Pediatric Herpes Simplex Virus Infections: An Evidence-Based Approach To Treatment
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Pediatric Herpes Simplex Virus Infections: An Evidence-Based Approach To Treatment

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Table of Contents
 
Table of Contents
  1. Abstract
  2. Case Presentation
  3. Introduction
  4. Critical Appraisal Of The Literature
  5. Etiology And Pathophysiology
    1. Epidemiology
    2. Neonatal Epidemiology
  6. Differential Diagnosis
    1. Neonates
    2. Oral Lesions
    3. Genital Lesions
    4. Encephalitis
  7. Prehospital Care
  8. Emergency Department Evaluation
    1. History
      1. Neonates
      2. Oral Lesions
      3. Genital Lesions
      4. Herpes Encephalitis
    2. Physical Examination
      1. Neonates
      2. Oral Lesions
      3. Genital Lesions
      4. Herpes Encephalitis
  9. Diagnostic Studies
    1. Viral Culture
    2. Serologic Testing
    3. Polymerase Chain Reaction Testing
    4. Tzanck Smear
    5. Direct Fluorescent Antibody Testing
    6. Lumbar Puncture
    7. Liver Function Tests
    8. Imaging Studies
    9. Other Studies
  10. Treatment
    1. Neonates
    2. Oral Lesions
    3. Genital Lesions
      1. First-Episode
      2. Recurrent Episodes
    4. Encephalitis
    5. Vaccine
  11. Special Circumstances
    1. Eczema Herpeticum
    2. Herpes Gladiatorum
    3. Herpetic Whitlow
    4. Ocular Herpes
  12. Controversies And Cutting Edge
  13. Disposition
  14. Summary
  15. Risk Management Pitfalls For Herpes Simplex Virus Infections
  16. Time- And Cost-Effective Strategies
  17. Case Conclusion
  18. Clinical Pathway For Management Of Herpes Simplex Virus Infection In Neonates
  19. Tables and Figures
    1. Table 1. Differential Diagnosis Of Herpes Simplex Virus Infections
    2. Table 2. Recommended Therapy For Herpes Labialis Infections In Immunocompetent Patients
    3. Table 3. Recommended Therapy For Genital Herpes Simplex Infections
    4. Figure 1. Neonatal Herpes Simplex Virus Pustules
    5. Figure 2. Herpetic Gingivostomatitis
    6. Figure 3. Eczema Herpeticum
    7. Figure 4. Herpetic Whitlow
  20. References

Abstract

Herpes simplex virus is a common virus that causes a variety of clinical presentations ranging from mild to life-threatening. Orolabial and genital herpes are common disorders that can often be managed in an outpatient setting; however, some patients do present to the emergency department with those conditions, and emergency clinicians should be aware of possible complications in the pediatric population. Neonatal herpes is a rare disorder, but prompt recognition and initiation of antiviral therapy is imperative, as the morbidity and mortality of the disease is high. Herpes encephalitis is an emergency that also requires a high index of suspicion to diagnose. Herpes simplex virus is also responsible for a variety of other clinical presentations, including herpes gladiatorum, herpetic whitlow, eczema herpeticum, and ocular herpes. This issue reviews the common clinical presentations of the herpes simplex virus, the life-threatening infections that require expedient identification and management, and recommended treatment regimens.

Key words: herpes simplex virus, HSV1, HSV2, neonatal herpes, herpes labialis, genital herpes, herpes encephalitis, eczema herpeticum, herpes gladiatorum, herpetic whitlow, ocular herpes, polymerase chain reaction testing, Tzanck smear, lumbar puncture, liver function tests, antiviral medications, acyclovir, famciclovir, valacyclovir

Case Presentation

A 10-day-old full-term girl is brought to the ED with a rectal temperature of 38.6°C. She has no cough, congestion, runny nose, vomiting, or diarrhea. She is formulafed and is tolerating her regular feeds. The mother received prenatal care, and the prenatal labs, including Group B Streptococcus, were negative for any pathology. The mother has no reported history of HSV, but she has had a fever and throat pain for the past few days. The infant is sleeping comfortably in her mother’s arms. On examination, the anterior fontanel is soft and flat, and the skin is negative for rash or lesions. Cardiac, respiratory, and abdominal examinations are within normal limits. The infant’s temperature is now 38.7°C rectally. You explain to the medical student working with you on the case that because the baby is < 28 days old and there are no symptoms other than fever, she will require a full sepsis workup, including a lumbar puncture. You inform the medical student that this is standard of care for neonates who present with a fever, and the diagnostics will aid in determining the cause of the fever. Even though the mother has no history of HSV, you have a high index of suspicion for this. The medical student asks you if the baby should be started on acyclovir.

Introduction

Herpes simplex virus (HSV) is a common virus that affects up to 90% of the population by adulthood.1 Approximately one-third of children contract a primary HSV1 infection by the age of 5 years.2 In the United States, neonatal HSV disease occurs in approximately 1 in 3200 deliveries, or 1500 new cases annually.3 Because HSV has many clinical presentations, the emergency clinician must maintain a high index of suspicion for HSV infections and be prepared to offer the appropriate management. The emergency clinician must also be aware of possible complications in the pediatric population as well as the recommended treatments.

Critical Appraisal Of The Literature

A search was performed in PubMed for articles published since 1960 pertaining to children aged < 18 years using multiple combinations of the search terms herpes simplex virus, neonatal herpes, acyclovir, treatment, herpes encephalitis, and genital herpes. The Cochrane Database of Systematic Reviews was also consulted. Articles relevant to pediatric HSV infections were selected and reviewed. Over 300 articles were reviewed, 122 of which were chosen for inclusion in this review, including a number of randomized controlled trials, meta-analyses, and clinical practice guidelines.

Risk Management Pitfalls For Herpes Simplex Virus Infections

  1. “The mother of the ill-appearing 15-day-old infant did not have a history of herpes, so the infant most likely has a bacterial infection rather than neonatal herpes.” Almost two-thirds of women who acquire genital herpes during pregnancy are asymptomatic and have no clinical findings to suggest genital HSV infection, as they have never had an HSV outbreak, nor have their partners had an outbreak.28,29,39,122
  2. “The lumbar puncture was not bloody, so the patient probably does not have HSV.” While the presence of red blood cells and xanthochromia on a lumbar puncture may be seen on CSF studies in patients with HSV encephalitis or CNS involvement, 5% to 10% of patients have normal CSF studies. Red blood cells in the CSF is not a feature of neonatal infection, even with CNS involvement.27 PCR should be completed on the CSF of all patients suspected of having HSV encephalitis or CNS involvement.73 In most cases of herpes with CNS involvement, patients have either an elevated CSF white blood cell count or elevated CSF protein level, which may heighten the emergency clinician’s suspicion for CNS herpes infection.74
  3. “The 3-day-old infant had pustules on the skin, so he probably has neonatal herpes.” The presence of pustules on an infant does not necessarily mean the patient has HSV. Pustular melanosis and erythema toxicum are both benign pustular eruptions that can mimic HSV.
  4. “The baby was born via cesarean delivery, so herpes does not need to be ruled out.” While cesarean delivery has successfully reduced the number of neonatal herpes cases, HSV may be transmitted to an infant despite cesarean delivery.
  5. “I did not see any dendrites on the fluorescein examination, so the patient does not have ocular herpes.” All patients who are suspected of having ocular herpes should be evaluated by an ophthalmologist. Findings may be subtle, and those with expertise in the evaluation of the cornea should be involved when there is any clinical concern for ocular HSV infection.
  6. “The child had swelling and pain near the fingertip, so I performed an incision and drainage.” Routine incision and drainage is not recommended in patients with herpetic whitlow. Herpetic whitlow is a self-limited disease. Vesicles may be unroofed to help relieve symptoms, but deep incisions should be avoided.
  7. “No lesions are visible on the external genital examination, so the patient does not have a herpes outbreak.” Patients with herpes outbreaks may not have lesions visualized on external examination. If lesions are not noted, a pelvic examination should be performed to evaluate for the presence of cervical lesions.
  8. “The Tzanck prep was negative on the skin lesion of the 15-day-old infant, so HSV was ruled out.” While the Tzanck prep may be a relatively reliable test for cutaneous lesions, it does not definitively rule out neonatal herpes. If suspicion is high for neonatal herpes infection, infants require the following testing: (1) CSF for indices; (2) HSV PCR and bacterial culture; (3) viral culture swabs from the base of any vesicles as well as swabs from the mouth, conjunctiva, nasopharynx, and rectum; (4) HSV PCR on whole blood; and (5) LFTs.
  9. “The CT scan on the febrile teenager with altered mental status was negative, so HSV PCR does not need to be sent on the CSF.” CT scans are less sensitive than MRI, but they may show changes (such as edema and hemorrhage) in patients with herpes encephalitis. However, early in the illness, CT and MRI may be normal, so clinical suspicion should guide management and workup.
  10. “LFTs are not part of the routine sepsis rule-out. They play no role in the evaluation of febrile infants.” Elevation of serum aspartate transaminase levels > 10 times normal have been associated with increased mortality in neonates with disseminated herpes.27,32,76 Elevation of LFTs have been noted in neonates with disseminated HSV75,77 and LFT levels may serve as a screening tool for disseminated disease in those infants undergoing a sepsis rule-out.

Tables and Figures

Table 1. Differential Diagnosis Of Herpes Simplex Virus Infections

Table 2. Recommended Therapy For Herpes Labialis Infections In Immunocompetent Patients

Table 3. Recommended Therapy For Genital Herpes Simplex Infections

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study will be included in bold type following the references, where available. The most informative references cited in this paper, as determined by the author, will be noted by an asterisk (*) next to the number of the reference.

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Publication Information
Authors

Jennifer E. Sanders, MD; Sylvia E. Garcia, MD

Publication Date

January 1, 2014

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