Herpes Simplex Follow-up

Because of the ubiquitous and cosmopolitan nature of herpes simplex virus (HSV), avoiding contact with individuals who (often asymptomatically) are excreting the virus in saliva or genital secretions is difficult. Daily antiviral therapy can be given to reduce episodes of asymptomatic genital shedding and to further reduce the risk of transmission; however, it is unclear how long this should be administered.

Although not easily applicable to oral-oral contact, barrier protection using latex condoms is recommended to minimize exposure to genital HSV infections.

Because HSV genital ulcers may occur outside of areas covered by the condom, transmission can occur in those areas.

Herpetic whitlow can be avoided with latex gloves when health care workers insert their hands into the oral cavity of patients. Transmission of genital virus to the hand can occur during unprotected finger-genital contact during sexual activities.

Suppressive antiviral therapy can be used in individuals with frequent and/or particularly symptomatic relapses, but clinical trials have shown variable results.

Despite therapy with high-dose antivirals, HSV transmission may occur during suppressive antiviral therapy. In 3 separate but complementary crossover trials, Johnston et al studied the effect of various drug regimens on viral shedding in individuals who were HSV-2 seropositive. Treatment with either acyclovir 400 mg BID (standard-dose acyclovir) or valacyclovir 500 mg BID (standard-dose valacyclovir) with acyclovir 800 mg TID (high-dose acyclovir) was compared to no medication. Standard-dose valacyclovir was also compared with valacyclovir 1 g TID (high-dose valacyclovir). Results showed short bursts of subclinical genital HSV reactivation were frequent, even during high-dose antiherpes therapy.^[31]

An investigational HSV vaccine was not effective in preventing HSV-2 disease or infection in a study population that was representative of the general population of HSV-1– and HSV-2–seronegative women. The investigational vaccine was effective in preventing HSV-1 genital disease and infection.^[32]

• Bacterial and fungal superinfections are not uncommon.

  • Balanitis can occur in an uncircumcised male as a result of bacterial infection of the herpetic ulcers.
  • Candidal vaginitis has been described in as many as 10% of women with primary genital herpes, particularly in women with diabetes. Care should be taken to confirm the diagnosis of candidiasis, as ulcerative herpetic disease can have whitish mucosal lesions that can be confused with yeast infection.
• Ocular infections

  • This complication is not uncommon in children as a result of autoinoculation during acute herpetic gingivostomatosis or asymptomatic oropharyngeal HSV infection.
  • Ocular infection is caused primarily by HSV-1, except in neonates, in whom it may be caused by HSV-2, and manifests as unilateral follicular conjunctivitis or as acute herpetic keratoconjuctivitis with dendritic corneal ulcers.^[13]
  • Recurrences occur in as many as 25% of patients and can be associated with progressive scarring of the cornea. HSV has been the leading infectious cause of blindness in the United States.
• Skin infections: Various cutaneous complications related to HSV can occur.

  • Eczema herpeticum: This occurs in individuals with underlying dermatitis and may be localized (which can be confused with herpes zoster) or disseminated. The process can also occur in patients with extensive skin breakdown as with burns, pemphigus, or Sézary syndrome.
  • Herpetic whitlow: HSV infections of the fingers occur at or near the cuticle or at other sites associated with trauma. When involving the nail area, it has been confused with a bacterial felon and been subjected, inappropriately, to incision and drainage. Herpetic whitlow is associated with HSV-1 in health care workers and children related to saliva exposure and with HSV-2 related to digital-genital exposure.
  • Herpes gladiatorum: Scattered cutaneous HSV-1 lesions have been observed in wrestlers who have had viral contact through exposure to infectious saliva during a match.
• Visceral infections: HSV infection of the visceral organs usually results from viremia, and multiple organ involvement is common. This may occur during otherwise asymptomatic primary infections and sometimes in seemingly immunocompetent hosts.

  • In most cases of disseminated herpes, the lesions are confined to the skin; however, fatal visceral dissemination can occur with or without vesicular skin lesions. Multiple organs are involved, but fulminant HSV hepatitis is usually clinically prominent.
  • It is associated with leukopenia, thrombocytopenia, and disseminated intravascular coagulation.
  • Disseminated HSV-1 and HSV-2 infections can also result in herpetic esophagitis, adrenal necrosis, interstitial HSV pneumonitis, HSV cystitis, HSV arthritis, HSV meningitis, and HSV encephalitis.
• Central nervous system complications^{[10, 14]}

  • Aseptic meningitis: This condition is an acute, generally benign lymphocytic meningitis. In one series, 36% of women and 13% of men with primary genital HSV-2 infection had meningeal symptoms on two consecutive examinations. It is more common with HSV-2 infection. Meningeal symptoms usually start 3-12 days after the onset of genital lesions; they reach a maximum 2-4 days into the illness and recede over 2-4 days. Signs and symptoms of encephalitis are unusual, and neurological sequelae are rare. HSV-1 also has been identified by PCR in the CSF of patients with benign lymphocytic recurrent meningitis (Mollaret meningitis), suggesting that HSV may be the cause of this so-called idiopathic syndrome.
  • Ganglionitis and myelitis: Genital and anorectal HSV infections may be complicated by urinary retention, sacral neuralgia, and sacral anesthesia. This is due to associated ganglionitis and radiculitis. The symptoms usually resolve in 1-2 weeks. Transverse myelitis is rarely reported.
  • Herpes simplex encephalitis: This is an acute necrotizing viral encephalitis that, beyond the neonatal period, is nearly always caused by HSV-1. It accounts for 10%-20% of all cases of encephalitis and is the most common cause of sporadic acute necrotizing encephalitis in the United States. Herpes simplex encephalitis occurs as a primary infection in about 50% of cases and may be due to recurrent infection or to reinfection with a different strain of HSV-1 in the remainder. Clinical features include the following:
    • Nonspecific findings common to all forms of encephalitis, which include headache, signs of meningeal irritation, altered mental status, and generalized seizures
    • Changes referable to focal necrosis of the orbitofrontal and temporal cortex and the limbic system, including anosmia, memory loss, olfactory and gustatory hallucinations, and focal seizures
    • Rapid development of hemiparesis and coma may occur. In some patients, the clinical picture is protracted, mimicking acute psychosis or delirium tremens.
    • The CSF has moderate pleocytosis with mixed mononuclear cells and polymorphonuclear cells, moderate RBC counts, and mildly elevated protein levels with normal glucose levels.
    • MRI is the most sensitive imaging procedure.
    • The most sensitive noninvasive method of diagnosis is the demonstration of HSV DNA by PCR.
    • The mortality rate is high (70%) in untreated patients. Even with treatment, a high incidence of neurological sequelae remains.
• Genital herpes and pregnancy

  • Recurrent genital herpes is similar in pregnant and nonpregnant women, although an increase in the number of recurrences in the course of pregnancy may occur.
  • Recurrent genital herpes accounts for 1%-2% of all cases of neonatal herpes. Cesarean delivery is recommended in mothers who have active genital lesions during labor. However, presence of active genital lesions is not a good indicator of HSV viral shedding.^[15] Thus the American College of Obstetricians and Gynecologists (ACOG) recommends that suppressive antiviral therapy be given to all women with a history of recurrent genital HSV in the last 4 weeks of pregnancy.^[16]
  • A large nationwide cohort study in Denmark did not find any association between first trimester in utero antiviral drug (ie, acyclovir, valacyclovir, famciclovir) exposure and birth congenital anomalies. In 1804 pregnancies exposed to an antiviral drug during the first trimester, 40 infants (2.2%) were diagnosed with a major birth defect compared with 19,920 (2.4%) unexposed pregnancies.^[17]
  • Primary genital infection during pregnancy
    • First-episode infections have more severe consequences to the mother and infant. Thus, identification of women at risk for primary infection (seronegative for HSV-2) is paramount.
    • Serological discordance between partners may be 15%-20%, so that the risk of a seronegative mother becoming infected from the father during pregnancy is 10%-15%.
    • Pregnant women may have widely disseminated infection with a high mortality rate (50%).
    • Infection in the third trimester of pregnancy is associated with neonatal HSV infections, intrauterine growth retardation, and prematurity.
• Neonatal HSV disease

  • Ninety percent of infections are acquired perinatally, 5%-8% are acquired congenitally, and a few are acquired postnatally.
  • Neonatal HSV infection is caused by contact with infected genital secretions.
  • In 70% of mothers, the infection is asymptomatic. The risk of transmission from a mother with primary infection is about 50%.^[18]
  • Neonates and infants (aged < 6 wk) have a very high frequency of visceral and CNS infections. Without therapy, the mortality rate is 65%, and a high degree of neurological sequelae exists.
  • The disease may be confined to the skin, eyes, or mouth, or it may manifest as encephalitis or disseminated visceral disease involving the lungs, liver, heart, adrenals, and skin. This neonate displayed a maculopapular outbreak on his feet due to congenitally acquired herpes simplex virus infection. Courtesy of the CDC/Judith Faulk.
• Copathogenesis with HIV: Multiple studies have shown that the presence of antibodies to HSV-2 increases the risk of becoming infected with HIV, independent of the presence of genital ulcers.^[19] While early studies in Africa have demonstrated a reduction of HIV viral load in patients with HIV infection receiving therapy directed toward HSV infection, the mechanism is unclear.^{[20, 21]} The association between HIV and HSV may change the epidemiologic approach to sexually transmitted diseases worldwide.

For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center and Teeth and Mouth Center. Also, see eMedicine's patient education articles Genital Herpes, Oral Herpes, Birth Control Overview, and Birth Control FAQs.