as novel treatment options for resistant cases 2

Severe Cases Requiring Hospitalization

When to Hospitalize

• Erythema multiforme major with multiple mucosal surface involvement 3
• Inability to maintain oral intake due to severe oral erosions 1
• Need for intravenous fluids and electrolyte repletion 1

Hospital Management

• Conservative supportive care with fluid and electrolyte management 1
• Treat any identified mycoplasmal infection 3
• Monitor for damage to other organ systems 3

Critical Pitfalls to Avoid

• Do not confuse with urticaria: Erythema multiforme lesions are fixed for minimum 7 days, whereas urticarial lesions resolve within 1 day 1
• Do not use systemic steroids routinely for minor forms—reserve for severe cases only 3
• Do not use hot showers or excessive soaps—these dehydrate skin and worsen xerosis 5
• Do not trim cuticles or manipulate skin lesions—increases risk of secondary infection 5
• Avoid greasy occlusive creams—may facilitate folliculitis 5