Neonatal HSV

Background

• Causative agent: HSV-1 or HSV-2
• Definition – “infection acquired peri-natally or postnatally without clinical manifestations at birth or in the first 24 hours of life but with subsequent clinical manifestations in the neonatal period (age less than 29 days)”
• ED prevalence:
  • 0.2% all neonates
  • 0.3% febrile neonates
  • 0.5% neonates undergoing LP
• Prevalence similar to meningitis (0.4%) in neonates presenting for SBI workup
• Risk associated with age <3 weeks, primary maternal HSV infection at delivery

Management Considerations

• Acyclovir if
  • Proven HSV disease
  • Suspected HSV disease (see clinical features) pending studies
  • At risk due to exposure (active genital lesions in mother)

• Many recommend acyclovir empirically in ill-appearing neonates with fever (including hypothermia) or aspetic meningitis until results of work-up are known

Classification

• Whitney-Kimberlin disease categories
  • Disseminated (liver, lung, adrenal glands, skin, eye, brain) - 25%
    • 2/3 have CNS involvement
  • CNS - 30%
  • SEM (skin, eye, mouth) - 45%
    • Conjunctival disease or minor skin lesions may be only manifestation
      • May go on to CNS, disseminated disease - workup and treat the same

Historical Features

• Not sensitive (maternal history of HSV), nor specific (maternal fever, vaginal delivery, preterm birth)
  • 80% of mothers have no history of genital lesions
• Vesicular lesions most specific, present in <1/2
  • Note: absence of vesicular rash does not rule out
• May be well appearing - maintain high clinical suspicion
• Ask about:
  • Temperature instability (fever, hypothermia)
  • Irritability
  • Lethargy
  • Seizures
  • Respiratory distress

Clinical Features

• General
  • Temperature instability (febrile or hypothermic)
  • May be well appearing in SEM
• Disseminated
  • Neutropenia
  • Thrombocytopenia
  • Hepatitis
  • Pneumonitis
  • DIC
  • +/- CNS disease
• CNS
  • Hypotonia
  • Seizures
  • Abnormal brain imaging
  • Abnormal EEG
  • CSF pleocytosis and/or proteinosis
• SEM
  • Characteristic skin lesions of HSV – skin, eye (kerato-conjunctivitis), or mouth
  • No evidence of systemic or CNS infection

Differential Diagnosis

Pediatric fever

• Upper respiratory infection (URI)
• UTI
• Sepsis
• Meningitis
• Febrile seizure
• Pneumonia
• Acute otitis media
• Whooping cough
• Unclear source
• Kawasaki disease
• Neonatal HSV
• Specific virus
  • COVID-19 (peds)

Evaluation

Work-up

• Should include the following
  • CBC with differential
  • Chem
  • LFT
  • Blood, urine culture
  • LP with CSF studies
  • Perform PCR/culture of:
    • Any visible lesions
    • Conjunctiva, nasopharynx, mouth, anus
      • Even in the absence of lesions
  • Consider CXR for respiratory symptoms
  • Suspected disease should get CT and EEG
  • Suspected ocular involvement should get optho consult

Evaluation

• Always consider neonatal HSV and perform appropriate work-up and treatment if:
  • Evidence of vesicular rash (even if minor)
  • Kerato-conjunctivitis
  • Seizure
  • Poor feeding
  • Lethargy
  • Irritability
  • Respiratory distress
  • Sepsis
  • Temperature instability
  • CSF pleocytosis
  • Thrombocytopenia
  • Transaminitis
  • SBI workups

Management

• Acyclovir 20 mg/kg IV every 8 hours (duration depends on classification)
• If ocular involvement:
  • 1% trifluridine, 0.1% iododeoxyuridine, or 3% vidarabine
  • Optho consult
• As for any febrile neonate SBI evaluation:
  • Ampicillin + gentamycin
    • May substitute gentamycin with cefotaxime/ceftazidime

Disposition

• Any neonate with suspected HSV (especially if CSF pleocytosis) should be treated and admitted
  • Consider covering all febrile neonates regardless pending CSF and culture studies

Outcomes

• SEM with treatment - all survive
  • If untreated 50-60% with SEM go on to CNS or disseminated disease
• Mortality high with CNS (4%) or disseminated (29%) disease even with treatment

See Also

• Neonatal conjunctivitis
• Pediatric fever of uncertain source
• Herpes viruses