Erythema Multiforme
BASICS
DESCRIPTION
- Erythema multiforme (EM) is an acute, self-limited hypersensitivity syndrome characterized by a mucocutaneous eruption with distinct cutaneous targetoid lesions.
- Although classically defined by the presence of target lesions at various stages of evolution, EM may appear as erythematous macules, papules, vesicles, or bullae.
- EM is considered an immune-mediated reaction, usually to infectious triggers; numerous additional triggers have been reported.
- Clinical presentation ranges from relatively mild cutaneous disease (EM minor) to severe forms with significant mucosal involvement (EM major).
- Chronic EM is categorized as either recurrent EM (6 episodes per year during an average of 6 to 10 years) or persistent EM.
- Historically viewed as a spectrum of diseases, EM is now considered to be a separate entity from Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS and TEN are distinguished from EM by differing patterns of mucocutaneous involvement, precipitating factors, and prognosis.
EPIDEMIOLOGY
- EM predominantly affects healthy young adults but can affect people of all ages, including 20% of cases in children. It is rarely seen in infants.
- There is a possible seasonal variation with increased frequency in spring and summer but with more severe form that is more frequent in winter.
- Recurrent EM may occur and is more common in male patients.
ETIOLOGY
- About 90% of cases are caused by an infectious agent, most commonly herpes simplex virus (HSV) type 1. Other common infectious etiologies are HSV type 2, Mycoplasma pneumoniae, Epstein-Barr virus, varicella, cytomegalovirus, group A streptococcus, COVID-19, and orf virus.
- About 10% of cases are secondary to drug exposure. Common culprits include nonsteroidal anti-inflammatory drugs (NSAIDs), sulfonamides, antiepileptics, and antibiotics.
- Other precipitants include the following:
- Chemical and physical exposures
- Immunizations, particularly in infants
- Autoimmune disease
- Often, the causative factor is not identified.
- HSV is the major cause of recurrent EM.
- M. pneumoniae is associated with a distinct entity in children, mycoplasma-induced rash, and mucositis (MIRM), and is characterized by more severe mucosal involvement (oral, ocular, and anogenital), with less extensive cutaneous involvement. Reactive infectious mucocutaneous eruption (RIME) is an umbrella term that includes adenovirus, influenza, COVID-19, and other respiratory pathogens. It is distinct from EM and SJS due to its prominent mucositis, fewer cutaneous lesions, and association with younger and male patients, and it has a better prognosis than SJS. It may be recurrent.
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Citation
Cabana, Michael D., editor. "Erythema Multiforme." 5-Minute Pediatric Consult, 9th ed., Wolters Kluwer, 2025. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617665/all/Erythema_Multiforme.
Erythema Multiforme. In: Cabana MDM, ed. 5-Minute Pediatric Consult. Wolters Kluwer; 2025. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617665/all/Erythema_Multiforme. Accessed June 10, 2026.
Erythema Multiforme. (2025). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult (9th ed.). Wolters Kluwer. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617665/all/Erythema_Multiforme
Erythema Multiforme [Internet]. In: Cabana MDM, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2025. [cited 2026 June 10]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617665/all/Erythema_Multiforme.
* Article titles in AMA citation format should be in sentence-case
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ED - Cabana,Michael D,
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5-Minute Pediatric Consult

