Erythema multiforme in Infant/Neonate
See also in: Anogenital,Oral Mucosal LesionAlerts and Notices
Synopsis

In older children and adults, herpes simplex virus (HSV) is a common etiology; however, HSV has not been reported as a significant etiology in infants. EM in neonates and infants is exceedingly rare. Reported triggers for infantile EM have included drugs (particularly penicillin), hepatitis, hepatitis B vaccination, Candida, and cow's milk.
Codes
ICD10CM:L51.9 – Erythema multiforme, unspecified
SNOMEDCT:
36715001 – Erythema multiforme
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
- EM is rare in infants and extremely rare in neonates (<1 month of age), and Kawasaki disease should be strongly considered as an alternative diagnosis. Infants with Kawasaki disease will appear ill and have a high fever. Kawasaki disease may be associated with cervical lymphadenopathy, edema of the hands and feet, and significantly elevated inflammatory markers, whereas EM is not.
- Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) – Histologic 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 crusts, 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.
- Urticaria multiforme – New lesions appear daily; lesions are transient and last less than 24 hours, and they are associated with edema of lips, face, hands, and feet. There is no evidence of epidermal damage in the center of urticarial lesions. Subcutaneous epinephrine injections will clear urticarial lesions but not EM lesions.
- 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. The oral mucosa can be involved. Histology will differentiate a fixed drug eruption from EM.
- Acute hemorrhagic edema of infancy – The child is well-appearing and may have edema of acral sites. Lesions may be urticarial, targetoid, or have 3 zones of color. Mucosal surfaces are spared. Skin biopsy will reveal leukocytoclastic vasculitis.
- Cutaneous small vessel vasculitis – Targetoid lesions may be present, but mucosal surfaces should be spared. Additionally, biopsy will reveal leukocytoclastic vasculitis.
- Viral exanthem
- Arthropod bites (insect bites)
- Neonatal lupus erythematosus
- Scabies
- Molluscum contagiosum
- Congenital syphilis
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Management Pearls
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Therapy
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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.Subscription Required
References
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Last Reviewed:12/19/2022
Last Updated:12/20/2022
Last Updated:12/20/2022


Overview
Erythema multiforme is an inflammatory skin reaction that occurs in response to medication, infection, or illness. There are two types of erythema multiforme: erythema multiforme minor and erythema multiforme major. Erythema multiforme major has systemic symptoms such as fever and joint pain.Who’s At Risk
Erythema multiforme often occurs as a drug reaction in response to barbiturates, penicillins, phenytoin, and sulfonamides. It can also develop after contracting herpes simplex virus or a mycoplasma infection.Signs & Symptoms
Symptoms of erythema multiforme include:- Fever
- Itchy skin
- Joint aches
- Sore, abnormal skin lesions
Self-Care Guidelines
Measures can be taken to manage symptoms:- Use moist compresses on the skin
- Take pain medication such as ibuprofen (Advil) or acetaminophen (Tylenol)
- Keep clean and maintain distance from others to prevent secondary infections
When to Seek Medical Care
Seek medical care if you suspect you may have erythema multiforme or if symptoms get worse.Treatments
Your health care provider may tell you to stop taking any medication that could be causing erythema multiforme.For mild symptoms, the following treatments may be given:
- Antihistamines to stop itching
- Oral antiviral medicine if herpes simplex is causing the problem
- Pain medication
- Topical anesthetics to reduce pain, especially if reaction is in your mouth
For more severe symptoms, your health care provider may prescribe:
- Antibiotics for skin infections
- Corticosteroids to reduce inflammation
Erythema multiforme in Infant/Neonate
See also in: Anogenital,Oral Mucosal Lesion