February 2006

Fig.3

Fig.4

Fig.5

Diagnosis: Congenital Herpes Simplex Infection.

Laboratory data:
HSV PCR was positive in skin lesions as well as from groin, rectal, and oral sites.

Histopathology : Dystrophic calcification of hair follicles with perifollicular granulomas (Figs. 3, 4, and 5). No split or vacuolar change of keratinocytes are seen at any level of the epidermis. Collagen IV immunohistochemical stain showed intact basement membrane.

Examination of placenta revealed acute chorioamnionitis and acute necrotizing villitis with herpes viral inclusions.

Hospital course:
As the prognosis was poor, given multiorgan failure with extensive necrosis and hemorrhage of the brain family meeting was conducted. Decision was made to withdraw support of care.

Discussion:
Herpes simplex virus (HSV) infection is a severe disease associated with significant morbidity and mortality in a newborn period. The estimated incidence is 1 case per 2000 - 5000 deliveries per year. HSV infection of the newborn can be acquired in utero, intrapartum, or postnatally. The majority of cases, 90% are acquired intrapartum at the time of delivery, during passage through the birth canal and contact with genital fluids. Risk factors include: 1) prolonged rupture of membranes, 2) multiple lesions, 3) high virus inoculum in vaginal secretions, 4) use of fetal scalp electrodes or other instrumentation during delivery and 5) cervical as opposed to vulvar or buttock lesions. Postnatal transmission through contact with HSV lesions of the breast has been reported, as well as contact with relatives excreting the virus, accounting for 10% of the cases.
Intrauterine infection is much less common, constituting approximately 5% of cases, and can develop through either ascending infection or, more rarely, from hematogenous transplacental spread. It is believed to occur most likely during primary infection because patients will have a higher viral load at this time. The American College of Obstetricians and Gynecologists recommends that all women with primary HSV infection in pregnancy receive systemic acyclovir to reduce viral shedding and enhance lesion healing. This policy is difficult to reliably implement because the presentation of primary herpes might be asymptomatic or atypical. In the largest case series on intrauterine HSV infections (13 infants), clinical evidence of primary genital HSV infection was present in 4 out of 13 mothers, and only 1 mother had a history compatible with recurrent gential HSV. It is not known whether acyclovir can prevent severe fetal infection.
The diagnostic criteria of intrauterine HSV infection consists of identification of infected infants in the first 48 h of life, virologic confirmation of infection, and exclusion of other pathologic conditions.
The classic triad of findings associated with congenital herpes infection includes skin and eye lesions, and neurologic damage. Although not available in the reported case above, 90% of infections tranmitted in utero are identified as HSV type 2. Risk factors associated with intrauterine transmission of the virus have not been identified. Both primary and recurrent maternal infection can result in congenital infection.
Symptoms of intrauterine infection manifest themselves within the first 48 h of life, whereas in intrapartum-acquired infections, they appear within 1-2 weeks, especially encephalitis associated with intrapartum herpes which usually presents in the second or third week of life. Cutaneous involvement is present in 94% of cases of intrauterine HSV infection, eye lesions are present in 59%, and brain anomalies are present in 79%. Chorioretinitis is the most common eye lesion. All three finding are present in 39% of cases. Other findings may include abdominal, thoracic, and cerebral calcifications. At birth, scarred skin lesions are observed especially at the sites of trauma and areas subject to pressure.

The differential diagnosis of cutaneous lesions include bacterial and other viral infections, with pathogens such as VZV, enterovirus, cytomegalovirus. In addition, other disorders including intrauterine aplasia cutis, epidermolysis bullosa, and incontinentia pigmenti must be considered.

References:

1. Baldwin S, Whitley RJ. Teratogen update: intrauterine herpes simplex virus infection. Teratology 1989; 39:1 10.
2. Bale JF, Miner LJ. Herpes Simplex Virus Infections of the Newborn. Curr Treat Options Neurol. 2005 Mar;7(2):151-156.
3. Fagnant RJ, Monif GRG. How rare is intrauterine herpes simplex? A literature review. J Reprod Med 1989; 34:417 22.
4. Hutto C, Arvin A, Jacobs R, et al. Intrauterine herpes simplex virus infections. J Pediatr 1987; 110:97 101.
5. Johansson AB, Rassart A, Blum D, Van Beers D, Liesnard C. Lower-limb hypoplasia due to intrauterine infection with herpes simplex virus type 2: possible confusion with intrauterine varicella-zoster syndrome. Clin Infect Dis. 2004 Apr 1;38(7):e57-62. Epub 2004 Mar 12.
6. Melichar J, Miletin J, Janota J, Kucera J, Cunat V, Sanakova P, Stranak Z. High doses of acyclovir: a new concept in the treatment of neonatal herpes simplex virus infection. Indian J Pediatr. 2004 Dec;71(12):e58-61.
7. Overall JC Jr. Herpes simplex virus infection of the fetus and newborn. Pediatr Ann 1994; 23:131 6.

This case was presented by Dr. Liana Abrimova

Presented by Dr. Beatriz Tapia