Erythema Multiforme in a 28-Year-Old Man

September 14, 2005
Robert Skinner, Jr., MD

,
Raymond T. Kuwahara, MD

,
Dena M. Jones, MD

A 28-year-old man presented to the emergency department with a 1-week history of multiple, concentric, erythemic, targetlike plaques over the entire body. Severe necrosis and hemorrhagic crusting were evident on the oral mucosa and lesions were present on the upper lip. The remainder of the physical examination was unremarkable. The patient had no known medical problems, was seronegative for HIV, and denied a history of herpes simplex virus (HSV) infection. He used no medications.

A 28-year-old man presented to the emergency department with a 1-week history of multiple, concentric, erythemic, targetlike plaques over the entire body. Severe necrosis and hemorrhagic crusting were evident on the oral mucosa and lesions were present on the upper lip. The remainder of the physical examination was unremarkable. The patient had no known medical problems, was seronegative for HIV, and denied a history of herpes simplex virus (HSV) infection. He used no medications.

Drs Robert Skinner, Raymond T. Kuwahara, and Dena M. Jones of the University of Tennessee, Memphis, considered bullous pemphigoid, erythema multiforme, herpangina, Stevens-Johnson syndrome (SJS), and HSV infection in the differential diagnosis. Erythema multiforme-a self-limited, usually mild and relapsing exanthematous reaction that is most often associated with HSV infection-was diagnosed clinically. Although the patient denied a history of such infection, he may be an asymptomatic HSV carrier.

Erythema multiforme is not uncommon; 1% of dermatology outpatient visits may be attributed to this disease.1 Only one mucosal surface is involved in patients with erythema multiforme. The target lesions do not spread on pressure to surrounding skin (a negative Nikolsky sign).

Although viral antigens and DNA can be demonstrated in this disease by direct immunofluorescence, attempts at culturing lesions have failed. The target lesions are not sites of HSV replication. While the pathogenic mechanism is unclear, erythema multiforme is now considered to be a cell-mediated immune reaction against HSV antigen expression.

Generally, erythema multiforme causes little discomfort; spontaneous regression occurs within 2 weeks of eruption. Symptomatic treatment with topical corticosteroids, analgesics, and antihistamines has little effect on the course of the disease but can ameliorate symptoms. Since this condition is thought to be triggered by HSV, most clinicians recommend treating outbreaks with oral antiviral therapy.

The symptoms of SJS, which was once called erythema multiforme major, are similar but much more severe. SJS is thought to be drug-induced; sulfa, barbiturates, phenytoin, and allopurinol are common culprits. Two or more mucosal sites may be involved in SJS, and a positive Nikolsky sign can be induced in severe cases. Patients need to be hospitalized, and suspect medications must be discontinued. The history and the physical examination can distinguish SJS from erythema multiforme. Be sure to examine the genitalia in female patients; when more than one mucosal area is involved, the risk of complications, such as infection and fluid imbalance, increases.

Bullous pemphigoid is a subepidermal blistering disease that usually affects persons older than 60 years. Immunofluorescence reveals C3 and IgG deposition at the basement membrane. Typically, bullous pemphigoid is self-limited and resolves without treatment; however, prednisone, gold, tetracycline, and nicotinamide can be prescribed to hasten resolution and ameliorate symptoms.

HSV infection usually begins with vesicles that subsequently rupture and form ulcers. A Tzanck test can be done by carefully deroofing a vesicle, scraping the bottom of the lesion, and staining the specimen with Giemsa or Wright stain. On microscopic examination, multinucleated giant cells confirm the presence of HSV.

Herpangina typically manifests as gray-white papulovesicular lesions on the palate of children. Often, fever accompanies the eruption. The cause is usually group A coxsackievirus, but other members of the Enterovirus genus of the Picornaviridae family of viruses can produce herpangina. The disease is usually self-limited and resolves in 4 days. Symptomatic pain relief with hydration and antihistamine mouthwash is the only treatment necessary.

A 7-day course of acyclovir was given to this patient. He was lost to followup. In patients who are HSV-positive, oral acyclovir can be given to prevent recurrence.

REFERENCE:1. Freedberg IM, Eisen AZ, Wolff K, et al, eds. Fitzpatrick's Dermatology in General Medicine. 5th ed. New York: The McGraw-Hill Companies; 1999:638.

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