Not Found

Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

Erythema Multiforme

By Mercedes E. Gonzalez, MD, Clinical Assistant Professor of Dermatology; Clinical Assistant Professor of Dermatology; Medical Director, University of Miami Miller School of Medicine; ; Florida International University Herbert Wertheim College of Medicine; Pediatric Dermatology of Miami

Click here for
Patient Education

Erythema multiforme (EM) 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.

For years, erythema multiforme was thought to represent the milder end of a spectrum of drug hypersensitivity disorders that included Stevens-Johnson syndrome and toxic epidermal necrolysis. Recent evidence suggests that EM is different from these other disorders.


The majority of cases are caused by

HSV-1 is more of a cause than HSV-2, although it is unclear whether EM lesions represent a specific or nonspecific reaction to the virus. Current thinking holds that EM is caused by a T-cell–mediated cytolytic reaction to HSV DNA fragments present in keratinocytes. A genetic disposition is presumed given that EM is such a rare clinical manifestation of HSV infection, and several HLA 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 SLE. EM that occurs in patients with SLE is sometimes referred to as Rowell syndrome.

Symptoms and Signs

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; spread to the trunk is common. Some patients have itching.

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


  • Clinical evaluation

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

Differential diagnosis includes essential urticaria, vasculitis, bullous pemphigoid, pemphigus, linear IgA dermatosis, acute febrile neutrophilic dermatosis, and dermatitis herpetiformis.

Oral lesions must be distinguished from aphthous stomatitis, pemphigus, herpetic stomatitis, and hand-foot-and-mouth disease.

Patients with widely disseminated purpuric macules and blisters and prominent involvement of the trunk and face are likely to have Stevens-Johnson syndrome rather than erythema multiforme.


  • Supportive care

  • Sometimes prophylactic antivirals

Erythema multiforme spontaneously resolves, so treatment is usually unnecessary. Topical corticosteroids and anesthetics may ameliorate symptoms and reassure patients. Recurrences are common, and empiric oral maintenance therapy with acyclovir 400 mg po q 12 h, famciclovir 250 mg po q 12 h, or valacyclovir 1000 mg po q 24 h can be attempted if symptoms recur more than 5 times/yr and HSV association is suspected or if recurrent EM is consistently preceded by herpes flares.

Key Points

  • Erythema multiforme is usually triggered by 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 EM supportively and consider prophylactic antiviral drugs if HSV is the suspected cause and recurrences are frequent.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade