Summary of clinical, laboratory, and radiographic findings and treatment of neonatal herpes simplex virus infection

	Proportion of cases	Clinical manifestations	Diagnostic testing for HSV^*				Other laboratory and radiographic findings	Recommended treatment
	Proportion of cases	Clinical manifestations	Viral culture or HSV PCR of surface swabs^¶	Viral culture or HSV PCR of skin lesion scrapings^Δ	Blood or plasma HSV PCR	CSF HSV PCR	Other laboratory and radiographic findings	Recommended treatment
SEM disease	35 to 45%	Characteristic vesicular lesions Conjunctivitis, excessive tearing Ulcerative lesions of the mouth, palate, and tongue	Positive in >90%	Positive in >90%	Positive in approximately 75%	Negative	Other laboratory and radiographic studies are typically normal	Initial treatment: Acyclovir 60 mg/kg per day intravenously divided every 8 hours for 14 days^◊ Followed by: Oral suppressive therapy: Acyclovir 300 mg/m² per dose orally 3 times per day for 6 months^◊ In addition, for ocular involvement: Topical ophthalmic solution (eg, 1% trifluridine, 0.1% idoxuridine [iododeoxyuridine]^§, or 0.15% ganciclovir) Referral to an ophthalmologist Longer duration of oral suppressive therapy may be warranted
CNS disease	30 to 35%	Seizures Lethargy Irritability Tremors Poor feeding Apnea Skin lesions are present in 60 to 70%	Positive in >90%	Positive in >90% if lesions are present; however, skin lesions are often not present at the onset of disease	Positive in approximately 65%	Positive in 75 to 100%	CSF analysis classically shows a mononuclear cell pleocytosis, normal or moderately low glucose concentration, and mildly elevated protein EEG may show focal or multifocal LPDs Neuroimaging studies may show parenchymal brain edema or attenuation, hemorrhage, or destructive lesions involving the temporal, frontal, parietal, or brainstem regions of the brain	Initial treatment: Acyclovir 60 mg/kg per day intravenously divided every 8 hours for a minimum of 21 days^◊ Followed by: Oral suppressive therapy: Acyclovir 300 mg/m² per dose orally 3 times per day for 6 months^◊
Disseminated disease	25 to 30%	Sepsis syndrome Fever or hypothermia Hepatitis Respiratory distress DIC Skin lesions are present in 60 to 80% CNS involvement occurs in 60 to 75%	Positive in >90%	Positive in >90% if lesions are present; however, skin lesions are often not present at the onset of disease	Positive in 100%	Positive in >90%	Elevated liver transaminases Thrombocytopenia Abnormal CSF, EEG, and neuroimaging studies, as above	Initial treatment: Acyclovir 60 mg/kg per day intravenously divided every 8 hours for a minimum of 21 days^◊ Followed by: Oral suppressive therapy: Acyclovir 300 mg/m² per dose orally 3 times per day for 6 months^◊

BSA: body surface area; CNS: central nervous system; CSF: cerebrospinal fluid; DFA: direct immunofluorescence assay; DIC: disseminated intravascular coagulopathy; EEG: electroencephalogram; HSV: herpes simplex virus; IV: intravenous; LPD: lateralized periodic discharges (previously known as PLEDs [periodic lateralized epileptiform discharges]); PCR: polymerase chain reaction; SEM: skin, eyes, mouth.

* All of these diagnostic tests should be performed in any neonate with suspected HSV infection.

¶ Surface swabs are performed on specimens collected from the conjunctivae, mouth, nasopharynx, and rectum. Some experts suggest these be obtained with a single swab, starting with eyes and ending with the rectum, and placed in 1 viral transport media tube. Alternatively, they may be collected with multiple swabs.

Δ DFA permits rapid detection of HSV antigens in skin lesion scrapings; however, DFA is not as sensitive as culture or PCR and therefore viral culture and/or PCR should also be performed.

◊ The dose of acyclovir must be adjusted for neonates with renal impairment and/or weight <1 kg. Refer to UpToDate Lexidrug for additional dosing information. If IV acyclovir is not available, ganciclovir is an alternative. Refer to the UpToDate's topic on management of neonatal HSV infection for additional information. Oral acyclovir dosing is based on BSA, which is calculated as follows: square root (height [cm] × weight [kg]/3600). The oral suppressive acyclovir dose should be adjusted each month to account for growth.

§ Idoxuridine (iododeoxyuridine) is not available in the United States.

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Summary of clinical, laboratory, and radiographic findings and treatment of neonatal herpes simplex virus infection