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)” [1]
  • 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 [2]
  • Risk associated with age <3 weeks, primary maternal HSV infection at delivery

Management Considerations

  • Acyclovir if [3][4][5]
    • 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) [1]
    • 80% of mothers have no history of genital lesions [6]
  • Vesicular lesions most specific, present in <1/2 [1]
    • 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

Evaluation

Work-up

  • Should include the following [6]
    • 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

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 [1]
    • 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 [6]

See Also

External Links

References

  1. 1.0 1.1 1.2 1.3 Caviness AC. Neonatal herpes simplex virus infection. Clin Ped Emerg Med. 2013;14(2):135-145
  2. Caviness AC, et al. The prevelance of neonatal herpes simplex virus compared with serious bacterial illness in hospitalized neonates. J Pediatr. 2008;153:164-169
  3. Caviness AC, et al. The prevalence of neonatal herpes simplex virus infection compared with serious bacterial illness in hospitalized neonates. J Pediatr. 2008;153(2):164
  4. Long SS. In defense of empiric ayclovir therapy in certain neonates. J Pediatr. 2008;153(2):157
  5. Kimberlin DW. When should you initiate acyclovir therapy in a neonate? J Pediatr. 2008;153(2):155
  6. 6.0 6.1 6.2 James SH, Kimberlin DW. Neonatal herpes simplex virus infection: epidemiology and treatment. Clin Perinatol. 2015;42(1):47-59