What is the best treatment approach for Erythema Multiforme?

Treatment of Erythema Multiforme

For erythema multiforme, immediately discontinue any suspected culprit medications, apply topical corticosteroids for symptomatic relief, and initiate prophylactic antiviral therapy if herpes simplex virus is the trigger. 1, 2

Immediate Actions

• Stop all suspected medications immediately and document everything the patient has taken in the previous 2 months, including over-the-counter drugs and supplements 1
• Examine all mucosal sites (oral cavity, eyes, genitals) and document the extent of skin involvement, specifically looking for characteristic target lesions on extensor surfaces of extremities 1, 2
• Apply emollients and skin moisturizers to all affected areas 1

First-Line Pharmacologic Treatment

For Skin Lesions

• Topical corticosteroids (hydrocortisone cream or high-potency corticosteroids) applied to affected areas provide symptomatic relief 1, 3
• Topical antihistamines can be used as an alternative or adjunct for pruritus 2, 3

For Mucosal Involvement

• Antiseptic or anesthetic mouthwashes (aluminum hydroxide/magnesium hydroxide/simethicone 400mg/400mg/40mg) for oral lesions 3, 4
• Topical 2% lidocaine gel for genital or urethral involvement 4

Etiology-Specific Treatment

Herpes Simplex Virus-Associated EM

• For recurrent EM triggered by HSV, initiate prophylactic antiviral therapy (acyclovir) as first-line treatment 2, 3
• This is the most effective intervention for preventing recurrences in HSV-associated cases 2, 3

Mycoplasma pneumoniae-Associated EM

• Treat the underlying infection with appropriate antibiotics (azithromycin) 5, 4

Drug-Induced EM

• Permanent avoidance of the culprit medication and structurally similar drugs 4

Systemic Therapy Indications

Systemic corticosteroids should be initiated for:

• Major EM with extensive mucosal involvement 3, 6
• Severe cases requiring hospitalization 2
• Patients not responding adequately to topical therapy after 2 weeks 1

The evidence shows systemic corticosteroids are effective in controlling outbreaks in all patients, though their role as maintenance therapy remains unclear 6

Second-Line Options for Refractory Recurrent EM

If antiviral prophylaxis fails in recurrent cases, consider 3:

• Immunosuppressive agents
• Antibiotics (doxycycline, azithromycin)
• Antimalarials
• Anthelmintics

Hospitalization Criteria

Admit patients with:

• Severe mucosal involvement requiring IV fluids and electrolyte repletion 2
• Inability to maintain oral intake 2
• Body surface area involvement >10% or clinical deterioration 7

Critical Pitfall to Avoid

Do not confuse erythema multiforme with Stevens-Johnson syndrome (SJS). EM presents with fixed targetoid lesions on extremities for ≥7 days and patients are typically constitutionally well, whereas SJS shows widespread erythematous or purpuric macules with blisters, mucosal involvement, and systemic toxicity 7, 2. This distinction is crucial because SJS requires different management including possible transfer to a burn unit 7.

Follow-Up Protocol

• Reassess after 2 weeks of treatment 1
• If worsening or no improvement, escalate therapy to systemic corticosteroids 1
• For recurrent cases, establish long-term prophylactic antiviral therapy if HSV-triggered 2, 3