What is the management of herpes simplex virus (HSV) infections in pediatric patients?

Management of Herpes Simplex Virus (HSV) Infections in Pediatric Patients

Acyclovir is the drug of choice for all HSV infections in pediatric patients, with dosing and duration determined by disease severity and anatomic location. 1

Neonatal HSV Disease (≤28 days of age)

Treatment Regimens by Disease Classification

For CNS or disseminated disease:

• Administer IV acyclovir 20 mg/kg/dose three times daily for 21 days 1
• Do not discontinue therapy until repeat CSF HSV DNA PCR is negative at day 19-21 of treatment 1
• Despite treatment, these infants remain at highest risk for severe neurologic sequelae 1

For skin, eye, and mouth (SEM) disease:

• Administer IV acyclovir 20 mg/kg/dose three times daily for 14 days 1, 2
• Monitor for cutaneous recurrences during the first 6 months after treatment, as 2-6% may develop later neurologic sequelae despite apparently successful treatment 1, 2

Diagnostic Approach for Suspected Neonatal HSV

Obtain cultures from multiple sites:

• Blood, skin vesicles, mouth/nasopharynx, eyes, urine, and stool/rectum 1
• Positive cultures from any site >48 hours after birth indicates viral replication rather than contamination 1
• CSF must be tested for HSV DNA by PCR (CSF cultures are usually negative) 1

Critical timing consideration: Localized disease typically appears at age 10-11 days 1

HSV Disease Outside the Neonatal Period

Disseminated Disease or Encephalitis

• Treat with IV acyclovir 10 mg/kg/dose (or 500 mg/m²/dose) three times daily for 21 days 1
• For suspected HSV encephalitis, CSF HSV DNA PCR has replaced brain biopsy as the diagnostic test of choice 1

Symptomatic Gingivostomatitis

For HIV-infected children:

• IV acyclovir 5-10 mg/kg/dose three times daily for 7-14 days, OR
• Oral acyclovir 20 mg/kg/dose three times daily for 7-14 days 1, 2

Clinical presentation to recognize:

• Fever, irritability, tender submandibular lymphadenopathy, and superficial painful ulcers in gingival/oral mucosa and perioral area 1, 3
• Disease typically lasts about 12 days in children 3
• Peak viral titers occur in the first 24 hours after lesion onset 3

Recurrent HSV in HIV-Infected Children

• Consider secondary suppressive therapy with oral acyclovir for severe oral HSV recurrences (>3-6 severe episodes per year) 1

Special Populations and Considerations

Immunocompromised Children

• Episodes are usually longer and more severe, potentially involving the entire oral cavity or extending across the face 3
• HIV-infected children with severe immunocompromise may develop disseminated disease involving liver, adrenals, lung, kidney, spleen, brain, esophagus, CNS, and genitals 1

Age-Specific Limitations

Valacyclovir is only FDA-approved for:

• Cold sores in patients ≥12 years 4
• Chickenpox in patients aged 2 to <18 years 4
• NOT established for genital herpes, herpes zoster, or suppressive therapy following neonatal HSV in patients <18 years 4

Critical Safety Monitoring

Acyclovir Toxicities to Monitor

• Neutropenia (absolute neutrophil count <1,000/mm³) is the major toxicity in infants receiving high-dose acyclovir for neonatal disease 1
• Phlebitis, renal toxicity, nausea, vomiting, and rash 1
• Dose adjustment required based on creatinine clearance in patients with renal insufficiency or failure 1

Long-term Suppressive Therapy Risks

• In infants receiving oral acyclovir suppressive therapy (300 mg/m²/dose 2-3 times daily) following neonatal HSV, neutropenia occurred in 46%, though most cases were self-limited 1

Transmission Prevention

Contagious Period for Cold Sores

• Viral shedding begins 1-2 days before visible lesions appear 5
• Adult is non-contagious once all lesions have completely crusted over, typically 4-7 days after rash onset 5
• Avoid kissing or direct facial contact with toddlers until complete crusting 5

Critical pitfall: HSV-1 can be transmitted even without visible cold sores through asymptomatic viral shedding 5

Diagnostic Methods Beyond Culture

• Direct immunofluorescence for HSV antigen on cells from skin, conjunctiva, or mucosal lesion scrapings 1, 2
• Giemsa staining (Tzanck preparation) shows multinucleated giant cells but does not differentiate HSV type from varicella-zoster virus and is not routinely recommended 1
• Virus can usually be detected in tissue culture cells within 1-3 days 1