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
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
- Conjunctival disease or minor skin lesions may be only manifestation
- Disseminated (liver, lung, adrenal glands, skin, eye, brain) - 25%
Herpes Virus Types
- HHV-1: Herpes Simplex Virus-1
- HHV-2: Herpes Simplex Virus-2
- Herpes B virus
- Varicella zoster virus
- Varicella (Chickenpox)
- Herpes zoster (Shingles)
- Herpes zoster ophthalmicus
- Herpes zoster oticus (Ramsay Hunt syndrome)
- HHV-6 (Roseola infantum)
- HHV-8 (Kaposi’s sarcoma)
- Epstein-Barr virus
- Cytomegalovirus
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 [3]
- 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
- Upper respiratory infection (URI)
- UTI
- Sepsis
- Meningitis
- Febrile seizure
- Juvenile rheumatoid arthritis
- Pneumonia
- Acute otitis media
- Whooping cough
- Unclear source
- Kawasaki disease
- Neonatal HSV
- Specific virus
Evaluation
Work-up
- Should include the following [3]
- CBC with differential
- Chem (if starting acyclovir)
- LFTs
- Whole blood HSV PCR
- Blood, urine culture, urinalysis
- LP with CSF studies including HSV PCR
- Perform PCR/culture of:
- Any visible lesions
- Conjunctiva, nasopharynx, mouth, anus
- Even in the absence of lesions
- Consider CXR for respiratory symptoms
- Suspected CNS disease should undergo EEG, with discussion of imaging with infectious disease and neurology consultants (does not need to be completed in the ED unless there is an abnormal neuro exam)
- 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)
- Keratoconjunctivitis
- Seizure
- Poor feeding
- Lethargy
- Irritability
- Respiratory distress
- Sepsis
- Temperature instability
- CSF pleocytosis
- Thrombocytopenia
- Transaminitis
- Working up for serious bacterial illness
Management
Management Considerations
- Acyclovir if [4][5][6]
- Proven HSV disease
- Suspected HSV disease (see clinical features) pending studies
- At risk due to exposure (active genital lesions in mother or history of cold sores in a contact)
- Many recommend acyclovir empirically in ill-appearing neonates with fever (including hypothermia) or aspetic meningitis until results of work-up are known
- 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
- Ampicillin + gentamycin
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 [3]
See Also
External Links
References
- ↑ 1.0 1.1 1.2 1.3 Caviness AC. Neonatal herpes simplex virus infection. Clin Ped Emerg Med. 2013;14(2):135-145
- ↑ 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
- ↑ 3.0 3.1 3.2 James SH, Kimberlin DW. Neonatal herpes simplex virus infection: epidemiology and treatment. Clin Perinatol. 2015;42(1):47-59
- ↑ 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
- ↑ Long SS. In defense of empiric ayclovir therapy in certain neonates. J Pediatr. 2008;153(2):157
- ↑ Kimberlin DW. When should you initiate acyclovir therapy in a neonate? J Pediatr. 2008;153(2):155