Published: 18 Jun 2025

ICD9: 695.19      ICD10: L51.8      ICD11: EB12

Erythema multiforme (EM) is an uncommon, acute, self-limiting skin condition considered to be an immune-mediated reaction, often triggered by an infection or medication.
It's characterized by distinctive target-like lesions, usually appearing suddenly.

Here's a breakdown of what's important to know about Erythema Multiforme:

Key Characteristics:

Target Lesions: These are the hallmark of EM. They typically have three zones:
A central dusky or dark red area (can be a blister or crust)
A paler ring surrounding the central area
An outer, erythematous (red) ring.
Sudden Onset: Lesions usually appear rapidly, often within 24-72 hours.
Symmetrical Distribution: The lesions are usually distributed symmetrically, commonly affecting the:
Extensor surfaces of the extremities (backs of hands, arms, legs, feet)
Face
Neck
Mucosal Involvement: While EM *minor* may have minimal or no mucosal involvement, EM *major* involves mucous membranes. This can affect the:
Mouth (most common mucosal site)
Eyes
Genitals
Self-Limiting: In most cases, EM resolves on its own within 2-4 weeks, as long as the trigger is removed.

Causes and Triggers:

Herpes Simplex Virus (HSV): The most common cause, especially for recurrent EM. The EM outbreak often occurs about 1-3 weeks after a herpes outbreak.
Medications: Certain drugs can trigger EM, including:
Antibiotics (e.g., sulfonamides, penicillins)
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)
Anticonvulsants
Other Infections: Less common triggers include:
Mycoplasma pneumoniae
Fungal infections
Bacterial infections

Types of Erythema Multiforme:

Erythema Multiforme Minor:
More common and milder form.
Typically, no or minimal mucosal involvement.
Limited number of skin lesions.
Erythema Multiforme Major:
More severe.
Involves mucous membranes (mouth, eyes, genitals).
More extensive skin involvement.
May be associated with systemic symptoms (fever, fatigue).

Diagnosis:

Clinical Evaluation: Diagnosis is primarily based on the characteristic appearance and distribution of the lesions.
History: The doctor will ask about recent illnesses, medications, and herpes simplex outbreaks.
Skin Biopsy: May be performed to confirm the diagnosis and rule out other conditions. Important to differentiate it from other conditions like Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).
Testing for HSV: Can be helpful to identify HSV as the trigger.

Treatment:

Identify and Eliminate Trigger: This is the most important step.
Symptomatic Treatment:
Antihistamines: To relieve itching.
Topical Corticosteroids: To reduce inflammation.
Mouthwashes or Lozenges: For oral lesions. Viscous lidocaine can help numb the mouth.
Pain Relief: Over-the-counter pain relievers like acetaminophen or ibuprofen.
Antiviral Medications: If HSV is the trigger, antiviral medications (e.g., acyclovir, valacyclovir) may be prescribed. In cases of recurrent EM due to HSV, suppressive antiviral therapy may be considered.
Systemic Corticosteroids: The use of systemic corticosteroids is controversial. Some studies suggest they may shorten the duration of the illness, while others have not found benefit and raise concerns about potential side effects. They are generally *not* recommended for HSV-associated EM.
Eye Care: If the eyes are involved, an ophthalmologist should be consulted.

Important Considerations:

Differentiation from SJS/TEN: It's crucial to distinguish EM from Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), as these are more severe conditions with significant mortality. SJS/TEN typically involve more extensive skin detachment and systemic involvement, and are more often drug-induced. The percentage of body surface area (BSA) affected is a key factor in distinguishing these conditions.
Recurrence: EM can recur, especially if triggered by HSV.
Complications: Complications are rare but can include:
Secondary skin infections
Eye damage (if the eyes are involved)
Scarring

When to See a Doctor:

It's important to see a doctor if you develop skin lesions that look like target lesions, especially if you have other symptoms like fever, mouth sores, or eye irritation. Early diagnosis and treatment can help prevent complications.

In summary, Erythema Multiforme is a skin condition characterized by distinctive target-like lesions, often triggered by an infection or medication. It's important to identify and eliminate the trigger, and to differentiate it from more severe conditions like SJS/TEN.