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 medication. 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, but it is now considered a different entity.
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 medications, vaccines, other bacterial or viral diseases (especially hepatitis C), or possibly systemic lupus erythematosus (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.
This photo shows target lesions (sometimes called iris lesions). Such lesions, which are typical of erythema multiforme, can appear on the palms.
Photo courtesy of Julia Benedetti, MD.
Erythema multiforme is characterized by target or iris lesions, which are annular lesions with a violaceous center and pink halo separated by a pale ring.
DR P. MARAZZI/SCIENCE PHOTO LIBRARY
This photo shows characteristic target or iris lesions of erythema multiforme on the abdomen. The palm is also affected.
Photo courtesy of Karen McKoy, MD.
This photo shows oral and palmar lesions.
Photo courtesy of Karen McKoy, MD.
This photo shows target lesions (sometimes called iris lesions). Such lesions, which are typical of erythema multiforme, can appear on the palms.
Photo courtesy of Julia Benedetti, MD.
Erythema multiforme is characterized by target or iris lesions, which are annular lesions with a violaceous center and pink halo separated by a pale ring.
DR P. MARAZZI/SCIENCE PHOTO LIBRARY
This photo shows characteristic target or iris lesions of erythema multiforme on the abdomen. The palm is also affected.
Photo courtesy of Karen McKoy, MD.
This photo shows oral and palmar lesions.
Photo courtesy of Karen McKoy, MD.
Oral lesions may 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, 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.
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, but sometimes antivirals are needed (1).
Treatment reference
1. Soares A, Sokumbi O. Recent Updates in the Treatment of Erythema Multiforme. Medicina (Kaunas). 2021;57(9):921. Published 2021 Sep 1. doi:10.3390/medicina57090921
Key Points
Erythema multiforme is usually triggered by herpes simplex virus (HSV) but can be caused by a medication.
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 medications if HSV is the suspected cause and recurrences are frequent.
