Herpes Simplex Virus (HSV)
The 5 Minute Pediatric Consult
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Herpes Simplex Virus (HSV) |
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Jane M. Gould
DEFINITION
Herpes simplex virus (HSV) is a moderately large double-stranded DNA virus. There are two serologically distinguishable subtypes: HSV-1 and HSV-2. HSV produces a wide spectrum of illness ranging from fever blisters to fatal viral encephalitis.
PATHOPHYSIOLOGY
- Initial viral replication occurs at the portal.
- Vesicular fluid contains infected epithelial cells.
- After primary HSV infection, the virus remains latent in sensory neural ganglia innervating portions of the skin or mucous membranes originally involved. The virus can be reactivated by an appropriate stimulus such as sunlight or immune suppression.
- HSV can be replicated easily in the laboratory in tissue cultures.
EPIDEMIOLOGY
- HSV-1 usually causes infections of the upper torso, head, and neck.
- HSV-2 usually causes genital infection. However, both forms can infect either oral or genital cells and thus the virus type is not a reliable indicator of the anatomic site of infection.
- Neonatal HSV infections are acquired from maternal strains and 75–85% are caused by HSV-2.
- After the neonatal period, HSV-1 infections predominate and 40–60% of children are seropositive for HSV-1 by age 5 years.
- During puberty and early adolescence, the prevalence of HSV-2 increases and 20–35% of adults are seropositive for HSV-2.
- Route of spread is usually by close bodily contact or trauma such as teething or a break in the skin.
- Incubation period is 2–12 days (average, 6 days).
ASSOCIATED DISEASES
- Neonatal infection is usually acquired from the maternal genitourinary tract and causes serious disease with high mortality and morbidity.
- Gingivostomatitis is the most common form of HSV primary infection in children.
- Encephalitis due to HSV accounts for 2–5% of all encephalitis in the United States.
- Vulvovaginitis due to primary infection with HSV-2 and sometimes HSV-1 has increased markedly in the past two years.
- Neonatal HSV infection must be distinguished from viral or bacterial sepsis especially in the first 4 weeks of life.
- HSV infection should be considered in all neonates with vesicular rash, chorioretinitis, microcephaly, or hepatosplenomegaly. It must be distinguished from other congenital viral infections such as rubella or CMV.
- Herpes gingivostomatitis must be distinguished from herpangina, an enteroviral infection usually presenting as posterior pharyngeal ulcers, and sometimes as hand-foot-and-mouth disease.
- HSV encephalitis must be distinguished from other viral encephalitis and from the HSV-induced aseptic meningitis syndrome, which is a complication of primary genital infection.
- HSV vulvovaginitis must be distinguished from chancroid and syphilis. Syphilis lesions are usually nonpainful hard ulcers. Chancroid lesions are multiple purulent ulcers from which Haemophilus ducreyi can be cultured.
HISTORY
Neonatal Infection
- HSV-2, the most common cause of neonatal infection, is usually acquired from maternal labial lesions, but a history of previous or current genital HSV infection is only present in 20–30% of mothers who deliver infected infants. HSV-2 can be transmitted to the infant without rupture of the amniotic membranes or after delivery by cesarean section.
- HSV-1 can be transmitted to a neonate by any adult with active herpes labialis.
- A vesicular rash or bullae are present at birth or within a few days in almost all infants.
- Disseminated infection (32% of cases) involves the liver, lungs, adrenals, and sometimes the central nervous system (CNS).
- Localized CNS infection (33% of cases) presents with irritability, bulging fontanelle, or seizures.
- Localized skin, eye or mouth infection (35% of cases) present with rash alone, or keratitis or chorioretinitis.
Gingivostomatitis
- Fever and irritability precede the development of vesicular lesions on the lips, gingiva, and tongue. The vesicles then break down and become gray ulcers that are friable and bleed easily.
- Children refuse to drink because of the mouth pain and are at risk of dehydration.
- The child usually starts to improve in 3–5 days and has recovered in 14 days.
- Latent virus causes recurrent stomatitis or labiitis.
Encephalitis
- The illness begins with fever malaise and irritability that last 1–7 days and progress to mental status changes, seizures, and coma. Meningeal signs are not common.
- Patients can develop hemiparesis, cranial nerve palsy, and visual field defects.
- No presence of oral or genital lesions
Vulvovaginitis
- 35–50% of patients with the first episode of genital herpes will be able to give a history of genital HSV infection in their contact.
- The primary illness is characterized by fever, headache, malaise, and myalgias. Local genital symptoms include severe pain, itching, dysuria, vaginal or urethral discharge, and tender inguinal adenopathy. The genital lesions begin as vesicles and progress to ulcers before they crust over. Lesions last for 2–3 weeks.
- An aseptic meningitis syndrome occurs in 1–35% of cases. Patients will have fever, headache, meningismus, and photophobia.
- Latent virus causes recurrent episodes, which are painful but less severe than in primary infections.
Neonatal Infection
- Samples for viral isolation can be obtained from viral transport media.
- Serologic tests are not useful for diagnosis of maternal or neonatal herpes during the acute phase of the disease.
- PCR testing of the CSF is now recommended, and in some studies is proving to be quite useful in making the diagnosis.
- Cells from the base of freshly unroofed vesicles can be smeared on a slide for monoclonal antibody immunofluorescence.
Encephalitis
- Cerebrospinal fluid (CSF) reveals a pleocytosis with up to 2000 WBC/mm3 and usually over 60% of the cells are lymphocytes.
- In an atraumatic lumbar puncture red blood cells, indicating hemorrhagic necrosis occur in 75 to 85 percent of cases.
- CSF protein is elevated (median, 80 mg/dL).
- HSV almost never grows from CSF.
- Electroencephalogram (EEG) can reveal a “typical pattern” of unilateral or bilateral focal spikes.
- A focal abnormality on EEG, CT, or MRI is highly suggestive of HSV encephalitis.
- The only definitive way to make the diagnosis is to perform a brain biopsy, which is essential to provide appropriate therapy.
Gingivostomatitis
Physicians usually make this diagnosis clinically since it is so common in young children.
Vulvovaginitis
- A Tzanck preparation from the base of a lesion will show multinucleate giant cells in 60% of cases.
- Viral culture obtained by unroofing a vesicle and rubbing a sterile swab over the base of the vesicle to have a sensitivity of 94% for early lesions. Sensitivity decreases to 27% for crusted lesions.
- Immunofluorescence has a sensitivity of 90%.
NEONATAL INFECTION
Intravenous acyclovir (30 mg/kg/d in 3 divided doses) is the preferred drug. Some experts give higher doses (45–60 mg/kg/d). The recommended minimal duration of therapy is 14 days, and sometimes courses as long as 21 days may be indicated. Infants with ocular involvement due to HSV infection should receive a topical ophthalmic drug (1–2% trifluridine, 1% iododeoxyuridine, or 3% vidarabine) in addition to parenteral antiviral therapy.
ENCEPHALITIS
Intravenous acyclovir (30 mg/kg/d) three times a day for 14–21 days is appropriate therapy for HSV encephalitis after the neonatal period. In addition to parenteral antiviral therapy appropriate management of fluids, intracranial pressure, and seizures is essential.
GINGIVOSTOMATITIS
Most patients are managed with symptomatic therapy including antipyretics and oral fluids like popsicles. Oral anesthetics can be harmful and result in self injury when children chew on anesthetized lips. Topical acyclovir is often used in the treatment of recurrent oral herpes. It decreases the duration of HSV shedding but has minimal effect on the symptoms.
VULVOVAGINITIS
Acyclovir (Zovirax) is the appropriate therapy for genital herpes infection. Oral acyclovir is used for patients with primary genital HSV infection. Intravenous acyclovir is used for patients with severe local or systemic or complications like aseptic meningitis syndrome.
PREVENTION
- Neonatal infection
- Cesarean section in a mother with active genital herpes at the time of delivery is the main way to prevent neonatal infection. The risk of HSV infection in an infant born vaginally to a mother with a first-episode primary genital infection is high (33–50%). The risk to an infant born to a mother with recurrent HSV infection at delivery is much lower (3–5%). However, this does not prevent all cases since 60–80% of mothers of infected infants are asymptomatic or have unrecognized infection.
- Postnatal infection
- Universal body substance precaution policies
- Adults with oral herpes must be particularly careful to use appropriate hygiene.
- Wrestlers with skin lesions suggestive of herpes
- Patients with genital lesions from HSV should not have intercourse until the lesions heal.
- Condoms can prevent the spread of virus.
PROGNOSIS
- Neonatal infection
- Overall mortality from untreated neonatal HSV infection is 50% and only 26% of survivors are normal.
- Combined treatment with vidarabine and acyclovir lowers mortality to 17% and increases survival.
- Infants with disseminated disease or localized CNS disease have the worst prognosis to 67%.
- The major sequelae in survivors are brain damage, seizures, and blindness.
| COMMON QUESTIONS AND ANSWERS |
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Q: What about recurrent cutaneous eruptions in a neonate? Should they be treated?
A: The need for retreatment of infants with recurrent skin lesions is undetermined and under study. Because of concerns about silent CNS recurrent infection, some experts are recommending acyclovir, 300 mg/m2 in three doses for 6–12 months. One needs to look for neutropenia, which will occur in 25% of patients.
Q: Is prophylactic therapy for recurrent herpes genitalia helpful? When is it indicated?
A: Antiviral therapy has minimal effect on recurrent genital herpes. Oral acyclovir initiated within 2 days of onset of symptoms shortens the course. Topical acyclovir is not helpful.
Q: What steps should be taken in the nursery for an infant born to an HSV-positive mother?
A: Neonates with documented perinatal exposure to HSV may be in the incubation phase of infection and should be observed carefully. Infants of mothers with active HSV should be isolated if they have been delivered vaginally or by cesarean section after membranes were ruptured for more than 4–6 hours. The risk of HSV infection in possibly exposed infants (e.g., those born to a mother with a history of recurrent genital herpes) is low, and isolation is not necessary.
ICD-9-CM 054.9
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Copyright © 2000 Lippincott Williams & Wilkins
M. William Schwartz, Louis M. Bell, Jr., Peter M. Bingham, Esther K. Chung, David F. Friedman and Andrew E. Mulberg, The 5 Minute Pediatric Consult