Neonatal herpes B00.2; B00.7

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Acute primary infection of the newborn with herpes simplex viruses; Herpes simplex neonatorum; Neonatal herpes infection; neonatal herpes infections; Neonatal herpes simplex infection

Definition
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Herpes neonatorum is a rare but significant infection that can be associated with severe morbidity and mortality, especially when the central nervous system is disseminated or involved. Neonatal infection with the herpes simplex virus (HSV type 2 causes this infection in about 75% of cases (HSV type 1 in 25% of cases), occurs in utero in 5% of cases, peripartal in 85% and postnatally in 10% (10%). The infection is either ascending after rupture of the bladder or, more frequently, through direct contact during birth. In some cases, infection occurs by spreading from one child to another, by the hospital staff or the family.

A diaplantar infection is possible. It can lead to abortion in up to 25% of cases before the 20th week of pregnancy. It is rare after the 20th week of pregnancy. A maternal genital primary infection in the 3rd trimester of pregnancy can lead to systemic dissemination with a high mortality rate (see below herpespsis of newborns P35.2).

Occurrence/Epidemiology
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The incidence is estimated at 1/3000-1/20,000 live births. In a larger Dutch study it was 4.7/100,000 live births (Hemelaar SJ et al. 2015). The infection is characterized by a lifelong infection with latency and reactivation periods.

Clinical features
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About 30% of infected newborns initially show the familiar herpetiform grouped umbilical vesicles. 30% of infected newborns remain skin free. 30% do not develop symptoms until between the 1st and 3rd week of life; in rare cases, however, only in the 4th week (Lautenschläger S 2018).

Newborns with skin symptoms may have local infections or a disseminated course.

Newborns with local infection: 50% of the cases develop as "minus variant" only symptoms on the skin, eyes and mouth and show no signs of a CNS infection or other organ involvement.

However, a proportion of infants (about 20%) develop encephalitis with the corresponding neurological symptoms and pleocytosis and protein elevation in the CSF, with or without simultaneous involvement of the skin) eyes and mouth.

Disseminated disease: newborns with disseminated disease and affection of the visceral organs develop hepatitis, pneumonitis, disseminated intravascular coagulation or a combination with or without encephalitis or skin symptoms. Other symptoms include temperature rise, lethargy, hypotension, respiratory failure, apnea and seizures.

The term "blueberry muffin" (TORCH) is used to describe skin changes that are often characterized by blueberry-like efflorescences shimmering through the skin. It is a transient cutaneous extramedullary haematopoiesis occurring exclusively in the neonatal period as a result of a serious underlying disease that leads to the temporary reactivation of embryonic or fetal haematopoietic mechanisms after birth.

TORCH is the acronym for the following pathogens: Toxoplasma gondii, Other (Treponema pallidum, Hepatitis B, Zoster), Rubella virus, (Cytomegalovirus, Herpes simplex virus.

Diagnosis
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HSV culture or PCR

Culture or HSV-PCR: Rapid and reliable diagnosis by culture or HSV-PCR is of great importance. The material can be obtained from the vesicles. Nasopharynx, eyes, rectum, blood and CSF should also be examined for herpetic lesions. In newborns with encephalitis, the virus can only be found in the CNS, among other things.

Tzanck test: If suitable virological laboratories are not available, a Tzanck test may reveal characteristic multinucleated giant cells and intranuclear inclusions from the base of the lesion. However, this test is less sensitive and may give false positive results.

Direct detection is also possible by electron microscopy.

Internal therapy
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Aciclovir should be given immediately and as a precautionary measure in suspected cases while waiting for confirmatory and diagnostic tests.

Systemic involvement: Drug of choice is acyclovir 3x/day 10-20mg/kgkgKG i.v. for 14-21 days.

CNS involvement: Infants with disseminated and/or central nervous system disorders receive acyclovir 3x/day 20 mg/kg bw i.v. for 21 days. With this therapy about 90% of newborns survive. The risk of defect healing (neurological deficits, mental retardation, epileptic seizures, amaurosis) is not uncommon.

Follow-up treatment: After the acute phase, children with CNS disease are recommended to continue oral therapy with Aciclovir: 2-3 times/day 300 mg/m for 6 months. This long-term therapy improves the neurological results at the age of 1 year (cave: neutropenia). Careful supportive treatment must be provided, including adequate fluid replacement, nutrition, respiratory support, correction of coagulation disorders and treatment of seizures.

For the localized disease (skin, mouth or conjunctiva), treatment with acyclovir 3x/day 20 mg/kg i.v. for 14 days.

In case of herpetic keratoconjunctivitis, accompanying topical treatment with substances such as trifluridine, iododeoxyuridine or vidarabine is required.

Progression/forecast
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The lethality of untreated disseminated disease is 85%. In industrialized countries, the mortality of infants with disseminated infection has decreased from 85% to 29% since the use of acyclovir. In patients with an infestation of the CNS, mortality decreased from 50% to 4% (Boyd RL et al. 2019).

Prophylaxis
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In principle, pregnant women with genital lesions should be serologically examined. In case of suspicious lesions, direct virological examinations are recommended (see above).

If active HSV lesions are present in the genital area on the day of delivery, a caesarean section before or 4-9 hours after rupture of the bladder is recommended. This measure has been proven to minimise transmission.

Monitoring of the fetal scalp of infants during labour should be avoided if active genital herpes is suspected in their mothers. Asymptomatic newborns of women with active genital lesions at the time of delivery should be examined and tested for HSV infection.

Oral Aciclovir or Valaciclovir from the 36th week of pregnancy in women at risk (genital HSV can prevent recurrences at the time of delivery and reduce the need for a section.

Note(s)
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Infants at increased risk of HSV infection should be detected early to prevent mother-to-child transmission. A worthwhile goal for the future is the development of new antiviral agents with higher efficacy (Bhatta AK et al. (2018).

Literature
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  1. Bhatta AK et al (2018) Vertical transmission of the herpes simplex virus: an update. J Dtsch Dermatol Ges 16:685-693.
  2. Boyd RL et al (2019) Herpes Simplex Neonatorum. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
  3. Hemelaar SJ et al (2015) Neonatal herpes infections in The Netherlands in the period 2006-2011 J Matern Fetal Neonatal Med 28: 905-909.
  4. Kimberlin DW et al (2013) Committee on infectious diseases, Committee on fetus and newborn: Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics 131: e635-646, 2013.
  5. Lute S (2018) Human herpes viruses. In: Braun-Falco`s Dermatology, Venerology Allergology G. Plewig et al (Hrsg) Springer Verlag S 107-109

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

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Last updated on: 29.10.2020