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Erythema multiforme in Child
See also in: Anogenital,Oral Mucosal Lesion
Other Resources UpToDate PubMed

Erythema multiforme in Child

See also in: Anogenital,Oral Mucosal Lesion
Contributors: Molly Plovanich MD, Belinda Tan MD, PhD, Susan Burgin MD
Other Resources UpToDate PubMed


Erythema multiforme (EM) is a self-limited hypersensitivity reaction of the skin and mucous membranes characterized by the acute onset of fixed lesions of concentric color change (target lesions). Two subtypes exist: EM major and EM minor. Key differences between the EM subtypes include mucosal involvement and systemic symptoms such as fever, arthralgias, and asthenias seen in the major subtype.

In the past, the conditions EM, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) were considered a continuum, but it is now recognized that EM does not progress to TEN. Therefore, EM is now considered a distinct hypersensitivity eruption, which can be distinguished from SJS/TEN based on the presence of target lesions, papular (rather than macular) atypical target lesions, and an acral distribution.

In adults, the primary trigger for EM is herpes simplex virus (HSV), which is estimated to incite about 90% of cases. Mycoplasma is another common trigger. In children, important additional triggers to consider include drugs (particularly penicillin), group A Streptococcus, and Epstein-Barr virus among other viruses and bacteria.

Typically, all cutaneous lesions appear within 24-72 hours and persist for 2 weeks before fading. The eruption recurs on repeated exposure to the inciting agent. 

Related topic: reactive infectious mucocutaneous eruption (RIME)


L51.9 – Erythema multiforme, unspecified

22972008 – Erythema multiforme, dermal type

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Differential Diagnosis & Pitfalls

  • Urticaria multiforme – New lesions appear daily; lesions are transient and last less than 24 hours, associated with edema of lips, face, hands, and feet. No evidence of epidermal damage in the center of urticarial lesions. Subcutaneous epinephrine injections will clear urticarial lesions but not EM lesions.
  • Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) – Histological features may not differentiate EM from SJS/TEN. Clinically, however, look for irregularly shaped, dusky red macular- or patch-like lesions on the trunk, face, and palms / soles. A positive Nikolsky sign can be found; there is mucosal involvement, including the eyes, lips, mouth, and genitalia. Look for hemorrhagic crust, bullae, and denudation in these areas. Systemic symptoms are commonly present but not invariable. Lesions are more pronounced on the trunk than on the extremities. Precipitating factors are usually medications.
  • Reactive infectious mucocutaneous eruption (RIME) – Usually occurs secondary to mycoplasma infection (as evidenced by clinical pneumonia, imaging studies, and/or mycoplasma serologies) although Chlamydia pneumoniae, human parainfluenza virus 2, rhinovirus, adenovirus, enterovirus, human metapneumovirus, and influenza B virus have more recently been recognized to cause a similar clinical picture. There is pronounced oral and ocular mucositis with absent, spare, or mild cutaneous involvement. Cutaneous lesions are most often tense vesiculobullae. Target or targetoid lesions may be present. Cutaneous lesions do not erode or desquamate as seen in SJS/TEN. (Note: erosion is seen in the genital and perianal skin, which are considered akin to mucosal surfaces.) Nikolsky sign is negative. Acute and convalescent mycoplasma titers may be employed to help to establish this diagnosis in the correct clinical scenario.
  • Kawasaki disease – Children with Kawasaki disease will appear ill and have a fever. Kawasaki disease may be associated with cervical lymphadenopathy, edema of the hands and feet, and significantly elevated inflammatory markers, whereas EM is not.
  • Generalized fixed drug eruption – Look for erythematous plaques that develop on the lips, face, distal extremities, and genitalia 1-2 weeks after initial exposure and within 24 hours after subsequent exposure. Oral mucosa can be involved. Histology will differentiate fixed drug eruption from EM.
  • Viral exanthem – Target lesions or mucosal involvement should not be present in a viral exanthem, differentiating it from EM.
  • Cutaneous small vessel vasculitis – Targetoid lesions may be present, but mucosal surfaces should be spared. Additionally, biopsy will reveal leukocytoclastic vasculitis.
  • Polymorphous light eruption – This will typically present with pruritic papules and papulovesicles in a photodistribution. Mucosal sites are spared.
  • Arthropod bites (insect bites)
  • Scabies
  • Molluscum contagiosum
  • Erythema annulare centrifugum
  • Erythema migrans (Lyme disease)
Differential diagnosis of hemorrhagic crusting of both lips:

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Updated:11/08/2022
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Erythema multiforme in Child
See also in: Anogenital,Oral Mucosal Lesion
A medical illustration showing key findings of Erythema multiforme : Bullae, Painful skin lesions, Palms and soles, Scattered many, Smooth plaque, Tense vesicles
Clinical image of Erythema multiforme - imageId=30005. Click to open in gallery.  caption: 'Edematous and erythematous papules and plaques, some with a target-like appearance on the leg.'
Edematous and erythematous papules and plaques, some with a target-like appearance on the leg.
Copyright © 2023 VisualDx®. All rights reserved.