Erythema Multiforme: Recognition and Management

 

Am Fam Physician. 2019 Jul 15;100(2):82-88.

Author disclosure: No relevant financial affiliations.

Erythema multiforme is an immune-mediated reaction that involves the skin and sometimes the mucosa. Classically described as target-like, the erythema multiforme lesions can be isolated, recurrent, or persistent. Most commonly, the lesions of erythema multiforme present symmetrically on the extremities (especially on extensor surfaces) and spread centripetally. Infections, especially herpes simplex virus and Mycoplasma pneumoniae, and medications constitute most of the causes of erythema multiforme; immunizations and autoimmune diseases have also been linked to erythema multiforme. Erythema multiforme can be differentiated from urticaria by the duration of individual lesions. Erythema multiforme lesions are typically fixed for a minimum of seven days, whereas individual urticarial lesions often resolve within one day. Erythema multiforme can be confused with the more serious condition, Stevens-Johnson syndrome; however, Stevens-Johnson syndrome usually contains widespread erythematous or purpuric macules with blisters. The management of erythema multiforme involves symptomatic treatment with topical steroids or antihistamines and treating the underlying etiology, if known. Recurrent erythema multiforme associated with the herpes simplex virus should be treated with prophylactic antiviral therapy. Severe mucosal erythema multiforme can require hospitalization for intravenous fluids and repletion of electrolytes.

Erythema multiforme is an acute, typically self-limited skin condition with lesions that can be isolated, recurrent, or persistent.1 Erythema minor affects only the skin and erythema major includes mucocutaneous involvement.1,2 Although it was previously thought that erythema multiforme was on the same pathologic spectrum as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis, it is now accepted that erythema multiforme is a distinct disease.3,4

The annual incidence of erythema multiforme is estimated at less than 1%.5,6 It is more common in adults younger than 40.6 There is no apparent association with race.7

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

Suspect erythema multiforme in patients with a target or iris lesion characterized by three concentric segments: a dark center, surrounded by a lighter pink ring, both of which are surrounded by a red ring.1

C

Expert opinion

Symptomatic treatment with topical steroids or antihistamines is recommended for acute episodes of uncomplicated erythema multiforme.1,21

C

Expert opinion

Oral anesthetics may be helpful in decreasing the pain of oral erythema multiforme lesions.1,4,6

C

Case series, expert opinion

Urgent ophthalmologic consultation is recommended for patients with any ocular erythema multiforme involvement.1

C

Expert opinion

Continuous prophylactic antiviral treatment is recommended for recurrent herpes simplex virus–associated erythema multiforme.41

B

Based on a single, double-blind, placebo-controlled trial


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

Suspect erythema multiforme in patients with a target or iris lesion characterized by three concentric segments: a dark center, surrounded by a lighter pink ring, both of which are surrounded by a red ring.1

C

Expert opinion

Symptomatic treatment with topical steroids or antihistamines is recommended for acute episodes of uncomplicated erythema multiforme.1,21

C

Expert opinion

Oral anesthetics may be helpful in decreasing the pain of oral erythema multiforme lesions.1,4,6

C

Case series, expert opinion

Urgent ophthalmologic consultation is recommended for patients with any ocular erythema multiforme involvement.1

C

Expert opinion

Continuous prophylactic antiviral treatment is recommended for recurrent herpes simplex virus–associated erythema multiforme.41

B

Based on a single, double-blind, placebo-controlled trial


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

Etiology

Erythema multiforme is caused by a cell-mediated immune response, and infections are associated with 90% of cases.6 Although herpes simplex virus (HSV) type 1 is the most commonly identified etiology, HSV-2 also has been shown to cause erythema multiforme8 (Figure 1). Mycoplasma pneumoniae

The Authors

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KATHRYN P. TRAYES, MD, is an assistant professor in the Department of Family and Community Medicine at Thomas Jefferson University Hospital, Philadelphia, Pa....

GILLIAN LOVE, MD, is a third-year resident in the Department of Family and Community Medicine at Thomas Jefferson University Hospital.

JAMES S. STUDDIFORD, MD, is a professor in the Department of Family and Community Medicine at Thomas Jefferson University Hospital.

Address correspondence to Kathryn P. Trayes, MD, 1020 Walnut St., Ste. 116, Philadelphia, PA 19107. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

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