Herpes Simplex Virus Infection

A 13-day-old full-term boy presented to the emergency department (ED) with dried, crusting lesions on his scalp and blisters on his hand that his mother had first noticed 3 days before presentation. Aside from a maternal chlamydial infection that had been diagnosed and successfully treated in the first trimester, the mother had no significant past medical history.

In the ED, physical examination revealed vesicular lesions with an erythematous base interspersed with dry, crusting lesions on the scalp (A). Examination of the hands revealed fluid-filled vesicles on the left thumb and index finger (B). The infant was otherwise well.

With the suspicion of neonatal herpetic infection, a diagnostic workup was performed, including swab specimens from the lesions, blood, and cerebrospinal fluid (CSF) being sent for laboratory analysis. The infant was admitted to the hospital for parenteral antiviral therapy. Results of fluid analysis were positive for herpes simplex virus 1 (HSV-1), and results of polymerase chain reaction (PCR) testing were positive for HSV-1 in the blood. CSF culture was negative for HSV-1.

Because the infection remained confined to the skin, the infant was treated for a duration of 14 days for skin, eyes, and mouth (SEM) herpes. During that time, the lesions showed marked improvement (C), and the infant was discharged home on a 6-month regimen of suppressive antiviral therapy.

The estimated annual U.S. incidence of neonatal HSV infection ranges from 1 in 3,000 to 1 in 20,000 births,¹ or approximately 1,500 cases per year.² HSV-2 accounts for 75% of herpes disease in U.S. neonates.¹ The most common method of acquiring neonatal HSV is via contact with the infected maternal genital tract during birth. However, ascending infection via amniotic membranes and, less commonly, postnatal transmission from nongenital infection from a caregiver can occur. The estimated rate of HSV transmission to a neonate is from 25% to 60% when the mother has a primary genital infection at the time of delivery. The risk of transmission is reduced to less than 2% if the neonate is born to a mother with HSV shedding secondary to a reactivation of the infection.¹ As many as 25% of neonates infected with HSV are born to mothers with no history or clinical findings of genital HSV infection during pregnancy,¹ as was the case with our patient.

Neonatal herpetic infections are grouped into 3 categories: disseminated disease involving multiple organs, including but not limited to the liver, lungs and central nervous system (CNS); localized CNS disease; or disease localized to the skin, eyes, and/or mouth (SEM disease). Approximately 45% of cases of neonatal HSV manifest as SEM disease, and as many as 80% of neonates with SEM disease develop skin vesicles.² Most infants with HSV infection present with symptoms before 6 weeks of age, but infants with SEM disease often present in the first or second week of life.

Once HSV is suspected in an infant, swab specimens should be obtained from the mouth, nasopharynx, conjunctiva, and anus for culture testing; blood, CSF, and skin vesicle specimens should be obtained for PCR testing.¹

Neonatal herpes infections are associated with high mortality and morbidity rates, even after antiviral therapy. Infants with HSV should be hospitalized and started on parenteral acyclovir at the recommended dosage of 60 mg/kg per day, divided in 3 doses. Duration of therapy is 14 days in cases of SEM disease and 21 days for CNS disease or disseminated disease.¹

Infants with disseminated disease have a poor prognosis, with up to 20% mortality despite antiviral therapy. Cutaneous recurrences occur in 50% of infants who survive neonatal HSV infection. Suppressive antiviral therapy for up to 6 months after initial treatment has been shown to lead to positive neurodevelopmental outcomes and to prevent cutaneous recurrence. The recommended suppressive antiviral therapy is 300 mg/m²/dose of acyclovir, administered 3 times a day for 6 months.¹

REFERENCES:

1. Herpes simplex. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:398-408.

2. Kimberlin DW. Herpes simplex virus infections of the newborn. Semin Perinatol. 2007; 31(1):19-25.

Deepak M. Kamat, MD, PhD––Series Editor:Dr Kamat is professor of pediatrics at Wayne State University in Detroit. He is also director of the
Institute of Medical Education and vice chair of education at Children’s Hospital of Michigan, both in Detroit.