Erythema Multiforme: Causes, Symptoms, Diagnosis, and Treatment
Comprehensive guide to erythema multiforme including causes, symptoms, diagnosis, treatment, and prevention tips.
Erythema multiforme (EM) is an acute, immune-mediated skin condition that presents with distinctive target-like lesions and can affect the skin, mucous membranes, or both. Understanding this condition is essential for proper identification, management, and prevention of complications.
What is Erythema Multiforme?
Erythema multiforme refers to a hypersensitivity reaction most often triggered by certain infections or medications. It can range from a mild, localized skin eruption to a more severe and extensive condition involving mucous membranes (mouth, eyes, genitals) and skin.
- EM Minor: Primarily involves the skin with classic target or iris lesions.
- EM Major: Involves one or more mucous membranes along with widespread skin involvement.
Causes and Risk Factors
EM typically results from an aberrant immune response to various triggers. The majority of cases are related to infections, with a smaller proportion linked to medications and other factors.
Common Causes of Erythema Multiforme
| Type | Trigger Examples |
|---|---|
| Viral Infections | Herpes simplex virus (HSV-1, HSV-2), Epstein-Barr virus, Cytomegalovirus, Influenza, Hepatitis viruses (A, B, C), Measles, Mumps, Coxsackievirus, Adenovirus, Varicella-zoster, Parvovirus B19, HIV |
| Bacterial Infections | Mycoplasma pneumoniae (especially in children), Streptococcus, Tuberculosis, Borrelia, Diphtheria, Legionella, Salmonella, Neisseria meningitidis, Staphylococcus, Treponema pallidum (syphilis), Catscratch disease |
| Fungal Infections | Candida (especially vulvovaginal infection) |
| Medications | Penicillins, Sulfonamides, Erythromycin, Nitrofurantoin, Tetracyclines, Nonsteroidal anti-inflammatory drugs (NSAIDs), Antiepileptics, Barbiturates, Phenothiazines, Statins, Tumor necrosis factor-alpha (TNF-α) inhibitors, Vaccines (MMR, hepatitis B, smallpox, meningococcal) |
| Other | Autoimmune diseases (e.g., lupus), Radiation, Immunizations, Sarcoidosis, Menstruation, Malignancy, Inflammatory bowel disease, Allergic contact dermatitis |
Who is at Risk?
- People with a history of herpes simplex virus infections (cold sores or genital herpes)
- Children and adolescents (due to higher rates of Mycoplasma pneumoniae infections)
- Individuals taking certain medications (e.g., antibiotics, antiepileptics, NSAIDs)
- People with weakened immune systems or underlying autoimmune diseases
Is Erythema Multiforme Contagious?
Erythema multiforme itself is not contagious. The underlying cause (such as an infection) may be contagious, but the rash and skin reaction do not spread from person to person.
Symptoms of Erythema Multiforme
The hallmark of EM is the sudden appearance of symmetrical, round, red patches or “target lesions” on the skin. These may be accompanied by blisters, ulcers, and sometimes systemic symptoms.
- Red patches with concentric rings (looks like a target or bullseye)
- Lesions often appear on the hands, feet, arms, legs, and sometimes the torso
- Sensitivity, itching, or burning of the affected skin
- Blistering and ulceration with severe cases
- Mucous membrane involvement (mouth, lips, eyes, genitals) causing painful sores
- Fever, malaise, muscle aches (occasionally)
The lesions may vary in number and severity, ranging from a few spots to widespread eruptions affecting large areas of the body.
Skin Lesion Characteristics
- Papular (raised), often with a dark center surrounded by pale edematous zone and red periphery
- Symmetrical distribution, especially on the extremities
- Often appear and evolve rapidly over several days
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Severity Levels
- Mild (EM minor): Most commonly, only the skin is affected, and symptoms resolve spontaneously.
- Severe (EM major): Mucosal involvement is more extensive, lesions may cause significant discomfort, and medical attention is required.
Diagnosis of Erythema Multiforme
Erythema multiforme is usually diagnosed clinically, based on the appearance and distribution of lesions and patient history. Further testing may be necessary in uncertain cases or to identify the underlying cause.
- Clinical examination: Classic target or iris lesions are diagnostic for EM.
- Medical history: Evaluation of recent infections, illnesses, medication usage, or immunization history.
- Blood tests: To rule out other conditions or identify infections (like Mycoplasma pneumoniae).
- Skin biopsy: Rarely needed, but may be performed when the diagnosis is unclear or to exclude similar conditions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).
How is Erythema Multiforme Managed?
Most cases of erythema multiforme are self-limiting and resolve within two weeks without major medical intervention. Management depends on severity and the presence of any identifiable underlying cause.
General Treatment Strategies
- Identify and remove the trigger: Discontinue the offending medication or treat the underlying infection (e.g., start antibiotics for Mycoplasma pneumoniae, initiate antiviral therapy for HSV).
- Supportive care: Symptom management is key during the acute phase of the disease.
Symptomatic Relief
- Antihistamines and topical corticosteroids for itch and discomfort
- Topical anesthetic gels or mouthwashes for mouth ulcers
- Antiseptics for skin lesions to prevent secondary infection
- Lubricating ointments (e.g., petroleum jelly) for chapped lips
- Vitamin A ointment for eye involvement
- Pain relievers such as acetaminophen or ibuprofen (avoid NSAIDs in suspected drug-induced EM)
In cases with significant pain, dehydration, or inability to eat or drink, hospitalization may be needed for intravenous fluids and monitoring.
Treatment of Underlying Conditions
- Herpes simplex-associated EM: Antiviral medications such as acyclovir or valacyclovir may be prescribed, particularly for recurrent episodes.
- Mycoplasma pneumoniae-associated EM: Antibiotics are indicated and may be started even before test results confirm infection, if clinical suspicion is high.
Recurrent Erythema Multiforme
- If EM recurs due to herpes simplex virus, chronic antiviral therapy may be considered to prevent future recurrences.
Severe Cases
- Systemic corticosteroids may be considered for severe inflammation or mucosal involvement, though evidence for efficacy is limited.
- Close monitoring of eye symptoms, with referral to an ophthalmologist if the eyes are affected.
- Intravenous immunoglobulin (IVIG) or other immunosuppressive therapies are rarely used and reserved for severe, resistant cases.
Prognosis
- Most cases resolve within 7 to 14 days without long-term effects.
- Lesions fade without scarring in mild cases.
- Recurrences are possible, especially with HSV as a trigger.
- Severe complications are rare but may include skin infection, dehydration, or visual problems if eyes are involved.
Prevention of Erythema Multiforme
- Avoid known triggers: People who have had EM should avoid medications or substances previously identified as causes.
- Control recurrent infections: For HSV-associated EM, suppressive antiviral therapy may help reduce the frequency of outbreaks.
- Promptly treat infections such as Mycoplasma pneumoniae in at-risk populations.
- Inform healthcare providers of any history of EM so that potentially offending medications can be avoided.
When to Seek Medical Attention
Seek medical care promptly if:
- The rash rapidly spreads or becomes painful/ulcerated
- There are symptoms of mouth, eye, or genital involvement
- The individual has trouble eating, drinking, or swallowing
- There are signs of dehydration, such as dry mouth, low urine output, or dizziness
- There is fever, severe discomfort, or systemic illness
Frequently Asked Questions (FAQ)
Q: Can erythema multiforme be prevented?
A: Some cases can be prevented by avoiding known triggers, particularly certain medications and recurrent herpes infections. For herpes-induced EM, long-term antiviral therapy may reduce recurrence risk.
Q: Is EM the same as Stevens-Johnson Syndrome?
A: No, EM is generally less severe and has distinct target lesions. Stevens-Johnson Syndrome (SJS) is a more serious condition involving widespread skin detachment and greater mucosal involvement.
Q: How long does it take for erythema multiforme to resolve?
A: Most cases resolve in 7–14 days without scarring. Some severe cases may last longer.
Q: Can EM cause permanent damage?
A: Most cases heal without lasting problems. Rarely, severe cases can result in complications, such as scarring or vision issues if the eyes are badly affected.
Q: Is erythema multiforme dangerous?
A: Most cases are mild and self-limiting. However, severe cases can cause significant discomfort and require medical attention, especially to prevent dehydration or complications from mucosal involvement.
Key Takeaways
- Erythema multiforme is an acute hypersensitivity reaction affecting skin and sometimes mucous membranes.
- The condition is typically caused by infections (especially herpes simplex virus or Mycoplasma pneumoniae) or medications.
- Classic target lesions and rapid onset are key diagnostic features.
- Treatment includes removal of the trigger, symptom support, and management of severe cases when necessary.
- Prognosis is excellent for most patients, but medical evaluation is crucial for severe or recurrent cases.
References
- https://www.aafp.org/pubs/afp/issues/2019/0715/p82.html
- https://www.ncbi.nlm.nih.gov/books/NBK470259/
- https://kidshealth.org/en/parents/erythema-multiforme.html
- https://www.mountsinai.org/health-library/diseases-conditions/erythema-multiforme
- https://my.clevelandclinic.org/health/diseases/24475-erythema-multiforme
- https://www.aocd.org/page/erythemamultiforme
- https://dermnetnz.org/topics/erythema-multiforme
- https://www.cedars-sinai.org/health-library/diseases-and-conditions/e/erythema-multiforme.html
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