A mild, self-limited, potentially recurring mucocutaneous inflammatory condition.
Characterized by target lesions that resemble a bull's eye. These usually erupt over 24 to 48 hours and last for 1 to 2 weeks.
Typically presents in a symmetrical distribution of lesions over the dorsal surfaces of the extensor extremities with minimal mucous membrane involvement.
Generally related to infectious diseases and not drug exposure. The most commonly associated infections are herpes simplex virus and Mycoplasma pneumoniae . Other associated infections include hepatitis B, Epstein-Barr virus, cytomegalovirus, histoplasmosis (with concomitant erythema nodosum), orf (parapox virus that can be transmitted from sheep or goats to humans), coccidioidomycosis, Kawasaki disease, herpes zoster, and gardnerella.
Associated drugs include aminopenicillins, docetaxel, TNF-alpha inhibitors, antimalarials, anticonvulsants, and lidocaine injections. Statin medications have been associated with photo-induced lesions. Hepatitis B vaccine and allergic response to contact allergens have also been known to elicit the disorder.
Supportive care and treatment of underlying infection remain the mainstay of therapy.
Erythema multiforme (EM) is typically an acute, self-limited but often relapsing, mucocutaneous inflammatory condition. It is a hypersensitivity reaction associated with certain infections, vaccinations, and, less commonly, medications. The disease is characterized clinically by target lesions, which can be described as annular erythematous rings with an outer erythematous zone and central blistering sandwiching a zone of normal skin tone. These are in direct contrast to targetoid lesions, which can also be present but are less common, in which the center is not blistered. Targetoid lesions can be drug-related, but are not associated with erythema multiforme. In general, the lesions cover <10% of the total body surface area. Mild symptoms of an upper respiratory infection, including low-grade fever, can sometimes be noted prior to and at the start of an episode. Orolabial lesions are noted in two-thirds of patients; 40.9% of cases have oral lesions alone. Erosions, blisters, and crusts can be noted in any of the mucous membranes and are typically painful and tender. This can lead to difficulty eating and urinating, requiring hospitalization.  
Department of Surgery
Rush University Medical Center
AK-V has received compensation for reviewing manuscripts for Rubriq from Research Square on a variety of topics, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. She is also a manuscript reviewer for several journals, without renumeration.
Dr Areta Kowal-Vern would like to gratefully acknowledge Dr Jonathan Silverberg and Dr Nanette Silverberg, the previous contributors to this monograph. JS and NS declare that they have no competing interests.
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