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Clinical Summary

Erythema multiforme (EM) begins with symmetric, erythematous, sharply defined extremity or trunk macules, and evolves into a “targetoid” or “bull’s eye” morphology (a flat, dusky, central area with two concentric, erythematous rings). Bullae may appear in the central dusky area (bullous EM). The mucous membranes, typically oral, may become involved and, when severe, raise concern for SJS. The typical targetoid lesions allow a diagnosis to be made clinically (bullae, purpura, and mucosal involvement should prompt a dermatology consultation). The rash usually persists for 1 to 4 weeks.

HSV (frequently labialis) is strongly associated but may not be clinically apparent. Other viruses, bacteria (M pneumoniae, Chlamydia, Salmonella, Mycobacterium), and fungi (Histoplasma capsulatum, dermatophytes) are also associated. Medications account for < 10%; NSAIDs, sulfonamides, anticonvulsants, allopurinol, and antibiotics are responsible for the majority. Physical factors such as trauma, ultraviolet light exposure, and cold have been reported to elicit EM.

Management and Disposition

Prevention of HSV recurrences is essential. Antivirals administered after lesions present have minimal clinical impact, but patients should be referred for future prophylaxis consideration. Use of facial sunscreens and lip balms may help prevent UVB-induced recurrences. With the distinctive clinical findings and no systemic symptoms, patients may be discharged home. Systemic symptoms and atypical presentations with mucous membrane involvement (suggestive of SJS/TEN require admission and dermatologic consultation). Systemic steroids are generally discouraged but can be considered in atypical or severe presentations.


Erythema Multiforme. Wrist, hand, and fingers with typical central dusky centers surrounded by the concentric “bull’s eye” rings. (Reproduced with permission from Prose N, Kristal L. Weinberg’s Color Atlas of Pediatric Dermatology. 5th ed. New York, NY: McGraw Hill; 2017: Fig. 16-10.)


  1. EM does not progress to TEN.

  2. The dusky centers help differentiate EM from typical morbilliform drug reactions (no dusky centers) and giant annular urticaria (normal central zone skin).

  3. Reassure patients the lesions will completely resolve without scarring.

  4. Eye involvement requires a slit-lamp examination and ophthalmologic consultation to exclude active HSV infection.

  5. Patients with immunosuppression are more prone to recurrent and prolonged episodes.


Erythema Multiforme. Symmetric distribution of targetoid macules and plaques. The dusky central zone is more obvious on the left waistline lesions. (Photo contributor: Michael Redman, PA-C.)


Bullous Erythema Multiforme. Atypical targetoid appearance (only two rings apparent) and bulla formation. (Photo contributor: J. Matthew Hardin, MD.)

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