Herpes Simplex Neonatorum


Article Author:
Roland Boyd


Article Editor:
Laura Kasman


Editors In Chief:
Ann Anderson Berry
Mark Hudak
Sumesh Parat


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
5/4/2019 3:19:13 PM

Introduction

With the development of acyclovir in the 1980s, there was a vast improvement in overall survival of these infected infants. At present, mortality of infants with the disseminated disease has decreased from 85% to 29%, and patients with central nervous system (CNS) disease has decreased from 50% to roughly 4% in industrialized countries. Unfortunately, it remains elevated in developing nations.

Etiology

At present, there are eight recognized groups of herpes viruses. These include herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster, human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8). Herpes simplex neonatorum is the transmission of either HSV-1 or HSV-2 from the mother to child during gestation via the placenta, during delivery via vaginal secretions, or perinatally via direct contact with active lesions.

Epidemiology

[0]The incidence of HSV-1 and HSV-2 has changed over the past few decades. Currently over one-third of the world’s population has recurrent HSV infection. By age 5, 35% of black children are infected by HSV-1, and 18% of white children are infected. Genital herpes is predominately caused by HSV-2 in the United States; however, in Japan, the predominant cause of genital herpes is caused by HSV-1.

Pathophysiology

The HSV is a double-stranded DNA virus which is large and has a surrounding lipid envelope. The DNA in HSV-1 and HSV-2 have many similarities thus causing much cross-reactivity in antibody production. The virus enters the body through epithelial cells or the mucous membranes. When it has replicated within the nucleus of the cells, it travels down the axon to the neurons where it can establish a latent infection.

History and Physical

[0]The cutaneous findings are scarring, active lesions, hypo and hyperpigmentation of the skin,  cutis aplasia and macular rashes. In the eyes, one may see, microphthalmia, retinal dysplasia, optic atrophy and or chorioretinitis. Neurologically one can see microcephaly, encephalomalacia, hydranencephaly and intracranial calcifications. Infants with the disseminated disease often present in the first 3 weeks of life with symptoms of sepsis. Multiple organ systems can be affected by this illness causing jaundice, abnormal liver function, hypoglycemia, hypotension, coagulopathy, pneumonia and even respiratory failure. Encephalitis is present 75% of the time in disseminated disease thus causing seizures.  Rarely do these infants present with vesicular lesions. Death usually results from shock, progressive liver failure, severe coagulopathy, respiratory failure, and progressive neurological deterioration. These infants usually present around the second or third week of life. They may initially have a fever, poor feeding or present with a sudden episode of seizures or apnea. Between 60% and 70% of babies classified as having CNS disease have associated skin lesions at some point in the course of their illness. Skin, eye and mouth disease also presents in the second to third week of life. Typical vesicular lesions on an erythematous base are the presenting sign. Rarely are lesions present in the mouth. Conjunctivitis is often present and left untreated may develop into herpetic keratitis and possibly even corneal blindness. SEM has a low mortality but reoccurs in 90% of patients.

Evaluation

[0]Viral culture is the “gold standard” for verification of HSV infection. Cultures should be obtained from lesions which are scraped or from the mucous membranes and transported to a viral lab on ice. The virus can also be cultured from cerebrospinal fluid (CSF), blood, urine, stool, rectum, oropharynx and the conjunctivae. After the virus is inoculated into the cell culture system and grows, it may be then further identified as HSV-1 or HSV-2. The greatest viral yield continues to be isolated from intact skin lesions which are scraped and from the conjunctivae. Polymerase chain reaction (PCR) allows for rapid diagnosis of HSV in the clinical setting. PCR is very accurate with a reported sensitivity of 80% and an overall specificity of 71%.  A Tzank smear looks for multi-nucleated giant cells in any lesion that may be suspicious of HSV. Other laboratory studies may be abnormal, but not diagnostic, yet may be suggestive of HSV infection include leukopenia, thrombocytopenia, elevated liver enzymes, hypoglycemia and elevated protein in the CSF.

Treatment / Management

[4][0][0]They may require intubation and placement on ventilators and or can have severe hypotension requiring volume boluses and pressors for blood pressure support. Once they are respiratory, neurologically and hemodynamically stable, one may start appropriate intravenous antiviral therapy. Congenital HSV infectioned infants still require therapy. Intravenous (IV) acyclovir for 21 days is thought to prevent further replication of the virus and to decrease the number of future outbreaks. CT or MRI of the brain should be performed to evaluate the brain for any signs of abnormal findings. A pediatric ophthalmologist should evaluate the eyes for signs of keratitis or optic atrophy.  Infants with disseminated or CNS disease should be treated with intravenous (IV) acyclovir 20 mg/kg/dose every 8 hrs for a total of 21 days. If CSF is unable to be obtained for culture or PCR, one should err on the side of caution and treat for a full 21 days.  Also, at the end of the 21-day treatment, a blood HSV PCR should be sent to ensure the virus has been eliminated. Morbidity from SEM disease has dramatically improved with the use of acyclovir.  Duration is limited to a 14-day treatment, and a blood HSV PCR should be obtained, and if the results are positive, the infant should be treated for another seven days or until a negative result is obtained. In premature infants with HSV disease requiring acyclovir, the dosing interval may need to be increased secondary to their decreased creatinine clearance. All patients receiving acyclovir should be followed twice weekly for signs of a low absolute neutrophil count, as this occurs in approximately one-fifth of all patients.

Pearls and Other Issues

All infants born to mothers with a history of genital HSV have surface and mucosal cultures performed at 24 hours of life and also a blood HSV PCR. If these studies are negative and the infant is asymptomatic, the infant may be discharged with the mother. Infants born to mothers with active genital lesions and having a prior history of HSV, whether it be C-section or vaginal delivery, are to be screened with mucosal  HSV cultures, blood for HSV PCR.

 


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Herpes Simplex Neonatorum - Questions

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Which of the following statements regarding neonatal herpes infection is FALSE?



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Which of the following statements about neonatal herpes simplex infections is incorrect?



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An infant is born via vaginal delivery in breech position. All is well until at day 10 the infant develops skin lesions. Which finding would indicate the need for hospitalization?



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A 3 week old male infant is brought in with crops of vesicles to the chest and abdomen. He has not had fever. Workup reveals Herpes Simplex Virus (HSV) lesion base viral culture positive, surface HSV viral culture (of skin, eye and mucous membrane) positive, Serum HSV DNA PCR positive, CSF HSV DNA PCR negative, and serum alanine aminotransferase (ALT) within normal limits. Which of the following is the correct treatment course?



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A woman is pregnant with her first child. Which of the following is the greatest risk factor for her baby to acquire herpes simplex infection in the neonatal period?



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Herpes Simplex Neonatorum - References

References

Kimberlin DW,Baley J, Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013 Feb     [PubMed]

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