How Do You Treat Drug-Induced Erythema Multiforme? A Comprehensive Guide

October 13, 2025 •

3 min read

While infections trigger up to 90% of erythema multiforme (EM) cases, medications are responsible for less than 10%. Learning how do you treat drug-induced erythema multiforme begins with identifying and stopping the causative agent, a crucial first step toward recovery.

Quick Summary

The primary treatment for drug-induced erythema multiforme is discontinuing the causative medication. Management then focuses on supportive care to relieve symptoms like pain and itching, with corticosteroids used for severe cases.

Key Points

Identify and Discontinue: The most critical first step in treatment is to identify and stop taking the medication that triggered the reaction.
Symptomatic Relief: For mild cases (EM minor), treatment focuses on relieving symptoms with topical corticosteroids for skin lesions and oral antihistamines for itching.
Mucosal Care: In EM major, painful mouth sores are managed with anesthetic mouthwashes, a soft diet, and antiseptic rinses to prevent infection.
Systemic Corticosteroids: Severe cases often require systemic corticosteroids to control the inflammation, typically over several weeks.
Hospitalization for Severe Cases: Patients with severe mucosal involvement, dehydration, or an inability to eat may require hospitalization for IV fluids, nutritional support, and advanced wound care.
Avoid Re-exposure: Once a drug has been identified as the cause, the patient must avoid that drug and chemically similar ones for life to prevent recurrence.
Distinction from SJS/TEN: Erythema multiforme is a distinct condition from Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are more severe and require different management strategies.

Understanding Drug-Induced Erythema Multiforme

Erythema multiforme (EM) is an acute hypersensitivity reaction affecting the skin and sometimes mucous membranes. Although typically linked to infections, medications cause less than 10% of cases. Drug-induced EM is characterized by target-like lesions on the skin.

EM is categorized into two main types:

Erythema Multiforme Minor: Characterized by skin lesions with minimal to no involvement of mucous membranes.
Erythema Multiforme Major: Involves skin lesions and one or more mucous membranes, such as those in the mouth, eyes, or genitals.

It's important to distinguish EM from more severe conditions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are now considered separate entities. SJS/TEN involve more widespread skin detachment.

The First and Most Critical Step: Discontinuation

The most important step in treating drug-induced EM is quickly identifying and stopping the responsible medication. A detailed look at medications started in the past two months is crucial.

Drugs commonly associated with causing EM include:

Antibiotics: Sulfonamides, penicillins, and cephalosporins.
Anticonvulsants: Phenobarbital, phenytoin, and carbamazepine.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).
Allopurinol.

Once the suspect drug is identified, it must be stopped immediately. To prevent recurrence, patients should avoid chemically similar drugs in the future.

Symptomatic and Supportive Care

After stopping the causative drug, treatment focuses on managing symptoms, as EM usually resolves within a few weeks.

For Mild to Moderate Cases (EM Minor)

For patients with limited skin lesions and no mucosal involvement, treatment aims for comfort:

Topical Corticosteroids: Applied to skin lesions to reduce inflammation and itching.
Oral Antihistamines: Help control itching.
Analgesics: Pain relievers for discomfort or fever.
Cool Compresses: Can soothe the skin.

Managing Mucosal Involvement (EM Major)

When mucous membranes are affected, especially in the mouth, symptoms can interfere with eating and drinking. Management includes:

Topical Anesthetics: Medicated mouthwashes, such as those with viscous lidocaine, to relieve mouth pain.
Antiseptic Mouth Rinses: To help prevent infection in oral lesions.
Dietary Modifications: Soft or liquid diets and avoiding irritating foods.
Eye Care: If eyes are involved, an ophthalmologist consultation is needed. Treatment may include lubricating drops and ointments.

Systemic Therapy for Severe Cases

Severe cases of EM major, involving extensive mucosal areas, significant pain, or difficulty with hydration and nutrition, may require hospitalization. Systemic corticosteroids are a primary intervention, though their use is debated.

Systemic Glucocorticoids: Often used for severe EM, typically involving a course over several weeks. Early treatment is thought to be more effective.
Intravenous Fluids: Provided if oral intake is poor.
Nutritional Support: May require a feeding tube in cases of severe oral pain.
Wound Care: Denuded skin areas are treated like burns to prevent infection. Silver sulfadiazine should be avoided due to potential for triggering EM.


Feature	Treatment for EM Minor	Treatment for EM Major	Stevens-Johnson Syndrome (SJS)
Primary Goal	Symptomatic relief	Control inflammation, supportive care	Intensive supportive care, stop trigger
Common Setting	Outpatient	Outpatient or Hospitalization	Hospitalization (often ICU/burn unit)
Skin Treatment	Topical corticosteroids, cool compresses	Topical care, systemic corticosteroids	Burn-like wound care, IV fluids
Oral Lesions	Usually absent or mild	Anesthetic/antiseptic mouthwashes	Critical supportive care, possible feeding tube
Systemic Meds	Usually not needed	Oral corticosteroids	Use of corticosteroids is controversial; other agents like cyclosporine or IVIG are considered

Conclusion

The treatment for drug-induced erythema multiforme varies based on severity. The essential first step is always discontinuing the causative drug. Mild cases are managed with supportive care for symptoms. Severe cases (EM major) involving mucosal areas often require systemic corticosteroids and potentially hospitalization for supportive care to prevent complications. Accurate diagnosis and a tailored plan are vital.

For more detailed information, consult authoritative sources such as the National Center for Biotechnology Information (NCBI). https://www.ncbi.nlm.nih.gov/books/NBK470259/

Frequently Asked Questions

The first and most important step is to identify and discontinue the suspected causative drug as soon as possible, after consulting with a healthcare provider.

Common medications that can cause erythema multiforme include certain antibiotics (especially sulfonamides and penicillins), anticonvulsants, and nonsteroidal anti-inflammatory drugs (NSAIDs).

Mild cases are treated symptomatically with topical corticosteroids to reduce inflammation, oral antihistamines to control itching, and cool compresses to soothe the skin.

Not always. Topical steroids are used for mild skin lesions, but systemic steroids are typically reserved for severe cases (Erythema Multiforme Major) with significant mucosal involvement. Their use is controversial and depends on the case's severity.

Erythema Multiforme Minor involves skin lesions with little to no mucous membrane involvement. Erythema Multiforme Major is more severe and is defined by the presence of lesions on mucous membranes like the mouth, eyes, or genitals, in addition to skin lesions.

Most cases of erythema multiforme are self-limiting and resolve on their own, typically within a few weeks to a month after the offending drug is stopped. Re-epithelialization of severe lesions usually takes 10-14 days.

No. Once a drug causes erythema multiforme, you should never be rechallenged with the same drug or any other drug of the same class or with a similar chemical structure to prevent a recurrence.