By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Neonatal herpes infection usually presents with seizure, vesicular rash, or critical illness. The subset of infected patients without those signs were younger than two weeks of age and/or had cerebrospinal fluid pleocytosis.

SOURCE: Curfman AL, Glissmeyer EW, Ahmad FA, et al. Initial presentation of neonatal herpes simplex virus infection. J Pediatr 2016;172:121-126.

Details of presenting findings of children with neonatal herpes over a 10-year period from 2002 through 2012 either at Saint Louis Children’s Hospital or at Salt Lake City’s Primary Children’s Hospital were reviewed retrospectively. Children with documented herpes infection (polymerase chain reaction [PCR] and/or culture positivity) were included if they were born after 34 weeks’ gestation and developed symptoms after their newborn hospitalization but before 42 days of age. (Children were excluded if the medical records were incomplete. One child also was excluded due to confounding ornithine transcarbamylase deficiency.)

A total of 49 infants were included in the study. Most (43 of 49, 88%) presented during the first 28 days of life. Half of the infected children were normothermic, but these all had seizures, vesicular rash, or a critically ill appearance. Of the 49 patients, 45% had disseminated disease (defined as infection with hepatitis and/or pneumonitis and/or disseminated intravascular coagulation), 33% had central nervous system involvement, and 20% had skin-eye-mouth involvement. All eight patients who had nonspecific presentations were younger than 14 days of age and/or had cerebrospinal fluid pleocytosis; six of these went on to develop seizures, rash, or signs of critical illness. Death was seen only in those with disseminated disease; seven (32%) of the 22 babies with disseminated herpes disease (7 or 14% of the 49 patients in the study) died.

Two-thirds of the patients were started on acyclovir during the first 24 hours of hospitalization, but the study was not powered to the point of determining if those treated early fared better than those started on acyclovir later. Half of the children with skin-eye-mouth disease had positive blood PCR tests for herpes and were treated with acyclovir for 21 days (with 14 days being currently recommended for these children without systemic illness).

COMMENTARY

Pediatric physicians often are asked to manage febrile or otherwise sick neonates, and it is generally assumed that even skilled clinicians are unable to rule out (or in) the possibility of serious bacterial infection without microbiologic testing; antibiotics are routinely given pending blood cultures.1,2 It is less clear, however, when clinicians should seek and presumptively treat possible herpes infection in newborns. These new data are useful to guide clinicians caring for febrile or otherwise sick newborns.

This study by Curfman and colleagues yields several pertinent findings to help clinicians keep neonatal herpes infection in context. First, neonatal herpes infections are uncommon. In two tertiary children’s hospitals combining to account for approximately 600 inpatient beds, there were only 49 neonates admitted with herpes infection over a 10-year period. Second, clinicians should think of possible herpes infection even in the absence of fever, especially when the child has a vesicular rash, seizures, or a critically ill appearance.

Thus, clinicians should consider the possibility of herpes infection when a newborn presents with vesicular rash, seizures, or a critically ill appearance. While considering bacterial etiologies of the illness, clinicians also would test and, presumptively, treat for herpes infection. Children with cerebrospinal fluid pleocytosis also could be treated for herpes while herpes testing (usually PCR testing) is pending. Similarly, as indicated by this study, children younger than 14 days of age with fever or other signs of illness could be tested and presumptively treated for herpes.

However, not every febrile or otherwise ill baby presenting in the first two months of life needs to undergo laboratory testing or be treated for herpes infection. These new data suggest that clinicians could maintain a low index of suspicion (and withhold treatment) for children older than 14 days of age without vesicular rash, seizures, cerebrospinal fluid pleocytosis, or critically ill appearance. The authors rightly point out that there has been a “creeping empiricism” of herpes testing and treatment.3 Omitting herpes testing and treatment during the second month of life for children without typical signs of herpes infection could reduce costs and complications without significantly increasing the risk of “missed” cases.3 Laura Brower and colleagues at Cincinnati Children’s Hospital reasonably propose standardizing care to limit herpes testing and treatment to those babies who are actually most at risk of infection.4 Brower suggests doing cerebrospinal fluid herpes testing on all babies younger than 21 days of age who are undergoing evaluation for serious bacterial infection and only starting presumptive acyclovir treatment in those with more concerning signs, such as vesicles or ill appearance.4

REFERENCES

  1. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: Evaluation of neonatal sepsis. Pediatr Clin North Am 2013;60:367-389.
  2. Arora R, Mahajan P. Evaluation of child with fever without source: Review of literature and update. Pediatr Clin North Am 2013;60:1049-1062.
  3. Gaensbauer JT, Birkholz M, Pfannenstein K, et al. Herpes PCR testing and empiric acyclovir use beyond the neonatal period. Pediatrics 2014;134:e651-e656.
  4. Brower L, Schondelmeyer A, Wilson P, et al. Testing and empiric treatment for neonatal herpes simplex virus: Challenges and opportunities for improving the value of care. Hosp Pediatr 2016;6:108-111.