Erythema multiforme is a mild, self-limiting, potentially recurring mucocutaneous inflammatory condition.
Characterised 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 less commonly 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, tumour necrosis factor-alpha inhibitors, antimalarials, anticonvulsants, and lidocaine injections. Phenylbutazone, triclocarban, paclitaxel, and statin medications have been associated with photo-induced lesions. Vaccines such as hepatitis B, smallpox, varicella, meningococcal, human papillomavirus, and hantavirus, 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-limiting but often relapsing, mucocutaneous inflammatory condition. It is a hypersensitivity reaction associated with certain infections, vaccinations, and, less commonly, medications. The disease is characterised clinically by target lesions, which can be described as annular erythematous rings with an outer erythematous zone and central blister 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 centre is not blistered. 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 hospitalisation.
History and exam
Key diagnostic factors
- presence of risk factors
- target lesions of the extremities
- recurrent disease
- mucosal erosions
Other diagnostic factors
- targetoid lesions
- rapid onset of lesions
- self-limiting course
- clustered vesicles on an erythematous base
- rhonchi, rales, and/or wheezes
- red tympanic membranes
- prior occurrence
- herpes simplex virus (HSV) infection
- cytomegalovirus (CMV) infection
- Epstein-Barr virus (EBV) infection
- Mycoplasma pneumonia
- hepatitis B virus infection
- HIV infection
- orf virus infection
- hepatitis B vaccine
1st investigations to order
- serum electrolytes
- herpes simplex virus (HSV) serology
- rapid polymerase chain reaction (PCR)
- cold-haemagglutination serology
- M pneumoniae titres
- auto-antibody titres
Investigations to consider
- haematoxylin and eosin biopsy
- immunofluorescence biopsy
- hepatitis B virus (HBV) serology
- anti-desmoplakin antibodies
Areta Kowal-Vern, MD
Adjunct Research Faculty
Arizona Burn Center
Maricopa Integrated Health Systems
AK-V declares that she has no competing interests.
Dr Areta Kowal-Vern would like to gratefully acknowledge Dr Jonathan Silverberg and Dr Nanette Silverberg, the previous contributors to this topic.
JS and NS declare that they have no competing interests.
Cristine Radojicic, MD
CR declares that she has no competing interests.
Brian Swick, MD
Clinical Assistant Professor
University of Iowa College of Medicine
BS declares that he has no competing interests.
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