Erythema multiforme in Infant/Neonate
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.
L51.9 – Erythema multiforme, unspecified
36715001 – Erythema multiforme
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
- Molluscum contagiosum
- Congenital syphilis
Drug Reaction Data