Category: Pediatrics
Posted: 8/6/2020 by Cathya Olivas Michels, MD
(Updated: 12/26/2024)
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Although rare, neonatal herpes simplex virus (HSV) infection causes devastating long-term sequelae and significant mortality. Mortality can be as high as 85% if left untreated, making it an essential diagnostic consideration for ED providers caring for pediatric patients. Neonatal HSV infection is clinically challenging to diagnose as manifestations can be subtle and nonspecific. Prompt evaluation and empiric use of antivirals in the ED can improve outcomes.
Risk factors: maternal history of HSV infection, maternal history of primary genital HSV near/at delivery, invasive fetal monitoring during delivery, preterm birth (<38 weeks). Note: Per CDC data, most mothers of infected neonates do not have a known history of genital HSV and report being asymptomatic at delivery.
Consider neonatal HSV infection in infants younger than 2 months of age (peak incidence occurs at 2-3 weeks of age) with the following symptoms:
- Fever or hypothermia
- Events concerning for seizures or changes in activity level
- Poor feeding
- Respiratory distress/apnea
- Conjunctivitis
- Mucous membrane or cutaneous vesicles
In your ED evaluation of these patients, consider obtaining the following:
- CBC, LFTs, coagulation studies
- CSF cell count, protein, glucose
o Note: CSF pleocytosis with mononuclear predominance is suggestive of HSV meningitis; however, absence of CSF leukocytosis does not rule it out.
- For definitive diagnosis, the AAP recommends obtaining the following:
o Mouth/nasopharyngeal/conjunctival/anal surface swabs for PCR or viral culture
o Swabs of skin lesions for PCR or viral culture
o CSF for HSV PCR
o Whole blood for HSV PCR
o PCR assays are preferred to cultures (more sensitive)
For patients in whom you highly suspect neonatal HSV, do not delay treatment. Empiric treatment = IV acyclovir 20mg/kg q8h. Always double check dosing with Micromedex Neofax (free through UMMC) or your friendly pediatric pharmacy specialist.
Bottom Line: Have a high index of suspicion for neonatal HSV infection in infants <2 months of age presenting with nonspecific signs and symptoms mimicking sepsis, even in the absence of fever or vesicular rash. If suspicion is high, obtain appropriate studies and begin empiric therapy with high dose IV acyclovir.
| AAP Clinical Subtypes of Neonatal HSV Infection | Proportion of Cases | Manifestations | Considerations: |
| Localized SEM (skin, eyes, mouth) | 45% | Vesicular lesions Conjunctivitis, keratitis Oropharyngeal ulcers |
|
| Localized CNS disease | 30% | Seizures Lethargy Irritability Bulging fontanelle Tremors Poor feeding +/- skin lesions | *Symptoms may not be apparent early in disease course. |
| Disseminated disease | 25% | Sepsis Temperature instability Hepatitis Pneumonitis, pneumonia DIC, thrombocytopenia +/- CNS involvement +/- skin lesions | *Up to 40% patients with disseminated disease do not develop skin findings. |
Keep in mind that 30-40% patients with localized CNS disease or disseminated disease will not have skin vesicles. Have a high index of suspicion for patients with these nonspecific signs and symptoms.
1.Caviness, A. C., Demmler, G. J. & Selwyn, B. J. Clinical and Laboratory Features of Neonatal Herpes Simplex Virus Infection: A Case-Control Study. The Pediatric Infectious Disease Journal 27, 425–430 (2008).
2.Cruz, A. T. et al. Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation. Pediatrics 141, e20171688 (2018).
3. Fidler, K., Pierce, C., Cubitt, W., Novelli, V. & Peters, M. Could neonatal disseminated herpes simplex virus infections be treated earlier? Journal of Infection 49, 141–146 (2004).
4.Ramgopal, S., Wilson, P. M. & Florin, T. A. Diagnosis and Management of Neonatal Herpes Simplex Infection in the Emergency Department. Pediatric Emergency Care 36, 7 (2020).
5. AAP Red Book Chapter on Herpes Simplex
