His seizures abate after administration of phenobarbital. He is noted to be febrile and sleepy after his seizure. Upon further questioning you find out he was born at term by vaginal delivery to a mother who received normal prenatal care and had no complications and no prior history of sexually transmitted or other diseases. The neonate is somnolent, has a bulging fontanelle, and is somewhat hypertonic. You decide to get blood, urine, and cerebrospinal fluid (CSF) analyses including cultures and start antibiotics. The medical student asks if you should start acyclovir to empirically treat neonatal HSV disease.

You correctly tell him:

A. This boy does not have neonatal HSV disease because he has no rash.

B. Neonatal HSV disease commonly occurs in the setting of negative maternal HSV history.

C. This boy has a high risk of neonatal HSV disease only if his mother has a history of genital HSV.

D. Central nervous system (CNS) involvement can be ruled out with a negative CSF HSV PCR.

E. Infants do not die from neonatal HSV infection.

The correct answer is “B.” Neonatal HSV disease is relatively uncommon, occurring in 1 in 3000 to 1 in 20,000 live births, but has high rates of morbidity and mortality, often even with antiviral therapy. Symptoms can be mild in the setting of skin, eye, and mouth disease (SEM), but can be severe in disseminated and CNS disease. Infants usually present before 6 weeks of age, most commonly at about 2 to 3 weeks of age. They very rarely have infection at birth. Symptoms include rash, fever, lethargy, seizures, or mucous membrane lesions depending on site of infection. Liver function tests are commonly elevated in disseminated disease. It is important to note that some infants with HSV never develop vesicular skin lesions and some may not have fever. Also important to remember is that initially well-appearing infants with skin vesicles may have more disseminated disease. A neonate who has a seizure should always have HSV infection on the differential diagnosis list. (See Figures 20–1 and 20–2.) Transmission most likely occurs during vaginal delivery but can occur postnatally as well (such as a person with a cold sore that kisses the neonate’s broken skin at the previous site of a scalp electrode). Rupture of membranes more than 4 hours before delivery increases risk in infants born vaginally and via cesarean section. Neonates born to mothers with first-time active genital lesions at time of delivery have about a 60% chance of developing neonatal HSV disease. This is thought to be due to lack of protective maternal antibodies. Such infants should be delivered by cesarean section to decrease this risk. Neonates born to mothers with history of prior genital HSV infection but no active lesions at the time of delivery have only a 2% chance of developing neonatal HSV disease. HSV can be shed intermittently in vaginal secretions without active lesions present. The majority of infants with neonatal HSV disease are born to mothers with no known history of HSV. Neonates with suspected HSV disease should be evaluated immediately and empiric acyclovir started pending results of testing. Acyclovir decreases mortality, but in the setting of disseminated and CNS disease there can still be significant morbidity despite therapy. Testing should include viral cultures of skin and mucous membranes, liver function tests, CSF indices, as well as PCR of blood, CSF, and lesion if present. CSF PCR can be falsely negative early in the disease and should be interpreted with caution. CSF PCR often remains positive for several days after the initiation of acyclovir, so administration of acyclovir should not be delayed to obtain a lumbar puncture if neonatal HSV disease is suspected. Imaging of the brain can be useful in the setting of CNS abnormalities such as seizures, altered mental status, or other related symptoms.

Sources:

Question & Explanation: Peterson AR, Wood KE. Pediatrics Examination and Board Review. New York, NY: McGraw-Hill Education; 2017.

Photo: Prose NS, Kristal L. Weinberg's Color Atlas of Pediatric Dermatology, 5e; 2017.