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Erythema Multiforme


Julia Benedetti

, MD, Harvard Medical School

Reviewed/Revised Apr 2022
Topic Resources

Erythema multiforme is an inflammatory reaction, characterized by target or iris skin lesions. Oral mucosa may be involved. Diagnosis is clinical. Lesions spontaneously resolve but frequently recur. Erythema multiforme usually occurs as a reaction to an infectious agent such as herpes simplex virus or mycoplasma but may be a reaction to a drug. Suppressive antiviral therapy may be indicated for patients with frequent or symptomatic recurrence due to herpes simplex virus.

Etiology of Erythema Multiforme

The majority of cases are caused by

HSV-1 is more often a cause than HSV-2, although it is unclear whether erythema multiforme lesions represent a specific or nonspecific reaction to the virus. Current thinking holds that erythema multiforme is caused by a T-cell–mediated cytolytic reaction to HSV DNA fragments present in keratinocytes. A genetic disposition is presumed given that erythema multiforme is such a rare clinical manifestation of HSV infection, and several human leukocyte antigen subtypes have been linked with the predisposition to develop lesions.

Less commonly, cases are caused by drugs, vaccines, other bacterial or viral diseases (especially hepatitis C), or possibly systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) (SLE). Erythema multiforme that occurs in patients with SLE is sometimes referred to as Rowell syndrome.

Symptoms and Signs of Erythema Multiforme

Erythema multiforme manifests as the sudden onset of asymptomatic, erythematous macules, papules, wheals, vesicles, bullae, or a combination on the distal extremities (often including palms and soles) and face. The classic lesion is annular with a violaceous center and pink halo separated by a pale ring (target or iris lesion). Distribution is symmetric and centripetal, sometimes spreading to the trunk. Some patients have itching.

Manifestations of Erythema Multiforme

Oral lesions include target lesions on the lips and vesicles and erosions on the palate and gingivae.

Diagnosis of Erythema Multiforme

  • Clinical evaluation

Diagnosis of erythema multiforme is by clinical appearance; biopsy is rarely necessary.

Differential diagnosis includes urticaria Urticaria Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin. Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation... read more Urticaria , vasculitis Overview of Vasculitis Vasculitis is inflammation of blood vessels, often with ischemia, necrosis, and organ inflammation. Vasculitis can affect any blood vessel—arteries, arterioles, veins, venules, or capillaries... read more Overview of Vasculitis , bullous pemphigoid Bullous Pemphigoid Bullous pemphigoid is a chronic autoimmune skin disorder resulting in generalized, pruritic, bullous lesions in older adults. Mucous membrane involvement is rare. Diagnosis is by skin biopsy... read more Bullous Pemphigoid , pemphigus, linear IgA dermatosis Linear Immunoglobulin A (IgA) Disease Linear immunoglobulin A (IgA) disease is an uncommon bullous disease distinguished from bullous pemphigoid and dermatitis herpetiformis by linear deposits of IgA in the basement membrane zone... read more Linear Immunoglobulin A (IgA) Disease , acute febrile neutrophilic dermatosis Acute Febrile Neutrophilic Dermatosis Acute febrile neutrophilic dermatosis is characterized by tender, indurated, dark-red papules and plaques with prominent edema in the upper dermis and dense infiltrate of neutrophils. The cause... read more Acute Febrile Neutrophilic Dermatosis , and dermatitis herpetiformis Dermatitis Herpetiformis Dermatitis herpetiformis is an intensely pruritic, chronic, autoimmune, papulovesicular cutaneous eruption strongly associated with celiac disease. Typical findings are clusters of intensely... read more Dermatitis Herpetiformis .

Treatment of Erythema Multiforme

  • Supportive care

  • Sometimes prophylactic antivirals

Erythema multiforme spontaneously resolves, so treatment is usually unnecessary. Topical corticosteroids and anesthetics and oral antihistamines may ameliorate symptoms and reassure patients.

Recurrences are common, and empiric oral maintenance therapy with antiherpetic drugs such as acyclovir 400 mg orally every 12 hours, famciclovir 250 mg orally every 12 hours, or valacyclovir 1000 mg orally every 24 hours can be attempted if symptoms recur more than 5 times/year and HSV association is suspected or if recurrent erythema multiforme is consistently preceded by herpes flares.

Key Points

  • Erythema multiforme is usually triggered by herpes simplex virus (HSV) but can be caused by a drug.

  • Target lesions and lesions on the palms and soles can be relatively specific findings.

  • Biopsy is rarely necessary.

  • Treat erythema multiforme supportively and consider prophylactic antiviral drugs if HSV is the suspected cause and recurrences are frequent.

Drugs Mentioned In This Article

Drug Name Select Trade
Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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