JHLXXX10.1177/0890334415596987Journal of Human LactationField

Case Report

Fatal Neonatal Herpes Simplex Infection Likely from Unrecognized Breast Lesions

Journal of Human Lactation 1­–3 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0890334415596987 jhl.sagepub.com

Scott S. Field, MD1,2,3

Abstract Type 1 herpes simplex virus (HSV-1) is very prevalent yet in rare circumstances can lead to fatal neonatal disease. Genital acquisition of type 2 HSV is the usual mode for neonatal herpes, but HSV-1 transmission by genital or extragenital means may result in greater mortality rates. A very rare scenario is presented in which the mode of transmission was likely through breast lesions. The lesions were seen by nurses as well as the lactation consultant and obstetrician in the hospital after delivery of the affected baby but not recognized as possibly being caused by herpes. The baby died 9 days after birth with hepatic failure and disseminated intravascular coagulation. Peripartum health care workers need to be aware of potential nongenital (including from the breast[s]) neonatal herpes acquisition, which can be lethal. Keywords breastfeeding, neonatal herpes simplex, type 1 herpes

Background Herpes simplex virus, especially type 1 (HSV-1), is a very prevalent human pathogen, and yet untimely acquisition with devastating consequences is extremely rare. The following case presentation and discussion is meant to raise awareness of the real and potentially preventable problem of disseminated fulminate neonatal herpes simplex disease from extragenital sources.

Case Report An uncomplicated pregnancy in a 31-year-old gravid 3, para 2 mother was completed at 38 weeks by repeat cesarean section. The 3051 g baby girl had a normal initial exam and was discharged from the hospital after 3 days. The baby was noted to have a small sore on her anterior chin prior to discharge, thought to be secondary to rubbing. The mother had developed sores near her nipples about 1 week prior to delivery and had asked the nurses, lactation consultant, and obstetrician about them during the hospitalization. They were thought to be impetigo and were treated with a topical antibiotic. Breastfeeding was stopped by 1 day after birth due to marked breast pain. The baby was not irritable and fed well but was noted after 2 days of age to be hypersomnolent. By 7 nights after birth, she became irritable. The next day, she had a small amount of blood in her stool, which increased that afternoon, and she became less responsive. She was taken to the emergency department where she was found to be hypothermic (33.3°C) and in a state of disseminated intravascular coagulation, yet her emergency room initial assessment was “well appearing—appears dry but good strong cry.”

Her workup included a glucose of 17 mg/dL, CO2 15 meq/L, urea nitrogen 33 mg/dL, creatinine 0.9 mg/dL, total bilirubin 2.5 mg/dL, ALT 2024 U/L, hemoglobin 12.3 g/dL, platelets 137 000 per cubic mL, PT > 100 seconds, PTT > 200 seconds, INR > 13.6, fibrinogen < 60 mg/dL, and positive reducing substances in her urine along with large protein, large blood, and large bacteria, but negative nitrites. She died approximately 12 hours after coming to the hospital at 9 days of age, despite prompt initiation of intravenous saline, glucose, antibiotics, and acyclovir. Postmortem lab tests included a ferritin of 303 250 ng/mL, iron 594 UG/dL, iron saturation 94%, and alpha-fetoprotein 8947 ng/mL, suggestive of neonatal hemachromatosis as a cause of acute hepatic failure. Other tests pointed toward fulminate HSV-1 infection, including positive HSV-1 by tissue culture from her nares and liver. Klebsiella pneumoniae grew from her admission blood culture, but bacteria did not grow from her postmortem liver. The baby’s serology was negative for HSV-1 and HSV-2 IgG and IgM. Four weeks later, the autopsy report confirmed hepatic failure secondary to disseminated HSV-1 (found by immunoperoxidase stain on a 1

Department of Pediatrics, Crestwood Medical Center, Huntsville, AL, USA 2 Department of Pediatrics, Huntsville Hospital, Huntsville, AL, USA 3 The University of Alabama at Birmingham School of Medicine, Huntsville, AL, USA Date submitted: March 28, 2015; Date accepted: July 1, 2015. Corresponding Author: Scott S. Field, MD, Field Pediatrics PC, 1106 Gleneagles Drive, Huntsville, AL 35801-6404, USA. Email: [email protected]

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Journal of Human Lactation 

tongue ulcer and in the esophagus, and by culture in the liver), which also caused the iron metabolism abnormalities. With the above findings, the mother agreed to personal herpes serology testing 1 month after her daughter’s demise and was found to be positive for HSV-1 IgG and IgM and negative for HSV-2 IgG but positive for HSV-2 IgM. The laboratory noted that “IgM reactivity to both HSV 1 and HSV 2 may represent crossreactive HSV antibodies rather than exposure to both HSV 1 and HSV 2.” Viral culture or PCR was not obtained on the active breast lesions, but PCR was attempted at the lesion site less than 2 months after birth and that was negative. The father had experienced fever blisters (herpetic lesions) most of his life but the mother and 2 older siblings had never had them. The father had a herpetic lesion when he made mouth-to-breast contact 11 days before delivery and a few days before the breast blisters developed. His lesion had resolved before birth and he did not kiss the baby on the face. The mother had never had genital herpes.

Discussion Whereas about 85% of neonatal herpes simplex virus infection cases result from natal acquisition of type 2 HSV from the mother’s genital tract, it also occurs from perinatal contact with HSV-1 infected individuals (including the mother) during and after birth.1 A very similar case to the present one was previously reported in which the infant contracted HSV-1 from a breast lesion, was admitted at 5 days of age, and died 6 days later despite receiving intravenous vidarabine started 1 day after admission.2 In that case as in the present, the father was likely the original source of the virus. That mother also lacked neutralizing antibody to HSV (present case implied by negative serology in the affected newborn). In the former case, the maternal breast lesion and the infected infant had matching HSV-1 DNA restriction endonuclease banding patterns. Such acquisition of HSV-1 from breast lesions was found in only 1 of 56 neonatal herpes infections from a large multicenter study.3 A 10-year London study of neonatal HSV with acute liver failure found 7 of 11 due to HSV-1, none of whom survived even with acyclovir treatment. Two of 4 HSV-2 infected infants survived with acyclovir treatment, 1 after a liver transplant. The most common presentations were poor feeding (6), fever (6), and lethargy (7).4 A 10-year University of Florida study of neonatal HSV hepatitis identified 15 such patients, only 1 with HSV-1, which was contracted from the mother’s oral lesion; no breast lesions were reported.5 A cluster of 3 cases from the summer of 1980 in Pittsburgh was reported in which all died within 10 days of birth with disseminated HSV-1.6 None of those mothers had evidence of genital herpes or fever blisters, but there was no mention of breast lesions. Another report from St Louis involved a neonate who survived disseminated HSV-1 after treatment with 10 days of adenine arabinoside.7 That baby probably contracted the virus from the mother’s milk, which was

culture-positive 9 days after birth even though she had no breast lesions on examination. Acquisition of fatal HSV-1 infections from other people soon after birth is previously documented.8-9 Type 1 herpes simplex virus as well as HSV-2 can be acquired at birth from the genital tract,10 in which case maternal HSV-1 antibodies provide little protection against HSV-2 infection.11 Severity of illness is largely associated with proximity to birth of viral acquisition by both mother and baby.12 Even transmission itself is greatly reduced if the mother has a history of recurrent herpes lesions prior to the third trimester compared to primary infection in the third trimester.10-12 This was attributed to increased viral shedding and lower or absent neutralizing antibodies with primary infections. Furthermore, neonatal HSV is more likely to occur in those exposed to HSV-1 compared to HSV-2.11 Prevention of neonatal herpes infections has primarily revolved around recognition of genital lesions in pregnant women and then the use of antivirals along with close monitoring and possible delivery by cesarean section. In a multicenter study, HSV-2 was more than 6 times as common a cause of neonatal HSV infections as HSV-1.3,13 Recognition of skin lesions on the mother’s breast and on a neonate can be difficult since they occur so rarely, but clinicians need to be aware that such recognition may be the only way of averting a catastrophic outcome as occurred in the present case. Special vigilance is needed with regard to direct HSV exposure to the newborn infant by any individual, related or not, which could most easily happen with a kiss from someone with fever blisters on the lips. That scenario with fatal outcome has been documented.8

Conclusion Devastating neonatal herpes infections may be prevented by perinatal health care workers only if they recognize risk of exposure to newborns by adults with herpetic sores on breasts (mother) or lips (including other individuals in contact with babies and sexual partners in contact with mothers late in the pregnancy) that may easily be mistaken for impetigo or eczema and/or dismissed as unimportant. Such recognition may make the difference between life and death. Declaration of Conflicting Interests The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author received no financial support for the research, authorship, and/or publication of this article.

References 1. Gantt S, Muller WJ. The immunologic basis for severe neonatal herpes disease and potential strategies for therapeutic intervention. Clin Dev Immunol. 2013;2013:1-16.

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Field 2. Sullivan-Bolyai JZ, Fafe KH, Jacobs RF, Miller Z, Corey L. Disseminated neonatal herpes simplex virus type 1 from a maternal breast lesion. Pediatrics. 1983;71(3):455-457. 3. Whitley RJ, Nahmias AJ, Visintine AM, Fleming CL, Alford CA. The natural history of herpes simplex virus infection of mother and newborn. Pediatrics. 1980;66(4):489-494. 4. Verma A, Dhawan A, Zuckerman M, Hadzic N, Baker AJ, Mieli-Vergani G. Neonatal herpes simplex virus infection presenting as acute liver failure: prevalent role of herpes simplex virus type 1. J Pediatr Gastroenterol Nutr. 2006;42(3):282-286. 5. McGoogan KE, Haafiz AB, Gonzalez Peralta RP. Herpes simplex virus hepatitis in infants: clinical outcomes and correlates of disease severity. J Pediatr. 2011;159(4):608-611. 6. Amortegui AJ, Macperson TA, Jarger JH. A cluster of neonatal herpes simplex infections without mucocutaneous manifestations. Pediatrics. 1984;73(2):194-198. 7. Dunkle LM, Schmidt RR, O’Connor DM. Neonatal herpes simplex infection possibly acquired via maternal breast milk. Pediatrics. 1970;63(2):250-251.

8. Douglas J, Schmidt O, Corey L. Acquisition of neonatal HSV-1 infection from a paternal source contact. J Pediatr. 1983;103(6):908-910. 9. Hufert FT, Diebold T, Ermisch B, Von Laer D, Meyer-Konig U, Neumann-Haefelin D. Liver failure due to disseminated HSV-1 infection in a newborn twin. Scand J Infect Dis. 1995;27(6):627-629. 10. Gunson RN, Jackson A, Aitken C. A case of neonatal sepsis with acute liver failure. J Clin Virol. 2011;50(4):266-269. 11. Brown EL, Gardella C, Malm G, et al. Effect of maternal herpes simplex virus (HSV) serostatus and HSV type on risk of neonatal herpes. Acta Obstetricia et Gynecologica. 2007;86(5): 523-529. 12. Robinson JL, Vaudry WL, Forgie SE, Lee BE. Prevention, recognition and management of neonatal HSV infections. Expert Rev Anti Infect Ther. 2012;10(6):675-685. 13. Whitley RJ, Nahmias AJ, Soong S, et al. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics. 1980;66(4):495-501.

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Fatal Neonatal Herpes Simplex Infection Likely from Unrecognized Breast Lesions.

Type 1 herpes simplex virus (HSV-1) is very prevalent yet in rare circumstances can lead to fatal neonatal disease. Genital acquisition of type 2 HSV ...
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