Can Metronidazole Cause Erythema Multiforme?

October 12, 2025 •

5 min read

While extremely rare, case reports and pharmacovigilance data have linked the antibiotic metronidazole to the development of erythema multiforme (EM), a hypersensitivity skin disorder characterized by distinctive target-like lesions. This drug-induced reaction is less common than EM triggered by infections like the herpes simplex virus but represents a serious potential adverse event.

Quick Summary

The antibiotic metronidazole is a rare but documented trigger for the hypersensitivity skin disorder erythema multiforme. This adverse reaction, which involves red, target-shaped skin lesions, requires prompt medical attention. While infections are the more frequent cause of EM, clinicians must be aware of its potential link to certain medications, including metronidazole.

Key Points

Metronidazole is a Rare Trigger: While not a common cause, metronidazole can, in rare cases, cause erythema multiforme as a hypersensitivity reaction.
Look for Target-Like Lesions: The characteristic sign of erythema multiforme is the presence of distinctive 'target' or iris-shaped lesions on the skin.
Distinguish from Severe Reactions: Erythema multiforme is distinct from more life-threatening reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which also have a rare association with metronidazole.
Stop the Medication Immediately: If a drug-induced erythema multiforme reaction is suspected, the causative medication, including metronidazole, must be discontinued immediately under medical guidance.
Infections are the More Common Cause: It is important to note that infections, particularly herpes simplex virus, are a more frequent cause of erythema multiforme than drug reactions.
Seek Immediate Medical Help: Any blistering, peeling skin, or signs of severe systemic illness should prompt a visit to the emergency room, as it could indicate a more severe condition.

The Connection Between Metronidazole and Erythema Multiforme

Medications are a known cause of erythema multiforme (EM), a hypersensitivity disorder that primarily affects the skin and mucous membranes. While the most common trigger for EM is an infection, especially the herpes simplex virus, a smaller percentage of cases are caused by drugs, with antibiotics being one of the more common culprits. Though relatively uncommon, metronidazole has been reported as a potential trigger for EM in medical literature. The reaction is considered an immune-mediated response, where the body's immune system overreacts to the presence of the drug.

Spectrum of Metronidazole-Induced Skin Reactions

Metronidazole can cause a variety of skin-related adverse effects, ranging from mild to severe. These include:

Maculopapular eruptions: A widespread rash with flat, red spots (macules) and small, raised bumps (papules).
Urticaria and angioedema: Hives and swelling of the deeper layers of the skin, respectively.
Fixed drug eruption (FDE): A type of allergic skin reaction that recurs in the same location(s) each time a person is exposed to the offending drug.
Erythema multiforme (EM): The characteristic target-like lesions, which may be accompanied by fever and mucosal involvement in more severe cases.
Severe Cutaneous Adverse Reactions (SCARs): These are extremely rare but life-threatening reactions that include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. SJS/TEN is distinguished by extensive blistering and skin detachment, while DRESS involves a widespread rash, fever, and organ dysfunction.

Understanding Erythema Multiforme (EM)

Erythema multiforme is an acute, self-limited, and often recurring mucocutaneous reaction. It is a hypersensitivity response, meaning it is an exaggerated immune reaction, most often to an infectious agent, but sometimes to medications.

Common Triggers for EM

Infections: Most commonly the herpes simplex virus (HSV), but also Mycoplasma pneumoniae (especially in children) and other bacteria or viruses.
Medications: Less common than infections, but known triggers include antibiotics (like sulfonamides, penicillins, and, rarely, metronidazole), nonsteroidal anti-inflammatory drugs (NSAIDs), and anti-epileptic drugs.

Features of EM Lesions

The hallmark of EM is the target lesion. This classic skin finding consists of three concentric zones:

Peripheral erythematous ring: A red, raised outer ring.
Mid-zone edema: A paler, often raised, swollen middle ring.
Central blister or crust: A blister or dark, crusty area at the center.

These lesions typically appear symmetrically on the extremities, such as the palms of the hands and soles of the feet, and can spread toward the trunk. Mucosal involvement, such as painful erosions and ulcerations in the mouth, is more characteristic of the major form of EM.

Comparison of Cutaneous Adverse Reactions

Distinguishing between EM and other severe cutaneous reactions is critical due to differences in severity and management. The following table provides a high-level comparison:


Feature	Erythema Multiforme (EM)	Stevens-Johnson Syndrome (SJS)	Toxic Epidermal Necrolysis (TEN)
Severity	Typically mild (EM minor) to moderate (EM major).	Severe, potentially life-threatening.	Most severe, potentially fatal.
Triggers	Most commonly infections (especially HSV). Medications are a less common cause.	Almost always triggered by a drug reaction in adults.	Almost always triggered by a drug reaction in adults.
Skin Involvement	Distinctive 'target' lesions, typically less than 10% of body surface area. Acral distribution (hands, feet) common.	Widespread painful blistering rash with skin detachment affecting <10% of body surface area.	Extensive skin detachment affecting >30% of body surface area.
Mucosal Involvement	Present in EM major, typically affecting one mucous membrane site (often oral).	Involves mucous membranes (oral, ocular, genital) in >90% of cases.	Extensive and severe mucosal involvement.
Timeline	Lesions erupt rapidly, often within days or weeks of exposure.	Can take 1-3 weeks for drug-induced SJS/TEN to occur.	Can take 1-3 weeks for drug-induced SJS/TEN to occur.

What to Do If a Reaction Occurs

If you are taking metronidazole and suspect you are experiencing a severe skin reaction, it is crucial to seek immediate medical attention. This is especially true if you notice target lesions, blistering, or any signs of systemic illness like fever or flu-like symptoms.

Immediate Steps:

Stop taking the medication: Do not take any more metronidazole until you have spoken with a healthcare provider. Never restart a medication that may have caused a severe allergic reaction.
Contact your doctor or seek emergency care: Depending on the severity of symptoms, call your doctor or go to the nearest emergency department. Severe symptoms, such as extensive skin detachment, widespread blistering, or trouble breathing, require emergency care.
Provide a complete medication history: Be prepared to tell your doctor about all medications, including over-the-counter drugs and supplements, that you have been taking.

Diagnosis and Management

The diagnosis of drug-induced erythema multiforme relies heavily on a detailed patient history, a thorough physical examination of the skin and mucous membranes, and establishing a temporal link between the drug's initiation and the onset of the rash. In some cases, a skin biopsy may be performed to confirm the diagnosis and rule out other conditions.

Management focuses on two main strategies:

Discontinuation of the Offending Drug: The most critical step is to identify and immediately stop the suspected medication. This is essential to prevent the reaction from worsening and to promote healing.
Supportive Care: Treatment is largely supportive and aims to manage symptoms. This may include topical corticosteroids for skin lesions, pain management, and addressing any potential dehydration or other complications, particularly in cases of mucosal involvement. Hospitalization may be necessary for severe cases, such as those with significant mucosal damage.

Patient Education and Awareness

For any patient prescribed metronidazole, it is beneficial to be aware of the signs of a hypersensitivity reaction. The following are important points to remember:

Skin rashes are a potential side effect, though severe reactions are rare.
Notify your healthcare provider immediately if you develop any rash, blistering, or target-like lesions.
Be vigilant for systemic symptoms such as fever, flu-like illness, and lymph node swelling, which could indicate a more severe reaction like DRESS or SJS.
Remember that even if you have taken metronidazole before without issues, a hypersensitivity reaction can develop upon subsequent exposure.

Conclusion

While erythema multiforme is a rare adverse effect of metronidazole, its potential to occur underscores the importance of patient and clinician awareness. Prompt identification and discontinuation of the drug are vital for a positive outcome. Recognizing the characteristic target lesions of EM and understanding the key differences between EM and more severe cutaneous reactions like SJS/TEN and DRESS syndrome are essential for proper management. Patients should always consult with their healthcare provider if they experience any concerning skin reactions while taking metronidazole or any other medication.

For more information on the wide range of medication side effects, consult with resources from reputable health organizations.

This article is intended for informational purposes only and does not constitute medical advice. Consult a qualified healthcare professional for any health concerns or before making any decisions related to your treatment.

Frequently Asked Questions

Erythema multiforme (EM) is a rare adverse effect of metronidazole. While the drug is known to cause a range of less severe skin rashes, the incidence of EM specifically linked to metronidazole use is very low.

Initial signs may include flu-like symptoms such as fever, malaise, or joint pain, followed by the rapid development of red, patchy skin lesions. These lesions can develop into the characteristic target or iris-shaped spots, often appearing on the hands and feet before spreading to other areas.

You should stop taking metronidazole immediately and seek medical attention from a healthcare provider. Do not wait for the rash to progress, as early intervention is key, especially if you experience blistering or systemic symptoms.

No, erythema multiforme is a distinct condition, though it is sometimes confused with SJS. EM is generally milder, with less extensive skin detachment and mucosal involvement, and is more often triggered by infections. SJS is a more severe, life-threatening reaction, primarily triggered by medications, with widespread blistering and skin peeling.

No, if you experience a systemic hypersensitivity reaction like erythema multiforme to oral metronidazole, you should avoid all forms of the drug. Cross-reactions can occur with topical applications and are not worth the risk.

The primary treatment is the immediate discontinuation of metronidazole. Management is largely supportive, focusing on symptom relief and preventing complications. For mild cases, this may involve topical steroids and antihistamines, while severe cases may require hospitalization and more intensive supportive care.

Most allergic rashes are mild, with symptoms like simple hives or itching. Erythema multiforme is a more specific type of hypersensitivity reaction characterized by unique target lesions. Severe drug reactions, including EM, are distinct from typical allergic rashes and require immediate medical evaluation.