What is the treatment for Erythema Multiforme (EM)?

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Last updated: July 7, 2025View editorial policy

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From the Guidelines

The treatment for Erythema Multiforme (EM) should focus on addressing the underlying cause, managing symptoms, and providing supportive care, as it is a reactive mucocutaneous disorder distinct from SJS/TEN, usually precipitated by infection and characterized by typical target lesions 1.

Key Considerations

  • Identify and remove any triggering factors such as medications or treat underlying infections, particularly herpes simplex virus.
  • For mild cases, supportive care is often sufficient, including oral antihistamines and topical corticosteroids to relieve itching and reduce inflammation.
  • In more severe cases, systemic corticosteroids may be necessary to manage symptoms.
  • For recurrent EM associated with herpes simplex virus, prophylactic antiviral therapy can prevent recurrences.

Management Approach

  • Supportive care is the mainstay of treatment for EM, with a focus on relieving symptoms and preventing complications 1.
  • Topical corticosteroids, such as triamcinolone 0.1% cream, can be applied 2-3 times daily to reduce inflammation.
  • Oral antihistamines, like diphenhydramine (25-50mg every 4-6 hours) or hydroxyzine (25mg 3-4 times daily), can relieve itching.
  • For oral lesions, topical anesthetics like viscous lidocaine 2% or magic mouthwash can provide relief.
  • Systemic corticosteroids, such as prednisone (0.5-1mg/kg/day for 1-2 weeks with taper), may be necessary in more severe cases.
  • Prophylactic antiviral therapy with acyclovir (400mg twice daily) or valacyclovir (500mg daily) can prevent recurrences in patients with recurrent EM associated with herpes simplex virus.

Patient Care

  • Patients should maintain good skin care, avoid sun exposure, and stay well-hydrated to support recovery and prevent complications.
  • Most EM cases are self-limiting and resolve within 2-4 weeks, but prompt treatment helps reduce discomfort and prevents complications 1.

From the FDA Drug Label

Dermatologic Diseases Pemphigus, Bullous dermatitis herpetiformis, severe erythema multiforme (stevens-Johnson syndrome), exfoliative dermatitis, mycosis fungoides, severe psoriasis, severe seborrheic dermatitis The treatment for Erythema Multiforme (EM) is prednisone (PO), as it is listed under dermatologic diseases for the treatment of severe erythema multiforme (Stevens-Johnson syndrome) 2.

  • Key points:
    • Prednisone (PO) is used for short-term administration to tide the patient over an acute episode or exacerbation.
    • It is essential to follow the recommended dosage and administration guidelines to ensure safe and effective treatment.

From the Research

Treatment Overview

The treatment for Erythema Multiforme (EM) is highly variable and depends on the etiology, the involvement of mucosal sites, and the chronicity of the disease 3.

Symptomatic Treatment

Symptomatic treatment with topical steroids or antihistamines is often used to relieve symptoms 4, 3.

Treatment of Underlying Cause

If the etiology or causal medication/infection is identified, then the medication is stopped and/or the infection is treated prior to initiating symptomatic treatment 3.

Recurrent EM Treatment

Treatment for recurrent EM is most successful when tailored to individual patients, and may include:

  • Systemic therapies such as corticosteroid therapy and antiviral prophylaxis 3
  • Topical therapies such as high-potency corticosteroids, and antiseptic or anesthetic solutions for mucosal involvement 3
  • Second-line therapies for patients who do not respond to antiviral medications, including immunosuppressive agents, antibiotics, anthelmintics, and antimalarials 3

Herpes-Associated EM Treatment

Oral acyclovir may be used to prevent herpes-associated erythema multiforme, and has been shown to be effective in reducing the frequency and severity of attacks 5.

Severe Cases

Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance 4, 6.

Specific Treatments

Specific treatments that have been used in the management of EM include:

  • Corticosteroids for inflammation 7
  • Acyclovir for HSV-1 7
  • Azithromycin for Mycoplasma pneumoniae 7
  • Vaseline for open lesions 7
  • Mouthwash consisting of aluminum hydroxide/magnesium hydroxide/simethicone for oral mucosa lesions 7
  • Topical 2% lidocaine gel for urinary discomfort 7
  • Fentanyl for pain control 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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